Diclofenac Prolongs Repolarization in Ventricular Muscle with Impaired Repolarization Reserve
Kristóf, Attila; Husti, Zoltán; Koncz, István; Kohajda, Zsófia; Szél, Tamás; Juhász, Viktor; Biliczki, Péter; Jost, Norbert; Baczkó, István; Papp, Julius Gy; Varró, András; Virág, László
2012-01-01
Background The aim of the present work was to characterize the electrophysiological effects of the non-steroidal anti-inflammatory drug diclofenac and to study the possible proarrhythmic potency of the drug in ventricular muscle. Methods Ion currents were recorded using voltage clamp technique in canine single ventricular cells and action potentials were obtained from canine ventricular preparations using microelectrodes. The proarrhythmic potency of the drug was investigated in an anaesthetized rabbit proarrhythmia model. Results Action potentials were slightly lengthened in ventricular muscle but were shortened in Purkinje fibers by diclofenac (20 µM). The maximum upstroke velocity was decreased in both preparations. Larger repolarization prolongation was observed when repolarization reserve was impaired by previous BaCl2 application. Diclofenac (3 mg/kg) did not prolong while dofetilide (25 µg/kg) significantly lengthened the QTc interval in anaesthetized rabbits. The addition of diclofenac following reduction of repolarization reserve by dofetilide further prolonged QTc. Diclofenac alone did not induce Torsades de Pointes ventricular tachycardia (TdP) while TdP incidence following dofetilide was 20%. However, the combination of diclofenac and dofetilide significantly increased TdP incidence (62%). In single ventricular cells diclofenac (30 µM) decreased the amplitude of rapid (IKr) and slow (IKs) delayed rectifier currents thereby attenuating repolarization reserve. L-type calcium current (ICa) was slightly diminished, but the transient outward (Ito) and inward rectifier (IK1) potassium currents were not influenced. Conclusions Diclofenac at therapeutic concentrations and even at high dose does not prolong repolarization markedly and does not increase the risk of arrhythmia in normal heart. However, high dose diclofenac treatment may lengthen repolarization and enhance proarrhythmic risk in hearts with reduced repolarization reserve. PMID:23300901
Diclofenac prolongs repolarization in ventricular muscle with impaired repolarization reserve.
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Attila Kristóf
Full Text Available BACKGROUND: The aim of the present work was to characterize the electrophysiological effects of the non-steroidal anti-inflammatory drug diclofenac and to study the possible proarrhythmic potency of the drug in ventricular muscle. METHODS: Ion currents were recorded using voltage clamp technique in canine single ventricular cells and action potentials were obtained from canine ventricular preparations using microelectrodes. The proarrhythmic potency of the drug was investigated in an anaesthetized rabbit proarrhythmia model. RESULTS: Action potentials were slightly lengthened in ventricular muscle but were shortened in Purkinje fibers by diclofenac (20 µM. The maximum upstroke velocity was decreased in both preparations. Larger repolarization prolongation was observed when repolarization reserve was impaired by previous BaCl(2 application. Diclofenac (3 mg/kg did not prolong while dofetilide (25 µg/kg significantly lengthened the QT(c interval in anaesthetized rabbits. The addition of diclofenac following reduction of repolarization reserve by dofetilide further prolonged QT(c. Diclofenac alone did not induce Torsades de Pointes ventricular tachycardia (TdP while TdP incidence following dofetilide was 20%. However, the combination of diclofenac and dofetilide significantly increased TdP incidence (62%. In single ventricular cells diclofenac (30 µM decreased the amplitude of rapid (I(Kr and slow (I(Ks delayed rectifier currents thereby attenuating repolarization reserve. L-type calcium current (I(Ca was slightly diminished, but the transient outward (I(to and inward rectifier (I(K1 potassium currents were not influenced. CONCLUSIONS: Diclofenac at therapeutic concentrations and even at high dose does not prolong repolarization markedly and does not increase the risk of arrhythmia in normal heart. However, high dose diclofenac treatment may lengthen repolarization and enhance proarrhythmic risk in hearts with reduced repolarization reserve.
DEFF Research Database (Denmark)
Thomsen, Morten Bækgaard; Truin, Michiel; van Opstal, Jurren M
2005-01-01
Increased proarrhythmia in dogs with chronic AV block (AVB) has been explained by ventricular remodeling causing a decrease in repolarization reserve. Beat-to-beat variability of repolarization (BVR) has been suggested to reflect repolarization reserve, in which high variability represents...... diminished reserve and larger propensity for repolarization-dependent ventricular arrhythmia. A subset of chronic AVB dogs (10%) suffers sudden cardiac death (SCD). With the assumption that repolarization defects constitute a potentially lethal proarrhythmic substrate, we hypothesized that BVR in SCD dogs...... are larger than in matched control chronic AVB dogs. From a population of 200 chronic AVB dogs, initially two groups were chosen retrospectively: 8 dogs that died suddenly (SCD) and 8 control dogs. Control dogs had a longer lifespan after AVB (10 to 18 weeks) than SCD dogs (5 to 10 weeks). All dogs had...
Cardiac action potential repolarization revisited: early repolarization shows all-or-none behaviour.
Trenor, Beatriz; Cardona, Karen; Saiz, Javier; Noble, Denis; Giles, Wayne
2017-11-01
In healthy mammalian hearts the action potential (AP) waveform initiates and modulates each contraction, or heartbeat. As a result, AP height and duration are key physiological variables. In addition, rate-dependent changes in ventricular AP duration (APD), and variations in APD at a fixed heart rate are both reliable biomarkers of electrophysiological stability. Present guidelines for the likelihood that candidate drugs will increase arrhythmias rely on small changes in APD and Q-T intervals as criteria for safety pharmacology decisions. However, both of these measurements correspond to the final repolarization of the AP. Emerging clinical evidence draws attention to the early repolarization phase of the action potential (and the J-wave of the ECG) as an additional important biomarker for arrhythmogenesis. Here we provide a mechanistic background to this early repolarization syndrome by summarizing the evidence that both the initial depolarization and repolarization phases of the cardiac action potential can exhibit distinct time- and voltage-dependent thresholds, and also demonstrating that both can show regenerative all-or-none behaviour. An important consequence of this is that not all of the dynamics of action potential repolarization in human ventricle can be captured by data from single myocytes when these results are expressed as 'repolarization reserve'. For example, the complex pattern of cell-to-cell current flow that is responsible for AP conduction (propagation) within the mammalian myocardium can change APD and the Q-T interval of the electrocardiogram alter APD stability, and modulate responsiveness to pharmacological agents (such as Class III anti-arrhythmic drugs). © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.
Na/K pump regulation of cardiac repolarization: insights from a systems biology approach
Bueno-Orovio, Alfonso
2013-05-15
The sodium-potassium pump is widely recognized as the principal mechanism for active ion transport across the cellular membrane of cardiac tissue, being responsible for the creation and maintenance of the transarcolemmal sodium and potassium gradients, crucial for cardiac cell electrophysiology. Importantly, sodium-potassium pump activity is impaired in a number of major diseased conditions, including ischemia and heart failure. However, its subtle ways of action on cardiac electrophysiology, both directly through its electrogenic nature and indirectly via the regulation of cell homeostasis, make it hard to predict the electrophysiological consequences of reduced sodium-potassium pump activity in cardiac repolarization. In this review, we discuss how recent studies adopting the systems biology approach, through the integration of experimental and modeling methodologies, have identified the sodium-potassium pump as one of the most important ionic mechanisms in regulating key properties of cardiac repolarization and its rate dependence, from subcellular to whole organ levels. These include the role of the pump in the biphasic modulation of cellular repolarization and refractoriness, the rate control of intracellular sodium and calcium dynamics and therefore of the adaptation of repolarization to changes in heart rate, as well as its importance in regulating pro-arrhythmic substrates through modulation of dispersion of repolarization and restitution. Theoretical findings are consistent across a variety of cell types and species including human, and widely in agreement with experimental findings. The novel insights and hypotheses on the role of the pump in cardiac electrophysiology obtained through this integrative approach could eventually lead to novel therapeutic and diagnostic strategies. © 2013 Springer-Verlag Berlin Heidelberg.
Na/K pump regulation of cardiac repolarization: insights from a systems biology approach.
Bueno-Orovio, Alfonso; Sánchez, Carlos; Pueyo, Esther; Rodriguez, Blanca
2014-02-01
The sodium-potassium pump is widely recognized as the principal mechanism for active ion transport across the cellular membrane of cardiac tissue, being responsible for the creation and maintenance of the transarcolemmal sodium and potassium gradients, crucial for cardiac cell electrophysiology. Importantly, sodium-potassium pump activity is impaired in a number of major diseased conditions, including ischemia and heart failure. However, its subtle ways of action on cardiac electrophysiology, both directly through its electrogenic nature and indirectly via the regulation of cell homeostasis, make it hard to predict the electrophysiological consequences of reduced sodium-potassium pump activity in cardiac repolarization. In this review, we discuss how recent studies adopting the systems biology approach, through the integration of experimental and modeling methodologies, have identified the sodium-potassium pump as one of the most important ionic mechanisms in regulating key properties of cardiac repolarization and its rate dependence, from subcellular to whole organ levels. These include the role of the pump in the biphasic modulation of cellular repolarization and refractoriness, the rate control of intracellular sodium and calcium dynamics and therefore of the adaptation of repolarization to changes in heart rate, as well as its importance in regulating pro-arrhythmic substrates through modulation of dispersion of repolarization and restitution. Theoretical findings are consistent across a variety of cell types and species including human, and widely in agreement with experimental findings. The novel insights and hypotheses on the role of the pump in cardiac electrophysiology obtained through this integrative approach could eventually lead to novel therapeutic and diagnostic strategies.
Ventricular repolarization measures for arrhythmic risk stratification
Institute of Scientific and Technical Information of China (English)
Francesco Monitillo; Marta Leone; Caterina Rizzo; Andrea Passantino; Massimo Iacoviello
2016-01-01
Ventricular repolarization is a complex electrical phenomenon which represents a crucial stage in electrical cardiac activity. It is expressed on the surface electrocardiogram by the interval between the start of the QRS complex and the end of the T wave or U wave(QT). Several physiological, pathological and iatrogenic factors can influence ventricular repolarization. It has been demonstrated that small perturbations in this process can be a potential trigger of malignant arrhythmias, therefore the analysis of ventricular repolarization represents an interesting tool to implement risk stratification of arrhythmic events in different clinical settings. The aim of this review is to critically revise the traditional methods of static analysis of ventricular repolarization as well as those for dynamic evaluation, their prognostic significance and the possible application in daily clinical practice.
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A. Yu. Tikhomirov
2017-01-01
Full Text Available Purpose. To study the effectiveness of various schemes of correction of repolarization disorder syndrome, including with the use of beta-blockers, in young athletes of the initial training group.Materials and methods. At the first stage, 410 children involved in sports sections were examined. The average age of the examined was 12.22 ± 3.11 years. At the second stage, the athletes (boys of the initial training group were selected from the surveyed contingent, engaged in martial arts. The groups were formed: A – people with violation of myocardial repolarization processes (72 patients, the average age 10,50 ± 0,35 years, the control group – people without changes in an electrocardiogram (33 people, the average age 10.36 ± 0, 62 years old. All underwent an electrocardiographic study at rest and after physical activity on the Innomed HS80GL apparatus with analysis of the main indicators. The vegetative status and the state of adaptation were estimated by Kerdo index and adaptive potential by Baevsky. After the examination, the subgroup A1 (40 people was prescribed metabolic and antioxidant drugs. Additionally, in the subgroup A2 (32 people, a non-selective beta-blocker was included in the treatment regimen. The course of treatment is 10 days. The analysis of indicators was carried out in 10 days and in a month after the initiation treatment. Statistical processing was carried out in the program Statistica.Results. An earlier disappearance of cardialgia was determined in the subgroup A2 (p < 0.05, whereas in the subgroup A1, 5% of patients had complaints not only at the end of the course, but also a month later after the initiation treatment. The more rapid positive dynamics of the electrocardiographic pattern with a more stable result was observed with the prescription of a beta-blocker.Conclusion. It was proved the advisability of prescribing of beta-blockers in the treatment of beginning athletes with violation of myocardial repolarization
Characterization of Myocardial Repolarization Reserve in Adolescent Females With Anorexia Nervosa.
Padfield, Gareth J; Escudero, Carolina A; DeSouza, Astrid M; Steinberg, Christian; Gibbs, Karen; Puyat, Joseph H; Lam, Pei Yoong; Sanatani, Shubhayan; Sherwin, Elizabeth; Potts, James E; Sandor, George; Krahn, Andrew D
2016-02-09
Patients with anorexia nervosa exhibit abnormal myocardial repolarization and are susceptible to sudden cardiac death. Exercise testing is useful in unmasking QT prolongation in disorders associated with abnormal repolarization. We characterized QT adaptation during exercise in anorexia. Sixty-one adolescent female patients with anorexia nervosa and 45 age- and sex-matched healthy volunteers performed symptom-limited cycle ergometry during 12-lead ECG monitoring. Changes in the QT interval during exercise were measured, and QT/RR-interval slopes were determined by using mixed-effects regression modeling. Patients had significantly lower body mass index than controls; however, resting heart rates and QT/QTc intervals were similar at baseline. Patients had shorter exercise times (13.7±4.5 versus 20.6±4.5 minutes; Panorexia nervosa. © 2016 American Heart Association, Inc.
Components of action potential repolarization in cerebellar parallel fibres.
Pekala, Dobromila; Baginskas, Armantas; Szkudlarek, Hanna J; Raastad, Morten
2014-11-15
Repolarization of the presynaptic action potential is essential for transmitter release, excitability and energy expenditure. Little is known about repolarization in thin, unmyelinated axons forming en passant synapses, which represent the most common type of axons in the mammalian brain's grey matter.We used rat cerebellar parallel fibres, an example of typical grey matter axons, to investigate the effects of K(+) channel blockers on repolarization. We show that repolarization is composed of a fast tetraethylammonium (TEA)-sensitive component, determining the width and amplitude of the spike, and a slow margatoxin (MgTX)-sensitive depolarized after-potential (DAP). These two components could be recorded at the granule cell soma as antidromic action potentials and from the axons with a newly developed miniaturized grease-gap method. A considerable proportion of fast repolarization remained in the presence of TEA, MgTX, or both. This residual was abolished by the addition of quinine. The importance of proper control of fast repolarization was demonstrated by somatic recordings of antidromic action potentials. In these experiments, the relatively broad K(+) channel blocker 4-aminopyridine reduced the fast repolarization, resulting in bursts of action potentials forming on top of the DAP. We conclude that repolarization of the action potential in parallel fibres is supported by at least three groups of K(+) channels. Differences in their temporal profiles allow relatively independent control of the spike and the DAP, whereas overlap of their temporal profiles provides robust control of axonal bursting properties.
Identification of local myocardial repolarization time by bipolar electrode potential.
Namba, Tsunetoyo; Todo, Takahiro; Yao, Takenori; Ashihara, Takashi; Haraguchi, Ryo; Nakazawa, Kazuo; Ikeda, Takanori; Ohe, Tohru
2007-01-01
The aim of this study was to investigate whether bipolar electrode potentials (BEPs) reflect local myocardial repolarization dynamics, using computer simulation. Simulated action potential and BEP mapping of myocardial tissue during fibrillation was performed. The BEP was modified to make all the fluctuations have the same polarity. Then, the modified BEP (mBEP) was transformed to "dynamic relative amplitude" (DRA) designed to make all the fluctuations have the similar amplitude. The repolarization end point corresponded to the end of the repolarization-related small fluctuation that clearly appeared in the DRA of mBEP. Using the DRA of mBEP, we could reproduce the repolarization dynamics in the myocardial tissue during fibrillation. The BEP may facilitate identifying the repolarization time. Furthermore, BEP mapping has the possibility that it would be available for evaluating repolarization behavior in myocardial tissue even during fibrillation. The accuracy of activation-recovery interval was also reconfirmed.
Heart rate profile during exercise in patients with early repolarization.
Cay, Serkan; Cagirci, Goksel; Atak, Ramazan; Balbay, Yucel; Demir, Ahmet Duran; Aydogdu, Sinan
2010-09-01
Both early repolarization and altered heart rate profile are associated with sudden death. In this study, we aimed to demonstrate an association between early repolarization and heart rate profile during exercise. A total of 84 subjects were included in the study. Comparable 44 subjects with early repolarization and 40 subjects with normal electrocardiogram underwent exercise stress testing. Resting heart rate, maximum heart rate, heart rate increment and decrement were analyzed. Both groups were comparable for baseline characteristics including resting heart rate. Maximum heart rate, heart rate increment and heart rate decrement of the subjects in early repolarization group had significantly decreased maximum heart rate, heart rate increment and heart rate decrement compared to control group (all P decrement (multiple-adjusted OR of the risk of presence of early repolarization was 2.98 (95%CI 1.21-7.34) (P = 0.018) and 7.73 (95%CI 2.84-21.03) (P decrement compared to higher levels, respectively. Subjects with early repolarization have altered heart rate profile during exercise compared to control subjects. This can be related to sudden death.
Diurnal modulation and sources of variation affecting ventricular repolarization in Warmblood horses
DEFF Research Database (Denmark)
Pedersen, Philip Juul; Moeller, Sine B.; Madsen, Mette Flethøj
2014-01-01
Te) are used as repolarization markers. To support the use of these markers in horses, we sought to describe the possible influence of the environment, time of day, day-to-day effects, T wave conformation, age, body weight (BW), and horse-to-horse variation on repolarization measurements. ANIMALS: 12 Warmblood...... affecting these intervals. RESULTS: Differences between individual horses were the largest source of repolarization variability although the environment had a significant effect on repolarization as well. Diurnal variation affected both the RR interval and the repolarization markers. The QT, QTc and Tp......, diurnal variation, the environment, and T wave conformation. These factors must be considered if markers of equine repolarization are used diagnostically....
Major rapid weight loss induces changes in cardiac repolarization
DEFF Research Database (Denmark)
Vedel-Larsen, Esben; Iepsen, Eva Winning; Lundgren, Julie
2016-01-01
INTRODUCTION: Obesity is associated with increased all-cause mortality, but weight loss may not decrease cardiovascular events. In fact, very low calorie diets have been linked to arrhythmias and sudden death. The QT interval is the standard marker for cardiac repolarization, but T-wave morphology...... analysis has been suggested as a more sensitive method to identify changes in cardiac repolarization. We examined the effect of a major and rapid weight loss on T-wave morphology. METHODS AND RESULTS: Twenty-six individuals had electrocardiograms (ECG) taken before and after eight weeks of weight loss......A1c (pweight loss induces changes in cardiac repolarization. Monitoring of MCS during calorie restriction makes it possible to detect repolarization changes with higher discriminative power than the QT-interval during major rapid weight...
Analysis of Ion Currents Contribution to Repolarization in Human Heart Failure Using Computer Models
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Marotta, F.; Paci, M.A.; Severi, S.; Trenor, B.
2016-07-01
The mechanisms underlying repolarization of the ventricular action potential (AP) are subject of research for anti-arrhythmic drugs. In fact, the prolongation of the AP occurs in several conditions of heart disease, such as heart failure, a major problem precursor for serious arrhythmias. In this study, we investigated the phenomena of repolarization reserve, defined as the capacity of the cell to repolarize in case of a functional loss, and the all-or-none repolarization, which depends on the delicate balance of inward and outward currents in the different phases of the AP, under conditions of human heart failure (HF). To simulate HF conditions, the O'Hara et al. human AP model was modified and specific protocols for all-or-none repolarization were applied. Our results show that in the early repolarization the threshold for all-or-none repolarization is not altered in HF even if a decrease in potassium currents can be observed. To quantify the contribution of the individual ion currents to HF induced AP prolongation, we used a novel piecewise-linear approximation approach proposed by Paci et al. In particular, INaL and ICaL are the main responsible for APD prolongation due to HF (85 and 35 ms respectively). Our results highlight this novel algorithm as a powerful tool to have a more complete picture of the complex ionic mechanisms underlying this disease and confirm the important role of the late sodium current in HF repolarization. (Author)
Histone Deacetylase Inhibitors Prolong Cardiac Repolarization through Transcriptional Mechanisms.
Spence, Stan; Deurinck, Mark; Ju, Haisong; Traebert, Martin; McLean, LeeAnne; Marlowe, Jennifer; Emotte, Corinne; Tritto, Elaine; Tseng, Min; Shultz, Michael; Friedrichs, Gregory S
2016-09-01
Histone deacetylase (HDAC) inhibitors are an emerging class of anticancer agents that modify gene expression by altering the acetylation status of lysine residues of histone proteins, thereby inducing transcription, cell cycle arrest, differentiation, and cell death or apoptosis of cancer cells. In the clinical setting, treatment with HDAC inhibitors has been associated with delayed cardiac repolarization and in rare instances a lethal ventricular tachyarrhythmia known as torsades de pointes. The mechanism(s) of HDAC inhibitor-induced effects on cardiac repolarization is unknown. We demonstrate that administration of structurally diverse HDAC inhibitors to dogs causes delayed but persistent increases in the heart rate corrected QT interval (QTc), an in vivo measure of cardiac repolarization, at timepoints far removed from the Tmax for parent drug and metabolites. Transcriptional profiling of ventricular myocardium from dogs treated with various HDAC inhibitors demonstrated effects on genes involved in protein trafficking, scaffolding and insertion of various ion channels into the cell membrane as well as genes for specific ion channel subunits involved in cardiac repolarization. Extensive in vitro ion channel profiling of various structural classes of HDAC inhibitors (and their major metabolites) by binding and acute patch clamp assays failed to show any consistent correlations with direct ion channel blockade. Drug-induced rescue of an intracellular trafficking-deficient mutant potassium ion channel, hERG (G601S), and decreased maturation (glycosylation) of wild-type hERG expressed by CHO cells in vitro correlated with prolongation of QTc intervals observed in vivo The results suggest that HDAC inhibitor-induced prolongation of cardiac repolarization may be mediated in part by transcriptional changes of genes required for ion channel trafficking and localization to the sarcolemma. These data have broad implications for the development of these drug classes and
ECG-Based Measurements of Drug-induced Repolarization Changes
DEFF Research Database (Denmark)
Bhuiyan, Tanveer Ahmed
The purpose of this thesis is to investigate the abnormal repolarization both in the cellular and the surface ECG along with their relationship. It has been identified that the certain morphological changes of the monophasic action potential are predictor of TdP arrhythmia. Therefore the proporti......The purpose of this thesis is to investigate the abnormal repolarization both in the cellular and the surface ECG along with their relationship. It has been identified that the certain morphological changes of the monophasic action potential are predictor of TdP arrhythmia. Therefore...... the proportional changes of the surface ECG which corresponds to the arrhythmia-triggering MAP morphology is warranted to increase the confidence of determining cardiotoxicity of drugs....
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Mehmet Kayrak
2012-01-01
Full Text Available Previous studies have demonstrated impaired ventricular repolarization in patients with β-TM. However, the effect of iron overload with cardiac T2* magnetic resonance imaging (MRI on cardiac repolarization remains unclear yet. We aimed to examine relationship between repolarization parameters and iron loading using cardiac T2* MRI in asymptomatic β-TM patients. Twenty-two β-TM patients and 22 age- and gender-matched healthy controls were enrolled to the study. From the 12-lead surface electrocardiography, regional and transmyocardial repolarization parameters were evaluated manually by two experienced cardiologists. All patients were also undergone MRI for cardiac T2* evaluation. Cardiac T2* score <20 msec was considered as iron overload status. Of the QT parameters, QT duration, corrected QT interval, and QT peak duration were significantly longer in the β-TM group compared to the healthy controls. Tp−Te and Tp−Te dispersions were also significantly prolonged in β-TM group compared to healthy controls. (Tp-Te/QT was similar between groups. There was no correlation between repolarization parameters and cardiac T2* MRI values. In conclusion, although repolarization parameters were prolonged in asymptomatic β-TM patients compared with control, we could not find any relation between ECG findings and cardiac iron load.
DEFF Research Database (Denmark)
Oosterhoff, Peter; Thomsen, Morten Bækgaard; Maas, Joep N
2010-01-01
-term variability of repolarization (STV) as a feedback parameter of arrhythmic risk. Methods and Results: The minimal signal sampling frequency required for measuring STV was determined through computer simulation. Arrhythmogenic response to dofetilide (25 µg/kg/5minutes) was tested at two different paced heart...
DEFF Research Database (Denmark)
Thomsen, Morten Bækgaard; Verduyn, S Cora; Stengl, Milan
2004-01-01
Identification of patients at risk for drug-induced torsades de pointes arrhythmia (TdP) is difficult. Increased temporal lability of repolarization has been suggested as being valuable to predict proarrhythmia. The predictive value of different repolarization parameters, including beat...
Klein, Michael G; Shou, Matie; Stohlman, Jayna; Solhjoo, Soroosh; Haigney, Myles; Tidwell, Richard R; Goldstein, Robert E; Flagg, Thomas P; Haigney, Mark C
2017-08-01
The failing heart exhibits an increased arrhythmia susceptibility that is often attributed to action potential (AP) prolongation due to significant ion channel remodeling. The inwardly rectifying K + current (I K1 ) has been reported to be reduced, but its contribution to shaping the AP waveform and cell excitability in the failing heart remains unclear. The purpose of this study was to define the effect of I K1 suppression on the cardiac AP and excitability in the normal and failing hearts. We used electrophysiological and pharmacological approaches to investigate I K1 function in a swine tachy-pacing model of heart failure (HF). Terminal repolarization of the AP (TRAP; the time constant of the exponential fit to terminal repolarization) was markedly prolonged in both myocytes and arterially perfused wedges from animals with HF. TRAP was increased by 54.1% in HF myocytes (P < .001) and 26.2% in HF wedges (P = .014). The increase in TRAP was recapitulated by the potent and specific I K1 inhibitor, PA-6 (pentamidine analog 6), indicating that I K1 is the primary determinant of the final phase of repolarization. Moreover, we find that I K1 suppression reduced the ratio of effective refractory period to AP duration at 90% of repolarization, permitting re-excitation before full repolarization, reduction of AP upstroke velocity, and likely promotion of slow conduction. Using an objective measure of terminal repolarization, we conclude that I K1 is the major determinant of the terminal repolarization time course. Moreover, suppression of I K1 prolongs repolarization and reduces postrepolarization refractoriness without marked effects on the overall AP duration. Collectively, these findings demonstrate how I K1 suppression may contribute to arrhythmogenesis in the failing heart. Published by Elsevier Inc.
[The influence of occupational lead exposure on transmural repolarization dispersion].
Zyśko, Dorota; Gajek, Jacek; Chlebda, Ewa; Mazurek, Walentyna
2005-02-01
The parts of QT interval: time from Q wave to the peak of T wave (QTp) representing the de- and repolarization of subepicardial layer and the time from the peak of T wave to its end (QTp-e) building the transmural dispersion of repolarization enable more exact assessment of repolarization period of the heart muscle. Occupational exposure to lead influences the electrophysiologic properties of the heart. The aim of our study was to assess the QTp and QTp-e interval in workers occupationally exposed to lead. The study was carried out in 22 copper smelters aged 41.8 +/- 8.7 years, occupationally exposed to lead. The control group consisted of 14 healthy men. In all studied subjects blood lead concentration (Pb) and the concentration of free protoporphyrins in erytrocytes were assessed. 24-hour ECG holter monitoring was done to study rhythm disturbances and the duration in lead CM5 of QT interval, QTp interval, RR interval preceding the assessed QT interval (pRR) during sleep, rest during the awake state and moderate daily activity. The QTp-e interval is the difference between the duration of QT and QTp interval. The duration of QTp and QTp-e in occupationally exposed workers and healthy persons did not differ significantly. These parameters were significantly lower in both groups during moderately physical activity comparing to the values during sleep. The QTp-e/ QTp ratio in occupationally exposed workers during night hours was significantly lower than during daily activity what was not the case in control persons. Occupational exposure to lead do not change significantly the transmural dispersion of repolarization. Occupational exposure to lead diminishes the QTp-e/QTp ratio during the night.
Directory of Open Access Journals (Sweden)
Oliver J. Britton
2017-05-01
Full Text Available Background: Cellular repolarization abnormalities occur unpredictably due to disease and drug effects, and can occur even in cardiomyocytes that exhibit normal action potentials (AP under control conditions. Variability in ion channel densities may explain differences in this susceptibility to repolarization abnormalities. Here, we quantify the importance of key ionic mechanisms determining repolarization abnormalities following ionic block in human cardiomyocytes yielding normal APs under control conditions.Methods and Results: Sixty two AP recordings from non-diseased human heart preparations were used to construct a population of human ventricular models with normal APs and a wide range of ion channel densities. Multichannel ionic block was applied to investigate susceptibility to repolarization abnormalities. IKr block was necessary for the development of repolarization abnormalities. Models that developed repolarization abnormalities over the widest range of blocks possessed low Na+/K+ pump conductance below 50% of baseline, and ICaL conductance above 70% of baseline. Furthermore, INaK made the second largest contribution to repolarizing current in control simulations and the largest contribution under 75% IKr block. Reversing intracellular Na+ overload caused by reduced INaK was not sufficient to prevent abnormalities in models with low Na+/K+ pump conductance, while returning Na+/K+ pump conductance to normal substantially reduced abnormality occurrence, indicating INaK is an important repolarization current.Conclusions: INaK is an important determinant of repolarization abnormality susceptibility in human ventricular cardiomyocytes, through its contribution to repolarization current rather than homeostasis. While we found IKr block to be necessary for repolarization abnormalities to occur, INaK decrease, as in disease, may amplify the pro-arrhythmic risk of drug-induced IKr block in humans.
Probing cardiac repolarization reserve in drug safety assessment
Nalos, L.
2011-01-01
Excessive prolongation of cardiac repolarization, manifested as QT prolongation on ECG, is common unwanted side effect of many drugs and drug candidates. Prolongation of QT interval may lead to life threatening cardiac arrhythmia – Torsade de Point (TdP). Number of drugs was withdrawn from the
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Michele Orini
Full Text Available The restitution of the action potential duration (APDR and conduction velocity (CVR are mechanisms whereby cardiac excitation and repolarization adapt to changes in heart rate. They modulate the vulnerability to dangerous arrhythmia, but the mechanistic link between restitution and arrhythmogenesis remains only partially understood.This paper provides an experimental and theoretical study of repolarization and excitation restitution properties and their interactions in the intact human epicardium. The interdependence between excitation and repolarization dynamic is studied in 8 patients (14 restitution protocols, 1722 restitution curves undergoing global epicardial mapping with multi-electrode socks before open heart surgery. A mathematical description of the contribution of both repolarization and conduction dynamics to the steepness of the APDR slope is proposed.This study demonstrates that the APDR slope is a function of both activation and repolarization dynamics. At short cycle length, conduction delay significantly increases the APDR slope by interacting with the diastolic interval. As predicted by the proposed mathematical formulation, the APDR slope was more sensitive to activation time prolongation than to the simultaneous shortening of repolarization time. A steep APDR slope was frequently identified, with 61% of all cardiac sites exhibiting an APDR slope > 1, suggesting that a slope > 1 may not necessarily promote electrical instability in the human epicardium. APDR slope did not change for different activation or repolarization times, and it was not a function of local baseline APD. However, it was affected by the spatial organization of electrical excitation, suggesting that in tissue APDR is not a unique function of local electrophysiological properties. Spatial heterogeneity in both activation and repolarization restitution contributed to the increase in the modulated dispersion of repolarization, which for short cycle length was
Britton, Oliver J; Bueno-Orovio, Alfonso; Virág, László; Varró, András; Rodriguez, Blanca
2017-01-01
Background: Cellular repolarization abnormalities occur unpredictably due to disease and drug effects, and can occur even in cardiomyocytes that exhibit normal action potentials (AP) under control conditions. Variability in ion channel densities may explain differences in this susceptibility to repolarization abnormalities. Here, we quantify the importance of key ionic mechanisms determining repolarization abnormalities following ionic block in human cardiomyocytes yielding normal APs under control conditions. Methods and Results: Sixty two AP recordings from non-diseased human heart preparations were used to construct a population of human ventricular models with normal APs and a wide range of ion channel densities. Multichannel ionic block was applied to investigate susceptibility to repolarization abnormalities. I Kr block was necessary for the development of repolarization abnormalities. Models that developed repolarization abnormalities over the widest range of blocks possessed low Na + /K + pump conductance below 50% of baseline, and I CaL conductance above 70% of baseline. Furthermore, I NaK made the second largest contribution to repolarizing current in control simulations and the largest contribution under 75% I Kr block. Reversing intracellular Na + overload caused by reduced I NaK was not sufficient to prevent abnormalities in models with low Na + /K + pump conductance, while returning Na + /K + pump conductance to normal substantially reduced abnormality occurrence, indicating I NaK is an important repolarization current. Conclusions: I NaK is an important determinant of repolarization abnormality susceptibility in human ventricular cardiomyocytes, through its contribution to repolarization current rather than homeostasis. While we found I Kr block to be necessary for repolarization abnormalities to occur, I NaK decrease, as in disease, may amplify the pro-arrhythmic risk of drug-induced I Kr block in humans.
Toib, Amir; Zhang, Chen; Borghetti, Giulia; Zhang, Xiaoxiao; Wallner, Markus; Yang, Yijun; Troupes, Constantine D; Kubo, Hajime; Sharp, Thomas E; Feldsott, Eric; Berretta, Remus M; Zalavadia, Neil; Trappanese, Danielle M; Harper, Shavonn; Gross, Polina; Chen, Xiongwen; Mohsin, Sadia; Houser, Steven R
2017-09-01
Hypertrophic cardiomyopathy (HCM) is one of the most common genetic cardiac diseases and among the leading causes of sudden cardiac death (SCD) in the young. The cellular mechanisms leading to SCD in HCM are not well known. Prolongation of the action potential (AP) duration (APD) is a common feature predisposing hypertrophied hearts to SCD. Previous studies have explored the roles of inward Na + and Ca 2+ in the development of HCM, but the role of repolarizing K + currents has not been defined. The objective of this study was to characterize the arrhythmogenic phenotype and cellular electrophysiological properties of mice with HCM, induced by myosin-binding protein C (MyBPC) knockout (KO), and to test the hypothesis that remodeling of repolarizing K + currents causes APD prolongation in MyBPC KO myocytes. We demonstrated that MyBPC KO mice developed severe hypertrophy and cardiac dysfunction compared with wild-type (WT) control mice. Telemetric electrocardiographic recordings of awake mice revealed prolongation of the corrected QT interval in the KO compared with WT control mice, with overt ventricular arrhythmias. Whole cell current- and voltage-clamp experiments comparing KO with WT mice demonstrated ventricular myocyte hypertrophy, AP prolongation, and decreased repolarizing K + currents. Quantitative RT-PCR analysis revealed decreased mRNA levels of several key K + channel subunits. In conclusion, decrease in repolarizing K + currents in MyBPC KO ventricular myocytes contributes to AP and corrected QT interval prolongation and could account for the arrhythmia susceptibility. NEW & NOTEWORTHY Ventricular myocytes isolated from the myosin-binding protein C knockout hypertrophic cardiomyopathy mouse model demonstrate decreased repolarizing K + currents and action potential and QT interval prolongation, linking cellular repolarization abnormalities with arrhythmia susceptibility and the risk for sudden cardiac death in hypertrophic cardiomyopathy. Copyright © 2017
The Role of Serotonin in Ventricular Repolarization in Pregnant Mice.
Cui, Shanyu; Park, Hyewon; Park, Hyelim; Mun, Dasom; Lee, Seung Hyun; Kim, Hyoeun; Yun, Nuri; Kim, Hail; Kim, Michael; Pak, Hui Nam; Lee, Moon Hyoung; Joung, Boyoung
2018-03-01
The mechanisms underlying repolarization abnormalities during pregnancy are not fully understood. Although maternal serotonin (5-hydroxytryptamine, 5-HT) production is an important determinant for normal fetal development in mice, its role in mothers remains unclear. We evaluated the role of serotonin in ventricular repolarization in mice hearts via 5Htr3 receptor (Htr3a) and investigated the mechanism of QT-prolongation during pregnancy. We measured current amplitudes and the expression levels of voltage-gated K⁺ (Kv) channels in freshly-isolated left ventricular myocytes from wild-type non-pregnant (WT-NP), late-pregnant (WT-LP), and non-pregnant Htr3a homozygous knockout mice (Htr3a(-/-)-NP). During pregnancy, serotonin and tryptophan hydroxylase 1, a rate-limiting enzyme for the synthesis of serotonin, were markedly increased in hearts and serum. Serotonin increased Kv current densities concomitant with the shortening of the QT interval in WT-NP mice, but not in WT-LP and Htr3a(-/-)-NP mice. Ondansetron, an Htr3 antagonist, decreased Kv currents in WT-LP mice, but not in WT-NP mice. Kv4.3 directly interacted with Htr3a, and this binding was facilitated by serotonin. Serotonin increased the trafficking of Kv4.3 channels to the cellular membrane in WT-NP. Serotonin increases repolarizing currents by augmenting Kv currents. Elevated serotonin levels during pregnancy counterbalance pregnancy-related QT prolongation by facilitating Htr3-mediated Kv currents. © Copyright: Yonsei University College of Medicine 2018
Pharmacokinetics and repolarization effects of intravenous and transdermal granisetron.
Mason, Jay W; Selness, Daniel S; Moon, Thomas E; O'Mahony, Bridget; Donachie, Peter; Howell, Julian
2012-05-15
The need for greater clarity about the effects of 5-HT(3) receptor antagonists on cardiac repolarization is apparent in the changing product labeling across this therapeutic class. This study assessed the repolarization effects of granisetron, a 5-HT(3) receptor antagonist antiemetic, administered intravenously and by a granisetron transdermal system (GTDS). In a parallel four-arm study, healthy subjects were randomized to receive intravenous granisetron, GTDS, placebo, or oral moxifloxacin (active control). The primary endpoint was difference in change from baseline in mean Fridericia-corrected QT interval (QTcF) between GTDS and placebo (ddQTcF) on days 3 and 5. A total of 240 subjects were enrolled, 60 in each group. Adequate sensitivity for detection of QTc change was shown by a 5.75 ms lower bound of the 90% confidence interval (CI) for moxifloxacin versus placebo at 2 hours postdose on day 3. Day 3 ddQTcF values varied between 0.2 and 1.9 ms for GTDS (maximum upper bound of 90% CI, 6.88 ms), between -1.2 and 1.6 ms for i.v. granisetron (maximum upper bound of 90% CI, 5.86 ms), and between -3.4 and 4.7 ms for moxifloxacin (maximum upper bound of 90% CI, 13.45 ms). Day 5 findings were similar. Pharmacokinetic-ddQTcF modeling showed a minimally positive slope of 0.157 ms/(ng/mL), but a very low correlation (r = 0.090). GTDS was not associated with statistically or clinically significant effects on QTcF or other electrocardiographic variables. This study provides useful clarification on the effect of granisetron delivered by GTDS on cardiac repolarization. ©2012 AACR.
Bossu, Alexandre; Varkevisser, Rosanne; Beekman, Henriette D.M.; Houtman, Marien J C; Van Der Heyden, Marcel A.G.; Vos, Marc A.
2017-01-01
Short-term variability (STV), to quantify beat-to-beat variability of repolarization, is a surrogate parameter that reliably identifies proarrhythmic risk in preclinical models. Examples include not only the use in the chronic atrioventricular block (CAVB) dog model whereby it was developed but also
Jani, Ylber; Kamberi, Ahmet; Xhunga, Sotir; Pocesta, Bekim; Ferati, Fatmir; Lala, Dali; Zeqiri, Agim; Rexhepi, Atila
2015-01-01
Objective: To assess the influence of type 2 DM and gender, on the QT dispersion, Tpeak-Tend dispersion of ventricular repolarization, in patients with sub-clinic left ventricular diastolic dysfunction of the heart. Background: QT dispersion, that reflects spatial inhomogeneity in ventricular repolarization, Tpeak-Tend dispersion, this on the other hand reflects transmural inhomogeneity in ventricular repolarization, that is increased in an early stage of cardiomyopathy, and in patients with ...
Arking, Dan E.; Pulit, Sara L.; Crotti, Lia; van der Harst, Pim; Munroe, Patricia B.; Koopmann, Tamara T.; Sotoodehnia, Nona; Rossin, Elizabeth J.; Morley, Michael; Wang, Xinchen; Johnson, Andrew D.; Lundby, Alicia; Gudbjartsson, Daníel F.; Noseworthy, Peter A.; Eijgelsheim, Mark; Bradford, Yuki; Tarasov, Kirill V.; Dörr, Marcus; Müller-Nurasyid, Martina; Lahtinen, Annukka M.; Nolte, Ilja M.; Smith, Albert Vernon; Bis, Joshua C.; Isaacs, Aaron; Newhouse, Stephen J.; Evans, Daniel S.; Post, Wendy S.; Waggott, Daryl; Lyytikäinen, Leo-Pekka; Hicks, Andrew A.; Eisele, Lewin; Ellinghaus, David; Hayward, Caroline; Navarro, Pau; Ulivi, Sheila; Tanaka, Toshiko; Tester, David J.; Chatel, Stéphanie; Gustafsson, Stefan; Kumari, Meena; Morris, Richard W.; Naluai, Åsa T.; Padmanabhan, Sandosh; Kluttig, Alexander; Strohmer, Bernhard; Panayiotou, Andrie G.; Torres, Maria; Knoflach, Michael; Hubacek, Jaroslav A.; Slowikowski, Kamil; Raychaudhuri, Soumya; Kumar, Runjun D.; Harris, Tamara B.; Launer, Lenore J.; Shuldiner, Alan R.; Alonso, Alvaro; Bader, Joel S.; Ehret, Georg; Huang, Hailiang; Kao, W.H. Linda; Strait, James B.; Macfarlane, Peter W.; Brown, Morris; Caulfield, Mark J.; Samani, Nilesh J.; Kronenberg, Florian; Willeit, Johann; Smith, J. Gustav; Greiser, Karin H.; zu Schwabedissen, Henriette Meyer; Werdan, Karl; Carella, Massimo; Zelante, Leopoldo; Heckbert, Susan R.; Psaty, Bruce M.; Rotter, Jerome I.; Kolcic, Ivana; Polašek, Ozren; Wright, Alan F.; Griffin, Maura; Daly, Mark J.; Arnar, David O.; Hólm, Hilma; Thorsteinsdottir, Unnur; Denny, Joshua C.; Roden, Dan M.; Zuvich, Rebecca L.; Emilsson, Valur; Plump, Andrew S.; Larson, Martin G.; O'Donnell, Christopher J.; Yin, Xiaoyan; Bobbo, Marco; D'Adamo, Adamo P.; Iorio, Annamaria; Sinagra, Gianfranco; Carracedo, Angel; Cummings, Steven R.; Nalls, Michael A.; Jula, Antti; Kontula, Kimmo K.; Marjamaa, Annukka; Oikarinen, Lasse; Perola, Markus; Porthan, Kimmo; Erbel, Raimund; Hoffmann, Per; Jöckel, Karl-Heinz; Kälsch, Hagen; Nöthen, Markus M.; consortium, HRGEN; den Hoed, Marcel; Loos, Ruth J.F.; Thelle, Dag S.; Gieger, Christian; Meitinger, Thomas; Perz, Siegfried; Peters, Annette; Prucha, Hanna; Sinner, Moritz F.; Waldenberger, Melanie; de Boer, Rudolf A.; Franke, Lude; van der Vleuten, Pieter A.; Beckmann, Britt Maria; Martens, Eimo; Bardai, Abdennasser; Hofman, Nynke; Wilde, Arthur A.M.; Behr, Elijah R.; Dalageorgou, Chrysoula; Giudicessi, John R.; Medeiros-Domingo, Argelia; Barc, Julien; Kyndt, Florence; Probst, Vincent; Ghidoni, Alice; Insolia, Roberto; Hamilton, Robert M.; Scherer, Stephen W.; Brandimarto, Jeffrey; Margulies, Kenneth; Moravec, Christine E.; Fabiola Del, Greco M.; Fuchsberger, Christian; O'Connell, Jeffrey R.; Lee, Wai K.; Watt, Graham C.M.; Campbell, Harry; Wild, Sarah H.; El Mokhtari, Nour E.; Frey, Norbert; Asselbergs, Folkert W.; Leach, Irene Mateo; Navis, Gerjan; van den Berg, Maarten P.; van Veldhuisen, Dirk J.; Kellis, Manolis; Krijthe, Bouwe P.; Franco, Oscar H.; Hofman, Albert; Kors, Jan A.; Uitterlinden, André G.; Witteman, Jacqueline C.M.; Kedenko, Lyudmyla; Lamina, Claudia; Oostra, Ben A.; Abecasis, Gonçalo R.; Lakatta, Edward G.; Mulas, Antonella; Orrú, Marco; Schlessinger, David; Uda, Manuela; Markus, Marcello R.P.; Völker, Uwe; Snieder, Harold; Spector, Timothy D.; Ärnlöv, Johan; Lind, Lars; Sundström, Johan; Syvänen, Ann-Christine; Kivimaki, Mika; Kähönen, Mika; Mononen, Nina; Raitakari, Olli T.; Viikari, Jorma S.; Adamkova, Vera; Kiechl, Stefan; Brion, Maria; Nicolaides, Andrew N.; Paulweber, Bernhard; Haerting, Johannes; Dominiczak, Anna F.; Nyberg, Fredrik; Whincup, Peter H.; Hingorani, Aroon; Schott, Jean-Jacques; Bezzina, Connie R.; Ingelsson, Erik; Ferrucci, Luigi; Gasparini, Paolo; Wilson, James F.; Rudan, Igor; Franke, Andre; Mühleisen, Thomas W.; Pramstaller, Peter P.; Lehtimäki, Terho J.; Paterson, Andrew D.; Parsa, Afshin; Liu, Yongmei; van Duijn, Cornelia; Siscovick, David S.; Gudnason, Vilmundur; Jamshidi, Yalda; Salomaa, Veikko; Felix, Stephan B.; Sanna, Serena; Ritchie, Marylyn D.; Stricker, Bruno H.; Stefansson, Kari; Boyer, Laurie A.; Cappola, Thomas P.; Olsen, Jesper V.; Lage, Kasper; Schwartz, Peter J.; Kääb, Stefan; Chakravarti, Aravinda; Ackerman, Michael J.; Pfeufer, Arne; de Bakker, Paul I.W.; Newton-Cheh, Christopher
2014-01-01
The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal Mendelian Long QT Syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals we identified 35 common variant QT interval loci, that collectively explain ∼8-10% of QT variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 novel QT loci in 298 unrelated LQTS probands identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode for proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies novel candidate genes for ventricular arrhythmias, LQTS,and SCD. PMID:24952745
Takahashi, Naohiko; Shinohara, Tetsuji; Hara, Masahide; Saikawa, Tetsunori
2012-01-01
We encountered a 39-year-old man with documented ventricular fibrillation (VF). His ECGs showed intermittent Wolff-Parkinson-White (WPW) syndrome pattern. During electrophysiological study, no ventricular preexcitation was observed. An accessory pathway located at the posterior mitral annulus was identified, and successfully eliminated by radiofrequency catheter ablation. VF was not induced. His ECGs in the absence of delta waves demonstrated early repolarization in the inferior leads. This case raises the possibility that patients with manifest WPW syndrome may have an arrhythmogenic substrate associated with early repolarization, and the characteristic J waves can be masked by the presence of ventricular preexcitation.
Early repolarization in Wolff-Parkinson-White syndrome: prevalence and clinical significance.
Mizumaki, Koichi; Nishida, Kunihiro; Iwamoto, Jotaro; Nakatani, Yosuke; Yamaguchi, Yoshiaki; Sakamoto, Tamotsu; Tsuneda, Takayuki; Inoue, Hiroshi; Sakabe, Masao; Fujiki, Akira
2011-08-01
Idiopathic ventricular fibrillation (IVF) with early repolarization (ER) has recently been reported; however, ER is a common finding in healthy subjects and is also found sporadically in patients with Wolff-Parkinson-White (WPW) syndrome. The present study was designed to evaluate the prevalence and clinical significance of ER in patients with WPW syndrome. One hundred and eleven patients with WPW syndrome were studied retrospectively. Early repolarization was defined as QRS slurring or notching with J-point elevation ≥ 1 mm. The prevalence of ER was determined before and after successful catheter ablation. Before ablation, ER was found in 35 of 75 patients with a left free wall, 6 of 23 with a right free wall, and 7 of 13 with a septal accessory pathway (48 of 111, 43% as a whole). Early repolarization was always observed in leads with positive deflection of the initial part of the delta wave. After successful ablation of accessory pathways, ER was preserved in 28 (25%), disappeared in 20 (18%), and newly developed in 8 (7%) patients. In the remaining 55 (50%) patients, ER was not observed either before or after ablation. In patients with persistent ER, the amplitude and width of ER were significantly decreased 3-7 days after the ablation (1.7 ± 0.7 vs. 1.4 ± 0.6 mm, P syndrome, ER could be partly related to early depolarization through the accessory pathway. However, persistent ER and new ER appearing after the ablation were frequently found. Therefore, in these patients, mechanisms other than early depolarization may be involved in the genesis of ER.
International Nuclear Information System (INIS)
Gavrilyachenko, V.G.; Semenchev, A.F.; Sklyarova, E.N.; Kuznetsova, E.M.
2006-01-01
One studied experimentally changes of the residual polarization in lead zirconate-titanate base ceramics with various ferroelectric hardness under the effect of a strong varying field. The twinning and untwinning of crystallites accompanying repolarization is assumed to be the basic mechanism of propagation of the crystalline structure defects governing the fatigue rates of the ferroelectric-soft ceramics. In ferroelectric-hard ceramics crystallites the stable configurations of mechanical twins, the result of the secondary twinning, are formed when the hysteresis loop is formed. At repolarization in the mentioned structures one observes no motion of the twin boundaries, and the fatigue rates are low ones [ru
The analysis of QT interval and repolarization morphology of the heart in chronic exposure to lead.
Kiełtucki, J; Dobrakowski, M; Pawlas, N; Średniawa, B; Boroń, M; Kasperczyk, S
2017-10-01
There are no common recommendations regarding electrocardiographic monitoring in occupationally exposed workers. Therefore, the present study was designed to investigate whether exposure to lead results in an increase of selected electrocardiography (ECG) pathologies, such as QT interval prolongation and repolarization disorders, in occupationally exposed workers. The study group included 180 workers occupationally exposed to lead compounds. The exposed group was divided according to the median of the mean blood lead level (PbB mean ) calculated based on a series of measurements performed during 5-year observation period (35 µg/dl) into two subgroups: low exposure (LE, PbB mean = 20.0-35.0 µg/dl) and high exposure (HE, PbB mean = 35.1-46.4 µg/dl). The control group consisted of 69 healthy workers without occupational exposure to lead. ECG evaluation included the analysis of heart rate (HR), QT interval and repolarization abnormalities. Mean QT interval was significantly greater in the exposed population than in the control group by 2%. In the HE group, mean QT interval was significantly greater than in the control group by 4% and significantly different from those noted in the LE group. Positive correlations between QT interval and lead exposure indices were also reported. Besides, there was a negative correlation between HR and blood lead level. Increased concentration of lead in the blood above 35 μg/dl is associated with the QT interval prolongation, which may trigger arrhythmias when combined with other abnormalities, such as long QT syndrome. Therefore, electrocardiographic evaluation should be a part of a routine monitoring of occupationally exposed populations.
DEFF Research Database (Denmark)
Speerschneider, T; Grubb, Søren Jahn; Olesen, S P
2017-01-01
) were measured in isolated hearts using floating microelectrodes. RESULTS: Proarrhythmia in WT and KChIP2(-/-) was not sensitive to changes in refractory periods. Action potentials were longer in KChIP2(-/-) hearts compared to WT hearts. Isolated WT hearts had large apico-basal dispersion...... of repolarization time, whereas hearts from KChIP2(-/-) mice had large left-to-right ventricular dispersion of repolarization time. Pacing from the right ventricle in KChIP2(-/-) mice in vivo revealed significant lower current pulse amplitudes needed to induce arrhythmias in these mice. CONCLUSION: Large...
The T-peak–T-end Interval as a Marker of Repolarization Abnormality
DEFF Research Database (Denmark)
Bhuiyan, Tanveer A.; Graff, Claus; Kanters, Jørgen K.
2015-01-01
BACKGROUND AND OBJECTIVE: The T-peak to T-end (TpTe) interval has been suggested as an index of transmural dispersion and as a marker of drug-induced abnormal repolarization. In this study, we investigate the relation between TpTe and the QT interval. METHODS: Electrocardiograms (ECGs) from five...
Directory of Open Access Journals (Sweden)
Jason Bradfield, MD
2014-07-01
Conclusion: CD patients with CM and BBB or BBB alone have increased evidence of dispersion of repolarization compared to controls. QTd and (Tp-Ted were associated with increased mortality and/or need for transplant.
Directory of Open Access Journals (Sweden)
Marine E. Martinez
2018-06-01
Full Text Available Alteration of action potential duration (APD heterogeneity contributes to arrhythmogenesis. Purkinje-muscle junctions (PMJs present differential electrophysiological properties including longer APD. The goal of this study was to determine if Purkinje-related or myocardial focal activation modulates ventricular repolarization differentially in healthy and ischemic myocardium. Simultaneous epicardial (EPI and endocardial (ENDO optical mapping was performed on sheep left ventricular (LV wedges with intact free-running Purkinje network (N = 7. Preparations were paced on either ENDO or EPI surfaces, or the free-running Purkinje fibers (PFs, mimicking normal activation. EPI and ENDO APDs were assessed for each pacing configuration, before and after (7 min of the onset of no-flow ischemia. Experiments were supported by simulations. In control conditions, maximal APD was found at endocardial PMJ sites. We observed a significant transmural APD gradient for PF pacing with PMJ APD = 347 ± 41 ms and EPI APD = 273 ± 36 ms (p < 0.001. A similar transmural gradient was observed when pacing ENDO (49 ± 31 ms; p = 0.005. However, the gradient was reduced when pacing EPI (37 ± 20 ms; p = 0.005. Global dispersion of repolarization was the most pronounced for EPI pacing. In ischemia, both ENDO and EPI APD were reduced (p = 0.005 and the transmural APD gradient (109 ± 55 ms was increased when pacing ENDO compared to control condition or when pacing EPI (p < 0.05. APD maxima remained localized at functional PMJs during ischemia. Local repolarization dispersion was significantly higher at the PMJ than at other sites. The results were consistent with simulations. We found that the activation sequence modulates repolarization heterogeneity in the ischemic sheep LV. PMJs remain active following ischemia and exert significant influence on local repolarization patterns.
Repolarization of hepatocytes in culture.
Talamini, M A; Kappus, B; Hubbard, A
1997-01-01
We have evaluated the biochemical, morphological, and functional redevelopment of polarity in freshly isolated hepatocytes cultured using a double layer collagen gel sandwich technique. Western blot analysis showed increased cellular levels of the cell adhesion protein uvomorulin as cultured hepatocytes repolarized. Immunofluorescence studies using antibodies against domain-specific membrane proteins showed polarity as early as 48 hours, although the pattern of the polymeric Immunoglobulin-A receptor (pIgA-R) differed from in vivo liver. Electron microscopy showed developing bile canaliculi at 1 day. However, the functional presence of tight junctions was absent at 1 day, but present at 5 days. We further showed functional polarity to be present at 4 days by documenting the ability of cultured hepatocytes to metabolize and excrete fluorescein diacetate into visible bile canaliculi. We conclude that hepatocytes cultured appropriately develop morphological and functional polarity. Hepatocyte culture is therefore a useful tool for the study of mechanisms responsible for the development of polarized function.
National Research Council Canada - National Science Library
Lass, Jaanus
2001-01-01
In order to reveal the possible correlation between the level of myocardial electrical instability assessed at Holter monitoring and certain ECG parameters characterizing ventricular repolarization...
Romero, Daniel; Ringborn, Michael; Demidova, Marina; Koul, Sasha; Laguna, Pablo; Platonov, Pyotr G; Pueyo, Esther
2012-12-01
In this study, several electrocardiogram (ECG)-derived indices corresponding to both ventricular depolarization and repolarization were evaluated during acute myocardial ischemia in an experimental model of myocardial infarction produced by 40 min coronary balloon inflation in 13 pigs. Significant changes were rapidly observed from minute 4 after the start of coronary occlusion, achieving their maximum values between 11 and 22 min for depolarization and between 9 and 12 min for repolarization indices, respectively. Subsequently, these maximum changes started to decrease during the latter part of the occlusion. Depolarization changes associated with the second half of the QRS complex showed a significant but inverse correlation with the myocardium at risk (MaR) estimated by scintigraphic images. The correlation between MaR and changes of the downward slope of the QRS complex, [Formula: see text], evaluated at the two more relevant peaks observed during the occlusion, was r = -0.75, p evolution, respectively. Repolarization changes, analyzed by evaluation of ST segment elevation at the main observed positive peak, also showed negative, however non-significant correlation with MaR: r = -0.34, p = 0.28. Our results suggest that changes evaluated in the latter part of the depolarization, such as those described by [Formula: see text], which are influenced by R-wave amplitude, QRS width and ST level variations simultaneously, correlate better with the amount of ischemia than other indices evaluated in the earlier part of depolarization or during the ST segment.
Coronary Artery Disease Alters Ventricular Repolarization Dynamics in Type 2 Diabetes
Vrtovec, Bojan; Sinkovec, Matjaz; Starc, Vito; Radovancevic, Branislav; Schlegel, Todd T.
2005-01-01
Ventricular repolarization dynamics (VRD) is an important predictor of outcome in diabetes. We examined the potential impact of coronary artery disease (CAD) on VRD in type 2 diabetic patients. We recorded 5-min high-resolution resting electrocardiograms (ECG) in 38 diabetic patients undergoing elective coronary angiography, and in 38 age- and gender- matched apparently healthy subjects (Controls). Using leads I and II, time-domain indices of VRD were calculated. Coronary angiography was regarded as positive if a 350% stenosis was found. Angiography was positive in 21 diabetic patients (55%). Patients with CAD had a significantly higher degree of VRD than Controls (SDNN(QT): 15.81+/-7.22 ms vs. 8.94+/-6.04 ms; P <0.001, rMSSD(QT): 21.02k7.07 ms vs. 11.18k7.45 ms; P <0.001). VRD in diabetic patients with negative angiograms did not differ from VRD in Controls (SDNN(QT): 8.94+/-6.04 ms vs. 7.44+/-5.72 ms; P=0.67, rMSSD(QT): 11.18+/-7.45 ms vs. 10.22+/-5.35 ms; P=O. 82). CAD increases VRD in patients with type 2 diabetes. Therefore, changes in ventricular repolarization in diabetic patients may be due to silent CAD rather than to diabetes per se.
Shimizu, Wataru
2010-01-01
This review article sought to describe patterns of repolarization on the surface electrocardiogram in inherited cardiac arrhythmias and to discuss how the knowledge of genetic makeup and cellular data can affect the analysis based on the data derived from the experimental studies using arterially perfused canine ventricular wedge preparations. Molecular genetic studies have established a link between a number of inherited cardiac arrhythmia syndromes and mutations in genes encoding cardiac ion channels or membrane components during the past 2 decades. Twelve forms of congenital long QT syndrome have been so far identified, and genotype-phenotype correlations have been investigated especially in the 3 major genotypes-LQT1, LQT2, and LQT3. Abnormal T waves are reported in the LQT1, LQT2, and LQT3, and the differences in the time course of repolarization of the epicardial, midmyocardial, and endocardial cells give rise to voltage gradients responsible for the manifestation of phenotypic appearance of abnormal T waves. Brugada syndrome is characterized by ST-segment elevation in leads V1 to V3 and an episode of ventricular fibrillation, in which 7 genotypes have been reported. An intrinsically prominent transient outward current (I(to))-mediated action potential notch and a subsequent loss of action potential dome in the epicardium, but not in the endocardium of the right ventricular outflow tract, give rise to a transmural voltage gradient, resulting in ST-segment elevation, and a subsequent phase 2 reentry-induced ventricular fibrillation. In conclusion, transmural electrical heterogeneity of repolarization across the ventricular wall profoundly affects the phenotypic manifestation of repolarization patterns on the surface electrocardiogram in inherited cardiac arrhythmias. Copyright © 2010 Elsevier Inc. All rights reserved.
Directory of Open Access Journals (Sweden)
Massimiliano Zaniboni
Full Text Available Electrical restitution (ER is a major determinant of repolarization stability and, under fast pacing rate, it reveals memory properties of the cardiac action potential (AP, whose dynamics have never been fully elucidated, nor their ionic mechanisms. Previous studies have looked at ER mainly in terms of changes in AP duration (APD when the preceding diastolic interval (DI changes and described dynamic conditions where this relationship shows hysteresis which, in turn, has been proposed as a marker of short-term AP memory and repolarization stability. By means of numerical simulations of a non-propagated human ventricular AP, we show here that measuring ER as APD versus the preceding cycle length (CL provides additional information on repolarization dynamics which is not contained in the companion formulation. We focus particularly on fast pacing rate conditions with a beat-to-beat variable CL, where memory properties emerge from APD vs CL and not from APD vs DI and should thus be stored in APD and not in DI. We provide an ion-currents characterization of such conditions under periodic and random CL variability, and show that the memory stored in APD plays a stabilizing role on AP repolarization under pacing rate perturbations. The gating kinetics of L-type calcium current seems to be the main determinant of this safety mechanism. We also show that, at fast pacing rate and under otherwise identical pacing conditions, a periodically beat-to-beat changing CL is more effective than a random one in stabilizing repolarization. In summary, we propose a novel view of short-term AP memory, differentially stored between systole and diastole, which opens a number of methodological and theoretical implications for the understanding of arrhythmia development.
D.E. Arking (Dan); S.L. Pulit (Sara); L. Crotti (Lia); P. van der Harst (Pim); P. Munroe (Patricia); T.T. Koopmann (Tamara); N. Sotoodehnia (Nona); E. Rossin (Elizabeth); M. Morley (Michael); X. Wang (Xinchen); A.D. Johnson (Andrew); A. Lundby (Alicia); D.F. Gudbjartsson (Daniel); P.A. Noseworthy (Peter); M. Eijgelsheim (Mark); Y. Bradford (Yuki); K.V. Tarasov (Kirill); M. Dörr (Marcus); M. Müller-Nurasyid (Martina); A.M. Lahtinen (Annukka); I.M. Nolte (Ilja); G.D. Smith; J.C. Bis (Joshua); A.J. Isaacs (Aaron); S.J. Newhouse (Stephen); D.S. Evans (Daniel); W.S. Post (Wendy S.); D. Waggott (Daryl); L.-P. Lyytikäinen (Leo-Pekka); A.A. Hicks (Andrew); L. Eisele (Lewin); D. Ellinghaus (David); C. Hayward (Caroline); P. Navarro (Pau); S. Ulivi (Shelia); T. Tanaka (Toshiko); D.J. Tester (David); S. Chatel (Stéphanie); S. Gustafsson (Stefan); M. Kumari (Meena); R. Morris (Richard); A.T. Naluai (Asa); S. Padmanabhan (Sandosh); A. Kluttig (Alexander); B. Strohmer (Bernhard); A.G. Panayiotou (Andrie); M. Torres (Maria); M. Knoflach (Michael); J.A. Hubacek (Jaroslav A.); K. Slowikowski (Kamil); S. Raychaudhuri (Soumya); R.D. Kumar (Runjun); T.B. Harris (Tamara); L.J. Launer (Lenore); A.R. Shuldiner (Alan); A. Alonso (Alvaro); J.S. Bader (Joel); G.B. Ehret (Georg); H. Huang (Hailiang); W.H.L. Kao (Wen); J.B. Strait (James); P.W. Macfarlane (Peter); M.J. Brown (Morris); M. Caulfield (Mark); N.J. Samani (Nilesh); F. Kronenberg (Florian); J. Willeit (Johann); J.G. Smith (J. Gustav); K.H. Greiser (Karin Halina); H.M. Zu Schwabedissen (Henriette Meyer); K. Werdan (Karl); C. Carella (Cintia); L. Zelante (Leopoldo); S.R. Heckbert (Susan); B.M. Psaty (Bruce); J.I. Rotter (Jerome); I. Kolcic (Ivana); O. Polasek (Ozren); A.F. Wright (Alan); M. Griffin (Maura); M.J. Daly (Mark); D.O. Arnar (David); H. Hólm (Hilma); U. Thorsteinsdottir (Unnur); J.C. Denny (Joshua); D.M. Roden (Dan); R.L. Zuvich (Rebecca); V. Emilsson (Valur); A.S. Plump (Andrew); M.G. Larson (Martin); C.J. O'Donnell (Christopher); X. Yin (Xiaoyan); M. Bobbo (Marco); P. d' Adamo (Pio); A. Iorio (Annamaria); G. Sinagra (Gianfranco); A. Carracedo (Angel); S.R. Cummings (Steven); M.A. Nalls (Michael); A. Jula (Antti); K.K. Kontula (Kimmo); A. Marjamaa (Annukka); L. Oikarinen (Lasse); M. Perola (Markus); K. Porthan (Kimmo); R. Erbel (Raimund); P. Hoffmann (Per); K.-H. Jöckel (Karl-Heinz); H. Kälsch (Hagen); M.M. Nöthen (Markus); M. den Hoed (Marcel); R.J.F. Loos (Ruth); D.S. Thelle (Dag); C. Gieger (Christian); T. Meitinger (Thomas); S. Perz (Siegfried); A. Peters (Annette); H. Prucha (Hanna); M.F. Sinner (Moritz); M. Waldenberger (Melanie); R.A. de Boer (Rudolf); L. Franke (Lude); P.A. van der Vleuten (Pieter); B.M. Beckmann (Britt); E. Martens (Eimo); A. Bardai (Abdennasser); N. Hofman (Nynke); A.A.M. Wilde (Arthur); E.R. Behr (Elijah ); C. Dalageorgou (Chrysoula); J.R. Giudicessi (John); A. Medeiros-Domingo (Argelia); J. Barc (Julien); F. Kyndt (Florence); V. Probst (Vincent); A. Ghidoni (Alice); R. Insolia (Roberto); R.M. Hamilton (Robert); S.W. Scherer (Stephen); J. Brandimarto (Jeffrey); K. Margulies (Kenneth); C.E. Moravec (Christine); F. Del Greco M (Fabiola); C. Fuchsberger (Christian); J.R. O'Connell (Jeffery); W.K. Lee (Wai); G.C.M. Watt (Graham); H. Campbell (Harry); S.H. Wild (Sarah); N.E. El Mokhtari (Nour); N. Frey (Norbert); F.W. Asselbergs (Folkert); I.M. Leach (Irene Mateo); G. Navis (Gerjan); M.P. van den Berg (Maarten); D.J. van Veldhuisen (Dirk); M. Kellis (Manolis); B.P. Krijthe (Bouwe); O.H. Franco (Oscar); A. Hofman (Albert); J.A. Kors (Jan); A.G. Uitterlinden (André); J.C.M. Witteman (Jacqueline); L. Kedenko (Lyudmyla); C. Lamina (Claudia); B.A. Oostra (Ben); G.R. Abecasis (Gonçalo); E. Lakatta (Edward); A. Mulas (Antonella); M. Orrù (Marco); D. Schlessinger (David); M. Uda (Manuela); M.R.P. Markus (Marcello R. P.); U. Völker (Uwe); H. Snieder (Harold); T.D. Spector (Timothy); J. Ärnlöv (Johan); L. Lind (Lars); J. Sundstrom (Johan); A.C. Syvanen; M. Kivimaki (Mika); M. Kähönen (Mika); K. Mononen (Kari); O. Raitakari (Olli); J. Viikari (Jorma); V. Adamkova (Vera); S. Kiechl (Stefan); M.-J. Brion (Maria); A.N. Nicolaides (Andrew); B. Paulweber (Bernhard); J. Haerting (Johannes); A. Dominiczak (Anna); F. Nyberg (Fredrik); P.H. Whincup (Peter); A. Hingorani (Aroon); J.-J. Schott (Jean-Jacques); C.R. Bezzina (Connie); E. Ingelsson (Erik); L. Ferrucci (Luigi); P. Gasparini (Paolo); J.F. Wilson (James); I. Rudan (Igor); A. Franke (Andre); T.W. Mühleisen (Thomas); P.P. Pramstaller (Peter Paul); T. Lehtimäki (Terho); A.D. Paterson (Andrew); A. Parsa (Afshin); Y. Liu (YongMei); C.M. van Duijn (Cornelia); D.S. Siscovick (David); V. Gudnason (Vilmundur); Y. Jamshidi (Yalda); V. Salomaa (Veikko); S.B. Felix (Stephan); S. Sanna (Serena); M.D. Ritchie (Marylyn); B.H.Ch. Stricker (Bruno); J-A. Zwart (John-Anker); L.A. Boyer (Laurie); T.P. Cappola (Thomas); J.V. Olsen (Jesper); P. Lage (Pedro); P.J. Schwartz (Peter); S. Kääb (Stefan); A. Chakravarti (Aravinda); M. Ackerman (Margaret); A. Pfeufer (Arne); P.I.W. de Bakker (Paul); C. Newton-Cheh (Christopher)
2014-01-01
textabstractThe QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome
DEFF Research Database (Denmark)
Arking, Dan E; Pulit, Sara L; Crotti, Lia
2014-01-01
The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Usi...
Arking, Dan E.; Pulit, Sara L.; Crotti, Lia; van der Harst, Pim; Munroe, Patricia B.; Koopmann, Tamara T.; Sotoodehnia, Nona; Rossin, Elizabeth J.; Morley, Michael; Wang, Xinchen; Johnson, Andrew D.; Lundby, Alicia; Gudbjartsson, Daníel F.; Noseworthy, Peter A.; Eijgelsheim, Mark; Bradford, Yuki; Tarasov, Kirill V.; Dörr, Marcus; Müller-Nurasyid, Martina; Lahtinen, Annukka M.; Nolte, Ilja M.; Smith, Albert Vernon; Bis, Joshua C.; Isaacs, Aaron; Newhouse, Stephen J.; Evans, Daniel S.; Post, Wendy S.; Waggott, Daryl; Lyytikäinen, Leo-Pekka; Hicks, Andrew A.; Eisele, Lewin; Ellinghaus, David; Hayward, Caroline; Navarro, Pau; Ulivi, Sheila; Tanaka, Toshiko; Tester, David J.; Chatel, Stéphanie; Gustafsson, Stefan; Kumari, Meena; Morris, Richard W.; Naluai, Åsa T.; Padmanabhan, Sandosh; Kluttig, Alexander; Strohmer, Bernhard; Panayiotou, Andrie G.; Torres, Maria; Knoflach, Michael; Hubacek, Jaroslav A.; Slowikowski, Kamil; Raychaudhuri, Soumya; Kumar, Runjun D.; Harris, Tamara B.; Launer, Lenore J.; Shuldiner, Alan R.; Alonso, Alvaro; Bader, Joel S.; Ehret, Georg; Huang, Hailiang; Kao, W. H. Linda; Strait, James B.; Macfarlane, Peter W.; Brown, Morris; Caulfield, Mark J.; Samani, Nilesh J.; Kronenberg, Florian; Willeit, Johann; Smith, J. Gustav; Greiser, Karin H.; Meyer zu Schwabedissen, Henriette; Werdan, Karl; Carella, Massimo; Zelante, Leopoldo; Heckbert, Susan R.; Psaty, Bruce M.; Rotter, Jerome I.; Kolcic, Ivana; Polašek, Ozren; Wright, Alan F.; Griffin, Maura; Daly, Mark J.; Arnar, David O.; Hólm, Hilma; Thorsteinsdottir, Unnur; Denny, Joshua C.; Roden, Dan M.; Zuvich, Rebecca L.; Emilsson, Valur; Plump, Andrew S.; Larson, Martin G.; O'Donnell, Christopher J.; Yin, Xiaoyan; Bobbo, Marco; D'Adamo, Adamo P.; Iorio, Annamaria; Sinagra, Gianfranco; Carracedo, Angel; Cummings, Steven R.; Nalls, Michael A.; Jula, Antti; Kontula, Kimmo K.; Marjamaa, Annukka; Oikarinen, Lasse; Perola, Markus; Porthan, Kimmo; Erbel, Raimund; Hoffmann, Per; Jöckel, Karl-Heinz; Kälsch, Hagen; Nöthen, Markus M.; den Hoed, Marcel; Loos, Ruth J. F.; Thelle, Dag S.; Gieger, Christian; Meitinger, Thomas; Perz, Siegfried; Peters, Annette; Prucha, Hanna; Sinner, Moritz F.; Waldenberger, Melanie; de Boer, Rudolf A.; Franke, Lude; van der Vleuten, Pieter A.; Beckmann, Britt Maria; Martens, Eimo; Bardai, Abdennasser; Hofman, Nynke; Wilde, Arthur A. M.; Behr, Elijah R.; Dalageorgou, Chrysoula; Giudicessi, John R.; Medeiros-Domingo, Argelia; Barc, Julien; Kyndt, Florence; Probst, Vincent; Ghidoni, Alice; Insolia, Roberto; Hamilton, Robert M.; Scherer, Stephen W.; Brandimarto, Jeffrey; Margulies, Kenneth; Moravec, Christine E.; del Greco M, Fabiola; Fuchsberger, Christian; O'Connell, Jeffrey R.; Lee, Wai K.; Watt, Graham C. M.; Campbell, Harry; Wild, Sarah H.; El Mokhtari, Nour E.; Frey, Norbert; Asselbergs, Folkert W.; Mateo Leach, Irene; Navis, Gerjan; van den Berg, Maarten P.; van Veldhuisen, Dirk J.; Kellis, Manolis; Krijthe, Bouwe P.; Franco, Oscar H.; Hofman, Albert; Kors, Jan A.; Uitterlinden, André G.; Witteman, Jacqueline C. M.; Kedenko, Lyudmyla; Lamina, Claudia; Oostra, Ben A.; Abecasis, Gonçalo R.; Lakatta, Edward G.; Mulas, Antonella; Orrú, Marco; Schlessinger, David; Uda, Manuela; Markus, Marcello R. P.; Völker, Uwe; Snieder, Harold; Spector, Timothy D.; Ärnlöv, Johan; Lind, Lars; Sundström, Johan; Syvänen, Ann-Christine; Kivimaki, Mika; Kähönen, Mika; Mononen, Nina; Raitakari, Olli T.; Viikari, Jorma S.; Adamkova, Vera; Kiechl, Stefan; Brion, Maria; Nicolaides, Andrew N.; Paulweber, Bernhard; Haerting, Johannes; Dominiczak, Anna F.; Nyberg, Fredrik; Whincup, Peter H.; Hingorani, Aroon D.; Schott, Jean-Jacques; Bezzina, Connie R.; Ingelsson, Erik; Ferrucci, Luigi; Gasparini, Paolo; Wilson, James F.; Rudan, Igor; Franke, Andre; Mühleisen, Thomas W.; Pramstaller, Peter P.; Lehtimäki, Terho J.; Paterson, Andrew D.; Parsa, Afshin; Liu, Yongmei; van Duijn, Cornelia M.; Siscovick, David S.; Gudnason, Vilmundur; Jamshidi, Yalda; Salomaa, Veikko; Felix, Stephan B.; Sanna, Serena; Ritchie, Marylyn D.; Stricker, Bruno H.; Stefansson, Kari; Boyer, Laurie A.; Cappola, Thomas P.; Olsen, Jesper V.; Lage, Kasper; Schwartz, Peter J.; Kääb, Stefan; Chakravarti, Aravinda; Ackerman, Michael J.; Pfeufer, Arne; de Bakker, Paul I. W.; Newton-Cheh, Christopher
2014-01-01
The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using
Directory of Open Access Journals (Sweden)
Kim Sung
2012-12-01
Full Text Available Abstract Background Risk stratification of the early repolarization pattern (ERP is needed to identify malignant early repolarization. J-point elevation with a horizontal ST segment was recently suggested as a malignant feature of the ERP. In this study, the prevalence of the ERP with a horizontal ST segment was examined among survivors of sudden cardiac arrest (SCA without structural heart disease to evaluate the value of ST-segment morphology in risk stratification of the ERP. Methods We reviewed the data of 83 survivors of SCA who were admitted from August 2005 to August 2010. Among them, 25 subjects without structural heart disease were included. The control group comprised 60 healthy subjects who visited our health promotion center; all control subjects were matched for age, sex, and underlying disease (diabetes mellitus, hypertension. Early repolarization was defined as an elevation of the J point of at least 0.1 mV above the baseline in at least two continuous inferior or lateral leads that manifested as QRS slurring or notching. An ST-segment pattern of Results The SCA group included 17 men (64% with a mean age of 49.7 ± 14.5 years. The corrected QTc was not significantly different between the SCA and control groups (432.7 ± 37.96 vs. 420.4 ± 26.3, respectively; p = 0.089. The prevalence of ERP was not statistically different between the SCA and control groups (5/25, 20% vs. 4/60, 6.7%, respectively; p = 0.116. The prevalence of early repolarization with a horizontal ST segment was more frequent in the SCA than in the control group (20% vs. 3.3%, respectively; p = 0.021. Four SCA subjects (16% and one control subject (1.7% had a J-point elevation of >2 mm (p = 0.025. Four SCA subjects (16% and one (1.7% control subject had an ERP in the inferior lead (p = 0.025. Conclusion The prevalence of ERP with a horizontal ST segment was higher in patients with aborted SCA than in matched controls. This result suggests that ST morphology has
DEFF Research Database (Denmark)
Hyltén-Cavallius, Louise; Iepsen, Eva W; Christiansen, Michael
2017-01-01
BACKGROUND: Both hypoglycemia and severe hyperglycemia constitute known risk factors for cardiac repolarization changes potentially leading to malignant arrhythmias. Patients with loss of function mutations in KCNQ1 are characterized by long QT syndrome (LQTS) and may be at increased risk...
International Nuclear Information System (INIS)
Flotats, A.; Camacho, V.; Mena, E.; Tembl, A.; Estorch, M.; Carrio, I.; Serra-Grima, R.; Borras, X.; Cinca, J.
2002-01-01
Aim: Marked ventricular re-polarization abnormalities (MRA) in athletes may suggest the presence of associated heart disease. Assessment of LV function during exercise may contribute to rule out heart disease and help to decide continuation of physical training. The aim of the study was to assess whether athletes with MRA show a particular response of LV function to exhausting exercise. Material and Methods: Thirty-nine male athletes underwent monitoring of LV function with a miniaturised radionuclide detector (VEST, Capintec, Inc.) during bicycle exhausting exercise. There were 22 athletes with MRA in the ECG at rest (negative T waves equal or more than 2mm in up to 3 ECG leads) and 17 with normal ECG. All were symptom free. Age and physical fitness were comparable in both groups. Clinical examination, ECG, exercise test and echocardiography were performed in all athletes. Results: In all cases LV wall thickness was that expected for highly conditioned sportsmen. Both groups of athletes attained a similar energy expenditure. During exercise, athletes with MRA showed a tendency to normalise re-polarization. There were no differences in heart rate, LV end-systolic volume, LVEF, cardiac output , and peak ejection and filling rates at rest, 50%, 75%, 85% and 100% of peak HR, nor at 2, 5 and 10 min of recovery between both groups of athletes. At rest stroke volume was lower in athletes with MRA (60% vs. 64%, p=0.044). There were also no differences in LV end-diastolic volume (EDV), except at peak HR, when EDV increased in athletes with normal ECG while it decreased in athletes with MRA (p=0.047). Conclusions: The presence of marked ventricular re-polarization abnormalities in athletes does not substantially affect exercise performance nor LV function and should not preclude physical training. The VEST is a useful means to assess LV function during exhausting upright bicycle exercise
Patocskai, Bence; Barajas-Martinez, Hector; Hu, Dan; Gurabi, Zsolt; Koncz, István; Antzelevitch, Charles
2016-06-01
Early repolarization syndrome (ERS) is associated with polymorphic ventricular tachycardia (PVT) and ventricular fibrillation, leading to sudden cardiac death. The present study tests the hypothesis that the transient outward potassium current (Ito)-blocking effect of phosphodiesterase-3 (PDE-3) inhibitors plays a role in reversing repolarization heterogeneities responsible for arrhythmogenesis in experimental models of ERS. Transmembrane action potentials (APs) were simultaneously recorded from epicardial and endocardial regions of coronary-perfused canine left ventricular (LV) wedge preparations, together with a transmural pseudo-electrocardiogram. The Ito agonist NS5806 (7-15 μM) and L-type calcium current (ICa) blocker verapamil (2-3 μM) were used to induce an early repolarization pattern and PVT. After stable induction of arrhythmogenesis, the PDE-3 inhibitors cilostazol and milrinone or isoproterenol were added to the coronary perfusate. All were effective in restoring the AP dome in the LV epicardium, thus abolishing the repolarization defects responsible for phase 2 reentry and PVT. Arrhythmic activity was suppressed in 7 of 8 preparations by cilostazol (10 μM), 6 of 7 by milrinone (2.5 μM), and 7 of 8 by isoproterenol (0.1-1 μM). Using voltage clamp techniques applied to LV epicardial myocytes, both cilostazol (10 μM) and milrinone (2.5 μM) were found to reduce Ito by 44.4% and 40.4%, respectively, in addition to their known effects to augment ICa. Our findings suggest that PDE-3 inhibitors exert an ameliorative effect in the setting of ERS by producing an inward shift in the balance of current during the early phases of the epicardial AP via inhibition of Ito as well as augmentation of ICa, thus reversing the repolarization defects underlying the development of phase 2 reentry and ventricular tachycardia/ventricular fibrillation. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
DEFF Research Database (Denmark)
Calloe, Kirstine; Di Diego, José M; Hansen, Rie Schultz
2016-01-01
in cultured canine cardiac myocytes and determined whether a dual K(+) current activator can normalize K(+) currents and restore action potential (AP) configuration. METHODS AND RESULTS: Ventricular myocytes were isolated and cultured for up to 48h. Current and voltage clamp recordings were made using patch...... of EADs. Our results suggest a potential benefit of K(+) current activators under conditions of reduced repolarization reserve including heart failure....
Elitok, Ali; Öz, Fahrettin; Panc, Cafer; Sarıkaya, Remzi; Sezikli, Selim; Pala, Yasin; Bugan, Övgü Sinem; Ateş, Müge; Parıldar, Hilal; Ayaz, Mustafa Buğra; Atıcı, Adem; Oflaz, Hüseyin
2015-11-01
Energy drinks (EDs) are widely consumed products of the beverage industry and are often chosen by teenagers and young adults. Several adverse cardiovascular events and malignant cardiac arrhythmias following consumption of EDs have been reported in the literature. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the dispersion of repolarization and that an increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. This study investigated the acute effects of Red Bull ED on ventricular repolarization as assessed by the Tp-e interval and Tp-e/QT ratio. A prospective, open-label study design was used. After an 8-h fast, 50 young, healthy subjects consumed 355 mL of Red Bull ED. The Tp-e interval, Tp-e/QTc ratio, and several other electrocardiographic parameters were measured at baseline and 2 h after ingestion of Red Bull ED. No significant changes in the Tp-e interval or Tp-e/QTc ratio were observed with Red Bull ED consumption. Red Bull ED consumption led to increases in both systolic and diastolic blood pressures, which were associated with an increased heart rate. Although ingestion of Red Bull ED increases the heart rate and diastolic and systolic blood pressures, it does not cause alterations in ventricular repolarization as assessed by the Tp-e interval and Tp-e/QTc ratio.
Elitok, Ali; Öz, Fahrettin; Panc, Cafer; Sarıkaya, Remzi; Sezikli, Selim; Pala, Yasin; Bugan, Övgü Sinem; Ateş, Müge; Parıldar, Hilal; Ayaz, Mustafa Buğra; Atıcı, Adem; Oflaz, Hüseyin
2016-01-01
Objective: Energy drinks (EDs) are widely consumed products of the beverage industry and are often chosen by teenagers and young adults. Several adverse cardiovascular events and malignant cardiac arrhythmias following consumption of EDs have been reported in the literature. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the dispersion of repolarization and that an increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. This study investigated the acute effects of Red Bull ED on ventricular repolarization as assessed by the Tp-e interval and Tp-e/QT ratio. Methods: A prospective, open-label study design was used. After an 8-h fast, 50 young, healthy subjects consumed 355 mL of Red Bull ED. The Tp-e interval, Tp-e/QTc ratio, and several other electrocardiographic parameters were measured at baseline and 2 h after ingestion of Red Bull ED. Results: No significant changes in the Tp-e interval or Tp-e/QTc ratio were observed with Red Bull ED consumption. Red Bull ED consumption led to increases in both systolic and diastolic blood pressures, which were associated with an increased heart rate. Conclusion: Although ingestion of Red Bull ED increases the heart rate and diastolic and systolic blood pressures, it does not cause alterations in ventricular repolarization as assessed by the Tp-e interval and Tp-e/QTc ratio. PMID:25868042
Meijborg, Veronique M F; Chauveau, Samuel; Janse, Michiel J; Anyukhovsky, Evgeny P; Danilo, Peter R; Rosen, Michael R; Opthof, Tobias; Coronel, Ruben
BACKGROUND: Long QT2 (LQT2) syndrome is characterized by bifid (or notched) T waves, whose mechanism is not understood. OBJECTIVE: The purpose of this study was to test whether increased interventricular dispersion of repolarization induces bifid T waves. METHODS: We simultaneously recorded surface
Janse, Michiel J.; Sosunov, Eugene A.; Coronel, Ruben; Opthof, Tobias; Anyukhovsky, Evgeny P.; de Bakker, Jacques M. T.; Plotnikov, Alexei N.; Shlapakova, Iryna N.; Danilo, Peter; Tijssen, Jan G. P.; Rosen, Michael R.
2005-01-01
Background - Questions remain about the contributions of transmural versus apicobasal repolarization gradients to the configuration of the T wave in control settings and after the induction of short-term cardiac memory. Methods and Results - Short-term cardiac memory is seen as T-wave changes
DEFF Research Database (Denmark)
Graff, Claus; Andersen, Mads P; Xue, Joel Q
2009-01-01
BACKGROUND: The electrocardiographic QT interval is used to identify drugs with potential harmful effects on cardiac repolarization in drug trials, but the variability of the measurement can mask drug-induced ECG changes. The use of complementary electrocardiographic indices of abnormal repolariz......BACKGROUND: The electrocardiographic QT interval is used to identify drugs with potential harmful effects on cardiac repolarization in drug trials, but the variability of the measurement can mask drug-induced ECG changes. The use of complementary electrocardiographic indices of abnormal...... are typical ECG patterns in LQT2. Blinded to labels, the new morphology measures were tested in a third group of 39 healthy subjects receiving sotalol. Over 3 days the sotalol group received 0, 160 and 320 mg doses, respectively, and a 12-lead Holter ECG was recorded for 22.5 hours each day. Drug...... with QTcF, p ECG patterns in LQT2 carriers effectively quantified repolarization changes induced by sotalol. Further studies are needed to validate whether this measure has...
Meijborg, Veronique M. F.; Chauveau, Samuel; Janse, Michiel J.; Anyukhovsky, Evgeny P.; Danilo, Peter R.; Rosen, Michael R.; Opthof, Tobias; Coronel, Ruben
2015-01-01
Long QT2 (LQT2) syndrome is characterized by bifid (or notched) T waves, whose mechanism is not understood. The purpose of this study was to test whether increased interventricular dispersion of repolarization induces bifid T waves. We simultaneously recorded surface ECG and unipolar electrograms at
Hancock, Jane M; Weatherall, Kate L; Choisy, Stéphanie C; James, Andrew F; Hancox, Jules C; Marrion, Neil V
2015-05-01
Activation of small conductance calcium-activated potassium (SK) channels is proposed to contribute to repolarization of the action potential in atrial myocytes. This role is controversial, as these cardiac SK channels appear to exhibit an uncharacteristic pharmacology. The objectives of this study were to resolve whether activation of SK channels contributes to atrial action potential repolarization and to determine the likely subunit composition of the channel. The effect of 2 SK channel inhibitors was assessed on outward current evoked in voltage clamp and on action potential duration in perforated patch and whole-cell current clamp recording from acutely isolated mouse atrial myocytes. The presence of SK channel subunits was assessed using immunocytochemistry. A significant component of outward current was reduced by the SK channel blockers apamin and UCL1684. Block by apamin displayed a sensitivity indicating that this current was carried by homomeric SK2 channels. Action potential duration was significantly prolonged by UCL1684, but not by apamin. This effect was accompanied by an increase in beat-to-beat variability and action potential triangulation. This pharmacology was matched by that of expressed heteromeric SK2-SK3 channels in HEK293 cells. Immunocytochemistry showed that atrial myocytes express both SK2 and SK3 channels with an overlapping expression pattern. Only proposed heteromeric SK2-SK3 channels are physiologically activated to contribute to action potential repolarization, which is indicated by the difference in pharmacology of evoked outward current and prolongation of atrial action potential duration. The effect of blocking this channel on the action potential suggests that SK channel inhibition during cardiac function has the potential to be proarrhythmic. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
Prevention of Pazopanib-Induced Prolonged Cardiac Repolarization and Proarrhythmic Effects
Directory of Open Access Journals (Sweden)
Tulay Akman
2014-11-01
Full Text Available Background: Pazopanib (PZP may induce prolonged cardiac repolarization and proarrhythmic effects, similarly to other tyrosine kinase inhibitors. Objectives: To demonstrate PZP-induced prolonged cardiac repolarization and proarrhythmic electrophysiological effects and to investigate possible preventive effects of metoprolol and diltiazem on ECG changes (prolonged QT in an experimental rat model. Methods: Twenty-four Sprague-Dawley adult male rats were randomly assigned to 4 groups (n = 6. The first group (normal group received 4 mL of tap water and the other groups received 100 mg/kg of PZP (Votrient® tablet perorally, via orogastric tubes. After 3 hours, the following solutions were intraperitoneally administered to the animals: physiological saline solution (SP, to the normal group and to the second group (control-PZP+SP group; 1 mg/kg metoprolol (Beloc, Ampule, AstraZeneca, to the third group (PZP+metoprolol group; and 1mg/kg diltiazem (Diltiazem, Mustafa Nevzat, to the fourth group (PZP+diltiazem group. One hour after, and under anesthesia, QTc was calculated by recording ECG on lead I. Results: The mean QTc interval values were as follows: normal group, 99.93 ± 3.62 ms; control-PZP+SP group, 131.23 ± 12.21 ms; PZP+metoprolol group, 89.36 ± 3.61 ms; and PZP+diltiazem group, 88.86 ± 4.04 ms. Both PZP+metoprolol and PZP+diltiazem groups had significantly shorter QTc intervals compared to the control-PZP+SP group (p < 0.001. Conclusion: Both metoprolol and diltiazem prevented PZP-induced QT interval prolongation. These drugs may provide a promising prophylactic strategy for the prolonged QTc interval associated with tyrosine kinase inhibitor use.
Double pharmacological challenge on repolarization opens new avenues for drug safety research
DEFF Research Database (Denmark)
Thomsen, Morten Bækgaard
2007-01-01
pointes (TdP) arrhythmia. Both the pharmaceutical industry and the regulatory bodies are neglecting the available proarrhythmia models. In vitro studies have suggested that combined pharmacological hits on repolarization will produce a superior substrate for in vivo proarrhythmia, compared to the single......-drug assessment. By using consecutive pharmacological challenges, a simple model is proposed, in which combinatorial pharmacology is employed to provoke TdP in the conscious dog. The pharmaceutical industry interested in evaluating the proarrhythmic potential of their present and future drugs now has a simple...
Heterogeneity of ventricular repolarization in newborns with intrauterine growth restriction.
Fouzas, Sotirios; Karatza, Ageliki A; Davlouros, Periklis A; Chrysis, Dionisios; Alexopoulos, Dimitrios; Mantagos, Stefanos; Dimitriou, Gabriel
2014-12-01
Intrauterine growth restriction (IUGR) is associated with structural and functional cardiac alterations but the electrophysiological consequences of these disturbances remain unknown. To explore the distribution of ventricular repolarization and its relation to myocardial mechanics in newborns with IUGR. STUDY DESIGN, SUBJECTS AND OUTCOME MEASUREMENTS: Conventional and tissue Doppler echocardiographic data, and electrocardiographic parameters used to describe the distribution of ventricular repolarization (dispersion of QT [QTd] and JT [JTd]), were obtained on the second (D2) and fifth (D5) postnatal day and compared between 25 IUGR newborns and 25 matched-for-gestational age controls. IUGR was associated with relative interventricular septum hypertrophy, increased left ventricular (LV) E/E' ratio and higher LV myocardial performance index (MPI). On both study days, the IUGR infants presented higher QTd and JTd compared to controls (QTd-D2: 66±20 ms vs. 36±12 ms, P<0.001; JTd-D2: 54±13 ms vs. 34±9 ms, P<0.001; QTd-D5: 61±14 ms vs. 27±12 ms, P<0.001; JTd-D5: 54±13 ms vs. 27±9 ms, P<0.001). The association between QTd and LV E/E' (D2: regression coefficient beta 0.747, R(2) 0.585; D5: beta 0.843, R(2) 0.646) and QTd and MPI (D2: beta 0.680, R(2) 0.576; D5: beta 0.698, R(2) 0.650) was also significant (P<0.001 for all analyses). Our findings suggest that IUGR is associated with electrophysiological remodeling of the neonatal heart, a process which is closely related to the underlying alterations in ventricular mechanics and might predispose to adverse electrophysiological events. Copyright © 2014 Elsevier Ltd. All rights reserved.
Coronel, Ruben; Opthof, Tobias; Plotnikov, Alexei N.; Wilms-Schopman, Francien J. G.; Shlapakova, Iryna N.; Danilo, Peter; Sosunov, Eugene A.; Anyukhovsky, Evgeny P.; Janse, Michiel J.; Rosen, Michael R.
2007-01-01
OBJECTIVE: The contribution of regional electrophysiologic heterogeneity to the T-wave changes of long-term cardiac memory (CM) is not known. We mapped activation and repolarization in dogs after induction of CM and in sham animals. METHODS AND RESULTS: CM was induced by three weeks of AV-sequential
Patocskai, Bence; Barajas-Martinez, Hector; Hu, Dan; Gurabi, Zsolt; Koncz, István; Antzelevitch, Charles
2016-01-01
Background Early Repolarization Syndrome (ERS) is associated with polymorphic ventricular tachycardia (PVT) and fibrillation (VF), leading to sudden cardiac death. Objective The present study tests the hypothesis that the Ito-blocking effect of phosphodiesterase-3 (PDE-3) inhibitors plays a role in reversing repolarization heterogeneities responsible for arrhythmogenesis in experimental models of ERS. Methods Transmembrane action potentials (AP) were simultaneously recorded from epicardial and endocardial regions of coronary-perfused canine left-ventricular (LV) wedge preparations, together with a transmural pseudo-ECG. The Ito-agonist NS5806 (7–15 μM) and ICa-blocker verapamil (2–3 uM) were used to induce an ER pattern and PVT. Results Following stable induction of arrhythmogenesis, the PDE-3 inhibitors cilostazol and milrinone or isoproterenol were added to the coronary perfusate. All were effective in restoring the AP dome in the LV epicardium, thus abolishing the repolarization defects responsible for phase-2-reentry (P2R) and PVT. Arrhythmic activity was suppressed in 7/8 preparations by cilostazol (10 μM), 6/7 by milrinone (2.5 μM) and 7/8 by isoproterenol (0.1–1μM). Using voltage clamp techniques applied to LV epicardial myocytes, both cilostazol (10 μM) and milrinone (2.5 μM) were found to reduce Ito by 44.4% and 40.4%, respectively, in addition to their known effects to augment ICa. Conclusions Our findings suggest that PDE-3 inhibitors exert an ameliorative effect in the setting of ERS by producing an inward shift in the balance of current in the early phases of the epicardial AP via inhibition of Ito as well as augmentation of ICa, thus reversing the repolarization defects underlying development of P2R and VT/VF. PMID:26820510
DEFF Research Database (Denmark)
Graff, Claus; Struijk, Johannes J.; Matz, J
2010-01-01
This study adds the dimension of a T-wave morphology composite score (MCS) to the QTc interval-based evaluation of drugs that affect cardiac repolarization. Electrocardiographic recordings from 62 subjects on placebo and 400 mg moxifloxacin were compared with those from 21 subjects on 160 and 320...
Rhee, Soo Hyun; Willcutt, Erik G.; Hartman, Christie A.; Pennington, Bruce F.; DeFries, John C.
2008-01-01
There is significant comorbidity between attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD). The conclusions of studies that examined the causes of comorbidity between ADHD and CD conflict, with some researchers finding support for the three independent disorders model and others finding support for the correlated risk…
Bai, Rong; Lü, Jiagao; Pu, Jun; Liu, Nian; Zhou, Qiang; Ruan, Yanfei; Niu, Huiyan; Zhang, Cuntai; Wang, Lin; Kam, Ruth
2005-10-01
Benefits of cardiac resynchronization therapy (CRT) are well established. However, less is understood concerning its effects on myocardial repolarization and the potential proarrhythmic risk. Healthy dogs (n = 8) were compared to a long QT interval (LQT) model (n = 8, induced by cesium chloride, CsCl) and a dilated cardiomyopathy with congestive heart failure (DCM-CHF, induced by rapid ventricular pacing, n = 5). Monophasic action potential (MAP) recordings were obtained from the subendocardium, midmyocardium, subepicardium, and the transmural dispersion of repolarization (TDR) was calculated. The QT interval and the interval from the peak to the end of the T wave (T(p-e)) were measured. All these characteristics were compared during left ventricular epicardial (LV-Epi), right ventricular endocardial (RV-Endo), and biventricular (Bi-V) pacing. In healthy dogs, TDR prolonged to 37.54 ms for Bi-V pacing and to 47.16 ms for LV-Epi pacing as compared to 26.75 ms for RV-Endo pacing (P canine models in addition to their intrinsic transmural heterogeneity in the intact heart. This mechanism may contribute to the development of malignant ventricular arrhythmias, such as torsades de pointes (TdP) in congestive heart failure (CHF) patients treated with CRT.
Jani, Ylber; Kamberi, Ahmet; Xhunga, Sotir; Pocesta, Bekim; Ferati, Fatmir; Lala, Dali; Zeqiri, Agim; Rexhepi, Atila
2015-01-01
To assess the influence of type 2 DM and gender, on the QT dispersion, Tpeak-Tend dispersion of ventricular repolarization, in patients with sub-clinic left ventricular diastolic dysfunction of the heart. QT dispersion, that reflects spatial inhomogeneity in ventricular repolarization, Tpeak-Tend dispersion, this on the other hand reflects transmural inhomogeneity in ventricular repolarization, that is increased in an early stage of cardiomyopathy, and in patients with left ventricular diastolic dysfunction, as well. The left ventricular diastolic dysfunction, a basic characteristic of diabetic heart disease (diabetic cardiomyopathy), that developes earlier than systolic dysfunction, suggests that diastolic markers might be sensitive for early cardiac injury. It is also demonstrated that gender has complex influence on indices of myocardial repolarization abnormalities such as QT interval and QT dispersion. We performed an observational study including 300 diabetic patients with similar epidemiological-demographic characteristics recruited in our institution from May 2009 to July 2014, divided into two groups. Demographic and laboratory echocardiographic data were obtained, twelve lead resting electrocardiography, QT, QTc, Tpeak-Tend-intervals and dispersion, were determined manually, and were compared between various groups. For statistical analysis a t-test, X(2) test, and logistic regression are used according to the type of variables. A p value <0.05 was considered statistically significant for a confidence interval of 95%. QTc max. interval, QTc dispersion and Tpeak-Tend dispersion, were significantly higher in diabetic group with subclinical LV (left ventricular) diastolic dysfunction, than in diabetic group with normal left ventricular diastolic function (445.24±14.7 ms vs. 433.55±14.4 ms, P<0.000; 44.98±18.78 ms vs. 32.05±17.9 ms, P<0.000; 32.60±1.6 ms vs. 17.46±2.0 ms, P<0.02. Prolonged QTc max. interval was found in 33% of patients, indiabetic group
Opthof, Tobias; Coronel, Ruben; Wilms-Schopman, Francien J. G.; Plotnikov, Alexei N.; Shlapakova, Iryna N.; Danilo, Peter; Rosen, Michael R.; Janse, Michiel J.
2007-01-01
BACKGROUND: The concept that the interval between the peak (T(peak)) and the end (T(end)) of the T wave (T(p-e)) is a measure of transmural dispersion of repolarization time is widely accepted but has not been tested rigorously by transmural mapping of the intact heart. OBJECTIVES: The purpose of
DEFF Research Database (Denmark)
Shakibfar, Saeed; Graff, Claus; Ehlers, Lars Holger
2012-01-01
Various parameters based on QTc and T-wave morphology have been shown to be useful discriminators for drug induced I(Kr)-blocking. Using different classification methods this study compares the potential of these two features for identifying abnormal repolarization on the ECG. A group of healthy ...... the approach has not been tested in this setting....
Cho, Jae Hyung; Zhang, Rui; Kilfoil, Peter J; Gallet, Romain; de Couto, Geoffrey; Bresee, Catherine; Goldhaber, Joshua I; Marbán, Eduardo; Cingolani, Eugenio
2017-11-21
Heart failure with preserved ejection fraction (HFpEF) represents approximately half of heart failure, and its incidence continues to increase. The leading cause of mortality in HFpEF is sudden death, but little is known about the underlying mechanisms. Dahl salt-sensitive rats were fed a high-salt diet (8% NaCl) from 7 weeks of age to induce HFpEF (n=38). Rats fed a normal-salt diet (0.3% NaCl) served as controls (n=13). Echocardiograms were performed to assess systolic and diastolic function from 14 weeks of age. HFpEF-verified and control rats underwent programmed electrical stimulation. Corrected QT interval was measured by surface ECG. The mechanisms of ventricular arrhythmias (VA) were probed by optical mapping, whole-cell patch clamp to measure action potential duration and ionic currents, and quantitative polymerase chain reaction and Western blotting to investigate changes in ion channel expression. After 7 weeks of a high-salt diet, 31 of 38 rats showed diastolic dysfunction and preserved ejection fraction along with signs of heart failure and hence were diagnosed with HFpEF. Programmed electric stimulation demonstrated increased susceptibility to VA in HFpEF rats ( P hearts demonstrated prolonged action potentials ( P hearts. Susceptibility to VA was markedly increased in rats with HFpEF. Underlying abnormalities include QT prolongation, delayed repolarization from downregulation of potassium currents, and multiple reentry circuits during VA. Our findings are consistent with the hypothesis that potassium current downregulation leads to abnormal repolarization in HFpEF, which in turn predisposes to VA and sudden cardiac death. © 2017 American Heart Association, Inc.
Langenickel, Thomas H; Jordaan, Pierre; Petruck, Jesika; Kode, Kiran; Pal, Parasar; Vaidya, Soniya; Chandra, Priya; Rajman, Iris
2016-08-01
Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA class II-IV) and reduced ejection fraction. This study was aimed to evaluate the effect of single oral therapeutic (400 mg) and supratherapeutic (1200 mg) doses of LCZ696 on cardiac repolarization. This randomized double-blind crossover study in healthy male subjects compared the effect of therapeutic and supratherapeutic doses of LCZ696 with placebo and moxifloxacin 400 mg (open-label treatment) as positive control. The primary assessment was mean baseline- and placebo-corrected QTcF (∆∆QTcF; Fridericia correction). Additional assessments included the ∆∆QTcB (Bazett's correction), PR interval, QRS duration, heart rate (HR), LCZ696 pharmacokinetics, pharmacokinetic/pharmacodynamic relationships, and safety. Of the 84 subjects enrolled, 81 completed the study. The maximum upper bound of the two-sided 90 % confidence interval for ∆∆QTcF for LCZ696 400 mg and 1200 mg were <10 ms, and assay sensitivity was confirmed with moxifloxacin. No relevant treatment-emergent changes were observed in any of the ECG-derived parameters with LCZ696 or placebo, and the incidence of adverse events was comparable among the treatment groups. Single therapeutic and supratherapeutic doses of LCZ696 did not affect cardiac repolarization as defined by the E14 ICH guidelines.
Directory of Open Access Journals (Sweden)
David Hurtado-de-Mendoza, MD
2017-06-01
Conclusion: Diffuse interstitial fibrosis is associated with increased dispersion of ventricular repolarization in leads, reflecting electrical activity in the hypertrophied septum. Interstitial fibrosis combined with ion channel/gap junction remodeling in the septum could lead to inhomogeneity of ventricular refractoriness, resulting in increased QTc dispersion in leads V1–V4.
DEFF Research Database (Denmark)
Skibsbye, Lasse; Poulet, Claire; Diness, Jonas Goldin
2014-01-01
(+) currents by ∼15% and prolonged action potential duration (APD), but no effect was observed in myocytes from AF patients. In trabeculae muscle strips from right atrial appendages of SR patients, both compounds increased APD and effective refractory period, and depolarized the resting membrane potential......, while only NS8593 induced these effects in tissue from AF patients. SK channel inhibition did not alter any electrophysiological parameter in human interventricular septum tissue. CONCLUSIONS: SK channels are present in human atria where they participate in repolarization. SK2 and SK3 were down...
Jani, Ylber; Kamberi, Ahmet; Xhunga, Sotir; Pocesta, Bekim; Ferati, Fatmir; Lala, Dali; Zeqiri, Agim; Rexhepi, Atila
2015-01-01
Objective: To assess the influence of type 2 DM and gender, on the QT dispersion, Tpeak-Tend dispersion of ventricular repolarization, in patients with sub-clinic left ventricular diastolic dysfunction of the heart. Background: QT dispersion, that reflects spatial inhomogeneity in ventricular repolarization, Tpeak-Tend dispersion, this on the other hand reflects transmural inhomogeneity in ventricular repolarization, that is increased in an early stage of cardiomyopathy, and in patients with left ventricular diastolic dysfunction, as well. The left ventricular diastolic dysfunction, a basic characteristic of diabetic heart disease (diabetic cardiomyopathy), that developes earlier than systolic dysfunction, suggests that diastolic markers might be sensitive for early cardiac injury. It is also demonstrated that gender has complex influence on indices of myocardial repolarization abnormalities such as QT interval and QT dispersion. Material and methods: We performed an observational study including 300 diabetic patients with similar epidemiological-demographic characteristics recruited in our institution from May 2009 to July 2014, divided into two groups. Demographic and laboratory echocardiographic data were obtained, twelve lead resting electrocardiography, QT, QTc, Tpeak-Tend-intervals and dispersion, were determined manually, and were compared between various groups. For statistical analysis a t-test, X2 test, and logistic regression are used according to the type of variables. A p value <0.05 was considered statistically significant for a confidence interval of 95%. Results: QTc max. interval, QTc dispersion and Tpeak-Tend dispersion, were significantly higher in diabetic group with subclinical LV (left ventricular) diastolic dysfunction, than in diabetic group with normal left ventricular diastolic function (445.24±14.7 ms vs. 433.55±14.4 ms, P<0.000; 44.98±18.78 ms vs. 32.05±17.9 ms, P<0.000; 32.60±1.6 ms vs. 17.46±2.0 ms, P<0.02. Prolonged QTc max
Female alcoholics: electrocardiographic changes and associated metabolic and electrolytic disorders
Directory of Open Access Journals (Sweden)
Borini Paulo
2003-01-01
Full Text Available OBJECTIVE: To identify the electrocardiographic changes and their associations with metabolic and electrolytic changes in female alcoholics. METHODS: The study comprised 44 female alcoholics with no apparent physical disorder. They underwent the following examinations: conventional electrocardiography; serologic tests for syphilis, Chagas' disease, and hepatitis B and C viruses; urinary pregnancy testing; hematimetric analysis; biochemical measurements of albumin, fibrinogen, fasting and postprandial glycemias, lipids, hepatic enzymes, and markers for tissue necrosis and inflammation. RESULTS: Some type of electrocardiographic change was identified in 33 (75% patients. In 17 (38.6% patients, more than one of the following changes were present: prolonged QTc interval in 24 (54.5%, change in ventricular repolarization in 11(25%, left ventricular hypertrophy in 6 (13.6%, sinus bradycardia in 4 (9.1%, sinus tachycardia in 3 (6.8%, and conduction disorder in 3 (6.8%. The patients had elevated mean serum levels of creatine phosphokinase, aspartate aminotransferases, and gamma glutamyl transferase, as well as hypocalcemia and low levels of total cholesterol and LDL-cholesterol. The patients with altered electrocardiograms had a more elevated age, a lower alcohol consumption, hypopotassemia, and significantly elevated levels of triglycerides, postprandial glucose, sodium and gamma glutamyl transferase than those with normal electrocardiograms. The opposite occurred with fasting glycemia, magnesium, and alanine aminotransferase. CONCLUSION: The electrocardiographic changes found were prolonged QTc interval, change in ventricular repolarization, and left ventricular hypertrophy. Patients with normal and abnormal electrocardiograms had different metabolic and electrolytic changes.
Dental Hypotheses: Seeks to Publish Hypotheses from All Areas of Dentistry
Directory of Open Access Journals (Sweden)
Edward F. Rossomando
2010-07-01
Full Text Available Starting a new open access journal in a rapid growing scientific panorama is a severe challenge. However, the first issue of dental hypotheses is now history and the even skeptics can appreciate that dental hypotheses is a success - it is a journal of high quality that provides an outlet for publication of articles that encourage readers to question dental paradigms. But dental hypotheses readers might have noticed that the majority of the articles published in the first issue of dental hypotheses concern clinical dentistry. However, dental hypotheses editors recognize that there are many other areas in dentistry that present challenges and that our readers may offer suggestions for their solution. Some of these challenges relate to: dental education; digital dental technology; teledentistry and access to dental care; dental practice issues, such as, dental office design, dental office management, the slow rate of acceptance of innovative technology in the dental office; and issues related to innovation and dental entrepreneurship including intellectual property protection. Nevertheless, the dental profession faces many challenges - in many areas - and with the publication of dental hypotheses our profession has a venue for presentation of possible solutions. If you have developed a hypothesis that might help, please share it with your colleagues. As many have noted, the intellectual power of the global village in which we now live is formidable. The internet has provided the technology to bring us together and dental hypotheses has provided the venue. Please use it. New radical, speculative and non-mainstream scientific ideas are always welcome.
Gurabi, Zsolt; Koncz, István; Patocskai, Bence; Nesterenko, Vladislav V.; Antzelevitch, Charles
2014-01-01
Background Hypothermia has been reported to induce ventricular tachycardia and fibrillation (VT/VF) in patients with early repolarization (ER) pattern. This study examines the cellular mechanisms underlying VT/VF associated with hypothermia in an experimental model of ER syndrome (ERS) and examines the effectiveness of quinidine, cilostazol and milrinone to prevent hypothermia-induced arrhythmias. Method and Results Transmembrane action potentials (AP) were simultaneously recorded from 2 epicardial and 1 endocardial site of coronary-perfused canine left-ventricular wedge preparations, together with a pseudo-ECG. A combination of NS5806 (3–10 µM) and verapamil (1µM) was used to pharmacologically model the genetic mutations responsible for ERS. Acetylcholine (3µM) was used to simulate increased parasympathetic tone, which is known to promote ER. In control, lowering the temperature of the coronary perfusate to induce mild hypothermia (32°C-34°C) resulted in increased J wave area on the ECG and accentuated epicardial AP notch but no arrhythmic activity. In the setting of ER, hypothermia caused further accentuation of the epicardial AP notch, leading to loss of the AP dome at some sites but not others, thus creating the substrate for development of phase-2-reentry and VT/VF. Addition of the Ito antagonist quinidine (5 µM) or the phosphodiesterase III inhibitors cilostazol (10 µM) or milrinone (5 µM), diminished the ER manifestations and prevented the hypothermia-induced phase 2 reentry and VT/VF. Conclusions Hypothermia leads to VT/VF in the setting of ER by exaggerating repolarization abnormalities, leading to development of phase-2-reentry. Quinidine, cilostazol and milrinone suppress the hypothermia-induced VT/VF by reversing the repolarization abnormalities. PMID:24429494
DEFF Research Database (Denmark)
Glasius, Susanne; Graff, Claus; Ellervik, Christina
2018-01-01
was influenced by the sport performed. MATERIALS AND METHODS: Digital electrocardiograms of 469 young elite athletes were analyzed for T-wave asymmetry, flatness and notching, and combined in the MCS. Athletes >22years were compared to a sex-and age matched control group from the general population (N=198......). RESULTS: MCS increased with increasing endurance component of the sport performed ranging from 0.79±0.15 (low) to 0.92±0.21 (high) (p... suggests that sport induces repolarization changes detected by T-wave morphology, and a greater level of changes is seen in athletes from high endurance sports....
DEFF Research Database (Denmark)
Dose, Nynne; Michelsen, Marie Mide; Mygind, Naja Dam
2018-01-01
OBJECTIVES: CMD could be the explanation of angina pectoris with no obstructive CAD and may cause ventricular repolarization changes. We compared T-wave morphology and QTc interval in women with angina pectoris with a control group as well as the associations with CMD. METHODS: Women with angina...... echocardiography. RESULTS: Women with angina pectoris had significantly longer QTc intervals (429±20ms) and increased MCS (IQR) (0.73 [0.64-0.80]) compared with the controls (419±20ms) and (0.63 [(0.53-0.73]), respectively (both p... was attenuated after multivariable adjustment (p=0.08). CONCLUSION: This study suggests that women with angina pectoris have alterations in T-wave morphology as well as longer QTc interval compared with a reference population. CMD might be an explanation....
Burnand, Gordon
2013-09-01
Problem theory points to an a priori relation between six key problems of living, to which people have adapted through evolution. Children are guided through the problems one by one, learning to switch between them automatically and unawares. The first problem of raising hope of certainty (about the environment), is dealt with in the right hemisphere (RH). The second of raising hope of freedom (or power to control), is dealt with in the left hemisphere (LH). Here adventurousness and ignoring the goodness of outcomes potentially create recklessness. When uncertainty rises the RH activates a backup with an override that substitutes immobility, takes over sensory inputs, but allows obedience to parental commands, and a cut-out that stops new work on the freedom problem. Support for the use of the backup by infants is found in the immobility that precedes the crying in strange conditions, and in childhood EEGs. The hypothesis that the backup is active in deep hypnosis imposes accord on findings that appear contradictory. For example it accounts for why observations during deep hypnosis emphasize the activity of the RH, but observations of responsive people not under hypnosis emphasize the activity of the LH. The hypothesis that the backup is active in post-traumatic stress disorder (PTSD) is supported by (a) fMRI observations that could reflect the cut-out, in that part of the precuneus has low metabolism, (b) the recall of motionlessness at the time of the trauma, (c) an argument that playing dead as a defence against predators is illogical, (d) the ease of hypnosis. With dissociative identity disorder (DID), the theory is consistent with up to six alters that have executive control and one trauma identity state where childhood traumas are re-experienced. Support for the cut-out affecting the trauma identity state comes from suppression of part of the precuneus and other parts of the parietal lobe when the trauma identity state is salient and a general script about a
DEFF Research Database (Denmark)
Petitprez, Séverine; Jespersen, Thomas; Pruvot, Etienne
2008-01-01
S SCN5A mutation. METHODS AND RESULTS: SCN5A was screened for mutations in a male patient with type-1 BrS pattern ECG. Wild-type (WT) and mutant Na(v)1.5 channels were expressed in HEK293 cells. Sodium currents (I(Na)) were analysed using the whole-cell patch-clamp technique at 37 degrees C......AIMS: Brugada syndrome (BrS) is characterized by arrhythmias leading to sudden cardiac death. BrS is caused, in part, by mutations in the SCN5A gene, which encodes the sodium channel alpha-subunit Na(v)1.5. Here, we aimed to characterize the biophysical properties and consequences of a novel Br....... The electrophysiological effects of the mutation were simulated using the Luo-Rudy model, into which the transient outward current (I(to)) was incorporated. A new mutation (C1850S) was identified in the Na(v)1.5 C-terminal domain. In HEK293 cells, mutant I(Na) density was decreased by 62% at -20 mV. Inactivation of mutant...
Mechanism of Proarrhythmic Effects of Potassium Channel Blockers
DEFF Research Database (Denmark)
Skibsbye, Lasse; Ravens, Ursula
2016-01-01
Any disturbance of electrical impulse formation in the heart and of impulse conduction or action potential (AP) repolarization can lead to rhythm disorders. Potassium (K(+)) channels play a prominent role in the AP repolarization process. In this review we describe the causes and mechanisms...
Giuliani, C; Agostinelli, A; Di Nardo, F; Fioretti, S; Burattini, L
2016-01-01
Electrocardiographic (ECG) T-wave endpoint (Tend) identification suffers lack of reliability due to the presence of noise and variability among leads. Tend identification can be improved by using global repolarization waveforms obtained by combining several leads. The dominant T-wave (DTW) is a global repolarization waveform that proved to improve Tend identification when computed using the 15 (I to III, aVr, aVl, aVf, V1 to V6, X, Y, Z) leads usually available in clinics, of which only 8 (I, II, V1 to V6) are independent. The aim of the present study was to evaluate if the 8 independent leads are sufficient to obtain a DTW which allows a reliable Tend identification. To this aim Tend measures automatically identified from 15-dependent-lead DTWs of 46 control healthy subjects (CHS) and 103 acute myocardial infarction patients (AMIP) were compared with those obtained from 8-independent-lead DTWs. Results indicate that Tend distributions have not statistically different median values (CHS: 340 ms vs. 340 ms, respectively; AMIP: 325 ms vs. 320 ms, respectively), besides being strongly correlated (CHS: ρ=0.97, AMIP: 0.88; Pautomatic Tend identification from DTW, the 8 independent leads can be used without a statistically significant loss of accuracy but with a significant decrement of computational effort. The lead dependence of 7 out of 15 leads does not introduce a significant bias in the Tend determination from 15 dependent lead DTWs.
Mermillod, Martial; Vermeulen, Nicolas; Droit-Volet, Sylvie; Jalenques, Isabelle; Durif, Franck; Niedenthal, Paula
2011-01-01
Parkinson's disease (PD) and Tourette's syndrome (TS) lead to important motor disorders among patients such as possible facial amimia in PD and tics in Tourette's syndrome. Under the grounded cognition framework that shows the importance of motor embodiment in emotional feeling (Niedenthal, 2007), both types of pathology with motor symptoms should be sufficient to induce potential impairments for these patients when recognizing emotional facial expressions (EFE). In this opinion paper, we describe a theoretical framework that assumes potential emotional disorders in Parkinson's disease and Tourette's syndrome based on motor disorders characterizing these two pathologies. We also review different methodological barriers in previous experimental designs that could enable the identification of emotional facial expressions despite emotional disorders in PD and TS.
Manni, Raffaele; Terzaghi, Michele; Ratti, Pietro-Luca; Repetto, Alessandra; Zangaglia, Roberta; Pacchetti, Claudio
2011-12-01
REM sleep behaviour disorder (RBD) is a REM sleep-related parasomnia which may be considered a "dissociated state of wakefulness and sleep", given that conflicting elements of REM sleep (dreaming) and of wakefulness (sustained muscle tone and movements) coexist during the episodes, leading to motor and behavioural manifestations reminiscent of an enacted dream. RBD has been reported in association with α-synucleinopathies: around a third of patients with Parkinson's disease (PD) have full-blown RBD. Recent data indicate that PD patients with RBD are more prone to hallucinations than PD patients without this parasomnia. However it is still not clear why RBD in PD is associated with an increased prevalence of VHs. Data exist which suggest that visual hallucinations in PD may be the result of untimely intrusions of REM visual imagery into wakefulness. RBD, which is characterised by a REM sleep dissociation pattern, might be a condition that particularly favours such intrusions. However, other hypotheses may be advanced. In fact, deficits in attentional, executive, visuoperceptual and visuospatial abilities have been documented in RBD and found to occur far more frequently in PD with RBD than in PD without RBD. Neuropsychological deficits involving visual perception and attentional processes are thought to play an important role in the pathophysiology of VHs. On this basis, RBD in PD could be viewed as a contributory risk factor for VHs. Copyright © 2010 Elsevier Inc. All rights reserved.
Gurabi, Zsolt; Koncz, István; Patocskai, Bence; Nesterenko, Vladislav V; Antzelevitch, Charles
2014-02-01
Hypothermia has been reported to induce ventricular tachycardia and fibrillation (VT/VF) in patients with early repolarization (ER) pattern. This study examines the cellular mechanisms underlying VT/VF associated with hypothermia in an experimental model of ER syndrome and examines the effectiveness of quinidine, cilostazol, and milrinone to prevent hypothermia-induced arrhythmias. Transmembrane action potentials were simultaneously recorded from 2 epicardial and 1 endocardial site of coronary-perfused canine left ventricular wedge preparations, together with a pseudo-ECG. A combination of NS5806 (3-10 μmol/L) and verapamil (1 μmol/L) was used to pharmacologically model the genetic mutations responsible for ER syndrome. Acetylcholine (3 μmol/L) was used to simulate increased parasympathetic tone, which is known to promote ER. In controls, lowering the temperature of the coronary perfusate to induce mild hypothermia (32°C-34°C) resulted in increased J-wave area on the ECG and accentuated epicardial action potential notch but no arrhythmic activity. In the setting of ER, hypothermia caused further accentuation of the epicardial action potential notch, leading to loss of the action potential dome at some sites but not others, thus creating the substrate for development of phase 2 reentry and VT/VF. Addition of the transient outward current antagonist quinidine (5 μmol/L) or the phosphodiesterase III inhibitors cilostazol (10 μmol/L) or milrinone (5 μmol/L) diminished the ER manifestations and prevented the hypothermia-induced phase 2 reentry and VT/VF. Hypothermia leads to VT/VF in the setting of ER by exaggerating repolarization abnormalities, leading to development of phase 2 reentry. Quinidine, cilostazol, and milrinone suppress the hypothermia-induced VT/VF by reversing the repolarization abnormalities.
Heart rate variability alters cardiac repolarization and electromechanical dynamics.
Phadumdeo, Vrishti M; Weinberg, Seth H
2018-04-07
Heart rate continuously varies due to autonomic regulation, stochasticity in pacemaking, and circadian rhythm, collectively termed heart rate variability (HRV), during normal physiological conditions. Low HRV is clinically associated with an elevated risk of cardiac arrhythmias. Alternans, a beat-to-beat alternation in action potential duration (APD) and/or intracellular calcium (Ca) transient, is a well-known risk factor associated with cardiac arrhythmias that is typically studied under conditions of a constant pacing rate, i.e., the absence of HRV. In this study, we investigate the effects of HRV on the interplay between APD, Ca, and electromechanical properties, employing a nonlinear discrete-time map model that governs APD and intracellular Ca cycling with a stochastic pacing period. We find that HRV can decrease variation in APD and peak Ca at fast pacing rates for which alternans is present. Further, increased HRV typically disrupts the alternating pattern for both APD and peak Ca and weakens the correlation between APD and peak Ca, thus decoupling Ca-mediated instabilities from repolarization alternation. We find that the efficacy of these effects is regulated by the sarcoplasmic reticulum Ca uptake rate. Overall, these results demonstrate that HRV disrupts arrhythmogenic alternans and suggests that HRV may be a significant factor in preventing life-threatening arrhythmias. Copyright © 2018 Elsevier Ltd. All rights reserved.
London, Barry; Baker, Linda C; Petkova-Kirova, Polina; Nerbonne, Jeanne M; Choi, Bum-Rak; Salama, Guy
2007-01-01
Enhanced dispersion of repolarization (DR) and refractoriness may be a unifying mechanism central to arrhythmia genesis in the long QT (LQT) syndrome. The role of DR in promoting arrhythmias was investigated in several strains of molecularly engineered mice: (a) Kv4.2 dominant negative transgenic (Kv4.2DN) that lacks the fast component of the transient outward current, I(to,f), have action potential (AP) and QT prolongation, but no spontaneous arrhythmias, (b) Kv1.4 targeted mice (Kv1.4-/-) that lack the slow component of I(to) (I(to,s)), have no QT prolongation and no spontaneous arrhythmias, and (c) double transgenic (Kv4.2DN x Kv1.4-/-) mice that lack both I(to,f) and I(to,s), have AP and QT prolongation, and spontaneous ventricular tachyarrhythmias. Hearts were perfused, stained with di-4-ANEPPS and optically mapped. Activation patterns and conduction velocities were similar between the strains but AP duration at 75% recovery (APD75) was longer in Kv4.2DN (28.0 +/- 2.5 ms, P mice than controls (20.3 +/- 1.0 ms, n = 5). Dispersion of refractoriness between apex and base was markedly reduced in Kv4.2DN (0.3 +/- 0.5 ms, n = 6, P mice compared with controls (10 +/- 2 ms, n = 5). A premature pulse elicited ventricular tachycardia (VT) in Kv1.4-/- (n = 4/5) and Kv4.2DN x Kv1.4-/- hearts (n = 5/5) but not Kv4.2DN hearts (n = 0/6). Voltage-clamp recordings showed that I(to,f) was 30% greater in myocytes from the apex than base which may account for the absence of DR in Kv4.2DN mice. Thus, dispersion of repolarization (DR) appears to be an important determinant of arrhythmia vulnerability.
Anheier, H.K.; Krlev, G.; Preuss, S.; Mildenberger, G.; Bekkers, R.H.F.P.; Brink Lund, A.
2014-01-01
This report brings together findings from the first ITSSOIN project working steps to formulate empirically testable hypotheses on the impact of the third sector and social innovation – in particular regarding the role of the third sector in generating social innovation but also with reference to
Zhu, Yujie; Ai, Xun; Oster, Robert A; Bers, Donald M; Pogwizd, Steven M
2013-06-01
Slow delayed rectifier potassium current (IKs) is important in action potential (AP) repolarization and repolarization reserve. We tested the hypothesis that there are sex-specific differences in IKs, AP, and their regulation by β-adrenergic receptors (β-AR's) using whole-cell patch-clamp. AP duration (APD90) was significantly longer in control female (F) than in control male (M) myocytes. Isoproterenol (ISO, 500 nM) shortened APD90 comparably in M and F, and was largely reversed by β1-AR blocker CGP 20712A (CGP, 300 nM). Inhibition of IKs with chromanol 293B (10 μM) resulted in less APD prolongation in F at baseline (3.0 vs 8.9 %, p < 0.05 vs M) and even in the presence of ISO (5.4 vs 20.9 %, p < 0.05). This suggests that much of the ISO-induced APD abbreviation in F is independent of IKs. In F, baseline IKs was 42 % less and was more weakly activated by ISO (19 vs 68 % in M, p < 0.01). ISO enhancement of IKs was comparably attenuated by CGP in M and F. After ovariectomy, IKs in F had greater enhancement by ISO (72 %), now comparable to control M. After orchiectomy, IKs in M was only slightly enhanced by ISO (23 %), comparable to control F. Pretreatment with thapsigargin (to block SR Ca release) had bigger impact on ISO-induced APD shortening in F than that in M (p < 0.01). In conclusion, we found that there are sex differences in IKs, AP, and their regulation by β-AR's that are modulated by sex hormones, suggesting the potential for sex-specific antiarrhythmic therapy.
Directory of Open Access Journals (Sweden)
Hidekazu Kondo, MD
2015-02-01
Full Text Available This case report describes a 19-year-old man with early repolarization (ER in the inferolateral leads and a normal QT interval who survived a cardiac arrest that was likely related to polymorphic ventricular tachycardia (VT. Electrocardiograms (ECGs also showed unifocal premature ventricular beats (PVBs with a relatively narrow QRS duration. A Holter ECG documented occasional short-coupled PVBs following non-sustained VTs. Pharmacological stress testing was also performed to assess the effects of anti-arrhythmic drugs on ER (the J wave and PVBs. We performed successful radiofrequency catheter ablation to prevent the recurrence of ventricular fibrillation after cardioverter-defibrillator implantation.
Paul R. Rosenbaum
2008-01-01
In certain circumstances, one wishes to test one hypothesis only if certain other hypotheses have been rejected. This ordering of hypotheses simplifies the task of controlling the probability of rejecting any true hypothesis. In an example from an observational study, a treated group is shown to be further from both of two control groups than the two control groups are from each other. Copyright 2008, Oxford University Press.
Self-disorders in schizophrenia-spectrum disorders
DEFF Research Database (Denmark)
Nordgaard, Julie; Nilsson, Lars Siersbæk; Sæbye, Ditte
2017-01-01
Self-disorders have been hypothesized to be an underlying and trait-like core feature of schizophrenia-spectrum disorders and a certain degree of temporal stability of self-disorders would therefore be expected. The aim of the study was to examine the persistence of self-disorders measured...... by the Examination of Anomalous Self Experiences over a time span of 5 years. 48 patients with schizophrenia-spectrum disorders were thoroughly assessed for psychopathology at baseline and 5 years later. Self-disorders were assessed by the Examination of Anomalous Self Experiences. The level of self-disorders...... was same at the two occasions for the full Examination of Anomalous Self Disorders and for four out of the five domains. For one domain, the level of self-disorders increased slightly from baseline to follow-up. The correlations between baseline and follow-up were moderate. 9 out of the 13 most...
Jiang, Dongdong; Du, Jinmei; Gu, Yan; Feng, Yujun
2012-03-01
The shock wave induced depoling current of Pb0.99[(Zr0.90Sn0.10)0.96Ti0.04]0.98Nb0.02O3 ceramics was investigated with a system composed of a resistive load and an unpoled ceramic. Disparity in the depoling current was explained by considering the drawing charge effect of unpoled ceramic. The drawing effect for poled ceramics was analysed by developing a model incorporating a time- and electric-field-dependent repolarization. This model predicts that the high-impedance current eventually becomes higher than the short-circuit current, which is consistent with the experimental results in the literature. This work indicates that both the repolarization of uncompressed ceramics caused by the self-generated electric field and depolarization of compressed ceramics caused by the shock wave govern the output current.
International Nuclear Information System (INIS)
Jiang Dongdong; Du Jinmei; Gu Yan; Feng Yujun
2012-01-01
The shock wave induced depoling current of Pb 0.99 [(Zr 0.90 Sn 0.10 ) 0.96 Ti 0.04 ] 0.98 Nb 0.02 O 3 ceramics was investigated with a system composed of a resistive load and an unpoled ceramic. Disparity in the depoling current was explained by considering the drawing charge effect of unpoled ceramic. The drawing effect for poled ceramics was analysed by developing a model incorporating a time- and electric-field-dependent repolarization. This model predicts that the high-impedance current eventually becomes higher than the short-circuit current, which is consistent with the experimental results in the literature. This work indicates that both the repolarization of uncompressed ceramics caused by the self-generated electric field and depolarization of compressed ceramics caused by the shock wave govern the output current. (paper)
DEFF Research Database (Denmark)
Atanasovska, Tania; Smith, Robert; Graff, Claus
2018-01-01
repolarization (QT hysteresis). Eleven healthy adults participated in a randomized, counterbalanced, double-blind trial receiving either 1000 µg salbutamol (SAL) or placebo (PLAC) by inhalation. Arterial plasma potassium concentration ([K+]a) was measured at rest, during 3 min intense rowing exercise and 60 min......-exercise (Peffect). [K+]a was lower after SAL than PLAC, from 2 min pre-exercise until 2.5 min during exercise, and at 50 and 60 min post-exercise (P...-exercise decline in [K+]a was correlated with QT hysteresis (r=0.343, n=112, pooled data, P=0.001). Thus the decrease in [K+]a from end-exercise by ~4 mM was associated with reduced QT hysteresis by ~75 ms. Whilst salbutamol lowered [K+]a during exercise, no additive hypokalemic effects occurred in early recovery...
Ghosh, Subham; Rhee, Edward K; Avari, Jennifer N; Woodard, Pamela K; Rudy, Yoram
2008-08-26
Cardiac memory refers to a change in ventricular repolarization induced by and persisting for minutes to months after cessation of a period of altered ventricular activation (eg, resulting from pacing or preexcitation in patients with Wolff-Parkinson-White syndrome). ECG imaging (ECGI) is a novel imaging modality for noninvasive electroanatomic mapping of epicardial activation and repolarization. Fourteen pediatric patients with Wolff-Parkinson-White syndrome and no other congenital disease, were imaged with ECGI a day before and 45 minutes, 1 week, and 1 month after successful catheter ablation. ECGI determined that preexcitation sites were consistent with sites of successful ablation in all cases to within a 1-hour arc of each atrioventricular annulus. In the preexcited rhythm, activation-recovery interval (ARI) was the longest (349+/-6 ms) in the area of preexcitation leading to high average base-to-apex ARI dispersion of 95+/-9 ms (normal is approximately 40 ms). The ARI dispersion remained the same 45 minutes after ablation, although the activation sequence was restored to normal. ARI dispersion was still high (79+/-9 ms) 1 week later and returned to normal (45+/-6 ms) 1 month after ablation. The study demonstrates that ECGI can noninvasively localize ventricular insertion sites of accessory pathways to guide ablation and evaluate its outcome in pediatric patients with Wolff-Parkinson-White syndrome. Wolff-Parkinson-White is associated with high ARI dispersion in the preexcited rhythm that persists after ablation and gradually returns to normal over a period of 1 month, demonstrating the presence of cardiac memory. The 1-month time course is consistent with transcriptional reprogramming and remodeling of ion channels.
Predicting Future Antisocial Personality Disorder in Males from a Clinical Assessment in Childhood
Lahey, Benjamin B.; Loeber, Rolf; Burke, Jeffrey D.; Applegate, Brooks
2005-01-01
It is essential to identify childhood predictors of adult antisocial personality disorder (APD) to target early prevention. It has variously been hypothesized that APD is predicted by childhood conduct disorder (CD), attention-deficit/hyperactivity disorder (ADHD), or both disorders. To test these competing hypotheses, the authors used data from a…
Reconstruction of action potential of repolarization in patients with congenital long-QT syndrome
International Nuclear Information System (INIS)
Kandori, Akihiko; Shimizu, Wataru; Yokokawa, Miki; Kamakura, Shiro; Miyatake, Kunio; Murakami, Masahiro; Miyashita, Tsuyoshi; Ogata, Kuniomi; Tsukada, Keiji
2004-01-01
A method for reconstructing an action potential during the repolarization period was developed. This method uses a current distribution-plotted as a current-arrow map (CAM)-calculated using magnetocardiogram (MCG) signals. The current arrows are summarized during the QRS complex period and subtracted during the ST-T wave period in order to reconstruct the action-potential waveform. To ensure the similarity between a real action potential and the reconstructed action potential using CAM, a monophasic action potential (MAP) and an MCG of the same patient with type-I long-QT syndrome were measured. Although the MAP had one notch that was associated with early afterdepolarization (EAD), the reconstructed action potential had two large and small notches. The small notch timing agreed with the occurrence of the EAD in the MAP. On the other hand, the initiation time of an abnormal current distribution coincides with the appearance timing of the first large notch, and its end time coincides with that of the second small notch. These results suggest that a simple reconstruction method using a CAM based on MCG data can provide a similar action-potential waveform to a MAP waveform without having to introduce a catheter
Novo Navarro, Patricia; Landin-Romero, Ramón; Guardiola-Wanden-Berghe, Rocio; Moreno-Alcázar, Ana; Valiente-Gómez, Alicia; Lupo, Walter; García, Francisca; Fernández, Isabel; Pérez, Víctor; Amann, Benedikt L
Eye movement desensitization and reprocessing (EMDR) is a relatively new psychotherapy that has gradually gained popularity for the treatment of post-traumatic stress disorder. In the present work, the standardised EMDR protocol is introduced, along with current hypotheses of its mechanism of action, as well as a critical review of the available literature on its clinical effectiveness in adult post-traumatic stress disorder. A systematic review of the published literature was performed using PubMed and PsycINFO databases with the keywords «eye movement desensitization and reprocessing» and «post-traumatic stress disorder» and its abbreviations «EMDR» and «PTSD». Fifteen randomised controlled trials of good methodological quality were selected. These studies compared EMDR with unspecific interventions, waiting lists, or specific therapies. Overall, the results of these studies suggest that EMDR is a useful, evidence-based tool for the treatment of post-traumatic stress disorder, in line with recent recommendations from different international health organisations. Copyright © 2016 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.
Co-occurrence of dissociative identity disorder and borderline personality disorder.
Ross, Colin A; Ferrell, Lynn; Schroeder, Elizabeth
2014-01-01
The literature indicates that, among individuals with borderline personality disorder, pathological dissociation correlates with a wide range of impairments and difficulties in psychological function. It also predicts a poorer response to dialectical behavior therapy for borderline personality disorder. We hypothesized that (a) dissociative identity disorder commonly co-occurs with borderline personality disorder and vice versa, and (b) individuals who meet criteria for both disorders have more comorbidity and trauma than individuals who meet criteria for only 1 disorder. We interviewed a sample of inpatients in a hospital trauma program using 3 measures of dissociation. The most symptomatic group was those participants who met criteria for both borderline personality disorder and dissociative identity disorder on the Dissociative Disorders Interview Schedule, followed by those who met criteria for dissociative identity disorder only, then those with borderline personality disorder only, and finally those with neither disorder. Greater attention should be paid to the relationship between borderline personality disorder and dissociative identity disorder.
Ritter, McKenzie L.; Guo, Wei; Samuels, Jack F.; Wang, Ying; Nestadt, Paul S.; Krasnow, Janice; Greenberg, Benjamin D.; Fyer, Abby J.; McCracken, James T.; Geller, Daniel A.; Murphy, Dennis L.; Knowles, James A.; Grados, Marco A.; Riddle, Mark A.; Rasmussen, Steven A.
2017-01-01
Objective: The aim of this study was to identify any potential genetic overlap between attention deficit hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). We hypothesized that since these disorders share a sub-phenotype, they may share common risk alleles. In this manuscript, we report the overlap found between these two disorders. Methods: A meta-analysis was conducted between ADHD and OCD, and polygenic risk scores (PRS) were calculated for both disorders. In addition, ...
Drug-Resistant Epilepsy: Multiple Hypotheses, Few Answers
Directory of Open Access Journals (Sweden)
Fei Tang
2017-07-01
Full Text Available Epilepsy is a common neurological disorder that affects over 70 million people worldwide. Despite the recent introduction of new antiseizure drugs (ASDs, about one-third of patients with epilepsy have seizures refractory to pharmacotherapy. Early identification of patients who will become refractory to ASDs could help direct such patients to appropriate non-pharmacological treatment, but the complexity in the temporal patterns of epilepsy could make such identification difficult. The target hypothesis and transporter hypothesis are the most cited theories trying to explain refractory epilepsy, but neither theory alone fully explains the neurobiological basis of pharmacoresistance. This review summarizes evidence for and against several major theories, including the pharmacokinetic hypothesis, neural network hypothesis, intrinsic severity hypothesis, gene variant hypothesis, target hypothesis, and transporter hypothesis. The discussion is mainly focused on the transporter hypothesis, where clinical and experimental data are discussed on multidrug transporter overexpression, substrate profiles of ASDs, mechanism of transporter upregulation, polymorphisms of transporters, and the use of transporter inhibitors. Finally, future perspectives are presented for the improvement of current hypotheses and the development of treatment strategies as guided by the current understanding of refractory epilepsy.
Dysfunctional Affect Regulation : in borderline personality disorder and somatoform disorder
van Dijke, A.
2011-01-01
The aim of this dissertation was to provide a systematic exploration of the nature and distribution of dysfunctional affect regulation, its associated phenomena, and retrospectively reported potentially traumatizing events in 475 patients diagnosed with borderline personality disorder (BPD), somatoform disorder (SoD), comorbid BPD+SoD, and a psychiatric comparison group (PC) to provide a baseline against which to compare the hypothesized elevations in dysfunctional self and affect regulation....
Predictive hypotheses are ineffectual in resolving complex biochemical systems.
Fry, Michael
2018-03-20
Scientific hypotheses may either predict particular unknown facts or accommodate previously-known data. Although affirmed predictions are intuitively more rewarding than accommodations of established facts, opinions divide whether predictive hypotheses are also epistemically superior to accommodation hypotheses. This paper examines the contribution of predictive hypotheses to discoveries of several bio-molecular systems. Having all the necessary elements of the system known beforehand, an abstract predictive hypothesis of semiconservative mode of DNA replication was successfully affirmed. However, in defining the genetic code whose biochemical basis was unclear, hypotheses were only partially effective and supplementary experimentation was required for its conclusive definition. Markedly, hypotheses were entirely inept in predicting workings of complex systems that included unknown elements. Thus, hypotheses did not predict the existence and function of mRNA, the multiple unidentified components of the protein biosynthesis machinery, or the manifold unknown constituents of the ubiquitin-proteasome system of protein breakdown. Consequently, because of their inability to envision unknown entities, predictive hypotheses did not contribute to the elucidation of cation theories remained the sole instrument to explain complex bio-molecular systems, the philosophical question of alleged advantage of predictive over accommodative hypotheses became inconsequential.
Borderline personality disorder and emotional intelligence
Peter, M.; Schuurmans, H.; Vingerhoets, A.J.J.M.; Smeets, G.; Verkoeijen, P.; Arntz, A.
2013-01-01
The present study investigated emotional intelligence (EI) in borderline personality disorder (BPD). It was hypothesized that patients with BPD (n = 61) compared with patients with other personality disorders (PDs; n = 69) and nonpatients (n = 248) would show higher scores on the ability to perceive
Quantitative linking hypotheses for infant eye movements.
Directory of Open Access Journals (Sweden)
Daniel Yurovsky
Full Text Available The study of cognitive development hinges, largely, on the analysis of infant looking. But analyses of eye gaze data require the adoption of linking hypotheses: assumptions about the relationship between observed eye movements and underlying cognitive processes. We develop a general framework for constructing, testing, and comparing these hypotheses, and thus for producing new insights into early cognitive development. We first introduce the general framework--applicable to any infant gaze experiment--and then demonstrate its utility by analyzing data from a set of experiments investigating the role of attentional cues in infant learning. The new analysis uncovers significantly more structure in these data, finding evidence of learning that was not found in standard analyses and showing an unexpected relationship between cue use and learning rate. Finally, we discuss general implications for the construction and testing of quantitative linking hypotheses. MATLAB code for sample linking hypotheses can be found on the first author's website.
Pearce element ratios: A paradigm for testing hypotheses
Russell, J. K.; Nicholls, Jim; Stanley, Clifford R.; Pearce, T. H.
Science moves forward with the development of new ideas that are encapsulated by hypotheses whose aim is to explain the structure of data sets or to expand existing theory. These hypotheses remain conjecture until they have been tested. In fact, Karl Popper advocated that a scientist's job does not finish with the creation of an idea but, rather, begins with the testing of the related hypotheses. In Popper's [1959] advocation it is implicit that there be tools with which we can test our hypotheses. Consequently, the development of rigorous tests for conceptual models plays a major role in maintaining the integrity of scientific endeavor [e.g., Greenwood, 1989].
Liu, Pin W.
2014-01-01
Kv2 family “delayed-rectifier” potassium channels are widely expressed in mammalian neurons. Kv2 channels activate relatively slowly and their contribution to action potential repolarization under physiological conditions has been unclear. We explored the function of Kv2 channels using a Kv2-selective blocker, Guangxitoxin-1E (GxTX-1E). Using acutely isolated neurons, mixed voltage-clamp and current-clamp experiments were done at 37°C to study the physiological kinetics of channel gating and action potentials. In both rat superior cervical ganglion (SCG) neurons and mouse hippocampal CA1 pyramidal neurons, 100 nm GxTX-1E produced near-saturating block of a component of current typically constituting ∼60–80% of the total delayed-rectifier current. GxTX-1E also reduced A-type potassium current (IA), but much more weakly. In SCG neurons, 100 nm GxTX-1E broadened spikes and voltage clamp experiments using action potential waveforms showed that Kv2 channels carry ∼55% of the total outward current during action potential repolarization despite activating relatively late in the spike. In CA1 neurons, 100 nm GxTX-1E broadened spikes evoked from −70 mV, but not −80 mV, likely reflecting a greater role of Kv2 when other potassium channels were partially inactivated at −70 mV. In both CA1 and SCG neurons, inhibition of Kv2 channels produced dramatic depolarization of interspike voltages during repetitive firing. In CA1 neurons and some SCG neurons, this was associated with increased initial firing frequency. In all neurons, inhibition of Kv2 channels depressed maintained firing because neurons entered depolarization block more readily. Therefore, Kv2 channels can either decrease or increase neuronal excitability depending on the time scale of excitation. PMID:24695716
[Co-occurrence of anxiety and autism. The social error and allostatic load hypotheses].
Paula-Perez, Isabel
2013-02-22
INTRODUCTION. The concept of comorbidity in neurodevelopmental disorders like autism is sometimes ambiguous. The co-occurrence of anxiety and autism is clinically significant, yet it is not always easy to determine whether it is a 'real' comorbidity, where the two comorbid conditions are phenotypically and aetiologically identical to what that anxiety would mean in persons with a neurotypical development, whether it is an anxiety that has been phenotypically modified by the pathological processes of the autism spectrum disorders, thus resulting in a specific variant of these latter, or whether we are dealing with a false comorbidity resulting from rather inaccurate differential diagnoses. DEVELOPMENT. The article puts forward two hypotheses to explain this co-occurrence, which provide each other with feedback and are little more than our reflections on the scientific evidence we have available today, but expressed aloud. The first is the 'social error' hypothesis, which considers that the maladjustments in the social behaviour of persons with autism (which arises from alterations affecting the processes involved in social cognition) help to aggravate anxiety in autism. The second hypothesis, referring to allostatic load, holds that anxiety is a response to chronic stress, wear or exhaustion that is produced by the hyperactivation of certain structures in the limbic system. CONCLUSIONS. The prototypical manifestations of anxiety present in the person with autism are not always related with the same biopsychosocial variables as those observed in persons without autism. Evidence points to hyper-reactive flee-or-fight responses (hypervigilance) when the person finds him or herself outside their comfort zone, and supports the hypotheses of 'social error' and of decompensation of the allostatic mechanism that makes it possible to cope with stress.
GENDER ROLE AND PERSONALITY DISORDERS
Klonsky, E. David; Jane, J. Serrita; Turkheimer, Eric; Oltmanns, Thomas F.
2002-01-01
Many researchers have hypothesized relationships between personality disorders and gender role (i.e., masculinity and femininity). However, research has not addressed if people who are masculine or feminine more often meet the criteria for personality disorders. The present study examined whether college students (N = 665, 60% women) higher in masculinity or femininity more often exhibited features of the 10 DSM-IV personality disorders. Feminine men exhibited more features of all the persona...
Mermillod, Martial; Vermeulen, Nicolas; Droit-Volet, Sylvie; Jalenques, Isabelle; Durif, Franck; Niedenthal, Paula
2011-01-01
Parkinson's disease (PD) and Tourette's syndrome (TS) lead to important motor disorders among patients such as possible facial amimia in PD and tics in Tourette's syndrome. Under the grounded cognition framework that shows the importance of motor embodiment in emotional feeling (Niedenthal, 2007), both types of pathology with motor symptoms should be sufficient to induce potential impairments for these patients when recognizing emotional facial expressions (EFE). In this opinion paper, we des...
HyQue: evaluating hypotheses using Semantic Web technologies
Directory of Open Access Journals (Sweden)
Callahan Alison
2011-05-01
Full Text Available Abstract Background Key to the success of e-Science is the ability to computationally evaluate expert-composed hypotheses for validity against experimental data. Researchers face the challenge of collecting, evaluating and integrating large amounts of diverse information to compose and evaluate a hypothesis. Confronted with rapidly accumulating data, researchers currently do not have the software tools to undertake the required information integration tasks. Results We present HyQue, a Semantic Web tool for querying scientific knowledge bases with the purpose of evaluating user submitted hypotheses. HyQue features a knowledge model to accommodate diverse hypotheses structured as events and represented using Semantic Web languages (RDF/OWL. Hypothesis validity is evaluated against experimental and literature-sourced evidence through a combination of SPARQL queries and evaluation rules. Inference over OWL ontologies (for type specifications, subclass assertions and parthood relations and retrieval of facts stored as Bio2RDF linked data provide support for a given hypothesis. We evaluate hypotheses of varying levels of detail about the genetic network controlling galactose metabolism in Saccharomyces cerevisiae to demonstrate the feasibility of deploying such semantic computing tools over a growing body of structured knowledge in Bio2RDF. Conclusions HyQue is a query-based hypothesis evaluation system that can currently evaluate hypotheses about the galactose metabolism in S. cerevisiae. Hypotheses as well as the supporting or refuting data are represented in RDF and directly linked to one another allowing scientists to browse from data to hypothesis and vice versa. HyQue hypotheses and data are available at http://semanticscience.org/projects/hyque.
HyQue: evaluating hypotheses using Semantic Web technologies
2011-01-01
Background Key to the success of e-Science is the ability to computationally evaluate expert-composed hypotheses for validity against experimental data. Researchers face the challenge of collecting, evaluating and integrating large amounts of diverse information to compose and evaluate a hypothesis. Confronted with rapidly accumulating data, researchers currently do not have the software tools to undertake the required information integration tasks. Results We present HyQue, a Semantic Web tool for querying scientific knowledge bases with the purpose of evaluating user submitted hypotheses. HyQue features a knowledge model to accommodate diverse hypotheses structured as events and represented using Semantic Web languages (RDF/OWL). Hypothesis validity is evaluated against experimental and literature-sourced evidence through a combination of SPARQL queries and evaluation rules. Inference over OWL ontologies (for type specifications, subclass assertions and parthood relations) and retrieval of facts stored as Bio2RDF linked data provide support for a given hypothesis. We evaluate hypotheses of varying levels of detail about the genetic network controlling galactose metabolism in Saccharomyces cerevisiae to demonstrate the feasibility of deploying such semantic computing tools over a growing body of structured knowledge in Bio2RDF. Conclusions HyQue is a query-based hypothesis evaluation system that can currently evaluate hypotheses about the galactose metabolism in S. cerevisiae. Hypotheses as well as the supporting or refuting data are represented in RDF and directly linked to one another allowing scientists to browse from data to hypothesis and vice versa. HyQue hypotheses and data are available at http://semanticscience.org/projects/hyque. PMID:21624158
HyQue: evaluating hypotheses using Semantic Web technologies.
Callahan, Alison; Dumontier, Michel; Shah, Nigam H
2011-05-17
Key to the success of e-Science is the ability to computationally evaluate expert-composed hypotheses for validity against experimental data. Researchers face the challenge of collecting, evaluating and integrating large amounts of diverse information to compose and evaluate a hypothesis. Confronted with rapidly accumulating data, researchers currently do not have the software tools to undertake the required information integration tasks. We present HyQue, a Semantic Web tool for querying scientific knowledge bases with the purpose of evaluating user submitted hypotheses. HyQue features a knowledge model to accommodate diverse hypotheses structured as events and represented using Semantic Web languages (RDF/OWL). Hypothesis validity is evaluated against experimental and literature-sourced evidence through a combination of SPARQL queries and evaluation rules. Inference over OWL ontologies (for type specifications, subclass assertions and parthood relations) and retrieval of facts stored as Bio2RDF linked data provide support for a given hypothesis. We evaluate hypotheses of varying levels of detail about the genetic network controlling galactose metabolism in Saccharomyces cerevisiae to demonstrate the feasibility of deploying such semantic computing tools over a growing body of structured knowledge in Bio2RDF. HyQue is a query-based hypothesis evaluation system that can currently evaluate hypotheses about the galactose metabolism in S. cerevisiae. Hypotheses as well as the supporting or refuting data are represented in RDF and directly linked to one another allowing scientists to browse from data to hypothesis and vice versa. HyQue hypotheses and data are available at http://semanticscience.org/projects/hyque.
Conscientiousness and Obsessive-Compulsive Personality Disorder
Samuel, Douglas B; Widiger, Thomas A
2011-01-01
A dimensional perspective on personality disorder hypothesizes that the current diagnostic categories represent maladaptive variants of general personality traits. However, a fundamental foundation of this viewpoint is that dimensional models can adequately account for the pathology currently described by these categories. While most of the personality disorders have well established links to dimensional models that buttress this hypothesis, obsessive-compulsive personality disorder (OCPD) ha...
Kotabe, Hiroki P; Kardan, Omid; Berman, Marc G
2017-08-01
Natural environments have powerful aesthetic appeal linked to their capacity for psychological restoration. In contrast, disorderly environments are aesthetically aversive, and have various detrimental psychological effects. But in our research, we have repeatedly found that natural environments are perceptually disorderly. What could explain this paradox? We present 3 competing hypotheses: the aesthetic preference for naturalness is more powerful than the aesthetic aversion to disorder (the nature-trumps-disorder hypothesis ); disorder is trivial to aesthetic preference in natural contexts (the harmless-disorder hypothesis ); and disorder is aesthetically preferred in natural contexts (the beneficial-disorder hypothesis ). Utilizing novel methods of perceptual study and diverse stimuli, we rule in the nature-trumps-disorder hypothesis and rule out the harmless-disorder and beneficial-disorder hypotheses. In examining perceptual mechanisms, we find evidence that high-level scene semantics are both necessary and sufficient for the nature-trumps-disorder effect. Necessity is evidenced by the effect disappearing in experiments utilizing only low-level visual stimuli (i.e., where scene semantics have been removed) and experiments utilizing a rapid-scene-presentation procedure that obscures scene semantics. Sufficiency is evidenced by the effect reappearing in experiments utilizing noun stimuli which remove low-level visual features. Furthermore, we present evidence that the interaction of scene semantics with low-level visual features amplifies the nature-trumps-disorder effect-the effect is weaker both when statistically adjusting for quantified low-level visual features and when using noun stimuli which remove low-level visual features. These results have implications for psychological theories bearing on the joint influence of low- and high-level perceptual inputs on affect and cognition, as well as for aesthetic design. (PsycINFO Database Record (c) 2017 APA, all
A survey of etiologic hypotheses among testicular cancer researchers.
Stang, A; Trabert, B; Rusner, C; Poole, C; Almstrup, K; Rajpert-De Meyts, E; McGlynn, K A
2015-01-01
Basic research results can provide new ideas and hypotheses to be examined in epidemiological studies. We conducted a survey among testicular cancer researchers on hypotheses concerning the etiology of this malignancy. All researchers on the mailing list of Copenhagen Testis Cancer Workshops and corresponding authors of PubMed-indexed articles identified by the search term 'testicular cancer' and published within 10 years (in total 2750 recipients) were invited to respond to an e-mail-based survey. Participants of the 8th Copenhagen Testis Cancer Workshop in May 2014 were subsequently asked to rate the plausibility of the suggested etiologic hypotheses on a scale of 1 (very implausible) to 10 (very plausible). This report describes the methodology of the survey, the score distributions by individual hypotheses, hypothesis group, and the participants' major research fields, and discuss the hypotheses that scored as most plausible. We also present plans for improving the survey that may be repeated at a next international meeting of experts in testicular cancer. Overall 52 of 99 (53%) registered participants of the 8th Copenhagen Testis Cancer Workshop submitted the plausibility rating form. Fourteen of 27 hypotheses were related to exposures during pregnancy. Hypotheses with the highest mean plausibility ratings were either related to pre-natal exposures or exposures that might have an effect during pregnancy and in post-natal life. The results of the survey may be helpful for triggering more specific etiologic hypotheses that include factors related to endocrine disruption, DNA damage, inflammation, and nutrition during pregnancy. The survey results may stimulate a multidisciplinary discussion about new etiologic hypotheses of testicular cancer. Published 2014. This article is a U. S. Government work and is in the public domain in the USA.
Brain Magnetic Resonance Spectroscopy in Tourette's Disorder
DeVito, Timothy J.; Drost, Dick J.; Pavlosky, William; Neufeld, Richard W.J.; Rajakumar, Nagalingam; McKinlay, B. Duncan; Williamson, Peter C.; Nicolson, Rob
2005-01-01
Objective: Although abnormalities of neural circuits involving the cortex, striatum, and thalamus are hypothesized to underlie Tourette's disorder, the neuronal abnormalities within components of these circuits are unknown. The purpose of this study was to examine the cellular neurochemistry within these circuits in Tourette's disorder using…
Testing competing hypotheses about single trial fMRI
DEFF Research Database (Denmark)
Hansen, Lars Kai; Purushotham, Archana; Kim, Seong-Ge
2002-01-01
We use a Bayesian framework to compute probabilities of competing hypotheses about functional activation based on single trial fMRI measurements. Within the framework we obtain a complete probabilistic picture of competing hypotheses, hence control of both type I and type II errors....
About hypotheses and paradigms: exploring the Discreetness-Chance Paradigm.
Kaellis, Eugene
2006-01-01
Hypotheses generally conform to paradigms which, over time, change, usually tardily, after they have become increasingly difficult to sustain under the impact of non-conforming evidence and alternative hypotheses, but more important, when they no longer are comfortably ensconced in the surrounding social-economic-political-cultural milieu. It is asserted that this milieu is the most important factor in shaping scientific theorizing. Some examples are cited: the rejection of the evidence that the world orbits around the sun (suspected by Pythagoras) in favor of centuries-long firm adherence to the Ptolemaic geocentric system; the early acceptance of Natural Selection in spite of its tautological essence and only conjectural supporting evidence, because it justified contemporaneous social-political ideologies as typified by, e.g., Spencer and Malthus. Economic, social, and cultural factors are cited as providing the ground, i.e., ideational substrate, for what is cited as the Discreetness-Chance Paradigm (DCP), that has increasingly dominated physics, biology, and medicine for over a century and which invokes small, discrete packets of energy/matter (quanta, genes, microorganisms, aberrant cells) functioning within an environment of statistical, not determined, causality. There is speculation on a possible paradigmatic shift from the DCP, which has fostered the proliferation, parallel with ("splitting") taxonomy, of alleged individual disease entities, their diagnoses, and, when available, their specific remedies, something particularly prominent in, e.g., psychiatry's Diagnostic and Statistical Manual, a codified compendium of alleged mental and behavioral disorders, but evident in any textbook of diagnosis and treatment of physical ailments. This presumed paradigm shift may be reflected in Western medicine, presently increasingly empirical and atomized, towards a growing acceptance of a more generalized, subject-oriented, approach to health and disease, a non
Neuroimaging of tic disorders with co-existing attention-deficit/hyperactivity disorder
DEFF Research Database (Denmark)
Plessen, Kerstin J; Royal, Jason M; Peterson, Bradley S
2007-01-01
BACKGROUND: Tourette syndrome (TS) and Attention-Deficit/Hyperactivity Disorder (ADHD) are common and debilitating neuropsychiatric illnesses that typically onset in the preschool years. Recently, both conditions have been subject to neuroimaging studies, with the aim of understanding...... contrast these findings with those in ADHD without comorbid tic disorders. RESULTS: The frequent comorbidity of TS and ADHD may reflect a common underlying neurobiological substrate, and studies confirm the hypothesized involvement of fronto-striatal circuits in both TS and ADHD. However, poor inhibitory...
Scientific 'Laws', 'Hypotheses' and 'Theories'
Indian Academy of Sciences (India)
verified, the hypothesis changes from the status of a 'mere' hypothesis, and ... a pre-existing law and the body of facts upon which that law is based. Hypotheses .... implicit belief that order objectively exists in nature, and that scientific laws ...
Familial and Temperamental Risk Factors for Social Anxiety Disorder
Hirshfeld-Becker, Dina R.
2010-01-01
Social anxiety disorder (SAD) is a common disorder that can lead to significant impairment. In this chapter, the author provides background on the disorder and reviews hypothesized familial and temperamental risk factors. In particular, it highlights the Massachusetts General Hospital (MGH) Longitudinal Study of Children at Risk for Anxiety, now…
DEFF Research Database (Denmark)
Larsen, Anders Peter; Olesen, Søren-Peter
2010-01-01
The repolarizing cardiac rapid delayed rectifier current, I(Kr), is composed of ERG1 channels. It has been suggested that two isoforms of the ERG1 protein, ERG1a and ERG1b, both contribute to I(Kr). Marked heterogeneity in the kinetic properties of native I(Kr) has been described. We hypothesized...
Volume of discrete brain structures in complex dissociative disorders : preliminary findings
Ehling, T.; Nijenhuis, E. R. S.; Krikke, A. P.; DeKloet, ER; Vermetten, E
2007-01-01
Based on findings in traumatized animals and patients with posttraumatic stress disorder, and on traumatogenic models of complex dissociative disorders, it was hypothesized that (1) patients with complex dissociative disorders have smaller volumes of hippocampus, parahippocampal gyrus, and amygdala
Scheeren, Anke M; Begeer, Sander; Banerjee, Robin; Meerum Terwogt, Mark; Koot, Hans M
2010-01-01
In order to examine hypothesized underlying neurocognitive processes in repetitive behaviour, children and adolescents (7-16 years) with autism spectrum disorder (ASD) and obsessive compulsive disorder (OCD) were compared on a range of executive function (EF) measures. Performance on
Scientific 'Laws', 'Hypotheses' and 'Theories'
Indian Academy of Sciences (India)
theories, defines a hypothesis as "any supposition which we may ... about the origin of the solar system are also hypotheses of this type. They are about the birth of the planets, an event, which has happened, in the past history of our Universe.
Scientific'Laws','Hypotheses' and'Theories'
Indian Academy of Sciences (India)
Home; Journals; Resonance – Journal of Science Education; Volume 3; Issue 12. Scientific 'Laws', 'Hypotheses' and 'Theories' - How are They Related? J R Lakshmana Rao. General Article Volume 3 Issue 12 December 1998 pp 55-61. Fulltext. Click here to view fulltext PDF. Permanent link:
[Conversion disorder : functional neuroimaging and neurobiological mechanisms].
Lejeune, J; Piette, C; Salmon, E; Scantamburlo, G
2017-04-01
Conversion disorder is a psychiatric disorder often encountered in neurology services. This condition without organic lesions was and still is sometimes referred as an imaginary illness or feigning. However, the absence of organic lesions does not exclude the possibility of cerebral dysfunction. The etiologic mechanisms underlying this disorder remain uncertain even today.The advent of cognitive and functional imaging opens up a field of exploration for psychiatry in understanding the neurobiological mechanisms underlying mental disorders and especially the conversion disorder. This article reports several neuroimaging studies of conversion disorder and attempts to generate hypotheses about neurobiological mechanisms.
Electrical storm in patients with brugada syndrome is associated with early repolarization.
Kaneko, Yoshiaki; Horie, Minoru; Niwano, Shinichi; Kusano, Kengo F; Takatsuki, Seiji; Kurita, Takashi; Mitsuhashi, Takeshi; Nakajima, Tadashi; Irie, Tadanobu; Hasegawa, Kanae; Noda, Takashi; Kamakura, Shiro; Aizawa, Yoshiyasu; Yasuoka, Ryobun; Torigoe, Katsumi; Suzuki, Hiroshi; Ohe, Toru; Shimizu, Akihiko; Fukuda, Keiichi; Kurabayashi, Masahiko; Aizawa, Yoshifusa
2014-12-01
Electrical storms (ESs) in patients with Brugada syndrome (BrS) are rare though potentially lethal. We studied 22 men with BrS and ES, defined as ≥3 episodes/d of ventricular fibrillation (VF) and compared their characteristics with those of 110 age-matched, control men with BrS without ES. BrS was diagnosed by a spontaneous or drug-induced type 1 pattern on the ECG in the absence of structural heart disease. Early repolarization (ER) was diagnosed by J waves, ie, >0.1 mV notches or slurs of the terminal portion of the QRS complex. The BrS ECG pattern was provoked with pilsicainide. A spontaneous type I ECG pattern, J waves, and horizontal/descending ST elevation were found, respectively, in 77%, 36%, and 88% of patients with ES, versus 28% (P<0.0001), 9% (P=0.003), and 60% (P=0.06) of controls. The J-wave amplitude was significantly higher in patients with than without ES (P=0.03). VF occurred during undisturbed sinus rhythm in 14 of 19 patients (74%), and ES were controlled by isoproterenol administration. All patients with ES received an implantable cardioverter defibrillator and over a 6.0±5.4 years follow-up, the prognosis of patients with ES was significantly worse than that of patients without ES. Bepridil was effective in preventing VF in 6 patients. A high prevalence of ER was found in a subgroup of patients with BrS associated with ES. ES appeared to be suppressed by isoproterenol or quinidine, whereas bepridil and quinidine were effective in the long-term prevention of VF in the highest-risk patients. © 2014 American Heart Association, Inc.
Testing hypotheses for differences between linear regression lines
Stanley J. Zarnoch
2009-01-01
Five hypotheses are identified for testing differences between simple linear regression lines. The distinctions between these hypotheses are based on a priori assumptions and illustrated with full and reduced models. The contrast approach is presented as an easy and complete method for testing for overall differences between the regressions and for making pairwise...
Merkel, W T; Pollard, C A; Wiener, R L; Staebler, C R
1993-01-01
It has been hypothesized that parents of patients with obsessive compulsive disorder exhibit specific traits. 320 consecutive inpatient admissions who met criteria for OCD, depression, and panic disorder checked a list of adjectives to describe their parents. Patients with OCD were 1) less likely to perceive their mothers as disorganized than depressives, 2) more likely to perceive their mothers as overprotective than depressives and 3) less likely to perceive their fathers as demanding than patients with panic.
Regression in autistic spectrum disorders.
Stefanatos, Gerry A
2008-12-01
A significant proportion of children diagnosed with Autistic Spectrum Disorder experience a developmental regression characterized by a loss of previously-acquired skills. This may involve a loss of speech or social responsitivity, but often entails both. This paper critically reviews the phenomena of regression in autistic spectrum disorders, highlighting the characteristics of regression, age of onset, temporal course, and long-term outcome. Important considerations for diagnosis are discussed and multiple etiological factors currently hypothesized to underlie the phenomenon are reviewed. It is argued that regressive autistic spectrum disorders can be conceptualized on a spectrum with other regressive disorders that may share common pathophysiological features. The implications of this viewpoint are discussed.
Sonuga-Barke, Edmund J S; Cortese, Samuele; Fairchild, Graeme; Stringaris, Argyris
2016-03-01
Ineffective decision making is a major source of everyday functional impairment and reduced quality of life for young people with mental disorders. However, very little is known about what distinguishes decision making by individuals with different disorders or the neuropsychological processes or brain systems underlying these. This is the focus of the current review. We first propose a neuroeconomic model of the decision-making process with separate stages for the prechoice evaluation of expected utility of future options; choice execution and postchoice management; the appraisal of outcome against expectation; and the updating of value estimates to guide future decisions. According to the proposed model, decision making is mediated by neuropsychological processes operating within three domains: (a) self-referential processes involved in autobiographical reflection on past, and prospection about future, experiences; (b) executive functions, such as working memory, inhibition, and planning, that regulate the implementation of decisions; and (c) processes involved in value estimation and outcome appraisal and learning. These processes are underpinned by the interplay of multiple brain networks, especially medial and lateralized cortical components of the default mode network, dorsal corticostriatal circuits underpinning higher order cognitive and behavioral control, and ventral frontostriatal circuits, connecting to brain regions implicated in emotion processing, that control valuation and learning processes. Based on clinical insights and considering each of the decision-making stages in turn, we outline disorder-specific hypotheses about impaired decision making in four childhood disorders: attention-deficit/hyperactivity disorder (ADHD), conduct disorder (CD), depression, and anxiety. We hypothesize that decision making in ADHD is deficient (i.e. inefficient, insufficiently reflective, and inconsistent) and impulsive (biased toward immediate over delayed
GENDER ROLE AND PERSONALITY DISORDERS
Klonsky, E. David; Jane, J. Serrita; Turkheimer, Eric; Oltmanns, Thomas F.
2015-01-01
Many researchers have hypothesized relationships between personality disorders and gender role (i.e., masculinity and femininity). However, research has not addressed if people who are masculine or feminine more often meet the criteria for personality disorders. The present study examined whether college students (N = 665, 60% women) higher in masculinity or femininity more often exhibited features of the 10 DSM-IV personality disorders. Feminine men exhibited more features of all the personality disorders except antisocial. Dependent traits were associated with higher femininity and lower masculinity. Antisocial traits were associated with masculinity. Both men and women who typically behaved consistent with their gender had more narcissistic and histrionic features, whereas participants who typically behaved unlike their gender had more features of the Cluster A personality disorders. PMID:12489312
In silico generation of alternative hypotheses using causal mapping (CMAP.
Directory of Open Access Journals (Sweden)
Gabriel E Weinreb
Full Text Available Previously, we introduced causal mapping (CMAP as an easy to use systems biology tool for studying the behavior of biological processes that occur at the cellular and molecular level. CMAP is a coarse-grained graphical modeling approach in which the system of interest is modeled as an interaction map between functional elements of the system, in a manner similar to portrayals of signaling pathways commonly used by molecular cell biologists. CMAP describes details of the interactions while maintaining the simplicity of other qualitative methods (e.g., Boolean networks.In this paper, we use the CMAP methodology as a tool for generating hypotheses about the mechanisms that regulate molecular and cellular systems. Furthermore, our approach allows competing hypotheses to be ranked according to a fitness index and suggests experimental tests to distinguish competing high fitness hypotheses. To motivate the CMAP as a hypotheses generating tool and demonstrate the methodology, we first apply this protocol to a simple test-case of a three-element signaling module. Our methods are next applied to the more complex phenomenon of cortical oscillations observed in spreading cells. This analysis produces two high fitness hypotheses for the mechanism that underlies this dynamic behavior and suggests experiments to distinguish the hypotheses. The method can be widely applied to other cellular systems to generate and compare alternative hypotheses based on experimentally observed data and using computer simulations.
Bipolar disorder, a precursor of Parkinson's disease?
Directory of Open Access Journals (Sweden)
Tânia M.S. Novaretti
Full Text Available ABSTRACT Parkinson's disease is a neurodegenerative disorder predominantly resulting from dopamine depletion in the substantia nigra pars compacta. Some psychiatric disorders may have dopaminergic dysfunction as their substrate. We describe a well-documented case of Parkinson's disease associated with Bipolar Disorder. Although there is some knowledge about the association between these diseases, little is known about its pathophysiology and correlation. We believe that among various hypotheses, many neurotransmitters are linked to this pathophysiology.
Personality disorders and treatment drop out in the homeless
Directory of Open Access Journals (Sweden)
Salavera C
2013-03-01
Full Text Available Carlos Salavera,1 José M Tricás,2 Orosia Lucha21Faculty of Education, University of Zaragoza, Zaragoza, Spain; 2Physiotherapy Research Unit, University of Zaragoza, Zaragoza, SpainAbstract: The homeless drop out of treatment relatively frequently. Also, prevalence rates of personality disorders are much higher in the homeless group than in the general population. We hypothesize that when both variables coexist – homelessness and personality disorders – the possibility of treatment drop out grows. The aim of this study was to analyze the hypotheses, that is, to study how the existence of personality disorders affects the evolution of and permanence in treatment. One sample of homeless people in a therapeutic community (N = 89 was studied. The structured clinical interview for the diagnostic and statistical manual of mental disorders (DSM-IV-TR was administered and participants were asked to complete the Millon Clinical Multiaxial Inventory-II (MCMI-II. Cluster B personality disorders (antisocial, borderline, and narcissistic avoided permanence in the treatment process while cluster C disorders, as dependent, favored adhesion to the treatment and improved the prognosis. Knowledge of these personality characteristics should be used to advocate for better services to support homeless people and prevent their dropping out before completing treatment.Keywords: MCMI-II, abandonment, personality disorder, homeless
New hypotheses regarding the Danish health puzzle.
Bakah, May; Raphael, Dennis
2017-12-01
Nordic welfare states have achieved admirable population health profiles as a result of public policies that provide economic and social security across the life course. Denmark has been an exception to this rule, as its life expectancies and infant mortality rates since the mid-1970s have lagged behind the other Nordic nations and, in the case of life expectancy, behind most Organisation for Economic Co-operation and Development nations. In this review paper, we identify a number of new hypotheses for why this may be the case. These hypotheses concern the health effects of neo-liberal restructuring of the economy and its institutions, the institution of flexi-security in Denmark's labour market and the influence of Denmark's tobacco and alcohol industries. Also of note is that Denmark experienced higher unemployment rates during its initial period of health stagnation, as well as its treatment of non-Western immigrants and high wealth inequality and, until recently, the fact that Denmark did not systematically address the issue of health inequalities. These hypotheses may serve as covering explanations for the usually provided accounts of elevated behavioural risks and psychosocial stress as being responsible for Denmark's health profile.
Modulation of KCNQ1 alternative splicing regulates cardiac IKs and action potential repolarization.
Lee, Hsiang-Chun; Rudy, Yoram; Po-Yuan, Phd; Sheu, Sheng-Hsiung; Chang, Jan-Gowth; Cui, Jianmin
2013-08-01
Slow delayed-rectifier potassium current (IKs) channels, made of the pore-forming KCNQ1 and auxiliary KCNE1 subunits, play a key role in determining action potential duration (APD) in cardiac myocytes. The consequences of drug-induced KCNQ1 splice alteration remain unknown. To study the modulation of KCNQ1 alternative splicing by amiloride and the consequent changes in IKs and action potentials (APs) in ventricular myocytes. Canine endocardial, midmyocardial, and epicardial ventricular myocytes were isolated. Levels of KCNQ1a and KCNQ1b as well as a series of splicing factors were quantified by using the reverse transcriptase-polymerase chain reaction and Western blot. The effect of amiloride-induced changes in the KCNQ1b/total KCNQ1 ratio on AP was measured by using whole-cell patch clamp with and without isoproterenol. With 50 μmol/L of amiloride for 6 hours, KCNQ1a at transcriptional and translational levels increased in midmyocardial myocytes but decreased in endo- and epicardial myocytes. Likewise, changes in splicing factors in midmyocardial were opposite to that in endo- and epicardial myocytes. In midmyocardial myocytes amiloride shortened APD and decreased isoproterenol-induced early afterdepolarizations significantly. The same amiloride-induced effects were demonstrated by using human ventricular myocyte model for AP simulations under beta-adrenergic stimulation. Moreover, amiloride reduced the transmural dispersion of repolarization in pseudo-electrocardiogram. Amiloride regulates IKs and APs with transmural differences and reduces arrhythmogenicity through the modulation of KCNQ1 splicing. We suggested that the modulation of KCNQ1 splicing may help prevent arrhythmia. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
The revelation effect: A meta-analytic test of hypotheses.
Aßfalg, André; Bernstein, Daniel M; Hockley, William
2017-12-01
Judgments can depend on the activity directly preceding them. An example is the revelation effect whereby participants are more likely to claim that a stimulus is familiar after a preceding task, such as solving an anagram, than without a preceding task. We test conflicting predictions of four revelation-effect hypotheses in a meta-analysis of 26 years of revelation-effect research. The hypotheses' predictions refer to three subject areas: (1) the basis of judgments that are subject to the revelation effect (recollection vs. familiarity vs. fluency), (2) the degree of similarity between the task and test item, and (3) the difficulty of the preceding task. We use a hierarchical multivariate meta-analysis to account for dependent effect sizes and variance in experimental procedures. We test the revelation-effect hypotheses with a model selection procedure, where each model corresponds to a prediction of a revelation-effect hypothesis. We further quantify the amount of evidence for one model compared to another with Bayes factors. The results of this analysis suggest that none of the extant revelation-effect hypotheses can fully account for the data. The general vagueness of revelation-effect hypotheses and the scarcity of data were the major limiting factors in our analyses, emphasizing the need for formalized theories and further research into the puzzling revelation effect.
Directory of Open Access Journals (Sweden)
Alessandra Mancini
2018-04-01
Full Text Available Imagery Rescripting (ImRs is a therapeutic technique that aims to reduce the distress associated with negative memories of early aversive experiences. It consists of prompting patients to rescript the autobiographical memory in line with their unmet needs. In recent years, ImRs was found effective in reducing symptoms of disorders such as depression, social phobia, obsessive-compulsive disorder, post-traumatic stress disorder, and personality disorders. However, the cognitive mechanisms underlying such broad effectiveness are currently an object of debate. Empirical evidence has shown that ImRs reduces the negative self-belief derived from aversive memories in different types of mental disorders. However, existing accounts are not very accurate in explaining how this change in self-belief occurs and therefore why ImRs is effective across psychopathologies. We propose that ImRs changes the semantic self-representation encapsulated in the aversive memory by reducing the meta-emotional problem (i.e., perceiving a negative emotion as problematic and unacceptable. Empirical evidence implicates the meta-emotional problem or “secondary problem” in the maintenance of different disorders and has shown that treating it leads to symptoms reduction. Here we hypothesize that: (i ImRs as a stand-alone treatment may lead to a reduction of symptoms; negative self-belief and the meta-emotional problem; and (ii the reduction of the meta-emotional problem might mediate the relation between symptoms and negative self-belief reduction. To test our hypothesis, we present an experimental procedure that could be used in future studies. We conclude discussing the existing theoretical frameworks that attempt to unravel the mechanisms that play a role in ImRs.
Electroconvulsive therapy's mechanism of action: neuroendocrine hypotheses.
Haskett, Roger F
2014-06-01
Despite a range of etiological theories since the introduction of electroconvulsive therapy (ECT) more than 75 years ago, its mechanism of action remains poorly understood. The neuroendocrine hypothesis is based on the seizure-related release of hypothalamic hormones into the blood and cerebrospinal fluid and evidence of endocrine dysfunction in many patients with severe mood disorder. The specific effect of ECT was hypothesized to result from the transverse passage of current through the brain with direct stimulation of axial structures including the diencephalon. The prompt release of adrenocorticotropic hormone, cortisol, and prolactin into blood followed ECT with a return to pretreatment baseline levels in several hours. The elevated levels of hormones were absorbed by the cerebrospinal fluid, providing contact with brain cells and central nervous system structures. An apparently specific pattern of ECT-induced hormone changes, limited to prolactin and cortisol, suggested that ECT released a substance with dopaminergic antagonist and antipsychotic properties. As hypothalamic dysfunction is a key finding in endogenomorphic depression and the abnormal endocrine and physiological functions usually normalize with recovery, this led to a search for biological markers that would supplement clinical assessment of diagnosis and treatment response. One of these, the overnight dexamethasone suppression test found that 40% to 50% of melancholic depressed patients had abnormal results, whereas 90% of control patients suppressed normally. This was followed by a period of uncritical overenthusiasm followed by wholesale rejection of the clinical neuroendocrine strategies. Several key methodological issues received inadequate attention, and there have been calls to revisit this topic.
Cardiac Delayed Rectifier Potassium Channels in Health and Disease
Chen, Lei; Sampson, Kevin J.; Kass, Robert S.
2016-01-01
Cardiac delayed rectifier potassium channels conduct outward potassium currents during the plateau phase of action potentials and play pivotal roles in cardiac repolarization. These include IKs, IKr and the atrial specific IKur channels. In this chapter, we will review the molecular identities and biophysical properties of these channels. Mutations in the genes encoding delayed rectifiers lead to loss- or gain-of-function phenotypes, disrupt normal cardiac repolarization and result in various cardiac rhythm disorders, including congenital Long QT Syndrome, Short QT Syndrome and familial atrial fibrillation. We will also discuss the possibility and prospect of using delayed rectifier channels as therapeutic targets to manage cardiac arrhythmia. PMID:27261823
Cardiac Delayed Rectifier Potassium Channels in Health and Disease.
Chen, Lei; Sampson, Kevin J; Kass, Robert S
2016-06-01
Cardiac delayed rectifier potassium channels conduct outward potassium currents during the plateau phase of action potentials and play pivotal roles in cardiac repolarization. These include IKs, IKr and the atrial specific IKur channels. In this article, we will review their molecular identities and biophysical properties. Mutations in the genes encoding delayed rectifiers lead to loss- or gain-of-function phenotypes, disrupt normal cardiac repolarization and result in various cardiac rhythm disorders, including congenital Long QT Syndrome, Short QT Syndrome and familial atrial fibrillation. We will also discuss the prospect of using delayed rectifier channels as therapeutic targets to manage cardiac arrhythmia. Copyright © 2016 Elsevier Inc. All rights reserved.
Atomoxetine-Induced Electrocardiogram Changes
Directory of Open Access Journals (Sweden)
J Gordon Millichap
2006-12-01
Full Text Available An 11-year-old boy with attention deficit hyperactivity disorder (ADHD who developed palpitations and unusual cardiac repolarization changes on the electrocardiogram (ECG during standard dose treatment with atomoxetine is reported from Parkview Clinic and Birmingham Children's Hospital, Birmingham, UK.
Singularity hypotheses a scientific and philosophical assessment
Moor, James; Søraker, Johnny; Steinhart, Eric
2012-01-01
Singularity Hypotheses: A Scientific and Philosophical Assessment offers authoritative, jargon-free essays and critical commentaries on accelerating technological progress and the notion of technological singularity. It focuses on conjectures about the intelligence explosion, transhumanism, and whole brain emulation. Recent years have seen a plethora of forecasts about the profound, disruptive impact that is likely to result from further progress in these areas. Many commentators however doubt the scientific rigor of these forecasts, rejecting them as speculative and unfounded. We therefore invited prominent computer scientists, physicists, philosophers, biologists, economists and other thinkers to assess the singularity hypotheses. Their contributions go beyond speculation, providing deep insights into the main issues and a balanced picture of the debate.
Directory of Open Access Journals (Sweden)
Emrah Kara
2015-03-01
Full Text Available Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, refers to a disorder in children who manifest symptoms of obsessive-compulsive disorder and/or tic disorders associated with acute exacerbations. Although autoimmune responses following infections with streptococcus have been hypothesized to be responsible, there is still controversies about the pathophysiology and treatment. In this article, the treatment methods of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections and the role of otolaryngologist were discussed.
Defense mechanisms in schizotypal, borderline, antisocial, and narcissistic personality disorders.
Perry, J Christopher; Presniak, Michelle D; Olson, Trevor R
2013-01-01
Numerous authors have theorized that defense mechanisms play a role in personality disorders. We reviewed theoretical writings and empirical studies about defenses in schizotypal, borderline, antisocial, and narcissistic personality disorders, developing hypotheses about these differential relationships. We then examined these hypotheses using dynamic interview data rated for defenses in a study of participants (n = 107) diagnosed with these four personality disorder types. Overall, the prevalence of immature defenses was substantial, and all four disorders fit within the broad borderline personality organization construct. Defenses predicted the most variance in borderline and the least variance in schizotypal personality disorder, suggesting that dynamic factors played the largest role in borderline and the least in schizotypal personality. Central to borderline personality were strong associations with major image-distorting defenses, primarily splitting of self and other's images, and the hysterical level defenses, dissociation and repression. Narcissistic and antisocial personality disorders shared minor image-distorting defenses, such as omnipotence or devaluation, while narcissistic also used splitting of self-images and antisocial used disavowal defenses like denial. Overall, differential relationships between specific defenses and personality disorder types were largely consistent with the literature, and consistent with the importance that the treatment literature ascribes to working with defenses.
Gender dysphoria and autism spectrum disorder: A narrative review.
Van Der Miesen, Anna I R; Hurley, Hannah; De Vries, Annelou L C
2016-01-01
The current literature shows growing evidence of a link between gender dysphoria (GD) and autism spectrum disorder (ASD). This study reviews the available clinical and empirical data. A systematic search of the literature was conducted using the following databases: PubMed, Web of Science, PsycINFO and Scopus; utilizing different combinations of the following search terms: autism, autism spectrum disorder (ASD), Asperger's disorder (AD), co-morbidity, gender dysphoria (GD), gender identity disorder (GID), transgenderism and transsexualism. In total, 25 articles and reports were selected and discussed. Information was grouped by found co-occurrence rates, underlying hypotheses and implications for diagnosis and treatment. GD and ASD were found to co-occur frequently - sometimes characterized by atypical presentation of GD, which makes a correct diagnosis and determination of treatment options for GD difficult. Despite these challenges there are several case reports describing gender affirming treatment of co-occurring GD in adolescents and adults with ASD. Various underlying hypotheses for the link between GD and ASD were suggested, but almost all of them lack evidence.
[Insomnia associated with psychiatric disorders].
Suzuki, Masahiro; Konno, Chisato; Furihata, Ryuji; Osaki, Koichi; Uchiyama, Makoto
2009-08-01
Most psychiatric disorders, such as schizophrenia, mood disorders, or neurotic disorders are associated with sleep disorders of various kinds, among which insomnia is most prevalent and important in psychiatric practice. Almost all patients suffering from major depression complain of insomnia. Pharmacological treatment of insomnia associated with major depression shortens the duration to achieve remission of depression. Insomnia has been recently reported to be a risk factor for depression. In patients with schizophrenia, insomnia is often an early indicator of the aggravation of psychotic symptoms. Electroencephalographic sleep studies have also revealed sleep abnormalities characteristic to mood disorders, schizophrenia and anxiety disorders. A shortened REM sleep latency has been regarded as a biological marker of depression. Reduced amount of deep non-REM sleep has been reported to be correlated with negative symptoms of schizophrenia. Recently, REM sleep abnormalities were found in teenagers having post-traumatic stress disorder after a boat accident. Although these facts indicate that insomnia plays an important role in the development of psychiatric disorders, there are few hypotheses explaining the cause and effect of insomnia in these disorders. Here, we reviewed recent articles on insomnia associated with psychiatric disorders together with their clinical managements.
Zorzi, Alessandro; Leoni, Loira; Di Paolo, Fernando M; Rigato, Ilaria; Migliore, Federico; Bauce, Barbara; Pelliccia, Antonio; Corrado, Domenico
2015-02-15
Early repolarization (ER) is typically observed in highly trained athletes as a physiologic consequence of increased vagal tone. The variant of anterior (V1 to V3) ER characterized by "domed" ST-segment elevation and negative T wave raises problems of differential diagnosis with the "coved-type" electrocardiographic pattern seen in Brugada syndrome (BS). This study was designed to identify electrocardiographic criteria for distinguishing athlete's ER from BS. The study compared the electrocardiographic tracings of 61 healthy athletes (80% men, median age 23 ± 8 years), showing "domed" ST-segment elevation and negative T wave in leads V1 to V3, with those of 92 consecutive age- and sex-matched BS patients with a "coved-type" electrocardiographic pattern. The electrocardiographic analysis focused on the ST-segment elevation at J point (STJ) and at 80 milliseconds after J point (ST₈₀). Athletes had a lower maximum amplitude of STJ (1.46 ± 0.7 vs 3.25 ± 0.6 mm, p 1) versus only 2 (3%) athletes (p <0.001). An upsloping ST-segment configuration (STJ/ST₈₀ <1) showed a sensitivity of 97%, a specificity of 100%, and a diagnostic accuracy of 98.7% for the diagnosis of ER. At multivariate analysis, STJ/ST₈₀ ratio remained the only independent predictor for ER (odds ratio 87, 95% confidence interval 19 to 357, p <0.001). In conclusion, the STJ/ST₈₀ ratio is a highly accurate electrocardiographic parameter for differential diagnosis between anterior ER of the athlete and BS. Our results may help in reducing the number of athletes who undergo expensive diagnostic workup or are unnecessarily disqualified from competition for changes that fall within the normal range of athlete's heart. Copyright © 2015 Elsevier Inc. All rights reserved.
DEFF Research Database (Denmark)
Graff, Claus; Matz, Jørgen; Christensen, Ellen B
2009-01-01
prolongation. Seventy-nine healthy subjects were included in this parallel study. After a baseline day during which no drug was given, 40 subjects received an I(Kr)-blocking antipsychotic compound (Lu 35-138) on 7 consecutive days while 39 subjects received placebo. Resting ECGs were recorded and used...... to determine a combined measure of repolarization morphology (morphology combination score [MCS]), based on asymmetry, flatness, and notching. Replicate measurements were used to determine reliable change and study power for both measures. Lu 35-138 increased the QTc interval with corresponding changes in T......-wave morphology as determined by MCS. For subjects taking Lu 35-138, T-wave morphology was a more reliable indicator of I(Kr) inhibition than QTcF (chi(2) = 20.3, P = .001). At 80% study power for identifying a 5-millisecond placebo-adjusted change from baseline for QTcF, the corresponding study power for MCS...
Cardinal, René; Pagé, Pierre; Vermeulen, Michel; Ardell, Jeffrey L; Armour, J Andrew
2009-01-28
Ganglionated plexuses (GPs) are major constituents of the intrinsic cardiac nervous system, the final common integrator of regional cardiac control. We hypothesized that nicotinic stimulation of individual GPs exerts divergent regional influences, affecting atrial as well as ventricular functions. In 22 anesthetized canines, unipolar electrograms were recorded from 127 atrial and 127 ventricular epicardial loci during nicotine injection (100 mcg in 0.1 ml) into either the 1) right atrial (RA), 2) dorsal atrial, 3) left atrial, 4) inferior vena cava-inferior left atrial, 5) right ventricular, 6) ventral septal ventricular or 7) cranial medial ventricular (CMV) GP. In addition to sinus and AV nodal function, neural effects on atrial and ventricular repolarization were identified as changes in the area subtended by unipolar recordings under basal conditions and at maximum neurally-induced effects. Animals were studied with intact AV node or following ablation to achieve ventricular rate control. Atrial rate was affected in response to stimulation of all 7 GPs with an incidence of 50-95% of the animals among the different GPs. AV conduction was affected following stimulation of 6/7 GP with an incidence of 22-75% among GPs. Atrial and ventricular repolarization properties were affected by atrial as well as ventricular GP stimulation. Distinct regional patterns of repolarization changes were identified in response to stimulation of individual GPs. RAGP predominantly affected the RA and posterior right ventricular walls whereas CMVGP elicited biatrial and biventricular repolarization changes. Spatially divergent and overlapping cardiac regions are affected in response to nicotinic stimulation of neurons in individual GPs.
Testing statistical hypotheses
Lehmann, E L
2005-01-01
The third edition of Testing Statistical Hypotheses updates and expands upon the classic graduate text, emphasizing optimality theory for hypothesis testing and confidence sets. The principal additions include a rigorous treatment of large sample optimality, together with the requisite tools. In addition, an introduction to the theory of resampling methods such as the bootstrap is developed. The sections on multiple testing and goodness of fit testing are expanded. The text is suitable for Ph.D. students in statistics and includes over 300 new problems out of a total of more than 760. E.L. Lehmann is Professor of Statistics Emeritus at the University of California, Berkeley. He is a member of the National Academy of Sciences and the American Academy of Arts and Sciences, and the recipient of honorary degrees from the University of Leiden, The Netherlands and the University of Chicago. He is the author of Elements of Large-Sample Theory and (with George Casella) he is also the author of Theory of Point Estimat...
Directory of Open Access Journals (Sweden)
Chih-Sheng Chu
2007-05-01
Full Text Available Emerging evidence suggests that statins have a favorable impact on the reduction of arrhythmia events and sudden cardiac death in patients with structural heart disease. We aimed to investigate the possibly and directly favorable effects of statins on ventricular late potentials, QT dispersion, and transmural dispersion of repolarization attained by analyzing clinical electrocardiography (ECG risk stratification parameters in patients with hypercholesterolemia without structural heart disease. In total, 82 patients (45 females; mean age, 62 ± 10 years with hypercholesterolemia were enrolled in this prospective study to examine the effects of statin therapy (atorvastatin 10mg/day for 3 months on ECG risk stratification parameters. Surface 12-lead ECG and signal-average ECG (SAECG were recorded before and after statin treatment. The SAECG parameters, QT dispersion, Bazett-corrected QT (QTc dispersion, T wave peak-to-end interval (Tpe, and percentage of Tpe/QT interval were calculated and compared before and after statin therapy. Twelve-lead ambulatory 24-hour ECGs were recorded in 12 patients. The results demonstrated that after statin therapy for 3 months, serum levels of total cholesterol and low-density lipoprotein cholesterol were significantly reduced (both p values < 0.001. However, neither significant changes of each SAECG parameter nor the frequency of late potentials were demonstrated after atorvastatin therapy. In addition, no significant changes in QT dispersion, QTc dispersion, Tpe, or Tpe/QT were found. However, 24-hour ambulatory ECG revealed a flattening effect of circadian variation of QTc dispersion after atorvastatin therapy. In conclusion, the favorable antiarrhythmia effect of atorvastatin (10 mg/day therapy cannot be directly reflected by analyzing these noninvasive ECG risk stratification parameters in low-risk patients with hypercholesterolemia.
Perplexities and Provocations of Eating Disorders
Halmi, Katherine A.
2009-01-01
Background: Etiological hypotheses of eating disorders, anorexia nervosa and bulimia nervosa have not produced informative research for predictably effective treatment. Methods: The rationale for applying a model of allostasis, a dysregulation of reward circuits with activation of brain and hormonal stress responses to maintain apparent stability,…
Conversion Disorder- Mind versus Body: A Review.
Ali, Shahid; Jabeen, Shagufta; Pate, Rebecca J; Shahid, Marwah; Chinala, Sandhya; Nathani, Milankumar; Shah, Rida
2015-01-01
In this article, the authors accentuate the signs and symptoms of conversion disorder and the significance of clinical judgment and expertise in order to reach the right diagnosis. The authors review the literature and provide information on the etiology, prevalence, diagnostic criteria, and the treatment methods currently employed in the management of conversion disorder. Of note, the advancements of neuropsychology and brain imaging have led to emergence of a relatively sophisticated picture of the neuroscientific psychopathology of complex mental illnesses, including conversion disorder. The available evidence suggests new methods with which to test hypotheses about the neural circuits underlying conversion symptoms. In context of this, the authors also explore the neurobiological understanding of conversion disorder.
Sexual Abuse and Eating Disorders: A Test of a Conceptual Model.
Tripp, Margaret M.; Petrie, Trent A.
2001-01-01
Tested a model that hypothesized an indirect relationship between sexual abuse and eating disorders, with the effects of sexual abuse being mediated through bodily shame and body disparagement. Surveys of female undergraduate students indicated that 60 percent had been sexually abused, 8 percent had diagnosable eating disorders, and 72.7 percent…
Testing statistical hypotheses of equivalence
Wellek, Stefan
2010-01-01
Equivalence testing has grown significantly in importance over the last two decades, especially as its relevance to a variety of applications has become understood. Yet published work on the general methodology remains scattered in specialists' journals, and for the most part, it focuses on the relatively narrow topic of bioequivalence assessment.With a far broader perspective, Testing Statistical Hypotheses of Equivalence provides the first comprehensive treatment of statistical equivalence testing. The author addresses a spectrum of specific, two-sided equivalence testing problems, from the
High prevalence of personality disorders among circadian rhythm sleep disorders (CRSD) patients.
Dagan, Y; Sela, H; Omer, H; Hallis, D; Dar, R
1996-10-01
The purpose of this study was to examine systematically our previous clinical impression regarding the prevalence of personality disorders in patients suffering from circadian rhythm sleep disorders (CRSD). We hypothesized that, in a group of patients suffering from CRSD, there would be a higher frequency of personality disorders than in a group of healthy controls. The experimental group consisted of CRSD patients diagnosed according to a clinical interview and actigraphic recordings. The control group consisted of healthy volunteers in whom CRSD had been ruled out by means of a self-administered questionnaire. Both groups were assessed for personality disorders using the MCMI, a diagnostic tool based on Millon's biopsychosocial theory of personality and the PRQ-R, a diagnostic tool based on the DMS-III-R. Both tests provided clear and significant support for the hypothesis that individuals suffering from CRSD are characterized to a greater extent by personality disorders than a control group. No specific characteristic pattern or profile of personality disorders was clearly detected. Correct early diagnosis and treatment of CRSD may improve afflicted individuals' adaptive capabilities and perhaps even prevent the development of a personality disorder. This suggests how important a greater awareness of CRSD on the part of the professional community may be.
Mirror bootstrap method for testing hypotheses of one mean
Varvak, Anna
2012-01-01
The general philosophy for bootstrap or permutation methods for testing hypotheses is to simulate the variation of the test statistic by generating the sampling distribution which assumes both that the null hypothesis is true, and that the data in the sample is somehow representative of the population. This philosophy is inapplicable for testing hypotheses for a single parameter like the population mean, since the two assumptions are contradictory (e.g., how can we assume both that the mean o...
Differential Social Comparison Processes in Women with and without Eating Disorder Symptoms
Corning, Alexandra F.; Krumm, Angela J.; Smitham, Lora A.
2006-01-01
On the basis of predictions from social comparison theory (L. Festinger, 1954) and informed by findings from the social comparison and eating disorder literatures, hypotheses were tested regarding the social comparison behaviors of women with eating disorder symptoms and their asymptomatic peers. Results indicated differentiating social-cognitive…
Attachment insecurity and psychological resources associated with adjustment disorders.
Ponizovsky, Alexander M; Levov, Kathy; Schultz, Yakov; Radomislensky, Ira
2011-04-01
This study examined the adult attachment styles, interpersonal distance from potential attachment figures and strangers, coping strategies, perceived social support, and stress-related self-variables among patients diagnosed with adjustment disorders (AJD). Seventy patients at an outpatient clinic and 61 matched controls completed a battery of standardized questionnaires. Univariate and multivariate statistical analyses were used to evaluate the parameters of interest. Using attachment theory (J. Bowlby, 1988) and the dynamic stress-vulnerability model of depressive disorder (G. W. Brown & T. O. Harris, 1989) as the analytical frameworks, the authors hypothesized that participants with AJD would: (a) display more insecure attachment styles, (b) be less tolerant of close interpersonal proximity, (c) use more emotion-oriented coping strategies, (d) display lower self-efficacy and self-esteem, and (e) perceive less social support from family, friends, and significant others. We further hypothesized that these variables would be predictive of depressive symptoms. All of the hypotheses were confirmed. The results suggest that the insecure fearful-avoidant attachment style is associated with severe depressive symptoms in patients with AJD. However, other psychosocial factors, such as low self-esteem and poor social support from friends, were more predictive of AJD symptoms. The findings warrant further studies on the risk and protective effects of these factors in the development of AJD and other stress-induced disorders. © 2011 American Orthopsychiatric Association.
Differential expression of KvLQT1 and its regulator IsK in mouse epithelia
Demolombe, S.; Franco, D.; de Boer, P.; Kuperschmidt, S.; Roden, D.; Pereon, Y.; Jarry, A.; Moorman, A. F.; Escande, D.
2001-01-01
KCNQ1 is the human gene responsible in most cases for the long QT syndrome, a genetic disorder characterized by anomalies in cardiac repolarization leading to arrhythmias and sudden death. KCNQ1 encodes a pore-forming K+ channel subunit termed KvLQT1 which, in association with its regulatory
Classification of the long-QT syndrome based on discriminant analysis of T-wave morphology
DEFF Research Database (Denmark)
Struijk, Johannes J.; Kanters, Jørgen K.; Andersen, M P
2006-01-01
The long QT syndrome (LQTS) is a genetic disorder, typically characterized by a prolonged QT interval in the ECG due to abnormal cardiac repolarization. LQTS may lead to syncopal episodes and sudden cardiac death. Various parameters based on T-wave morphology, as well as the QT interval itself ha...
III SBC Guidelines on the Analysis and Issuance of Electrocardiographic Reports - Executive Summary
Directory of Open Access Journals (Sweden)
Carlos Alberto Pastore
Full Text Available Abstract The third version of the guidelines covers recently described topics, such as ion channel diseases, acute ischemic changes, the electrocardiogram in athletes, and analysis of ventricular repolarization. It sought to revise the criteria for overloads, conduction disorders, and analysis of data for internet transmission.
Preliminary testing of flow-ecology hypotheses developed for the GCP LCC region
Brewer, Shannon K.; Davis, Mary
2014-01-01
The Ecological Limits of Hydrological Alteration (ELOHA) framework calls for the development of flow-ecology hypotheses to support protection of the flow regime from ecologically harmful alteration due to human activities. As part of a larger instream flow project for the Gulf Coast Prairie Landscape Conservation Cooperative (GCP LCC), regional flow-ecology hypotheses were developed for fish, mussels, birds, and riparian vegetation (Davis and Brewer 20141). The objective of this study was to assess the usefulness of existing ecological and hydrological data to test these hypotheses or others that may be developed in the future. Several databases related to biological collections and hydrologic data from Oklahoma, Texas, and Louisiana were compiled. State fish-community data from Oklahoma and Louisiana were summarized and paired with existing USGS gage data having at least a 40-year period of record that could be separated into reference and current conditions for comparison. The objective of this study was not to conduct exhaustive analyses of these data, the hypotheses, or analyses interpretation, but rather to use these data to determine if existing data were adequate to statistically test the regional flow-ecology hypotheses. The regional flow-ecology hypotheses were developed for the GCP LCC by a committee chaired by Shannon Brewer and Mary Davis (Davis and Brewer 2014). Existing data were useful for informing the hypotheses and suggest support for some hypotheses, but also highlight the need for additional testing and development as some results contradicted hypotheses. Results presented here suggest existing data are adequate to support some flow-ecology hypotheses; however, lack of sampling effort reported with the fish collections and the need for ecoregion-specific analyses suggest more data would be beneficial to analyses in some ecoregions. Additional fish sampling data from Texas and Louisiana will be available for future analyses and may ameliorate
Sex Differences in Internalizing Problems during Adolescence in Autism Spectrum Disorder
Oswald, Tasha M.; Winter-Messiers, Mary Ann; Gibson, Brandon; Schmidt, Alexandra M.; Herr, Cynthia M.; Solomon, Marjorie
2016-01-01
We hypothesized that the double hit conferred by sex and diagnosis increases the risk for internalizing disorders in adolescent females with autism spectrum disorder (ASD). In a sample of 32 adolescents with ASD and 32 controls, we examined the effects of sex, diagnostic factors, and developmental stages on depression and anxiety. A 3-way…
Evaluation of Extremal Hypotheses as a Criterion to Resolve Channel Indeterminacy
Tranmer, A.
2012-12-01
Design criteria for river restoration and sustainable development have significantly advanced in recent decades, yet complete deterministic formulations to address channel form and sinuosity still prove elusive. Many hypotheses have been presented to ascertain the dynamic-equilibrium of a stream at both the cross sectional and reach level. These efforts to better understand the functioning of alluvial systems include regime theory, stability theory, perturbation analysis, threshold theory, reference reach comparison, downstream hydraulic geometry, and extremal hypotheses. The latter of these theories, the extremal hypothesis, is based on optimizing one variable or criterion in the alluvial system in order to find closure to the channel design problem. Currently, there is no method to directly compare the various hypotheses at the system scale, understanding of their sensitivity to the various formulae employed or consensus regarding which hypothesis is most appropriate. This study analyzed the various extremal hypotheses in as close to a pristine environment as exists (a remote part of Patagonia, Chile), in order to assess which hypothesis (or collective hypotheses) is most appropriate for channel design. Extremal hypotheses were applied in the longitudinal direction, under the assumption of a space-for-time substitution, to evaluate the geomorphic trends of a river evolving during deglaciation. The space-for-time model assumes the watershed reaches stable, dynamic-equilibrium in its lower meandering reaches and the point of equilibrium extends upstream through its braiding reaches as the watershed adapts to new climatic and environmental conditions. Extremal hypotheses applied in a downstream fashion are then expected to predict chaotic and oversized channel characteristics in the upstream reaches and trend towards a point of equilibrium (minimum/maximum of tested hypothesis). Initial findings indicate that many hypotheses predict similar geometry and sinuosity
Self-esteem in patients with borderline and avoidant personality disorders.
Lynum, L I; Wilberg, T; Karterud, S
2008-10-01
This study compared self-esteem in patients with avoidant personality disorder (APD) and borderline personality disorder (BPD). Patients diagnosed with one or more personality disorders answered the questionnaire Index of Self Esteem as part of a comprehensive evaluation within the setting of a treatment trial. Our hypotheses were that (1) both patients with APD and patients with BPD would report low levels of self-esteem, (2) patients with APD would report lower self-esteem than patients with BPD. We further expected that (3) patients with higher levels of depression would report lower levels of self-esteem, but that (4) both borderline and avoidant personality pathology would contribute to explained variance in self-esteem beyond what would be accounted for by depression. All of our hypotheses were supported. The results from our study showed a significant difference in self-esteem level between the two personality disorders, patients with APD reporting lower self-esteem than patients with BPD. Subjects with both disorders were measured to have self-esteem levels within the range that presumes clinical problems. Self-esteem represents an important quality of subjective experience of the self, and the study of self-esteem in PDs can offer new and important knowledge of PDs as self-pathology.
Bai, Rong; Pu, Jun; Liu, Nian; Lu, Jia-Gao; Zhou, Qiang; Ruan, Yan-Fei; Niu, Hui-Yan; Wang, Lin
2003-12-25
In order to verify the hypothesis that left ventricular epicardial (LV-Epi) pacing and biventricular (BiV) pacing unavoidably influence the myocardial electrophysiological characters and may result in high risk of malignant ventricular arrhythmia, we calculated, in both normal mongrel dogs and dog models with rapid-right-ventricular-pacing induced dilated cardiomyopathy congestive heart failure (DCM-CHF), the monophasic action potential duration (MAPD) and the transmural dispersion of repolarization (TDR) in intracardiac electrogram together with the QT interval and T(peak)-T(end) (T(p(-T(e)) interval in surface electrocardiogram (ECG) during LV-Epi and BiV pacing, compared with those during right ventricular endocardial (RV-Endo) pacing. To prepare the DCM-CHF dog model, rapid right ventricular pacing (250 bpm) was performed for 23.6+/-2.57 days to the dog. All the normal and DCM-CHF dogs were given radio frequency catheter ablation (RFCA) to His bundle with the guide of X-ray fluoroscopy. After the RFCA procedures, the animals were under the situation of complete atrioventricular block so that the canine heart rates could be voluntarily controlled in the following experiments. After a thoracotomy, ECG and monophasic action potentials (MAP) of subendocardial, subepicardial and mid-layer myocardium were recorded synchronously in 8 normal and 5 DCM-CHF dogs during pacing from endocardium of RV apex (RV-Endo), epicardium of LV anterior wall (LV-Epi) and simultaneously both of the above (biventricular, BiV), the later was similar to the ventricular resynchronization therapy to congestive heart failure patients in clinic. The Tp-Te) meant the interval from the peak to the end of T wave, which was a representative index of TDR in surface ECG. The TDR was defined as the difference between the longest and the shortest MAPD of subendocardial, subepicardial and mid-layer myocardium. Our results showed that in normal dogs, pacing participating of LV (LV-Epi, BiV) prolonged
Neuroimaging of tic disorders with co-existing attention-deficit/hyperactivity disorder
DEFF Research Database (Denmark)
Plessen, Kerstin J; Royal, Jason M; Peterson, Bradley S
2007-01-01
BACKGROUND: Tourette syndrome (TS) and Attention-Deficit/Hyperactivity Disorder (ADHD) are common and debilitating neuropsychiatric illnesses that typically onset in the preschool years. Recently, both conditions have been subject to neuroimaging studies, with the aim of understanding...... contrast these findings with those in ADHD without comorbid tic disorders. RESULTS: The frequent comorbidity of TS and ADHD may reflect a common underlying neurobiological substrate, and studies confirm the hypothesized involvement of fronto-striatal circuits in both TS and ADHD. However, poor inhibitory...... their underlying neurobiological correlates. OBJECTIVE: The relation of TS and ADHD is discussed against the background of findings from previous Magnetic Resonance Imaging (MRI) studies. METHODS: We review the designs and major findings of previous studies that have examined TS with comorbid ADHD, and we briefly...
Stice, Eric; Marti, C. Nathan; Rohde, Paul; Shaw, Heather
2011-01-01
Objective: Test the hypothesis that reductions in thin-ideal internalization and body dissatisfaction mediate the effects of a dissonance-based eating disorder prevention program on reductions in eating disorder symptoms over 1-year follow-up. Method: Data were drawn from a randomized effectiveness trial in which 306 female high school students…
Orloff, Natalia C.; Hormes, Julia M.
2014-01-01
Women in the United States experience an increase in food cravings at two specific times during their life, (1) perimenstrually and (2) prenatally. The prevalence of excess gestational weight gain (GWG) is a growing concern due to its association with adverse health outcomes in both mothers and children. To the extent that prenatal food cravings may be a determinant of energy intake in pregnancy, a better understanding of craving etiology could be crucial in addressing the issue of excessive GWG. This paper reviews the available literature to corroborate and/or dispute some of the most commonly accepted hypotheses regarding the causes of food cravings during pregnancy, including a role of (1) hormonal changes, (2) nutritional deficits, (3) pharmacologically active ingredients in the desired foods, and (4) cultural and psychosocial factors. An existing model of perimenstrual chocolate craving etiology serves to structure the discussion of these hypotheses. The main hypotheses discussed receive little support, with the notable exception of a postulated role of cultural and psychosocial factors. The presence of cravings during pregnancy is a common phenomenon across different cultures, but the types of foods desired and the adverse impact of cravings on health may be culture-specific. Various psychosocial factors appear to correlate with excess GWG, including the presence of restrained eating. Findings strongly suggest that more research be conducted in this area. We propose that future investigations fall into one of the four following categories: (1) validation of food craving and eating-related measures specifically in pregnant populations, (2) use of ecological momentary assessment to obtain real time data on cravings during pregnancy, (3) implementation of longitudinal studies to address causality between eating disorder symptoms, food cravings, and GWG, and (4) development of interventions to ensure proper prenatal nutrition and prevent excess GWG. PMID:25295023
Directory of Open Access Journals (Sweden)
Natalia C. Orloff
2014-09-01
Full Text Available Women in the United States experience an increase in food cravings at two specific times during their life, 1 perimenstrually and 2 prenatally. The prevalence of excess gestational weight gain (GWG is a growing concern due to its association with adverse health outcomes in both mothers and children. To the extent that prenatal food cravings may be a determinant of energy intake in pregnancy, a better understanding of craving etiology could be crucial in addressing the issue of excessive GWG. This paper reviews the available literature to corroborate and/or dispute some of the most commonly accepted hypotheses regarding the causes of food cravings during pregnancy, including a role of 1 hormonal changes, 2 nutritional deficits, 3 pharmacologically active ingredients in the desired foods, and 4 cultural and psychosocial factors. An existing model of perimenstrual chocolate craving etiology serves to structure the discussion of these hypotheses. The main hypotheses discussed receive little support, with the notable exception of a postulated role of cultural and psychosocial factors. The presence of cravings during pregnancy is a common phenomenon across different cultures, but the types of foods desired and the adverse impact of cravings on health may be culture-specific. Various psychosocial factors appear to correlate with excess GWG, including the presence of restrained eating. Findings strongly suggest that more research be conducted in this area. We propose that future investigations fall into one of the four following categories: 1 validation of food craving and eating-related measures specifically in pregnant populations, 2 use of ecological momentary assessment to obtain real time data on cravings during pregnancy, 3 implementation of longitudinal studies to address causality between eating disorder symptoms, food cravings, and gestational weight gain, and 4 development of interventions to ensure proper prenatal nutrition and prevent excess
Cale, Ellison M; Lilienfeld, Scott O
2002-02-01
Little is known about the etiology of histrionic personality disorder (HPD) or its relation to other personality disorders. In this study, we examined whether HPD is etiologically related to psychopathy and more specifically whether HPD and antisocial personality disorder (ASPD) are sex-typed alternative manifestations of psychopathy. In addition, based on Newman's (1987) response modulation hypothesis of psychopathy, we examined the associations between psychopathic, HPD, and ASPD features and performance on laboratory measures of passive avoidance errors and interference effects. Seventy-five live theater actors completed self-report questionnaires and two laboratory measures of response modulation, and peers completed questionnaires concerning the participants' personality disorder features. The results provided weak and inconsistent support for the hypotheses that HPD is a female-typed variant of psychopathy and that ASPD is a male-typed variant of psychopathy. Contrary to previous findings, scores on response modulation tasks were not significantly related to psychopathy, or to either HPD or ASPD. The limitations of this study and possibilities for future research in this area are outlined.
Evaluating hypotheses in geolocation on a very large sample of Twitter
DEFF Research Database (Denmark)
Salehi, Bahar; Søgaard, Anders
2017-01-01
Recent work in geolocation has madeseveral hypotheses about what linguisticmarkers are relevant to detect where peoplewrite from. In this paper, we examinesix hypotheses against a corpus consistingof all geo-tagged tweets from theUS, or whose geo-tags could be inferred,in a 19% sample of Twitter...
Sensory and Attention Abnormalities in Autistic Spectrum Disorders
Liss, Miriam; Saulnier, Celine; Fein, Deborah; Kinsbourne, Marcel
2006-01-01
Individuals with autistic spectrum disorders (ASDs) often experience, describe and exhibit unusual patterns of sensation and attention. These anomalies have been hypothesized to result from overarousal and consequent overfocused attention. Parents of individuals with ASD rated items in three domains, "sensory overreactivity",…
Patrono, Enrico; Gasbarri, Antonella; Tomaz, Carlos; Nishijo, Hisao
2016-08-01
Addiction is a chronic compulsion and relapsing disorder. It involves several brain areas and circuits, which encode vary functions such as reward, motivation, and memory. Drug addiction is defined as a "pathological pattern of use of a substance", characterized by the loss of control on drug-taking-related behaviors, the pursuance of those behaviors even in the presence of negative consequences, and a strong motivated activity to assume substances. Three different theories guide experimental research on drug addiction. Each of these theories consider singles features, such as an aberrant motivation, a hedonic dysregulation, and an aberrant habit learning as the main actor to explain the entire process of the addictive behaviors. The major goal of this study is to present a new hypotheses of transitionality from a controlled use to abuse of addictive substances trough the overview of the three different theories, considering all the single features of each single theory together on the same "temporal continuum" from use to abuse of addictive substances. Recently, it has been suggested that common neural systems may be activated by natural and pharmacological stimuli, raising the hypotheses that binge-eating disorders could be considered as addictive behaviors. The second goal of this study is to present evidences in order to highlight a possible psycho-bio-physiological superimposition between drug and "food addiction". Finally, interesting questions are brought up starting from last findings about a theoretical/psycho-bio-physiological superimposition between drug and "food addiction" and their possibly same transitionality along the same "temporal continuum" from use to abuse of addictive substances in order to investigate new therapeutic strategies based on new therapeutic strategies based on the individual moments characterizing the transition from the voluntary intake of substances to the maladaptive addictive behavior. Copyright © 2016. Published by Elsevier
Explanatory hypotheses formation and the anomalous β spectrum
Energy Technology Data Exchange (ETDEWEB)
Gauderis, Tjerk [Centre for Logic and Philosophy of Science, Ghent University (Belgium)
2013-07-01
Between 1928 and 1934, a persevering anomaly mystified the physics community: while alpha decay behaved perfectly according to the new quantum mechanics, the energy of electrons emitted in beta decay displayed a broad continuous spectrum. This puzzle invoked a lively debate among the most established physicists at the time. But the curious thing was that they all suggested hypotheses of very different formal types: Rutherford and Chadwick thought of varying internal energies, Bohr suggested to restrict the energy conservation principle, Heisenberg tinkered with a new quantization of space, and Pauli suggested the existence of a new elementary particle - all these hypotheses being radical and highly controversial. In physics, an anomalous experimental result can trigger the formation of formally very different hypotheses. A scientist confronted with such a result has no strict guidelines to help her decide whether she should explain this result by withdrawing or adapting a constraint (e.g. a law) of the current theory, or by presupposing the existence of a hitherto unobserved entity (e.g. a particle) that makes the anomaly fit within that theory. In this talk I aim to gain some insights how scientists make this choice, by examining in the above case study how the choice of the various mentioned physicists depended on their previous experiences and their specific perception of the problem.
Causes of bat fatalities at wind turbines: Hypotheses and predictions
Cryan, P.M.; Barclay, R.M.R.
2009-01-01
Thousands of industrial-scale wind turbines are being built across the world each year to meet the growing demand for sustainable energy. Bats of certain species are dying at wind turbines in unprecedented numbers. Species of bats consistently affected by turbines tend to be those that rely on trees as roosts and most migrate long distances. Although considerable progress has been made in recent years toward better understanding the problem, the causes of bat fatalities at turbines remain unclear. In this synthesis, we review hypothesized causes of bat fatalities at turbines. Hypotheses of cause fall into 2 general categoriesproximate and ultimate. Proximate causes explain the direct means by which bats die at turbines and include collision with towers and rotating blades, and barotrauma. Ultimate causes explain why bats come close to turbines and include 3 general types: random collisions, coincidental collisions, and collisions that result from attraction of bats to turbines. The random collision hypothesis posits that interactions between bats and turbines are random events and that fatalities are representative of the bats present at a site. Coincidental hypotheses posit that certain aspects of bat distribution or behavior put them at risk of collision and include aggregation during migration and seasonal increases in flight activity associated with feeding or mating. A surprising number of attraction hypotheses suggest that bats might be attracted to turbines out of curiosity, misperception, or as potential feeding, roosting, flocking, and mating opportunities. Identifying, prioritizing, and testing hypothesized causes of bat collisions with wind turbines are vital steps toward developing practical solutions to the problem. ?? 2009 American Society of Mammalogists.
Beşiroğlu, Lütfullah; Ağargün, Mehmet Yücel; Ozbebit, Ozgür; Sözen, Mehmet; Dilek, Imdat; Güleç, Mustafa
2007-01-01
The acronym PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) has been assigned to a subgroup of patients experiencing pediatric onset obsessive-compulsive symptoms and tics as a result of autoimmune response to group A beta-hemolytic streptococcal infection. It has been hypothesized that an immune process initiated by infection affects the basal ganglia and causes neuropsychiatric symptoms. In cases with severe neuropsychiatric symptoms, the use of treatment strategies that interrupt the autoimmune process responsible for the pathogenesis of PANDAS, such as therapeutic plasmapheresis or intravenous immunoglobulin, has been proposed. In this paper, we discuss the effect of plasmapheresis treatment in 4 adult cases of obsessive-compulsive disorder and tic disorder triggered by streptococcal infections.
van Zutphen, Linda; Siep, Nicolette; Jacob, Gitta A; Domes, Gregor; Sprenger, Andreas; Willenborg, Bastian; Goebel, R.; Arntz, Arnoud
2018-01-01
BACKGROUND: Borderline personality disorder (BPD) is characterized by emotion dysregulation; however, it is unclear whether this is restricted to negative emotional stimuli or to what degree this is specific to BPD. We investigated neural correlates of hypothesized increased emotional sensitivity
Adaptive hatching hypotheses do not explain asynchronous ...
African Journals Online (AJOL)
At the core of the suite of adaptive hatching hypotheses advanced to explain asynchronous hatching in birds is the assumption that if food is not limited then all the hatchlings will develop normally to adulthood. In this study Brown-headed Parrot Poicephalus cryptoxanthus chicks were hand fed and weighed on a daily basis.
Review: The nucleation of disorder
International Nuclear Information System (INIS)
Cahn, R.W.; Johnson, W.L.
1986-01-01
Four types of phase transformation that involve the conversion of crystalline phases into more disordered forms are reviewed: melting, disordering of superlattices, amorphization by diffusion between crystalline phases, and irradation amorphization. In the review emphasis is placed on evidence for the heterogeneous nucleation of the product phases; in this connection, the role of surfaces, antiphase domain boundaries, dislocations, vacancies, and grain boundaries is specifically discussed. All of these features have been either observed, or hypothesized, to play a role as heterogeneous nucleation sites in one or more of the four transformations. An attempt is made to draw parallels between nucleation mechanisms in the various processes
Depression and coping in subthreshold eating disorders.
Dennard, E Eliot; Richards, C Steven
2013-08-01
The eating disorder literature has sought to understand the role of comorbid psychiatric diagnoses and coping in relation to eating disorders. The present research extends these findings by studying the relationships among depression, coping, and the entire continuum of disordered eating behaviors, with an emphasis on subthreshold eating disorders. 109 undergraduate females completed questionnaires to assess disordered eating symptoms, depressive symptoms, and the use of active and avoidant coping mechanisms. Hypotheses were tested using bivariate linear regression and multivariate linear regression. Results indicated that depression was a significant predictor of disordered eating symptoms after controlling for relationships between depression and coping. Although avoidant coping was positively associated with disordered eating, it was not a significant predictor after controlling for depression and coping. Previous research has found associations between depression and diagnosable eating disorders, and this research extends those findings to the entire continuum of disordered eating. Future research should continue to investigate the predictors and correlates of the disordered eating continuum using more diverse samples. Testing for mediation and moderation among these variables may also be a fruitful area of investigation. Published by Elsevier Ltd.
Premorbid self-disorders and lifetime diagnosis in the schizophrenia spectrum
DEFF Research Database (Denmark)
Parnas, Josef; Carter, John; Frederiksen, Julie E Nordgaard
2016-01-01
assessment, we hypothesized that a proxy scale drawn from the Minnesota Multiphasic Personality Inventory (MMPI) could distinguish those who later developed a schizophrenia-spectrum disorder (N = 68) from those who remained healthy (N = 64). The Self-Disorder Scale comprised 32 items whose content suggested......AIM: The notion of a disordered self as a core disturbance of schizophrenia was proposed in many foundational texts. Recent studies, spurred by the development of the Examination of Anomalous Self-Experience (EASE), seem to indicate that self-disorders are a specific manifestation of schizophrenia......), the overlap did not account for the Self-Disorder Scale's predictive efficacy. CONCLUSION: The results support the notion of self-disorders as a core vulnerability feature in schizophrenia, detectable premorbidly in those developing later schizophrenia-spectrum disorders....
Directory of Open Access Journals (Sweden)
Roberto Canitano
2017-05-01
Full Text Available Autism spectrum disorders (ASD and schizophrenia spectrum disorders (SSD share clinical and genetic components that have long been recognized. The two disorders co-occur more frequently than would be predicted by their respective prevalence, suggesting that a complex, multifactor association is involved. However, DSM-5 maintains the distinction between ASD, with core social and communication impairments, and SSD, including schizophrenia (SCZ, with hallucinations, delusions, and thought disorder as essential features. ASD and SSD have common biological underpinnings that may emerge early in development and unfold over time. One of the hypotheses supporting the similarities in the social and cognitive disturbances of ASD and SSD relates to abnormalities in the ratio of excitatory to inhibitory cortical activity (E/I imbalance. E/I imbalance in neurodevelopmental disorders could be the consequence of abnormalities in genes coding for glutamatergic and GABAergic receptors or synaptic proteins followed by system derangements. SSD and ASD have been characterized as polygenic disorders in which to the onset and progression of disease is triggered by interactions among multiple genes. Mammalian target of rapamycin signaling is under intense investigation as a convergent altered pathway in the two spectrum disorders. Current understanding of shared and divergent patterns between ASD and SSD from molecular to clinical aspects is still incomplete and may be implemented by the research domain criteria approach.
Neuronal migration, apoptosis and bipolar disorder.
Uribe, Ezequiel; Wix, Richard
2012-01-01
Bipolar disorder, like the majority of psychiatric disorders, is considered a neurodevelopment disease of neurodevelopment. There is an increased rate of neuronal birth and death during this development period. In the particular case of the processes that determine neuronal death, it is known that those neurons that establish connections have to be removed from the central nervous system. There is a deficit of GABAergic interneurons in the cerebral cortex in bipolar disorder, accompanied by overexpression of proapoptic genes. There is also an alteration in the expression of molecules that mediate in the migration of these neurons and their inclusion in functional synapsis during the foetal stage. The role of these molecules in the neuronal death pathways by apoptosis will be reviewed here in an attempt to establish biological hypotheses of the genesis of bipolar disorder. Copyright © 2011 SEP y SEPB. Published by Elsevier Espana. All rights reserved.
Cancer stem cell hypotheses: Impact on modern molecular
Indian Academy of Sciences (India)
basis for the so-called cancer stem cell (CSC) hypotheses. The first exact proof of CSC ... or less equal ability for tumour regeneration and repopulation. (Nowell 1976 .... Also, there are reports that the 'stemness' (stem-like properties) of brain.
A novel approach to generating CER hypotheses based on mining clinical data.
Zhang, Shuo; Li, Lin; Yu, Yiqin; Sun, Xingzhi; Xu, Linhao; Zhao, Wei; Teng, Xiaofei; Pan, Yue
2013-01-01
Comparative effectiveness research (CER) is a scientific method of investigating the effectiveness of alternative intervention methods. In a CER study, clinical researchers typically start with a CER hypothesis, and aim to evaluate it by applying a series of medical statistical methods. Traditionally, the CER hypotheses are defined manually by clinical researchers. This makes the task of hypothesis generation very time-consuming and the quality of hypothesis heavily dependent on the researchers' skills. Recently, with more electronic medical data being collected, it is highly promising to apply the computerized method for discovering CER hypotheses from clinical data sets. In this poster, we proposes a novel approach to automatically generating CER hypotheses based on mining clinical data, and presents a case study showing that the approach can facilitate clinical researchers to identify potentially valuable hypotheses and eventually define high quality CER studies.
Personality in panic disorder with agoraphobia: a Rorschach study
de Ruiter, C.; Cohen, L.
1992-01-01
In this study, we tested several hypotheses derived from self psychology (Diamond, 1987) regarding personality features of patients suffering from panic disorder and agoraphobia (PDA). PDA patients are thought to suffer from a deficit in negative affect-regulating capacity, surrounded by defenses
Attention deficit hyperactivity disorder symptoms mediate early-onset smoking
Huizink, A.C.; Van Lier, P.A.C.; Crijnen, A.A.M.
2009-01-01
Background/Aims: Symptoms of attention deficit hyperactivity disorder (ADHD) have often been associated with early-onset smoking. We hypothesize that reductions in ADHD symptoms due to an intervention have a mediating effect on early-onset smoking. Methods: In a universal, school-based, randomized
Attention Deficit Hyperactivity Disorder Symptoms Mediate Early-Onset Smoking
Huizink, A.C.; Lier, P.A.C. van; Crijnen, A.A.M.
2009-01-01
Background/Aims: Symptoms of attention deficit hyperactivity disorder (ADHD) have often been associated with early-onset smoking. We hypothesize that reductions in ADHD symptoms due to an intervention have a mediating effect on early-onset smoking. Methods: In a universal, school-based, randomized
Attention deficit hyperactivity disorder symptoms mediate early-onset smoking
A.C. Huizink (Anja); P.A.C. van Lier (Pol); A.A.M. Crijnen (Alfons)
2008-01-01
textabstractBackground/Aims: Symptoms of attention deficit hyperactivity disorder (ADHD) have often been associated with early-onset smoking. We hypothesize that reductions in ADHD symptoms due to an intervention have a mediating effect on early-onset smoking. Methods: In a universal, school-based,
Directory of Open Access Journals (Sweden)
Mehri Moradi
2014-06-01
Full Text Available Attention is an important factor in information processing; obsessive- compulsive disorder (OCD and generalized anxiety disorder (GAD are two main emotional disorders with a chronic course. This research examined the relationship among attentional control and intrusive thoughts (worry, rumination and obsession in these disorders. It was hypothesized that attentional control is a common factor in OCD and GAD. In addition, we compared worry, rumination and obsession among OCD, GAD and non- clinical participants.The research sample included three groups: OCD (n = 25, GAD (n = 30 and non- clinical samples (n = 56. Data were collected using the Attentional Control Scale (ACS, Rumination Response Scale (RRS, Pennsylvania State Worry Questionnaire (PSWQ, Beck Depression Inventory (BDI, Beck Anxiety Inventory (BAI, Obsessive-Compulsive Inventory-Revised (OCI-R and General Health Questionnaire (GHQ-28. Data were analyzed using MANOVA and MANCOVA by SPSS-17.Multivariate Analysis of Variance revealed that the OCD and GAD groups reported greater deficits in attentional control, higher obsessive-compulsive symptoms, rumination, worry, anxiety and depression compared to the control group.This research indicated a great attentional deficit in obsessive- compulsive disorder and generalized anxiety disorder. However, no significant difference was found between these two disorders.
Luna, B; Sweeney, J A
2001-01-01
Although neurodevelopmental models of schizophrenia are now widely accepted, there is minimal direct human evidence of dysmaturation in schizophrenia to support this theory. This is especially the case regarding maturational changes during late childhood and adolescence, which immediately precede the typical age of onset of the disorder. By integrating new noninvasive methods of functional magnetic resonance imaging with techniques of developmental cognitive neuroscience, it is now possible to begin systematic research programs to directly test hypotheses of neurodevelopmental abnormalities in schizophrenia. In this article, we describe strategies for characterizing developmental changes taking place during the critical period of adolescence that can elucidate dysmaturation processes in schizophrenia. We emphasize the need for studies characterizing normal development before examining at-risk or clinical populations, and the potential value of using neurobehavioral and neuroimaging approaches to directly characterize the dysmaturation associated with schizophrenia.
Premenstrual disorders and rumination.
Craner, Julia R; Sigmon, Sandra T; Martinson, Amber A; McGillicuddy, Morgan L
2014-01-01
Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) involve emotional, behavioral, and physical symptoms; however, there is little understanding of psychological factors that contribute to these disorders. It was hypothesized that rumination, a form of depressive self-focused attention, is related to premenstrual distress. Study 1 involved women (N = 735) meeting criteria for No/Mild PMS, Moderate/Severe PMS, and PMDD using retrospective self-report. Study 2 involved women (N = 85) meeting diagnostic criteria for PMS or PMDD (i.e., PMD group) and healthy controls (i.e., No PMD group) following 60-day symptom monitoring. Participants in both studies completed questionnaires of rumination, anxiety sensitivity, and coping styles. Rumination was strongly related to premenstrual disorders using both retrospective and prospective reports, as well as both categorical and continuous approaches to classification of premenstrual distress. Rumination, a transdiagnostic factor in psychopathology, may contribute to the onset and maintenance of premenstrual distress. © 2013 Wiley Periodicals, Inc.
Self-disorder and subjective dimensions of suicidality in schizophrenia
DEFF Research Database (Denmark)
Skodlar, Borut; Parnas, Josef
2010-01-01
We studied 25 schizophrenia patients using the Examination of Anomalous Self-Experience phenomenological interview framework. In a previous study, this sample was qualitatively interviewed concerning subjective reasons for suicidal ideation. We hypothesized that 2 main identified reasons for suic...... on suicidality in schizophrenia: it appears to be partly motivated by a disordered sense of self. These findings, if replicated, may have considerable therapeutic and preventive implications.......We studied 25 schizophrenia patients using the Examination of Anomalous Self-Experience phenomenological interview framework. In a previous study, this sample was qualitatively interviewed concerning subjective reasons for suicidal ideation. We hypothesized that 2 main identified reasons...... for suicidality, that is, sense of solitude and inferiority feelings, would be associated with disturbances measured by the Examination of Anomalous Self-Experience scale, that is, disorders of self-awareness and self-presence. The hypothesis was empirically supported. The results shed some additional light...
Self-disorder and subjective dimensions of suicidality in schizophrenia
DEFF Research Database (Denmark)
Skodlar, Borut; Parnas, Josef
2009-01-01
We studied 25 schizophrenia patients using the Examination of Anomalous Self-Experience phenomenological interview framework. In a previous study, this sample was qualitatively interviewed concerning subjective reasons for suicidal ideation. We hypothesized that 2 main identified reasons for suic...... on suicidality in schizophrenia: it appears to be partly motivated by a disordered sense of self. These findings, if replicated, may have considerable therapeutic and preventive implications.......We studied 25 schizophrenia patients using the Examination of Anomalous Self-Experience phenomenological interview framework. In a previous study, this sample was qualitatively interviewed concerning subjective reasons for suicidal ideation. We hypothesized that 2 main identified reasons...... for suicidality, that is, sense of solitude and inferiority feelings, would be associated with disturbances measured by the Examination of Anomalous Self-Experience scale, that is, disorders of self-awareness and self-presence. The hypothesis was empirically supported. The results shed some additional light...
Parenting style and the risk for eating disorders among teenage girls
Semiramida Manaj
2017-01-01
The aim of this study was to explore the role of parenting styles and the risk to develop an eating disordered behavior among teenage girls. This study was designed to test the hypotheses that parenting style are correlated with the risk to have an eating disordered behavior among female teenagers. It was predicted that the teenage girls at risk for developing an eating disorder would report experiencing their parents style as high in control and low in warmth or low in control and high in wa...
Cognitive Discernible Factors between Schizophrenia and Schizoaffective Disorder
Stip, Emmanuel; Sepehry, Amir Ali; Prouteau, Antoniette; Briand, Catherine; Nicole, Luc; Lalonde, Pierre; Lesage, Alain
2005-01-01
Background: Schizophrenia (SZ) and schizoaffective disorders (SA) are associated with cognitive deficits. Generally, a schizoaffective diagnosis is associated with better prognosis on the level of social integration. It is also well established that cognition is an important factor for good social outcome in schizophrenia. We hypothesized that,…
Testing hypotheses involving Cronbach's alpha using marginal models
Kuijpers, R.E.; van der Ark, L.A.; Croon, M.A.
2013-01-01
We discuss the statistical testing of three relevant hypotheses involving Cronbach's alpha: one where alpha equals a particular criterion; a second testing the equality of two alpha coefficients for independent samples; and a third testing the equality of two alpha coefficients for dependent
A Bayesian decision procedure for testing multiple hypotheses in DNA microarray experiments.
Gómez-Villegas, Miguel A; Salazar, Isabel; Sanz, Luis
2014-02-01
DNA microarray experiments require the use of multiple hypothesis testing procedures because thousands of hypotheses are simultaneously tested. We deal with this problem from a Bayesian decision theory perspective. We propose a decision criterion based on an estimation of the number of false null hypotheses (FNH), taking as an error measure the proportion of the posterior expected number of false positives with respect to the estimated number of true null hypotheses. The methodology is applied to a Gaussian model when testing bilateral hypotheses. The procedure is illustrated with both simulated and real data examples and the results are compared to those obtained by the Bayes rule when an additive loss function is considered for each joint action and the generalized loss 0-1 function for each individual action. Our procedure significantly reduced the percentage of false negatives whereas the percentage of false positives remains at an acceptable level.
Lahey, Benjamin B.; Applegate, Brooks; Chronis, Andrea M.; Jones, Heather A.; Williams, Stephanie Hall; Loney, Jan; Waldman, Irwin D.
2008-01-01
Lahey and Waldman proposed a developmental propensity model in which three dimensions of children's emotional dispositions are hypothesized to transact with the environment to influence risk for conduct disorder, heterogeneity in conduct disorder, and comorbidity with other disorders. To prepare for future tests of this model, a new measure of…
Gazelle, Heidi; Workman, Jamie Olson; Allan, Wesley
2010-01-01
It was hypothesized that children identified by their peers at school as anxious solitary would report more symptoms of social anxiety disorder on a self report questionnaire and, on the basis of child and parent clinical interviews, receive more diagnoses of social anxiety disorder and additional anxiety and mood disorders. Participants were 192…
Stice, Eric; Desjardins, Christopher D
2018-06-01
Because no study has tested for interactions between risk factors in the prediction of future onset of each eating disorder, this exploratory study addressed this lacuna to generate hypotheses to be tested in future confirmatory studies. Data from three prevention trials that targeted young women at high risk for eating disorders due to body dissatisfaction (N = 1271; M age 18.5, SD 4.2) and collected diagnostic interview data over 3-year follow-up were combined to permit sufficient power to predict onset of anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), and purging disorder (PD) using classification tree analyses, an analytic technique uniquely suited to detecting interactions. Low BMI was the most potent predictor of AN onset, and body dissatisfaction amplified this relation. Overeating was the most potent predictor of BN onset, and positive expectancies for thinness and body dissatisfaction amplified this relation. Body dissatisfaction was the most potent predictor of BED onset, and overeating, low dieting, and thin-ideal internalization amplified this relation. Dieting was the most potent predictor of PD onset, and negative affect and positive expectancies for thinness amplified this relation. Results provided evidence of amplifying interactions between risk factors suggestive of cumulative risk processes that were distinct for each disorder; future confirmatory studies should test the interactive hypotheses generated by these analyses. If hypotheses are confirmed, results may allow interventionists to target ultra high-risk subpopulations with more intensive prevention programs that are uniquely tailored for each eating disorder, potentially improving the yield of prevention efforts. Copyright © 2018 Elsevier Ltd. All rights reserved.
Müller, Kai W; Wölfling, Klaus; Beutel, Manfred E; Stark, Birgit; Quiring, Oliver; Aufenanger, Stefan; Schemer, Christian; Weber, Mathias; Reinecke, Leonard
2018-02-01
Problematic Internet use (PIU) that has recently been referred to as Internet-related disorder is a growing health concern. Yet, it is unclear why some adolescents are developing problematic use, whereas others sustain control. Based on previous research, we hypothesize that personality traits (low conscientiousness and high neuroticism) act as predispositions for PIU. We further hypothesize that PIU can be understood as a maladaptive reaction toward critical life events and that these maladaptive reactions are exacerbated by dysfunctional personality traits. The study investigates the prevalence of distinct subtypes of PIU among a sample of adolescents (n = 1,489; 10-17 years). Personality traits (Big Five Inventory-10 [BFI-10]), perceived stress (Perceived Stress Scale 4 [PSS-4]), and their relations to PIU (Scale for the Assessment of Internet and Computer Game Addiction [AICA-S]) were examined. As novel research questions, associations between PIU and adjustment disorders (Adjustment Disorder-New Module [ADNM]-6) and the mediating role of personality were investigated. The prevalence of PIU was 2.5%; girls (3.0%) were more often affected than boys (1.9%). Social networking sites in girls and online games in boys were most often associated with PIU. Low conscientiousness and high neuroticism generally predicted PIU. Significantly more adolescents with PIU (70%) reported critical life events compared with those without PIU (42%). PIU was related to heightened stress and higher adjustment disorder symptoms. These associations were exacerbated by conscientiousness and neuroticism. Although the overall prevalence for PIU is in line with previous studies, it appeared unexpectedly that girls were affected more often than boys. Adjustment disorders and stress showed strong associations with PIU. This bears implications for adapting etiopathological assumptions and early intervention strategies. Copyright © 2017 The Society for Adolescent Health and Medicine
Symptomatic Response to Divalproex in Subtypes of Conduct Disorder
Padhy, Ranjit; Saxena, Kirti; Remsing, Lisa; Huemer, Julia; Plattner, Belinda; Steiner, Hans
2011-01-01
To investigate response to Divalproex sodium (DVPX) with respect to Reactive/Affective/Defensive/Impulsive (RADI) and Proactive/Instrumental/Premeditated (PIP) aggression among adolescent males with conduct disorder (CD), using results from a randomized, double-blind, placebo-controlled trial. It was hypothesized that DVPX response among…
Data-driven efficient score tests for deconvolution hypotheses
Langovoy, M.
2008-01-01
We consider testing statistical hypotheses about densities of signals in deconvolution models. A new approach to this problem is proposed. We constructed score tests for the deconvolution density testing with the known noise density and efficient score tests for the case of unknown density. The
Cortez, Daniel; Svensson, Anneli; Carlson, Jonas; Graw, Sharon; Sharma, Nandita; Brun, Francesca; Spezzacatene, Anita; Mestroni, Luisa; Platonov, Pyotr G
2017-10-13
Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) carries a risk of sudden death. We aimed to assess whether vectorcardiographic (VCG) parameters directed toward the right heart and a measured angle of the S-wave would help differentiate ARVD/C with otherwise normal electrocardiograms from controls. Task Force 2010 definite ARVD/C criteria were met for all patients. Those who did not fulfill Task Force depolarization or repolarization criteria (-ECG) were compared with age and gender-matched control subjects. Electrocardiogram measures of a 3-dimentional spatial QRS-T angle, a right-precordial-directed orthogonal QRS-T (RPD) angle, a root mean square of the right sided depolarizing forces (RtRMS-QRS), QRS duration (QRSd) and the corrected QT interval (QTc), and a measured angle including the upslope and downslope of the S-wave (S-wave angle) were assessed. Definite ARVD/C was present in 155 patients by 2010 Task Force criteria (41.7 ± 17.6 years, 65.2% male). -ECG ARVD/C patients (66 patients) were compared to 66 control patients (41.7 ± 17.6 years, 65.2% male). All parameters tested except the QRSd and QTc significantly differentiated -ECG ARVD/C from control patients (p right-sided VCG or measured angle markers better than the spatial QRS-T angle, the QRSd or QTc, in the absence of Taskforce ECG criteria.
Terband, H.; Maassen, B.; Guenther, F.H.; Brumberg, J.
2014-01-01
Background/Purpose Differentiating the symptom complex due to phonological-level disorders, speech delay and pediatric motor speech disorders is a controversial issue in the field of pediatric speech and language pathology. The present study investigated the developmental interaction between neurological deficits in auditory and motor processes using computational modeling with the DIVA model. Method In a series of computer simulations, we investigated the effect of a motor processing deficit alone (MPD), and the effect of a motor processing deficit in combination with an auditory processing deficit (MPD+APD) on the trajectory and endpoint of speech motor development in the DIVA model. Results Simulation results showed that a motor programming deficit predominantly leads to deterioration on the phonological level (phonemic mappings) when auditory self-monitoring is intact, and on the systemic level (systemic mapping) if auditory self-monitoring is impaired. Conclusions These findings suggest a close relation between quality of auditory self-monitoring and the involvement of phonological vs. motor processes in children with pediatric motor speech disorders. It is suggested that MPD+APD might be involved in typically apraxic speech output disorders and MPD in pediatric motor speech disorders that also have a phonological component. Possibilities to verify these hypotheses using empirical data collected from human subjects are discussed. PMID:24491630
Zhou, Xin; Bueno-Orovio, Alfonso; Orini, Michele; Hanson, Ben; Hayward, Martin; Taggart, Peter; Lambiase, Pier D; Burrage, Kevin; Rodriguez, Blanca
2016-01-22
Repolarization alternans (RA) are associated with arrhythmogenesis. Animal studies have revealed potential mechanisms, but human-focused studies are needed. RA generation and frequency dependence may be determined by cell-to-cell variability in protein expression, which is regulated by genetic and external factors. To characterize in vivo RA in human and to investigate in silico using human models, the ionic mechanisms underlying the frequency-dependent differences in RA behavior identified in vivo. In vivo electrograms were acquired at 240 sites covering the epicardium of 41 patients at 6 cycle lengths (600-350 ms). In silico investigations were conducted using a population of biophysically detailed human models incorporating variability in protein expression and calibrated using in vivo recordings. Both in silico and in vivo, 2 types of RA were identified, with Fork- and Eye-type restitution curves, based on RA persistence or disappearance, respectively, at fast pacing rates. In silico simulations show that RA are strongly correlated with fluctuations in sarcoplasmic reticulum calcium, because of strong release and weak reuptake. Large L-type calcium current conductance is responsible for RA disappearance at fast frequencies in Eye-type (30% larger in Eye-type versus Fork-type; Psilico, 2 types of RA are identified, with RA persistence/disappearance as frequency increases. In silico, L-type calcium current and Na(+)/Ca(2+) exchanger current determine RA human cell-to-cell differences through intracellular and sarcoplasmic reticulum calcium regulation. © 2015 The Authors.
Neurochemical alterations associated with borderline personality disorder.
Atmaca, Murad; Karakoc, Tevfik; Mermi, Osman; Gurkan Gurok, M; Yildirim, Hanefi
2015-01-01
In neuroimaging on borderline personality disorder, prior studies focused on the hippocampus and amygdala, as mentioned above. However, no study investigated whether there were neurochemical changes in the patients with borderline personality disorder. Therefore, in the present study, we aimed to investigate neurochemical change of patients diagnosed with borderline disorder and hypothesized that neurochemicals would change in the hippocampus region of these patients. Seventeen patients and the same number of healthy control subjects were analyzed by using a 1.5 Tesla GE Signa Imaging System. N-acetylaspartate (NAA), choline compounds (CHO), and creatine (CRE) values of hippocampal region were measured. The mean NAA/CRE ratio in the hippocampus region was significantly reduced in the patients with borderline personality disorder compared to that of healthy control subjects, In addition, NAA/CHO ratio of the patients with borderline personality disorder was also significantly reduced when compared to that of healthy subjects. There was no difference in the ratio of CHO/CRE. In summary, we present evidence for reduced NAA in the patients with borderline personality disorder. © 2015, The Author(s).
Evolutionary Perspectives on Genetic and Environmental Risk Factors for Psychiatric Disorders.
Keller, Matthew C
2018-05-07
Evolutionary medicine uses evolutionary theory to help elucidate why humans are vulnerable to disease and disorders. I discuss two different types of evolutionary explanations that have been used to help understand human psychiatric disorders. First, a consistent finding is that psychiatric disorders are moderately to highly heritable, and many, such as schizophrenia, are also highly disabling and appear to decrease Darwinian fitness. Models used in evolutionary genetics to understand why genetic variation exists in fitness-related traits can be used to understand why risk alleles for psychiatric disorders persist in the population. The usual explanation for species-typical adaptations-natural selection-is less useful for understanding individual differences in genetic risk to disorders. Rather, two other types of models, mutation-selection-drift and balancing selection, offer frameworks for understanding why genetic variation in risk to psychiatric (and other) disorders exists, and each makes predictions that are now testable using whole-genome data. Second, species-typical capacities to mount reactions to negative events are likely to have been crafted by natural selection to minimize fitness loss. The pain reaction to tissue damage is almost certainly such an example, but it has been argued that the capacity to experience depressive symptoms such as sadness, anhedonia, crying, and fatigue in the face of adverse life situations may have been crafted by natural selection as well. I review the rationale and strength of evidence for this hypothesis. Evolutionary hypotheses of psychiatric disorders are important not only for offering explanations for why psychiatric disorders exist, but also for generating new, testable hypotheses and understanding how best to design studies and analyze data.
Toward Valid Measurement of Stephen Pepper's World Hypotheses.
Johnson, John A.
Two measures of the "world hypotheses" of Stephen Pepper were mailed to 100 sociobiologists, 87 behaviorists, 79 personality psychologists, and 45 human developmentalists. The World Hypothesis Scale (WHS) was designed to measure Pepper's four world views: (1) formism; (2) mechanism; (3) organicism; and (4) contextualism. The…
Autobiographical memory specificity in dissociative identity disorder.
Huntjens, Rafaële J C; Wessel, Ineke; Hermans, Dirk; van Minnen, Agnes
2014-05-01
A lack of adequate access to autobiographical knowledge has been related to psychopathology. More specifically, patients suffering from depression or a history of trauma have been found to be characterized by overgeneral memory, in other words, they show a relative difficulty in retrieving a specific event from memory located in time and place. Previous studies of overgeneral memory have not included patients with dissociative disorders. These patients are interesting to consider, as they are hypothesized to have the ability to selectively compartmentalize information linked to negative emotions. This study examined avoidance and overgeneral memory in patients with dissociative identity disorder (DID; n = 12). The patients completed the autobiographical memory test (AMT). Their performance was compared with control groups of posttraumatic stress disorder (PTSD) patients (n = 26), healthy controls (n = 29), and DID simulators (n = 26). Specifically, we compared the performance of separate identity states in DID hypothesized to diverge in the use of avoidance as a coping strategy to deal with negative affect. No significant differences in memory specificity were found between the separate identities in DID. Irrespective of identity state, DID patients were characterized by a lack of memory specificity, which was similar to the lack of memory specificity found in PTSD patients. The converging results for DID and PTSD patients add empirical evidence for the role of overgeneral memory involved in the maintenance of posttraumatic psychopathology.
Autophagic dysfunction in a lysosomal storage disorder due to impaired proteolysis
Elrick, Matthew J.; Lieberman, Andrew P.
2013-01-01
Alterations in macroautophagy (hereafter referred to as “autophagy”) are a common feature of lysosomal storage disorders, and have been hypothesized to play a major role in the pathogenesis of these diseases. We have recently reported multiple defects in autophagy contributing to the lysosomal storage disorder Niemann-Pick type C (NPC). These include increased formation of autophagosomes, slowed turnover of autophagosomes secondary to impaired lysosomal proteolysis, and delivery of stored lip...
What Is the Problem of Ad Hoc Hypotheses?
Bamford, Greg
1999-01-01
Philosophers' attempts to convincingly explicate the received view of an ad hoc hypothesis--that it accounts for only the observations it was designed to account for--have been unsuccessful. Familiar and firmer criteria for evaluating the hypotheses or modified theories so classified are characteristically available. Contains 41 references.…
Black/White Differences in Adolescent Drug Use: A Test of Six Hypotheses
Rote, Sunshine M.; Taylor, John
2014-01-01
Six specific hypotheses have been developed to account for why Caucasians have higher rates of drug use compared to African-Americans. This article utilizes data from a South Florida-based community study of 893 young adults (1998-2002) to test these hypotheses. Specifically, Caucasians (1) initiate drug use at younger ages than African-Americans…
Accessing and Selecting Word Meaning in Autism Spectrum Disorder
Henderson, L. M.; Clarke, P. J.; Snowling, M. J.
2011-01-01
Background: Comprehension difficulties are commonly reported in autism spectrum disorder (ASD) but the causes of these difficulties are poorly understood. This study investigates how children with ASD access and select meanings of ambiguous words to test four hypotheses regarding the nature of their comprehension difficulties: semantic deficit,…
Emotion Regulation and Heterogeneity in Attention-Deficit/Hyperactivity Disorder
Musser, Erica D.; Galloway-Long, Hilary S.; Frick, Paul J.; Nigg, Joel T.
2013-01-01
Objective: How best to capture heterogeneity in attention-deficit/hyperactivity disorder (ADHD) using biomarkers has been elusive. This study evaluated whether emotion reactivity and regulation provide a means to achieve this. Method: Participants were classified into three groups: children with ADHD plus low prosocial behavior (hypothesized to be…
Trottier, Kathryn; MacDonald, Danielle E
2017-08-01
This paper provides an updated review of the literature on the relationship between psychological trauma exposure, other severe adverse experiences, and eating disorders. Trauma exposure and other severe adverse experiences (e.g., emotional abuse) in both childhood and adulthood are associated with eating disorders. The relationship between traumatic and other adverse experiences and eating disorders appears to be mediated by emotional and behavioral dysregulation, as well as by cognitive factors such as self-criticism. Biological vulnerabilities may also be relevant to this relationship. Overall, the literature is limited by predominantly cross-sectional designs. There is clear evidence of a correlational relationship between trauma exposure and other severe adverse events, and eating disorders. Both risk and maintenance factor hypotheses have been put forth; however, prospective research testing these hypotheses remains limited. Future research should use prospective designs and focus on trauma-related symptoms (rather than trauma exposure) in order to advance research on risk and maintaining factors for eating disorders and inform treatment directions.
Rousseau, Jean-Philippe; Tenorio-Lopes, Luana; Baldy, Cécile; Janes, Tara Adele; Fournier, Stéphanie; Kinkead, Richard
2017-11-01
The environment plays a critical role in shaping development and function of the brain. Stress, especially when experienced early in life, can interfere with these processes. In the context of respiratory control, perinatal stress can therefore alter the ability to achieve the "fine-tuning" necessary for proper detection of chemosensory stimuli and production of an adequate motor (respiratory) command. Depending on the timing, intensity, and duration, the detrimental consequences of perinatal exposure to adverse conditions on the respiratory network become manifest at various life stages and can persist into adulthood. During early life, respiratory diseases commonly associated with dysfunction of neural networks include apnea of prematurity (AOP) and cardio-respiratory failure leading to sudden infant death syndrome (SIDS). Sleep disordered breathing (SDB) can occur at various life stages, including adulthood. Regardless of age, a common element of these disorders is their greater prevalence in males. While this sexual dimorphism points to a potential role of sex hormones, our understanding of the neuroendocrine mechanisms remain poorly understood. In addition to their modulatory influence on breathing, gonadal hormones regulate sexual differentiation of the brain. Stress alters these effects, and over the years our laboratory has used various perinatal stress protocols to gain insight into the origins of sex-based differences in respiratory disorders. This review discusses our recent advances with a focus on the sex-specific impact of early life stress on O 2 -chemoreflex function both in newborn and adult rats. We conclude by discussing the basic principles emerging from this work, potential mechanisms, and clinical relevance. Copyright © 2017 Elsevier B.V. All rights reserved.
Allen, Karina L; Byrne, Susan M; Crosby, Ross D
2015-08-01
Binge eating disorder and purging disorder have gained recognition as distinct eating disorder diagnoses, but risk factors for these conditions have not yet been established. This study aimed to evaluate a prospective, mediational model of risk for the full range of binge eating and purging eating disorders, with attention to possible diagnostic differences. Specific aims were to determine, first, whether eating, weight and shape concerns at age 14 would mediate the relationship between parent-perceived childhood overweight at age 10 and a binge eating or purging eating disorder between age 15 and 20, and, second, whether this mediational model would differ across bulimia nervosa, binge eating disorder, and purging disorder. Participants (N = 1,160; 51 % female) were drawn from the Western Australian Pregnancy Cohort (Raine) Study, which has followed children from pre-birth to age 20. Eating disorders were assessed via self-report questionnaires when participants were aged 14, 17 and 20. There were 146 participants (82 % female) with a binge eating or purging eating disorder with onset between age 15 and 20 [bulimia nervosa = 81 (86 % female), binge eating disorder = 43 (74 % female), purging disorder = 22 (77 % female)]. Simple mediation analysis with bootstrapping was used to test the hypothesized model of risk, with early adolescent eating, weight and shape concerns positioned as a mediator between parent-perceived childhood overweight and later onset of a binge eating or purging eating disorder. Subsequently, a conditional process model (a moderated mediation model) was specified to determine if model pathways differed significantly by eating disorder diagnosis. In the simple mediation model, there was a significant indirect effect of parent-perceived childhood overweight on risk for a binge eating or purging eating disorder in late adolescence, mediated by eating, weight and shape concerns in early adolescence. In the conditional process model
Modernity and narcissistic personality disorder.
Paris, Joel
2014-04-01
Narcissistic personality disorder (NPD) is a trait-based disorder that can be understood as a pathological amplification of narcissistic traits. While temperamental vulnerability and psychological adversity are risk factors for NPD, sociocultural factors are also important. This review hypothesizes that increases in narcissistic traits and cultural narcissism could be associated with changes in the prevalence of NPD. These shifts seem to be a relatively recent phenomenon, driven by social changes associated with modernity. While the main treatment for NPD remains psychotherapy, that form of treatment is itself a product of modernity and individualism. The hypothesis is presented that psychological treatment, unless modified to address the specific problems associated with NPD, could run the risk of supporting narcissism. PsycINFO Database Record (c) 2014 APA, all rights reserved
Naragon-Gainey, K; Watson, D
2011-07-01
The anxiety disorders are robust correlates/predictors of suicidal ideation, but it is unclear whether (a) the anxiety disorders are specifically associated with suicidal ideation or (b) the association is due to co-morbidity with depression and other disorders. One means of modeling co-morbidity is through the personality traits neuroticism/negative emotionality (N/NE) and extraversion/positive emotionality (E/PE), which account for substantial shared variance among the internalizing disorders. The current study examines the association between the internalizing disorders and suicidal ideation, after controlling for co-morbidity via N/NE and E/PE. The sample consisted of 327 psychiatric out-patients. Multiple self-report and interview measures were collected for internalizing disorders [depression, generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), social anxiety, panic and specific phobia] and suicidal ideation, as well as self-report measures for N/NE and E/PE. A model was hypothesized in which each disorder and suicidal ideation was regressed on N/NE, and depression and social anxiety were regressed on E/PE. Structural equation modeling (SEM) was used to examine the unique association of suicidality with each disorder, beyond shared variance with N/NE and E/PE. The hypothesized model was an acceptable fit to the data. Although zero-order analyses indicated that suicidal ideation was moderately to strongly correlated with all of the disorders, only depression and PTSD remained significantly associated with suicidal ideation in the SEM analyses. In a latent variable model that accounts for measurement error and a broad source of co-morbidity, only depression and PTSD were uniquely associated with suicidal ideation; panic, GAD, social anxiety and specific phobia were not.
Pituitary volumes are changed in patients with conversion disorder.
Atmaca, Murad; Baykara, Sema; Mermi, Osman; Yildirim, Hanefi; Akaslan, Unsal
2016-03-01
Our study group previously measured pituitary volumes and found a relationship between somatoform disoders and pituitary volumes. Therefore, in conversion disorder, another somatoform disorder, we hypothesized that pituitary gland volumes would be reduced. Twenty female patients and healthy controls were recruited to the present investigation. The volumes of the pituitary gland were determined by using a 1.5 Tesla magnetic resonance scanner. We found that the pituitary gland volumes of the patients with conversion disorder were significantly smaller than those of healthy control subjects. In the patients with conversion disorder but not in the healthy control group, a significant negative correlation between the duration of illness and pituitary gland volume was determined. In summary, in the present study, we suggest that the patients with conversion disorder have smaller pituitary volumes compared to those of healthy control subjects. Further studies should confirm our data and ascertain whether volumetric alterations determined in the patients with conversion disorder can be changed with treatment or if they change over time.
Psychosocial well-being in Dutch adults with disorders of sex development
de Neve-Enthoven, Nita G M; Callens, Nina; van Kuyk, Maaike; van Kuppenveld, Jet H.; Drop, Stenvert L S; Cohen-Kettenis, Peggy T.; Dessens, Arianne B.
2016-01-01
OBJECTIVE: Atypical sex development is associated with psychosocial vulnerability. We investigated psychosocial well-being in individuals with disorders of sex development (DSD) and hypothesized that psychosocial well-being was related to degree of genital atypicality at birth. METHODS: 120 male
Directory of Open Access Journals (Sweden)
Tokatli A
2015-07-01
Full Text Available Alptug Tokatli,1 Omer Yiginer,2 Gokhan Degirmencioglu,2 Fethi Kilicaslan,3 Mehmet Uzun2 1Department of Cardiology, Golcuk Military Hospital, Kocaeli, 2Department of Cardiology, GATA Haydarpasa Hospital, 3Department of Cardiology, Medipol University, Istanbul, TurkeyWe read with great interest the article entitled “P-wave and QT dispersion in patients with conversion disorder” by Izci et al1 in Therapeutics and Clinical Risk Management. In this well designed research, Izci et al studied QT dispersion (QTd and P-wave dispersion (Pd in patients with conversion disorder (CD. In conclusion, they reported that corrected QT (QTc and QTd values were significantly altered in patients with CD when compared to healthy controls, but that there was no significant difference in terms of Pd.Read the original article
Twelve testable hypotheses on the geobiology of weathering
S.L. Brantley; J.P. Megonigal; F.N. Scatena; Z. Balogh-Brunstad; R.T. Barnes; M.A. Bruns; P. van Cappelen; K. Dontsova; H.E. Hartnett; A.S. Hartshorn; A. Heimsath; E. Herndon; L. Jin; C.K. Keller; J.R. Leake; W.H. McDowell; F.C. Meinzer; T.J. Mozdzer; S. Petsch; J. Pett-Ridge; K.S. Pretziger; P.A. Raymond; C.S. Riebe; K. Shumaker; A. Sutton-Grier; R. Walter; K. Yoo
2011-01-01
Critical Zone (CZ) research investigates the chemical, physical, and biological processes that modulate the Earth's surface. Here, we advance 12 hypotheses that must be tested to improve our understanding of the CZ: (1) Solar-to-chemical conversion of energy by plants regulates flows of carbon, water, and nutrients through plant-microbe soil networks, thereby...
The Iowa Gambling Task and the three fallacies of dopamine in gambling disorder
DEFF Research Database (Denmark)
Linnet, Jakob
2013-01-01
Gambling disorder sufferers prefer immediately larger rewards despite long term losses on the Iowa Gambling Task (IGT), and these impairments are associated with dopamine dysfunctions. Dopamine is a neurotransmitter linked with temporal and structural dysfunctions in substance use disorder, which...... has supported the idea of impaired decision-making and dopamine dysfunctions in gambling disorder. However, evidence from substance use disorders cannot be directly transferred to gambling disorder. This article focuses on three hypotheses of dopamine dysfunctions in gambling disorder, which appear...... to be “fallacies,” i.e., have not been supported in a series of positron emission tomography (PET) studies. The first “fallacy” suggests that gambling disorder sufferers have lower dopamine receptor availability, as seen in substance use disorders. However, no evidence supported this hypothesis. The second...
Transfer factor - hypotheses for its structure and function.
Shifrine, M; Scibienski, R
1975-01-01
Transfer factor (TF) is a dialyzable extract from primed lymphocytes that is able to transfer specific delayed hypersensitivity from one animal to another. On the basis of available data we suggest that TF is a polypeptide with a molecular weight below 15,000 daltons. We hypothesize that TF is the variable light or heavy chain domain of immunoglobulin: such a molecule conforms with the accepted properties of TF and also has the necessary specificity requirements. We also hypothesize that TF is part of a receptor site. beta-2-microglobulin, a molecule that is an integral part of cell surfaces, could be the anchor for TF. beta-2-microglobulin has homologies with the constant portion of immunoglobulin light or heavy chain and thus would combine with the variable domain (TF) to form a complete receptor site for a specific antigen. The properties of TF suggest its mode of action, which is discussed in detail in the text. The biologic advantages of TF is its ability to confer immediate (immunologie specific) protection while the 'normal' immune response develops.
A model for diagnosing and explaining multiple disorders.
Jamieson, P W
1991-08-01
The ability to diagnose multiple interacting disorders and explain them in a coherent causal framework has only partially been achieved in medical expert systems. This paper proposes a causal model for diagnosing and explaining multiple disorders whose key elements are: physician-directed hypotheses generation, object-oriented knowledge representation, and novel explanation heuristics. The heuristics modify and link the explanations to make the physician aware of diagnostic complexities. A computer program incorporating the model currently is in use for diagnosing peripheral nerve and muscle disorders. The program successfully diagnoses and explains interactions between diseases in terms of underlying pathophysiologic concepts. The model offers a new architecture for medical domains where reasoning from first principles is difficult but explanation of disease interactions is crucial for the system's operation.
A survey of etiologic hypotheses among testicular cancer researchers
DEFF Research Database (Denmark)
Stang, A; Trabert, B; Rusner, C
2015-01-01
Basic research results can provide new ideas and hypotheses to be examined in epidemiological studies. We conducted a survey among testicular cancer researchers on hypotheses concerning the etiology of this malignancy. All researchers on the mailing list of Copenhagen Testis Cancer Workshops...... and corresponding authors of PubMed-indexed articles identified by the search term 'testicular cancer' and published within 10 years (in total 2750 recipients) were invited to respond to an e-mail-based survey. Participants of the 8th Copenhagen Testis Cancer Workshop in May 2014 were subsequently asked to rate...... that scored as most plausible. We also present plans for improving the survey that may be repeated at a next international meeting of experts in testicular cancer. Overall 52 of 99 (53%) registered participants of the 8th Copenhagen Testis Cancer Workshop submitted the plausibility rating form. Fourteen of 27...
Mpofu, Elias
1997-01-01
Discusses social learning family therapy hypotheses on the development and sustenance of conduct disorder in early childhood, together with treatment approaches that use parents as the primary agents of change. Reviews research showing that parent training procedures hold much promise for the treatment of conduct disorder in childhood. (JPB)
ADOPTING SOCIO-DEMOGRAPHIC CHARACTERISTICS IN PROFILING GREEN CONSUMERS: A REVIEW OF HYPOTHESES
Directory of Open Access Journals (Sweden)
Arif Hartono
2009-02-01
Full Text Available In the last three decades worldwide environmental consciousness has increased dramatically as well as profiling green consumers have gained tremendous attention in the past. Segmenting and targeting markets base on pro-environmental purchase behavior are essential when companies positioning their green products. Socio-demographic characteristics have gained a lot of attention as the key profiling variables. Such characteristics have been employed by many scholars more frequently for the bases of segmenting and profiling green consumers. However, most existing studies of green consumers’ socio-demographic were US based. The present article attempts to review the common hypotheses of socio-demographic characteristics in profiling green consumers. The present article reviews five general hypotheses relating to socio-demographics and environmental consciousness of green consumers, namely the gender, age, education level, income, and occupation hypotheses, as well as the theoretical explanation for each hypothesis. Most previous studies tend to have the same conclusion in the gender, age, education level, and income characteristics. Critics to socio-demographic characteristics and a need to conduct green marketing research in Indonesia was also reviewed.Key words: profiling, socio-demographic, green consumer, hypotheses.
Landscape moderation of biodiversity patterns and processes - eight hypotheses
Tscharntke, T.; Tylianakis, J.M.; Rand, T.A.; Didham, R.K.; Fahrig, L.; Batary, P.; Bengtsson, J.; Clough, Y.; Crist, T.O.; Dormann, C.; Ewers, R.M.; Frund, J.; Holt, R.D.; Holzschuh, A.; Klein, A.M.; Kleijn, D.; Kremen, C.; Landis, D.A.; Laurance, W.F.; Lindenmayer, D.B.; Scherber, C.; Sodhi, N.; Steffan-Dewenter, I.; Thies, C.; Putten, van der W.H.; Westphal, C.
2012-01-01
Understanding how landscape characteristics affect biodiversity patterns and ecological processes at local and landscape scales is critical for mitigating effects of global environmental change. In this review, we use knowledge gained from human-modified landscapes to suggest eight hypotheses, which
Francx, Winke; Oldehinkel, Marianne; Oosterlaan, Jaap; Heslenfeld, Dirk; Hartman, Catharina A.; Hoekstra, Pieter J.; Franke, Barbara; Beckmann, Christian F.; Buitelaar, Jan K.; Mennes, Maarten
2015-01-01
Background: One neurodevelopmental theory hypothesizes remission of attention-deficit/hyperactivity disorder (ADHD) to result from improved prefrontal top-down control, while ADHD, independent of the current diagnosis, is characterized by stable non-cortical deficits (Halperin & Schulz, 2006). We
Towards Self-Learning Based Hypotheses Generation in Biomedical Text Domain.
Gopalakrishnan, Vishrawas; Jha, Kishlay; Xun, Guangxu; Ngo, Hung Q; Zhang, Aidong
2017-12-26
The overwhelming amount of research articles in the domain of bio-medicine might cause important connections to remain unnoticed. Literature Based Discovery is a sub-field within biomedical text mining that peruses these articles to formulate high confident hypotheses on possible connections between medical concepts. Although many alternate methodologies have been proposed over the last decade, they still suffer from scalability issues. The primary reason, apart from the dense inter-connections between biological concepts, is the absence of information on the factors that lead to the edge-formation. In this work, we formulate this problem as a collaborative filtering task and leverage a relatively new concept of word-vectors to learn and mimic the implicit edge-formation process. Along with single-class classifier, we prune the search-space of redundant and irrelevant hypotheses to increase the efficiency of the system and at the same time maintaining and in some cases even boosting the overall accuracy. We show that our proposed framework is able to prune up to 90% of the hypotheses while still retaining high recall in top-K results. This level of efficiency enables the discovery algorithm to look for higher-order hypotheses, something that was infeasible until now. Furthermore, the generic formulation allows our approach to be agile to performboth open and closed discovery.We also experimentally validate that the core data-structures upon which the system bases its decision has a high concordance with the opinion of the experts.This coupled with the ability to understand the edge formation process provides us with interpretable results without any manual intervention. The relevant JAVA codes are available at: https://github.com/vishrawas/Medline-Code_v2. vishrawa@buffalo.edukishlayj@buffalo.edu. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email
[Exercise addiction: an emergent behavioral disorder].
Márquez, Sara; de la Vega, Ricardo
2015-06-01
Regular physical activity plays a relevant role in health maintenance and disease prevention. However, excess exercise may generate adverse effects both on physical and mental activity. To provide a state-of-the-art overview on exercise addiction, considering its concept, symptoms, diagnosis, epidemiological aspects, etiological factors, and potential interventions. Articles related to the topic were reviewed through Pubmed, Sportdiscus, PsycINFO, Scopus and Web of Science databases, using combinations of the following keywords: "exercise", "addiction" and "dependence". Regular exercise taken into excess may result in adverse health consequences and quality of life impairment. Diagnosis of exercise addiction requires the employment of questionnaires such as the Exercise Dependence Scale (EDS) and the Exercise Addiction Inventory (EAI). These instruments have allowed the estimation of a 3% prevalence among exercise practitioners. Proposed hypotheses to explain the etiology of this disorder include both physiological and psychological mechanisms. Treatment is based on the cognitive-behavioral approach, but effectiveness needs to be evaluated. Although different hypotheses have been proposed to explain exercise dependence, integrative models are still necessary. A clinical validation of diagnostic instruments and a deepening into the relationship with behavioral eating disorders are also required. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.
Dyl, Jennifer; Kittler, Jennifer; Phillips, Katharine A.; Hunt, Jeffrey I.
2006-01-01
Background: This study assessed prevalence and clinical correlates of body dysmorphic disorder (BDD), eating disorders (ED), and other clinically significant body image concerns in 208 consecutively admitted adolescent inpatients. It was hypothesized that adolescents with BDD would have higher levels of depression, anxiety, and suicidality.…
Do personality traits predict first onset in depressive and bipolar disorder?
DEFF Research Database (Denmark)
Christensen, Maj Vinberg; Kessing, Lars Vedel
2006-01-01
The aim was to investigate whether personality traits predict onset of the first depressive or manic episode (the vulnerability hypothesis) and whether personality might be altered by the mood disorder (the scar hypothesis). A systematic review of population-based and high-risk studies concerning...... personality traits and affective disorder in adults was conducted. Nine cross-sectional high-risk studies, seven longitudinal high-risk studies and nine longitudinal population-based studies were found. Most studies support the vulnerability hypothesis and there is evidence that neuroticism is a premorbid...... risk factor for developing depressive disorder. The evidence for the scar hypothesis is sparse, but the studies with the strongest design showed evidence for both hypotheses. Only few studies of bipolar disorder were found and the association between personality traits and bipolar disorder is unclear...
Eating Disorders, Autoimmune, and Autoinflammatory Disease.
Zerwas, Stephanie; Larsen, Janne Tidselbak; Petersen, Liselotte; Thornton, Laura M; Quaranta, Michela; Koch, Susanne Vinkel; Pisetsky, David; Mortensen, Preben Bo; Bulik, Cynthia M
2017-12-01
Identifying factors associated with risk for eating disorders is important for clarifying etiology and for enhancing early detection of eating disorders in primary care. We hypothesized that autoimmune and autoinflammatory diseases would be associated with eating disorders in children and adolescents and that family history of these illnesses would be associated with eating disorders in probands. In this large, nationwide, population-based cohort study of all children and adolescents born in Denmark between 1989 and 2006 and managed until 2012, Danish medical registers captured all inpatient and outpatient diagnoses of eating disorders and autoimmune and autoinflammatory diseases. The study population included 930 977 individuals (48.7% girls). Cox proportional hazards regression models and logistic regression were applied to evaluate associations. We found significantly higher hazards of eating disorders for children and adolescents with autoimmune or autoinflammatory diseases: 36% higher hazard for anorexia nervosa, 73% for bulimia nervosa, and 72% for an eating disorder not otherwise specified. The association was particularly strong in boys. Parental autoimmune or autoinflammatory disease history was associated with significantly increased odds for anorexia nervosa (odds ratio [OR] = 1.13, confidence interval [CI] = 1.01-1.25), bulimia nervosa (OR = 1.29; CI = 1.08-1.55) and for an eating disorder not otherwise specified (OR = 1.27; CI = 1.13-1.44). Autoimmune and autoinflammatory diseases are associated with increased risk for eating disorders. Ultimately, understanding the role of immune system disturbance for the etiology and pathogenesis of eating disorders could point toward novel treatment targets. Copyright © 2017 by the American Academy of Pediatrics.
White, Daniela; Tavakoli, Sason
2015-08-01
Repetitive transcranial magnetic stimulation (rTMS) has shown promising results in treating individuals with behavioral disorders such as major depressive disorder (MDD), posttraumatic stress disorder, obsessive-compulsive disorder, and social anxiety disorder. A number of applications of rTMS to different regions of the left and right prefrontal cortex have been used to treat these disorders, but no study of treatment for MDD with generalized anxiety disorder (GAD) has been conducted with application of rTMS to both the left and right prefrontal cortex. We hypothesized that applying low-frequency rTMS to the right dorsolateral prefrontal cortex (DLPFC) before applying it to the left DLPFC for the treatment of depression would be anxiolytic in patients with MDD with GAD. Thirteen adult patients with comorbid MDD and GAD received treatment with rTMS in an outpatient setting. The number of treatments ranged from 24 to 36 over 5 to 6 weeks. Response was defined as a ≥ 50% reduction in symptoms from baseline, and remission was defined as a score of anxiety symptoms on the 7-item Generalized Anxiety Disorder (GAD-7) scale and depressive symptoms on the 21-item Hamilton Rating Scale for Depression (HAM-D-21). At the end of the treatment period, for the GAD-7 scale, 11 out of 13 (84.6%) patients' anxiety symptoms were in remission, achieving a score of depressive symptoms. In this small pilot study of 13 patients with comorbid MDD and GAD, significant improvement in anxiety symptoms along with depressive symptoms was achieved in a majority of patients after bilateral rTMS application.
Chelation Treatment for Autism Spectrum Disorders: A Systematic Review
Davis, Tonya N.; O'Reilly, Mark; Kang, Soyeon; Lang, Russell; Rispoli, Mandy; Sigafoos, Jeff; Lancioni, Giulio; Copeland, Daelynn; Attai, Shanna; Mulloy, Austin
2013-01-01
Chelation treatment is used to eliminate specific metals from the body, such as mercury. It has been hypothesized that mercury poisoning may be a factor in autism and data suggest that perhaps 7% of individuals with autism spectrum disorder (ASD) have received chelation treatment. It would therefore seem timely to review studies investigating the…
Cairney, John; Hay, John; Veldhuizen, Scott; Faught, Brent
2011-01-01
Developmental coordination disorder (DCD) is a neuro-developmental disorder characterized by poor fine and/or gross motor coordination. Children with DCD are hypothesized to be at increased risk for overweight and obesity from inactivity due to their motor coordination problems. Although previous studies have found evidence to support this…
Bekker, M.H.J.; Boselie, A.H.M.
2002-01-01
The present study was, first, aimed at examining the relationship between eating disorders, feminine gender role stress and other types of stress. In addition, we investigated whether eating disordered women compared to non-clinical controls use depressogenic coping more often. We hypothesized that
Schretlen, David J; Peña, Javier; Aretouli, Eleni; Orue, Izaskun; Cascella, Nicola G; Pearlson, Godfrey D; Ojeda, Natalia
2013-06-01
We sought to determine whether a single hypothesized latent factor structure would characterize cognitive functioning in three distinct groups. We assessed 576 adults (340 community controls, 126 adults with bipolar disorder, and 110 adults with schizophrenia) using 15 measures derived from nine cognitive tests. Confirmatory factor analysis (CFA) was conducted to examine the fit of a hypothesized six-factor model. The hypothesized factors included attention, psychomotor speed, verbal memory, visual memory, ideational fluency, and executive functioning. The six-factor model provided an excellent fit for all three groups [for community controls, root mean square error of approximation (RMSEA) schizophrenia, RMSEA = 0.06 and CFI = 0.98]. Alternate models that combined fluency with processing speed or verbal and visual memory reduced the goodness of fit. Multi-group CFA results supported factor invariance across the three groups. Confirmatory factor analysis supported a single six-factor structure of cognitive functioning among patients with schizophrenia or bipolar disorder and community controls. While the three groups clearly differ in level of performance, they share a common underlying architecture of information processing abilities. These cognitive factors could provide useful targets for clinical trials of treatments that aim to enhance information processing in persons with neurological and neuropsychiatric disorders. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Galbraith, Todd; Heimberg, Richard G; Wang, Shuai; Schneier, Franklin R; Blanco, Carlos
2014-01-01
Social anxiety disorder (SAD) and antisocial personality disorder (ASPD) are not often thought of as being comorbid. However, recent research suggests the existence of a SAD subtype with characteristics atypical of SAD but common to ASPD. Thus, we explored two competing hypotheses: (1) SAD and ASPD represent opposite ends of a single dimension, or (2) SAD and ASPD exist on two separate dimensions that may be positively correlated. Data were obtained from the National Epidemiological Survey on Alcohol and Related Conditions. SAD-ASPD was related to greater impairment and psychiatric comorbidity than either disorder alone. The SAD-ASPD group was also more likely to seek treatment for their SAD symptoms and to drink before/during antisocial acts than the SAD only group. The presence of SAD for individuals with ASPD (and vice versa) does not appear to provide any "protective benefits." SAD and ASPD appear to be two separate but correlated disorders. Copyright © 2013 Elsevier Ltd. All rights reserved.
Galbraith, Todd; Heimberg, Richard G.; Wang, Shuai; Schneier, Franklin R.; Blanco, Carlos
2013-01-01
Social anxiety disorder (SAD) and antisocial personality disorder (ASPD) are not often thought of as being comorbid. However, recent research suggests the existence of a SAD subtype with characteristics atypical of SAD but common to ASPD. Thus, we explored two competing hypotheses: 1) SAD and ASPD represent opposite ends of a single dimension, or 2) SAD and ASPD exist on two separate dimensions that may be positively correlated. Data were obtained from the National Epidemiological Survey on Alcohol and Related Conditions. SAD-ASPD was related to greater impairment and psychiatric comorbidity than either disorder alone. The SAD-ASPD group was also more likely to seek treatment for their SAD symptoms and to drink before/during antisocial acts than the SAD only group. The presence of SAD for individuals with ASPD (and vice versa) does not appear to provide any “protective benefits.” SAD and ASPD appear to be two separate but correlated disorders. PMID:24384071
Testing Hypotheses About Glacial Cycles Against the Observational Record
DEFF Research Database (Denmark)
Kaufmann, Robert; Juselius, Katarina
2013-01-01
We estimate an identified cointegrated vector autoregression (CVAR) model of the climate system to test hypotheses about the physical mechanisms that may drive glacial cycles during the late Pleistocene. Results indicate that a permanent doubling of CO2 generates a 11.1oC rise in Antarctic...
Conviser, Jenny H; Fisher, Sheehan D; McColley, Susanna A
2018-03-01
Pediatric chronic illnesses (CI) can affect a child's mental health. Chronic illnesses with treatment regimens that specify a therapeutic diet may place the child at increased risk for disordered eating and specific eating disorders (ED). The aim of this review is to examine the relation between diet-treated CI and disordered eating and to determine the order of onset to infer directionality. Diet-treated CI is hypothesized to precede and to be associated with disordered eating. A comprehensive search of empirical articles that examine the relation between diet-treated CI (diabetes, cystic fibrosis, celiac disease, gastrointestinal disorders, and inflammatory bowel diseases) and disordered eating was conducted in Medline and PsycINFO using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A table of the sample's characteristics, ED measures, major pertinent findings, and the onset of CI in relation to ED were provided. Diet-treated CI was associated with disordered eating and ED. Diet-treated CI had onset prior to disordered eating in most studies, except for inflammatory bowel diseases. Disordered eating and unhealthy weight management practices put children at risk for poor medical outcomes. Interventions for diet-treated CI require a focus on diet and weight, but may increase the risk for disordered eating. Future research is needed to elucidate the mechanisms that transform standard treatment practices into pathological eating, including characteristics and behaviors of the child, parents/care providers, family, and treatment providers. © 2018 Wiley Periodicals, Inc.
Directory of Open Access Journals (Sweden)
Hiroyuki Ito, MD
2007-01-01
Full Text Available Introduction: Some studies have reported that transmural dispersion of repolarization (TDR is involved in the onset of ventricular arrhythmia. We investigated the effects of nicorandil (NIC and nifekalant (NIF injected into the pericardial space, on TDR and T waves in the pig. Methods and Results: We injected NIC 4 or 8 mg and NIF 50 or 100 mg at intervals into the pericardial space for eleven pigs. The effects of these drugs were investigated on the effective refractory period (ERP between the endocardial and epicardial myocardial cells, as well as on QT time, QT peak-end (QTcpe as an index of TDR, and T waveforms, respectively. QTcpe increased from 91 ± 21 to 116 ± 19 msec, 2.8 min after injection of NIC (p < 0.01, although corrected QT (QTc interval did not changed. But 5.5 min after injection, QTc decreased while QTcpe recovered. T wave amplitude significantly increased, and epicardium ERP decreased. When NIF was injected, TDR decreased from 55 ± 10 msec to 44 ± 8 msec (p < 0.01 although QTc did not change. In a later phase, QTc increased (p < 0.01 and QTcpe recovered. T wave amplitude rapidly decreased and became negative. Conclusion: Injected into the pericardial space, NIC and NIF brought about certain changes in ERP, QT and T waveform. Furthermore, NIC increased TDR while NIF decreased TDR.
Psychopathology in offspring of mothers with borderline personality disorder: a pilot study.
Weiss, M; Zelkowitz, P; Feldman, R B; Vogel, J; Heyman, M; Paris, J
1996-06-01
Children of mothers with borderline personality disorder (BPD) were hypothesized to be at greater risk for psychopathology, particularly impulse spectrum disorders, than children of mothers with other personality disorders. Twenty-one index children were compared with 23 children of mothers with a nonborderline personality disorder. Diagnoses were obtained using the Kiddie Schedule for Affective Disorders and Schizophrenia-Episodic Version (KSADS-E) and the Child Diagnostic Interview for BPD (CDIB), and functioning was rated with the Child Global Assessment Schedule (CGAS). Physical, sexual, and verbal abuse, as well as family violence and placements, were also assessed. The children of the borderline mothers, as compared with controls, had more psychiatric diagnoses, more impulse control disorders, a higher frequency of child BPD, and lower CGAS scores. There were no differences between the groups for trauma. The offspring of borderline mothers are at high risk for psychopathology.
Colquhoun, Heather L; Carroll, Kelly; Eva, Kevin W; Grimshaw, Jeremy M; Ivers, Noah; Michie, Susan; Sales, Anne; Brehaut, Jamie C
2017-09-29
Audit and feedback (A&F) is a common strategy for helping health providers to implement evidence into practice. Despite being extensively studied, health care A&F interventions remain variably effective, with overall effect sizes that have not improved since 2003. Contributing to this stagnation is the fact that most health care A&F interventions have largely been designed without being informed by theoretical understanding from the behavioral and social sciences. To determine if the trend can be improved, the objective of this study was to develop a list of testable, theory-informed hypotheses about how to design more effective A&F interventions. Using purposive sampling, semi-structured 60-90-min telephone interviews were conducted with experts in theories related to A&F from a range of fields (e.g., cognitive, health and organizational psychology, medical decision-making, economics). Guided by detailed descriptions of A&F interventions from the health care literature, interviewees described how they would approach the problem of designing improved A&F interventions. Specific, theory-informed hypotheses about the conditions for effective design and delivery of A&F interventions were elicited from the interviews. The resulting hypotheses were assigned by three coders working independently into themes, and categories of themes, in an iterative process. We conducted 28 interviews and identified 313 theory-informed hypotheses, which were placed into 30 themes. The 30 themes included hypotheses related to the following five categories: A&F recipient (seven themes), content of the A&F (ten themes), process of delivery of the A&F (six themes), behavior that was the focus of the A&F (three themes), and other (four themes). We have identified a set of testable, theory-informed hypotheses from a broad range of behavioral and social science that suggest conditions for more effective A&F interventions. This work demonstrates the breadth of perspectives about A&F from non
Automatic Bayes Factors for Testing Equality- and Inequality-Constrained Hypotheses on Variances.
Böing-Messing, Florian; Mulder, Joris
2018-05-03
In comparing characteristics of independent populations, researchers frequently expect a certain structure of the population variances. These expectations can be formulated as hypotheses with equality and/or inequality constraints on the variances. In this article, we consider the Bayes factor for testing such (in)equality-constrained hypotheses on variances. Application of Bayes factors requires specification of a prior under every hypothesis to be tested. However, specifying subjective priors for variances based on prior information is a difficult task. We therefore consider so-called automatic or default Bayes factors. These methods avoid the need for the user to specify priors by using information from the sample data. We present three automatic Bayes factors for testing variances. The first is a Bayes factor with equal priors on all variances, where the priors are specified automatically using a small share of the information in the sample data. The second is the fractional Bayes factor, where a fraction of the likelihood is used for automatic prior specification. The third is an adjustment of the fractional Bayes factor such that the parsimony of inequality-constrained hypotheses is properly taken into account. The Bayes factors are evaluated by investigating different properties such as information consistency and large sample consistency. Based on this evaluation, it is concluded that the adjusted fractional Bayes factor is generally recommendable for testing equality- and inequality-constrained hypotheses on variances.
Talarczyk, Małgorzata
2012-01-01
The point of the article is to analyse and reflect on certain symptoms of anorexia nervosa in light of Karl Jaspers and Erich Fromm's ideas and social constructivism. Contemplating the disorder in view of the philosophical ideas mentioned earlier, the author analyses such aspects of patients as: functioning on the verge of life and death, the paradoxical struggle to escape from freedom in search of independence, as well as various understandings and descriptions of anorexia in consideration of social constructivism. The author shares thoughts and poses hypotheses, trying to view anorexia in light of selected philosophical and psychological ideas, which in their general assumptions were not concerned with defining nor analysing anorexia nervosa. In view of Karl Jaspers' ideas, the author focuses on the so called 'limit-situations', in the ideas of Erich Fromm she takes notice in "Escape from Freedom" to new relations. Finally in the light of social constructivism the author focuses on the cultural context.
Cognitive and behavioral disorders in Parkinson's disease: an update. II: behavioral disorders.
Trojano, Luigi; Papagno, Costanza
2018-01-01
Patients with Parkinson's disease (PD) can experience several behavioral symptoms, such as apathy, agitation, hypersexuality, stereotypic movements, pathological gambling, abuse of antiparkinsonian drugs, and REM sleep behavioral disorders. Psychoses and hallucinations, depression and anxiety disorders, and difficulties in recognizing and experiencing emotions also impair behavior and can cause severe psychosocial problems in patients with PD. Symptoms can be present since early stages of the disease, sometimes even before the appearance of classical motor symptoms, likely in relation to dopamine depletion in basal ganglia and/or to dysfunctions of other neurotrasmitter systems, and others can develop later, in some cases in relation to dopaminergic treatment. In this paper, we review recent literature, with particular attention to the last 5 years, on the main behavioral and emotional disturbances described in PD patients as well as the hypothesized neurofunctional substrate of such impairments. Finally, we provide some suggestions on the most suitable instruments to check and assess PD-associated behavioral defects over time.
Prevalence of attention-deficit/hyperactivity disorder and conduct disorder among substance abusers.
Schubiner, H; Tzelepis, A; Milberger, S; Lockhart, N; Kruger, M; Kelley, B J; Schoener, E P
2000-04-01
This cross-sectional study sought to determine the prevalence of attention-deficit/hyperactivity disorder (ADHD) and conduct disorder among adults admitted to 2 chemical dependency treatment centers. It was hypothesized that ADHD alone or in combination with conduct disorder would be overrepresented in a population of patients with psychoactive substance use disorders. Two hundred one participants were selected randomly from 2 chemical dependency treatment centers. Standardized clinical interviews were conducted using the Structured Clinical Interview for DSM-IV, the Addiction Severity Index, and DSM-IV criteria for ADHD. Reliabilities for the diagnostic categories were established using the Cohen kappa, and the subgroups of individuals with and without ADHD and conduct disorder were compared. Forty-eight (24%) of the participants were found to meet DSM-IV criteria for ADHD. The prevalence of ADHD was 28% in men (30/106) and 19% in women (18/95; NS). Seventy-nine participants (39%) met criteria for conduct disorder, and 34 of these individuals also had ADHD. Overall, individuals with ADHD (compared with those without ADHD) were more likely to have had more motor vehicle accidents. Women with ADHD (in comparison with women without ADHD) had a higher number of treatments for alcohol abuse. Individuals with conduct disorder (in comparison with those without conduct disorder) were younger, had a greater number of jobs as adults, and were more likely to repeat a grade in school, have a learning disability, be suspended or expelled from school, have an earlier age at onset of alcohol dependence, and have had a greater number of treatments for drug abuse. They were more likely to have a lifetime history of abuse of and/or dependence on cocaine, stimulants, hallucinogens, and/or cannabis. A significant overrepresentation of ADHD exists among inpatients with psychoactive substance use disorders. Over two thirds of those with ADHD in this sample also met criteria for conduct
Gao, Qianqian; Ma, Guorong; Zhu, Qisha; Fan, Hongying; Wang, Wei
2016-01-01
Detecting personality disorders in the illiterate population is a challenge, but nonverbal tools measuring personality traits such as the Five-Factor Nonverbal Personality Questionnaire (FFNPQ) might help. We hypothesized that FFNPQ traits are associated with personality disorder functioning styles in a predictable way, especially in a sample of personality disorder patients. We therefore invited 106 personality disorder patients and 205 healthy volunteers to answer the FFNPQ and the Parker Personality Measure (PERM) which measures 11 personality disorder functioning styles. Patients scored significantly higher on the FFNPQ neuroticism and conscientiousness traits and all 11 PERM styles. In both groups, the 5 FFNPQ traits displayed extensive associations with the 11 PERM styles, respectively, and the associations were more specific in patients. Associations between neuroticism, extraversion and agreeableness traits and most PERM styles were less exclusive, but conscientiousness was associated with antisocial (-) and obsessive-compulsive styles, and openness to experience with schizotypal and dependent (-) styles. Our study has demonstrated correlations between FFNPQ traits and PERM styles, and implies the nonverbal measure of personality traits is capable of aiding the diagnoses of personality disorders in the illiterate population. Enlarging sample size and including the illiterate might make for more stable results. © 2016 S. Karger AG, Basel.
Terband, H; Maassen, B; Guenther, F H; Brumberg, J
2014-01-01
Differentiating the symptom complex due to phonological-level disorders, speech delay and pediatric motor speech disorders is a controversial issue in the field of pediatric speech and language pathology. The present study investigated the developmental interaction between neurological deficits in auditory and motor processes using computational modeling with the DIVA model. In a series of computer simulations, we investigated the effect of a motor processing deficit alone (MPD), and the effect of a motor processing deficit in combination with an auditory processing deficit (MPD+APD) on the trajectory and endpoint of speech motor development in the DIVA model. Simulation results showed that a motor programming deficit predominantly leads to deterioration on the phonological level (phonemic mappings) when auditory self-monitoring is intact, and on the systemic level (systemic mapping) if auditory self-monitoring is impaired. These findings suggest a close relation between quality of auditory self-monitoring and the involvement of phonological vs. motor processes in children with pediatric motor speech disorders. It is suggested that MPD+APD might be involved in typically apraxic speech output disorders and MPD in pediatric motor speech disorders that also have a phonological component. Possibilities to verify these hypotheses using empirical data collected from human subjects are discussed. The reader will be able to: (1) identify the difficulties in studying disordered speech motor development; (2) describe the differences in speech motor characteristics between SSD and subtype CAS; (3) describe the different types of learning that occur in the sensory-motor system during babbling and early speech acquisition; (4) identify the neural control subsystems involved in speech production; (5) describe the potential role of auditory self-monitoring in developmental speech disorders. Copyright © 2014 Elsevier Inc. All rights reserved.
DEFF Research Database (Denmark)
Knudsen, Stine; Gammeltoft, Steen; Jennum, Poul J
2010-01-01
Rapid eye movement sleep behaviour disorder is characterized by dream-enacting behaviour and impaired motor inhibition during rapid eye movement sleep. Rapid eye movement sleep behaviour disorder is commonly associated with neurodegenerative disorders, but also reported in narcolepsy with cataplexy....... Most narcolepsy with cataplexy patients lack the sleep-wake, and rapid eye movement sleep, motor-regulating hypocretin neurons in the lateral hypothalamus. In contrast, rapid eye movement sleep behaviour disorder and hypocretin deficiency are rare in narcolepsy without cataplexy. We hypothesized...... that rapid eye movement sleep behaviour disorder coexists with cataplexy in narcolepsy due to hypocretin deficiency. In our study, rapid eye movement sleep behaviour disorder was diagnosed by the International Classification of Sleep Disorders (2nd edition) criteria in 63 narcolepsy patients with or without...
Feldner, Matthew T; Smith, Rose C; Babson, Kimberly A; Sachs-Ericsson, Natalie; Schmidt, Norman B; Zvolensky, Michael J
2009-02-01
Posttraumatic stress disorder (PTSD) frequently co-occurs with panic spectrum problems. Relatively little empirical work has tested possible mechanisms accounting for this association. Nicotine dependence often ensues subsequent to PTSD onset and research suggests smoking high numbers of cigarettes daily may lead to panic problems. The current study tested the hypotheses that nicotine dependence partially mediates the relations between PTSD and both panic attacks and panic disorder within a nationally representative sample of 5,692 (3,020 women; M(Age) = 45, SD = 18) adults from the National Comorbidity Survey-Replication. Results were consistent with hypotheses. These findings support the theory suggesting smoking among people with PTSD may be involved in the development of panic problems.
Roy, Arunima; Oldehinkel, Albertine J; Verhulst, Frank C; Ormel, Johan; Hartman, Catharina A
Objective: The progression to depression in children with attention-deficit/hyperactivity disorder (ADHD) is not clearly understood. To clarify this relationship, we tested the following hypotheses in a population-based study: (1) children with ADHD have a higher risk of developing depression than
Sharp, Andrew J.; Hansen, Sierra; Selzer, Rebecca R.; Cheng, Ze; Regan, Regina; Hurst, Jane A.; Stewart, Helen; Price, Sue M.; Blair, Edward; Hennekam, Raoul C.; Fitzpatrick, Carrie A.; Segraves, Rick; Richmond, Todd A.; Guiver, Cheryl; Albertson, Donna G.; Pinkel, Daniel; Eis, Peggy S.; Schwartz, Stuart; Knight, Samantha J. L.; Eichler, Evan E.
2006-01-01
Genomic disorders are characterized by the presence of flanking segmental duplications that predispose these regions to recurrent rearrangement. Based on the duplication architecture of the genome, we investigated 130 regions that we hypothesized as candidates for previously undescribed genomic
Inohara, Taku; Kohsaka, Shun; Okamura, Tomonori; Watanabe, Makoto; Nakamura, Yasuyuki; Higashiyama, Aya; Kadota, Aya; Okuda, Nagako; Murakami, Yoshitaka; Ohkubo, Takayoshi; Miura, Katsuyuki; Okayama, Akira; Ueshima, Hirotsugu
2014-12-01
Various cohort studies have shown a close association between long-term cardiovascular disease (CVD) outcomes and individual electrocardiographic (ECG) abnormalities such as axial, structural, and repolarization changes. The combined effect of these ECG abnormalities, each assumed to be benign, has not been thoroughly investigated. Community-dwelling Japanese residents from the National Integrated Project for Perspective Observation of Non-Communicable Disease and its Trends in the Aged, 1980-2004 and 1990-2005 (NIPPON DATA80 and 90), were included in this study. Baseline ECG findings were classified using the Minnesota Code and categorized into axial (left axis deviation, clockwise rotation), structural (left ventricular hypertrophy, atrial enlargement), and repolarization (minor and major ST-T changes) abnormalities. The hazard ratios of the cumulative impacts of ECG findings on long-term CVD death were estimated by stratified Cox proportional hazard models, including adjustments for cohort strata. In all, 16,816 participants were evaluated. The average age was 51.2 ± 13.5 years; 42.7% participants were male. The duration of follow up was 300,924 person-years (mean 17.9 ± 5.8 years); there were 1218 CVD deaths during that time. Overall, 4203 participants (25.0%) had one or more categorical ECG abnormalities: 3648 (21.7%) had a single abnormality, and 555 (3.3%) had two or more. The risk of CVD mortality increased as the number of abnormalities accumulated (single abnormality HR 1.29, 95% CI 1.13-1.48; ≥2 abnormalities HR 2.10, 95% CI 1.73-2.53). Individual ECG abnormalities had an additive effect in predicting CVD outcome risk in our large-scale cohort study. © The European Society of Cardiology 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
Dooley, K O; Farmer, A
1988-08-01
Neurolinguistic programming's hypothesized eye movements were measured independently using videotapes of 10 nonfluent aphasic and 10 control subjects matched for age and sex. Chi-squared analysis indicated that eye-position responses were significantly different for the groups. Although earlier research has not supported the hypothesized eye positions for normal subjects, the present findings support the contention that eye-position responses may differ between neurologically normal and aphasic individuals.
Hardaway, J A; Crowley, N A; Bulik, C M; Kash, T L
2015-01-01
Eating disorders are complex brain disorders that afflict millions of individuals worldwide. The etiology of these diseases is not fully understood, but a growing body of literature suggests that stress and anxiety may play a critical role in their development. As our understanding of the genetic and environmental factors that contribute to disease in clinical populations like anorexia nervosa, bulimia nervosa and binge eating disorder continue to grow, neuroscientists are using animal models to understand the neurobiology of stress and feeding. We hypothesize that eating disorder clinical phenotypes may result from stress-induced maladaptive alterations in neural circuits that regulate feeding, and that these circuits can be neurochemically isolated using animal model of eating disorders. © 2014 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.
Stephenson, Chris P; Baguley, Ian J
2018-02-01
Functional Neurological Symptom Disorder (FND) is a relatively common neurological condition, accounting for approximately 3-6% of neurologist referrals. FND is considered a transient disorder of neuronal function, sometimes linked to physical trauma and psychological stress. Despite this, chronic disability is common, for example, around 40% of adults with motor FND have permanent disability. Building on current theoretical models, this paper proposes that microglial dysfunction could perpetuate functional changes within acute motor FND, thus providing a pathophysiological mechanism underlying the chronic stage of the motor FND phenotypes seen clinically. Core to our argument is microglia's dual role in modulating neuroimmunity and their control of synaptic plasticity, which places them at a pathophysiological nexus wherein coincident physical trauma and psychological stress could cause long-term change in neuronal networks without producing macroscopic structural abnormality. This model proposes a range of hypotheses that are testable with current technologies. Copyright © 2017. Published by Elsevier Ltd.
Risk, innovation, electricity infrastructure and construction cost overruns: Testing six hypotheses
International Nuclear Information System (INIS)
Sovacool, Benjamin K.; Gilbert, Alex; Nugent, Daniel
2014-01-01
This study investigates the frequency and magnitude of cost and time overruns occurring during the construction of 401 electricity projects built between 1936 and 2014 in 57 countries. In aggregate, these projects required approximately $820 billion in investment, and amounted to 325,515 MW of installed capacity and 8495 km of transmission lines. We use this sample of projects to test six hypotheses about construction cost overruns related to (1) diseconomies of scale, (2) project delays, (3) technological learning, (4) regulation and markets, (5) decentralization and modularity, and (6) normalization of results to scale. We find that nuclear reactors are the riskiest technology in terms of mean cost escalation as a percentage of budget and frequency; that hydroelectric dams stand apart for their mean cost escalation in total dollars; that many of the hypotheses grounded in the literature appear wrong; and that financing, partnerships, modularity, and accountability may have more to do with overruns than technology. - Highlights: • Many hypotheses about construction overruns grounded in the literature appear wrong. • Nuclear reactors are the most prone to cost overruns as a percentage of budget and frequency. • Hydroelectric dams stand apart for their mean cost escalation in total dollars. • Solar and wind energy systems are least at risk to cost overruns
Janssen, E.; Everaerd, W.; van Lunsen, R. H.; Oerlemans, S.
1994-01-01
This study compared reflexogenic and psychogenic penile responses in men with and without erectile disorder. It was hypothesized that men with psychogenic erectile dysfunction respond minimally to vibrotactile stimulation. An enhancement of penile responses was expected when vibration was combined
Experienced physicians benefit from analyzing initial diagnostic hypotheses
Bass, Adam; Geddes, Colin; Wright, Bruce; Coderre, Sylvain; Rikers, Remy; McLaughlin, Kevin
2013-01-01
Background Most incorrect diagnoses involve at least one cognitive error, of which premature closure is the most prevalent. While metacognitive strategies can mitigate premature closure in inexperienced learners, these are rarely studied in experienced physicians. Our objective here was to evaluate the effect of analytic information processing on diagnostic performance of nephrologists and nephrology residents. Methods We asked nine nephrologists and six nephrology residents at the University of Calgary and Glasgow University to diagnose ten nephrology cases. We provided presenting features along with contextual information, after which we asked for an initial diagnosis. We then primed participants to use either hypothetico-deductive reasoning or scheme-inductive reasoning to analyze the remaining case data and generate a final diagnosis. Results After analyzing initial hypotheses, both nephrologists and residents improved the accuracy of final diagnoses (31.1% vs. 65.6%, p inductive reasoning (odds ratio [95% confidence interval] 5.69 [1.59, 20.33], p = 0.07), whereas the performance of experienced nephrologists did not differ between strategies (odds ratio 0.57 [0.23, 1.39], p = 0.20). Discussion Experienced nephrologists and nephrology residents can improve their performance by analyzing initial diagnostic hypotheses. The explanation of the interaction between experience and the effect of different reasoning strategies is unclear, but may relate to preferences in reasoning strategy, or the changes in knowledge structure with experience. PMID:26451203
Kolmogorov's refined similarity hypotheses for turbulence and general stochastic processes
International Nuclear Information System (INIS)
Stolovitzky, G.; Sreenivasan, K.R.
1994-01-01
Kolmogorov's refined similarity hypotheses are shown to hold true for a variety of stochastic processes besides high-Reynolds-number turbulent flows, for which they were originally proposed. In particular, just as hypothesized for turbulence, there exists a variable V whose probability density function attains a universal form. Analytical expressions for the probability density function of V are obtained for Brownian motion as well as for the general case of fractional Brownian motion---the latter under some mild assumptions justified a posteriori. The properties of V for the case of antipersistent fractional Brownian motion with the Hurst exponent of 1/3 are similar in many details to those of high-Reynolds-number turbulence in atmospheric boundary layers a few meters above the ground. The one conspicuous difference between turbulence and the antipersistent fractional Brownian motion is that the latter does not possess the required skewness. Broad implications of these results are discussed
Global warming and neurodegenerative disorders: speculations on their linkage.
Habibi, Laleh; Perry, George; Mahmoudi, Morteza
2014-01-01
Climate change is having considerable impact on biological systems. Eras of ice ages and warming shaped the contemporary earth and origin of creatures including humans. Warming forces stress conditions on cells. Therefore, cells evolved elaborate defense mechanisms, such as creation of heat shock proteins, to combat heat stress. Global warming is becoming a crisis and this process would yield an undefined increasing rate of neurodegenerative disorders in future decades. Since heat stress is known to have a degenerative effects on neurons and, conversely, cold conditions have protective effect on these cells, we hypothesize that persistent heat stress forced by global warming might play a crucial role in increasing neurodegenerative disorders.
Wakefield, Jerome C; Kirk, Stuart A; Pottick, Kathleen J; Hsieh, Derek K; Tian, Xin
2006-03-01
Conduct disorder (CD) must be distinguished from nondisordered delinquent behaviour to avoid false positives, especially when diagnosing youth from difficult environments. However, the nature of this distinction remains controversial. The DSM-IV observes that its own syndromal CD diagnostic criteria conflict with its definition of mental disorder, which requires that symptoms be considered a manifestation of internal dysfunction to warrant disorder diagnosis. Previous research indicates that professional judgments tend to be guided by the dysfunction requirement, not syndromal symptoms alone. However, there are almost no data on lay conceptualizations. Thus it remains unknown whether judgments about CD are anchored in a broadly shared understanding of mental disorder that provides a basis for professional-lay consensus. The present study tests which conception of CD, syndromal-symptoms or dysfunction-requirement, corresponds most closely to lay judgments of disorder or nondisorder and compares lay and professional judgments. We hypothesized that lay disorder judgments, like professional judgments, tend to presuppose the dysfunction requirement. Three lay samples (nonclinical social workers, nonpsychiatric nurses, and undergraduates) rated their agreement that youths described in clinical vignettes have a mental disorder. All vignettes satisfied DSM-IV CD diagnostic criteria. Vignettes were varied to present syndromal symptoms only, symptoms suggesting internal dysfunction, and symptoms resulting from reactions to negative circumstances, without dysfunction. All lay samples attributed disorder more often to youths whose symptoms suggested internal dysfunction than to youths with similar symptoms but without a likely dysfunction. The dysfunction requirement appears to reflect a widely shared lay and professional concept of disorder.
Constant conditional entropy and related hypotheses
International Nuclear Information System (INIS)
Ferrer-i-Cancho, Ramon; Dębowski, Łukasz; Moscoso del Prado Martín, Fermín
2013-01-01
Constant entropy rate (conditional entropies must remain constant as the sequence length increases) and uniform information density (conditional probabilities must remain constant as the sequence length increases) are two information theoretic principles that are argued to underlie a wide range of linguistic phenomena. Here we revise the predictions of these principles in the light of Hilberg’s law on the scaling of conditional entropy in language and related laws. We show that constant entropy rate (CER) and two interpretations for uniform information density (UID), full UID and strong UID, are inconsistent with these laws. Strong UID implies CER but the reverse is not true. Full UID, a particular case of UID, leads to costly uncorrelated sequences that are totally unrealistic. We conclude that CER and its particular cases are incomplete hypotheses about the scaling of conditional entropies. (letter)
Neurodevelopmental Disorders and Environmental Toxicants: Epigenetics as an Underlying Mechanism
2017-01-01
The increasing prevalence of neurodevelopmental disorders, especially autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD), calls for more research into the identification of etiologic and risk factors. The Developmental Origin of Health and Disease (DOHaD) hypothesizes that the environment during fetal and childhood development affects the risk for many chronic diseases in later stages of life, including neurodevelopmental disorders. Epigenetics, a term describing mechanisms that cause changes in the chromosome state without affecting DNA sequences, is suggested to be the underlying mechanism, according to the DOHaD hypothesis. Moreover, many neurodevelopmental disorders are also related to epigenetic abnormalities. Experimental and epidemiological studies suggest that exposure to prenatal environmental toxicants is associated with neurodevelopmental disorders. In addition, there is also evidence that environmental toxicants can result in epigenetic alterations, notably DNA methylation. In this review, we first focus on the relationship between neurodevelopmental disorders and environmental toxicants, in particular maternal smoking, plastic-derived chemicals (bisphenol A and phthalates), persistent organic pollutants, and heavy metals. We then review studies showing the epigenetic effects of those environmental factors in humans that may affect normal neurodevelopment. PMID:28567415
Neurodevelopmental Disorders and Environmental Toxicants: Epigenetics as an Underlying Mechanism
Directory of Open Access Journals (Sweden)
Nguyen Quoc Vuong Tran
2017-01-01
Full Text Available The increasing prevalence of neurodevelopmental disorders, especially autism spectrum disorders (ASD and attention deficit hyperactivity disorder (ADHD, calls for more research into the identification of etiologic and risk factors. The Developmental Origin of Health and Disease (DOHaD hypothesizes that the environment during fetal and childhood development affects the risk for many chronic diseases in later stages of life, including neurodevelopmental disorders. Epigenetics, a term describing mechanisms that cause changes in the chromosome state without affecting DNA sequences, is suggested to be the underlying mechanism, according to the DOHaD hypothesis. Moreover, many neurodevelopmental disorders are also related to epigenetic abnormalities. Experimental and epidemiological studies suggest that exposure to prenatal environmental toxicants is associated with neurodevelopmental disorders. In addition, there is also evidence that environmental toxicants can result in epigenetic alterations, notably DNA methylation. In this review, we first focus on the relationship between neurodevelopmental disorders and environmental toxicants, in particular maternal smoking, plastic-derived chemicals (bisphenol A and phthalates, persistent organic pollutants, and heavy metals. We then review studies showing the epigenetic effects of those environmental factors in humans that may affect normal neurodevelopment.
A set working hypotheses towards a unified view of the universe
International Nuclear Information System (INIS)
Kecher, J.-C.; Vigier, J.P.; Centre National de la Recherche Scientifique, 75 - Paris; Paris-6 Univ., 75
1976-01-01
Some observation evidence (anisotropy and inhomogeneity of the Hubble constant, abnormal red shifts) led the authors to formulate working hypotheses compatible with these observations. The logics of these hypotheses led to consider the universe as a ''hierarchical'' universe similar to Charlier one, and to find the cause of the apparent expansion in the interactions affecting the path of the photons. As, in some cases, intrinsic red shifts are very important this reduces the distance of the considered objects and their absolute luminosity, and forces to link them with ordinary galaxies; a scheme of evolution of extragalactic objects is suggested, to account for the geometrical location of abnormal objects, and for some aspects of their morphology. Coherent picture of the universe might emerge from the suggested studies
[Panic disorder--psychobiological aspects of personality dimensions].
Draganić-Rajić, Saveta; Lecić-Tosevski, Dusica; Paunović, Vladimir R; Cvejić, Vesna; Svrakić, Dragan
2005-01-01
Attempts to understand the underlying mechanisms of association between psychological factors and panic disorder have been mostly based on psychodynamic description. Evidence of the importance of serotonergic (5-HT) system in panic disorder (PD), however, has substanti ally increased in recent years. The objective of our study was to determine whether there was a specific personality profile of panic disorder patients and how it was related to possible neurobiological mechanisms underlying personality dimensions. Sample consisted of 14 inpatients with ICD-X diagnosis of panic disorder and 34 healthy control subjects. Personality dimensions were assessed by Minnesota Multiphasic Personality Inventory (MMPI-201) and Tridimensional Personality Questionnaire (TPQ). To assess central 5-HT function, platelet monoamine-oxidase (MAO) activity was measured. In panic disorder group, higher scores of histrionic, depressive and hypochondriac subscales and significant increase of harm avoidance (HA) scale as well as low MAO activity were found. Negative correlation was established between MAO activity and psychopathic deviance MMPI scale. The obtained results might indicate a specific personality profile of patients with panic disorder, which is characterized by high neuroticism, fearfulness, inhibition, shyness and apprehensive worry. Low MAO activity and high HA scores possibly indicate underlying hyperserotonergic state. The observed correlation between personality traits and MAO activity provide additional support for the hypothesized functional relationship between underlying central monoaminergic activity and temperament traits associated with anxiety, depression and impulsivity.
Bishop-Fitzpatrick, Lauren; Mazefsky, Carla A; Eack, Shaun M
2017-06-01
Identifying modifiable correlates of good quality of life in adults with autism spectrum disorder is of paramount importance for intervention development as the population of adults with autism spectrum disorder increases. This study sought to examine social support and perceived stress as potential modifiable correlates of quality of life in adults with autism spectrum disorder. We hypothesized that adults with autism spectrum disorder without co-occurring intellectual disabilities ( N = 40; aged 18-44 years) would report lower levels of social support and quality of life than typical community volunteers who were matched for age, sex, and race ( N = 25). We additionally hypothesized that social support would buffer the effect of perceived stress on quality of life in adults with autism spectrum disorder. Results indicated that adults with autism spectrum disorder reported significantly lower levels of social support and quality of life than matched typical community volunteers. In addition, findings showed significant direct effects of social support and perceived stress on quality of life in adults with autism spectrum disorder. Social support did not buffer the effect of perceived stress on quality of life. Interventions that teach adults with autism spectrum disorder skills to help them better manage stress and cultivate supportive social relationships have the potential to improve quality of life.
Association of Rigid-Compulsive Behavior with Functional Constipation in Autism Spectrum Disorder
Marler, Sarah; Ferguson, Bradley J.; Lee, Evon Batey; Peters, Brittany; Williams, Kent C.; McDonnell, Erin; Macklin, Eric A.; Levitt, Pat; Margolis, Kara Gross; Beversdorf, David Q.; Veenstra-VanderWeele, Jeremy
2017-01-01
Based upon checklist data from the Autism Speaks Autism Treatment Network, we hypothesized that functional constipation (FC) would be associated with rigid-compulsive behavior in children with autism spectrum disorder (ASD). We used the Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III to assess FC symptoms in 108 children with ASD. As…
Chen, Mu-Hong; Su, Tung-Ping; Chen, Ying-Sheue; Hsu, Ju-Wei; Huang, Kai-Lin; Chang, Wen-Han; Chen, Tzeng-Ji; Bai, Ya-Mei
2013-01-01
Background: Previous cross-sectional studies have suggested an association between asthma and attention-deficit/hyperactivity disorder (ADHD), but the temporal relationship was not determined. Using a nationwide population-based prospective case-control cohort study (1:4, age-/gender-matched), we hypothesized that asthma in infanthood or early…
Rigid-Compulsive Behaviors Are Associated with Mixed Bowel Symptoms in Autism Spectrum Disorder
Peters, Brittany; Williams, Kent C.; Gorrindo, Phillip; Rosenberg, Daniel; Lee, Evon Batey; Levitt, Pat; Veenstra-VanderWeele, Jeremy
2014-01-01
Based on clinical experience, we hypothesized that rigid-compulsive behaviors are associated with severe constipation and co-occurring diarrhea or underwear staining in children with autism spectrum disorder. Using data from the Autism Treatment Network, we evaluated the association between these gastrointestinal symptoms and measures of rigid…
Slaats-Willemse, D.I.E.; Swaab-Barneveld, H.J.; Sonneville, L.M. de; Buitelaar, J.K.
2007-01-01
This study examined familiality of attentional control and mental flexibility in multiplex attention-deficit/hyperactivity disorder (ADHD) families. The authors hypothesized that siblings of ADHD probands, although not behaviorally expressing ADHD, have deficits in these executive functions and that
Jacobson, Robert B.; Parsley, Michael J.; Annis, Mandy L.; Colvin, Michael E.; Welker, Timothy L.; James, Daniel A.
2016-01-20
This report documents a process of filtering of hypotheses that relate Missouri River Scaphirhynchus albus (pallid sturgeon) population dynamics to management actions including flow alterations, channel reconfigurations, and pallid sturgeon population augmentation. The filtering process was a partnership among U.S. Geological Survey, U.S. Army Corps of Engineers, and U.S. Fish and Wildlife Service to contribute to the Missouri River Recovery Management Plan process. The objective of the filtering process was to produce a set of hypotheses with high relevance to pallid sturgeon population dynamics and decision making on the Missouri River. The Missouri River Pallid Sturgeon Effects Analysis team filtered hundreds of potential hypotheses implicit in conceptual ecological models to develop a set of 40 candidate dominant hypotheses that were identified by experts as being important in pallid sturgeon population dynamics. Using a modified Delphi process and additional expert opinion, the team reduced this set of hypotheses to 23 working dominant hypotheses. We then matched the 23 hypotheses with management actions that could influence the biotic outcomes, resulting in as many as 176 potential effects between management actions and pallid sturgeon in the Missouri River. This number was consolidated to a candidate set of 53 working management hypotheses because some management actions applied to multiple life stages of the pallid sturgeon. We used an additional round of expert surveys to identify a set of 30 working management hypotheses. Finally, the set of working management hypotheses was filtered by the U.S. Army Corps of Engineers, Missouri River Recovery Program for actions that were within the agency’s authority and jurisdiction. This round resulted in a set of 21 hypotheses for initial modeling of linkages from management to pallid sturgeon population responses.
Common and distinct brain networks underlying panic and social anxiety disorders.
Kim, Yong-Ku; Yoon, Ho-Kyoung
2018-01-03
Although panic disorder (PD) and phobic disorders are independent anxiety disorders with distinct sets of diagnostic criteria, there is a high level of overlap between them in terms of pathogenesis and neural underpinnings. Functional connectivity research using resting-state functional magnetic resonance imaging (rsfMRI) shows great potential in identifying the similarities and differences between PD and phobias. Understanding common and distinct networks between PD and phobic disorders is critical for identifying both specific and general neural characteristics of these disorders. We review recent rsfMRI studies and explore the clinical relevance of resting-state functional connectivity (rsFC) in PD and phobias. Although findings differ between studies, there are some meaningful, consistent findings. Social anxiety disorder (SAD) and PD share common default mode network alterations. Alterations within the sensorimotor network are observed primarily in PD. Increased connectivity in the salience network is consistently reported in SAD. This review supports hypotheses that PD and phobic disorders share common rsFC abnormalities and that the different clinical phenotypes between the disorders come from distinct brain functional network alterations. Copyright © 2017 Elsevier Inc. All rights reserved.
[An approach to the executive functions in autism spectrum disorder].
Martos-Pérez, Juan; Paula-Pérez, Isabel
2011-03-01
The psychological hypothesis of executive dysfunction plays a crucial role in explaining the behavioural phenotype of persons with autism spectrum disorders (ASD), along with other hypotheses such as the deficit in the theory of mind or the weak central coherence hypothesis. Yet, none of these hypotheses are mutually exclusive and behaviours that have their origins in one of these three hypotheses are also shaped and upheld by other processes and factors. This article reviews the behavioural manifestation and current state of research on the executive functions in persons with ASD. It also examines its impact on planning, mental flexibility and cognitive skills, generativity, response inhibition, mentalist skills and sense of activity. Although executive dysfunction has become more significant as a hypothesis explaining persons with ASD, there remain some important difficulties in need of further, more detailed research. Moreover, very few intervention programmes have been proved to be effective in minimising the effects of executive dysfunction in autism.
Gender Differences in Animal Models of Posttraumatic Stress Disorder
Directory of Open Access Journals (Sweden)
Hagit Cohen
2011-01-01
Full Text Available Epidemiological studies report higher prevalence rates of stress-related disorders such as acute stress disorder and post-traumatic stress disorder (PTSD in women than in men following exposure to trauma. It is still not clear whether this greater prevalence in woman reflects a greater vulnerability to stress-related psychopathology. A number of individual and trauma-related characteristics have been hypothesized to contribute to these gender differences in physiological and psychological responses to trauma, differences in appraisal, interpretation or experience of threat, coping style or social support. In this context, the use of an animal model for PTSD to analyze some of these gender-related differences may be of particular utility. Animal models of PTSD offer the opportunity to distinguish between biological and socio-cultural factors, which so often enter the discussion about gender differences in PTSD prevalence.
Opioid peptides and gastrointestinal symptoms in autism spectrum disorders
Directory of Open Access Journals (Sweden)
Cristiane P. Lázaro
2016-01-01
Full Text Available Autism spectrum disorders (ASDs are characterized by deficits in the individual’s ability to socialize, communicate, and use the imagination, in addition to stereotyped behaviors. These disorders have a heterogenous phenotype, both in relation to symptoms and regarding severity. Organic problems related to the gastrointestinal tract are often associated with ASD, including dysbiosis, inflammatory bowel disease, exocrine pancreatic insufficiency, celiac disease, indigestion, malabsorption, food intolerance, and food allergies, leading to vitamin deficiencies and malnutrition. In an attempt to explain the pathophysiology involved in autism, a theory founded on opioid excess has been the focus of various investigations, since it partially explains the symptomatology of the disorder. Another hypothesis has been put forward whereby the probable triggers of ASDs would be related to the presence of bacteria in the bowel, oxidative stress, and intestinal permeability. The present update reviews these hypotheses.
Juang, Kai Dih; Yang, Chin-Yi
2014-04-01
The fifth edition of the Diagnostic and Statistic Manual (DSM-5) reclassified some mental disorders recently. Post-traumatic stress disorder (PTSD) is in a new section termed "trauma- and stressor-related disorder". Community-based studies have shown that PTSD is associated with a notably high suicidal risk. In addition to previous findings of comorbidity between chronic daily headache (CDH) and both depressive disorders and anxiety disorders, recent data suggest that frequency of childhood maltreatment, PTSD, and suicidality are also increased in CDH. CDH patients with migraine aura are especially at risk of suicidal ideation. Research suggests that migraine attack, aura, frequency, and chronicity may all be related to serotonergic dysfunction. Vulnerability to PTSD and suicidality are also linked to brain serotonin function, including polymorphisms in the serotonin transporter gene (5-HTTLPR). In the present review, we focus on recent advances in knowledge of traumatic experiences in childhood, PTSD, and suicidality in relation to migraine and CDH. We hypothesize that vulnerability to PTSD is associated with migraine attack, migraine aura, and CDH. We further postulate that these associations may explain some of the elevated suicidal risks among patients with migraine, migraine aura, and/or CDH. Field studies are required to support these hypotheses.
Assessing hypotheses about nesting site occupancy dynamics
Bled, Florent; Royle, J. Andrew; Cam, Emmanuelle
2011-01-01
Hypotheses about habitat selection developed in the evolutionary ecology framework assume that individuals, under some conditions, select breeding habitat based on expected fitness in different habitat. The relationship between habitat quality and fitness may be reflected by breeding success of individuals, which may in turn be used to assess habitat quality. Habitat quality may also be assessed via local density: if high-quality sites are preferentially used, high density may reflect high-quality habitat. Here we assessed whether site occupancy dynamics vary with site surrogates for habitat quality. We modeled nest site use probability in a seabird subcolony (the Black-legged Kittiwake, Rissa tridactyla) over a 20-year period. We estimated site persistence (an occupied site remains occupied from time t to t + 1) and colonization through two subprocesses: first colonization (site creation at the timescale of the study) and recolonization (a site is colonized again after being deserted). Our model explicitly incorporated site-specific and neighboring breeding success and conspecific density in the neighborhood. Our results provided evidence that reproductively "successful'' sites have a higher persistence probability than "unsuccessful'' ones. Analyses of site fidelity in marked birds and of survival probability showed that high site persistence predominantly reflects site fidelity, not immediate colonization by new owners after emigration or death of previous owners. There is a negative quadratic relationship between local density and persistence probability. First colonization probability decreases with density, whereas recolonization probability is constant. This highlights the importance of distinguishing initial colonization and recolonization to understand site occupancy. All dynamics varied positively with neighboring breeding success. We found evidence of a positive interaction between site-specific and neighboring breeding success. We addressed local
Corrigendum to: Bayesian evaluation of informative hypotheses in SEM using Mplus
van de Schoot, R.; Verhoeven, Marjolein; Hoijtink, H.
2014-01-01
This paper corrects: van de Schoot, R., Verhoeven, M., & Hoijtink, H. (2013). Bayesian evaluation ofinformative hypotheses in SEM using Mplus: A black bear story. EuropeanJournal of Developmental Psychology, 10, 81 –98.
Lithium in drinking water and the incidence of bipolar disorder
DEFF Research Database (Denmark)
Kessing, Lars V; Gerds, Thomas A; Knudsen, Nikoline N
2017-01-01
OBJECTIVE: Animal data suggest that subtherapeutic doses, including micro doses, of lithium may influence mood, and lithium levels in drinking water have been found to correlate with the rate of suicide. It has never been investigated whether consumption of lithium may prevent the development...... of bipolar disorder (primary prophylaxis). In a nation-wide population-based study, we investigated whether long-term exposure to micro levels of lithium in drinking water correlates with the incidence of bipolar disorder in the general population, hypothesizing an inverse association in which higher long......-term lithium exposure is associated with lower incidences of bipolar disorder. METHODS: We included longitudinal individual geographical data on municipality of residence, data from drinking water lithium measurements and time-specific data from all cases with a hospital contact with a diagnosis of mania...
van Ee, Elisa; Jongmans, Marian J; van der Aa, Niels; Kleber, Rolf J
2016-01-01
It has been hypothesized that adult attachment representations guide caregiving behavior and influence parental sensitivity, and thus affect the child's socio-emotional development. Several studies have shown a link between posttraumatic stress disorder (PTSD) and reduced parental sensitivity, so it
[Management of insomnia and hypersomnia associated with psychiatric disorders].
Uchiyama, Makoto; Suzuki, Masahiro; Konno, Chisato; Furihata, Ryuji; Osaki, Koichi; Konno, Michiko; Takahashi, Sakae
2010-01-01
Most psychiatric disorders, such as schizophrenia, mood disorders, or neurotic disorders are associated with sleep disorders of various kinds, among which insomnia is most prevalent and important in psychiatric practice. Almost all patients suffering from major depression complain of insomnia. Pharmacological treatment of insomnia associated with major depression shortens the duration to achieve remission of depression. Insomnia has been recently reported to be a risk factor for depression. Hypersomnia is also a major sleep problem in patient suffering from depression. There have been no clinical guide to treat the symptoms of hypersomnia in depression, but some clinical trials treating them with NDRI or adjunctive administration of psychostimulants. In patients with schizophrenia, insomnia is often an early indicator of the aggravation of psychotic symptoms. Electroencephalographic sleep studies have also revealed sleep abnormalities characteristic to mood disorders, schizophrenia and anxiety disorders. A shortened REM sleep latency has been regarded as a biological marker of depression. Reduced amount of deep Non-REM sleep has been reported to be correlated with negative symptoms of schizophrenia. Recently, REM sleep abnormalities were found in teenagers having post-traumatic stress disorder after a boat accident. Although these facts indicate that insomnia plays an important role in the development of psychiatric disorders, there are few hypotheses explaining the cause and effect of insomnia in these disorders. Here, we reviewed recent articles on insomnia and hypersomnia associated with psychiatric disorders together with their clinical managements.
Deformational plagiocephaly in normal infants: a systematic review of causes and hypotheses.
De Bock, Freia; Braun, Volker; Renz-Polster, Herbert
2017-06-01
Deformational plagiocephaly (DP) is one of the most prevalent abnormal findings in infants and a frequent reason for parents to seek paediatric advice. To systematically review the literature and identify evidence and hypotheses on the aetiology and determinants of DP in otherwise healthy infants. Systematic keyword search in all major biomedical databases to identify peer-reviewed publications reporting (a) empirical research or (b) hypotheses on the aetiology of DP in healthy, term infants. 3150 studies published between 1985 and 2016 and containing relevant keywords were screened. In a two-pronged approach, results were summarised separately for the body of empirical work (22 studies) and the body of hypotheses (110 articles). Only a few empirical studies have examined risk factors in non-selected patient populations on a higher grade methodological level. The most commonly reported risk factors were: male gender, supine sleep position, limited neck rotation or preference in head position, first-born child, lower level of activity and lack of tummy time. Agreement between empirical studies was poor for most exposures, including supine sleep position, tummy time and use of car seats. The articles reporting hypotheses on the aetiology of DP cover a wide field of environmental and biological factors, but include little suggestions as to the potential influence of the everyday care environment of the baby. The evidence on the aetiology of DP is fragmentary and heterogeneous. In addition, factors possibly relevant to the development of DP have not been appreciated in the scientific discussion. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Wilde, V
1992-02-01
This paper addresses methodological issues that emerged unexpectedly during a qualitative study set up to explore nurses' descriptions of difficult, challenging and satisfying experiences at work. The purpose of the study had been to look for critical factors influencing nurses' perceptions of their performance in specific situations, and their labelling of each event. Ten nurses were asked to describe in detail three events; a difficult situation in which they had coped well, a difficult situation in which they would like to have coped better, and a satisfying or rewarding situation. The critical incident technique was used. Rich descriptions were obtained, tape recorded, transcribed verbatum, and analysed by constant comparative analysis, following the principles of grounded theory. Some suprising hypotheses emerged regarding the methodology of the informal interview in qualitative research. This paper addresses these hypotheses, which focus on the interaction between the researcher and informant, the role conflict facing the nurse researcher, the effect of the researcher's past experience on the interaction, the use of counselling strategies and the principle of self-disclosure. These hypotheses were incidental to the original area of study and were more exciting in their emergence because of this.
Bicanic, Iva A. E.; Postma, Riemke M.; Sinnema, Gerben; de Roos, Carlijn; Olff, Miranda; van Wesel, Floryt; van de Putte, Elise M.
2013-01-01
In chronic sexual abuse victims with post traumatic stress disorder (PTSD), the hypothalamic pituitary adrenal (HPA) axis can be dysregulated. In single rape victims, PTSD symptoms are hypothesized to function as a chronic stressor leading to similar HPA-axis dysregulation. The objective of the
Estimating the Proportion of True Null Hypotheses in Multiple Testing Problems
Directory of Open Access Journals (Sweden)
Oluyemi Oyeniran
2016-01-01
Full Text Available The problem of estimating the proportion, π0, of the true null hypotheses in a multiple testing problem is important in cases where large scale parallel hypotheses tests are performed independently. While the problem is a quantity of interest in its own right in applications, the estimate of π0 can be used for assessing or controlling an overall false discovery rate. In this article, we develop an innovative nonparametric maximum likelihood approach to estimate π0. The nonparametric likelihood is proposed to be restricted to multinomial models and an EM algorithm is also developed to approximate the estimate of π0. Simulation studies show that the proposed method outperforms other existing methods. Using experimental microarray datasets, we demonstrate that the new method provides satisfactory estimate in practice.
Gender identity and sexual orientation in autism spectrum disorder.
George, Rita; Stokes, Mark A
2017-09-01
Clinical impressions indicate that there is an overrepresentation of gender-dysphoria within the autism spectrum disorder. However, little is presently known about the demographics of gender-identity issues in autism spectrum disorder. Based upon what little is known, we hypothesized that there would be an increased prevalence of gender-dysphoria among those with autism spectrum disorder compared to a typically developing population. We surveyed gender-dysphoria with the Gender-Identity/Gender-Dysphoria Questionnaire among 90 males and 219 females with autism spectrum disorder and compared these rates to those of 103 males and 158 females without autism spectrum disorder. When compared to typically developing individuals, autistic individuals reported a higher number of gender-dysphoric traits. Rates of gender-dysphoria in the group with autism spectrum disorder were significantly higher than reported in the wider population. Mediation analysis found that the relationship between autistic traits and sexual orientation was mediated by gender-dysphoric traits. Results suggest that autism spectrum disorder presents a unique experience to the formation and consolidation of gender identity, and for some autistic individuals, their sexual orientation relates to their gender experience. It is important that clinicians working with autism spectrum disorder are aware of the gender-diversity in this population so that the necessary support for healthy socio-sexual functioning and mental well-being is provided.
Electrocardiographic features of sudden unexpected death in epilepsy.
Chyou, Janice Y; Friedman, Daniel; Cerrone, Marina; Slater, William; Guo, Yu; Taupin, Daniel; O'Rourke, Sean; Priori, Silvia G; Devinsky, Orrin
2016-07-01
Sudden unexpected death in epilepsy (SUDEP) is the most common cause of epilepsy-related mortality. We hypothesized that electrocardiography (ECG) features may distinguish SUDEP cases from living subjects with epilepsy. Using a matched case-control design, we compared ECG studies of 12 consecutive cases of SUDEP over 10 years and 22 epilepsy controls matched for age, sex, epilepsy type (focal, generalized, or unknown/mixed type), concomitant antiepileptic, and psychotropic drug classes. Conduction intervals and prevalence of abnormal ventricular conduction diagnosis (QRS ≥110 msec), abnormal ventricular conduction pattern (QRS <110 msec, morphology of incomplete right or left bundle branch block or intraventricular conduction delay), early repolarization, and features of inherited cardiac channelopathies were assessed. Abnormal ventricular conduction diagnosis and pattern distinguished SUDEP cases from matched controls. Abnormal ventricular conduction diagnosis was present in two cases and no controls. Abnormal ventricular conduction pattern was more common in cases than controls (58% vs. 18%, p = 0.04). Early repolarization was similarly prevalent in cases and controls, but the overall prevalence exceeded that of published community-based cohorts. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.
Sutherland, Kevin S.; Singh, Nirbhay N.
2004-01-01
Students with emotional or behavioral disorders (E/BD) are characterized by academic deficits and classroom behavioral problems. The relationship between problem behavior and academic difficulties is complex, and some researchers have hypothesized that the classroom behavior problems of students with E/BD are responses to aversive stimuli, namely…
Murphy, T K; Storch, E A; Turner, A; Reid, J M; Tan, J; Lewin, A B
2010-12-15
A commonality across a number of pediatric neuropsychiatric disorders is a higher than typical rate of familial - and especially maternal - autoimmune disease. Of recent interest, a subtype of obsessive-compulsive disorder (OCD) and tic disorders known collectively as Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) is believed to be secondary to central nervous system (CNS) autoimmunity that occurs in relation to group A streptococcal infection. Thus, we hypothesized that a sample of children with OCD and/or tics would have an increased maternal risk for an autoimmune response relative to population norms. We also expected maternal prevalence of various autoimmune diseases to be higher among those participants that met the putative criteria for PANDAS. We examined, via structured interview, the medical history of the biological mothers of 107 children with OCD and/or tics. Autoimmune disorders were reported in 17.8% of study mothers, which is significantly greater than the general prevalence among women in the United States (approximately 5%). Further, study mothers were more likely to report having an autoimmune disease if their children were considered "likely PANDAS" cases versus "unlikely PANDAS" cases. The results offer preliminary support for hypothesized links between maternal autoimmune disease and both OCD/tics and PANDAS in youth. Further research is necessary to clarify these general associations; links to specific autoimmune disease; and relevance of autoimmune disease in other family members (e.g., fathers). Copyright © 2010 Elsevier B.V. All rights reserved.
Association between otalgia, tinnitus, vertigo and hypoacusia, with temporomandibular disorders
Directory of Open Access Journals (Sweden)
Francisco Guedes Pereira de Alencar Junior
2009-01-01
Full Text Available Because nonespecific symptoms and signs are associated with others well-established in the temporomandibular disorders, it is difficult for the clinician to decide what symptoms and signs should be considered during the diagnosis and the treatment plan. Therefore, the aim of this literature review was to evaluate the prevalence of aural symptoms (otalgias, tinnitus, dizziness and deafness in patients with orofacial pain. Although several hypotheses have been proposed to explain the association between aural symptoms and temporomandibular disorders, the results of the previous studies differed in magnitude. For this reason, it is difficult to establish the prevalence of these aural symptoms concomitantly with temporomandibular disorders. Moreover, such relationship does not necessarily imply a cause-effect relationship. Because of the diagnosis complexity, different treatments must be considered, so the nonespecific symptoms of temporomandibular disorders can be effectively controlled as well. It is crucial for the the clinician to be aware of the possible etiology of aural symptoms, so he should determine if such symptoms may be associated with temporomandibular disorders and thus include them in the treatment.
Treatment dropout in drug-addicted women: are eating disorders implicated?
Bonfà, F; Cabrini, S; Avanzi, M; Bettinardi, O; Spotti, R; Uber, E
2008-06-01
A high prevalence of eating disorders among drug-addicted female patients has been noted, and it could be associated to psychopathological underlying factors. Our aim was to assess eating disorder traits in women approaching a residential program for drug addiction. We hypothesized that these traits would correlate to more general psychopathological factors, and would influence treatment relapse. A sample of 204 substance dependent women attending a residential treatment was screened for psychopathological indices, and follow-up data were obtained at the end of the treatment. Clients had a high risk for eating disorders (15%), and lifetime prevalence was even higher (20%). Disordered eating was associated to psychopathological distress, in particular harm avoidance resulted significantly lower (p=0.005), evoking higher unresponsiveness to danger. Drug addiction treatment outcome is associated to completion of defined programs, and eating disorder was a key covariable in determining treatment relapse or success (p=0.03). Clinicians should be aware of this potential co-morbidity, and concurrent treatments should be attempted, in order to prevent symptomatic shifting.
Support for major hypotheses in invasion biology is uneven and declining
Czech Academy of Sciences Publication Activity Database
Jeschke, J.M.; Aparicio, L.G.; Haider, S.; Heger, T.; Lortie, C. J.; Pyšek, Petr; Strayer, D.L.
2012-01-01
Roč. 2012, č. 14 (2012), s. 1-20 ISSN 1619-0033 R&D Projects: GA ČR(CZ) GAP504/11/1028 Institutional support: RVO:67985939 Keywords : biological invasions * hypotheses * testing Subject RIV: EF - Botanics
Global warming and neurodegenerative disorders: speculations on their linkage
Habibi, Laleh; Perry, George; Mahmoudi, Morteza
2014-01-01
Climate change is having considerable impact on biological systems. Eras of ice ages and warming shaped the contemporary earth and origin of creatures including humans. Warming forces stress conditions on cells. Therefore, cells evolved elaborate defense mechanisms, such as creation of heat shock proteins, to combat heat stress. Global warming is becoming a crisis and this process would yield an undefined increasing rate of neurodegenerative disorders in future decades. Since heat stress is known to have a degenerative effects on neurons and, conversely, cold conditions have protective effect on these cells, we hypothesize that persistent heat stress forced by global warming might play a crucial role in increasing neurodegenerative disorders. PMID:25671171
Axelsson, Erland; Andersson, Erik; Ljótsson, Brjánn; Wallhed Finn, Daniel; Hedman, Erik
2016-06-01
Somatic symptom disorder (SSD) and illness anxiety disorder (IAD) are two new diagnoses introduced in the DSM-5. There is a need for reliable instruments to facilitate the assessment of these disorders. We therefore developed a structured diagnostic interview, the Health Preoccupation Diagnostic Interview (HPDI), which we hypothesized would reliably differentiate between SSD, IAD, and no diagnosis. Persons with clinically significant health anxiety (n = 52) and healthy controls (n = 52) were interviewed using the HPDI. Diagnoses were then compared with those made by an independent assessor, who listened to audio recordings of the interviews. Ratings generally indicated moderate to almost perfect inter-rater agreement, as illustrated by an overall Cohen's κ of .85. Disagreements primarily concerned (a) the severity of somatic symptoms, (b) the differential diagnosis of panic disorder, and (c) SSD specifiers. We conclude that the HPDI can be used to reliably diagnose DSM-5 SSD and IAD.
Serial Learning Process: Test of Chaining, Position, and Dual-Process Hypotheses
Giurintano, S. L.
1973-01-01
The chaining, position, and dual-process hypotheses of serial learning (SL) as well as serial recall, reordering, and relearning of paired-associate learning were examined to establish learning patterns. Results provide evidence for dual-process hypothesis. (DS)
Breslau, Joshua; Borges, Guilherme; Tancredi, Daniel; Saito, Naomi; Kravitz, Richard; Hinton, Ladson; Vega, William; Medina-Mora, Maria Elena; Aguilar-Gaxiola, Sergio
2013-01-01
Objective To test the hypothesized increase in risk for depressive and anxiety disorders following arrival in the US among Mexican-origin migrants. Method Data from surveys conducted in Mexico and the US were combined. The surveys were conducted separately, but used the same structured diagnostic interview. Discrete time survival models were specified to estimate the relative odds of first onset of depressive (major depressive episode, dysthymia) and anxiety (generalized anxiety disorder, social phobia, panic disorder, posttraumatic stress disorder) disorders among migrants after their arrival in the US compared with non-migrant Mexicans who have a migrant in their immediate family. Results After arrival in the US, migrants had signficantly higher risk for first onset of any depressive or anxiety disorder than non-migrant family members of migrants in Mexico (OR=1.4, 95% CI =1.04–1.94). Associations between migration and disorder varied across birth cohorts. Elevated risk among migrants relative to non-migrants was restricted to the two younger cohorts, those 18–25 or 26–35 years old at interview. In the most recent cohort, the association between migration and first onset of any depressive or anxiety disorder was particularly strong (OR=3.89, 95% CI=2.74–5.53). Conclusions This is the first study to compare risk for first onset of psychaitric disorder between representative samples of migrants in the US and non-migrants in Mexico. The findings are consistent with the hypothesized adverse effect of migration from Mexico to the US on the mental health of migrants, but only among migrants in recent birth cohorts. PMID:21464367
Lanza, Gaetano Antonio; Argirò, Alessia; Mollo, Roberto; De Vita, Antonio; Spera, Francesco; Golino, Michele; Rota, Elisabetta; Filice, Monica; Crea, Filippo
2017-12-01
"Early repolarization" (ER) is a frequent finding at standard electrocardiogram (ECG). In this study we assessed whether ER is associated with an increased risk of events, as recently suggested by some studies. We prospectively enrolled 4,176 consecutive subjects without any heart disease who underwent routine ECG recording. ER was diagnosed in case of typical concave ST-segment elevation ≥0.1 mV; a J wave was diagnosed when the QRS showed a notch or a slur in its terminal part. In this study we compared the 6-year outcome of all 687 subjects with ER/J wave and 687 matched subjects without ER/J wave (controls). Both groups included 335 males and 352 females, and age was 48.8 ± 18 years. Overall, 145 deaths occurred (11%), only 11 of which attributed to cardiac causes. No sudden death was reported. Cardiac deaths occurred in 5 (0.8%) and 6 (0.9%) ER/J wave subjects and controls, respectively (odds ratio [OR] 0.85, 95% confidence interval [CI] 0.26 to 2.80, p = 0.79). Both ER (OR 1.68, 95% CI 0.21 to 13.3, p = 0.62) and J wave (OR 0.91, 95% CI 0.28 to 3.00, p = 0.88) showed no association with cardiac death. Total mortality was 11.5% in the ER/J wave group and 10.6% in the control group (OR 1.10, 95% CI 0.78 to 1.56, p = 0.58). Both ER (OR 0.44, 95% CI 0.16 to 1.24, p = 0.12) and J wave (OR 1.20, 95% CI 0.85 to 1.70, p = 0.30) showed also no association with all-cause death. In subjects without any evidence of heart disease, we found no significant association of ER/J wave with the risk of cardiac, as well as all-cause, death at medium-term follow-up. Copyright © 2017 Elsevier Inc. All rights reserved.
DEFF Research Database (Denmark)
Knudsen, Stine; Gammeltoft, Steen; Jennum, Poul J
2010-01-01
variables were analysed in relation to cataplexy and hypocretin deficiency with uni- and multivariate logistic/linear regression models, controlling for possible rapid eye movement sleep behaviour disorder biasing factors (age, gender, disease duration, previous anti-cataplexy medication). Only hypocretin......Rapid eye movement sleep behaviour disorder is characterized by dream-enacting behaviour and impaired motor inhibition during rapid eye movement sleep. Rapid eye movement sleep behaviour disorder is commonly associated with neurodegenerative disorders, but also reported in narcolepsy with cataplexy....... Most narcolepsy with cataplexy patients lack the sleep-wake, and rapid eye movement sleep, motor-regulating hypocretin neurons in the lateral hypothalamus. In contrast, rapid eye movement sleep behaviour disorder and hypocretin deficiency are rare in narcolepsy without cataplexy. We hypothesized...
The Role of Emotion Perception in Adaptive Functioning of People with Autism Spectrum Disorders
Hudepohl, Margaret B.; Robins, Diana L.; King, Tricia Z.; Henrich, Christopher C.
2015-01-01
Cognitive functioning has historically been used to predict adaptive outcomes of people with autism spectrum disorders; however, research shows that it is not a complete predictor. The current study explored whether emotion perception was a predictor of adaptive outcomes, and more specifically, hypothesized that emotion perception (Diagnostic…
Klein, Harriet B.; Liu-Shea, May
2009-01-01
Purpose: This study was designed to identify and describe between-word simplification patterns in the continuous speech of children with speech sound disorders. It was hypothesized that word combinations would reveal phonological changes that were unobserved with single words, possibly accounting for discrepancies between the intelligibility of…
Skin Stem Cell Hypotheses and Long Term Clone Survival - Explored Using Agent-based Modelling
Li, X.; Upadhyay, A.K.; Bullock, A.J.; Dicolandrea, T.; Xu, J.; Binder, R.L.; Robinson, M.K.; Finlay, D.R.; Mills, K.J.; Bascom, C.C.; Kelling, C.K.; Isfort, R.J.; Haycock, J.W.; MacNeil, S.; Smallwood, R.H.
2013-01-01
Epithelial renewal in skin is achieved by the constant turnover and differentiation of keratinocytes. Three popular hypotheses have been proposed to explain basal keratinocyte regeneration and epidermal homeostasis: 1) asymmetric division (stem-transit amplifying cell); 2) populational asymmetry (progenitor cell with stochastic fate); and 3) populational asymmetry with stem cells. In this study, we investigated lineage dynamics using these hypotheses with a 3D agent-based model of the epiderm...
Neuromotor Deficits in Developmental Coordination Disorder: Evidence from a Reach-to-Grasp Task
Biancotto, Marina; Skabar, Aldo; Bulgheroni, Maria; Carrozzi, Marco; Zoia, Stefania
2011-01-01
Developmental coordination disorder (DCD) has been classified as a specific learning disability, nonetheless the underlying cognitive mechanisms are still a matter of discussion. After a summary of the main hypotheses on the principal neuromotor causes of DCD, this study applies a causal model framework to describe the possible coexistence of more…
Mechanistic Mathematical Modeling Tests Hypotheses of the Neurovascular Coupling in fMRI.
Directory of Open Access Journals (Sweden)
Karin Lundengård
2016-06-01
Full Text Available Functional magnetic resonance imaging (fMRI measures brain activity by detecting the blood-oxygen-level dependent (BOLD response to neural activity. The BOLD response depends on the neurovascular coupling, which connects cerebral blood flow, cerebral blood volume, and deoxyhemoglobin level to neuronal activity. The exact mechanisms behind this neurovascular coupling are not yet fully investigated. There are at least three different ways in which these mechanisms are being discussed. Firstly, mathematical models involving the so-called Balloon model describes the relation between oxygen metabolism, cerebral blood volume, and cerebral blood flow. However, the Balloon model does not describe cellular and biochemical mechanisms. Secondly, the metabolic feedback hypothesis, which is based on experimental findings on metabolism associated with brain activation, and thirdly, the neurotransmitter feed-forward hypothesis which describes intracellular pathways leading to vasoactive substance release. Both the metabolic feedback and the neurotransmitter feed-forward hypotheses have been extensively studied, but only experimentally. These two hypotheses have never been implemented as mathematical models. Here we investigate these two hypotheses by mechanistic mathematical modeling using a systems biology approach; these methods have been used in biological research for many years but never been applied to the BOLD response in fMRI. In the current work, model structures describing the metabolic feedback and the neurotransmitter feed-forward hypotheses were applied to measured BOLD responses in the visual cortex of 12 healthy volunteers. Evaluating each hypothesis separately shows that neither hypothesis alone can describe the data in a biologically plausible way. However, by adding metabolism to the neurotransmitter feed-forward model structure, we obtained a new model structure which is able to fit the estimation data and successfully predict new
Huguelet, Philippe; Guillaume, Sébastien; Vidal, Sonia; Mohr, Sylvia; Courtet, Philippe; Villain, Lucile; Girod, Chloé; Hasler, Roland; Prada, Paco; Olié, Emilie; Perroud, Nader
2016-06-08
Recovery is a personal process of growth that involves hope, self-identity, meaning in life and responsibility. Determinants of meaning have not been explored among populations of patients with persistent psychiatric conditions. However, an evidence-based approach aiming at assessing such determinants should provide some insight into the psychotherapeutic aspects of recovery. We tested a model hypothesizing that some symptoms and social parameters of patients are related to values, and secondarily to meaning in life, and in turn that meaning is associated with various parameters, such as depressiveness and self-esteem. We assessed 176 patients with schizophrenia, anorexia, borderline personality disorder and bipolar disorder. Overall, our hypotheses proved correct: firstly, characteristics such as depression, hopelessness, self-esteem and the number of relationships influenced values; secondly, the presence and an enactment of values were associated with meaning, and thirdly, meaning was associated with some symptoms and social characteristics. This model was confirmed in the four psychiatric populations under study. These results support the relevance of addressing values and meaning in the recovery-oriented care of patients with persistent psychiatric disorders, in addition to other psychosocial interventions which are more systematically considered in this area.
DEFF Research Database (Denmark)
Romijn, Geke; Riper, Heleen; Kok, Robin
2015-01-01
BACKGROUND: Anxiety disorders are among the most prevalent psychiatric conditions, and are associated with poor quality of life and substantial economic burden. Cognitive behavioural therapy is an effective treatment to reduce anxiety symptoms, but is also costly and labour intensive. Cost......-effectiveness could possibly be improved by delivering cognitive behavioural therapy in a blended format, where face-to-face sessions are partially replaced by online sessions. The aim of this trial is to determine the cost-effectiveness of blended cognitive behavioural therapy for adults with anxiety disorders, i.......e. panic disorder, social phobia or generalized anxiety disorder, in specialized mental health care settings compared to face-to-face cognitive behavioural therapy. In this paper, we present the study protocol. It is hypothesized that blended cognitive behavioural therapy for anxiety disorders...
Vestigial Biological Structures: A Classroom-Applicable Test of Creationist Hypotheses
Senter, Phil; Ambrocio, Zenis; Andrade, Julia B.; Foust, Katanya K.; Gaston, Jasmine E.; Lewis, Ryshonda P.; Liniewski, Rachel M.; Ragin, Bobby A.; Robinson, Khanna L.; Stanley, Shane G.
2015-01-01
Lists of vestigial biological structures in biology textbooks are so short that some young-Earth creationist authors claim that scientists have lost confidence in the existence of vestigial structures and can no longer identify any verifiable ones. We tested these hypotheses with a method that is easily adapted to biology classes. We used online…
Political Participation Online: The Replacement and the Mobilisation Hypotheses Revisited
DEFF Research Database (Denmark)
Jensen, Jakob Linaa
2013-01-01
This article discusses the state of political participation online more than ten years after the Internet’s great popular breakthrough as an everyday medium. Denmark is used as a case study to critically re-examine the frequently discussed replacement and mobilisation hypotheses on behalf of the ...... participation, efficacy and social capital seem to have less impact on online political participation. In the end, these findings are related to more overall discussions on the democratising potential of the Internet.......This article discusses the state of political participation online more than ten years after the Internet’s great popular breakthrough as an everyday medium. Denmark is used as a case study to critically re-examine the frequently discussed replacement and mobilisation hypotheses on behalf...... of the Internet. The pure replacement hypothesis is rejected. Instead, it is found that the Internet still supplements rather than replaces other media, even among heavy Internet users. The Internet is one among several media used by ‘media omnivores’, and political participation online supplements rather than...
Panic disorder: Psychobiological aspects of personality dimensions
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Draganić-Gajić Saveta
2005-01-01
Full Text Available Attempts to understand the underlying mechanisms of association between psychological factors and panic disorder have been mostly based on psychodynamic description. Evidence of the importance of serotonergic (5-HT system in panic disorder (PD, however, has substanti ally increased in recent years. OBJECTIVE The objective of our study was to determine whether there was a specific personality profile of panic disorder patients and how it was related to possible neurobiological mechanisms underlying personality dimensions. PATIENTS AND METHODS Sample consisted of 14 inpatients with ICD-X diagnosis of panic disorder and 34 healthy control subjects. Personality dimensions were assessed by Minnesota Multiphasic Personality Inventory (MMPI-201 and Tridimensional Personality Questionnaire (TPQ. To assess central 5-HT function, platelet monoamine-oxidase (MAO activity was measured. RESULTS In panic disorder group, higher scores of histrionic, depressive and hypochondriac subscales and significant increase of harm avoidance (HA scale as well as low MAO activity were found. Negative correlation was established between MAO activity and psychopathic deviance MMPI scale. CONCLUSION The obtained results might indicate a specific personality profile of patients with panic disorder, which is characterized by high neuroticism, fearfulness, inhibition, shyness and apprehensive worry. Low MAO activity and high HA scores possibly indicate underlying hyperserotonergic state. The observed correlation between personality traits and MAO activity provide additional support for the hypothesized functional relationship between underlying central monoaminergic activity and temperament traits associated with anxiety, depression and impulsivity.
Eating disorders: Insights from imaging and behavioral approaches to treatment.
Stice, Eric; Shaw, Heather
2017-11-01
Understanding factors that contribute to eating disorders, which affect 13% of females, is critical to developing effective prevention and treatment programs. In this paper, we summarize results from prospective studies that identified factors predicting onset and persistence of eating disorders and core symptom dimensions. Next, implications for intervention targets for prevention, and treatment interventions from the risk- and maintenance-factor findings are discussed. Third, given that evidence suggests eating disorders are highly heritable, implying biological risk and maintenance factors for eating disorders, we offer working hypotheses about biological factors that might contribute to eating disorders, based on extant risk factor findings, theory, and cross-sectional studies. Finally, potentially fruitful directions for future research are presented. We suggest that it would be useful for experimental therapeutics trials to evaluate the effects of reducing the risk factors on future onset of eating pathology and on reducing maintenance factors on the risk for persistence of eating pathology, and encourage researchers to utilize prospective high-risk studies so that knowledge regarding potential intervention targets for prevention and treatment interventions for eating disorders can be advanced. Using the most rigorous research designs should help improve the efficacy of prevention and treatment interventions for eating disorders.
Khamis, Vivian
2012-01-01
This study was designed to assess whether the symptoms of posttraumatic stress mediate or moderate the relationship between political stressors and emotional and behavioral disorders in Palestinian children. It was hypothesized that (a) posttraumatic stress and worry mediate the effect of political stressors on behavioral and emotional disorders and (b) the relationship between political stressors and behavioral and emotional disorders should be attenuated for children with low levels of worry and posttraumatic stress and strengthened for children with high levels of worry and posttraumatic stress. The total sample was 1267 school age children of both sexes with a mean age of 11.97 years. Interviews were conducted with children at school. As hypothesized, the results indicated that posttraumatic stress and worry mediated and moderated the relationship between political stressors and emotional and behavioral disorders in children. Cognitive-behavioral therapy may be used to reduce the incidence of posttraumatic stress and decrease self-reported worry, somatic symptoms, general anxiety, and depression among children exposed to political trauma. Cognitive-behavioral treatment that exclusively targets excessive worry can lead to clinical change in the other interacting subsystems at the cognitive, physiological, affective and behavioral levels.
Resick, Patricia A.; Williams, Lauren F.; Suvak, Michael K.; Monson, Candice M.; Gradus, Jaimie L.
2012-01-01
Objective: We conducted a long-term follow-up (LTFU) assessment of participants from a randomized controlled trial comparing cognitive processing therapy (CPT) with prolonged exposure (PE) for posttraumatic stress disorder (PTSD). Competing hypotheses for positive outcomes (i.e., additional therapy, medication) were examined. Method:…
Anxiety, stress and perfectionism in bipolar disorder.
Corry, Justine; Green, Melissa; Roberts, Gloria; Frankland, Andrew; Wright, Adam; Lau, Phoebe; Loo, Colleen; Breakspear, Michael; Mitchell, Philip B
2013-12-01
Previous reports have highlighted perfectionism and related cognitive styles as a psychological risk factor for stress and anxiety symptoms as well as for the development of bipolar disorder symptoms. The anxiety disorders are highly comorbid with bipolar disorder but the mechanisms that underpin this comorbidity are yet to be determined. Measures of depressive, (hypo)manic, anxiety and stress symptoms and perfectionistic cognitive style were completed by a sample of 142 patients with bipolar disorder. Mediation models were used to explore the hypotheses that anxiety and stress symptoms would mediate relationships between perfectionistic cognitive styles, and bipolar disorder symptoms. Stress and anxiety both significantly mediated the relationship between both self-critical perfectionism and goal attainment values and bipolar depressive symptoms. Goal attainment values were not significantly related to hypomanic symptoms. Stress and anxiety symptoms did not significantly mediate the relationship between self-critical perfectionism and (hypo)manic symptoms. 1. These data are cross-sectional; hence the causality implied in the mediation models can only be inferred. 2. The clinic patients were less likely to present with (hypo)manic symptoms and therefore the reduced variability in the data may have contributed to the null findings for the mediation models with (hypo) manic symptoms. 3. Those patients who were experiencing current (hypo)manic symptoms may have answered the cognitive styles questionnaires differently than when euthymic. These findings highlight a plausible mechanism to understand the relationship between bipolar disorder and the anxiety disorders. Targeting self-critical perfectionism in the psychological treatment of bipolar disorder when there is anxiety comorbidity may result in more parsimonious treatments. © 2013 Published by Elsevier B.V.
Swanson, Sonja A; Labrecque, Jeremy; Hernán, Miguel A
2018-05-02
Sometimes instrumental variable methods are used to test whether a causal effect is null rather than to estimate the magnitude of a causal effect. However, when instrumental variable methods are applied to time-varying exposures, as in many Mendelian randomization studies, it is unclear what causal null hypothesis is tested. Here, we consider different versions of causal null hypotheses for time-varying exposures, show that the instrumental variable conditions alone are insufficient to test some of them, and describe additional assumptions that can be made to test a wider range of causal null hypotheses, including both sharp and average causal null hypotheses. Implications for interpretation and reporting of instrumental variable results are discussed.
Using personality neuroscience to study personality disorder.
Abram, Samantha V; DeYoung, Colin G
2017-01-01
Personality neuroscience integrates techniques from personality psychology and neuroscience to elucidate the neural basis of individual differences in cognition, emotion, motivation, and behavior. This endeavor is pertinent not only to our understanding of healthy personality variation, but also to the aberrant trait manifestations present in personality disorders and severe psychopathology. In the current review, we focus on the advances and limitations of neuroimaging methods with respect to personality neuroscience. We discuss the value of personality theory as a means to link specific neural mechanisms with various traits (e.g., the neural basis of the "Big Five"). Given the overlap between dimensional models of normal personality and psychopathology, we also describe how researchers can reconceptualize psychopathological disorders along key dimensions, and, in turn, formulate specific neural hypotheses, extended from personality theory. Examples from the borderline personality disorder literature are used to illustrate this approach. We provide recommendations for utilizing neuroimaging methods to capture the neural mechanisms that underlie continuous traits across the spectrum from healthy to maladaptive. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Katzmann, Josepha; Goertz-Dorten, Anja; Hautmann, Christopher; Doepfner, Manfred
2018-01-19
Social-cognitive information processing, social skills, and social interactions are problem-maintaining variables for aggressive behavior in children. We hypothesized that these factors may be possible mediators of the mechanism of change in the child-centered treatment of conduct disorders (CDs). The aim of the present study (Clinical trials.gov Identifier: NCT01406067) was to examine putative mechanisms of change for the decrease in oppositional-defiant behavior resulting from child-centered treatment of patients with oppositional-defiant disorder (ODD) or CD. 91 children (age 6-12 years) with ODD/CD were randomized to receive either social skills training or to a resource activating play group. Mediator analyses were conducted using path analyses. The assumed mediating effects were not significant. However, alternative models with the putative mediators and outcome in reversed positions showed significant indirect effects of the oppositional-defiant symptoms as mediator for the decrease of disturbance of social-information processing, social skills, and social interactions. The proposed model for mechanisms of change could not be confirmed, with the results pointing to a reversed causality. Variables other than those hypothesized must be responsible for mediating the effects of the intervention on child oppositional-defiant behavior. Possible mechanisms of change were discussed.
Assessment of DSM-5 Section II Personality Disorders With the MMPI-2-RF in a Nonclinical Sample.
Sellbom, Martin; Smith, Alexander
2017-01-01
The Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF; Ben-Porath & Tellegen, 2008 / 2011 ) is frequently used in clinical practice. However, there has been a dearth of literature on how well this instrument can assess symptoms associated with personality disorders (PDs). This investigation examined a range of hypothesized MMPI-2-RF scales in predicting PD symptoms. We evaluated these associations in a sample of 397 university students who had been administered the MMPI-2-RF and the Structured Clinical Interview for DSM-IV Axis II Disorders-Personality Questionnaire (First, Gibbon, Spitzer, Williams, & Benjamin, 1997 ). Zero-order correlation analyses and negative binomial regression models indicated that a wide range of MMPI-2-RF scale hypotheses were supported; however, the least support was available for predicting schizoid and obsessive-compulsive PDs. Implications for MMPI-2-RF interpretation and PD diagnosis are discussed.
Is panic disorder a disorder of physical fitness? A heuristic proposal
Perna, Giampaolo; Caldirola, Daniela
2018-01-01
Currently, panic disorder (PD) is considered a mental disorder based on the assumptions that panic attacks (PAs) are “false alarms” that arise from abnormally sensitive defense systems in the central nervous system and that PD is treated with therapies specifically acting on anxiety or fear mechanisms. This article aims to propose an alternative perspective based on the results of some experimental studies. Our heuristic proposal suggests not only that PD may be a mental disorder but also that patients with PD have real abnormal body functioning, mainly involving cardiorespiratory and balance systems, leading to a decline in global physical fitness. PAs, as well as physical symptoms or discomfort in some environmental situations, may be “real alarms” signaling that the adaptability resources of an organism are insufficient to respond appropriately to some internal or external changes, thus representing the transient conscious awareness of an imbalance in body functioning. The antipanic properties of several modern treatments for PD may include their beneficial effects on body functions. Although anxiety or fear mechanisms are evidently involved in PD, we hypothesize that a reduction of physical fitness is the “primum movens” of PD, while anxiety or fear is induced and sustained by repeated signals of impaired body functioning. We propose considering panic in a broader perspective that offers a central role to the body and to contemplate the possible role of somatic treatments in PD. PMID:29623195
Gender identity disorder in a five-year-old boy.
Herman, S. P.
1983-01-01
Markedly effeminate behavior in a young boy is a source of concern and confusion for parents, teachers, and the child. It also represents a therapeutic dilemma for the child psychiatrist. The case of a five-year-old boy with gender identity disorder of childhood is presented and the literature on hypotheses of etiology, treatment, and long-term follow-up is reviewed. The ethical and philosophical questions posed by such a case are discussed.
Global changes of climate through human activities. New clues and hypotheses
Energy Technology Data Exchange (ETDEWEB)
Grassl, H
1988-02-01
New clues to world-wide changes of climate through human activities have been found or corroborated: Precipitation belts have shifted during the last 30 years; ozone over Antarctica in spring has fallen to its lowest level ever (1956); near-ground ozone in our latitudes has at least doubled in this century. Newly discussed hypotheses are: The oxidation capacity and, consequently, the purification capacity of the atmosphere decreases in the southern hemisphere owing above all to the increase in methane. Increased backscatter of solar radiation through low clouds during periods of turbid air in the atmosphere attenuates the greenhouse effect, the increase in icy clouds through condensation trails of jets flying at high altitudes intensifies the greenhouse effect of the atmosphere. The paper analyses these hypotheses and shows that the distinction between change of climate on the one hand and ecological damage on the other is not justifiable any longer. (orig./HSCH).
Using potential performance theory to test five hypotheses about meta-attribution.
Trafimow, David; Hunt, Gayle; Rice, Stephen; Geels, Kasha
2011-01-01
Based on I. Kant's (1991) distinction between perfect and imperfect duties and the attribution literature pertaining to that distinction, the authors proposed and tested 5 hypotheses about meta-attribution. More specifically, violations of perfect duties have been shown to arouse both more negative affect and stronger correspondent inferences than do violations of imperfect duties (e.g., D. Trafimow, I. K. Bromgard, K. A. Finlay, & T. Ketelaar, 2005). But when it comes to making meta-attributions-that is, guessing the attributions others would make-is the affect differential an advantage or a disadvantage? In addition to the null hypothesis of no effect, the authors proposed and tested additional hypotheses about how negative affect might increase or decrease the effectiveness of people's meta-attribution strategies and how even if there is no effect on strategy effectiveness, negative affect could increase or decrease the consistencies with which these strategies could be used.
Anterior Cortical Development During Adolescence in Bipolar Disorder.
Najt, Pablo; Wang, Fei; Spencer, Linda; Johnston, Jennifer A Y; Cox Lippard, Elizabeth T; Pittman, Brian P; Lacadie, Cheryl; Staib, Lawrence H; Papademetris, Xenophon; Blumberg, Hilary P
2016-02-15
Increasing evidence supports a neurodevelopmental model for bipolar disorder (BD), with adolescence as a critical period in its development. Developmental abnormalities of anterior paralimbic and heteromodal frontal cortices, key structures in emotional regulation processes and central in BD, are implicated. However, few longitudinal studies have been conducted, limiting understanding of trajectory alterations in BD. In this study, we performed longitudinal neuroimaging of adolescents with and without BD and assessed volume changes over time, including changes in tissue overall and within gray and white matter. Larger decreases over time in anterior cortical volumes in the adolescents with BD were hypothesized. Gray matter decreases and white matter increases are typically observed during adolescence in anterior cortices. It was hypothesized that volume decreases over time in BD would reflect alterations in those processes, showing larger gray matter contraction and decreased white matter expansion. Two high-resolution magnetic resonance imaging scans were obtained approximately 2 years apart for 35 adolescents with bipolar I disorder (BDI) and 37 healthy adolescents. Differences over time between groups were investigated for volume overall and specifically for gray and white matter. Relative to healthy adolescents, adolescents with BDI showed greater volume contraction over time in a region including insula and orbitofrontal, rostral, and dorsolateral prefrontal cortices (p adolescence in BDI in anterior cortices, including altered developmental trajectories of anterior gray and white matter. Published by Elsevier Inc.
Change in Binge Eating and Binge Eating Disorder Associated with Migration from Mexico to the US
Swanson, Sonja A.; Saito, Naomi; Borges, Guilherme; Benjet, Corina; Aguilar-Gaxiola, Sergio; Medina-Mora, Maria Elena; Breslau, Joshua
2011-01-01
Exposure to Western popular culture is hypothesized to increase risk for eating disorders. This study tests this hypothesis with respect to the proposed diagnosis of Binge Eating Disorder (BED) in an epidemiological sample of people of Mexican origin in Mexico and the US. Data come from the Mexico National Comorbidity Survey, National Comorbidity Survey Replication, and National Latino and Asian American Survey (N=2268). Diagnoses were assessed with the WMH-CIDI. Six groups were compared: Mex...
Concurrent hypokalemic periodic paralysis and bipolar disorder
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Chia-Lin Lin
2015-01-01
Full Text Available Primary periodic paralysis is a rare autosomal dominant disorder of ion-channel dysfunction, manifested by episodic flaccid paresis secondary to abnormal sarcolemma excitability. Membrane destabilization involving Na, K-ATPase has been hypothesized to be a biological etiology of the bipolar disorder (BD and the mechanisms underlying lithium therapy have been linked to it. To date, there has been only one reported case of BD comorbid with periodic paralysis. Herein, we reported another case of concurrent bipolar mania and hypokalemic periodic paralysis (HPP, one special form of periodic paralysis. Consistent with the previous case, our patient responded well to lithium treatment for both bipolar mania and HPP. This might provide some support to the hypothesis that the therapeutic effects of lithium in both BD and HPP could be due to the correction of the underlying common pathophysiology.
Neuropsychological findings in personality disorders: A.R. Luria’s Approach.
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Pluzhnikov I.V.
2015-06-01
Full Text Available There is a lack of information concerning the features of cognitive processes in personality disorders, as well as the brain mechanisms of the pathogenesis of these diseases. Luria’s neuropsychological approach demonstrated its heuristicity in estimating the cognitive status of patients with mental disorders and can be employed to identify the brain bases of non-psychotic mental disorders (including personality disorders. The objective of this research is to study the features of neurocognitive functioning in patients with schizoid personality disorder and schizotypal personality disorder (against the norm, employing Luria’s neuropsychological methodology. Hypotheses: 1 While both types of personality disorders are related to schizophrenia spectrum disorders, the specificity of the neurocognitive functioning of each personality disorder will be observed in addition to general neuropsychological signs. Specific neuropsychological symptoms point to different brain deficits, which allows conclusion to be drawn regarding differences in the pathogenesis of each personality disorder; and 2 Luria’s methodology neuropsychology is adequate for the study of neurocognitive functioning in personality disorders. The study was conducted using qualitative and quantitative analyses (according to Luria of neuropsychological testing data in a group of fifty male patients aged 19,2±3,7 years with pathocharacteristic domain disorders. The group consisted of 30 schizoid personality disorder patients and 20 schizotypal personality disorder patients. Statistically significant differences (p <0,005 in neurocognitive function (regulatory processes, memory, spatial function between the healthy controls and patients with personality disorders were observed. Specific cognitive disorders pointing to the dysfunction of front-thalamoparietal connections were characteristic of both groups. Lateral differences were discovered for both patient groups. The
INFLUENCES ON AND FROM THE SEGMENTATION OF NETWORKS - HYPOTHESES AND TESTS
BAERVELDT, C; SNIJDERS, T
This article discusses (a) the influence of network structure on the diffusion of (new) cultural behavior within the network and (b) the influence of external events, especially of social programs, on the diffusion of (new) cultural behavior, and on the network structure. Hypotheses are formulated
Autophagic dysfunction in a lysosomal storage disorder due to impaired proteolysis.
Elrick, Matthew J; Lieberman, Andrew P
2013-02-01
Alterations in macroautophagy (hereafter referred to as "autophagy") are a common feature of lysosomal storage disorders, and have been hypothesized to play a major role in the pathogenesis of these diseases. We have recently reported multiple defects in autophagy contributing to the lysosomal storage disorder Niemann-Pick type C (NPC). These include increased formation of autophagosomes, slowed turnover of autophagosomes secondary to impaired lysosomal proteolysis, and delivery of stored lipids to the lysosome via autophagy. The study summarized here describes novel methods for the interrogation of individual stages of the autophagic pathway, and suggests mechanisms by which lipid storage may result in broader lysosomal dysfunction.
Editorial: hypotheses about protein folding - the proteomic code and wonderfolds
Directory of Open Access Journals (Sweden)
Agutter Paul S
2009-12-01
Full Text Available Abstract Theoretical biology journals can contribute in many ways to the progress of knowledge. They are particularly well-placed to encourage dialogue and debate about hypotheses addressing problematical areas of research. An online journal provides an especially useful forum for such debate because of the option of posting comments within days of the publication of a contentious article.
Is ADHD an early stage in the development of borderline personality disorder?
DEFF Research Database (Denmark)
Storebø, Ole Jakob; Simonsen, Erik
2014-01-01
BACKGROUND: Several studies report associations between adults with borderline personality disorder (BPD) and a history of attention-deficit hyperactivity (ADHD) symptoms in childhood. AIMS: To explore the association between BPD and a history of ADHD in childhood. METHOD: A comprehensive search......: Most of the 15 articles showed a statistical association between ADHD and BPD. The data, most strongly provided a basis for the hypotheses that ADHD is either an early developmental stage of BPD, or that the two disorders share an environmental and genetic aetiology. Furthermore, one of the disorders...... seems to give a synergic effect, reinforce the other or complicate the disorders. In one prospective study, the risk factor for children with ADHD to develop BPD was as high as odds ratio 13.16. No studies have looked at treatment of ADHD as a mediator of the risk for BPD. CONCLUSIONS: Many studies...
Factors related to depression and eating disorders: self-esteem, body image, and attractiveness.
Grubb, H J; Sellers, M I; Waligroski, K
1993-06-01
To test hypotheses that women suffering from some form of eating disorder would experience lower self-esteem and higher depression and that women with lower self-esteem and greater depression would rate their attractiveness lower and see themselves as heavier than less depressed individuals, 42 college undergraduate women were individually administered the Eating Disorders Inventory, Beck Depression Inventory, Coopersmith Self-esteem Inventory, and a Body Image/Attractiveness Perception Scale. A Pearson correlation indicated a substantial relation between scores on depression and scores on eating disorders, but nonsignificant values between self-esteem scores and scores on either eating disorders or on depression. Depression scores correlated significantly with rated body size, but not attractiveness, while self-esteem scores were significantly correlated with rated attractiveness, not body size. These results contradict literature on the relation between self-esteem and depression. Directions for additional research are discussed.
Merino, Hipólito; Senra, Carmen; Ferreiro, Fátima
2016-01-01
This study examines the relationships between neuroticism (higher-order vulnerability factor), the cognitive styles of worry, brooding and reflection (second-order vulnerability factors) and symptoms of anxiety and depression in three groups of patients: patients with Generalized Anxiety Disorder (GAD), with Major Depressive Disorder (MDD) and with Mixed Anxiety-Depressive Disorder (MADD). One hundred and thirty four patients completed a battery of questionnaires including measures of neuroticism, worry, rumination (brooding and reflection), anxiety and depression. Multiple mediation analyses indicate that worry may act as a mediating mechanism linking neuroticism and anxiety symptoms in the three diagnostic groups, whereas brooding-rumination may play a mediating role between neuroticism and depressive symptoms in patients with MDD and MADD and, with less certainty, in patients with GAD. Overall, our findings suggest that neuroticism may increase the risk of anxious and depressive symptoms via specific links involving either worry or brooding, respectively, and that both worry and brooding may operate in the three groups examined, irrespectively of whether anxiety or depression are the main emotions or whether they coexist without any clear predominance; consequently, we hypothesize the existence of "specific transdiagnostic" mechanisms.
Merino, Hipólito; Ferreiro, Fátima
2016-01-01
This study examines the relationships between neuroticism (higher-order vulnerability factor), the cognitive styles of worry, brooding and reflection (second-order vulnerability factors) and symptoms of anxiety and depression in three groups of patients: patients with Generalized Anxiety Disorder (GAD), with Major Depressive Disorder (MDD) and with Mixed Anxiety-Depressive Disorder (MADD). One hundred and thirty four patients completed a battery of questionnaires including measures of neuroticism, worry, rumination (brooding and reflection), anxiety and depression. Multiple mediation analyses indicate that worry may act as a mediating mechanism linking neuroticism and anxiety symptoms in the three diagnostic groups, whereas brooding-rumination may play a mediating role between neuroticism and depressive symptoms in patients with MDD and MADD and, with less certainty, in patients with GAD. Overall, our findings suggest that neuroticism may increase the risk of anxious and depressive symptoms via specific links involving either worry or brooding, respectively, and that both worry and brooding may operate in the three groups examined, irrespectively of whether anxiety or depression are the main emotions or whether they coexist without any clear predominance; consequently, we hypothesize the existence of "specific transdiagnostic" mechanisms. PMID:27243462
Directory of Open Access Journals (Sweden)
Hipólito Merino
Full Text Available This study examines the relationships between neuroticism (higher-order vulnerability factor, the cognitive styles of worry, brooding and reflection (second-order vulnerability factors and symptoms of anxiety and depression in three groups of patients: patients with Generalized Anxiety Disorder (GAD, with Major Depressive Disorder (MDD and with Mixed Anxiety-Depressive Disorder (MADD. One hundred and thirty four patients completed a battery of questionnaires including measures of neuroticism, worry, rumination (brooding and reflection, anxiety and depression. Multiple mediation analyses indicate that worry may act as a mediating mechanism linking neuroticism and anxiety symptoms in the three diagnostic groups, whereas brooding-rumination may play a mediating role between neuroticism and depressive symptoms in patients with MDD and MADD and, with less certainty, in patients with GAD. Overall, our findings suggest that neuroticism may increase the risk of anxious and depressive symptoms via specific links involving either worry or brooding, respectively, and that both worry and brooding may operate in the three groups examined, irrespectively of whether anxiety or depression are the main emotions or whether they coexist without any clear predominance; consequently, we hypothesize the existence of "specific transdiagnostic" mechanisms.
Parenting style and the risk for eating disorders among teenage girls
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Semiramida Manaj
2017-11-01
Full Text Available The aim of this study was to explore the role of parenting styles and the risk to develop an eating disordered behavior among teenage girls. This study was designed to test the hypotheses that parenting style are correlated with the risk to have an eating disordered behavior among female teenagers. It was predicted that the teenage girls at risk for developing an eating disorder would report experiencing their parents style as high in control and low in warmth or low in control and high in warmth. Specifically, the permissive and the authoritarian parenting style will be positively correlated with the risk to develop an eating disordered behavior. The sample of this research was composed by 100 teenage girls 15-18 years old. The selection of the participant was totally random and they were selected on the schools they frequented. There were found significant correlations between daughters approach to eating and mothers parenting style. These results support the impact of mothers parenting style on the risk to have an eating disorder, but more research needs to be conducted in examining the relationship between parenting style and eating disordered behavior.
Hypotheses about geoglyphs at Nasca, Peru: new discoveries
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Jaroslav Klokočník
2016-07-01
Full Text Available The known hypotheses about the reasons why the geoglyphs in the Nasca and Palpa region of Peru were created are many: roads/paths, rituals/ceremonials, use of hallucinogens, astronomical meaning, influence of extraterrestrials, underground water… and so on. We present a new hypothesis, formulated by J. Sonnek (first published in 2011 in the context of all previous hypotheses.1 Sonnek explains the geoglyphs as tidied work areas for the production of rope and nets, although he goes much further than Stierlin. This eccentric hypothesis now has not only experimental but also archaeological and ethnographical support, which is presented here. Geoglyphs of a special shape were discovered in the pampas; they may represent technical objects – different types of ‘rope twisters’. Following this idea, Sonnek made technical devices (using today’s materials and tested them in practice; they work perfectly, see his YouTube videos.2 In November 2012, wooden pieces, which may be the remnants of ropemaking, were collected from the pampa near the towns of Nasca and Palpa, in vicinity of these hypothetic ropemaking places. Radiocarbon testing by 14C standardized radio-carbon age according to Stuiver-Polach convention and Accelerator Mass Spectroscopy (AMS of these wood pieces shows the age to be in a wide range from Early Nasca to the 17th century (and to our epoch with a fake geoglyph, too, thus supporting (but surely not proving the new hypothesis. Moreover, in the Quechua language, the word huasca, waskha (read: uasca means a rope or cord or place where these are produced. This word is very similar to ‘nasca’.
Experienced physicians benefit from analyzing initial diagnostic hypotheses
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Adam Bass
2013-03-01
Full Text Available Background: Most incorrect diagnoses involve at least one cognitive error, of which premature closure is the most prevalent. While metacognitive strategies can mitigate premature closure in inexperienced learners, these are rarely studied in experienced physicians. Our objective here was to evaluate the effect of analytic information processing on diagnostic performance of nephrologists and nephrology residents. Methods: We asked nine nephrologists and six nephrology residents at the University of Calgary and Glasgow University to diagnose ten nephrology cases. We provided presenting features along with contextual information, after which we asked for an initial diagnosis. We then primed participants to use either hypothetico-deductive reasoning or scheme-inductive reasoning to analyze the remaining case data and generate a final diagnosis. Results: After analyzing initial hypotheses, both nephrologists and residents improved the accuracy of final diagnoses (31.1% vs. 65.6%, p < 0.001, and 40.0% vs. 70.0%, p < 0.001, respectively. We found a significant interaction between experience and analytic processing strategy (p = 0.002: nephrology residents had significantly increased odds of diagnostic success when using scheme-inductive reasoning (odds ratio [95% confidence interval] 5.69 [1.59, 20.33], p = 0.007, whereas the performance of experienced nephrologists did not differ between strategies (odds ratio 0.57 [0.23, 1.39], p = 0.2. Discussion: Experienced nephrologists and nephrology residents can improve their performance by analyzing initial diagnostic hypotheses. The explanation of the interaction between experience and the effect of different reasoning strategies is unclear, but may relate to preferences in reasoning strategy, or the changes in knowledge structure with experience.
Ecker, Willi; Kupfer, Jochen; Gönner, Sascha
2014-01-01
This paper examines the contribution of incompleteness/'not just right experiences' (NJREs) to an understanding of the relationship between obsessive-compulsive disorder (OCD) and obsessive-compulsive personality traits (OCPTs). It investigates the association of specific OCD symptom dimensions with OCPTs, conceptualized as continuous phenomena that are also observable below the diagnostic threshold. As empirical findings and clinical observation suggest that incompleteness feelings/NJREs may play a significant affective and motivational role for certain OCD subtypes, but also for patients with accentuated OCPTs, we hypothesized that OCPTs are selectively linked with incompleteness-associated OCD symptom dimensions (ordering, checking, hoarding and counting). Moreover, we assumed that this selective relationship cannot be demonstrated any more after statistical control of incompleteness, whereas it is preserved after statistical control of anxiety, depression, pathological worry and harm avoidance. Results from a study with a large clinical sample (n = 185) partially support these hypotheses and suggest that NJREs may be an important connecting link between specific OCD symptom dimensions, in particular ordering and checking, and accentuated OCPTs. Obsessive-compulsive personality traits (OCPTs) are positively related to obsessive-compulsive disorder symptom dimensions (ordering, checking, hoarding and counting) hypothesized or found to be associated with incompleteness/'not just right experiences' (NJREs), but not to washing and obsessions. This positive relationship, which is strongest for ordering and checking, is eliminated when NJREs are statistically controlled. Ordering, checking and accentuated OCPTs may share NJREs as a common affective-motivational underpinning.Dysfunctional behaviour patterns of people with accentuated OCPTs or obsessive-compulsive personality disorder (OCPD) may be viewed as efforts to avoid or reduce subjectively intolerable NJREs
García-Villamisar, Domingo; Dattilo, John; Del Pozo, Araceli
2012-01-01
Although perfectionism has long been established as an important risk factor for depressive mood and eating disorders, the mechanisms through which this temperamental predisposition mediates the relationship between depressive mood and eating disorder symptoms are still relatively unclear. In this study we hypothesized that both perfectionism dimensions, self-oriented perfectionism and socially prescribed perfectionism, would mediate the relationship between current symptoms of depression and eating disorders in a non-clinical sample of Spanish undergraduate females. Two hundred sixteen female undergraduate students of the University Complutense of Madrid (Spain) completed the Spanish versions of the Eating Attitudes Test (EAT-40), the Multidimensional Perfectionism Scale (MPS), OBQ-44, and BDI-II and BAI. Results demonstrated the importance of socially prescribed perfectionism in mediation of the relationship between depressive mood and symptoms of eating disorders. Socially prescribed perfectionism mediates the relationship between depressive mood and eating disorder symptoms for female college students.
Gordijn, M. C. M.; 't Mannetje, D.; Meesters, Y.
Background: One of the most frequently investigated hypotheses of the pathophysiology underlying Seasonal Affective Disorder (SAD) is a disturbance of circadian rhythms. Since the circadian system as well as other non-visual effects is especially sensitive to blue light, a new light therapy device
Mother-Infant Attachment and the Intergenerational Transmission of Posttraumatic Stress Disorder
Enlow, Michelle Bosquet; Egeland, Byron; Carlson, Elizabeth; Blood, Emily; Wright, Rosalind J.
2013-01-01
Evidence for the intergenerational transmission of posttraumatic stress disorder (PTSD) is documented in the literature, though the underlying mechanisms are poorly understood. Attachment theory provides a framework for elucidating the ways in which maternal PTSD may increase offspring PTSD vulnerability. The current study utilized two independent prospective datasets to test the hypotheses that (a) maternal PTSD increases the probability of developing an insecure mother-infant attachment rel...
Validity of the Environmental Kuznets Curve Hypotheses in Water Pollution A Case Study
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Hediyeh Alishiri
2017-03-01
Full Text Available Among the different environmental pollutions, water pollution is of especial importance due to the rather unchanging supply of this vital resource on a global scale and because of the dire consequences of its pollution for human health. The relationship between water production and its pollution can thus established and used as a measure of environmental degradation. This relationship can then be captured and analyzed in terms of environmental Kuznets hypotheses. It may be claimed that the early stages of economic growth is associated with lower per capita income and water pollution but the trend is reversed with increasing per capita income and improved economic growth. The present study was conducted using the panel data technique and the Kuznets environmental hypotheses were examined for the two groups of developed and developing countries under the two scenarios of using either per capita GDP or the share of industry to the added value in GDP as an indicator of economic growth. Results indicate that under both scenarios, Kuznets hypotheses are confirmed when studying the situation in developing countries but refuted in the case of developed countries.
Borderline personality disorder and emotional intelligence.
Peter, Mathell; Schuurmans, Hanneke; Vingerhoets, Ad J J M; Smeets, Guus; Verkoeijen, Peter; Arntz, Arnoud
2013-02-01
The present study investigated emotional intelligence (EI) in borderline personality disorder (BPD). It was hypothesized that patients with BPD (n = 61) compared with patients with other personality disorders (PDs; n = 69) and nonpatients (n = 248) would show higher scores on the ability to perceive emotions and impairments in the ability to regulate emotions. EI was assessed with the Mayer-Salovey-Caruso Emotional Intelligence Test (Mayer, Salovey, and Caruso [New York: MHS, 2002]). As compared with the PD group and the nonpatient group, the patients with BPD displayed the anticipated deficits in their ability to understand, whereas no differences emerged with respect to their ability to perceive, use, and regulate emotions. In addition, a negative relationship was found between the severity of BPD and total EI score. However, this relationship disappeared when intelligence quotient was partialled out. These results suggest that BPD is associated with emotion understanding deficits, whereas temporary severity of BPD is associated with emotion regulation deficits.
Hypotheses on citation practices as revealed in the literature of the ...
African Journals Online (AJOL)
Citations found in two historical articles, which appeared in Cancer Research, a top American Journal, were used to show both positive and negative attitudes towards my 22 historical publications on cancer carriage in the body. Therefore, scientific information concepts are cited critically and two hypotheses are advanced ...
Examining Preservice Science Teachers' Skills of Formulating Hypotheses and Identifying Variables
Aydogdu, Bülent
2015-01-01
The aim of this study is to examine preservice science teachers' skills of formulating hypotheses and identifying variables. The research has a phenomenological research design. The data was gathered qualitatively. In this study, preservice science teachers were first given two scenarios (Scenario-1 & Scenario-2) containing two different…
Lenzenweger, Mark F
2010-11-01
It is argued that personality pathology represents the final emergent product of a complex interaction of underlying neurobehavioral systems as well as environment inputs. A number of factors may be involved in the developmental pathway and a cascading of effects is plausible, although a unifying cascade for all personality disorders is not likely. The present study suggests a possible cascade relevant to one personality disorder: schizoid personality disorder in emerging adulthood. In brief, it is hypothesized that the absence of a relationship characterized by a rich degree of psychological proximal process in early childhood, which is associated with nurturance and the facilitation of more complex development, predicts impairment in the actualization of the affiliation system (i.e., that system that facilitates interpersonal connectedness and social bonds in human beings and is under substantial genetic influence), and this impairment in the affiliation system predicts the appearance of schizoid personality disorder symptoms in emerging adulthood (late teens/early 20s), which persists over time into emerging adulthood. The impairment in the affiliation system is argued to proceed through childhood sociality as reflected in temperament on through adult personality as reflected in communal positive emotion. Furthermore, it is also hypothesized that the relationship between proximal processes and the affiliation system maintains irrespective of other childhood temperament factors that might adversely impact early parent/caregiver and child relations. The data for a preliminary illustration of this possible cascade are drawn from The Longitudinal Study of Personality Disorders, which is a prospective, multiwave study of personality disorders, personality, and temperament in a large sample of adults drawn from a nonclinical population.
Ohayon, MM; Guilleminault, C; Priest, RG; Zulley, J; Smirne, S
Objective: Sleep-disordered breathing has been hypothesized to have a close relationship with hypertension but previous studies have reported mixed results. This is an important health issue that requires further clarification because of the potential impact on the prevention and control of
Sensory processing disorder: any of a nurse practitioner's business?
Byrne, Mary W
2009-06-01
Children who exhibit the confusing symptom patterns associated with sensory processing deficits are often seen first by primary care providers, including family and pediatric nurse practitioners (NPs). The purpose of this article is to alert NPs to the state of the science for these disorders and to the roles NPs could play in filling the knowledge gaps in assessment, treatment, education, and research. Literature searches using PubMed and MedLine databases and clinical practice observations. Sensory integration disorders have only begun to be defined during the past 35 years. They are not currently included in the DSM IV standard terminology, and are not yet substantively incorporated into most health disciplines' curricula or practice, including those of the NP. NPs are in a unique position to test hypothesized terminology for Sensory Processing Disorder (SPD) by contributing precise clinical descriptions of children who match as well as deviate from the criteria for three proposed diagnostic groups: Sensory Modulation Disorder (SMD), Sensory Discrimination Disorder (SDD), and Sensory-Based Motor Disorder (SBMD). Beyond the SPD diagnostic debate, for children with sensory deficit patterns the NP role can incorporate participating in interdisciplinary treatment plans, refining differential diagnoses, providing frontline referral and support for affected children and their families, and making both secondary prevention and critical causal research possible through validation of consistently accepted diagnostic criteria.
Age at fatherhood: heritability and associations with psychiatric disorders.
Frans, E M; Lichtenstein, P; Hultman, C M; Kuja-Halkola, R
2016-10-01
Advancing paternal age has been linked to psychiatric disorders. These associations might be caused by the increased number of de novo mutations transmitted to offspring of older men. It has also been suggested that the associations are confounded by a genetic liability for psychiatric disorders in parents. The aim of this study was to indirectly test the confounding hypotheses by examining if there is a genetic component to advancing paternal age and if men with a genetic liability for psychiatric disorders have children at older ages. We examined the genetic component to advancing paternal age by utilizing the twin model in a cohort of male twins (N = 14 679). We also studied ages at childbirth in men with or without schizophrenia, bipolar disorder and/or autism spectrum disorder. Ages were examined in: (1) healthy men, (2) affected men, (3) healthy men with an affected sibling, (4) men with healthy spouses, (5) men with affected spouses, and (6) men with healthy spouses with an affected sibling. The twin analyses showed that late fatherhood is under genetic influence (heritability = 0.33). However, affected men or men with affected spouses did not have children at older ages. The same was found for healthy individuals with affected siblings. Instead, these men were generally having children at younger ages. Although there is a genetic component influencing late fatherhood, our data suggest that the associations are not explained by psychiatric disorders or a genetic liability for psychiatric disorders in the parent.
Directory of Open Access Journals (Sweden)
Keller Benjamin J
2010-11-01
Full Text Available Abstract Background Lithium is an effective treatment for Bipolar Disorder (BD and significantly reduces suicide risk, though the molecular basis of lithium's effectiveness is not well understood. We seek to improve our understanding of this effectiveness by posing hypotheses based on new experimental data as well as published data, testing these hypotheses in silico, and posing new hypotheses for validation in future studies. We initially hypothesized a gene-by-environment interaction where lithium, acting as an environmental influence, impacts signal transduction pathways leading to differential expression of genes important in the etiology of BD mania. Results Using microarray and rt-QPCR assays, we identified candidate genes that are differentially expressed with lithium treatment. We used a systems biology approach to identify interactions among these candidate genes and develop a network of genes that interact with the differentially expressed candidates. Notably, we also identified cocaine as having a potential influence on the network, consistent with the observed high rate of comorbidity for BD and cocaine abuse. The resulting network represents a novel hypothesis on how multiple genetic influences on bipolar disorder are impacted by both lithium treatment and cocaine use. Testing this network for association with BD and related phenotypes, we find that it is significantly over-represented for genes that participate in signal transduction, consistent with our hypothesized-gene-by environment interaction. In addition, it models related pharmacogenomic, psychiatric, and chemical dependence phenotypes. Conclusions We offer a network model of gene-by-environment interaction associated with lithium's effectiveness in treating BD mania, as well as the observed high rate of comorbidity of BD and cocaine abuse. We identified drug targets within this network that represent immediate candidates for therapeutic drug testing. Posing novel
Seed dormancy and germination - Emerging mechanisms and new hypotheses
Directory of Open Access Journals (Sweden)
Hiroyuki eNonogaki
2014-05-01
Full Text Available Seed dormancy has played a significant role in adaptation and evolution of seed plants. While its biological significance is clear, molecular mechanisms underlying seed dormancy induction, maintenance and alleviation still remain elusive. Intensive efforts have been made to investigate gibberellin and abscisic acid metabolism in seeds, which greatly contributed to the current understanding of seed dormancy mechanisms. Other mechanisms, which might be independent of hormones, or specific to the seed dormancy pathway, are also emerging from genetic analysis of seed dormancy mutants. These studies suggest that chromatin remodeling through histone ubiquitination, methylation and acetylation, which could lead to transcription elongation or gene silencing, may play a significant role in seed dormancy regulation. Small interfering RNA and/or long non-coding RNA might be a trigger of epigenetic changes at the seed dormancy or germination loci, such as DELAY OF GERMINATION1. While new mechanisms are emerging from genetic studies of seed dormancy, novel hypotheses are also generated from seed germination study with high throughput gene expression analysis. Recent studies on tissue-specific gene expression in tomato and Arabidopsis seeds, which suggested possible mechanosensing in the regulatory mechanisms, advanced our understanding of embryo-endosperm interaction and have potential to re-draw the traditional hypotheses or integrate them into a comprehensive scheme. The progress in basic seed science will enable knowledge translation, another frontier of research to be expanded for food and fuel production.
Internet Gaming Disorder: Investigating the Clinical Relevance of a New Phenomenon.
Przybylski, Andrew K; Weinstein, Netta; Murayama, Kou
2017-03-01
The American Psychiatric Association (APA) identified Internet gaming disorder as a new potential psychiatric disorder and has recognized that little is known about the prevalence, validity, or cross-cultural robustness of proposed Internet gaming disorder criteria. In response to this gap in our understanding, the present study, a first for this research topic, estimated the period prevalence of this new potential psychiatric disorder using APA guidance, examined the validity of its proposed indicators, evaluated reliability cross-culturally and across genders, compared it to gold-standard research on gambling addiction and problem gaming, and estimated its impact on physical, social, and mental health. Four survey studies (N=18,932) with large international cohorts employed an open-science methodology wherein the analysis plans for confirmatory hypotheses were registered prior to data collection. Among those who played games, more than 2 out of 3 did not report any symptoms of Internet gaming disorder, and findings showed that a very small proportion of the general population (between 0.3% and 1.0%) might qualify for a potential acute diagnosis of Internet gaming disorder. Comparison to gambling disorder revealed that Internet-based games may be significantly less addictive than gambling and similarly dysregulating as electronic games more generally. The evidence linking Internet gaming disorder to game engagement was strong, but links to physical, social, and mental health outcomes were decidedly mixed.
Hippocampus and amygdala volumes in parents of children with autistic disorder.
Rojas, Donald C; Smith, J Allegra; Benkers, Tara L; Camou, Suzanne L; Reite, Martin L; Rogers, Sally J
2004-11-01
Structural and functional abnormalities in the medial temporal lobe, particularly the hippocampus and amygdala, have been described in people with autism. The authors hypothesized that parents of children with a diagnosis of autistic disorder would show similar changes in these structures. Magnetic resonance imaging scans were performed in 17 biological parents of children with a diagnosis of DSM-IV autistic disorder. The scans were compared with scans from 15 adults with autistic disorder and 17 age-matched comparison subjects with no personal or familial history of autism. The volumes of the hippocampus, amygdala, and total brain were measured in all participants. The volume of the left hippocampus was larger in both the parents of children with autistic disorder and the adults with autistic disorder, relative to the comparison subjects. The hippocampus was significantly larger in the adults with autistic disorder than in the parents of children with autistic disorder. The left amygdala was smaller in the adults with autistic disorder, relative to the other two groups. No differences in total brain volume were observed between the three groups. The finding of larger hippocampal volume in autism is suggestive of abnormal early neurodevelopmental processes but is partly consistent with only one prior study and contradicts the findings of several others. The finding of larger hippocampal volume for the parental group suggests a potential genetic basis for hippocampal abnormalities in autism.
Genetic Influences on Conduct Disorder
Salvatore, Jessica E.; Dick, Danielle M.
2016-01-01
Conduct disorder (CD) is a moderately heritable psychiatric disorder of childhood and adolescence characterized by aggression toward people and animals, destruction of property, deceitfulness or theft, and serious violation of rules. Genome-wide scans using linkage and association methods have identified a number of suggestive genomic regions that are pending replication. A small number of candidate genes (e.g., GABRA2, MAOA, SLC6A4, AVPR1A) are associated with CD related phenotypes across independent studies; however, failures to replicate also exist. Studies of gene-environment interplay show that CD genetic predispositions also contribute to selection into higher-risk environments, and that environmental factors can alter the importance of CD genetic factors and differentially methylate CD candidate genes. The field’s understanding of CD etiology will benefit from larger, adequately powered studies in gene identification efforts; the incorporation of polygenic approaches in gene-environment interplay studies; attention to the mechanisms of risk from genes to brain to behavior; and the use of genetically informative data to test quasi-causal hypotheses about purported risk factors. PMID:27350097
Breslau, Joshua; Borges, Guilherme; Tancredi, Daniel; Saito, Naomi; Kravitz, Richard; Hinton, Ladson; Vega, William; Medina-Mora, Maria Elena; Aguilar-Gaxiola, Sergio
2011-04-01
Migration is suspected to increase risk for depressive and anxiety disorders. To test the hypothesized increase in risk for depressive and anxiety disorders after arrival in the United States among Mexican migrants. We combined data from surveys conducted separately in Mexico and the United States that used the same diagnostic interview. Discrete time survival models were specified to estimate the relative odds of first onset of depressive disorders (major depressive episode and dysthymia) and anxiety disorders (generalized anxiety disorder, social phobia, panic disorder, and posttraumatic stress disorder) among migrants after their arrival in the United States compared with nonmigrant Mexicans who have a migrant in their immediate family. Population surveys in the United States and Mexico. Two thousand five hundred nineteen nonmigrant family members of migrants in Mexico and 554 Mexican migrants in the United States. First onset of any depressive or anxiety disorder. After arrival in the United States, migrants had a significantly higher risk for first onset of any depressive or anxiety disorder than did nonmigrant family members of migrants in Mexico (odds ratio, 1.42; 95% confidence interval, 1.04-1.94). Associations between migration and disorder varied across birth cohorts. Elevated risk among migrants relative to nonmigrants was restricted to the 2 younger cohorts (those aged 18-25 or 26-35 years at interview). In the most recent birth cohort, the association between migration and first onset of any depressive or anxiety disorder was particularly strong (odds ratio, 3.89; 95% confidence interval, 2.74-5.53). This is, to our knowledge, the first study to compare risk for first onset of psychiatric disorder between representative samples of migrants in the United States and nonmigrants in Mexico. The findings are consistent with the hypothesized adverse effect of migration from Mexico to the United States on the mental health of migrants, but only among
Economic and evolutionary hypotheses for cross-population variation in parochialism
Daniel Jacob Hruschka; Joseph eHenrich
2013-01-01
Human populations differ reliably in the degree to which people favor family, friends and community members over strangers and outsiders. In the last decade, researchers have begun to propose several economic and evolutionary hypotheses for these cross-population differences in parochialism. In this paper, we outline major current theories and review recent attempts to test them. We also discuss the key methodological challenges in assessing these diverse economic and evolutionary theories...
Fairholme, Christopher P; Manber, Rachel
2014-03-01
Theoretical and empirical support for the role of dysfunctional beliefs, safety behaviors, and increased sleep effort in the maintenance of insomnia has begun to accumulate. It is not yet known how these factors predict sleep disturbance and fatigue occurring in the context of anxiety and mood disorders. It was hypothesized that these three insomnia-specific cognitive-behavioral factors would be uniquely associated with insomnia and fatigue among patients with emotional disorders after adjusting for current symptoms of anxiety and depression and trait levels of neuroticism and extraversion. Outpatients with a current anxiety or mood disorder (N = 63) completed self-report measures including the Dysfunctional Beliefs About Sleep Scale (DBAS), Sleep-Related Safety Behaviors Questionnaire (SRBQ), Glasgow Sleep Effort Scale (GSES), Pittsburgh Sleep Quality Index (PSQI), NEO Five-Factor Inventory (FFI), and the 21-item Depression Anxiety and Stress Scale (DASS). Multivariate path analysis was used to evaluate study hypotheses. SRBQ (B = .60, p relationship between safety behaviors and fatigue was strongest among individuals with greater levels of dysfunctional beliefs. Findings are consistent with cognitive behavioral models of insomnia and suggest that sleep-specific factors might be important treatment targets among patients with anxiety and depressive disorders with disturbed sleep. Copyright © 2013 Elsevier Inc. All rights reserved.
Hypothesized eye movements of neurolinguistic programming: a statistical artifact.
Farmer, A; Rooney, R; Cunningham, J R
1985-12-01
Neurolinguistic programming's hypothesized eye-movements were measured independently from videotapes of 30 subjects, aged 15 to 76 yr., who were asked to recall visual pictures, recorded audio sounds, and textural objects. chi 2 indicated that subjects' responses were significantly different from those predicted. When chi 2 comparisons were weighted by number of eye positions assigned to each modality (3 visual, 3 auditory, 1 kinesthetic), subjects' responses did not differ significantly from the expected pattern. These data indicate that the eye-movement hypothesis may represent randomly occurring rather than sensory-modality-related positions.
Blom, Rianne M; van Wingen, Guido A; van der Wal, Sija J; Luigjes, Judy; van Dijk, Milenna T; Scholte, H Steven; Denys, D.
2016-01-01
BACKGROUND: Body Integrity Identity Disorder (BIID) is a condition in which individuals perceive a mismatch between their internal body scheme and physical body shape, resulting in an absolute desire to be either amputated or paralyzed. The condition is hypothesized to be of congenital nature, but
Duloxetine in panic disorder with somatic gastric pain
Directory of Open Access Journals (Sweden)
Preve M
2013-11-01
Full Text Available Matteo Preve,1 Cristiana Nisita,1 Massimo Bellini,2 Liliana Dell'Osso1 1Department of Psychiatry, Neurobiology, Pharmacology and Biotechnology, 2Department of Gastroenterology, Gastrointestinal Unit, University of Pisa, Pisa, Italy Abstract: Panic disorder is the most common type of anxiety disorder, and its most common expression is panic attacks characterized with sudden attacks of anxiety with numerous symptoms, including palpitations, tachycardia, tachypnea, nausea, and vertigo: ie, cardiovascular, gastroenterologic, respiratory, and neuro-otologic symptoms. In clinical practice, panic disorder manifests with isolated gastroenteric or cardiovascular symptoms, requiring additional clinical visits after psychiatric intervention. The first-line treatment for anxiety disorders, and in particular for panic disorder, is the selective serotonin reuptake inhibitors. However, these drugs can have adverse effects, including sexual dysfunction, increased bodyweight, and abnormal bleeding, that may be problematic for some patients. Here we report the case of a 29-year-old Caucasian woman affected by panic disorder with agoraphobia who was referred to our clinic for recurrent gastroenteric panic symptoms. The patient reported improvement in her anxiety symptoms and panic attacks while on a selective serotonin reuptake inhibitor, but not in her gastric somatic problems, so the decision was taken to start her on duloxetine, a serotonin-norepinephrine reuptake inhibitor. After 6 months of treatment, the patient achieved complete remission of her gastric and panic-related symptoms, and was able to stop triple gastric therapy. Other authors have hypothesized and confirmed that duloxetine has greater initial noradrenergic effects than venlafaxine and is effective in patients with panic disorder. This case report underscores the possibility of tailoring therapeutic strategies for the gastroenteric expression of panic disorder. Keywords: anxiety disorder, panic
Morey, Leslie C; Bender, Donna S; Skodol, Andrew E
2013-09-01
The authors sought to determine whether a 5-point global rating of personality dysfunction on the Level of Personality Functioning Scale proposed as a severity index for Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), would be related to DSM-IV personality disorder diagnosis as well as to other key clinical judgments. Data were collected from a national sample of 337 mental health clinicians who provided complete diagnostic information relevant to DSM-IV and proposed DSM-5 personality disorder diagnoses, as well as demographic information and other clinical judgments, on one of their patients. Of the 337 patients described, 248 met criteria for 1 of the 10 specific DSM-IV personality disorders. A "moderate" or greater rating of impairment in personality functioning on the Level Scale demonstrated 84.6% sensitivity and 72.7% specificity for identifying patients meeting criteria for a specific DSM-IV personality disorder. The Level of Personality Functioning Scale had significant and substantial validity correlations with other measures of personality pathology and with clinical judgments regarding functioning, risk, prognosis, and optimal treatment intensity. Furthermore, the single-item Level of Personality Functioning rating was viewed as being as clinically useful as the 10 DSM-IV categories for treatment planning and patient description and was a better predictor of clinician ratings of broad psychosocial functioning than were the 10 DSM-IV categories combined. These results confirm hypotheses that the single-item Level of Personality Functioning Scale rating provides an indication of severity of personality pathology that predicts both assignment of personality disorder diagnosis and clinician appraisals of functioning, risk, prognosis, and needed treatment intensity.
Emotional intelligence, personality, and gender as factors in disordered eating patterns.
Zysberg, Leehu
2014-08-01
We examined the hypotheses that proposing higher levels of emotional intelligence (ability test and self-report) and lower neuroticism, extraversion, and agreeableness associate with lower levels of disordered eating. In a correlational study, 126 Israeli college students completed two measures of emotional intelligence, a brief five-factor personality test, demographic data questionnaires, and questionnaires assessing food preoccupation, namely, the Body Weight, Image and Self-Esteem Scale and the Appearance Schema Inventory. Results suggested that ability emotional intelligence is associated with disordered eating beyond gender and personality. Self-reported emotional intelligence did not associate with any of the outcomes after controlling for personality. Implications and applications are briefly discussed. © The Author(s) 2013.
Tessitore, Alessandro; De Micco, Rosa; Giordano, Alfonso; di Nardo, Federica; Caiazzo, Giuseppina; Siciliano, Mattia; De Stefano, Manuela; Russo, Antonio; Esposito, Fabrizio; Tedeschi, Gioacchino
2017-12-01
Impulse control disorders can be triggered by dopamine replacement therapies in patients with PD. Using resting-state functional MRI, we investigated the intrinsic brain network connectivity at baseline in a cohort of drug-naive PD patients who successively developed impulse control disorders over a 36-month follow-up period compared with patients who did not. Baseline 3-Tesla MRI images of 30 drug-naive PD patients and 20 matched healthy controls were analyzed. The impulse control disorders' presence and severity at follow-up were assessed by the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease Rating Scale. Single-subject and group-level independent component analysis was used to investigate functional connectivity differences within the major resting-state networks. We also compared internetwork connectivity between patients. Finally, a multivariate Cox regression model was used to investigate baseline predictors of impulse control disorder development. At baseline, decreased connectivity in the default-mode and right central executive networks and increased connectivity in the salience network were detected in PD patients with impulse control disorders at follow-up compared with those without. Increased default-mode/central executive internetwork connectivity was significantly associated with impulse control disorders development (P impulse control disorders while on dopaminergic treatment. We hypothesize that these divergent cognitive and limbic network connectivity changes could represent a potential biomarker and an additional risk factor for the emergence of impulse control disorders. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.
Neural Correlates of Irritability in Disruptive Mood Dysregulation and Bipolar Disorders.
Wiggins, Jillian Lee; Brotman, Melissa A; Adleman, Nancy E; Kim, Pilyoung; Oakes, Allison H; Reynolds, Richard C; Chen, Gang; Pine, Daniel S; Leibenluft, Ellen
2016-07-01
Bipolar disorder and disruptive mood dysregulation disorder (DMDD) are clinically and pathophysiologically distinct, yet irritability can be a clinical feature of both illnesses. The authors examine whether the neural mechanisms mediating irritability differ between bipolar disorder and DMDD, using a face emotion labeling paradigm because such labeling is deficient in both patient groups. The authors hypothesized that during face emotion labeling, irritability would be associated with dysfunctional activation in the amygdala and other temporal and prefrontal regions in both disorders, but that the nature of these associations would differ between DMDD and bipolar disorder. During functional MRI acquisition, 71 youths (25 with DMDD, 24 with bipolar disorder, and 22 healthy youths) performed a labeling task with happy, fearful, and angry faces of varying emotional intensity. Participants with DMDD and bipolar disorder showed similar levels of irritability and did not differ from each other or from healthy youths in face emotion labeling accuracy. Irritability correlated with amygdala activity across all intensities for all emotions in the DMDD group; such correlation was present in the bipolar disorder group only for fearful faces. In the ventral visual stream, associations between neural activity and irritability were found more consistently in the DMDD group than in the bipolar disorder group, especially in response to ambiguous angry faces. These results suggest diagnostic specificity in the neural correlates of irritability, a symptom of both DMDD and bipolar disorder. Such evidence of distinct neural correlates suggests the need to evaluate different approaches to treating irritability in the two disorders.
Choosing how to feel: emotion regulation choice in bipolar disorder.
Hay, Aleena C; Sheppes, Gal; Gross, James J; Gruber, June
2015-04-01
Individuals with bipolar disorder experience emotion regulation difficulties, even during remission, but are able to effectively employ emotion regulation strategies when instructed. We hypothesized that this puzzling discrepancy might be due to their maladaptive emotion regulation choices. To test this hypothesis, we used a previously validated paradigm (Sheppes, Scheibe, Suri, & Gross, 2011; Sheppes et al., 2014), and asked remitted individuals with bipolar I disorder (n = 25) and healthy individuals (n = 26) to view standardized positive and negative images of high and low intensity, and choose reappraisal or distraction to decrease their emotion intensity. Replicating and extending prior results, participants across both groups showed a pattern of choosing distraction more for high versus low intensity positive and negative images, but no between-groups differences were evident. These results suggest that emotion regulation choice patterns may be robust across samples, and add to growing evidence that several basic emotion regulation elements may remain intact in bipolar disorder. (c) 2015 APA, all rights reserved).
Molecular pathways towards psychiatric disorders
International Nuclear Information System (INIS)
Chela-Flores, J.
1987-07-01
The observed fibrillar-neuronal organization of the cerebral cortex suggests that in the aetiology of certain psychiatric disorders the genomic response of the neuron to the challenge presented by stress or insults at various stages of development, is to set off a programmed chain of molecular events (or ''pathways''), as demonstrated in previous genetic studies. The understanding of these pathways is important in order to enhance our ability to influence these illnesses, and are hypothesized to be initiated by a nucleolar mechanism for inducing abnormal synthesis of the nerve growth factor (NGF). The hypothesis is used to approach tentatively the still open question regarding the pathogenesis of mental retardation (MR) and senile dementia (SD). (author). 25 refs
Panic disorder: a different perspective.
Ranganathan, A; Beitman, B D
1998-02-01
Panic disorder is a chronic and debilitating illness. In this article, we present an algorithm of the diagnosis and treatment of the illness. We place much importance upon the patient variables associated with the treatment decisions. We emphasize strong patient involvement in treatment as a way to become panic free and improve level of functioning. Panic disorder is defined in DSM-IV1 as "The presence of recurrent panic attacks followed by at least one month of persistent concern about having another panic attack, worry about the possible implications or consequences of the panic attack, or a significant behavioral change related to the attacks." A panic attack is defined as "a discrete period of intense fear or discomfort, in which four or more of the following symptoms developed abruptly and reached a peak within 10 minutes." 1) Palpitations, pounding heart or accelerated heart rate; 2) sweating; 3) trembling or shaking; 4) sensations of shortness of breath or smothering; 5) feeling of choking; 6) chest pain or discomfort; 7) nausea or abdominal distress; 8) feeling dizzy, unsteady, light-headed or faint; 9) derealization or depersonalization; 10) fear of losing control or going crazy; 11) fear of dying; 12) paresthesias; 13) chills or hot flashes. The following hypotheses have been used to conceptualize panic disorder from a psychiatrist's perspective.
Fetal programming of neuropsychiatric disorders.
Faa, Gavino; Manchia, Mirko; Pintus, Roberta; Gerosa, Clara; Marcialis, Maria Antonietta; Fanos, Vassilios
2016-09-01
Starting from the Developmental Origins of Health and Disease (DOHaD) hypotheses proposed by David Barker, namely fetal programming, in the past years, there is a growing evidence of the major role played by epigenetic factors during the intrauterine life and the perinatal period. Furthermore, it has been assessed that these factors can affect the health status in infancy and even in adulthood. In this review, we focus our attention on the fetal programming of the brain, analyzing the most recent literature concerning the epigenetic factors that can influence the development of neuropsychiatric disorders such as bipolar disorders, major depressive disorders, and schizophrenia. The perinatal epigenetic factors have been divided in two main groups: maternal factors and fetal factors. The maternal factors include diet, smoking, alcoholism, hypertension, malnutrition, trace elements, stress, diabetes, substance abuse, and exposure to environmental toxicants, while the fetal factors include hypoxia/asphyxia, placental insufficiency, prematurity, low birth weight, drugs administered to the mother or to the baby, and all factors causing intrauterine growth restriction. A better comprehension of the possible mechanisms underlying the pathogenesis of these diseases may help researchers and clinicians develop new diagnostic tools and treatments to offer these patients a tailored medical treatment strategy to improve their quality of life. Birth Defects Research (Part C) 108:207-223, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Conscientiousness and obsessive-compulsive personality disorder.
Samuel, Douglas B; Widiger, Thomas A
2011-07-01
A dimensional perspective on personality disorder hypothesizes that the current diagnostic categories represent maladaptive variants of general personality traits. However, a fundamental foundation of this viewpoint is that dimensional models can adequately account for the pathology currently described by these categories. While most of the personality disorders have well established links to dimensional models that buttress this hypothesis, obsessive-compulsive personality disorder (OCPD) has obtained only inconsistent support. The current study administered multiple measures of 1) conscientiousness-related personality traits, 2) DSM-IV OCPD, and 3) specific components of OCPD (e.g., compulsivity and perfectionism) to a sample of 536 undergraduates who were oversampled for elevated OCPD scores. Six existing measures of conscientiousness-related personality traits converged strongly with each other supporting their assessment of a common trait. These measures of conscientiousness correlated highly with scales assessing specific components of OCPD, but obtained variable relationships with measures of DSM-IV OCPD. More specifically, there were differences within the conscientiousness instruments such that those designed to assess general personality functioning had small to medium relationships with OCPD, but those assessing more maladaptive variants obtained large effect sizes. These findings support the view that OCPD does represent a maladaptive variant of normal-range conscientiousness.
van Lang, NDJ; Bouma, A; Sytema, S; Kraijer, DW; Minderaa, RB; Van Lang, J.D.; Kraijer, S.W
2006-01-01
Central coherence theory hypothesizes individuals with autism process information in a detail-focused fashion. The present study examined whether adolescents with an intellectual disability and comorbid autism spectrum disorder showed a weaker central coherence than age- and IQ-matched controls. The
Blom, Rianne M.; van Wingen, Guido A.; van der Wal, Sija J.; Luigjes, Judy; van Dijk, Milenna T.; Scholte, H. Steven; Denys, Damiaan
2016-01-01
Body Integrity Identity Disorder (BIID) is a condition in which individuals perceive a mismatch between their internal body scheme and physical body shape, resulting in an absolute desire to be either amputated or paralyzed. The condition is hypothesized to be of congenital nature, but evidence for
Poole, Julia C; Kim, Hyoun S; Dobson, Keith S; Hodgins, David C
2017-12-01
Adverse childhood experiences (ACEs), such as sexual and physical abuse, have been established as risk factors for the development of disordered gambling. The underlying mechanism by which ACEs influence disordered gambling, however, remains unknown. The aims of the present research were to comprehensively investigate ten types of childhood adversity and their relationships to disordered gambling in adulthood, and to test whether emotion dysregulation mediated the relationship between ACEs and disordered gambling. A sample of community gamblers (N = 414) completed self-report measures of ACEs, emotion dysregulation, and gambling severity. Results revealed a significant association between all but one type (physical abuse) of ACEs and disordered gambling. Further, the results highlighted the cumulative impact of ACEs on gambling. Specifically, individuals who experienced three or more types of ACEs were more than three times as likely to report disordered gambling as compared to individuals with no history of childhood adversity. Importantly, as hypothesized, emotion dysregulation mediated the relationship between ACEs and disordered gambling. Findings from this research describe the association between ACEs and gambling and indicate a causal link between childhood adversity and disordered gambling. Results suggest that treatment initiatives may do well to address both ACEs and emotion dysregulation in the treatment of problem gambling.
Hug, Bruce; Abbas, Richat; Leister, Cathie; Burns, Jaime; Sonnichsen, Daryl
2010-08-01
Neratinib is an orally administered, small-molecule, irreversible pan-ErbB inhibitor in development for the treatment of ErbB2-positive breast cancer. This study assessed the effects of therapeutic and supratherapeutic neratinib concentrations on cardiac repolarization, in accordance with current regulatory guidance. This was a two-part study in healthy subjects. In part 1, subjects were randomized to receive placebo, 400 mg moxifloxacin, or 240 mg neratinib (therapeutic dose) following a high-fat meal. In part 2, after a washout period, subjects received placebo plus 400 mg ketoconazole or 240 mg neratinib plus ketoconazole (supratherapeutic dose). ANOVA was used to compare the baseline-adjusted QTc interval for neratinib with that of placebo (reference), and for neratinib plus ketoconazole with that of placebo plus ketoconazole (reference). Pharmacokinetic/pharmacodynamic analyses and categorical summaries of interval data were done. Assay sensitivity was evaluated by the effect of moxifloxacin on QTc compared with placebo. Sixty healthy subjects were enrolled in this study. The upper bounds of the 90% confidence interval for baseline-adjusted QTcN (population-specific corrected QT) were neratinib. Pharmacokinetic/pharmacodynamic analysis revealed no relationship between neratinib concentrations and QTc interval. No subjects had QTcI, QTcF, or QTcN intervals >450 milliseconds or change from baseline >30 milliseconds. Moxifloxacin produced a significant increase in QTcN compared with placebo (P neratinib do not prolong the QTc interval in healthy subjects. (c) 2010 AACR.
NegaWatt 2011-2050 scenario - Hypotheses and method. Technical report, May 2014
International Nuclear Information System (INIS)
2014-05-01
This report proposes an analysis of the negaWatt 2011 scenario. It describes in detail the methodology adopted to elaborate this prospective scenario, and presents the major part of the hypotheses which structure this scenario. A first part presents the approach and methodology (constraints, scenario, model). The second part addresses the issue of energy saving and energy efficiency through a sector-based analysis (housing and office building, transports, industrial and agricultural production). The third part studies the substitution by renewable energies through a supply analysis: energy production based on biomass, renewable energies, and fissile and fossil energies. It outlines the major role of grids in the supply-demand balance. The results of the negaWatt 2011 scenario are presented in terms of final energy, primary energies, and impact on greenhouse gas emissions. Hypotheses and results related to the different sectors (building, transports, industry and agriculture, energy production) are given in appendix
DEFF Research Database (Denmark)
Linnet, Karen Markussen; Wisborg, Kirsten; Secher, Niels Jørgen
2008-01-01
Aim: Based on hypotheses from experimental studies, we studied the association between intrauterine exposure to coffee and the risk of clinically verified hyperkinetic disorder and attention-deficit hyperactivity disorder (ADHD). Methods: A cohort study with prospectively collected data from...... 88 children with hyperkinetic disorder and ADHD. Information about coffee consumption during pregnancy was obtained at 16 weeks of gestation from self-administrated questionnaires. Potential confounding factors were evaluated using Cox regression analyses. Results: We found that intrauterine exposure...... to 10 or more cups of coffee per day was associated with a threefold increased risk of hyperkinetic disorder and ADHD. After adjustments for a number of confounding factors, the risk decreased and became statistically insignificant (RR 2.3, 95% CI 0.9-5.9). Conclusion: Prenatal exposure to high levels...
Economic and evolutionary hypotheses for cross-population variation in parochialism.
Hruschka, Daniel J; Henrich, Joseph
2013-09-11
Human populations differ reliably in the degree to which people favor family, friends, and community members over strangers and outsiders. In the last decade, researchers have begun to propose several economic and evolutionary hypotheses for these cross-population differences in parochialism. In this paper, we outline major current theories and review recent attempts to test them. We also discuss the key methodological challenges in assessing these diverse economic and evolutionary theories for cross-population differences in parochialism.
Kostrubiec, Viviane; Huys, Raoul; Jas, Brunhilde; Kruck, Jeanne
2018-01-01
Abnormal perceptual-motor coordination is hypothesized here to be involved in social deficits of autism spectrum disorder (ASD). To test this hypothesis, high functioning children with ASD and typical controls, similar in age as well as verbal and perceptive performance, performed perceptual-motor coordination tasks and several social competence…
Kuiper, Rebecca M; Nederhoff, Tim; Klugkist, Irene
2015-05-01
In this paper, the performance of six types of techniques for comparisons of means is examined. These six emerge from the distinction between the method employed (hypothesis testing, model selection using information criteria, or Bayesian model selection) and the set of hypotheses that is investigated (a classical, exploration-based set of hypotheses containing equality constraints on the means, or a theory-based limited set of hypotheses with equality and/or order restrictions). A simulation study is conducted to examine the performance of these techniques. We demonstrate that, if one has specific, a priori specified hypotheses, confirmation (i.e., investigating theory-based hypotheses) has advantages over exploration (i.e., examining all possible equality-constrained hypotheses). Furthermore, examining reasonable order-restricted hypotheses has more power to detect the true effect/non-null hypothesis than evaluating only equality restrictions. Additionally, when investigating more than one theory-based hypothesis, model selection is preferred over hypothesis testing. Because of the first two results, we further examine the techniques that are able to evaluate order restrictions in a confirmatory fashion by examining their performance when the homogeneity of variance assumption is violated. Results show that the techniques are robust to heterogeneity when the sample sizes are equal. When the sample sizes are unequal, the performance is affected by heterogeneity. The size and direction of the deviations from the baseline, where there is no heterogeneity, depend on the effect size (of the means) and on the trend in the group variances with respect to the ordering of the group sizes. Importantly, the deviations are less pronounced when the group variances and sizes exhibit the same trend (e.g., are both increasing with group number). © 2014 The British Psychological Society.
The Iowa Gambling Task and the Three Fallacies of Dopamine in Gambling Disorder.
Directory of Open Access Journals (Sweden)
Jakob eLinnet
2013-10-01
Full Text Available Gambling disorder sufferers prefer immediately larger rewards despite long term losses on the Iowa Gambling Task (IGT, and these impairments are associated with dopamine dysfunctions. Dopamine is a neurotransmitter linked with temporal and structural dysfunctions in substance use disorder, which has supported the idea of impaired decision-making and dopamine dysfunctions in gambling disorder. However, evidence from substance use disorders cannot be directly transferred to gambling disorder. This article focuses on three hypotheses of dopamine dysfunctions in gambling disorder, which appear to be fallacies, i.e., have not been supported in a series of positron emission tomography (PET studies. The first fallacy suggests that gambling disorder suffers, similar to substance use disorders, have lower dopamine receptor availability. No evidence supported this hypothesis. The second fallacy suggests that maladaptive decision-making in gambling disorder is associated with higher dopamine release during gambling. No evidence supported the hypothesis, and the literature on substance use disorders offers limited support for this hypothesis. The third fallacy suggests that maladaptive decision-making in gambling disorder is associated with higher dopamine release during winning. The evidence did not support this hypothesis either. Instead, dopaminergic coding of reward prediction and uncertainty might better account for dopamine dysfunctions in gambling disorder. Studies of reward prediction and reward uncertainty shows a sustained dopamine response towards stimuli with maximum uncertainty, which may explain the continued dopamine release and gambling despite losses in gambling disorder. The findings from the studies presented here are consistent with the notion of dopaminergic dysfunctions of reward prediction and reward uncertainty signals in gambling disorder.
Schlagbauer, Bernhard; Mink, Maurice; Müller, Hermann J; Geyer, Thomas
2017-02-01
Observers are able to resume an interrupted search trial faster relative to responding to a new, unseen display. This finding of rapid resumption is attributed to short-term perceptual hypotheses generated on the current look and confirmed upon subsequent looks at the same display. It has been suggested that the contents of perceptual hypotheses are similar to those of other forms of memory acquired long-term through repeated exposure to the same search displays over the course of several trials, that is, the memory supporting "contextual cueing." In three experiments, we investigated the relationship between short-term perceptual hypotheses and long-term contextual memory. The results indicated that long-term, contextual memory of repeated displays neither affected the generation nor the confirmation of short-term perceptual hypotheses for these displays. Furthermore, the analysis of eye movements suggests that long-term memory provides an initial benefit in guiding attention to the target, whereas in subsequent looks guidance is entirely based on short-term perceptual hypotheses. Overall, the results reveal a picture of both long- and short-term memory contributing to reliable performance gains in interrupted search, while exerting their effects in an independent manner.
van der Meer, Dennis; Hartman, Catharina A.; van Rooij, Daan; Franke, Barbara; Heslenfeld, Dirk J.; Oosterlaan, Jaap; Faraone, Stephen V.; Buitelaar, Jan K.; Hoekstra, Pieter J.
2017-01-01
Background: Attention-deficit/hyperactivity disorder (ADHD) is often accompanied by impaired response inhibition; both have been associated with aberrant dopamine signalling. Given that prenatal exposure to alcohol or smoking is known to affect dopamine-rich brain regions, we hypothesized that
Meer, D. van der; Hartman, C.A.; Rooij, D. van; Franke, B.; Heslenfeld, D.J.; Oosterlaan, J.; Faraone, S.V; Buitelaar, J.K.; Hoekstra, P.J.
2017-01-01
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is often accompanied by impaired response inhibition; both have been associated with aberrant dopamine signalling. Given that prenatal exposure to alcohol or smoking is known to affect dopamine-rich brain regions, we hypothesized that
van der Meer, Dennis; Hartman, Catharina A.; van Rooij, Daan; Franke, Barbara; Heslenfeld, Dirk J.; Oosterlaan, Jaap; Faraone, Stephen V.; Buitelaar, Jan K.; Hoekstra, Pieter J.
Background Attention-deficit/hyperactivity disorder (ADHD) is often accompanied by impaired response inhibition; both have been associated with aberrant dopamine signalling. Given that prenatal exposure to alcohol or smoking is known to affect dopamine-rich brain regions, we hypothesized that
De bruikbaarheid van de ‘shaken baby syndroom’-hypothese in het strafproces
Hoving, R.A.
In het Nederlandse strafproces wordt regelmatig gebruik gemaakt van deskundigenbewijs van deskundigen die uitgaan van de ‘shaken baby syndroom’-hypothese om aan te tonen dat een verdachte een baby heeft mishandeld of gedood. In onder meer de Verenigde Staten en Engeland woedt een felle discussie
The Ranschburg Effect: Tests of the Guessing-Bias and Proactive Interference Hypotheses
Walsh, Michael F.; Schwartz, Marian
1977-01-01
The guessing-bias and proactive interference hypotheses of the Ranschburg Effect were investigated by giving three groups different instructions as to guessing during recall. Results failed to support the prediction that the effect should be reduced or eliminated on shift trials. Neither hypothesis received significant support. (CHK)
Use of hypotheses for analysis of variance Models: Challenging the current practice
van Wesel, F.; Boeije, H.R.; Hoijtink, H
2013-01-01
In social science research, hypotheses about group means are commonly tested using analysis of variance. While deemed to be formulated as specifically as possible to test social science theory, they are often defined in general terms. In this article we use two studies to explore the current
Conner, Kenneth R; Bossarte, Robert M; Lu, Naiji; Kaukeinen, Kimberly; Chan, Grace; Wyman, Peter; Tu, Xin M; Goldston, David B; Houston, Rebecca J; Bucholz, Kathleen K; Hesselbrock, Victor M
2014-01-01
Parents with psychopathology such as alcohol use disorder (AUD) that confers risk for suicide attempt (SA) may have children who are more likely to develop such psychopathology and to attempt suicide, suggesting that risk may be "transmitted" from parents to children. We examined this phenomenon during the transition from childhood to adolescence, when risk for SA increases dramatically. A cohort of 418 children were examined at average age 9.4 (range 7-14) years at enrollment (Time 1, childhood) and approximately 5 years later, prior to reaching age 18 (Time 2, adolescence). One or both biological parents, oversampled for AUD, were also interviewed. Structural equation models (SEM) examined father-child, mother-child, and either/both parent-child associations. The primary outcome was SA over follow-up among offspring, assessed at Time 2. As hypothesized, parental antisocial personality disorder predicted conduct disorder symptoms in offspring both during childhood and adolescence (parent-child model, father-child model) and maternal AUD predicted conduct disorder symptoms during childhood (mother-child model). However, we did not find evidence to support transmission of depression from parents to offspring either during childhood or adolescence, and parent psychopathology did not show statistically significant associations with SA during adolescence. In conclusion, we conducted a rare study of parent-to-child "transmission" of risk for SA that used a prospective research design, included diagnostic interviews with both parents and offspring, and examined the transition from childhood to adolescence, and the first such study in children of parents with AUD. Results provided mixed support for hypothesized parent-child associations.
Transactional processes in the development of adult personality disorder symptoms.
Carlson, Elizabeth A; Ruiz, Sarah K
2016-08-01
The development of adult personality disorder symptoms, including transactional processes of relationship representational and behavioral experience from infancy to early adolescence, was examined using longitudinal data from a risk sample (N = 162). Significant preliminary correlations were found between early caregiving experience and adult personality disorder symptoms and between representational and behavioral indices across time and adult symptomatology. Significant correlations were also found among diverse representational assessments (e.g., interview, drawing, and projective narrative) and between concurrent representational and observational measures of relationship functioning. Path models were analyzed to investigate the combined relations of caregiving experience in infancy; relationship representation and experience in early childhood, middle childhood, and early adolescence; and personality disorder symptoms in adulthood. The hypothesized model representing interactive contributions of representational and behavioral experience represented the data significantly better than competing models representing noninteractive contributions. Representational and behavioral indicators mediated the link between early caregiving quality and personality disorder symptoms. The findings extend previous studies of normative development and support an organizational developmental view that early relationship experiences contribute to socioemotional maladaptation as well as adaptation through the progressive transaction of mutually informing expectations and experience.
Zinc in Gut-Brain Interaction in Autism and Neurological Disorders
Vela, Guillermo; Stark, Peter; Socha, Michael; Sauer, Ann Katrin; Hagmeyer, Simone; Grabrucker, Andreas M.
2015-01-01
A growing amount of research indicates that abnormalities in the gastrointestinal (GI) system during development might be a common factor in multiple neurological disorders and might be responsible for some of the shared comorbidities seen among these diseases. For example, many patients with Autism Spectrum Disorder (ASD) have symptoms associated with GI disorders. Maternal zinc status may be an important factor given the multifaceted effect of zinc on gut development and morphology in the offspring. Zinc status influences and is influenced by multiple factors and an interdependence of prenatal and early life stress, immune system abnormalities, impaired GI functions, and zinc deficiency can be hypothesized. In line with this, systemic inflammatory events and prenatal stress have been reported to increase the risk for ASD. Thus, here, we will review the current literature on the role of zinc in gut formation, a possible link between gut and brain development in ASD and other neurological disorders with shared comorbidities, and tie in possible effects on the immune system. Based on these data, we present a novel model outlining how alterations in the maternal zinc status might pathologically impact the offspring leading to impairments in brain functions later in life. PMID:25878905
Economic and evolutionary hypotheses for cross-population variation in parochialism
Directory of Open Access Journals (Sweden)
Daniel Jacob Hruschka
2013-09-01
Full Text Available Human populations differ reliably in the degree to which people favor family, friends and community members over strangers and outsiders. In the last decade, researchers have begun to propose several economic and evolutionary hypotheses for these cross-population differences in parochialism. In this paper, we outline major current theories and review recent attempts to test them. We also discuss the key methodological challenges in assessing these diverse economic and evolutionary theories for cross-population differences in parochialism.
Human female orgasm as evolved signal: a test of two hypotheses.
Ellsworth, Ryan M; Bailey, Drew H
2013-11-01
We present the results of a study designed to empirically test predictions derived from two hypotheses regarding human female orgasm behavior as an evolved communicative trait or signal. One hypothesis tested was the female fidelity hypothesis, which posits that human female orgasm signals a woman's sexual satisfaction and therefore her likelihood of future fidelity to a partner. The other was sire choice hypothesis, which posits that women's orgasm behavior signals increased chances of fertilization. To test the two hypotheses of human female orgasm, we administered a questionnaire to 138 females and 121 males who reported that they were currently in a romantic relationship. Key predictions of the female fidelity hypothesis were not supported. In particular, orgasm was not associated with female sexual fidelity nor was orgasm associated with male perceptions of partner sexual fidelity. However, faked orgasm was associated with female sexual infidelity and lower male relationship satisfaction. Overall, results were in greater support of the sire choice signaling hypothesis than the female fidelity hypothesis. Results also suggest that male satisfaction with, investment in, and sexual fidelity to a mate are benefits that favored the selection of orgasmic signaling in ancestral females.
Lahav, Noam
1993-12-01
The applicability of the RNA-world and co-evolution hypotheses to the study of the very first stages of the origin of life is discussed. The discussion focuses on the basic differences between the two hypotheses and their implications, with regard to the reconstruction methodology, ribosome emergence, balance between ribozymes and protein enzymes, and their major difficulties. Additional complexities of the two hypotheses, such as membranes and the energy source of the first reactions, are not treated in the present work. A central element in the proposed experimental strategies is the study of the catalytic activities of very small peptides and RNA-like oligomers, according to existing, as well as to yet-to-be-invented scenarios of the two hypotheses under consideration. It is suggested that the noveldirected molecular evolution technology, andmolecular computational modeling, can be applied to this research. This strategy is assumed to be essential for the suggested goal of future studies of the origin of life, namely, the establishment of a ‘Primordial Darwinian entity’.
Zickgraf, Hana F.; Franklin, Martin E.; Rozin, Paul
2016-01-01
Background One presentation of Avoidant/Restrictive Food Intake Disorder (ARFID) is characterized by picky eating, i.e., selective eating based on the sensory properties of food. The present study has two aims. The first is to describe distress and impairment in individuals with ARFID secondary to picky eating. The second is to determine whether eating behaviors hypothesized to be specific to picky eating can differentiate picky eaters with and without ARFID from typical eaters (e.g., individ...
Testing evolutionary hypotheses for phenotypic divergence using landscape genetics.
Funk, W Chris; Murphy, Melanie A
2010-02-01
Understanding the evolutionary causes of phenotypic variation among populations has long been a central theme in evolutionary biology. Several factors can influence phenotypic divergence, including geographic isolation, genetic drift, divergent natural or sexual selection, and phenotypic plasticity. But the relative importance of these factors in generating phenotypic divergence in nature is still a tantalizing and unresolved problem in evolutionary biology. The origin and maintenance of phenotypic divergence is also at the root of many ongoing debates in evolutionary biology, such as the extent to which gene flow constrains adaptive divergence (Garant et al. 2007) and the relative importance of genetic drift, natural selection, and sexual selection in initiating reproductive isolation and speciation (Coyne & Orr 2004). In this issue, Wang & Summers (2010) test the causes of one of the most fantastic examples of phenotypic divergence in nature: colour pattern divergence among populations of the strawberry poison frog (Dendrobates pumilio) in Panama and Costa Rica (Fig. 1). This study provides a beautiful example of the use of the emerging field of landscape genetics to differentiate among hypotheses for phenotypic divergence. Using landscape genetic analyses, Wang & Summers were able to reject the hypotheses that colour pattern divergence is due to isolation-by-distance (IBD) or landscape resistance. Instead, the hypothesis left standing is that colour divergence is due to divergent selection, in turn driving reproductive isolation among populations with different colour morphs. More generally, this study provides a wonderful example of how the emerging field of landscape genetics, which has primarily been applied to questions in conservation and ecology, now plays an essential role in evolutionary research.
Bedics, Jamie D; Atkins, David C; Comtois, Katherine Anne; Linehan, Marsha M
2012-06-01
The purpose of the present study was to examine theory-driven hypotheses of the therapeutic relationship and patient introject in dialectical behavior therapy (DBT; Linehan, 1993) for the treatment of borderline personality disorder. A total of 14 DBT therapists provided weekly ratings of the therapeutic relationship and patient introject (N=41) during the course of a randomized controlled trial of DBT for the treatment of borderline personality disorder. Using hierarchical linear modeling (Raudenbush & Bryk, 2002), we tested four hypotheses of the therapeutic relationship as predicted by DBT and behavioral theory. Results supported three of our four predicted hypotheses of the therapeutic relationship, including the effective use of balancing autonomy and control in the therapeutic relationship, the importance of therapists' maintaining a nonpejorative stance toward the patient, and the use of therapist warmth and autonomy as a contingency for improved intrapsychic outcome. Results did not support a modeling hypothesis of the therapeutic relationship. The study supported a DBT and behavioral model of the therapeutic relationship from the perspective of the treating clinician. PsycINFO Database Record (c) 2012 APA, all rights reserved.
Post, Robert M.; Altshuler, Lori L.; Kupka, Ralph; McElroy, Susan L.; Frye, Mark A.; Rowe, Michael; Grunze, Heinz; Suppes, Trisha; Keck, Paul E.; Nolen, Willem A.
2017-01-01
Background: Patients with bipolar disorder from the US have more early-onset illness and a greater familial loading for psychiatric problems than those from the Netherlands or Germany (abbreviated here as Europe). We hypothesized that these regional differences in illness burden would extend to the
Olivier, J D A; Van Der Hart, M G C; Van Swelm, R P L; Dederen, P J; Homberg, J R; Cremers, T; Deen, P M T; Cuppen, E; Cools, A R; Ellenbroek, B A
2008-01-01
Human studies have shown that a reduction of 5-HT transporter (SERT) increases the vulnerability for anxiety and depression. Moreover, women are more vulnerable to develop depression and anxiety disorders than men. For that reason we hypothesized that homozygous 5-HT transporter knockout rat
Reciprocal deletion and duplication at 2q23.1 indicates a role for MBD5 in autism spectrum disorder
Mullegama, S.V.; Rosenfeld, J.A.; Orellana, C.; Bon, B.W.M. van; Halbach, S.; Repnikova, E.A.; Brick, L.; Li, C.; Dupuis, L.; Rosello, M.; Aradhya, S.; Stavropoulos, D.J.; Manickam, K.; Mitchell, E.; Hodge, J.C.; Talkowski, M.E.; Gusella, J.F.; Keller, K.; Zonana, J.; Schwartz, S.; Pyatt, R.E.; Waggoner, D.J.; Shaffer, L.G.; Lin, A.E.; Vries, B. de; Mendoza-Londono, R.; Elsea, S.H.
2014-01-01
Copy number variations associated with abnormal gene dosage have an important role in the genetic etiology of many neurodevelopmental disorders, including intellectual disability (ID) and autism. We hypothesize that the chromosome 2q23.1 region encompassing MBD5 is a dosage-dependent region, wherein
Olivier, J.; Van Der Hart, M.G.C.; Van Swelm, R.P.L.; Dederen, P.J.; Homberg, J.R.; Cremers, T.; Deen, P.M.T.; Cuppen, E.; Cools, A.R.; Ellenbroek, B.A.
2008-01-01
Human studies have shown that a reduction of 5-HT transporter (SERT) increases the vulnerability for anxiety and depression. Moreover, women are more vulnerable to develop depression and anxiety disorders than men. For that reason we hypothesized that homozygous 5-HT transporter knockout rat
Autism spectrum disorders: toward a gendered embodiment model.
Cheslack-Postava, Keely; Jordan-Young, Rebecca M
2012-06-01
One of the most consistent observations in the epidemiology of autism spectrum disorders (ASD) is the preponderance of male cases. A few hypotheses have been put forth which attempt to explain this divergence in terms of sex-linked biology, with limited success. Feminist epidemiologists suggest the importance of investigating specific mechanisms for male-female differences in health outcomes, which may include sex-linked biology and/or gender relations, as well as complex biosocial interactions. Neither domain has been systematically investigated for autism, and the possible role of gender has been particularly neglected. In this article, we posit hypotheses about how social processes based on perception of persons as male or female, particularly patterns of social and physical interaction in early development, may affect the observed occurrence and diagnosis of ASD. We gesture toward an embodiment model, incorporating hypotheses about initial biological vulnerabilities to autism--which may or may not be differentially distributed in relation to sex biology--and their interactions with gender relations, which are demonstrably different for male and female infants. Toward building such a model, we first review the epidemiology of ASD with an eye toward male-female differences, then present a theory of gender as a "pervasive developmental environment" with relevance for the excess burden of autism among males. Finally, we suggest research strategies to further investigate this issue. Copyright © 2011 Elsevier Ltd. All rights reserved.
Wang, Mingyang; Zhang, Feifei; Song, Chao; Shi, Pengfei; Zhu, Jin
2016-07-01
Innovation in hypotheses is a key transformative driver for scientific development. The conventional centralized hypothesis formulation approach, where a dominant hypothesis is typically derived from a primary phenomenon, can, inevitably, impose restriction on the range of conceivable experiments and legitimate hypotheses, and ultimately impede understanding of the system of interest. We report herein the proposal of a decentralized approach for the formulation of hypotheses, through initial preconception-free phenomenon accumulation and subsequent reticular logical reasoning processes. The two-step approach can provide an unbiased, panoramic view of the system and as such should enable the generation of a set of more coherent and therefore plausible hypotheses. As a proof-of-concept demonstration of the utility of this open-ended approach, a hierarchical model has been developed for a prion self-assembled system, allowing insight into hitherto elusive static and dynamic features associated with this intriguing structure.
Schlumpf, Yolanda R.; Nijenhuis, Ellert R. S.; Chalavi, Sima; Weder, Ekaterina V.; Zimmermann, Eva; Luechinger, Roger; La Marca, Roberto; Reinders, A. A. T. Simone; Jaencke, Lutz
2013-01-01
Objective: The Theory of Structural Dissociation of the Personality (TSDP) proposes that dissociative identity disorder (DID) patients are fixed in traumatic memories as "Emotional Parts" (EP), but mentally avoid these as "Apparently Normal Parts" of the personality (ANP). We tested the hypotheses
Bullying Victimization and Adolescent Self-Harm: Testing Hypotheses from General Strain Theory
Hay, Carter; Meldrum, Ryan
2010-01-01
Self-harm is widely recognized as a significant adolescent social problem, and recent research has begun to explore its etiology. Drawing from Agnew's (1992) social psychological strain theory of deviance, this study considers this issue by testing three hypotheses about the effects of traditional and cyber bullying victimization on deliberate…
Mukherjee, Sumit; Baidoo, Juliet N E; Sampat, Samay; Mancuso, Andrew; David, Lovena; Cohen, Leah S; Zhou, Shuiqin; Banerjee, Probal
2018-01-18
Glioblastoma (GBM) is a deadly brain tumor with a current mean survival of 12-15 months. Despite being a potent anti-cancer agent, the turmeric ingredient curcumin (C) has limited anti-tumor efficacy in vivo due to its low bioavailability. We have reported earlier a strategy involving the use two other polyphenols, epicatechin gallate (E) from green tea and resveratrol (R) from red grapes at a unique, synergistic molar ratio with C (C:E:R: 4:1:12.5, termed TriCurin) to achieve superior potency against HPV+ tumors than C alone at C:E:R (μM): 32:8:100 (termed 32 μM+ TriCurin). We have now prepared liposomal TriCurin (TrLp) and demonstrated that TrLp boosts activated p53 in cultured GL261 mouse GBM cells to trigger apoptosis of GBM and GBM stem cells in vitro. TrLp administration into mice yielded a stable plasma concentration of 210 nM C for 60 min, which, though sub-lethal for cultured GL261 cells, was able to cause repolarization of M2-like tumor (GBM)-associated microglia/macrophages to the tumoricidal M1-like phenotype and intra-GBM recruitment of activated natural killer cells. The intratumor presence of such tumoricidal immune cells was associated with concomitant suppression of tumor-load, and apoptosis of GBM and GBM stem cells. Thus, TrLp is a potential onco-immunotherapeutic agent against GBM tumors.
Directory of Open Access Journals (Sweden)
Sumit Mukherjee
2018-01-01
Full Text Available Glioblastoma (GBM is a deadly brain tumor with a current mean survival of 12–15 months. Despite being a potent anti-cancer agent, the turmeric ingredient curcumin (C has limited anti-tumor efficacy in vivo due to its low bioavailability. We have reported earlier a strategy involving the use two other polyphenols, epicatechin gallate (E from green tea and resveratrol (R from red grapes at a unique, synergistic molar ratio with C (C:E:R: 4:1:12.5, termed TriCurin to achieve superior potency against HPV+ tumors than C alone at C:E:R (μM: 32:8:100 (termed 32 μM+ TriCurin. We have now prepared liposomal TriCurin (TrLp and demonstrated that TrLp boosts activated p53 in cultured GL261 mouse GBM cells to trigger apoptosis of GBM and GBM stem cells in vitro. TrLp administration into mice yielded a stable plasma concentration of 210 nM C for 60 min, which, though sub-lethal for cultured GL261 cells, was able to cause repolarization of M2-like tumor (GBM-associated microglia/macrophages to the tumoricidal M1-like phenotype and intra-GBM recruitment of activated natural killer cells. The intratumor presence of such tumoricidal immune cells was associated with concomitant suppression of tumor-load, and apoptosis of GBM and GBM stem cells. Thus, TrLp is a potential onco-immunotherapeutic agent against GBM tumors.
Rhea, Deborah J; Thatcher, W Gregory
2013-01-01
The purpose of this study was two-fold: to determine the relationship between ethnic identity and self-esteem as dimensions of one's self-concept; and to determine if differences exist among one's ethnicity, ethnic identity, and/or self-esteem when examining at-risk eating disordered behaviors. A total of 893 urban adolescent females completed three behavioral subscales: the Eating Disorder Inventory, Rosenberg's Self-Esteem Scale, and Phinney's Multigroup Ethnic Identity Measure. As hypothesized, ethnic identity was significantly associated with self-esteem to form one's self-concept. When compared to Mexican American and White females, only Black females who were in the higher ethnic identity and self-esteem categories had significantly lower at-risk eating disordered scores. Our findings suggest eating disorder status in Mexican American and White females may not be associated as much with ethnic identity as with other acculturation and self-concept factors. Further, this study demonstrated ethnicity, self-esteem, and ethnic identity play significant roles in eating disorder risks.
Gait unsteadiness and fall risk in two affective disorders: a preliminary study
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Peng Chung-Kang
2004-11-01
Full Text Available Abstract Background In older adults, depression has been associated with increased fall risk, but the reasons for this link are not fully clear. Given parallels between major depression and Parkinson's disease, we hypothesized that major depression and related affective disorders would be associated with impairment in the ability to regulate the stride-to-stride fluctuations in gait cycle timing. Methods We measured stride-to-stride fluctuations of patients with two forms of mood disorders, unipolar major depressive disorder (MDD and bipolar disorder, and compared their gait to that of a healthy control group. The primary outcomes were two measures of gait unsteadiness that have been associated with fall risk: stride time variability and swing time variability. Results Compared to the control group, the two patient groups tended to walk more slowly and with decreased swing time and increased stride time. However, none of these differences was statistically significant. Compared to the control group, swing time variability was significantly larger in the subjects with bipolar disorder (p Conclusions Patients with MDD and patients with bipolar disorder display gait unsteadiness. This perturbation in gait may provide a mechanistic link connecting depression and falls. The present findings also suggest the possibility that measurement of variability of gait may provide a readily quantifiable objective approach to monitoring depression and related affective disorders.
Integrated approach to yoga therapy and autism spectrum disorders
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Shantha Radhakrishna
2010-01-01
Full Text Available A specially designed Integrated Approach to Yoga Therapy module was applied to Autism Spectrum Disorders over a period of two academic years. Despite low numbers (six in each arm, consistency and magnitude of effects make the findings significant. Parental participation, allowing firm guidance to be given to each child, resulted in significant improvements in imitation and other skills, and in behavior at home and family relationships. We hypothesize that guided imitation of therapist body positions stimulated mirror neuron activation, resulting in improved sense of self.
Lost in the chaos: Flawed literature should not generate new disorders
Van Rooij, Antonius J.; Kardefelt-Winther, Daniel
2017-01-01
The paper by Kuss, Griffiths, and Pontes (2016) titled “Chaos and confusion in DSM-5 diagnosis of Internet Gaming Disorder: Issues, concerns, and recommendations for clarity in the field” examines issues relating to the concept of Internet Gaming Disorder. We agree that there are serious issues and extend their arguments by suggesting that the field lacks basic theory, definitions, patient research, and properly validated and standardized assessment tools. As most studies derive data from survey research in functional populations, they exclude people with severe functional impairment and provide only limited information on the hypothesized disorder. Yet findings from such studies are widely used and often exaggerated, leading many to believe that we know more about the problem behavior than we do. We further argue that video game play is associated with several benefits and that formalizing this popular hobby as a psychiatric disorder is not without risks. It might undermine children’s right to play or encourage repressive treatment programs, which ultimately threaten children’s right to protection against violence. While Kuss et al. (2016) express support for the formal implementation of a disorder, we argue that before we have a proper evidence base, a sound theory, and validated assessment tools, it is irresponsible to support a formal category of disorder and doing so would solidify a confirmatory approach to research in this area. PMID:28301968
Educational Transitions in Israel: A Test of the Industrialization and Credentialism Hypotheses.
Shavit, Yossi; Kraus, Vered
1990-01-01
Explores the industrialization and credentialism hypotheses and predictions of educational attainment levels. Finds the effects of the father's education and occupation were stable for those attending school in the 1940s, 1950s, and 1960s. Notes that the effects of ethnicity declined in the transition from primary to secondary school. (NL)
International Nuclear Information System (INIS)
Gibson, C.H.
1991-01-01
Kolmogorov's three universal similarity hypotheses are extrapolated to describe scalar fields like temperature mixed by turbulence. The analogous first and second hypotheses for scalars include the effects of Prandtl number and rate-of-strain mixing. Application of velocity and scalar similarity hypotheses to the ocean must take into account the damping of active turbulence by density stratification and the Earth's rotation to form fossil turbulence. By the analogous Kolmogorov third hypothesis for scalars, temperature dissipation rates χ averaged over lengths r > L K should be lognormally distributed with intermittency factors σ 2 that increase with increasing turbulence energy length scales L O as σ ln r 2 approx = μ θ ln(L O /r). Tests of kolmogorovian velocity and scalar universal similarity hypotheses for very large ranges of turbulence length and timescales are provided by data from the ocean and the galactic interstellar medium. These ranges are from 1 to 9 decades in the ocean, and over 12 decades in the interstellar medium. The universal constant for turbulent mixing intermittency μ θ is estimated from oceanic data to be 0.44±0.01, which is remarkably close to estimates for Kolmorgorov's turbulence intermittency constant μ of 0.45±0.05 from galactic as well as atmospheric data. Extreme intermittency complicates the oceanic sampling problem, and may lead to quantitative and qualitative undersampling errors in estimates of mean oceanic dissipation rates and fluxes. Intermittency of turbulence and mixing in the interstellar medium may be a factor in the formation of stars. (author)
Directory of Open Access Journals (Sweden)
Hanna E Stevens
2010-09-01
Full Text Available There is increasing appreciation for the neurodevelopmental underpinnings of many psychiatric disorders. Disorders that begin in childhood such as autism, language disorders or mental retardation as well as adult-onset mental disorders may have origins early in neurodevelopment. Neural stem cells (NSCs can be defined as self-renewing, multipotent cells that are present in both the embryonic and adult brain. Several recent research findings demonstrate that psychiatric illness may begin with abnormal specification, growth, expansion and differentiation of embryonic NSCs. For example, candidate susceptibility genes for schizophrenia, autism and major depression include the signaling molecule Disrupted In Schizophrenia-1 (DISC-1, the homeodomain gene engrailed-2 (EN-2, and several receptor tyrosine kinases (RTKs, including MET, brain-derived growth factor (BDNF and fibroblast growth factors (FGF, all of which have been shown to play important roles in NSCs or neuronal precursors. We will discuss here stem cell biology, signaling factors that affect these cells, and the potential contribution of these processes to the etiology of neuropsychiatric disorders. Hypotheses about how some of these factors relate to psychiatric disorders will be reviewed.
Animal models of tic disorders: a translational perspective.
Godar, Sean C; Mosher, Laura J; Di Giovanni, Giuseppe; Bortolato, Marco
2014-12-30
Tics are repetitive, sudden movements and/or vocalizations, typically enacted as maladaptive responses to intrusive premonitory urges. The most severe tic disorder, Tourette syndrome (TS), is a childhood-onset condition featuring multiple motor and at least one phonic tic for a duration longer than 1 year. The pharmacological treatment of TS is mainly based on antipsychotic agents; while these drugs are often effective in reducing tic severity and frequency, their therapeutic compliance is limited by serious motor and cognitive side effects. The identification of novel therapeutic targets and development of better treatments for tic disorders is conditional on the development of animal models with high translational validity. In addition, these experimental tools can prove extremely useful to test hypotheses on the etiology and neurobiological bases of TS and related conditions. In recent years, the translational value of these animal models has been enhanced, thanks to a significant re-organization of our conceptual framework of neuropsychiatric disorders, with a greater focus on endophenotypes and quantitative indices, rather than qualitative descriptors. Given the complex and multifactorial nature of TS and other tic disorders, the selection of animal models that can appropriately capture specific symptomatic aspects of these conditions can pose significant theoretical and methodological challenges. In this article, we will review the state of the art on the available animal models of tic disorders, based on genetic mutations, environmental interventions as well as pharmacological manipulations. Furthermore, we will outline emerging lines of translational research showing how some of these experimental preparations have led to significant progress in the identification of novel therapeutic targets for tic disorders. Copyright © 2014 Elsevier B.V. All rights reserved.
Animal models of tic disorders: A translational perspective
Godar, Sean C.; Mosher, Laura J.; Di Giovanni, Giuseppe; Bortolato, Marco
2014-01-01
Tics are repetitive, sudden movements and/or vocalizations, typically enacted as maladaptive responses to intrusive premonitory urges. The most severe tic disorder, Tourette syndrome (TS), is a childhood-onset condition featuring multiple motor and at least one phonic tic for a duration longer than 1 year. The pharmacological treatment of TS is mainly based on antipsychotic agents; while these drugs are often effective in reducing tic severity and frequency, their therapeutic compliance is limited by serious motor and cognitive side effects. The identification of novel therapeutic targets and development of better treatments for tic disorders is conditional on the development of animal models with high translational validity. In addition, these experimental tools can prove extremely useful to test hypotheses on the etiology and neurobiological bases of TS and related conditions. In recent years, the translational value of these animal models has been enhanced, thanks to a significant re-organization of our conceptual framework of neuropsychiatric disorders, with a greater focus on endophenotypes and quantitative indices, rather than qualitative descriptors. Given the complex and multifactorial nature of TS and other tic disorders, the selection of animal models that can appropriately capture specific symptomatic aspects of these conditions can pose significant theoretical and methodological challenges. In this article, we will review the state of the art on the available animal models of tic disorders, based on genetic mutations, environmental interventions as well as pharmacological manipulations. Furthermore, we will outline emerging lines of translational research showing how some of these experimental preparations have led to significant progress in the identification of novel therapeutic targets for tic disorders. PMID:25244952
The Iowa Gambling Task and the three fallacies of dopamine in gambling disorder
Linnet, Jakob
2013-01-01
Gambling disorder sufferers prefer immediately larger rewards despite long term losses on the Iowa Gambling Task (IGT), and these impairments are associated with dopamine dysfunctions. Dopamine is a neurotransmitter linked with temporal and structural dysfunctions in substance use disorder, which has supported the idea of impaired decision-making and dopamine dysfunctions in gambling disorder. However, evidence from substance use disorders cannot be directly transferred to gambling disorder. This article focuses on three hypotheses of dopamine dysfunctions in gambling disorder, which appear to be “fallacies,” i.e., have not been supported in a series of positron emission tomography (PET) studies. The first “fallacy” suggests that gambling disorder sufferers have lower dopamine receptor availability, as seen in substance use disorders. However, no evidence supported this hypothesis. The second “fallacy” suggests that maladaptive decision-making in gambling disorder is associated with higher dopamine release during gambling. No evidence supported the hypothesis, and the literature on substance use disorders offers limited support for this hypothesis. The third “fallacy” suggests that maladaptive decision-making in gambling disorder is associated with higher dopamine release during winning. The evidence did not support this hypothesis either. Instead, dopaminergic coding of reward prediction and uncertainty might better account for dopamine dysfunctions in gambling disorder. Studies of reward prediction and reward uncertainty show a sustained dopamine response toward stimuli with maximum uncertainty, which may explain the continued dopamine release and gambling despite losses in gambling disorder. The findings from the studies presented here are consistent with the notion of dopaminergic dysfunctions of reward prediction and reward uncertainty signals in gambling disorder. PMID:24115941
Prevalence of Vitamin D Deficiency in Adult Outpatients With Bipolar Disorder or Schizophrenia.
Boerman, Remco; Cohen, Dan; Schulte, Peter F J; Nugter, Annet
2016-12-01
Several studies show an association between schizophrenia and low levels of vitamin D. To date, there are only few studies about the prevalence of vitamin D deficiency in patients with bipolar disorder. We hypothesized that vitamin D deficiency is less common among patients with bipolar disorder than among patients with schizophrenia or schizoaffective disorder. A second hypothesis is that vitamin D deficiency is more prevalent among patients with schizophrenia, schizoaffective disorder, or bipolar disorders than among the general Dutch population.Most studies have been conducted with hospitalized patients; in this study, we only included outpatients. All outpatients of a center for bipolar disorders and all outpatients of 3 flexible assertive community treatment teams were asked to participate in this cross-sectional study. We included 118 patients with bipolar disorder and 202 patients with schizophrenia or schizoaffective disorder. Vitamin D levels were deficient in 30.3% (95% confidence interval, 25.5-35.6) of the cases. The type of psychiatric disorder was not a predictor of vitamin D deficiency. The absolute difference in risk of deficiency between the study population and the Dutch Caucasian population was 23.8% (95% confidence interval, 18.3%-29.3%). In this study, vitamin D deficiency was 4.7 times more common among outpatients with bipolar disorder, schizophrenia, or schizoaffective disorder than among the Dutch general population.Given the high prevalence of vitamin D deficiency, we believe that outpatients with bipolar disorder, schizophrenia, or schizoaffective disorder should be considered at risk of having low levels of vitamin D. Annual measurement of vitamin D levels in psychiatric outpatients with these disorders seems to be justified to maintain bone health, muscle strength, and to prevent osteoporosis.
Limits on hypothesizing new quantum numbers
International Nuclear Information System (INIS)
Goldstein, G.R.; Moravcsik, M.J.
1986-01-01
According to a recent theorem, for a general quantum-mechanical system undergoing a process, one can tell from measurements on this system whether or not it is characterized by a quantum number, the existence of which is unknown to the observer, even though the detecting equipment used by the observer is unable to distinguish among the various possible values of the ''secret'' quantum number and hence always averages over them. The present paper deals with situations in which this averaging is avoided and hence the ''secret'' quantum number remains ''secret.'' This occurs when a new quantum number is hypothesized in such a way that all the past measurements pertain to the system with one and the same value of the ''secret'' quantum number, or when the new quantum number is related to the old ones by a specific dynamical model providing a one-to-one correspondence. In the first of these cases, however, the one and the same state of the ''secret'' quantum number needs to be a nondegenerate one. If it is degenerate, the theorem can again be applied. This last feature provides a tool for experimentally testing symmetry breaking and the reestablishment of symmetries in asymptotic regions. The situation is illustrated on historical examples like isospin and strangeness, as well as on some contemporary schemes involving spaces of higher dimensionality
Is the population properly informed about sleep disorders?
Directory of Open Access Journals (Sweden)
Eleida Pereira Camargo
2013-02-01
Full Text Available OBJECTIVE: To measure the prior knowledge about sleep disorders and patient's ability to report their problems adequately to health professionals. METHODS: We analyzed 208 patient's records and extracted the following information: date of birth, gender, medical diagnostic hypotheses, patient's primary complaint in their words, considering the most appropriated semantic approximation to the perceptual phenomena, either by their own or by reasoning information from the partner. We compared the agreement (Kappa's test between patient's complaint and medical diagnosis. The 95% confidence interval was used to analyze proportions. RESULTS: We found strong correlations for bruxism; moderate for snoring, insomnia, nightmares, somniloquy, and restless legs syndrome; fair for excessive movement during sleep (EMDS and obstructive sleep apnea syndrome (OSA. CONCLUSIONS: The observed correlations were heterogeneous, but important diseases such as OSA and EMDS in children showed fair and weak correlations. This suggests an unsatisfactory knowledge level among the population about these disorders, despite their high prevalence and impact on patient's overall health.
Associations between Familial Rates of Psychiatric Disorders and De Novo Genetic Mutations in Autism
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Kyleen Luhrs
2017-01-01
Full Text Available The purpose of this study was to examine the confluence of genetic and familial risk factors in children with Autism Spectrum Disorder (ASD with distinct de novo genetic events. We hypothesized that gene-disrupting mutations would be associated with reduced rates of familial psychiatric disorders relative to structural mutations. Participants included families of children with ASD in four groups: de novo duplication copy number variations (DUP, n=62, de novo deletion copy number variations (DEL, n=74, de novo likely gene-disrupting mutations (LGDM, n=267, and children without a known genetic etiology (NON, n=2111. Familial rates of psychiatric disorders were calculated from semistructured interviews. Results indicated overall increased rates of psychiatric disorders in DUP families compared to DEL and LGDM families, specific to paternal psychiatric histories, and particularly evident for depressive disorders. Higher rates of depressive disorders in maternal psychiatric histories were observed overall compared to paternal histories and higher rates of anxiety disorders were observed in paternal histories for LGDM families compared to DUP families. These findings support the notion of an additive contribution of genetic etiology and familial factors are associated with ASD risk and highlight critical need for continued work targeting these relationships.
Tachibana, Yoshiyuki; Takehara, Kenji; Kakee, Naoko; Mikami, Masashi; Inoue, Eisuke; Mori, Rintaro; Ota, Erika; Koizumi, Tomoe; Okuyama, Makiko; Kubo, Takahiko
2017-11-14
Previous work has suggested that maternal developmental disorder traits related to autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) are significantly associated with child maltreatment. However, there may be other important maternal characteristics that contribute to child maltreatment. We hypothesized that maternal impulse control disability may also affect child maltreatment in addition to maternal developmental disorder traits. We aimed to test this hypothesis via a cohort study performed in Tokyo (n = 1,260). Linear regression analyses using the Behavioural Inhibition/Behavioural Activation Scales, the self-administered short version of the Pervasive Developmental Disorders Autism Society Japan Rating Scale, the short form of the Adult Attention-Deficit Hyperactivity Disorder Self-Report Scale, and the Child Maltreatment Scale, revealed that excessive inhibition of behaviour and affect, which is impulse control disability, is significantly associated with child maltreatment (b = 0.031, p = 0.018) in addition to maternal developmental disorder traits (ASD: b = 0.052, p = 0.004; ADHD: b = 0.178, p child maltreatment, while ADHD was associated (AOR = 1.034, p = 0.022) with severe child maltreatment. These maternal characteristics may inform the best means for prevention and management of child maltreatment cases.
Smartphone data as an electronic biomarker of illness activity in bipolar disorder
DEFF Research Database (Denmark)
Faurholt-Jepsen, Maria; Vinberg, Maj; Frost, Mads
2015-01-01
Objectives Objective methods are lacking for continuous monitoring of illness activity in bipolar disorder. Smartphones offer unique opportunities for continuous monitoring and automatic collection of real-time data. The objectives of the paper were to test the hypotheses that (i) daily electronic...... self-monitored data and (ii) automatically generated objective data collected using smartphones correlate with clinical ratings of depressive and manic symptoms in patients with bipolar disorder. Methods Software for smartphones (the MONARCA I system) that collects automatically generated objective......-monitored data (i.e., mood and activity) and scores on the YMRS. Finally, the automatically generated objective data were able to discriminate between affective states. Conclusions Automatically generated objective data and self-monitored data collected using smartphones correlate with clinically rated...
Rhinitis and sleep disorders: The trigeminocardiac reflex link?
Bindu, Barkha; Singh, Gyaninder Pal; Chowdhury, Tumul; Schaller, Bernhard
2017-06-01
Rhinitis, allergic or non-allergic, is an inflammatory condition of the nose. It is associated with a wide range of sleep disorders that are generally attributed to nasal congestion and presence of inflammatory mediators like cytokines and interleukins. However, the pathophysiological mechanisms behind these sleep disorders remain unclear. On the other hand, the trigeminocardiac reflex (TCR) has recently been linked to various sleep disorders like obstructive sleep apnea, sleep bruxism and rapid eye movement (REM) sleep apnea. TCR can be incited by stimulation of the trigeminal nerve or the area innervated by its branches including the nasal mucosa. Trigeminal nasal afferents can be activated on exposure to noxious stimuli (mechanical or chemical) like ammonia vapors, carbon-dioxide, nicotine, hypertonic saline, air-puffs and smoke. In rhinitis, there is associated neuronal hyper-responsiveness of sensory nasal afferents due to inflammation (which can be suppressed by steroids). This may further lead to increased occurrence of TCR in rhinitis. Moreover, there is involvement of autonomic nervous system both in rhinitis and TCR. In TCR, parasympathetic over activity and sympathetic inhibition leads to sudden onset bradycardia, hypotension, apnea and gastric motility. Also, the autonomic imbalance reportedly plays a significant role in the pathophysiology of rhinitis. Thus, considering these facts we hypothesize that the TCR could be the link between rhinitis and sleep disorders and we believe that further research in this direction may yield significant development in our understanding of sleep disorders in rhinitis. Copyright © 2017 Elsevier Ltd. All rights reserved.
An automated framework for hypotheses generation using literature
Directory of Open Access Journals (Sweden)
Abedi Vida
2012-08-01
Full Text Available Abstract Background In bio-medicine, exploratory studies and hypothesis generation often begin with researching existing literature to identify a set of factors and their association with diseases, phenotypes, or biological processes. Many scientists are overwhelmed by the sheer volume of literature on a disease when they plan to generate a new hypothesis or study a biological phenomenon. The situation is even worse for junior investigators who often find it difficult to formulate new hypotheses or, more importantly, corroborate if their hypothesis is consistent with existing literature. It is a daunting task to be abreast with so much being published and also remember all combinations of direct and indirect associations. Fortunately there is a growing trend of using literature mining and knowledge discovery tools in biomedical research. However, there is still a large gap between the huge amount of effort and resources invested in disease research and the little effort in harvesting the published knowledge. The proposed hypothesis generation framework (HGF finds “crisp semantic associations” among entities of interest - that is a step towards bridging such gaps. Methodology The proposed HGF shares similar end goals like the SWAN but are more holistic in nature and was designed and implemented using scalable and efficient computational models of disease-disease interaction. The integration of mapping ontologies with latent semantic analysis is critical in capturing domain specific direct and indirect “crisp” associations, and making assertions about entities (such as disease X is associated with a set of factors Z. Results Pilot studies were performed using two diseases. A comparative analysis of the computed “associations” and “assertions” with curated expert knowledge was performed to validate the results. It was observed that the HGF is able to capture “crisp” direct and indirect associations, and provide knowledge
An automated framework for hypotheses generation using literature.
Abedi, Vida; Zand, Ramin; Yeasin, Mohammed; Faisal, Fazle Elahi
2012-08-29
In bio-medicine, exploratory studies and hypothesis generation often begin with researching existing literature to identify a set of factors and their association with diseases, phenotypes, or biological processes. Many scientists are overwhelmed by the sheer volume of literature on a disease when they plan to generate a new hypothesis or study a biological phenomenon. The situation is even worse for junior investigators who often find it difficult to formulate new hypotheses or, more importantly, corroborate if their hypothesis is consistent with existing literature. It is a daunting task to be abreast with so much being published and also remember all combinations of direct and indirect associations. Fortunately there is a growing trend of using literature mining and knowledge discovery tools in biomedical research. However, there is still a large gap between the huge amount of effort and resources invested in disease research and the little effort in harvesting the published knowledge. The proposed hypothesis generation framework (HGF) finds "crisp semantic associations" among entities of interest - that is a step towards bridging such gaps. The proposed HGF shares similar end goals like the SWAN but are more holistic in nature and was designed and implemented using scalable and efficient computational models of disease-disease interaction. The integration of mapping ontologies with latent semantic analysis is critical in capturing domain specific direct and indirect "crisp" associations, and making assertions about entities (such as disease X is associated with a set of factors Z). Pilot studies were performed using two diseases. A comparative analysis of the computed "associations" and "assertions" with curated expert knowledge was performed to validate the results. It was observed that the HGF is able to capture "crisp" direct and indirect associations, and provide knowledge discovery on demand. The proposed framework is fast, efficient, and robust in
Capitao, Liliana; Sampaio, Adriana; Fernandez, Montse; Sousa, Nuno; Pinheiro, Ana; Goncalves, Oscar F.
2011-01-01
Individuals with Williams syndrome display indiscriminate approach towards strangers. Neuroimaging studies conducted so far have linked this social profile to structural and/or functional abnormalities in WS amygdala and prefrontal cortex. In this study, the neuropsychological hypotheses of amygdala and prefrontal cortex involvement in WS…
EEG asymmetry in borderline personality disorder and depression following rejection.
Beeney, Joseph E; Levy, Kenneth N; Gatzke-Kopp, Lisa M; Hallquist, Michael N
2014-04-01
Borderline personality disorder (BPD) and major depressive disorder (MDD) share numerous features, including dysphoric affect, irritability, suicidality, and a heightened sensitivity to perceived interpersonal rejection. However, these disorders are associated with divergent profiles of reactivity to rejection: Individuals with MDD are more likely to respond with withdrawal and isolation, and those with BPD appear to respond with increased approach behaviors and greater hostility. Potential mechanisms underlying these divergent patterns of response have not been elaborated. The goal of the present study was to assess whether prefrontal cortical asymmetry is associated with these behavioral profiles. EEG alpha activity was recorded at baseline and after individuals with BPD, MDD and healthy controls (HCs) participated in a rejection task. Although no differences were found at baseline, results demonstrated that following rejection, individuals with BPD showed greater left cortical activation, consistent with approach motivation, whereas those with MDD showed greater right cortical activation, consistent with withdrawal motivation. HCs evidenced a more balanced cortical profile, as hypothesized. Although BPD and MDD are highly comorbid, are easily confused, and are phenomenologically similar in a number of ways, individuals with these two disorders respond in very different ways to perceived rejection. PsycINFO Database Record (c) 2014 APA, all rights reserved
Autistic spectrum disorders as functional disconnection syndrome.
Melillo, Robert; Leisman, Gerry
2009-01-01
We outline the basis of how functional disconnection with reduced activity and coherence in the right hemisphere would explain all of the symptoms of autistic spectrum disorder as well as the observed increases in sympathetic activation. If the problem of autistic spectrum disorder is primarily one of desynchronization and ineffective interhemispheric communication, then the best way to address the symptoms is to improve coordination between areas of the brain. To do that the best approach would include multimodal therapeusis that would include a combination of somatosensory, cognitive, behavioral, and biochemical interventions all directed at improving overall health, reducing inflammation and increasing right hemisphere activity to the level that it becomes temporally coherent with the left hemisphere. We hypothesize that the unilateral increased hemispheric stimulation has the effect of increasing the temporal oscillations within the thalamocortical pathways bringing it closer to the oscillation rate of the adequately functioning hemisphere. We propose that increasing the baseline oscillation speed of one entire hemisphere will enhance the coordination and coherence between the two hemispheres allowing for enhanced motor and cognitive binding.
Food insecurity and eating disorder pathology.
Becker, Carolyn Black; Middlemass, Keesha; Taylor, Brigitte; Johnson, Clara; Gomez, Francesca
2017-09-01
The primary aim of this study was to investigate eating disorder (ED) pathology in those living with food insecurity. A secondary aim was to investigate whether any-reason dietary restraint, weight self-stigma, and worry increased as level of food insecurity increased. Participants (N = 503) seeking food from food pantries completed questionnaires assessing level of food insecurity, demographics, ED pathology, dietary restraint, weight self-stigma, and worry. Consistent with hypotheses, participants with the highest level of food insecurity (i.e., adults who reported having hungry children in their household) also endorsed significantly higher levels of binge eating, overall ED pathology, any-reason dietary restraint, weight self-stigma, and worry compared to participants with lower levels of food insecurity. Contrary to hypotheses, compensatory behaviors also increased as level of food insecurity worsened. Overall, 17% of those in the child hunger food insecurity group reported clinically significant ED pathology. This is the first study to assess the full spectrum of ED pathology in a low-income, marginalized population with food insecurity. Given that food insecurity is a global concern, results from this study suggest that greater attention to the association between ED pathology and food insecurity is warranted by researchers around the world. © 2017 Wiley Periodicals, Inc.
Willis, Kelcie; Timmons, Lisa; Pruitt, Megan; Schneider, Hoa Lam; Alessandri, Michael; Ekas, Naomi V.
2016-01-01
This study examined gender differences in the relationship between dispositional optimism, coping, and depressive symptoms of Hispanic mothers (n = 46) and fathers (n = 43) of children with autism spectrum disorder. Coping was hypothesized to mediate the relationship between optimism and depressive symptoms. The results revealed that mothers…
Coping with the Stigma of Mental Illness: Empirically-Grounded Hypotheses from Computer Simulations
Kroska, Amy; Har, Sarah K.
2011-01-01
This research demonstrates how affect control theory and its computer program, "Interact", can be used to develop empirically-grounded hypotheses regarding the connection between cultural labels and behaviors. Our demonstration focuses on propositions in the modified labeling theory of mental illness. According to the MLT, negative societal…
Ruhe, Henricus G.; Koster, Michiel; Booij, Jan; van Herk, Marcel; Veltman, Dick J.; Schene, Aart H.
2014-01-01
Amygdala hyperactivation in major depressive disorder (MDD) might be attenuated by selective serotonin reuptake inhibitors (SSRls), but the working mechanism remains unclear. We hypothesized that higher amygdala serotonin transporter (SERT) occupancy by paroxetine results in greater attenuation of
Ruhé, Henricus G.; Koster, Michiel; Booij, Jan; van Herk, Marcel; Veltman, Dick J.; Schene, Aart H.
2014-01-01
Amygdala hyperactivation in major depressive disorder (MDD) might be attenuated by selective serotonin reuptake inhibitors (SSRIs), but the working mechanism remains unclear. We hypothesized that higher amygdala serotonin transporter (SERT) occupancy by paroxetine results in greater attenuation of
Cardiac potassium channel subtypes
DEFF Research Database (Denmark)
Schmitt, Nicole; Grunnet, Morten; Olesen, Søren-Peter
2014-01-01
About 10 distinct potassium channels in the heart are involved in shaping the action potential. Some of the K(+) channels are primarily responsible for early repolarization, whereas others drive late repolarization and still others are open throughout the cardiac cycle. Three main K(+) channels...... drive the late repolarization of the ventricle with some redundancy, and in atria this repolarization reserve is supplemented by the fairly atrial-specific KV1.5, Kir3, KCa, and K2P channels. The role of the latter two subtypes in atria is currently being clarified, and several findings indicate...... that they could constitute targets for new pharmacological treatment of atrial fibrillation. The interplay between the different K(+) channel subtypes in both atria and ventricle is dynamic, and a significant up- and downregulation occurs in disease states such as atrial fibrillation or heart failure...
From themes to hypotheses: following up with quantitative methods.
Morgan, David L
2015-06-01
One important category of mixed-methods research designs consists of quantitative studies that follow up on qualitative research. In this case, the themes that serve as the results from the qualitative methods generate hypotheses for testing through the quantitative methods. That process requires operationalization to translate the concepts from the qualitative themes into quantitative variables. This article illustrates these procedures with examples that range from simple operationalization to the evaluation of complex models. It concludes with an argument for not only following up qualitative work with quantitative studies but also the reverse, and doing so by going beyond integrating methods within single projects to include broader mutual attention from qualitative and quantitative researchers who work in the same field. © The Author(s) 2015.
[Acute tryptophan depletion in eating disorders].
Díaz-Marsa, M; Lozano, C; Herranz, A S; Asensio-Vegas, M J; Martín, O; Revert, L; Saiz-Ruiz, J; Carrasco, J L
2006-01-01
This work describes the rational bases justifying the use of acute tryptophan depletion technique in eating disorders (ED) and the methods and design used in our studies. Tryptophan depletion technique has been described and used in previous studies safely and makes it possible to evaluate the brain serotonin activity. Therefore it is used in the investigation of hypotheses on serotonergic deficiency in eating disorders. Furthermore, and given the relationship of the dysfunctions of serotonin activity with impulsive symptoms, the technique may be useful in biological differentiation of different subtypes, that is restrictive and bulimic, of ED. 57 female patients with DSM-IV eating disorders and 20 female controls were investigated with the tryptophan depletion test. A tryptophan-free amino acid solution was administered orally after a two-day low tryptophan diet to patients and controls. Free plasma tryptophan was measured at two and five hours following administration of the drink. Eating and emotional responses were measured with specific scales for five hours following the depletion. A study of the basic characteristics of the personality and impulsivity traits was also done. Relationship of the response to the test with the different clinical subtypes and with the temperamental and impulsive characteristics of the patients was studied. The test was effective in considerably reducing plasma tryptophan in five hours from baseline levels (76%) in the global sample. The test was well tolerated and no severe adverse effects were reported. Two patients withdrew from the test due to gastric intolerance. The tryptophan depletion test could be of value to study involvement of serotonin deficits in the symptomatology and pathophysiology of eating disorders.
Body image quality of life in eating disorders
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Ignacio Jáuregui Lobera
2011-03-01
Full Text Available Ignacio Jáuregui Lobera1, Patricia Bolaños Ríos21Department of Nutrition and Bromatology, Pablo de Olavide University, Seville, Spain; 2Behavior Sciences Institute, Seville, SpainPurpose: The objective was to examine how body image affects quality of life in an eating-disorder (ED clinical sample, a non-ED clinical sample, and a nonclinical sample. We hypothesized that ED patients would show the worst body image quality of life. We also hypothesized that body image quality of life would have a stronger negative association with specific ED-related variables than with other psychological and psychopathological variables, mainly among ED patients. On the basis of previous studies, the influence of gender on the results was explored, too.Patients and methods: The final sample comprised 70 ED patients (mean age 22.65 ± 7.76 years; 59 women and 11 men; 106 were patients with other psychiatric disorders (mean age 28.20 ± 6.52; 67 women and 39 men, and 135 were university students (mean age 21.57 ± 2.58; 81 women and 54 men, with no psychiatric history. After having obtained informed consent, the following questionnaires were administered: Body Image Quality of Life Inventory-Spanish version (BIQLI-SP, Eating Disorders Inventory-2 (EDI-2, Perceived Stress Questionnaire (PSQ, Self-Esteem Scale (SES, and Symptom Checklist-90-Revised (SCL-90-R.Results: The ED patients' ratings on the BIQLI-SP were the lowest and negatively scored (BIQLI-SP means: +20.18, +5.14, and —6.18, in the student group, the non-ED patient group, and the ED group, respectively. The effect of body image on quality of life was more negative in the ED group in all items of the BIQLI-SP. Body image quality of life was negatively associated with specific ED-related variables, more than with other psychological and psychopathological variables, but not especially among ED patients.Conclusion: Body image quality of life was affected not only by specific pathologies related to body
New Vehicle Detection Method with Aspect Ratio Estimation for Hypothesized Windows
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Jisu Kim
2015-12-01
Full Text Available All kinds of vehicles have different ratios of width to height, which are called the aspect ratios. Most previous works, however, use a fixed aspect ratio for vehicle detection (VD. The use of a fixed vehicle aspect ratio for VD degrades the performance. Thus, the estimation of a vehicle aspect ratio is an important part of robust VD. Taking this idea into account, a new on-road vehicle detection system is proposed in this paper. The proposed method estimates the aspect ratio of the hypothesized windows to improve the VD performance. Our proposed method uses an Aggregate Channel Feature (ACF and a support vector machine (SVM to verify the hypothesized windows with the estimated aspect ratio. The contribution of this paper is threefold. First, the estimation of vehicle aspect ratio is inserted between the HG (hypothesis generation and the HV (hypothesis verification. Second, a simple HG method named a signed horizontal edge map is proposed to speed up VD. Third, a new measure is proposed to represent the overlapping ratio between the ground truth and the detection results. This new measure is used to show that the proposed method is better than previous works in terms of robust VD. Finally, the Pittsburgh dataset is used to verify the performance of the proposed method.
Astragalus Granule Prevents Ca2+ Current Remodeling in Heart Failure by the Downregulation of CaMKII
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Sinai Li
2017-01-01
Full Text Available Background. Astragalus was broadly used for treating heart failure (HF and arrhythmias in East Asia for thousands of years. Astragalus granule (AG, extracted from Astragalus, shows beneficial effect on the treatment of HF in clinical research. We hypothesized that administration of AG prevents the remodeling of L-type Ca2+ current (ICa-L in HF mice by the downregulation of Ca2+/calmodulin-dependent protein kinase II (CaMKII. Methods. HF mice were induced by thoracic aortic constriction (TAC. After 4 weeks of AG treatment, cardiac function and QT interval were evaluated. Single cardiac ventricular myocyte was then isolated and whole-cell patch clamp was used to record action potential (AP and ICa-L. The expressions of L-type calcium channel alpha 1C subunit (Cav1.2, CaMKII, and phosphorylated protein kinase A (p-PKA were examined by western blot. Results. The failing heart manifested distinct electrical remodeling including prolonged repolarization time and altered ICa-L kinetics. AG treatment attenuated this electrical remodeling, supported by AG-related shortened repolarization time, decreased peak ICa-L, accelerated ICa-L inactivation, and positive frequency-dependent ICa-L facilitation. In addition, AG treatment suppressed the overexpression of CaMKII, but not p-PKA, in the failing heart. Conclusion. AG treatment protected the failing heart against electrical remodeling and ICa-L remodeling by downregulating CaMKII.
Delinquency and Peer Acceptance in Adolescence: A Within-Person Test of Moffitt's Hypotheses
Rulison, Kelly L.; Kreager, Derek A.; Osgood, D. Wayne
2014-01-01
We tested 2 hypotheses derived from Moffitt's (1993) taxonomic theory of antisocial behavior, both of which are central to her explanation for the rise in delinquency during adolescence. We tested whether persistently delinquent individuals become more accepted by their peers during adolescence and whether individuals who abstain from delinquent…
Evaluation of Tp-e interval and Tp-e/QT ratio in patients with ankylosing spondylitis.
Acar, Gurkan; Yorgun, Hikmet; Inci, Mehmet Fatih; Akkoyun, Murat; Bakan, Betul; Nacar, Alper Bugra; Dirnak, Imran; Cetin, Gozde Yildirim; Bozoglan, Orhan
2014-03-01
Ankylosing spondylitis (AS) is a chronic multi-systemic inflammatory rheumatic disorder. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the transmural dispersion of repolarization and that increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. The aim of this study was to evaluate ventricular repolarization by using Tp-e interval and Tp-e/QT ratio in patients with AS, and to assess the relation with inflammation. Sixty-two patients with AS and 50 controls were included. Tp-e interval and Tp-e/QT ratio were measured from a 12-lead electrocardiogram, and the Tp-e interval corrected for heart rate. The plasma level of high sensitive C-reactive protein (hsCRP) was measured. These parameters were compared between groups. In electrocardiographic parameters analysis, QT dispersion (QTd) and corrected QTd were significantly increased in AS patients compared to the controls (31.7 ± 9.6 vs 28.2 ± 7.4 and 35.8 ± 11.5 vs 30.6 ± 7.9 ms, P = 0.03 and P = 0.007, respectively). cTp-e interval and Tp-e/QT ratio were also significantly higher in AS patients (92.1 ± 10.2 vs 75.8 ± 8.4 and 0.22 ± 0.02 vs 0.19 ± 0.02 ms, all P values ratio were significantly correlated with hsCRP (r = 0.63, P ratio were increased in AS patients. These electrocardiographic ventricular repolarization indexes were significantly correlated with the plasma level of hsCRP.
Daalder, A.L.; Bogaerts, S.; Bijleveld, C.
2013-01-01
In this article, the relationship between childhood abuse and neglect and post-traumatic stress disorder (PTSD) in adulthood is examined in a sample of 123 female indoor sex workers in the Netherlands. It was hypothesized that the severity of childhood abuse and neglect is associated with the
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Marcio Melo
Full Text Available In medical practice, diagnostic hypotheses are often made by physicians in the first moments of contact with patients; sometimes even before they report their symptoms. We propose that generation of diagnostic hypotheses in this context is the result of cognitive processes subserved by brain mechanisms that are similar to those involved in naming objects or concepts in everyday life.To test this proposal we developed an experimental paradigm with functional magnetic resonance imaging (fMRI using radiological diagnosis as a model. Twenty-five radiologists diagnosed lesions in chest X-ray images and named non-medical targets (animals embedded in chest X-ray images while being scanned in a fMRI session. Images were presented for 1.5 seconds; response times (RTs and the ensuing cortical activations were assessed. The mean response time for diagnosing lesions was 1.33 (SD ±0.14 seconds and 1.23 (SD ±0.13 seconds for naming animals. 72% of the radiologists reported cogitating differential diagnoses during trials (3.5 seconds. The overall pattern of cortical activations was remarkably similar for both types of targets. However, within the neural systems shared by both stimuli, activation was significantly greater in left inferior frontal sulcus and posterior cingulate cortex for lesions relative to animals.Generation of diagnostic hypotheses and differential diagnoses made through the immediate visual recognition of clinical signs can be a fast and automatic process. The co-localization of significant brain activation for lesions and animals suggests that generating diagnostic hypotheses for lesions and naming animals are served by the same neuronal systems. Nevertheless, diagnosing lesions was cognitively more demanding and associated with more activation in higher order cortical areas. These results support the hypothesis that medical diagnoses based on prompt visual recognition of clinical signs and naming in everyday life are supported by similar
Haynos, Ann F; Roberto, Christina A; Attia, Evelyn
2015-07-01
There is growing interest in the role of emotion regulation in anorexia nervosa (AN). Although anxiety is also hypothesized to impact symptoms of AN, little is known about how emotion regulation, anxiety, and eating disorder symptoms interact in AN. In this study, we examined the associations between emotion regulation, anxiety, and eating disorder symptom severity in AN. Questionnaires and interviews assessing emotion regulation difficulties, anxiety, eating disorder symptoms, and eating disorder-related clinical impairment were collected from group of underweight individuals with AN (n=59) at admission to inpatient treatment. Hierarchical linear regressions were used to examine the associations of emotion regulation difficulties, anxiety, and the interaction of these constructs with eating disorder symptoms and eating disorder-related clinical impairment. Emotion regulation difficulties were significantly positively associated with eating disorder symptoms and related clinical impairment only when anxiety levels were low and anxiety was significantly positively associated with eating disorder symptoms and related clinical impairment only when emotion regulation problems were not elevated. This study adds to a growing literature suggesting that emotion regulation deficits are associated with eating disorder symptoms in AN. Certain individuals with AN may especially benefit from a focus on developing emotion regulation skills in the acute stages of illness. Copyright © 2015 Elsevier Inc. All rights reserved.
Exploration of miRNA families for hypotheses generation.
Kamanu, T.K.
2013-10-15
Technological improvements have resulted in increased discovery of new microRNAs (miRNAs) and refinement and enrichment of existing miRNA families. miRNA families are important because they suggest a common sequence or structure configuration in sets of genes that hint to a shared function. Exploratory tools to enhance investigation of characteristics of miRNA families and the functions of family-specific miRNA genes are lacking. We have developed, miRNAVISA, a user-friendly web-based tool that allows customized interrogation and comparisons of miRNA families for hypotheses generation, and comparison of per-species chromosomal distribution of miRNA genes in different families. This study illustrates hypothesis generation using miRNAVISA in seven species. Our results unveil a subclass of miRNAs that may be regulated by genomic imprinting, and also suggest that some miRNA families may be species-specific, as well as chromosome- and/or strand-specific.
N-acetyl Aspartate Levels in Adolescents With Bipolar and/or Cannabis Use Disorders
Bitter, Samantha M.; Weber, Wade A.; Chu, Wen-Jang; Adler, Caleb M.; Eliassen, James C.; Strakowski, Stephen M.; DelBello, Melissa P.
2014-01-01
Objective Bipolar and cannabis use disorders commonly co-occur during adolescence, and neurochemical studies may help clarify the pathophysiology underlying this co-occurrence. This study compared metabolite concentrations in the left ventral lateral prefrontal cortex among: adolescents with bipolar disorder (bipolar group; n=14), adolescents with a cannabis use disorder (cannabis use group, n=13), adolescents with cannabis use and bipolar disorders (bipolar and cannabis group, n=25), and healthy adolescents (healthy controls, n=15). We hypothesized that adolescents with bipolar disorder (with or without cannabis use disorder) would have decreased N-acetyl aspartate levels in the ventral lateral prefrontal cortex compared to the other groups, and that the bipolar and cannabis group would have the lowest N-acetyl aspartate levels of all groups. Methods N-acetyl aspartate concentrations in the left ventral lateral prefrontal cortex were obtained using Proton Magnetic Resonance Spectroscopy. Results Adolescents with bipolar disorder showed significantly lower left ventral lateral prefrontal cortex N-acetyl aspartate levels, but post-hoc analyses indicated that this was primarily due to increased N-acetyl aspartate levels in the cannabis group. The cannabis use disorder group had significantly higher N-acetyl aspartate levels compared to the bipolar disorder and the bipolar and cannabis groups (p=0.0002 and p=0.0002, respectively). Pearson correlations revealed a significant positive correlation between amount of cannabis used and N-acetyl aspartate concentrations. Conclusions Adolescents with cannabis use disorder showed higher levels of N-acetyl aspartate concentrations that were significantly positively associated with the amount of cannabis used; however, this finding was not present in adolescents with comorbid bipolar disorder. PMID:24729763
DEFF Research Database (Denmark)
Haugaard, Maria Mathilde; Hesselkilde, Eva Zander; Pehrson, Steen Michael
2015-01-01
and ventricular cardiomyocytes and contribute to atrial repolarization. Inhibition by NS8593 terminates pacing-induced AF of short duration and decreases AF duration and vulnerability without affecting ventricular conduction and repolarization. Thus, inhibition by NS8593 demonstrates clear atrial antiarrhythmic...
Progressive neurostructural changes in adolescent and adult patients with bipolar disorder.
Lisy, Megan E; Jarvis, Kelly B; DelBello, Melissa P; Mills, Neil P; Weber, Wade A; Fleck, David; Strakowski, Stephen M; Adler, Caleb M
2011-06-01
Several lines of evidence suggest that bipolar disorder is associated with progressive changes in gray matter volume (GMV), particularly in brain structures involved in emotional regulation and expression. The majority of these studies however, have been cross-sectional in nature. In this study we compared baseline and follow-up scans in groups of bipolar disorder and healthy subjects. We hypothesized bipolar disorder subjects would demonstrate significant GMV changes over time. A total of 58 bipolar disorder and 48 healthy subjects participated in structural magnetic resonance imaging (MRI). Subjects were rescanned 3-34 months after their baseline MRI. MRI images were segmented, normalized to standard stereotactic space, and compared voxel-by-voxel using statistical parametrical mapping software (SPM2). A model was developed to investigate differences in GMV at baseline, and associated with time and episodes, as well as in comparison to healthy subjects. We observed increases in GMV in bipolar disorder subjects across several brain regions at baseline and over time, including portions of the prefrontal cortex as well as limbic and subcortical structures. Time-related changes differed to some degree between adolescent and adult bipolar disorder subjects. The interval between scans positively correlated with GMV increases in bipolar disorder subjects in portions of the prefrontal cortex, and both illness duration and number of depressive episodes were associated with increased GMV in subcortical and limbic structures. Our findings support suggestions that widely observed progressive neurofunctional changes in bipolar disorder patients may be related to structural brain abnormalities in anterior limbic structures. Abnormalities largely involve regions previously noted to be integral to emotional expression and regulation, and appear to vary by age. © 2011 John Wiley and Sons A/S.
Personality disorder traits, risk factors, and suicide ideation among older adults.
Jahn, Danielle R; Poindexter, Erin K; Cukrowicz, Kelly C
2015-11-01
Personality disorder traits are relatively prevalent among older adults, and can be associated with complex and chronic difficulties, including suicide risk. However, there is a lack of research regarding personality disorders and suicide ideation in older adults. Depressive symptoms and hopelessness may be important to the relation between personality disorders and suicide risk. Additionally, variables from the interpersonal theory of suicide, perceived burdensomeness and thwarted belongingness, may be critical risk factors for suicide in this population. We hypothesized that perceived burdensomeness and thwarted belongingness, theory-based variables, would act as parallel mediators of the relation between personality disorder traits and suicide ideation, whereas depressive symptoms and hopelessness would not. The hypothesis was tested in a sample of 143 older adults recruited from a primary care setting. Participants completed self-report questionnaires of personality traits, suicide ideation, depressive symptoms, hopelessness, perceived burdensomeness, and thwarted belongingness. Findings from a non-parametric bootstrapping procedure indicated that perceived burdensomeness, thwarted belongingness, and depressive symptoms mediated the relation between total personality disorder traits and suicide ideation. Hopelessness did not act as a mediator. These findings indicate that perceived burdensomeness, thwarted belongingness, and depressive symptoms are likely important risk factors for suicide ideation among older adults. Clinicians should be aware of these issues when assessing and treating suicide risk among older adults.
Attention Patterns in Children with Attention Deficit Disorder with or without Hyperactivity
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Gil Zalsman
2003-01-01
Full Text Available The objective of this study was to differentiate the attention patterns associated with attention deficit disorder with or without hyperactivity using continuous performance test (CPT. The diagnoses were based on the DSM-III, III-R, and IV criteria and of the 39 children who participated in the study, 14 had attention deficit disorder with hyperactivity (ADDH and 11 had attention deficit disorder without hyperactivity (ADDWO, while 14 normal children served as a control group. Attention patterns were examined according to the performance of subjects on the CPT and parental scores on the ADHD Rating Scale, the Child Attention Profile, and the Conners Rating Scale. CPT performances were assessed before and after administration of 10 mg methylphenidate. We found as hypothesized that the CPT differentiated between the ADDH and ADDWO groups. However, contrary to our expectations, the ADDH children made more omission errors than the ADDWO children; they also showed more hyperactivity and impulsivity. The performance of both groups improved to an equal degree after the administration of methylphenidate. It is conluded that different subtypes of the attention deficit disorders are characterized by different attention profiles and that methylphenidate improves scores on test of continuous performance.
Genro, Júlia Pasqualini; Roman, Tatiana; Rohde, Luis Augusto; Hutz, Mara Helena
2012-01-01
Attention-Deficit/Hyperactivity Disorder (ADHD) is a common psychiatric condition of children worldwide. This disorder is defined by a combination of symptoms of inattention and hyperactivity/impulsivity. Diagnosis is based on a sufficient number of symptoms causing impairment in these two domains determining several problems in personal and academic life. Although genetic and environmental factors are important in ADHD etiology, how these factors influence the brain and consequently behavior is still under debate. It seems to be consensus that a frontosubcortical dysfunction is responsible, at least in part, for the ADHD phenotype spectrum. The main results from association and pharmacogenetic studies performed in Brazil are discussed. The investigations performed so far on ADHD genetics in Brazil and elsewhere are far from conclusive. New plausible biological hypotheses linked to neurotransmission and neurodevelopment, as well as new analytic approaches are needed to fully disclose the genetic component of the disorder. PMID:23411749
Thaler, Nicholas S; Allen, Daniel N; Sutton, Griffin P; Vertinski, Mary; Ringdahl, Erik N
2013-12-01
While it is well-established that patients with schizophrenia and bipolar disorder exhibit deficits in social cognition, few studies have separately examined bipolar disorder with and without psychotic features. The current study addressed this gap by comparing patients with bipolar disorder with (BD+) and without (BD-) psychotic features, patients with schizophrenia (SZ), and healthy controls (NC) across social cognitive measures. Principal factor analysis on five social cognition tasks extracted a two-factor structure comprised of social/emotional processing and theory of mind. Factor scores were compared among the four groups. Results identified differential patterns of impairment between the BD+ and BD- group on the social/emotional processing factor while all clinical groups performed poorer than controls on the theory of mind factor. This provides evidence that a history of psychosis should be taken into account while evaluating social cognition in patients with bipolar disorder and also raises hypotheses about the relationship between social cognition and psychosis. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Ormrod, Robert P.; Henneberg, Stephan C. M.
2007-01-01
an integrated construct of political marketing strategy which is exemplified by the derivation of hypotheses of the relationships between organizational stances on the one hand, and attitudinal and behavioural aspects of political market orientation on the other. We propose two levels of hypotheses: Firstly......Recently, the areas of strategic political marketing as well as political market orientation have been the subject of several conceptual articles (e.g., Henneberg 2006a; O'Cass 1996; Ormrod 2005, 2007). These have laid the theoretical foundations for further empirical work (e.g., Henneberg 2006b; O......'Cass 1996, 2001a, 2001b; Ormrod et al. 2007; Ormrod and Henneberg 2008 forthcoming). However, despite the close conceptual relatedness between some of these concepts they have yet to be integrated to provide a more nuanced picture which researchers but also political marketing practitioners can utilise...
Skin stem cell hypotheses and long term clone survival--explored using agent-based modelling.
Li, X; Upadhyay, A K; Bullock, A J; Dicolandrea, T; Xu, J; Binder, R L; Robinson, M K; Finlay, D R; Mills, K J; Bascom, C C; Kelling, C K; Isfort, R J; Haycock, J W; MacNeil, S; Smallwood, R H
2013-01-01
Epithelial renewal in skin is achieved by the constant turnover and differentiation of keratinocytes. Three popular hypotheses have been proposed to explain basal keratinocyte regeneration and epidermal homeostasis: 1) asymmetric division (stem-transit amplifying cell); 2) populational asymmetry (progenitor cell with stochastic fate); and 3) populational asymmetry with stem cells. In this study, we investigated lineage dynamics using these hypotheses with a 3D agent-based model of the epidermis. The model simulated the growth and maintenance of the epidermis over three years. The offspring of each proliferative cell was traced. While all lineages were preserved in asymmetric division, the vast majority were lost when assuming populational asymmetry. The third hypothesis provided the most reliable mechanism for self-renewal by preserving genetic heterogeneity in quiescent stem cells, and also inherent mechanisms for skin ageing and the accumulation of genetic mutation.
Energy Technology Data Exchange (ETDEWEB)
Gottfried, Rudolf J.
2009-07-01
The author of the contribution under consideration addresses to all persons which are interested scientifically and also are ready for leaving the well-trodden paths of conventional conceptions occasionally if it is shown that the paths mislead when continuing. In particular, here it is a matter of the controversy of the hydrogen conception of the world against hypothesis inflation. This book does not set up new hypotheses which are arranged in the numerously existing hypotheses according to the picture of the world. It is time to deliver the secured facts from the crusts of rigid hypotheses in order to look for new realizations without prejudices and in order to arrange the hypotheses meaningfully.
Korda, Joanna B; Pfaus, James G; Kellner, Charles H; Goldstein, Irwin
2009-10-01
This is the second case report of a woman with bipolar disorder type I who noted the onset of persistent genital arousal disorder (PGAD) symptoms after abrupt cessation of paroxetine. With the worsening of PGAD symptoms, she developed severe depression and suicidal thoughts, resulting in her undergoing electroconvulsive therapy (ECT) as management. To describe a case of PGAD and develop hypotheses to explain the beneficial actions of ECT on PGAD based on 4 years of ECT administration. Patient self-report after obtaining consent, as well as literature review. After the fourth ECT, the patient's PGAD symptoms abated serendipitously. She was placed on ECT on demand for the treatment of her PGAD. With each ECT treatment, PGAD symptoms immediately disappeared, relapsing slowly over time until the next ECT was administered. The patient has, thus far, received a total of 30 treatments of ECT. Side effects continue to be minimal and include brief short-term memory loss, headache, and muscle aches. ECT is known to induce cerebral excitatory and inhibitory neurotransmitter changes after acute and chronic administration. Sexual arousal is stimulated by the action of hypothalamic and limbic dopamine, noradrenaline, melanocortin, and oxytocin, and inhibited by serotonin, cerebral opioids, and endocannabinoids. Based on the patient's bipolar disorder, the mechanism of action of ECT and the observation of ECT effectiveness on her PGAD, we hypothesize the following: (i) bipolar disorder led to central hyperactive dopamine release, an important component in the pathophysiology of her PGAD; (ii) central serotonin deficiency after selective serotonin-reuptake inhibitor (SSRI) withdrawal resulted in a lack of inhibition of sexual excitement; (iii) ECT resulted in lowering of the hyperstimulated central dopamine release; and (iv) ECT led to an increase in sexual inhibition by stimulating serotonin activity. Further research in the central control of sexual arousal is needed.
Brain reward region responsivity of adolescents with and without parental substance use disorders.
Stice, Eric; Yokum, Sonja
2014-09-01
The present study tested the competing hypotheses that adolescents at risk for future substance abuse and dependence by virtue of parental substance use disorders show either weaker or stronger responsivity of brain regions implicated in reward relative to youth without parental history of substance use disorders. Adolescents (n = 52) matched on demographics with and without parental substance use disorders, as determined by diagnostic interviews, who denied substance use in the past year were compared on functional MRI (fMRI) paradigms assessing neural response to receipt and anticipated receipt of monetary and food reward. Parental-history-positive versus -negative adolescents showed greater activation in the left dorsolateral prefrontal cortex and bilateral putamen, and less activation in the fusiform gyrus and inferior temporal gyrus in response to anticipating winning money, as well as greater activation in the left midbrain and right paracentral lobule, and less activation in the right middle frontal gyrus in response to milkshake receipt. Results indicate that adolescents at risk for future onset of substance use disorders show elevated responsivity of brain regions implicated in reward, extending results from 2 smaller prior studies that found that individuals with versus without parental alcohol use disorders showed greater reward region response to anticipated monetary reward and pictures of alcohol. Collectively, results provide support for the reward surfeit model of substance use disorders, rather than the reward deficit model.
Baryshnikov, Ilya; Aaltonen, Kari; Suvisaari, Jaana; Koivisto, Maaria; Heikkinen, Martti; Joffe, Grigori; Isometsä, Erkki
2018-03-01
Psychosis-like experiences (PEs) are common in patients with non-psychotic disorders. Several factors predict reporting of PEs in mood disorders, including mood-associated cognitive biases, anxiety and features of borderline personality disorder (BPD). Childhood traumatic experiences (CEs), often reported by patients with BPD, are an important risk factor for mental disorders. We hypothesized that features of BPD may mediate the relationship between CEs and PEs. In this study, we investigated the relationships between self-reported PEs, CEs and features of BPD in patients with mood disorders. As part of the Helsinki University Psychiatric Consortium study, McLean Screening Instrument (MSI), Community Assessment of Psychic Experiences (CAPE-42) and Trauma and Distress Scale (TADS) were filled in by patients with mood disorders (n = 282) in psychiatric care. Correlation coefficients between total scores of scales and their dimensions were estimated, multiple regression and mediation analyses were conducted. Total scores of MSI correlated strongly with scores of the CAPE-42 dimension "frequency of positive symptoms" (rho = 0.56; p ≤ 0.001) and moderately with scores of TADS (rho = 0.4; p ≤ 0.001). Total score of MSI and its dimension "cognitive symptoms", including identity disturbance, distrustfulness and dissociative symptoms, fully mediated the relation between TADS and CAPE-42. Each cognitive symptom showed a partial mediating role (dissociative symptoms 43% (CI = 25-74%); identity disturbance 40% (CI = 30-73%); distrustfulness 18% (CI = 12-50%)). Self-reported cognitive-perceptual symptoms of BPD fully mediate, while affective, behavioural and interpersonal symptoms only partially mediate the relationships between CEs and PEs. Recognition of co-morbid features of BPD in patients with mood disorders reporting PEs is essential. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
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Lenice de Castro Muniz de Quadros
Full Text Available This study aimed to evaluate the relationship between mental disorders at 30 years of age and social mobility by formally testing three hypotheses: Risk Accumulation; Critical Period; and Social Mobility. The study was performed using data from the 30-year follow-up of the Pelotas Birth Cohort Study, conducted in 1982, and data from previous follow-ups. The tool used to evaluate mental health was the Self Report Questionnaire (SRQ-20. For the statistical analysis, the chi-square test with the Yates correction was used to estimate the prevalence of mental disorder, and the Poisson regression with robust variance was used to formally test the hypotheses according to the Risk Accumulation, Critical Period and Social Mobility Models. The analyses were stratified by gender. The prevalence of Common Mental Disorders (CMDs was 24.3% (95% CI 22.9-25.7 when the whole sample was considered. The highest prevalence, 27.1% (95% CI 25.1-29.2, was found in women, and the difference between genders was significant (p < 0.001. CMDs were more frequent in participants who remained "poor" in the three follow-ups. In both men and women, the best fit was obtained with the Risk Accumulation Model, with p = 0.6348 and p = 0.2105, respectively. The results indicate the need to rethink public income maintenance policies. Finally, we suggest further studies to investigate the role of different public policies in decreasing the prevalence of mental disorders and thus contribute proposals of new policies that may contribute to the prevention of these disorders.
Directory of Open Access Journals (Sweden)
David Cohen
Full Text Available BACKGROUND: In a previous report, we hypothesized that responses to placebo were high in child and adolescent depression because of specific psychopathological factors associated with youth major depression. The purpose of this study was to compare the placebo response rates in pharmacological trials for major depressive disorder (MDD, obsessive compulsive disorder (OCD and other anxiety disorders (AD-non-OCD. METHODOLOGY AND PRINCIPAL FINDINGS: We reviewed the literature relevant to the use of psychotropic medication in children and adolescents with internalized disorders, restricting our review to double-blind studies including a placebo arm. Placebo response rates were pooled and compared according to diagnosis (MDD vs. OCD vs. AD-non-OCD, age (adolescent vs. child, and date of publication. From 1972 to 2007, we found 23 trials that evaluated the efficacy of psychotropic medication (mainly non-tricyclic antidepressants involving youth with MDD, 7 pertaining to youth with OCD, and 10 pertaining to youth with other anxiety disorders (N = 2533 patients in placebo arms. As hypothesized, the placebo response rate was significantly higher in studies on MDD, than in those examining OCD and AD-non-OCD (49.6% [range: 17-90%] vs. 31% [range: 4-41%] vs. 39.6% [range: 9-53], respectively, ANOVA F = 7.1, p = 0.002. Children showed a higher stable placebo response within all three diagnoses than adolescents, though this difference was not significant. Finally, no significant effects were found with respect to the year of publication. CONCLUSION: MDD in children and adolescents appears to be more responsive to placebo than other internalized conditions, which highlights differential psychopathology.
Donner, L.
2009-12-01
The certainty of climate change projected under various scenarios of emissions using general circulation models is an issue of vast societal importance. Unlike numerical weather prediction, a problem to which general circulation models are also applied, projected climate changes usually lie outside of the range of external forcings for which the models generating these changes have been directly evaluated. This presentation views climate models as complex scientific hypotheses and thereby frames these models within a well-defined process of both advancing scientific knowledge and recognizing its limitations. Karl Popper's Logik der Forschung (The Logic of Scientific Discovery, 1934) and 1965 essay “On Clocks and Clouds” capture well the methodologies and challenges associated with constructing climate models. Indeed, the process of a problem situation generating tentative theories, refined by error elimination, characterizes aptly the routine of general circulation model development. Limitations on certainty arise from the distinction Popper perceived in types of natural processes, which he exemplified by clocks, capable of exact measurement, and clouds, subject only to statistical approximation. Remarkably, the representation of clouds in general circulation models remains the key uncertainty in understanding atmospheric aspects of climate change. The asymmetry of hypothesis falsification by negation and much vaguer development of confidence in hypotheses consistent with some of their implications is an important practical challenge to confirming climate models. The presentation will discuss the ways in which predictions made by climate models for observable aspects of the present and past climate can be regarded as falsifiable hypotheses. The presentation will also include reasons why “passing” these tests does not provide complete confidence in predictions about the future by climate models. Finally, I will suggest that a “reductionist” view, in
Directory of Open Access Journals (Sweden)
Teodor T. Postolache
2007-01-01
Full Text Available Although growing evidence supports an association between allergy, allergens and depression, it remains unknown if this relationship is between “states” (possible triggers or “traits” (possible vulnerabilities. We hypothesized that patients with recurrent mood disorders who are sensitized to tree pollen (as determined by allergen specific IgE antibodies, in comparison to those who are not sensitized, would report larger negative changes in mood during exposure to tree pollen in spring. We also hypothesized that differences between high and low tree pollen periods in self reported allergy symptoms would correlate positively with differences in self reported depression scores. We present 1-year preliminary data on the first 51 patients with unipolar or bipolar disorder (age: 19-63 years, 65% female, twelve patients were tree-pollen IgE positive. Ratings of mood and allergic disease status were performed once during the peak airborne pollen counts and once during the period of low airborne pollen counts, as reported by two local pollen counting stations. Linear regression models were developed to examine associations of changes in depression scores (dependent variable with tree pollen sensitization, changes in the allergy symptom severity score, adjusted for gender and order of testing. We did not confirm the hypothesized relationship between a specific tree pollen sensitization and changes in mood during tree pollen exposure. We did confirm the hypothesized positive relationship between the changes in allergy symptoms and changes in subjects' depression scores (adjusted p<0.05. This result is consistent with previous epidemiological evidence connecting allergy with depression, as well as our recent reports of increased expression of cytokines in the prefrontal cortex in victims of suicide and in experimental animals sensitized and exposed to tree pollen. A relationship between changes in allergy symptom scores and changes in depression
Blum, Kenneth; Giordano, John; Oscar-Berman, Marlene; Bowirrat, Abdalla; Simpatico, Thomas; Barh, Debmalya
2012-01-01
There is a need for understanding and treating post-traumatic stress disorder (PTSD), in soldiers returning to the United States of America after combat. Likewise, it would be beneficial to finding a way to reduce violence committed by soldiers, here and abroad, who are suspected of having post-traumatic stress disorder (PTSD). We hypothesize that even before combat, soldiers with a childhood background of violence (or with a familial susceptibility risk) would benefit from being genotyped fo...
What's eating the internet? Content and perceived harm of pro-eating disorder websites.
Steakley-Freeman, Diana M; Jarvis-Creasey, Zachary L; Wesselmann, Eric D
2015-12-01
The internet is a popular tool for information dissemination and community building, serving many purposes from social networking to support seeking. However, there may be a downside to using some online support communities. For individuals with eating disorders (EDs), it is possible that certain online communities may reinforce the negative social aspects that encourage these disorders, rather than positive aspects that would facilitate treatment and recovery. Previous research identified several linguistic themes present on pro-eating disorder websites in an attempt to better understand the web-based conversation in the pro-eating disorder movement. We hypothesized that differences in theme presentation may predict changes in perceived harm. The present study sought to understand the perceived harm, and presentation patterns of pro-eating disorder (Pro-ED) website content. We replicated and extended previous research by having laypersons code these websites' content using previously identified linguistic themes and rate perceived harm. Our data replicate and extend the previous research by finding the same associations between co-occurring themes, and investigating associated perceived harm. We found that themes of Sacrifice, Control, Deceit, and Solidarity were associated with the highest perceived harm scores. In addition, we suggest an initial conceptualization of the "Eating Disorder Lifestyle", and its associations with the themes of Isolation, Success, and Solidarity. This research may provide clinicians with information to better understand the potential influence these sites have on eating disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.
Song, X.M.
2001-01-01
This article examines how the perceived quality of extrafunctional information improves the innovation management process and contributes to success with innovations. Data collected from 420 Japanese managers and 270 US managers are used to test hypotheses about the antecedents of satisfaction with
DEFF Research Database (Denmark)
Peitersen, Torben; Grunnet, Morten; Benson, Alan P
2008-01-01
BACKGROUND: Dysfunction or pharmacologic inhibition of repolarizing cardiac ionic currents can lead to fatal arrhythmias. The hERG potassium channel underlies the repolarizing current I(Kr), and mutations therein can produce both long and short QT syndromes (LQT2 and SQT1). We previously reported...
The evolution of parental care in insects: A test of current hypotheses
Gilbert, James D J; Manica, Andrea
2015-01-01
Which sex should care for offspring is a fundamental question in evolution. Invertebrates, and insects in particular, show some of the most diverse kinds of parental care of all animals, but to date there has been no broad comparative study of the evolution of parental care in this group. Here, we test existing hypotheses of insect parental care evolution using a literature-compiled phylogeny of over 2000 species. To address substantial uncertainty in the insect phylogeny, we use a brute force approach based on multiple random resolutions of uncertain nodes. The main transitions were between no care (the probable ancestral state) and female care. Male care evolved exclusively from no care, supporting models where mating opportunity costs for caring males are reduced—for example, by caring for multiple broods—but rejecting the “enhanced fecundity” hypothesis that male care is favored because it allows females to avoid care costs. Biparental care largely arose by males joining caring females, and was more labile in Holometabola than in Hemimetabola. Insect care evolution most closely resembled amphibian care in general trajectory. Integrating these findings with the wealth of life history and ecological data in insects will allow testing of a rich vein of existing hypotheses. PMID:25825047
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Ling Fan1
2017-04-01
Full Text Available Objective: To investigate the changes of left ventricular papillary muscle action potentials in guinea pigs with iron deficiency anemia and heart failure. Methods: A total of 20 cases of iron deficiency anemia with heart failure were treated with experimental group and 10 normal guinea pigs as control group. Blood samples were collected to determine hemoglobin content, red blood cell number and whole blood iron index, and the changes of cardiac function and hemodynamics were detected by 6 240 biological signal collection system to determine whether the model was successful or not, Intracellular microelectrode technique was used to determine the action potentials of the papillary muscles in the model group and the control group. the potential amplitudes (APA, overshoot values (APA, maximum depolarization rate (Vmax, 20 % of repolarization, 50 % and 90 % of repolarization (APD20, APD50 and APD90 and the average velocity of repolarization were measured. Compare statistical difference between the model group and the control group. Results: 14 cases of model group survived completely, compared with control group, APD50 and APD90 prolonged, and the average velocity decreased. Conclusions: the action potential repolarization duration in the guinea pig papillary muscle of iron deficiency anemia with heart failure is prolonged, and the average repolarization velocity is slow.
Emotional reasoning and anxiety sensitivity: associations with social anxiety disorder in childhood.
Alkozei, Anna; Cooper, Peter J; Creswell, Cathy
2014-01-01
Two specific cognitive constructs that have been implicated in the development and maintenance of anxiety symptoms are anxiety sensitivity and emotional reasoning, both of which relate to the experience and meaning of physical symptoms of arousal or anxiety. The interpretation of physical symptoms has been particularly implicated in theories of social anxiety disorder, where internal physical symptoms are hypothesized to influence the individual's appraisals of the self as a social object. The current study compared 75 children on measures of anxiety sensitivity and emotional reasoning: 25 with social anxiety disorder, 25 with other anxiety disorders, and 25 nonanxious children (aged 7-12 years). Children with social anxiety disorder reported higher levels of anxiety sensitivity and were more likely than both other groups to view ambiguous situations as anxiety provoking, whether physical information was present or not. There were no group differences in the extent to which physical information altered children's interpretation of hypothetical scenarios. This study is the first to investigate emotional reasoning in clinically anxious children and therefore replication is needed. In addition, those in both anxious groups commonly had comorbid conditions and, consequently, specific conclusions about social anxiety disorder need to be treated with caution. The findings highlight cognitive characteristics that may be particularly pertinent in the context of social anxiety disorder in childhood and which may be potential targets for treatment. Furthermore, the findings suggest that strategies to modify these particular cognitive constructs may not be necessary in treatments of some other childhood anxiety disorders. © 2013 The Authors. Published by Elsevier B.V. All rights reserved.
Emotional reasoning and anxiety sensitivity: Associations with social anxiety disorder in childhood☆
Alkozei, Anna; Cooper, Peter J.; Creswell, Cathy
2014-01-01
Background Two specific cognitive constructs that have been implicated in the development and maintenance of anxiety symptoms are anxiety sensitivity and emotional reasoning, both of which relate to the experience and meaning of physical symptoms of arousal or anxiety. The interpretation of physical symptoms has been particularly implicated in theories of social anxiety disorder, where internal physical symptoms are hypothesized to influence the individual's appraisals of the self as a social object. Method The current study compared 75 children on measures of anxiety sensitivity and emotional reasoning: 25 with social anxiety disorder, 25 with other anxiety disorders, and 25 nonanxious children (aged 7–12 years). Results Children with social anxiety disorder reported higher levels of anxiety sensitivity and were more likely than both other groups to view ambiguous situations as anxiety provoking, whether physical information was present or not. There were no group differences in the extent to which physical information altered children's interpretation of hypothetical scenarios. Limitations This study is the first to investigate emotional reasoning in clinically anxious children and therefore replication is needed. In addition, those in both anxious groups commonly had comorbid conditions and, consequently, specific conclusions about social anxiety disorder need to be treated with caution. Conclusion The findings highlight cognitive characteristics that may be particularly pertinent in the context of social anxiety disorder in childhood and which may be potential targets for treatment. Furthermore, the findings suggest that strategies to modify these particular cognitive constructs may not be necessary in treatments of some other childhood anxiety disorders. PMID:24120086
Martel, Michelle M
2013-11-01
Despite the well-established sex difference in prevalence of many childhood and adolescent psychopathological conditions, no integrative metatheory of sex differences in psychopathology exists. This review attempts to provide a metatheoretical framework to guide empirical examination of sex differences in prevalence of childhood-onset "externalizing" and adolescent-onset "internalizing" disorders, based on sexual selection evolutionary theory. Sexual selection theory suggests important between-sex differences in markers, mechanisms, etiology, and developmental timing of risk and resilience relevant to psychopathology. Namely, sexual selection theory hypothesizes that disinhibition and sensation-seeking may be important proximate risk markers for childhood-onset externalizing disorders in males. The theory suggests that these male-biased markers may be a product of their higher exposure to prenatal testosterone, which makes them more susceptible to prenatal stressors with downstream effects on dopaminergic neurotransmission, especially for those with genetic alleles associated with lower dopaminergic function. In contrast, sexual selection theory hypothesizes that negative emotionality, empathy, and cognitive rumination may be important proximate risk markers for adolescent-onset internalizing disorders in females. The theory suggests that these markers are propagated by rapidly rising levels of estradiol at puberty that interact with cortisol and oxytocin. These hormones exert downstream effects on the serotonergic system in such a way as to increase females' sensitivity to interpersonal stressors particularly at puberty and especially for those with lower functional serotonergic activity. Such a metatheory can help integrate prior ideas about sex differences and can also generate new predictions of sex differences in markers, etiology, mechanisms, and developmental timing of common forms of psychopathology. © 2013 American Psychological Association
McKenna, Dillon; Peever, John
2017-05-01
During healthy rapid eye movement sleep, skeletal muscles are actively forced into a state of motor paralysis. However, in rapid eye movement sleep behavior disorder-a relatively common neurological disorder-this natural process is lost. A lack of motor paralysis (atonia) in rapid eye movement sleep behavior disorder allows individuals to actively move, which at times can be excessive and violent. At first glance this may sound harmless, but it is not because rapid eye movement sleep behavior disorder patients frequently injure themselves or the person they sleep with. It is hypothesized that the degeneration or dysfunction of the brain stem circuits that control rapid eye movement sleep paralysis is an underlying cause of rapid eye movement sleep behavior disorder. The link between brain stem degeneration and rapid eye movement sleep behavior disorder stems from the fact that rapid eye movement sleep behavior disorder precedes, in the majority (∼80%) of cases, the development of synucleinopathies such as Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, which are known to initially cause degeneration in the caudal brain stem structures where rapid eye movement sleep circuits are located. Furthermore, basic science and clinical evidence demonstrate that lesions within the rapid eye movement sleep circuits can induce rapid eye movement sleep-specific motor deficits that are virtually identical to those observed in rapid eye movement sleep behavior disorder. This review examines the evidence that rapid eye movement sleep behavior disorder is caused by synucleinopathic neurodegeneration of the core brain stem circuits that control healthy rapid eye movement sleep and concludes that rapid eye movement sleep behavior disorder is not a separate clinical entity from synucleinopathies but, rather, it is the earliest symptom of these disorders. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and
Heaner, Martica K; Walsh, B Timothy
2013-06-01
During the last 25 years, the careful examination of the eating behavior of individuals with eating disorders has provided critical insights into the nature of these disorders. Crucially, studies investigating components of different eating behaviors have documented that Anorexia Nervosa (AN), Bulimia Nervosa (BN), and Binge Eating Disorder (BED) are characterized by objective disturbances in eating patterns that are significantly different than behaviors exhibited by individuals who do not have these eating disorders. The detailed description of the disturbances in eating behavior has helped to identify diagnostic criteria associated with each disorder, and has led to important hypotheses about the underlying pathophysiology. These advances in understanding have provided, and continue to provide, a foundation for translational research and for the development of novel treatment interventions. This review is based on a presentation given by B. Timothy Walsh, M.D. at the 40th anniversary symposium of the Columbia University Appetite talks outlining the evolution of the discovery of the characteristic eating disturbances seen with each disorder. Copyright © 2013 Elsevier Ltd. All rights reserved.
Gender Relations and Economic Development: Hypotheses about the Reversal of Fortune in EurAsia
de Pleijt, A.M.; van Zanden, J.L.; Carmichael, S.G.
2016-01-01
This paper develops an interrelated set of hypotheses about the links between gender relations, family systems and economic development in EurAsia. Firstly, we briefly discuss a number of ideas from the recent literature about the links between gender relations and economic development. Secondly, we
Reduced striatal dopamine D2/3 receptor availability in Body Dysmorphic Disorder.
Vulink, Nienke C; Planting, Robin S; Figee, Martijn; Booij, Jan; Denys, Damiaan
2016-02-01
Though the dopaminergic system is implicated in Obsessive Compulsive and Related Disorders (OCRD), the dopaminergic system has never been investigated in-vivo in Body Dysmorphic Disorder (BDD). In line with consistent findings of reduced striatal dopamine D2/3 receptor availability in Obsessive Compulsive Disorder (OCD), we hypothesized that the dopamine D2/3 receptor availability in the striatum will be lower in patients with BDD in comparison to healthy subjects. Striatal dopamine D2/3 receptor Binding Potential (BPND) was examined in 12 drug-free BDD patients and 12 control subjects pairwise matched by age, sex, and handedness using [(123)I]iodobenzamide Single Photon Emission Computed Tomography (SPECT; bolus/constant infusion technique). Regions of interest were the caudate nucleus and the putamen. BPND was calculated as the ratio of specific striatal to binding in the occipital cortex (representing nonspecific binding). Compared to controls, dopamine D2/3 receptor BPND was significantly lower in BDD, both in the putamen (p=0.017) and caudate nucleus (p=0.022). This study provides the first evidence of a disturbed dopaminergic system in BDD patients. Although previously BDD was classified as a separate disorder (somatoform disorder), our findings give pathophysiological support for the recent reclassification of BDD to the OCRD in DSM-5. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.
Impaired sense of agency in functional movement disorders: An fMRI study.
Directory of Open Access Journals (Sweden)
Fatta B Nahab
Full Text Available The sense of agency (SA is an established framework that refers to our ability to exert and perceive control over our own actions. Having an intact SA provides the basis for the human perception of voluntariness, while impairments in SA are hypothesized to lead to the perception of movements being involuntary that may be seen many neurological or psychiatric disorders. Individuals with functional movement disorders (FMD experience a lack of control over their movements, yet these movements appear voluntary by physiology. We used fMRI to explore whether alterations in SA in an FMD population could explain why these patients feel their movements are involuntary. We compared the FMD group to a control group that was previously collected using an ecologically valid, virtual-reality movement paradigm that could modulate SA. We found selective dysfunction of the SA neural network, whereby the dorsolateral prefrontal cortex and pre-supplementary motor area on the right did not respond differentially to the loss of movement control. These findings provide some of the strongest evidence to date for a physiological basis underlying these disabling disorders.
Zhou, Rong-Yi; Wang, Jiao-Jiao; Sun, Ji-Chao; You, Yue; Ying, Jing-Nang; Han, Xin-Min
2017-10-01
Attention deficit hyperactivity disorder (ADHD) is a common behavioral disorder. Previous research has indicated that genetic factors, family education, environment and dietary habits are associated with ADHD. It has been determined that in China many children with ADHD also have allergic rhinitis or asthma. These children are more susceptible to the common cold or upper respiratory infections compared with normal healthy children. Additionally, the common cold or an upper respiratory infection may lead to disease recurrence or worsen the symptoms in these children. Previous studies have determined that ADHD may have a close association with allergic disease. Based on the clinically observed phenomenon and previous studies, it was hypothesized that ADHD is a high inflammation and immune‑associated disease. Therefore, the authors designed clinical and animal experiments to test this hypothesis in the future. Immune system disorders may be a novel part of the etiology of ADHD. The current report may have implications for future clinical practice.
Simons, G R; Newby, K H; Kearney, M M; Brandon, M J; Natale, A
1998-02-01
The objective of this study was to assess the safety and efficacy of transvenous low energy cardioversion of atrial fibrillation in patients with ventricular tachycardia and atrial fibrillation and to study the mechanisms of proarrhythmia. Previous studies have demonstrated that cardioversion of atrial fibrillation using low energy, R wave synchronized, direct current shocks applied between catheters in the coronary sinus and right atrium is feasible. However, few data are available regarding the risk of ventricular proarrhythmia posed by internal atrial defibrillation shocks among patients with ventricular arrhythmias or structural heart disease. Atrial defibrillation was performed on 32 patients with monomorphic ventricular tachycardia and left ventricular dysfunction. Shocks were administered during atrial fibrillation (baseline shocks), isoproterenol infusion, ventricular pacing, ventricular tachycardia, and atrial pacing. Baseline shocks were also administered to 29 patients with a history of atrial fibrillation but no ventricular arrhythmias. A total of 932 baseline shocks were administered. No ventricular proarrhythmia was observed after well-synchronized baseline shocks, although rare inductions of ventricular fibrillation occurred after inappropriate T wave sensing. Shocks administered during wide-complex rhythms (ventricular pacing or ventricular tachycardia) frequently induced ventricular arrhythmias, but shocks administered during atrial pacing at identical ventricular rates did not cause proarrhythmia. The risk of ventricular proarrhythmia after well-synchronized atrial defibrillation shocks administered during narrow-complex rhythms is low, even in patients with a history of ventricular tachycardia. The mechanism of proarrhythmia during wide-complex rhythms appears not to be related to ventricular rate per se, but rather to the temporal relationship between shock delivery and the repolarization time of the previous QRS complex.
Directory of Open Access Journals (Sweden)
Michael eNoll-Hussong
2014-06-01
Full Text Available Conversion disorder is a medical condition in which a person has paralysis, blindness, or other neurological symptoms that cannot be clearly explained physiologically. To date, there is neither specific nor conclusive treatment. In this paper, we draw together a number of disparate pieces of knowledge to propose a novel intervention to provide transient alleviation for this condition. As caloric vestibular stimulation (CVS has been demonstrated to modulate transiently a variety of cognitive functions associated with brain activations, especially in the temporal-parietal cortex, anterior cingulate cortex, and insular cortex, there is evidence to assume an effect in specific mental disorders. Therefore, we go on to hypothesize that lateralized cold vestibular caloric stimulation will be effective in treating conversion disorder and we present provisional evidence from one patient that supports this conclusion. If our hypothesis is correct, this will be the first time in psychiatry and neurology that a clinically well-known mental disorder, long considered difficult to understand and to treat, is relieved by a simple or common, non-invasive medical procedure.
Autism Spectrum Disorders - Diagnosis and Management.
Mukherjee, Sharmila Banerjee
2017-04-01
Autism Spectrum Disorder (ASD) is a neuro-developmental disorder commonly seen in children. It is characterized by age inappropriate, impaired social communication and the presence of stereotypic behavior. This disorder is hypothesized to result from cerebral dysfunction arising from a complex interaction between genetic, epigenetic and environmental factors. ASD should be suspected in children failing ASD specific screening tests, in the presence of red flags in social, language and/or play domains, in children with developmental or language delay, abnormal behavior, poor school performance or in those who are at high risk. Comprehensive assessment comprises of a step-wise approach that includes taking a detailed history, performing a holistic examination and observing the child closely in relation to play, social interaction and behavior. Diagnosis is established by application of the diagnostic criteria for ASD of the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM V). The degree of severity, intellectual and language impairment and presence of other illnesses should be specified. Functional assessment identifies an individual's strengths and weaknesses. All these are important to formulate a customized intervention plan along with the family. The goal is to build up skills enabling optimal and as far as possible normal functioning while simultaneously reducing maladaptive behavior. This is achieved by a multi-disciplinary team comprising of various personnel experienced in tackling issues in ASD related to their respective areas of expertise. Intervention is primarily non-pharmacological, based on behavioral modification strategies. Drugs are only indicated in the reduction of target symptoms refractory to behavioral intervention. Although there is no cure, timely and appropriate intervention can improve the quality of life significantly.
Decreased inward rectifier potassium current IK1 in dystrophin-deficient ventricular cardiomyocytes.
Rubi, Lena; Koenig, Xaver; Kubista, Helmut; Todt, Hannes; Hilber, Karlheinz
2017-03-04
Kir2.x channels in ventricular cardiomyocytes (most prominently Kir2.1) account for the inward rectifier potassium current I K1 , which controls the resting membrane potential and the final phase of action potential repolarization. Recently it was hypothesized that the dystrophin-associated protein complex (DAPC) is important in the regulation of Kir2.x channels. To test this hypothesis, we investigated potential I K1 abnormalities in dystrophin-deficient ventricular cardiomyocytes derived from the hearts of Duchenne muscular dystrophy mouse models. We found that I K1 was substantially diminished in dystrophin-deficient cardiomyocytes when compared to wild type myocytes. This finding represents the first functional evidence for a significant role of the DAPC in the regulation of Kir2.x channels.
Watts, Ashley K. Smith; Patel, Deepika; Corley, Robin P.; Friedman, Naomi P.; Hewitt, John K.; Robinson, JoAnn L.; Rhee, Soo H.
2014-01-01
Studies have reported an inverse association between language development and behavioral inhibition or shyness across childhood, but the direction of this association remains unclear. This study tested alternative hypotheses regarding this association in a large sample of toddlers. Data on behavioral inhibition and expressive and receptive…