Bercik, Premysl; Verdu, Elena F; Foster, Jane A; Macri, Joseph; Potter, Murray; Huang, Xiaxing; Malinowski, Paul; Jackson, Wendy; Blennerhassett, Patricia; Neufeld, Karen A; Lu, Jun; Khan, Waliul I; Corthesy-Theulaz, Irene; Cherbut, Christine; Bergonzelli, Gabriela E; Collins, Stephen M
Clinical and preclinical studies have associated gastrointestinal inflammation and infection with altered behavior. We investigated whether chronic gut inflammation alters behavior and brain biochemistry and examined underlying mechanisms. AKR mice were infected with the noninvasive parasite Trichuris muris and given etanercept, budesonide, or specific probiotics. Subdiaphragmatic vagotomy was performed in a subgroup of mice before infection. Gastrointestinal inflammation was assessed by histology and quantification of myeloperoxidase activity. Serum proteins were measured by proteomic analysis, circulating cytokines were measured by fluorescence activated cell sorting array, and serum tryptophan and kynurenine were measured by liquid chromatography. Behavior was assessed using light/dark preference and step-down tests. In situ hybridization was used to assess brain-derived neurotrophic factor (BDNF) expression in the brain. T muris caused mild to moderate colonic inflammation and anxiety-like behavior that was associated with decreased hippocampal BDNF messenger RNA (mRNA). Circulating tumor necrosis factor-α and interferon-γ, as well as the kynurenine and kynurenine/tryptophan ratio, were increased. Proteomic analysis showed altered levels of several proteins related to inflammation and neural function. Administration of etanercept, and to a lesser degree of budesonide, normalized behavior, reduced cytokine and kynurenine levels, but did not influence BDNF expression. The probiotic Bifidobacterium longum normalized behavior and BDNF mRNA but did not affect cytokine or kynurenine levels. Anxiety-like behavior was present in infected mice after vagotomy. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry, which can be normalized by inflammation-dependent and -independent mechanisms, neither of which requires the integrity of the vagus nerve. Copyright © 2010 AGA Institute. Published by Elsevier Inc
Onakomaiya, Marie M.; Porter, Donna M.; Oberlander, Joseph G.; Henderson, Leslie P.
Anabolic androgenic steroids (AAS) are taken by both sexes to enhance athletic performance and body image, nearly always in conjunction with an exercise regime. Although taken to improve physical attributes, chronic AAS use can promote negative behavior, including anxiety. Few studies have directly compared the impact of AAS use in males versus females or assessed the interaction of exercise and AAS. We show that AAS increase anxiety-like behaviors in female but not male mice and that voluntary exercise accentuates these sex-specific differences. We also show that levels of the anxiogenic peptide corticotrophin releasing factor (CRF) are significantly greater in males, but that AAS selectively increase CRF levels in females, thus abrogating this sex-specific difference. Exercise did not ameliorate AAS-induced anxiety or alter CRF levels in females. Exercise was anxiolytic in males, but this behavioral outcome did not correlate with CRF levels. Brain-derived neurotrophic factor (BDNF) has also been implicated in the expression of anxiety. As with CRF, levels of hippocampal BDNF mRNA were significantly greater in males than females. AAS and exercise were without effect on BDNF mRNA in females. In males, anxiolytic effects of exercise correlated with increased BDNF mRNA, however AAS-induced changes in BDNF mRNA and anxiety did not. In sum, we find that AAS elicit sex-specific differences in anxiety and that voluntary exercise accentuates these differences. In addition, our data suggest that these behavioral outcomes may reflect convergent actions of AAS and exercise on a sexually differentiated CRF signaling system within the extended amygdala. PMID:24768711
Caruso, Michael J; Crowley, Nicole A; Reiss, Dana E; Caulfield, Jasmine I; Luscher, Bernhard; Cavigelli, Sonia A; Kamens, Helen M
Early-life stress is a risk factor for comorbid anxiety and nicotine use. Because little is known about the factors underlying this comorbidity, we investigated the effects of adolescent stress on anxiety-like behavior and nicotine responses within individual animals. Adolescent male and female C57BL/6J mice were exposed to chronic variable social stress (CVSS; repeated cycles of social isolation + social reorganization) or control conditions from postnatal days (PND) 25-59. Anxiety-like behavior and social avoidance were measured in the elevated plus-maze (PND 61-65) and social approach-avoidance test (Experiment 1: PND 140-144; Experiment 2: 95-97), respectively. Acute nicotine-induced locomotor, hypothermic, corticosterone responses, (Experiment 1: PND 56-59; Experiment 2: PND 65-70) and voluntary oral nicotine consumption (Experiment 1: PND 116-135; Experiment 2: 73-92) were also examined. Finally, we assessed prefrontal cortex (PFC) and nucleus accumbens (NAC) synaptic transmission (PND 64-80); brain regions that are implicated in anxiety and addiction. Mice exposed to adolescent CVSS displayed increased anxiety-like behavior relative to controls. Further, CVSS altered synaptic excitability in PFC and NAC neurons in a sex-specific manner. For males, CVSS decreased the amplitude and frequency of spontaneous excitatory postsynaptic currents in the PFC and NAC, respectively. In females, CVSS decreased the amplitude of spontaneous inhibitory postsynaptic currents in the NAC. Adolescent CVSS did not affect social avoidance or nicotine responses and anxiety-like behavior was not reliably associated with nicotine responses within individual animals. Taken together, complex interactions between PFC and NAC function may contribute to adolescent stress-induced anxiety-like behavior without influencing nicotine responses. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.
Costine, Beth A; Oberlander, Joseph G; Davis, Matthew C; Penatti, Carlos A A; Porter, Donna M; Leaton, Robert N; Henderson, Leslie P
Summary In the past several decades, the therapeutic use of anabolic androgenic steroids (AAS) has been overshadowed by illicit use of these drugs by elite athletes and a growing number of adolescents to enhance performance and body image. As with adults, AAS use by adolescents is associated with a range of behavioral effects, including increased anxiety and altered responses to stress. It has been suggested that adolescents, especially adolescent females, may be particularly susceptible to the effects of these steroids, but few experiments in animal models have been performed to test this assertion. Here we show that chronic exposure of adolescent female mice to a mixture of three commonly abused AAS (testosterone cypionate, nandrolone decanoate and methandrostenolone; 7.5 mg/kg/day for 5 days) significantly enhanced anxiety-like behavior as assessed by the acoustic startle response (ASR), but did not augment the fear-potentiated startle response (FPS) or alter sensorimotor gating as assessed by prepulse inhibition of the acoustic startle response (PPI). AAS treatment also significantly increased the levels of corticotropin releasing factor (CRF) mRNA and somal-associated CRF immunoreactivity in the central amygdala (CeA), as well as neuropil-associated immunoreactivity in the dorsal aspect of the anterolateral division of the bed nucleus of the stria terminalis (dBnST). AAS treatment did not alter CRF receptor 1 or 2 mRNA in either the CeA or the dBnST; CRF immunoreactivity in the ventral BNST, the paraventricular nucleus (PVN) or the median eminence (ME); or peripheral levels of corticosterone. These results suggest that chronic AAS treatment of adolescent female mice may enhance generalized anxiety, but not sensorimotor gating or learned fear, via a mechanism that involves increased CRF-mediated signaling from CeA neurons projecting to the dBnST. PMID:20537804
Full Text Available The presence of the neurotrophin receptor p75NTR in adult basal forebrain cholinergic neurons, precursor cells in the subventricular cell layer and the subgranular cell layer of the hippocampus has been linked to alterations in learning as well as anxiety- and depression- related behaviors. In contrast to previous studies performed in a p75NTR exonIII-/- model still expressing the short isoform of the p75NTR, we focused on locomotor and anxiety–associated behavior in p75NTR exonIV-/- mice lacking both p75NTR isoforms. Comparing p75NTR exonIV-/- and wildtype mice for both male and female animals showed an anxiolytic-like behavior as evidenced by increased central activities in the open field paradigm and flex field activity system as well as higher numbers of open arm entries in the elevated plus maze test in female p75NTR knockout mice.Morphometrical analyses of dorsal and ventral hippocampus revealed a reduction of width of the dentate gyrus and the granular cell layer in the dorsal but not ventral hippocampus in male and female p75NTR exonIV -/- mice. We conclude that germ-line deletion of p75NTR seems to differentially affect morphometry of dorsal and ventral dentate gyrus and that p75NTR may play a role in anxiety-like behavior, specifically in female mice.
Generalized Anxiety Disorder and Social Anxiety Disorder, but Not Panic Anxiety Disorder, Are Associated with Higher Sensitivity to Learning from Negative Feedback: Behavioral and Computational Investigation
Khdour, Hussain Y.; Abushalbaq, Oday M.; Mughrabi, Ibrahim T.; Imam, Aya F.; Gluck, Mark A.; Herzallah, Mohammad M.; Moustafa, Ahmed A.
Anxiety disorders, including generalized anxiety disorder (GAD), social anxiety disorder (SAD), and panic anxiety disorder (PAD), are a group of common psychiatric conditions. They are characterized by excessive worrying, uneasiness, and fear of future events, such that they affect social and occupational functioning. Anxiety disorders can alter behavior and cognition as well, yet little is known about the particular domains they affect. In this study, we tested the cognitive correlates of me...
Crofton, Elizabeth J.; Nenov, Miroslav N.; Zhang, Yafang; Scala, Federico; Page, Sean A.; McCue, David L.; Li, Dingge; Hommel, Jonathan D.; Laezza, Fernanda; Green, Thomas A.
Psychiatric disorders such as anxiety, depression and addiction are often comorbid brain pathologies thought to share common mechanistic biology. As part of the cortico-limbic circuit, the nucleus accumbens shell (NAcSh) plays a fundamental role in integrating information in the circuit, such that modulation of NAcSh circuitry alters anxiety, depression, and addiction-related behaviors. Intracellular kinase cascades in the NAcSh have proven important mediators of behavior. To investigate glycogen-synthase kinase 3 (GSK3) beta signaling in the NAcSh in vivo we knocked down GSK3beta expression with a novel adeno-associated viral vector (AAV2) and assessed changes in anxiety- and depression-like behavior and cocaine self-administration in GSK3beta knockdown rats. GSK3beta knockdown reduced anxiety-like behavior while increasing depression-like behavior and cocaine self-administration. Correlative electrophysiological recordings in acute brain slices were used to assess the effect of AAV-shGSK3beta on spontaneous firing and intrinsic excitability of tonically active interneurons (TANs), cells required for input and output signal integration in the NAcSh and for processing reward-related behaviors. Loose-patch recordings showed that TANs transduced by AAV-shGSK3beta exhibited reduction in tonic firing and increased spike half width. When assessed by whole-cell patch clamp recordings these changes were mirrored by reduction in action potential firing and accompanied by decreased hyperpolarization-induced depolarizing sag potentials, increased action potential current threshold, and decreased maximum rise time. These results suggest that silencing of GSK3beta in the NAcSh increases depression- and addiction-related behavior, possibly by decreasing intrinsic excitability of TANs. However, this study does not rule out contributions from other neuronal sub-types. PMID:28126496
Michael K Skinner
Full Text Available Embryonic exposure to the endocrine disruptor vinclozolin during gonadal sex determination promotes an epigenetic reprogramming of the male germ-line that is associated with transgenerational adult onset disease states. Further analysis of this transgenerational phenotype on the brain demonstrated reproducible changes in the brain transcriptome three generations (F3 removed from the exposure. The transgenerational alterations in the male and female brain transcriptomes were distinct. In the males, the expression of 92 genes in the hippocampus and 276 genes in the amygdala were transgenerationally altered. In the females, the expression of 1,301 genes in the hippocampus and 172 genes in the amygdala were transgenerationally altered. Analysis of specific gene sets demonstrated that several brain signaling pathways were influenced including those involved in axon guidance and long-term potentiation. An investigation of behavior demonstrated that the vinclozolin F3 generation males had a decrease in anxiety-like behavior, while the females had an increase in anxiety-like behavior. These observations demonstrate that an embryonic exposure to an environmental compound appears to promote a reprogramming of brain development that correlates with transgenerational sex-specific alterations in the brain transcriptomes and behavior. Observations are discussed in regards to environmental and transgenerational influences on the etiology of brain disease.
Allsop, Stephen A.; Vander Weele, Caitlin M.; Wichmann, Romy; Tye, Kay M.
Many psychiatric illnesses are characterized by deficits in the social domain. For example, there is a high rate of co-morbidity between autism spectrum disorders and anxiety disorders. However, the common neural circuit mechanisms by which social deficits and other psychiatric disease states, such as anxiety, are co-expressed remains unclear. Here, we review optogenetic investigations of neural circuits in animal models of anxiety-related behaviors and social behaviors and discuss the important role of the amygdala in mediating aspects of these behaviors. In particular, we focus on recent evidence that projections from the basolateral amygdala (BLA) to the ventral hippocampus (vHPC) modulate anxiety-related behaviors and also alter social interaction. Understanding how this circuit influences both social behavior and anxiety may provide a mechanistic explanation for the pathogenesis of social anxiety disorder, as well as the prevalence of patients co-diagnosed with autism spectrum disorders and anxiety disorders. Furthermore, elucidating how circuits that modulate social behavior also mediate other complex emotional states will lead to a better understanding of the underlying mechanisms by which social deficits are expressed in psychiatric disease. PMID:25076878
Full Text Available Objective:To investigate the effects of ethanol exposure in adolescent rats during adulthood by assesssing aggression and anxiety-like behaviors and measuring the levels of inflammatory markers.Methods:Groups of male Wistar rats (mean weight 81.4 g, n = 36 were housed in groups of four until postnatal day (PND 60. From PNDs 30 to 46, rats received one of three treatments: 3 g/kg of ethanol (15% w/v, orally, n = 16, 1.5 g/kg of ethanol (12.5% w/v, PO, n = 12, or water (n = 12 every 48 hours. Animals were assessed for aggressive behavior (resident x intruder test and anxiety-like behaviors (elevated plus maze during adulthood.Results:Animals that received low doses of alcohol showed reduced levels of brain-derived neurotrophic factor (BDNF in the hippocampus as compared to the control group. No significant difference was found in prefrontal cortex.Conclusions:Intermittent exposure to alcohol during adolescence is associated with lower levels of BDNF in the hippocampus, probably due the episodic administration of alcohol, but alcohol use did not alter the level agression toward a male intruder or anxiety-like behaviors during the adult phase.
Samaco, Rodney C; Mandel-Brehm, Caleigh; McGraw, Christopher M; Shaw, Chad A; McGill, Bryan E; Zoghbi, Huda Y
Genomic duplications spanning Xq28 are associated with a spectrum of phenotypes, including anxiety and autism. The minimal region shared among affected individuals includes MECP2 and IRAK1, although it is unclear which gene when overexpressed causes anxiety and social behavior deficits. We report that doubling MECP2 levels causes heightened anxiety and autism-like features in mice and alters the expression of genes that influence anxiety and social behavior, such as Crh and Oprm1. To test the hypothesis that alterations in these two genes contribute to heightened anxiety and social behavior deficits, we analyzed MECP2 duplication mice (MECP2-TG1) that have reduced Crh and Oprm1 expression. In MECP2-TG1 animals, reducing the levels of Crh or its receptor, Crhr1, suppressed anxiety-like behavior; in contrast, reducing Oprm1 expression improved abnormal social behavior. These data indicate that increased MeCP2 levels affect molecular pathways underlying anxiety and social behavior and provide new insight into potential therapies for MECP2-related disorders.
McCall, Jordan G; Siuda, Edward R; Bhatti, Dionnet L; Lawson, Lamley A; McElligott, Zoe A; Stuber, Garret D; Bruchas, Michael R
Increased tonic activity of locus coeruleus noradrenergic (LC-NE) neurons induces anxiety-like and aversive behavior. While some information is known about the afferent circuitry that endogenously drives this neural activity and behavior, the downstream receptors and anatomical projections that mediate these acute risk aversive behavioral states via the LC-NE system remain unresolved. Here we use a combination of retrograde tracing, fast-scan cyclic voltammetry, electrophysiology, and in vivo optogenetics with localized pharmacology to identify neural substrates downstream of increased tonic LC-NE activity in mice. We demonstrate that photostimulation of LC-NE fibers in the BLA evokes norepinephrine release in the basolateral amygdala (BLA), alters BLA neuronal activity, conditions aversion, and increases anxiety-like behavior. Additionally, we report that β-adrenergic receptors mediate the anxiety-like phenotype of increased NE release in the BLA. These studies begin to illustrate how the complex efferent system of the LC-NE system selectively mediates behavior through distinct receptor and projection-selective mechanisms.
Matthew S Stratton
Full Text Available Neurons of the paraventricular nucleus of the hypothalamus (PVN regulate the hypothalamic- pituitary-adrenal (HPA axis and the autonomic nervous system. Females lacking functional GABA(B receptors because of a genetic disruption of the R1 subunit have altered cellular characteristics in and around the PVN at birth. The genetic disruption precluded appropriate assessments of physiology or behavior in adulthood. The current study was conducted to test the long term impact of a temporally restricting pharmacological blockade of the GABA(B receptor to a 7-day critical period (E11-E17 during embryonic development. Experiments tested the role of GABA(B receptor signaling in fetal development of the PVN and later adult capacities for adult stress related behaviors and physiology. In organotypic slices containing fetal PVN, there was a female specific, 52% increase in cell movement speeds with GABA(B receptor antagonist treatment that was consistent with a sex-dependent lateral displacement of cells in vivo following 7 days of fetal exposure to GABA(B receptor antagonist. Anxiety-like and depression-like behaviors, open-field activity, and HPA mediated responses to restraint stress were measured in adult offspring of mothers treated with GABA(B receptor antagonist. Embryonic exposure to GABA(B receptor antagonist resulted in reduced HPA axis activation following restraint stress and reduced depression-like behaviors. There was also increased anxiety-like behavior selectively in females and hyperactivity in males. A sex dependent response to disruptions of GABA(B receptor signaling was identified for PVN formation and key aspects of physiology and behavior. These changes correspond to sex specific prevalence in similar human disorders, namely anxiety disorders and hyperactivity.
Cissé, Yasmine M; Peng, Juan; Nelson, Randy J
Dim light at night (dLAN) disrupts circadian organization and influences adult behavior. We examined early dLAN exposure on adult affective responses. Beginning 3 (juvenile) or 5 weeks (adolescent) of age, mice were maintained in standard light-dark cycles or exposed to nightly dLAN (5 lx) for 5 weeks, then anxiety-like and fear responses were assessed. Hypothalami were collected around the clock to assess core clock genes. Exposure to dLAN at either age increased anxiety-like responses in adults. Clock and Rev-ERB expression were altered by exposure to dLAN. In contrast to adults, dLAN exposure during early life increases anxiety and fear behavior.
Mocelin, Ricieri; Herrmann, Ana P; Marcon, Matheus; Rambo, Cassiano L; Rohden, Aline; Bevilaqua, Fernanda; de Abreu, Murilo Sander; Zanatta, Leila; Elisabetsky, Elaine; Barcellos, Leonardo J G; Lara, Diogo R; Piato, Angelo L
Despite the recent advances in understanding the pathophysiology of anxiety disorders, the pharmacological treatments currently available are limited in efficacy and induce serious side effects. A possible strategy to achieve clinical benefits is drug repurposing, i.e., discovery of novel applications for old drugs, bringing new treatment options to the market and to the patients who need them. N-acetylcysteine (NAC), a commonly used mucolytic and paracetamol antidote, has emerged as a promising molecule for the treatment of several neuropsychiatric disorders. The mechanism of action of this drug is complex, and involves modulation of antioxidant, inflammatory, neurotrophic and glutamate pathways. Here we evaluated the effects of NAC on behavioral parameters relevant to anxiety in zebrafish. NAC did not alter behavioral parameters in the novel tank test, prevented the anxiety-like behaviors induced by an acute stressor (net chasing), and increased the time zebrafish spent in the lit side in the light/dark test. These data may indicate that NAC presents an anti-stress effect, with the potential to prevent stress-induced psychiatric disorders such as anxiety and depression. The considerable homology between mammalian and zebrafish genomes invests the current data with translational validity for the further clinical trials needed to substantiate the use of NAC in anxiety disorders. Copyright © 2015 Elsevier Inc. All rights reserved.
Geng, Haiyang; Wang, Yi; Gu, Ruolei; Luo, Yue-Jia; Xu, Pengfei; Huang, Yuxia; Li, Xuebing
In the research field of anxiety, previous studies generally focus on emotional responses following threat. A recent model of anxiety proposes that altered anticipation prior to uncertain threat is related with the development of anxiety. Behavioral findings have built the relationship between anxiety and distinct anticipatory processes including attention, estimation of threat, and emotional responses. However, few studies have characterized the brain organization underlying anticipation of uncertain threat and its role in anxiety. In the present study, we used an emotional anticipation paradigm with functional magnetic resonance imaging (fMRI) to examine the aforementioned topics by employing brain activation and general psychophysiological interactions (gPPI) analysis. In the activation analysis, we found that high trait anxious individuals showed significantly increased activation in the thalamus, middle temporal gyrus (MTG), and dorsomedial prefrontal cortex (dmPFC), as well as decreased activation in the precuneus, during anticipation of uncertain threat compared to the certain condition. In the gPPI analysis, the key regions including the amygdala, dmPFC, and precuneus showed altered connections with distributed brain areas including the ventromedial prefrontal cortex (vmPFC), dorsolateral prefrontal cortex (dlPFC), inferior parietal sulcus (IPS), insula, para-hippocampus gyrus (PHA), thalamus, and MTG involved in anticipation of uncertain threat in anxious individuals. Taken together, our findings indicate that during the anticipation of uncertain threat, anxious individuals showed altered activations and functional connectivity in widely distributed brain areas, which may be critical for abnormal perception, estimation, and emotion reactions during the anticipation of uncertain threat. © 2018 Wiley Periodicals, Inc.
Yorgason, Jordan T; España, Rodrigo A; Konstantopoulos, Joanne K; Weiner, Jeffrey L; Jones, Sara R
Social isolation (SI) rearing, a model of early life stress, results in profound behavioral alterations, including increased anxiety-like behavior, impaired sensorimotor gating and increased self-administration of addictive substances. These changes are accompanied by alterations in mesolimbic dopamine function, such as increased dopamine and metabolite tissue content, increased dopamine responses to cues and psychostimulants, and increased dopamine neuron burst firing. Using voltammetric techniques, we examined the effects of SI rearing on dopamine transporter activity, vesicular release and dopamine D2-type autoreceptor activity in the nucleus accumbens core. Long-Evans rats were housed in group (GH; 4/cage) or SI (1/cage) conditions from weaning into early adulthood [postnatal day (PD) 28-77]. After this initial housing period, rats were assessed on the elevated plus-maze for an anxiety-like phenotype, and then slice voltammetry experiments were performed. To study the enduring effects of SI rearing on anxiety-like behavior and dopamine terminal function, another cohort of similarly reared rats was isolated for an additional 4 months (until PD 174) and then tested. Our findings demonstrate that SI rearing results in lasting increases in anxiety-like behavior, dopamine release and dopamine transporter activity, but not D2 activity. Interestingly, GH-reared rats that were isolated as adults did not develop the anxiety-like behavior or dopamine changes seen in SI-reared rats. Together, our data suggest that early life stress results in an anxiety-like phenotype, with lasting increases in dopamine terminal function. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.
Ramos-Ortolaza, Dinah L; Doreste-Mendez, Raura J; Alvarado-Torres, John K; Torres-Reveron, Annelyn
Chronic social isolation could lead to a disruption in the Hypothalamic-Pituitary-Adrenal (HPA) axis, resulting in anxiety and depressive-like behaviors but cycling estrogens could modify these behaviors. The aim of this study was to determine if changes in ovarian hormones during the normal cycle could interact with social isolation to alter anxiety and depressive-like behaviors. In parallel, we examined the expression of glucocorticoid receptor (GR) and synaptic vesicle protein synaptophysin in the hippocampus and hypothalamus of Sprague Dawley normal cycling female rats. We assigned rats to either isolated or paired housing for 8 weeks. To assess anxiety and depressive-like behaviors, we used the open field test and forced swim test, respectively. Female rats were tested at either diestrus, estrus, or proestrus stage of the estrous cycle. After behaviors, rats were perfused and brains collected. Brain sections containing hippocampus and hypothalamus were analyzed using immunohistochemistry for synaptophysin and glucocorticoid receptor (GR) levels. We found an increase in depressive-like behaviors for isolated animals compared to paired housed rats, regardless of the estrous cycle stage. Interestingly, we found a decrease in anxiety behaviors in females in the estrus stage accompanied by a decrease in GR expression in hippocampal DG and CA3. However, no changes in synaptophysin were observed in any of the areas of studied. Our results support the beneficial effects of circulating ovarian hormones in anxiety, possibly by decreasing GR expression. Copyright © 2017 Elsevier B.V. All rights reserved.
Dworkin, Sebastian; Auden, Alana; Partridge, Darren D; Daglas, Maria; Medcalf, Robert L; Mantamadiotis, Theo; Georgy, Smitha R; Darido, Charbel; Jane, Stephen M; Ting, Stephen B
The highly conserved Grainyhead-like (Grhl) family of transcription factors, comprising three members in vertebrates (Grhl1-3), play critical regulatory roles during embryonic development, cellular proliferation, and apoptosis. Although loss of Grhl function leads to multiple neural abnormalities in numerous animal models, a comprehensive analysis of Grhl expression and function in the mammalian brain has not been reported. Here they show that only Grhl3 expression is detectable in the embryonic mouse brain; particularly within the habenula, an organ known to modulate repressive behaviors. Using both Grhl3-knockout mice (Grhl3 -/- ), and brain-specific conditional deletion of Grhl3 in adult mice (Nestin-Cre/Grhl3 flox/flox ), they performed histological expression analyses and behavioral tests to assess long-term effects of Grhl3 loss on motor co-ordination, spatial memory, anxiety, and stress. They found that complete deletion of Grhl3 did not lead to noticeable structural or cell-intrinsic defects in the embryonic brain; however, aged Grhl3 conditional knockout (cKO) mice showed enlarged lateral ventricles and displayed marked changes in motor function and behaviors suggestive of decreased fear and anxiety. They conclude that loss of Grhl3 in the brain leads to significant alterations in locomotor activity and decreased self-inhibition, and as such, these mice may serve as a novel model of human conditions of impulsive behavior or hyperactivity. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 775-788, 2017. © 2017 Wiley Periodicals, Inc.
Arentsen, Tim; Khalid, Roksana; Qian, Yu; Diaz Heijtz, Rochellys
Peptidoglycan recognition proteins (PGRPs) are key sensing-molecules of the innate immune system that specifically detect bacterial peptidoglycan (PGN) and its derivates. PGRPs have recently emerged as potential key regulators of normal brain development and behavior. To test the hypothesis that PGRPs play a role in motor control and anxiety-like behavior in later life, we used 15-month old male and female peptidoglycan recognition protein 2 (Pglyrp2) knockout (KO) mice. Pglyrp2 is an N-acetylmuramyl-l-alanine amidase that hydrolyzes PGN between the sugar backbone and the peptide chain (which is unique among the mammalian PGRPs). Using a battery of behavioral tests, we demonstrate that Pglyrp2 KO male mice display decreased levels of anxiety-like behavior compared with wild type (WT) males. In contrast, Pglyrp2 KO female mice show reduced rearing activity and increased anxiety-like behavior compared to WT females. In the accelerated rotarod test, however, Pglyrp2 KO female mice performed better compared to WT females (i.e., they had longer latency to fall off the rotarod). Further, Pglyrp2 KO male mice exhibited decreased expression levels of synaptophysin, gephyrin, and brain-derived neurotrophic factor in the frontal cortex, but not in the amygdala. Pglyrp2 KO female mice exhibited increased expression levels of spinophilin and alpha-synuclein in the frontal cortex, while exhibiting decreased expression levels of synaptophysin, gephyrin and spinophilin in the amygdala. Our findings suggest a novel role for Pglyrp2asa key regulator of motor and anxiety-like behavior in late life. Copyright © 2017. Published by Elsevier Inc.
Lee, Hyunchan; Noh, Jihyun
Social connection reduces the physiological reactivity to stressors, while social exclusion causes emotional distress. Stressful experiences in rats result in the facilitation of aversive memory and induction of anxiety. To determine the effect of social interaction, such as social connection, social exclusion and equality or inequality, on emotional change in adolescent distressed rats, the emotional alteration induced by restraint stress in individual rats following exposure to various social interaction circumstances was examined. Rats were assigned to one of the following groups: all freely moving rats, all rats restrained, rats restrained in the presence of freely moving rats and freely moving rats with a restrained rat. No significant difference in fear-memory and sucrose consumption between all groups was found. Change in body weight significantly increased in freely moving rats with a restrained rat, suggesting that those rats seems to share the stressful experience of the restrained rat. Interestingly, examination of the anxiety-like behavior revealed only rats restrained in the presence of freely moving rats to have a significant increase, suggesting that emotional distress intensifies in positions of social exclusion. These results demonstrate that unequally excluded social interaction circumstances could cause the amplification of distressed status and anxiety-related emotional alteration. Copyright © 2015 Elsevier B.V. All rights reserved.
Wong, M-L; Inserra, A; Lewis, M D; Mastronardi, C A; Leong, L; Choo, J; Kentish, S; Xie, P; Morrison, M; Wesselingh, S L; Rogers, G B; Licinio, J
The inflammasome is hypothesized to be a key mediator of the response to physiological and psychological stressors, and its dysregulation may be implicated in major depressive disorder. Inflammasome activation causes the maturation of caspase-1 and activation of interleukin (IL)-1β and IL-18, two proinflammatory cytokines involved in neuroimmunomodulation, neuroinflammation and neurodegeneration. In this study, C57BL/6 mice with genetic deficiency or pharmacological inhibition of caspase-1 were screened for anxiety- and depressive-like behaviors, and locomotion at baseline and after chronic stress. We found that genetic deficiency of caspase-1 decreased depressive- and anxiety-like behaviors, and conversely increased locomotor activity and skills. Caspase-1 deficiency also prevented the exacerbation of depressive-like behaviors following chronic stress. Furthermore, pharmacological caspase-1 antagonism with minocycline ameliorated stress-induced depressive-like behavior in wild-type mice. Interestingly, chronic stress or pharmacological inhibition of caspase-1 per se altered the fecal microbiome in a very similar manner. When stressed mice were treated with minocycline, the observed gut microbiota changes included increase in relative abundance of Akkermansia spp. and Blautia spp., which are compatible with beneficial effects of attenuated inflammation and rebalance of gut microbiota, respectively, and the increment in Lachnospiracea abundance was consistent with microbiota changes of caspase-1 deficiency. Our results suggest that the protective effect of caspase-1 inhibition involves the modulation of the relationship between stress and gut microbiota composition, and establishes the basis for a gut microbiota-inflammasome-brain axis, whereby the gut microbiota via inflammasome signaling modulate pathways that will alter brain function, and affect depressive- and anxiety-like behaviors. Our data also suggest that further elucidation of the gut microbiota
Diaz, Marvin R; Mooney, Sandra M; Varlinskaya, Elena I
Our previous research has shown that in Long Evans rats acute prenatal exposure to a high dose of ethanol on gestational day (G) 12 produces social deficits in male offspring and elicits substantial decreases in social preference relative to controls, in late adolescents and adults regardless of sex. In order to generalize the observed detrimental effects of ethanol exposure on G12, pregnant female Sprague Dawley rats were exposed to ethanol or saline and their offspring were assessed in a modified social interaction (SI) test as early adolescents, late adolescents, or young adults. Anxiety-like behavior was also assessed in adults using the elevated plus maze (EPM) or the light/dark box (LDB) test. Age- and sex-dependent social alterations were evident in ethanol-exposed animals. Ethanol-exposed males showed deficits in social investigation at all ages and age-dependent alterations in social preference. Play fighting was not affected in males. In contrast, ethanol-exposed early adolescent females showed no changes in social interactions, whereas older females demonstrated social deficits and social indifference. In adulthood, anxiety-like behavior was decreased in males and females prenatally exposed to ethanol in the EPM, but not the LDB. These findings suggest that social alterations associated with acute exposure to ethanol on G12 are not strain-specific, although they are more pronounced in Long Evans males and Sprague Dawley females. Furthermore, given that anxiety-like behaviors were attenuated in a test-specific manner, this study indicates that early ethanol exposure can have differential effects on different forms of anxiety. Copyright © 2016 Elsevier B.V. All rights reserved.
Leo, Giuseppina; Guescini, Michele; Genedani, Susanna; Stocchi, Vilberto; Carone, Chiara; Filaferro, Monica; Sisti, Davide; Marcoli, Manuela; Maura, Guido; Cortelli, Pietro; Guidolin, Diego; Fuxe, Kjell; Agnati, Luigi Francesco
Several clinical observations have demonstrated a link between heart rate and anxiety or panic disorders. In these patients, β-adrenergic receptor function was altered. This prompted us to investigate whether the β-adrenergic receptor agonist isoproterenol, at a dose that stimulates peripheral β-adrenergic system but has no effects at the central nervous system, can induce anxiety-like behavior in rats. Moreover, some possible messengers involved in the peripheral to brain communication were investigated. Our results showed that isoproterenol (5 mg kg(-1) i.p.) increased heart rate, evoked anxiety-like behavior, did not result in motor impairments and increased extracellular vesicle content in the blood. Plasma corticosterone level was unmodified as well as vesicular Hsp70 content. Vesicular miR-208 was also unmodified indicating a source of increased extracellular vesicles different from cardiomyocytes. We can hypothesize that peripheral extracellular vesicles might contribute to the β-adrenergic receptor-evoked anxiety-like behavior, acting as peripheral signals in modulating the mental state. Copyright © 2015 Elsevier Inc. All rights reserved.
Mandela, Prashant; Yan, Yan; LaRese, Taylor; Eipper, Betty A.; Mains, Richard E.
Kalirin, a Rho GDP/GTP exchange factor for Rac1 and RhoG, is known to play an essential role in the formation and maintenance of excitatory synapses and in the secretion of neuropeptides. Mice unable to express any of the isoforms of Kalrn in cells that produce POMC at any time during development (POMC cells) exhibited reduced anxiety-like behavior and reduced acquisition of passive avoidance behavior, along with sex-specific alteration in the corticosterone response to restraint stress. Strikingly, lack of Kalrn expression in POMC cells closely mimicked the effects of global Kalrn knockout on anxiety-like behavior and passive avoidance conditioning without causing the other deficits noted in Kalrn knockout mice. Our data suggest that deficits in excitatory inputs onto POMC neurons are responsible for the behavioral phenotypes observed. PMID:25014196
Guarda, Angela S; Schreyer, Colleen C; Boersma, Gretha J; Tamashiro, Kellie L; Moran, Timothy H
The high comorbidity between anorexia nervosa (AN) and anxiety disorders is well recognized. AN is a motivated behavioral disorder in which habit formation is likely to contribute to the persistence of abnormal eating and exercise behaviors. Secondary alterations in brain circuitry underlying the reward value of food and exercise, along with disturbances in neuroendocrine hunger and satiety signaling arising from starvation and excessive exercise, are likely contributors to the maintenance of anorectic behaviors in genetically vulnerable individuals. The potential role of fear conditioning in facilitating onset of AN, or of impaired fear extinction in contributing to the high relapse rates observed following weight restoration, is of interest. Evidence from animal models of anxiety and human laboratory studies indicate that low estrogen impairs fear extinction. Low estradiol levels in AN may therefore play a role in perpetuating fear of food and fat in recently weight restored patients. Translational models including the activity based anorexia (ABA) rodent model of AN, and neuroimaging studies of fear extinction and conditioning, could help clarify the underlying molecular mechanisms and neurocircuitry involved in food avoidance behaviors in AN. Moreover, the adaptation of novel treatment interventions with efficacy in anxiety disorders may contribute to the development of new treatments for this impairing disorder. Copyright © 2015. Published by Elsevier Inc.
Mandela, Prashant; Yan, Yan; LaRese, Taylor; Eipper, Betty A; Mains, Richard E
Kalirin, a Rho GDP/GTP exchange factor for Rac1 and RhoG, is known to play an essential role in the formation and maintenance of excitatory synapses and in the secretion of neuropeptides. Mice unable to express any of the isoforms of Kalrn in cells that produce POMC at any time during development (POMC cells) exhibited reduced anxiety-like behavior and reduced acquisition of passive avoidance behavior, along with sex-specific alteration in the corticosterone response to restraint stress. Strikingly, lack of Kalrn expression in POMC cells closely mimicked the effects of global Kalrn knockout on anxiety-like behavior and passive avoidance conditioning without causing the other deficits noted in Kalrn knockout mice. Our data suggest that deficits in excitatory inputs onto POMC neurons are responsible for the behavioral phenotypes observed. Copyright © 2014 Elsevier Inc. All rights reserved.
Yen, Cheng-Fang; Chen, Yu-Min; Cheng, Jen-Wen; Liu, Tai-Ling; Huang, Tzu-Yu; Wang, Peng-Wei; Yang, Pinchen; Chou, Wen-Jiun
The aims of this intervention study were to examine the effects of individual cognitive-behavioral therapy (CBT) based on the modified Coping Cat Program on improving anxiety symptoms and behavioral problems in Taiwanese children with anxiety disorders and parenting stress perceived by their mothers. A total of 24 children with anxiety disorders in the treatment group completed the 17-session individual CBT based on the modified Coping Cat Program, and 26 children in the control group received the treatment as usual intervention. The Taiwanese version of the MASC (MASC-T), the Child Behavior Checklist for Ages 6-18 (CBCL/6-18) and the Chinese version of the Parenting Stress Index (C-PSI) were applied to assess the severities of anxiety symptoms, behavioral problems and parenting stress, respectively. The effects of CBT on improving anxiety symptoms, behavioral problems and parenting stress were examined by using linear mixed-effect model with maximum likelihood estimation. The results indicated that the CBT significantly improved the severities of MASC-T Physical Symptoms and Social Anxiety subscales, CBCL/6-18 DSM-oriented Anxiety Problem subscale, and C-PSI Child domains Mood and Adaptability subscales. Individual CBT based on the modified Coping Cat Program can potentially improve anxiety symptoms in Taiwanese children with anxiety disorders and some child domains of parenting stress perceived by their mothers.
Wohleb, Eric S.; Powell, Nicole D.
Social stress is associated with altered immunity and higher incidence of anxiety-related disorders. Repeated social defeat (RSD) is a murine stressor that primes peripheral myeloid cells, activates microglia, and induces anxiety-like behavior. Here we show that RSD-induced anxiety-like behavior corresponded with an exposure-dependent increase in circulating monocytes (CD11b+/SSClo/Ly6Chi) and brain macrophages (CD11b+/SSClo/CD45hi). Moreover, RSD-induced anxiety-like behavior corresponded with brain region-dependent cytokine and chemokine responses involved with myeloid cell recruitment. Next, LysM-GFP+ and GFP+ bone marrow (BM)-chimeric mice were used to determine the neuroanatomical distribution of peripheral myeloid cells recruited to the brain during RSD. LysM-GFP+ mice showed that RSD increased recruitment of GFP+ macrophages to the brain and increased their presence within the perivascular space (PVS). In addition, RSD promoted recruitment of GFP+ macrophages into the PVS and parenchyma of the prefrontal cortex, amygdala, and hippocampus of GFP+ BM-chimeric mice. Furthermore, mice deficient in chemokine receptors associated with monocyte trafficking [chemokine receptor-2 knockout (CCR2KO) or fractalkine receptor knockout (CX3CR1KO)] failed to recruit macrophages to the brain and did not develop anxiety-like behavior following RSD. Last, RSD-induced macrophage trafficking was prevented in BM-chimeric mice generated with CCR2KO or CX3CR1KO donor cells. These findings indicate that monocyte recruitment to the brain in response to social stress represents a novel cellular mechanism that contributes to the development of anxiety. PMID:23966702
Thomas, Sarah A.; Weeks, Justin W.; Dougherty, Lea R.; Lipton, Melanie F.; Daruwala, Samantha E.; Kline, Kathryn
Social anxiety often develops in adolescence, and precedes the onset of depression and substance use disorders. The link between social anxiety and use of behaviors to minimize distress in social situations (i.e., safety behaviors) is strong and for some patients, this link poses difficulty for engaging in, and benefiting from, exposure-based treatment. Yet, little is known about whether individual differences may moderate links between social anxiety and safety behaviors, namely variations in genetic alleles germane to anxiety. We examined the relation between adolescent social anxiety and expressions of safety behaviors, and whether allelic variation for anxiety moderates this relation. Adolescents (n=75; ages 14–17) were recruited from two larger studies investigating measurement of family relationships or adolescent social anxiety. Adolescents completed self-report measures about social anxiety symptoms and use of safety behaviors. They also provided saliva samples to assess allelic variations for anxiety from two genetic polymorphisms (BDNF rs6265; TAQ1A rs1800497). Controlling for adolescent age and gender, we observed a significant interaction between social anxiety symptoms and allelic variation (β=0.37, t=2.41, p=.02). Specifically, adolescents carrying allelic variations for anxiety evidenced a statistically significant and relatively strong positive relation between social anxiety symptoms and safety behaviors (β=0.73), whereas adolescents not carrying allelic variation evidenced a statistically non-significant and relatively weak relation (β=0.22). These findings have important implications for treating adolescent social anxiety, in that we identified an individual difference variable that can be used to identify people who evidence a particularly strong link between use of safety behaviors and expressing social anxiety. PMID:26692635
Mahbod, Parinaz; Smith, Eric P; Fitzgerald, Maureen E; Morano, Rachel L; Packard, Benjamin A; Ghosal, Sriparna; Scheimann, Jessie R; Perez-Tilve, Diego; Herman, James P; Tong, Jenny
Ghrelin is a 28-amino acid polypeptide that regulates feeding, glucose metabolism, and emotionality (stress, anxiety, and depression). Plasma ghrelin circulates as desacyl ghrelin (DAG) or, in an acylated form, acyl ghrelin (AG), through the actions of ghrelin O-acyltransferase (GOAT), exhibiting low or high affinity, respectively, for the growth hormone secretagogue receptor (GHSR) 1a. We investigated the role of endogenous AG, DAG, and GHSR1a signaling on anxiety and stress responses using ghrelin knockout (Ghr KO), GOAT KO, and Ghsr stop-floxed (Ghsr null) mice. Behavioral and hormonal responses were tested in the elevated plus maze and light/dark (LD) box. Mice lacking both AG and DAG (Ghr KO) increased anxiety-like behaviors across tests, whereas anxiety reactions were attenuated in DAG-treated Ghr KO mice and in mice lacking AG (GOAT KO). Notably, loss of GHSR1a (Ghsr null) did not affect anxiety-like behavior in any test. Administration of AG and DAG to Ghr KO mice with lifelong ghrelin deficiency reduced anxiety-like behavior and decreased phospho-extracellular signal-regulated kinase phosphorylation in the Edinger-Westphal nucleus in wild-type mice, a site normally expressing GHSR1a and involved in stress- and anxiety-related behavior. Collectively, our data demonstrate distinct roles for endogenous AG and DAG in regulation of anxiety responses and suggest that the behavioral impact of ghrelin may be context dependent. Copyright © 2018 Endocrine Society.
Human and animals studies support the idea that there is a gender-related co-morbidity of pain-related and inflammatory gastrointestinal (GI) diseases with psychological disorders. This co-morbidity is the evidence for the existence of GI-brain axis which consists of immune (cytokines), neural (vagus nerve) and neuroendocrine (HPA axis) pathways. Psychological stress causes disturbances in GI physiology, such as altered GI barrier function, changes in motility and secretion, development of visceral hypersensitivity, and dysfunction of inflammatory responses. Whether GI inflammation would exert impact on psychological behavior is not well established. We examined the effect of experimental gastritis on anxiety- and depression-like behaviors in male and female Sprague–Dawley rats, and evaluated potential mechanisms of action. Gastritis was induced by adding 0.1% (w/v) iodoacetamide (IAA) to the sterile drinking water for 7 days. Sucrose preference test assessed the depression-like behavior, open field test and elevated plus maze evaluated the anxiety-like behavior. IAA treatment induced gastric inflammation in rats of either gender. No behavioral abnormality or dysfunction of GI-brain axis was observed in male rats with IAA-induced gastritis. Anxiety- and depression-like behaviors were apparent and the HPA axis was hyperactive in female rats with IAA-induced gastritis. Our results show that gastric inflammation leads to anxiety- and depression-like behaviors in female but not male rats via the neuroendocrine (HPA axis) pathway, suggesting that the GI inflammation can impair normal brain function and induce changes in psychological behavior in a gender-related manner through the GI-to-brain signaling. PMID:24345032
Wakabayashi, Chisato; Numakawa, Tadahiro; Odaka, Haruki; Ooshima, Yoshiko; Kiyama, Yuji; Manabe, Toshiya; Kunugi, Hiroshi; Iwakura, Yoichiro
Interleukin 1 (IL-1) plays a critical role in stress responses, and its mRNA is induced in the brain by restraint stress. Previously, we reported that IL-1 receptor antagonist (IL-1Ra) knockout (KO) mice, which lacked IL-1Ra molecules that antagonize the IL-1 receptor, showed anti-depression-like behavior via adrenergic modulation at the age of 8 weeks. Here, we report that IL-1Ra KO mice display an anxiety-like phenotype that is induced spontaneously by aging in the elevated plus-maze (EPM) test. This anxiety-like phenotype was improved by the administration of diazepam. The expression of the anxiety-related molecule glucocorticoid receptor (GR) was significantly reduced in 20-week-old but not in 11-week-old IL-1Ra KO mice compared to wild-type (WT) littermates. The expression of the mineralocorticoid receptor (MR) was not altered between IL-1Ra KO mice and WT littermates at either 11 or 20 weeks old. Analysis of monoamine concentration in the hippocampus revealed that tryptophan, the serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA), and the dopamine metabolite homovanillic acid (HVA) were significantly increased in 20-week-old IL-1Ra KO mice compared to littermate WT mice. These findings strongly suggest that the anxiety-like behavior observed in older mice was caused by the complicated alteration of monoamine metabolism and/or GR expression in the hippocampus. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
O’Neill, Casey E.; Newsom, Ryan J.; Stafford, Jacob; Scott, Talia; Archuleta, Solana; Levis, Sophia C.; Spencer, Robert L.; Campeau, Serge; Bachtell, Ryan K.
Caffeine is a commonly used psychoactive substance and consumption by children and adolescents continues to rise. Here, we examine the lasting effects of adolescent caffeine consumption on anxiety-related behaviors and several neuroendocrine measures in adulthood. Adolescent male Sprague-Dawley rats consumed caffeine (0.3 g/L) for 28 consecutive days from postnatal day 28 (P28) to P55. Age-matched control rats consumed water. Behavioral testing for anxiety-related behavior began in adulthood (P62) 7 days after removal of caffeine. Adolescent caffeine consumption enhanced anxiety-related behavior in an open field, social interaction test, and elevated plus maze. Similar caffeine consumption in adult rats did not alter anxiety-related behavior after caffeine removal. Characterization of neuroendocrine measures was next assessed to determine whether the changes in anxiety were associated with modifications in the HPA axis. Blood plasma levels of corticosterone (CORT) were assessed throughout the caffeine consumption procedure in adolescent rats. Adolescent caffeine consumption elevated plasma CORT 24 h after initiation of caffeine consumption that normalized over the course of the 28-day consumption procedure. CORT levels were also elevated 24 h after caffeine removal and remained elevated for 7 days. Despite elevated basal CORT in adult rats that consumed caffeine during adolescence, the adrenocorticotropic hormone (ACTH) and CORT response to placement on an elevated pedestal (a mild stressor) was significantly blunted. Lastly, we assessed changes in basal and stress-induced c-fos and corticotropin-releasing factor (Crf) mRNA expression in brain tissue collected at 7 days withdrawal from adolescent caffeine. Adolescent caffeine consumption increased basal c-fos mRNA in the paraventricular nucleus of the hypothalamus. Adolescent caffeine consumption had no other effects on the basal or stress-induced c-fos mRNA changes. Caffeine consumption during adolescence
O'Neill, Casey E; Newsom, Ryan J; Stafford, Jacob; Scott, Talia; Archuleta, Solana; Levis, Sophia C; Spencer, Robert L; Campeau, Serge; Bachtell, Ryan K
Caffeine is a commonly used psychoactive substance and consumption by children and adolescents continues to rise. Here, we examine the lasting effects of adolescent caffeine consumption on anxiety-related behaviors and several neuroendocrine measures in adulthood. Adolescent male Sprague-Dawley rats consumed caffeine (0.3g/L) for 28 consecutive days from postnatal day 28 (P28) to P55. Age-matched control rats consumed water. Behavioral testing for anxiety-related behavior began in adulthood (P62) 7 days after removal of caffeine. Adolescent caffeine consumption enhanced anxiety-related behavior in an open field, social interaction test, and elevated plus maze. Similar caffeine consumption in adult rats did not alter anxiety-related behavior after caffeine removal. Characterization of neuroendocrine measures was next assessed to determine whether the changes in anxiety were associated with modifications in the HPA axis. Blood plasma levels of corticosterone (CORT) were assessed throughout the caffeine consumption procedure in adolescent rats. Adolescent caffeine consumption elevated plasma CORT 24h after initiation of caffeine consumption that normalized over the course of the 28-day consumption procedure. CORT levels were also elevated 24h after caffeine removal and remained elevated for 7 days. Despite elevated basal CORT in adult rats that consumed caffeine during adolescence, the adrenocorticotropic hormone (ACTH) and CORT response to placement on an elevated pedestal (a mild stressor) was significantly blunted. Lastly, we assessed changes in basal and stress-induced c-fos and corticotropin-releasing factor (Crf) mRNA expression in brain tissue collected at 7 days withdrawal from adolescent caffeine. Adolescent caffeine consumption increased basal c-fos mRNA in the paraventricular nucleus of the hypothalamus. Adolescent caffeine consumption had no other effects on the basal or stress-induced c-fos mRNA changes. Caffeine consumption during adolescence increased
Iwadare, Yoshitaka; Kamei, Yuichi; Usami, Masahide; Ushijima, Hirokage; Tanaka, Tetsuya; Watanabe, Kyota; Kodaira, Masaki; Saito, Kazuhiko
Sleep disorders are frequently associated with childhood behavioral problems and mental illnesses such as anxiety disorder. To identify promising behavioral targets for pediatric anxiety disorder therapy, we investigated the associations between specific sleep and behavioral problems. We conducted retrospective reviews of 105 patients aged 4-12 years who met the DSM-IV criteria for primary diagnosis of generalized anxiety disorder (n = 33), separation anxiety disorder (n = 23), social phobia (n = 21), or obsessive compulsive disorder (n = 28). Sleep problems were evaluated using the Children's Sleep Habits Questionnaire (CSHQ) and behavioral problems by the Spence Children's Anxiety Scale, Oppositional Defiant Behavior Inventory (ODBI), and Depression Self-Rating Scale for Children. Depressive behavior was weakly correlated with CSHQ subscores for sleep onset delay and night waking but not with total sleep disturbance. Anxiety was correlated with bedtime resistance, night waking, and total sleep disturbance score. Oppositional defiance was correlated with bedtime resistance, daytime sleepiness, sleep onset delay, and most strongly with total sleep disturbance. On multiple regression analysis ODBI score had the strongest positive association with total sleep disturbance and the strongest negative association with total sleep duration. Sleep problems in children with anxiety disorders are closely related to anxiety and oppositional defiant symptoms. © 2015 Japan Pediatric Society.
Budinger, Meghan Crosby; Drazdowski, Tess K.; Ginsburg, Golda S.
While parenting behaviors among anxious parents have been implicated in the familial transmission of anxiety, little is known about whether these parenting behaviors are unique to specific parental anxiety disorders. The current study examined differences in the use of five specific parenting behaviors (i.e., warmth/positive affect, criticism,…
Gonzalez, Ketty P.; And Others
Thirty-nine boys in classes for students with behavioral disturbances were given questionnaires on trait anxiety, social anxiety, empathy, depression, and self-esteem, while teachers rated their aggression. Results showed that anxiety and empathy scores were not correlated with aggression, while social anxiety was positively correlated with trait…
Erfanparast, Leila; Vafaei, Ali; Sohrabi, Azin; Ranjkesh, Bahram; Bahadori, Zahra; Pourkazemi, Maryam; Dadashi, Shabnam; Shirazi, Sajjad
Background and aims. Different factors affect children’s behavior during dental treatment, including psychological and behavioral characteristics. The aim of this study was to evaluate the correlation of self-concept on child’s anxiety and behavior during dental treatment in 4 to 6-year-old children. Materials and methods. A total of 235 preschoolers aged 4 to 6 years were included in this descriptive analytic study. Total self-concept score for each child was assessed according to Primary Self-concept Scale before dental treatment. Child’s anxiety and child’s behavior were assessed, during the restoration of mandibular primary molar, using clinical anxiety rating scale and Frankl Scale, respectively. Spearman’s correlation coefficient was used to evaluate the correlation between the total self-concept score with the results of clinical anxiety rating scale and Frankl Scale. Results. There was a moderate inverse correlation between the self-concept and clinical anxiety rating scale scores (r = -0.545, P self-concept and child’s behavior scores (r = 0.491, P self-concept had lower anxiety level and better behavioral feedback during dental treatment. PMID:26697152
Erfanparast, Leila; Vafaei, Ali; Sohrabi, Azin; Ranjkesh, Bahram; Bahadori, Zahra; Pourkazemi, Maryam; Dadashi, Shabnam; Shirazi, Sajjad
Background and aims . Different factors affect children's behavior during dental treatment, including psychological and behavioral characteristics. The aim of this study was to evaluate the correlation of self-concept on child's anxiety and behavior during dental treatment in 4 to 6-year-old children. Materials and methods. A total of 235 preschoolers aged 4 to 6 years were included in this descriptive analytic study. Total self-concept score for each child was assessed according to Primary Self-concept Scale before dental treatment. Child's anxiety and child's behavior were assessed, during the restoration of mandibular primary molar, using clinical anxiety rating scale and Frankl Scale, respectively. Spearman's correlation coefficient was used to evaluate the correlation between the total self-concept score with the results of clinical anxiety rating scale and Frankl Scale. Results. There was a moderate inverse correlation between the self-concept and clinical anxiety rating scale scores (r = -0.545, P self-concept and child's behavior scores (r = 0.491, P self-concept had lower anxiety level and better behavioral feedback during dental treatment.
Zhao, Liping; Kim, Ki Woo; Ikeda, Yayoi; Anderson, Kimberly K; Beck, Laurel; Chase, Stephanie; Tobet, Stuart A; Parker, Keith L
Steroidogenic factor 1 (SF-1) plays key roles in adrenal and gonadal development, expression of pituitary gonadotropins, and development of the ventromedial hypothalamic nucleus (VMH). If kept alive by adrenal transplants, global knockout (KO) mice lacking SF-1 exhibit delayed-onset obesity and decreased locomotor activity. To define specific roles of SF-1 in the VMH, we used the Cre-loxP system to inactivate SF-1 in a central nervous system (CNS)-specific manner. These mice largely recapitulated the VMH structural defect seen in mice lacking SF-1 in all tissues. In multiple behavioral tests, mice with CNS-specific KO of SF-1 had significantly more anxiety-like behavior than wild-type littermates. The CNS-specific SF-1 KO mice had diminished expression or altered distribution in the mediobasal hypothalamus of several genes whose expression has been linked to stress and anxiety-like behavior, including brain-derived neurotrophic factor, the type 2 receptor for CRH (Crhr2), and Ucn 3. Moreover, transfection and EMSAs support a direct role of SF-1 in Crhr2 regulation. These findings reveal important roles of SF-1 in the hypothalamic expression of key regulators of anxiety-like behavior, providing a plausible molecular basis for the behavioral effect of CNS-specific KO of this nuclear receptor.
Hill, Ryan M; Castellanos, Daniel; Pettit, Jeremy W
This paper reviews empirical evidence of the association between suicide-related behaviors and anxiety among children and adolescents. It begins with a review of suicide-related behaviors and anxiety, discusses methodological issues related to measurement, and reviews empirical findings published since the last review of this topic in 1988. Evidence is summarized on four criteria necessary to establish anxiety as a causal risk factor for suicide-related behaviors among children and adolescents. There is consistent evidence for a significant association between anxiety and suicide-related behaviors (Criterion 1). Evidence that the influence of anxiety on suicide-related behaviors is not due to a third variable (Criterion 2) is mixed and hindered by methodological limitations. The literature is also unclear as to whether anxiety temporally precedes suicide-related behaviors (Criterion 3). Finally, this review found no evidence to support or refute anxiety's stability independent of and across instances of suicide-related behaviors (Criterion 4). Theoretical and clinical implications of these findings and directions for future research are discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.
Full Text Available Background and aims. Different factors affect children’s behavior during dental treatment, including psychological and behavioral characteristics. The aim of this study was to evaluate the correlation of self-concept on child’s anxiety and be-havior during dental treatment in 4 to 6-year-old children. Materials and methods. A total of 235 preschoolers aged 4 to 6 years were included in this descriptive analytic study. Total self-concept score for each child was assessed according to Primary Self-concept Scale before dental treatment. Child’s anxiety and child’s behavior were assessed, during the restoration of mandibular primary molar, using clinical anxi-ety rating scale and Frankl Scale, respectively. Spearman’s correlation coefficient was used to evaluate the correlation be-tween the total self-concept score with the results of clinical anxiety rating scale and Frankl Scale. Results. There was a moderate inverse correlation between the self-concept and clinical anxiety rating scale scores (r = −0.545, P < 0.001, and a moderate correlation between the self-concept and child’s behavior scores (r = 0.491, P < 0.001. A strong inverse relation was also found between the anxiety and behavior scores (r = −0.91, P < 0.001. Conclusion. Children with higher self-concept had lower anxiety level and better behavioral feedback during dental treat-ment.
Md Golam Abbas
Full Text Available Neuropeptides orexin A and orexin B, which are exclusively produced by neurons in the lateral hypothalamic area, play an important role in the regulation of a wide range of behaviors and homeostatic processes, including regulation of sleep/wakefulness states and energy homeostasis. The orexin system has close anatomical and functional relationships with systems that regulate the autonomic nervous system, emotion, mood, the reward system and sleep/wakefulness states. Recent pharmacological studies using selective antagonists have suggested that orexin receptor-1 (OX1R is involved in physiological processes that regulate emotion, the reward system and autonomic nervous system. Here, we examined Ox1r-/- mice with a comprehensive behavioral test battery to screen additional OX1R functions. Ox1r-/- mice showed increased anxiety-like behavior, altered depression-like behavior, slightly decreased spontaneous locomotor activity, reduced social interaction, increased startle response and decreased prepulse inhibition. These results suggest that OX1R plays roles in social behaviour and sensory motor gating in addition to roles in mood and anxiety.
Full Text Available Theories of anxiety disorders and phobias have ascribed a critical role to avoidance behavior in explaining the persistence of fear and anxiety, but knowledge about the role of avoidance behavior in the maintenance of anxiety in social anxiety disorder relative to specific phobia is lacking. This study examined the extent to which avoidance behavior moderates the relationship between general anxiety at baseline and 18 months later in women with a diagnosed social anxiety disorder (n = 91 and women with a diagnosed specific phobia (n = 130 at baseline. Circumscribed avoidance of social and specific situations were clinician-rated using the Anxiety Disorders Interview Schedule-Lifetime (ADIS-IV-L, and general anxiety was measured using the Beck Anxiety Inventory (BAI. Moderated regression analyses revealed that (a general anxiety at baseline predicted general anxiety at follow-up in both women with a specific phobia and women with a social anxiety disorder and (b avoidance behavior moderated this relationship in women with a specific phobia but not in women with a social anxiety disorder. Specifically, high avoidance behavior was found to amplify the effect between general anxiety at baseline and follow-up in specific phobia. Reasons for the absence of a similar moderating effect of avoidance behavior within social anxiety disorder are discussed.
Rudaz, Myriam; Ledermann, Thomas; Margraf, Jürgen; Becker, Eni S.; Craske, Michelle G.
Theories of anxiety disorders and phobias have ascribed a critical role to avoidance behavior in explaining the persistence of fear and anxiety, but knowledge about the role of avoidance behavior in the maintenance of anxiety in social anxiety disorder relative to specific phobia is lacking. This study examined the extent to which avoidance behavior moderates the relationship between general anxiety at baseline and 18 months later in women with a diagnosed social anxiety disorder (n = 91) and women with a diagnosed specific phobia (n = 130) at baseline. Circumscribed avoidance of social and specific situations were clinician-rated using the Anxiety Disorders Interview Schedule-Lifetime (ADIS-IV-L), and general anxiety was measured using the Beck Anxiety Inventory (BAI). Moderated regression analyses revealed that (a) general anxiety at baseline predicted general anxiety at follow-up in both women with a specific phobia and women with a social anxiety disorder and (b) avoidance behavior moderated this relationship in women with a specific phobia but not in women with a social anxiety disorder. Specifically, high avoidance behavior was found to amplify the effect between general anxiety at baseline and follow-up in specific phobia. Reasons for the absence of a similar moderating effect of avoidance behavior within social anxiety disorder are discussed. PMID:28671977
Rudaz, Myriam; Ledermann, Thomas; Margraf, Jürgen; Becker, Eni S; Craske, Michelle G
Theories of anxiety disorders and phobias have ascribed a critical role to avoidance behavior in explaining the persistence of fear and anxiety, but knowledge about the role of avoidance behavior in the maintenance of anxiety in social anxiety disorder relative to specific phobia is lacking. This study examined the extent to which avoidance behavior moderates the relationship between general anxiety at baseline and 18 months later in women with a diagnosed social anxiety disorder (n = 91) and women with a diagnosed specific phobia (n = 130) at baseline. Circumscribed avoidance of social and specific situations were clinician-rated using the Anxiety Disorders Interview Schedule-Lifetime (ADIS-IV-L), and general anxiety was measured using the Beck Anxiety Inventory (BAI). Moderated regression analyses revealed that (a) general anxiety at baseline predicted general anxiety at follow-up in both women with a specific phobia and women with a social anxiety disorder and (b) avoidance behavior moderated this relationship in women with a specific phobia but not in women with a social anxiety disorder. Specifically, high avoidance behavior was found to amplify the effect between general anxiety at baseline and follow-up in specific phobia. Reasons for the absence of a similar moderating effect of avoidance behavior within social anxiety disorder are discussed.
Alexopoulou, Peggy; Kotsopoulou, Anastasia
Multitasking information behavior involves multiple forms of information searching such as library and Web search. Few researchers, however, have explored multitasking information behavior and information task switching in libraries in conjunction with psychological variables. This study explored this behavior in terms of anxiety under time pressure. This was an exploratory case study. Participant searched information for three unrelated everyday life information topics during a library visit, in a timeframe of one hour. The data collection tools used were: diary, observation, interview, and the State-Trait Anxiety Inventory test. Participant took the Trait-anxiety test before the library visit to measure anxiety level as a personal characteristic. She also took State-anxiety test before, during and after the library visit to measure anxiety levels regarding the information seeking behavior. The results suggested that participant had high levels of anxiety at the beginning of the multitasking information behavior. The reason for that was the concern about the performance as well as the identification of the right resources. During the multitasking information behavior, participant still had anxiety to find the right information. The levels of anxiety, however, were less due to library’s good organized structure. At the end of the information seeking process, the levels of anxiety dropped significant and therefore calm and safety returned. Finally, participant searched information for topics that were more important and for which she had prior knowledge When people, under time pressure, have access to well organized information, the levels of anxiety might decrease
Alexopoulou, Peggy; Kotsopoulou, Anastasia
Multitasking information behavior involves multiple forms of information searching such as library and Web search. Few researchers, however, have explored multitasking information behavior and information task switching in libraries in conjunction with psychological variables. This study explored this behavior in terms of anxiety under time pressure. This was an exploratory case study. Participant searched information for three unrelated everyday life information topics during a library visit, in a timeframe of one hour. The data collection tools used were: diary, observation, interview, and the State-Trait Anxiety Inventory test. Participant took the Trait-anxiety test before the library visit to measure anxiety level as a personal characteristic. She also took State-anxiety test before, during and after the library visit to measure anxiety levels regarding the information seeking behavior. The results suggested that participant had high levels of anxiety at the beginning of the multitasking information behavior. The reason for that was the concern about the performance as well as the identification of the right resources. During the multitasking information behavior, participant still had anxiety to find the right information. The levels of anxiety, however, were less due to library's good organized structure. At the end of the information seeking process, the levels of anxiety dropped significant and therefore calm and safety returned. Finally, participant searched information for topics that were more important and for which she had prior knowledge When people, under time pressure, have access to well organized information, the levels of anxiety might decrease.
Alexopoulou, Peggy, E-mail: firstname.lastname@example.org, E-mail: email@example.com; Kotsopoulou, Anastasia, E-mail: firstname.lastname@example.org, E-mail: email@example.com [City Unity College, Thiseos 15-17, Athens, 105 62 (Greece)
Multitasking information behavior involves multiple forms of information searching such as library and Web search. Few researchers, however, have explored multitasking information behavior and information task switching in libraries in conjunction with psychological variables. This study explored this behavior in terms of anxiety under time pressure. This was an exploratory case study. Participant searched information for three unrelated everyday life information topics during a library visit, in a timeframe of one hour. The data collection tools used were: diary, observation, interview, and the State-Trait Anxiety Inventory test. Participant took the Trait-anxiety test before the library visit to measure anxiety level as a personal characteristic. She also took State-anxiety test before, during and after the library visit to measure anxiety levels regarding the information seeking behavior. The results suggested that participant had high levels of anxiety at the beginning of the multitasking information behavior. The reason for that was the concern about the performance as well as the identification of the right resources. During the multitasking information behavior, participant still had anxiety to find the right information. The levels of anxiety, however, were less due to library’s good organized structure. At the end of the information seeking process, the levels of anxiety dropped significant and therefore calm and safety returned. Finally, participant searched information for topics that were more important and for which she had prior knowledge When people, under time pressure, have access to well organized information, the levels of anxiety might decrease.
Salari, Ali-Akbar; Amani, Mohammad
Gamma-aminobutyric acid (GABA) plays an inhibitory role in the mature brain, and has a complex and bidirectional effect in different parts of the immature brain which affects proliferation, migration and differentiation of neurons during development. There is also increasing evidence suggesting that activation or blockade of the GABA-A receptors during early life can induce brain and behavioral abnormalities in adulthood. We investigated whether neonatal blockade of the GABA-A receptors by bicuculline can alter anxiety- and depression-like behaviors, body weight, food intake, corticosterone and testosterone levels in adult mice (postnatal days 80-95). To this end, neonatal mice were treated with either DMSO or bicuculline (70, 150 and 300μg/kg) during postnatal days 7, 9 and 11. When grown to adulthood, mice were exposed to behavioral tests to measure anxiety- (elevated plus-maze and light-dark box) and depression-like behaviors (tail suspension test and forced swim test). Stress-induced serum corticosterone and testosterone levels, body weight and food intake were also evaluated. Neonatal bicuculline exposure at dose of 300μg/kg decreased anxiety-like behavior, stress-induced corticosterone levels and increased testosterone levels, body weight and food intake, without significantly influencing depression-like behavior in adult male mice. However, no significant changes in these parameters were observed in adult females. These findings suggest that neonatal blockade of GABA-A receptors affects anxiety-like behavior, physiological and hormonal parameters in a sex-dependent manner in mice. Taken together, these data corroborate the concept that GABA-A receptors during early life have an important role in programming neurobehavioral phenotypes in adulthood. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.
Struntz, Katelyn H; Siegel, Jessica A
Methamphetamine (MA) is a psychomotor stimulant drug that can alter behavior, the stress response system, and the dopaminergic system. The effects of MA can be modulated by age, however relatively little research has examined the acute effects of MA in adolescents and how the effects compare to those found in adults. The hippocampal dopamine system is altered by MA exposure and can modulate anxiety-like behavior, but the effects of MA on the hippocampal dopamine system have not been well studied, especially in adolescent animals. In order to assess potential age differences in the effects of MA exposure, this research examined the effects of acute MA exposure on locomotor and anxiety-like behavior in the open field test, plasma corticosterone levels, and hippocampal total tyrosine hydroxylase and phosphorylated tyrosine hydroxylase levels in adolescent and adult male C57BL/6 J mice. Tyrosine hydroxylase is the rate limiting enzyme in the synthesis of dopamine and was used as a marker of the hippocampal dopaminergic system. Mice were exposed to saline or 4 mg/kg MA and locomotor and anxiety-like behavior were measured in the open field test. Serum and brains were collected immediately after testing and plasma corticosterone and hippocampal total tyrosine hydroxylase and phosphorylated tyrosine hydroxylase levels measured. MA-exposed mice showed increased locomotor activity and anxiety-like behavior in the open field test compared with saline controls, regardless of age. There was no effect of MA on plasma corticosterone levels or hippocampal total tyrosine hydroxylase or phosphorylated tyrosine hydroxylase levels in either adolescent or adult mice. These data suggest that acute MA exposure during adolescence and adulthood increases locomotor activity and anxiety-like behavior but does not alter plasma corticosterone levels or hippocampal total tyrosine hydroxylase or phosphorylated tyrosine hydroxylase levels, and that these effects are not modulated by age
Abbas, Md. G.; Shoji, Hirotaka; Soya, Shingo; Hondo, Mari; Miyakawa, Tsuyoshi; Sakurai, Takeshi
Neuropeptides orexin A and orexin B, which are exclusively produced by neurons in the lateral hypothalamic area, play an important role in the regulation of a wide range of behaviors and homeostatic processes, including regulation of sleep/wakefulness states and energy homeostasis. The orexin system has close anatomical and functional relationships with systems that regulate the autonomic nervous system, emotion, mood, the reward system, and sleep/wakefulness states. Recent pharmacological studies using selective antagonists have suggested that orexin receptor-1 (OX1R) is involved in physiological processes that regulate emotion, the reward system, and autonomic nervous system. Here, we examined Ox1r−/− mice with a comprehensive behavioral test battery to screen additional OX1R functions. Ox1r−/− mice showed increased anxiety-like behavior, altered depression-like behavior, slightly decreased spontaneous locomotor activity, reduced social interaction, increased startle response, and decreased prepulse inhibition. These results suggest that OX1R plays roles in social behavior and sensory motor gating in addition to roles in mood and anxiety. PMID:26696848
Sansar, Wafa; Bouyatas, My Mustapha; Ahboucha, Samir; Gamrani, Halima
Chronic lead exposure has been shown to produce behavioral disturbances in human and animal models. These disturbances are associated with alterations in monoaminergic neurotransmission in the central nervous system (CNS), some of which have been attributed to serotonin (5-HT). This study was undertaken to investigate the chronic effects of lead exposure on the serotoninergic system in the dorsal raphe nucleus (DRN) and the consequences of its toxicity on rat behavior. Adult male Wistar rats were chronically exposed for 3 months to 0.5% lead acetate in drinking water. The serotoninergic system was evaluated using immunohistochemistry and the anxiety behavior was assessed by the light/dark box test. The results show that chronic lead exposure induces a significant increase of blood and brain lead levels in treated rats compared with controls. The density of the immunoreactive serotoninergic cell bodies was significantly higher in treated rats in all parts of the DRN. Assessment of animal behavior using the light/dark box test showed that lead-treated rats spent significantly more time in the light chamber compared with controls (P=0.001). These findings suggest that lead exposure may possibly induce increased anxiety as a consequence of changes in neuronal 5-HT content in the DRN. Copyright © 2011 Elsevier GmbH. All rights reserved.
Sauer, Aisha V.; Hernandez, Raisa Jofra; Fumagalli, Francesca; Bianchi, Veronica; Poliani, Pietro L.; Dallatomasina, Chiara; Riboni, Elisa; Politi, Letterio S.; Tabucchi, Antonella; Carlucci, Filippo; Casiraghi, Miriam; Carriglio, Nicola; Cominelli, Manuela; Forcellini, Carlo Alberto; Barzaghi, Federica; Ferrua, Francesca; Minicucci, Fabio; Medaglini, Stefania; Leocani, Letizia; la Marca, Giancarlo; Notarangelo, Lucia D.; Azzari, Chiara; Comi, Giancarlo; Baldoli, Cristina; Canale, Sabrina; Sessa, Maria; D’Adamo, Patrizia; Aiuti, Alessandro
Adenosine Deaminase (ADA) deficiency is an autosomal recessive variant of severe combined immunodeficiency (SCID) caused by systemic accumulation of ADA substrates. Neurological and behavioral abnormalities observed in ADA-SCID patients surviving after stem cell transplantation or gene therapy represent an unresolved enigma in the field. We found significant neurological and cognitive alterations in untreated ADA-SCID patients as well as in two groups of patients after short- and long-term enzyme replacement therapy with PEG-ADA. These included motor dysfunction, EEG alterations, sensorineural hypoacusia, white matter and ventricular alterations in MRI as well as a low mental development index or IQ. Ada-deficient mice were significantly less active and showed anxiety-like behavior. Molecular and metabolic analyses showed that this phenotype coincides with metabolic alterations and aberrant adenosine receptor signaling. PEG-ADA treatment corrected metabolic adenosine-based alterations, but not cellular and signaling defects, indicating an intrinsic nature of the neurological and behavioral phenotype in ADA deficiency. PMID:28074903
Roeckner, Alyssa R; Bowling, Alexandra; Butler, Tracy R
chronic stress during adolescence. Conversely, and contrary to our hypothesis, female rats' anxiety-like behavior, CORT level, and ethanol intake/preference were not altered by CSI. New paradigms must continue to be explored for study of clinically relevant relationships in female preclinical models. Copyright © 2017 Elsevier Inc. All rights reserved.
Barbot, Antoine; Carrasco, Marisa
The ability to swiftly detect and prioritize the processing of relevant information around us is critical for the way we interact with our environment. Selective attention is a key mechanism that serves this purpose, improving performance in numerous visual tasks. Reflexively attending to sudden information helps detect impeding threat or danger, a possible reason why emotion modulates the way selective attention affects perception. For instance, the sudden appearance of a fearful face potentiates the effects of exogenous (involuntary, stimulus-driven) attention on performance. Internal states such as trait anxiety can also modulate the impact of attention on early visual processing. However, attention does not only improve performance; it also alters the way visual information appears to us, e.g. by enhancing perceived contrast. Here we show that emotion potentiates the effects of exogenous attention on both performance and perceived contrast. Moreover, we found that trait anxiety mediates these effects, with stronger influences of attention and emotion in anxious observers. Finally, changes in performance and appearance correlated with each other, likely reflecting common attentional modulations. Altogether, our findings show that emotion and anxiety interact with selective attention to truly alter how we see.
van Honk, Jack; Bos, Peter A.; Terburg, David; Heany, Sarah; Stein, Dan J.
Social anxiety disorder (SAD) is a highly prevalent and disabling disorder with key behavioral traits of social fearfulness, social avoidance, and submissiveness. Here we argue that hormonal systems play a key role in mediating social anxiety, and so may be important in SAD. Hormonal alterations,
Paulus, Frank W; Backes, Aline; Sander, Charlotte S; Weber, Monika; von Gontard, Alexander
This study assessed the prevalence of anxiety disorders in preschool children and their associations with behavioral inhibition as a temperamental precursor. A representative sample of 1,342 children aged 4–7 years (M = 6;1, SD = 4.80) was examined with a standardized parental questionnaire, including items referring to anxiety disorders at the current age and behavioral inhibition at the age of 2 years. The total prevalence of anxiety disorders was 22.2 %. Separation anxiety (SAD) affected 7 %, social phobia (SOC) 10.7 %, specific phobia (PHOB) 9.8 % and depression/generalized anxiety (MDD/GAD) 3.4 % of children. The prevalence of most types of anxiety was higher in girls except for separation anxiety, which affected more boys. Behavioral inhibition in the second year of life was associated with all types of anxiety. Anxiety disorders are common but frequently overlooked in preschool children. Different subtypes can be differentiated and are often preceded by behavioral inhibition. Assessment, prevention and treatment of anxiety disorders are recommended in preschool children.
Fatima, S.; Khan, I.; Bashir, M.S.; Fatima, M.
To find level of anxiety and disordered eating behavior among young female athletes. Methodology: A questionnaire based survey was undertaken among 71 athletes (15-25 years old) athletes from University of Lahore and Lahore College for Women University. Then the level of anxiety and disordered eating behavior calculated. Data were statistically analyzed by SPSS version 16. Results: Out of 71 athletes, 56 (78.87%) had anxiety due to eating disorder and 15 (21.12%) had no eating disorder. And 67 (94.3%) athletes had raised anxiety levels while 3 (4.2%) had no anxiety. Conclusion: Dieting behavior and binge eating that prompted eating disorder are the main cause of anxiety among young female athletes. (author)
Rudaz, Myriam; Ledermann, Thomas; Margraf, J?rgen; Becker, Eni S.; Craske, Michelle G.
Theories of anxiety disorders and phobias have ascribed a critical role to avoidance behavior in explaining the persistence of fear and anxiety, but knowledge about the role of avoidance behavior in the maintenance of anxiety in social anxiety disorder relative to specific phobia is lacking. This study examined the extent to which avoidance behavior moderates the relationship between general anxiety at baseline and 18 months later in women with a diagnosed social anxiety disorder (n = 91) and...
Rudaz, Myriam; Ledermann, Thomas; Margraf, Jürgen; Becker, Eni S.; Craske, Michelle G.
Theories of anxiety disorders and phobias have ascribed a critical role to avoidance behavior in explaining the persistence of fear and anxiety, but knowledge about the role of avoidance behavior in the maintenance of anxiety in social anxiety disorder relative to specific phobia is lacking. This study examined the extent to which avoidance behavior moderates the relationship between general anxiety at baseline and 18 months later in women with a diagnosed social anxiety disorder (n = 91) and...
Creswell, Cathy; Apetroaia, Adela; Murray, Lynne; Cooper, Peter
Parental emotional distress, particularly high maternal anxiety, is one of the most consistent predictors of child anxiety treatment outcome. In order to identify the cognitive, affective, and behavioral parenting characteristics of mothers of children with anxiety disorders who themselves have an anxiety disorder, we assessed the expectations, appraisals, and behaviors of 88 mothers of anxious children (44 mothers who were not anxious [NONANX] and 44 mothers with a current anxiety disorder [ANX]) when interacting with their 7-12-year-old children. There were no observed differences in anxiety and avoidance among children of ANX and NONANX mothers, but, compared with NONANX mothers, ANX mothers held more negative expectations, and they differed on observations of intrusiveness, expressed anxiety, warmth, and the quality of the relationship. Associations were moderated by the degree to which children expressed anxiety during the tasks. Maternal-reported negative emotions during the task significantly mediated the association between maternal anxiety status and the observed quality of the relationship. These findings suggest that maternal anxiety disorder is associated with reduced tolerance of children's negative emotions. This may interfere with the maintenance of a positive, supportive mother-child interaction under conditions of stress and, as such, this may impede optimum treatment outcomes. The findings identify potential cognitive, affective, and behavioral targets to improve treatment outcomes for children with anxiety disorders in the context of a current maternal anxiety disorder. 2013 APA, all rights reserved
Kewir D. Nyuyki
Full Text Available Crohn’s disease (CD and ulcerative colitis (UC are incurable lifelong inflammatory bowel diseases (IBD with a rising worldwide incidence. IBD is characterized by diarrhea, rectal bleeding, severe cramping and weight loss. However, there is a growing evidence that IBD is also associated with anxiety- and depression-related disorders, which further increase the societal burden of these diseases. Given the limited knowledge of central nervous system (CNS changes in IBD, we investigated CNS-related comorbidities in a mouse model of experimental colitis induced by dextran sulfate sodium (DSS administration in drinking water for 5 days. In male and female C57BL6J mice, DSS treatment caused increased brain excitability, revealed by a decrease in seizure onset times after intraperitoneal administration of kainic acid. Moreover, both sexes showed increased anxiety-related behavior in the elevated plus-maze (EPM and open field (OF paradigms. We assessed somatic pain levels, because they may influence behavioral responses. Only male mice were hyperalgesic when tested with calibrated von Frey hairs and on the hotplate for mechanical and thermal pain sensitivity respectively. Administration of diazepam (DZP; ip, 1 mg/kg 30 min before EPM rescued the anxious phenotype and improved locomotion, even though it significantly increased thermal sensitivity in both sexes. This indicates that the altered behavioral response is unlikely attributable to an interference with movement due to somatic pain in females. We show that experimental colitis increases CNS excitability in response to administration of kainic acid, and increases anxiety-related behavior as revealed using the EPM and OF tests.
Settipani, Cara A; Kendall, Philip C
Social functioning was assessed using the Child Behavior Checklist and Teacher Report Form for children with anxiety disorders who participated in a randomized clinical trial (N = 161, aged 7-14). Significant relationships were found between severity of children's principal anxiety disorder and most measures of social functioning, such that poorer social functioning was associated with more severe anxiety. Among youth who received cognitive-behavioral therapy (n = 111), significant associations were found between parent-reported social competence and both absence of principal anxiety disorder and lower anxiety severity at posttreatment and 1-year follow-up, controlling for the severity of the child's principal anxiety disorder at pretreatment. Findings support a relationship between anxiety severity and social difficulties, and suggest the importance of social competence for a favorable treatment response.
Zhang, Jiliang; Zhang, Chunnuan; Sun, Ping; Shao, Xian
Effects of tributyltin (TBT) on reproduction are well established in many fish species. However, few studies report the effects of TBT on non-reproductive behaviors, which is a novel aspect of endocrine disruption in fish. Thus, the present study used rare minnow (Gobiocypris rarus) to investigate the effects of TBT, at environmental concentrations of 1, 10 and 100ng/L, on shoaling and anxiety behaviors. The results showed that fish exposed to TBT had less group cohesion during the course of the 10-min observation period as compared with the control fish. Further, TBT altered the shoaling in the Novel tank test, where shoaling is determined as the tendency to leave a shoal of littermates trapped behind a Plexiglas barrier at one end of the test tank. Fish exposed to TBT had shorter latency before leaving shoal mates and spent more time away from shoal than control fish. In addition, we also used Novel tanks to study the anxiety behavior as the tendency to stay at the bottom when introduced into an unfamiliar environment. The fish exposed to TBT showed increased anxiety, manifested as increased latency to enter the upper half and decreased time in upper half when compared with the control fish. TBT exposure increased the levels of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid, and decreased the levels of 5-hydroxytryptamine and its metabolite 5-hydroxy indole acetic acid in the brain. Thus, the hypofunction of the dopaminergic system or of the serotoninergic system or the combination of the two may underlie the observed behavioral change, which might affect the fitness of fish in their natural environment. Copyright © 2016 Elsevier B.V. All rights reserved.
Boulle, F.; Pawluski, J.L.; Homberg, J.R.; Machiels, B.; Kroeze, Y.; Kumar, N.; Steinbusch, H.W.; Kenis, G.; Hove, D.L. van den
A growing number of infants are exposed to selective serotonin reuptake inhibitor (SSRI) medications during the perinatal period. Perinatal exposure to SSRI medications alter neuroplasticity and increase depressive- and anxiety-related behaviors, particularly in male offspring as little work has
Full Text Available Noise is a psychological, environmental stressor that activates limbic sites in the brain. Limbic sites such as the amygdala and the amygdaloid corticotropin-releasing hormone (CRH system play an important role in integrating stress response. We investigated the association between noise exposures, CRH-related molecules in the amygdala, and behavioral alterations. In total 54 Sprague-Dawley rats were divided into the following three groups: Control (CON, acute noise exposure (ANE, and chronic noise exposure (CNE. The ANE group was exposed to 100 dB white noise only once in 4 h and the CNE group was exposed to the same for 4 h per day for 30 days. Expression profiles of CRH and its receptors CRH-R1 and CRH-R2 were analyzed by quantitative real-time polymerase chain reaction (qPCR. The same stress procedure was applied to the ANE and CNE groups for behavior testing. The anxiety responses of the animals after acute and chronic stress exposure were measured in the defensive withdrawal test. CNE upregulated CRH and CRH-R1 mRNA levels but downregulated CRH-R2 mRNA levels. ANE led to a decrease in both CRH-R1 and CRH-R2 expression. In the defensive withdrawal test, while the ANE increased, CNE reduced anxiety-like behaviors. The present study shows that the exposure of rats to white noise (100 dB leads to behavioral alterations and molecule-specific changes in the CRH system. Behavioral alterations can be related to these molecular changes in the amygdala.
Eraslan, Evren; Akyazi, Ibrahim; Erg L-Ekiz, Elif; Matur, Erdal
Noise is a psychological, environmental stressor that activates limbic sites in the brain. Limbic sites such as the amygdala and the amygdaloid corticotropin-releasing hormone (CRH) system play an important role in integrating stress response. We investigated the association between noise exposures, CRH-related molecules in the amygdala, and behavioral alterations. In total 54 Sprague-Dawley rats were divided into the following three groups: Control (CON), acute noise exposure (ANE), and chronic noise exposure (CNE). The ANE group was exposed to 100 dB white noise only once in 4 h and the CNE group was exposed to the same for 4 h per day for 30 days. Expression profiles of CRH and its receptors CRH-R1 and CRH-R2 were analyzed by quantitative real-time polymerase chain reaction (qPCR). The same stress procedure was applied to the ANE and CNE groups for behavior testing. The anxiety responses of the animals after acute and chronic stress exposure were measured in the defensive withdrawal test. CNE upregulated CRH and CRH-R1 mRNA levels but downregulated CRH-R2 mRNA levels. ANE led to a decrease in both CRH-R1 and CRH-R2 expression. In the defensive withdrawal test, while the ANE increased, CNE reduced anxiety-like behaviors. The present study shows that the exposure of rats to white noise (100 dB) leads to behavioral alterations and molecule-specific changes in the CRH system. Behavioral alterations can be related to these molecular changes in the amygdala.
Zhao Xiaohu; Wang Peijun; Li Chunbo; Hu Zhenghui; Xi Qian; Wu Wenyuan; Tang Xiaowei
Anxiety disorder, a common mental disorder in our clinical practice, is characterized by unprovoked anxiety. Medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC), which closely involved in emotional processing, are critical regions in the default mode network. We used functional magnetic resonance imaging (fMRI) to investigate whether default mode network activity is altered in patients with anxiety disorder. Ten anxiety patients and 10 healthy controls underwent fMRI while listening to emotionally neutral words alternating with rest (Experiment 1) and threat-related words alternating with emotionally neutral words (Experiment 2). In Experiment 1, regions of deactivation were observed in patients and controls. In Experiment 2, regions of deactivation were observed only in patients. The observed deactivation patterns in the two experiments, which included MPFC, PCC, and inferior parietal cortex, were similar and consistent with the default model network. Less deactivation in MPFC and greater deactivation in PCC were observed for patients group comparing to controls in Experiment 1. Our observations suggest that the default model network is altered in anxiety patients and dysfunction in MPFC and PCC may play an important role in anxiety psychopathology
Breinholst, Sonja; Esbjørn, Barbara Hoff; Reinholdt-Dunne, Marie Louise
A few studies have examined the relative contribution of insecure attachment and negative parental rearing behaviors on childhood anxiety, but none have examined if insecure attachment mediates the association between negative parental rearing behavior and anxiety. The present study investigated...... the direct, as well as the indirect, relation between attachment to parents, parental rearing behaviors and anxiety symptoms in a sample of 1134 normal developing children and adolescent. Attachment relation was measured by the Security Scale (SEC), negative parental rearing behavior was measured...... by the Rearing Behavior Questionnaire (RBQ), and anxiety was assessed using the Screen for Anxiety Related Emotional Disorders-Revised (SCARED-R). We found, in accordance with previous research, that insecure attachment, maternal rejection and overprotection, each accounted for a significant proportion...
Green, Sheryl M; Haber, Erika; Frey, Benicio N; McCabe, Randi E
Along with physical and biological changes, a tremendous amount of upheaval and adjustment accompany the pregnancy and postpartum period of a woman's life that together can often result in what is commonly known as postpartum depression. However, anxiety disorders have been found to be more frequent than depression during pregnancy and at least as common, if not more so, during the postpartum period, e.g., Brockington et al., (Archieves Women's Ment Health 9:253-263, 2006; Wenzel et al. (J Anxiety Disord, 19:295-311, 2005). Cognitive-behavioral therapy (CBT) is a well-established psychological treatment of choice for anxiety; however, few studies have specifically examined a cognitive-behavioral intervention targeting perinatal anxiety. This pilot study examined the effectiveness of a cognitive-behavioral group treatment (CBGT) program specifically tailored to address perinatal anxiety in 10 women who were either pregnant or within 12 months postpartum. Participants were recruited from a women's clinic at an academic hospital setting, with anxiety identified as their principal focus of distress. Following a diagnostic interview confirming a primary anxiety disorder and completion of assessment measures, participants completed a 6-week CBGT program. There was a statistically significant reduction in anxiety and depressive symptoms following the CBGT program (all p anxiety. These findings suggest that CBGT for perinatal anxiety is a promising treatment for both anxiety and depressive symptoms experienced during the perinatal period. Further studies are needed to evaluate the treatment efficacy through larger controlled trials.
Schmidt, Norman B; Buckner, Julia D; Pusser, Andrea; Woolaway-Bickel, Kelly; Preston, Jennifer L; Norr, Aaron
We tested the efficacy of a unified cognitive-behavioral therapy protocol for anxiety disorders. This group treatment protocol, termed false safety behavior elimination therapy (F-SET), is a cognitive-behavioral approach designed for use across various anxiety disorders such as panic disorder (PD), social anxiety disorder (SAD), and generalized anxiety disorder (GAD). F-SET simplifies, as well as broadens, key therapeutic elements of empirically validated treatments for anxiety disorders to allow for easier delivery to heterogeneous groups of patients with anxiety psychopathology. Patients with a primary anxiety disorder diagnosis (N=96) were randomly assigned to F-SET or a wait-list control. Data indicate that F-SET shows good efficacy and durability when delivered to mixed groups of patients with anxieties (i.e., PD, SAD, GAD) by relatively inexperienced clinicians. Findings are discussed in the context of balancing treatment efficacy and clinical utility. Copyright © 2012. Published by Elsevier Ltd.
Rudaz, M.; Ledermann, T.; Margraf, J.; Becker, E.S.; Craske, M.G.
Theories of anxiety disorders and phobias have ascribed a critical role to avoidance behavior in explaining the persistence of fear and anxiety, but knowledge about the role of avoidance behavior in the maintenance of anxiety in social anxiety disorder relative to specific phobia is lacking. This
Teetsel, Rebekah N; Ginsburg, Golda S; Drake, Kelly L
The majority of research identifying anxiety-promoting parenting behaviors has been conducted with mothers, leaving a gap in current knowledge about the role of fathers' parenting behaviors. In an attempt to fill this gap, this study compared anxiety-promoting parenting behaviors of anxious mothers and fathers. Parents completed self-report measures of parenting behavior and independent coders rated parenting behaviors (i.e., overcontrol, granting of autonomy, warmth, hostility, anxious behavior) of mothers (n = 34) and fathers (n = 21) during a challenging parent-child interaction task (children were ages 6-12). Results indicated that anxious fathers were observed to be more controlling than anxious mothers; while anxious mothers reported using more punishment and reinforcement of children's dependence in anxiety provoking situations compared to fathers. Findings extend our knowledge about anxious fathers, and highlight the need for additional research on the impact of fathers' parenting with respect to the development of child anxiety.
Zheng Lin Zhao
Full Text Available Previously, we demonstrated acupuncture at acupoint HT7 (Shen-Men attenuated ethanol withdrawal syndrome by normalizing the dopamine release in nucleus accumbens shell. In the present study, we investigated the effect of acupuncture on anxiety-like behavior in rats and its relevant mechanism by studying neuro-endocrine parameters during ethanol withdrawal. Rats were treated with 3 g kg−1day−1 of ethanol (20%, w/v or saline by intraperitoneal injections for 28 days. The rats undergoing ethanol withdrawal exhibited anxiety-like behavior 72 h after the last dose of ethanol characterized by the decrease of time spent in the open arms of the elevated plus maze compared with the saline-treated rats (P < .05. Radioimmunoassay exhibited there were notably increased concentrations of plasma corticosterone in ethanol-withdrawn rats compared with saline-treated rats (P < .05. Additionally, high performance liquid chromatography analysis also showed the levels of norepinephrine and 3-methoxy-4-hydroxy-phenylglycol were markedly increased while the levels of dopamine and 3,4-dihydroxyphenylacetic acid were significantly decreased in the central nucleus of the amygdala of ethanol-withdrawn rats compared with saline-treated rats (P < .01. Acupuncture groups were treated with acupuncture at acupoint HT7 or PC6 (Nei-Guan. Acupuncture at HT7 but not PC6 greatly attenuated the anxiety-like behavior during ethanol withdrawal as evidenced by significant increases in the percentage of time spent in open arms (P < .05. In the meantime, acupuncture at HT7 also markedly inhibited the alterations of neuro-endocrine parameters induced by ethanol withdrawal (P < .05. These results suggest that acupuncture may attenuate anxiety-like behavior during ethanol withdrawal through regulation of neuro-endocrine system.
Lundegaard, Pia R.; Anastasaki, Corina; Grant, Nicola J.
Altered phosphodiesterase (PDE)-cyclic AMP (cAMP) activity is frequently associated with anxiety disorders, but current therapies act by reducing neuronal excitability rather than targeting PDE-cAMP-mediated signaling pathways. Here, we report the novel repositioning of anti-cancer MEK inhibitors...... as anxiolytics in a zebrafish model of anxiety-like behaviors. PDE inhibitors or activators of adenylate cyclase cause behaviors consistent with anxiety in larvae and adult zebrafish. Small-molecule screening identifies MEK inhibitors as potent suppressors of cAMP anxiety behaviors in both larvae and adult...... zebrafish, while causing no anxiolytic behavioral effects on their own. The mechanism underlying cAMP-induced anxiety is via crosstalk to activation of the RAS-MAPK signaling pathway. We propose that targeting crosstalk signaling pathways can be an effective strategy for mental health disorders, and advance...
Teetsel, Rebekah N.; Ginsburg, Golda S.; Drake, Kelly L.
The majority of research identifying anxiety-promoting parenting behaviors has been conducted with mothers, leaving a gap in current knowledge about the role of fathers’ parenting behaviors. In an attempt to fill this gap, this study compared anxiety-promoting parenting behaviors of anxious mothers and fathers. Parents completed self-report measures of parenting behavior and independent coders rated parenting behaviors (i.e., overcontrol, granting of autonomy, warmth, hostility, anxious behavior) of mothers (n = 34) and fathers (n = 21) during a challenging parent-child interaction task (children were ages 6–12). Results indicated that anxious fathers were observed to be more controlling than anxious mothers; while anxious mothers reported using more punishment and reinforcement of children’s dependence in anxiety provoking situations compared to fathers. Findings extend our knowledge about anxious fathers, and highlight the need for additional research on the impact of fathers’ parenting with respect to the development of child anxiety. PMID:23677528
Kline, R. H.; Exposto, F. G.; O’Buckley, S. C.; Westlund, K. N.; Nackley, A. G.
Reduced catechol-O-methyltransferase (COMT) activity resulting from genetic variation or pharmacological depletion results in enhanced pain perception in humans and nociceptive behaviors in animals. Using phasic mechanical and thermal reflex tests (e.g. von Frey, Hargreaves), recent studies show that acute COMT-dependent pain in rats is mediated by β-adrenergic receptors (βARs). In order to more closely mimic the characteristics of human chronic pain conditions associated with prolonged reductions in COMT, the present study sought to determine volitional pain-related and anxiety-like behavioral responses following sustained as well as acute COMT inhibition using an operant 10–45°C thermal place preference task and a light/dark preference test. In addition, we sought to evaluate the effects of sustained COMT inhibition on generalized body pain by measuring tactile sensory thresholds of the abdominal region. Results demonstrated that acute and sustained administration of the COMT inhibitor OR486 increased pain behavior in response to thermal heat. Further, sustained administration of OR486 increased anxiety behavior in response to bright light, as well as abdominal mechanosensation. Finally, all pain-related behaviors were blocked by the non-selective βAR antagonist propranolol. Collectively, these findings provide the first evidence that stimulation of ARs following acute or chronic COMT inhibition drives cognitive-affective behaviors associated with heightened pain that affects multiple body sites. PMID:25659347
Reeb-Sutherland, Bethany C.; Williams, Lela Rankin; Degnan, Kathryn A.; Pérez-Edgar, Koraly; Chronis-Tuscano, Andrea; Leibenluft, Ellen; Pine, Daniel S.; Pollak, Seth D.; Fox, Nathan A.
The current study examined differences in emotion expression identification between adolescents characterized with behavioral inhibition (BI) in childhood with and without a lifetime history of anxiety disorder. Participants were originally assessed for behavioral inhibition during toddlerhood and for social reticence during childhood. During adolescence, participants returned to the laboratory and completed a facial-emotion identification task and a clinical psychiatric interview. Results revealed that behaviorally inhibited adolescents with a lifetime history of anxiety disorder displayed a lower threshold for identifying fear relative to anger emotion expressions compared to non-anxious behaviorally inhibited adolescents and non-inhibited adolescents with or without anxiety. These findings were specific to behaviorally inhibited adolescents with a lifetime history of social anxiety disorder. Thus, adolescents with a history of both BI and anxiety, specifically social anxiety, are more likely to differ from other adolescents in their identification of fearful facial expressions. This offers further evidence that perturbations in the processing of emotional stimuli may underlie the etiology of anxiety disorders. PMID:24800906
Full Text Available The anxiety status is changed along with memory impairments in intracerebroventricular colchicine injected rat model of Alzheimer Disease (cAD due to neurodegeneration, which has been indicated to be mediated by inflammation. Inducible cox-2, involved in inflammation, may have important role in the colchicine induced alteration of anxiety status. Therefore, the present study was designed to investigate the role of cox-2 on the anxiety behavior (response to novelty in an elevated open field space of cAD by inhibiting it with three different doses (10, 20, and 30 mg of etoricoxib (a cox-2 blocker in two time points (14 and 21 days. The results showed anxiolytic behavior in cAD along with lower serum corticosterone level, both of which were recovered at all the doses of etoricoxib on day 21. On day 14 all of the anxiety parameters showed similar results to that of day 21 at high doses but not at 10 mg/kg body weight. Results indicate that the parameters of anxiety were dependent on neuronal circuitries that were probably sensitive to etoricoxib induced blocking of neurodegeneration. The present study showed that anxiolytic behavior in cADr is predominantly due to cox-2 mediated neuroinflammation induced neurodegeneration in the brain.
Marks, David R; Tucker, Kristal; Cavallin, Melissa A; Mast, Thomas G; Fadool, Debra A
The role of insulin pathways in olfaction is of significant interest with the widespread pathology of diabetes mellitus and its associated metabolic and neuronal comorbidities. The insulin receptor (IR) kinase is expressed at high levels in the olfactory bulb, in which it suppresses a dominant Shaker ion channel (Kv1.3) via tyrosine phosphorylation of critical N- and C-terminal residues. We optimized a 7 d intranasal insulin delivery (IND) in awake mice to ascertain the biochemical and behavioral effects of insulin to this brain region, given that nasal sprays for insulin have been marketed notwithstanding our knowledge of the role of Kv1.3 in olfaction, metabolism, and axon targeting. IND evoked robust phosphorylation of Kv1.3, as well as increased channel protein-protein interactions with IR and postsynaptic density 95. IND-treated mice had an increased short- and long-term object memory recognition, increased anxiolytic behavior, and an increased odor discrimination using an odor habituation protocol but only moderate change in odor threshold using a two-choice paradigm. Unlike Kv1.3 gene-targeted deletion that alters metabolism, adiposity, and axonal targeting to defined olfactory glomeruli, suppression of Kv1.3 via IND had no effect on body weight nor the size and number of M72 glomeruli or the route of its sensory axon projections. There was no evidence of altered expression of sensory neurons in the epithelium. In mice made prediabetic via diet-induced obesity, IND was no longer effective in increasing long-term object memory recognition nor increasing anxiolytic behavior, suggesting state dependency or a degree of insulin resistance related to these behaviors.
Full Text Available The study of Mathematics has been and is still a source of frustration and anxiety for a large number of students. The purpose of this study was to inquire systematically upon levels of test anxiety through behavioral and physiological procedures before and after a Math test, in 205 senior high school students. Academic worries were assessed by means of a computerized task based on the emotional version of the Stroop paradigm designed ex profeso to measure school anxiety (Hernández-Pozo, Macías & Torres, 2004. The Stroop task was administered, along with recordings of blood pressure and pulse, before and after the first Math test of the course. Academic general scores were inverse to the behavioral anxiety level, however the best Math scores were associated to middle levels of behavioral anxiety. Contradictory findings between academic performance in Math and global score, and the apparent lack of gender difference in anxiety measured through behavioral procedures suggests the need to review the generality of previous assertions relating academic performance inversely with levels of anxiety of high school students.
Balsevich, Georgia; Baumann, Valentin; Uribe, Andres; Chen, Alon; Schmidt, Mathias V
There is growing evidence that maternal obesity and prenatal exposure to a high-fat diet program fetal development to regulate the physiology and behavior of the offspring in adulthood. Yet the extent to which the maternal dietary environment contributes to adult disease vulnerability remains unclear. In the current study we tested whether prenatal exposure to maternal obesity increases the offspring's vulnerability to stress-related psychiatric disorders. We used a mouse model of maternal diet-induced obesity to investigate whether maternal obesity affects the response to adult chronic stress exposure in young adult (3-month-old) and aged adult (12-month-old) offspring. Long-lasting, delayed impairments to anxiety-like behaviors and stress coping strategies resulted on account of prenatal exposure to maternal obesity. Although maternal obesity did not change the offspring's behavioral response to chronic stress per se, we demonstrate that the behavioral outcomes induced by prenatal exposure to maternal obesity parallel the deleterious effects of adult chronic stress exposure in aged male mice. We found that the glucocorticoid receptor (GR, Nr3c1) is upregulated in various hypothalamic nuclei on account of maternal obesity. In addition, gene expression of a known regulator of the GR, FKBP51, is increased specifically within the paraventricular nucleus. These findings indicate that maternal obesity parallels the deleterious effects of adult chronic stress exposure, and furthermore identifies GR/FKBP51 signaling as a novel candidate pathway regulated by maternal obesity. © 2015 S. Karger AG, Basel.
Full Text Available The comorbidity of type 2 diabetes (T2D with several psychiatric diseases is well established. While environmental factors may partially account for these co-occurrences, common genetic susceptibilities could also be implicated in the confluence of these diseases. In support of shared genetic burdens, TCF7L2, the strongest genetic determinant for T2D risk in the human population, has been recently implicated in schizophrenia (SCZ risk, suggesting that this may be one of many loci that pleiotropically influence both diseases. To investigate whether Tcf7l2 is involved in behavioral phenotypes in addition to its roles in glucose metabolism, we conducted several behavioral tests in mice with null alleles of Tcf7l2 or overexpressing Tcf7l2. We identified a role for Tcf7l2 in anxiety-like behavior and a dose-dependent effect of Tcf7l2 alleles on fear learning. None of the mutant mice showed differences in prepulse inhibition (PPI, which is a well-established endophenotype for SCZ. These results show that Tcf7l2 alters behavior in mice. Importantly, these differences are observed prior to the onset of detectable glucose metabolism abnormalities. Whether these differences are related to human anxiety-disorders or schizophrenia remains to be determined. These animal models have the potential to elucidate the molecular basis of psychiatric comorbidities in diabetes and should therefore be studied further.
Patki, Gaurav; Solanki, Naimesh; Atrooz, Fatin; Allam, Farida; Salim, Samina
In the present study, we have examined the behavioral and biochemical effect of induction of psychological stress using a modified version of the resident-intruder model for social stress (social defeat). At the end of the social defeat protocol, body weights, food and water intake were recorded, depression and anxiety-like behaviors as well as memory function was examined. Biochemical analysis including oxidative stress measurement, inflammatory markers and other molecular parameters, critical to behavioral effects were examined. We observed a significant decrease in the body weight in the socially defeated rats as compared to the controls. Furthermore, social defeat increased anxiety-like behavior and caused memory impairment in rats (PSocially defeated rats made significantly more errors in long term memory tests (Psocially defeated rats, when compared to control rats. We suggest that social defeat stress alters ERK1/2, IL-6, GLO1, GSR1, CAMKIV, CREB, and BDNF levels in specific brain areas, leading to oxidative stress-induced anxiety-depression-like behaviors and as well as memory impairment in rats. © 2013 Published by Elsevier B.V.
Kline, R H; Exposto, F G; O'Buckley, S C; Westlund, K N; Nackley, A G
Reduced catechol-O-methyltransferase (COMT) activity resulting from genetic variation or pharmacological depletion results in enhanced pain perception in humans and nociceptive behaviors in animals. Using phasic mechanical and thermal reflex tests (e.g. von Frey, Hargreaves), recent studies show that acute COMT-dependent pain in rats is mediated by β-adrenergic receptors (βARs). In order to more closely mimic the characteristics of human chronic pain conditions associated with prolonged reductions in COMT, the present study sought to determine volitional pain-related and anxiety-like behavioral responses following sustained as well as acute COMT inhibition using an operant 10-45°C thermal place preference task and a light/dark preference test. In addition, we sought to evaluate the effects of sustained COMT inhibition on generalized body pain by measuring tactile sensory thresholds of the abdominal region. Results demonstrated that acute and sustained administration of the COMT inhibitor OR486 increased pain behavior in response to thermal heat. Further, sustained administration of OR486 increased anxiety behavior in response to bright light, as well as abdominal mechanosensation. Finally, all pain-related behaviors were blocked by the non-selective βAR antagonist propranolol. Collectively, these findings provide the first evidence that stimulation of βARs following acute or chronic COMT inhibition drives cognitive-affective behaviors associated with heightened pain that affects multiple body sites. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
Diliberto, Rachele A; Kearney, Christopher A
Selective mutism (SM) is a debilitating condition in which a child does not speak in social situations where speech is expected. The clinical conceptualization of SM has been debated historically, with evidence pointing partly to anxious and oppositional behavior profiles. Behavioral characteristics were examined in a clinical sample of 57 youth formally diagnosed with selective mutism. Parents rated children across internalizing and externalizing behaviors on the Child Behavior Checklist. Eighteen highly rated items were subjected to exploratory and then confirmatory factor analysis. Anxiety and oppositional behavior factors were derived. The anxious behavior profile was associated with social anxiety disorder symptoms, social problems, and aggressive behaviors but not oppositional defiant disorder symptoms. The oppositional behavior profile was associated with aggressive behaviors, oppositional defiant disorder symptoms, social problems, and inversely to social anxiety disorder symptoms. Results are consistent with emerging research regarding subgroups of children with SM. Behavior profiles are discussed as well with respect to assessment and treatment implications. Readers will learn about the nature of children with selective mutism as well as behaviors that differentiate anxious and oppositional behavior profiles. Items that comprise anxious and oppositional behavior profiles are presented. These item profiles may have ramifications for assessment and treatment. Copyright © 2015 Elsevier Inc. All rights reserved.
Mika, Agnieszka; Gaffney, Michelle; Roller, Rachel; Hills, Abigail; Bouchet, Courtney A; Hulen, Kristina A; Thompson, Robert S; Chichlowski, Maciej; Berg, Brian M; Fleshner, Monika
Early life nutrition is critical for brain development. Dietary prebiotics and bioactive milk fractions support brain development by increasing plasticity and altering activity in brain regions important for cognition and emotion regulation, perhaps through the gut-microbiome-brain axis. Here we examined the impact of a diet containing prebiotics, lactoferrin, and milk fat globule membrane (test diet) on beneficial gut bacteria, basal gene expression for activity and plasticity markers within brain circuits important for cognition and anxiety, and anxiety-related behavior in the open field. Juvenile male F344 rats were fed the test diet or a calorically matched control diet beginning postnatal day 24. After 4 weeks on diets, rats were sacrificed and brains were removed. Test diet significantly increased mRNA expression for cfos, brain derived neurotropic factor, and the GluN1 subunit of the NMDA receptor in the prefrontal cortex and reduced cfos mRNA within the amygdala. Diet-induced increases in fecal Lactobacillus spp., measured using selective bacterial culture, positively correlated with altered gene expression for cfos and serotonin receptors within multiple brain regions. In a separate cohort of juvenile rats, 4 weeks of the test diet increased time spent in the center of the open field, a behavior indicative of reduced anxiety. These data demonstrate that early life diets containing prebiotics and bioactive milk fractions can adaptively alter genes in neural circuits underlying emotion regulation and decrease anxiety-related behavior. Copyright © 2018. Published by Elsevier B.V.
Kuniishi, Hiroshi; Ichisaka, Satoshi; Yamamoto, Miki; Ikubo, Natsuko; Matsuda, Sae; Futora, Eri; Harada, Riho; Ishihara, Kohei; Hata, Yoshio
The open field test is one of the most popular ethological tests to assess anxiety-like behavior in rodents. In the present study, we examined the effect of early deprivation (ED), a model of early life stress, on anxiety-like behavior in rats. In ED animals, we failed to find significant changes in the time spent in the center or thigmotaxis area of the open field, the common indexes of anxiety-like behavior. However, we found a significant increase in high-leaning behavior in which animals lean against the wall standing on their hindlimbs while touching the wall with their forepaws at a high position. The high-leaning behavior was decreased by treatment with an anxiolytic, diazepam, and it was increased under intense illumination as observed in the center activity. In addition, we compared the high-leaning behavior and center activity under various illumination intensities and found that the high-leaning behavior is more sensitive to illumination intensity than the center activity in the particular illumination range. These results suggest that the high-leaning behavior is a novel anxiety-like behavior in the open field test that can complement the center activity to assess the anxiety state of rats. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.
Emine Gül Kapçı
Full Text Available Objective: The study examined the effectiveness of a school-based cognitive-behavioral therapy (CBT program for school aged children with high levels of anxiety symptoms. Method: The study design was a randomized controlled trial (RCT comparing CBT to a waitlist-control condition. A total of 61 children (37 girls and 24 boys; age range 8-13 with high scores on either self-report or parental reports of anxiety participated in the study. The treatment group received 10 weekly sessions over three months that was administered using the Cool Kids treatment manual (Lyneham 2003. Outcome measures included parent-rated scales of anxiety and anxiety interference, and child self-report scales of anxiety, anxiety interference, depression and self-esteem. Both study groups were comparable at baseline for clinical and demographic variables. A mixed design ANOVA with pre-post treatment as within and CBT vs waitlist groups as between group variable was used for statistical analysis. Results: At post-test, CBT group had lower scores on anxiety, interference of anxiety and depression scales and higher scores on self-esteem scales of scholastic competence, social acceptance and behavioral conduct, but not physical appearance and athletic ability compared to the waitlist control group. Conclusions: The study presents empirical evidence for the effectiveness of a school based CBT Cool Kids program for reducing anxiety symptoms and increasing self-esteem in elementary school children. Future studies may examine the durability of treatment gains
Grossi, Dario; Longarzo, Mariachiara; Quarantelli, Mario; Salvatore, Elena; Cavaliere, Carlo; De Luca, Paolofabrizio; Trojano, Luigi; Aiello, Marco
Interoception collects all information coming from the body and is sustained by several brain areas such as insula and cingulate cortex. Here, we used resting-state functional magnetic resonance imaging to investigate functional connectivity (FC) of networks implied in interoception in patients with Illness anxiety disorders (IADs). We observed significantly reduced FC between the left extrastriate body area (EBA) and the paracentral lobule compared to healthy controls. Moreover, the correlation analysis between behavioural questionnaires and ROI to ROI FC showed that higher levels of illness anxiety were related to hyper-connectivity between EBA and amygdala and hippocampus. Scores on a questionnaire for interoceptive awareness were significantly correlated with higher FC between right hippocampus and nucleus accumbens bilaterally, and with higher connectivity between left anterior cingulate cortex (ACC) and left orbitofrontal cortex (OFC). Last, patients showed increased interoceptive awareness, measured by Self-Awareness Questionnaire (SAQ), and reduced capability in recognizing emotions, indicating inverse correlation between interoception and emotional awareness. Taken together our results suggested that, in absence of structural and micro-structural changes, patients with IADs show functional alteration in the neural network involved in the self-body representation; such functional alteration might be the target of possible treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.
Koo, Hoon Jung; Woo, Sungbum; Yang, Eunjoo; Kwon, Jung Hye
The present study aimed to investigate how online and offline social behavior interact with each other ultimately to affect the well-being of socially anxious adolescents. Based on previous studies, it was assumed that there might be three-way interactive effects among online social behavior, offline social behavior, and social anxiety regarding the relationship with well-being. To measure social anxiety, online and offline social behavior, and mental well-being, self-report questionnaires such as the Korean-Social Avoidance and Distress Scale, Korean version of the Relational Maintenance Behavior Questionnaire, and Korean version of Mental Health Continuum Short Form were administered to 656 Korean adolescents. Hierarchical regression analysis revealed that the three-way interaction of online social behavior, offline social behavior, and social anxiety was indeed significant. First, online social behavior was associated with lower well-being of adolescents with higher social anxiety under conditions of low engagement in offline social behavior. In contrast, a higher level of online social behavior predicted greater well-being for individuals with high social anxiety under conditions of more engagement in offline social behavior. Second, online social behavior was not significantly related to well-being in youths with low social anxiety under conditions of both high and low engagement in offline social behavior. Implications and limitations of this study were discussed.
Yeo, Sun Kyung; Lee, Woo Kyeong
Skin picking behavior involves an individual picking or biting their skin repeatedly. Although this behavior commonly occurs at a young age, little research has addressed its harmful effects among the Korean population. Therefore, we examined the characteristics of South Korean adolescents who reported skin picking behavior. South Korean students aged 12-16 years participated (N=410, females=52.2%). They completed questionnaires that addressed skin picking behavior, academic stress, impulsivity, and anxiety. The survey was conducted in Seoul and Gyeonggi-do from February-March 2016. Among participants, 66.8% reported that they had picked their skin and 15.4% did so currently. Skin picking was positively correlated with academic stress, impulsivity, and anxiety. Students who picked their skin more often displayed more anxiety, academic stress, and impulsivity. Future studies should address skin picking adolescents' characteristics, especially regarding anxiety and academic stress. Educational programs should be implemented to help adolescents decrease their anxiety and academic stress and prevent the worsening of skin picking behavior. Copyright © 2017 Elsevier B.V. All rights reserved.
Sørensen, Lin; Plessen, Kerstin J; Nicholas, Jude
compared to BRIEF reports in a group of children with a "pure" ADHD (n = 23), a "pure" anxiety (n = 24) and a group without any diagnosis (n = 104) in a 2 (ADHD vs. no ADHD) x 2 (anxiety vs. no anxiety) design. Results: The children with ADHD and anxiety disorder scored significantly higher on the Inhibit...... scale than children within the other three groups. Main effects of diagnosis appeared in ADHD children on the Inhibit, Emotional Control, and Working Memory scales, and on the Shift and Emotional Control scales in anxious children. Conclusion: The results indicate that a behavioral dysregulation in ADHD......Background: The present study investigated the impact of coexisting anxiety disorder in children with ADHD on their ability to regulate behavior. Method: Parent reports on the Behavior Rating Inventory of Executive Function (BRIEF) in a comorbid group of children with ADHD and anxiety (n = 11) were...
Mellon, Robert C; Moutavelis, Adrianos G
Schoolchildren reported their parents' use of aversive control and positive reinforcement contingencies in their educational interventions, as well as parental non-responsiveness to their requests for educational assistance. They also reported their own levels of six dimensions of anxiety disorder-related phenomena. Both parental use of aversive control and non-responsiveness were directly related to overall levels of child anxiety disorder-related behavior; these correlations were more robust than those observed in previous investigations of more diffuse dimensions of parenting style and trait anxiety. Panic disorder/agoraphobia and Generalized anxiety disorder were the dimensions most strongly correlated with both parental aversive control and non-responsiveness, while Compulsive behavior was uniquely uncorrelated with parental non-responsiveness and uniquely correlated with parental use of positive reinforcement contingencies. Differences in the magnitudes of correlations between anxiety disorder-related dimensions and parental educational practices are interpreted in terms of the probable differential effectiveness of their constituent behaviors in terminating parent-mediated negative reinforcers. Copyright © 2011 Elsevier Ltd. All rights reserved.
Lønfeldt, Nicole N.; Esbjørn, Barbara H.; Normann, Nicoline
anxiety-related metacognitions and clinical anxiety develop. Objective: We hypothesized that there are positive relationships between mother and corresponding child anxiety-related metacognitions even after controlling for maternal depression, anxiety and stress symptoms. We also hypothesized...... that maternal beliefs about child anxiety and maternal controlling behavior would be positively related to child metacognitions and would account for any associations between mother and child metacognitions. Methods: The study employed a cross-sectional design in a community sample of 7–12 year old children...... and their mothers. Mothers and children completed questionnaires to assess anxiety-related metacognitions and an interaction task to assess mothers’ overinvolvement. Mothers also completed questionnaires regarding their beliefs about child anxiety and controlling rearing behavior. We examined correlations between...
Hrncic, Dragan; Mikić, Jelena; Rasic-Markovic, Aleksandra; Velimirović, Milica; Stojković, Tihomir; Obrenović, Radmila; Rankov-Petrović, Bojana; Šušić, Veselinka; Djuric, Dragan; Petronijević, Nataša; Stanojlovic, Olivera
The aim of this study was to examine the effects of a methionine-enriched diet on anxiety-related behavior in rats and to determine the role of the brain oxidative status in these alterations. Adult male Wistar rats were fed from the 30th to 60th postnatal day with standard or methionine-enriched diet (double content comparing with standard diet: 7.7 g/kg). Rats were tested in open field and light-dark tests and afterwards oxidative status in the different brain regions were determined. Hyperhomocysteinemia induced by methionine-enriched diet in this study decreased the number of rearings, as well as the time that these animals spent in the center of the open field, but increased index of thigmotaxy. Oxidative status was selectively altered in the examined regions. Lipid peroxidation was significantly increased in the cortex and nc. caudatus of rats developing hyperhomocysteinemia, but unaltered in the hippocampus and thalamus. Based on the results of this research, it could be concluded that hyperhomocysteinemia induced by methionine nutritional overload increased anxiety-related behavior in rats. These proanxiogenic effects could be, at least in part, a consequence of oxidative stress in the rat brain.
Babri, Shirin; Doosti, Mohammad-Hossein; Salari, Ali-Akbar
A nascent literature suggests that neonatal infection is a risk factor for the development of brain, behavior and hypothalamic-pituitary-adrenal axis which can affect anxiety- and depression-related behaviors in later life. It has been documented that neonatal infection raises the concentrations of tumor necrosis factor-alpha (TNF-α) in neonate rodents and such infections may result in neonatal brain injury, at least in part, through pro-inflammatory cytokines. In addition, previous studies have shown that TNF-α is involved in cellular differentiation, neurogenesis and programmed cell death during the development of the central nervous system. We investigated for the first time whether neonatal exposure to TNF-α can affect body weight, stress-induced corticosterone (COR), anxiety- and depression-related behaviors in adult mice. In the present study, neonatal mice were treated to recombinant mouse TNF-α (0.2, 0.4, 0.7 and 1 μg/kg) or saline on postnatal days 3 and 5, then adult male and female mice were exposed to different behavioral tests. The results indicated that neonatal TNF-α treatment reduced body weight in neonatal period in both sexes. In addition, this study presents findings indicating that high doses of TNF- increase stress-induced COR levels, anxiety- and depression-related behaviors in adult males, but increase levels of anxiety without significantly influencing depression in adult female mice [corrected]. Our findings suggest that TNF-α exposure during neonatal period can alter brain and behavior development in a dose and sex-dependent manner in mice. Copyright © 2014 Elsevier B.V. All rights reserved.
Gere, Martina K; Villabø, Marianne A; Torgersen, Svenn; Kendall, Philip C
The relationship between overprotective parenting and child anxiety has been examined repeatedly because theories emphasize its role in the maintenance of child anxiety. No study has yet tested whether this relationship is unique to child anxiety, by controlling for commonly co-occurring behavior problems within the same children. The current study examined 190 children (age 7-13, 118 [corrected] boys) referred to mental health clinics and their parents. Results revealed that significant correlations between overprotective parenting and child anxiety symptoms disappear after controlling for co-occurring child behavior symptoms. It appears that overprotection is not uniquely related to child anxiety. Furthermore, overprotective parenting was significantly and uniquely related to child behavior symptoms. Researchers and practitioners need to consider co-occurring child behavior problems when working with the parents of anxious children. Copyright © 2012 Elsevier Ltd. All rights reserved.
Hosamani, Ravikumar; Wan, Judy; Marcu, Oana; Bhattacharya, Sharmila
Microgravity and mechanical stress are important factors of the spaceflight environment, and affect astronaut health and behavior. Structural, functional, and behavioral mechanisms of all cells and organisms are adapted to Earth's gravitational force, 1G, while altered gravity can pose challenges to their adaptability to this new environment. On ground, hypergravity paradigms have been used to predict and complement studies on microgravity. Even small changes that take place at a molecular and genetic level during altered gravity may result in changes in phenotypic behavior. Drosophila provides a robust and simple, yet very reliable model system to understand the complexity of hypergravity-induced altered behavior, due to availability of a plethora of genetic tools. Locomotor behavior is a sensitive parameter that reflects the array of molecular adaptive mechanisms recruited during exposure to altered gravity. Thus, understanding the genetic basis of this behavior in a hypergravity environment could potentially extend our understanding of mechanisms of adaptation in microgravity. In our laboratory we are trying to dissect out the cellular and molecular mechanisms underlying hypergravity-induced oxidative stress, and its potential consequences on behavioral alterations by using Drosophila as a model system. In the present study, we employed pan-neuronal and mushroom body specific knock-down adult flies by using Gal4/UAS system to express inverted repeat transgenes (RNAi) to monitor and quantify the hypergravity-induced behavior in Drosophila. We established that acute hypergravity (3G for 60 min) causes a significant and robust decrease in the locomotor behavior in adult Drosophila, and that this change is dependent on genes related to Parkinson's disease, such as DJ-1α , DJ-1β , and parkin. In addition, we also showed that anatomically the control of this behavior is significantly processed in the mushroom body region of the fly brain. This work links a molecular
Nautiyal, Katherine M.; Ribeiro, Ana C.; Pfaff, Donald W.; Silver, Rae
Mast cells are resident in the brain and contain numerous mediators, including neurotransmitters, cytokines, and chemokines, that are released in response to a variety of natural and pharmacological triggers. The number of mast cells in the brain fluctuates with stress and various behavioral and endocrine states. These properties suggest that mast cells are poised to influence neural systems underlying behavior. Using genetic and pharmacological loss-of-function models we performed a behavioral screen for arousal responses including emotionality, locomotor, and sensory components. We found that mast cell deficient KitW−sh/W−sh (sash−/−) mice had a greater anxiety-like phenotype than WT and heterozygote littermate control animals in the open field arena and elevated plus maze. Second, we show that blockade of brain, but not peripheral, mast cell activation increased anxiety-like behavior. Taken together, the data implicate brain mast cells in the modulation of anxiety-like behavior and provide evidence for the behavioral importance of neuroimmune links. PMID:19004805
Losada, Andrés; Márquez-González, María; Pachana, Nancy A; Wetherell, Julie L; Fernández-Fernández, Virginia; Nogales-González, Celia; Ruiz-Díaz, Miguel
Research on the behavioral correlates of anxiety in older adults is sparse. The aim of this study was to explore the association of anxiety with behavioral patterns defined by health, activity, emotional and social variables. A convenience sample of 395 older adults completed measures of health, activity, emotions, social variables and experiential avoidance. Cross-sectional data were analysed using cluster analysis. Five clusters were identified: active healthy, healthy, active vulnerable, lonely inactive and frail lonely. Participants in the active healthy and healthy clusters showed the highest scores on health variables (vitality and physical function), and adaptive scores on the rest of variables. They also reported the lowest scores on anxiety and included the lowest number of cases with clinically significant anxiety levels. Active vulnerable showed high scores on social support, leisure activities and capitalization on them but low scores in vitality and physical functioning. Participants in the lonely inactive cluster reported the highest mean score in experiential avoidance and high scores on boredom and loneliness, and low scores on social support, leisure activities capitalizing on pleasant activities and health variables. Frail lonely represent a particularly vulnerable profile of participants, similar to that of lonely inactive, but with significantly lower scores on health variables and higher scores on boredom and hours watching TV. Anxiety in older adults is not only linked to poor health, but also to dysfunctional social behavior, loneliness, boredom and experiential avoidance. Maladaptive profiles of older adults with regard to these variables have been identified.
Siara K. Rouzer
Full Text Available Among the numerous consequences of prenatal alcohol exposure (PAE is an increase in anxiety-like behavior that can prove debilitating to daily functioning. A significant body of literature has linked gestational day 12 (G12 heavy ethanol exposure with social anxiety, evident in adolescent males and females. However, the association between non-social anxiety-like behavior and moderate alcohol exposure, a more common pattern of drinking in pregnant women, is yet unidentified. To model moderate PAE (mPAE, we exposed pregnant Sprague-Dawley rats to either room air or vaporized ethanol for 6 h on G12. Adolescent offspring were then tested on postnatal days (P 41–47 in one of the following four anxiety assays: novelty-induced hypophagia (NIH, elevated plus maze (EPM, light-dark box (LDB and open-field (OF. Our findings revealed significant increases in measures of anxiety-like behavior in male PAE offspring in the NIH, LDB and OF, with no differences observed in females on any test. Additionally, male offspring who demonstrated heightened anxiety-like behavior as adolescents demonstrated decreased anxiety-like behavior in adulthood, as measured by a marble-burying test (MBT, while females continued to be unaffected in adulthood. These results suggest that mPAE leads to dynamic changes in anxiety-like behavior exclusively in male offspring.
Xiao, Hui-Wen; Ge, Chang; Feng, Guo-Xing; Li, Yuan; Luo, Dan; Dong, Jia-Li; Li, Hang; Wang, Haichao; Cui, Ming; Fan, Sai-Jun
Excessive alcohol consumption remains a major public health problem that affects millions of people worldwide. Accumulative experimental evidence has suggested an important involvement of gut microbiota in the modulation of host's immunological and neurological functions. However, it is previously unknown whether enteric microbiota is implicated in the formation of alcohol withdrawal-induced anxiety. Using a murine model of chronic alcoholism and withdrawal, we examined the impact of alcohol consumption on the possible alterations of gut microbiota as well as alcohol withdrawal-induced anxiety and behavior changes. The 16S rRNA sequencing revealed that alcohol consumption did not alter the abundance of bacteria, but markedly changed the composition of gut microbiota. Moreover, the transplantation of enteric microbes from alcohol-fed mice to normal healthy controls remarkably shaped the composition of gut bacteria, and elicited behavioral signs of alcohol withdrawal-induced anxiety. Using quantitative real-time polymerase chain reaction, we further confirmed that the expression of genes implicated in alcohol addiction, BDNF, CRHR1 and OPRM1, was also altered by transplantation of gut microbes from alcohol-exposed donors. Collectively, our findings suggested a possibility that the alterations of gut microbiota composition might contribute to the development of alcohol withdrawal-induced anxiety, and reveal potentially new etiologies for treating alcohol addiction. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.
Fluoxetine normalizes disrupted light-induced entrainment, fragmented ultradian rhythms and altered hippocampal clock gene expression in an animal model of high trait anxiety- and depression-related behavior.
Schaufler, Jörg; Ronovsky, Marianne; Savalli, Giorgia; Cabatic, Maureen; Sartori, Simone B; Singewald, Nicolas; Pollak, Daniela D
Disturbances of circadian rhythms are a key symptom of mood and anxiety disorders. Selective serotonin reuptake inhibitors (SSRIs) - commonly used antidepressant drugs - also modulate aspects of circadian rhythmicity. However, their potential to restore circadian disturbances in depression remains to be investigated. The effects of the SSRI fluoxetine on genetically based, depression-related circadian disruptions at the behavioral and molecular level were examined using mice selectively bred for high anxiety-related and co-segregating depression-like behavior (HAB) and normal anxiety/depression behavior mice (NAB). The length of the circadian period was increased in fluoxetine-treated HAB as compared to NAB mice while the number of activity bouts and light-induced entrainment were comparable. No difference in hippocampal Cry2 expression, previously reported to be dysbalanced in untreated HAB mice, was observed, while Per2 and Per3 mRNA levels were higher in HAB mice under fluoxetine treatment. The present findings provide evidence that fluoxetine treatment normalizes disrupted circadian locomotor activity and clock gene expression in a genetic mouse model of high trait anxiety and depression. An interaction between the molecular mechanisms mediating the antidepressant response to fluoxetine and the endogenous regulation of circadian rhythms in genetically based mood and anxiety disorders is proposed.
Hedman, Erik; Andersson, Erik; Lekander, Mats; Ljótsson, Brjánn
Severe health anxiety can be effectively treated with exposure-based Internet-delivered cognitive behavior therapy (ICBT), but information about which factors that predict outcome is scarce. Using data from a recently conducted RCT comparing ICBT (n = 79) with Internet-delivered behavioral stress management (IBSM) (n = 79) the presented study investigated predictors of treatment outcome. Analyses were conducted using a two-step linear regression approach and the dependent variable was operationalized both as end state health anxiety at post-treatment and as baseline-to post-treatment improvement. A hypothesis driven approach was used where predictors expected to influence outcome were based on a previous predictor study by our research group. As hypothesized, the results showed that baseline health anxiety and treatment adherence predicted both end state health anxiety and improvement. In addition, anxiety sensitivity, treatment credibility, and working alliance were significant predictors of health anxiety improvement. Demographic variables, i.e. age, gender, marital status, computer skills, educational level, and having children, had no significant predictive value. We conclude that it is possible to predict a substantial proportion of the outcome variance in ICBT and IBSM for severe health anxiety. The findings of the present study can be of high clinical value as they provide information about factors of importance for outcome in the treatment of severe health anxiety. Copyright © 2014 Elsevier Ltd. All rights reserved.
Wohleb, Eric S; Hanke, Mark L; Corona, Angela W; Powell, Nicole D; Stiner, La'Tonia M; Bailey, Michael T; Nelson, Randy J; Godbout, Jonathan P; Sheridan, John F
Psychosocial stress is associated with altered immune function and development of psychological disorders including anxiety and depression. Here we show that repeated social defeat in mice increased c-Fos staining in brain regions associated with fear and threat appraisal and promoted anxiety-like behavior in a β-adrenergic receptor-dependent manner. Repeated social defeat also significantly increased the number of CD11b(+)/CD45(high)/Ly6C(high) macrophages that trafficked to the brain. In addition, several inflammatory markers were increased on the surface of microglia (CD14, CD86, and TLR4) and macrophages (CD14 and CD86) after social defeat. Repeated social defeat also increased the presence of deramified microglia in the medial amygdala, prefrontal cortex, and hippocampus. Moreover, mRNA analysis of microglia indicated that repeated social defeat increased levels of interleukin (IL)-1β and reduced levels of glucocorticoid responsive genes [glucocorticoid-induced leucine zipper (GILZ) and FK506 binding protein-51 (FKBP51)]. The stress-dependent changes in microglia and macrophages were prevented by propranolol, a β-adrenergic receptor antagonist. Microglia isolated from socially defeated mice and cultured ex vivo produced markedly higher levels of IL-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 after stimulation with lipopolysaccharide compared with microglia from control mice. Last, repeated social defeat increased c-Fos activation in IL-1 receptor type-1-deficient mice, but did not promote anxiety-like behavior or microglia activation in the absence of functional IL-1 receptor type-1. These findings indicate that repeated social defeat-induced anxiety-like behavior and enhanced reactivity of microglia was dependent on activation of β-adrenergic and IL-1 receptors.
Wheeler, Anne; Raspa, Melissa; Bann, Carla; Bishop, Ellen; Hessl, David; Sacco, Pat; Bailey, Donald B
Behavior problems are a common challenge for individuals with fragile X syndrome (FXS) and constitute the primary clinical outcome domain in trials testing new FXS medications. However, little is known about the relationship between caregiver-reported behavior problems and co-occurring conditions such as anxiety and attention problems. In this study, 350 caregivers, each with at least one son or daughter with full-mutation FXS, rated one of their children with FXS using the Aberrant Behavior Checklist-Community Version (ABC-C); the Anxiety subscale of the Anxiety, Depression, and Mood Scale; and the Attention/Hyperactivity Items from the Symptom Inventories. In addition to examining family consequences of these behaviors, this study also sought to replicate psychometric findings for the ABC-C in FXS, to provide greater confidence for its use in clinical trials with this population. Psychometric properties and baseline ratings of problem behavior were consistent with other recent studies, further establishing the profile of problem behavior in FXS. Cross-sectional analyses suggest that selected dimensions of problem behavior, anxiety, and hyperactivity are age related; thus, age should serve as an important control in any studies of problem behavior in FXS. Measures of anxiety, attention, and hyperactivity were highly associated with behavior problems, suggesting that these factors at least coincide with problem behavior. However, these problems generally did not add substantially to variance in caregiver burden predicted by elevated behavior problems. The results provide further evidence of the incidence of problem behaviors and co-occurring conditions in FXS and the impact of these behaviors on the family. © 2013 Wiley Periodicals, Inc.
Mcneill, Ilona M.; Dunlop, Patrick D.; Skinner, Timothy C.
Past research suggests that indecisiveness and trait anxiety may both decrease the likelihood of performing risk-mitigating preparatory behaviors (e.g., preparing for natural hazards) and suggests two cognitive processes (perceived control and worrying) as potential mediators. However, no single...... control over wildfire-related outcomes. Trait anxiety did not uniquely predict preparedness or perceived control, but it did uniquely predict worry, with higher trait anxiety predicting more worrying. Also, worry trended toward uniquely predicting preparedness, albeit in an unpredicted positive direction...
Biedermann, Sarah V; Biedermann, Daniel G; Wenzlaff, Frederike; Kurjak, Tim; Nouri, Sawis; Auer, Matthias K; Wiedemann, Klaus; Briken, Peer; Haaker, Jan; Lonsdorf, Tina B; Fuss, Johannes
A dearth of laboratory tests to study actual human approach-avoidance behavior has complicated translational research on anxiety. The elevated plus-maze (EPM) is the gold standard to assess approach-avoidance behavior in rodents. Here, we translated the EPM to humans using mixed reality through a combination of virtual and real-world elements. In two validation studies, we observed participants' anxiety on a behavioral, physiological, and subjective level. Participants reported higher anxiety on open arms, avoided open arms, and showed an activation of endogenous stress systems. Participants' with high anxiety exhibited higher avoidance. Moreover, open arm avoidance was moderately predicted by participants' acrophobia and sensation seeking, with opposing influences. In a randomized, double blind, placebo controlled experiment, GABAergic stimulation decreased avoidance of open arms while alpha-2-adrenergic antagonism increased avoidance. These findings demonstrate cross-species validity of open arm avoidance as a translational measure of anxiety. We thus introduce the first ecologically valid assay to track actual human approach-avoidance behavior under laboratory conditions.
Muris, Peter; Meesters, Cor; Bouwman, Leanne; Notermans, Sabine
This study examined relationships between the self-conscious emotions of shame and guilt, behavioral inhibition (as an index of anxiety proneness), and anxiety disorder symptoms in non-clinical children aged 8-13 years (N = 126), using children's self-report data. Results showed that there were positive and significant correlations between shame and guilt, behavioral inhibition, and anxiety disorders symptoms. When controlling for the overlap between shame and guilt, it was found that shame (but not guilt) remained significantly associated with higher levels of anxiety proneness and anxiety symptoms. Further, when controlling for the effect of behavioral inhibition, shame still accounted for a significant proportion of the variance of total anxiety and generalized anxiety scores. For these anxiety problems, support emerged for a model in which shame acted as a partial mediator in the relation between behavioral inhibition and anxiety. These results indicate that the self-conscious emotion of shame is a robust correlate of anxiety pathology in children.
Caulfield, Jasmine I; Caruso, Michael J; Michael, Kerry C; Bourne, Rebecca A; Chirichella, Nicole R; Klein, Laura C; Craig, Timothy; Bonneau, Robert H; August, Avery; Cavigelli, Sonia A
Human and animal studies have shown that physical challenges and stressors during adolescence can have significant influences on behavioral and neurobiological development associated with internalizing disorders such as anxiety and depression. Given the prevalence of asthma during adolescence and increased rates of internalizing disorders in humans with asthma, we used a mouse model to test if and which symptoms of adolescent allergic asthma (airway inflammation or labored breathing) cause adult anxiety- and depression-related behavior and brain function. To mimic symptoms of allergic asthma in young BALB/cJ mice (postnatal days [P] 7-57; N=98), we induced lung inflammation with repeated intranasal administration of house dust mite extract (most common aeroallergen for humans) and bronchoconstriction with aerosolized methacholine (non-selective muscarinic receptor agonist). Three experimental groups, in addition to a control group, included: (1) "Airway inflammation only", allergen exposure 3 times/week, (2) "Labored breathing only", methacholine exposure once/week, and (3) "Airway inflammation+Labored breathing", allergen and methacholine exposure. Compared to controls, mice that experienced methacholine-induced labored breathing during adolescence displayed a ∼20% decrease in time on open arms of the elevated plus maze in early adulthood (P60), a ∼30% decrease in brainstem serotonin transporter (SERT) mRNA expression and a ∼50% increase in hippocampal serotonin receptor 1a (5Htr1a) and corticotropin releasing hormone receptor 1 (Crhr1) expression in adulthood (P75). This is the first evidence that experimentally-induced clinical symptoms of adolescent asthma alter adult anxiety-related behavior and brain function several weeks after completion of asthma manipulations. Copyright © 2017 Elsevier B.V. All rights reserved.
Lee, Bombi; Yun, Hye-Yeon; Shim, Insop; Lee, Hyejung; Hahm, Dae-Hyun
Previous studies have demonstrated that repeated restraint stress in rodents produces increases in depression and anxietylike behaviors and alters the expression of corticotrophinreleasing factor (CRF) in the hypothalamus. The current study focused on the impact of Bupleurum falcatum (BF) extract administration on repeated restraint stress-induced behavioral responses using the forced swimming test (FST) and elevated plus maze (EPM) test. Immunohistochemical examinations of tyrosine hydroxylase (TH) expression in rat brain were also conducted. Male rats received daily doses of 20, 50, or 100 mg/kg (i.p.) BF extract for 15 days, 30 min prior to restraint stress (4 h/day). Hypothalamicpituitary- adrenal axis activation in response to repeated restraint stress was confirmed base on serum corticosterone levels and CRF expression in the hypothalamus. Animals that were pre-treated with BF extract displayed significantly reduced immobility in the FST and increased open-arm exploration in the EPM test in comparison with controls. BF also blocked the increase in TH expression in the locus coeruleus of treated rats that experienced restraint stress. Together, these results demonstrate that BF extract administration prior to restraint stress significantly reduces depression and anxiety-like behaviors, possibly through central adrenergic mechanisms, and they suggest a role for BF extract in the treatment of depression and anxiety disorders.
Villarosa, Margo C; Madson, Michael B; Zeigler-Hill, Virgil; Noble, Jeremy J; Mohn, Richard S
The impact of social anxiety on negative alcohol-related behaviors among college students has been studied extensively. Drinking motives are considered the most proximal indicator of college student drinking behavior. The current study examined the mediating role of drinking motives in the relationship that social anxiety symptoms have with problematic (alcohol consumption, harmful drinking, and negative consequences) and safe (protective behavioral strategies) drinking behaviors. Participants were 532 undergraduates who completed measures of social anxiety, drinking motives, alcohol use, harmful drinking patterns, negative consequences of alcohol use, and protective behavioral strategy use. Our results show that students with higher levels of social anxiety symptoms who were drinking for enhancement motives reported more harmful drinking and negative consequences, and used fewer protective behavioral strategies. Thus, students who were drinking to increase their positive mood were participating in more problematic drinking patterns compared with students reporting fewer social anxiety symptoms. Further, conformity motives partially mediated the relationship between social anxiety symptoms and negative consequences. Thus, students with more symptoms of social anxiety who were drinking in order to be accepted by their peers were more likely than others to experience negative consequences. Clinical and research implications are discussed.
Bach, Dominik R
The combination of reward and potential threat is termed approach/avoidance conflict and elicits specific behaviors, including passive avoidance and behavioral inhibition (BI). Anxiety-relieving drugs reduce these behaviors, and a rich psychological literature has addressed how personality traits dominated by BI predispose for anxiety disorders. Yet, a formal understanding of the cognitive inference and planning processes underlying anxiety-like BI is lacking. Here, we present and empirically test such formalization in the terminology of reinforcement learning. We capitalize on a human computer game in which participants collect sequentially appearing monetary tokens while under threat of virtual "predation." First, we demonstrate that humans modulate BI according to experienced consequences. This suggests an instrumental implementation of BI generation rather than a Pavlovian mechanism that is agnostic about action outcomes. Second, an internal model that would make BI adaptive is expressed in an independent task that involves no threat. The existence of such internal model is a necessary condition to conclude that BI is under model-based control. These findings relate a plethora of human and nonhuman observations on BI to reinforcement learning theory, and crucially constrain the quest for its neural implementation. (PsycINFO Database Record (c) 2016 APA, all rights reserved).
Ste-Marie, Chantal; Gupta, Rina; Derevensky, Jeffrey L.
The relationship between anxiety, social stress, substance use, and gambling behavior was examined in a sample of 1,044 high school students from grades 7-11. Adolescents completed several instruments assessing their state, trait, and generalized anxiety, social stress, substance use, and gambling behavior. Results reveal that probable…
Chen, Edison; Lallai, Valeria; Sherafat, Yasmine; Grimes, Nickolas P; Pushkin, Anna N; Fowler, J P; Fowler, Christie D
The recent development of transgenic rodent lines expressing cre recombinase in a cell-specific manner, along with advances in engineered viral vectors, has permitted in-depth investigations into circuit function. However, emerging evidence has begun to suggest that genetic modifications may introduce unexpected caveats. In the current studies, we sought to extensively characterize male and female mice from both the ChAT (BAC) -Cre mouse line, created with the bacterial artificial chromosome (BAC) method, and ChAT (IRES) -Cre mouse line, generated with the internal ribosome entry site (IRES) method. ChAT (BAC) -Cre transgenic and wild-type mice did not differ in general locomotor behavior, anxiety measures, drug-induced cataplexy, nicotine-mediated hypolocomotion, or operant food training. However, ChAT (BAC) -Cre transgenic mice did exhibit significant deficits in intravenous nicotine self-administration, which paralleled an increase in vesicular acetylcholine transporter and choline acetyltransferase (ChAT) hippocampal expression. For the ChAT (IRES) -Cre line, transgenic mice exhibited deficits in baseline locomotor, nicotine-mediated hypolocomotion, and operant food training compared with wild-type and hemizygous littermates. No differences among ChAT (IRES) -Cre wild-type, hemizygous, and transgenic littermates were found in anxiety measures, drug-induced cataplexy, and nicotine self-administration. Given that increased cre expression was present in the ChAT (IRES) -Cre transgenic mice, as well as a decrease in ChAT expression in the hippocampus, altered neuronal function may underlie behavioral phenotypes. In contrast, ChAT (IRES) -Cre hemizygous mice were more similar to wild-type mice in both protein expression and the majority of behavioral assessments. As such, interpretation of data derived from ChAT-Cre rodents must consider potential limitations dependent on the line and/or genotype used in research investigations. SIGNIFICANCE STATEMENT Altered
Wang, B; Zheng, Y; Shi, H; Du, X; Zhang, Y; Wei, B; Luo, M; Wang, H; Wu, X; Hua, X; Sun, M; Xu, X
Zfp462 is a newly identified vertebrate-specific zinc finger protein that contains nearly 2500 amino acids and 23 putative C2H2-type zinc finger domains. So far, the functions of Zfp462 remain unclear. In our study, we showed that Zfp462 is expressed predominantly in the developing brain, especially in the cerebral cortex and hippocampus regions from embryonic day 7.5 to early postnatal stage. By using a piggyBac transposon-generated Zfp462 knockout (KO) mouse model, we found that Zfp462 KO mice exhibited prenatal lethality with normal neural tube patterning, whereas heterozygous (Het) Zfp462 KO (Zfp462 +/- ) mice showed developmental delay with low body weight and brain weight. Behavioral studies showed that Zfp462 +/- mice presented anxiety-like behaviors with excessive self-grooming and hair loss, which were similar to the pathological grooming behaviors in Hoxb8 KO mice. Further analysis of grooming microstructure showed the impairment of grooming patterning in Zfp462 +/- mice. In addition, the mRNA levels of Pbx1 (pre-B-cell leukemia homeobox 1, an interacting protein of Zfp462) and Hoxb8 decreased in the brains of Zfp462 +/- mice, which may be the cause of anxiety-like behaviors. Finally, imipramine, a widely used and effective anti-anxiety medicine, rescued anxiety-like behaviors and excessive self-grooming in Zfp462 +/- mice. In conclusion, Zfp462 deficiency causes anxiety-like behaviors with excessive self-grooming in mice. This provides a novel genetic mouse model for anxiety disorders and a useful tool to determine potential therapeutic targets for anxiety disorders and screen anti-anxiety drugs. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.
Full Text Available Objective: That the bone-derived hormone osteocalcin is necessary to promote normal brain development and function, along with its recently described sufficiency in reversing cognitive manifestations of aging, raises novel questions. One of these is to assess whether bone health, which deteriorates rapidly with aging, is a significant determinant of cognition and anxiety-like behavior. Methods: To begin addressing this question, we used mice haploinsufficient for Runx2, the master gene of osteoblast differentiation and the main regulator of Osteocalcin expression. Control and Runx2+/− mice were evaluated for the expression of osteocalcin's target genes in the brain and for behavioral parameters, using two assays each for cognition and anxiety-like behavior. Results: We found that adult Runx2+/− mice had defects in bone resorption, reduced circulating levels of bioactive osteocalcin, and reduced expression of osteocalcin's target genes in the brain. Consequently, they had significant impairment in cognitive function and increased anxiety-like behavior. Conclusions: These results indicate that bone remodeling is a determinant of brain function. Keywords: Runx2, Osteocalcin, Bone remodeling, Cognition
Moskowitz, Lauren J; Walsh, Caitlin E; Mulder, Emile; McLaughlin, Darlene Magito; Hajcak, Greg; Carr, Edward G; Zarcone, Jennifer R
There is little research on the functional assessment and treatment of anxiety and related problem behavior in children with autism spectrum disorder (ASD), particularly those with intellectual and developmental disability (IDD). In a recent study, we evaluated a multimethod strategy for assessing anxiety in children with ASD and IDD (Am J Intellect Dev Disabil 118:419-434, 2013). In the present study, we developed treatments for the anxiety and associated problem behavior in these same children. A multiple baseline design was used to evaluate the effectiveness of a multicomponent intervention package, incorporating individualized strategies from Positive Behavior Support and Cognitive Behavioral Therapy. During intervention, all three participants showed substantial decreases in anxiety and problem behavior and significant increases in respiratory sinus arrhythmia in the situations that had previously been identified as anxiety-provoking.
Masoud Gholamali Lavasani; Farah Khandan
Present project assess the effectiveness of cooperative learning over the mathematic anxiety and review the behavior of help seeking in first grade high school girl students. The experimental research procedure was in the form of pre-post tests after a period of 8 sessions of teaching. To measure the variables, the questionnaire of mathematic anxiety (Shokrani, 2002) and the questionnaire of help seeking technique (Ghadampour, 1998) were practiced (accepting or avoiding help seeking).To perfo...
Sabihi, Sara; Durosko, Nicole E; Dong, Shirley M; Leuner, Benedetta
The neuropeptide oxytocin (OT) is anxiolytic in rodents and humans. However, the specific brain regions where OT acts to regulate anxiety requires further investigation. The medial prefrontal cortex (mPFC) has been shown to play a role in the modulation of anxiety-related behavior. In addition, the mPFC contains OT-sensitive neurons, expresses OT receptors, and receives long range axonal projections from OT-producing neurons in the hypothalamus, suggesting that the mPFC may be a target where OT acts to diminish anxiety. To investigate this possibility, female rats were administered OT bilaterally into the prelimbic (PL) region of the mPFC and anxiety-like behavior assessed. In addition, to determine if the effects of OT on anxiety-like behavior are sex dependent and to evaluate the specificity of OT, male and female anxiety-like behavior was tested following delivery of either OT or the closely related neuropeptide arginine vasopressin (AVP) into the PL mPFC. Finally, the importance of endogenous OT in the regulation of anxiety-like behavior was examined in male and female rats that received PL infusions of an OT receptor antagonist (OTR-A). Overall, even though males and females showed some differences in their baseline levels of anxiety-like behavior, OT in the PL region of the mPFC decreased anxiety regardless of sex. In contrast, neither AVP nor an OTR-A affected anxiety-like behavior in males or females. Together, these findings suggest that although endogenous OT in the PL region of the mPFC does not influence anxiety, the PL mPFC is a site where exogenous OT may act to attenuate anxiety-related behavior independent of sex. Copyright © 2014 Elsevier Ltd. All rights reserved.
Kumari, Anita; Singh, Padmanabh; Baghel, Meghraj Singh; Thakur, M K
Adverse early life experience is prominent risk factors for numerous psychiatric illnesses, including mood and anxiety disorders. It imposes serious long-term costs on the individual as well as health and social systems. Hence, developing therapies that prevent the long-term consequences of early life stress is of utmost importance, and necessitates a better understanding of the mechanisms by which early life stress triggers long-lasting alterations in gene expression and behavior. Post-weaning isolation rearing of rodents models the behavioral consequences of adverse early life experiences in humans and it is reported to cause anxiety like behavior which is more common in case of females. Therefore, in the present study, we have studied the impact of social isolation of young female mice for 8weeks on the anxiety like behavior and the underlying molecular mechanism. Elevated plus maze and open field test revealed that social isolation caused anxiety like behavior. BDNF, a well-known molecule implicated in the anxiety like behavior, was up-regulated both at the message and protein level in cerebral cortex by social isolation. CREB-1 and CBP, which play a crucial role in BDNF transcription, were up-regulated at mRNA level in cerebral cortex by social isolation. HDAC-2, which negatively regulates BDNF expression, was down-regulated at mRNA and protein level in cerebral cortex by social isolation. Furthermore, BDNF acts in concert with Limk-1, miRNA-132 and miRNA-134 for the regulation of structural and morphological plasticity. Social isolation resulted in up-regulation of Limk-1 mRNA and miRNA-132 expression in the cerebral cortex. MiRNA-134, which inhibits the translation of Limk-1, was decreased in cerebral cortex by social isolation. Taken together, our study suggests that social isolation mediated anxiety like behavior is associated with up-regulation of BDNF expression and concomitant increase in the expression of CBP, CREB-1, Limk-1 and miRNA-132, and decrease
Sarro, E C; Sullivan, R M; Barr, G
Anxiety-related disorders are among the most common psychiatric illnesses, thought to have both genetic and environmental causes. Early-life trauma, such as abuse from a caregiver, can be predictable or unpredictable, each resulting in increased prevalence and severity of a unique set of disorders. In this study, we examined the influence of early unpredictable trauma on both the behavioral expression of adult anxiety and gene expression within the amygdala. Neonatal rats were exposed to unpaired odor-shock conditioning for 5 days, which produces deficits in adult behavior and amygdala dysfunction. In adulthood, we used the Light/Dark box test to measure anxiety-related behaviors, measuring the latency to enter the lit area and quantified urination and defecation. The amygdala was then dissected and a microarray analysis was performed to examine changes in gene expression. Animals that had received early unpredictable trauma displayed significantly longer latencies to enter the lit area and more defecation and urination. The microarray analysis revealed over-represented genes related to learning and memory, synaptic transmission and trans-membrane transport. Gene ontology and pathway analysis identified highly represented disease states related to anxiety phenotypes, including social anxiety, obsessive-compulsive disorders, post-traumatic stress disorder and bipolar disorder. Addiction-related genes were also overrepresented in this analysis. Unpredictable shock during early development increased anxiety-like behaviors in adulthood with concomitant changes in genes related to neurotransmission, resulting in gene expression patterns similar to anxiety-related psychiatric disorders. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.
Full Text Available Disrupted circadian rhythms are a core feature of mood and anxiety disorders. Circadian rhythms are coordinated by a light-entrainable master clock located in the suprachiasmatic nucleus. Animal models of mood and anxiety disorders often exhibit blunted rhythms in locomotor activity and clock gene expression. Interestingly, the changes in circadian rhythms correlate with mood-related behaviours. Although animal models of depression and anxiety exhibit aberrant circadian rhythms in physiology and behavior, it is possible that the methodology being used to induce the behavioral phenotype (e.g., brain lesions, chronic stress, global gene deletion affect behavior independently of circadian system. This study investigates the relationship between individual differences in circadian locomotor parameters and mood-related behaviors in healthy rats. The circadian phenotype of male Lewis rats was characterized by analyzing wheel running behavior under standard 12h:12h LD conditions, constant dark, constant light, and rate of re-entrainment to a phase advance. Rats were then tested on a battery of behavioral tests: activity box, restricted feeding, elevated plus maze, forced swim test, and fear conditioning. Under 12h:12h LD conditions, percent of daily activity in the light phase and variability in activity onset were associated with longer latency to immobility in the forced swim test. Variability in onset also correlated positively with anxiety-like behavior in the elevated plus maze. Rate of re-entrainment correlated positively with measures of anxiety in the activity box and elevated plus maze. Lastly, we found that free running period under constant dark was associated with anxiety-like behaviors in the activity box and elevated plus maze. Our results provide a previously uncharacterized relationship between circadian locomotor parameters and mood-related behaviors in healthy rats and provide a basis for future examination into circadian clock
Crişan, Liviu G.; Vulturar, Romana; Miclea, Mircea; Miu, Andrei C.
Recent research indicates that subclinical social anxiety is associated with dysfunctions at multiple psychological and biological levels, in a manner that seems reminiscent of social anxiety disorder (SAD). This study aimed to describe multidimensional responses to laboratory-induced social stress in an analog sample selected for social anxiety symptoms. State anxiety, cognitive biases related to negative social evaluation, speech anxiety behaviors, and cortisol reactivity were assessed in the Trier Social Stress Test (TSST). Results showed that social anxiety symptoms were associated with increased state anxiety, biased appraisals related to the probability and cost of negative social evaluations, behavioral changes in facial expression that were consistent with speech anxiety, and lower cortisol reactivity. In addition, multiple interrelations between responses in the TSST were found, with positive associations between subjective experience, cognitive appraisals, and observable behavior, as well as negative associations between each of the former two types of response and cortisol reactivity. These results show that in response to social stressors, subclinical social anxiety is associated with significant changes in emotional experience, cognitive appraisals, behaviors, and physiology that could parallel those previously found in SAD samples. PMID:26858658
Buzzell, George A; Troller-Renfree, Sonya V; Barker, Tyson V; Bowman, Lindsay C; Chronis-Tuscano, Andrea; Henderson, Heather A; Kagan, Jerome; Pine, Daniel S; Fox, Nathan A
Behavioral inhibition (BI) is a temperament identified in early childhood that is a risk factor for later social anxiety. However, mechanisms underlying the development of social anxiety remain unclear. To better understand the emergence of social anxiety, longitudinal studies investigating changes at behavioral neural levels are needed. BI was assessed in the laboratory at 2 and 3 years of age (N = 268). Children returned at 12 years, and an electroencephalogram was recorded while children performed a flanker task under 2 conditions: once while believing they were being observed by peers and once while not being observed. This methodology isolated changes in error monitoring (error-related negativity) and behavior (post-error reaction time slowing) as a function of social context. At 12 years, current social anxiety symptoms and lifetime diagnoses of social anxiety were obtained. Childhood BI prospectively predicted social-specific error-related negativity increases and social anxiety symptoms in adolescence; these symptoms directly related to clinical diagnoses. Serial mediation analysis showed that social error-related negativity changes explained relations between BI and social anxiety symptoms (n = 107) and diagnosis (n = 92), but only insofar as social context also led to increased post-error reaction time slowing (a measure of error preoccupation); this model was not significantly related to generalized anxiety. Results extend prior work on socially induced changes in error monitoring and error preoccupation. These measures could index a neurobehavioral mechanism linking BI to adolescent social anxiety symptoms and diagnosis. This mechanism could relate more strongly to social than to generalized anxiety in the peri-adolescent period. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. All rights reserved.
Möller, E.L.; Majdandžić, M.; Bögels, S.M.
Most studies investigating the role of parenting behavior in the intergenerational transmission of anxiety from parents to children have focused on mothers. However, recent research suggests that mothers and fathers may parent differently and may differentially affect the development of child
Sorensen, Lin; Plessen, Kerstin J.; Nicholas, Jude; Lundervold, Astri J.
Background: The present study investigated the impact of coexisting anxiety disorder in children with ADHD on their ability to regulate behavior. Method: Parent reports on the Behavior Rating Inventory of Executive Function (BRIEF) in a comorbid group of children with ADHD and anxiety (n = 11) were compared to BRIEF reports in a group of children…
Settipani, Cara A.; Kendall, Philip C.
Social functioning was assessed using the Child Behavior Checklist and Teacher Report Form for children with anxiety disorders who participated in a randomized clinical trial (N = 161, aged 7-14). Significant relationships were found between severity of children's principal anxiety disorder and most measures of social functioning, such that poorer…
Mathe, A.; Wegener, Gregers; Finger, B.
Background: Neuropeptide S (NPS) and its receptor (NPSR) have been implicated in the mediation of anxiolytic-like behavior in rodents. However, little knowledge is available to what extent the NPS system is involved in depression-related behaviors. The aim of the present work was to characterize...... the effects of centrally administered NPS on depression- and anxiety-related behaviors, using a well validated animal model of depression, the Flinders Sensitive Line (FSL) rats and their controls the Flinders Resistant Line (FRL). Methods: Male and female were tested. Seven days following insertion....... In selected animals effect of NPS on home cage activity was explored. Finally, brains from separate groups of naive animals were harvested; hippocampi, amygdalae and PVN punched out, and mRNA transcripts measured with the real-time quantitative polymerase chain reaction (rt-qPCR). Results: The most salient...
Varlinskaya, Elena I; Spear, Linda P
Repeated exposure to stressors has been found to increase anxiety-like behavior in laboratory rodents, with the social anxiety induced by repeated restraint being extremely sensitive to anxiolytic effects of ethanol in both adolescent and adult rats. No studies, however, have compared social anxiogenic effects of acute stress or the capacity of ethanol to reverse this anxiety in adolescent and adult animals. Therefore, the present study was designed to investigate whether adolescent [postnatal day (P35)] Sprague-Dawley rats differ from their adult counterparts (P70) in the impact of acute restraint stress on social anxiety and in their sensitivity to the social anxiolytic effects of ethanol. Animals were restrained for 90 min, followed by examination of stress- and ethanol-induced (0, 0.25, 0.5, 0.75, and 1 g/kg) alterations in social behavior using a modified social interaction test in a familiar environment. Acute restraint stress increased anxiety, as indexed by reduced levels of social investigation at both ages, and decreased social preference among adolescents. These increases in anxiety were dramatically reversed among adolescents by acute ethanol. No anxiolytic-like effects of ethanol emerged following restraint stress in adults. The social suppression seen in response to higher doses of ethanol was reversed by restraint stress in animals of both ages. To the extent that these data are applicable to humans, the results of the present study provide some experimental evidence that stressful life events may increase the attractiveness of alcohol as an anxiolytic agent for adolescents. Copyright © 2011 Elsevier Inc. All rights reserved.
Ramsawh, Holly J; Bomyea, Jessica; Stein, Murray B; Cissell, Shadha H; Lang, Ariel J
Despite the ubiquity of sleep complaints among individuals with anxiety disorders, few prior studies have examined whether sleep quality improves during anxiety treatment. The current study examined pre- to posttreatment sleep quality improvement during cognitive behavioral therapy (CBT) for panic disorder (PD; n = 26) or generalized anxiety disorder (GAD; n = 24). Among sleep quality indices, only global sleep quality and sleep latency improved significantly (but modestly) during CBT. Sleep quality improvement was greater for treatment responders, but did not vary by diagnosis. Additionally, poor baseline sleep quality was independently associated with worse anxiety treatment outcome, as measured by higher intolerance of uncertainty. Additional intervention targeting sleep prior to or during CBT for anxiety may be beneficial for poor sleepers.
Lee, Hyunchan; Jang, Minji; Noh, Jihyun
Initial tobacco use is initiated with rewarding and aversive properties of nicotine and aversive response to nicotine plays a critical role in nicotine dependency. Decrease of nicotine aversion increases the nicotine use that causes behavioral and neuronal changes of animals. Oxytocin influences drug abuse and reciprocally affect vulnerability to drug use. To assess the effect of oxytocin on initial nicotine aversion and anxiety, we examined voluntary oral nicotine intake and anxiety-like behavior following oxytocin treatment in adolescent rats. Sprague-Dawley male rats (4 weeks old) were used. For oxytocin administration, rats were injected subcutaneously with saline or oxytocin (0.01, 0.1 and 1mg/kg) according to the assigned groups. Voluntary oral nicotine consumption test was performed by two bottle free-choice paradigm. To examine anxiety-like behavior in rats, we performed a light/dark box test. Oxytocin not only significantly increased the nicotine intake but also alleviated nicotine aversion after acclimation to nicotine solution in a concentration dependent manner. Meanwhile, oxytocin significantly reduced anxiety-like behavior. We suggest that oxytocin itself mitigates aversive response toward initial nicotine intake and anxiety-like behavior. These results widen the psychophysiological perspective on oxytocin for better understanding of nicotine addiction related behaviors influenced by diverse social factors. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.
Arcia, Emily; Castillo, Hector; Fernández, María C
This study was undertaken to describe how Caribbean Latina mothers understand distress in children, the behaviors that they attribute to it, and the labels that they use to express their cognitions. Findings from 62 mothers of young children with disruptive behaviors indicated that mothers made attributions about anxiety in 40% of the children with a high likelihood of clinical anxiety. Hyperactive and restless behavior, but not children's fears, was understood by mothers to reflect anxiety. References to 'nervios' could be categorized into: an illness condition, a crisis condition, and a temperament type. Only temperament usage was applied to children.
Bart, Orit; Bar-Shalita, Tami; Mansour, Hanin; Dar, Reuven
To explore relationships between sensory responsiveness, anxiety, and ritual behaviors in boys with typical and atypical sensory responsiveness. Forty-eight boys, ages 5-9 participated in the study (28 boys with atypical sensory responsiveness and 20 controls). Atypical sensory responsiveness was defined as a score of ≤154 on the Short Sensory Profile. Parents completed the Sensory Profile, the Screen for Child Anxiety Related Emotional Disorders, and the Childhood Routines Inventory. Children with atypical sensory responsiveness had significantly higher levels of anxiety and a higher frequency of ritual behaviors than controls. Atypical sensory responsiveness was significantly related to both anxiety and ritual behaviors, with anxiety mediating the relationship between sensory modulation and ritual behaviors. The findings elucidate the potential consequences of atypical sensory responsiveness and could support the notion that ritual behaviors develop as a coping mechanism in response to anxiety stemming from primary difficulty in modulating sensory input.
Enes-Marques, Silvia; Giusti-Paiva, Alexandre
Maternal behavior has a substantial impact on the behavioral, endocrine, and neural development of the pups. This study investigated the effect of altering the neonatal nutritional environment by modifying the litter size on maternal care and anxiety- and fear-like behaviors in rats during adulthood. On postnatal day (PND) 2, litters were adjusted to a small litter (SL) size of three pups per dam or normal litter (NL) size of 12 pups per dam. Maternal behaviors were scored daily during lactation (PND2-21). The weight gain, food intake, adiposity, and biochemical landmarks of offspring rats were evaluated. On PND60, performances in the open field, elevated plus-maze (EPM), and fear conditioning test were measured. The reduction of the litter size enhanced maternal care in lactating rats, increasing the arched-back posture and licking pups. SL offspring exhibited accelerated weight gain, hyperphagia, increased visceral fat mass, dyslipidemia, and hyperleptinemia in adulthood. The SL offspring of both sexes showed an increase in the anti-thigmotactic effect in the open field, an intact anxious-phenotype in the EPM, and a decrease in the time spent freezing during the fear-conditioning test, compared to NL. The neonatal environment as determined by litter size plays a crucial role in programming the adult metabolic phenotype as well as behavioral responses to stressful stimuli, with an impact on anxiety-like and fear behaviors. These behavioral changes in offspring may be, at least in part, a result of increased maternal care.
Full Text Available Manganese is a very well known neurotoxic agent. It has been mainly linked to impaired motor skills and disturbed psychomotor development. However, very few aspects are known about the cognitive deficits and behavioral consequences of chronic manganese exposure. In this context, we report herein our findings regarding short-term spatial memory, motor and anxiety-like behavior assessments in male Wistar rats exposed for 45 days to two different doses (3 mg/kg b.w., i.p. and 10 mg/kg b.w., i.p. of manganese. Behavior testing (Y-maze task and elevated plus maze was performed after 45 days of manganese administration. Chronic manganese exposure in Wistar rats led to behavioral alterations consisting of cognitive deficiencies in the Y-maze task and anxiety/compulsive-like behaviors in the elevated plus maze, but no motor disturbances as tested by the number of arm entries in the Y-maze. Additional work is necessary to understand the longterm effects of different doses and dosing regimens of manganese on cognitive/affective and motor functioning.
Majdandžić, Mirjana; Möller, Eline L; de Vente, Wieke; Bögels, Susan M; van den Boom, Dymphna C
Recent models on parenting propose different roles for fathers and mothers in the development of child anxiety. Specifically, it is suggested that fathers' challenging parenting behavior, in which the child is playfully encouraged to push her limits, buffers against child anxiety. In this longitudinal study, we explored whether the effect of challenging parenting on children's social anxiety differed between fathers and mothers. Fathers and mothers from 94 families were separately observed with their two children (44 % girls), aged 2 and 4 years at Time 1, in three structured situations involving one puzzle task and two games. Overinvolved and challenging parenting behavior were coded. Child social anxiety was measured by observing the child's response to a stranger at Time 1, and half a year later at Time 2, and by parental ratings. In line with predictions, father's challenging parenting behavior predicted less subsequent observed social anxiety of the 4-year-old child. Mothers' challenging behavior, however, predicted more observed social anxiety of the 4-year-old. Parents' overinvolvement at Time 1 did not predict change in observed social anxiety of the 4-year-old child. For the 2-year-old child, maternal and paternal parenting behavior did not predict subsequent social anxiety, but early social anxiety marginally did. Parent-rated social anxiety was predicted by previous parental ratings of social anxiety, and not by parenting behavior. Challenging parenting behavior appears to have favorable effects on observed 4-year-old's social anxiety when displayed by the father. Challenging parenting behavior emerges as an important focus for future research and interventions.
Palotai, Miklós; Telegdy, Gyula; Tanaka, Masaru; Bagosi, Zsolt; Jászberényi, Miklós
Little is known about the action of neuropeptide AF (NPAF) on anxiety and depression. Only our previous study provides evidence that NPAF induces anxiety-like behavior in rats. Therefore, the aim of the present study was to investigate the action of NPAF on depression-like behavior and the underlying neurotransmissions in mice. In order to determine whether there are species differences between rats and mice, we have investigated the action of NPAF on anxiety-like behavior in mice as well. A modified forced swimming test (mFST) and an elevated plus maze test (EPMT) were used to investigate the depression and anxiety-related behaviors, respectively. Mice were treated with NPAF 30min prior to the tests. In the mFST, the animals were pretreated with a non-selective muscarinic acetylcholine receptor antagonist, atropine, a non-selective 5-HT2 serotonergic receptor antagonist, cyproheptadine, a mixed 5-HT1/5-HT2 serotonergic receptor antagonist, methysergide, a D2/D3/D4 dopamine receptor antagonist, haloperidol, a α1/α2β-adrenergic receptor antagonist, prazosin or a non-selective β-adrenergic receptor antagonist, propranolol 30min before the NPAF administration. In the mFST, NPAF decreased the immobility time and increased the climbing and swimming times. This action was reversed completely by methysergide and partially by atropine, whereas cyproheptadine, haloperidol, prazosin and propranolol were ineffective. In the EPMT, NPAF decreased the time spent in the arms (open/open+closed). Our results demonstrate that NPAF induces anti-depressant-like behavior in mice, which is mediated, at least in part, through 5HT2-serotonergic and muscarinic cholinergic neurotransmissions. In addition, the NPAF-induced anxiety is species-independent, since it develops also in mice. Copyright © 2014 Elsevier B.V. All rights reserved.
Meyer, Neele; Jenikejew, Julia; Richter, S Helene; Kaiser, Sylvia; Sachser, Norbert
Adolescence has lately been recognized as a key developmental phase during which an individual's behavior can be shaped. In a recent study with male mice varying in the expression of the serotonin transporter, escapable adverse social experiences during adolescence led to decreased anxiety-like behavior and increased exploratory and aggressive behavior compared to throughout beneficial experiences. Since in this study some behavioral tests took place with a delay of one week after the last social experiences have been made, it was not clear whether the observed effects really reflected the consequences of the experienced different social environments. To test this, the present study focused on the direct effects of beneficial and adverse social experiences on aggressiveness and anxiety-like behavior in C57BL/6J mice. In contrast to the previous study, behavioral testing took place immediately after the last social experiences had been made. Interestingly, whereas individuals from an escapable adverse environment showed significantly lower levels of anxiety-like and higher levels of exploratory behavior than animals from a beneficial environment, aggressive behavior was not affected. From this, we conclude that different social experiences during adolescence exert immediate effects on anxiety-like but not aggressive behavior in male mice. Copyright © 2017 Elsevier B.V. All rights reserved.
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Background and Objectives: Cannabinoids produce a wide array of effects on different species and interact with different neurotransmitter systems in the brain. In the present study, the effects of histaminergic and cannabinoidregic systems as well as their interactions on anxiety-related behaviors were examined on mice. Methods: In this study, at first mice were anesthetized with intra-peritoneal injection of ketamine hydrochloride and xylazine. They were then placed in a stereotaxic apparatus. Two stainless-steel cannuale were placed one mm above CA1 regions of the dorsal hippocampus. After that, seventeen groups of animals were tested with hole board apparatus for measuring anxiety behavior. For the statistical analysis, One-way analysis of variance (ANOVA and Dunnett's test were used. Results: Intra-CA1 injection of WIN55,212-2 (0.1, 0.5µg/mice did not modify anxiety-related behaviors in mice. But administration of AM251 (25 and 50ng/mice, histamine or ranitidine (5µg/mice induced anxiogenic-like response. Also, co-administration of WIN55, 212-2 with histaminergic agents, decreased the anxiogenic-like response of histamine, but not that of ranitidine. Co-administration of an ineffective dose of AM251 with histaminergic drugs did not alter the response induced by these drugs. In all the experiments, locomotor activity was not significantly changed. Conclusion: These results showed that there may be a partial interaction between the cannabinoidergic and the histaminergic systems of the dorsal hippocampus on anxiety-like behaviors.
Barrot, Michel; Wallace, Deanna L.; Bolaños, Carlos A.; Graham, Danielle L.; Perrotti, Linda I.; Neve, Rachael L.; Chambliss, Heather; Yin, Jerry C.; Nestler, Eric J.
Sexual deficits and other behavioral disturbances such as anxiety-like behaviors can be observed in animals that have undergone social isolation, especially in species having important social interactions. Using a model of protracted social isolation in adult rats, we observed increased anxiety-like behavior and deficits in both the latency to initiate sexual behavior and the latency to ejaculate. We show, using transgenic cAMP response element (CRE)-LacZ reporter mice, that protracted social isolation also reduces CRE-dependent transcription within the nucleus accumbens. This decrease in CRE-dependent transcription can be mimicked in nonisolated animals by local viral gene transfer of a dominant negative mutant of CRE-binding protein (CREB). We previously showed that this manipulation increases anxiety-like behavior. We show here that it also impairs initiation of sexual behavior in nonisolated animals, a deficit that can be corrected by anxiolytic drug treatment. This local reduction in CREB activity, however, has no influence on ejaculation parameters. Reciprocally, we used the viral transgenic approach to overexpress CREB in the nucleus accumbens of isolated animals. We show that this local increase in CREB activity completely rescued the anxiety phenotype of the isolated animals, as well as their deficit in initiating sexual behavior, but failed to rescue the deficit in ejaculation. Our data suggest a role for the nucleus accumbens in anxiety responses and in specific aspects of sexual behavior. The results also provide insight into the molecular mechanisms by which social interactions affect brain plasticity and behavior. PMID:15923261
Full Text Available Like various stressors, the addictive use of nicotine (NC is associated with emotional symptoms such as anxiety and depression, although the underlying mechanisms have not yet been fully elucidated due to the complicated involvement of target neurotransmitter systems. In the elicitation of these emotional symptoms, the fundamental involvement of epigenetic mechanisms such as histone acetylation has recently been suggested. Furthermore, among the interacting neurotransmitter systems implicated in the effects of NC and stressors, the endocannabinoid (ECB system is considered to contribute indispensably to anxiety and depression. In the present study, the epigenetic involvement of histone acetylation induced by histone deacetylase (HDAC inhibitors was investigated in anxiety- and depression-related behavioral alterations caused by NC and/or immobilization stress (IM. Moreover, based on the contributing roles of the ECB system, the interacting influence of ECB ligands on the effects of HDAC inhibitors was evaluated in order to examine epigenetic therapeutic interventions. Anxiety-like (elevated plus-maze test and depression-like (forced swimming test behaviors, which were observed in mice treated with repeated (4 days NC (subcutaneous 0.8 mg/kg and/or IM (10 min, were blocked by the HDAC inhibitors sodium butyrate (SB and valproic acid (VA. The cannabinoid type 1 (CB1 agonist ACPA (arachidonylcyclopropylamide; AC also antagonized these behaviors. Conversely, the CB1 antagonist SR 141716A (SR, which counteracted the effects of AC, attenuated the anxiolytic-like effects of the HDAC inhibitors commonly in the NC and/or IM groups. SR also attenuated the antidepressant-like effects of the HDAC inhibitors, most notably in the IM group. From these results, the combined involvement of histone acetylation and ECB system was shown in anxiety- and depression-related behaviors. In the NC treatment groups, the limited influence of SR against the HDAC inhibitor
Scott, Julia A; Goodrich-Hunsaker, Naomi; Kalish, Kristopher; Lee, Aaron; Hunsaker, Michael R; Schumann, Cynthia M; Carmichael, Owen T; Simon, Tony J
Individuals with 22q11.2 deletion syndrome (22q11.2DS) have an elevated risk for schizophrenia, which increases with history of childhood anxiety. Altered hippocampal morphology is a common neuroanatomical feature of 22q11.2DS and idiopathic schizophrenia. Relating hippocampal structure in children with 22q11.2DS to anxiety and impaired cognitive ability could lead to hippocampus-based characterization of psychosis-proneness in this at-risk population. We measured hippocampal volume using a semiautomated approach on MRIs collected from typically developing children and children with 22q11.2DS. We then analyzed hippocampal morphology with Localized Components Analysis. We tested the modulating roles of diagnostic group, hippocampal volume, sex and age on local hippocampal shape components. Lastly, volume and shape components were tested as covariates of IQ and anxiety. We included 48 typically developing children and 69 children with 22q11.2DS in our study. Hippocampal volume was reduced bilaterally in children with 22q11.2DS, and these children showed greater variation in the shape of the anterior hippocampus than typically developing children. Children with 22q11.2DS had greater inward deformation of the anterior hippocampus than typically developing children. Greater inward deformation of the anterior hippocampus was associated with greater severity of anxiety, specifically fear of physical injury, within the 22q11.2DS group. Shape alterations are not specific to hippocampal subfields. Alterations in the structure of the anterior hippocampus likely affect function and may impact limbic circuitry. We suggest these alterations potentially contribute to anxiety symptoms in individuals with 22q11.2DS through modulatory pathways. Altered hippocampal morphology may be uniquely linked to anxiety risk factors for schizophrenia, which could be a powerful neuroanatomical marker of schizophrenia risk and hence protection.
Smith, Allison M; Flannery-Schroeder, Ellen C; Gorman, Kathleen S; Cook, Nathan
Strong evidence supports cognitive-behavioral therapy (CBT) for the treatment of childhood anxiety. Many studies suggest that parents play an etiological role in the development and maintenance of child anxiety. This pilot study examined the efficacy of a cognitive-behavioral intervention delivered to the parents of 31 anxious children (ages 7-13). Parents were randomly assigned to an individual parent-only CBT intervention (PCBT, n = 18) or wait-list control (WL, n = 13). PCBT demonstrated significant reductions in children's number of anxiety disorder diagnoses, parent-rated interference and clinician-rated severity of anxiety, and maternal protective behaviors at post-treatment, which were maintained at 3-months. WL did not demonstrate significant changes. There were no significant differences between conditions in child self-reported or parent-report of child anxiety symptoms. Findings were replicated in a combined sample of treated participants, as well as in an intent-to-treat sample. Parent-only CBT may be an effective treatment modality for child anxiety, though future research is warranted. Copyright © 2014 Elsevier Ltd. All rights reserved.
Blocher, Jacquelyn B; Fujikawa, Mayu; Sung, Connie; Jackson, Daren C; Jones, Jana E
Anxiety disorders are prevalent in children with epilepsy. The purpose of this study was to evaluate the efficacy, adaptability, and feasibility of a manual-based, computer-assisted cognitive behavioral therapy (CBT) intervention for anxiety disorders in children with epilepsy. Fifteen anxious youth (aged 8-13 years) with epilepsy completed 12 weeks of manualized computer-assisted CBT. The children and parents completed a semi-structured interview at baseline, and questionnaires assessing symptoms of anxiety, depression, and behavior problems were completed prior to treatment, at treatment midpoint, after treatment completion, and at three months posttreatment. There were significant reductions in the symptoms of anxiety and depression reported by the children at completion of the intervention and at the three-month follow-up. Similarly, the parents reported fewer symptoms of anxiety and a reduction in behavior problems. No adverse events were reported. This CBT intervention for children with epilepsy and anxiety disorders appears to be safe, effective, and feasible and should be incorporated into future intervention studies. Copyright © 2012 Elsevier Inc. All rights reserved.
Goletz, Hildegard; Yang, Young-Im; Suhr-Dachs, Lydia; Walter, Daniel; Döpfner, Manfred
Only few studies have examined whether the efficacy of cognitive-behavioral therapy for childhood anxiety disorders as demonstrated in randomized controlled trials (RCTs) generalizes to clinical practice. This study examines the effectiveness of cognitive-behavioral therapy for juvenile anxiety disorders under routine care conditions in a university-based psychiatric outpatient clinic. 92 children and adolescents with parent-ratings regarding anxiety and comorbid symptoms and 61 children and adolescents with self-ratings regarding anxiety and comorbid symptoms were treated with cognitive-behavioral interventions. Pre/post mean comparisons, effect sizes, and the clinical significance of changes in symptoms were examined. The effect size for reduction of anxiety symptoms was .81 for children whose parents had completed the rating scale and .79 for children who had filled in a self-rating scale. Effect sizes for reduction of comorbid symptoms varied between .37 and .84 for parent ratings and between .21 and .62 for self-ratings. The percentage of children and adolescents who achieved clinically significant improvements in anxiety symptoms was 55.1 % according to the parent ratings and 65.7 % according to the children's self-ratings. More than 50 % of parents and children reported clinically significant improvements in comorbid symptoms. Significant reductions in both anxiety and comorbid symptoms were demonstrated over the course of cognitive-behavioral therapy of juvenile anxiety disorders in a university psychiatric outpatient clinic. The effect sizes for anxiety symptoms were found to be comparable to the effect sizes reported in RCTs. Similarly, clinically significant improvements were as frequent as the rates of remission of anxiety symptoms reported in RCTs.
Rouzer, Siara K.; Cole, Jesse M.; Johnson, Julia M.; Varlinskaya, Elena I.; Diaz, Marvin R.
Among the numerous consequences of prenatal alcohol exposure (PAE) is an increase in anxiety-like behavior that can prove debilitating to daily functioning. A significant body of literature has linked gestational day 12 (G12) heavy ethanol exposure with social anxiety, evident in adolescent males and females. However, the association between non-social anxiety-like behavior and moderate alcohol exposure, a more common pattern of drinking in pregnant women, is yet unidentified. To model modera...
Mallott, Michael A; Maner, Jon K; DeWall, Nathan; Schmidt, Norman B
Managing perceived or actual social rejection is an important facet of meeting basic needs for affiliation. Social anxiety disorder (SAD) is characterized by significant distress and debilitation relating to affiliation and recent work suggests higher levels of social anxiety symptoms may adversely affect responses to social rejection. This study examined emotional and behavioral responding to a social rejection stressor to explore whether social anxiety moderates the effects of social rejection on prosocial compensatory behaviors. Individuals (N=37) evaluated on social anxiety symptoms were assigned to either a social rejection condition or control condition. Consistent with expectation, rejection promoted renewed interest in connecting with sources of positive social interaction among participants low in social anxiety. Participants with higher levels of social anxiety, however, failed to react to rejection in a positive or prosocial manner and exhibited some evidence of negative social responses. Such differential compensatory responding could have important implications for the genesis, maintenance, and treatment of SAD.
Full Text Available Background and Objectives: Anxiety has a significant impact on academic and social performance as well as quality of life. The present study was conducted to investigate the relationship between brain/behavioral systems and difficulties in emotion regulation with cognitive and physical aspects of social anxiety. Methods: In this descriptive-correlational study, 306 students were selected from the student population of the Urmia University using multistage cluster sampling. Data collection was performed using measuring scales of social anxiety dimensions, behavioral activation and inhibition system, and difficulties in emotion regulation. Data were analyzed using descriptive indicators, correlation, simultaneous multiple regression analysis, and t-test analysis. Results: In this study, there was a significant positive correlation between behavioral inhibition system and social anxiety dimensions (p<0.001, Also, examination of the relationships of difficulties in emotion regulation and social anxiety indicated a significant positive correlation between difficulties in emotion regulation and social anxiety (p<0.001. In the comparison between women and men in terms of social anxiety components, both groups were different in cognitive dimension of social anxiety, so that the women obtained higher scores than men in the cognitive dimensions. Conclusion: According to the results of this study, individual differences in using negative emotion regulation strategies and personality traits play an important role in the onset and maintenance of anxiety.
Hu, Xu; Wang, Tao; Luo, Jia; Liang, Shan; Li, Wei; Wu, Xiaoli; Jin, Feng; Wang, Li
Cholesterol is an essential component of brain and nerve cells and is essential for maintaining the function of the nervous system. Epidemiological studies showed that patients suffering from anxiety disorders have higher serum cholesterol levels. In this study, we investigated the influence of high cholesterol diet on anxiety-like behavior in elevated plus maze in animal model and explored the relationship between cholesterol and anxiety-like behavior from the aspect of central neurochemical changes. Young (3 weeks old) and adult (20 weeks old) rats were given a high cholesterol diet for 8 weeks. The anxiety-like behavior in elevated plus maze test and changes of central neurochemical implicated in anxiety were measured. In young rats, high cholesterol diet induced anxiolytic-like behavior, decreased serum corticosterone (CORT), increased hippocampal brain-derived neurotrophic factor (BDNF), increased hippocampal mineralocorticoid receptor (MR) and decreased glucocorticoid receptor (GR). In adult rats, high cholesterol diet induced anxiety-like behavior and increase of serum CORT and decrease of hippocampal BDNF comparing with their respective control group that fed the regular diet. High cholesterol diet induced age-dependent effects on anxiety-like behavior and central neurochemical changes. High cholesterol diet might affect the central nervous system (CNS) function differently, and resulting in different behavior performance of anxiety in different age period.
Moylan, Steven; Gustavson, Kristin; Karevold, Evalill; Øverland, Simon; Jacka, Felice N.; Pasco, Julie A.; Berk, Michael
Cigarette smoking is increased in people with trait anxiety and anxiety disorders, however no longitudinal data exist illuminating whether smoking in adolescence can influence the developmental trajectory of anxiety symptoms from early vulnerability in infancy to adult anxiety expression. Using The Tracing Opportunities and Problems in Childhood and Adolescence (TOPP) Study, a community-based cohort of children and adolescents from Norway who were observed from the age of 18months to age 18–19years, we explored the relationship between adolescent smoking, early vulnerability for anxiety in infancy (e.g. shyness, internalizing behaviors, emotional temperaments) and reported early adult anxiety. Structural equation modeling demonstrated that adolescent active smoking was positively associated with increased early adulthood anxiety (β = 0.17, panxiety did not predict early adult smoking. Adolescent active smoking was a significant effect modifier in the relationship between some infant vulnerability factors and later anxiety; smoking during adolescence moderated the relationship between infant internalizing behaviors (total sample: active smokers: β = 0.85,panxiety in early adulthood. The results support a model where smoking acts as an exogenous risk factor in the development of anxiety, and smoking may alter the developmental trajectory of anxiety from infant vulnerability to early adult anxiety symptom expression. Although alternative non-mutually exclusive models may explain these findings, the results suggest that adolescent smoking may be a risk factor for adult anxiety, potentially by influencing anxiety developmental trajectories. Given the known adverse health effects of cigarette smoking and significant health burden imposed by anxiety disorders, this study supports the importance of smoking prevention and cessation programs targeting children and adolescence. PMID:23696803
Gelinas, Bethany L; Hadjistavropoulos, Heather
Although mental illness anxiety is described in the literature, there is very little information on which to draw when treating individuals who present with fears and worries about mental health. In fact, we identified no previous case descriptions focused on this form of anxiety and treated from a cognitive behavioral perspective. The current case study aims to advance the understanding of the clinical picture of mental illness anxiety, and facilitate the understanding of how cognitive behavioral techniques for health anxiety can be effectively adapted and implemented for such a case. A case study approach was adopted in which a baseline condition and repeated assessments were conducted during an 8-week treatment and 2-month follow-up period. In the current case study, we discuss the assessment, conceptualization, and cognitive behavioral treatment of a 24-year old woman who presented with mental illness anxiety. Several common health anxiety assessment tools and cognitive behavioural techniques were adapted for her particular clinical presentation. Consistent with research evidence for health anxiety, significant improvements in health anxiety and anxiety sensitivity were seen after eight sessions of therapy and maintained at 2-month follow-up. The results provide preliminary evidence that cognitive behavioral techniques for health anxiety can be effectively and efficiently adapted for mental illness anxiety. However, the lack of available research pertaining to mental illness anxiety contributes to challenges in conceptualization, assessment and treatment.
Palm Reed, Kathleen M; Cameron, Amy Y; Ameral, Victoria E
There is a growing literature focusing on the emerging idea that behavioral flexibility, rather than particular emotion regulation strategies per se, provides greater promise in predicting and influencing anxiety-related psychopathology. Yet this line of research and theoretical analysis appear to be plagued by its own challenges. For example, middle-level constructs, such as behavioral flexibility, are difficult to define, difficult to measure, and difficult to interpret in relation to clinical interventions. A key point that some researchers have made is that previous studies examining flexible use of emotion regulation strategies (or, more broadly, coping) have failed due to a lack of focus on context. That is, examining strategies in isolation of the context in which they are used provides limited information on the suitability, rigid adherence, or effectiveness of a given strategy in that situation. Several of these researchers have proposed the development of new models to define and measure various types of behavioral flexibility. We would like to suggest that an explanation of the phenomenon already exists and that we can go back to our behavioral roots to understand this phenomenon rather than focusing on defining and capturing a new process. Indeed, thorough contextual behavioral analyses already yield a useful account of what has been observed. We will articulate a model explaining behavioral flexibility using a functional, contextual framework, with anxiety-related disorders as an example.
Yao, Rongying; Chen, Jun; Zhang, Qin; Peng, Wenjia; Fu, Lianguo
To explore the effect of emotion management ability on the social anxiety and aggressive behavior among 4 - 6 grade pupils. The grade four, five and six pupils from Bengbu City were investigated using stratified cluster random sampling. The questionnaire contents included general condition, emotion management ability, aggressive behavior and social anxiety, and the relationships of which were analyzed using partial correlation and hierarchical regression method. The score of aggressive behavior in boys (72. 74 ± 18. 09) was higher than that in girls (66. 31 ± 17. 53) (P behaviors in grade five students (71. 76 ± 18. 06) were higher than that in grade four (69. 24 ± 18. 95) and six students (68. 40 ± 17. 19) (P behaviors were negatively correlated with emotion management ability (r = - 0. 463, P social anxiety (r = 0. 229, P social anxiety ( r = - 0. 234, P social anxiety and aggressive behavior (P social anxiety and aggressive behavior in 4 - 6 grade pupils. Improving the emotion management abilities can reduce their social anxieties and aggressive behaviors.
V. S. Lima
Full Text Available Nowadays, the world population has been affected by two serious psychological disorders, anxiety and depression, but there are few discoveries for new therapies to combat them. Studies have shown that music therapy has its beneficial behavioral effects. Therefore, the aim of the present study it was to investigate the possible effects of two music styles in some lipids and carbohydrate metabolism parameters resulting from behavioral changes related to anxiety and depression. So, mice were used with 30 days of age, divided into 6 groups: G1: saline, G2: Diazepam (DZP, G3: Fluoxetine (FLX, G4: control (no treatment, G5: Rock, and G6: Mozart Sonata. The animals from groups G1, G2 and G3 received treatments by oral route (gavage for 15 days. The music therapy sessions (2x/day 4 hours/day occurred in the same period of time at a 65dB frequency for G5 and G6 groups. After being evaluated in spontaneous locomotion, elevated plus maze and forced swimming tests, the animals were euthanized. The lactate, total cholesterol and plasma glucose levels were measured from the blood. No change was observed in spontaneous locomotion test and elevated plus maze. In the forced swimming test animals exposed to Rock showed an increase in immobility time. Furthermore, it was observed an increase in glucose and a reduction in cholesterol levels in the groups exposed to Rock and Mozart, while a decrease of lactate was observed only in group Rock. It was concluded that the auditory stimulus caused by music in mice was able to encourage depressive behavior and alter some lipids and carbohydrate metabolism parameters dependently of the musical style.
Fu, Ailing; Li, Xiaorong; Zhao, Baoquan
There are evidence suggesting that the function of adrenergic receptor is affected in the amygdala of animals with anxiety-like behavior. However, beta-adrenoceptor (beta-AR) subtypes, consisting of three subtypes, exert different effects on anxiety regulation. In order to determine the function of the beta1-AR subtype in anxiety-like behavior, we investigated the change of beta1-AR expression by immunostaining in the basolateral amygdala (BLA) of rats treated by conditional fear training. The results indicated that the level of beta1-AR was significantly increased in the BLA of fear-conditioned animals as compared that of controls. In animal behavioral tests, animals treated with selective beta1-AR antagonist metoprolol before conditional fear training exhibited a significant attenuation of anxiety-like behavior characterized by increased percentage of time spent and percentage of entries in the open arms, and increased number of head-dips in the elevated plus-maze (EPM) test compared with the animals treated with only saline. Furthermore, the rats pretreated with metoprolol in the conditional fear training significantly decreased the freezing behavior in the test compared with the controls. The results suggested that the beta1-AR played an important role in anxiety-like behavior, and inhibition of the beta1-AR in the BLA could produce anxiolytic effect.
Boersma, Gretha J; Treesukosol, Yada; Cordner, Zachary A; Kastelein, Anneke; Choi, Pique; Moran, Timothy H; Tamashiro, Kellie L
Relapse rates are high amongst cases of anorexia nervosa (AN) suggesting that some alterations induced by AN may remain after weight restoration. To study the consequences of AN without confounds of environmental variability, a rodent model of activity-based anorexia (ABA) can be employed. We hypothesized that exposure to ABA during adolescence may have long-term consequences in taste function, cognition, and anxiety-like behavior after weight restoration. To test this hypothesis, we exposed adolescent female rats to ABA (1.5 h food access, combined with voluntary running wheel access) and compared their behavior to that of control rats after weight restoration was achieved. The rats were tested for learning/memory, anxiety, food preference, and taste in a set of behavioral tests performed during the light period. Our data show that ABA exposure leads to reduced performance during the novel object recognition task, a test for contextual learning, without altering performance in the novel place recognition task or the Barnes maze, both tasks that test spatial learning. Furthermore, we do not observe alterations in unconditioned lick responses to sucrose nor quinine (described by humans as "sweet" and "bitter," respectively). Nor Do we find alterations in anxiety-like behavior during an elevated plus maze or an open field test. Finally, preference for a diet high in fat is not altered. Overall, our data suggest that ABA exposure during adolescence impairs contextual learning in adulthood without altering spatial leaning, taste, anxiety, or fat preference. © 2015 Wiley Periodicals, Inc.
Brown, Amy M; Deacon, Brett J; Abramowitz, Jonathan S; Dammann, Julie; Whiteside, Stephen P
Cognitive-behavioral therapy (CBT) and pharmacotherapy are the most well-established treatments for childhood anxiety disorders. This study examined how parents (N=71) seeking treatment for their child's anxiety disorder perceive the acceptability, believability, and effectiveness of these treatments. While both treatments were perceived favorably, CBT was rated as more acceptable, believable, and effective in the short- and long-term. Children's treatment history influenced parents' perceptions of pharmacotherapy, with parents of children with no treatment history perceiving medication treatment as less acceptable and believable than parents of children with a history of medication alone or in combination with behavior therapy. No effect of treatment history was found for perceptions of CBT. Significant positive correlations emerged between parents' perceived acceptance and believability for pharmacotherapy and child age and level of dysfunction due to their child's anxiety, respectively. The level of the child's anxiety was not significantly correlated with parents' perceptions of either CBT or pharmacotherapy. Our results suggest that parents of anxious children prefer CBT to medication for the treatment of their child's anxiety disorder. Directions for future research are discussed.
Möller, Eline L; Nikolić, Milica; Majdandžić, Mirjana; Bögels, Susan M
In this meta-analysis we investigated differential associations between maternal and paternal parenting behaviors (overcontrol, overprotection, overinvolvement, autonomy granting, challenging parenting) and anxiety and its precursors (fearful temperament, behavioral inhibition, shyness) in children (0-5years). Two meta-analyses were conducted, one for mothers (k=28, N=5,728), and one for fathers (k=12, N=1,019). In general, associations between parenting and child anxiety were small. Associations between child anxiety and overcontrol, overprotection, and overinvolvement did not differ for mothers and fathers. Maternal autonomy granting was not significantly related to child anxiety, and no studies examined fathers' autonomy granting. A significant difference was found for challenging parenting; mothers' challenging parenting was not significantly related to child anxiety, whereas fathers' challenging parenting was related to less child anxiety. Post-hoc meta-analyses revealed that mothers' and fathers' parenting was more strongly related to children's anxiety symptoms than to child anxiety precursors. Moreover, the association between parenting and child anxiety symptoms was stronger for fathers than for mothers. In conclusion, although parenting plays only a small role in early childhood anxiety, fathers' parenting is at least as important as mothers'. Paternal challenging behavior even seems more important than maternal challenging behavior. Research is needed to determine whether challenging fathering can prevent child anxiety development. Copyright © 2016 Elsevier Ltd. All rights reserved.
Full Text Available Depression and anxiety are generally considered to be the most important psychopathological comorbidities of cancer patients and experienced by approximately one-third of cancer patients. In the literature, studies have reported that patient characteristics such as gender, age, education level and disease characteristics such as recurrence, stage of cancer and metestazis are associated with anxiety and depression among cancer patients. Cognitive Behavioral Therapy (CBT and techniques are one of the most frequently used approach in studying the effects of psychological intervention on anxiety and depression in cancer patients and its value has been demonstrated in reducing distress with diverse cancer populations. The aim of cognitive-behavioral interventions is to change particular thoughts and behaviors and teach specific coping skills, such as cognitive restructuring, behavior modification, relaxation training and activity plan by using specific techniques. Cognitive restructing, stress management and desensitization, relaxation and activity scheduling with use of diary sheet are most used among CBT techniques. This review summarizes the diagnosis, prevalence, risk factors and treatment of depression and anxiety in patients with cancer and CBT techniques applied to these symptoms and study findings related to treatment. [JCBPR 2015; 4(1.000: 54-63
Manti, Maria; Fornes, Romina; Qi, Xiaojuan; Folmerz, Elin; Lindén Hirschberg, Angelica; de Castro Barbosa, Thais; Maliqueo, Manuel; Benrick, Anna; Stener-Victorin, Elisabet
Maternal polycystic ovary syndrome (PCOS), a condition associated with hyperandrogenism, is suggested to increase anxiety-like behavior in the offspring. Because PCOS is closely linked to obesity, we investigated the impact of an adverse hormonal or metabolic maternal environment and offspring obesity on anxiety in the offspring. The obese PCOS phenotype was induced by chronic high-fat-high-sucrose (HFHS) consumption together with prenatal dihydrotestosterone exposure in mouse dams. Anxiety-like behavior was assessed in adult offspring with the elevated-plus maze and open-field tests. The influence of maternal androgens and maternal and offspring diet on genes implicated in anxiety were analyzed in the amygdala and hypothalamus with real-time PCR ( n = 47). Independent of diet, female offspring exposed to maternal androgens were more anxious and displayed up-regulation of adrenoceptor α 1B in the amygdala and up-regulation of hypothalamic corticotropin-releasing hormone ( Crh). By contrast, male offspring exposed to a HFHS maternal diet had increased anxiety-like behavior and showed up-regulation of epigenetic markers in the amygdala and up-regulation of hypothalamic Crh. Overall, there were substantial sex differences in gene expression in the brain. These findings provide novel insight into how maternal androgens and obesity exert sex-specific effects on behavior and gene expression in the offspring of a PCOS mouse model.-Manti, M., Fornes, R., Qi, X., Folmerz, E., Lindén Hirschberg, A., de Castro Barbosa, T., Maliqueo, M., Benrick, A., Stener-Victorin, E. Maternal androgen excess and obesity induce sexually dimorphic anxiety-like behavior in the offspring.
Yu, X D; Yu, J C; Wu, Q F; Chen, J Y; Wang, Y C; Yan, D; Teng, S W; Zhao, Y T; Cao, J P; Li, S Q; Yan, Y Q; Gong, J; Yao, K; Zhou, H; Wang, Z Z
Objective: To investigate the relationship among depression, anxiety, stress and addictive substance use behavior in secondary vocational students. Methods: Cluster sampling method and the Adolescent Health-related Behaviors Questionnaire were used to collect demographic characteristics, psychological symptoms, and addictive substance usage among 5 935 students in nine vocational schools in Chongqing, Zhaoqing, Ningbo, and Taiyuan. Multivariate logistic regression analysis was used to analyze the relationship between the addictive substance use behavior and psychological factors. Results: The detection rates of depression, anxiety and stress were 46.5% ( n= 2 762), 58.7% ( n= 3 483), and 29.8% ( n= 1 770), respectively. The prevalence of addictive substances was 74.8% ( n =4 440), traditional drugs was 0.8% ( n= 50), new drugs was 2.8% ( n= 166), other addictive drugs was 4.1% ( n= 241). Multivariate logistic regression analysis showed that compared with the normal psychological states of secondary vocational students, the OR value of mild depression tendency alcohol and tobacco use behavior of secondary vocational students was 1.45; the OR values of mild anxiety, moderate anxiety, severe anxiety and very serious anxiety were 1.46, 1.46, 1.71, and 1.83, respectively; the traditional drugs use behaviors were 5.51, and 2.61, respectively, for the severe anxiety and very serious anxiety. Compared with the normal psychological state of secondary vocational students, the OR values of the severe anxiety and very severe anxiety were 2.56, and 2.66, respectively, for severe anxiety and very serious anxiety. Compared with normal psychological status of secondary vocational students, the OR values of mild, moderate, severe, and very severe anxiety were 2.14, 2.47, 2.39, and 3.45, respectively; all P values Anxiety and mild depression were risk factors of tobacco and alcohol use in secondary vocational students; severe and above anxiety were the risk factors of drug use in
de Cossío, Lourdes Fernández; Fourrier, Célia; Sauvant, Julie; Everard, Amandine; Capuron, Lucile; Cani, Patrice D; Layé, Sophie; Castanon, Nathalie
Mounting evidence shows that the gut microbiota, an important player within the gut-brain communication axis, can affect metabolism, inflammation, brain function and behavior. Interestingly, gut microbiota composition is known to be altered in patients with metabolic syndrome (MetS), who also often display neuropsychiatric symptoms. The use of prebiotics, which beneficially alters the microbiota, may therefore be a promising way to potentially improve physical and mental health in MetS patients. This hypothesis was tested in a mouse model of MetS, namely the obese and type-2 diabetic db/db mice, which display emotional and cognitive alterations associated with changes in gut microbiota composition and hippocampal inflammation compared to their lean db/+ littermates. We assessed the impact of chronic administration (8weeks) of prebiotics (oligofructose) on both metabolic (body weight, food intake, glucose homeostasis) and behavioral (increased anxiety-like behavior and impaired spatial memory) alterations characterizing db/db mice, as well as related neurobiological correlates, with particular attention to neuroinflammatory processes. Prebiotic administration improved excessive food intake and glycemic dysregulations (glucose tolerance and insulin resistance) in db/db mice. This was accompanied by an increase of plasma anti-inflammatory cytokine IL-10 levels and hypothalamic mRNA expression of the anorexigenic cytokine IL-1β, whereas unbalanced mRNA expression of hypothalamic orexigenic (NPY) and anorexigenic (CART, POMC) peptides was unchanged. We also detected signs of improved blood-brain-barrier integrity in the hypothalamus of oligofructose-treated db/db mice (normalized expression of tight junction proteins ZO-1 and occludin). On the contrary, prebiotic administration did not improve behavioral alterations and associated reduction of hippocampal neurogenesis displayed by db/db mice, despite normalization of increased hippocampal IL-6 mRNA expression. Of note
Background Cholesterol is an essential component of brain and nerve cells and is essential for maintaining the function of the nervous system. Epidemiological studies showed that patients suffering from anxiety disorders have higher serum cholesterol levels. In this study, we investigated the influence of high cholesterol diet on anxiety-like behavior in elevated plus maze in animal model and explored the relationship between cholesterol and anxiety-like behavior from the aspect of central neurochemical changes. Methods Young (3 weeks old) and adult (20 weeks old) rats were given a high cholesterol diet for 8 weeks. The anxiety-like behavior in elevated plus maze test and changes of central neurochemical implicated in anxiety were measured. Results In young rats, high cholesterol diet induced anxiolytic-like behavior, decreased serum corticosterone (CORT), increased hippocampal brain-derived neurotrophic factor (BDNF), increased hippocampal mineralocorticoid receptor (MR) and decreased glucocorticoid receptor (GR). In adult rats, high cholesterol diet induced anxiety-like behavior and increase of serum CORT and decrease of hippocampal BDNF comparing with their respective control group that fed the regular diet. Discussion High cholesterol diet induced age-dependent effects on anxiety-like behavior and central neurochemical changes. High cholesterol diet might affect the central nervous system (CNS) function differently, and resulting in different behavior performance of anxiety in different age period. PMID:25179125
Aminabadi, Naser-Asl; Pourkazemi, Maryam; Babapour, Jalil; Oskouei, Sina-Ghertasi
The present study investigated the correlations between maternal emotional intelligence (EQ), parenting style, child trait anxiety and child behavior in the dental setting. One-hundred seventeen children, aged 4-6 years old (mean 5.24 years), and their mothers participated in the study. The BarOn Emotional Quotient Inventory and Bumrind's parenting style questionnaire were used to quantify maternal emotional intelligence and parenting style. Children's anxiety and behavior was evaluated using the Spence Children's Anxiety Scale (SCAS) and Frankl behavior scale. Significant correlation was found between maternal EQ and child behavior (r=0.330; pparenting style and child behavior. There was no significant correlation between mother's total EQ and child's total anxiety; however, some subscales of EQ and anxiety showed significant correlations. There were significant correlations between authoritarian parenting style and separation anxiety (r=0.186; pauthoritative parenting style and mother's EQ (r=0.286; pauthoritative parenting style.
Rasmussen, Dennis D; Kincaid, Carrie L; Froehlich, Janice C
Stress-induced anxiety is a risk factor for relapse to alcohol drinking. The aim of this study was to test the hypothesis that the central nervous system (CNS)-active α 1 -adrenergic receptor antagonist, prazosin, would block the stress-induced increase in anxiety that occurs during alcohol deprivations. Selectively bred male alcohol-preferring (P) rats were given three cycles of 5 days of ad libitum voluntary alcohol drinking interrupted by 2 days of alcohol deprivation, with or without 1 h of restraint stress 4 h after the start of each of the first two alcohol deprivation cycles. Prazosin (1.0 or 1.5 mg/kg, IP) or vehicle was administered before each restraint stress. Anxiety-like behavior during alcohol deprivation following the third 5-day cycle of alcohol drinking (7 days after the most recent restraint stress ± prazosin treatment) was measured by performance in an elevated plus-maze and in social approach/avoidance testing. Rats that received constant alcohol access, or alcohol access and deprivations without stress or prazosin treatments in the first two alcohol deprivations did not exhibit augmented anxiety-like behavior during the third deprivation. In contrast, rats that had been stressed during the first two alcohol deprivations exhibited increased anxiety-like behavior (compared with control rats) in both anxiety tests during the third deprivation. Prazosin given before stresses in the first two cycles of alcohol withdrawal prevented increased anxiety-like behavior during the third alcohol deprivation. Prazosin treatment before stresses experienced during alcohol deprivations may prevent the increased anxiety during subsequent deprivation/abstinence that is a risk factor for relapse to alcohol drinking. Administration of prazosin before stresses during repetitive alcohol deprivations in male alcohol-preferring (P) rats prevents increased anxiety during a subsequent deprivation without further prazosin treatment. Prazosin treatment during repeated
White, Lauren K.; McDermott, Jennifer Martin; Degnan, Kathryn A.; Henderson, Heather A.; Fox, Nathan A.
Behavioral inhibition (BI), a temperament identified in early childhood, is associated with social reticence in childhood and an increased risk for anxiety problems in adolescence and adulthood. However, not all behaviorally inhibited children remain reticent or develop an anxiety disorder. One possible mechanism accounting for the variability in the developmental trajectories of BI is a child’s ability to successfully recruit cognitive processes involved in the regulation of negative reactivity. However, separate cognitive processes may differentially moderate the association between BI and later anxiety problems. The goal of the current study was to examine how two cognitive processes - attention shifting and inhibitory control - laboratory assessed at 48 months of age moderated the association between 24-month BI and anxiety symptoms in the preschool years. Results revealed that high levels of attention shifting decreased the risk for anxiety symptoms in children with high levels of BI, whereas high levels of inhibitory control increased this risk for anxiety symptoms. These findings suggest that different cognitive processes may influence relative levels of risk or adaptation depending upon a child’s temperamental reactivity. PMID:21301953
Macher, Daniel; Paechter, Manuela; Papousek, Ilona; Ruggeri, Kai
The present study investigated the relationship between statistics anxiety, individual characteristics (e.g., trait anxiety and learning strategies), and academic performance. Students enrolled in a statistics course in psychology (N = 147) filled in a questionnaire on statistics anxiety, trait anxiety, interest in statistics, mathematical…
Pourkazemi, Maryam; Babapour, Jalil; Oskouei, Sina-Ghertasi
Objective. The present study investigated the correlations between maternal emotional intelligence (EQ), parenting style, child trait anxiety and child behavior in the dental setting. Study design. One-hundred seventeen children, aged 4-6 years old (mean 5.24 years), and their mothers participated in the study. The BarOn Emotional Quotient Inventory and Bumrind�s parenting style questionnaire were used to quantify maternal emotional intelligence and parenting style. Children�s anxiety and behavior was evaluated using the Spence Children�s Anxiety Scale (SCAS) and Frankl behavior scale. Results. Significant correlation was found between maternal EQ and child behavior (r=0.330; pparenting style and child behavior. There was no significant correlation between mother�s total EQ and child�s total anxiety; however, some subscales of EQ and anxiety showed significant correlations. There were significant correlations between authoritarian parenting style and separation anxiety (r=0.186; pparenting style and mother�s EQ (r=0.286; pbehavior (r = -0.81). Regression analysis revealed maternal EQ is effective in predicting child behavior (?=0.340; pbehavior in the dental setting is correlated to mother�s emotional intelligence. Emotionally intelligent mothers were found to have predominantly authoritative parenting style. Key words:Anxiety, child behavior, parenting, pediatric dentistry. PMID:22926462
Wood, Jeffrey J.; Piacentini, John C.; Southam-Gerow, Michael; Chu, Brian C.; Sigman, Marian
Objective: This study compared family-focused cognitive behavioral therapy (CBT: the Building Confidence Program) with traditional child-focused CBT with minimal family involvement for children with anxiety disorders. Method: Forty clinically anxious youth (6-13 years old) were randomly assigned to a family- or child-focused cognitive-behavioral…
Pires, Gabriel N; Tufik, Sergio; Andersen, Monica L
Increased anxiety is a classic effect of sleep deprivation. However, results regarding sleep deprivation-induced anxiety-like behavior are contradictory in rodent models. The grooming analysis algorithm is a method developed to examine anxiety-like behavior and stress in rodents, based on grooming characteristics and microstructure. This study evaluated the applicability of the grooming analysis algorithm to distinguish sleep-deprived and control rats in comparison to traditional grooming analysis. Forty-six animals were distributed into three groups: control (n=22), paradoxical sleep-deprived (96 h, n=10) and total sleep deprived (6 h, n=14). Immediately after the sleep deprivation protocol, grooming was evaluated using both the grooming analysis algorithm and traditional measures (grooming latency, frequency and duration). Results showed that both paradoxical sleep-deprived and total sleep-deprived groups displayed grooming in a fragmented framework when compared to control animals. Variables from the grooming analysis algorithm were successful in distinguishing sleep-deprived and normal sleep animals regarding anxiety-like behavior. The grooming analysis algorithm and traditional measures were strongly correlated. In conclusion, the grooming analysis algorithm is a reliable method to assess the relationship between anxiety-like behavior and sleep deprivation. Copyright © 2012 Elsevier Inc. All rights reserved.
Richendrfer, Holly; Pelkowski, Sean D.; Colwill, Ruth M.; Créton, Robbert
Neurobehavioral disorders such as anxiety, autism, and attention deficit hyperactivity disorders are typically influenced by genetic and environmental factors. Although several genetic risk factors have been identified in recent years, little is known about the environmental factors that either cause neurobehavioral disorders or contribute to their progression in genetically predisposed individuals. One environmental factor that has raised concerns is chlorpyrifos, an organophosphate pesticide that is widely used in agriculture and is found ubiquitously in the environment. In the present study, we examined the effects of sub-chronic chlorpyrifos exposure on anxiety-related behavior during development using zebrafish larvae. We found that sub-chronic exposure to 0.01 or 0.1 μM chlorpyrifos during development induces specific behavioral defects in 7-day-old zebrafish larvae. The larvae displayed decreases in swim speed and thigmotaxis, yet no changes in avoidance behavior were seen. Exposure to 0.001 μM chlorpyrifos did not affect swimming, thigmotaxis, or avoidance behavior and exposure to 1 μM chlorpyrifos induced behavioral defects, but also induced defects in larval morphology. Since thigmotaxis, a preference for the edge, is an anxiety-related behavior in zebrafish larvae, we propose that sub-chronic chlorpyrifos exposure interferes with the development of anxiety-related behaviors. The results of this study provide a good starting point for examination of the molecular, cellular, developmental, and neural mechanisms that are affected by environmentally relevant concentrations of organophosphate pesticides. A more detailed understanding of these mechanisms is important for the development of predictive models and refined health policies to prevent toxicant-induced neurobehavioral disorders. PMID:22579535
Ecker, Anthony H.; Buckner, Julia D.
Objective: Individuals with greater social anxiety are particularly vulnerable to cannabis-related impairment. Descriptive norms (beliefs about others’ use) and injunctive norms (beliefs regarding others’ approval of risky use) may be particularly relevant to cannabis-related behaviors among socially anxious persons if they use cannabis for fear of evaluation for deviating from what they believe to be normative behaviors. Yet, little research has examined the impact of these social norms on the relationships between social anxiety and cannabis use behaviors. Method: The current study investigated whether the relationships of social anxiety to cannabis use and use-related problems varied as a function of social norms. The sample comprised 230 (63.0% female) current cannabis-using undergraduates. Results: Injunctive norms (regarding parents, not friends) moderated the relationship between social anxiety and cannabis-related problem severity. Post hoc probing indicated that among participants with higher (but not lower) social anxiety, those with greater norm endorsement reported the most severe impairment. Injunctive norms (parents) also moderated the relationship between social anxiety and cannabis use frequency such that those with higher social anxiety and lower norm endorsement used cannabis less frequently. Descriptive norms did not moderate the relationship between social anxiety and cannabis use frequency. Conclusions: Socially anxious cannabis users appear to be especially influenced by beliefs regarding parents’ approval of risky cannabis use. Results underscore the importance of considering reference groups and the specific types of norms in understanding factors related to cannabis use behaviors among this vulnerable population. PMID:24411799
Comprehensive behavioral analysis of the Cdkl5 knockout mice revealed significant enhancement in anxiety- and fear-related behaviors and impairment in both acquisition and long-term retention of spatial reference memory.
Okuda, Kosuke; Takao, Keizo; Watanabe, Aya; Miyakawa, Tsuyoshi; Mizuguchi, Masashi; Tanaka, Teruyuki
Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental disorders. Recently we have generated Cdkl5 KO mice by targeting exon 2 on the C57BL/6N background, and demonstrated postsynaptic overaccumulation of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors in the hippocampus. In the current study, we subjected the Cdkl5 KO mice to a battery of comprehensive behavioral tests, aiming to reveal the effects of loss of CDKL5 in a whole perspective of motor, emotional, social, and cognition/memory functions, and to identify its undetermined roles. The neurological screen, rotarod, hot plate, prepulse inhibition, light/dark transition, open field, elevated plus maze, Porsolt forced swim, tail suspension, one-chamber and three-chamber social interaction, 24-h home cage monitoring, contextual and cued fear conditioning, Barnes maze, and T-maze tests were applied on adult Cdkl5 -/Y and +/Y mice. Cdkl5 -/Y mice showed a mild alteration in the gait. Analyses of emotional behaviors revealed significantly enhanced anxiety-like behaviors of Cdkl5 -/Y mice. Depressive-like behaviors and social interaction of Cdkl5 -/Y mice were uniquely altered. The contextual and cued fear conditioning of Cdkl5 -/Y mice were comparable to control mice; however, Cdkl5 -/Y mice showed a significantly increased freezing time and a significantly decreased distance traveled during the pretone period in the altered context. Both acquisition and long-term retention of spatial reference memory were significantly impaired. The morphometric analysis of hippocampal CA1 pyramidal neurons revealed impaired dendritic arborization and immature spine development in Cdkl5 -/Y mice. These results indicate that CDKL5 plays significant roles in regulating emotional behaviors especially on anxiety- and fear-related responses, and in both acquisition and long-term retention of spatial reference memory, which suggests that focus and special attention should be paid to the
Comprehensive behavioral analysis of the Cdkl5 knockout mice revealed significant enhancement in anxiety- and fear-related behaviors and impairment in both acquisition and long-term retention of spatial reference memory.
Full Text Available Mutations in the Cyclin-dependent kinase-like 5 (CDKL5 gene cause severe neurodevelopmental disorders. Recently we have generated Cdkl5 KO mice by targeting exon 2 on the C57BL/6N background, and demonstrated postsynaptic overaccumulation of GluN2B-containing N-methyl-D-aspartate (NMDA receptors in the hippocampus. In the current study, we subjected the Cdkl5 KO mice to a battery of comprehensive behavioral tests, aiming to reveal the effects of loss of CDKL5 in a whole perspective of motor, emotional, social, and cognition/memory functions, and to identify its undetermined roles. The neurological screen, rotarod, hot plate, prepulse inhibition, light/dark transition, open field, elevated plus maze, Porsolt forced swim, tail suspension, one-chamber and three-chamber social interaction, 24-h home cage monitoring, contextual and cued fear conditioning, Barnes maze, and T-maze tests were applied on adult Cdkl5 -/Y and +/Y mice. Cdkl5 -/Y mice showed a mild alteration in the gait. Analyses of emotional behaviors revealed significantly enhanced anxiety-like behaviors of Cdkl5 -/Y mice. Depressive-like behaviors and social interaction of Cdkl5 -/Y mice were uniquely altered. The contextual and cued fear conditioning of Cdkl5 -/Y mice were comparable to control mice; however, Cdkl5 -/Y mice showed a significantly increased freezing time and a significantly decreased distance traveled during the pretone period in the altered context. Both acquisition and long-term retention of spatial reference memory were significantly impaired. The morphometric analysis of hippocampal CA1 pyramidal neurons revealed impaired dendritic arborization and immature spine development in Cdkl5 -/Y mice. These results indicate that CDKL5 plays significant roles in regulating emotional behaviors especially on anxiety- and fear-related responses, and in both acquisition and long-term retention of spatial reference memory, which suggests that focus and special attention should be
Comprehensive behavioral analysis of the Cdkl5 knockout mice revealed significant enhancement in anxiety- and fear-related behaviors and impairment in both acquisition and long-term retention of spatial reference memory
Okuda, Kosuke; Takao, Keizo; Watanabe, Aya; Miyakawa, Tsuyoshi; Mizuguchi, Masashi
Mutations in the Cyclin-dependent kinase-like 5 (CDKL5) gene cause severe neurodevelopmental disorders. Recently we have generated Cdkl5 KO mice by targeting exon 2 on the C57BL/6N background, and demonstrated postsynaptic overaccumulation of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors in the hippocampus. In the current study, we subjected the Cdkl5 KO mice to a battery of comprehensive behavioral tests, aiming to reveal the effects of loss of CDKL5 in a whole perspective of motor, emotional, social, and cognition/memory functions, and to identify its undetermined roles. The neurological screen, rotarod, hot plate, prepulse inhibition, light/dark transition, open field, elevated plus maze, Porsolt forced swim, tail suspension, one-chamber and three-chamber social interaction, 24-h home cage monitoring, contextual and cued fear conditioning, Barnes maze, and T-maze tests were applied on adult Cdkl5 -/Y and +/Y mice. Cdkl5 -/Y mice showed a mild alteration in the gait. Analyses of emotional behaviors revealed significantly enhanced anxiety-like behaviors of Cdkl5 -/Y mice. Depressive-like behaviors and social interaction of Cdkl5 -/Y mice were uniquely altered. The contextual and cued fear conditioning of Cdkl5 -/Y mice were comparable to control mice; however, Cdkl5 -/Y mice showed a significantly increased freezing time and a significantly decreased distance traveled during the pretone period in the altered context. Both acquisition and long-term retention of spatial reference memory were significantly impaired. The morphometric analysis of hippocampal CA1 pyramidal neurons revealed impaired dendritic arborization and immature spine development in Cdkl5 -/Y mice. These results indicate that CDKL5 plays significant roles in regulating emotional behaviors especially on anxiety- and fear-related responses, and in both acquisition and long-term retention of spatial reference memory, which suggests that focus and special attention should be paid to the
Russell, Paul Swamidhas Sudhakar; Nair, M K C; Chandra, Abhiram; Subramaniam, Vinod Shanmukham; Bincymol, K; George, Babu; Samuel, Beulah
The risk of suicidal behavior associated with Anxiety Disorders (AD) among adolescents is known. However, concurrent mood disorders complicate these findings, and no data is available from India as well as from the community. This study aimed to address the suicidal risk associated with AD from different perspectives. The authors prospectively collected data for 500 adolescents in a community with independent, trained raters. Risk for suicidal behavior was measured with SADPERSONS scale, socio-economic status with Modified Kuppuswamy Scale, depression and anxiety disorders with Beck Depression Inventory and Screen for Child Anxiety Related Emotional Disorders respectively. The relationship between predictors and need for preventive action was analyzed with univariate and multivariate regression analyses and a predictive model was built. Suicidal behavior was increased by the presence of AD (adjusted OR = 6.28), the number of co-morbid AD (adjusted OR = 2.04), severity of the AD (adjusted OR = 4.98). Being a boy increased the risk of suicidal behavior associated with AD (adjusted OR = 9.37), Generalized Anxiety Disorder (adjusted OR = 5.65), Separation Anxiety Disorder (unadjusted OR = 3.28), Social Anxiety Disorder (unadjusted OR = 5.91) while controlling for the confounding effect of Depressive Disorder. Gender did not have an influence on Panic Disorder. Presence of AD and co-morbid Depressive Disorder significantly contributed to a risk model for suicidal behavior. Anxiety Disorder is associated with the risk for potential suicidal behavior. Adolescent boys with AD and Depressive Disorder need to be identified as the high risk group for suicide prevention in the community.
Edinger, Kassandra L; Frye, Cheryl A
Testosterone (T) and its 5alpha-reduced metabolite, dihydrotestosterone (DHT), can decrease anxiety-like behavior; however, the mechanisms underlying these effects have not been established. First, we hypothesized that if T reduces anxiety-like behavior through actions of its 5alpha-reduced metabolite, DHT, then gonadectomy (GDX) would increase anxiety-like behavior, an effect which would be reversed by systemic administration of DHT. Second, we hypothesized that if T and DHT reduce anxiety-like behavior in part through actions at intracellular androgen receptors in the hippocampus, then administration of an androgen receptor antagonist, flutamide, directly to the hippocampus should increase anxiety-like behavior of intact and DHT-replaced, but not GDX, male rats. Inserts that were empty or contained flutamide were applied directly to the dorsal hippocampus of intact, GDX, or GDX and DHT-replaced rats 2 h prior to testing in the open field, elevated plus maze, or defensive freezing tasks. GDX rats exhibited significantly more anxiety-like behaviors than intact or DHT-replaced rats. Intact and DHT-replaced rats administered flutamide to the hippocampus showed significantly more anxiety-like behavior than did intact and DHT-replaced controls. However, flutamide alone did not increase anxiety-like behavior of GDX rats. Together, these findings suggest that androgens can decrease anxiety-like behavior of male rats in part through DHT's actions at androgen receptors in the hippocampus.
Kumar, Anil; Goyal, Richa
Hypoxia is an environmental stressor that is known to elicit alterations in both the autonomic nervous system and endocrine functions. The free radical or oxidative stress theory holds that oxidative reactions are mainly underlying neurodegenerative disorders. In fact among complex metabolic reactions occurring during hypoxia, many could be related to the formation of oxygen derived free radicals, causing a wide spectrum of cell damage. In present study, we investigated possible involvement of GABAergic mechanism in the protective effect of zolpidem against acute hypoxia-induced behavioral modification and biochemical alterations in mice. Mice were subjected to acute hypoxic stress for a period of 2 h. Acute hypoxic stress for 2 h caused significant impairment in locomotor activity, anxiety-like behavior, and antinocioceptive effect in mice. Biochemical analysis revealed a significant increased malondialdehyde, nitrite concentrations and depleted reduced glutathione and catalase levels. Pretreatment with zolpidem (5 and 10 mg/kg, i.p.) significantly improved locomotor activity, anti-anxiety effect, reduced tail flick latency and attenuated oxidative damage (reduced malondialdehyde, nitrite concentration, and restoration of reduced glutathione and catalase levels) as compared to stressed control (hypoxia) (P zolpidem (5 mg/kg) was blocked significantly by picrotoxin (1.0 mg/kg) or flumazenil (2 mg/kg) and potentiated by muscimol (0.05 mg/kg) in hypoxic animals (P zolpidem (5 mg/kg) per se (P zolpidem against hypoxic stress.
GABA-BZD Receptor Modulating Mechanism of Panax quinquefolius against 72-h Sleep Deprivation Induced Anxiety like Behavior: Possible Roles of Oxidative Stress, Mitochondrial Dysfunction and Neuroinflammation
Chanana, Priyanka; Kumar, Anil
Rationale: Panax quinquefolius (American Ginseng) is known for its therapeutic potential against various neurological disorders, but its plausible mechanism of action still remains undeciphered. GABA (Gamma Amino Butyric Acid) plays an important role in sleep wake cycle homeostasis. Thus, there exists rationale in exploring the GABA-ergic potential of Panax quinquefolius as neuroprotective strategy in sleep deprivation induced secondary neurological problems. Objective: The present study was designed to explore the possible GABA-ergic mechanism in the neuro-protective effect of Panax quinquefolius against 72-h sleep deprivation induced anxiety like behavior, oxidative stress, mitochondrial dysfunction, HPA-axis activation and neuroinflammation. Materials and Methods: Male laca mice were sleep deprived for 72-h by using Grid suspended over water method. Panax quinquefolius (American Ginseng 50, 100, and 200 mg/kg) was administered alone and in combination with GABA modulators (GABA Cl− channel inhibitor, GABA-benzodiazepine receptor inhibitor and GABAA agonist) for 8 days, starting 5 days prior to 72-h sleep deprivation period. Various behavioral (locomotor activity, mirror chamber test), biochemical (lipid peroxidation, reduced glutathione, catalase, nitrite levels), mitochondrial complexes, neuroinflammation marker (Tumor Necrosis Factor, TNF-alpha), serum corticosterone, and histopathological sections of brains were assessed. Results: Seventy two hours sleep deprivation significantly impaired locomotor activity, caused anxiety-like behavior, conditions of oxidative stress, alterations in mitochondrial enzyme complex activities, raised serum corticosterone levels, brain TNFα levels and led to neuroinflammation like signs in discrete brain areas as compared to naive group. Panax quinquefolius (100 and 200 mg/kg) treatment restored the behavioral, biochemical, mitochondrial, molecular and histopathological alterations. Pre-treatment of GABA Cl− channel
White, Emily K; Warren, Cortney S
Social anxiety and eating pathology frequently co-occur. However, there is limited research examining the relationship between anxiety and body checking, aside from one study in which social physique anxiety partially mediated the relationship between body checking cognitions and body checking behavior (Haase, Mountford, & Waller, 2007). In an independent sample of 567 college women, we tested the fit of Haase and colleagues' foundational model but did not find evidence of mediation. Thus we tested the fit of an expanded path model that included eating pathology and clinical impairment. In the best-fitting path model (CFI=.991; RMSEA=.083) eating pathology and social physique anxiety positively predicted body checking, and body checking positively predicted clinical impairment. Therefore, women who endorse social physique anxiety may be more likely to engage in body checking behaviors and experience impaired psychosocial functioning. Published by Elsevier Ltd.
Tokunaga, Mari; Ida, Ituro; Mikuni, Masahiko; Higuchi, Teruhiko.
123 I-iomazenil (IMZ), a newly developed radioligand which acts on benzodiazepine receptors (BZR) as a partial inverse agonist, made it possible to evaluate the function of central BZR by single photon emission tomography (SPECT). To examine the alterations of the binding potential (BP) in the anxiety state, 123 I-IMZ SPECT was performed in five patients with anxiety and somatoform disorders, and five epileptic patients without anxiety symptoms served as a reference. The BP of BZR was determined by using a table look-up procedure based on a three-compartment, two-parameter model in the bilateral superior frontal, inferior frontal, temporal, parietal, occipital, and cerebellar cortex. The mean BP of patients with anxiety and somatoform disorders was significantly decreased in the superior frontal, temporal, and parietal cortex, in comparison with that of epileptic patients. A significant correlation was observed between the anxiety levels scored on the Hamilton anxiety scale and BP in the right temporal cortex and left superior frontal cortex. These changes in BZR revealed by SPECT suggest the usefulness of 123 I-IMZ SPECT to objectively evaluate anxiety levels in patients with anxiety symptoms. (author)
Stoltenberg, Scott F; Christ, Christa C; Carlo, Gustavo
There is growing evidence that the serotonin system influences prosocial behavior. We examined whether anxiety mediated the association between variation in the serotonin transporter gene regulatory region (5-HTTLPR) and prosocial behavior. We collected self-reported tendencies to avoid certain situations and history of helping others using standard instruments and buccal cells for standard 5-HTTLPR genotyping from 398 undergraduate students. Triallelic 5-HTTLPR genotype was significantly associated with prosocial behavior and the effect was partially mediated by social anxiety, such that those carrying the S' allele reported higher levels of social avoidance and lower rates of helping others. These results are consistent with accounts of the role of serotonin on anxiety and prosocial behavior and suggest that targeted efforts to reduce social anxiety in S' allele carriers may enhance prosocial behavior.
In this study, it is aimed to review efficacy of Cognitive Behavioral Therapy (CBT) and Cognitive Behavioral Group Therapy (CBGT) on childhood and adolescence in mood and anxiety disorders. Many researches have shown that cognitive behaviour therapy (CBT) can be effective in the treatment of depression and anxiety in children and adolescents. Child and adolescent depression and anxiety are frequent disorders which may have a recurring and chronic course. PsycINFO, Medline and the Turkish P...
Thomas W Elston
Full Text Available There is a growing community of individuals who self-administer the nootropic aniracetam for its purported cognitive enhancing effects. Aniracetam is believed to be therapeutically useful for enhancing cognition, alleviating anxiety, and treating various neurodegenerative conditions. Physiologically, aniracetam enhances both glutamatergic neurotransmission and long-term potentiation. Previous studies of aniracetam have demonstrated the cognition-restoring effects of acute administration in different models of disease. No previous studies have explored the effects of aniracetam in healthy subjects. We investigated whether daily 50 mg/kg oral administration improves cognitive performance in naïve C57BL/6J mice in a variety of aspects of cognitive behavior. We measured spatial learning in the Morris water maze test; associative learning in the fear conditioning test; motor learning in the accelerating rotarod test; and odor discrimination. We also measured locomotion in the open field test, anxiety through the elevated plus maze test and by measuring time in the center of the open field test. We measured repetitive behavior through the marble burying test. We detected no significant differences between the naive, placebo, and experimental groups across all measures. Despite several studies demonstrating efficacy in impaired subjects, our findings suggest that aniracetam does not alter behavior in normal healthy mice. This study is timely in light of the growing community of healthy humans self-administering nootropic drugs.
Elston, Thomas W.; Pandian, Ashvini; Smith, Gregory D.; Holley, Andrew J.; Gao, Nanjing; Lugo, Joaquin N.
There is a growing community of individuals who self-administer the nootropic aniracetam for its purported cognitive enhancing effects. Aniracetam is believed to be therapeutically useful for enhancing cognition, alleviating anxiety, and treating various neurodegenerative conditions. Physiologically, aniracetam enhances both glutamatergic neurotransmission and long-term potentiation. Previous studies of aniracetam have demonstrated the cognition-restoring effects of acute administration in different models of disease. No previous studies have explored the effects of aniracetam in healthy subjects. We investigated whether daily 50 mg/kg oral administration improves cognitive performance in naïve C57BL/6J mice in a variety of aspects of cognitive behavior. We measured spatial learning in the Morris water maze test; associative learning in the fear conditioning test; motor learning in the accelerating rotarod test; and odor discrimination. We also measured locomotion in the open field test, anxiety through the elevated plus maze test and by measuring time in the center of the open field test. We measured repetitive behavior through the marble burying test. We detected no significant differences between the naive, placebo, and experimental groups across all measures. Despite several studies demonstrating efficacy in impaired subjects, our findings suggest that aniracetam does not alter behavior in normal healthy mice. This study is timely in light of the growing community of healthy humans self-administering nootropic drugs. PMID:25099639
Heshmati, Mitra; Golden, Sam A; Pfau, Madeline L; Christoffel, Daniel J; Seeley, Elena L; Cahill, Michael E; Khibnik, Lena A; Russo, Scott J
Mefloquine continues to be a key drug used for malaria chemoprophylaxis and treatment, despite reports of adverse events like depression and anxiety. It is unknown how mefloquine acts within the central nervous system to cause depression and anxiety or why some individuals are more vulnerable. We show that intraperitoneal injection of mefloquine in mice, when coupled to subthreshold social defeat stress, is sufficient to produce depression-like social avoidance behavior. Direct infusion of mefloquine into the nucleus accumbens (NAc), a key brain reward region, increased stress-induced social avoidance and anxiety behavior. In contrast, infusion into the ventral hippocampus had no effect. Whole cell recordings from NAc medium spiny neurons indicated that mefloquine application increases the frequency of spontaneous excitatory postsynaptic currents, a synaptic adaptation that we have previously shown to be associated with increased susceptibility to social defeat stress. Together, these data demonstrate a role for the NAc in mefloquine-induced depression and anxiety-like behaviors. Copyright © 2015 Elsevier Ltd. All rights reserved.
Pinjarkar, Ravikant G; Sudhir, Paulomi M; Math, Suresh Bada
Context: Cognitive behavior therapy (CBT) is the treatment of choice in anxiety disorders. However, there is little evidence for the effectiveness brief CBT in social anxiety. Aims: We examined the effectiveness of a brief CBT of six sessions in patients with social anxiety disorder. Settings and Design: A single case design study baseline; post and 1 month follow-up was adopted. Materials and Methods: Seven patients with a DSM IV diagnosis of social anxiety underwent 6 weekly sessions of bri...
Inui, A; Okita, M; Nakajima, M; Momose, K; Ueno, N; Teranishi, A; Miura, M; Hirosue, Y; Sano, K; Sato, M; Watanabe, M; Sakai, T; Watanabe, T; Ishida, K; Silver, J; Baba, S; Kasuga, M
Neuropeptide Y (NPY), one of the most abundant peptide transmitters in the mammalian brain, is assumed to play an important role in behavior and its disorders. To understand the long-term modulation of neuronal functions by NPY, we raised transgenic mice created with a novel central nervous system (CNS) neuron-specific expression vector of human Thy- gene fragment linked to mouse NPY cDNA. In situ hybridization analysis demonstrated transgene-derived NPY expression in neurons (e.g., in the hippocampus, cerebral cortex, and the arcuate nucleus of the hypothalamus) in the transgenic mice. The modest increase of NPY protein in the brain was demonstrated by semiquantitative immunohistochemical analysis and by radioreceptor assay (115% in transgenic mice compared to control littermates). Double-staining experiments indicated colocalization of the transgene-derived NPY message and NPY protein in the same neurons, such as in the arcuate nucleus. The transgenic mice displayed behavioral signs of anxiety and hypertrophy of adrenal zona fasciculata cells, but no change in food intake was observed. The anxiety-like behavior of transgenic mice was reversed, at least in part, by administration of corticotropin-releasing factor (CRF) antagonists, alpha-helical CRF9-41, into the third cerebral ventricle. These results suggest that NPY has a role in anxiety and behavioral responses to stress partly via the CRF neuronal system. This genetic model may provide a unique opportunity to study human anxiety and emotional disorders.
Katayama, K; Yamada, K; Ornthanalai, V G; Inoue, T; Ota, M; Murphy, N P; Aruga, J
Mutations in SLITRK1 are found in patients with Tourette's syndrome and trichotillomania. SLITRK1 encodes a transmembrane protein containing leucine-rich repeats that is produced predominantly in the nervous system. However, the role of this protein is largely unknown, except that it can modulate neurite outgrowth in vitro. To clarify the role of Slitrk1 in vivo, we developed Slitrk1-knockout mice and analyzed their behavioral and neurochemical phenotypes. Slitrk1-deficient mice exhibited elevated anxiety-like behavior in the elevated plus-maze test as well as increased immobility time in forced swimming and tail suspension tests. Neurochemical analysis revealed that Slitrk1-knockout mice had increased levels of norepinephrine and its metabolite 3-methoxy-4-hydroxyphenylglycol. Administration of clonidine, an alpha2-adrenergic agonist that is frequently used to treat patients with Tourette's syndrome, attenuated the anxiety-like behavior of Slitrk1-deficient mice in the elevated plus-maze test. These results lead us to conclude that noradrenergic mechanisms are involved in the behavioral abnormalities of Slitrk1-deficient mice. Elevated anxiety due to Slitrk1 dysfunction may contribute to the pathogenesis of neuropsychiatric diseases such as Tourette's syndrome and trichotillomania.
Wangsiriwech, Tawatchai; Pisitsungkagarn, Kullaya; Jarukasemthawee, Somboon
With its high prevalence and debilitating impact on students, math anxiety is well studied within the educational context. However, the problem has yet to be examined from the psychological perspective, which is necessary in order to produce a more comprehensive perspective and to pave the way for therapeutic intervention. The current study, therefore, was conducted to identify cognitive and behavioral factors relevant to the occurrence and maintenance of math anxiety. Data were collected from 300 grade 9 students (150 females and 150 males) from public and private schools in Bangkok, Thailand. Participants responded to the measures of math anxiety, negative math beliefs, negative math appraisals and math avoidance. Structural equation modeling was conducted. Model fit indices obtained consistently suggested the good fitness of the model to the data [e.g. χ2/df = 0.42, root mean square error of approximation (RMSEA) = 0.00]. Negative math beliefs, negative math appraisals and math avoidance had a significant direct effect on math anxiety. Additionally, the indirect effect of negative math appraisal was observed between negative math beliefs and math anxiety. In summary, the proposed model accounted for 84.5% of the variance in the anxiety. The findings are discussed with particular focus on implications for therapeutic intervention for math anxiety.
Nieuwenhuys, A.; Oudejans, R.R.D.
The current pilot study aimed at providing an initial assessment of how anxiety influences police officers' shooting behavior. Seven police officers participated and completed an identical shooting exercise under two experimental conditions: low anxiety, against a non-threatening opponent, and high
Storch, Eric A; Nadeau, Joshua M; Johnco, Carly; Timpano, Kiara; McBride, Nicole; Jane Mutch, P; Lewin, Adam B; Murphy, Tanya K
This study examined the nature and correlates of hoarding among youth with autism spectrum disorders (ASD). Forty children with ASD and a comorbid anxiety disorder were administered a battery of clinician-administered measures assessing presence of psychiatric disorders and anxiety severity. Parents completed questionnaires related to child hoarding behaviors, social responsiveness, internalizing and externalizing behaviors, and functional impairment. We examined the impact of hoarding behaviors on treatment response in a subsample of twenty-six youth who completed a course of personalized cognitive-behavioral therapy targeting anxiety symptoms. Hoarding symptoms were common and occurred in a clinically significant manner in approximately 25 % of cases. Overall hoarding severity was associated with increased internalizing and anxiety/depressive symptoms, externalizing behavior, and attention problems. Discarding items was associated with internalizing and anxious/depressive symptoms, but acquisition was not. Hoarding decreased following cognitive-behavioral therapy but did not differ between treatment responders and non-responders. These data are among the first to examine hoarding among youth with ASD; implications of study findings and future directions are highlighted.
Guarraci, Fay A; Gonzalez, Chantal M F; Lucero, Devon; Womble, Paige D; Abdel-Rahim, Heba; DeVore, Jennie; Kunkel, Marcela Nicole; Quadlander, Emma; Stinnett, Morgan; Boyette-Davis, Jessica
The present study characterized the effects of ketamine on sexual behavior and anxiety in female rats. In Experiment 1, female subjects received an injection of ketamine (10.0mg/kg) or saline 30min prior to a sexual partner-preference test during which each female subject was given the opportunity to interact with a female stimulus or a sexually vigorous male stimulus. Immediately afterwards, female subjects were tested for locomotion in an open field test. Ketamine-treated subjects spent significantly more time with the male stimulus than saline-treated subjects. No other measures of mating behavior (i.e., paced mating behavior, lordosis) were affected by ketamine. Ketamine also had no effect on locomotion. In Experiment 2, female subjects received an injection of ketamine (10.0mg/kg), or saline daily for 10days to investigate the possibility that sexual dysfunction emerges only after repeated exposure. Similar to the results of Experiment 1, ketamine-treated subjects spent significantly more time with the male stimulus than saline-treated subjects. Chronic ketamine treatment also decreased the likelihood of leaving the male after mounts, without affecting any other measures of sexual behavior. Chronic ketamine had no effect on locomotion. In Experiment 3, female subjects received an injection of ketamine (10.0mg/kg) or saline and were tested for anxiety in an elevated plus maze test and for locomotion in an open field test. Acute ketamine had no effect on anxiety or locomotion. In Experiment 4, female subjects received an injection of ketamine (10.0mg/kg) or saline daily for 10days to investigate the possibility that anxiety emerges only after repeated exposure. Chronic ketamine exposure had no effect on any measure of anxiety. However, chronic ketamine exposure increased locomotion. The results from these experiments indicate that unlike other medications prescribed for depression, neither acute nor chronic ketamine treatment causes anxiety or disruption of
Vreeke, Leonie J; Muris, Peter; Mayer, Birgit; Huijding, Jorg; Rapee, Ronald M
This study examined behavioral inhibition and overprotective parenting as correlates and predictors of anxiety disorder symptoms in preschoolers with a multi-cultural background (N=168). Parents of 3- to 6-year-old children completed a set of questionnaires twice, 12 months apart. Parents were also interviewed with the Anxiety Disorders Interview Schedule for DSM-IV at the 12-month point to assess the clinical severity of children's anxiety symptoms. Behavioral inhibition consistently emerged as a significant concurrent correlate of anxiety symptoms and this was particularly true for social anxiety symptoms. Overprotective parenting also emerged as a significant correlate of anxiety, but only in the case of non-social anxiety symptoms and mainly in non-native Dutch children. Prospective analyses revealed that behavioral inhibition was a significant predictor of social anxiety symptoms, while overprotective parenting did not explain significant variance in the development of children's anxiety over time. The support for an interactive effect of behavioral inhibition and overprotective parenting was unconvincing. Finally, it was found that children who exhibited stable high levels of behavioral inhibition throughout the study ran the greatest risk for developing an anxiety disorder. Copyright © 2013 Elsevier Ltd. All rights reserved.
Villarosa, Margo C; Moorer, Kayla D; Madson, Michael B; Zeigler-Hill, Virgil; Noble, Jeremy J
The link between social anxiety and alcohol-related negative consequences among college students has been well documented. Protective behavioral strategies are cognitive-behavioral strategies that college students use in an effort to reduce harm while they are drinking. In the current study we examined the mediating role of the 2 categories of protective behavioral strategies (i.e., controlled consumption and serious harm reduction) in the relationship that social anxiety symptoms have with alcohol-related negative consequences. Participants were 572 undergraduates who completed measures of social anxiety, alcohol use, negative consequences of alcohol use, and protective behavioral strategy use. Only serious harm reduction strategies emerged as a mediator of the association that social anxiety symptoms had with alcohol-related negative consequences. Clinical and research implications are discussed.
Wu, Sarah S.; Willcutt, Erik G.; Escovar, Emily; Menon, Vinod
Although behavioral difficulties are well documented in reading disabilities, little is known about the relationship between math ability and internalizing and externalizing behaviors. Here, we use standardized measures to investigate the relation among early math ability, math anxiety, and internalizing and externalizing behaviors in a group of…
Lundervold, Duane A.; Pahwa, Rajesh; Lyons, Kelly E.
Effects of brief Behavioral Relaxation Training (BRT) on anxiety and dyskinesia of a 57-year-old female, with an 11-year history of Parkinson's disease (PD) and 18-months post-deep brain stimulation of the subthalamic nucleus, were evaluated. Multiple process and outcome measures were used including the Clinical Anxiety Scale (CAS), Subjective…
Levita, Liat; Salas Duhne, Paulina Gonzalez; Girling, Carla; Waller, Glenn
Psychological therapists commonly fail to adhere to treatment protocols in everyday clinical practice. In part, this pattern of drift is attributable to anxious therapists being less likely to undertake some elements of evidence-based therapies - particularly the exposure-based elements. This study considers what facets of anxiety (cognitive, behavioral, physiological) are related to junior clinicians' reported use of cognitive-behavioral therapy techniques. Thirty-two clinicians (mean age = 28.9 years; mean length of CBT experience = 1.5 years; 23 female, nine male) who offered CBT were assessed for their cognitive, behavioral and physiological characteristics (Intolerance of Uncertainty scale; risk taking; skin conductance response and heart rate variability). While the three different facets of anxiety were relatively poorly associated with each other, as is usual in this literature, each facet was linked differently to the reported delivery of CBT techniques (P behavioral or cognitive methods. Of the three facets of anxiety, only physiological reactivity showed an association with the clinicians' temporal characteristics, with more experienced therapists being more likely to have greater skin conductance responses to positive and negative outcomes. These findings suggest that clinicians who are more anxious are less likely to deliver the full evidence-based form of CBT and to focus instead on less challenging elements of the therapy. Potential ways of overcoming this limitation are discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.
Crişan, Liviu G.; Vulturar, Romana; Miclea, Mircea; Miu, Andrei C.
Recent research indicates that subclinical social anxiety is associated with dysfunctions at multiple psychological and biological levels, in a manner that seems reminiscent of social anxiety disorder (SAD). This study aimed to describe multidimensional responses to laboratory-induced social stress in an analog sample selected for social anxiety symptoms. State anxiety, cognitive biases related to negative social evaluation, speech anxiety behaviors, and cortisol reactivity were assessed in t...
Stjerneklar, Silke; Hougaard, Esben; Nielsen, Amalie D.
Background: Cognitive behavioral therapy (CBT) is a well-documented effective method for the treatment of anxiety disorders in children and adolescents. While internet based CBT (ICBT) programs for adults have been widely investigated, research on ICBT programs for anxiety disorders in youth...
Sagarkar, Sneha; Bhamburkar, Tanmayi; Shelkar, Gajanan; Choudhary, Amit; Kokare, Dadasaheb M; Sakharkar, Amul J
Minimal traumatic brain injury (MTBI) often transforms into chronic neuropsychiatric conditions including anxiety, the underlying mechanisms of which are largely unknown. In the present study, we employed the closed-head injury paradigm to induce MTBI in rats and examined whether DNA methylation can explain long-term changes in the expression of the brain-derived neurotrophic factor (BDNF) in the amygdala as well as trauma-induced anxiety-like behaviors. The MTBI caused anxiety-like behaviors and altered the expression of DNA methyltransferase (DNMT) isoforms (DNMT1, DNMT3a, and DNMT3b) and factors involved in DNA demethylation such as the growth arrest and DNA damage 45 (GADD45a and GADD45b). After 30days of MTBI, the over-expression of DNMT3a and DNMT3b corresponded to heightened DNMT activity, whereas the mRNA levels of GADD45a and GADD45b were declined. The methylated cytosine levels at the BDNF promoters (Ip, IVp and IXp) were increased in the amygdala of the trauma-induced animals; these coincided negatively with the mRNA levels of exon IV and IXa, but not of exon I. Interestingly, treatment with 5-azacytidine, a pan DNMT inhibitor, normalized the MTBI-induced DNMT activity and DNA hypermethylation at exon IVp and IXp. Furthermore, 5-azacytidine also corrected the deficits in the expression of exons IV and IXa and reduced the anxiety-like behaviors. These results suggest that the DNMT-mediated DNA methylation at the BDNF IVp and IXp might be involved in the regulation of BDNF gene expression in the amygdala. Further, it could also be related to MTBI-induced anxiety-like behaviors via the regulation of synaptic plasticity. Copyright © 2017 Elsevier Inc. All rights reserved.
Bali, Anjana; Jaggi, Amteshwar Singh
Ghrelin is orexigenic hormone primarily synthesized by endocrine X/A-like cells of gastric oxyntic mucosa to stimulate appetite and food intake along with regulation of growth hormone and insulin secretion; glucose and lipid metabolism; gastrointestinal motility; blood pressure, heart rate and neurogenesis. Furthermore, peripherally (after crossing the blood brain barrier) as well as centrally synthesized ghrelin (in the hypothalamus) regulates diverse functions of central nervous system including stress-associated behavioral functions. Exposure to stress alters the ghrelin levels and alteration in ghrelin levels significantly affects neuro-endocrinological parameters; metabolism-related physiology, behavior and mood. Studies have shown both anxiolytic and anxiogenic role of ghrelin suggesting its dual role in modulating anxiety-related behavior. However, it is proposed that increase in ghrelin levels during stress condition is an endogenous stress coping behavior and increased ghrelin levels may be required to prevent excessive anxiety. In preclinical and clinical studies, an elevation in ghrelin levels during depression has been correlated with their antidepressant activities. Ghrelin-induced modulation of stress and associated conditions has been linked to alteration in hypothalamic-pituitary-adrenal (HPA) axis; autonomic nervous system (mainly sympathetic nervous system and serotonergic neurotransmission. A reciprocal relationship has been reported between corticotropin-releasing hormone (CRH) and ghrelin as ghrelin increases the release of CRH, ACTH and corticosteroids; while CRH decreases the expression of ghrelin. Similarly, ghrelin increases the serotonin turnover and in turn, serotonin controls ghrelin signaling to modulate anxiety-related behavior. The present review discusses the dual role of ghrelin in stress and related behavioral disorders along with possible mechanisms.
Gail A Alvares
Full Text Available Social anxiety disorder is characterized by excessive fear and habitual avoidance of social situations. Decision-making models suggest that patients with anxiety disorders may fail to exhibit goal-directed control over actions. We therefore investigated whether such biases may also be associated with social anxiety and to examine the relationship between such behavior with outcomes from cognitive-behavioral therapy. Patients diagnosed with social anxiety and controls completed an instrumental learning task in which two actions were performed to earn food outcomes. After outcome devaluation, where one outcome was consumed to satiety, participants were re-tested in extinction. Results indicated that, as expected, controls were goal-directed, selectively reducing responding on the action that previously delivered the devalued outcome. Patients with social anxiety, however, exhibited no difference in responding on either action. This loss of a devaluation effect was associated with greater symptom severity and poorer response to therapy. These findings indicate that variations in goal-directed control in social anxiety may represent both a behavioral endophenotype and may be used to predict individuals who will respond to learning-based therapies.
Shahnavaz, S; Hedman, E; Grindefjord, M; Reuterskiöld, L; Dahllöf, G
Dental anxiety affects approximately 9% of children and is associated with poor oral health, pain, and psychosocial problems. The objective of this study was to investigate the efficacy of cognitive behavioral therapy (CBT) for children with dental anxiety in specialist pediatric dentistry. The study used a parallel-group superiority randomized controlled trial design. The primary outcome measure was the behavioral avoidance test; assessors were blind to treatment allocation. Participants were 8 boys and 22 girls 7 to 18 y old (mean ± SD, 10 ± 3.1). Children fulfilling the diagnostic criteria for dental anxiety were randomized to CBT (n = 13) or treatment as usual (n = 17), such as various sedation methods. Psychologists provided 10 h of CBT based on a treatment manual. Treatments were conducted in a naturalistic real-world clinical setting. Assessments were conducted before the treatment, 3 mo after the start of treatment, and at 1-y follow-up. The analyses of the primary outcome measure by repeated-measures analysis of variance and independent t test showed that children receiving CBT made superior, statistically significant improvements at follow-up (16.8 ± 2.4) compared with treatment as usual (11.4 ± 3.1, P Knowledge transfer statement: The results of this study can be used by decision makers and clinicians when planning to implement evidence-based treatment in pediatric dentistry and give children and adolescents access to methods for treating dental anxiety. The results can also be used by parents of children with dental anxiety when asking dentists to cooperate with psychologists using cognitive behavioral therapy.
Kysil, Elana V; Meshalkina, Darya A; Frick, Erin E; Echevarria, David J; Rosemberg, Denis B; Maximino, Caio; Lima, Monica Gomes; Abreu, Murilo S; Giacomini, Ana C; Barcellos, Leonardo J G; Song, Cai; Kalueff, Allan V
Modeling of stress and anxiety in adult zebrafish (Danio rerio) is increasingly utilized in neuroscience research and central nervous system (CNS) drug discovery. Representing the most commonly used zebrafish anxiety models, the novel tank test (NTT) focuses on zebrafish diving in response to potentially threatening stimuli, whereas the light-dark test (LDT) is based on fish scototaxis (innate preference for dark vs. bright areas). Here, we systematically evaluate the utility of these two tests, combining meta-analyses of published literature with comparative in vivo behavioral and whole-body endocrine (cortisol) testing. Overall, the NTT and LDT behaviors demonstrate a generally good cross-test correlation in vivo, whereas meta-analyses of published literature show that both tests have similar sensitivity to zebrafish anxiety-like states. Finally, NTT evokes higher levels of cortisol, likely representing a more stressful procedure than LDT. Collectively, our study reappraises NTT and LDT for studying anxiety-like states in zebrafish, and emphasizes their developing utility for neurobehavioral research. These findings can help optimize drug screening procedures by choosing more appropriate models for testing anxiolytic or anxiogenic drugs.
Villarosa-Hurlocker, Margo C; Whitley, Robert B; Capron, Daniel W; Madson, Michael B
College students with social anxiety disorder experience more alcohol-related negative consequences, regardless of the amount of alcohol they consume. Social anxiety refers to psychological distress and physiological arousal in social situations due to an excessive fear of negative evaluation by others. The current study examined within-group differences in alcohol-related negative consequences of students who met or exceeded clinically-indicated social anxiety symptoms. In particular, we tested a sequential mediation model of the cognitive (i.e., fear of negative evaluation) and behavioral (protective behavioral strategies) mechanisms for the link between social anxiety disorder subtypes (i.e., interaction and performance-type) and alcohol-related negative consequences. Participants were 412 traditional-age college student drinkers who met or exceeded the clinically-indicated threshold for social anxiety disorder and completed measures of fear of negative evaluation, protective behavioral strategies (controlled consumption and serious harm reduction), and alcohol-related negative consequences. Fear of negative evaluation and serious harm reduction strategies sequentially accounted for the relationship between interaction social anxiety disorder and alcohol-related negative consequences, such that students with more severe interaction social anxiety symptoms reported more fear of negative evaluation, which was related to more serious harm reduction strategies, which predicted fewer alcohol-related negative consequences. Future directions and implications are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.
Storch, Eric A; Zavrou, Sophia; Collier, Amanda B; Ung, Danielle; Arnold, Elysse B; Mutch, P Jane; Lewin, Adam B; Murphy, Tanya K
Anxiety symptoms are common in youth with autism spectrum disorders (ASD) and directly associated with symptom severity and functional impairment. Family accommodation occurs frequently among individuals with obsessive-compulsive and anxiety disorders; to date, no data exist on the nature and correlates of family accommodation in youth with ASD and anxiety, as well as its relationship to cognitive-behavioral therapy outcome. Forty children with ASD and a comorbid anxiety disorder participated. Clinicians administered measures of ASD and anxiety disorder caseness, anxiety symptom severity, and family accommodation; parents completed questionnaires assessing social responsiveness, internalizing and externalizing behaviors, and functional impairment. A subsample of youth (n = 24) completed a course of cognitive-behavioral therapy. Family accommodation was common and positively correlated with anxiety symptom severity, but not functional impairment, general internalizing symptoms, externalizing behavior, or social responsiveness. Family accommodation decreased following cognitive-behavioral therapy with decreases in family accommodation being associated with decreases in anxiety levels. Treatment responders reported lower family accommodation frequency and lower parent impact relative to non-responders. Clinical implications of this study in assessing and psychotherapeutically treating youth with ASD and comorbid anxiety are discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.
Lundervold, Duane A.; Talley, Chris; Buermann, Michael
Effects of Behavioral Activation Treatment (BAT) on pain anxiety, depression, and pain interference on a 43-year-old female with an 11-year history of chronic fibromyalgia pain are described. Analgesic, anxyiolytic, and antidepressant medications were stabilized prior to participation. Dependent measures were the Behavioral Relaxation Scale, a…
Culotta, Carmen M.; Goldstein, Sara E.
The authors examined how relational aggression, physical aggression, and proactive prosocial behavior were associated with jealousy and social anxiety in a diverse sample of 60 middle school students. After the authors controlled for gender and race, jealousy predicted relational aggression and proactive prosocial behavior, but it did not predict…
Urakawa, Susumu; Takamoto, Kouich; Hori, Etsuro; Sakai, Natsuko; Ono, Taketoshi; Nishijo, Hisao
Early life experiences including physical exercise, sensory stimulation, and social interaction can modulate development of the inhibitory neuronal network and modify various behaviors. In particular, alteration of parvalbumin-expressing neurons, a gamma-aminobutyric acid (GABA)ergic neuronal subpopulation, has been suggested to be associated with psychiatric disorders. Here we investigated whether rearing in enriched environment could modify the expression of parvalbumin-positive neurons in the basolateral amygdala and anxiety-like behavior. Three-week-old male rats were divided into two groups: those reared in an enriched environment (EE rats) and those reared in standard cages (SE rats). After 5 weeks of rearing, the EE rats showed decreased anxiety-like behavior in an open field than the SE rats. Under another anxiogenic situation, in a beam walking test, the EE rats more quickly traversed an elevated narrow beam. Anxiety-like behavior in the open field was significantly and negatively correlated with walking time in the beam-walking test. Immunohistochemical tests revealed that the number of parvalbumin-positive neurons significantly increased in the basolateral amygdala of the EE rats than that of the SE rats, while the number of calbindin-D28k-positive neurons did not change. These parvalbumin-positive neurons had small, rounded soma and co-expressed the glutamate decarboxylase (GAD67). Furthermore, the number of parvalbumin-positive small cells in the basolateral amygdala tended to positively correlate with emergence in the center arena of the open field and negatively correlated with walking time in the beam walking test. Rearing in the enriched environment augmented the number of parvalbumin-containing specific inhibitory neuron in the basolateral amygdala, but not that of calbindin-containing neuronal phenotype. Furthermore, the number of parvalbumin-positive small neurons in the basolateral amygdala was negatively correlated with walking time in the
Díaz, Daniel; Rico-Rosillo, Guadalupe; Vega-Robledo, Gloria Bertha; Zambrano, Elena
Metabolic syndrome (MS) is a cluster of signs that increases the risk to develop diabetes mellitus type 2 and cardiovascular disease. In the last years, a growing interest to study the relationship between MS and psychiatric disorders, such as depression and anxiety, has emerged obtaining conflicting results. Diet-induced MS rat models have only examined the effects of high-fat or mixed cafeteria diets to a limited extent. We explored whether an anxiety-like behavior was associated with MS in non-stressed rats chronically submitted to a high-sucrose diet (20% sucrose in drinking water) using three different anxiety paradigms: the shock-probe/burying test (SPBT), the elevated plus-maze (EPM) and the open-field test (OFT). Behaviorally, the high-sucrose diet group showed an increase in burying behavior in the SPBT. Also, these animals displayed both avoidance to explore the central part of the arena and a significant increase in freezing behavior in the OFT and lack of effects in the EPM. Also, high-sucrose diet group showed signs of an MS-like condition: significant increases in body weight and body mass index, abdominal obesity, hypertension, hyperglycemia, hyperinsulinemia, and dyslipidemia. Plasma leptin and resistin levels were also increased. No changes in plasma corticosterone levels were found. These results indicate that rats under a 24-weeks high-sucrose diet develop an MS associated with an anxiety-like behavior. Although the mechanisms underlying this behavioral outcome remain to be investigated, the role of leptin is emphasized. PMID:28463967
Rudoy, C A; Van Bockstaele, E J
Anxiety has been indicated as one of the main symptoms of the cocaine withdrawal syndrome in human addicts and severe anxiety during withdrawal may potentially contribute to relapse. As alterations in noradrenergic transmission in limbic areas underlie withdrawal symptomatology for many drugs of abuse, the present study sought to determine the effect of cocaine withdrawal on beta-adrenergic receptor (beta(1) and beta(2)) expression in the amygdala. Male Sprague Dawley rats were administered intraperitoneal (i.p.) injections of cocaine (20 mg/kg) once daily for 14 days. Two days following the last cocaine injection, amygdala brain regions were micro-dissected and processed for Western blot analysis. Results showed that beta(1)-adrenergic receptor, but not beta(2)-adrenergic receptor expression was significantly increased in amygdala extracts of cocaine-withdrawn animals as compared to controls. This finding motivated further studies aimed at determining whether treatment with betaxolol, a highly selective beta(1)-adrenergic receptor antagonist, could ameliorate cocaine withdrawal-induced anxiety. In these studies, betaxolol (5 mg/kg via i.p. injection) was administered at 24 and then 44 h following the final chronic cocaine administration. Anxiety-like behavior was evaluated using the elevated plus maze test approximately 2 h following the last betaxolol injection. Following behavioral testing, betaxolol effects on beta(1)-adrenergic receptor protein expression were examined by Western blotting in amygdala extracts from rats undergoing cocaine withdrawal. Animals treated with betaxolol during cocaine withdrawal exhibited a significant attenuation of anxiety-like behavior characterized by increased time spent in the open arms and increased entries into the open arms compared to animals treated with only saline during cocaine withdrawal. In contrast, betaxolol did not produce anxiolytic-like effects in control animals treated chronically with saline. Furthermore
Vahid-Ansari, Faranak; Daigle, Mireille; Manzini, M Chiara; Tanaka, Kenji F; Hen, René; Geddes, Sean D; Béïque, Jean-Claude; James, Jonathan; Merali, Zul; Albert, Paul R
Freud-1/Cc2d1a represses the gene transcription of serotonin-1A (5-HT1A) autoreceptors, which negatively regulate 5-HT tone. To test the role of Freud-1 in vivo , we generated mice with adulthood conditional knock-out of Freud-1 in 5-HT neurons ( cF1ko ). In cF1ko mice, 5-HT1A autoreceptor protein, binding and hypothermia response were increased, with reduced 5-HT content and neuronal activity in the dorsal raphe. The cF1ko mice displayed increased anxiety- and depression-like behavior that was resistant to chronic antidepressant (fluoxetine) treatment. Using conditional Freud-1/5-HT1A double knock-out ( cF1/1A dko ) to disrupt both Freud-1 and 5-HT1A genes in 5-HT neurons, no increase in anxiety- or depression-like behavior was seen upon knock-out of Freud-1 on the 5-HT1A autoreceptor-negative background; rather, a reduction in depression-like behavior emerged. These studies implicate transcriptional dysregulation of 5-HT1A autoreceptors by the repressor Freud-1 in anxiety and depression and provide a clinically relevant genetic model of antidepressant resistance. Targeting specific transcription factors, such as Freud-1, to restore transcriptional balance may augment response to antidepressant treatment. SIGNIFICANCE STATEMENT Altered regulation of the 5-HT1A autoreceptor has been implicated in human anxiety, major depression, suicide, and resistance to antidepressants. This study uniquely identifies a single transcription factor, Freud-1, as crucial for 5-HT1A autoreceptor expression in vivo Disruption of Freud-1 in serotonin neurons in mice links upregulation of 5-HT1A autoreceptors to anxiety/depression-like behavior and provides a new model of antidepressant resistance. Treatment strategies to reestablish transcriptional regulation of 5-HT1A autoreceptors could provide a more robust and sustained antidepressant response. Copyright © 2017 the authors 0270-6474/17/3711967-12$15.00/0.
Boulle, Fabien; Pawluski, Jodi L; Homberg, Judith R; Machiels, Barbie; Kroeze, Yvet; Kumar, Neha; Steinbusch, Harry W M; Kenis, Gunter; van den Hove, Daniel L A
A growing number of infants are exposed to selective serotonin reuptake inhibitor (SSRI) medications during the perinatal period. Perinatal exposure to SSRI medications alter neuroplasticity and increase depressive- and anxiety-related behaviors, particularly in male offspring as little work has been done in female offspring to date. The long-term effects of SSRI on development can also differ with previous exposure to prenatal stress, a model of maternal depression. Because of the limited work done on the role of developmental SSRI exposure on neurobehavioral outcomes in female offspring, the aim of the present study was to investigate how developmental fluoxetine exposure affects anxiety and depression-like behavior, as well as the regulation of hippocampal brain-derived neurotrophic factor (BDNF) signaling in the hippocampus of adult female offspring. To do this female Sprague-Dawley rat offspring were exposed to prenatal stress and fluoxetine via the dam, for a total of four groups of female offspring: 1) No Stress+Vehicle, 2) No Stress+Fluoxetine, 3) Prenatal Stress+Vehicle, and 4) Prenatal Stress+Fluoxetine. Primary results show that, in adult female offspring, developmental SSRI exposure significantly increases behavioral despair measures on the forced swim test, decreases hippocampal BDNF exon IV mRNA levels, and increases levels of the repressive histone 3 lysine 27 tri-methylated mark at the corresponding promoter. There was also a significant negative correlation between hippocampal BDNF exon IV mRNA levels and immobility in the forced swim test. No effects of prenatal stress or developmental fluoxetine exposure were seen on tests of anxiety-like behavior. This research provides important evidence for the long-term programming effects of early-life exposure to SSRIs on female offspring, particularily with regard to affect-related behaviors and their underlying molecular mechanisms. Copyright © 2016 Elsevier Inc. All rights reserved.
Becker, Kimberly D.; Ginsburg, Golda S.; Domingues, Janine; Tein, Jenn-Yun
This study tested components of a proposed model of child anxiety and examined the mediational roles of (1) maternal control behavior, (2) maternal external locus of control, and (3) child external locus of control in the association between maternal and child anxiety. Thirty-eight clinically anxious mothers and 37 nonanxious mothers participated…
Houghton, Stephen; Alsalmi, Nadiyah; Tan, Carol; Taylor, Myra; Durkin, Kevin
To evaluate an 8-week cognitive behavior therapy (CBT) treatment specifically designed for adolescents with ADHD and comorbid anxiety. Using a multiple baseline design, nine adolescents (13 years to 16 years 9 months) received a weekly CBT, which focused on four identified anxiety-arousing times. Participants self-recorded their levels of anxiety for each of the four times during baseline, intervention, and a maintenance phase. Anxiety was also assessed using the Multidimensional Anxiety Scale for Children (MASC). Paired samples t tests supported the success of the intervention. Interrupted time-series data for each participant revealed varying rates of success across the four times, however. The MASC data revealed significant reductions in Physical Symptoms of Anxiety, Social Anxiety, Separation Anxiety, Harm Avoidance, and Total Anxiety. The data demonstrate the efficacy of a CBT program for the treatment of comorbid anxiety in adolescents with ADHD.
Erta, Maria; Giralt, Mercedes; Esposito, Flavia Lorena; Fernandez-Gayol, Olaya; Hidalgo, Juan
Interleukin-6 (IL-6) is a major cytokine in the central nervous system, secreted by different brain cells and with roles in a number of physiological functions. We herewith confirm and expand the importance of astrocytic production of and response to IL-6 by using transgenic mice deficient in astrocytic IL-6 (Ast-IL-6 KO) or in its receptor (Ast-IL-6R KO) in full C57Bl/6 genetic background. A major prosurvival effect of astrocytic IL-6 at early ages was clearly demonstrated. Robust effects were also evident in the control of activity and anxiety in the hole-board and elevated plus-maze, and in spatial learning in the Morris water-maze. The results also suggest an inhibitory role of IL-6 in the mechanism controlling the consolidation of hippocampus-dependent spatial learning. Less robust effects of astrocytic IL-6 system were also observed in despair behavior in the tail suspension test, and social behavior in the dominance and resident-intruder tests. The behavioral phenotype was highly dependent on age and/or sex in some cases. The phenotype of Ast-IL-6R KO mice mimicked only partially that of Ast-IL-6KO mice, which indicates both a role of astrocytes in behavior and the participation of other cells besides astrocytes. No evidences of altered function of the hypothalamic-pituitary-adrenal axis were observed. These results demonstrate that astrocytic IL-6 (acting at least partially in astrocytes) regulates normal behavior in mice. Copyright © 2015 Elsevier Inc. All rights reserved.
Full Text Available Background: Medical education is inherently stressful and demanding to deal with various stressors, which may cause impaired judgment, reduced concentration, lack of self-steam, increased anxiety and depression. Materials and Methods: A cross sectional study was conducted on 250 medical students from 6 month period to graduation in medical college of Tehran university of Medical sciences in order to assess their anxiety and practice of health behaviors and also the relation between the two variables and some other related factors.. Results: The results of study show that of 6.6% medical students suffer from severe state and 4.9% from trait anxiety. The finding of this study shows that 83.3% of girls and 84.6% of boys have practicing risky health behaviors. No statistical relationships found between, anxiety and practicing health behaviors. The relation between anxiety and health satisfaction was Statistically significant; mental and physical (P<0.001. Conclusion: The information found in this research, can help medical education institute to capitalize an opportunities to help their students in preventing risky behaviors, and different stress management techniques should be taught at medical schools.
Buff, Christine; Brinkmann, Leonie; Bruchmann, Maximilian; Becker, Michael P I; Tupak, Sara; Herrmann, Martin J; Straube, Thomas
Sustained anticipatory anxiety is central to Generalized Anxiety Disorder (GAD). During anticipatory anxiety, phasic threat responding appears to be mediated by the amygdala, while sustained threat responding seems related to the bed nucleus of the stria terminalis (BNST). Although sustained anticipatory anxiety in GAD patients was proposed to be associated with BNST activity alterations, firm evidence is lacking. We aimed to explore temporal characteristics of BNST and amygdala activity during threat anticipation in GAD patients. Nineteen GAD patients and nineteen healthy controls (HC) underwent functional magnetic resonance imaging (fMRI) during a temporally unpredictable threat anticipation paradigm. We defined phasic and a systematic variation of sustained response models for blood oxygen level-dependent responses during threat anticipation, to disentangle temporally dissociable involvement of the BNST and the amygdala. GAD patients relative to HC responded with increased phasic amygdala activity to onset of threat anticipation and with elevated sustained BNST activity that was delayed relative to the onset of threat anticipation. Both the amygdala and the BNST displayed altered responses during threat anticipation in GAD patients, albeit with different time courses. The results for the BNST activation hint towards its role in sustained threat responding, and contribute to a deeper understanding of pathological sustained anticipatory anxiety in GAD. © The Author (2017). Published by Oxford University Press.
Mendes, Natalia Ferreira; Castro, Gisele; Guadagnini, Dioze; Tobar, Natalia; Cognuck, Susana Quiros; Elias, Lucila Leico Kagohara; Boer, Patricia Aline; Prada, Patricia Oliveira
Protein tyrosine phosphatase 1B (PTP1B) has been extensively implicated in the regulation of body weight, food intake, and energy expenditure. The role of PTP1B appears to be cell and brain region dependent. Herein, we demonstrated that chronic high-fat feeding enhanced PTP1B expression in the central nucleus of the amygdala (CeA) of rats compared to rats on chow. Knocking down PTP1B with oligonucleotide antisense (ASO) decreased its expression and was sufficient to improve the anorexigenic effect of insulin through IR/Akt signaling in the CeA. ASO treatment reduces body weight, fat mass, serum leptin levels, and food intake and also increases energy expenditure, without altering ambulatory activity. These changes were explained, at least in part, by the improvement of insulin sensitivity in the CeA, decreasing NPY and enhancing oxytocin expression. There was a slight decline in fasting blood glucose and serum insulin levels possibly due to leanness in rats treated with ASO. Surprisingly, the elevated plus maze test revealed an anxiolytic behavior after reduction of PTP1B in the CeA. Thus, the present study highlights the deleterious role that the amygdalar PTP1B has on energy homeostasis in obesity states. The reduction of PTP1B in the CeA may be a strategy for the treatment of obesity, insulin resistance and anxiety disorders. Copyright © 2017 Elsevier Inc. All rights reserved.
Kang, Silvia S; Jeraldo, Patricio R; Kurti, Aishe; Miller, Margret E Berg; Cook, Marc D; Whitlock, Keith; Goldenfeld, Nigel; Woods, Jeffrey A; White, Bryan A; Chia, Nicholas; Fryer, John D
The ingestion of a high-fat diet (HFD) and the resulting obese state can exert a multitude of stressors on the individual including anxiety and cognitive dysfunction. Though many studies have shown that exercise can alleviate the negative consequences of a HFD using metabolic readouts such as insulin and glucose, a paucity of well-controlled rodent studies have been published on HFD and exercise interactions with regard to behavioral outcomes. This is a critical issue since some individuals assume that HFD-induced behavioral problems such as anxiety and cognitive dysfunction can simply be exercised away. To investigate this, we analyzed mice fed a normal diet (ND), ND with exercise, HFD diet, or HFD with exercise. We found that mice on a HFD had robust anxiety phenotypes but this was not rescued by exercise. Conversely, exercise increased cognitive abilities but this was not impacted by the HFD. Given the importance of the gut microbiome in shaping the host state, we used 16S rRNA hypervariable tag sequencing to profile our cohorts and found that HFD massively reshaped the gut microbial community in agreement with numerous published studies. However, exercise alone also caused massive shifts in the gut microbiome at nearly the same magnitude as diet but these changes were surprisingly orthogonal. Additionally, specific bacterial abundances were directly proportional to measures of anxiety or cognition. Thus, behavioral domains and the gut microbiome are both impacted by diet and exercise but in unrelated ways. These data have important implications for obesity research aimed at modifications of the gut microbiome and suggest that specific gut microbes could be used as a biomarker for anxiety or cognition or perhaps even targeted for therapy.
Dhanda, Saurabh; Sandhir, Rajat
The present study was designed to evaluate the role of biogenic amines in behavioral alterations observed in rat model of hepatic encephalopathy (HE) following bile duct ligation (BDL). Male Wistar rats subjected to BDL developed biliary fibrosis after four weeks which was supported by altered liver function tests, increased ammonia levels and histological staining (Sirius red). Animals were assessed for their behavioral performance in terms of cognitive, anxiety and motor functions. The levels of dopamine (DA), serotonin (5-HT), epinephrine and norepinephrine (NE) were estimated in different regions of brain viz. cortex, hippocampus, striatum and cerebellum using HPLC along with activity of monoamine oxidase (MAO). Cognitive assessment of BDL rats revealed a progressive decline in learning, memory formation, retrieval, exploration of novel environment and spontaneous locomotor activity along with decrease in 5-HT and NE levels. This was accompanied by an increase in MAO activity. Motor functions of BDL rats were also altered which were evident from decrease in the time spent on the rotating rod and higher foot faults assessed using narrow beam walk task. A global decrease was observed in the DA content along with an increase in MAO activity. Histopathological studies using hematoxylin-eosin (H&E) and cresyl violet exhibited marked neuronal degeneration, wherein neurons appeared more pyknotic, condensed and damaged. The results reveal that dopaminergic and serotonergic pathways are disturbed in chronic liver failure post-BDL which may be responsible for behavioral impairments observed in HE. Copyright © 2015 Elsevier B.V. All rights reserved.
Yang, Tae Young; Jang, Eun Young; Ryu, Yeonhee; Lee, Gyu Won; Lee, Eun Byeol; Chang, Suchan; Lee, Jong Han; Koo, Jin Suk; Yang, Chae Ha; Kim, Hee Young
Acupuncture has been used as a common therapeutic tool in many disorders including anxiety and depression. Serotonin transporter (SERT) plays an important role in the pathology of anxiety and other mood disorders. The aim of this study was to evaluate the effects of acupuncture on lipopolysaccharide (LPS)-induced anxiety-like behaviors and SERT in the dorsal raphe nuclei (DRN). Rats were given acupuncture at ST41 (Jiexi), LI11 (Quchi) or SI3 (Houxi) acupoint in LPS-treated rats. Anxiety-like behaviors of elevated plus maze (EPM) and open field test (OFT) were measured and expressions of SERT and/or c-Fos were also examined in the DRN using immunohistochemistry. The results showed that 1) acupuncture at ST41 acupoint, but neither LI11 nor SI3, significantly attenuated LPS-induced anxiety-like behaviors in EPM and OFT, 2) acupuncture at ST41 decreased SERT expression increased by LPS in the DRN. Our results suggest that acupuncture can ameliorate anxiety-like behaviors, possibly through regulation of SERT in the DRN.
Labaka, Ainitze; Gómez-Lázaro, Eneritz; Vegas, Oscar; Pérez-Tejada, Joana; Arregi, Amaia; Garmendia, Larraitz
Evidence indicates that release of pro-inflammatory cytokines induced by social stress contributes to affective disorders. Additionally, there are known sex differences in both the stress response and the stressors that can elicit this response. In this regard, the chronic social instability (CSI) rodent model of stress appears to be the best fit for the social nature of females. This study analyzed the effects of CSI on female mouse behavior, hippocampal cytokine expression, tryptophan metabolism and monoaminergic activity. The activity of hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes were also measured. Results showed a decrease in sucrose consumption in stressed subjects, indicative of anhedonic behavior and an increase in climbing activity in the forced swimming test (FST) and in whisking behavior, which have been associated with anxiety. Decreased interleukin-10 (IL-10) expression was found in the hippocampus of the stressed mice, while no differences in pro-inflammatory cytokine expression and tryptophan (TRYP), kynurenine (KYN) or 3-hydroxy kynurenine (3-HK) levels were found. Increased hippocampal serotoninergic and noradrenergic activity was observed in stressed mice. The higher plasma corticosterone and lower hypothalamic glucocorticoid receptor (GR) expression levels showed an increase in HPA activity after CSI. No differences were found in the plasma estradiol levels or the central estrogen receptors (ERα and ERβ) expression levels. These data indicate that the CSI stress-induced behavioral and physiological changes associated with anxiety and depressive disorders. Although additional studies are warranted, the results suggest an involvement of anti-inflammatory cytokines in the biobehavioral effects of social stress in female mice. Copyright © 2017 Elsevier B.V. All rights reserved.
Suveg, Cynthia; Kingery, Julie Newman; Davis, Molly; Jones, Anna; Whitehead, Monica; Jacob, Marni L
Social experiences are an integral part of normative development for youth and social functioning difficulties are related to poor outcomes. Youth with anxiety disorders, and particularly social anxiety disorder, experience difficulties across many aspects of social functioning that may place them at risk for maladjustment. The goal of this paper was to compare social experiences of youth across anxiety diagnoses and examine whether treatment is helpful in improving social functioning. Ninety-two children (age 7-12 years; 58% male; 87.0% White) with a primary diagnosis of generalized anxiety disorder, separation anxiety disorder, and/or social anxiety disorder participated in cognitive behavioral therapy. At both pre- and post-treatment, children with social anxiety disorder self-reported greater loneliness than youth without social anxiety disorder, though levels of peer victimization and receipt of prosocial behavior were similar across groups. Parents reported greater social problems for youth with social anxiety disorder compared to those without social anxiety disorder. All youth experienced improved social functioning following treatment per child- and parent-reports. The results call for an increased focus on the social experiences of youth with anxiety disorders, and particularly loneliness, for children with social anxiety disorder. The results document ways that evidenced-based practice can improve social functioning for youth with anxiety disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.
Andrews, Gavin; Newby, Jill M; Williams, Alishia D
Anxiety disorders are common and disabling. Cognitive behavior therapy is the treatment of choice but is often difficult to obtain. Automated, internet-delivered, cognitive behavior therapy (iCBT) courses may be an answer. There are three recent systematic reviews of randomized controlled trials
Barker, Tyson V; Reeb-Sutherland, Bethany; Degnan, Kathryn A; Walker, Olga L; Chronis-Tuscano, Andrea; Henderson, Heather A; Pine, Daniel S; Fox, Nathan A
Behavioral inhibition (BI), a temperament characterized in early childhood by wariness and avoidance of novelty, is a risk factor for anxiety disorders. An enhanced startle response has been observed in adolescents characterized with BI in childhood, particularly when they also manifest concurrent symptoms of anxiety. However, no prior study has examined relations among BI, startle responsivity, and anxiety in a prospective manner. Data for the present study were from a longitudinal study of infant temperament. Maternal reports and observations of BI were assessed at ages 2 and 3. At age 7, participants completed a startle procedure, while electromyography was collected, where participants viewed different colors on a screen that were associated with either the delivery of an aversive stimulus (i.e., puff of air to the larynx; threat cue) or the absence of the aversive stimulus (i.e., safety cue). Parental reports of child anxiety were collected when children were 7 and 9 years of age. Results revealed that startle responses at age 7 moderated the relation between early BI and 9-year anxiety. These findings provide insight into one potential mechanism that may place behaviorally inhibited children at risk for anxiety. © 2015 Society for Psychophysiological Research.
Davies, Carolyn D; Niles, Andrea N; Pittig, Andre; Arch, Joanna J; Craske, Michelle G
Identifying for whom and under what conditions a treatment is most effective is an essential step toward personalized medicine. The current study examined pre-treatment physiological and behavioral variables as predictors and moderators of outcome in a randomized clinical trial comparing cognitive behavioral therapy (CBT) and acceptance and commitment therapy (ACT) for anxiety disorders. Sixty individuals with a DSM-IV defined principal anxiety disorder completed 12 sessions of either CBT or ACT. Baseline physiological and behavioral variables were measured prior to entering treatment. Self-reported anxiety symptoms were assessed at pre-treatment, post-treatment, and 6- and 12-month follow-up from baseline. Higher pre-treatment heart rate variability was associated with worse outcome across ACT and CBT. ACT outperformed CBT for individuals with high behavioral avoidance. Subjective anxiety levels during laboratory tasks did not predict or moderate treatment outcome. Due to small sample sizes of each disorder, disorder-specific predictors were not tested. Future research should examine these predictors in larger samples and across other outcome variables. Lower heart rate variability was identified as a prognostic indicator of overall outcome, whereas high behavioral avoidance was identified as a prescriptive indicator of superior outcome from ACT versus CBT. Investigation of pre-treatment physiological and behavioral variables as predictors and moderators of outcome may help guide future treatment-matching efforts. Copyright © 2014 Elsevier Ltd. All rights reserved.
Levin-Decanini, Tal; Connolly, Sucheta D; Simpson, David; Suarez, Liza; Jacob, Suma
Elucidating differences in social-behavioral profiles of children with comorbid presentations, utilizing caregiver as well as teacher reports, will refine our understanding of how contextual symptoms vary across anxiety-related disorders. In our pediatric anxiety clinic, the most frequent diagnoses and comorbidities were mixed anxiety (MA; ≥ 1 anxiety disorder; N = 155), anxiety with comorbid attention-deficit hyperactivity disorder (MA/ADHD, N = 47) and selective mutism (SM, N = 48). Behavioral measures (CPRS, CTRS) were analyzed using multiple one-way multivariate analyses of covariance tests. Differences between the three diagnostic groups were examined using completed parent and teacher reports (N = 135, 46, and 48 for MA, MA/ADHD, and SM groups, respectively). Comparisons across the MA, MA/ADHD, and SM groups indicate a significant multivariate main effect of group for caregiver and teacher responses (P < 0.01). Caregivers reported that children with SM are similar in profile to those with MA, and both groups were significantly different from the MA/ADHD group. Teachers reported that children with SM had more problems with social behaviors than with the MA or MA/ADHD groups. Further comparison indicates a significant main effect of group (P < 0.001), such that children with SM have the greatest differences in behavior observed by teachers versus caregivers. Clinical profiles between MA/ADHD, MA, and SM groups varied, illustrating the importance of multi-rater assessment scales to capture subtle distinctions and to inform treatment planning given that comorbidities occur frequently in children who present with anxiety. © 2013 Wiley Periodicals, Inc.
Lyons, D N; Kniffin, T C; Zhang, L P; Danaher, R J; Miller, C S; Bocanegra, J L; Carlson, C R; Westlund, K N
Our laboratory previously developed a novel neuropathic and inflammatory facial pain model for mice referred to as the Trigeminal Inflammatory Compression (TIC) model. Rather than inducing whole nerve ischemia and neuronal loss, this injury induces only slight peripheral nerve demyelination triggering long-term mechanical allodynia and cold hypersensitivity on the ipsilateral whisker pad. The aim of the present study is to further characterize the phenotype of the TIC injury model using specific behavioral assays (i.e. light-dark box, open field exploratory activity, and elevated plus maze) to explore pain- and anxiety-like behaviors associated with this model. Our findings determined that the TIC injury produces hypersensitivity 100% of the time after surgery that persists at least 21 weeks post injury (until the animals are euthanized). Three receptive field sensitivity pattern variations in mice with TIC injury are specified. Animals with TIC injury begin displaying anxiety-like behavior in the light-dark box preference and open field exploratory tests at week eight post injury as compared to sham and naïve animals. Panic anxiety-like behavior was shown in the elevated plus maze in mice with TIC injury if the test was preceded with acoustic startle. Thus, in addition to mechanical and cold hypersensitivity, the present study identified significant anxiety-like behaviors in mice with TIC injury resembling the clinical symptomatology and psychosocial impairments of patients with chronic facial pain. Overall, the TIC injury model's chronicity, reproducibility, and reliability in producing pain- and anxiety-like behaviors demonstrate its usefulness as a chronic neuropathic facial pain model. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
Nadorff, Michael R; Porter, Ben; Rhoades, Howard M; Greisinger, Anthony J; Kunik, Mark E; Stanley, Melinda A
This study investigated the relation between generalized anxiety disorder (GAD) and frequency of bad dreams in older adults. A secondary analysis from a randomized clinical trial comparing cognitive behavioral therapy (CBT) for anxiety to enhanced usual care (EUC) assessed bad dream frequency at baseline, post treatment (3 months), and at 6, 9, 12, and 15 months. Of 227 participants (mean age = 67.4), 134 met GAD diagnostic criteria (CBT = 70, EUC = 64), with the remaining 93 serving as a comparison group. Patients with GAD had significantly more bad dreams than those without, and bad dream frequency was significantly associated with depression, anxiety, worry, and poor quality of life. CBT for anxiety significantly reduced bad dream frequency at post treatment and throughout follow up compared to EUC.
Anderson, Page L; Zimand, Elana; Hodges, Larry F; Rothbaum, Barbara O
This study used an open clinical trial to test a cognitive-behavioral treatment for public-speaking anxiety that utilized virtual reality as a tool for exposure therapy. Treatment was completed by participants (n = 10) meeting the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria for social phobia, or panic disorder with agoraphobia in which public speaking was the predominantly feared stimulus. Treatment was conducted by a licensed psychologist in an outpatient clinic. Treatment consisted of eight individual therapy sessions, including four sessions of anxiety management training and four sessions of exposure therapy using a virtual audience, according to a standardized treatment manual. Participants completed standardized self-report questionnaires assessing public-speaking anxiety at pre-treatment, post-treatment, and 3-month follow-up. Participants were asked to give a speech to an actual audience at pre- and post-treatment. Results showed decreases on all self-report measures of public-speaking anxiety from pre- to post-treatment, which were maintained at follow-up (n = 8; all P = 05). Participants were no more likely to complete a speech post-treatment than at pre-treatment. This study provides preliminary evidence that a cognitive-behavioral treatment using virtual reality for exposure to public speaking may reduce public-speaking anxiety and suggests that further research with a controlled design is needed. Copyright 2005 Wiley-Liss, Inc.
Selles, Robert R.; Arnold, Elysse B.; Phares, Vicky; Lewin, Adam B.; Murphy, Tanya K.; Storch, Eric A.
Cognitive-behavioral therapy for anxiety in youth with an autism spectrum disorder appears efficacious; however, maintenance of treatment gains has not yet been studied. Using a sample of 32 youth who had benefited at least minimally from a past trial of cognitive-behavioral therapy for anxiety in autism spectrum disorder, this study assessed…
Dincheva, Iva; Yang, Jianmin; Li, Anfei; Marinic, Tina; Freilingsdorf, Helena; Huang, Chienchun; Casey, B J; Hempstead, Barbara; Glatt, Charles E; Lee, Francis S; Bath, Kevin G; Jing, Deqiang
Adolescence is a developmental stage in which the incidence of psychiatric disorders, such as anxiety disorders, peaks. Selective serotonin reuptake inhibitors (SSRIs) are the main class of agents used to treat anxiety disorders. However, the impact of SSRIs on the developing brain during adolescence remains unknown. The authors assessed the impact of developmentally timed SSRI administration in a genetic mouse model displaying elevated anxiety-like behaviors. Knock-in mice containing a common human single-nucleotide polymorphism (Val66Met; rs6265) in brain-derived neurotrophic factor (BDNF), a growth factor implicated in the mechanism of action of SSRIs, were studied based on their established phenotype of increased anxiety-like behavior. Timed administration of fluoxetine was delivered during one of three developmental periods (postnatal days 21-42, 40-61, or 60-81), spanning the transition from childhood to adulthood. Neurochemical and anxiety-like behavioral analyses were performed. We identified a "sensitive period" during periadolescence (postnatal days 21-42) in which developmentally timed fluoxetine administration rescued anxiety-like phenotypes in BDNF Val66Met mice in adulthood. Compared with littermate controls, BDNF Met/Met mice exhibited diminished maturation of serotonergic fibers projecting particularly to the prefrontal cortex, as well as decreased expression of the serotonergic trophic factor S100B in the dorsal raphe. Interestingly, deficient serotonergic innervation, as well as S100B levels, were rescued with fluoxetine administration during periadolescence. These findings suggest that SSRI administration during a "sensitive period" during periadolescence leads to long-lasting anxiolytic effects in a genetic mouse model of elevated anxiety-like behaviors. These persistent effects highlight the role of BDNF in the maturation of the serotonin system and the capacity to enhance its development through a pharmacological intervention.
Ketamine facilitates extinction of avoidance behavior and enhances synaptic plasticity in a rat model of anxiety vulnerability: Implications for the pathophysiology and treatment of anxiety disorders.
Fortress, Ashley M; Smith, Ian M; Pang, Kevin C H
Anxiety disorders and posttraumatic stress disorder (PTSD) share a common feature of pathological avoidance behavior. The Wistar Kyoto (WKY) rat has been used as a model of anxiety vulnerability, expressing a behaviorally inhibited temperament, acquiring avoidance behavior more rapidly and displaying extinction-resistant avoidance compared to Sprague Dawley (SD) rats. Subanesthetic levels of ketamine have gained attention as a rapid antidepressant in treatment-resistant depression. While traditional antidepressants are commonly used to treat anxiety disorders and PTSD, the therapeutic utility of ketamine for these disorders is much less understood. The hippocampus is critical for the actions of antidepressants, is a structure of implicated in anxiety disorders and PTSD, and is necessary for extinction of avoidance in SD rats. WKY rats have impaired hippocampal long-term potentiation (LTP), suggesting that persistent avoidance in WKY rats may be due to deficient hippocampal synaptic plasticity. In the present study, we hypothesized that ketamine would facilitate extinction of avoidance learning in WKY rats, and do so by enhancing hippocampal synaptic plasticity. As predicted, ketamine facilitated extinction of avoidance behavior in a subset of WKY rats (responders), with effects lasting at least three weeks. Additionally, LTP in these rats was enhanced by ketamine. Ketamine was not effective in facilitating avoidance extinction or in modifying LTP in WKY non-responders. The results suggest that subanesthetic levels of ketamine may be useful for treating anxiety disorders by reducing avoidance behaviors when combined with extinction conditions. Moreover, ketamine may have its long-lasting behavioral effects through enhancing hippocampal synaptic plasticity. Copyright © 2018. Published by Elsevier Ltd.
Boka, Vasiliki; Arapostathis, Konstantinos; Kotsanos, Nikolaos; Karagiannis, Vassilis; van Loveren, Cor; Veerkamp, Jaap
The aims of this study were to determine: 1) the relationship between children's psychological functioning, dental anxiety and cooperative behavior before and during local anesthesia, 2) the relationship of parental dental anxiety with all the above child characteristics. There was a convenient sample of 100 children (4-12 years). Child dental anxiety and psychological functioning were measured using the "Children's Fear Survey Schedule" (CFSS-DS) and the "Strengths and Difficulties Questionnaire" (SDQ) respectively. Parental dental anxiety was measured using the "Modified Dental Anxiety Scale" (MDAS). All questionnaires were completed by parents. Before and during local anesthesia, the child behavior was scored by one experienced examiner, using the Venham scale. Non-parametric tests and correlations (Mann-Whitney, Spearman's rho) were used for the analysis. The mean SDQ score was 10±5.6 for boys (n=60) and 8.3±4.8 for girls (n=40) (p=0.038), but there was no correlation with children's age. The mean CFSS-DS score was 33.1±11.86 and there was no correlation with age or gender. Children with higher levels in the pro-social subscale of the SDQ had significantly less anxiety and better behavior before local anesthesia. Higher mean CFSS-DS scores were significantly associated with uncooperative behavior during local anesthesia (p=0.04). There was no correlation between parents' and their children's dental anxiety, psychological functioning and behavior. 46% of the children had previous dental experience in the last 6 months. As time since the last dental treatment increased, an improvement was found in children's behavior during local anesthesia. Child psychological functioning was related to dental anxiety and behavior during dental appointment involving local anesthesia.
Chronis-Tuscano, Andrea; Degnan, Kathryn Amey; Pine, Daniel S.; Perez-Edgar, Koraly; Henderson, Heather A.; Diaz, Yamalis; Raggi, Veronica L.; Fox, Nathan A.
The odds of a lifetime diagnosis of social anxiety disorder increased by 3.79 times for children who had a stable report of behavioral inhibition from their mothers. This finding has important implications for the early identification and prevention of social anxiety disorder.
Pyndt Jørgensen, Bettina; Winther, Gudrun; Kihl, Pernille; Nielsen, Dennis S; Wegener, Gregers; Hansen, Axel K; Sørensen, Dorte B
Magnesium deficiency has been associated with anxiety in humans, and rodent studies have demonstrated the gut microbiota to impact behaviour. We investigated the impact of 6 weeks of dietary magnesium deficiency on gut microbiota composition and anxiety-like behaviour and whether there was a link between the two. A total of 20 C57BL/6 mice, fed either a standard diet or a magnesium-deficient diet for 6 weeks, were tested using the light-dark box anxiety test. Gut microbiota composition was analysed by denaturation gradient gel electrophoresis. We demonstrated that the gut microbiota composition correlated significantly with the behaviour of dietary unchallenged mice. A magnesium-deficient diet altered the gut microbiota, and was associated with altered anxiety-like behaviour, measured by decreased latency to enter the light box. Magnesium deficiency altered behavior. The duration of magnesium deficiency is suggested to influence behaviour in the evaluated test.
Dossat, Amanda M; Sanchez-Gonzalez, Marcos A; Koutnik, Andrew P; Leitner, Stefano; Ruiz, Edda L; Griffin, Brittany; Rosenberg, Jens T; Grant, Samuel C; Fincham, Francis D; Pinto, Jose R; Kabbaj, Mohamed
Cardiovascular dysfunction is highly comorbid with mood disorders, such as anxiety and depression. However, the mechanisms linking cardiovascular dysfunction with the core behavioral features of mood disorder remain poorly understood. In this study, we used mice bearing a knock-in sarcomeric mutation, which is exhibited in human hypertrophic cardiomyopathy (HCM), to investigate the influence of HCM over the development of anxiety and depression. We employed behavioral, MRI, and biochemical techniques in young (3-4 mo) and aged adult (7-8 mo) female mice to examine the effects of HCM on the development of anxiety- and depression-like behaviors. We focused on females because in both humans and rodents, they experience a 2-fold increase in mood disorder prevalence vs. males. Our results showed that young and aged HCM mice displayed echocardiographic characteristics of the heart disease condition, yet only aged HCM females displayed anxiety- and depression-like behaviors. Electrocardiographic parameters of sympathetic nervous system activation were increased in aged HCM females vs. controls and correlated with mood disorder-related symptoms. In addition, when compared with controls, aged HCM females exhibited adrenal gland hypertrophy, reduced volume in mood-related brain regions, and reduced hippocampal signaling proteins, such as brain-derived neurotrophic factor and its downstream targets vs. controls. In conclusion, prolonged systemic HCM stress can lead to development of mood disorders, possibly through inducing structural and functional brain changes, and thus, mood disorders in patients with heart disease should not be considered solely a psychologic or situational condition.-Dossat, A. M., Sanchez-Gonzalez, M. A., Koutnik, A. P., Leitner, S., Ruiz, E. L., Griffin, B., Rosenberg, J. T., Grant, S. C., Fincham, F. D., Pinto, J. R. Kabbaj, M. Pathogenesis of depression- and anxiety-like behavior in an animal model of hypertrophic cardiomyopathy. © FASEB.
Yang, Liu; Shi, Li-Jun; Yu, Jin; Zhang, Yu-Qiu
Social defeat (SD) stress induces social avoidance and anxiety-like phenotypes. Amygdala is recognized as an emotion-related brain region such as fear, aversion and anxiety. It is conceivable to hypothesize that activation of amygdala is involved in SD-dependent behavioral defects. SD model was established using C57BL/6J mice that were physically defeated by different CD-1 mice for 10 days. Stressed mice exhibited decreased social interaction level in social interaction test and significant anxiety-like behaviors in elevated plus maze and open field tests. Meanwhile, a higher phosphorylation of PKA and CREB with a mutually linear correlation, and increased Fos labeled cells in the basolateral amygdala (BLA) were observed. Activation of PKA in the BLA by 8-Br-cAMP, a PKA activitor, significantly upregulated pCREB and Fos expression. To address the role of PKA activation on SD stress-induced social avoidance and anxiety-like behaviors, 8-Br-cAMP or H-89, a PKA inhibitor, was continuously administered into the bilateral BLA by a micro-osmotic pump system during the 10-day SD period. Neither H-89 nor 8-Br-cAMP affected the social behavior. Differently, 8-Br-cAMP significantly relieved anxiety-like behaviors in both general and moderate SD protocols. H-89 per se did not have anxiogenic effect in naïve mice, but aggravated moderate SD stress-induced anxiety-like behaviors. The antidepressant clomipramine reduced SD-induced anxiety and up-regulated pPKA level in the BLA. These results suggest that SD-driven PKA activation in the basolateral amygdala is actually a compensatory rather than pathogenic response in the homeostasis, and modulating amygdaloid PKA may exhibit potency in the therapy of social derived disorders.
Wang, Cui; Qian, Yi; Zhang, Xiaofeng; Chen, Fang; Zhang, Quan; Li, Zhuoyu; Zhao, Meirong
Field residue of fipronil can interfere with the physiological characters of the domesticated fish; thus, lethal dose test and the general biomarker cannot delineate the low-level situation. Manipulating by video track, we observed an anxiety-like behavior including high speed and abnormal photoperiod accommodation after exposure to fipronil at environmental typical dose in zebrafish larvae. Examining the unbiased metabolomic profiles, we found perturbation in several metabolic pathways, including the increased contents of fatty acids and glycerol and the decreased levels of the glycine, serine, and branched amino acid. We presumed that observed enhanced fatty acid utility was in response to increase energy demands caused by anxiety like behavior. Additionally, the body burden of neurotransmitter such as glycine and L-glutamate may concurrently stimulate the swimming behavior. The insight of this study showed that integral perturbation such as metabolism helps us to further understand the risk to aquatic fish at the environmentally relevant levels. - Highlights: • Fipronil increased the swimming speed at 10 μg/L to zebrafish larvae. • Accommodation to light–dark photoperiod switch was disturbed by fipronil. • Metabolomics indicated an increase energy availability for anxiety-like behavior. • Anxiety-like behavior induced by fipronil may attribute to neurotransmitter changes. - Zebrafish larvae exposed to environmentally relevant concentrations of fipronil display anxiety like behavior that may attribute to observed changes in energy utilization and neurotransmitter disturbances.
Muris, Peter; Mayer, Birgit; den Adel, Madelon; Roos, Tamara; van Wamelen, Julie
The purpose of the present study was to evaluate negative automatic thoughts and anxiety control as predictors of change produced by cognitive-behavioral treatment of youths with anxiety disorders. Forty-five high-anxious children aged between 9 and 12 years who were selected from the primary school population, received a standardized CBT…
Hatipoglu, Z; Gulec, E; Lafli, D; Ozcengiz, D
: Preoperative anxiety is a critical issue in children, and associated with postoperative behavioral changes. : The purpose of the current study is to evaluate how audiovisual and auditory presentations about the perioperative period impact preoperative anxiety and postoperative behavioral disturbances of children undergoing elective ambulatory surgery. : A total of 99 patients between the ages of 5-12, scheduled to undergo outpatient surgery, participated in this study. Participants were randomly assigned to one of three groups; audiovisual group (Group V, n = 33), auditory group (Group A, n = 33), and control group (Group C, n = 33). During the evaluation, the Modified Yale Preoperative Anxiety Scale (M-YPAS) and the posthospitalization behavioral questionnaire (PHBQ) were used. : There were no significant differences in demographic characteristics between the groups. M-YPAS scores were significantly lower in Group V than in Groups C and A (P audiovisual presentations, in terms of being memorable and interesting, may be more effective in reducing children's anxiety. In addition, we can suggest that both methods can be equally effective for postoperative behavioral changes.
Full Text Available Chronic inflammatory pain can induce emotional diseases. Electroacupuncture (EA has effects on chronic pain and pain-related anxiety. Protein kinase Mzeta (PKMzeta has been proposed to be essential for the maintenance of pain and may interact with GluR1 to maintain CNS plasticity in the anterior cingulate cortex (ACC. We hypothesized that the PKMzeta-GluR1 pathway in the ACC may be involved in anxiety-like behaviors of chronic inflammatory pain and that the mechanism of EA regulation of pain emotion may involve the PKMzeta pathway in the ACC. Our results showed that chronic inflammatory pain model decreased the paw withdrawal threshold (PWT and increased anxiety-like behaviors. The protein expression of PKCzeta, p-PKCzeta (T560, PKMzeta, p-PKMzeta (T560, and GluR1 in the ACC of the model group were remarkably enhanced. EA increased PWT and alleviated anxiety-like behaviors. EA significantly inhibited the protein expression of p-PKMzeta (T560 in the ACC, and only a downward trend effect for other substances. Further, the microinjection of ZIP remarkably reversed PWT and anxiety-like behaviors. The present study provides direct evidence that the PKCzeta/PKMzeta-GluR1 pathway is related to pain and pain-induced anxiety-like behaviors. EA treatment both increases pain-related somatosensory behavior and decreases pain-induced anxiety-like behaviors by suppressing PKMzeta activity in the ACC.
Tsai, Meng-Li; Kozłowska, Anna; Li, Yu-Sheng; Shen, Wen-Ling; Huang, Andrew Chih Wei
The present study examines whether housing style (e.g., single housing, same-strain-grouped housing, and different-strain-grouped housing) and rat strain (e.g., spontaneous hypertension rats [SHR] and Wistar-Kyoto rats [WKY]) mediate motor function and anxiety behavior in the open field task. From week 4 through week 10 following birth, the rats were measured 30min for locomotor activity and anxiety once per week in the open field task. The SHR rats exhibited hyperactivity in total distance traveled and movement time to form the animal model of ADHD. The SHR rats spent more time inside the square and crossed the inside-outside line more often than the WKY rats, indicating the SHR rats exhibited less anxiety behavior. The different-strain-grouped housing style (but neither the same-strain-grouped housing style nor the single housing style) decreased total distance traveled and facilitated anxiety behavior. The motor function was negatively correlated with anxiety behavior for SHR rats but not for WKY rats. Housing styles had a negative correlation between motor function and anxiety behavior. The present findings provide some insights regarding how social factors (such as housing style) affect motor function and anxiety behavior related to ADHD in a clinical setting. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.
Sangenstedt, Susanne; Jaljuli, Iman; Sachser, Norbert; Kaiser, Sylvia
The early social environment can profoundly affect behavioral and physiological phenotypes. We investigated how male wild cavy offspring, whose mothers had either lived in a stable (SE) or an unstable social environment (UE) during pregnancy and lactation, differed in their anxiety-like behavior and stress responsiveness. At two different time points in life, we tested the offspring's anxiety-like behavior in a dark-light test and their endocrine reaction to challenge in a cortisol reactivity test. Furthermore, we analyzed whether individual traits remained stable over time. There was no effect of the early social environment on anxiety-like behavior and stress responsiveness. However, at an individual level, anxiety-like behavior was stable over time in UE- but not in SE-sons. Stress responsiveness, in turn, was rather inconsistent in UE-sons and temporally stable in SE-sons. Conclusively, we showed for the first time that the early social environment differentially shapes the stability of behavioral and endocrine traits. At first glance, these results may be surprising, but they can be explained by the different functions anxiety-like behavior and stress responsiveness have. Copyright © 2017 Elsevier Inc. All rights reserved.
Necla Taspinar Goveci
In the analyses relating to comparison; in terms of total exam anxiety, perception, delusion sublevel and trait anxiety points of the students, psychodrama techniques applied in the first group have been more affective with reference to the cognitive behavioral techniques applied in the second group. No meaningful difference has been detected when two experimental groups have been compared according to continuity anxiety points. [JCBPR 2017; 6(1.000: 22-30
Ricci, Lesley A; Morrison, Thomas R; Melloni, Richard H
In the U.S. and worldwide anabolic/androgenic steroid use remains high in the adolescent population. This is concerning given that anabolic/androgenic steroid use is associated with a higher incidence of aggressive behavior during exposure and anxiety during withdrawal. This study uses pubertal Syrian hamsters (Mesocricetus auratus) to investigate the hypothesis that an inverse behavioral relationship exists between anabolic/androgenic steroid-induced aggression and anxiety across adolescent exposure and withdrawal. In the first experiment, we examined aggression and anxiety during adolescent anabolic/androgenic steroid exposure and withdrawal. Adolescent anabolic/androgenic steroid administration produced significant increases in aggression and decreases in anxiety during the exposure period followed by significant decreases in aggression and increases in anxiety during anabolic/androgenic steroid withdrawal. In a second experiment, anabolic/androgenic steroid exposed animals were separated into groups based on their aggressive response during the exposure period and then tested for anxiety during exposure and then for both aggression and anxiety during withdrawal. Data were analyzed using a within-subjects repeated measures predictive analysis. Linear regression analysis revealed that the difference in aggressive responding between the anabolic/androgenic steroid exposure and withdrawal periods was a significant predictor of differences in anxiety for both days of testing. Moreover, the combined data suggest that the decrease in aggressive behavior from exposure to withdrawal predicts an increase in anxiety-like responding within these same animals during this time span. Together these findings indicate that early anabolic/androgenic steroid exposure has potent aggression- and anxiety-eliciting effects and that these behavioral changes occur alongside a predictive relationship that exists between these two behaviors over time. © 2013.
Skelly, Mary J; Weiner, Jeff L
Alcohol use disorders have been linked to increased anxiety, and enhanced central noradrenergic signaling may partly explain this relationship. Pharmacological interventions believed to reduce the excitatory effects of norepinephrine have proven effective in attenuating ethanol intake in alcoholics as well as in rodent models of ethanol dependence. However, most preclinical investigations into the effectiveness of these drugs in decreasing ethanol intake have been limited to acute observations, and none have concurrently assessed their anxiolytic effects. The purpose of these studies was to examine the long-term effectiveness of pharmacological interventions presumed to decrease norepinephrine signaling on concomitant ethanol self-administration and anxiety-like behavior in adult rats with relatively high levels of antecedent anxiety-like behavior. Adult male Long-Evans rats self-administered ethanol on an intermittent access schedule for eight to ten weeks prior to being implanted with osmotic minipumps containing either an a1-adrenoreceptor antagonist (prazosin, 1.5 mg/kg/day), a β1/2-adrenoreceptor antagonist (propranolol, 2.5 mg/kg/day), a serotonin/norepinephrine reuptake inhibitor (duloxetine, 1.5 mg/kg/day) or vehicle (10% dimethyl sulfoxide). These drugs were continuously delivered across four weeks, during which animals continued to have intermittent access to ethanol. Anxiety-like behavior was assessed on the elevated plus maze before treatment and again near the end of the drug delivery period. Our results indicate that chronic treatment with a low dose of prazosin or duloxetine significantly decreases ethanol self-administration (P chronic treatment with putative inhibitors of central noradrenergic signaling may attenuate ethanol intake via a reduction in anxiety-like behavior.
Nadorff, Michael R.; Porter, Ben; Rhoades, Howard M.; Greisinger, Anthony J.; Kunik, Mark E.; Stanley, Melinda A.
This study investigated the relation between generalized anxiety disorder (GAD) and frequency of bad dreams in older adults. A secondary analysis from a randomized clinical trial comparing cognitive behavioral therapy for anxiety (CBT) to enhanced usual care (EUC), it assessed bad dream frequency at baseline, post-treatment (3 months), and 6, 9, 12 and 15 months. Of 227 participants (mean age = 67.4), 134 met GAD diagnostic criteria (CBT = 70, EUC = 64), with the remaining 93 serving as a comparison group. Patients with GAD had significantly more bad dreams than those without, and bad dream frequency was significantly associated with depression, anxiety, worry, and poor quality of life. CBT for anxiety significantly reduced bad dream frequency at post-treatment and throughout follow-up compared to EUC. PMID:23470116
Walf, Alicia A.; Frye, Cheryl A.
The ovarian hormone, 17β-estradiol (E2), has numerous targets in the body and brain, and can influence cognitive, affective, and social behavior. However, functional effects of commonly prescribed E2-based hormone therapies are less known. The effects of conjugated equine estrogen (CEE) on middle-aged female rats for cognitive (object recognition), anxiety (open field, plus maze), and social (social interaction, lordosis) behavior were compared-with vehicle. Our hypothesis that CEE would enha...
Erica R. Glasper
Full Text Available Early-life experiences with caregivers can significantly affect offspring development in human and non-human animals. While much of our knowledge of parent-offspring relationships stem from mother-offspring interactions, increasing evidence suggests interactions with the father are equally as important and can prevent social, behavioral, and neurological impairments that may appear early in life and have enduring consequences in adulthood. In the present study, we utilized the monogamous and biparental California mouse (Peromyscus californicus. California mouse fathers provide extensive offspring care and are essential for offspring survival. Non-sibling virgin male and female mice were randomly assigned to one of two experimental groups following the birth of their first litter: (1 biparental care: mate pairs remained with their offspring until weaning; or (2 paternal deprivation (PD: paternal males were permanently removed from their home cage on postnatal day (PND 1. We assessed neonatal mortality rates, body weight, survival of adult born cells in the dentate gyrus of the hippocampus, and anxiety-like and passive stress-coping behaviors in male and female young adult offspring. While all biparentally-reared mice survived to weaning, PD resulted in a ~35% reduction in survival of offspring. Despite this reduction in survival to weaning, biparentally-reared and PD mice did not differ in body weight at weaning or into young adulthood. A sex-dependent effect of PD was observed on new cell survival in the dentate gyrus of the hippocampus, such that PD reduced cell survival in female, but not male, mice. While PD did not alter classic measures of anxiety-like behavior during the elevated plus maze task, exploratory behavior was reduced in PD mice. This observation was irrespective of sex. Additionally, PD increased some passive stress-coping behaviors (i.e., percent time spent immobile during the forced swim task—an effect that was also not sex
Mathewson, Karen J; Schmidt, Louis A; Miskovic, Vladimir; Santesso, Diane L; Duku, Eric; McCabe, Randi E; Antony, Martin M; Moscovitch, David A
Modifying dysfunctional emotion regulation is an important goal in psychological treatments for social anxiety disorder (SAD). Antecedent-focused strategies learned in cognitive behavioral therapy (CBT), such as cognitive reappraisal, have proven more effective in reducing social anxiety than response-focused strategies, such as expressive suppression. Still, not all patients with SAD respond well to CBT. Medications and physiological factors may also influence the clinical response. The purpose of the present study was to examine the role that these factors play in determining treatment response following CBT for SAD. Using multilevel modeling, we examined associations across four separate laboratory visits between change in self-reported anxiety and indices of reappraisal, suppression, medication status, and resting respiratory sinus arrhythmia (RSA), a proxy measure of self-regulatory capacity, in 23 socially anxious adults during a 12-week program of CBT. Most participants were ultimately classified as responders to CBT (n=15), but in some, anxiety levels remained unchanged (n=8). Medication use explained substantial variance related to individual differences in anxiety among participants. When modeled separately, reappraisal, suppression, and RSA each accounted for significant variance related to anxiety. However, the best-fitting model included reappraisal and RSA. Moreover, RSA reactivity (change in RSA levels over time) was more important for predicting anxiety reduction than were baseline levels of RSA. These findings suggest that reappraisal and parasympathetic responsiveness may be important in reducing anxiety in adults with SAD who respond well to CBT. Copyright © 2013 Elsevier B.V. All rights reserved.
Previous research from our laboratory has shown that exposure to chronic psychosocial stress increased voluntary ethanol consumption and preference as well as acquisition of ethanol-induced conditioned place preference (CPP) in mice. This study was done to determine whether an enriched environment could have "curative" effects on chronic psychosocial stress-induced ethanol intake and CPP. For this purpose, experimental mice "intruders" were exposed to the chronic subordinate colony (CSC) housing for 19 consecutive days in the presence of an aggressive "resident" mouse. At the end of that period, mice were tested for their anxiety-like behavior using the elevated plus maze (EPM) test then housed in a standard or enriched environment (SE or EE respectively). Anxiety and ethanol-related behaviors were investigated using the open field (OF) test, a standard two-bottle choice drinking paradigm, and the CPP procedure. As expected, CSC exposure increased anxiety-like behavior and reduced weight gain as compared to single housed colony (SHC) controls. In addition, CSC exposure increased voluntary ethanol intake and ethanol-CPP. Interestingly, we found that EE significantly and consistently reduced anxiety and ethanol consumption and preference. However, neither tastants' (saccharin and quinine) intake nor blood ethanol metabolism were affected by EE. Finally, and most importantly, EE reduced the acquisition of CPP induced by 1.5g/kg ethanol. Taken together, these results support the hypothesis that EE can reduce voluntary ethanol intake and ethanol-induced conditioned reward and seems to be one of the strategies to reduce the behavioral deficits and the risk of anxiety-induced alcohol abuse. Copyright © 2017 Elsevier Inc. All rights reserved.
Jangra, Ashok; Sriram, Chandra Shaker; Lahkar, Mangala
Oxido-nitrosative stress, neuroinflammation, and reduced level of neurotrophins are implicated in the pathophysiology of anxiety and depressive illness. A few recent studies have revealed the role of endoplasmic reticulum (ER) stress in the pathophysiology of stress and depression. The aim of the present study is to investigate the neuroprotective potential of sodium phenylbutyrate (SPB), an ER stress inhibitor against lipopolysaccharide (LPS)-induced anxiety and depressive-like behavior in Swiss albino mice. Anxiety and depressive-like behavior was induced by LPS (0.83 mg/kg; i.p.) administration. Various behavioral tests were conducted to evaluate the anxiety and depressive-like behavior in mice. Real-time PCR was employed for the detection and expression of ER stress markers (78-kDa glucose-regulated protein (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP)). Pretreatment with SPB significantly ameliorated the LPS-induced anxiety and depressive-like behavior as revealed by behavioral paradigm results. LPS-induced oxidative stress was ameliorated by SPB pretreatment in hippocampus (HC) and prefrontal cortex (PFC) region. Neuroinflammation was significantly reduced by SPB pretreatment in LPS-treated mice as evident from reduction in proinflammatory cytokines (IL-1β and TNF-α). Importantly, LPS administration significantly up-regulated the GRP78 mRNA expression level in the HC which suggests the involvement of unfolded protein response (UPR) in LPS-evoked behavioral anomalies. These results highlight the neuroprotective potential of SPB in LPS-induced anxiety and depressive illness model which may be partially due to inhibition of oxidative stress-neuroinflammatory cascade.
Separation anxiety is a common behavioral problem in dogs. Treatment is based on developing a behavior modification protocol that gradually desensitizes and counter-conditions the dog to being left alone, by rewarding calm, relaxed behavior. Judicious use of pharmacotherapy can be a useful adjunct to a behavior modification program.
Wen, Di; Zhao, Peng; Hui, Rongji; Wang, Jian; Shen, Qianchao; Gong, Miao; Guo, Hongyan; Cong, Bin; Ma, Chunling
Hydrogen therapy is a new medical approach for a wide range of diseases. The effects of hydrogen on central nervous system-related diseases have recently become increasingly appreciated, but little is known about whether hydrogen affects the morphine withdrawal process. This study aims to investigate the potential effects of hydrogen-rich saline (HRS) administration on naloxone-precipitated withdrawal symptoms and morphine withdrawal-induced anxiety-like behaviors. Mice received gradually increasing doses (25-100 mg/kg, i.p.) of morphine over 3 days. In the naloxone-precipitated withdrawal procedure, the mice were treated with three HRS (20 μg/kg, i.p.) injections, and naloxone (1 mg/kg, i.p.) was given 30 min after HRS administration. Body weight, jumping behavior and wet-dog shakes were immediately assessed. In the spontaneous withdrawal procedure, the mice were treated with HRS (20 μg/kg, i.p.) every 8-h. Mice underwent naloxone-precipitated or spontaneous withdrawal were tested for anxiety-like behaviors in the elevated plus-maze (EPM) and light/dark box (L/D box) paradigm, respectively. In addition, the levels of plasma corticosterone were measured. We found that HRS administration significantly reduced body weight loss, jumping behavior and wet-dog shakes in mice underwent naloxone-precipitated withdrawal, and attenuated anxiety-like behaviors in the EPM and L/D box tests after naloxone-precipitated withdrawal or a 2-day spontaneous withdrawal period. Hypo-activity or motor impairment after HRS administration was not observed in the locomotion tests. Furthermore, HRS administration significantly decreased the levels of corticosterone in morphine-withdrawn mice. These are the first findings to indicate that hydrogen might ameliorate withdrawal symptoms and exert an anxiolytic-like effect in morphine-withdrawal mice. Copyright © 2017 Elsevier Ltd. All rights reserved.
Rudoy, C.A.; Van Bockstaele, E.J.
Background Anxiety has been indicated as one of the main symptoms of the cocaine withdrawal syndrome in human addicts and severe anxiety during withdrawal may potentially contribute to relapse. As alterations in noradrenergic transmission in limbic areas underlie withdrawal symptomatology for many drugs of abuse, the present study sought to determine the effect of cocaine withdrawal on β-adrenergic receptor (β1 and β2) expression in the amygdala. Methods Male Sprague Dawley rats were administered intraperitoneal (i.p.) injections of cocaine (20 mg/kg) once daily for 14 days. Two days following the last cocaine injection, amygdala brain regions were micro-dissected and processed for Western blot analysis. Results showed that β1–adrenergic receptor, but not β2–adrenergic receptor expression was significantly increased in amygdala extracts of cocaine-withdrawn animals as compared to controls. This finding motivated further studies aimed at determining whether treatment with betaxolol, a highly selective β1–adrenergic receptor antagonist, could ameliorate cocaine withdrawal-induced anxiety. In these studies, betaxolol (5 mg/kg via i.p. injection) was administered at 24 and then 44 hours following the final chronic cocaine administration. Anxiety-like behavior was evaluated using the elevated plus maze test approximately 2 hours following the last betaxolol injection. Following behavioral testing, betaxolol effects on β1-adrenergic receptor protein expression were examined by Western blotting in amygdala extracts from rats undergoing cocaine withdrawal. Results Animals treated with betaxolol during cocaine withdrawal exhibited a significant attenuation of anxiety-like behavior characterized by increased time spent in the open arms and increased entries into the open arms compared to animals treated with only saline during cocaine withdrawal. In contrast, betaxolol did not produce anxiolytic-like effects in control animals treated chronically with saline
Schwartz, Orli S.; Dudgeon, Paul; Sheeber, Lisa B.; Yap, Marie B. H.; Simmons, Julian G.; Allen, Nicholas B.
This study investigated the prospective, longitudinal relations between parental behaviors observed during parent-adolescent interactions, and the development of depression and anxiety symptoms in a community-based sample of 194 adolescents. Positive and negative parental behaviors were examined, with negative behaviors operationalized to…
Thompson, Trey; Grabowski-Boase, Laura; Tarantino, Lisa M
Understanding and effectively treating anxiety disorders are a challenge for both scientists and clinicians. Despite a variety of available therapies, the efficacy of current treatments is still not optimal and adverse side effects can result in non-compliance. Animal models have been useful for studying the underlying biology of anxiety and assessing the anxiolytic properties of potential therapeutics. The open field (OF) is a commonly used assay of anxiety-like behavior. The OF was developed and validated in rats and then transferred to use in the mouse with only limited validation. The present study tests the efficacy of prototypical benzodiazepine anxiolytics, chlordiazepoxide (CDP) and diazepam (DZ), for increasing center time in the OF in C57BL/6J (B6) mice. Multiple doses of CDP and DZ did not change time spent in the center of the OF. Increasing illumination in the OF did not alter these results. The non-benzodiazepine anxiolytic, buspirone (BUSP) also failed to increase center time in the OF while the anxiogenic meta-chlorophenylpiperazine (mCPP) increased center time. Additional inbred mouse strains, BALB/cJ (BALB) and DBA/2J (D2) did not show any change in center time in response to CDP. Moreover, evaluation of CDP in B6 mice in the elevated plus maze (EPM), elevated zero maze (EZM) and light dark assay (LD) did not reveal changes in anxiety-like behavior while stress-induced hyperthermia (SIH) was decreased by DZ. Pharmacokinetic (PK) studies suggest that adequate CDP is present to induce anxiolysis. We conclude that the measure of center time in the OF does not show predictive validity for anxiolysis in these inbred mouse strains. Copyright © 2015 Elsevier Inc. All rights reserved.
Chronic restraint stress causes anxiety- and depression-like behaviors, downregulates glucocorticoid receptor expression, and attenuates glutamate release induced by brain-derived neurotrophic factor in the prefrontal cortex.
Chiba, Shuichi; Numakawa, Tadahiro; Ninomiya, Midori; Richards, Misty C; Wakabayashi, Chisato; Kunugi, Hiroshi
Stress and the resulting increase in glucocorticoid levels have been implicated in the pathophysiology of depressive disorders. We investigated the effects of chronic restraint stress (CRS: 6 hours × 28 days) on anxiety- and depression-like behaviors in rats and on the possible changes in glucocorticoid receptor (GR) expression as well as brain-derived neurotrophic factor (BDNF)-dependent neural function in the prefrontal cortex (PFC). We observed significant reductions in body weight gain, food intake and sucrose preference from 1 week after the onset of CRS. In the 5th week of CRS, we conducted open-field (OFT), elevated plus-maze (EPM) and forced swim tests (FST). We observed a decrease in the number of entries into open arms during the EPM (anxiety-like behavior) and increased immobility during the FST (depression-like behavior). When the PFC was removed after CRS and subject to western blot analysis, the GR expression reduced compared with control, while the levels of BDNF and its receptors remained unchanged. Basal glutamate concentrations in PFC acute slice which were measured by high performance liquid chromatography were not influenced by CRS. However, BDNF-induced glutamate release was attenuated after CRS. These results suggest that reduced GR expression and altered BDNF function may be involved in chronic stress-induced anxiety--and depression-like behaviors. Copyright © 2012 Elsevier Inc. All rights reserved.
Buckner, Julia D; Heimberg, Richard G; Matthews, Russell A; Silgado, Jose
Individuals with elevated social anxiety appear particularly vulnerable to marijuana-related problems. In fact, individuals with social anxiety may be more likely to experience marijuana-related impairment than individuals with other types of anxiety. It is therefore important to determine whether constructs particularly relevant to socially anxious individuals play a role in the expression of marijuana-related problems in this vulnerable population. Given that both social avoidance and using marijuana to cope with negative affect broadly have been found to play a role in marijuana-related problems, the current study utilized a new measure designed to simultaneously assess social avoidance and using marijuana to cope in situations previously identified as anxiety-provoking among those with elevated social anxiety. The Marijuana Use to Cope with Social Anxiety Scale (MCSAS) assessed behaviors regarding 24 social situations: marijuana use to cope in social situations (MCSAS-Cope) and avoidance of social situations if marijuana was unavailable. In Study 1, we found preliminary support for the convergent and discriminant validity and internal consistency of the MCSAS scales. In Study 2, we examined if MCSAS scores were related to marijuana problems among those with (n = 44) and without (n = 44) clinically elevated social anxiety. Individuals with clinically meaningful social anxiety were more likely to use marijuana to cope in social situations and to avoid social situations if marijuana was unavailable. Of importance, MCSAS-Cope uniquely mediated the relationship between social anxiety group status and marijuana-related problems. Results highlight the importance of contextual factors in assessing marijuana-related behaviors among high-risk populations. PsycINFO Database Record (c) 2012 APA, all rights reserved.
Full Text Available Objectives: This study aimed at evaluating the effectiveness of cognitive-behavioral group therapy on craving, symptoms of depression and anxiety among the patients under MMT. Methods: In this experimental study, 36 opiate addicts under MMT were selected out of all the patients referring to Iranian National Center of Addiction Studies on a judgmental sampling method and were randomly allocated to two experimental and control groups. In experimental group, a total sum of 8 sessions (one session per week of cognitive behavioral group therapy were delivered. The main theme of these sessions were efficient management of craving, negative mood and anxiety. Data were gathered with different questionnaires including the questionnaire of demographic data, RPS for craving assessment, BDI-II for depression and BAI for anxiety. Different methods of statistical analysis were implemented. Results: The results indicated that post test and follow-up scores of craving index were decreased significantly (P<0.05. Depression and Anxiety scores showed significant decrease as well. Discussion: Considering the above mentioned findings, we concluded that cognitive-behavioral group therapy was effective in significantly decreasing craving and symptoms of anxiety and depression in opiate addicts under MMT.
Mazzone, C M; Pati, D; Michaelides, M; DiBerto, J; Fox, J H; Tipton, G; Anderson, C; Duffy, K; McKlveen, J M; Hardaway, J A; Magness, S T; Falls, W A; Hammack, S E; McElligott, Z A; Hurd, Y L; Kash, T L
The bed nucleus of the stria terminalis (BNST) is a brain region important for regulating anxiety-related behavior in both humans and rodents. Here we used a chemogenetic strategy to investigate how engagement of G protein-coupled receptor (GPCR) signaling cascades in genetically defined GABAergic BNST neurons modulates anxiety-related behavior and downstream circuit function. We saw that stimulation of vesicular γ-aminobutyric acid (GABA) transporter (VGAT)-expressing BNST neurons using hM3Dq, but neither hM4Di nor rM3Ds designer receptors exclusively activated by a designer drug (DREADD), promotes anxiety-like behavior. Further, we identified that activation of hM3Dq receptors in BNST VGAT neurons can induce a long-term depression-like state of glutamatergic synaptic transmission, indicating DREADD-induced changes in synaptic plasticity. Further, we used DREADD-assisted metabolic mapping to profile brain-wide network activity following activation of G q -mediated signaling in BNST VGAT neurons and saw increased activity within ventral midbrain structures, including the ventral tegmental area and hindbrain structures such as the locus coeruleus and parabrachial nucleus. These results highlight that G q -mediated signaling in BNST VGAT neurons can drive downstream network activity that correlates with anxiety-like behavior and points to the importance of identifying endogenous GPCRs within genetically defined cell populations. We next used a microfluidics approach to profile the receptorome of single BNST VGAT neurons. This approach yielded multiple G q -coupled receptors that are associated with anxiety-like behavior and several potential novel candidates for regulation of anxiety-like behavior. From this, we identified that stimulation of the G q -coupled receptor 5-HT 2C R in the BNST is sufficient to elevate anxiety-like behavior in an acoustic startle task. Together, these results provide a novel profile of receptors within genetically defined BNST VGAT
Qintar, Mohammed; George, Jason J; Panko, Melanie
, but higher anxiety was associated with recent and total number of shocks. The small pilot study suggested that a simple program of CBT might lower moderate-high anxiety with lasting effects to 1 year and supports the need for a larger trial to validate these results. CLINICAL TRIAL REGISTRATION: Clinical......PURPOSE: Stress and anxiety are potential consequences from arrhythmias and implantable cardioverter defibrillator (ICD) shocks that can contribute to substantial morbidity. We assessed anxiety associated with an ICD and whether cognitive behavioral therapy (CBT) reduces anxiety. METHODS: The study...... consisted of two parts: part 1 (N = 690) was a prospective cross-sectional observational study of consecutive ICD patients. Patients completed the Beck Anxiety Inventory (BAI), Generalized Anxiety Disorder Scale (GAD-7), Florida Shock Anxiety Scale (FSAS), and Florida Patient Acceptance Survey (FPAS...
Full Text Available Emotional eating is an attempt to avoid, control, or cope with negative emotions through eating a large amount of calorie dense sweet and/or high fat foods. Several factors, including various attentional mechanisms, negative affect, and stress, impact emotional eating behavior. For example, attentional narrowing on negative events may increase attentional stickiness and thereby prevent the processing of more peripheral events, such as eating behavior. This study contributes to the extant literature by examining the neural correlates underlying the attentional conflict between processing negative events and regulating behavior within a task that emulates how negative life experiences might contribute to unrestrained eating behavior. We explore this question within a normative sample that varies in their self-reported anxiety symptoms. Dense-array EEG was collected while participants played the attentional blink game—a task in which excessive attentional resource allocated to one event (e.g., negative picture interferes with the adequate attentional processing of a second event that requires action. To assess the attentional conflict, we measured N2 activation, an event-related potentials (ERPs; averaged EEG associated with conflict processing. Results revealed that N2 activation moderates the association between anxiety and emotional-eating behavior. Thus, increased anxiety combined with more negative N2 activation can contribute to emotional-eating behavior. These results are discussed in the context of ineffective conflict processing contributing to poor emotion regulation.
Bernardo, Melissa A; Singer, Michael S
Research on parasite-altered feeding behavior in insects is contributing to an emerging literature that considers possible adaptive consequences of altered feeding behavior for the host or the parasite. Several recent ecoimmunological studies show that insects can adaptively alter their foraging behavior in response to parasitism. Another body of recent work shows that infection by parasites can change the behavior of insect hosts to benefit the parasite; manipulations of host feeding behavior may be part of this phenomenon. Here, we address both the functional and the underlying physiological frontiers of parasite-altered feeding behavior in order to spur research that better integrates the two. Functional categories of parasite-altered behavior that are adaptive for the host include prophylaxis, therapy and compensation, while host manipulation is adaptive for the parasite. To better understand and distinguish prophylaxis, therapy and compensation, further study of physiological feedbacks affecting host sensory systems is especially needed. For host manipulation in particular, research on mechanisms by which parasites control host feedbacks will be important to integrate with functional approaches. We see this integration as critical to advancing the field of parasite-altered feeding behavior, which may be common in insects and consequential for human and environmental health. © 2017. Published by The Company of Biologists Ltd.
Myers, Brent; Carvalho-Netto, Eduardo; Wick-Carlson, Dayna; Wu, Christine; Naser, Sam; Solomon, Matia B; Ulrich-Lai, Yvonne M; Herman, James P
The posterior hypothalamic nucleus (PH) stimulates autonomic stress responses. However, the role of the PH in behavioral correlates of psychiatric illness, such as social and anxiety-like behavior, is largely unexplored, as is the neurochemistry of PH connectivity with limbic and neuroendocrine systems. Thus, the current study tested the hypothesis that GABAergic signaling within the PH is a critical link between forebrain behavior-regulatory nuclei and the neuroendocrine hypothalamus, integrating social and anxiety-related behaviors with physiological stress reactivity. To address this hypothesis, GABAA receptor pharmacology was used to locally inhibit or disinhibit the PH immediately before behavioral measures of social and anxiety-like behavior in rats. Limbic connectivity of the PH was then established by simultaneous co-injection of anterograde and retrograde tracers. Further, the role of PH GABAergic signaling in neuroendocrine stress responses was tested via inhibition/disinhibition of the PH. These studies determined a prominent role for the PH in the expression of anxiety-related behaviors and social withdrawal. Histological analyses revealed divergent stress-activated limbic input to the PH, emanating predominantly from the prefrontal cortex, lateral septum, and amygdala. PH projections also targeted both parvicellular and magnocellular peptidergic neurons in the paraventricular and supraoptic hypothalamus. Further, GABAA receptor pharmacology determined an excitatory effect of the PH on neuroendocrine responses to stress. These data indicate that the PH represents an important stress-integrative center, regulating behavioral processes and connecting the limbic forebrain with neuroendocrine systems. Moreover, the PH appears to be uniquely situated to have a role in stress-related pathologies associated with limbic-hypothalamic dysfunction.
Chen, Chih-Ming; Wang, Jung-Ying; Chen, Yong-Ting; Wu, Jhih-Hao
To reduce effectively the reading anxiety of learners while reading English articles, a C4.5 decision tree, a widely used data mining technique, was used to develop a personalized reading anxiety prediction model (PRAPM) based on individual learners' reading annotation behavior in a collaborative digital reading annotation system (CDRAS). In…
Sulakhiya, Kunjbihari; Kumar, Parveen; Gurjar, Satendra S; Barua, Chandana C; Hazarika, Naba K
Anxiety disorders are commonly occurring co-morbid neuropsychiatric disorders with chronic inflammatory conditions such as live damage. Numerous studies revealed that peripheral inflammation, oxidative stress and brain derived neurotrophic factor (BDNF) play important roles in the pathophysiology of anxiety disorders. Honokiol (HNK) is a polyphenol, possessing multiple biological activities including antioxidant, anti-inflammatory, anxiolytic, antidepressant and hepatoprotection. The present study was designed to investigate the effect of HNK, in lipopolysaccharide (LPS)-induced anxiety-like behavior and liver damage in mice. Mice (n=6-10/group) were pre-treated with different doses of HNK (2.5 and 5mg/kg; i.p.) for two days, and challenged with saline or LPS (0.83mg/kg; i.p.) on third day. Anxiety-like behavior was monitored using elevated plus maze (EPM) and open field test (OFT). Animals were sacrificed to evaluate various biochemical parameters in plasma and liver. HNK pre-treatment provided significant (P<0.01) protection against LPS-induced reduction in body weight, food and water intake in mice. HNK at higher dose significantly (P<0.05) attenuated LPS-induced anxiety-like behavior by increasing the number of entries and time spent in open arm in EPM test, and by increasing the frequency in central zone in OFT. HNK pre-treatment ameliorated LPS-induced peripheral inflammation by reducing plasma IL-1β, IL-6, TNF-α level, and also improved the plasma BDNF level, prevented liver damage via attenuating transaminases (AST, ALT), liver oxidative stress and TNF-α activity in LPS challenged mice. In conclusion, the current investigation suggests that HNK provided beneficial effect against LPS-induced anxiety-like behavior and liver damage which may be governed by inhibition of cytokines production, oxidative stress and depletion of plasma BDNF level. Our result suggests that HNK could be a therapeutic approach for the treatment of anxiety and other
Pires, Gabriel Natan; Bezerra, Andréia Gomes; Tufik, Sergio; Andersen, Monica Levy
Increased acute anxiety is a commonly reported behavioral consequence of sleep deprivation in humans. However, rodent studies conducted so far produced inconsistent results, failing to reproduce the same sleep deprivation induced-anxiety observed in clinical experiments. While some presented anxiogenesis as result of sleep deprivation, others reported anxiolysis. In face of such inconsistencies, this article explores the effects of experimental sleep deprivation on anxiety-like behavior in animal research through a systematic review and a series of meta-analyses. A total of 50 of articles met our inclusion criteria, 30 on mice, 19 on rats and one on Zebrafish. Our review shows that sleep deprivation induces a decrease in anxiety-like behavior in preclinical models, which is opposite to results observed in human settings. These results were corroborated in stratified analyses according to species, sleep deprivation method and anxiety measurement technique. In conclusion, the use of animal models for the evaluation of the relationship between sleep deprivation lacks translational applicability and new experimental tools are needed to properly evaluate sleep deprivation-induced anxiogenesis in rodents. Copyright © 2016 Elsevier Ltd. All rights reserved.
Enea, Violeta; Dafinoiu, Ion; Bogdan, Georgiana; Matei, Carmen
Most of the studies concerning nonsuicidal self-injury behaviors of persons deprived of liberty were on female participants. This cross-sectional comparative study compared the levels of death anxiety, pain catastrophizing, dissociative experiences, and state-trait anger among male inmates with nonsuicidal self-injury behaviors and noninjuring controls. The results indicated high levels of death anxiety, dissociation, and pain catastrophizing in both groups of participants and the absence of significant differences between the groups. The implications of the results suggest the need of taking into consideration these variables in the behavior management plans used with inmates who engage in self-injurious behavior.
Becker, Jérôme A J; Kieffer, Brigitte L; Le Merrer, Julie
Unified theories of addiction are challenged by differing drug-seeking behaviors and neurobiological adaptations across drug classes, particularly for narcotics and psychostimulants. We previously showed that protracted abstinence to opiates leads to despair behavior and social withdrawal in mice, and we identified a transcriptional signature in the extended amygdala that was also present in animals abstinent from nicotine, Δ9-tetrahydrocannabinol (THC) and alcohol. Here we examined whether protracted abstinence to these four drugs would also share common behavioral features, and eventually differ from abstinence to the prototypic psychostimulant cocaine. We found similar reduced social recognition, increased motor stereotypies and increased anxiety with relevant c-fos response alterations in morphine, nicotine, THC and alcohol abstinent mice. Protracted abstinence to cocaine, however, led to strikingly distinct, mostly opposing adaptations at all levels, including behavioral responses, neuronal activation and gene expression. Together, these data further document the existence of common hallmarks for protracted abstinence to opiates, nicotine, THC and alcohol that develop within motivation/emotion brain circuits. In our model, however, these do not apply to cocaine, supporting the notion of unique mechanisms in psychostimulant abuse. © 2016 Society for the Study of Addiction.
Pınar, Neslihan; Akillioglu, Kubra; Sefil, Fatih; Alp, Harun; Sagir, Mustafa; Acet, Ahmet
Atypical antipsychotics have been used to treat fear and anxiety disturbance that are highly common in schizophrenic patients. It is suggested that disruptions of N-methyl-d-aspartate (NMDA)-mediated transmission of glutamate may underlie the pathophysiology of schizophrenia. The present study was conducted to analyze the effectiveness of clozapine on the anxiety-related behavior and locomotor function of the adult brain, which had previously undergone NMDA receptor blockade during a developmental period. In order to block the NMDA receptor, male mice were administered 0.25 mg/kg of MK-801 on days 7 to 10 postnatal. In adulthood, they were administered intraperitoneally 0.5 mg/kg of clozapine and tested with open-field and elevated plus maze test, to assess their emotional behavior and locomotor activity. In the group receiving MK-801 in the early developmental period the elevated plus maze test revealed a reduction in the anxiety-related behavior (ptest indicated a decrease in locomotor activity (plocomotor activity and anxiety-related behavior, induced by administration of the MK-801 in neonatal period.
Safir, Marilyn P; Wallach, Helene S; Bar-Zvi, Margalit
Public speaking anxiety (PSA) is a common social phobia. Although cognitive-behavior therapy (CBT) is the treatment of choice, difficulties arise with both in vivo and in vitro exposure (lack of therapist control, patient's inability to imagine, self-flooding, and a lack of confidentiality resulting from public exposure). Virtual reality CBT (VRCBT) enables a high degree of therapist control, thus overcoming these difficulties. In a previous publication, the authors reported on their findings that VRCBT (n = 28) and CBT (n = 30) groups were significantly more effective than a wait-list control (WLC; n = 30) group in anxiety reduction on four of five anxiety measures as well as on participant's self-rating of anxiety during a behavioral task. No significant differences were found between VRCBT and CBT. However, twice as many clients dropped out of CBT (15) than from VRCBT (6). Results demonstrated that VRCBT is an effective and brief treatment regimen, equal to CBT. This brief report examined durability of these changes. They found that both VRCBT (25) and CBT (24) groups maintained their improvement from post treatment to follow-up, on all five measures. In addition, they found that the CBT group continued to improve from post treatment to follow-up on Liebowitz Social Anxiety Scale (LSAS) fear. Thus, treatment gains were maintained at a 1-year follow-up.
Thompson, Elaine Adams; Mazza, James J.; Herting, Jerald R.; Randell, Brooke P.; Eggert, Leona L.
The purpose of this study was to explore the roles of anxiety, depression, and hopelessness as mediators between known risk factors and suicidal behaviors among 1,287 potential high school dropouts. As a step toward theory development, a model was tested that posited the relationships among these variables and their effects on suicidal behaviors.…
Moree, Brittany N.; Davis, Thompson E., III
Anxiety disorders have been found to be highly comorbid with autism spectrum disorders (ASDs). Even so, the identification and dissemination of empirically supported treatments for anxiety in adults or children who have ASD has lagged behind the larger evidence-based trend. This review examines the efficacy of cognitive-behavioral therapy as a…
Nilgun Ongider-Gregory; Burak Baykara
Objective: It was aimed to investigate efficacy of Cognitive behavioral group therapy (CBGT) in childhood anxiety disorders by pre and post therapy. Method: Trial sample was obtained from an university outpatient child psychiatry clinic. Therapy group (n=12) was selected from children and their parents whom was diagnosed as DSM-IV childhood anxiety disorder. And comparation group (n=12) was selected from children and their parents whom was in the waiting list. The total sample includes...
Bartlett, Andrew A; Singh, Rumani; Hunter, Richard G
Anxiety disorders are highly prevalent psychiatric disorders often comorbid with depression and substance abuse. Twin studies have shown that anxiety disorders are moderately heritable. Yet, genome-wide association studies (GWASs) have failed to identify gene(s) significantly associated with diagnosis suggesting a strong role for environmental factors and the epigenome. A number of anxiety disorder subtypes are considered "stress related." A large focus of research has been on the epigenetic and anxiety-like behavioral consequences of stress. Animal models of anxiety-related disorders have provided strong evidence for the role of stress on the epigenetic control of the hypothalamic-pituitary-adrenal (HPA) axis and of stress-responsive brain regions. Neuroepigenetics may continue to explain individual variation in susceptibility to environmental perturbations and consequently anxious behavior. Behavioral and pharmacological interventions aimed at targeting epigenetic marks associated with anxiety may prove fruitful in developing treatments.
Kendall R Walker
Full Text Available Golgi-localized γ-ear-containing ARF binding protein 3 (GGA3 is a monomeric clathrin adaptor that has been shown to regulate the trafficking of the Beta-site APP-cleaving enzyme (BACE1, which is required for production of the Alzheimer's disease (AD-associated amyloid βpeptide. Our previous studies have shown that BACE1 is degraded via the lysosomal pathway and that depletion of GGA3 results in increased BACE1 levels and activity owing to impaired lysosomal trafficking and degradation. We further demonstrated the role of GGA3 in the regulation of BACE1 in vivo by showing that BACE1 levels are increased in the brain of GGA3 null mice. We report here that GGA3 deletion results in novelty-induced hyperactivity and decreased anxiety-like behaviors. Given the pivotal role of GABAergic transmission in the regulation of anxiety-like behaviors, we performed electrophysiological recordings in hippocampal slices and found increased phasic and decreased tonic inhibition in the dentate gyrus granule cells (DGGC. Moreover, we found that the number of inhibitory synapses is increased in the dentate gyrus of GGA3 null mice in further support of the electrophysiological data. Thus, the increased GABAergic transmission is a leading candidate mechanism underlying the reduced anxiety-like behaviors observed in GGA3 null mice. All together these findings suggest that GGA3 plays a key role in GABAergic transmission. Since BACE1 levels are elevated in the brain of GGA3 null mice, it is possible that at least some of these phenotypes are a consequence of increased processing of BACE1 substrates.
Walker, Kendall R; Modgil, Amit; Albrecht, David; Lomoio, Selene; Haydon, Philip G; Moss, Stephen J; Tesco, Giuseppina
Golgi-localized γ-ear-containing ARF binding protein 3 (GGA3) is a monomeric clathrin adaptor that has been shown to regulate the trafficking of the Beta-site APP-cleaving enzyme (BACE1), which is required for production of the Alzheimer's disease (AD)-associated amyloid βpeptide. Our previous studies have shown that BACE1 is degraded via the lysosomal pathway and that depletion of GGA3 results in increased BACE1 levels and activity owing to impaired lysosomal trafficking and degradation. We further demonstrated the role of GGA3 in the regulation of BACE1 in vivo by showing that BACE1 levels are increased in the brain of GGA3 null mice. We report here that GGA3 deletion results in novelty-induced hyperactivity and decreased anxiety-like behaviors. Given the pivotal role of GABAergic transmission in the regulation of anxiety-like behaviors, we performed electrophysiological recordings in hippocampal slices and found increased phasic and decreased tonic inhibition in the dentate gyrus granule cells (DGGC). Moreover, we found that the number of inhibitory synapses is increased in the dentate gyrus of GGA3 null mice in further support of the electrophysiological data. Thus, the increased GABAergic transmission is a leading candidate mechanism underlying the reduced anxiety-like behaviors observed in GGA3 null mice. All together these findings suggest that GGA3 plays a key role in GABAergic transmission. Since BACE1 levels are elevated in the brain of GGA3 null mice, it is possible that at least some of these phenotypes are a consequence of increased processing of BACE1 substrates.
Walczak, Monika; Esbjørn, Barbara H; Breinholst, Sonja
Parental factors have been linked to childhood anxiety, hence, parental involvement in cognitive behavioral therapy (CBT) for anxious children has been examined. However, findings do not consistently show added effects of parent-enhanced CBT, longitudinal investigations are scarce and long...
Thai, Nhi; Taber-Thomas, Bradley C; Pérez-Edgar, Koraly E
Behavioral inhibition (BI) is a biologically-based temperament characterized by vigilance toward threat. Over time, many children with BI increasingly fear social circumstances and display maladaptive social behavior. BI is also one of the strongest individual risk factors for developing social anxiety disorder. Although research has established a link between BI and anxiety, its causal mechanism remains unclear. Attention biases may underlie this relation. The current study examined neural markers of the BI-attention-anxiety link in children ages 9-12 years (N=99, Mean=9.97, SD=0.97). ERP measures were collected as children completed an attention-bias (dot-probe) task with neutral and angry faces. P2 and N2 amplitudes were associated with social anxiety and attention bias, respectively. Specifically, augmented P2 was related to decreased symptoms of social anxiety and moderated the relation between BI and social anxiety, suggesting that increasing attention mobilization may serve as a compensatory mechanism that attenuates social anxiety in individuals with high BI. The BI by N2 interaction found that larger N2 related to threat avoidance with increasing levels of BI, consistent with over-controlled socio-emotional functioning. Lastly, children without BI (BN) showed an augmented P1 to probes replacing angry faces, suggesting maintenance of attentional resources in threat-related contexts. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
Full Text Available Several severe stressful situations, e.g., natural disaster, infectious disease out break, and mass casualty, are known to cause anxiety, depression and cognitive impairment, and preventive intervention for these stress complications is worth exploring. We have previously reported that the serotonin-norepinephrine-dopamine reuptake inhibitor, venlafaxine, as well as voluntary wheel running are effective in the treatment of anxiety- and depression-like behaviors in stressed rats. But whether they are able to prevent deleterious consequences of restraint stress in rats, such as anxiety/depression-like behaviors and memory impairment that occur afterward, was not known. Herein, male Wistar rats were pre-treated for 4 weeks with anti-anxiety/anti-depressive drugs, agomelatine and venlafaxine, or voluntary wheel running, followed by 4 weeks of restraint-induced stress. During the stress period, rats received neither drug nor exercise intervention. Our results showed that restraint stress induced mixed anxiety- and depression-like behaviors, and memory impairment as determined by elevated plus-maze, elevated T-maze, open field test (OFT, forced swimming test (FST, and Morris water maze (MWM. Both pharmacological pre-treatments and running successfully prevented the anxiety-like behavior, especially learned fear, in stressed rats. MWM test suggested that agomelatine, venlafaxine, and running could prevent stress-induced memory impairment, but only pharmacological treatments led to better novel object recognition behavior and positive outcome in FST. Moreover, western blot analysis demonstrated that venlafaxine and running exercise upregulated brain-derived neurotrophic factor (BDNF expression in the hippocampus. In conclusion, agomelatine, venlafaxine as well as voluntary wheel running had beneficial effects, i.e., preventing the restraint stress-induced anxiety/depression-like behaviors and memory impairment.
von der Embse, Nathaniel P.; Scott, Emma-Catherine; Kilgus, Stephen P.
Multitiered frameworks of service delivery have traditionally underserved students with mental health needs. Whereas research has supported the assessment and intervention of social and academic behavior across tiers, evidence is limited with regard to mental health concerns including internalizing behaviors (e.g., anxiety and depression). In…
Shahnavaz, Shervin; Rutley, Sara; Larsson, Karin; Dahllöf, Göran
There is a high prevalence of dental anxiety in children and adolescents. Cognitive behavioral therapy is emerging as a treatment option. The purpose of this study is to explore how children with dental anxiety and their parents experience cognitive behavioral therapy (CBT) in dentistry. We interviewed 12 children and one of their parents and conducted a thematic analysis of the transcribed interviews. Perspective shift emerged as overarching theme in our thematic analysis. This theme consisted of three main themes, which were mastery, safety, and reduced fear. Six subthemes were also identified according to our analyses. Mastery includes two subthemes, gradual exposure and autonomy and control. Subthemes and sources for safety feeling were therapeutic alliance and changed appraisal. The theme reduced fear also consisted of two subthemes; reduced anticipatory anxiety and coping. The results show that parents and children had positive experiences of CBT and its outcome and were able to benefit from this psychological treatment when dealing with dental anxiety. © 2015 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Peterman, Jeremy S; Carper, Matthew M; Elkins, R Meredith; Comer, Jonathan S; Pincus, Donna B; Kendall, Philip C
The present study examined (a) whether sleep related problems (SRPs) improved following cognitive-behavioral therapy (CBT) for youth with anxiety disorders, (b) whether variables that may link anxiety and SRPs (e.g., pre-sleep arousal, family accommodation, sleep hygiene) changed during treatment, and (c) whether such changes predicted SRPs at posttreatment. Youth were diagnosed with anxiety at pretreatment and received weekly CBT that targeted their principal anxiety diagnosis at one of two specialty clinics (N=69 completers, Mage=10.86). Results indicated that parent-reported SRPs improved from pre- to post-treatment and that treatment responders with regard to anxiety yielded greater SRP improvements than nonresponders. Parent report of bedtime resistance and sleep anxiety showed significant improvements. Youth reported lower rates of SRPs compared to their parents and did not demonstrate pre- to post-treatment changes in SRPs. Pre-sleep arousal and family accommodation decreased over treatment but did not predict lower SRPs at posttreatment. Higher accommodation was correlated with greater SRPs. Sleep hygiene evidenced no change and did not mediate links between accommodation and posttreatment SRPs. Copyright © 2015 Elsevier Ltd. All rights reserved.
Morrison, Thomas R; Ricci, Lesley A; Melloni, Richard H
Adolescent Syrian hamsters (Mesocricetus auratus) treated with anabolic/androgenic steroids display increased offensive aggression and decreased anxiety correlated with an increase in vasopressin afferent development, synthesis, and neural signaling within the anterior hypothalamus. Upon withdrawal from anabolic/androgenic steroids, this neurobehavioral relationship shifts as hamsters display decreased offensive aggression and increased anxiety correlated with a decrease in anterior hypothalamic vasopressin. This study investigated the hypothesis that alterations in anterior hypothalamic vasopressin neural signaling modulate behavioral shifting between adolescent anabolic/androgenic steroid-induced offensive aggression and anxiety. To test this, adolescent male hamsters were administered anabolic/androgenic steroids and tested for offensive aggression or anxiety following direct pharmacological manipulation of vasopressin V1A receptor signaling within the anterior hypothalamus. Blockade of anterior hypothalamic vasopressin V1A receptor signaling suppressed offensive aggression and enhanced general and social anxiety in hamsters administered anabolic/androgenic steroids during adolescence, effectively reversing the pattern of behavioral response pattern normally observed during the adolescent exposure period. Conversely, activation of anterior hypothalamic vasopressin V1A receptor signaling enhanced offensive aggression in hamsters exposed to anabolic/androgenic steroids during adolescence. Together, these findings suggest that the state of vasopressin neural development and signaling in the anterior hypothalamus plays an important role in behavioral shifting between aggression and anxiety following adolescent exposure to anabolic/androgenic steroids. Copyright © 2016 Elsevier Inc. All rights reserved.
Leibrock, Christina; Ackermann, Teresa F; Hierlmeier, Michael; Lang, Florian; Borgwardt, Stefan; Lang, Undine E
The economic burden associated with major depressive disorder and anxiety disorders render both disorders the most common and debilitating psychiatric illnesses. To date, the exact cellular and molecular mechanisms underlying the pathophysiology, successful treatment and prevention of these highly associated disorders have not been identified. Akt2 is a key protein in the phosphatidylinositide-3 (PI3K) / glycogen synthase 3 kinase (GSK3) signaling pathway, which in turn is involved in brain-derived neurotrophic factor (BDNF) effects on fear memory, mood stabilisation and action of several antidepressant drugs. The present study thus explored the impact of Akt2 on behaviour of mice. Behavioural studies (Open-Field, Light-Dark box, O-Maze, Forced Swimming Test, Emergence Test, Object Exploration Test, Morris Water Maze, Radial Maze) have been performed with Akt2 knockout mice (akt(-/-)) and corresponding wild type mice (akt(+/+)). Anxiety and depressive behavior was significantly higher in akt(-/-) than in akt(+/+) mice. The akt(-/-) mice were cognitively unimpaired but displayed increased anxiety in several behavioral tests (O-Maze test, Light-Dark box, Open Field test). Moreover, akt(-/-) mice spent more time floating in the Forced Swimming test, which is a classical feature of experimental depression. Akt2 might be a key factor in the pathophysiology of depression and anxiety. © 2013 S. Karger AG, Basel.
Full Text Available Background: The economic burden associated with major depressive disorder and anxiety disorders render both disorders the most common and debilitating psychiatric illnesses. To date, the exact cellular and molecular mechanisms underlying the pathophysiology, successful treatment and prevention of these highly associated disorders have not been identified. Akt2 is a key protein in the phosphatidylinositide-3 (PI3K / glycogen synthase 3 kinase (GSK3 signaling pathway, which in turn is involved in brain-derived neurotrophic factor (BDNF effects on fear memory, mood stabilisation and action of several antidepressant drugs. The present study thus explored the impact of Akt2 on behaviour of mice. Methods: Behavioural studies (Open-Field, Light-Dark box, O-Maze, Forced Swimming Test, Emergence Test, Object Exploration Test, Morris Water Maze, Radial Maze have been performed with Akt2 knockout mice (akt-/- and corresponding wild type mice (akt+/+. Results: Anxiety and depressive behavior was significantly higher in akt-/- than in akt+/+ mice. The akt-/- mice were cognitively unimpaired but displayed increased anxiety in several behavioral tests (O-Maze test, Light-Dark box, Open Field test. Moreover, akt-/- mice spent more time floating in the Forced Swimming test, which is a classical feature of experimental depression. Conclusion: Akt2 might be a key factor in the pathophysiology of depression and anxiety.
Yu, Dafu; Zhou, Heng; Yang, Yuan; Jiang, Yong; Wang, Tianchao; Lv, Liang; Zhou, Qixin; Yang, Yuexiong; Dong, Xuexian; He, Jianfeng; Huang, Xiaoyan; Chen, Jijun; Wu, Kunhua; Xu, Lin; Mao, Rongrong
Thyroid hormone disorders have long been linked to depression, but the causal relationship between them remains controversial. To address this question, we established rat models of hypothyroidism using (131)iodine ((131)I) and hyperthyroidism using levothyroxine (LT4). Serum free thyroxine (FT4) and triiodothyronine (FT3) significantly decreased in the hypothyroid of rats with single injections of (131)I (5mCi/kg). These rats exhibited decreased depression-like behaviors in forced swimming test and sucrose preference tests, as well as decreased anxiety-like behaviors in an elevated plus maze. Diminished levels of brain serotonin (5-HT) and increased levels of hippocampal brain-derived neurotrophic factor (BDNF) were found in the hypothyroid rats compared to the control saline-vehicle administered rats. LT4 treatment reversed the decrease in thyroid hormones and depression-like behaviors. In contrast, hyperthyroidism induced by weekly injections of LT4 (15μg/kg) caused a greater than 10-fold increase in serum FT4 and FT3 levels. The hyperthyroid rats exhibited higher anxiety- and depression-like behaviors, higher brain 5-HT level, and lower hippocampal BDNF levels than the controls. Treatment with the antidepressant imipramine (15mg/kg) diminished serum FT4 levels as well as anxiety- and depression-like behaviors in the hyperthyroid rats but led to a further increase in brain 5-HT levels, compared with the controls or the hypothyroid rats. Together, our results suggest that hypothyroidism and hyperthyroidism have bidirectional effects on anxiety- and depression-like behaviors in rats, possibly by modulating hippocampal BDNF levels. Copyright © 2015 Elsevier Inc. All rights reserved.
Müller, Mitho; Tronick, Ed; Zietlow, Anna-Lena; Nonnenmacher, Nora; Verschoor, Stephan; Träuble, Birgit
We investigated the links between maternal bonding, maternal anxiety disorders, and infant self-comforting behaviors. Furthermore, we looked at the moderating roles of infant gender and age. Our sample (n = 69) comprised 28 mothers with an anxiety disorder (according to DSM-IV criteria) and 41 controls, each with their 2.5- to 8-month-old infant (41 females and 28 males). Infant behaviors were recorded during the Face-to-Face Still-Face paradigm. Maternal bonding was assessed by the Postpartum Bonding Questionnaire. Conditional process analyses revealed that lower maternal bonding partially mediated between maternal anxiety disorders and increased self-comforting behaviors but only in older female infants (over 5.5 months of age). However, considering maternal anxiety disorders without the influence of bonding, older female infants (over 5.5 months of age) showed decreased rates of self-comforting behaviors, while younger male infants (under 3 months of age) showed increased rates in the case of maternal anxiety disorder. The results suggest that older female infants (over 5.5 months of age) are more sensitive to lower maternal bonding in the context of maternal anxiety disorders. Furthermore, results suggest a different use of self-directed regulation strategies for male and female infants of mothers with anxiety disorders and low bonding, depending on infant age. The results are discussed in the light of gender-specific developmental trajectories. © 2016 S. Karger AG, Basel.
Kas, Martien J H; de Mooij-van Malsen, Annetrude J G; Olivier, Berend; Spruijt, Berry M; van Ree, Jan M
Traditional behavioral tests, such as the open field test, measure an animal's responsiveness to a novel environment. However, it is generally difficult to assess whether the behavioral response obtained from these tests relates to the expression level of motor activity and/or to avoidance of anxiogenic areas. Here, an automated home cage environment for mice was designed to obtain independent measures of motor activity levels and of sheltered feeding preference during three consecutive days. Chronic treatment with the anxiolytic drug chlordiazepoxide (5 and 10 mg/kg/day) in C57BL/6J mice reduced sheltered feeding preference without altering motor activity levels. Furthermore, two distinct chromosome substitution strains, derived from C57BL/6J (host strain) and A/J (donor strain) inbred strains, expressed either increased sheltering preference in females (chromosome 15) or reduced motor activity levels in females and males (chromosome 1) when compared to C57BL/6J. Longitudinal behavioral monitoring revealed that these phenotypic differences maintained after adaptation to the home cage. Thus, by using new automated behavioral phenotyping approaches, behavior can be dissociated into distinct behavioral domains (e.g., anxiety-related and motor activity domains) with different underlying genetic origin and pharmacological responsiveness.
Korn, Christoph W; Vunder, Johanna; Miró, Júlia; Fuentemilla, Lluís; Hurlemann, Rene; Bach, Dominik R
Rodent approach-avoidance conflict tests are common preclinical models of human anxiety disorder. Their translational validity mainly rests on the observation that anxiolytic drugs reduce rodent anxiety-like behavior. Here, we capitalized on a recently developed approach-avoidance conflict computer game to investigate the impact of benzodiazepines and of amygdala lesions on putative human anxiety-like behavior. In successive epochs of this game, participants collect monetary tokens on a spatial grid while under threat of virtual predation. In a preregistered, randomized, double-blind, placebo-controlled trial, we tested the effect of a single dose (1 mg) of lorazepam (n = 59). We then compared 2 patients with bilateral amygdala lesions due to Urbach-Wiethe syndrome with age- and gender-matched control participants (n = 17). Based on a previous report, the primary outcome measure was the effect of intra-epoch time (i.e., an adaptation to increasing potential loss) on presence in the safe quadrant of the spatial grid. We hypothesized reduced loss adaptation in this measure under lorazepam and in patients with amygdala lesions. Lorazepam and amygdala lesions reduced loss adaptation in the primary outcome measure. We found similar results in several secondary outcome measures. The relative reduction of anxiety-like behavior in patients with amygdala lesions was qualitatively and quantitatively indistinguishable from an impact of anterior hippocampus lesions found in a previous report. Our results establish the translational validity of human approach-avoidance conflict tests in terms of anxiolytic drug action. We identified the amygdala, in addition to the hippocampus, as a critical structure in human anxiety-like behavior. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Lapmanee, Sarawut; Charoenphandhu, Jantarima; Charoenphandhu, Narattaphol
Rodents exposed to mild but repetitive stress may develop anxiety- and depression-like behaviors. Whether this stress response could be alleviated by pharmacological treatments or exercise interventions, such as wheel running, was unknown. Herein, we determined anxiety- and depression-like behaviors in restraint stressed rats (2h/day, 5 days/week for 4 weeks) subjected to acute diazepam treatment (30min prior to behavioral test), chronic treatment with fluoxetine, reboxetine or venlafaxine (10mg/kg/day for 4 weeks), and/or 4-week voluntary wheel running. In elevated plus-maze (EPM) and forced swimming tests (FST), stressed rats spent less time in the open arms and had less swimming duration than the control rats, respectively, indicating the presence of anxiety- and depression-like behaviors. Stressed rats also developed learned fear as evaluated by elevated T-maze test (ETM). Although wheel running could reduce anxiety-like behaviors in both EPM and ETM, only diazepam was effective in the EPM, while fluoxetine, reboxetine, and venlafaxine were effective in the ETM. Fluoxetine, reboxetine, and wheel running, but not diazepam and venlafaxine, also reduced depression-like behavior in FST. Combined pharmacological treatment and exercise did not further reduce anxiety-like behavior in stressed rats. However, stressed rats treated with wheel running plus reboxetine or venlafaxine showed an increase in climbing duration in FST. In conclusion, regular exercise (voluntary wheel running) and pharmacological treatments, especially fluoxetine and reboxetine, could alleviate anxiety- and depression-like behaviors in stressed male rats. Copyright © 2013 Elsevier B.V. All rights reserved.
Li, Xiang; Sun, Ming-Zhu; Li, Xu; Zhang, Shu-Hui; Dai, Liang-Ti; Liu, Xing-Yu; Zhao, Xin; Chen, Dong-Yan; Feng, Xi-Zeng
The extensive usage of xenobiotic endocrine disrupting chemicals (XEDCs), such as Bisphenol A (BPA), has created obvious threat to aquatic ecosystems worldwide. Although a comprehensive understanding of the adverse effect of BPA on behaviors and physiology have been proven, the potential impact of low-dose BPA on altering the basic ability of aquatic organism in adapting to the surrounded complex environment still remains elusive. In this research, we report that treatment of adult male zebrafish with chronic (7 weeks) low-dose (0.22 nM-2.2 nM) BPA, altered the ability in adapting the complex environment by disturbing the natural color preference patterns. In addition, chronic 50 ng/L (0.22 nM) BPA exposure alleviated the anxiety behavior of male zebrafish confronted with the novel environment by enhancing the preference towards light in the light/dark preference test. This phenotype was associated with less expression of serotonin (5-TH) in the hypothalamus and the down-regulation of tyrosine hydroxylase (TH) in brain tissues. As such, our results show that low-dose BPA remnant in surface waters altered zebrafish behavior that are known to have ecological and evolutionary consequences. Here we reported that the impact of chronic low-dose BPA exposure on the basic capability of zebrafish to adapt to the environmental complexity. Specifically, BPA at low concentration, under the environmental safety level and 3000-fold lower than the accepted human daily exposure, interfered with the ability to discriminate color and alleviate anxiety induced by the novel environment, which finally altered the capability of male zebrafish to adapt to the environmental complexity. These findings revealed the ecological effect of low-dose BPA and regular BPA concentration standard are not necessarily safe. The result also provided the consideration of retuning the hazard concentration level of BPA. Copyright © 2017 Elsevier Ltd. All rights reserved.
Sobota, Rosanna; Mihara, Takuma; Forrest, Alexandra; Featherstone, Robert E; Siegel, Steven J
Standard dopamine therapies for schizophrenia are not efficacious for negative symptoms of the disease, including asociality. This reduced social behavior may be due to glutamatergic dysfunction within the amygdala, leading to increased fear and social anxiety. Several studies have demonstrated the prosocial effects of oxytocin in schizophrenia patients. Therefore, this study evaluates the effect of subchronic oxytocin on EEG activity in amygdala of mice during performance of the three-chamber social choice and open field tests following acute ketamine as a model of glutamatergic dysfunction. Oxytocin did not restore social deficits introduced by ketamine but did significantly increase sociality in comparison to the control group. Ketamine had no effect on time spent in the center during the open field trials, whereas oxytocin increased overall center time across all groups, suggesting a reduction in anxiety. Amygdala activity was consistent across all drug groups during social and nonsocial behavioral trials. However, oxytocin reduced overall amygdala EEG power during the two behavioral tasks. Alternatively, ketamine did not significantly affect EEG power throughout the tasks. Decreased EEG power in the amygdala, as caused by oxytocin, may be related to both reduced anxiety and increased social behaviors. Data suggest that separate prosocial and social anxiety pathways may mediate social preference. (c) 2015 APA, all rights reserved).
Klarer, Melanie; Arnold, Myrtha; Günther, Lydia; Winter, Christine; Langhans, Wolfgang; Meyer, Urs
Vagal afferents are an important neuronal component of the gut-brain axis allowing bottom-up information flow from the viscera to the CNS. In addition to its role in ingestive behavior, vagal afferent signaling has been implicated modulating mood and affect, including distinct forms of anxiety and fear. Here, we used a rat model of subdiaphragmatic vagal deafferentation (SDA), the most complete and selective vagal deafferentation method existing to date, to study the consequences of complete disconnection of abdominal vagal afferents on innate anxiety, conditioned fear, and neurochemical parameters in the limbic system. We found that compared with Sham controls, SDA rats consistently displayed reduced innate anxiety-like behavior in three procedures commonly used in preclinical rodent models of anxiety, namely the elevated plus maze test, open field test, and food neophobia test. On the other hand, SDA rats exhibited increased expression of auditory-cued fear conditioning, which specifically emerged as attenuated extinction of conditioned fear during the tone re-exposure test. The behavioral manifestations in SDA rats were associated with region-dependent changes in noradrenaline and GABA levels in key areas of the limbic system, but not with functional alterations in the hypothalamus-pituitary-adrenal grand stress. Our study demonstrates that innate anxiety and learned fear are both subjected to visceral modulation through abdominal vagal afferents, possibly via changing limbic neurotransmitter systems. These data add further weight to theories emphasizing an important role of afferent visceral signals in the regulation of emotional behavior. Copyright © 2014 the authors 0270-6474/14/347067-10$15.00/0.
Curley, JP; Jensen, CL; Franks, B; Champagne, FA
The relationship between anxiety and maternal behavior has been explored across species using a variety of approaches, yet there is no clear consensus on the nature or direction of this relationship. In the current study, we have assessed stable individual differences in anxiety-like behavior in a large cohort (n=57) of female F2 hybrid mice. Using open-field behavior as a continuous and categorical (high vs. low) measure we examined the relationship between the anxiety-like behavior of virgin F2 females and the subsequent maternal behavior of these females. In addition, we quantified oxytocin (OTR) and vasopressin (V1a) receptor density within the lateral septum to determine the possible correlation with anxiety-like and maternal behavior. We find that, though activity levels within the open-field do predict latency to engage in pup retrieval, anxiety-like measures on this test are otherwise not associated with subsequent maternal behavior. OTR density in the dorsal lateral septum was found to be negatively correlated with activity levels in the open-field and positively correlated with frequency of nursing behavior. V1a receptor density was significantly correlated with postpartum licking/grooming of pups. Though we do not find support for the hypothesis that individual differences in trait anxiety predict variation in maternal behavior, we do find evidence for the role of OTR and V1a receptors in predicting maternal behavior in mice and suggest possible methodological issues (such as distinguishing between trait and state anxiety) that will be a critical consideration for subsequent studies of the anxiety-maternal behavior relationship. PMID:22300676
Nesibe Olgun Kaval
Full Text Available The aim of the study was to review the articles on the effectiveness of cognitive-behavioral group therapy programs for the treatment of social anxiety disorder in children and adolescents. In this systematic review, articles in English and Turkish that were published between the years of 2000 and 2015 (March have been searched in the national and international databases. 20 studies that were met the search criteria were examined in terms of research method, therapy characteristics and results. The findings of the articles revealed that cognitive behavioral group therapy is effective for symptoms of social anxiety and the problems that accompany social anxiety (depression, anxiety, etc. in children and adolescents. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2016; 8(Supplement 1: 3-22
Green, Shulamite A; Goff, Bonnie; Gee, Dylan G; Gabard-Durnam, Laurel; Flannery, Jessica; Telzer, Eva H; Humphreys, Kathryn L; Louie, Jennifer; Tottenham, Nim
Significant disruption in caregiving is associated with increased internalizing symptoms, most notably heightened separation anxiety symptoms during childhood. It is also associated with altered functional development of the amygdala, a neurobiological correlate of anxious behavior. However, much less is known about how functional alterations of amygdala predict individual differences in anxiety. Here, we probed amygdala function following institutional caregiving using very subtle social-affective stimuli (trustworthy and untrustworthy faces), which typically result in large differences in amygdala signal, and change in separation anxiety behaviors over a 2-year period. We hypothesized that the degree of differentiation of amygdala signal to trustworthy versus untrustworthy face stimuli would predict separation anxiety symptoms. Seventy-four youths mean (SD) age = 9.7 years (2.64) with and without previous institutional care, who were all living in families at the time of testing, participated in an fMRI task designed to examine differential amygdala response to trustworthy versus untrustworthy faces. Parents reported on their children's separation anxiety symptoms at the time of scan and again 2 years later. Previous institutional care was associated with diminished amygdala signal differences and behavioral differences to the contrast of untrustworthy and trustworthy faces. Diminished differentiation of these stimuli types predicted more severe separation anxiety symptoms 2 years later. Older age at adoption was associated with diminished differentiation of amygdala responses. A history of institutional care is associated with reduced differential amygdala responses to social-affective cues of trustworthiness that are typically exhibited by comparison samples. Individual differences in the degree of amygdala differential responding to these cues predict the severity of separation anxiety symptoms over a 2-year period. These findings provide a biological
Stevens, Stephan; Cludius, Barbara; Bantin, Trisha; Hermann, Christiane; Gerlach, Alexander L
Social anxiety disorder and alcohol use disorders are highly comorbid. It remains unclear, however, if and how alcohol influences attentional processes and physical symptoms in social anxiety. In a balanced-placebo-design, high and normally socially anxious participants gave a speech while performing a task, which simultaneously measures internal and external attention. Only high anxious participants showed a preferential processing of external probes, which was eliminated by alcohol or the mere expectation of drinking alcohol. Furthermore, alcohol reduced facial blushing as well as self-reported social anxiety during public speaking. Decreases in anxiety were significantly associated with a reduction of the external focus in the high anxious group. Understanding alcohol as a substance influencing cognitive processes as well as physiological symptoms of anxiety further contributes to our understanding of alcohol use as a safety behavior in social anxiety disorder. Copyright © 2013 Elsevier B.V. All rights reserved.
Khalsa, Manjit K.; Greiner-Ferris, Julie M.; Hofmann, Stefan G.; Khalsa, Sat Bir S.
Cognitive behavioral therapy is an effective treatment for generalized anxiety disorder (GAD), but there is still room for improvement. The aim of the present study was to examine the potential benefit of enriching cognitive behavioral therapy (CBT) with Kundalini Yoga (Y-CBT). Participants consisted of treatment resistant clients at a community mental health clinic. A total of 32 participants enrolled in the study and 22 completed the program. After the Y-CBT intervention, pre-post comparisons showed statistically significant improvements in state and trait anxiety, depression, panic, sleep, and quality of life. Results from this preliminary study suggest that Y-CBT may have potential as a promising treatment for those suffering from GAD. PMID:24804619
Towers, Albert E; Oelschlager, Maci L; Patel, Jay; Gainey, Stephen J; McCusker, Robert H; Freund, Gregory G
Inflammation within the central nervous system (CNS) is frequently comorbid with anxiety. Importantly, the pro-inflammatory cytokine most commonly associated with anxiety is IL-1β. The bioavailability and activity of IL-1β are regulated by caspase-1-dependent proteolysis vis-a-vis the inflammasome. Thus, interventions regulating the activation or activity of caspase-1 should reduce anxiety especially in states that foster IL-1β maturation. Male C57BL/6j, C57BL/6j mice treated with the capase-1 inhibitor biotin-YVAD-cmk, caspase-1 knockout (KO) mice and IL-1R1 KO mice were fasted for 24h or allowed ad libitum access to food. Immediately after fasting, caspase-1 activity was measured in brain region homogenates while activated caspase-1 was localized in the brain by immunohistochemistry. Mouse anxiety-like behavior and cognition were tested using the elevated zero maze and novel object/object location tasks, respectively. A 24h fast in mice reduced the activity of caspase-1 in whole brain and in the prefrontal cortex, amygdala, hippocampus, and hypothalamus by 35%, 25%, 40%, 40%, and 40% respectively. A 24h fast also reduced anxiety-like behavior by 40% and increased novel object and object location recognition by 21% and 31%, respectively. IL-1β protein, however, was not reduced in the brain by fasting. ICV administration of YVAD decreased caspase-1 activity in the prefrontal cortex and amygdala by 55%, respectively leading to a 64% reduction in anxiety like behavior. Importantly, when caspase-1 KO or IL1-R1 KO mice are fasted, no fasting-dependent reduction in anxiety-like behavior was observed. Results indicate that fasting decrease anxiety-like behavior and improves memory by a mechanism tied to reducing caspase-1 activity throughout the brain. Copyright © 2017 Elsevier Inc. All rights reserved.
White, Susan W.; Albano, Anne Marie; Johnson, Cynthia R.; Kasari, Connie; Ollendick, Thomas; Klin, Ami; Oswald, Donald; Scahill, Lawrence
Anxiety is a common co-occurring problem among young people with autism spectrum disorders (ASD). Characterized by deficits in social interaction, communication problems, and stereotyped behavior and restricted interests, this group of disorders is more prevalent than previously realized. When present, anxiety may compound the social deficits of young people with ASD. Given the additional disability and common co-occurrence of anxiety in ASD, we developed a manual-based cognitive-behavioral t...
Ahmadalipour, A; Sadeghzadeh, J; Vafaei, A A; Bandegi, A R; Mohammadkhani, R; Rashidy-Pour, A
Prenatal morphine exposure throughout pregnancy can induce a series of neurobehavioral and neurochemical disturbances by affecting central nervous system development. This study was designed to investigate the effects of an enriched environment on behavioral deficits and changes in hippocampal brain-derived neurotrophic factor (BDNF) levels induced by prenatal morphine in rats. On pregnancy days 11-18, female Wistar rats were randomly injected twice daily with saline or morphine. Offspring were weaned on postnatal day (PND) 21. They were subjected to a standard rearing environment or an enriched environment on PNDs 22-50. On PNDs 51-57, the behavioral responses including anxiety and depression-like behaviors, and passive avoidance memory as well as hippocampal BDNF levels were investigated. The light/dark (L/D) box and elevated plus maze (EPM) were used for the study of anxiety, forced swimming test (FST) was used to assess depression-like behavior and passive avoidance task was used to evaluate learning and memory. Prenatal morphine exposure caused a reduction in time spent in the EPM open arms and a reduction in time spent in the lit side of the L/D box. It also decreased step-through latency and increased time spent in the dark side of passive avoidance task. Prenatal morphine exposure also reduced immobility time and increased swimming time in FST. Postnatal rearing in an enriched environment counteracted with behavioral deficits in the EPM and passive avoidance task, but not in the L/D box. This suggests that exposure to an enriched environment during adolescence period alters anxiety profile in a task-specific manner. Prenatal morphine exposure reduced hippocampal BDNF levels, but enriched environment significantly increased BDNF levels in both saline- and morphine-exposed groups. Our results demonstrate that exposure to an enriched environment alleviates behavioral deficits induced by prenatal morphine exposure and up-regulates the decreased levels of BDNF
Full Text Available Bisphenol A (BPA, an environmental endocrine-disrupting compound, has drawn a great attention for its adverse effect on behavioral development. Maternal exposure to this compound has been reported to induce anxiety and depression in offspring, but the effect of its paternal exposure is rarely discussed. This study investigated whether preconception paternal BPA exposure can affect the emotions of male rats and their offspring. Eighteen adult male rats (F0 received either a vehicle or 50 μg/kg/day BPA diet for 21 weeks and were then mated with non-exposed females to produce offspring (F1. The affective behaviors of F0 and F1 rats were evaluated in the open-field test, the elevated-plus maze and the forced swimming test, and their serum corticosterone were then examined. BPA exposure induced increased anxiety behaviors along with increased serum corticosterone in F0 rats. This paternal exposure also led to increased anxiety behaviors in F1 females and aggravated depression behaviors in both sexes of F1 rats. Furthermore, only F1 females exhibited increased serum corticosterone. Overall, these data indicate that preconception paternal exposure to a low dose of BPA may induce transgenerational sex-specific impairments in the affection of adult rats.
Hogendoorn, Sanne M; Prins, Pier J M; Boer, Frits; Vervoort, Leentje; Wolters, Lidewij H; Moorlag, Harma; Nauta, Maaike H; Garst, Harry; Hartman, Catharina A; de Haan, Else
The purpose is to investigate whether a change in putative mediators (negative and positive thoughts, coping strategies, and perceived control over anxious situations) precedes a change in anxiety symptoms in anxiety-disordered children and adolescents receiving cognitive behavioral therapy (CBT).
Fairholme, Christopher P; Manber, Rachel
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.
Lau, Adeline A; Crawley, Allison C; Hopwood, John J; Hemsley, Kim M
Mucopolysaccharidosis (MPS) IIIA, or Sanfilippo syndrome, is a lysosomal storage disorder characterized by severe and progressive neuropathology. Following an asymptomatic period, patients may present with sleep disturbances, cognitive decline, aggressive tendencies and hyperactivity. A naturally-occurring mouse model of MPS IIIA also exhibits many of these behavioral features and has been recently back-crossed onto a C57BL/6 genetic background. To more thoroughly characterize the behavioral phenotype of congenic MPS IIIA mice, we assessed exploratory activity and unconditioned anxiety-related behavior in the elevated plus maze (EPM) and open field locomotor activity. Although MPS IIIA male mice were less active in the EPM at 18 and 20 weeks of age, they were more likely to explore the open arms than their normal counter-parts suggesting reduced anxiety. Repeated EPM testing reduced exploration of the open arms in MPS IIIA mice. In the open field test, significant reductions in activity were evident in naïve-tested male MPS IIIA mice from 10 weeks of age. Female normal and MPS IIIA mice displayed similar exploratory activity in the open field test. These differences in anxiety and locomotor activity will allow us to evaluate the efficacy of therapeutic regimes for MPS IIIA as a forerunner to developing safe and effective therapies for Sanfilippo patients.
Kim, Hyun Jin; Lee, Joo Han; Yun, Kyunghwa; Kim, Joung-Hun
Drug addiction is a severe psychiatric disorder characterized by the compulsive pursuit of drugs of abuse despite potential adverse consequences. Although several decades of studies have revealed that psychostimulant use can result in extensive alterations of neural circuits and physiology, no effective therapeutic strategies or medicines for drug addiction currently exist. Changes in neuronal connectivity and regulation occurring after repeated drug exposure contribute to addiction-like behaviors in animal models. Among the involved brain areas, including those of the reward system, the striatum is the major area of convergence for glutamate, GABA, and dopamine transmission, and this brain region potentially determines stereotyped behaviors. Although the physiological consequences of striatal neurons after drug exposure have been relatively well documented, it remains to be clarified how changes in striatal connectivity underlie and modulate the expression of addiction-like behaviors. Understanding how striatal circuits contribute to addiction-like behaviors may lead to the development of strategies that successfully attenuate drug-induced behavioral changes. In this review, we summarize the results of recent studies that have examined striatal circuitry and pathway-specific alterations leading to addiction-like behaviors to provide an updated framework for future investigations.
Moskowitz, Lauren J.; Walsh, Caitlin E.; Mulder, Emile; McLaughlin, Darlene Magito; Hajcak, Greg; Carr, Edward G.; Zarcone, Jennifer R.
There is little research on the functional assessment and treatment of anxiety and related problem behavior in children with autism spectrum disorder (ASD), particularly those with intellectual and developmental disability (IDD). In a recent study, we evaluated a multimethod strategy for assessing anxiety in children with ASD and IDD ("Am J…
Glassman, Lisa Hayley
Individuals with public speaking phobia experience fear and avoidance that can cause extreme distress, impaired speaking performance, and associated problems in psychosocial functioning. Most extant interventions for public speaking phobia focus on the reduction of anxiety and avoidance, but neglect performance. Additionally, very little is known about the relationship between verbal working memory and social performance under conditions of high anxiety. The current study compared the efficacy of two cognitive behavioral treatments, traditional Cognitive Behavioral Therapy (tCBT) and acceptance-based behavior therapy (ABBT), in enhancing public speaking performance via coping with anxiety. Verbal working memory performance, as measured by the backwards digit span (BDS), was measured to explore the relationships between treatment type, anxiety, performance, and verbal working memory. We randomized 30 individuals with high public speaking anxiety to a 90-minute ABBT or tCBT intervention. As this pilot study was underpowered, results are examined in terms of effect sizes as well as statistical significance. Assessments took place at pre and post-intervention and included self-rated and objective anxiety measurements, a behavioral assessment, ABBT and tCBT process measures, and backwards digit span verbal working memory tests. In order to examine verbal working memory during different levels of anxiety and performance pressure, we gave each participant a backwards digit span task three times during each assessment: once under calm conditions, then again while experiencing anticipatory anxiety, and finally under conditions of acute social performance anxiety in front of an audience. Participants were asked to give a video-recorded speech in front of the audience at pre- and post-intervention to examine speech performance. Results indicated that all participants experienced a very large and statistically significant decrease in anxiety (both during the speech and BDS
Hendershott, Taylor R; Cronin, Marie E; Langella, Stephanie; McGuinness, Patrick S; Basu, Alo C
The influence of housing on cognition and emotional regulation in mice presents a problem for the study of genetic and environmental risk factors for neuropsychiatric disorders: standard laboratory housing may result in low levels of cognitive function or altered levels of anxiety that leave little room for assessment of deleterious effects of experimental manipulations. The use of enriched environment (EE) may allow for the measurement of a wider range of performance in cognitive domains. Cognitive and behavioral effects of EE in male mice have not been widely reproduced, perhaps due to variability in the application of enrichment protocols, and the effects of EE in female mice have not been widely studied. We have developed an EE protocol using common laboratory equipment that, without a running wheel for exercise, results in significant cognitive and behavioral effects relative to standard laboratory housing conditions. We compared male and female wild-type C57BL/6J mice reared from weaning age in an EE to those reared in a standard environment (SE), using common measures of anxiety-like behavior, sensory gating, sociability, and spatial learning and memory. Sex was a significant factor in relevant elevated plus maze (EPM) measures, and bordered on significance in a social interaction (SI) assay. Effects of EE on anxiety-like behavior and sociability were indicative of a general increase in exploratory activity. In male and female mice, EE resulted in reduced prepulse inhibition (PPI) of the acoustic startle response, and enhanced spatial learning and use of spatially precise strategies in a Morris water maze task. Copyright © 2016 Elsevier B.V. All rights reserved.
Full Text Available Abstract Background and aim: According to the American Psychiatric Association female sexual dysfunction are classified in four categories: sexual desire disorders, arousal, orgasm and pain. Having chronic Sexual dysfunction can lead to anxiety, depression, aggression and create problems in other aspects of life. The aim of this study was to Investigate the effect of cognitive-behavior counseling on anxiety and aggression in women with sexual dysfunction. Methods: In this clinical trial, 20 women were referred to Taleghani Hospital in Tehran with anxiety and aggression of sexual problems selected to measure sexual satisfaction. Glombok Rust questionnaire was used to measured the sexual satisfaction and Spielberger Questionnaire 40-item for Anxiety and Buss and Mark Perry questionnaire for aggression. Data were statistically analyzed by t test. Results: in general, the mean total of sexual satisfaction decreased from 79.05 at pretest to 7.35 at posttest p <0.05. the mean pretest of physical aggression from 28.2 and verbal aggression from 17.3 and nervous aggression from 28.95 followed by the aggression of the enemy from 29.95, have declined in post test to 12. 55 , 7.8, 12.3, and 3/12 respectively ( p <0.05. the results of Spielberger questionnaire showed that the mean pre-test state and trait anxiety were decreased from 63 and 62.5 to 35.1 and 34.15 respectively (p <0.05. Conclusion: Cognitive-behavioral counseling may not only have a significant effect in reducing sexual dysfunction in women, but also a significant role in reducing anxiety and aggression as reactions with this disorder. Key words: Sexual Dysfunction, Anxiety, Aggression, Women
Full Text Available Childhood emotional trauma contributes significantly to certain psychopathologies, such as post-traumatic stress disorder. In experimental animals, however, whether or not early-life stress results in behavioral abnormalities in adult animals still remains controversial. Here, we investigated both short-term and long-term changes of anxiety- and depression-like behaviors of Wistar rats after being exposed to chronic feral cat stress in juvenile ages. The 2-week predator stress decreased spontaneous activities immediately following stress but did not increase depression- or anxiety-like behaviors 4 weeks after the stimulation in adulthood. Instead, juvenile predator stress had some protective effects, though not very obvious, in adulthood. We also exposed genetic depression model rats, Wistar Kyoto (WKY rats, to the same predator stress. In WKY rats, the same early-life predator stress did not enhance anxiety- or depression-like behaviors in both the short-term and long-term. However, the stressed WKY rats showed slightly reduced depression-like behaviors in adulthood. These results indicate that in both normal Wistar rats and WKY rats, early-life predator stress led to protective, rather than negative, effects in adulthood.
Barcaccia, Barbara; Balestrini, Viviana; Saliani, Angelo M; Baiocco, Roberto; Mancini, Francesco; Schneider, Barry H
Extensive research has implicated identification with characters in mass media in the emergence of disordered eating behavior in adolescents. We explored the possible influence of the models offered by television (TV) on adolescents' body image, body uneasiness, eating-disordered behavior, depression, and anxiety. Three hundred and one adolescents (aged 14-19) from southern Italy participated. They completed a questionnaire on media exposure and body dissatisfaction, the Eating Disorder Inventory-2, the Body Uneasiness Test, the Beck Depression Inventory, and the State-Trait Anxiety Inventory - Form Y. The main factors contributing to females' eating-disordered behaviors were their own desires to be similar to TV characters, the amount of reality and entertainment TV they watched, and the discrepancy between their perceptions of their bodies and those of TV characters. Friends' desire to be similar to TV characters contributed most to depression, anxiety, body uneasiness, and eating disorders for both males and females. Our data confirm that extensive watching of reality and entertainment TV correlates with eating-disordered behavior among females. Moreover, the well-known negative effects of the media on adolescents' eating-disordered behaviors may also be indirectly transmitted by friends who share identification with TV characters.
Chen, Lu-jing; Shen, Bing-qing; Liu, Dan-dan; Li, Sheng-tian
Childhood emotional trauma contributes significantly to certain psychopathologies, such as post-traumatic stress disorder. In experimental animals, however, whether or not early-life stress results in behavioral abnormalities in adult animals still remains controversial. Here, we investigated both short-term and long-term changes of anxiety- and depression-like behaviors of Wistar rats after being exposed to chronic feral cat stress in juvenile ages. The 2-week predator stress decreased spontaneous activities immediately following stress but did not increase depression- or anxiety-like behaviors 4 weeks after the stimulation in adulthood. Instead, juvenile predator stress had some protective effects, though not very obvious, in adulthood. We also exposed genetic depression model rats, Wistar Kyoto (WKY) rats, to the same predator stress. In WKY rats, the same early-life predator stress did not enhance anxiety- or depression-like behaviors in both the short-term and long-term. However, the stressed WKY rats showed slightly reduced depression-like behaviors in adulthood. These results indicate that in both normal Wistar rats and WKY rats, early-life predator stress led to protective, rather than negative, effects in adulthood. PMID:24839560
Balcı Şengül, Melike Ceyhan; Kaya, Vildan; Şen, Cenk Ahmet; Kaya, Kemal
The aim of this study was to determine the relationship between suicidal behavior and associated factors such as depression, anxiety, and perceived social support level in cancer patients. The study group included 102 patients who were under treatment in the oncology department and the control group included 100 individuals with similar sociodemographic features. A sociodemographic information form, Beck depression inventory, Beck anxiety inventory, suicidal behavior inventory, suicidal ideation inventory, and multidimensional inventory of perceived social support were used. The mean Beck depression inventory and Beck anxiety inventory scores in the study group were significantly higher compared to the control group. Thirteen patients in the study group attempted suicide, whereas 3 individuals attempted suicide in the control group. Similarly, the mean suicide behavior and ideation scores in the study group were significantly higher compared to the control group. The mean total multidimensional inventories of perceived social support score, as well as the mean family and friend sub-inventory scores in the control group were significantly higher compared to the study group. This study revealed that depression and anxiety occur frequently in cancer patients. Suicide attempts and ideation are higher in cancer patients compared to the control group. Social support perceived from family and friends is lower in cancer patients. Suicide attempts are correlated with depression, anxiety, low level of perceived social support, and advanced disease stage.
Vermeiren, Yannick; Le Bastard, Nathalie; Van Hemelrijck, An; Drinkenburg, Wilhelmus H; Engelborghs, Sebastiaan; De Deyn, Peter P
Behavioral and psychological signs and symptoms of dementia (BPSD) are a heterogeneous group of behavioral and psychiatric disturbances occurring in dementia patients of any etiology. Research suggests that altered activities of dopaminergic, serotonergic, (nor)adrenergic, as well as amino acid neurotransmitter systems play a role in the etiopathogenesis of BPSD. In this study we attempted to identify cerebrospinal fluid (CSF) neurochemical correlates of BPSD to provide further insight into its underlying neurochemical pathophysiological mechanisms. Patients with probable Alzheimer's disease (AD; n = 202), probable AD with cerebrovascular disease (n = 37), probable frontotemporal dementia (FTD; n = 32), and probable dementia with Lewy bodies (DLB; n = 26) underwent behavioral assessment and lumbar puncture. CSF levels of six amino acids and several biogenic amines and metabolites were analyzed using ultraperformance liquid chromatography with fluorescence detection and reversed-phase high-performance liquid chromatography with fluorescence detection. In the AD patients, CSF homovanillic acid/5-hydroxyindoleacetic acid (HVA/5HIAA) ratios correlated positively with anxieties/phobias, whereas CSF levels of taurine correlated negatively with depression and behavioral disturbances in general. In FTD patients, CSF levels of glutamate correlated negatively with verbally agitated behavior. In DLB patients, CSF levels of HVA correlated negatively with hallucinations. Several neurotransmitter systems can be linked to one specific behavioral syndrome depending on the dementia subtype. In addition to biogenic amines and metabolites, amino acids seem to play a major role in the neurochemical etiology of BPSD as well. Copyright © 2013 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
Ma, Jie; Wang, Fang; Yang, Jingyu; Dong, Yingxu; Su, Guangyue; Zhang, Kuo; Pan, Xing; Ma, Ping; Zhou, Tingshuo; Wu, Chunfu
Xiaochaihutang (XCHT), as a classical herbal formula for the treatment of "Shaoyang syndrome" has been demonstrated to exert an antidepressant effect in multiple animal models of depression as shown in our previous studies. However, the effects of XCHT on social isolation (SI)-reared mice have not been investigated. This study aims to explore the effects of XCHT on depressive/anxiety-like behaviors of SI-reared mice, and its implicated mechanisms, including alterations in the monoaminergic system, neurogenesis and neurotrophin expression. Male C57 BL/6J mice (aged 4 weeks after weaning) were reared isolatedly for 8 weeks and XCHT (0.8, 2.3, 7.0g/kg) were given by gavage once a day. Forced swimming test (FST), tail suspension test (TST), open field test (OFT), elevated-plus maze test (EPM) and intruder-induced aggression test were used to explore the effects of XCHT on depressive/anxiety-like behaviors of SI-reared mice after administration of XCHT for 6 weeks. HPLC-MS/MS was performed to quantify the levels of neurotransmitters in the hippocampus by in vivo microdialysis, while western immunoblotting was used to evaluate the action of XCHT on the synthesis, transport and degradation of monoamine neurotransmitters. Immunofluorescence was used to study the effects of XCHT on neurogenesis and neurotrophin expression, including Ki-67, DCX, BrdU and BDNF. Our results showed that administration of XCHT (0.8, 2.3 and 7.0g/kg) for 6 weeks significantly attenuated the increase in immobility time in TST and FST, improved the anxiety-like behaviors in OFT and EPM, and improved the aggressive behaviors of SI-reared mice. XCHT significantly elevated monoamine neurotransmitters levels and inhibited 5-HT turnover (5-HIAA/5-HT) in hippocampal microdialysates of SI-reared mice. In addition, we found XCHT enhanced monoamine neurotransmitter synthesis enzymes (TPH2 and TH) expressions, inhibited serotonin transporter (SERT) expression and decreased monoamine neurotransmitter
Helgadóttir, Fjóla Dögg; Menzies, Ross G; Onslow, Mark; Packman, Ann; O'Brian, Sue
Social anxiety is common for those who stutter and efficacious cognitive behavior therapy (CBT) for them appears viable. However, there are difficulties with provision of CBT services for anxiety among those who stutter. Standalone Internet CBT treatment is a potential solution to those problems. CBTpsych is a fully automated, online social anxiety intervention for those who stutter. This report is a Phase I trial of CBTpsych. Fourteen participants were allowed 5 months to complete seven sections of CBTpsych. Pre-treatment and post-treatment assessments tested for social anxiety, common unhelpful thoughts related to stuttering, quality of life and stuttering frequency. Significant post-treatment improvements in social anxiety, unhelpful thoughts, and quality of life were reported. Five of seven participants diagnosed with social anxiety lost those diagnoses at post-treatment. The two participants who did not lose social anxiety diagnoses did not complete all the CBTpsych modules. CBTpsych did not improve stuttering frequency. Eleven of the fourteen participants who began treatment completed Section 4 or more of the CBTpsych intervention. CBTpsych provides a potential means to provide CBT treatment for social anxiety associated with stuttering, to any client without cost, regardless of location. Further clinical trials are warranted. At the end of this activity the reader will be able to: (a) describe that social anxiety is common in those who stutter; (b) discuss the origin of social anxiety and the associated link with bullying; (c) summarize the problems in provision of effective evidence based cognitive behavior therapy for adults who stutter; (d) describe a scalable computerized treatment designed to tackle the service provision gap; (e) describe the unhelpful thoughts associated with stuttering that this fully automated computer program was able to tackle; (f) list the positive outcomes for individuals who stuttered that participated in this trial such as the
Full Text Available Background and Objectives: Hemodialysis as a treatment manner in chronic renal failure is a stressful process and has several various psycho-cognitive and social complications. The present study evaluated effect of cognitive-behavioral group therapy on anxiety and depression in hemodialysis patients. Methods: This research was a clinical trial study. Samples were young adults who were 18-45 years old. The Participants were divided into two groups (case & control. The Beck depression & anxiety inventories were used as a measure of psychological symptoms at pretest and posttest and Cognitive-behavioral group therapy as intervention was done at week12. Data Were analyzed with SPSS-16 and t-test, chi square. A p<0.05 was considered significant. Results: In this study, there was not a significant difference in the demographic characteristics between the two groups. Before of intervention, mean Anxiety score of the experimental group was 25.72±5.87, and in the case group it was 25.22±7.56 as well as mean Depression score in the two groups was 35.44±14.97, 33.11±9.2 respectively. The difference of the two groups in anxiety and depression scores was not significant. After the intervention, the mean anxiety score of experimental group was 15.94±6.23, and in the case group it was 28.05±10.04 (p<0.05. Mean of depression score in the experimental group was 22.27±13.32, and in the case group it was 33.94±9.46 (p<0.01.Conclusion: This research showed that group therapy (cognitive-behavioral decreased depression and anxiety remarkably in dialysis patients. Therefore, it is suggested that in addition to the prescription of medication, psychological interventions be done for such patients.
Xu, Tanya J; Reichelt, Amy C
Caffeinated sugar-sweetened "energy" drinks are a subset of soft drinks that are popular among young people worldwide. High sucrose diets impair cognition and alter aspects of emotional behaviour in rats, however, little is known about sucrose combined with caffeine. Rats were allocated to 2 h/day 10% sucrose (Suc), 10% sucrose plus 0.04% caffeine (CafSuc) or control (water) conditions. The addition of caffeine to sucrose appeared to increase the rewarding aspect of sucrose, as the CafSuc group consumed more solution than the Suc group. After 14 days of intermittent Suc or CafSuc access, anxiety was assessed in the elevated plus maze (EPM) prior to their daily solution access, whereby CafSuc and Suc rats spent more time in the closed arms, indicative of increased anxiety. Following daily solution access, CafSuc, but not Suc, rats showed reduced anxiety-like behaviour in the open-field. Control and CafSuc rats displayed intact place and long-term object memory, while Suc showed impaired memory performance. Sucrose reduced parvalbumin immunoreactivity in the hippocampus, but no differences were observed between Control and CafSuc conditions. Parvalbumin reactivity in the basolateral amygdala did not differ between conditions. Reduced doublecortin immunoreactivity in the dentate gyrus relative to controls was seen in the CafSuc, but not Suc, treatment conditions. These findings indicate that the addition of caffeine to sucrose attenuated cognitive deficits. However, the addition of caffeine to sucrose evoked anxiety-like responses under certain testing conditions, suggesting that frequent consumption of caffeinated energy drinks may promote emotional alterations and brain changes compared to standard soft drinks. Copyright © 2018 Elsevier Ltd. All rights reserved.
Full Text Available Abstract Background The anesthetic drug ketamine (KT has been reported to be an abused drug and fatal cases have been observed in polydrug users. In the present study, considering the possibility of KT-enhanced toxic effects of other drugs, and KT-induced promotion of an overdose without making the subject aware of the danger due to the attenuation of several painful subjective symptoms, the intraperitoneal (i.p. KT-induced alterations in behaviors and toxic interactions with popular co-abused drugs, the psychostimulants cocaine (COC and methamphetamine (MA, were examined in ICR mice. Results A single dose of KT caused hyperlocomotion in a low (30 mg/kg, i.p. dose group, and hypolocomotion followed by hyperlocomotion in a high (100 mg/kg, i.p. dose group. However, no behavioral alterations derived from enhanced stress-related depression or anxiety were observed in the forced swimming or the elevated plus-maze test. A single non-fatal dose of COC (30 mg/kg, i.p. or MA (4 mg/kg, i.p. caused hyperlocomotion, stress-related depression in swimming behaviors in the forced swimming test, and anxiety-related behavioral changes (preference for closed arms in the elevated plus-maze test. For the COC (30 mg/kg or MA (4 mg/kg groups of mice simultaneously co-treated with KT, the psychostimulant-induced hyperlocomotion was suppressed by the high dose KT, and the psychostimulant-induced behavioral alterations in the above tests were reversed by both low and high doses of KT. For the toxic dose COC (70 mg/kg, i.p.- or MA (15 mg/kg, i.p.-only group, mortality and severe seizures were observed in some animals. In the toxic dose psychostimulant-KT groups, KT attenuated the severity of seizures dose-dependently. Nevertheless, the mortality rate was significantly increased by co-treatment with the high dose KT. Conclusion Our results demonstrated that, in spite of the absence of stress-related depressive and anxiety-related behavioral alterations following a single
Rahm-Knigge, Ryan L; Prince, Mark A; Conner, Bradley T
Individuals with social interaction anxiety, a facet of social anxiety disorder, withdraw from or avoid social encounters and generally avoid risks. However, a subset engages in health risk sexual behavior (HRSB). Because sensation seeking, emotion dysregulation, and impulsivity predict engagement in HRSB among adolescents and young adults, the present study hypothesized that latent classes of social interaction anxiety and these personality traits would differentially predict likelihood of engagement in HRSB. Finite mixture modeling was used to discern four classes: two low social interaction anxiety classes distinguished by facets of emotion dysregulation, positive urgency, and negative urgency (Low SIAS High Urgency and Low SIAS Low Urgency) and two high social interaction anxiety classes distinguished by positive urgency, negative urgency, risk seeking, and facets of emotion dysregulation (High SIAS High Urgency and High SIAS Low Urgency). HRSB were entered into the model as auxiliary distal outcomes. Of importance to this study were findings that the High SIAS High Urgency class was more likely to engage in most identified HRSB than the High SIAS Low Urgency class. This study extends previous findings on the heterogeneity of social interaction anxiety by identifying the effects of social interaction anxiety and personality on engagement in HRSB. Copyright © 2018 Elsevier Ltd. All rights reserved.
Kendall, Philip C; Hudson, Jennifer L; Gosch, Elizabeth; Flannery-Schroeder, Ellen; Suveg, Cynthia
This randomized clinical trial compared the relative efficacy of individual (child) cognitive-behavioral therapy (ICBT), family cognitive-behavioral therapy (FCBT), and a family-based education/support/ attention (FESA) active control for treating anxiety disordered youth ages 7-14 years (M = 10.27). Youth (N = 161; 44% female; 85% Caucasian, 9% African American, 3% Hispanic, 3% other/mixed) with a principal diagnosis of separation anxiety disorder, social phobia, or generalized anxiety disorder and their parents participated. Outcome analyses were conducted using hierarchical linear models on the intent-to-treat sample at posttreatment and 1-year follow-up using diagnostic severity, child self-reports, parent reports, and teacher reports. Chi-square analyses were also conducted on diagnostic status at post and 1-year follow-up. Children evidenced treatment gains in all conditions, although FCBT and ICBT were superior to FESA in reducing the presence and principality of the principal anxiety disorder, and ICBT outperformed FCBT and FESA on teacher reports of child anxiety. Treatment gains, when found, were maintained at 1-year follow-up. FCBT outperformed ICBT when both parents had an anxiety disorder. Implications for treatment and suggestions for research are discussed. PsycINFO Database Record (c) 2008 APA, all rights reserved.
Dalle Molle, R; Portella, A K; Goldani, M Z; Kapczinski, F P; Leistner-Segala, S; Salum, G A; Manfro, G G; Silveira, P P
Adverse early-life environment is associated with anxiety-like behaviors and disorders. Brain-derived neurotrophic factor (BDNF) is sensitive to this environment and could be a marker of underlying brain changes. We aimed at evaluating the development of anxiety-like behaviors in a rat model of early adversity, as well as the possible association with BDNF levels. Similar associations were investigated in a sample of adolescent humans. For the rat study, Wistar rat litters were divided into: early-life stress (ELS, limited access to nesting material) and control groups. Maternal behavior was observed from days 1 to 9 of life and, as adults, rats were subjected to behavioral testing and BDNF measurements in plasma, hippocampus, amygdala and periaqueductal gray. For the human study, 129 adolescents were evaluated for anxiety symptoms and perceived parental care. Serum BDNF levels and the Val66Met polymorphism of the BDNF gene were investigated. We found that ELS dams showed more pure contact, that is, contact with low care and high control, toward pups, and their adult offspring demonstrated higher anxiety-like behaviors and plasma BDNF. Also the pure contact correlated positively with adult peripheral BDNF. Similarly in humans, there was a positive correlation between maternal overprotection and serum BDNF only in Met carriers. We also found negative correlations between maternal warmth and separation anxiety, social phobia and school phobia. Finally, our translational approach revealed that ELS, mediated through variations in maternal care, is associated with anxiety in both rats and humans and increased peripheral BDNF may be marking these phenomena. PMID:23168995
Price, Matthew; Anderson, Page L
Individuals with social anxiety are prone to engage in post event processing (PEP), a post mortem review of a social interaction that focuses on negative elements. The extent that PEP is impacted by cognitive behavioral therapy (CBT) and the relation between PEP and change during treatment has yet to be evaluated in a controlled study. The current study used multilevel modeling to determine if PEP decreased as a result of treatment and if PEP limits treatment response for two types of cognitive behavioral treatments, a group-based cognitive behavioral intervention and individually based virtual reality exposure. These hypotheses were evaluated using 91 participants diagnosed with social anxiety disorder. The findings suggested that PEP decreased as a result of treatment, and that social anxiety symptoms for individuals reporting greater levels of PEP improved at a slower rate than those with lower levels of PEP. Further research is needed to understand why PEP attenuates response to treatment. Copyright © 2010 Elsevier Ltd. All rights reserved.
Price, Matthew; Anderson, Page L.
Individuals with social anxiety are prone to engage in post event processing (PEP), a post mortem review of a social interaction that focuses on negative elements. The extent that PEP is impacted by cognitive behavioral therapy (CBT) and the relation between PEP and change during treatment has yet to be evaluated in a controlled study. The current study used multilevel modeling to determine if PEP decreased as a result of treatment and if PEP limits treatment response for two types of cognitive behavioral treatments, a group-based cognitive behavioral intervention and individually based virtual reality exposure. These hypotheses were evaluated using 91 participants diagnosed with social anxiety disorder. The findings suggested that PEP decreased as a result of treatment, and that social anxiety symptoms for individuals reporting greater levels of PEP improved at a slower rate than those with lower levels of PEP. Further research is needed to understand why PEP attenuates response to treatment. PMID:21159328
Harper, Kathryn M; Knapp, Darin J; Park, Meredith A; Breese, George R
Behavioral and neuroimmune vulnerability to withdrawal from chronic alcohol varies with age. The relation of anxiety-like behavior to amygdalar CCL2 responses following stress after withdrawal from chronic intermittent alcohol (CIA) was investigated in adolescent and adult rats. Adolescent and adult Wistar rats were exposed to CIA (three 5-day blocks of dietary alcohol separated by 2 days of withdrawal) at concentrations that created similar blood alcohol levels across age. Twenty-four hours into the final withdrawal, half of the rats were exposed to 1 h of restraint stress. Four hours post-stress, rats were used for behavior or tissue assays. Anxiety-like behavior was increased versus controls by CIA in adolescents and by CIA + stress in adults. CCL2 mRNA was increased versus controls by CIA in adolescents and by CIA and CIA + stress in adults. CCL2 co-localization with neuronal marker NeuN was decreased versus controls by CIA in adolescents and by CIA + stress in adults. CCL2 co-localization with astrocytic marker GFAP was decreased versus controls by CIA and CIA + stress in adolescents, but experimental groups did not differ from controls in adults. CCL2 co-localization with microglial marker Iba1 was decreased versus controls by stress alone in adolescents and by CIA + stress in adults. Changes in CCL2 protein might control behavior at either age but are particularly associated with CIA alone in adolescents and with CIA + stress in adults. That the number of CeA neurons expressing CCL2 was altered after CIA and stress is consistent with CCL2 involvement in neural function.
Nauta, MH; Scholing, A; Emmelkamp, PMG; Minderaa, RB
To evaluate a 12-week cognitive-behavioral treatment program for children with anxiety disorders and the additional value of a seven-session cognitive parent training program. Method: Seventy-nine children with an anxiety disorder (aged 7-18 years) were randomly assigned to a cognitive behavioral
AR Jamshidzehi ShahBakhsh
Full Text Available Introduction: The mitral valve prolapse is a heart syndrome that is characterized by considerable physical and psychological consequences for affected patients. This study aimed to assess the efficacy of cognitive-behavioral therapy in reducing worrying, generalized anxiety and panic attacks in patients with mitral valve prolapse. Methods: This study is quasi-experimental research with pretest-posttest and control group. 16 patients with mitral valve prolapse divided into to two groups: experimental (n = 8 and control (n = 8 groups. CBT was used during 10 sessions twice a week with a focus on cognitive restructuring, modification of cognitive distortions and training of behavioral techniques for the experimental group. For participants health concerns spot and doush (HCQ, Generalized anxiety disorder (GAD- 7 and Albania panic scales as pre-test, post-test. Results: Data were analyzed by covariance analysis. The results showed that worrying, anxiety, and panic attacks significantly reduced in the experimental group. Discussion: Cognitive behavioral therapy is remarkably effective for reducing fear, anxiety and panic patients with mitral valve prolapse. Therefore, it is recommended for the patients with mitral valve prolapse that cognitive behavioral therapy can be used as a complementary therapy.
Pagani, J H; Williams Avram, S K; Cui, Z; Song, J; Mezey, É; Senerth, J M; Baumann, M H; Young, W S
Serotonin and oxytocin influence aggressive and anxiety-like behaviors, though it is unclear how the two may interact. That the oxytocin receptor is expressed in the serotonergic raphe nuclei suggests a mechanism by which the two neurotransmitters may cooperatively influence behavior. We hypothesized that oxytocin acts on raphe neurons to influence serotonergically mediated anxiety-like, aggressive and parental care behaviors. We eliminated expression of the oxytocin receptor in raphe neurons by crossing mice expressing Cre recombinase under control of the serotonin transporter promoter (Slc6a4) with our conditional oxytocin receptor knockout line. The knockout mice generated by this cross are normal across a range of behavioral measures: there are no effects for either sex on locomotion in an open-field, olfactory habituation/dishabituation or, surprisingly, anxiety-like behaviors in the elevated O and plus mazes. There was a profound deficit in male aggression: only one of 11 raphe oxytocin receptor knockouts showed any aggressive behavior, compared to 8 of 11 wildtypes. In contrast, female knockouts displayed no deficits in maternal behavior or aggression. Our results show that oxytocin, via its effects on raphe neurons, is a key regulator of resident-intruder aggression in males but not maternal aggression. Furthermore, this reduction in male aggression is quite different from the effects reported previously after forebrain or total elimination of oxytocin receptors. Finally, we conclude that when constitutively eliminated, oxytocin receptors expressed by serotonin cells do not contribute to baseline anxiety-like behaviors or maternal care. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.
Ragnauth, A.; Schuller, A.; Morgan, M.; Chan, J.; Ogawa, S.; Pintar, J.; Bodnar, R. J.; Pfaff, D. W.
The endogenous opioid system has been implicated in sexual behavior, palatable intake, fear, and anxiety. The present study examined whether ovariectomized female transgenic preproenkephalin-knockout (PPEKO) mice and their wild-type and heterozygous controls displayed alterations in fear and anxiety paradigms, sucrose intake, and lordotic behavior. To examine stability of responding, three squads of the genotypes were tested across seasons over a 20-month period. In a fear-conditioning paradigm, PPEKO mice significantly increased freezing to both fear and fear + shock stimuli relative to controls. In the open field, PPEKO mice spent significantly less time and traversed significantly less distance in the center of an open field than wild-type controls. Further, PPEKO mice spent significantly less time and tended to be less active on the light side of a dark–light chamber than controls, indicating that deletion of the enkephalin gene resulted in exaggerated responses to fear or anxiety-provoking environments. These selective deficits were observed consistently across testing squads spanning 20 months and different seasons. In contrast, PPEKO mice failed to differ from corresponding controls in sucrose, chow, or water intake across a range (0.0001–20%) of sucrose concentrations and failed to differ in either lordotic or female approach to male behaviors when primed with estradiol and progesterone, thereby arguing strongly for the selectivity of a fear and anxiety deficit which was not caused by generalized and nonspecific debilitation. These transgenic data strongly suggest that opioids, and particularly enkephalin gene products, are acting naturally to inhibit fear and anxiety. PMID:11172058
The Effects of a Brief Acceptance-Based Behavioral Treatment Versus Traditional Cognitive-Behavioral Treatment for Public Speaking Anxiety: An Exploratory Trial Examining Differential Effects on Performance and Neurophysiology.
Glassman, Lisa H; Forman, Evan M; Herbert, James D; Bradley, Lauren E; Foster, Elizabeth E; Izzetoglu, Meltem; Ruocco, Anthony C
Individuals with public speaking anxiety (PSA) experience fear and avoidance that can cause extreme distress, impaired speaking performance, and associated problems in psychosocial functioning. Most extant interventions for PSA emphasize anxiety reduction rather than enhancing behavioral performance. We compared the efficacy of two brief cognitive-behavioral interventions, a traditional cognitive-behavior treatment (tCBT) and an acceptance-based behavior treatment (ABBT), on public speaking performance and anxiety in a clinical sample of persons with PSA. The effects of treatment on prefrontal brain activation were also examined. Participants (n = 21) were randomized to 90 min of an ABBT or a tCBT intervention. Assessments took place at pre- and post-treatment and included self-rated anxiety and observer-rated performance measures, a behavioral assessment, and prefrontal cortical activity measurements using functional near-infrared spectroscopy (fNIRS). Exploratory results indicated that participants in the ABBT condition experienced greater improvements in observer-rated performance relative to those in the tCBT condition, while those in the tCBT condition experienced greater reductions in subjective anxiety levels. Individuals in the ABBT condition also exhibited a trend toward greater treatment-related reductions in blood volume in the left dorsolateral prefrontal cortex relative to those who received tCBT. Overall, these findings preliminarily suggest that acceptance-based treatments may free more cognitive resources in comparison with tCBT, possibly resulting in greater improvements in objectively rated behavioral performances for ABBT interventions. © The Author(s) 2016.
Mochari-Greenberger, Heidi; Vue, Lee; Luka, Andi; Peters, Aimee; Pande, Reena L
Depression is prevalent among individuals with diabetes and associated with suboptimal self-management. Little is known about the feasibility and potential impact of tele-behavioral therapy to improve depressive symptoms and self-management among diabetes patients. This was a retrospective observational study of consecutive graduates enrolled in a national 8-week diabetes behavioral telehealth program between August 1, 2014, and January 31, 2015 (N = 466; mean age 56.8 ± 5.0 years; 56% female). Participant characteristics (demographics, comorbidities) were obtained by standardized questionnaire. Depression, anxiety, and stress symptoms (DASS; validated Depression Anxiety and Stress Scale 21 survey), and glucose self-testing frequency and values (point-of-care monitor) were measured at program start and completion. Changes in DASS severity and glucose self-testing frequency were assessed by chi-square tests. Changes in DASS and blood glucose levels were evaluated by paired t-tests. At baseline, approximately one in three participants had elevated depression (32%), anxiety (33%), or stress (31%) scores. Significant reductions in average DASS, depression (-8.8), anxiety (-6.9), and stress (-9.9), scores were observed at graduation among those with elevated baseline scores (p depression, anxiety, or stress categories. Improved glucose self-testing frequency (69% vs. 60% tested ≥once per week; p = 0.0005) and significant reductions in mean morning glucose levels (-12.3 mg/dL; p = 0.0002) were observed from baseline to graduation. Participants with normal versus non-normal depression scores were more likely to have lower (depression, anxiety, stress, and glucose levels, as well as increased frequency of glucose self-testing, among participants in a diabetes behavioral telehealth program.
Full Text Available Objective: Extensive research has implicated identification with characters in mass media in the emergence of disordered eating behavior in adolescents. We explored the possible influence of the models offered by television (TV on adolescents’ body image, body uneasiness, eating-disordered behavior, depression, and anxiety. Methods: Three hundred and one adolescents (aged 14-19 from southern Italy participated. They completed a questionnaire on media exposure and body dissatisfaction, the Eating Disorder Inventory-2, the Body Uneasiness Test, the Beck Depression Inventory, and the State-Trait Anxiety Inventory – Form Y. Results: The main factors contributing to females’ eating-disordered behaviors were their own desires to be similar to TV characters, the amount of reality and entertainment TV they watched, and the discrepancy between their perceptions of their bodies and those of TV characters. Friends’ desire to be similar to TV characters contributed most to depression, anxiety, body uneasiness, and eating disorders for both males and females. Conclusion: Our data confirm that extensive watching of reality and entertainment TV correlates with eating-disordered behavior among females. Moreover, the well-known negative effects of the media on adolescents’ eating-disordered behaviors may also be indirectly transmitted by friends who share identification with TV characters.
Full Text Available Accumulating evidence implicates that subchronic arsenic exposure causes cerebral neurodegeneration leading to behavioral disturbances relevant to psychiatric disorders. However, there is still little information regarding the influence of subchronic exposure to arsenic-contaminated drinking water on mood disorders and its underlying mechanisms in the cerebral prefrontal cortex. The aim of this study is to assess the effects of subchronic arsenic exposure (10 mg/LAs2O3 in drinking water on the anxiety- and depression-like behaviors in normal mice and in the chemically induced mouse model of depression by reserpine pretreatment. Our findings demonstrated that 4 weeks of arsenic exposure enhance anxiety-like behaviors on elevated plus maze (EPM and open field test (OFT in normal mice, and 8 weeks of arsenic exposure augment depression-like behaviors on tail suspension test (TST and forced swimming test (FST in the reserpine pretreated mice. In summary, in this present study, we demonstrated that subchronic arsenic exposure induces only the anxiety-like behaviors in normal mice and enhances the depression-like behaviors in the reserpine induced mouse model of depression, in which the cerebral prefrontal cortex BDNF-TrkB signaling pathway is involved. We also found that eight weeks of subchronic arsenic exposure are needed to enhance the depression-like behaviors in the mouse model of depression. These findings imply that arsenic could be an enhancer of depressive symptoms for those patients who already had the attribute of depression.
Jennifer T. Wolstenholme
Full Text Available Adolescents primarily consume alcohol in binges, which can be particularly harmful to the developing frontal cortex and increase risk for an adult alcohol use disorder. We conducted a study investigating immediate and long lasting changes to the prefrontal cortex (PFC transcriptome to determine the molecular mechanisms underlying adult ethanol behavioral sensitivity following binge ethanol in adolescence. DBA/2J mice were orally dosed with 4 g/kg ethanol intermittently from day 29 to 42. Adolescent mice were tested for anxiety-like behavior and ethanol sensitivity using the loss of righting reflex task. As adults, mice were tested for cognitive changes using the novel object recognition task, ethanol-induced anxiolysis and ethanol sensitivity. Adolescent binge ethanol altered ethanol sensitivity in young mice and led to lasting memory deficits in the object recognition test and greater ethanol sensitivity in adulthood. Using genomic profiling of transcripts in the PFC, we found that binge ethanol reduced myelin-related gene expression and altered chromatin modifying genes involved in histone demethylation at H3K9 and H3K36. We hypothesize that ethanol’s actions on histone methylation may be a switch for future transcriptional changes that underlie the behavioral changes lasting into adulthood.
Bredewold, Remco; Smith, Caroline J. W.; Dumais, Kelly M.; Veenema, Alexa H.
We recently demonstrated that vasopressin (AVP) in the lateral septum modulates social play behavior differently in male and female juvenile rats. However, the extent to which different social contexts (i.e., exposure to an unfamiliar play partner in different environments) affect the regulation of social play remains largely unknown. Given that AVP and the closely related neuropeptide oxytocin (OXT) modulate social behavior as well as anxiety-like behavior, we hypothesized that these neuropeptides may regulate social play behavior differently in novel (novel cage) as opposed to familiar (home cage) social environments. Administration of the specific AVP V1a receptor (V1aR) antagonist (CH2)5Tyr(Me2)AVP into the lateral septum enhanced home cage social play behavior in males but reduced it in females, confirming our previous findings. These effects were context-specific because V1aR blockade did not alter novel cage social play behavior in either sex. Furthermore, social play in females was reduced by AVP in the novel cage and by OXT in the home cage. Additionally, females administered the specific OXT receptor antagonist desGly-NH2,d(CH2)5−[Tyr(Me)2,Thr4]OVT showed less social play in the novel as compared to the home cage. AVP enhanced anxiety-related behavior in males (tested on the elevated plus-maze), but failed to do so in females, suggesting that exogenous AVP alters social play and anxiety-related behavior via distinct and sex-specific mechanisms. Moreover, none of the other drug treatments that altered social play had an effect on anxiety, suggesting that these drug-induced behavioral alterations are relatively specific to social behavior. Overall, we showed that AVP and OXT systems in the lateral septum modulate social play in juvenile rats in neuropeptide-, sex- and social context-specific ways. These findings underscore the importance of considering not only sex, but also social context, in how AVP and OXT modulate social behavior. PMID:24982623
Full Text Available We recently demonstrated that vasopressin (AVP in the lateral septum modulates social play behavior differently in male and female juvenile rats. However, the extent to which different social contexts (i.e., exposure to an unfamiliar play partner in different environments affect the regulation of social play remains largely unknown. Given that AVP and the closely related neuropeptide oxytocin (OXT modulate social behavior as well as anxiety-like behavior, we hypothesized that these neuropeptides may regulate social play behavior differently in novel (novel cage as opposed to familiar (home cage social environments. Administration of the specific AVP V1a receptor (V1aR antagonist (CH25Tyr(Me2AVP into the lateral septum enhanced home cage social play behavior in males but reduced it in females, confirming our previous findings. These effects were context-specific because V1aR blockade did not alter novel cage social play behavior in either sex. Furthermore, social play in females was reduced by AVP in the novel cage and by OXT in the home cage. Additionally, females administered the specific OXT receptor antagonist desGly-NH2,d(CH25-[Tyr(Me2,Thr4]OVT showed less social play in the novel as compared to the home cage. AVP enhanced anxiety-related behavior in males (tested on the elevated plus-maze, but failed to do so in females, suggesting that exogenous AVP alters social play and anxiety-related behavior via distinct and sex-specific mechanisms. Moreover, none of the other drug treatments that altered social play had an effect on anxiety, suggesting that these drug-induced behavioral alterations are relatively specific to social behavior. Overall, we showed that AVP and OXT systems in the lateral septum modulate social play in juvenile rats in neuropeptide-, sex- and social context-specific ways. These findings underscore the importance of considering not only sex, but also social context, in how AVP and OXT modulate social behavior.
Full Text Available Purpose: The aims of this study were to assess the prevalence and also some related demographic and dental factors of dental anxiety and behavioral problems in school-aged children. Subjects and Methods: A total of 150 children of 6-12 years old were selected according to the inclusion criteria. Prior to the dental visit, the mothers were asked to answer a questionnaire of dental and demographic background and a Corah dental anxiety scale (CDAS. At the same time, a faces version of the modified child dental anxiety scale (MCDAS was completed by the child. Next, the child was guided to the operating room. According to the treatment plan, local anesthesia solution was injected and the child′s cooperative behaviors were quantified based on the Frankle index duration the injection stage. Analysis of Variance and Linear regression models were used for the statistical analysis. Results: The mean scores of the child′s dental anxiety and cooperative behavior were 20.81 (±6.97 and 3.04 (±0.86, respectively. Forty four children (29.33% had severe dental anxiety. Child′s age and regular dental visit are predictive factors for the child′s dental anxiety (P < 0.05. Dental behavioral problems had been identified in 43 children (28.67%. Unpleasant previous dental experience is an important factor affecting the child′s cooperative behaviors (P < 0.05. Conclusion: High prevalence of severe dental anxiety may be seen in early years of school. It seems that general factors such as family factors have less impact on behavior of school aged children in a dental visit.
Kertz, Sarah J; Koran, Jennifer; Stevens, Kimberly T; Björgvinsson, Thröstur
Repetitive negative thinking (RNT) is a common symptom across depression and anxiety disorders and preliminary evidence suggests that decreases in rumination and worry are related to improvement in depression and anxiety symptoms. However, despite its prevalence, relatively little is known about transdiagnostic RNT and its temporal associations with symptom improvement during treatment. The current study was designed to examine the influence of RNT on subsequent depression and anxiety symptoms during treatment. Participants (n = 131; 52% female; 93% White; M = 34.76 years) were patients presenting for treatment in a brief, cognitive behavior therapy based, partial hospitalization program. Participants completed multiple assessments of depression (Center for the Epidemiological Studies of Depression-10 scale), anxiety (the 7-item Generalized Anxiety Disorder Scale), and repetitive negative thinking (Perseverative Thinking Questionnaire) over the course of treatment. Results indicated statistically significant between and within person effects of RNT on depression and anxiety, even after controlling for the effect of time, previous symptom levels, referral source, and treatment length. RNT explained 22% of the unexplained variability in depression scores and 15% of the unexplained variability in anxiety scores beyond that explained by the control variables. RNT may be an important transdiagnostic treatment target for anxiety and depression. Copyright © 2015 Elsevier Ltd. All rights reserved.
Full Text Available Zebrafish, Danio rerio, is an emerging model organism in stress and neurobehavioral studies. In nature, the species forms shoals, yet when kept in pairs it exhibits an agonistic and anxiety-like behavior that leads to the establishment of dominant-subordinate relationships. Fluoxetine, a selective serotonin reuptake inhibitor, is used as an anxiolytic tool to alter aggressive behavior in several vertebrates and as an antidepressant drug in humans. Pairs of male zebrafish were held overnight to develop dominant—subordinate behavior, either treated or non-treated for 2 h with fluoxetine (5 mg L−1, and allowed to interact once more for 1 h. Behavior was recorded both prior and after fluoxetine administration. At the end of the experiment, trunk and brain samples were also taken for cortisol determination and mRNA expression studies, respectively. Fluoxetine treatment significantly affected zebrafish behavior and the expression levels of several genes, by decreasing offensive aggression in dominants and by eliminating freezing in the subordinates. There was no statistically significant difference in whole-trunk cortisol concentrations between dominant and subordinate fish, while fluoxetine treatment resulted in higher (P = 0.004 cortisol concentrations in both groups. There were statistically significant differences between dominant and subordinate fish in brain mRNA expression levels of genes involved in stress axis (gr, mr, neural activity (bdnf, c-fos, and the serotonergic system (htr2b, slc6a4b. The significant decrease in the offensive and defensive aggression following fluoxetine treatment was concomitant with a reversed pattern in c-fos expression levels. Overall, an acute administration of a selective serotonin reuptake inhibitor alters aggressive behavior in male zebrafish in association with changes in the neuroendocrine mediators of coping styles.
Jia, Rui; Tai, Fadao; An, Shucheng; Zhang, Xia; Broders, Hugh
This study examined whether neonatal paternal deprivation (PD: father was removed and pups were raised just by mother) or early deprivation (ED: pups were raised by both parents except separated from not only the dam but also the peers for three hours a day from PND 0 to 13) has long-term effects on anxiety and social behaviors of adult mandarin voles. Newborn mandarin voles of F2 generation were randomly assigned to one of three groups: bi-parental care (PC: pups were raised by both parents), PD and ED. The parental care behaviors of F1 generation were observed at the age of 0, 13 and 21 days (PND 0, 13, 21) of F2 generation of PC and PD groups. Moreover, each mandarin vole of F2 generation received an open field test and a social interaction test on PND 70 and PND 75, respectively. No significant differences of parental behavior were observed between mothers and fathers from PC families, showing typical parental behavior of socially monogamous rodents. In addition, no significant differences of maternal behaviors were found between mothers from PC and PD families, indicating no maternal compensation towards pups for the absence of the paternal care. In the open field test, mandarin voles from both PD and ED families displayed higher levels of anxiety and lower locomotor activity, relative to offspring of PC family. In the social interaction test, both PD and ED mandarin voles also showed lower levels of social behavior and higher levels of anxiety. Thus, both PD and ED significantly increase anxiety and reduce social behavior of adult mandarin voles, suggesting that variation in parental investment may lead to variation in anxiety and social behaviors in rodents with different mating systems.
Kaye, Walter H; Frank, Guido K; Bailer, Ursula F; Henry, Shannan E; Meltzer, Carolyn C; Price, Julie C; Mathis, Chester A; Wagner, Angela
Anorexia nervosa (AN) and bulimia nervosa (BN) are related disorders with relatively homogenous presentations such as age of onset and gender distribution. In addition, they share symptoms, such as extremes of food consumption, body image distortion, anxiety and obsessions, and ego-syntonic neglect, raises the possibility that these symptoms reflect disturbed brain function that contributes to the pathophysiology of this illness. Recent brain imaging studies have identified altered activity in frontal, cingulate, temporal, and parietal cortical regions in AN and BN. Importantly, such disturbances are present when subjects are ill and persist after recovery, suggesting that these may be traits that are independent of the state of the illness. Emerging data point to a dysregulation of serotonin pathways in cortical and limbic structures that may be related to anxiety, behavioral inhibition, and body image distortions. In specific, recent studies using PET with serotonin specific radioligands implicate alterations of 5-HT1A and 5-HT2A receptors and the 5-HT transporter. Alterations of these circuits may affect mood and impulse control as well as the motivating and hedonic aspects of feeding behavior. Such imaging studies may offer insights into new pharmacology and psychotherapy approaches.
Qiu, Changjian; Feng, Yuan; Meng, Yajing; Liao, Wei; Huang, Xiaoqi; Lui, Su; Zhu, Chunyan; Chen, Huafu; Gong, Qiyong; Zhang, Wei
Objective We hypothesize that the amplitude of low-frequency fluctuations (ALFF) is involved in the altered regional baseline brain function in social anxiety disorder (SAD). The aim of the study was to analyze the altered baseline brain activity in drug-naive adult patients with SAD. Methods We investigated spontaneous and baseline brain activities by obtaining the resting-state functional magnetic resonance imaging data of 20 drug-na?ve adult SAD patients and 19 healthy controls. Voxels wer...
Martin, Cédric BP; Martin, Vincent S.; Trigo, José M.; Chevarin, Caroline; Maldonado, Rafael; Fink, Latham H.; Cunningham, Kathryn A.; Hamon, Michel; Lanfumey, Laurence
Background: Desensitization and blockade of 5-HT2C receptors (5-HT2CR) have long been thought to be central in the therapeutic action of antidepressant drugs. However, besides behavioral pharmacology studies, there is little in vivo data documenting antidepressant-induced 5-HT2CR desensitization in specific brain areas. Methods: Mice lacking the 5-HT reuptake carrier (5-HTT-/-) were used to model the consequences of chronic 5-HT reuptake inhibition with antidepressant drugs. The effect of this mutation on 5-HT2CR was evaluated at the behavioral (social interaction, novelty-suppressed feeding, and 5-HT2CR–induced hypolocomotion tests), the neurochemical, and the cellular (RT-qPCR, mRNA editing, and c-fos–induced expression) levels. Results: Although 5-HTT-/- mice had an anxiogenic profile in the novelty-suppressed feeding test, they displayed less 5-HT2CR–mediated anxiety in response to the agonist m-chlorophenylpiperazine in the social interaction test. In addition, 5-HT2CR–mediated inhibition of a stress-induced increase in 5-HT turnover, measured in various brain areas, was markedly reduced in 5-HTT-/- mutants. These indices of tolerance to 5-HT2CR stimulation were associated neither with altered levels of 5-HT2CR protein and mRNA nor with changes in pre-mRNA editing in the frontal cortex. However, basal c-fos mRNA production in cells expressing 5-HT2CR was higher in 5-HTT-/- mutants, suggesting an altered basal activity of these cells following sustained 5-HT reuptake carrier inactivation. Furthermore, the increased c-fos mRNA expression in 5-HT2CR–like immune-positive cortical cells observed in wild-type mice treated acutely with the 5-HT2CR agonist RO-60,0175 was absent in 5-HTT-/- mutants. Conclusions: Such blunted responsiveness of the 5-HT2CR system, observed at the cell signaling level, probably contributes to the moderation of the anxiety phenotype in 5-HTT-/- mice. PMID:25522398
Seibenhener, Michael L; Wooten, Michael C
Animal models have proven to be invaluable to researchers trying to answer questions regarding the mechanisms of behavior. The Open Field Maze is one of the most commonly used platforms to measure behaviors in animal models. It is a fast and relatively easy test that provides a variety of behavioral information ranging from general ambulatory ability to data regarding the emotionality of the subject animal. As it relates to rodent models, the procedure allows the study of different strains of mice or rats both laboratory bred and wild-captured. The technique also readily lends itself to the investigation of different pharmacological compounds for anxiolytic or anxiogenic effects. Here, a protocol for use of the open field maze to describe mouse behaviors is detailed and a simple analysis of general locomotor ability and anxiety-related emotional behaviors between two strains of C57BL/6 mice is performed. Briefly, using the described protocol we show Wild Type mice exhibited significantly less anxiety related behaviors than did age-matched Knock Out mice while both strains exhibited similar ambulatory ability.
Seillier, Alexandre; Giuffrida, Andrea
Social withdrawal should not be considered a direct measure of the negative symptoms of schizophrenia as it may result not only from asociality (primary negative symptom) but also from other altered processes such as anxiety. To understand the contribution of these two factors to social deficit, we investigated whether the social withdrawal observed in the subchronic phencyclidine (PCP) rat model of schizophrenia could be attributed to increased anxiety. Compared to saline controls, PCP-treated rats (5 mg/kg, twice daily for 7 days, followed by a washout period) spent significantly less time in social interaction, but did not show anxiety-like behaviors in different relevant behavioral paradigms. In addition, their social deficit was not affected by a behavioral procedure known to reduce anxiety-like behavior (repeated exposure to the same partner) nor by systemic administration of the classical anxiolytic diazepam. In contrast, PCP-induced social withdrawal was reversed by the cannabinoid agonist CP55,940, a drug with known anxiogenic properties. Furthermore, when using the social approach task, PCP-treated animals performed similarly to control animals treated with diazepam, but not to those treated with the anxiogenic compound pentylenetetrazole. Taken together, our results indicate that PCP-induced social withdrawal cannot be attributed to increased anxiety. These data are discussed in the context of primary versus secondary negative symptoms and the deficit syndrome of schizophrenia.
Lamb, Ashley L; Hess, Debra E; Edenborn, Sherie; Ubinger, Elizabeth; Carrillo, Andres E; Appasamy, Pierette M
Previous reports indicate that regular, but not excessive, exercise can moderate the response to anxiety and alter the immune response, therefore we hypothesized that college student athletes who were actively participating on an NCAA Division III athletics team ("in-season") would have lower levels of anxiety and higher salivary IgA levels than similar college athletes who were in their "off-season". NCAA Division III athletes participate in athletics at a level of intensity that is more moderate compared to other NCAA divisions. Alterations in the microbiome have been associated with alterations in psychosocial well-being and with exercise. Therefore, we also proposed that the oral microbiota would be different in "in-season" versus "off-season" athletes. In this pilot study, nineteen female students participating on a NCAA Division III athletic team (hockey="in-season"; soccer="off-season") were compared for level of fitness (modified Balke test of VO 2 max), salivary IgA levels by immunoassay, anxiety (using a GAD-7 survey), salivary cortisol levels by immunoassay, and numbers of culturable bacteria by growth of CFU/ml on blood agar, mitis salivarius agar and Staphylococcus 110 agar. The proportion of subjects reporting "severe anxiety" on an anxiety scale (GAD-7) were significantly greater in the "off-season" group compared to the "in-season" group (p=0.047, Chi-squared test). "In-season" athletes had significantly higher salivary IgA/total protein levels than "off-season" athletes (one-sided Student's t-test; p=0.03). Cortisol levels were not significantly different in the two groups. The total culturable bacteria counts were higher among "in-season" athletes (p=0.0455, Wilcoxon Rank Sum test), as measured by CFUs on blood agar plates, an estimate of total culturable bacteria, including pathogenic and non-pathogenic bacteria. In contrast, there was a decrease in the growth of bacteria from the oral cavity of the "in-season" athletes, when the growth of
Lei, Zhuofan; Liu, Bei; Wang, Jin-Hui
Anxiety disorders are presumably associated with negative memory. Psychological therapies are widely used to treat this mental deficit in human beings based on the view that positive memory competes with negative memory and relieves anxiety status. Cellular and molecular processes underlying psychological therapies remain elusive. Therefore, we have investigated its mechanisms based on a mouse model in which food reward at one open-arm of the elevated plus-maze was used for training mice to form reward memory and challenge the open arms. Mice with the reward training showed increased entries and stay time in reward open-arm versus neutral open-arm as well as in open-arms versus closed-arms. Accompanying with reward memory formation and anxiety relief, glutamatergic synaptic transmission in dentate gyrus in vivo and dendritic spines in granule cells became upregulated. This synaptic up-regulation was accompanied by the expression of more protein kinase C (PKC) in the dendritic spines. The inhibition of PKC by chelerythrine impaired the formation of reward memory, the relief of anxiety-related behavior and the up-regulation of glutamate synapses. Our results suggest that reward-induced positive memory relieves mouse anxiety-related behavior by strengthening synaptic efficacy and PKC in the hippocampus, which imply the underlying cellular and molecular processes involved in the beneficial effects of psychological therapies treating anxiety disorders. © 2015 Wiley Periodicals, Inc.
Full Text Available The Glucocorticoid Receptor (GR is a transcription factor ubiquitously expressed in the brain. Activation of brain GRs by high levels of glucocorticoid (GC hormones modifies a large variety of physiological and pathological-related behaviors. Unfortunately the specific cellular targets of GR-mediated behavioral effects of GC are still largely unknown. To address this issue, we generated a mutated form of the GR called DeltaGR. DeltaGR is a constitutively transcriptionally active form of the GR that is localized in the nuclei and activates transcription without binding to glucocorticoids. Using the tetracycline-regulated system (Tet-OFF, we developed an inducible transgenic approach that allows the expression of the DeltaGR in specific brain areas. We focused our study on a mouse line that expressed DeltaGR almost selectively in the glutamatergic neurons of the dentate gyrus (DG of the hippocampus. This restricted expression of the DeltaGR increased anxiety-related behaviors without affecting other behaviors that could indirectly influence performance in anxiety-related tests. This behavioral phenotype was also associated with an up-regulation of the MAPK signaling pathway and Egr-1 protein in the DG. These findings identify glutamatergic neurons in the DG as one of the cellular substrate of stress-related pathologies.
Goldin, Philippe R.; Ziv, Michal; Jazaieri, Hooria; Werner, Kelly; Kraemer, Helena; Heimberg, Richard G.; Gross, James J.
Objective: To examine whether changes in cognitive reappraisal self-efficacy (CR-SE) mediate the effects of individually administered cognitive-behavioral therapy (I-CBT) for social anxiety disorder (SAD) on severity of social anxiety symptoms. Method: A randomized controlled trial in which 75 adult patients (21-55 years of age; 53% male; 57%…
Butler, Tracy R; Carter, Eugenia; Weiner, Jeffrey L
Clinically, early life stress and anxiety disorders are associated with increased vulnerability for alcohol use disorders. In male rats, early life stress, imparted by adolescent social isolation, results in long-lasting increases in a number of behavioral risk factors for alcoholism, including greater anxiety-like behaviors and ethanol (EtOH) intake. Several recent studies have begun to use this model to gain insight into the relationships among anxiety measures, stress, EtOH intake, and neurobiological correlates driving these behaviors. As prior research has noted significant sex differences in the impact of adolescent stress on anxiety measures and EtOH drinking, the current study was conducted to determine if this same model produces an "addiction vulnerable" phenotype in female rodents. Female Long Evans rats were socially isolated (SI; 1/cage) or group housed (GH; 4/cage) for 6 weeks during adolescence. After this housing manipulation, behavioral assessment was conducted using the elevated plus maze, response to novelty in an open field environment, and the light/dark box. After behavioral testing, home cage EtOH drinking was assessed across an 8-week period. No group differences were detected in any of the behavioral measures of unconditioned anxiety-like behavior. Greater EtOH intake and preference were observed in SI females but these differences did not persist. The SI/GH model, which results in robust and enduring increases in anxiety measures and EtOH self-administration in male Long Evans rats, did not result in similar behavioral changes in female rats. These data, and that of others, suggest that adolescent social isolation is not a useful model with which to study neurobiological substrates linking antecedent anxiety and addiction vulnerability in female rats. Given the compelling epidemiological evidence that the relationship between chronic adolescent stress and alcohol addiction is particularly strong in women, there is clearly an urgent need
Schoneveld, E.A.; Lichtwarck-Aschoff, A.; Granic, I.
A large proportion of children experience subclinical levels of anxiety and cognitive-behavioral therapy (CBT) aimed at preventing anxiety disorders is moderately effective. However, most at-risk children do not seek help or drop out of programs prematurely because of stigma, lack of motivation, and
Full Text Available Hormonal action is one of the main factors for behavioral change observed in women, during the menstrual cycle, and especially in the premenstrual period, most women report a variation of mood and anxiety. The aim of this work was to verify the degrees of anxiety during the menstrual cycle, charting their variation and the possible influence of oral contraceptive use. For this purpose 32 women, divided in two groups according to the use (B or not use (A of oral contraceptive, with selfapplication of the STAI (State-Trait Anxiety Inventory at three different times: before, during and after menstruation. The data was tabulated and analyzed statistically, indicating a variation of anxiety level for different menstrual periods, but with no significance as to anxiety type (trait or state or to the ingestion of contraceptive. For Trait-Anxiety, the post-test (Boferroni T-Test of variation among periods indicated significant difference for post-menstrual and other periods, in the A group; and between the premenstrual and menstrual periods, in the B group. For State Anxiety, the data indicated significant differences between the premenstrual and menstrual periods, in the A group, and between the premenstrual and menstrual periods and the menstrual and post-menstrual in the B group. The results indicate that: 1 the menstrual cycle is a generator of variations of related anxiety; 2 the use of oral contraceptives does not alter this relation; and 3 the correlated diminution of the Trait Anxiety may indicate alteration in self-perception of women during the menstrual cycle. Keywords: anxiety; mestrual cycle; STAI.
Holder, Mary K.; Blaustein, Jeffrey D.
Puberty and adolescence are major life transitions during which an individual’s physiology and behavior changes from that of a juvenile to that of an adult. Here we review studies documenting the effects of stressors during pubertal and adolescent development on the adult brain and behavior. The experience of complex or compound stressors during puberty/adolescence generally increases stress reactivity, increases anxiety and depression, and decreases cognitive performance in adulthood. These behavioral changes correlate with decreased hippocampal volumes and alterations in neural plasticity. Moreover, stressful experiences during puberty disrupt behavioral responses to gonadal hormones both in sexual performance and on cognition and emotionality. These behavioral changes correlate with altered estrogen receptor densities in some estrogen-concentrating brain areas, suggesting a remodeling of the brain’s response to hormones. A hypothesis is presented that activation of the immune system results in chronic neuroinflammation that may mediate the alterations of hormone-modulated behaviors in adulthood. PMID:24184692
Lewis-Morrarty, Erin; Degnan, Kathryn A; Chronis-Tuscano, Andrea; Pine, Daniel S; Henderson, Heather A; Fox, Nathan A
Insecure attachment and behavioral inhibition (BI) increase risk for internalizing problems, but few longitudinal studies have examined their interaction in predicting adolescent anxiety. This study included 165 adolescents (ages 14-17 years) selected based on their reactivity to novelty at 4 months. Infant attachment was assessed with the Strange Situation. Multimethod BI assessments were conducted across childhood. Adolescents and their parents independently reported on anxiety. The interaction of attachment and BI significantly predicted adolescent anxiety symptoms, such that BI and anxiety were only associated among adolescents with histories of insecure attachment. Exploratory analyses revealed that this effect was driven by insecure-resistant attachment and that the association between BI and social anxiety was significant only for insecure males. Clinical implications are discussed. © 2014 The Authors. Child Development © 2014 Society for Research in Child Development, Inc.
Linck, V M; da Silva, A L; Figueiró, M; Caramão, E B; Moreno, P R H; Elisabetsky, E
Aromatherapy uses essential oils (EOs) for several medical purposes, including relaxation. The association between the use of aromas and a decrease in anxiety could be a valuable instrument in managing anxiety in an ever increasing anxiogenic daily life style. Linalool is a monoterpene commonly found as the major volatile component of EOs in several aromatic plant species. Adding to previously reported sedative effects of inhaled linalool, the aim of this study was to investigate the effects of inhaled linalool on anxiety, aggressiveness and social interaction in mice. Additionally, we investigated the effects of inhaled linalool on the acquisition phase of a step-down memory task in mice. Inhaled linalool showed anxiolytic properties in the light/dark test, increased social interaction and decreased aggressive behavior; impaired memory was only seen the higher dose of linalool. These results strengthen the suggestion that inhaling linalool rich essential oils can be useful as a mean to attain relaxation and counteract anxiety. (c) 2009 Elsevier GmbH. All rights reserved.
Wang, Lei; Hiller, Helmut; Smith, Justin A; de Kloet, Annette D; Krause, Eric G
This study tested the hypothesis that deletion of angiotensin type 1a receptors (AT1a) from the paraventricular nucleus of hypothalamus (PVN) attenuates anxiety-like behavior, hypothalamic-pituitary-adrenal (HPA) axis activity, and cardiovascular reactivity. We used the Cre/LoxP system to generate male mice with AT1a specifically deleted from the PVN. Deletion of the AT1a from the PVN reduced anxiety-like behavior as indicated by increased time spent in the open arms of the elevated plus maze. In contrast, PVN AT1a deletion had no effect on HPA axis activation subsequent to an acute restraint challenge but did reduce hypothalamic mRNA expression for corticotropin-releasing hormone (CRH). To determine whether PVN AT1a deletion inhibits cardiovascular reactivity, we measured systolic blood pressure, heart rate, and heart rate variability (HRV) using telemetry and found that PVN AT1a deletion attenuated restraint-induced elevations in systolic blood pressure and elicited changes in HRV indicative of reduced sympathetic nervous activity. Consistent with the decreased HRV, PVN AT1a deletion also decreased adrenal weight, suggestive of decreased adrenal sympathetic outflow. Interestingly, the altered stress responsivity of mice with AT1a deleted from the PVN was associated with decreased hypothalamic microglia and proinflammatory cytokine expression. Collectively, these results suggest that deletion of AT1a from the PVN attenuates anxiety, CRH gene transcription, and cardiovascular reactivity and reduced brain inflammation may contribute to these effects. Copyright © 2016 the American Physiological Society.
Kudwa, Andrea E; McGivern, Robert F; Handa, Robert J
The hypothalamic-pituitary-adrenal (HPA) axis is activated in response to stressors and is controlled by neurons residing in the paraventricular nucleus of the hypothalamus (PVN). Although gonadal steroid hormones can influence HPA reactivity to stressors, the exact mechanism of action is not fully understood. It is known, however, that estrogen receptor β (ERβ) inhibits HPA reactivity and decreases anxiety-like behavior in rodents. Since ERβ is co-expressed with oxytocin (OT) in neurons of the PVN, an ERβ-selective agonist was utilized to test the whether ERβ decreases stress-induced HPA reactivity and anxiety-like behaviors via an OTergic pathway. Adult gonadectomized male and female rats were administered diarylpropionitrile, or vehicle, peripherally for 5days. When tested for anxiety-like behavior on the elevated plus maze (EPM), diarylpropionitrile-treated males and females significantly increased time on the open arm of the EPM compared to vehicle controls indicating that ERβ reduces anxiety-like behaviors. One week after behavioral evaluation, rats were subjected to a 20minute restraint stress. Treatment with diarylpropionitrile reduced CORT and ACTH responses in both males and females. Subsequently, another group of animals was implanted with cannulae directed at the lateral ventricle. One week later, rats underwent the same protocol as above but with the additional treatment of intracerebroventricular infusion with an OT antagonist (des Gly-NH2 d(CH2)5 [Tyr(Me)(2), Thr(4)] OVT) or VEH, 20min prior to behavioral evaluation. OT antagonist treatment blocked the effects of diarylpropionitrile on the display of anxiety-like behaviors and plasma CORT levels. These data indicate that ERβ and OT interact to modulate the HPA reactivity and the display of anxiety-like behaviors. Copyright © 2014 Elsevier Inc. All rights reserved.
Monahan, Kathryn C.; Goldweber, Aska; Meyer, Kristen; Cauffman, Elizabeth
The present study examines how perceptions of social prominence and attitudes toward antisocial behavior among peers moderate the association between anxiety and antisocial behavior among incarcerated females. Latent profile analysis identified two classes of females distinguished by their perceptions and attitudes. Individuals in both classes…
Cao, Bo; Ni, Huan-Yu; Li, Jun; Zhou, Ying; Bian, Xin-Lan; Tao, Yan; Cai, Cheng-Yun; Qin, Cheng; Wu, Hai-Yin; Chang, Lei; Luo, Chun-Xia; Zhu, Dong-Ya
Fear- and anxiety-related psychiatric disorders have been one of the major chronic diseases afflicting patients for decades, and new compounds for treating such disorders remain to be developed. (+)-Borneol, a bicyclic monoterpene found in several species of Artemisia and Dipterocarpaceae, is widely used for anxiety, pain and anesthesia in Chinese medicine. Meanwhile, it can potentiate GABA (γ-aminobutyric acid) activity directly in recombinant GABAA receptors. The present study was to investigate the effects of (+)-Borneol on both contextual and cued fear recall. Interestingly, microinjection of (+)-Borneol into the dorsal hippocampus inhibited 24 h and 7 d contextual fear, whereas its infusion into ventral hippocampus only reduced 24 h cued fear responses. Moreover, microinjection of (+)-Borneol into dorsal but not ventral hippocampus suppressed anxiety-like behaviors in the open field test, light/dark exploration and the elevated plus maze test. As selective GABA A receptor antagonist bicuculline reversed the effect of (+)-Borneol on contextual fear paradigm and the drug potentiated GABA-evoked currents in acute hippocampus slices, modulation of the GABAergic neurotransmission may explain the effects of (+)-Borneol. Our findings suggest that (+)-Borneol can serve as a new therapeutic in fear- and anxiety-related disorders. Copyright © 2017 Elsevier Inc. All rights reserved.
Full Text Available Abstract Background Previous studies have demonstrated essential roles for alpha-calcium/calmodulin-dependent protein kinase II (alpha-CaMKII in learning, memory and long-term potentiation (LTP. However, previous studies have also shown that alpha-CaMKII (+/- heterozygous knockout mice display a dramatic decrease in anxiety-like and fearful behaviors, and an increase in defensive aggression. These findings indicated that alpha-CaMKII is important not only for learning and memory but also for emotional behaviors. In this study, to understand the roles of alpha-CaMKII in emotional behavior, we generated transgenic mice overexpressing alpha-CaMKII in the forebrain and analyzed their behavioral phenotypes. Results We generated transgenic mice overexpressing alpha-CaMKII in the forebrain under the control of the alpha-CaMKII promoter. In contrast to alpha-CaMKII (+/- heterozygous knockout mice, alpha-CaMKII overexpressing mice display an increase in anxiety-like behaviors in open field, elevated zero maze, light-dark transition and social interaction tests, and a decrease in locomotor activity in their home cages and novel environments; these phenotypes were the opposite to those observed in alpha-CaMKII (+/- heterozygous knockout mice. In addition, similarly with alpha-CaMKII (+/- heterozygous knockout mice, alpha-CaMKII overexpressing mice display an increase in aggression. However, in contrast to the increase in defensive aggression observed in alpha-CaMKII (+/- heterozygous knockout mice, alpha-CaMKII overexpressing mice display an increase in offensive aggression. Conclusion Up-regulation of alpha-CaMKII expression in the forebrain leads to an increase in anxiety-like behaviors and offensive aggression. From the comparisons with previous findings, we suggest that the expression levels of alpha-CaMKII are associated with the state of emotion; the expression level of alpha-CaMKII positively correlates with the anxiety state and strongly affects
Weersing, V Robin; Brent, David A; Rozenman, Michelle S; Gonzalez, Araceli; Jeffreys, Megan; Dickerson, John F; Lynch, Frances L; Porta, Giovanna; Iyengar, Satish
Anxiety and depression affect 30% of youth but are markedly undertreated compared with other mental disorders, especially in Hispanic populations. To examine whether a pediatrics-based behavioral intervention targeting anxiety and depression improves clinical outcome compared with referral to outpatient community mental health care. This 2-center randomized clinical trial with masked outcome assessment conducted between brief behavioral therapy (BBT) and assisted referral to care (ARC) studied 185 youths (aged 8.0-16.9 years) from 9 pediatric clinics in San Diego, California, and Pittsburgh, Pennsylvania, recruited from October 6, 2010, through December 5, 2014. Youths who met DSM-IV criteria for full or probable diagnoses of separation anxiety disorder, generalized anxiety disorder, social phobia, major depression, dysthymic disorder, and/or minor depression; lived with a consenting legal guardian for at least 6 months; and spoke English were included in the study. Exclusions included receipt of alternate treatment for anxiety or depression, presence of a suicidal plan, bipolar disorder, psychosis, posttraumatic stress disorder, substance dependence, current abuse, intellectual disability, or unstable serious physical illness. The BBT consisted of 8 to 12 weekly 45-minute sessions of behavioral therapy delivered in pediatric clinics by master's-level clinicians. The ARC families received personalized referrals to mental health care and check-in calls to support accessing care from master's-level coordinators. The primary outcome was clinically significant improvement on the Clinical Global Impression-Improvement scale (score ≤2). Secondary outcomes included the Pediatric Anxiety Rating Scale, Children's Depression Rating Scale-Revised, and functioning. A total of 185 patients were enrolled in the study (mean [SD] age, 11.3 [2.6] years; 107 [57.8%] female; 144 [77.8%] white; and 38 [20.7%] Hispanic). Youths in the BBT group (n = 95), compared with those in
Ruan, Chun-Sheng; Yang, Chun-Rui; Li, Jia-Yi; Luo, Hai-Yun; Bobrovskaya, Larisa; Zhou, Xin-Fu
Exposure to stressful life events plays a central role in the development of mood disorders in vulnerable individuals. However, the mechanisms that link mood disorders to stress are poorly understood. Brain-derived neurotrophic factor (BDNF) has long been implicated in positive regulation of depression and anxiety, while its precursor (proBDNF) recently showed an opposing effect on such mental illnesses. P75(NTR) and sortilin are co-receptors of proBDNF, however, the role of these receptors in mood regulation is not established. Here, we aimed to investigate the role of sortilin in regulating mood-related behaviors and its role in the proBDNF-mediated mood abnormality in mice. We found that sortilin was up-regulated in neocortex (by 78.3%) and hippocampus (by 111%) of chronically stressed mice as assessed by western blot analysis. These changes were associated with decreased mobility in the open field test and increased depression-like behavior in the forced swimming test. We also found that sortilin deficiency in mice resulted in hyperlocomotion in the open field test and increased anxiety-like behavior in both the open field and elevated plus maze tests. No depression-like behavior in the forced swimming test and no deficit in spatial cognition in the Morris water maze test were found in the Sort1-deficient mice. Moreover, the intracellular and extracellular levels of mature BDNF and proBDNF were not changed when sortilin was absent in vivo and in vitro. Finally, we found that both WT and Sort1-deficient mice injected with proBDNF in lateral ventricle displayed increased depression-like behavior in the forced swimming test but not anxiety-like behaviors in the open field and elevated plus maze tests. The present study suggests that sortilin functions as a negative regulator of mood performance and can be a therapeutic target for the treatment of mental illness. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.
Full Text Available Louise Mewton, Jessica Smith, Pieter Rossouw, Gavin Andrews Clinical Research Unit for Anxiety and Depression, St Vincent’s Hospital, Sydney, NSW, Australia Abstract: The aim of the current review is to provide a summary of research into Internet-delivered cognitive behavioral therapy (iCBT for anxiety disorders. We include 37 randomized controlled trials that examined the efficacy of iCBT programs in adults (aged over 18 years, as compared with waiting list or active control. The included studies were identified from Medline searches and from reference lists, and only published data were included. Several trials of iCBT for generalized anxiety disorder, panic disorder, and social phobia were identified. Two trials of iCBT for obsessive-compulsive disorder were identified, whilst one trial each was identified for hypochondriasis, specific phobia (spiders, and post-traumatic stress disorder. Finally, there were five trials that focused on transdiagnostic therapy for either a range of comorbid anxiety disorders or comorbid anxiety and depression. Between-group effect sizes were moderate to large for all disorders, and ranged from 0.30 to 2.53. iCBT was found to be commensurate with face-to-face cognitive behavioral therapy whether delivered individually or in group format. Guidance may not be necessary for iCBT to be effective for immediate gains, but may be more important in longer-term maintenance of symptom improvement and maximizing patient adherence. The clinical experience of the individual providing guidance does not appear to impact treatment outcomes. Future research needs to focus on the optimal level of guidance required to generate maximum patient benefits, whilst balancing the efficient use of clinician time and resources. Evidence-based contraindications to iCBT should also be developed so that the choice of treatment modality accurately reflects patients’ needs. Further research should be conducted into the effective elements of
Walker, Jerry V., III
This article reviews the recent empirical literature on the various parental factors that detract from the effectiveness of cognitive-behavioral treatment for children with anxiety. Interventions such as treating parental anxiety and increasing parental involvement in the therapeutic process may combat these factors. Newer strategies such as…
Full Text Available Deva Priya Appukuttan Department of Periodontics, Sri Ramakrishna Mission Dental College and Hospital, Chennai, India Abstract: Dental anxiety and phobia result in avoidance of dental care. It is a frequently encountered problem in dental offices. Formulating acceptable evidence-based therapies for such patients is essential, or else they can be a considerable source of stress for the dentist. These patients need to be identified at the earliest opportunity and their concerns addressed. The initial interaction between the dentist and the patient can reveal the presence of anxiety, fear, and phobia. In such situations, subjective evaluation by interviews and self-reporting on fear and anxiety scales and objective assessment of blood pressure, pulse rate, pulse oximetry, finger temperature, and galvanic skin response can greatly enhance the diagnosis and enable categorization of these individuals as mildly, moderately, or highly anxious or dental phobics. Broadly, dental anxiety can be managed by psychotherapeutic interventions, pharmacological interventions, or a combination of both, depending on the level of dental anxiety, patient characteristics, and clinical situations. Psychotherapeutic interventions are either behaviorally or cognitively oriented. Pharmacologically, these patients can be managed using either sedation or general anesthesia. Behavior-modification therapies aim to change unacceptable behaviors through learning, and involve muscle relaxation and relaxation breathing, along with guided imagery and physiological monitoring using biofeedback, hypnosis, acupuncture, distraction, positive reinforcement, stop-signaling, and exposure-based treatments, such as systematic desensitization, “tell-show-do”, and modeling. Cognitive strategies aim to alter and restructure the content of negative cognitions and enhance control over the negative thoughts. Cognitive behavior therapy is a combination of behavior therapy and cognitive therapy
King, Lauren A; Urbach, John R; Stewart, Karen E
Eating difficulties are commonly present in medical and psychiatric settings. Some eating problems are resultant from fears about food consumption and can be conceptualized as anxiety disorders conditioned by perception of feared outcomes associated with eating and maintained by avoidance. The authors present a case in which a female patient with limited food intake is successfully treated with cognitive-behavioral therapy. Illness anxiety disorder and avoidant/restrictive food intake disorder, both newly included in DSM-V, are applied in this case. Copyright © 2015. Published by Elsevier Ltd.
Gruen, Margaret E; Case, Beth C; Foster, Melanie L; Lazarowski, Lucia; Fish, Richard E; Landsberg, Gary; DePuy, Venita; Dorman, David C; Sherman, Barbara L
Previous studies have shown that the playing of thunderstorm recordings during an open-field task elicits fearful or anxious responses in adult beagles. The goal of our study was to apply this open field test to assess sound-induced behaviors in Labrador retrievers drawn from a pool of candidate improvised explosive devices (IED)-detection dogs. Being robust to fear-inducing sounds and recovering quickly is a critical requirement of these military working dogs. This study presented male and female dogs, with 3 minutes of either ambient noise (Days 1, 3 and 5), recorded thunderstorm (Day 2), or gunfire (Day 4) sounds in an open field arena. Behavioral and physiological responses were assessed and compared to control (ambient noise) periods. An observer blinded to sound treatment analyzed video records of the 9-minute daily test sessions. Additional assessments included measurement of distance traveled (activity), heart rate, body temperature, and salivary cortisol concentrations. Overall, there was a decline in distance traveled and heart rate within each day and over the five-day test period, suggesting that dogs habituated to the open field arena. Behavioral postures and expressions were assessed using a standardized rubric to score behaviors linked to canine fear and anxiety. These fear/anxiety scores were used to evaluate changes in behaviors following exposure to a sound stressor. Compared to control periods, there was an overall increase in fear/anxiety scores during thunderstorm and gunfire sound stimuli treatment periods. Fear/anxiety scores were correlated with distance traveled, and heart rate. Fear/anxiety scores in response to thunderstorm and gunfire were correlated. Dogs showed higher fear/anxiety scores during periods after the sound stimuli compared to control periods. In general, candidate IED-detection Labrador retrievers responded to sound stimuli and recovered quickly, although dogs stratified in their response to sound stimuli. Some dogs were
Bloch, Michael H.; Panza, Kaitlyn E.; Reichow, Brian
BACKGROUND Anxiety is a common and impairing problem in children and adolescents with autism spectrum disorder (ASD). There is emerging evidence that cognitive-behavioral therapy (CBT) could reduce anxiety in children with high-functioning ASD. OBJECTIVE: To systematically review the evidence of using CBT to treat anxiety in children and adolescents with ASD. Methods for this review were registered with PROSPERO (CRD42012002722). METHODS: We included randomized controlled trials published in English in peer-reviewed journals comparing CBT with another treatment, no treatment control, or waitlist control. Two authors independently screened 396 records obtained from database searches and hand searched relevant journals. Two authors independently extracted and reconciled all data used in analyses from study reports. RESULTS: Eight studies involving 469 participants (252 treatment, 217 comparison) met our inclusion criteria and were included in meta-analyses. Overall effect sizes for clinician- and parent-rated outcome measures of anxiety across all studies were d = 1.19 and d = 1.21, respectively. Five studies that included child self-report yielded an average d = 0.68 across self-reported anxiety. CONCLUSIONS: Parent ratings and clinician ratings of anxiety are sensitive to detecting treatment change with CBT for anxiety relative to waitlist and treatment-as-usual control conditions in children with high-functioning ASD. Clinical studies are needed to evaluate CBT for anxiety against attention control conditions in samples of children with ASD that are well characterized with regard to ASD diagnosis and co-occurring anxiety symptoms. PMID:24167175
alterations in specific DARPP-32-mediated signaling mechanisms. 15. SUBJECT TERMS Autism , self-injurious behavior, neuroscience, dopamine , DARPP-32...Injurious Behavior: An Animal Model of an Autism Endophenotype Darragh Devine University of Florida Gainesville, FL 32611 Autism , self...injurious behavior, neuroscience, dopamine , DARPP-32, stress, anxiety Abstract on next page. 75 firstname.lastname@example.org REPORT DOCUMENTATION PAGE Form Approved
Steiger, V R; Brühl, A B; Weidt, S; Delsignore, A; Rufer, M; Jäncke, L; Herwig, U; Hänggi, J
Social anxiety disorder (SAD) is characterized by fears of social and performance situations. Cognitive behavioral group therapy (CBGT) has in general positive effects on symptoms, distress and avoidance in SAD. Prior studies found increased cortical volumes and decreased fractional anisotropy (FA) in SAD compared with healthy controls (HCs). Thirty-three participants diagnosed with SAD attended in a 10-week CBGT and were scanned before and after therapy. We applied three neuroimaging methods-surface-based morphometry, diffusion tensor imaging and network-based statistics-each with specific longitudinal processing protocols, to investigate CBGT-induced structural brain alterations of the gray and white matter (WM). Surface-based morphometry revealed a significant cortical volume reduction (pre- to post-treatment) in the left inferior parietal cortex, as well as a positive partial correlation between treatment success (indexed by reductions in Liebowitz Social Anxiety Scale) and reductions in cortical volume in bilateral dorsomedial prefrontal cortex. Diffusion tensor imaging analysis revealed a significant increase in FA in bilateral uncinate fasciculus and right inferior longitudinal fasciculus. Network-based statistics revealed a significant increase of structural connectivity in a frontolimbic network. No partial correlations with treatment success have been found in WM analyses. For, we believe, the first time, we present a distinctive pattern of longitudinal structural brain changes after CBGT measured with three established magnetic resonance imaging analyzing techniques. Our findings are in line with previous cross-sectional, unimodal SAD studies and extent them by highlighting anatomical brain alterations that point toward the level of HCs in parallel with a reduction in SAD symptomatology.
Silveira, Marushka L; Whitcomb, Brian W; Pekow, Penelope; Carbone, Elena T; Chasan-Taber, Lisa
Maternal periodontal disease is associated with adverse perinatal outcomes. Anxiety and depression adversely impact oral health in nonpregnant women; however, this association has not been evaluated during pregnancy, a time characterized by higher rates of anxiety and depression. Therefore, we examined the association between these factors and oral disease and oral healthcare utilization among 402 pregnant respondents to the 2010 Behavioral Risk Factor Surveillance System. Self-reported lifetime diagnoses of anxiety, depression, and current depression were assessed. Oral health outcomes included self-reported tooth loss and dental visits in the past year. One-fifth (21.2 percent) of respondents reported a tooth loss and 32.5 percent reported nonuse of oral health services. The prevalence of lifetime diagnosed anxiety and depression was 13.6 percent and 11.3 percent, respectively, whereas 10.6 percent reported current depression. After adjusting for risk factors, pregnant women with diagnosed anxiety had increased odds of one or more tooth loss [odds ratio (OR) = 3.30; 95 percent confidence interval (CI): 1.01-10.77] compared with those without the disorder. Similarly, after adjusting for socioeconomic factors, women with anxiety had increased odds of nonuse of oral health services (OR = 2.67; 95 percent CI: 1.03-6.90); however, this was no longer significant after adjusting for health behaviors and body mass index. We observed no significant association with depression. In this population-based sample, we found a two- to threefold increased odds of tooth loss and nonuse of oral health services among pregnant women with a lifetime diagnosis of anxiety. To our knowledge, this is the first study to examine these associations among pregnant women. © 2015 American Association of Public Health Dentistry.
Nielsen, Amalie; Gaardsvig, Majken Maria; Stjerneklar, Silke
-17 years. Inclusion criteria were an anxiety disorder as primary diagnosis, access to a computer and the Internet at home, and ability to read and write in Danish. Exclusion criteria were comorbid depression (CSR ≥ 6), school absenteeism above 50%, self-harm, suicidal ideation, substance dependence......Aim Only a small proportion of children and adolescents with anxiety disorders receive treatment, despite evidence of the efficacy of CBT (cognitive behavioral therapy) (Reynolds, Wilson, Austin & Hooper, 2012). Lately there has been an increase in the development of ICBT (internet-based CBT......) programs to reduce costs and enhance accessibility of psychological interventions. ICBT has proven efficacious towards adults with anxiety disorders (Haug, Nordgreen, Ost & Havik, 2012; Reger & Gahm, 2009). Research in ICBT with children and adolescents is still in its infancy and no program targeting...
Full Text Available The aim of this study was to evaluate the behavioral effects of chronic (six weeks nandrolone decanoate (ND, 20 mg/kg, s.c., weekly in single dose administration (in order to mimic heavy human abuse, and exercise (swimming protocol of 60 minutes a day, five days in a row/two days break, applied alone and simultaneously with ND, in male rats (n = 40. Also, we evaluated the effects of those protocols on hippocampal parvalbumin (PV content and the possible connection between the alterations in certain parts of hippocampal GABAergic system and behavioral patterns. Both ND and exercise protocols induced increase in testosterone, dihydrotestosterone and estradiol blood levels. Our results confirmed anxiogenic effects of ND observed in open field (OF test (decrease in the locomotor activity, as well as in frequency and cumulative duration in the centre zone and in elevated plus maze (EPM test (decrease in frequency and cumulative duration in open arms, and total exploratory activity, that were accompanied with a mild decrease in the number of PV interneurons in hippocampus. Chronic exercise protocol induced significant increase in hippocampal PV neurons (dentate gyrus and CA1 region, followed by anxiolytic-like behavioral changes, observed in both OF and EPM (increase in all estimated parameters, and in evoked beam-walking test (increase in time to cross the beam, compared to ND treated animals. The applied dose of ND was sufficient to attenuate beneficial effects of exercise in rats by means of decreased exercise-induced anxiolytic effect, as well as to reverse exercise-induced augmentation in number of PV immunoreactive neurons in hippocampus. Our results implicate the possibility that alterations in hippocampal PV interneurons (i.e. GABAergic system may be involved in modulation of anxiety level induced by ND abuse and/or extended exercise protocols.
Selakovic, Dragica; Joksimovic, Jovana; Zaletel, Ivan; Puskas, Nela; Matovic, Milovan; Rosic, Gvozden
The aim of this study was to evaluate the behavioral effects of chronic (six weeks) nandrolone decanoate (ND, 20 mg/kg, s.c., weekly in single dose) administration (in order to mimic heavy human abuse), and exercise (swimming protocol of 60 minutes a day, five days in a row/two days break), applied alone and simultaneously with ND, in male rats (n = 40). Also, we evaluated the effects of those protocols on hippocampal parvalbumin (PV) content and the possible connection between the alterations in certain parts of hippocampal GABAergic system and behavioral patterns. Both ND and exercise protocols induced increase in testosterone, dihydrotestosterone and estradiol blood levels. Our results confirmed anxiogenic effects of ND observed in open field (OF) test (decrease in the locomotor activity, as well as in frequency and cumulative duration in the centre zone) and in elevated plus maze (EPM) test (decrease in frequency and cumulative duration in open arms, and total exploratory activity), that were accompanied with a mild decrease in the number of PV interneurons in hippocampus. Chronic exercise protocol induced significant increase in hippocampal PV neurons (dentate gyrus and CA1 region), followed by anxiolytic-like behavioral changes, observed in both OF and EPM (increase in all estimated parameters), and in evoked beam-walking test (increase in time to cross the beam), compared to ND treated animals. The applied dose of ND was sufficient to attenuate beneficial effects of exercise in rats by means of decreased exercise-induced anxiolytic effect, as well as to reverse exercise-induced augmentation in number of PV immunoreactive neurons in hippocampus. Our results implicate the possibility that alterations in hippocampal PV interneurons (i.e. GABAergic system) may be involved in modulation of anxiety level induced by ND abuse and/or extended exercise protocols.
McHugh, R Kathryn; Votaw, Victoria R; Barlow, David H; Fitzmaurice, Garrett M; Greenfield, Shelly F; Weiss, Roger D
Opioid use disorder is a highly disabling psychiatric disorder, and is associated with both significant functional disruption and risk for negative health outcomes such as infectious disease and fatal overdose. Even among those who receive evidence-based pharmacotherapy for opioid use disorder, many drop out of treatment or relapse, highlighting the importance of novel treatment strategies for this population. Over 60% of those with opioid use disorder also meet diagnostic criteria for an anxiety disorder; however, efficacious treatments for this common co-occurrence have not be established. This manuscript describes the rationale and methods for a behavioral treatment development study designed to develop and test an integrated cognitive-behavioral therapy for those with co-occurring opioid use disorder and anxiety disorders. The aims of the study are (1) to develop and pilot test a new manualized cognitive behavioral therapy for co-occurring opioid use disorder and anxiety disorders, (2) to test the efficacy of this treatment relative to an active comparison treatment that targets opioid use disorder alone, and (3) to investigate the role of stress reactivity in both prognosis and recovery from opioid use disorder and anxiety disorders. Our overarching aim is to investigate whether this new treatment improves both anxiety and opioid use disorder outcomes relative to standard treatment. Identifying optimal treatment strategies for this population are needed to improve outcomes among those with this highly disabling and life-threatening disorder. Copyright © 2017 Elsevier Inc. All rights reserved.
Porritt, J; Rodd, H; Morgan, A; Williams, C; Gupta, E; Kirby, J; Creswell, C; Newton, T; Stevens, K; Baker, S; Prasad, S; Marshman, Z
Cognitive Behavioral Therapy (CBT) is an evidence-based treatment for dental anxiety; however, access to therapy is limited. The current study aimed to develop a self-help CBT resource for reducing dental anxiety in children, and to assess the feasibility of conducting a trial to evaluate the treatment efficacy and cost-effectiveness of such an intervention. A mixed methods design was employed. Within phase 1, a qualitative "person-based" approach informed the development of the self-help CBT resource. This also employed guidelines for the development and evaluation of complex interventions. Within phase 2, children, aged between 9 and 16 y, who had elevated self-reported dental anxiety and were attending a community dental service or dental hospital, were invited to use the CBT resource. Children completed questionnaires, which assessed their dental anxiety and health-related quality of life (HRQoL) prior to and following their use of the resource. Recruitment and completion rates were recorded. Acceptability of the CBT resource was explored using interviews and focus groups with children, parents/carers and dental professionals. For this analysis, the authors adhered to the Mixed Methods Appraisal Tool criteria. There were 24 families and 25 dental professionals participating in the development and qualitative evaluation of the CBT resource for children with dental anxiety. A total of 56 children agreed to trial the CBT resource (66% response rate) and 48 of these children completed the study (86% completion rate). There was a significant reduction in dental anxiety (mean score difference = 7.7, t = 7.9, df = 45, P < 0.001, Cohen's d ES = 1.2) and an increase in HRQoL following the use of the CBT resource (mean score difference = -0.03, t = 2.14, df = 46, P < 0.05, Cohen's d ES = 0.3). The self-help approach had high levels of acceptability to stakeholders. These findings provide preliminary evidence for the effectiveness and acceptability of the resource in
Mathur, Jyoti; Diwanji, Amish; Sarvaiya, Bhumi; Sharma, Dipal
To develop a simple method to assess the level of anxiety by using children's drawings and correlating them with Frankl's behavior rating scale. A total of 178 patients aged of 3 to 14 years were handed out two-page forms which contained three sections on coloring and drawing, along with general information, and Frankl's behavior rating scale for the visit. The three types of drawing exercises given to the patients were geometric copy drawings, coloring a nonthreatening figure, and an empty sheet for freehand drawing. Out of 178 patients, 60 showed definitely positive behavior, 73 exhibited positive behavior, 37 showed negative behavior, and 8 were definitely negative on Frankl's behavior rating scale; 133 children had none or, 1 stress marker and 45 exhibited 2 or 3 stress markers in their drawings. Chi-square (χ 2 ) analysis was done with a 2 × 2 contingency table. Observed χ 2 value was 46.166, which at 1 degree of freedom was much greater than that at 0.995 percentile. Therefore, the result was highly significant. Children requiring specialized behavioral techniques can be identified by the presence of stress markers in their drawings. This nonverbal activity by itself can have an overall positive effect on the behavior displayed in the dental clinic. Mathur J, Diwanji A, Sarvaiya B, Sharma D. Identifying Dental Anxiety in Children's Drawings and correlating It with Frankl's Behavior Rating Scale. Int J Clin Pediatr Dent 2017;10(1):24-28.
Zhang, Zhuan; Hong, Juan; Zhang, Suyun; Zhang, Tingting; Sha, Sha; Yang, Rong; Qian, Yanning; Chen, Ling
Postpartum estrogen withdrawal is known to be a particularly vulnerable time for depressive symptoms. Ovariectomized adult mice (OVX-mice) treated with hormone-simulated pregnancy (HSP mice) followed by a subsequent estradiol benzoate (EB) withdrawal (EW mice) exhibited depression- and anxiety-like behaviors, as assessed by forced swim, tail suspension and elevated plus-maze, while HSP mice, OVX mice or EB-treated OVX mice (OVX/EB mice) did not. The survival and neurite growth of newborn neurons in hippocampal dentate gyrus were examined on day 5 after EW. Compared with controls, the numbers of 28-day-old BrdU(+) and BrdU(+)/NeuN(+) cells were increased in HSP mice but significantly decreased in EW mice; the numbers of 10-day-old BrdU(+) cells were increased in HSP mice and OVX/EB mice; and the density of DCX(+) fibers was reduced in EW mice and OVX mice. The phosphorylation of hippocampal NMDA receptor (NMDAr) NR2B subunit or Src was increased in HSP mice but decreased in EW mice. NMDAr agonist NMDA prevented the loss of 28-day-old BrdU(+) cells and the depression- and anxiety-like behaviors in EW mice. NR2B inhibitor Ro25-6981 or Src inhibitor dasatinib caused depression- and anxiety-like behaviors in HSP mice with the reduction of 28-day-old BrdU(+) cells. The hippocampal BDNF levels were reduced in EW mice and OVX mice. TrkB receptor inhibitor K252a reduced the density of DCX(+) fibers in HSP mice without the reduction of 28-day-old BrdU(+) cells, or the production of affective disorder. Collectively, these results indicate that postpartum estrogen withdrawal impairs hippocampal neurogenesis in mice that show depression- and anxiety-like behaviors. Copyright © 2016 Elsevier Ltd. All rights reserved.
Kahana, Shoshana Y.; Feeny, Norah C.
Although illness phobias are fairly common disorders, their treatment has been scarcely addressed in the literature. The current article discusses the treatment of a 9-year-old female diagnosed with health-related anxiety--specifically, a phobia of vomiting. A variety of cognitive-behavioral techniques, such as relaxation training (e.g., deep…
Möller, E.L.; Nikolić, M.; Majdandžić, M.; Bögels, S.M.
In this meta-analysis we investigated differential associations between maternal and paternal parenting behaviors (overcontrol, overprotection, overinvolvement, autonomy granting, challenging parenting) and anxiety and its precursors (fearful temperament, behavioral inhibition, shyness) in children
Abreu, Murilo S; Giacomini, Ana C V V; Koakoski, Gessi; Piato, Angelo L; Barcellos, Leonardo J G
Jundiá (Rhamdia quelen) is a suitable species for aquaculture in regions of temperate or subtropical climate. This species has received great attention regarding several aspects of physiology as well as an organism to study the impact of environmental contaminations. However, experiments using validated and objective tests to evaluate the jundiá behavior are scarce. The effects of acute stress have been studied in other fish species, such as zebrafish (Danio rerio), however, the effects in jundiá are lacking. Thus, we evaluated the effects of acute stress (net chasing) on anxiety-like and social behavior in jundiá. For these purpose, all behavioral analyses were carried out using automated tracking software. We showed that the acute stress protocol increased cortisol levels and induced anxiogenic-like behavior in the novel tank test, and decreased social behavior in jundiá. The antidepressant fluoxetine was able to prevent the effects of acute stress on social behavior. Here we show a behavioral evaluation of Rhamdia quelen using consolidated tests and computerized analysis, which allows more measurable, reliable and comparable results. Copyright © 2016 Elsevier Inc. All rights reserved.
Hirshfeld-Becker, Dina R.; Masek, Bruce; Henin, Aude; Blakely, Lauren Raezer; Pollock-Wurman, Rachel A.; McQuade, Julia; DePetrillo, Lillian; Briesch, Jacquelyn; Ollendick, Thomas H.; Rosenbaum, Jerrold F.; Biederman, Joseph
Objective: To examine the efficacy of a developmentally appropriate parent-child cognitive behavioral therapy (CBT) protocol for anxiety disorders in children ages 4-7 years. Method: Design: Randomized wait-list controlled trial. Conduct: Sixty-four children (53% female, mean age 5.4 years, 80% European American) with anxiety disorders were…
Majdandžić, M.; Möller, E.L.; de Vente, W.; Bögels, S.M.; van den Boom, D.C.
Recent models on parenting propose different roles for fathers and mothers in the development of child anxiety. Specifically, it is suggested that fathers’ challenging parenting behavior, in which the child is playfully encouraged to push her limits, buffers against child anxiety. In this
Butler, Tracy R; Karkhanis, Anushree N; Jones, Sara R; Weiner, Jeffrey L
Individuals diagnosed with anxiety-related illnesses are at increased risk of developing alcoholism, exhibit a telescoped progression of this disease and fare worse in recovery, relative to alcoholics that do not suffer from a comorbid anxiety disorder. Similarly, preclinical evidence supports the notion that stress and anxiety represent major risk factors for the development of alcohol use disorder (AUD). Despite the importance of understanding the link between anxiety and alcoholism, much remains unknown about the neurobiological substrates underlying this relationship. One stumbling block has been the lack of animal models that reliably reproduce the spectrum of behaviors associated with increased vulnerability to these diseases. Here, we review the literature that has examined the behavioral and neurobiological outcomes of a simple rodent adolescent social isolation procedure and discuss its validity as a model of vulnerability to comorbid anxiety disorders and alcoholism. Recent studies have provided strong evidence that adolescent social isolation of male rats leads to the expression of a variety of behaviors linked with increased vulnerability to anxiety and/or AUD, including deficits in sensory gating and fear extinction, and increases in anxiety measures and ethanol drinking. Neurobiological studies are beginning to identify mesolimbic adaptations that may contribute to the behavioral phenotype engendered by this model. Some of these changes include increased excitability of ventral tegmental area dopamine neurons and pyramidal cells in the basolateral amygdala and significant alterations in baseline and stimulated catecholamine signaling. A growing body of evidence suggests that adolescent social isolation may represent a reliable rodent model of heightened vulnerability to anxiety disorders and alcoholism in male rats. These studies provide initial support for the face, construct, and predictive validity of this model and highlight its utility in
A growing body of literature suggests that parents play a critical role in the development and/or maintenance of child anxiety. One of the main purposes of this article is to identify common parental involvement techniques and most common obstacles derived from parents in cognitive behavioral therapy (CBT) with anxious children. Another purpose of the present study is to revise empirical studies comparing child-focused CBT with and without parental involvement. The PsycARTICLES, MEDLINE and PubMed databases were searched to identify articles in English that were published between the years of 1990 and 2012 (October) using the following keywords; (1) anxiety, (2) cognitive behavioral therapy, (3) parental involvement. Studies were only included in this review if they were comparing the treatment effect of child-only CBT and CBT with additional parental components. Thirteen studies were introduced in the context of method (diagnosis of children, age range of children, follow-up, results, etc.) and therapy characteristics (number of sessions, frequency of sessions, treatment components both child focused CBT and CBT with parental involvement, etc.). The common techniques of therapy with parental involvement are psychoeducation, contingency management, cognitive restructuring, reducing parental anxiety, improving parent-child relationship, and relapse prevention. Parental psychopathology, parental inappropriate expectations and family dysfunctions are important difficulties derived from parents in CBT with anxious children. The results of the studies suggested that parental involvement have increased the efficacy of the treatment in CBT especially working with young children and having at least one anxious parent.
Pentkowski, Nathan S; Berkowitz, Laura E; Thompson, Shannon M; Drake, Emma N; Olguin, Carlos R; Clark, Benjamin J
Alzheimer's disease (AD) is characterized by progressive cognitive decline and the presence of aggregates of amyloid beta (plaques) and hyperphosphorylated tau (tangles). Early diagnosis through neuropsychological testing is difficult due to comorbidity of symptoms between AD and other types of dementia. As a result, there is a need to identify the range of behavioral phenotypes expressed in AD. In the present study, we utilized a transgenic rat (TgF344-AD) model that bears the mutated amyloid precursor protein as well as presenilin-1 genes, resulting in progressive plaque and tangle pathogenesis throughout the cortex. We tested young adult male and female TgF344-AD rats in a spatial memory task in the Morris water maze and for anxiety-like behavior in the elevated plus-maze. Results indicated that regardless of sex, TgF344-AD rats exhibited increased anxiety-like behavior in the elevated plus-maze, which occurred without significant deficits in the spatial memory. Together, these results indicate that enhanced anxiety-like behavior represents an early-stage behavioral marker in the TgF344-AD rat model. Copyright © 2017 Elsevier Inc. All rights reserved.
Moon, Chung-Man; Yang, Jong-Chul; Jeong, Gwang-Woo
Generalized anxiety disorder (GAD) is associated with brain function and morphological alterations. This study investigated explicit verbal memory impairment in patients with GAD in terms of brain functional deficits in combination with morphologic changes. Seventeen patients with GAD and 17 healthy controls matched for age, sex, and education level underwent high-resolution T1-weighted MRI and fMR imaging at 3 T during explicit verbal memory tasks with emotionally neutral and anxiety-inducing words. In response to the neutral words, the patients showed significantly lower activities in the regions of the hippocampus (Hip), middle cingulate gyrus (MCG), putamen (Pu) and head of the caudate nucleus (HCd) compared with healthy controls. In response to the anxiety-inducing words, the patients showed significantly higher activities in the ventrolateral prefrontal cortex and precentral gyrus. However, they showed lower activities in the Hip, MCG, Pu and HCd. In addition, patients with GAD showed a significant reduction in gray matter volumes, especially in the regions of the Hip, midbrain, thalamus, insula and superior temporal gyrus, compared with healthy controls. This study examined a small sample sizes in each of the groups, and there was no consideration of a medication effect on brain activity and volume changes. This study provides evidence for the association between brain functional deficits and morphometric alterations in an explicit verbal memory task for patients with GAD. This finding is helpful for understanding explicit verbal memory impairment in connection with GAD symptoms. Copyright © 2015 Elsevier B.V. All rights reserved.
Salari, Elham; Shahrivar, Zahra; Mahmoudi-Gharaei, Javad; Shirazi, Elham; Sepasi, Mitra
Parents play an important role in development and continuation of anxiety disorders in children. Yet the evidence on parent contribution in cognitive behavioral therapy (CBT) for childhood anxiety is limited. This open randomized trial examined the effectiveness of a parent-directed group CBT to manage children with anxiety disorders. Parents of 42 children aged 6-12 with primary anxiety disorders were allocated to a six, two-hour weekly intervention and a wait-list (WL) control. The Revised Children's Manifest Anxiety, Children's Depression Inventory, Strengths and Difficulties Questionnaire-Home Version, Depression-Anxiety-Stress Scale, Children Global Assessment Scale, and Global Relational Assessment of Functioning were used to assess children's and parents' functioning and emotional symptoms. Parents completed consumer satisfaction questionnaire. Parents in the CBT group reported significant improvement in their depressive symptoms (p=0.006) and the family functioning (p=0.04), as well as reduction in children's emotional symptoms (p=0.007). Clinician rating of children's functioning showed significant improvement in the CBT group(p=0.001). There was no significant difference in children rating of their anxiety within groups from pre- to post-intervention. Parents were satisfied mostly with the intervention. A brief parent-only CBT based intervention can be effective in the management of childhood anxiety.
Stoyanova, Milena; Hope, Debra A
Despite the well-documented gender effect in anxiety, less is known about contributing factors to women's greater risk for anxiety and fears. The present study examined the relationship between gender, gender role orientation (i.e., expressivity/instrumentality) and fear of harmless insects (tarantula), using a multimodal approach of self-report measures, a Behavioral Approach Test (BAT), and physiological reactivity. Participants (144 college students; 67 women, 77 men) completed a questionnaire packet and then were instructed to approach a tarantula. We were unable to replicate Pierce and Kirkpatrick's (1992) findings that men underreport anxiety. Consistent with the literature, women in the study experienced greater anxiety and avoidance compared to men. However, men and women did not differ on physiological reactivity during the first 2 min of the BAT. The concordance across avoidance, anxiety and heart rate reactivity differed by gender, suggesting that men and women have different experiences when faced with a fearful object. Furthermore, instrumentality (masculinity) was negatively related to anticipatory anxiety for women but not for men. Copyright © 2011 Elsevier Ltd. All rights reserved.
Full Text Available Diminished estrogen influence at menopause is reported to be associated with cognitive decline, heightened anxiety and hypertension. While estrogen therapy is often prescribed to overcome these behavioral and physiological deficits, antioxidants which have been shown beneficial are gaining nutritional intervention and popularity. Therefore, in the present study, utilizing the antioxidant properties of grapes, we have examined effect of 3 weeks of grape powder (GP; 15 g/L dissolved in tap water treatment on anxiety-like behavior, learning-memory impairment and high blood pressure in ovariectomized (OVX rats. Four groups of female Wistar rats were used; sham control, sham-GP treated, OVX and OVX+GP treated. We observed a significant increase in systolic and diastolic blood pressure in OVX rats as compared to sham-controls. Furthermore, ovariectomy increased anxiety-like behavior and caused learning and memory impairment in rats as compared to sham-controls. Interestingly, providing grape powder treated water to OVX rats restored both systolic and diastolic blood pressure, decreased anxiety-like behavior and improved memory function. Moreover, OVX rats exhibited an impaired long term potentiation which was restored with grape powder treatment. Furthermore, ovariectomy increased oxidative stress in the brain, serum and urine, selectively decreasing antioxidant enzyme, glyoxalase-1 protein expression in the hippocampus but not in the cortex and amygdala of OVX rats, while grape powder treatment reversed these effects. Other antioxidant enzyme levels, including manganese superoxide dismutase (SOD and Cu/Zn SOD remained unchanged. We suggest that grape powder by regulating oxidative stress mechanisms exerts its protective effect on blood pressure, learning-memory and anxiety-like behavior. Our study is the first to examine behavioral, biochemical, physiological and electrophysiological outcome of estrogen depletion in rats and to test protective role
Hedman, Erik; Hesser, Hugo; Andersson, Erik; Axelsson, Erland; Ljótsson, Brjánn
Exposure-based cognitive behavior therapy (CBT) has been shown to be effective in the treatment of severe health anxiety, but little is known about mediators of treatment effect. The aim of the present study was to investigate mindful non-reactivity as a putative mediator of health anxiety outcome using data from a large scale randomized controlled trial. We assessed mindful non-reactivity using the Five Facets Mindfulness Questionnaire-Non-Reactivity scale (FFMQ-NR) and health anxiety with the Short Health Anxiety Inventory (SHAI). Participants with severe health anxiety (N=158) were randomized to internet-delivered exposure-based CBT or behavioral stress management (BSM) and throughout the treatment, both the mediator and outcome were measured weekly. As previously reported, exposure-based CBT was more effective than BSM in reducing health anxiety. In the present study, latent process growth modeling showed that treatment condition had a significant effect on the FFMQ-NR growth trajectory (α-path), estimate=0.18, 95% CI [0.04, 0.32], p=.015, indicating a larger increase in mindful non-reactivity among participants receiving exposure-based CBT compared to the BSM group. The FFMQ-NR growth trajectory was significantly correlated with the SHAI trajectory (β-path estimate=-1.82, 95% CI [-2.15, -1.48], panxiety. Copyright © 2017 Elsevier Ltd. All rights reserved.
Bogels, Susan M.; Siqueland, Lynne
Objective: A family cognitive-behavioral therapy for children and adolescents ages 8 to 18 years with clinical anxiety disorders was developed and evaluated. Method: Seventeen families were measured before and after waitlist, after treatment, and at 3-month and 1-year follow-up. Results: No children changed their diagnostic status during waitlist,…
Crowe, Katherine; McKay, Dean
A review of meta-analyses of cognitive-behavioral therapy (CBT) for childhood anxiety and depression was conducted. A total of 36 meta-analyses were identified that met inclusion criteria for this review. In most cases, medium-to-large effect sizes for treatment reduction were observed when CBT was compared to non-active control conditions. Small-to-medium effects were observed when CBT was compared to active control treatments. The available meta-analyses generally did not examine, or data were not sufficient to evaluate, potential moderators of outcome, differential effects for parental involvement, or changes in quality of life or functional outcomes associated with treatment. Accordingly, while CBT should be broadly considered an effective treatment approach for childhood anxiety and depression, additional research is warranted in order to establish guidelines for service delivery for complicating factors in client presentation. Copyright © 2017 Elsevier Ltd. All rights reserved.
Fisher, M; Schneider, M; Pegler, C; Napolitano, B
In order to determine whether adolescent females with abnormal eating attitudes display lower levels of self-esteem and higher levels of anxiety than their peers, and whether these adolescents participate in health-risk behaviors to a greater or lesser degree than their peers, we administered a series of questionnaires to the females attending a suburban high school in New York State. The questionnaires, completed by 268 students (mean age, 16.2 years), included data on health-risk behaviors and weight attitudes, an Eating Attitudes Test, a self-esteem scale, and an anxiety inventory. Results indicated that almost two-thirds of the students described themselves as overweight, almost three-quarters felt they were above the healthiest weight for their age and height, and almost four-fifths were above the weight at which they would be most happy; 18% of the students scored 30 or more on the Eating Attitudes Test, a score suggestive of an eating disorder. Use of Spearman-rank correlation coefficients and multiple linear regression analysis revealed that those with more unhappiness with their weight and higher scores on the eating attitudes test were more likely to have lower self-esteem and higher anxiety and to participate more in health-risk behaviors, including cigarette smoking, alcohol use, drug use, and sexual activity with more total partners. The data from this study further corroborate the growing belief that health-risk behaviors tend to cluster together in vulnerable adolescents and demonstrate that abnormal eating attitudes and behaviors may be part of this cluster, especially in females with low self-esteem and high levels of anxiety.
Kumar, Anil; Garg, Ruchika
Chronic fatigue syndrome (CFS) is characterized by profound fatigue, which substantially interferes with daily activities. The aim of this study was to explore the protective effects of antidepressants in an animal model of CFS in mice. Male albino mice were forced to swim individually for a period of 6-min session each for 7 days. Imipramine (10 and 20 mg/kg), desipramine (10 and 20 mg/kg) and citalopram (5 and 10 mg/kg) were administered 30 min before forced swimming test on each day. Various behavior tests (immobility time, locomotor activity, anxiety-like behavior by plus maze and mirror chamber) followed by biochemical parameters (lipid peroxidation, reduced glutathione, catalase and nitrite level) were assessed in chronic stressed mice. Chronic forced swimming for 7 days significantly caused increase in immobility period, impairment in locomotor activity, anxiety-like behavior, and oxidative stress (raised lipid peroxidation, nitrite activity and reduced glutathione and catalase activity) as compared with naïve mice (P immobility time, improved locomotor activity and anti-anxiety effect (in both plus maze and mirror chamber test), and attenuated oxidative stress in chronic stressed mice as compared with control (chronic fatigues) (P < 0.05). These results suggested that these drugs have protective effect and could be used in the management of chronic fatigue like conditions.
Zohar, J.; Insel, T.R.; Berman, K.F.; Foa, E.B.; Hill, J.L.; Weinberger, D.R.
To investigate the relationship between anxiety and regional cerebral blood flow, we administered behavioral challenges to 10 patients with obsessive-compulsive disorder while measuring regional cerebral blood flow with the xenon 133 inhalation technique. Each patient was studied under three conditions: relaxation, imaginal flooding, and in vivo (actual) exposure to the phobic stimulus. Subjective anxiety, obsessive-compulsive ratings, and autonomic measures (heart rate, blood pressure) increased significantly, but respiratory rate and PCO 2 did not change across the three conditions. Regional cerebral blood flow increased slightly (in the temporal region) during imaginal flooding, but decreased markedly in several cortical regions during in vivo exposure, when anxiety was highest by subjective and peripheral autonomic measures. These results demonstrate that intense anxiety can be associated with decreased rather than increased cortical perfusion and that ostensibly related states of anxiety (eg, anticipatory and obsessional anxiety) may be associated with opposite effects on regional cerebral blood flow
Didem Behice ÖZTOP
Full Text Available Currently, Cognitive Behavioral Therapy (CBT becomes one of the leading approaches in the psychotherapy. However,use of CBT in childhood psychotherapy is considerably novel. After 1990s, it has been understood that it is an effectivemethod for children and adolescents. Anxiety disorders are one of the most common problems in the field of childhoodand adolescent psychiatry. In the studies conducted, the effectiveness of CBT was demonstrated in anxiety disorders ofthe children and adolescents. Moreover, it was suggested that this effectiveness is permanent in some studies. Prioritygoal of CBT is to change inappropriate learning and thinking patterns in the children and adolescents. By “now and here”fashion, it is attempted to reveal the origin of current problems. During the process, the factors are considered, whichcause to maintain the symptoms. It is attempted to decrease signs caused to stress by improving coping skills duringtherapy. To this end, methods including observation, relaxation training, systematic desensitization, social skills training,cognitive restructuring and exposure therapy are applied in sessions by taking child’s problems into consideration. Scalesspecific to anxiety disorders are used in the assessment and follow-up. Age and development level of the child should beparticularly taken into account while using assessment tools and therapeutic modality.
Li, Yu-Chen; Meng, Ya-Jing; Yuan, Min-Lan; Zhu, Hong-Ru; Ren, Zheng-Jia; Qiu, Chang-Jian; Zhang, Wei
To evaluate the effect of group cognitive behavioral therapy (GCBT) on social anxiety disorders (SAD). A total of 50 patients with SAD were recruited in this study. A survey containing the Liebowitz social anxiety scale (LSAS),the automatic thoughts questionnaire (ATQ),the fear of negative evaluation questionnaire (FNE),the social support rating scale (SSRS),the tridimensional personality questionnaire (TPQ),and the egna minnen barndoms uppfostran (EMBU) was administered before and (one week) after the GCBT,including in the 50 healthy controls. About 21 patients completed the eight-week GCBT (once a week,2 h a session). Follow-up surveys were conducted on 40 patients (22 patients treated with GCBT and 18 untreated) over a 1-5 year period. Significant differences were found between the SAD patients and healthy controls in thinking mode,personality characteristics,social support,parental rearing styles,and social anxiety symptoms. Significant decrease in social anxiety symptom ( t =4.06, P =0.000) , negative automatic thoughts ( t =4.58, P =0.000) and fear for rejection ( t =3.85, P =0.000) were observed after the GCBT therapy. Such improvement was positively correlated with subjective social support ( r =0.361, P =0.022) ,and negatively correlated with rejection of father ( r =-0.431, P =0.005) . There was also statistical difference between the patients with and without the GCBT therapy ( P =0.033) . GCBT treatment can relieve SAD symptoms by changing the negative cognitive of SAD patients. Social support and rejection of father affects the prognosis of SAD.
Background Stress and anxiety-related behaviors are seen in many organisms. Studies have shown that in humans and other animals, treatment with selective serotonin reuptake inhibitors (e.g. fluoxetine) can reduce anxiety and anxiety-related behaviors. The efficacies and side effects, however, can vary between individuals. Fluoxetine can modulate anxiety in a stereospecific manner or with equal efficacy regardless of stereoisomer depending on the mechanism of action (e.g. serotonergic or GABAergic effects). Zebrafish are an emerging and valuable translational model for understanding human health related issues such as anxiety. In this study we present data showing the behavioral and whole brain transcriptome changes with fluoxetine treatment in wild-derived zebrafish and suggest additional molecular mechanisms of this widely-prescribed drug. Results We used automated behavioral analyses to assess the effects of racemic and stereoisomeric fluoxetine on male wild-derived zebrafish. Both racemic and the individual isomers of fluoxetine reduced anxiety-related behaviors relative to controls and we did not observe stereospecific fluoxetine effects. Using RNA-sequencing of the whole brain, we identified 411 genes showing differential expression with racemic fluoxetine treatment. Several neuropeptides (neuropeptide Y, isotocin, urocortin 3, prolactin) showed consistent expression patterns with the alleviation of stress and anxiety when anxiety-related behavior was reduced with fluoxetine treatment. With gene ontology and KEGG pathway analyses, we identified lipid and amino acid metabolic processes, and steroid biosynthesis among other terms to be over-enriched. Conclusion Our results demonstrate that fluoxetine reduces anxiety-related behaviors in wild-derived zebrafish and alters their neurogenomic state. We identify two biological processes, lipid and amino acid metabolic synthesis that characterize differences in the fluoxetine treated fish. Fluoxetine may be acting on
Vollert, Craig; Ohia, Odochi; Akasaka, Hironari; Berridge, Casey; Ruan, Ke-He; Eriksen, Jason L
Prostacyclin is an endogenous lipid metabolite with properties of vasodilation and anti-platelet aggregation. While the effects of prostacyclin on the vascular protection have been well-documented, the role of this eicosanoid in the central nervous system has not been extensively studied. Recently, a transgenic mouse containing a hybrid enzyme, of cyclooxygenase-1 linked to prostacyclin synthase, was developed that produces elevated levels of prostacyclin in vivo. The goal of this study was to investigate whether increased prostacyclin biosynthesis could affect behavioral phenotypes in mice. Our results uncovered that elevated levels of prostacyclin broadly affect both cognitive and non-cognitive behaviors, including decreased anxiety-like behavior and improved learning in the fear-conditioning memory test. This study demonstrates that prostacyclin plays an important, but previously unrecognized, role in central nervous system function and behavior. Copyright © 2013 Elsevier B.V. All rights reserved.
P.E.H.M. Muris (Peter); A.M.L. van Brakel (Anna); A. Arntz (Arnoud); E. Schouten (Erik)
textabstractThis longitudinal study examined the additive and interactive effects of behavioral inhibition and a wide range of other vulnerability factors in the development of anxiety problems in youths. A sample of 261 children, aged 5 to 8 years, 124 behaviorally inhibited and 137 control
Reimer, Adriano Edgar; de Oliveira, Amanda Ribeiro; Diniz, Juliana Belo; Hoexter, Marcelo Queiroz; Chiavegatto, Silvana; Brandão, Marcus Lira
Individual differences are important biological predictors for reactivity to stressful stimulation. The extent to which trait differences underlie animal's reactions to conditioned and unconditioned fear stimuli, for example, is still to be clarified. Although grooming behavior has been associated with some aspects of the obsessive-compulsive disorder in humans, its relation with other anxiety disorders is still unknown. Given that grooming behavior could be a component of the whole spectrum of these disorders, in the present study we allocated male Wistar rats in low, intermediate and high self-grooming groups according to the duration of such behavior in the elevated plus-maze (EPM). These groups were then evaluated in unconditioned fear tests, such as the EPM and the open-field, and in conditioned fear tests, such as fear-potentiated startle and fear extinction retention. Additionally, we studied the expression of unconditioned behaviors in marble burying test and the sensorimotor gate function with prepulse inhibition test. Neurochemicals and neuroendocrine parameters were also evaluated, with the quantification of basal corticosterone in the plasma, and dopamine, serotonin and their metabolites in brain structures involved with fear processing. In general, rats classified according to grooming expression showed similar performance in all behavioral tests. Accordingly, corticosterone and monoamine concentrations were similar among groups. Thus, despite grooming expression elicited by different approaches--especially pharmacological ones--has been related with some aspects of anxiety disorders, rats with different expression of spontaneous self-grooming in the EPM do not differ in anxiety-like behaviors nor in neurochemical and neuroendocrine parameters generally associated with anxiety disorders. Copyright © 2015 Elsevier B.V. All rights reserved.
Mello, Bruna Stefânia Ferreira; Chaves Filho, Adriano José Maia; Custódio, Charllyany Sabino; Cordeiro, Rafaela Carneiro; Miyajima, Fabio; de Sousa, Francisca Cléa Florenço; Vasconcelos, Silvânia Maria Mendes; de Lucena, David Freitas; Macedo, Danielle
Peripheral inflammation induced by lipopolysaccharide (LPS) causes a behavioral syndrome with translational relevance for depression. This mental disorder is twice more frequent among women. Despite this, the majority of experimental studies investigating the neurobiological effects of inflammatory models of depression have been performed in males. Here, we sought to determine sex influences in behavioral and oxidative changes in brain regions implicated in the pathophysiology of mood disorders (hypothalamus, hippocampus and prefrontal cortex - PFC) in adult mice 24 h post LPS challenge. Myeloperoxidase (MPO) activity and interleukin (IL)-1β levels were measured as parameters of active inflammation, while reduced glutathione (GSH) and lipid peroxidation as parameters of oxidative imbalance. We observed that male mice presented behavioral despair, while females anxiety-like alterations. Both sexes were vulnerable to LPS-induced anhedonia. Both sexes presented increased MPO activity in the PFC, while male only in the hippocampus. IL-1β increased in the PFC and hypothalamus of animals of both sexes, while in the hippocampus a relative increase of this cytokine in males compared to females was detected. GSH levels were decreased in all brain areas investigated in animals of both sexes, while increased lipid peroxidation was observed in the hypothalamus of females and in the hippocampus of males after LPS exposure. Therefore, the present study gives additional evidence of sex influence in LPS-induced behavioral alterations and, for the first time, in the oxidative changes in brain areas relevant for mood regulation. Copyright © 2018 Elsevier B.V. All rights reserved.
Brzozowska, Natalia I; Smith, Kristie L; Zhou, Cilla; Waters, Peter M; Cavalcante, Ligia Menezes; Abelev, Sarah V; Kuligowski, Michael; Clarke, David J; Todd, Stephanie M; Arnold, Jonathon C
P-glycoprotein (P-gp) is an ABC transporter expressed at the blood brain barrier and regulates the brain uptake of various xenobiotics and endogenous mediators including glucocorticoid hormones which are critically important to the stress response. Moreover, P-gp is expressed on microglia, the brain's immune cells, which are activated by stressors and have an emerging role in psychiatric disorders. We therefore hypothesised that germline P-gp deletion in mice might alter the behavioral and microglial response to stressors. Female P-gp knockout mice displayed an unusual, frantic anxiety response to intraperitoneal injection stress in the light-dark test. They also tended to display reduced conditioned fear responses compared to wild-type (WT) mice in a paradigm where a single electric foot-shock stressor was paired to a context. Foot-shock stress reduced social interaction and decreased microglia cell density in the amygdala which was not varied by P-gp genotype. Independently of stressor exposure, female P-gp deficient mice displayed increased depression-like behavior, idiosyncratic darting behavior, age-related social withdrawal and hyperactivity, facilitated sensorimotor gating and altered startle reactivity. In addition, P-gp deletion increased microglia cell density in the CA3 region of the hippocampus, and the microglial cells exhibited a reactive, hypo-ramified morphology. Further, female P-gp KO mice displayed increased glucocorticoid receptor (GR) expression in the hippocampus. In conclusion, this research shows that germline P-gp deletion affected various behaviors of relevance to psychiatric conditions, and that altered microglial cell activity and enhanced GR expression in the hippocampus may play a role in mediating these behaviors. Copyright © 2017 Elsevier Inc. All rights reserved.
Russell Vivienne A
and prefrontal cortex while SD prefrontal cortex released more [3H]norepinephrine than WKY. SHR were resilient, cross-fostering did not reduce their ADHD-like behavior or change their neurochemistry. Cross-fostering of SD pups onto SHR or WKY dams increased their exploratory behavior without altering their anxiety-like behavior. Conclusion The ADHD-like behavior of SHR and their neurochemistry is genetically determined and not dependent on nurturing by SHR dams. The similarity between WKY and SD supports the continued use of WKY as a control for SHR and suggests that SD may be a useful additional reference strain for SHR. The fact that SD behaved similarly to WKY in the elevated-plus maze argues against the use of WKY as a model for anxiety-like disorders.
Full Text Available Tainaê Santos,1 Monaliza Marizete Baungratz,1 Suellen Priscila Haskel,2 Daniela Delwing de Lima,3 Júlia Niehues da Cruz,4 Débora Delwing Dal Magro,5 José Geraldo Pereira da Cruz51Department of Medicine, 2Department of Physiotherapy, Regional University of Blumenau, Santa Catarina, Brazil; 3Department of Pharmacy, University of Joinville Region, Santa Catarina, Brazil; 4Department of Medicine, University of the Extreme South of Santa Catarina, Santa Catarina, Brazil; 5Department of Natural Sciences, Regional University of Blumenau, Santa Catarina, BrazilAbstract: Simvastatin inhibits 3-hydroxy-3-methylglutaryl CoA reductase, the rate-limiting enzyme in the cholesterol biosynthetic pathway, and is widely used to control plasma cholesterol levels and prevent cardiovascular disease. However, emerging evidence indicates that the beneficial effects of simvastatin extend to the central nervous system. The effects of simvastatin combined with fluoxetine provide an exciting and potential paradigm to decreased anxiety and depression. Thus, the present paper investigates the possibility of synergistic interactions between simvastatin and fluoxetine in models of anxiety and depression. We investigated the effects of subchronically administered simvastatin (1 or 10 mg/kg/day combined with fluoxetine (2 or 10 mg/kg at 24, 5, and 1 hour on adult rats before conducting behavioral tests. The results indicate that simvastatin and/or fluoxetine treatment reduces anxiety-like behaviors in the elevated plus-maze and open-field tests. Our results showed that simvastatin and/or fluoxetine induced a significant increase in the swimming activity during the forced swimming test (antidepressant effect, with a concomitant increase in climbing time in simvastatin-treated animals only (noradrenergic activation. We hypothesize that anxiolytic and antidepressant effects of simvastatin and/or fluoxetine produce their behavioral effects through similar mechanisms and provide
Cohen, Joshua L; Glover, Matthew E; Pugh, Phyllis C; Fant, Andrew D; Simmons, Rebecca K; Akil, Huda; Kerman, Ilan A; Clinton, Sarah M
The early-life environment critically influences neurodevelopment and later psychological health. To elucidate neural and environmental elements that shape emotional behavior, we developed a rat model of individual differences in temperament and environmental reactivity. We selectively bred rats for high versus low behavioral response to novelty and found that high-reactive (bred high-responder, bHR) rats displayed greater risk-taking, impulsivity and aggression relative to low-reactive (bred low-responder, bLR) rats, which showed high levels of anxiety/depression-like behavior and certain stress vulnerability. The bHR/bLR traits are heritable, but prior work revealed bHR/bLR maternal style differences, with bLR dams showing more maternal attention than bHRs. The present study implemented a cross-fostering paradigm to examine the contribution of maternal behavior to the brain development and emotional behavior of bLR offspring. bLR offspring were reared by biological bLR mothers or fostered to a bLR or bHR mother and then evaluated to determine the effects on the following: (1) developmental gene expression in the hippocampus and amygdala and (2) adult anxiety/depression-like behavior. Genome-wide expression profiling showed that cross-fostering bLR rats to bHR mothers shifted developmental gene expression in the amygdala (but not hippocampus), reduced adult anxiety and enhanced social interaction. Our findings illustrate how an early-life manipulation such as cross-fostering changes the brain's developmental trajectory and ultimately impacts adult behavior. Moreover, while earlier studies highlighted hippocampal differences contributing to the bHR/bLR phenotypes, our results point to a role of the amygdala as well. Future work will pursue genetic and cellular mechanisms within the amygdala that contribute to bHR/bLR behavior either at baseline or following environmental manipulations. © 2015 S. Karger AG, Basel.
Schwarting, R.K.W.; Wöhr, M. [Experimental and Physiological Psychology, Philipps-University of Marburg, Marburg (Germany)
In the present review, the phenomenon of ultrasonic vocalization in rats will be outlined, including the three classes of vocalizations, namely 40-kHz calls of pups, and 22- and 50-kHz calls of juvenile and adult rats, their general relevance to behavioral neuroscience, and their special relevance to research on anxiety, fear, and defense mechanisms. Here, the emphasis will be placed on 40- and 22-kHz calls, since they are typical for various situations with aversive properties. Among other topics, we will discuss whether such behavioral signals can index a certain affective state, and how these signals can be used in social neuroscience, especially with respect to communication. Furthermore, we will address the phenomenon of inter-individual variability in ultrasonic calling and what we currently know about the mechanisms, which may determine such variability. Finally, we will address the current knowledge on the neural and pharmacological mechanisms underlying 22-kHz ultrasonic vocalization, which show a substantial overlap with mechanisms known from other research on fear and anxiety, such as those involving the periaqueductal gray or the amygdala.
Schwarting, R.K.W.; Wöhr, M.
In the present review, the phenomenon of ultrasonic vocalization in rats will be outlined, including the three classes of vocalizations, namely 40-kHz calls of pups, and 22- and 50-kHz calls of juvenile and adult rats, their general relevance to behavioral neuroscience, and their special relevance to research on anxiety, fear, and defense mechanisms. Here, the emphasis will be placed on 40- and 22-kHz calls, since they are typical for various situations with aversive properties. Among other topics, we will discuss whether such behavioral signals can index a certain affective state, and how these signals can be used in social neuroscience, especially with respect to communication. Furthermore, we will address the phenomenon of inter-individual variability in ultrasonic calling and what we currently know about the mechanisms, which may determine such variability. Finally, we will address the current knowledge on the neural and pharmacological mechanisms underlying 22-kHz ultrasonic vocalization, which show a substantial overlap with mechanisms known from other research on fear and anxiety, such as those involving the periaqueductal gray or the amygdala
Weinstein, A; Mezig, Hila; Mizrachi, S; Lejoyeux, M
Compulsive buying is a chronic, repetitive behavior that becomes a primary response to negative events and feelings. Compulsive buyers are obsessed by buying and their behavior occurs in response to negative emotions and results in a decrease in the intensity of negative emotions. Euphoria or relief from negative emotions is the most common consequence of compulsive buying. A large number of studies have investigated the association between compulsive buying and anxiety, and some studies have used the Spielberger trait-state anxiety inventory. Compulsive buying, state and trait anxiety and general obsessive-compulsive measures were assessed among 120 habitual internet shoppers (2+ times a week, 70 men and 50 women). Results showed that Edwards Compulsive Buying scale measures were associated with Spielberger trait and not state anxiety measures. Spielberger Trait anxiety measures were also correlated with measures of Yale-Brown Obsessive-Compulsive scale (Y-Bocs). Finally, there were no sex differences in this sample. The results of this study support existing evidence for an association between compulsive buying and anxiety and they will be discussed in view of current research on comorbidity of behavioural addiction. Copyright © 2014 Elsevier Inc. All rights reserved.
Ehrlich, David E.; Neigh, Gretchen N.; Bourke, Chase H.; Nemeth, Christina L.; Hazra, Rimi; Ryan, Steven J.; Rowson, Sydney; Jairam, Nesha; Sholar, Courtney; Rainnie, Donald G.; Stowe, Zachary N.; Owens, Michael J.
Depression during pregnancy has been linked to in utero stress and is associated with long-lasting symptoms in offspring, including anxiety, helplessness, attentional deficits, and social withdrawal. Depression is diagnosed in 10-20% of expectant mothers, but the impact of antidepressant treatment on offspring development is not well documented, particularly for females. Here, we used a prenatal stress model of maternal depression to test the hypothesis that in utero antidepressant treatment could mitigate the effects of prenatal stress. We also investigated the effects of prenatal stress and antidepressant treatment on gene expression related to GABAergic and serotonergic neurotransmission in the amygdala, which may underlie behavioral effects of prenatal stress. Nulliparous female rats were implanted with osmotic minipumps delivering clinically-relevant concentrations of escitalopram and mated. Pregnant dams were exposed to 12 days of mixed-modality stressors, and offspring were behaviorally assessed in adolescence (postnatal day 28) and adulthood (beyond day 90) to determine the extent of behavioral change. We found that in utero stress exposure, regardless of escitalopram treatment, increased anxiety-like behavior in adolescent females and profoundly influenced amygdala expression of the chloride transporters KCC2 and NKCC1, which regulate GABAergic function. In contrast, prenatal escitalopram exposure alone elevated amygdala expression of 5-HT1A receptors. In adulthood, anxiety-like behavior returned to baseline and gene expression effects in the amygdala abated, whereas deficits emerged in novel object recognition for rats exposed to stress during gestation. These findings suggest prenatal stress causes age-dependent deficits in anxiety-like behavior and amygdala function in female offspring, regardless of antidepressant exposure. PMID:26032436
Newby, Jill M; Smith, Jessica; Uppal, Shivani; Mason, Elizabeth; Mahoney, Alison E J; Andrews, Gavin
To examine the efficacy of an Internet-delivered cognitive-behavioral therapy (iCBT) program for health anxiety compared to an active psychoeducation control group. Individuals (N = 86, mean age: 30 years, 87% female) with a Diagnostic and Statistical Manual of Mental Disorders (5th ed.) diagnosis of illness anxiety disorder or somatic symptom disorder with health anxiety were randomized to either a 6-lesson clinician-guided iCBT program for health anxiety (n = 45) or an active control group who received anxiety psychoeducation, clinical support, and monitoring (control, n = 41) over a 12-week period. Both groups experienced significant improvements between baseline and posttreatment on self-report measures of health anxiety, depression, general anxiety, and functional impairment. Intention-to-treat analyses indicated that the iCBT group experienced greater improvements in health anxiety on the Short Health Anxiety Inventory (SHAI) compared to controls (between-groups effect size = 1.39, 95% confidence interval [0.87, 1.93]), and a greater proportion of the iCBT group showed clinically reliable change on the SHAI (84% vs. 34% in the control group). Similarly, the iCBT group outperformed the control group on secondary measures of depression, generalized anxiety, functional impairment, maladaptive cognitions, body hypervigilance, safety behaviors and avoidance, and intolerance of uncertainty. Gains were maintained at 3-month follow-up in the iCBT group. iCBT for health anxiety is more effective than psychoeducation, clinical support, and monitoring, and presents an efficacious and accessible treatment option for people with health anxiety. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
Sung, Min; Ooi, Yoon Phaik; Goh, Tze Jui; Pathy, Pavarthy; Fung, Daniel S. S.; Ang, Rebecca P.; Chua, Alina; Lam, Chee Meng
We compared the effects of a 16-week Cognitive-Behavioral Therapy (CBT) program and a Social Recreational (SR) program on anxiety in children with Autism Spectrum Disorders (ASD). Seventy children (9-16 years old) were randomly assigned to either of the programs (n CBT = 36; n SR = 34). Measures on child's anxiety using the Spence Child Anxiety…
Visagie, Lisa; Loxton, Helene; Stallard, Paul; Silverman, Wendy K.
Introduction: Anxiety is the most common psychological problem reported among children with visual impairments. Although cognitive behavior therapy interventions have proven successful in treating childhood anxiety, it is unclear whether they are suitable and accessible for children who have visual impairments. This study aimed to determine if and…
Arch, Joanna J.; Eifert, Georg H.; Davies, Carolyn; Vilardaga, Jennifer C. Plumb; Rose, Raphael D.; Craske, Michelle G.
Objective: Randomized comparisons of acceptance-based treatments with traditional cognitive behavioral therapy (CBT) for anxiety disorders are lacking. To address this gap, we compared acceptance and commitment therapy (ACT) to CBT for heterogeneous anxiety disorders. Method: One hundred twenty-eight individuals (52% female, mean age = 38, 33%…
Dissanayaka, Nadeeka N W; Pye, Deidre; Mitchell, Leander K; Byrne, Gerard J; O'Sullivan, John D; Marsh, Rodney; Pachana, Nancy A
Anxiety negatively impacts the quality of life of Parkinson's disease (PD) patients and caregivers. Despite high prevalence, there is a paucity of trials investigating effective treatments for anxiety in PD. This uncontrolled study investigated the use of a manualized and tailored Cognitive Behavior Therapy (CBT) for anxiety in PD. Participants completed 6 weekly CBT sessions. Pre-, post- and follow-up (3 and 6 months) assessments were made. Change in outcomes were analysed using t-tests and Reliability Change Index. Of 17 PD patients who agreed to CBT, 12 completed the intervention. This study showed a significant reduction in Hamilton Anxiety Rating Scale scores in PD immediately post CBT (t(11) = 3.59, p < .01), maintained at 3-month (t(8) = 2.83, p = .02) and 6-month (t(7) = 2.07, p = .04) follow-up. A reduction in caregiver burden (t(11) = 2.68, p = .03) was observed post intervention. Improvements in motor disability (t(11) = 2.41, p = .04) and cognitive scores (t(11) = -2.92, p = .01) were also observed post intervention and at follow-up. Tailored CBT can be used to treat anxiety in PD. This study provides preliminary evidence suggesting that tailored CBT reduces anxiety in PD with persisting benefits, and lowers caregiver burden.
Full Text Available Personality traits have traditionally been viewed as stable, but recent studies suggest that they could be affected through psychological treatment. Internet-based cognitive behavior therapy (ICBT for severe health anxiety (DSM-IV hypochondriasis has been shown to be effective in reducing health anxiety, but its effect on measures of personality traits has not been investigated. The main aim of this study was to investigate the impact of ICBT on personality traits in the three broad dimensions--neuroticism, extraversion and aggression. We hypothesized that participants in ICBT would reduce their level of neuroticism compared to controls that did not receive the active treatment. No specific predictions were made regarding extraversion and aggression. Data from a randomized controlled trial were used in which participants were allocated to 12 weeks of ICBT (n = 40 or to a basic attention control condition (n = 41. Personality traits were assessed with the Swedish Universities Scales of Personality and the primary outcome of health anxiety was the Health Anxiety Inventory. There was a significant interaction effect of group and time on neuroticism-related scales, indicating larger pre- to post-treatment reductions in the Internet-based CBT group compared to the control condition. Analyses at 6-month follow-up showed that changes were stable. Traits relating to extraversion and aggression were largely unchanged. This study is the first to demonstrate that a brief ICBT intervention for severe health anxiety causes long-term changes in measures of personality traits related to neuroticism. The treatment thus has a broader impact than just reducing health anxiety.Clinicaltrials.gov (ID NCT00828152.
Jessen, Heather M; Kolodkin, Mira H; Bychowski, Meaghan E; Auger, Catherine J; Auger, Anthony P
Nuclear receptor function on DNA is regulated by the balanced recruitment of coregulatory complexes. Recruited proteins that increase gene expression are called coactivators, and those that decrease gene expression are called corepressors. Little is known about the role of corepressors, such as nuclear receptor corepressor (NCoR), on the organization of behavior. We used real-time PCR to show that NCoR mRNA levels are sexually dimorphic, that females express higher levels of NCoR mRNA within the developing amygdala and hypothalamus, and that NCoR mRNA levels are reduced by estradiol treatment. To investigate the functional role of NCoR on juvenile social behavior, we infused small interfering RNA targeted against NCoR within the developing rat amygdala and assessed the enduring impact on juvenile social play behavior, sociability, and anxiety-like behavior. As expected, control males exhibited higher levels of juvenile social play than control females. Reducing NCoR expression during development further increased juvenile play in males only. Interestingly, decreased NCoR expression within the developing amygdala had lasting effects on increasing juvenile anxiety-like behavior in males and females. These data suggest that the corepressor NCoR functions to blunt sex differences in juvenile play behavior, a sexually dimorphic and hormone-dependent behavior, and appears critical for appropriate anxiety-like behavior in juvenile males and females.