Long-Term Fine Particulate Matter Exposure and Major Depressive Disorder in a Community-Based Urban Cohort

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Kim, Kyoung-Nam; Lim, Youn-Hee; Bae, Hyun Joo; Kim, Myounghee; Jung, Kweon; Hong, Yun-Chul

2016-01-01

Background: Previous studies have associated short-term air pollution exposure with depression. Although an animal study showed an association between long-term exposure to particulate matter ≤ 2.5 μm (PM2.5) and depression, epidemiological studies assessing the long-term association are scarce. Objective: We aimed to determine the association between long-term PM2.5 exposure and major depressive disorder (MDD). Methods: A total of 27,270 participants 15–79 years of age who maintained an address within the same districts in Seoul, Republic of Korea, throughout the entire study period (between 2002 and 2010) and without a previous MDD diagnosis were analyzed. We used three district-specific exposure indices as measures of long-term PM2.5 exposure. Cox proportional hazards models adjusted for potential confounding factors and measured at district and individual levels were constructed. We further conducted stratified analyses according to underlying chronic diseases such as diabetes mellitus, cardiovascular disease, and chronic obstructive pulmonary disease. Results: The risk of MDD during the follow-up period (2008–2010) increased with an increase of 10 μg/m3 in PM2.5 in 2007 [hazard ratio (HR) = 1.44; 95% CI: 1.17, 1.78], PM2.5 between 2007 and 2010 (HR = 1.59; 95% CI: 1.02, 2.49), and 12-month moving average of PM2.5 until an event or censor (HR = 1.47; 95% CI: 1.14, 1.90). The association between long-term PM2.5 exposure and MDD was greater in participants with underlying chronic diseases than in participants without these diseases. Conclusion: Long-term PM2.5 exposure increased the risk of MDD among the general population. Individuals with underlying chronic diseases are more vulnerable to long-term PM2.5 exposure. Citation: Kim KN, Lim YH, Bae HJ, Kim M, Jung K, Hong YC. 2016. Long-term fine particulate matter exposure and major depressive disorder in a community-based urban cohort. Environ Health Perspect 124:1547–1553; http://dx.doi.org/10

Hypertension impairs hippocampus-related adult neurogenesis, CA1 neuron dendritic arborization and long-term memory.

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Shih, Y-H; Tsai, S-F; Huang, S-H; Chiang, Y-T; Hughes, M W; Wu, S-Y; Lee, C-W; Yang, T-T; Kuo, Y-M

2016-05-13

Hypertension is associated with neurodegenerative diseases and cognitive impairment. Several studies using spontaneous hypertensive rats to study the effect of hypertension on memory performance and adult hippocampal neurogenesis have reached inconsistent conclusions. The contradictory findings may be related to the genetic variability of spontaneous hypertensive rats due to the conventional breeding practices. The objective of this study is to examine the effect of hypertension on hippocampal structure and function in isogenic mice. Hypertension was induced by the '2 kidneys, 1 clip' method (2K1C) which constricted one of the two renal arteries. The blood pressures of 2K1C mice were higher than the sham group on post-operation day 7 and remained high up to day 28. Mice with 2K1C-induced hypertension had impaired long-term, but not short-term, memory. Dendritic complexity of CA1 neurons and hippocampal neurogenesis were reduced by 2K1C-induced hypertension on post-operation day 28. Furthermore, 2K1C decreased the levels of hippocampal brain-derived neurotrophic factor, while blood vessel density and activation status of astrocytes and microglia were not affected. In conclusion, hypertension impairs hippocampus-associated long-term memory, dendritic arborization and neurogenesis, which may be caused by down-regulation of brain-derived neurotrophic factor signaling pathways. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Opioid withdrawal for 4 days prevents synaptic depression induced by low dose of morphine or naloxone in rat hippocampal CA1 area in vivo.

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Dong, Zhifang; Han, Huili; Cao, Jun; Xu, Lin

2010-02-01

The formation of memory is believed to depend on experience- or activity-dependent synaptic plasticity, which is exquisitely sensitive to psychological stress since inescapable stress impairs long-term potentiation (LTP) but facilitates long-term depression (LTD). Our recent studies demonstrated that 4 days of opioid withdrawal enables maximal extents of both hippocampal LTP and drug-reinforced behavior; while elevated-platform stress enables these phenomena at 18 h of opioid withdrawal. Here, we examined the effects of low dose of morphine (0.5 mg kg(-1), i.p.) or the opioid receptor antagonist naloxone (1 mg kg(-1), i.p.) on synaptic efficacy in the hippocampal CA1 region of anesthetized rats. A form of synaptic depression was induced by low dose of morphine or naloxone in rats after 18 h but not 4 days of opioid withdrawal. This synaptic depression was dependent on both N-methyl-D-aspartate receptor and synaptic activity, similar to the hippocampal long-term depression induced by low frequency stimulation. Elevated-platform stress given 2 h before experiment prevented the synaptic depression at 18 h of opioid withdrawal; in contrast, the glucocorticoid receptor (GR) antagonist RU38486 treatment (20 mg kg(-1), s.c., twice per day for first 3 days of withdrawal), or a high dose of morphine reexposure (15 mg kg(-1), s.c., 12 h before experiment), enabled the synaptic depression on 4 days of opioid withdrawal. This temporal shift of synaptic depression by stress or GR blockade supplements our previous findings of potentially correlated temporal shifts of LTP induction and drug-reinforced behavior during opioid withdrawal. Our results therefore support the idea that stress experience during opioid withdrawal may modify hippocampal synaptic plasticity and play important roles in drug-associated memory. (c) 2009 Wiley-Liss, Inc.

Self-reported depression and perceived financial burden among long-term rectal cancer survivors.

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Chongpison, Yuda; Hornbrook, Mark C; Harris, Robin B; Herrinton, Lisa J; Gerald, Joe K; Grant, Marcia; Bulkley, Joanna E; Wendel, Christopher S; Krouse, Robert S

2016-11-01

Types of surgery for rectal cancer (RC), including permanent ostomy (PO) or temporary ostomy followed by anastomosis (TO) or initial anastomosis (AN), can affect psychological and financial well-being during active treatment. However, these relationships have not been well studied among long-term survivors (≥5 years post-diagnosis). A mailed survey with 576 long-term RC survivors who were members of Kaiser Permanente was conducted in 2010-2011. Prevalence of current depression was ascertained using a score of ≤45.6 on the Short Form-12 version 2 mental component summary. Perceived financial burden was assessed using a Likert scale ranging from 0 (none) to 10 (severe). Regression analyses were used to measure associations after adjustment for covariates. The overall prevalence of depression was 24% among RC survivors with the highest prevalence among those with a history of PO (31%). The adjusted odds of depression among TO and AN survivors were lower than that among PO survivors, 0.42 (CI 95% 0.20-0.89) and 0.59 (CI 95% 0.37-0.93), respectively. Twenty-two percent perceived moderate-to-high current financial burden (≥4 points). PO survivors also reported higher mean financial burden than AN survivors (2.6 vs. 1.6, respectively; p = 0.002), but perceived burden comparably to TO survivors (2.3). Self-reported depression was associated with higher perceived financial burden (p reported frequently among these long-term RC survivors, particularly among PO survivors. Depression was associated with greater perception of financial burden. Screening for depression and assessing financial well-being might improve care among long-term RC survivors.Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Depression and quality of life in patients on long term hemodialysis ...

African Journals Online (AJOL)

Depression and quality of life in patients on long term hemodialysis at a national ... Quality of Life instrument were used to assess depression and quality of life. ... Haemodialysis patients who obtained low scores on quality of life measures ...

Adolescent mice show anxiety- and aggressive-like behavior and the reduction of long-term potentiation in mossy fiber-CA3 synapses after neonatal maternal separation.

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Shin, S Y; Han, S H; Woo, R-S; Jang, S H; Min, S S

2016-03-01

Exposure to maternal separation (MS) during early life is an identified risk factor for emotional disorders such as anxiety and depression later in life. This study investigated the effects of neonatal MS on the behavior and long-term potentiation (LTP) as well as basic synaptic transmission at hippocampal CA3-CA1 and mossy fiber (MF)-CA3 synapses in adolescent mice for 19days. When mice were adolescents, we measured depression, learning, memory, anxious and aggressive behavior using the forced swimming test (FST), Y-maze, Morris water maze (MWM), elevated plus maze (EPM), three consecutive days of the open field test, the social interaction test, the tube-dominance test and the resident-intruder test. The results showed that there was no difference in FST, Y-maze, and MWM performance. However, MS mice showed more anxiety-like behavior in the EPM test and aggressive-like behavior in the tube-dominance and resident-intruder tests. In addition, the magnitude of LTP and release probability in the MF-CA3 synapses was reduced in the MS group but not in the CA3-CA1 synapse. Our results indicate that early life stress due to MS may induce anxiety- and aggressive-like behavior during adolescence, and these effects are associated with synaptic plasticity at the hippocampal MF-CA3 synapses. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Muscarinic Long-Term Enhancement of Tonic and Phasic GABAA Inhibition in Rat CA1 Pyramidal Neurons

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Domínguez, Soledad; Fernández de Sevilla, David; Buño, Washington

2016-01-01

Acetylcholine (ACh) regulates network operation in the hippocampus by controlling excitation and inhibition in rat CA1 pyramidal neurons (PCs), the latter through gamma-aminobutyric acid type-A receptors (GABAARs). Although, the enhancing effects of ACh on GABAARs have been reported (Dominguez et al., 2014, 2015), its role in regulating tonic GABAA inhibition has not been explored in depth. Therefore, we aimed at determining the effects of the activation of ACh receptors on responses mediated by synaptic and extrasynaptic GABAARs. Here, we show that under blockade of ionotropic glutamate receptors ACh, acting through muscarinic type 1 receptors, paired with post-synaptic depolarization induced a long-term enhancement of tonic GABAA currents (tGABAA) and puff-evoked GABAA currents (pGABAA). ACh combined with depolarization also potentiated IPSCs (i.e., phasic inhibition) in the same PCs, without signs of interactions of synaptic responses with pGABAA and tGABAA, suggesting the contribution of two different GABAA receptor pools. The long-term enhancement of GABAA currents and IPSCs reduced the excitability of PCs, possibly regulating plasticity and learning in behaving animals. PMID:27833531

Hippocampal long-term depression is facilitated by the acquisition and updating of memory of spatial auditory content and requires mGlu5 activation.

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Dietz, Birte; Manahan-Vaughan, Denise

2017-03-15

Long-term potentiation (LTP) and long-term depression (LTD) are key cellular processes that support memory formation. Whereas increases of synaptic strength by means of LTP may support the creation of a spatial memory 'engram', LTD appears to play an important role in refining and optimising experience-dependent encoding. A differentiation in the role of hippocampal subfields is apparent. For example, LTD in the dentate gyrus (DG) is enabled by novel learning about large visuospatial features, whereas in area CA1, it is enabled by learning about discrete aspects of spatial content, whereby, both discrete visuospatial and olfactospatial cues trigger LTD in CA1. Here, we explored to what extent local audiospatial cues facilitate information encoding in the form of LTD in these subfields. Coupling of low frequency afferent stimulation (LFS) with discretely localised, novel auditory tones in the sonic hearing, or ultrasonic range, facilitated short-term depression (STD) into LTD (>24 h) in CA1, but not DG. Re-exposure to the now familiar audiospatial configuration ca. 1 week later failed to enhance STD. Reconfiguration of the same audiospatial cues resulted anew in LTD when ultrasound, but not non-ultrasound cues were used. LTD facilitation that was triggered by novel exposure to spatially arranged tones, or to spatial reconfiguration of the same tones were both prevented by an antagonism of the metabotropic glutamate receptor, mGlu5. These data indicate that, if behaviourally salient enough, the hippocampus can use audiospatial cues to facilitate LTD that contributes to the encoding and updating of spatial representations. Effects are subfield-specific, and require mGlu5 activation, as is the case for visuospatial information processing. These data reinforce the likelihood that LTD supports the encoding of spatial features, and that this occurs in a qualitative and subfield-specific manner. They also support that mGlu5 is essential for synaptic encoding of spatial

Stargazin regulates AMPA receptor trafficking through adaptor protein complexes during long-term depression

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Matsuda, Shinji; Kakegawa, Wataru; Budisantoso, Timotheus; Nomura, Toshihiro; Kohda, Kazuhisa; Yuzaki, Michisuke

2013-11-01

Long-term depression (LTD) underlies learning and memory in various brain regions. Although postsynaptic AMPA receptor trafficking mediates LTD, its underlying molecular mechanisms remain largely unclear. Here we show that stargazin, a transmembrane AMPA receptor regulatory protein, forms a ternary complex with adaptor proteins AP-2 and AP-3A in hippocampal neurons, depending on its phosphorylation state. Inhibiting the stargazin-AP-2 interaction disrupts NMDA-induced AMPA receptor endocytosis, and inhibiting that of stargazin-AP-3A abrogates the late endosomal/lysosomal trafficking of AMPA receptors, thereby upregulating receptor recycling to the cell surface. Similarly, stargazin’s interaction with AP-2 or AP-3A is necessary for low-frequency stimulus-evoked LTD in CA1 hippocampal neurons. Thus, stargazin has a crucial role in NMDA-dependent LTD by regulating two trafficking pathways of AMPA receptors—transport from the cell surface to early endosomes and from early endosomes to late endosomes/lysosomes—through its sequential binding to AP-2 and AP-3A.

Ca isotopes, chemical weathering, and geomorphic controls on long-term climate

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Moore, J.; Jacobson, A. D.; Holmden, C. E.; Craw, D.

2009-12-01

Calcium isotope geochemistry (δ44Ca) offers a unique opportunity to directly quantify proportions of riverine Ca originating from silicate versus carbonate weathering, which is essential for understanding how geomorphic processes affecting landscape evolution, such as tectonic uplift and glaciation, influence the long-term cycling of atmospheric CO2. We measured the elemental and δ44Ca chemistry of river and rock samples from the New Zealand Southern Alps. In combination with our geochemical data, we used runoff and suspended sediment fluxes to elucidate relationships between chemical weathering, mechanical erosion, and long-term climate. The S. Alps have uniform bedrock chemistry but significant tectonic and climatic gradients. West of the main topographic divide, watersheds drain schist and experience high runoff, uplift, and erosion rates. East of the main divide, watersheds drain greywacke or schist and experience lower runoff, uplift, and erosion rates. Glaciated watersheds with high erosion rates are present throughout the mountain range. Both schist and greywacke contain up to 3% metamorphic and hydrothermal calcite. Waters exhibit two-component mixing between calcite and silicate end-members when plotted as δ44Ca versus Ca/Sr. Scatter about the mixing curve is generally smaller than the analytical uncertainty of the measurements and likely reflects variability of the end-member compositions rather than fractionation. We used the mixing relationships to calculate percentages of Ca from silicate weathering. Rivers draining greywacke average 27.6% of Ca from silicate weathering with glaciated and non-glaciated watersheds yielding 41.8 and 19.5%, respectively. Rivers draining schist average 9.8% with glaciated and non-glaciated watersheds yielding 17.7 and 3.9%, respectively. Although Ca fluxes are larger west of the main divide where erosion and runoff are higher, the percentage of Ca from silicate weathering is smaller. Hence, long-term atmospheric CO2

Hypoxia-Induced neonatal seizures diminish silent synapses and long-term potentiation in hippocampal CA1 neurons

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Zhou, Chengwen; Bell, Jocelyn J. Lippman; Sun, Hongyu; Jensen, Frances E.

2012-01-01

Neonatal seizures can lead to epilepsy and long-term cognitive deficits in adulthood. Using a rodent model of the most common form of human neonatal seizures, hypoxia-induced seizures (HS), we aimed to determine whether these seizures modify long-term potentiation (LTP) and “silent” N-methyl-D-aspartate receptor (NMDAR)-only synapses in hippocampal CA1. At 48-72 hours (hrs) post-HS, electrophysiology and immunofluorescent confocal microscopy revealed a significant decrease in the incidence of silent synapses, and an increase in amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) at the synapses. Coincident with this decrease in silent synapses, there was an attenuation of LTP elicited by either tetanic stimulation of Schaffer collaterals or a pairing protocol, and persistent attenuation of LTP in slices removed in later adulthood after P10 HS. Furthermore, post-seizure treatment in vivo with the AMPAR antagonist 2,3-dihydroxy-6-nitro-7-sulfonyl-benzo[f]quinoxaline (NBQX) protected against the HS-induced depletion of silent synapses and preserved LTP. Thus, this study demonstrates a novel mechanism by which early-life seizures could impair synaptic plasticity, suggesting a potential target for therapeutic strategies to prevent long-term cognitive deficits. PMID:22171027

A computational simulation of long-term synaptic potentiation inducing protocol processes with model of CA3 hippocampal microcircuit.

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Świetlik, D; Białowąs, J; Kusiak, A; Cichońska, D

2018-01-01

An experimental study of computational model of the CA3 region presents cog-nitive and behavioural functions the hippocampus. The main property of the CA3 region is plastic recurrent connectivity, where the connections allow it to behave as an auto-associative memory. The computer simulations showed that CA3 model performs efficient long-term synaptic potentiation (LTP) induction and high rate of sub-millisecond coincidence detection. Average frequency of the CA3 pyramidal cells model was substantially higher in simulations with LTP induction protocol than without the LTP. The entropy of pyramidal cells with LTP seemed to be significantly higher than without LTP induction protocol (p = 0.0001). There was depression of entropy, which was caused by an increase of forgetting coefficient in pyramidal cells simulations without LTP (R = -0.88, p = 0.0008), whereas such correlation did not appear in LTP simulation (p = 0.4458). Our model of CA3 hippocampal formation microcircuit biologically inspired lets you understand neurophysiologic data. (Folia Morphol 2018; 77, 2: 210-220).

Tiagabine improves hippocampal long-term depression in rat pups subjected to prenatal inflammation.

Directory of Open Access Journals (Sweden)

Aline Rideau Batista Novais

Full Text Available Maternal inflammation during pregnancy is associated with the later development of cognitive and behavioral impairment in the offspring, reminiscent of the traits of schizophrenia or autism spectrum disorders. Hippocampal long-term potentiation and long-term depression of glutamatergic synapses are respectively involved in memory formation and consolidation. In male rats, maternal inflammation with lipopolysaccharide (LPS led to a premature loss of long-term depression, occurring between 12 and 25 postnatal days instead of after the first postnatal month, and aberrant occurrence of long-term potentiation. We hypothesized this would be related to GABAergic system impairment. Sprague Dawley rats received either LPS or isotonic saline ip on gestational day 19. Male offspring's hippocampus was studied between 12 and 25 postnatal days. Morphological and functional analyses demonstrated that prenatal LPS triggered a deficit of hippocampal GABAergic interneurons, associated with presynaptic GABAergic transmission deficiency in male offspring. Increasing ambient GABA by impairing GABA reuptake with tiagabine did not interact with the low frequency-induced long-term depression in control animals but fully prevented its impairment in male offspring of LPS-challenged dams. Tiagabine furthermore prevented the aberrant occurrence of paired-pulse triggered long-term potentiation in these rats. Deficiency in GABA seems to be central to the dysregulation of synaptic plasticity observed in juvenile in utero LPS-challenged rats. Modulating GABAergic tone may be a possible therapeutic strategy at this developmental stage.

Influx of extracellular Zn(2+) into the hippocampal CA1 neurons is required for cognitive performance via long-term potentiation.

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Takeda, A; Suzuki, M; Tempaku, M; Ohashi, K; Tamano, H

2015-09-24

Physiological significance of synaptic Zn(2+) signaling was examined in the CA1 of young rats. In vivo CA1 long-term potentiation (LTP) was induced using a recording electrode attached to a microdialysis probe and the recording region was locally perfused with artificial cerebrospinal fluid (ACSF) via the microdialysis probe. In vivo CA1 LTP was inhibited under perfusion with CaEDTA and ZnAF-2DA, extracellular and intracellular Zn(2+) chelators, respectively, suggesting that the influx of extracellular Zn(2+) is required for in vivo CA1 LTP induction. The increase in intracellular Zn(2+) was chelated with intracellular ZnAF-2 in the CA1 1h after local injection of ZnAF-2DA into the CA1, suggesting that intracellular Zn(2+) signaling induced during learning is blocked with intracellular ZnAF-2 when the learning was performed 1h after ZnAF-2DA injection. Object recognition was affected when training of object recognition test was performed 1h after ZnAF-2DA injection. These data suggest that intracellular Zn(2+) signaling in the CA1 is required for object recognition memory via LTP. Surprisingly, in vivo CA1 LTP was affected under perfusion with 0.1-1μM ZnCl2, unlike the previous data that in vitro CA1 LTP was enhanced in the presence of 1-5μM ZnCl2. The influx of extracellular Zn(2+) into CA1 pyramidal cells has bidirectional action in CA1 LTP. The present study indicates that the degree of extracellular Zn(2+) influx into CA1 neurons is critical for LTP and cognitive performance. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

5-HT4-receptors modulate induction of long-term depression but not potentiation at hippocampal output synapses in acute rat brain slices.

Directory of Open Access Journals (Sweden)

Matthias Wawra

Full Text Available The subiculum is the principal target of CA1 pyramidal cells and mediates hippocampal output to various cortical and subcortical regions of the brain. The majority of subicular pyramidal cells are burst-spiking neurons. Previous studies indicated that high frequency stimulation in subicular burst-spiking cells causes presynaptic NMDA-receptor dependent long-term potentiation (LTP whereas low frequency stimulation induces postsynaptic NMDA-receptor-dependent long-term depression (LTD. In the present study, we investigate the effect of 5-hydroxytryptamine type 4 (5-HT4 receptor activation and blockade on both forms of synaptic plasticity in burst-spiking cells. We demonstrate that neither activation nor block of 5-HT4 receptors modulate the induction or expression of LTP. In contrast, activation of 5-HT4 receptors facilitates expression of LTD, and block of the 5-HT4 receptor prevents induction of short-term depression and LTD. As 5-HT4 receptors are positively coupled to adenylate cyclase 1 (AC1, 5-HT4 receptors might modulate PKA activity through AC1. Since LTD is blocked in the presence of 5-HT4 receptor antagonists, our data are consistent with 5-HT4 receptor activation by ambient serotonin or intrinsically active 5-HT4 receptors. Our findings provide new insight into aminergic modulation of hippocampal output.

Observer-rated depression in long-term care: frequency and risk factors.

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McCusker, Jane; Cole, Martin G; Voyer, Philippe; Monette, Johanne; Champoux, Nathalie; Ciampi, Antonio; Vu, Minh; Dyachenko, Alina; Belzile, Eric

2014-01-01

The objectives of this study were: (1) to describe the prevalence and 6-month incidence of observer-rated depression in residents age 65 and over of long-term care (LTC) facilities; (2) to describe risk factors for depression, at baseline and over time. A multisite, prospective observational study was conducted in residents aged 65 and over of 7 LTC facilities. The Cornell Scale for Depression in Dementia (CSDD) was completed by nurses monthly for 6 months. We measured demographic, medical, and functional factors at baseline and monthly intervals, using data from research assessments, nurse interviews, and chart reviews. 274 residents were recruited and completed baseline depression assessments. The prevalence of depression (CSDD score of 6+) was 19.0%. The incidence of depression among those without prevalent depression was 73.3 per 100 person-years. A delirium diagnosis, pain, and diabetes were independently associated with prevalent depression. CSDD score at baseline and development of severe cognitive impairment at follow-up were independent risk factors for incident depression. A diagnosis of delirium and uncorrected visual impairment at follow-up occurred concurrently with incident depression. The results of this study have implications for the detection and prevention of depression in LTC. Delirium diagnosis, pain and diabetes at baseline were associated with prevalent depression; depression symptoms at baseline and development of severe cognitive impairment at follow-up were risk factors for incident depression. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Acute deviations from long-term trait depressive symptoms predict systemic inflammatory activity.

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Rohleder, Nicolas; Miller, Gregory E

2008-07-01

Depressive symptoms increase morbidity and mortality from coronary heart disease and systemic inflammation has been proposed as the underlying mechanism. While higher levels of inflammatory mediators have been found in dysphoric individuals, it is not known whether long-term or short-term mood changes are responsible for this phenomenon. A sample of 65 young women provided weekly web-based self-ratings of depressive mood over a period of 20 weeks using the CES-D, and systemic inflammation was assessed by measuring plasma interleukin-6 (IL-6) and C-reactive protein (CRP) before and after the observation period. CES-D ratings were used to develop state and trait indicators of depressed mood and evaluate their relationship with inflammatory mediators. Hierarchical linear regressions controlling for baseline inflammation, age, and BMI revealed that trait levels of depressive symptoms were not associated with IL-6 (beta=0.09; n.s.) and CRP (beta=0.01; n.s.) concentrations after the observation period. In contrast, state levels of depressive symptoms were associated with changes in IL-6, but not CRP, particularly when they were indexed as the disparity between a person's trait level of symptoms and her CES-D score just prior to IL-6 assessment (beta=0.35; p=0.03). These results lead us to conclude that in young women, state, rather than trait depressed mood stimulates peripheral inflammation as measured by IL-6. This pattern suggests that in this age group, fast-reacting inflammatory mediators such as IL-6 probably respond to short-term changes, for example, in stress hormones or stress hormone sensitivity, rather than long-term dysregulations of allostatic mechanisms.

CaV1.3 L-type Ca2+ channels modulate depression-like behaviour in mice independent of deaf phenotype.

Science.gov (United States)

Busquet, Perrine; Nguyen, Ngoc Khoi; Schmid, Eduard; Tanimoto, Naoyuki; Seeliger, Mathias W; Ben-Yosef, Tamar; Mizuno, Fengxia; Akopian, Abram; Striessnig, Jörg; Singewald, Nicolas

2010-05-01

Mounting evidence suggests that voltage-gated L-type Ca2+ channels can modulate affective behaviour. We therefore explored the role of CaV1.3 L-type Ca2+ channels in depression- and anxiety-like behaviours using CaV1.3-deficient mice (CaV1.3-/-). We showed that CaV1.3-/- mice displayed less immobility in the forced swim test as well as in the tail suspension test, indicating an antidepressant-like phenotype. Locomotor activity in the home cage or a novel open-field test was not influenced. In the elevated plus maze (EPM), CaV1.3-/- mice entered the open arms more frequently and spent more time there indicating an anxiolytic-like phenotype which was, however, not supported in the stress-induced hyperthermia test. By performing parallel experiments in Claudin 14 knockout mice (Cldn14-/-), which like CaV1.3-/- mice are congenitally deaf, an influence of deafness on the antidepressant-like phenotype could be ruled out. On the other hand, a similar EPM behaviour indicative of an anxiolytic phenotype was also found in the Cldn14-/- animals. Using electroretinography and visual behavioural tasks we demonstrated that at least in mice, CaV1.3 channels do not significantly contribute to visual function. However, marked morphological changes were revealed in synaptic ribbons in the outer plexiform layer of CaV1.3-/- retinas by immunohistochemistry suggesting a possible role of this channel type in structural plasticity at the ribbon synapse. Taken together, our findings indicate that CaV1.3 L-type Ca2+ channels modulate depression-like behaviour but are not essential for visual function. The findings raise the possibility that selective modulation of CaV1.3 channels could be a promising new therapeutic concept for the treatment of mood disorders.

Relapse rates after psychotherapy for depression - stable long-term effects? A meta-analysis.

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Steinert, Christiane; Hofmann, Mareike; Kruse, Johannes; Leichsenring, Falk

2014-10-01

Depression is the most common mental disorder. Effective psychotherapeutic treatments for depression exist; however, data on their long-term effectiveness beyond a time span of two years is still scarce. Our aim was to perform a meta-analysis, investigating (a) overall rates of relapse more than two years after psychotherapy (meta-analysis 1), and (b) if psychotherapy has more enduring effects than non-psychotherapeutic comparison conditions (e.g. pharmacotherapy, treatment as usual), again beyond a time span of two years post-therapy (meta-analysis 2). We searched electronic databases Medline, PsycINFO and the COCHRANE Library. Main selection criteria were (i) RCT of psychotherapy with follow-up interval of more than 2 years, (ii) primary diagnosis of depression, assessed by observer ratings, (iii) report of relapse at follow-up. We identified 11 studies, 6 of which included a non-psychotherapeutic comparison condition. Together they comprised long-term data of 966 patients. Mean follow-up duration was 4.4 years. The overall relapse rate at long-term follow-up was 0.39 (95% CI 0.29, 0.50). Psychotherapy resulted in significantly less relapses (53.1% vs. 71.1%, OR 0.51; 95% CI 0.32, 0.82, p=0.005) than comparison treatments. This finding corresponded to a number needed to treat (NNT) of 5.55. Results can only be preliminary as data was sparse and studies differed methodologically. Heterogeneity in the first meta-analysis was high (I(2)=82%). Results indicated publication bias. The relapse rate more than two years after psychotherapy is relatively high, but significantly lower compared to non-psychotherapeutic treatments. Multiannual follow-ups should routinely be included in future psychotherapy RCTs. Copyright © 2014 Elsevier B.V. All rights reserved.

12-lipoxygenase regulates hippocampal long-term potentiation by modulating L-type Ca2+ channels

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DeCostanzo, Anthony J.; Voloshyna, Iryna; Rosen, Zev B.; Feinmark, Steven J.; Siegelbaum, Steven A.

2010-01-01

Although long-term potentiation (LTP) has been intensely studied, there is disagreement as to which molecules mediate and modulate LTP. This is partly due to the presence of mechanistically distinct forms of LTP that are induced by different patterns of stimulation and that depend on distinct Ca2+ sources. Here we report a novel role for the arachidonic acid-metabolizing enzyme 12-lipoxygenase (12-LO) in LTP at CA3-CA1 hippocampal synapses that is dependent on the pattern of tetanic stimulation. We find that 12-LO activity is required for the induction of LTP in response to a theta-burst stimulation (TBS) protocol, which depends on Ca2+ influx through both NMDA receptors and L-type voltage-gated Ca2+ channels. In contrast, LTP induced by 100 Hz tetanic stimulation, which requires Ca2+ influx through NMDA receptors but not L-type channels, does not require 12-LO. We find that 12-LO regulates LTP by enhancing postsynaptic somatodendritic Ca2+ influx through L-type channels during theta burst stimulation, an action exerted via 12(S)-HPETE, a downstream metabolite of 12-LO. These results help define the role of a long-disputed signaling enzyme in LTP. PMID:20130191

Long-term work disability and absenteeism in anxiety and depressive disorders

NARCIS (Netherlands)

Hendriks, S.M.; Spijker, J.; Licht, C.M.M.; Hardeveld, F.; Graaf, R. de; Batelaan, N.M.; Penninx, B.W.J.H.; Beekman, A.T.F.

2015-01-01

Background: This longitudinal study aims to compare long-term work disability and absenteeism between anxiety and depressive disorders focusing on the effects of different course trajectories (remission, recurrence and chronic course) and specific symptom dimensions (anxiety arousal, avoidance

Long-term work disability and absenteeism in anxiety and depressive disorders

NARCIS (Netherlands)

Hendriks, S.M.; Spijker, J.; Licht, C.M.M.; Hardevel, F.; de Graaf, R.; Batelaan, N.M.; Penninx, B.W.; Beekman, A.T.

2015-01-01

Background This longitudinal study aims to compare long-term work disability and absenteeism between anxiety and depressive disorders focusing on the effects of different course trajectories (remission, recurrence and chronic course) and specific symptom dimensions (anxiety arousal, avoidance

Long-term work disability and absenteeism in anxiety and depressive disorders

NARCIS (Netherlands)

Hendriks, S.M.; Spijker, J.; Licht, C.M.; Hardeveld, F.; Graaf, R. de; Batelaan, N.M.; Penninx, B.W.; Beekman, A.T.

2015-01-01

BACKGROUND: This longitudinal study aims to compare long-term work disability and absenteeism between anxiety and depressive disorders focusing on the effects of different course trajectories (remission, recurrence and chronic course) and specific symptom dimensions (anxiety arousal, avoidance

Single fluoxetine treatment before but not after stress prevents stress-induced hippocampal long-term depression and spatial memory retrieval impairment in rats

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Han, Huili; Dai, Chunfang; Dong, Zhifang

2015-01-01

A growing body of evidence has shown that chronic treatment with fluoxetine, a widely prescribed medication for treatment of depression, can affect synaptic plasticity in the adult central nervous system. However, it is not well understood whether acute fluoxetine influences synaptic plasticity, especially on hippocampal CA1 long-term depression (LTD), and if so, whether it subsequently impacts hippocampal-dependent spatial memory. Here, we reported that LTD facilitated by elevated-platform stress in hippocampal slices was completely prevented by fluoxetine administration (10 mg/kg, i.p.) 30 min before stress. The LTD was not, however, significantly inhibited by fluoxetine administration immediately after stress. Similarly, fluoxetine incubation (10 μM) during electrophysiological recordings also displayed no influence on the stress-facilitated LTD. In addition, behavioral results showed that a single fluoxetine treatment 30 min before but not after acute stress fully reversed the impairment of spatial memory retrieval in the Morris water maze paradigm. Taken together, these results suggest that acute fluoxetine treatment only before, but not after stress, can prevent hippocampal CA1 LTD and spatial memory retrieval impairment caused by behavioral stress in adult animals. PMID:26218751

The prevalence of long-term symptoms of depression and anxiety after breast cancer treatment : A systematic review

NARCIS (Netherlands)

Maass, S. W. M. C.; Roorda, C.; Berendsen, A. J.; Verhaak, P. F. M.; de Bock, G. H.

Objectives: It is unclear whether breast cancer survivors have a higher risk of long-term symptoms of depression or anxiety. The aim of this study was to systematically review the evidence about long-term symptoms of depression and anxiety in breast cancer survivors. Study design: Systematic review.

The prevalence of long-term symptoms of depression and anxiety after breast cancer treatment: a systematic review.

NARCIS (Netherlands)

Maass, S.W.M.C.; Roorda, C.; Berendsen, A.J.; Verhaak, P.F.M.; Bock, G.H. de

2015-01-01

Objectives: It is unclear whether breast cancer survivors have a higher risk of long-term symptoms of depression or anxiety. The aim of this study was to systematically review the evidence about long-term symptoms of depression and anxiety in breast cancer survivors. Study design: Systematic review.

The prevalence of long-term symptoms of depression and anxiety after breast cancer treatment : A systematic review

NARCIS (Netherlands)

Maass, S.W.M.C.; Roorda, Carriene; Berendsen, A.J.; Verhaak, P.F.M.; de Bock, G.H.

Objectives It is unclear whether breast cancer survivors have a higher risk of long-term symptoms of depression or anxiety. The aim of this study was to systematically review the evidence about long-term symptoms of depression and anxiety in breast cancer survivors. Study design Systematic review.

Comparison of major depressive disorder and subthreshold depression among older adults in community long-term care.

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Lee, Mi Jin; Hasche, Leslie K; Choi, Sunha; Proctor, Enola K; Morrow-Howell, Nancy

2013-01-01

This study extends existing knowledge regarding the continuum between major depression (MD) and subthreshold depression (SD) by examining differences in symptomology and associative factors for a subpopulation of older adults with functional disability. Our sample consisted of clients age 60 and above entering public community long term care derived from the baseline survey of a longitudinal study (315 non-depressed, 74 MD, and 221 SD). We used the Diagnostic Interview Schedule to establish diagnoses of MD, the Center for Epidemiological Studies Depression Scale (CES-D) to assess SD, and other self-report measures to explore potential associative factors of demographics, comorbidity, social support, and stressors. No differences in CES-D identified symptoms occurred between the two groups. MD and SD were both associated with lower education, poorer social support, more severe medical conditions, and higher stress when compared to non-depressed older adults. Younger age and being female were associated solely with MD; whereas, worse perceived health and more trouble affording food were associated solely with SD. The only associative factor significantly different between MD and SD was age. Those with MD were more likely to be younger than those with SD. Our findings of symptom profiles and associative factors lend support to the continuum notion of depression. Identification of only older adults within the community long-term care service system who meet criteria for MD would leave many older adults, who also face multiple comorbidities, high levels of stress and social isolation, and substantial depressive symptoms undiagnosed and untreated.

长时程增强与长时程抑制的研究%Advances in long - term potentiation and long - term depression

Institute of Scientific and Technical Information of China (English)

张敬军; 夏作理

2000-01-01

The impairment of learning and memory function in the central nervous system(CNS)is one of the main features of aging and Alzheimer' s disease (AD). Many experimental results have showed that long- term memory(LTM) is related to long- term potentiation(LTP) and long- term depression (LTD). They intluenee each other. The relationship between LTP and LTD is complex. Therefore, it is important to study the learning and memory mechanism from LTP、LTD and gene expression in the CNS.

The long-term effects of maternal depression: early childhood physical health as a pathway to offspring depression.

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Raposa, Elizabeth; Hammen, Constance; Brennan, Patricia; Najman, Jake

2014-01-01

Cross-sectional and retrospective studies have highlighted the long-term negative effects of maternal depression on offspring physical, social, and emotional development, but longitudinal research is needed to clarify the pathways by which maternal depression during pregnancy and early childhood affects offspring outcomes. The current study tested one developmental pathway by which maternal depression during pregnancy might negatively impact offspring mental health in young adulthood, via poor physical health in early childhood. The sample consisted of 815 Australian youth and their mothers who were followed for 20 years. Mothers reported on their own depressive symptoms during pregnancy and offspring early childhood. Youth completed interviews about health-related stress and social functioning at age 20 years, and completed a questionnaire about their own depressive symptoms 2 to 5 years later. Path analysis indicated that prenatal maternal depressive symptoms predicted worse physical health during early childhood for offspring, and this effect was partially explained by ongoing maternal depression in early childhood. Offspring poor physical health during childhood predicted increased health-related stress and poor social functioning at age 20. Finally, increased health-related stress and poor social functioning predicted increased levels of depressive symptoms later in young adulthood. Maternal depression had a significant total indirect effect on youth depression via early childhood health and its psychosocial consequences. Poor physical health in early childhood and its effects on young adults' social functioning and levels of health related stress is one important pathway by which maternal depression has long-term consequences for offspring mental health. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Inhibition of long-term potentiation in the schaffer-CA1 pathway by repetitive high-intensity sound stimulation.

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Cunha, A O S; de Oliveira, J A C; Almeida, S S; Garcia-Cairasco, N; Leão, R M

2015-12-03

High-intensity sound can induce seizures in susceptible animals. After repeated acoustic stimuli changes in behavioural seizure repertoire and epileptic EEG activity might be seen in recruited limbic and forebrain structures, a phenomenon known as audiogenic kindling. It is postulated that audiogenic kindling can produce synaptic plasticity events leading to the spread of epileptogenic activity to the limbic system. In order to test this hypothesis, we investigated if long-term potentiation (LTP) of hippocampal Schaffer-CA1 synapses and spatial navigation memory are altered by a repeated high-intensity sound stimulation (HISS) protocol, consisting of one-minute 120 dB broadband noise applied twice a day for 10 days, in normal Wistar rats and in audiogenic seizure-prone rats (Wistar Audiogenic Rats - WARs). After HISS all WARs exhibited midbrain seizures and 50% of these animals developed limbic recruitment, while only 26% of Wistar rats presented midbrain seizures and none of them had limbic recruitment. In naïve animals, LTP in hippocampal CA1 neurons was induced by 50- or 100-Hz high-frequency stimulation of Schaffer fibres in slices from both Wistar and WAR animals similarly. Surprisingly, HISS suppressed LTP in CA1 neurons in slices from Wistar rats that did not present any seizure, and inhibited LTP in slices from Wistar rats with only midbrain seizures. However HISS had no effect on LTP in CA1 neurons from slices of WARs. Interestingly HISS did not alter spatial navigation and memory in both strains. These findings show that repeated high-intensity sound stimulation prevent LTP of Schaffer-CA1 synapses from Wistar rats, without affecting spatial memory. This effect was not seen in hippocampi from audiogenic seizure-prone WARs. In WARs the link between auditory stimulation and hippocampal LTP seems to be disrupted which could be relevant for the susceptibility to seizures in this strain. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Work Characteristics and Return to Work in Long-Term Sick-Listed Employees with Depressive Symptoms.

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Huijs, Jenny J J M; Koppes, Lando L J; Taris, Toon W; Blonk, Roland W B

2017-12-01

Purpose The present study investigated the relations between work characteristics, depressive symptoms and duration until full return to work (RTW) among long-term sick-listed employees. This knowledge may add to the development of effective interventions and prevention, especially since work characteristics can be subjected to interventions more easily than many disorder-related or personal factors. Methods this prospective cohort study with a two-year follow-up employs a sample of 883 Dutch employees who had been sick-listed for at least 13 weeks at baseline, who filled out three questionnaires: at 19 weeks, 1 and 2 years after the start of sick leave. The dependent measure was duration until full RTW. Results not working (partially) at baseline, low decision authority, high psychological demands, low supervisor support and low RTW self-efficacy were related to more depressive symptoms. The duration until full RTW was longer for employees with depressive symptoms. Low physical exertion, high RTW self-efficacy, working partially at baseline, being married or cohabiting, and young age were related to less time until full RTW. Other work characteristics appeared no independent predictors of RTW. Conclusions although the role of job demands and job resources in the RTW process is limited for long-term sick-listed employees with depressive symptoms, a few work characteristics are prognostic factors of full RTW. Focus on these elements in the selection or development of interventions may be helpful in preventing sickness absence, and in supporting long-term sick-listed employees towards full RTW.

Synaptic plasticity in the hippocampal area CA1-subiculum projection: implications for theories of memory.

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O'Mara, S M; Commins, S; Anderson, M

2000-01-01

This paper reviews investigations of synaptic plasticity in the major, and underexplored, pathway from hippocampal area CA1 to the subiculum. This brain area is the major synaptic relay for the majority of hippocampal area CA1 neurons, making the subiculum the last relay of the hippocampal formation prior to the cortex. The subiculum thus has a very major role in mediating hippocampal-cortical interactions. We demonstrate that the projection from hippocampal area CA1 to the subiculum sustains plasticity on a number of levels. We show that this pathway is capable of undergoing both long-term potentiation (LTP) and paired-pulse facilitation (PPF, a short-term plastic effect). Although we failed to induce long-term depression (LTD) of this pathway with low-frequency stimulation (LFS) and two-pulse stimulation (TPS), both protocols can induce a "late-developing" potentiation of synaptic transmission. We further demonstrate that baseline synaptic transmission can be dissociated from paired-pulse stimulation of the same pathway; we also show that it is possible, using appropriate protocols, to change PPF to paired-pulse depression, thus revealing subtle and previously undescribed mechanisms which regulate short-term synaptic plasticity. Finally, we successfully recorded from individual subicular units in the freely-moving animal, and provide a description of the characteristics of such neurons in a pellet-chasing task. We discuss the implications of these findings in relation to theories of the biological consolidation of memory.

Long-term effects of parental divorce timing on depression: A population-based longitudinal study.

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Chun, Sung-Youn; Jang, Suk-Yong; Choi, Jae-Woo; Shin, Jaeyong; Park, Eun-Cheol

2016-09-08

We examined the long-term effects of parental divorce timing on depression using longitudinal data from the Korean Welfare Panel Study. Depression symptoms were measured using the 11 items of Center for Epidemiologic Scale for Depression (CES-D-11), and we categorized parental divorce timing into 'early childhood', 'adolescent' and 'none'. Although participants who experienced parental divorce during adolescence exhibited a significantly higher CES-D-11 score (p = .0468), 'early childhood' participants displayed the most increased CES-D-11 score compared to the control group (p = .0007). Conversely, among participants who were unsatisfied with their marriage, those who experienced parental divorce in early childhood showed lower CES-D-11 scores, while 'adolescent period' participants exhibited significantly higher CES-D-11 scores (p = .0131). We concluded that timing of parental divorce exerts substantial yet varied effects on long-term depression symptoms and future marriage satisfaction. © The Author(s) 2016.

Long-term effects of a home-visiting intervention for depressed mothers and their infants

NARCIS (Netherlands)

Kersten-Alvarez, L.E.; Hosman, C.M.H.; Riksen-Walraven, J.M.A.; Doesum, K.T.M. van; Hoefnagels, C.C.J.

2010-01-01

Background - Whereas preventive interventions for depressed mothers and their infants have yielded positive short-term outcomes, few studies have examined their long-term effectiveness. The present follow-up of a randomised controlled trial (RCT) is one of the first to examine the longer-term

Neural 17β-estradiol facilitates long-term potentiation in the hippocampal CA1 region.

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Grassi, S; Tozzi, A; Costa, C; Tantucci, M; Colcelli, E; Scarduzio, M; Calabresi, P; Pettorossi, V E

2011-09-29

In the hippocampal formation many neuromodulators are possibly implied in the synaptic plasticity such as the long-term potentiation (LTP) induced by high-frequency stimulation (HFS) of afferent fibers. We investigated the involvement of locally synthesized neural 17β-estradiol (nE(2)) in the induction of HFS-LTP in hippocampal slices from male rats by stimulating the Schaffer collateral fibers and recording the evoked field excitatory postsynaptic potential (fEPSP) in the CA1 region. We demonstrated that either the blockade of nE(2) synthesis by the aromatase inhibitor letrozole, or the antagonism of E(2) receptors (ERs) by ICI 182,780 did not prevent the induction of HFS-LTP, but reduced its amplitude by ∼60%, without influencing its maintenance. Moreover, letrozole and ICI 182,780 did not affect the first short-term post-tetanic component of LTP and the paired-pulse facilitation (PPF). These findings demonstrate that nE(2) plays an important role in the induction phase of HFS-dependent LTP. Since the basal responses were not affected by the blocking agents, we suggest that the synthesis of nE(2) is induced or enhanced by HFS through aromatase activation. In this context, the local production of nE(2) seems to be a very effective mechanism to modulate the amplitude of LTP. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Involvement of N-methyl-D-aspartate receptor subunits in zinc-mediated modification of CA1 long-term potentiation in the developing hippocampus.

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Takeda, Atsushi; Itagaki, Kosuke; Ando, Masaki; Oku, Naoto

2012-03-01

Zinc is an endogenous N-methyl-D-aspartate (NMDA) receptor blocker. It is possible that zinc-mediated modification of hippocampal CA1 long-term potentiation (LTP) is linked to the expression of NMDA receptor subunits, which varies with postnatal development. In the present study, the effect of ZnCl(2) and CaEDTA, a membrane-impermeable zinc chelator, on CA1 LTP induction was examined in hippocampal slices from immature (3-week-old) and young (6-week-old) rats. Tetanus (10-100 Hz, 1 sec)-induced CA1 LTP was more greatly enhanced in 3-week-old rats. CA1 LTP was inhibited in the presence of 2-amino-5-phosphonovalerate (APV), an NMDA receptor antagonist, and CaEDTA in 3-week-old rats, as in the case of 6-week-old rats reported previously. In 3-week-old rats, on the other hand, 5 μM ZnCl(2) attenuated NMDA receptor-mediated EPSPs more than in 6-week-old rats and significantly attenuated CA1 LTP. Moreover, 5 μM ZnCl(2) significantly attenuated CA1 LTP in the presence of (2R,4S)-4-(3-phosphonopropyl)-2-piperidinecarboxylic acid (PPPA), an NR2A antagonist, in 3-week-old rats, but not that in the presence of ifenprodil, an NR2B antagonist, suggesting that zinc-mediated attenuation of CA1 LTP is associated with the preferential expression of NR2B subunit in 3-week-old rats. In 6-week-old rats, however, 5 μM ZnCl(2) significantly potentiated CA1 LTP and also CA1 LTP in the presence of PPPA. The present study demonstrates that endogenous zinc may participate in the induction of CA1 LTP. It is likely that the changes in expression of NMDA receptor subunits are involved in the zinc-mediated modification of CA1 LTP in the developing hippocampus. Copyright © 2011 Wiley Periodicals, Inc.

Effect of long-term exposure to air pollution on anxiety and depression in adults: A cross-sectional study.

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Vert, Cristina; Sánchez-Benavides, Gonzalo; Martínez, David; Gotsens, Xavier; Gramunt, Nina; Cirach, Marta; Molinuevo, José Luis; Sunyer, Jordi; Nieuwenhuijsen, Mark J; Crous-Bou, Marta; Gascon, Mireia

2017-08-01

The association between exposure to air pollutants and mental disorders among adults has been suggested, although results are not consistent. To analyze the association between long-term exposure to air pollution and history of anxiety and depression disorders and of medication use (benzodiazepines and antidepressants) in adults living in Barcelona. A total of 958 adults (45-74 years old) residents in Barcelona, most of them having at least one of their parents diagnosed with dementia (86%), and participating in the ALFA (Alzheimer and Families) study, were included. We used Land Use Regression (LUR) models to estimate long-term residential exposure (period 2009-2014) to PM 2.5 , PM 2.5 absorbance (PM 2.5 abs), PM 10 , PM coarse, NO 2 and NO x . Between 2013 and 2014 participants self-reported their history of anxiety and depression disorders and related medication use. The analysis was focused on those participants reporting outcome occurrence from 2009 onwards (until 2014). We observed an increased odds of history of depression disorders with increasing concentrations of all air pollutants [e.g. an increased odds of depression of 2.00 (95% CI; 1.37, 2.93) for each 10μg/m 3 NO 2 increase]. Such associations were consistent with an increased odds of medication use in relation to higher concentrations of air pollutants [e.g. an increased odds of antidepressants use of 1.23 (1.04, 1.44) for each 20μg/m 3 NO x increase]. Associations regarding anxiety disorders did not reach statistical significance. Our study shows that increasing long-term exposure to air pollution may increase the odds of depression and the use of antidepressants and benzodiazepines. Further studies are needed to replicate our results and confirm this association. Copyright © 2017 Elsevier GmbH. All rights reserved.

The long-term risk of recognized and unrecognized myocardial infarction for depression in older men.

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Jovanova, O; Luik, A I; Leening, M J G; Noordam, R; Aarts, N; Hofman, A; Franco, O H; Dehghan, A; Tiemeier, H

2016-07-01

The association between myocardial infarction (MI) and depression is well described. Yet, the underlying mechanisms are unclear and the contribution of psychological factors is uncertain. We aimed to determine the risk of recognized (RMI) and unrecognized (UMI) myocardial infections on depression, as both have a similar impact on cardiovascular health but differ in psychological epiphenomena. Participants of the Rotterdam Study, 1823 men aged ⩾55 years, were followed for the occurrence of depression. RMI and UMI were ascertained using electrocardiography and medical history at baseline. We determined the strength of the association of RMI and UMI with mortality, and we studied the relationship of RMI and UMI with depressive symptoms and the occurrence of major depression. The risk of mortality was similar in men with RMI [adjusted hazard ratio (aHR) 1.71, 95% confidence interval (CI) 1.45-2.03] and UMI (aHR 1.58, 95% CI 1.27-1.97). Men with RMI had on average [unstandardized regression coefficient (B) 1.14, 95% CI 0.07-2.21] higher scores for depressive symptoms. By contrast, we found no clear association between UMI and depressive symptoms (B 0.55, 95% CI -0.51 to 1.62) in men. Analysis including occurrence of major depression as the outcome were consistent with the pattern of association. The discrepant association of RMI and UMI with mortality compared to depression suggests that the psychological burden of having experienced an MI contributes to the long-term risk of depression.

Gender and the Association between Long-Term Prescription Opioid Use and New-Onset Depression.

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Salas, Joanne; Scherrer, Jeffrey F; Ahmedani, Brian K; Copeland, Laurel A; Bucholz, Kathleen K; Sullivan, Mark D; Burroughs, Thomas; Schneider, F David; Lustman, Patrick J

2018-01-01

Women have a higher prevalence of chronic noncancer pain conditions and report more severe pain, yet, it is not known if the association between long-term opioid analgesic use (OAU) and risk of a new depression episode (NDE) differs according to gender. We analyzed patient data from the Veterans Health Administration (VHA; 2000-2012; n = 70,997) and a large private-sector health care organization (2003-2012; n = 22,981) to determine whether long-term OAU and risk of NDE differed according to gender. Patients were free of depression and OAU for 2 years before baseline. OAU duration was defined as 1 to 30, 31 to 90 and more than 90 days, and NDE was defined according to International Classification of Diseases, Ninth Revision codes. Gender-stratified Cox proportional hazard models were used to estimate hazard ratios (HRs). Propensity scores and subsequent inverse probability of treatment weighting controlled for confounding. In the VHA, more than 90 compared with 1- to 30-day OAU was more strongly associated with NDE among female than male patients (female: HR = 1.79 [95% confidence interval (CI), 1.45-2.22] vs male HR = 1.25 [95% CI, 1.16-1.34], P = .002). In private sector patients, there was no gender difference in the association between more than 90-day OAU and NDE (female HR = 1.97 [95% CI, 1.64-2.37] vs male HR = 1.99 [95% CI, 1.44-2.74]). Risk of NDE after long-term OAU is similar in men and women in private sector patients but may differ for VHA patients. Future prospective studies are needed to identify mechanisms for the association between longer OAU and NDE. Existing research is mixed regarding gender differences in outcomes after long-term prescription opioid use. This study found both genders have increased risk of an NDE after more than 90 days of opioid use. Women and men may benefit from closer monitoring of mood associated with chronic opioid use. Copyright © 2017 The American Pain Society. Published by Elsevier Inc. All

Long-term cumulative depressive symptom burden and risk of cognitive decline and dementia among very old women.

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Zeki Al Hazzouri, Adina; Vittinghoff, Eric; Byers, Amy; Covinsky, Ken; Blazer, Dan; Diem, Susan; Ensrud, Kristine E; Yaffe, Kristine

2014-05-01

Depressive symptoms and cognitive outcomes are strongly interrelated. Despite that rates of depressive symptoms fluctuate during late life, little is known about the impact of long-term cumulative depressive symptom burden on cognitive decline and dementia in older adults. This study examines the association of nearly 20 years of cumulative depressive symptoms with cognitive outcomes in a cohort of older women. We assessed depressive symptoms in 7,240 women using the Geriatric Depression scale (GDS) at serial visits. We used a Poisson model with random slopes to estimate GDS trajectories for each participant from baseline to death or end of follow-up, and then characterized depressive symptom burden by quartile of the area under the curve. We assessed cognitive outcomes using repeated measures of the Mini-Mental State Examination (MMSE) and Trails B score over 20 years, Year-20 neuropsychological test battery, and adjudicated dementia and mild cognitive impairment (MCI). Adjusting for potential confounders, compared with women in the lowest quartile of cumulative depressive symptoms burden, women in the highest quartile had 21% more MMSE errors over time (95% CI = 17%, 26%), 20% worse Trails B score over time (95% CI = 17%, 23%), worse scores on most of the Year-20 cognitive tests, and a twofold greater likelihood of developing dementia or MCI (95% CI = 1.48, 3.11). Long-term cumulative depressive symptom burden was associated with cognitive decline and risk of dementia or MCI. Older adults with a history of depression should be closely monitored for recurrent episodes or unresolved depressive symptoms as well as any cognitive deficits.

Long-term outcome of major depressive disorder in psychiatric patients is variable.

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Holma, K Mikael; Holma, Irina A K; Melartin, Tarja K; Rytsälä, Heikki J; Isometsä, Erkki T

2008-02-01

The prevailing view of outcome of major depressive disorder (MDD), based on mostly inpatient cohorts sampled from tertiary centers, emphasizes chronicity and frequent recurrences. We investigated the long-term outcome of a regionally representative psychiatric MDD cohort comprising mainly outpatients. The Vantaa Depression Study included 163 patients with DSM-IV MDD (71.5% of those eligible) diagnosed using structured and semistructured interviews and followed up at 6 months, 18 months, and 5 years with a life chart between February 1, 1997, and April 30, 2004. The effects of comorbid disorders and other predictors on outcome were comprehensively investigated. Over the 5-year follow-up, 98.8% of patients achieved a symptom state below major depressive episode (MDE) criteria, and 88.4% reached full remission, with the median time to full remission being 11.0 months. Nearly one third (29.3%) had no recurrences, whereas 30.0% experienced 1, 12.9% experienced 2, and 27.9% experienced 3 or more recurrences. Preceding dysthymic disorder (p = .028), cluster C personality disorder (p = .041), and longer MDE duration prior to entry (p = .011) were the most significant predictors of longer time in achieving full remission. Severity of MDD and comorbidity, especially social phobia, predicted probability of, shorter time to, and number of recurrences. Previous literature on mostly inpatient MDD may have, by generalizing from patients with the most severe psychopathology, overemphasized chronicity of MDD. The long-term outcome of MDD in psychiatric care is variable, with about one tenth of patients having poor, one third having intermediate, and one half having favorable outcomes. In addition to known predictors, cluster C personality disorders and social phobia warrant further attention as predictors of MDD outcome among outpatients.

Rapamycin inhibits mTOR/p70S6K activation in CA3 region of the hippocampus of the rat and impairs long term memory.

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Lana, D; Di Russo, J; Mello, T; Wenk, G L; Giovannini, M G

2017-01-01

The present study was aimed at establishing whether the mTOR pathway and its downstream effector p70S6K in CA3 pyramidal neurons are under the modulation of the cholinergic input to trigger the formation of long term memories, similar to what we demonstrated in CA1 hippocampus. We performed in vivo behavioral experiments using the step down inhibitory avoidance test in adult Wistar rats to evaluate memory formation under different conditions. We examined the effects of rapamycin, an inhibitor of mTORC1 formation, scopolamine, a muscarinic receptor antagonist or mecamylamine, a nicotinic receptor antagonist, on short and long term memory formation and on the functionality of the mTOR pathway. Acquisition was conducted 30min after i.c.v. injection of rapamycin. Recall testing was performed 1h, 4h or 24h after acquisition. We found that (1) mTOR and p70S6K activation in CA3 pyramidal neurons were involved in long term memory formation; (2) rapamycin significantly inhibited mTOR and of p70S6K activation at 4h, and long term memory impairment 24h after acquisition; (3) scopolamine impaired short but not long term memory, with an early increase of mTOR/p70S6K activation at 1h followed by stabilization at longer times; (4) mecamylamine and scopolamine co-administration impaired short term memory at 1h and 4h and reduced the scopolamine-induced increase of mTOR/p70S6K activation at 1h and 4h; (5) mecamylamine and scopolamine treatment did not impair long term memory formation; (6) unexpectedly, rapamycin increased mTORC2 activation in microglial cells. Our results demonstrate that in CA3 pyramidal neurons the mTOR/p70S6K pathway is under the modulation of the cholinergic system and is involved in long-term memory encoding, and are consistent with the hypothesis that the CA3 region of the hippocampus is involved in memory mechanisms based on rapid, one-trial object-place learning and recall. Furthermore, our results are in accordance with previous reports that selective

Intermittent hypercapnia-induced phrenic long-term depression is revealed after serotonin receptor blockade with methysergide in anaesthetized rats.

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Valic, Maja; Pecotic, Renata; Pavlinac Dodig, Ivana; Valic, Zoran; Stipica, Ivona; Dogas, Zoran

2016-02-01

What is the central question of this study? Intermittent hypercapnia is a concomitant feature of breathing disorders. Hypercapnic stimuli evoke a form of respiratory plasticity known as phrenic long-term depression in experimental animals. This study was performed to investigate the putative role of serotonin receptors in the initiation of phrenic long-term depression in anaesthetized rats. What is the main finding and its importance? Phrenic nerve long-term depression was revealed in animals pretreated with the serotonin broad-spectrum antagonist, methysergide. This study highlights that serotonin receptors modulate respiratory plasticity evoked by acute intermittent hypercapnia in anaesthetized rats. This study was performed to test the hypothesis that intermittent hypercapnia can evoke a form of respiratory plasticity known as long-term depression of the phrenic nerve (pLTD) and that 5-HT receptors play a role in the initiation of pLTD. Adult male urethane-anaesthetized, vagotomized, paralysed, mechanically ventilated Sprague-Dawley rats were exposed to an acute intermittent hypercapnia protocol. One group received i.v. injection of the non-selective 5-HT receptor antagonist methysergide and another group received i.v. injection of the selective 5-HT1A receptor antagonist WAY-100635 20 min before exposure to intermittent hypercapnia. A control group received i.v. injection of saline. Peak phrenic nerve activity and respiratory rhythm parameters were analysed at baseline (T0), during each of five hypercapnic episodes, and 15, 30 and 60 min (T60) after the last hypercapnia. Intravenous injection of methysergide before exposure to acute intermittent hypercapnia induced development of amplitude pLTD at T60 (decreased by 46.1 ± 6.9%, P = 0.003). Conversely, in control and WAY-100635-pretreated animals, exposure to acute intermittent hypercapnia did not evoke amplitude pLTD. However, a long-term decrease in phrenic nerve frequency was evoked both in control (42 ± 4

Dopamine D1-like receptor in lateral habenula nucleus affects contextual fear memory and long-term potentiation in hippocampal CA1 in rats.

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Chan, Jiangping; Guan, Xin; Ni, Yiling; Luo, Lilu; Yang, Liqiang; Zhang, Pengyue; Zhang, Jichuan; Chen, Yanmei

2017-03-15

The Lateral Habenula (LHb) plays an important role in emotion and cognition. Recent experiments suggest that LHb has functional interaction with the hippocampus and plays an important role in spatial learning. LHb is reciprocally connected with midbrain monoaminergic brain areas such as the ventral tegmental area (VTA). However, the role of dopamine type 1 receptor (D1R) in LHb in learning and memory is not clear yet. In the present study, D1R agonist or antagonist were administered bilaterally into the LHb in rats. We found that both D1R agonist and antagonist impaired the acquisition of contextual fear memory in rats. D1R agonist or antagonist also impaired long term potentiation (LTP) in hippocampal CA3-CA1 synapses in freely moving rats and attenuated learning induced phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) subunit 1 (GluA1) at Ser831 and Ser845 in hippocampus. Taken together, our results suggested that dysfunction of D1R in LHb affected the function of hippocampus. Copyright © 2016 Elsevier B.V. All rights reserved.

Anisomycin Injection in Area CA3 of the Hippocampus Impairs Both Short-Term and Long-Term Memories of Contextual Fear

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Remaud, Jessica; Ceccom, Johnatan; Carponcy, Julien; Dugué, Laura; Menchon, Gregory; Pech, Stéphane; Halley, Helene; Francés, Bernard; Dahan, Lionel

2014-01-01

Protein synthesis is involved in the consolidation of short-term memory into long-term memory. Previous electrophysiological data concerning LTP in CA3 suggest that protein synthesis in that region might also be necessary for short-term memory. We tested this hypothesis by locally injecting the protein synthesis inhibitor anisomycin in hippocampal…

The effects of CCK-8S on spatial memory and long-term potentiation at CA1 during induction of stress in rats

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Malihe Sadeghi

2017-12-01

Full Text Available Objective(s: Cholecystokinin (CCK has been proposed as a mediator in stress. However, it is still not fully documented what are its effects. We aimed to evaluate the effects of systemic administration of CCK exactly before induction of stress on spatial memory and synaptic plasticity at CA1 in rats. Materials and Methods: Male Wistar rats were divided into 4 groups: the control, the control-CCK, the stress and the stress-CCK. Restraint stress was induced 6 hr per day, for 24 days. Cholecystokinin sulfated octapeptide (CCK-8S was injected (1.6 µg/kg, IP before each session of stress induction. Spatial memory was evaluated by Morris water maze test. Long term potentiation (LTP in Schaffer collateral-CA1 synapses was assessed (by 100 Hz tetanization in order to investigate synaptic plasticity. Results: Stress impaired spatial memory significantly (P

Characterization of stress-induced suppression of long-term potentiation in the hippocampal CA1 field of freely moving rats.

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Hirata, Riki; Togashi, Hiroko; Matsumoto, Machiko; Yamaguchi, Taku; Izumi, Takeshi; Yoshioka, Mitsuhiro

2008-08-21

Several lines of evidence have shown that exposure to stress impairs long-term potentiation (LTP) in the CA1 field of the hippocampus, but the detailed mechanisms for this effect remain to be clarified. The present study elucidated the synaptic mechanism of stress-induced LTP suppression in conscious, freely moving rats using electrophysiological approaches. Open field stress (i.e., novel environment stress) and elevated platform stress (i.e., uncontrollable stress) were employed. Basal synaptic transmission was significantly reduced during exposure to elevated platform stress but not during exposure to open field stress. LTP induction was blocked by elevated platform stress but not influenced by open field stress. Significant increases in serum corticosterone levels were observed in the elevated platform stress group compared with the open field stress group. Furthermore, LTP suppression induced by elevated platform stress was prevented by pretreatment with an anxiolytic drug diazepam (1 mg/kg, i.p.). These results suggest that stress-induced LTP suppression depends on the relative intensity of the stressor. The inhibitory synaptic response induced by an intense psychological stress, such as elevated platform stress, may be attributable to LTP impairment in the CA1 field of the hippocampus.

Anxiety and depression in long-term testicular germ cell tumor survivors.

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Vehling, S; Mehnert, A; Hartmann, M; Oing, C; Bokemeyer, C; Oechsle, K

2016-01-01

Despite a good prognosis, the typically young age at diagnosis and physical sequelae may cause psychological distress in germ cell tumor survivors. We aimed to determine the frequency of anxiety and depression and analyze the impact of demographic and disease-related factors. We enrolled N=164 testicular germ cell tumor survivors receiving routine follow-up care at the University Cancer Center Hamburg and a specialized private practice (mean, 11.6 years after diagnosis). Patients completed the Generalized Anxiety Disorder Screener-7, the Patient Health Questionnaire-9 and the Memorial Symptom Assessment Scale-Short Form. We found clinically significant anxiety present in 6.1% and depression present in 7.9% of survivors. A higher number of physical symptoms and having children were significantly associated with higher levels of both anxiety and depression in multivariate regression analyses controlling for age at diagnosis, cohabitation, socioeconomic status, time since diagnosis, metastatic disease and relapse. Younger age at diagnosis and shorter time since diagnosis were significantly associated with higher anxiety. Although rates of clinically relevant anxiety and depression were comparably low, attention toward persisting physical symptoms and psychosocial needs related to a young age at diagnosis and having children will contribute to address potential long-term psychological distress in germ cell tumor survivors. Copyright © 2016 Elsevier Inc. All rights reserved.

The role of GABA in NMDA-dependent long term depression (LTD) of rat medial vestibular nuclei.

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Grassi, S; Della Torre, G; Capocchi, G; Zampolini, M; Pettorossi, V E

1995-11-20

The role of GABA in NMDA-dependent long term depression (LTD) in the medial vestibular nuclei (MVN) was studied on rat brainstem slices. High frequency stimulation (HFS) of the primary vestibular afferents induces a long lasting reduction of the polysynaptic (N2) component of the field potentials recorded in the dorsal portion of the MVN. The induction but not the maintenance of this depression was abolished by AP5, a specific blocking agent for glutamate NMDA receptors. The involvement of GABA in mediating the depression was checked by applying the GABAA and GABAB receptor antagonists, bicuculline and saclofen, before and after HFS. Under bicuculline and saclofen perfusion, HFS provoked a slight potentiation of the N2 wave, while the N2 depression clearly emerged after drug wash-out. This indicates that GABA is not involved in inducing the long term effect, but it is necessary for its expression. Similarly, the LTD reversed and a slight potentiation appeared when both drugs were administered after its induction. Most of these effects were due to the bicuculline, suggesting that GABAA receptors contribute to LTD more than GABAB do. According to our results, it is unlikely that the long lasting vestibular depression is the result of a homosynaptic LTD. On the contrary, our findings suggest that the depression is due to an enhancement of the GABA inhibitory effect, caused by an HFS dependent increase in gabaergic interneuron activity, which resets vestibular neuron excitability at a lower level.

Comparison of quality of sleep, depression, and life satisfaction between older adults in nursing homes and long-term care hospitals in Korea.

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Kim, Kon Hee; Hwang, Eun Hee

2017-01-01

The purpose of the present study was to identify the sleep quality, depression, and life satisfaction between nursing home and long-term care hospital residents. Data was collected through a structured questionnaire survey of 61 nursing home residents and 74 long-term care hospital residents. Descriptive statistics, t-test, χ 2 -test, anova, Pearson's correlation were used to analyze the data. The residents living in a nursing home showed higher subjective health status and sleep quality than long-term care hospital residents. Depression did not show a significant difference between them. However, there was a significant difference in depression score by subjective health status. Sleep quality and depression showed a significant negative correlation for both residents. In terms of depression and life satisfaction, nursing home residents showed a significant negative correlation, and long-term care hospital residents showed a significant positive correlation. These results show that environmental management is essential to enhance sleep quality, thus depression and subjective health status will be improved. Geriatr Gerontol Int 2017; 17: 142-149. © 2015 Japan Geriatrics Society.

Persistent changes in ability to express long-term potentiation/depression in the rat hippocampus after juvenile/adult stress.

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Maggio, Nicola; Segal, Menahem

2011-04-15

The ventral hippocampus (VH) was recently shown to express lower magnitude long-term potentiation (LTP) compared with the dorsal hippocampus (DH). Exposure to acute stress reversed this difference, and VH slices from stressed rats expressed larger LTP than that produced in the DH, which was reduced by stress. Stressful experience in adolescence has been shown to produce long-lasting effects on animal behavior and on ability to express LTP/long-term depression (LTD) of reactivity to afferent stimulation in the adult. We are interested in possible interactions between juvenile and adult stress in their effects of adult plasticity. We studied the effects of a composite juvenile (28-30 days) stress, followed by a reminder stressful experience in the young adult (60 days) rat, on the ability to produce LTP and LTD in CA1 region of slices of the VH and DH. Juvenile or adult stress produced a transient decrease in ability to express LTP in DH and a parallel increase in LTP in VH. Stress in the young adult after juvenile stress produced a striking prolongation of the DH/VH disparity with respect to the ability to express both LTP and LTD into the adulthood of the rat. These results have important implications for the impact of juvenile stress on adult neuronal plasticity and on the understanding the functions of the different sectors of the hippocampus. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Associations between Depressive State and Impaired Higher-Level Functional Capacity in the Elderly with Long-Term Care Requirements.

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Ogata, Soshiro; Hayashi, Chisato; Sugiura, Keiko; Hayakawa, Kazuo

2015-01-01

Depressive state has been reported to be significantly associated with higher-level functional capacity among community-dwelling elderly. However, few studies have investigated the associations among people with long-term care requirements. We aimed to investigate the associations between depressive state and higher-level functional capacity and obtain marginal odds ratios using propensity score analyses in people with long-term care requirements. We conducted a cross-sectional study based on participants aged ≥ 65 years (n = 545) who were community dwelling and used outpatient care services for long-term preventive care. We measured higher-level functional capacity, depressive state, and possible confounders. Then, we estimated the marginal odds ratios (i.e., the change in odds of impaired higher-level functional capacity if all versus no participants were exposed to depressive state) by logistic models using generalized linear models with the inverse probability of treatment weighting (IPTW) for propensity score and design-based standard errors. Depressive state was used as the exposure variable and higher-level functional capacity as the outcome variable. The all absolute standardized differences after the IPTW using the propensity scores were functional capacity.

Long Term Effectiveness of Cognitive Behavioral Group Therapy for Treatment of Major Depressive Disorder: A Systematic Review

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Ceren Gokdag

2016-03-01

Full Text Available The aim of the study was to conduct systematic review the articles on long term effectiveness of cognitive-behavioral group therapy for treatment of major depressive disorder. Articles in English and Turkish published between the years of 2000 and 2015 (January were searched in national and international databases. The articles that did not include follow-up studies were excluded. Although the main aim of this study is to evaluate permanent effect of the cognitive behavioral group therapy, 21 articles that met the criteria were examined also in terms of some other variables such as research method, therapy characteristics and post test results. The findings of the articles revealed that cognitive-behavioral group therapy is effective for major depressive disorder and post therapy gains are maintained for a long time. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2016; 8(Supplement 1: 23-38

Development of a Curriculum for Long-Term Care Nurses to Improve Recognition of Depression in Dementia

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Williams, Christine L.; Molinari, Victor; Bond, Jennifer; Smith, Michael; Hyer, Kathryn; Malphurs, Julie

2006-01-01

There is increasing recognition of the severe consequences of depression in long-term care residents with dementia. Most health care providers are unprepared to recognize and to manage the complexity of depression in dementia. Targeted educational initiatives in nursing homes are needed to address this growing problem. This paper describes the…

Prevalence of depression among recently admitted long-term care patients in Norwegian nursing homes: associations with diagnostic workup and use of antidepressants.

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Iden, Kristina Riis; Engedal, Knut; Hjorleifsson, Stefan; Ruths, Sabine

2014-01-01

We aimed to establish the prevalence of depression among recently admitted long-term care patients and to examine associations with diagnostic initiatives and treatment as recorded in patients' medical records. Eighty-eight long-term care patients were included. Depression was diagnosed according to the ICD-10 criteria; patients were screened for depression using the Cornell Scale for Depression in Dementia (CSDD) and for dementia with the Clinical Dementia Rating (CDR) scale. Depression was found in 25% of the patients according to the ICD-10 criteria and in 31% according to a CSDD sum score of ≥ 8. Diagnostic initiatives were documented in the medical records of half of the patients with depression. Forty-four percent of the patients were prescribed antidepressants and 23% actually received them for the treatment of depression. Depression was prevalent among recently admitted long-term care patients, but diagnostic initiatives were too rarely used. Antidepressants were commonly prescribed, but depression was the indication for treatment in only half of the cases. Screening for depression should be mandatory on admission.

Long-term deficiency of circulating and hippocampal insulin-like growth factor I induces depressive behavior in adult mice: A potential model of geriatric depression

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Mitschelen, Matthew; Yan, Han; Farley, Julie A.; Warrington, Junie P.; Han, Song; Hereñú, Claudia B.; Csiszar, Anna; Ungvari, Zoltan; Bailey-Downs, Lora C.; Bass, Caroline E.; Sonntag, William E.

2011-01-01

Numerous studies support the hypothesis that deficiency of insulin-like growth factor I (IGF-1) in adults contributes to depression, but direct evidence is limited. Many psychological and pro-cognitive effects have been attributed to IGF-1, but appropriate animal models of adult-onset IGF-1 deficiency are lacking. In this study, we use a viral-mediated Cre-loxP system to knockout the Igf1 gene in either the liver, neurons of the CA1 region of the hippocampus, or both. Knockout of liver Igf1 reduced serum IGF-1 levels by 40% and hippocampal IGF-1 levels by 26%. Knockout of Igf1 in CA1 reduced hippocampal IGF-1 levels by 13%. The most severe reduction in hippocampal IGF-1 occurred in the group with knockouts in both liver and CA1 (36% reduction), and was associated with a 3.5-fold increase in immobility in the forced swim test. Reduction of either circulating or hippocampal IGF-1 levels did not alter anxiety measured in an open field and elevated plus maze, nor locomotion in the open field. Furthermore, local compensation for deficiencies in circulating IGF-1 did not occur in the hippocampus, nor were serum levels of IGF-1 upregulated in response to the moderate decline of hippocampal IGF-1 caused by the knockouts in CA1. We conclude that adult-onset IGF-1 deficiency alone is sufficient to induce a depressive phenotype in mice. Furthermore, our results suggest that individuals with low brain levels of IGF-1 are at increased risk for depression and these behavioral effects are not ameliorated by increased local IGF-1 production or transport. Our study supports the hypothesis that the natural IGF-1 decline in aging humans may contribute to geriatric depression. PMID:21524689

Six-month outcomes of co-occurring delirium, depression, and dementia in long-term care.

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McCusker, Jane; Cole, Martin G; Voyer, Philippe; Monette, Johanne; Champoux, Nathalie; Ciampi, Antonio; Vu, Minh; Belzile, Eric

2014-12-01

To describe the 6-month outcomes of co-occurring delirium (full syndrome and subsyndromal symptoms), depression, and dementia in a long-term care (LTC) population. Observational, prospective cohort study with 6-month follow-up conducted from 2005 to 2009. Seven LTC facilities in the province of Quebec, Canada. Newly admitted and long-term residents recruited consecutively from lists of residents aged 65 and older admitted for LTC, with stratification into groups with and without severe cognitive impairment. The study sample comprised 274 residents with complete data at baseline on delirium, dementia, and depression. Outcomes were 6-month mortality, functional decline (10-point decline from baseline on 100-point Barthel scale), and cognitive decline (3-point decline on 30-point Mini-Mental State Examination). Predictors included delirium (full syndrome or subsyndromal symptoms, using the Confusion Assessment Method), depression (Cornell Scale for Depression in Dementia), and dementia (chart diagnosis). The baseline prevalences of delirium, subsyndromal symptoms of delirium (SSD), depression, and dementia were 11%, 44%, 19%, and 66%, respectively. By 6 months, 10% of 274 had died, 19% of 233 had experienced functional decline, and 17% of 246 had experienced cognitive decline. An analysis using multivariable generalized linear models found the following significant interaction effects (P delirium and depression for functional decline, and between SSD and dementia for cognitive decline. Co-occurrence of delirium, SSD, depression, and dementia in LTC residents appears to affect some 6-month outcomes. Because of limited statistical power, it was not possible to draw conclusions about the effects of the co-occurrence of some syndromes on poorer outcomes. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

Hippocampal Focal Knockout of CBP Affects Specific Histone Modifications, Long-Term Potentiation, and Long-Term Memory

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Barrett, Ruth M; Malvaez, Melissa; Kramar, Eniko; Matheos, Dina P; Arrizon, Abraham; Cabrera, Sara M; Lynch, Gary; Greene, Robert W; Wood, Marcelo A

2011-01-01

To identify the role of the histone acetyltransferase (HAT) CREB-binding protein (CBP) in neurons of the CA1 region of the hippocampus during memory formation, we examine the effects of a focal homozygous knockout of CBP on histone modifications, gene expression, synaptic plasticity, and long-term memory. We show that CBP is critical for the in vivo acetylation of lysines on histones H2B, H3, and H4. CBP's homolog p300 was unable to compensate for the loss of CBP. Neurons lacking CBP maintained phosphorylation of the transcription factor CREB, yet failed to activate CREB:CBP-mediated gene expression. Loss of CBP in dorsal CA1 of the hippocampus resulted in selective impairments to long-term potentiation and long-term memory for contextual fear and object recognition. Together, these results suggest a necessary role for specific chromatin modifications, selectively mediated by CBP in the consolidation of memories. PMID:21508930

The effects of light therapy on depression and sleep disruption in older adults in a long-term care facility.

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Wu, Mann-Chian; Sung, Huei-Chuan; Lee, Wen-Li; Smith, Graeme D

2015-10-01

This study aims to evaluate the effect of light therapy on depression and sleep disruption in older adults residing in a long-term care facility. Psychological morbidity is a problem commonly seen in older adults residing in long-term care facilities. Limited research has addressed the effect of light therapy on depression in this population. A quasi-experimental pretest and posttest design was used. Thirty-four participants in the experimental group received light therapy by sitting in front of a 10000-lux light box 30 min in the morning, three times a week for 4 weeks. Thirty-one participants in the control group received routine care without light therapy. Depression was measured by Geriatric Depression Scale-Short Form at baseline and week 4. After receiving 4 weeks of light therapy, the mean depression score in the experimental group decreased from 7.24 (SD3.42) at pretest to 5.91 (SD 3.40) at posttest, and had a significant reduction (t = 2.22, P = 0.03). However, there was no significant difference in depression score and sleep disruption between the experimental group and control group. Light therapy might have the potential to reduce depressive symptoms and sleep disruption and may be a viable intervention to improve mental health of older adults in the long-term care facilities. © 2014 Wiley Publishing Asia Pty Ltd.

Relationship Between Depressive Symptoms and Social Cognitive Processing in Partners of Long-Term Breast Cancer Survivors.

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Cohee, Andrea A; Adams, Rebecca N; Fife, Betsy L; Von Ah, Diane M; Monahan, Patrick O; Zoppi, Kathleen A; Cella, David; Champion, Victoria L

2017-01-01

To determine (a) if depressive symptoms in partners of long-term breast cancer survivors (BCSs) could be predicted by social cognitive processing theory and (b) if partners of younger and older BCSs were differentially affected by the cancer experience.
. A cross-sectional, descriptive study using self-report questionnaires.
. Indiana University in Bloomington and 97 ECOG-ACRIN Cancer Research Group sites in the United States.
. 508 partners of BCSs diagnosed three to eight years prior to the study. 
. Secondary data mediation analyses were conducted to determine if cognitive processing mediated the relationship between social constraints and depressive symptoms. Age-related differences on all scales were tested.
. Depressive symptoms; secondary variables included social constraints, cognitive processing (avoidance and intrusive thoughts), and potentially confounding variables.
. Cognitive processing mediated the relationship between social constraints and depressive symptoms for partners. Partners of younger BCSs reported worse outcomes on all measures than partners of older BCSs.
. As predicted by the social cognitive processing theory, cognitive processing mediated the relationship between social constraints and depressive symptoms. In addition, partners of younger BCSs fared worse on social constraints, intrusive thoughts, and depressive symptoms than partners of older BCSs. 
. Results provide support for using the social cognitive processing theory in an intervention design with partners of long-term BCSs to decrease depressive symptoms.

Association of long-term patterns of depressive symptoms and attention/executive function among older men with and without human immunodeficiency virus.

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Armstrong, Nicole M; Surkan, Pamela J; Treisman, Glenn J; Sacktor, Ned C; Irwin, Michael R; Teplin, Linda A; Stall, Ron; Martin, Eileen M; Becker, James T; Munro, Cynthia; Levine, Andrew J; Jacobson, Lisa P; Abraham, Alison G

2017-08-01

Older HIV-infected men are at higher risk for both depression and cognitive impairments, compared to HIV-uninfected men. We evaluated the association between longitudinal patterns of depressive symptoms and attention/executive function in HIV-infected and HIV-uninfected men aged 50+ years to understand whether HIV infection influenced the long-term effect of depression on attention/executive function. Responses to the Center for Epidemiologic Studies-Depression scale and attention/executive function tests (Trail Making Test Part B and Symbol Digit Modalities Test) were collected semiannually from May 1986 to April 2015 in 1611 men. Group-based trajectory models, stratified by HIV status, were used to identify latent patterns of depressive symptoms and attention/executive function across 12 years of follow-up. We identified three depression patterns for HIV-infected and HIV-uninfected men (rare/never 50.0 vs. 60.6%, periodically depressed 29.6 vs. 24.5%, chronic high 20.5 vs.15.0%, respectively) and three patterns of attention/executive function for HIV-infected and HIV-uninfected men (worst-performing 47.4 vs. 45.1%; average 41.9 vs. 47.0%; best-performing 10.7 vs. 8.0%, respectively). Multivariable logistic regression models were used to assess associations between depression patterns and worst-performing attention/executive function. Among HIV-uninfected men, those in the periodically depressed and chronic high depressed groups had higher odds of membership in the worst-performing attention/executive function group (adjusted odds ratio [AOR] = 1.45, 95% CI 1.04, 2.03; AOR = 2.25, 95% CI 1.49, 3.39, respectively). Among HIV-infected men, patterns of depression symptoms were not associated with patterns of attention/executive function. Results suggest that HIV-uninfected, but not HIV-infected, men with chronic high depression are more likely to experience a long-term pattern of attention/executive dysfunction.

Neo-synthesis of estrogenic or androgenic neurosteroids determine whether long-term potentiation or depression is induced in hippocampus of male rat.

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Di Mauro, Michela; Tozzi, Alessandro; Calabresi, Paolo; Pettorossi, Vito Enrico; Grassi, Silvarosa

2015-01-01

Estrogenic and androgenic steroids synthesized in the brain may rapidly modulate synaptic plasticity interacting with specific membrane receptors. We explored by electrophysiological recordings in hippocampal slices of male rat the influence of 17β-estradiol (E2) and 5α-dihydrotestosterone (DHT) neo-synthesis on the synaptic changes induced in the CA1 region. Induction of long-term depression (LTD) and depotentiation (DP) by low frequency stimulation (LFS, 15 min-1 Hz) and of long-term potentiation (LTP) by high frequency stimulation (HFS, 1 s-100 Hz), medium (MFS, 1 s-50 Hz), or weak (WFS, 1 s-25 Hz) frequency stimulation was assayed under inhibitors of enzymes converting testosterone (T) into DHT (5α-reductase) and T into E2 (P450-aromatase). We found that LFS-LTD depends on DHT synthesis, since it was fully prevented under finasteride, an inhibitor of DHT synthesis, and rescued by exogenous DHT, while the E2 synthesis was not involved. Conversely, the full development of HFS-LTP requires the synthesis of E2, as demonstrated by the LTP reduction observed under letrozole, an inhibitor of E2 synthesis, and its full rescue by exogenous E2. For intermediate stimulation protocols DHT, but not E2 synthesis, was involved in the production of a small LTP induced by WFS, while the E2 synthesis was required for the MFS-dependent LTP. Under the combined block of DHT and E2 synthesis all stimulation frequencies induced partial LTP. Overall, these results indicate that DHT is required for converting the partial LTP into LTD whereas E2 is needed for the full expression of LTP, evidencing a key role of the neo-synthesis of sex neurosteroids in determining the direction of synaptic long-term effects.

Neo-synthesis of estrogenic or androgenic neurosteroids determine whether long-term potentiation or depression is induced in hippocampus of male rat

Directory of Open Access Journals (Sweden)

Michela eDi Mauro

2015-10-01

Full Text Available Estrogenic and androgenic steroids synthesized in the brain may rapidly modulate synaptic plasticity interacting with specific membrane receptors. We explored by electrophysiological recordings in hippocampal slices of male rat the influence of 17b-estradiol (E2 and 5a-dihydrotestosterone (DHT neo-synthesis on the synaptic changes induced in the CA1 region. Induction of long-term depression (LTD and depotentiation (DP by low frequency stimulation (LFS, 15 min-1 Hz and of long-term potentiation (LTP by high (HFS, 1 s-100 Hz, medium (MFS, 1 s-50 Hz, or weak (WFS, 1 s-25 Hz frequency stimulation was assayed under inhibitors of enzymes converting testosterone (T into DHT (5a-reductase and T into E2 (P450-aromatase. We found that LFS-LTD depends on DHT synthesis, since it was fully prevented under finasteride, an inhibitor of DHT synthesis, and rescued by exogenous DHT, while the E2 synthesis was not involved. Conversely, the full development of HFS-LTP requires the synthesis of E2, as demonstrated by the LTP reduction observed under letrozole, an inhibitor of E2 synthesis, and its full rescue by exogenous E2. For intermediate stimulation protocols DHT, but not E2 synthesis, was involved in the production of a small LTP induced by WFS, while the E2 synthesis was required for the MFS-dependent LTP. Under the combined block of DHT and E2 synthesis all stimulation frequencies induced partial LTP. Overall, these results indicate that DHT is required for converting the partial LTP into LTD whereas E2 is needed for the full expression of LTP, evidencing a key role of the neo-synthesis of sex neurosteroids in determining the direction of synaptic long-term effects.

Presynaptic D2 dopamine receptors control long-term depression expression and memory processes in the temporal hippocampus.

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Rocchetti, Jill; Isingrini, Elsa; Dal Bo, Gregory; Sagheby, Sara; Menegaux, Aurore; Tronche, François; Levesque, Daniel; Moquin, Luc; Gratton, Alain; Wong, Tak Pan; Rubinstein, Marcelo; Giros, Bruno

2015-03-15

Dysfunctional mesocorticolimbic dopamine signaling has been linked to alterations in motor and reward-based functions associated with psychiatric disorders. Converging evidence from patients with psychiatric disorders and use of antipsychotics suggests that imbalance of dopamine signaling deeply alters hippocampal functions. However, given the lack of full characterization of a functional mesohippocampal pathway, the precise role of dopamine transmission in memory deficits associated with these disorders and their dedicated therapies is unknown. In particular, the positive outcome of antipsychotic treatments, commonly antagonizing D2 dopamine receptors (D2Rs), on cognitive deficits and memory impairments remains questionable. Following pharmacologic and genetic manipulation of dopamine transmission, we performed anatomic, neurochemical, electrophysiologic, and behavioral investigations to uncover the role of D2Rs in hippocampal-dependent plasticity and learning. Naïve mice (n = 4-21) were used in the different procedures. Dopamine modulated both long-term potentiation and long-term depression in the temporal hippocampus as well as spatial and recognition learning and memory in mice through D2Rs. Although genetic deletion or pharmacologic blockade of D2Rs led to the loss of long-term potentiation expression, the specific genetic removal of presynaptic D2Rs impaired long-term depression and performances on spatial memory tasks. Presynaptic D2Rs in dopamine fibers of the temporal hippocampus tightly modulate long-term depression expression and play a major role in the regulation of hippocampal learning and memory. This direct role of mesohippocampal dopamine input as uncovered here adds a new dimension to dopamine involvement in the physiology underlying deficits associated with neuropsychiatric disorders. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Do psychosocial working conditions modify the effect of depressive symptoms on long-term sickness absence?

DEFF Research Database (Denmark)

Hjarsbech, Pernille U.; Christensen, Karl Bang; Andersen, Rikke Voss

2013-01-01

, but not psychosocial working conditions, predicted LTSA. Psychosocial working conditions did not statistically significantly modify the effect of depressive symptoms on LTSA. Conclusions: Psychosocial working conditions did not modify the effect of depressive symptoms on LTSA. The results, however, need......Background: The objective of this study was to investigate whether work unit-levels of psychosocial working conditions modify the effect of depressive symptoms on risk of long-term sickness absence (LTSA). Methods: A total of 5,416 Danish female eldercare workers from 309 work units were surveyed...... using questionnaires assessing depressive symptoms and psychosocial working conditions. LTSA was derived from a national register. We aggregated scores of psychosocial working conditions to the work unit-level and conducted multi-level Poisson regression analyses. Results: Depressive symptoms...

Work characteristics and return to work in long-term sick-listed employees with depressive symptoms.

NARCIS (Netherlands)

Huijs, J.J.J.M.; Koppes, L.L.J.; Taris, T.W.; Blonk, R.W.B.

2017-01-01

Purpose: The present study investigated the relations between work characteristics, depressive symptoms and duration until full return to work (RTW) among long-term sick-listed employees. This knowledge may add to the development of effective interventions and prevention, especially since work

Work characteristics and return to work in long-term sick-listed employees with depressive symptoms

NARCIS (Netherlands)

Huijs, Jenny; Koppes, L.L.J.; Taris, A.W.; Blonk, R.W.B.

2017-01-01

Purpose The present study investigated the relations between work characteristics, depressive symptoms and duration until full return to work (RTW) among long-term sick-listed employees. This knowledge may add to the development of effective interventions and prevention, especially since work

Work Characteristics and Return to Work in Long-Term Sick-Listed Employees with Depressive Symptoms

NARCIS (Netherlands)

Huijs, J.J.J.M.; Koppes, L.L.J.; Taris, T.W.; Blonk, R.WE.B.

2017-01-01

Purpose The present study investigated the relations between work characteristics, depressive symptoms and duration until full return to work (RTW) among long-term sick-listed employees. This knowledge may add to the development of effective interventions and prevention, especially since work

CaMKII knockdown affects both early and late phases of olfactory long-term memory in the honeybee.

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Scholl, Christina; Kübert, Natalie; Muenz, Thomas S; Rössler, Wolfgang

2015-12-01

Honeybees are able to solve complex learning tasks and memorize learned information for long time periods. The molecular mechanisms mediating long-term memory (LTM) in the honeybee Apis mellifera are, to a large part, still unknown. We approached this question by investigating the potential function of the calcium/calmodulin-dependent protein kinase II (CaMKII), an enzyme known as a 'molecular memory switch' in vertebrates. CaMKII is able to switch to a calcium-independent constitutively active state, providing a mechanism for a molecular memory and has further been shown to play an essential role in structural synaptic plasticity. Using a combination of knockdown by RNA interference and pharmacological manipulation, we disrupted the function of CaMKII during olfactory learning and memory formation. We found that learning, memory acquisition and mid-term memory were not affected, but all manipulations consistently resulted in an impaired LTM. Both early LTM (24 h after learning) and late LTM (72 h after learning) were significantly disrupted, indicating the necessity of CaMKII in two successive stages of LTM formation in the honeybee. © 2015. Published by The Company of Biologists Ltd.

Notation of Depression in Case Records of Older Adults in Community Long-Term Care

Science.gov (United States)

Proctor, Enola K.

2008-01-01

Although significant numbers of social service clients experience mental health problems, virtually no research has examined the responsiveness of social service agencies to mental disorder. This article examines the extent to which client depression is reflected in records of a public social service agency, community long-term care (CLTC).…

Layer 2/3 synapses in monocular and binocular regions of tree shrew visual cortex express mAChR-dependent long-term depression and long-term potentiation.

Science.gov (United States)

McCoy, Portia; Norton, Thomas T; McMahon, Lori L

2008-07-01

Acetylcholine is an important modulator of synaptic efficacy and is required for learning and memory tasks involving the visual cortex. In rodent visual cortex, activation of muscarinic acetylcholine receptors (mAChRs) induces a persistent long-term depression (LTD) of transmission at synapses recorded in layer 2/3 of acute slices. Although the rodent studies expand our knowledge of how the cholinergic system modulates synaptic function underlying learning and memory, they are not easily extrapolated to more complex visual systems. Here we used tree shrews for their similarities to primates, including a visual cortex with separate, defined regions of monocular and binocular innervation, to determine whether mAChR activation induces long-term plasticity. We find that the cholinergic agonist carbachol (CCh) not only induces long-term plasticity, but the direction of the plasticity depends on the subregion. In the monocular region, CCh application induces LTD of the postsynaptic potential recorded in layer 2/3 that requires activation of m3 mAChRs and a signaling cascade that includes activation of extracellular signal-regulated kinase (ERK) 1/2. In contrast, layer 2/3 postsynaptic potentials recorded in the binocular region express long-term potentiation (LTP) following CCh application that requires activation of m1 mAChRs and phospholipase C. Our results show that activation of mAChRs induces long-term plasticity at excitatory synapses in tree shrew visual cortex. However, depending on the ocular inputs to that region, variation exists as to the direction of plasticity, as well as to the specific mAChR and signaling mechanisms that are required.

Long-term sustainability of microbial-induced CaCO3 precipitation in aqueous media.

Science.gov (United States)

Gat, Daniella; Ronen, Zeev; Tsesarsky, Michael

2017-10-01

Microbially induced CaCO 3 precipitation (MICP) via urea hydrolysis is an emerging technique for soil amelioration, building materials rehabilitation and pollutants sequestration amongst other various environmental applications. The successful application of MICP requires the sustainability of the precipitated CaCO 3 ; to which the fate of ammonia, the main by-product of ureolysis, is potentially significante. Ammonia volatilization and biological ammonia oxidation both induce a pH decrease, which, in turn, might cause CaCO 3 dissolution. To examine the potential effect of accumulated ammonia on precipitated CaCO 3 , we conducted a long-term MICP batch experiment, using environmental enrichment cultures of ureolytic bacteria. Here we show that CaCO 3 precipitation was completed within 15-27 days, along with a rise in ammonium concentration. Following completion of ureolysis and precipitation, ammonium concentrations decreased, leading to a pH decrease. About 30 days after precipitation was completed, as much as 30% CaCO 3 dissolution, was observed. A two-step model, describing urea hydrolysis followed by the removal of ammonia from the precipitation solution, predicted CaCO 3 dissolution due to ammonia volatilization. We suggest that ureolytic MICP might result in ammonia volatilization, leading to significant CaCO 3 dissolution. These results provide basic insights into the sustainability of ureolytic MICP and should further encourage removal of the accumulated ammonia from the treated site. Copyright © 2017 Elsevier Ltd. All rights reserved.

A pilot study of the feasibility of long-term human bone balance during perimenopause using a 41Ca tracer

International Nuclear Information System (INIS)

Hui, S.K.; Prior, J.; Gelbart, Z.; Johnson, R.R.; Lentle, B.C.; Paul, M.

2007-01-01

The mechanisms governing calcium fluxes during bone remodeling processes in perimenopausal women are poorly known. Despite higher, albeit erratic, estradiol levels in perimenopause, spine bone loss is greater than during the first five years past the final menstrual flow when estradiol becomes low. Understanding changes during this dynamic transition are important to prevent fragility fractures in midlife and older women. The exploration of long-lived 41 Ca (T 1/2 = 1.04 x 10 5 yrs) tracer measurements using accelerator mass spectrometry (AMS) leads to the possibility of monitoring bone remodeling balance. With this new technology, we explored a pilot long-term feasibility study of bone health by measuring the 41 Ca trace element in urine for six years from premenopausal to later perimenopausal phases in one midlife woman. We measured bone mineral density in parallel

Ethanol attenuation of long-term depression in the nucleus accumbens can be overcome by activation of TRPV1 receptors.

Science.gov (United States)

Renteria, Rafael; Jeanes, Zachary M; Morrisett, Richard A

2014-11-01

Altered expression of synaptic plasticity within the nucleus accumbens (NAc) constitutes a critical neuroadaptive response to ethanol (EtOH) and other drugs of abuse. We have previously reported that N-methyl-D-aspartate receptor (NMDAR)-dependent long-term depression (LTD) is markedly affected by chronic intermittent ethanol exposure in vivo; however, endocannabinoid (eCB)-dependent synaptic depression, despite being very well-documented in the dorsal striatum, is much less well understood in the NAc. Whole cell patch clamp electrophysiology was used to investigate interactions between these different plasticity-induction systems. Excitatory postsynaptic currents (EPSCs) were measured in the NAc shell and NMDAR-LTD was induced by a pairing protocol (500 stimuli at 1 Hz stimulation [low-frequency stimulation (LFS)] paired with postsynaptic depolarization to -50 mV). AM251, a CB1 receptor antagonist, was used to determine whether this form of LTD is modulated by eCBs. To determine the effect of EtOH on a purely eCB-dependent response in the NAc, depolarization-induced suppression of excitation (DSE) was used in the presence of 40 mM EtOH. Finally, we determined whether the enhancement of eCB signaling with URB597, a fatty acid amide hydrolase inhibitor, and AM404, an anandamide re-uptake inhibitor would also modulate LFS LTD in the presence of NMDAR blockade or EtOH. In the presence of AM251, the LFS pairing protocol resulted in NMDAR-dependent long-term potentiation that was blocked with either EtOH or DL-APV. We also found that DSE in the NAc shell was blocked by AM251 and suppressed by EtOH. Enhanced eCB signaling rescued NAc-LTD expression in the presence of EtOH through a distinct mechanism requiring activation of TRPV1 receptors. EtOH modulation of synaptic plasticity in the NAc is dependent upon a complex interplay between NMDARs, eCBs, and TRPV1 receptors. These findings demonstrate a novel form of TRPV1-dependent LTD in the NAc shell that may be critical

Changes in prefrontal-limbic function in major depression after 15 months of long-term psychotherapy.

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Anna Buchheim

Full Text Available Neuroimaging studies of depression have demonstrated treatment-specific changes involving the limbic system and regulatory regions in the prefrontal cortex. While these studies have examined the effect of short-term, interpersonal or cognitive-behavioural psychotherapy, the effect of long-term, psychodynamic intervention has never been assessed. Here, we investigated recurrently depressed (DSM-IV unmedicated outpatients (N = 16 and control participants matched for sex, age, and education (N = 17 before and after 15 months of psychodynamic psychotherapy. Participants were scanned at two time points, during which presentations of attachment-related scenes with neutral descriptions alternated with descriptions containing personal core sentences previously extracted from an attachment interview. Outcome measure was the interaction of the signal difference between personal and neutral presentations with group and time, and its association with symptom improvement during therapy. Signal associated with processing personalized attachment material varied in patients from baseline to endpoint, but not in healthy controls. Patients showed a higher activation in the left anterior hippocampus/amygdala, subgenual cingulate, and medial prefrontal cortex before treatment and a reduction in these areas after 15 months. This reduction was associated with improvement in depressiveness specifically, and in the medial prefrontal cortex with symptom improvement more generally. This is the first study documenting neurobiological changes in circuits implicated in emotional reactivity and control after long-term psychodynamic psychotherapy.

Changes in Prefrontal-Limbic Function in Major Depression after 15 Months of Long-Term Psychotherapy

Science.gov (United States)

Buchheim, Anna; Viviani, Roberto; Kessler, Henrik; Kächele, Horst; Cierpka, Manfred; Roth, Gerhard; George, Carol; Kernberg, Otto F.; Bruns, Georg; Taubner, Svenja

2012-01-01

Neuroimaging studies of depression have demonstrated treatment-specific changes involving the limbic system and regulatory regions in the prefrontal cortex. While these studies have examined the effect of short-term, interpersonal or cognitive-behavioural psychotherapy, the effect of long-term, psychodynamic intervention has never been assessed. Here, we investigated recurrently depressed (DSM-IV) unmedicated outpatients (N = 16) and control participants matched for sex, age, and education (N = 17) before and after 15 months of psychodynamic psychotherapy. Participants were scanned at two time points, during which presentations of attachment-related scenes with neutral descriptions alternated with descriptions containing personal core sentences previously extracted from an attachment interview. Outcome measure was the interaction of the signal difference between personal and neutral presentations with group and time, and its association with symptom improvement during therapy. Signal associated with processing personalized attachment material varied in patients from baseline to endpoint, but not in healthy controls. Patients showed a higher activation in the left anterior hippocampus/amygdala, subgenual cingulate, and medial prefrontal cortex before treatment and a reduction in these areas after 15 months. This reduction was associated with improvement in depressiveness specifically, and in the medial prefrontal cortex with symptom improvement more generally. This is the first study documenting neurobiological changes in circuits implicated in emotional reactivity and control after long-term psychodynamic psychotherapy. PMID:22470470

Long-term corticosterone exposure decreases insulin sensitivity and induces depressive-like behaviour in the C57BL/6NCrl mouse.

Directory of Open Access Journals (Sweden)

Eva L van Donkelaar

Full Text Available Chronic stress or long-term administration of glucocorticoids disrupts the hypothalamus-pituitary-adrenal system leading to continuous high levels of glucocorticoids and insulin resistance (IR. This pre-diabetic state can eventually develop into type 2 diabetes mellitus and has been associated with a higher risk to develop depressive disorders. The mechanisms underlying the link between chronic stress, IR and depression remains unclear. The present study aimed to establish a stress-depression model in mice to further study the effects of stress-induced changes upon insulin sensitivity and behavioural consequences. A pilot study was conducted to establish the optimal administration route and a pragmatic measurement of IR. Subsequently, 6-month-old C57BL/6NCrl mice were exposed to long-term oral corticosterone treatment via the drinking water. To evaluate insulin sensitivity changes, blood glucose and plasma insulin levels were measured at different time-points throughout treatment and mice were behaviourally assessed in the elevated zero maze (EZM, forced swimming test (FST and open field test to reveal behavioural changes. Long-term corticosterone treatment increased body weight and decreased insulin sensitivity. The latter was revealed by a higher IR index and increased insulin in the plasma, whereas blood glucose levels remained unchanged. Corticosterone treatment induced longer immobility times in the FST, reflecting depressive-like behaviour. No effects were observed upon anxiety as measured in the EZM. The effect of the higher body weight of the CORT treated animals at time of testing did not influence behaviour in the EZM or FST, as no differences were found in general locomotor activity. Long-term corticosterone treatment via the drinking water reduces insulin sensitivity and induces depressive-like behaviour in the C57BL/6 mouse. This mouse model could thus be used to further explore the underlying mechanisms of chronic stress-induced T2

Effects of inhaled anesthetic isoflurane on long-term potentiation of CA3 pyramidal cell afferents in vivo

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Ballesteros KA

2012-11-01

Full Text Available Kristen A Ballesteros,1 Angela Sikorski,2 James E Orfila,3 Joe L Martinez Jr41Department of Biology, The University of Texas at San Antonio, San Antonio, TX, USA; 2Texas A&M University Texarkana, Texarkana, TX, USA; 3University of Colorado in Denver, Denver, CO, USA; 4University of Illinois in Chicago, Chicago, IL, USAAbstract: Isoflurane is a preferred anesthetic, due to its properties that allow a precise concentration to be delivered continually during in vivo experimentation. The major mechanism of action of isoflurane is modulation of the γ-amino butyric acid (GABAA receptor-chloride channel, mediating inhibitory synaptic transmission. Animal studies have shown that isoflurane does not cause cell death, but it does inhibit cell growth and causes long-term hippocampal learning deficits. As there are no studies characterizing the effects of isoflurane on electrophysiological aspects of long-term potentiation (LTP in the hippocampus, it is important to determine whether isoflurane alters the characteristic responses of hippocampal afferents to cornu ammonis region 3 (CA3. We investigated the effects of isoflurane on adult male rats during in vivo induction of LTP, using the mossy fiber pathway, the lateral perforant pathway, the medial perforant pathway, and the commissural CA3 (cCA3 to CA3, with intracranial administration of Ringer’s solution, naloxone, RS-aminoindan-1, 5-dicarboxylic acid (AIDA, or 3-[(R-2-carboxypiperazin-4-yl]-propo-2-enyl-1-phosphonic acid (CPP. Then, we compared these responses to published electrophysiological data, using sodium pentobarbital as an anesthetic, under similar experimental conditions. Our results showed that LTP was exhibited in animals anesthetized with isoflurane under vehicle conditions. With the exception of AIDA in the lateral perforant pathway, the defining characteristics of the four pathways appeared to remain intact, except for the observation that LTP was markedly reduced in animals

Clinical and non-clinical depressive symptoms and risk of long-term sickness absence among female employees in the Danish eldercare sector

DEFF Research Database (Denmark)

Hjarsbech, PU; Andersen, Rikke Voss; Christensen, Karl Bang

2011-01-01

was stronger for each subsequent group: MDI scores of 5–9: HR=1.07 (95% CI: 0.93–1.24); 10–14: 1.38 (1.15–1.66); 15–19: 1.54 (1.20–1.98); =20: 1.96 (1.45–2.64); clinical depression: 2.32 (1.59–3.38); after adjustment for previous LTSA, age, family status, smoking, leisure time physical activity, BMI......Background: Depression has a high point and life time prevalence and is a major cause of reduced work ability and long-term sickness absence (LTSA). Less is known of the extent to which non-clinical depressive symptoms are related to the risk of LTSA. The aim of this study was to investigate how...... non-clinical and clinical depressive symptoms are prospectively associated to subsequent LTSA. Methods: In a cohort study of 6985 femaleemployees fromthe Danish eldercare sector depressive symptoms were measured by the Major Depression Inventory (MDI) and scores (0–50) were divided into groups of 0...

A training program to enhance recognition of depression in nursing homes, assisted living, and other long-term care settings: Description and evaluation.

Science.gov (United States)

Abrams, Robert C; Nathanson, Mark; Silver, Stephanie; Ramirez, Mildred; Toner, John A; Teresi, Jeanne A

2017-01-01

Low levels of symptom recognition by staff have been "gateway" barriers to the management of depression in long-term care. The study aims were to refine a depression training program for front-line staff in long-term care and provide evaluative knowledge outcome data. Three primary training modules provide an overview of depression symptoms; a review of causes and situational and environmental contributing factors; and communication strategies, medications, and clinical treatment strategies. McNemar's chi-square tests and paired t-tests were used to examine change in knowledge. Data were analyzed for up to 143 staff members, the majority from nursing. Significant changes (p depressive disorder.

Depression treatment after myocardial infarction and long-term risk of subsequent cardiovascular events and mortality: A randomized controlled trial

NARCIS (Netherlands)

Zuidersma, M.; Conradi, H.J.; van Melle, J.P.; Ormel, J.; de Jonge, P.

2013-01-01

Objective: Evaluating the effects of implementing an antidepressant treatment strategy in depressed myocardial infarction (MI)-patients on long-term cardiovascular outcomes and all-cause mortality. Methods: MI-patients were evaluated for the presence of a diagnosis of post-MI depression at 3, 6, 9

Depression treatment after myocardial infarction and long-term risk of subsequent cardiovascular events and mortality : A randomized controlled trial

NARCIS (Netherlands)

Zuidersma, Marij; Conradi, Henk Jan; van Melle, Joost P.; Ormel, Johan; de Jonge, Peter

Objective: Evaluating the effects of implementing an antidepressant treatment strategy in depressed myocardial infarction (MI)-patients on long-term cardiovascular outcomes and all-cause mortality. Methods: MI-patients were evaluated for the presence of a diagnosis of post-MI depression at 3, 6, 9

Alterations in synaptic curvature in the dentate gyrus following induction of long-term potentiation, long-term depression, and treatment with the N-methyl-D-aspartate receptor antagonist CPP

Czech Academy of Sciences Publication Activity Database

Medvedev, N. I.; Popov, V. I.; Dallerac, G.; Davies, H.A.; Laroche, S.; Kraev, I. V.; Rodríguez Arellano, Jose Julio; Doyere, V.; Stewart, M.G.

2010-01-01

Roč. 171, č. 2 (2010), s. 390-397 ISSN 0306-4522 Institutional research plan: CEZ:AV0Z50390703 Keywords : D synaptic ultrastructure * hippocampus * long term potentiation and depression Subject RIV: FH - Neurology Impact factor: 3.215, year: 2010

A pilot study of the feasibility of long-term human bone balance during perimenopause using a {sup 41}Ca tracer

Energy Technology Data Exchange (ETDEWEB)

Hui, S.K. [Racah Institute of Physics, Hebrew University, Jerusalem 91904 (Israel) and Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota, 420 Delaware Street SE, Mayo Mail Code 494, Minneapolis, MN 55455 (United States)]. E-mail: huixx019@umn.edu; Prior, J. [Deparment of Medicine/Endocrinology, University of British Columbia, Vancouver, B.C., V5Z 1C6 (Canada); Gelbart, Z. [TRIUMF, Vancouver, B.C., V6T2A3 (Canada); Johnson, R.R. [TRIUMF, Vancouver, B.C., V6T2A3 (Canada); Lentle, B.C. [Department of Radiology, University of British Columbia, British Columbia, V8M 1V4 (Canada); Paul, M. [Racah Institute of Physics, Hebrew University, Jerusalem 91904 (Israel)

2007-06-15

The mechanisms governing calcium fluxes during bone remodeling processes in perimenopausal women are poorly known. Despite higher, albeit erratic, estradiol levels in perimenopause, spine bone loss is greater than during the first five years past the final menstrual flow when estradiol becomes low. Understanding changes during this dynamic transition are important to prevent fragility fractures in midlife and older women. The exploration of long-lived {sup 41}Ca (T {sub 1/2} = 1.04 x 10{sup 5} yrs) tracer measurements using accelerator mass spectrometry (AMS) leads to the possibility of monitoring bone remodeling balance. With this new technology, we explored a pilot long-term feasibility study of bone health by measuring the {sup 41}Ca trace element in urine for six years from premenopausal to later perimenopausal phases in one midlife woman. We measured bone mineral density in parallel.

BDNF val66met Polymorphism Impairs Hippocampal Long-Term Depression by Down-Regulation of 5-HT3 Receptors

Directory of Open Access Journals (Sweden)

Rui Hao

2017-10-01

Full Text Available Brain-derived neurotrophic factor (BDNF is a key regulator of neuronal plasticity and cognitive functions. BDNF val66met polymorphism, a human single-nucleotide polymorphism (SNP in the pro-domain of BDNF gene, is associated with deficits in activity-dependent BDNF secretion and hippocampus-dependent memory. However, the underlying mechanism remains unclear. Here we show that in the BDNFMet/Met mouse line mimicking the human SNP, BDNF expression in the hippocampus was decreased. There was a reduction in the total number of cells in hippocampal CA1 region, while hippocampal expression of mRNAs for NR2a, 2b, GluR1, 2 and GABAARβ3 subunits were up-regulated. Although basal glutamatergic neurotransmission was unaltered, hippocampal long-term depression (LTD induced by low-frequency stimulation was impaired, which was partially rescued by exogenous application of BDNF. Interestingly, 5-HT3a receptors were down-regulated in the hippocampus of BDNFMet/Met mice, whereas 5-HT2c receptors were up-regulated. Moreover, impaired LTD in BDNFMet/Met mice was reversed by 5-HT3aR agonist. Thus, these observations indicate that BDNF val66met polymorphism changes hippocampal synaptic plasticity via down-regulation of 5-HT3a receptors, which may underlie cognition dysfunction of Met allele carriers.

Posttraumatic stress disorder increases sensitivity to long term losses among patients with major depressive disorder.

Science.gov (United States)

Engelmann, Jan B; Maciuba, Britta; Vaughan, Christopher; Paulus, Martin P; Dunlop, Boadie W

2013-01-01

Decisions under risk and with outcomes that are delayed in time are ubiquitous in real life and can have a significant impact on the health and wealth of the decision-maker. Despite its potential relevance for real-world choices, the degree of aberrant risky and intertemporal decision-making in patients suffering from major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) has received little attention to date. We used a case-control design to compare decision-making in healthy control subjects (N=16) versus untreated depressed subjects in a current major depressive episode (N=20). In order to examine how major depressive disorder (MDD) may impact decision-making, subjects made decisions over (1) risky outcomes and (2) delayed outcomes in the domain of gains and losses using choice paradigms from neuroeconomics. In a pre-planned analysis, depressed subjects were subdivided into those with primary PTSD along with comorbid MDD (MDD+PTSD) versus those with primary MDD without PTSD (MDD-only). Choice behavior was modeled via a standard econometric model of intertemporal choice, a quasi-hyperbolic temporal discounting function, which was estimated for each subject group separately. Under conditions of potential gain, depressed subjects demonstrated greater discounting for gains across all time frames compared to controls. In the realm of losses, both subgroups of depressed subjects discounted more steeply than controls for short time frames. However, for delayed losses ranging from >1-10 years, MDD+PTSD subjects showed shallower discounting rates relative to MDD-only subjects, who continued to discount future losses steeply. Risk attitudes did not contribute to differences in intertemporal choice. Depressed patients make choices that minimize current pain and maximize current reward, despite severe later consequences or lost opportunities. Anxiety associated with PTSD may serve as a partially protective factor in decision-making about long-term

Long-term potentiation and depression after unilateral labyrinthectomy in the medial vestibular nucleus of rats.

Science.gov (United States)

Pettorossi, Vito Enrico; Dutia, Mayank; Frondaroli, Adele; Dieni, Cristina; Grassi, Silvarosa

2003-01-01

We previously demonstrated in rat brainstem slices that high-frequency stimulation (HFS) of the vestibular afferents induces long-term potentiation (LTP) in the ventral part (Vp) of the medial vestibular nucleus (MVN) and long-term depression (LTD) in the dorsal part (Dp). Both LTP and LTD depend on N-methyl-D-aspartate receptor activation, which increases synaptic efficacy; however, in the Dp, LTP reverses to LTD because of the activation of gamma-aminobutyric acid-ergic neurons. Here we show that the probability of inducing long-term effects in the MVN of rat brainstem slices is altered after unilateral labyrinthectomy (UL). In fact, LTP occurs less frequently in the ventral contra-lesional side compared with sham-operated rats. In the dorsal ipsi-lesional side, LTD is reduced and LTP enhanced, while the opposite occurs in the dorsal contra-lesional side. These changes in synaptic plasticity may be useful for re-balancing the tonic discharge of the MVN of the two sides during vestibular compensation, and for enhancing the dynamic responses of the deafferented MVN neurons in the long term.

The longitudinal relationship between the use of long-term care and depressive symptoms in older adults

NARCIS (Netherlands)

Pot, A.M.; Deeg, D.J.H.; Twisk, J.W.R.; Beekman, A.T.F.; Zarit, S.H.

2005-01-01

PURPOSE: The aim of this study was to estimate the longitudinal relationship between transitions in the use of long-term care and older adults' depressive symptoms and to investigate whether this relationship could be explained by markers of older adults' underlying health, or other variables

Long-term odor recognition memory in unipolar major depression and Alzheimer׳s disease.

Science.gov (United States)

Naudin, Marine; Mondon, Karl; El-Hage, Wissam; Desmidt, Thomas; Jaafari, Nematollah; Belzung, Catherine; Gaillard, Philippe; Hommet, Caroline; Atanasova, Boriana

2014-12-30

Major depression and Alzheimer׳s disease (AD) are often observed in the elderly. The identification of specific markers for these diseases could improve their screening. The aim of this study was to investigate long-term odor recognition memory in depressed and AD patients, with a view to identifying olfactory markers of these diseases. We included 20 patients with unipolar major depressive episodes (MDE), 20 patients with mild to moderate AD and 24 healthy subjects. We investigated the cognitive profile and olfactory memory capacities (ability to recognize familiar and unfamiliar odors) of these subjects. Olfactory memory test results showed that AD and depressed patients were characterized by significantly less correct responses and more wrong responses than healthy controls. Detection index did not differ significantly between patients with major depression and those with AD when the results were analyzed for all odors. However, MDE patients displayed an impairment of olfactory memory for both familiar and unfamiliar odors, whereas AD subjects were impaired only in the recognition of unfamiliar odors, with respect to healthy subjects. If preservation of olfactory memory for familiar stimuli in patients with mild to moderate AD is confirmed, this test could be used in clinical practice as a complementary tool for diagnosis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The effects of CCK-8S on spatial memory and long-term potentiation at CA1 during induction of stress in rats.

Science.gov (United States)

Sadeghi, Malihe; Reisi, Parham; Radahmadi, Maryam

2017-12-01

Cholecystokinin (CCK) has been proposed as a mediator in stress. However, it is still not fully documented what are its effects. We aimed to evaluate the effects of systemic administration of CCK exactly before induction of stress on spatial memory and synaptic plasticity at CA1 in rats. Male Wistar rats were divided into 4 groups: the control, the control-CCK, the stress and the stress-CCK. Restraint stress was induced 6 hr per day, for 24 days. Cholecystokinin sulfated octapeptide (CCK-8S) was injected (1.6 µg/kg, IP) before each session of stress induction. Spatial memory was evaluated by Morris water maze test. Long-term potentiation (LTP) in Schaffer collateral-CA1 synapses was assessed (by 100 Hz tetanization) in order to investigate synaptic plasticity. Stress impaired spatial memory significantly ( P stress group. With respect to the control group, both fEPSP amplitude and slope were significantly ( P stress group. However, there were no differences between responses of the control-CCK and Stress-CCK groups compared to the control group. The present results suggest that high levels of CCK-8S during induction of stress can modulate the destructive effects of stress on hippocampal synaptic plasticity and memory. Therefore, the mediatory effects of CCK in stress are likely as compensatory responses.

Potential long-term effects of a mind-body intervention for women with major depressive disorder: sustained mental health improvements with a pilot yoga intervention.

Science.gov (United States)

Kinser, Patricia Anne; Elswick, R K; Kornstein, Susan

2014-12-01

Despite pharmacologic and psychotherapeutic advances over the past decades, many individuals with major depressive disorder (MDD) experience recurrent depressive episodes and persistent depressive symptoms despite treatment with the usual care. Yoga is a mind-body therapeutic modality that has received attention in both the lay and research literature as a possible adjunctive therapy for depression. Although promising, recent findings about the positive mental health effects of yoga are limited because few studies have used standardized outcome measures and none of them have involved long-term follow-up beyond a few months after the intervention period. The goal of our research study was to evaluate the feasibility, acceptability, and effects of a yoga intervention for women with MDD using standardized outcome measures and a long follow-up period (1year after the intervention). The key finding is that previous yoga practice has long-term positive effects, as revealed in both qualitative reports of participants' experiences and in the quantitative data about depression and rumination scores over time. Although generalizability of the study findings is limited because of a very small sample size at the 1-year follow-up assessment, the trends in the data suggest that exposure to yoga may convey a sustained positive effect on depression, ruminations, stress, anxiety, and health-related quality of life. Whether an individual continues with yoga practice, simple exposure to a yoga intervention appears to provide sustained benefits to the individual. This is important because it is rare that any intervention, pharmacologic or non-pharmacologic, for depression conveys such sustained effects for individuals with MDD, particularly after the treatment is discontinued. Copyright © 2014 Elsevier Inc. All rights reserved.

Long-term treatment with calcium-alpha-ketoglutarate corrects secondary hyperparathyroidism.

Science.gov (United States)

Zimmermann, E; Wassmer, S; Steudle, V

1996-01-01

Calcium-alpha-ketoglutarate (Ca-ket) is known as a highly effective phosphate (P) binder in hemodialysis (HD) patients. In addition, alpha-ketoglutarate has been shown to improve metabolic alterations. We investigated the effect of long-term P-binding therapy with Ca-ket to determine whether P accumulation is the main reason of secondary hyperparathyroidism (HPT) in HD patients or not. Ca-ket was prescribed to 14 HD patients as a soluble preparation in a mean dosage of 4.5 g/day (0.975 g elemental Ca) for a period of 36 months. Serum P continuously dropped from prestudy 2.6 +/- 0.1 (mean +/- SEM) to 1.9 +/- 0.07 mmol/l (p < 0.001), whereas serum Ca increased from 2.2 +/- 0.1 to 2.47 +/- 0.08 mmol/l (p < 0.05). Thus, Ca/P ratio in serum converted significantly from 0.91 +/- 0.02 (prestudy) to 1.28 +/- 0.01 (p < 0.001). Intact parathyroid hormone (iPTH) continuously normalized in all patients from 29 +/- 5 to 8 +/- 2 pmol/l (p < 0.001). The present data show that long-term treatment with Ca-ket normalizes secondary HPT by simultaneously P binding and correcting Ca/P ratio in serum without vitamin D treatment.

The Longitudinal Relationship between the Use of Long-Term Care and Depressive Symptoms in Older Adults

Science.gov (United States)

Pot, Anne Margriet; Deeg, Dorly J.H.; Twisk, Jos W.R.; Beekman, Aartjan T.F.; Zarit, Steven H.

2005-01-01

Purpose: The aim of this study was to estimate the longitudinal relationship between transitions in the use of long-term care and older adults' depressive symptoms and to investigate whether this relationship could be explained by markers of older adults' underlying health, or other variables including demographics, personality, and partner…

The effects of co-morbidity in defining major depression subtypes associated with long-term course and severity

NARCIS (Netherlands)

Wardenaar, K. J.; van Loo, H. M.; Cai, T.; Fava, M.; Gruber, M. J.; Li, J.; de Jonge, P.; Nierenberg, A. A.; Petukhova, M. V.; Rose, S.; Sampson, N. A.; Schoevers, R. A.; Wilcox, M. A.; Alonso, J.; Bromet, E. J.; Bunting, B.; Florescu, S. E.; Fukao, A.; Gureje, O.; Hu, C.; Huang, Y. Q.; Karam, A. N.; Levinson, D.; Medina Mora, M. E.; Posada-Villa, J.; Scott, K. M.; Taib, N. I.; Viana, M. C.; Xavier, M.; Zarkov, Z.; Kessler, R. C.

2014-01-01

Background. Although variation in the long-term course of major depressive disorder (MDD) is not strongly predicted by existing symptom subtype distinctions, recent research suggests that prediction can be improved by using machine learning methods. However, it is not known whether these

Effects of short term and long term Extremely Low Frequency Magnetic Field on depressive disorder in mice: Involvement of nitric oxide pathway.

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Madjid Ansari, Alireza; Farzampour, Shahrokh; Sadr, Ali; Shekarchi, Babak; Majidzadeh-A, Keivan

2016-02-01

Previous reports on the possible effects of Extremely Low Frequency Magnetic Fields (ELF MF) on mood have been paradoxical in different settings while no study has yet been conducted on animal behavior. In addition, it was shown that ELF MF exposure makes an increase in brain nitric oxide level. Therefore, in the current study, we aimed to assess the possible effect(s) of ELF MF exposure on mice Forced Swimming Test (FST) and evaluate the probable role of the increased level of nitric oxide in the observed behavior. Male adult mice NMRI were recruited to investigate the short term and long term ELF MF exposure (0.5 mT and 50 Hz, single 2h and 2 weeks 2h a day). Locomotor behavior was assessed by using open-field test (OFT) followed by FST to evaluate the immobility time. Accordingly, NΩ-nitro-l-arginine methyl ester 30 mg/kg was used to exert anti-depressant like effect. According to the results, short term exposure did not alter the immobility time, whereas long term exposure significantly reduces immobility time (pmice, whereas short term exposure has no significant effect. Also, reversing the anti-depressant activity of L-NAME indicates a probable increase in the brain nitric oxide. Copyright © 2016 Elsevier Inc. All rights reserved.

Long-term follow-up on health-related quality of life in major depressive disorder: a 2-year European cohort study.

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Saragoussi, Delphine; Christensen, Michael Cronquist; Hammer-Helmich, Lene; Rive, Benoît; Touya, Maëlys; Haro, Josep Maria

2018-01-01

Major depressive disorder (MDD) is associated with significant impairments in health-related quality of life (HRQoL) and everyday functioning. This cohort study investigated the long-term development of HRQoL in patients with MDD and its association with patient characteristics, including depressive symptom severity and cognitive symptoms. The Prospective Epidemiological Research on Functioning Outcomes Related to Major depressive disorder (PERFORM) study was a longitudinal cohort study conducted in 1,159 outpatients aged 18-65 years with MDD in France, Germany, Spain, Sweden, and the UK. The patients were either initiating antidepressant monotherapy or undergoing their first switch of antidepressant. HRQoL was assessed using the Medical Outcomes Study Short-Form 12-item Health Survey (SF-12) up to month 12 and the EuroQol Five Dimensions questionnaire up to month 24 (UK only). Depressive symptom severity was assessed up to month 24 by the patient-reported Patient Health Questionnaire and cognitive symptoms by the Perceived Deficit Questionnaire. Multivariate analyses were performed to identify patient characteristics associated with HRQoL. Mental HRQoL was severely impaired at baseline versus normative data (mean [SD] SF-12 mental component summary [MCS], 26.5 [9.2]); mean (SD) physical component summary (PCS) total score was 45.2 (12.1). SF-12 MCS improved over 12 months of follow-up (38.7 [11.6] at month 12), while SF-12 PCS remained stable (45.3 [11.1]). At each assessment time point, there was a clear pattern of lower SF-12 MCS and PCS total score in patients experiencing greater cognitive problems. The mean EuroQol Five Dimensions questionnaire utility index score generally decreased (i.e., worsened) with increasing severity of cognitive and depressive symptoms at all time points up to 24 months. Multivariate analyses identified both depression severity and cognitive symptoms as strongly and significantly associated with poor HRQoL. These findings highlight

Posttraumatic stress disorder increases sensitivity to long term losses among patients with major depressive disorder.

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Jan B Engelmann

Full Text Available BACKGROUND: Decisions under risk and with outcomes that are delayed in time are ubiquitous in real life and can have a significant impact on the health and wealth of the decision-maker. Despite its potential relevance for real-world choices, the degree of aberrant risky and intertemporal decision-making in patients suffering from major depressive disorder (MDD and posttraumatic stress disorder (PTSD has received little attention to date. METHOD: We used a case-control design to compare decision-making in healthy control subjects (N=16 versus untreated depressed subjects in a current major depressive episode (N=20. In order to examine how major depressive disorder (MDD may impact decision-making, subjects made decisions over (1 risky outcomes and (2 delayed outcomes in the domain of gains and losses using choice paradigms from neuroeconomics. In a pre-planned analysis, depressed subjects were subdivided into those with primary PTSD along with comorbid MDD (MDD+PTSD versus those with primary MDD without PTSD (MDD-only. Choice behavior was modeled via a standard econometric model of intertemporal choice, a quasi-hyperbolic temporal discounting function, which was estimated for each subject group separately. RESULTS: Under conditions of potential gain, depressed subjects demonstrated greater discounting for gains across all time frames compared to controls. In the realm of losses, both subgroups of depressed subjects discounted more steeply than controls for short time frames. However, for delayed losses ranging from >1-10 years, MDD+PTSD subjects showed shallower discounting rates relative to MDD-only subjects, who continued to discount future losses steeply. Risk attitudes did not contribute to differences in intertemporal choice. CONCLUSIONS: Depressed patients make choices that minimize current pain and maximize current reward, despite severe later consequences or lost opportunities. Anxiety associated with PTSD may serve as a partially

Input-Timing-Dependent Plasticity in the Hippocampal CA2 Region and Its Potential Role in Social Memory.

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Leroy, Felix; Brann, David H; Meira, Torcato; Siegelbaum, Steven A

2017-08-30

Input-timing-dependent plasticity (ITDP) is a circuit-based synaptic learning rule by which paired activation of entorhinal cortical (EC) and Schaffer collateral (SC) inputs to hippocampal CA1 pyramidal neurons (PNs) produces a long-term enhancement of SC excitation. We now find that paired stimulation of EC and SC inputs also induces ITDP of SC excitation of CA2 PNs. However, whereas CA1 ITDP results from long-term depression of feedforward inhibition (iLTD) as a result of activation of CB1 endocannabinoid receptors on cholecystokinin-expressing interneurons, CA2 ITDP results from iLTD through activation of δ-opioid receptors on parvalbumin-expressing interneurons. Furthermore, whereas CA1 ITDP has been previously linked to enhanced specificity of contextual memory, we find that CA2 ITDP is associated with enhanced social memory. Thus, ITDP may provide a general synaptic learning rule for distinct forms of hippocampal-dependent memory mediated by distinct hippocampal regions. Copyright © 2017 Elsevier Inc. All rights reserved.

Long-Term Effects of the Family Check-Up in Public Secondary School on Diagnosed Major Depressive Disorder in Adulthood.

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Connell, Arin M; Dishion, Thomas J

2017-03-01

Given the public health importance of depression, the identification of prevention programs with long-term effects on reducing the rate of depression is of critical importance, as is the examination of factors that may moderate the magnitude of such prevention effects. This study examines the impact of the Family Check-Up, delivered in public secondary schools beginning in sixth grade, on the development of major depression in adulthood (aged 28-30). The multilevel intervention program included (a) a universal classroom-based intervention focused on problem solving and peer relationship skills, (b) the Family Check-Up (selected), a brief assessment-based intervention designed to motivate parents to improve aspects of family functioning when warranted, and (c) family management treatment (indicated), focused on improving parenting skills. Demographic (gender and ethnicity) and baseline risk factors (family conflict, academic problems, antisocial behavior, and peer deviance) were examined as possible moderators in logistic regression analyses. Intervention effects on depression were moderated by baseline family conflict and academic performance, with stronger intervention effects for youth with low grade point averages and from low-conflict families at baseline. Such findings extend the emerging literature on prevention programs with long-term effects on depression, and highlight directions for future research to enhance such effects.

Long-Term Effects of Chemical Warfare on Post-traumatic Stress Disorder, Depression, and Chronic Medical Conditions in Veterans.

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Safi-Aghdam, Hamideh; Shafie, Mehrzad; Khoshdel, Alireza; Moazen-Zadeh, Ehsan; Avakh, Farhad; Rahmani, Arash

2018-04-24

We investigated the association between exposure to chemical warfare and chronic mental/physical conditions. This was a secondary analysis of data from a case-control study on Iranian male veterans. Participants with neuropsychiatric disorders other than depressive/anxiety disorders, anatomical defects, or malignancies were excluded. Compared to non-exposed veterans, exposed veterans demonstrated significantly higher odds of PTSD [OR (95% CI) = 5.23 (1.98-13.85)], hypertension [OR (95% CI) = 5.57 (1.68-18.48)], coronary heart disease [OR (95% CI) = 6.8 (1.62-28.49)], and diabetes [OR (95% CI) = 3.88 (1.35-11.16)], and marginally higher odds of moderate to severe depressive symptoms [OR (95% CI) = 2.21 (0.93-5.28)]. This study provides preliminary evidence on association of exposure to chemical warfare with long-term mental disorders as well as chronic medical conditions.

Depression of voltage-activated Ca2+ release in skeletal muscle by activation of a voltage-sensing phosphatase.

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Berthier, Christine; Kutchukian, Candice; Bouvard, Clément; Okamura, Yasushi; Jacquemond, Vincent

2015-04-01

Phosphoinositides act as signaling molecules in numerous cellular transduction processes, and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) regulates the function of several types of plasma membrane ion channels. We investigated the potential role of PtdIns(4,5)P2 in Ca(2+) homeostasis and excitation-contraction (E-C) coupling of mouse muscle fibers using in vivo expression of the voltage-sensing phosphatases (VSPs) Ciona intestinalis VSP (Ci-VSP) or Danio rerio VSP (Dr-VSP). Confocal images of enhanced green fluorescent protein-tagged Dr-VSP revealed a banded pattern consistent with VSP localization within the transverse tubule membrane. Rhod-2 Ca(2+) transients generated by 0.5-s-long voltage-clamp depolarizing pulses sufficient to elicit Ca(2+) release from the sarcoplasmic reticulum (SR) but below the range at which VSPs are activated were unaffected by the presence of the VSPs. However, in Ci-VSP-expressing fibers challenged by 5-s-long depolarizing pulses, the Ca(2+) level late in the pulse (3 s after initiation) was significantly lower at 120 mV than at 20 mV. Furthermore, Ci-VSP-expressing fibers showed a reversible depression of Ca(2+) release during trains, with the peak Ca(2+) transient being reduced by ∼30% after the application of 10 200-ms-long pulses to 100 mV. A similar depression was observed in Dr-VSP-expressing fibers. Cav1.1 Ca(2+) channel-mediated current was unaffected by Ci-VSP activation. In fibers expressing Ci-VSP and a pleckstrin homology domain fused with monomeric red fluorescent protein (PLCδ1PH-mRFP), depolarizing pulses elicited transient changes in mRFP fluorescence consistent with release of transverse tubule-bound PLCδ1PH domain into the cytosol; the voltage sensitivity of these changes was consistent with that of Ci-VSP activation, and recovery occurred with a time constant in the 10-s range. Our results indicate that the PtdIns(4,5)P2 level is tightly maintained in the transverse tubule membrane of the muscle fibers

Dim light at night provokes depression-like behaviors and reduces CA1 dendritic spine density in female hamsters.

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Bedrosian, Tracy A; Fonken, Laura K; Walton, James C; Haim, Abraham; Nelson, Randy J

2011-08-01

The prevalence of major depression has increased in recent decades; however, the underlying causes of this phenomenon remain unspecified. One environmental change that has coincided with elevated rates of depression is increased exposure to artificial light at night. Shift workers and others chronically exposed to light at night are at increased risk of mood disorders, suggesting that nighttime illumination may influence brain mechanisms mediating affect. We tested the hypothesis that exposure to dim light at night may impact affective responses and alter morphology of hippocampal neurons. Ovariectomized adult female Siberian hamsters (Phodopus sungorus) were housed for 8 weeks in either a light/dark cycle (LD) or a light/dim light cycle (DM), and then behavior was assayed. DM-hamsters displayed more depression-like responses in the forced swim and the sucrose anhedonia tests compared with LD-hamsters. Conversely, in the elevated plus maze DM-hamsters reduced anxiety-like behaviors. Brains from the same animals were processed using the Golgi-Cox method and hippocampal neurons within CA1, CA3, and the dentate gyrus were analyzed for morphological characteristics. In CA1, DM-hamsters significantly reduced dendritic spine density on both apical and basilar dendrites, an effect which was not mediated by baseline cortisol, as concentrations were equivalent between groups. These results demonstrate dim light at night is sufficient to reduce synaptic spine connections to CA1. Importantly, the present results suggest that night-time low level illumination, comparable to levels that are pervasive in North America and Europe, may contribute to the increasing prevalence of mood disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

Mild Concussion, but Not Moderate Traumatic Brain Injury, Is Associated with Long-Term Depression-Like Phenotype in Mice.

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Nikita M Bajwa

Full Text Available Mild traumatic brain injuries can lead to long-lasting cognitive and motor deficits, increasing the risk of future behavioral, neurological, and affective disorders. Our study focused on long-term behavioral deficits after repeated injury in which mice received either a single mild CHI (mCHI, a repeated mild CHI (rmCHI consisting of one impact to each hemisphere separated by 3 days, or a moderate controlled cortical impact injury (CCI. Shams received only anesthesia. Behavioral tests were administered at 1, 3, 5, 7, and 90 days post-injury (dpi. CCI animals showed significant motor and sensory deficits in the early (1-7 dpi and long-term (90 dpi stages of testing. Interestingly, sensory and subtle motor deficits in rmCHI animals were found at 90 dpi. Most importantly, depression-like behaviors and social passiveness were observed in rmCHI animals at 90 dpi. These data suggest that mild concussive injuries lead to motor and sensory deficits and affective disorders that are not observed after moderate TBI.

Depressive symptoms among older adults with long-term spinal cord injury: Associations with secondary health conditions, sense of coherence, coping strategies and physical activity

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Sophie Jörgensen

2017-07-01

Full Text Available Objectives: To assess the presence of depressive symptoms among older adults with long-term spinal cord injury and investigate the association with sociodemographic and injury characteristics; and to determine how potentially modifiable factors, i.e. secondary health conditions, sense of coherence, coping strategies and leisure-time physical activity, are associated with depressive symptoms. Design: Cross-sectional study. Subjects: A total of 122 individuals (70% men, injury levels C1–L5, American Spinal Injury Association Impairment Scale A–D, mean age 63 years, mean time since injury 24 years. Methods: Data from the Swedish Aging with Spinal Cord Injury Study, collected using the Geriatric Depression Scale-15, the 13-item Sense of Coherence Scale, the Spinal Cord Lesion-related Coping Strategies Questionnaire and the Physical Activity Recall Assessment for people with Spinal Cord Injury. Associations were analysed using multivariable linear regression. Results: A total of 29% reported clinically relevant depressive symptoms and 5% reported probable depression. Sense of coherence, the coping strategy Acceptance, neuropathic pain and leisure-time physical activity explained 53% of the variance in depressive symptoms. Conclusion: Older adults with long-term spinal cord injury report a low presence of probable depression. Mental health may be supported through rehabilitation that strengthens the ability to understand and confront life stressors, promotes acceptance of the injury, provides pain management and encourages participation in leisure-time physical activity.

AD-venture program: therapeutic biking for the treatment of depression in long-term care residents with dementia.

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Buettner, Linda L; Fitzsimmons, Suzanne

2002-01-01

This project tested an innovative intervention in a controlled clinical investigation of a nonpharmacological treatment of depression in long-term care residents with dementia. This treatment utilized a wheelchair bicycle in a recreation therapy protocol, which combined small group activity therapy and one-to-one bike rides with a staff member. Depression levels were significantly reduced in the two-week portion of the study with levels maintained in the 10-week maintenance period. Improvements were also found in sleep and levels of activity engagement.

Ca isotopes reveal weak control of tectonic uplift on long-term climate change

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Moore, J.; Jacobson, A. D.; Holmden, C. E.; Craw, D.

2010-12-01

, which are longer on the eastern side of the main divide. After correcting for this input, we apportion Ca in all rivers to silicate versus carbonate weathering using a two-component mixing equation. For non-glaciated streams, the δ44/40Ca method and a conventional Ca/Na method agree within 2%. Silicate weathering contributes less Ca west of the main divide where uplift rates are highest. For actively glaciated catchments, the δ44/40Ca method attributes 26% more Ca to silicate weathering than the Ca/Na method. We ascribe this difference to non-stoichiometric leaching of Ca from freshly cleaved rock surfaces. This reaction must occur even faster than carbonate weathering, which dominates in adjacent non-glaciated watersheds. Our results support the assertion that mountain uplift does not dramatically elevate long-term atmospheric CO2 consumption rates compared to tectonically stable landscapes. However, δ44/40Ca reveals that glaciation, which is genetically linked to mountain uplift, yields moderately higher CO2 consumption rates than previously realized. Additionally, our study highlights how biological processes can influence the terrestrial Ca cycle.

Reduced juvenile long-term depression in tuberous sclerosis complex is mitigated in adults by compensatory recruitment of mGluR5 and Erk signaling.

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Wyatt B Potter

Full Text Available Tuberous sclerosis complex (TSC is a multisystem genetic disease that manifests with mental retardation, tumor formation, autism, and epilepsy. Heightened signaling through the mammalian target of rapamycin (mTOR pathway is involved in TSC pathology, however it remains unclear how other signaling pathways are perturbed and contribute to disease symptoms. Reduced long-term depression (LTD was recently reported in TSC mutant mice. We find that although reduced LTD is a feature of the juvenile mutant hippocampus, heightened expression of metabotropic glutamate receptor 5 and constitutively activated Erk signaling in the adult hippocampus drives wild-type levels of LTD. Increased mGluR5 and Erk results in a novel mTOR-independent LTD in CA1 hippocampus of adult mice, and contributes to the development of epileptiform bursting activity in the TSC2(+/- CA3 region of the hippocampus. Inhibition of mGluR5 or Erk signaling restores appropriate mTOR-dependence to LTD, and significantly reduces epileptiform bursting in TSC2(+/- hippocampal slices. We also report that adult TSC2(+/- mice exhibit a subtle perseverative behavioral phenotype that is eliminated by mGluR5 antagonism. These findings highlight the potential of modulating the mGluR5-Erk pathway in a developmental stage-specific manner to treat TSC.

The long-term effects of methamphetamine exposure during pre-adolescence on depressive-like behaviour in a genetic animal model of depression.

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Mouton, Moné; Harvey, Brian H; Cockeran, Marike; Brink, Christiaan B

2016-02-01

Methamphetamine (METH) is a psychostimulant and drug of abuse, commonly used early in life, including in childhood and adolescence. Adverse effects include psychosis, anxiety and mood disorders, as well as increased risk of developing a mental disorder later in life. The current study investigated the long-term effects of chronic METH exposure during pre-adolescence in stress-sensitive Flinders Sensitive Line (FSL) rats (genetic model of depression) and control Flinders Resistant Line (FRL) rats. METH or vehicle control was administered twice daily from post-natal day 19 (PostND19) to PostND34, followed by behavioural testing at either PostND35 (early effects) or long-lasting after withdrawal at PostND60 (early adulthood). Animals were evaluated for depressive-like behaviour, locomotor activity, social interaction and object recognition memory. METH reduced depressive-like behaviour in both FSL and FRL rats at PostND35, but enhanced this behaviour at PostND60. METH also reduced locomotor activity on PostND35 in both FSL and FRL rats, but without effect at PostND60. Furthermore, METH significantly lowered social interaction behaviour (staying together) in both FRL and FSL rats at PostND35 and PostND60, whereas self-grooming time was significantly reduced only at PostND35. METH treatment enhanced exploration of the familiar vs. novel object in the novel object recognition test (nORT) in FSL and FRL rats on PostND35 and PostND60, indicative of reduced cognitive performance. Thus, early-life METH exposure induce social and cognitive deficits. Lastly, early-life exposure to METH may result in acute antidepressant-like effects immediately after chronic exposure, whereas long-term effects after withdrawal are depressogenic. Data also supports a role for genetic predisposition as with FSL rats.

Long-Term Effects of Child Corporal Punishment on Depressive Symptoms in Young Adults: Potential Moderators and Mediators

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Turner, Heather A.; Muller, Paul A.

2004-01-01

Based on a sample of 649 students from 3 New England colleges, this study examined the long-term effects of childhood corporal punishment on symptoms of depression and considered factors that may moderate or mediate the association. Similar to national studies, approximately 40% of the sample reported experiencing some level of corporal punishment…

Parents' Faith and Hope during the Pediatric Palliative Phase and the Association with Long-Term Parental Adjustment.

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van der Geest, Ivana M M; van den Heuvel-Eibrink, Marry M; Falkenburg, Nette; Michiels, Erna M C; van Vliet, Liesbeth; Pieters, Rob; Darlington, Anne-Sophie E

2015-05-01

The loss of a child is associated with an increased risk for developing psychological problems. However, studies investigating the impact of parents' faith and hope for a cure during the palliative phase on long-term parental psychological functioning are limited. The study's objective was to explore the role of faith and hope as a source of coping and indicator of long-term parental adjustment. Eighty-nine parents of 57 children who died of cancer completed questionnaires retrospectively, exploring faith, hope, and sources of coping, and measuring parents' current level of grief and depression. For 19 parents (21%) faith was very important during the palliative phase. The majority of parents remained hopeful for a meaningful time with their child (n=68, 76%); a pain-free death (n=58, 65%); and a cure (n=30, 34%). Their child (n=70, 79%) was parents' main source of coping. Twelve parents (14%) suffered from traumatic grief, and 22 parents (25%) showed symptoms of depression. Parents' faith was not associated with less long-term traumatic grief (OR=0.86, p=0.51) or symptoms of depression (OR=0.95, p=0.74), and parents' hope for a cure was not related to more long-term traumatic grief (OR=1.07, p=0.71) or symptoms of depression (OR=1.12, p=0.47). Faith was important for a minority of parents and was not associated with less long-term traumatic grief or symptoms of depression. The majority of parents remained hopeful. Hope for a cure was not associated with more long-term traumatic grief or symptoms of depression.

Depressive symptoms and the risk of long-term sickness absence: a prospective study among 4747 employees in Denmark

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Bültmann, Ute; Rugulies, Reiner; Lund, Thomas

2006-01-01

BACKGROUND: The aim of this paper is to examine the impact of depressive symptoms on long-term sickness absence in a representative sample of the Danish workforce. METHODS: This prospective study is based on 4,747 male and female employees, participating in the Danish Work Environment Cohort Study...

Long working hours and depressive symptoms

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Virtanen, Marianna; Jokela, Markus; Madsen, Ida Eh

2018-01-01

Objectives This systematic review and meta-analysis combined published study-level data and unpublished individual-participant data with the aim of quantifying the relation between long working hours and the onset of depressive symptoms. Methods We searched PubMed and Embase for published....... In the majority of cohorts, long working hours was defined as working ≥55 hours per week. In multivariable-adjusted meta-analyses of 189 729 participants from 35 countries [96 275 men, 93 454 women, follow-up ranging from 1-5 years, 21 747 new-onset cases), there was an overall association of 1.14 (95% confidence...... interval (CI) 1.03-1.25] between long working hours and the onset of depressive symptoms, with significant evidence of heterogeneity (I 2=45.1%, P=0.004). A moderate association between working hours and depressive symptoms was found in Asian countries (1.50, 95% CI 1.13-2.01), a weaker association...

Long working hours and depressive symptoms

DEFF Research Database (Denmark)

Virtanen, Marianna; Jokela, Markus; Madsen, Ida Eh

2018-01-01

. In the majority of cohorts, long working hours was defined as working ≥55 hours per week. In multivariable-adjusted meta-analyses of 189 729 participants from 35 countries [96 275 men, 93 454 women, follow-up ranging from 1-5 years, 21 747 new-onset cases), there was an overall association of 1.14 (95% confidence......Objectives This systematic review and meta-analysis combined published study-level data and unpublished individual-participant data with the aim of quantifying the relation between long working hours and the onset of depressive symptoms. Methods We searched PubMed and Embase for published...... interval (CI) 1.03-1.25] between long working hours and the onset of depressive symptoms, with significant evidence of heterogeneity (I 2=45.1%, P=0.004). A moderate association between working hours and depressive symptoms was found in Asian countries (1.50, 95% CI 1.13-2.01), a weaker association...

Decreasing soil water Ca2+ reduces DOC adsorption in mineral soils: implications for long-term DOC trends in an upland forested catchment in southern Ontario, Canada.

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Kerr, Jason Grainger; Eimers, M Catherine

2012-06-15

Positive trends in dissolved organic carbon (DOC) concentration have been observed in surface waters throughout North America and northern Europe. Although adsorption in mineral soils is an important driver of DOC in upland streams, little is known about the potential for changes in DOC adsorption to contribute to these trends. We hypothesized that long-term declines in soil water Ca(2+) levels, in response to declining acid deposition, might influence DOC adsorption and that this could contribute to long-term DOC trends in an upland forested catchment in south-central Ontario, Canada. Between 1987 and 2009, DOC concentrations increased significantly (pDOC concentration (DOC(np)), which is a measure of the soil water DOC concentration at equilibrium with the soil, ranged from 1.27 to 3.75 mg L(-1) in B horizon soils. This was similar to the mean DOC concentrations of B horizon soil water (2.04-6.30 mg L(-1)) and stream water (2.20 mg L(-1)), indicating that soil and stream water DOC concentrations are controlled by equilibrium processes at the soil-water interface. Adsorption experiments using variable Ca(2+) concentrations demonstrated that as Ca(2+) decreased the DOC(np) increased (1.96 to 4.74 mg L(-1)), which was consistent with the observed negative correlation between DOC and Ca(2+) in B horizon soil water (pDOC adsorption (p>0.05), indicating that changes in DOC adsorption might be related to cation bridging. We conclude that declines in soil water Ca(2+) concentration can contribute to increasing DOC trends in upland streams by reducing DOC adsorption in mineral soils. Copyright © 2012 Elsevier B.V. All rights reserved.

Long-term sick-leavers with fibromyalgia: Comparing their multidisciplinarily assessed characteristics with those  of others with chronic pain conditions and depression

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Jürgen Linder

2009-01-01

Full Text Available Jürgen Linder1, Kristina Schüldt Ekholm2,3,4, Göran Lundh1, Jan Ekholm2,31Diagnostic Centre, Division of Psychiatry, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; 2Division of Rehabilitation Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden; 3Stockholm University Rehabilitation Medicine Clinic, Danderyd Hospital, Stockholm, Sweden; 4Division of Rehabilitation Science, Department of Health Science, Mid-Sweden University, Campus Östersund, SwedenObjective: The aim was to gain knowledge of fibromyalgia (FM patients on long-term sick leave and with particular difficulties in resuming work, and to compare them with patients with myalgia, back or joint diagnoses, and depression.Methods: Patients were identified by and referred from social insurance offices and were multidisciplinarily examined by three board-certified specialists in psychiatry, orthopedic surgery and rehabilitation medicine. Ninety-two women were diagnosed with FM only. Three female comparison groups were chosen: depression, back/joint diagnoses, and myalgia.Results and conclusions: Ceaseless pain was reported by 73% of FM patients, 54% of back/joint diagnoses patients, 43% of myalgia patients, and 35% of depression patients. The distribution of pain (>50% in FM patients was to almost all regions of the body, and in depression patients to the lower dorsal neck, upper shoulders and lumbosacral back but not in the anterior body. Reduced sleep was more evident in FM patients. FM patients did not meet more criteria for personality disorder than patients with the other somatic pain conditions. The most common dimension of “personality traits” of somatic pain conditions was the “obsessive compulsive” but at a level clearly below that indicating a personality disorder. More FM patients experienced disabilities, the most common being in the mobility and domestic-life areas.Keywords: fibromyalgia

Developmental shift from long-term depression to long-term potentiation in the rat medial vestibular nuclei: role of group I metabotropic glutamate receptors.

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Puyal, Julien; Grassi, Silvarosa; Dieni, Cristina; Frondaroli, Adele; Demêmes, Danielle; Raymond, Jaqueline; Pettorossi, Vito Enrico

2003-12-01

The effects of high frequency stimulation (HFS) of the primary vestibular afferents on synaptic transmission in the ventral part of the medial vestibular nuclei (vMVN) were studied during postnatal development and compared with the changes in the expression of the group I metabotropic glutamate receptor (mGluR) subtypes, mGluR1 and mGluR5. During the first stages of development, HFS always induced a mGluR5- and GABAA-dependent long-term depression (LTD) which did not require NMDA receptor and mGluR1 activation. The probability of inducing LTD decreased progressively throughout the development and it was zero at about the end of the second postnatal week. Conversely, long-term potentiation (LTP) appeared at the beginning of the second week and its occurrence increased to reach the adult value at the end of the third week. Of interest, the sudden change in the LTP frequency occurred at the time of eye opening, about the end of the second postnatal week. LTP depended on NMDA receptor and mGluR1 activation. In parallel with the modifications in synaptic plasticity, we observed that the expression patterns and localizations of mGluR5 and mGluR1 in the medial vestibular nuclei (MVN) changed during postnatal development. At the earlier stages the mGluR1 expression was minimal, then increased progressively. In contrast, mGluR5 expression was initially high, then decreased. While mGluR1 was exclusively localized in neuronal compartments and concentrated at the postsynaptic sites at all stages observed, mGluR5 was found mainly in neuronal compartments at immature stages, then preferentially in glial compartments at mature stages. These results provide the first evidence for a progressive change from LTD to LTP accompanied by a distinct maturation expression of mGluR1 and mGluR5 during the development of the MVN.

Perceived impeding factors for return-to-work after long-term sickness absence due to major depressive disorder: a concept mapping approach.

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Gabe de Vries

Full Text Available The purpose of the present study was to explore various stakeholder perspectives regarding factors that impede return-to-work (RTW after long-term sickness absence related to major depressive disorder (MDD.Concept mapping was used to explore employees', supervisors' and occupational physicians' perspectives on these impeding factors.Nine perceived themes, grouped in three meta-clusters were found that might impede RTW: Person, (personality / coping problems, symptoms of depression and comorbid (health problems, employee feels misunderstood, and resuming work too soon, Work (troublesome work situation, too little support at work, and too little guidance at work and Healthcare (insufficient mental healthcare and insufficient care from occupational physician. All stakeholders regarded personality/coping problems and symptoms of depression as the most important impeding theme. In addition, supervisors emphasized the importance of mental healthcare underestimating the importance of the work environment, while occupational physicians stressed the importance of the lack of safety and support in the work environment.In addition to the reduction of symptoms, more attention is needed on coping with depressive symptoms and personality problems in the work environment support in the work environment and for RTW in mental healthcare, to prevent long term sickness absence.

Perceived impeding factors for return-to-work after long-term sickness absence due to major depressive disorder: a concept mapping approach.

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de Vries, Gabe; Hees, Hiske L; Koeter, Maarten W J; Lagerveld, Suzanne E; Schene, Aart H

2014-01-01

The purpose of the present study was to explore various stakeholder perspectives regarding factors that impede return-to-work (RTW) after long-term sickness absence related to major depressive disorder (MDD). Concept mapping was used to explore employees', supervisors' and occupational physicians' perspectives on these impeding factors. Nine perceived themes, grouped in three meta-clusters were found that might impede RTW: Person, (personality / coping problems, symptoms of depression and comorbid (health) problems, employee feels misunderstood, and resuming work too soon), Work (troublesome work situation, too little support at work, and too little guidance at work) and Healthcare (insufficient mental healthcare and insufficient care from occupational physician). All stakeholders regarded personality/coping problems and symptoms of depression as the most important impeding theme. In addition, supervisors emphasized the importance of mental healthcare underestimating the importance of the work environment, while occupational physicians stressed the importance of the lack of safety and support in the work environment. In addition to the reduction of symptoms, more attention is needed on coping with depressive symptoms and personality problems in the work environment support in the work environment and for RTW in mental healthcare, to prevent long term sickness absence.

COMPLIANCE TO LONG-TERM TREATMENT OF CARDIOLOGIC PATIENTS WITH MILD TO MODERATE DEPRESSION: INEFFECTIVENESS OF ANTIDEPRESSIVE THERAPY WITH PIRLINDOL IN RANDOMIZED STUDY

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E. V. Strokova

2015-12-01

Full Text Available Aim. To evaluate the influence of antidepressant therapy with pirlindol on compliance to the long-term treatment and quality of life in patients with cardiovascular diseases and mild to moderate depression. Material and methods. 61 patients with cardiovascular diseases and mild to moderate depression (according to Beck depression scale were randomized into two groups. Patients of intervention group received pirlindol, while patients of control group did not receive this drug. Compliance to cardiovascular and antidepressant treatment were estimated in 3 and 6 months. Adverse reactions and patients self-assessment of their well-being and global satisfaction in treatmen were also registered.  Results. 24 (75%, 2 (6% and 0 patients of intervention group continue pirlindol treatment in 1, 3 and 6 months, respectively. In 3 months of observation patients of intervention group took drugs for cardiovascular diseases more often than these in control group (81% vs 72%, respectively , р<0.05, they also less frequently showed adverse reactions (56% vs 72%, respectively ,p=0.01 and more often — improvement of their well-being (65% vs 50%, respectively , р=0.03. Compliance to cardiovascular therapy did not differ significantly in patients of both groups by the end the study.  Conclusion. Antidepressant therapy with pirlindol did not influence compliance to long-term cardiovascular treatment in patients with cardiovascular diseases and mild to moderate depression, apparently because of low compliance to pirlindol therapy.

Calcium regulation in long-term changes of neuronal excitability in the hippocampal formation

Energy Technology Data Exchange (ETDEWEB)

Mody, I.

1985-01-01

The regulation of calcium (Ca/sup 2 +/) was examined during long-term changes of neuronal excitability in the mammalian CNS. The preparations under investigation included the kindling model of epilepsy, a genetic form of epilepsy and long-term potentiation (LTP) of neuronal activity. The study also includes a discussion of the possible roles of a neuron-specific calcium-binding protein (CaBP). The findings are summarized as follows: (1) CaBP was found to have an unequal distribution in various cortical areas of the rat with higher levels in ventral structures. (2) The decline in CaBP was correlated to the number of evoked afterdischarges (AD's) during kindling-induced epilepsy. (3) Marked changes in CaBP levels were also found in the brains of the epileptic strain of mice (El). The induction of seizures further decreased the levels of CaBP in the El mice, indicating a possible genetic impairment of neuronal Ca/sup 2 +/ homeostasis in the El strain. (4) The levels of total hippocampal Ca/sup 2 +/ and Zn/sup 2 +/ were measured by atomic absorption spectrophotometry in control and commissural-kindled animals. (5) To measure Ca/sup 2 +/-homeostasis, the kinetic analysis of /sup 45/Ca uptake curves was undertaken in the in vitro hippocampus. (6) The kinetic analysis of /sup 45/Ca uptake curves revealed that Ca/sup 2 +/-regulation of the hippocampus is impaired following amygdala- and commissural kindling. (7). A novel form of long-term potentiation (LTP) of neuronal activity in the CA1 region of the hippocampus is described. The findings raise the possibility that the Ca/sup 2 +/ necessary for induction of LTP may be derived from an intraneuronal storage site.

Long-term course of severe depression: late remission and recurrence may be found in a follow-up after 38-53 years

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Lisa Crona

2012-07-01

Full Text Available This study is a follow-up of inpatients diagnosed with severe depression/melancholia between 1956 and 1969. During this period, all inpatients at the Department of Psychiatry, University Hospital, Lund, were rated on a multidimensional diagnostic schedule on discharge. There were 471 patients born from 1920 onward. In the present follow-up, 2006 to 2010, 169 survivors could be traced. They were asked to participate in the study involving a telephone interview, in which a structured life chart was used. Of the patients contacted, 16 were ill or confused and 3 did not remember ever being depressed, leaving 150 who could participate. Seventy-five of these agreed to participate in the study. Long-term course of depression was evaluated by cluster analysis and compared to background variables, such as heredity for depression, perceived parental rearing behaviour, and treatment of index depressive episode. Using a cluster analysis the patients could be separated into six clusters describing the course: i single or few episodes followed by long-lasting remission; ii single or few episodes followed by long-lasting remission, although shorter; iii single or few episodes followed by late recurrence; iv single or few episodes, but more frequently ill, followed by late recurrence; v several episodes followed by lasting remission; vi chronic course of episodes. Remission or recurrence could there- fore occur even after more than a decade. In summary, there was a short-term course with or without recurrence or a chronic course with or without late remission. Heredity for depression was significantly related to a chronic course with or without late remission.

A Videotape-Based Training Method for Improving the Detection of Depression in Residents of Long-Term Care Facilities

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Wood, Stacey; Cummings, Jeffrey L.; Schnelle, Betha; Stephens, Mary

2002-01-01

Purpose: This article reviews the effectiveness of a new training program for improving nursing staffs' detection of depression within long-term care facilities. The course was designed to increase recognition of the Minimal Data Set (MDS) Mood Trigger items, to be brief, and to rely on images rather than didactics. Design and Methods: This study…

Long Term Depression in Rat Hippocampus and the Effect of Ethanol during Fetal Life

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Olivier Pierrefiche

2017-11-01

Full Text Available Alcohol (ethanol disturbs cognitive functions including learning and memory in humans, non-human primates, and laboratory animals such as rodents. As studied in animals, cellular mechanisms for learning and memory include bidirectional synaptic plasticity, long-term potentiation (LTP, and long-term depression (LTD, primarily in the hippocampus. Most of the research in the field of alcohol has analyzed the effects of ethanol on LTP; however, with recent advances in the understanding of the physiological role of LTD in learning and memory, some authors have examined the effects of ethanol exposure on this particular signal. In the present review, I will focus on hippocampal LTD recorded in rodents and the effects of fetal alcohol exposure on this signal. A synthesis of the findings indicates that prenatal ethanol exposure disturbs LTD concurrently with LTP in offspring and that both glutamatergic and γ-aminobutyric acid (GABA neurotransmissions are altered and contribute to LTD disturbances. Although the ultimate mode of action of ethanol on these two transmitter systems is not yet clear, novel suggestions have recently appeared in the literature.

Symptoms of Eating Disorders and Depression in Emerging Adults with Early-Onset, Long-Duration Type 1 Diabetes and Their Association with Metabolic Control.

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Christina Bächle

Full Text Available This study analyzed the prevalence of and association between symptoms of eating disorders and depression in female and male emerging adults with early-onset, long-duration type 1 diabetes and investigated how these symptoms are associated with metabolic control.In a nationwide population-based survey, 211 type 1 diabetes patients aged 18-21 years completed standardized questionnaires, including the SCOFF questionnaire for eating disorder symptoms and the Patient Health Questionnaire (PHQ-9 for symptoms of depression and severity of depressive symptoms (PHQ-9 score. Multiple linear and logistic regression models were used to analyze the association between eating disorder and depressive symptoms and their associations with HbA1c.A total of 30.2% of the women and 9.5% of the men were screening positive for eating disorders. The mean PHQ-9 score (standard deviation was 5.3 (4.4 among women and 3.9 (3.6 among men. Screening positive for an eating disorder was associated with more severe depressive symptoms among women (βwomen 3.8, p<0.001. However, neither eating disorder symptoms nor severity of depressive symptoms were associated with HbA1c among women, while HbA1c increased with the severity of depressive symptoms among men (βmen 0.14, p=0.006.Because of the high prevalence of eating disorder and depressive symptoms, their interrelationship, and their associations with metabolic control, particularly among men, regular mental health screening is recommended for young adults with type 1 diabetes.

LONG-TERM OUTCOME IN PEDIATRIC TRICHOTILLOMANIA.

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Schumer, Maya C; Panza, Kaitlyn E; Mulqueen, Jilian M; Jakubovski, Ewgeni; Bloch, Michael H

2015-10-01

To examine long-term outcome in children with trichotillomania. We conducted follow-up clinical assessments an average of 2.8 ± 0.8 years after baseline evaluation in 30 of 39 children who previously participated in a randomized, double-blind, placebo-controlled trial of N-acetylcysteine (NAC) for pediatric trichotillomania. Our primary outcome was change in hairpulling severity on the Massachusetts General Hospital Hairpulling Hospital Hairpulling Scale (MGH-HPS) between the end of the acute phase and follow-up evaluation. We also obtained secondary measures examining styles of hairpulling, comorbid anxiety and depressive symptoms, as well as continued treatment utilization. We examined both correlates and predictors of outcome (change in MGH-HPS score) using linear regression. None of the participants continued to take NAC at the time of follow-up assessment. No significant changes in hairpulling severity were reported over the follow-up period. Subjects reported significantly increased anxiety and depressive symptoms but improvement in automatic pulling symptoms. Increased hairpulling symptoms during the follow-up period were associated with increased depression and anxiety symptoms and increased focused pulling. Older age and greater focused pulling at baseline assessment were associated with poor long-term prognosis. Our findings suggest that few children with trichotillomania experience a significant improvement in trichotillomania symptoms if behavioral treatments are inaccessible or have failed to produce adequate symptom relief. Our findings also confirm results of previous cross-sectional studies that suggest an increased risk of depression and anxiety symptoms with age in pediatric trichotillomania. Increased focused pulling and older age among children with trichotillomania symptoms may be associated with poorer long-term prognosis. © 2015 Wiley Periodicals, Inc.

miR-191 and miR-135 are required for long-lasting spine remodelling associated with synaptic long-term depression

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Hu, Zhonghua; Yu, Danni; Gu, Qin-Hua; Yang, Yanqin; Tu, Kang; Zhu, Jun; Li, Zheng

2014-02-01

Activity-dependent modification of dendritic spines, subcellular compartments accommodating postsynaptic specializations in the brain, is an important cellular mechanism for brain development, cognition and synaptic pathology of brain disorders. NMDA receptor-dependent long-term depression (NMDAR-LTD), a prototypic form of synaptic plasticity, is accompanied by prolonged remodelling of spines. The mechanisms underlying long-lasting spine remodelling in NMDAR-LTD, however, are largely unclear. Here we show that LTD induction causes global changes in miRNA transcriptomes affecting many cellular activities. Specifically, we show that expression changes of miR-191 and miR-135 are required for maintenance but not induction of spine restructuring. Moreover, we find that actin depolymerization and AMPA receptor exocytosis are regulated for extended periods of time by miRNAs to support long-lasting spine plasticity. These findings reveal a miRNA-mediated mechanism and a role for AMPA receptor exocytosis in long-lasting spine plasticity, and identify a number of candidate miRNAs involved in LTD.

Impaired memory of eyeblink conditioning in CaMKIV KO mice.

Science.gov (United States)

Lee, Ka Hung; Chatila, Talal A; Ram, Rana A; Thompson, Richard F

2009-04-01

The calcium/calmodulin-dependent protein kinase type IV (CaMKIV) is highly expressed in cerebellar cortical granule cells and deep nuclear neurons in the cerebellum. It mediates the phosphorylation and activation of the cAMP-dependent response element binding protein (CREB). In several paradigms CREB-dependent transcription is required for cellular events underlying long-term memory processes. Also, CaMKIV deficiency results in impaired long-term depression (LTD) induction in cerebellar cortex. To investigate the function of CaMKIV in the cerebellum, Wild-type (WT) and CaMKIV KO mice were tested with delay eyeblink conditioning. KO and WT mice did not differ in acquisition, but the KO mice showed a significantly lower conditioned response (CR) percentage than the WT mice in the retention testing and retraining period. The CR peak latencies for the two groups did not differ in acquisition but were shorter for the KO mice in the testing period. No significant differences were found between KO and WT mice in spontaneous eyeblink activity, auditory brainstem response (ABR) amplitudes, and tail-flick latency. The results suggest an important role for CaMKIV in long-term memory in the cerebellum. (c) 2009 APA, all rights reserved.

Combined Racial and Gender Differences in the Long-Term Predictive Role of Education on Depressive Symptoms and Chronic Medical Conditions.

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Assari, Shervin

2017-06-01

Despite a well-established literature on the protective effect of education on health, less is known about group differences in the mechanisms underlying this association. Using a life course approach and cumulative advantage theory, this study compared Black men, Black women, White men, and White women to assess the long-term gradient (education as a continuous measure) and threshold (>12 years) effects of baseline education on change in chronic medical conditions (CMC) and depressive symptoms (DS) from baseline to 25 years later. Data came from the Americans' Changing Lives Study, 1986-2011. The study followed Black and White respondents for up to 25 years, among whom 1271 individuals who had survived and were under follow-up were interviewed in 2011 and reported their number of chronic medical conditions and depressive symptoms (Center for Epidemiological Studies-Depression; CES-D 11). Multi-group structural equation modeling was used to compare gradient and threshold effects of education on change in chronic medical conditions and depressive symptoms from baseline (1986) to 25 years later (2011) among Black men, Black women, White men, and White women. There were group differences in the long-term association between education measured as a gradient and the change in depressive symptoms and chronic medical conditions during the follow-up, and in the association between education measured at the threshold of 12 years on change in depressive symptoms from baseline to follow-up. However, the association between education measured at this threshold and change in chronic medical conditions did not differ across race-gender groups. With the exception of Black men, who showed a gradient protective effect for baseline education against increase in the number of chronic medical associations (threshold or gradient) with change in chronic medical conditions. Among White men and White women, education had a threshold protective effect against increase in depressive

Effect of Talbinah food consumption on depressive symptoms among elderly individuals in long term care facilities, randomized clinical trial

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Badrasawi MM

2013-03-01

Full Text Available Manal M Badrasawi, Suzana Shahar, Zahara Abd Manaf, Hasnah HaronDietetics program, School of Health Care Sciences, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, MalaysiaAbstract: Talbinah is a barley syrup cooked with milk and sweetened by honey. In his famous Hadith on Talbinah, the Prophet Mohammad (SAW recommended it when sad events happen for its effect on soothing hearts and relieving sadness. This 3-week crossover designed, randomized clinical trial was conducted to determine the effect of Talbinah on mood and depression among institutionalized elderly people in Seremban. A sample of 30 depressed elderly subjects (21 men and 9 women was selected from the long term care facility. Three different interview-based validated scales (Geriatric Depression Scale, Depression Anxiety Stress Scales, and Profile of Mood States were used to determine mood, depression, stress, and anxiety at week 0, 3, 4, and 7. The nutritional value of Talbinah was examined using proximate food analysis, minerals content analysis, and differential amino acid analysis. The results indicated that Talbinah is a high carbohydrate food (86.4% and has a high tryptophan: branch chain amino acids ratio (1:2. A Wilcoxon nonparametric test showed that there was a statistically significant decrease on depression, stress, and mood disturbances scores among the intervention group (P < 0.05 for all parameters. In conclusion, Talbinah has the potential to reduce depression and enhance mood among the subjects. Ingestion of functional foods such as Talbinah may provide a mental health benefit to elderly people.Keywords: Talbinah, food and depression, cross over study, elderly

Neutron investigation of Ru-doped Nd1/2Ca1/2MnO3. Comparison with Cr-doped Nd1/2Ca1/2MnO3

International Nuclear Information System (INIS)

Moritomo, Yutaka; Nonobe, Toshihiko; Machida, Akihiko; Ohoyama, Kenji

2002-01-01

Lattice and magnetic properties are investigated for 3% Ru- and Cr-doped Nd 1/2 Ca 1/2 MnO 3 . The parent Nd 1/2 Ca 1/2 MnO 3 is a charge-ordered insulator (T CO =250K). With decreasing temperature below ≅210K, these compounds are separated into two perovskite phases, that is, the long-c and short-c phases. The long-c region shows a ferromagnetic transition at T C ≅210K for the Ru-doped compound and ≅130K for the Cr-doped compound, while the short-c region shows antiferromagnetic transition at T N ≅150K for Ru and ≅110K for Cr. We discuss the origin of the enhanced T C for the Ru-doped compound in terms of the effective one-electron bandwidth W of the e g -band. (author)

Long-Term Mental Health Problems after Delirium in the ICU

NARCIS (Netherlands)

Wolters, Annemiek E.; Peelen, Linda M.; Welling, Maartje C.; Kok, Lotte; De Lange, Dylan W.; Cremer, Olaf L.; Van Dijk, Diederik; Slooter, Arjen J C; Veldhuijzen, Dieuwke S.

2016-01-01

Objectives: To determine whether delirium during ICU stay is associated with long-term mental health problems defined as symptoms of anxiety, depression, and posttraumatic stress disorder.  Design: Prospective cohort study.  Setting: Survey study, 1 year after discharge from a medical-surgical ICU

Gaba mediated long-term depression (LTD) in the rat medial vestibular nuclei.

Science.gov (United States)

Grassi, S; Della Torre, G; Zampolini, M; Pettorossi, V E

1995-01-01

As previously demonstrated, high frequency stimulation (HFS) of the primary vestibular afferents always induces a clear, long lasting depression of the polysynaptic (N2) component of the field potentials recorded in the dorsal portion of the medial vestibular nuclei (MVN). The induction of the HFS effect was mediated by the activation of glutamate NMDA receptors, since it was blocked by AP5. The mechanisms at the basis of such a depression were studied. Our results demonstrate that Gaba, acting on both GabaA and GabaB receptors, is involved in mediating this phenomenon. In fact, HFS applied during Bicuculline and Saclofen perfusion, was no longer able to induce an N2 depression, but provoked a slight potentiation. However, the N2 depression clearly emerged after drug wash-out. Furthermore, Bicuculline and Saclofen fully abolished the N2 depression and highlighted the potentiation, when administered after HFS. The possibility that the N2 depression is the result of a homosynaptic LTD can be excluded on the basis of our results. On the contrary, our findings suggest that the depression is due to an enhancement of the Gaba inhibitory effect due to an HFS dependent increase in gabaergic interneuron activity, which resets vestibular neuron excitability at a lower level.

A multi-wave study of organizational justice at work and long-term sickness absence among employees with depressive symptoms

DEFF Research Database (Denmark)

Hjarsbech, Pernille U; Christensen, Karl Bang; Bjørner, Jakob

2014-01-01

OBJECTIVES: Mental health problems are strong predictors of long-term sickness absence (LTSA). In this study, we investigated whether organizational justice at work - fairness in resolving conflicts and distributing work - prevents risk of LTSA among employees with depressive symptoms. METHODS......: In a longitudinal study with five waves of data collection, we examined a cohort of 1034 employees with depressive symptoms. Depressive symptoms and organizational justice were assessed by self-administered questionnaires and information on LTSA was derived from a national register. Using Poisson regression...... analyses, we calculated rate ratios (RR) for the prospective association of organizational justice and change in organizational justice with time to onset of LTSA. All analyses were sex stratified. RESULTS: Among men, intermediate levels of organizational justice were statistically significantly associated...

Perceived impeding factors for return-to-work after long-term sickness absence due to major depressive disorder: a concept mapping approach

NARCIS (Netherlands)

Vries, G. de; Hees, H.L.; Koeter, M.W.; Lagerveld, S.E.; Schene, A.H.

2014-01-01

OBJECTIVE: The purpose of the present study was to explore various stakeholder perspectives regarding factors that impede return-to-work (RTW) after long-term sickness absence related to major depressive disorder (MDD). METHODS: Concept mapping was used to explore employees', supervisors' and

Perceived impeding factors for return-to-work after long-term sickness absence due to major depressive disorder: a concept mapping approach

NARCIS (Netherlands)

de Vries, Gabe; Hees, Hiske L.; Koeter, Maarten W. J.; Lagerveld, Suzanne E.; Schene, Aart H.

2014-01-01

The purpose of the present study was to explore various stakeholder perspectives regarding factors that impede return-to-work (RTW) after long-term sickness absence related to major depressive disorder (MDD). Concept mapping was used to explore employees', supervisors' and occupational physicians'

Perceived impeding factors for return-to-work after long-term sickness absence due to major depressive disorder: A concept mapping approach

NARCIS (Netherlands)

Vries, G. de; Hees, H.L.; Koeter, M.W.J.; Lagerveld, S.E.; Schene, A.H.

2014-01-01

Objective: The purpose of the present study was to explore various stakeholder perspectives regarding factors that impede return-to-work (RTW) after long-term sickness absence related to major depressive disorder (MDD). Methods: Concept mapping was used to explore employees', supervisors' and

26 CFR 1.471-10 - Applicability of long-term contract methods.

Science.gov (United States)

2010-04-01

... 26 Internal Revenue 6 2010-04-01 2010-04-01 false Applicability of long-term contract methods. 1... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Inventories § 1.471-10 Applicability of long-term contract methods. See § 1.460-2 for rules providing for the application of the long-term contract methods to...

Long term effect of depression care management on mortality in older adults: follow-up of cluster randomized clinical trial in primary care

OpenAIRE

Gallo, Joseph J; Morales, Knashawn H; Bogner, Hillary R; Raue, Patrick J; Zee, Jarcy; Bruce, Martha L; Reynolds, Charles F

2013-01-01

Objective To investigate whether an intervention to improve treatment of depression in older adults in primary care modified the increased risk of death associated with depression. Design Long term follow-up of multi-site practice randomized controlled trial (PROSPECT?Prevention of Suicide in Primary Care Elderly: Collaborative Trial). Setting 20 primary care practices in New York City, Philadelphia, and Pittsburgh, USA, randomized to intervention or usual care. Participants 1226 participants...

Loss of long-term depression in the insular cortex after tail amputation in adult mice.

Science.gov (United States)

Liu, Ming-Gang; Zhuo, Min

2014-01-08

The insular cortex (IC) is an important forebrain structure involved in pain perception and taste memory formation. Using a 64-channel multi-electrode array system, we recently identified and characterized two major forms of synaptic plasticity in the adult mouse IC: long-term potentiation (LTP) and long-term depression (LTD). In this study, we investigate injury-related metaplastic changes in insular synaptic plasticity after distal tail amputation. We found that tail amputation in adult mice produced a selective loss of low frequency stimulation-induced LTD in the IC, without affecting (RS)-3,5-dihydroxyphenylglycine (DHPG)-evoked LTD. The impaired insular LTD could be pharmacologically rescued by priming the IC slices with a lower dose of DHPG application, a form of metaplasticity which involves activation of protein kinase C but not protein kinase A or calcium/calmodulin-dependent protein kinase II. These findings provide important insights into the synaptic mechanisms of cortical changes after peripheral amputation and suggest that restoration of insular LTD may represent a novel therapeutic strategy against the synaptic dysfunctions underlying the pathophysiology of phantom pain.

BDNF Regains Function in Hippocampal Long-Term Potentiation Deficits Caused by Diencephalic Damage

Science.gov (United States)

Vedder, Lindsey C.; Savage, Lisa M.

2017-01-01

Thiamine deficiency (TD), commonly associated with chronic alcoholism, leads to diencephalic damage, hippocampal dysfunction, and spatial learning and memory deficits. We show a decrease in the magnitude of long-term potentiation (LTP) and paired-pulse facilitation (PPF) at CA3-CA1 synapses, independent of sex, following diencephalic damage…

High conductive and long-term phase stable anode materials for SOFCs: A2FeMoO6 (A = Ca, Sr, Ba)

Science.gov (United States)

Huan, Yu; Li, Yining; Yin, Baoyi; Ding, Dong; Wei, Tao

2017-08-01

In this work, the mixed oxide-ion/electron conductor (MIEC) double-perovskite compounds A2FeMoO6 (AFMO, A = Ca, Sr, Ba) are investigated as anode materials for O2--ion conducting solid-oxide fuel cells (SOFCs). Several advantages are outlined here; 1) under H2 atmosphere, the conductivities of Ba2FeMoO6 (BFMO), Sr2FeMoO6 (SFMO) and Ca2FeMoO6 (CFMO) reach as high as 243, 302 and 561 S cm-1, respectively, which can be comparable with the commercial NiO-electrolyte anode; 2) excellent structure and phase stability at high temperature and in H2 atmosphere; 3) matched thermodynamic compatibility (such as TECs) with electrolyte materials; 4) fast oxidization for fuel with O2- ions accepted by oxygen vacancies from the electrolyte. Moreover, with H2 as fuel gas, the cell power output, cell's long-term stabilities and the structural parameter are also been examined to evaluate the AFMO anode.

Subthreshold pharmacological and genetic approaches to analyzing CaV2.1-mediated NMDA receptor signaling in short-term memory.

Science.gov (United States)

Takahashi, Eiki; Niimi, Kimie; Itakura, Chitoshi

2010-10-25

Ca(V)2.1 is highly expressed in the nervous system and plays an essential role in the presynaptic modulation of neurotransmitter release machinery. Recently, the antiepileptic drug levetiracetam was reported to inhibit presynaptic Ca(V)2.1 functions, reducing glutamate release in the hippocampus, although the precise physiological role of Ca(V)2.1-regulated synaptic functions in cognitive performance at the system level remains unknown. This study examined whether Ca(V)2.1 mediates hippocampus-dependent spatial short-term memory using the object location and Y-maze tests, and perirhinal cortex-dependent nonspatial short-term memory using the object recognition test, via a combined pharmacological and genetic approach. Heterozygous rolling Nagoya (rol/+) mice carrying the Ca(V)2.1alpha(1) mutation had normal spatial and nonspatial short-term memory. A 100mg/kg dose of levetiracetam, which is ineffective in wild-type controls, blocked spatial short-term memory in rol/+ mice. At 5mg/kg, the N-methyl-D-aspartate (NMDA) receptor blocker (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), which is ineffective in wild-type controls, also blocked the spatial short-term memory in rol/+ mice. Furthermore, a combination of subthreshold doses of levetiracetam (25 mg/kg) and CPP (2.5mg/kg) triggered a spatial short-term memory deficit in rol/+ mice, but not in wild-type controls. Similar patterns of nonspatial short-term memory were observed in wild-type and rol/+ mice when injected with levetiracetam (0-300 mg/kg). These results indicate that Ca(V)2.1-mediated NMDA receptor signaling is critical in hippocampus-dependent spatial short-term memory and differs in various regions. The combination subthreshold pharmacological and genetic approach presented here is easily performed and can be used to study functional signaling pathways in neuronal circuits. Copyright © 2010 Elsevier B.V. All rights reserved.

Influence of visual experience on developmental shift from long-term depression to long-term potentiation in the rat medial vestibular nuclei.

Science.gov (United States)

Grassi, Silvarosa; Dieni, Cristina; Frondaroli, Adele; Pettorossi, Vito Enrico

2004-11-01

The influence of visual experience deprivation on changes in synaptic plasticity during postnatal development was studied in the ventral part of the rat medial vestibular nuclei (vMVN). We analysed the differences in the occurrence, expressed as a percentage, of long-term depression (LTD) and long-term potentiation (LTP) induced by high frequency stimulation (HFS) of the primary vestibular afferents in rats reared in the light (LR) and those in the dark (DR). In LR rats, HFS only induced LTD in the early stages of development, but the occurrence of LTD progressively decreased to zero before their eyes opened, while that of LTP enhanced from zero to about 50%. Once the rats' eyes had opened, LTD was no longer inducible while LTP occurrence gradually reached the normal adult value (70%). In DR rats, a similar shift from LTD to LTP was observed before their eyes opened, showing only a slightly slower LTD decay and LTP growth, and the LTD annulment was delayed by 1 day. By contrast, the time courses of LTD and LTP development in DR and LR rats showed remarkable differences following eye opening. In fact, LTD occurrence increased to about 50% in a short period of time and remained high until the adult stage. In addition, the occurrence of LTP slowly decreased to less than 20%. The effect of light-deprivation was reversible, since the exposure of DR rats to light, 5 days after eye opening, caused a sudden disappearance of LTD and a partial recover of LTP occurrence. In addition, we observed that a week of light deprivation in LR adult rats did not affect the normal adult LTP occurrence. These results provide evidence that in a critical period of development visual input plays a crucial role in shaping synaptic plasticity of the vMVN, and suggest that the visual guided shift from LTD to LTP during development may be necessary to refine and consolidate vestibular circuitry.

Long-term effects of ayahuasca in patients with recurrent depression: a 5-year qualitative follow-up

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Rafael G. Dos Santos

Full Text Available Abstract Background Ayahuasca is a botanical hallucinogenic preparation traditionally used by indigenous populations of Northwestern Amazonian countries for ritual and therapeutic purposes. It is rich in β-carboline alkaloids and N,N-dimethyltryptamine (DMT. Preclinical, observational, and experimental studies suggest that ayahuasca and its alkaloids have anxiolytic and antidepressive effects. We recently reported in an open-label trial that ayahuasca administration was associated with significant decreases in depression symptoms for 2-3 weeks after the experimental session in 17 patients with treatment-resistant major depressive disorder. Objectives To investigate if the experiment had any long-lasting effects on patients Methods Eight patients were interviewed 4 to 7 years after ayahuasca intake. Results Our results suggest that ayahuasca was well tolerated and that symptom reductions were limited to a few weeks. Importantly, most patients believed that the experience was among the most important of their lives, even 4-7 years later. Discussion To the best of our knowledge, this is the first long-term follow-up of a clinical sample that participated in an ayahuasca trial. Further studies with different and repeated dosing should be designed to further explore the antidepressive and anxiolytic effects of ayahuasca.

Long-term plasticity determines the postsynaptic response to correlated afferents with multivesicular short-term synaptic depression

Directory of Open Access Journals (Sweden)

Alexander David Bird

2014-01-01

Full Text Available Synchrony in a presynaptic population leads to correlations in vesicle occupancy at the active sites for neurotransmitter release. The number of independent release sites per presynaptic neuron, a synaptic parameter recently shown to be modifed during long-term plasticity, will modulate these correlations and therefore have a significant effect on the firing rate of the postsynaptic neuron. To understand how correlations from synaptic dynamics and from presynaptic synchrony shape the postsynaptic response, we study a model of multiple release site short-term plasticity and derive exact results for the crosscorrelation function of vesicle occupancy and neurotransmitter release, as well as the postsynaptic voltage variance. Using approximate forms for the postsynaptic firing rate in the limits of low and high correlations, we demonstrate that short-term depression leads to a maximum response for an intermediate number of presynaptic release sites, and that this leads to a tuning-curve response peaked at an optimal presynaptic synchrony setby the number of neurotransmitter release sites per presynaptic neuron. These effects arise because, above a certain level of correlation, activity in the presynaptic population is overly strong resulting in wastage of the pool of releasable neurotransmitter. As the nervous system operates under constraints of efficient metabolism it is likely that this phenomenon provides an activity-dependent constraint on network architecture.

Long-term potentiation in the CA1 hippocampus induced by NR2A subunit-containing NMDA glutamate receptors is mediated by Ras-GRF2/Erk map kinase signaling.

Directory of Open Access Journals (Sweden)

Shan-xue Jin

Full Text Available BACKGROUND: NMDA-type glutamate receptors (NMDARs are major contributors to long-term potentiation (LTP, a form of synaptic plasticity implicated in the process of learning and memory. These receptors consist of calcium-permeating NR1 and multiple regulatory NR2 subunits. A majority of studies show that both NR2A and NR2B-containing NMDARs can contribute to LTP, but their unique contributions to this form of synaptic plasticity remain poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we show that NR2A and NR2B-containing receptors promote LTP differently in the CA1 hippocampus of 1-month old mice, with the NR2A receptors functioning through Ras-GRF2 and its downstream effector, Erk Map kinase, and NR2B receptors functioning independently of these signaling molecules. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that NR2A-, but not NR2B, containing NMDA receptors induce LTP in pyramidal neurons of the CA1 hippocampus from 1 month old mice through Ras-GRF2 and Erk. This difference add new significance to the observation that the relative levels of these NMDAR subtypes is regulated in neurons, such that NR2A-containing receptors become more prominent late in postnatal development, after sensory experience and synaptic activity.

Long-Term Mental Health Problems After Delirium in the ICU.

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Wolters, Annemiek E; Peelen, Linda M; Welling, Maartje C; Kok, Lotte; de Lange, Dylan W; Cremer, Olaf L; van Dijk, Diederik; Slooter, Arjen J C; Veldhuijzen, Dieuwke S

2016-10-01

To determine whether delirium during ICU stay is associated with long-term mental health problems defined as symptoms of anxiety, depression, and posttraumatic stress disorder. Prospective cohort study. Survey study, 1 year after discharge from a medical-surgical ICU in the Netherlands. One-year ICU survivors of an ICU admission lasting more than 48 hours, without a neurologic disorder or other condition that would impede delirium assessment during ICU stay. None. One year after discharge, ICU survivors received a survey containing the Hospital Anxiety and Depression Scale with a subscale for symptoms of depression and a subscale for symptoms of anxiety, and the Impact of Event Scale 15 item measuring symptoms of posttraumatic stress disorder. Participants were classified as having experienced no delirium (n = 270; 48%), a single day of delirium (n = 86; 15%), or multiple days of delirium (n = 211; 37%) during ICU stay. Log-binomial regression was used to assess the association between delirium and symptoms of anxiety, depression, and posttraumatic stress disorder. The study population consisted of 567 subjects; of whom 246 subjects (43%) reported symptoms of anxiety (Hospital Anxiety and Depression Scale with a subscale for anxiety, ≥ 8), and 254 (45%) symptoms of depression (Hospital Anxiety and Depression Scale with a subscale for depression, ≥ 8). In 220 patients (39%), the Impact of Event Scale 15 item was greater than or equal to 35, indicating a high probability of posttraumatic stress disorder. There was substantial overlap between these mental health problems-63% of the subjects who scored positive for the presence of any three of the mental health problems, scored positive for all three. No association was observed between either a single day or multiple days of delirium and symptoms of anxiety, depression, or posttraumatic stress disorder. Although symptoms of anxiety, depression, and posttraumatic stress disorder were found to be common 1 year after

Long-Term Physical Functioning and Its Association With Somatic Comorbidity and Comorbid Depression in Patients With Established Rheumatoid Arthritis: A Longitudinal Study

NARCIS (Netherlands)

van den Hoek, J.; Roorda, L.D.; Boshuizen, H.C.; van Hees, J.; Rupp, I.; Tijhuis, G.J.; Dekker, J.; van den Bos, G.A.M.

2013-01-01

Objective To describe long-term physical functioning and its association with somatic comorbidity and comorbid depression in patients with established rheumatoid arthritis (RA). Methods Longitudinal data over a period of 11 years were collected from 882 patients with RA at study inclusion.

Long-Term Physical Functioning and Its Association With Somatic Comorbidity and Comorbid Depression in Patients With Established Rheumatoid Arthritis: A Longitudinal Study

NARCIS (Netherlands)

Hoek, J.; Roorda, L.D.; Boshuizen, H.C.; Hees, van J.; Rupp, I.; Tijhuis, G.J.; Dekker, J.; Bos, van den G.A.M.

2013-01-01

ObjectiveTo describe long-term physical functioning and its association with somatic comorbidity and comorbid depression in patients with established rheumatoid arthritis (RA). MethodsLongitudinal data over a period of 11 years were collected from 882 patients with RA at study inclusion.

Influence of depressive and eating disorders on short- and long-term course of weight after surgical and nonsurgical weight loss treatment.

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Legenbauer, Tanja; Petrak, Frank; de Zwaan, Martina; Herpertz, Stephan

2011-01-01

To investigate the influence of depressive and eating disorders on short- and long-term weight loss after surgical and non-surgical weight-reduction treatment. Covariations between the disorders were considered. In a longitudinal naturalistic study, current diagnoses at baseline and lifetime diagnoses of depressive and eating disorders were assessed in participants who were undertaking a very-low-calorie diet (n = 250) and in bariatric surgery patients (n = 153). Lifetime diagnosis of a mental disorder was defined as presence of a mental disorder only in the past. Body weight was measured at baseline, 1 year after baseline, and 4 years after baseline. Mental comorbidity was assessed through use of standardized interviews at baseline. A structural equation modeling procedure was applied to test the associations between course of weight and mental disorders. Analyses were based on the intention to treat samples. Missing values were replaced by use of multiple imputation procedures. Neither depression nor eating disorders were associated with weight changes at the 1-year follow-up, but a specific effect emerged for bariatric surgery patients after 4 years: depression (current and lifetime) predicted smaller body mass index loss, whereas lifetime diagnosis of eating disorder was associated with greater weight loss. Individuals who report depressive disorders prior to bariatric surgery should be monitored more closely in order to identify patients who would benefit from additional therapy with the goal of improving weight-loss outcome. Copyright © 2011 Elsevier Inc. All rights reserved.

Differences in symptoms, functioning, and quality of life between women on long-term sick-leave with musculoskeletal pain with and without concomitant depression

Directory of Open Access Journals (Sweden)

Schüldt Ekholm K

2011-08-01

Full Text Available Gunilla Brodda Jansen1,2, Jürgen Linder3, Kristina Schüldt Ekholm4,5, Jan Ekholm2,41Department of Pain Management, Capio St Göran’s Hospital, 2Department of Clinical Sciences, Division of Rehabilitation Medicine, Karolinska Institutet, Danderyd Hospital, 3Diagnostic Centre, Division of Psychiatry, Department of Clinical Neuroscience, Karolinska Institutet, 4Stockholm Rehabilitation Medicine University Clinic, Danderyd Hospital; 5Section of Rehabilitation Science, Department of Health Sciences, Mid Sweden University, Campus Östersund, SwedenObjective: The aim was to describe the differences in symptoms, functioning and quality of life between women on long-term sick-leave due to protracted musculoskeletal pain with and without concomitant depression.Design: Descriptive and comparisons with/without comorbid depression.Methods: 332 female patients were examined by three specialist physicians in psychiatry, orthopedic surgery, and rehabilitation medicine and assigned to four groups according to the ICD-10 diagnoses: low back/joint disorders (LBJ, n = 150, myalgia (M, n = 43, fibromyalgia (FM, n = 87, or depression without somatic pain diagnosis (DE, n = 52.Results: Patients with somatic pain conditions LBJ, M, or FM showed more activity-related difficulties if concomitant depression was present during the activities ‘focusing attention’, ‘making decisions’, and ‘undertaking a single task’; and in the domains ‘energy level’, ‘memory functions’, ‘emotional functions’, and ‘optimism/pessimism’. Patients with FM and concomitant depression perceived higher pain intensity than patients in group DE. No statistically significant differences in physically related activities were noted between each of the somatic pain conditions with and without coexisting depression. FM patients with coexisting depression reported fewer painful sites on their pain drawings compared with FM-patients without depression. Patients with LBJ or FM

Chelation of hippocampal zinc enhances long-term potentiation and synaptic tagging/capture in CA1 pyramidal neurons of aged rats: implications to aging and memory.

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Shetty, Mahesh Shivarama; Sharma, Mahima; Sajikumar, Sreedharan

2017-02-01

Aging is associated with decline in cognitive functions, prominently in the memory consolidation and association capabilities. Hippocampus plays a crucial role in the formation and maintenance of long-term associative memories, and a significant body of evidence shows that impairments in hippocampal function correlate with aging-related memory loss. A number of studies have implicated alterations in hippocampal synaptic plasticity, such as long-term potentiation (LTP), in age-related cognitive decline although exact mechanisms underlying are not completely clear. Zinc deficiency and the resultant adverse effects on cognition have been well studied. However, the role of excess of zinc in synaptic plasticity, especially in aging, is not addressed well. Here, we have investigated the hippocampal zinc levels and the impairments in synaptic plasticity, such as LTP and synaptic tagging and capture (STC), in the CA1 region of acute hippocampal slices from 82- to 84-week-old male Wistar rats. We report increased zinc levels in the hippocampus of aged rats and also deficits in the tetani-induced and dopaminergic agonist-induced late-LTP and STC. The observed deficits in synaptic plasticity were restored upon chelation of zinc using a cell-permeable chelator. These data suggest that functional plasticity and associativity can be successfully established in aged neural networks by chelating zinc with cell-permeable chelating agents. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Alteration in plasma corticosterone levels following long term oral administration of lead produces depression like symptoms in rats.

Science.gov (United States)

Haider, Saida; Saleem, Sadia; Tabassum, Saiqa; Khaliq, Saima; Shamim, Saima; Batool, Zehra; Parveen, Tahira; Inam, Qurat-ul-ain; Haleem, Darakhshan J

2013-03-01

Lead toxicity is known to induce a broad range of physiological, biochemical and behavioral dysfunctions that may result in adverse effects on several organs, including the central nervous system. Long-term exposure to low levels of lead (Pb(2+)) has been shown to produce behavioral deficits in rodents and humans by affecting hypothalamic-pituitary-adrenal (HPA) axis. These deficits are thought to be associated with altered brain monoamine neurotransmission and due to changes in glucocorticoids levels. This study was designed to investigate the effects of Pb(2+)exposure on growth rate, locomotor activity, anxiety, depression, plasma corticosterone and brain serotonin (5-HT) levels in rats. Rats were exposed to lead in drinking water (500 ppm; lead acetate) for 5 weeks. The assessment of depression was done using the forced swimming test (FST). Estimation of brain 5-HT was determined by high-performance liquid chromatography with electrochemical detection. Plasma corticosterone was determined by spectrofluorimetric method. The present study showed that long term exposure to Pb(2+) significantly decreased the food intake followed by the decrease in growth rate in Pb(2+)exposed rats as compared to control group. No significant changes in open field activity were observed following Pb(2+)exposure while significant increase in anxiogenic effect was observed. Increased plasma corticosterone and decreased 5-HT levels were exhibited by Pb(2+)exposed rats as compared to controls. A significant increase in depressive like symptoms was exhibited by Pb(2+)exposed rats as compared to control rats. The results are discussed in the context of Pb(2+) inducing a stress-like response in rats leading to changes in plasma corticosterone and brain 5-HT levels via altering tryptophan pyrrolase activity.

Long-term exposure to endogenous levels of tributyltin decreases GluR2 expression and increases neuronal vulnerability to glutamate

International Nuclear Information System (INIS)

Nakatsu, Yusuke; Kotake, Yaichiro; Takishita, Tomoko; Ohta, Shigeru

2009-01-01

Tributyltin (TBT), an endocrine-disrupting chemical, has been used commercially as a heat stabilizer, agricultural pesticide and component of antifouling paints. In this study, we investigated the effect of long-term exposure to endogenous levels of TBT on neuronal glutamate receptors. Cultured rat cortical neurons were exposed to 1-50 nM TBT for 9 days (from day 2 to day 10 in vitro). The number of neurons was reduced by long-term exposure to 50 nM TBT, but not to 1-20 nM TBT. Long-term exposure to 20 nM TBT decreased the mRNA expression of glutamate receptors NR1, NR2A, GluR1 and GluR2, and increased that of NR2B, GluR3 and GluR4. GluR2 protein was also reduced by long-term exposure to TBT. Because AMPA receptor lacking GluR2 exhibits Ca 2+ permeability, we investigated whether Ca 2+ influx or glutamate toxicity was affected. Indeed, glutamate-induced Ca 2+ influx was increased in TBT-treated neurons. Consistent with this, neurons became more susceptible to glutamate toxicity as a result of long-term exposure to TBT and this susceptibility was abolished by an antagonist of GluR2-lacking AMPA receptor. Thus, it is suggested that long-term exposure to endogenous levels of TBT induces a decrease of GluR2 protein, causing neurons become more susceptible to glutamate toxicity.

Long-term exposure to endogenous levels of tributyltin decreases GluR2 expression and increases neuronal vulnerability to glutamate.

Science.gov (United States)

Nakatsu, Yusuke; Kotake, Yaichiro; Takishita, Tomoko; Ohta, Shigeru

2009-10-15

Tributyltin (TBT), an endocrine-disrupting chemical, has been used commercially as a heat stabilizer, agricultural pesticide and component of antifouling paints. In this study, we investigated the effect of long-term exposure to endogenous levels of TBT on neuronal glutamate receptors. Cultured rat cortical neurons were exposed to 1-50 nM TBT for 9 days (from day 2 to day 10 in vitro). The number of neurons was reduced by long-term exposure to 50 nM TBT, but not to 1-20 nM TBT. Long-term exposure to 20 nM TBT decreased the mRNA expression of glutamate receptors NR1, NR2A, GluR1 and GluR2, and increased that of NR2B, GluR3 and GluR4. GluR2 protein was also reduced by long-term exposure to TBT. Because AMPA receptor lacking GluR2 exhibits Ca2+ permeability, we investigated whether Ca2+ influx or glutamate toxicity was affected. Indeed, glutamate-induced Ca2+ influx was increased in TBT-treated neurons. Consistent with this, neurons became more susceptible to glutamate toxicity as a result of long-term exposure to TBT and this susceptibility was abolished by an antagonist of GluR2-lacking AMPA receptor. Thus, it is suggested that long-term exposure to endogenous levels of TBT induces a decrease of GluR2 protein, causing neurons become more susceptible to glutamate toxicity.

Personality and psychological distress among older adult, long-term cancer survivors.

Science.gov (United States)

Deimling, Gary T; Albitz, Casey; Monnin, Kara; Renzhofer Pappada, Holly T; Nalepa, Elizabeth; Boehm, Melinda Laroco; Mitchell, Claire

2017-01-01

This research examines a model of how personality (Five-Factor Model) is related to adjustment to cancer in later life in terms of the presence of continuing cancer-related worry and depression among older adult, long-term cancer survivors. Data from an NCI-funded study with 275 older adult (age 60+), long-term (5+ years) survivors of breast, prostate, and colorectal cancer were examined. Regression analyses identified neuroticism as the strongest predictor of cancer-related worry along with continuing cancer-related symptoms. For depression, three personality dimensions (neuroticism, conscientiousness, and agreeableness) were significant predictors. Findings suggest the importance of considering the central role that survivors' personality characteristics play in understanding cancer-related worries and depression. Understanding these dispositional characteristics is key for social workers and health-care practitioners in counseling survivors experiencing these common mental health effects.

The predictive value of mental health for long-term sickness absence: the Major Depression Inventory (MDI) and the Mental Health Inventory (MHI-5) compared.

Science.gov (United States)

Thorsen, Sannie Vester; Rugulies, Reiner; Hjarsbech, Pernille U; Bjorner, Jakob Bue

2013-09-17

Questionnaires are valuable for population surveys of mental health. Different survey instruments may however give different results. The present study compares two mental health instruments, the Major Depression Inventory (MDI) and the Mental Health Inventory (MHI-5), in regard to their prediction of long-term sickness absence. Questionnaire data was collected from N = 4153 Danish employees. The questionnaire included the MDI and the MHI-5. The information of long-term sickness absence was obtained from a register. We used Cox regression to calculate covariance adjusted hazard ratios for long-term sickness absence for both measures. Both the MDI and the MHI-5 had a highly significant prediction of long-term sickness absence. A one standard deviation change in score was associated with an increased risk of long-term sickness absence of 27% for the MDI and 37% for the MHI-5. When both measures were included in the same analysis, the MHI-5 performed best. In general population surveys, the MHI-5 is a better predictor of long-term sickness absence than the MDI.

Perceived stress and anhedonia predict short-and long-term weight change, respectively, in healthy adults.

Science.gov (United States)

Ibrahim, Mostafa; Thearle, Marie S; Krakoff, Jonathan; Gluck, Marci E

2016-04-01

Perceived stress; emotional eating; anhedonia; depression and dietary restraint, hunger, and disinhibition have been studied as risk factors for obesity. However, the majority of studies have been cross-sectional and the directionality of these relationships remains unclear. In this longitudinal study, we assess their impact on future weight change. Psychological predictors of weight change in short- (6month) and long-term (>1year) periods were studied in 65 lean and obese individuals in two cohorts. Subjects participated in studies of food intake and metabolism that did not include any type of medication or weight loss interventions. They completed psychological questionnaires at baseline and weight change was monitored at follow-up visits. At six months, perceived stress predicted weight gain (r(2)=0.23, P=0.02). There was a significant interaction (r(2)=.38, P=0.009) between perceived stress and positive emotional eating, such that higher scores in both predicted greater weight gain, while those with low stress but high emotional eating scores lost weight. For long-term, higher anhedonia scores predicted weight gain (r(2)=0.24, P=0.04). Depression moderated these effects such that higher scores in both predicted weight gain but higher depression and lower anhedonia scores predicted weight loss. There are different behavioral determinants for short- and long-term weight change. Targeting perceived stress may help with short-term weight loss while depression and anhedonia may be better targets for long-term weight regulation. Copyright © 2016 Elsevier Ltd. All rights reserved.

The GABA[subscript A] Receptor Agonist Muscimol Induces an Age- and Region-Dependent Form of Long-Term Depression in the Mouse Striatum

Science.gov (United States)

Zhang, Xiaoqun; Yao, Ning; Chergui, Karima

2016-01-01

Several forms of long-term depression (LTD) of glutamatergic synaptic transmission have been identified in the dorsal striatum and in the nucleus accumbens (NAc). Such experience-dependent synaptic plasticity might play important roles in reward-related learning. The GABA[subscript A] receptor agonist muscimol was recently found to trigger a…

The effects of lifestyle interventions on (long-term) weight management, cardiometabolic risk and depressive symptoms in people with psychotic disorders : A meta-analysis

NARCIS (Netherlands)

Bruins, Jojanneke; Jörg, Frederike; Bruggeman, Richard; Slooff, C. J.; Corpeleijn, Eva; Pijnenborg, Marieke

2014-01-01

AIMS: The aim of this study was to estimate the effects of lifestyle interventions on bodyweight and other cardiometabolic risk factors in people with psychotic disorders. Additionally, the long-term effects on body weight and the effects on depressive symptoms were examined. MATERIAL AND METHODS:

Cryo-EM Structure of a KCNQ1/CaM Complex Reveals Insights into Congenital Long QT Syndrome.

Science.gov (United States)

Sun, Ji; MacKinnon, Roderick

2017-06-01

KCNQ1 is the pore-forming subunit of cardiac slow-delayed rectifier potassium (I Ks ) channels. Mutations in the kcnq1 gene are the leading cause of congenital long QT syndrome (LQTS). Here, we present the cryoelectron microscopy (cryo-EM) structure of a KCNQ1/calmodulin (CaM) complex. The conformation corresponds to an "uncoupled," PIP 2 -free state of KCNQ1, with activated voltage sensors and a closed pore. Unique structural features within the S4-S5 linker permit uncoupling of the voltage sensor from the pore in the absence of PIP 2 . CaM contacts the KCNQ1 voltage sensor through a specific interface involving a residue on CaM that is mutated in a form of inherited LQTS. Using an electrophysiological assay, we find that this mutation on CaM shifts the KCNQ1 voltage-activation curve. This study describes one physiological form of KCNQ1, depolarized voltage sensors with a closed pore in the absence of PIP 2 , and reveals a regulatory interaction between CaM and KCNQ1 that may explain CaM-mediated LQTS. Copyright © 2017 Elsevier Inc. All rights reserved.

Depression, anxiety and quality of life in long-term survivors of malignant melanoma: a register-based cohort study.

Directory of Open Access Journals (Sweden)

Manfred E Beutel

Full Text Available The purpose of the study was to determine anxiety and depression, quality of life, and their determinants in long-term survivors of malignant melanoma.In a state cancer registry a cohort of survivors of malignant melanoma was contacted via the physician registered. Of 1302 contactable patients, 689 (52.2% completed a questionnaire including the Patient Health Questionnaire with generalized anxiety (GAD-7 and depression (PHQ-9 and the EORTC Quality of Life Questionnaire (EORTC QLQ 30. Based on multiple regression analysis, predictors of quality of life and distress were identified. Comparison data were assessed in two waves of representative face-to-face household surveys of the adult German population.An average of 8.4 (5.7 to 12.2 years after diagnosis, distress was higher in women compared to men and in middle adulthood (vs. older patients. Symptoms were higher in women than in men, and there was a decline of functioning and increase of symptoms across the age range of both genders. Compared to the general population, there were slightly increased depression and anxiety (only women, but no impaired global quality of life. Yet, survivors evidenced functional decline and more physical symptoms. Distress and reduced quality of life were consistently predicted by lack of social support, fear of recurrence, pessimism and self-blame. Distress was increased by a family history of melanoma, and additional mental and somatic diseases.Overall, long-term survivors have adjusted well achieving a global quality of life comparable to the general population. Yet, compromised functional dimensions, physical symptoms and distress indicate the need for integrating psychooncological screening into oncological follow-up, which might be guided by predictors such as family history or social support. Further prospective study is needed to determine the course of adaptation to the disease and corroborate the risk factors identified.

Hampered long-term depression and thin spine loss in the nucleus accumbens of ethanol-dependent rats.

Science.gov (United States)

Spiga, Saturnino; Talani, Giuseppe; Mulas, Giovanna; Licheri, Valentina; Fois, Giulia R; Muggironi, Giulia; Masala, Nicola; Cannizzaro, Carla; Biggio, Giovanni; Sanna, Enrico; Diana, Marco

2014-09-02

Alcoholism involves long-term cognitive deficits, including memory impairment, resulting in substantial cost to society. Neuronal refinement and stabilization are hypothesized to confer resilience to poor decision making and addictive-like behaviors, such as excessive ethanol drinking and dependence. Accordingly, structural abnormalities are likely to contribute to synaptic dysfunctions that occur from suddenly ceasing the use of alcohol after chronic ingestion. Here we show that ethanol-dependent rats display a loss of dendritic spines in medium spiny neurons of the nucleus accumbens (Nacc) shell, accompanied by a reduction of tyrosine hydroxylase immunostaining and postsynaptic density 95-positive elements. Further analysis indicates that "long thin" but not "mushroom" spines are selectively affected. In addition, patch-clamp experiments from Nacc slices reveal that long-term depression (LTD) formation is hampered, with parallel changes in field potential recordings and reductions in NMDA-mediated synaptic currents. These changes are restricted to the withdrawal phase of ethanol dependence, suggesting their relevance in the genesis of signs and/or symptoms affecting ethanol withdrawal and thus the whole addictive cycle. Overall, these results highlight the key role of dynamic alterations in dendritic spines and their presynaptic afferents in the evolution of alcohol dependence. Furthermore, they suggest that the selective loss of long thin spines together with a reduced NMDA receptor function may affect learning. Disruption of this LTD could contribute to the rigid emotional and motivational state observed in alcohol dependence.

Safety analysis SFR 1. Long-term safety

Energy Technology Data Exchange (ETDEWEB)

2008-12-15

An updated assessment of the long-term safety of SKB's final repository for radioactive operational waste, SFR 1, is presented in this report. The report is included in the safety analysis report for SFR 1. The most recent account of long-term safety was submitted to the regulatory authorities in 2001. The present report has been compiled on SKB's initiative to address the regulatory authorities' viewpoints regarding the preceding account of long-term safety. Besides the new mode of working with safety functions there is another important difference between the 2001 safety assessment and the current assessment: The time horizon in the current assessment has been extended to 100,000 years in order to include the effect of future climate changes. The purpose of this renewed assessment of the long-term safety of SFR 1 is to show with improved data that the repository is capable of protecting human health and the environment against ionizing radiation in a long-term perspective. This is done by showing that calculated risks lie below the risk criteria stipulated by the regulatory authorities. SFR 1 is built to receive, and after closure serve as a passive repository for, low. and intermediate-level radioactive waste. The disposal chambers are situated in rock beneath the sea floor, covered by about 60 metres of rock. The underground part of the facility is reached via two tunnels whose entrances are near the harbour. The repository has been designed so that it can be abandoned after closure without further measures needing to be taken to maintain its function. The waste in SFR 1 is short-lived low- and intermediate-level waste. After 100 years the activity is less than half, and after 1,000 years only about 2% of the original activity remains. The report on long-term safety comprises eleven chapters. Chapter 1 Introduction. The chapter describes the purpose, background, format and contents of SAR-08, applicable regulations and injunctions, and the regulatory

Safety analysis SFR 1. Long-term safety

International Nuclear Information System (INIS)

2008-12-01

An updated assessment of the long-term safety of SKB's final repository for radioactive operational waste, SFR 1, is presented in this report. The report is included in the safety analysis report for SFR 1. The most recent account of long-term safety was submitted to the regulatory authorities in 2001. The present report has been compiled on SKB's initiative to address the regulatory authorities' viewpoints regarding the preceding account of long-term safety. Besides the new mode of working with safety functions there is another important difference between the 2001 safety assessment and the current assessment: The time horizon in the current assessment has been extended to 100,000 years in order to include the effect of future climate changes. The purpose of this renewed assessment of the long-term safety of SFR 1 is to show with improved data that the repository is capable of protecting human health and the environment against ionizing radiation in a long-term perspective. This is done by showing that calculated risks lie below the risk criteria stipulated by the regulatory authorities. SFR 1 is built to receive, and after closure serve as a passive repository for, low. and intermediate-level radioactive waste. The disposal chambers are situated in rock beneath the sea floor, covered by about 60 metres of rock. The underground part of the facility is reached via two tunnels whose entrances are near the harbour. The repository has been designed so that it can be abandoned after closure without further measures needing to be taken to maintain its function. The waste in SFR 1 is short-lived low- and intermediate-level waste. After 100 years the activity is less than half, and after 1,000 years only about 2% of the original activity remains. The report on long-term safety comprises eleven chapters. Chapter 1 Introduction. The chapter describes the purpose, background, format and contents of SAR-08, applicable regulations and injunctions, and the regulatory

Safety analysis SFR 1. Long-term safety

Energy Technology Data Exchange (ETDEWEB)

2008-12-15

An updated assessment of the long-term safety of SKB's final repository for radioactive operational waste, SFR 1, is presented in this report. The report is included in the safety analysis report for SFR 1. The most recent account of long-term safety was submitted to the regulatory authorities in 2001. The present report has been compiled on SKB's initiative to address the regulatory authorities' viewpoints regarding the preceding account of long-term safety. Besides the new mode of working with safety functions there is another important difference between the 2001 safety assessment and the current assessment: The time horizon in the current assessment has been extended to 100,000 years in order to include the effect of future climate changes. The purpose of this renewed assessment of the long-term safety of SFR 1 is to show with improved data that the repository is capable of protecting human health and the environment against ionizing radiation in a long-term perspective. This is done by showing that calculated risks lie below the risk criteria stipulated by the regulatory authorities. SFR 1 is built to receive, and after closure serve as a passive repository for, low. and intermediate-level radioactive waste. The disposal chambers are situated in rock beneath the sea floor, covered by about 60 metres of rock. The underground part of the facility is reached via two tunnels whose entrances are near the harbour. The repository has been designed so that it can be abandoned after closure without further measures needing to be taken to maintain its function. The waste in SFR 1 is short-lived low- and intermediate-level waste. After 100 years the activity is less than half, and after 1,000 years only about 2% of the original activity remains. The report on long-term safety comprises eleven chapters. Chapter 1 Introduction. The chapter describes the purpose, background, format and contents of SAR-08, applicable regulations and injunctions, and the

Levothyroxine rescues the lead-induced hypothyroidism and impairment of long-term potentiation in hippocampal CA1 region of the developmental rats

International Nuclear Information System (INIS)

Wu Chuanyun; Liu Bing; Wang Huili; Ruan Diyun

2011-01-01

Lead (Pb) exposure during development has been associated with impaired long-term potentiation (LTP). Hypothyroidism happening upon subjects with occupational exposure to Pb is suggestive of an adverse effect of Pb on thyroid homeostasis, leading to the hypothesis that Pb exposure may alter thyroid hormone homeostasis. Hippocampus is one of the targets of Pb exposure, and is sensitive to and dependent on thyroid hormones, leading us to explore whether levothyroxine (L-T 4 ) administration could alter the thyroid disequilibrium and impairment of LTP in rat hippocampus caused by Pb exposure. Our results show that Pb exposure caused a decrease in triiodothyronine (T 3 ) and tetraiodothyronine (T 4 ) levels accompanied by a dramatic decrease of TSH and application of L-T 4 restored these changes to about control levels. Hippocampal and blood Pb concentration were significantly reduced following L-T 4 treatment. L-T 4 treatment rescued the impairment of LTP induced by the Pb exposure. These results suggest that Pb exposure may lead to thyroid dysfunction and induce hypothyroidism and provide a direct electrophysiological proof that L-T 4 relieves chronic Pb exposure-induced impairment of synaptic plasticity. - Highlights: → Lead may interfere with thyroid hormone homeostasis and induce hypothyroidism. → Levothyroxine decreases the hippocampal and blood Pb concentration. → Levothyroxine amends the T 3 , T 4 and TSH levels in blood. → Levothyroxine rescues the impaired LTP in CA1.

Long-lasting spatial learning and memory impairments caused by chronic cerebral hypoperfusion associate with a dynamic change of HCN1/HCN2 expression in hippocampal CA1 region.

Science.gov (United States)

Luo, Pan; Lu, Yun; Li, Changjun; Zhou, Mei; Chen, Cheng; Lu, Qing; Xu, Xulin; He, Zhi; Guo, Lianjun

2015-09-01

Chronic cerebral hypoperfusion (CCH) causes learning and memory impairments and increases the risk of Alzheimer disease (AD) and vascular dementia (VD) through several biologically plausible pathways, yet the mechanisms underlying the disease process remained unclear particularly in a temporal manner. We performed permanent bilateral occlusion of the common carotid arteries (two-vessel occlusion, 2VO) to induce CCH. To determine whether hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are altered at different stages of cognitive impairment caused by CCH, adult male SD rats were randomly distributed into sham-operated 4, 8 and 12weeks group, 2VO 4, 8 and 12weeks group. Learning and memory performance were evaluated with Morris water maze (MWM) and long-term potentiation (LTP) was used to address the underlying synaptic mechanisms. Expression of NeuN, HCN1 and HCN2 in hippocampal CA1, DG and CA3 areas was quantified by immunohistochemistry and western blotting. Our data showed that CCH induced a remarkable spatial learning and memory deficits in rats of 2VO 4, 8, and 12weeks group although neuronal loss only occurred after 4weeks of 2VO surgery in CA1. In addition, a significant reduction of HCN1 surface expression in CA1 was observed in the group that suffered 4weeks ischemia but neither 8 nor 12weeks. However, HCN2 surface expression in CA1 increased throughout the ischemia time-scales (4, 8 and 12w). Our findings indicate spatial learning and memory deficits in the CCH model are associated with disturbed HCN1 and HCN2 surface expression in hippocampal CA1. The altered patterns of both HCN1 and HCN2 surface expression may be implicated in the early stage (4w) of spatial learning and memory impairments; and the stable and long-lasting impairments of spatial learning and memory may partially attribute to the up-regulated HCN2 surface expression. Copyright © 2015 Elsevier Inc. All rights reserved.

Depressive morbidity among elderly individuals who are hospitalized, reside at long-term care facilities, and are under outpatient care in Brazil: a meta-analysis

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Luís Fernando S. Castro-de-Araújo

2013-06-01

Full Text Available Objectives: i To investigate studies published between 1991 and 2010 on the prevalence of depressive morbidity (major depressive disorder [MDD], dysthymia and clinically significant depressive symptoms [CSDS] among elderly Brazilians assisted at healthcare facilities; ii to establish the prevalence of depression and identify its related factors; and iii to conduct a meta-analysis to assess the prevalence of depressive syndrome among elderly individuals assisted or hospitalized at healthcare facilities. Methods: Studies were selected from articles dated between January 1991 and June 2010 and extracted from the MEDLINE, LILACS, and SciELO databases. Results: The final analysis consisted of 15 studies, distributed as follows: i four sampled hospitalized patients, totaling 299 individuals, and found a prevalence of CSDS varying between 20 and 56%; ii four sampled outpatients, totaling 1,454 individuals; the prevalence of CSDS varied between 11 and 65%, and the prevalence of MDD varied between 23 and 42%; and iii seven sampled elderly individuals residing in long-term care facilities (LTCF, totaling 839 individuals, and the prevalence of CSDS varied between 11 and 65%. Conclusion: The present review indicated a higher prevalence of both MDD and CSDS among elderly Brazilians assisted at healthcare facilities.

A Protein Synthesis and Nitric Oxide-Dependent Presynaptic Enhancement in Persistent Forms of Long-Term Potentiation

Science.gov (United States)

Johnstone, Victoria P. A.; Raymond, Clarke R.

2011-01-01

Long-term potentiation (LTP) is an important process underlying learning and memory in the brain. At CA3-CA1 synapses in the hippocampus, three discrete forms of LTP (LTP1, 2, and 3) can be differentiated on the basis of maintenance and induction mechanisms. However, the relative roles of pre- and post-synaptic expression mechanisms in LTP1, 2,…

Long-Term Prediction of Severe Hypoglycemia in Type 1 Diabetes

DEFF Research Database (Denmark)

Henriksen, Marie Moth; Færch, Louise; Thorsteinsson, Birger

2016-01-01

BACKGROUND: Prediction of risk of severe hypoglycemia (SH) in patients with type 1 diabetes is important to prevent future episodes, but it is unknown if it is possible to predict the long-term risk of SH. The aim of the study is to assess if long-term prediction of SH is possible in type 1...... diabetes. METHODS: A follow-up study was performed with 98 patients with type 1 diabetes. At baseline and at follow-up, the patients filled in a questionnaire about diabetes history and complications, number of SH in the preceding year and state of awareness, and HbA1c and C-peptide levels were measured......-up. CONCLUSIONS: Long-term prediction of severe hypoglycemia in type 1 diabetes was not possible, although baseline hypoglycemia unawareness tended to remain a predictor for risk of SH at follow-up. Therefore, it is important repeatedly to assess the different risk factors of SH to determine the actual risk....

Serotonin-1A receptor imaging in recurrent depression: replication and literature review

International Nuclear Information System (INIS)

Drevets, Wayne C.; Thase, Michael E.; Moses-Kolko, Eydie L.; Price, Julie; Frank, Ellen; Kupfer, David J.; Mathis, Chester

2007-01-01

exists disagreement within the literature, however, regarding the presence and direction of 5-HT 1A R-binding abnormalities in depression, which may be explained in some cases by differences in anatomical location (e.g., [Stockmeier CA, Shapiro LA, Dilley GE, Kolli TN, Friedman L, Rajkowska G. Increase in serotonin-1A autoreceptors in the midbrain of suicide victims with major depression - postmortem evidence for decreased serotonin activity. J Neurosci 1998;18(18):7394-401]) and in other cases by pathophysiological heterogeneity within MDD (e.g., some depressives hypersecrete cortisol, which would be expected to down-regulate 5-HT 1A R expression [Lopez JF, Chalmers DT, Little KY, Watson SJ. Regulation of serotonin 1A, glucocorticoid, and mineralocorticoid receptor in rat and human hippocampus: implications for neurobiology of depression. Biol Psychiatry 1998;43:547-73]). Antidepressant drug treatment does not alter these abnormalities in 5-HT 1A R binding [Sargent PA, Kjaer KH, Bench CJ, Rabiner EA, Messa C, Meyer J, Gunn RN, Grasby PM, Cowen PJ. Brain serotonin 1A receptor binding measured by positron emission tomography with [ 11 C]WAY-100635: effects of depression and antidepressant treatment. Arch Gen Psychiatry 2000;57(2):174-80; Moses-Kolko EL, Price JC, Thase ME, Meltzer CC, Kupfer DJ, Mathis CA, Bogers WD, Berman SR, Houck PR, Schneider TN, Drevets WC. Measurement of 5-HT(1A) receptor binding in depressed adults before and after antidepressant drug treatment using positron emission tomography and [ 11 C]WAY-100635. Synapse 2007;61(7):523-30] but may compensate for blunted 5-HT 1A R function by increasing post-synaptic 5-HT 1A R transmission [Chaput Y, de Montigny C, Blier P. Presynaptic and postsynaptic modifications of the serotonin system by long-term administra tion of antidepressant treatments. An in vivo electrophysiologic study in the rat. Neuropsychopharmacology 1991;5(4):219-29

Long-term maintenance of pediatric asthma: focus on budesonide/formoterol inhalation aerosol

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Peter N Huynh

2010-02-01

Full Text Available Peter N Huynh1, Lyne G Scott1, Kenny YC Kwong21Division of Allergy-Immunology, Department of Pediatrics, Los Angeles County, University of Southern California Medical Center, Los Angeles, CA, USA; 2Division of Allergy-Immunology, Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, USAAbstract: Current national and international asthma guidelines recommend treatment of children with asthma towards achieving and maintaining asthma control. These guidelines provide more stringent recommendations to increase therapy for patients with uncontrolled asthma in order to reduce asthma-related morbidity and mortality. Newer combination agents such as budesonide and formoterol have been shown to be safe and effective in treatment of asthma in children. Use of long-term controller agents like this in combination with improved compliance and treatment of co-morbid conditions have been successful in this endeavor. This review discusses control of pediatric asthma with focus on the use of budesonide in combination with formoterol.Keywords: asthma, control, children, budesonide, formoterol, long-term

Improvement of Depression and Anxiety After Discontinuation of Long- Term Efavirenz Treatment

NARCIS (Netherlands)

Mothapo, K.M.; Schellekens, A.F.A.; Crevel, R. van; Keuter, M.; Grintjes-Huisman, K.; Koopmans, P.; Ven, A. van der

2015-01-01

Neuropsychiatric symptoms in human immunodeficiency virus (HIV)-infected patients may be a late complication of efavirenz treatment. This study: 1) assessed the level of neuropsychiatric symptoms in HIV-infected patients on long-term efavirenz therapy; 2) explored the effect of a switch to

Long term psychological effects of a no sedation protocol in critically ill Patients

DEFF Research Database (Denmark)

Stroem, Thomas; Stylsvig, Mette; Toft, Palle

2011-01-01

interviewed (13 from each group). No difference was found with respect to quality of life (SF-36). Both mental and physical components were non-significant. Becks depression index was low in both groups (1 patient in intervention group vs. 3 patients in the control group were depressed, P=0.32). Evaluated...... applied to critically ill patients undergoing mechanical ventilation does not increase the risk of long term psychological sequelae after intensive care compared to standard treatment with sedation....

Short-term and long-term plasticity interaction in human primary motor cortex.

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Iezzi, Ennio; Suppa, Antonio; Conte, Antonella; Li Voti, Pietro; Bologna, Matteo; Berardelli, Alfredo

2011-05-01

Repetitive transcranial magnetic stimulation (rTMS) over primary motor cortex (M1) elicits changes in motor evoked potential (MEP) size thought to reflect short- and long-term forms of synaptic plasticity, resembling short-term potentiation (STP) and long-term potentiation/depression (LTP/LTD) observed in animal experiments. We designed this study in healthy humans to investigate whether STP as elicited by 5-Hz rTMS interferes with LTP/LTD-like plasticity induced by intermittent and continuous theta-burst stimulation (iTBS and cTBS). The effects induced by 5-Hz rTMS and iTBS/cTBS were indexed as changes in MEP size. We separately evaluated changes induced by 5-Hz rTMS, iTBS and cTBS applied alone and those induced by iTBS and cTBS delivered after priming 5-Hz rTMS. Interactions between 5-Hz rTMS and iTBS/cTBS were investigated under several experimental conditions by delivering 5-Hz rTMS at suprathreshold and subthreshold intensity, allowing 1 and 5 min intervals to elapse between 5-Hz rTMS and TBS, and delivering one and ten 5-Hz rTMS trains. We also investigated whether 5-Hz rTMS induces changes in intracortical excitability tested with paired-pulse transcranial magnetic stimulation. When given alone, 5-Hz rTMS induced short-lasting and iTBS/cTBS induced long-lasting changes in MEP amplitudes. When M1 was primed with 10 suprathreshold 5-Hz rTMS trains at 1 min before iTBS or cTBS, the iTBS/cTBS-induced after-effects disappeared. The 5-Hz rTMS left intracortical excitability unchanged. We suggest that STP elicited by suprathreshold 5-Hz rTMS abolishes iTBS/cTBS-induced LTP/LTD-like plasticity through non-homeostatic metaplasticity mechanisms. Our study provides new information on interactions between short-term and long-term rTMS-induced plasticity in human M1. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Physiological and Pathological Roles of CaMKII-PP1 Signaling in the Brain

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Norifumi Shioda

2017-12-01

Full Text Available Ca2+/calmodulin (CaM-dependent protein kinase II (CaMKII, a multifunctional serine (Ser/threonine (Thr protein kinase, regulates diverse activities related to Ca2+-mediated neuronal plasticity in the brain, including synaptic activity and gene expression. Among its regulators, protein phosphatase-1 (PP1, a Ser/Thr phosphatase, appears to be critical in controlling CaMKII-dependent neuronal signaling. In postsynaptic densities (PSDs, CaMKII is required for hippocampal long-term potentiation (LTP, a cellular process correlated with learning and memory. In response to Ca2+ elevation during hippocampal LTP induction, CaMKIIα, an isoform that translocates from the cytosol to PSDs, is activated through autophosphorylation at Thr286, generating autonomous kinase activity and a prolonged Ca2+/CaM-bound state. Moreover, PP1 inhibition enhances Thr286 autophosphorylation of CaMKIIα during LTP induction. By contrast, CaMKII nuclear import is regulated by Ser332 phosphorylation state. CaMKIIδ3, a nuclear isoform, is dephosphorylated at Ser332 by PP1, promoting its nuclear translocation, where it regulates transcription. In this review, we summarize physio-pathological roles of CaMKII/PP1 signaling in neurons. CaMKII and PP1 crosstalk and regulation of gene expression is important for neuronal plasticity as well as survival and/or differentiation.

D-Serine rescues the deficits of hippocampal long-term potentiation and learning and memory induced by sodium fluoroacetate.

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Han, Huili; Peng, Yan; Dong, Zhifang

2015-06-01

It is well known that bidirectional glia-neuron interactions play important roles in the neurophysiological and neuropathological processes. It is reported that impairing glial functions with sodium fluoroacetate (FAC) impaired hippocampal long-term depression (LTD) and spatial memory retrieval. However, it remains unknown whether FAC impairs hippocampal long-term potentiation (LTP) and learning and/or memory, and if so, whether pharmacological treatment with exogenous d-serine can recuse the impairment. Here, we reported that systemic administration of FAC (3mg/kg, i.p.) before training resulted in dramatic impairments of spatial learning and memory in water maze and fear memory in contextual fear conditioning. Furthermore, the behavioral deficits were accompanied by impaired LTP induction in the hippocampal CA1 area of brain slices. More importantly, exogenous d-serine treatment succeeded in recusing the deficits of hippocampal LTP and learning and memory induced by FAC. Together, these results suggest that astrocytic d-serine may be essential for hippocampal synaptic plasticity and memory, and that alteration of its levels may be relevant to the induction and potentially treatment of psychiatric and neurological disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of maternal postpartum depression in a well-resourced sample: Early concurrent and long-term effects on infant cognitive, language, and motor development.

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Smith-Nielsen, Johanne; Tharner, Anne; Krogh, Marianne Thode; Vaever, Mette Skovgaard

2016-12-01

This study examined early and long-term effects of maternal postpartum depression on cognitive, language, and motor development in infants of clinically depressed mothers. Participants were 83 mothers and their full-term born children from the urban region of Copenhagen, Denmark. Of this group, 28 mothers were diagnosed with postnatal depression three to four months postpartum in a diagnostic interview. Cognitive, language, and motor development was assessed with the Bayley Scales of Infant and Toddler Development third edition, when the infants were 4 and 13 months of age. We found that maternal postpartum depression was associated with poorer cognitive development at infant age four months, the effect size being large (Cohen's d = 0.8) and with similar effects for boys and girls. At 13 months of age infants of clinical mothers did not differ from infants of non-clinical mothers. At this time most (79%) of the clinical mothers were no longer, or not again, depressed. These results may indicate that maternal depression can have an acute, concurrent effect on infant cognitive development as early as at four months postpartum. At the same time, in the absence of other risk factors, this effect may not be enduring. The main weaknesses of the study include the relatively small sample size and that depression scores were only available for 35 of the non-clinical mothers at 13 months. © 2016 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

[Long-term psychiatric hospitalizations].

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Plancke, L; Amariei, A

2017-02-01

Long-term hospitalizations in psychiatry raise the question of desocialisation of the patients and the inherent costs. Individual indicators were extracted from a medical administrative database containing full-time psychiatric hospitalizations for the period 2011-2013 of people over 16 years old living in the French region of Nord-Pas-de-Calais. We calculated the proportion of people who had experienced a hospitalization with a duration of 292 days or more during the study period. A bivariate analysis was conducted, then ecological data (level of health-care offer, the deprivation index and the size of the municipalities of residence) were included into a multilevel regression model in order to identify the factors significantly related to variability of long-term hospitalization rates. Among hospitalized individuals in psychiatry, 2.6% had had at least one hospitalization of 292 days or more during the observation period; the number of days in long-term hospitalization represented 22.5% of the total of days of full-time hospitalization in psychiatry. The bivariate analysis revealed that seniority in the psychiatric system was strongly correlated with long hospitalization rates. In the multivariate analysis, the individual indicators the most related to an increased risk of long-term hospitalization were: total lack of autonomy (OR=9.0; 95% CI: 6.7-12.2; P<001); diagnoses of psychological development disorders (OR=9.7; CI95%: 4.5-20.6; P<.001); mental retardation (OR=4.5; CI95%: 2.5-8.2; P<.001): schizophrenia (OR=3.0; CI95%: 1.7-5.2; P<.001); compulsory hospitalization (OR=1.7; CI95%: 1.4-2.1; P<.001); having experienced therapeutic isolation (OR=1.8; CI95%: 1.5-2.1; P<.001). Variations of long-term hospitalization rates depending on the type of establishment were very high, but the density of hospital beds or intensity of ambulatory activity services were not significantly linked to long-term hospitalization. The inhabitants of small urban units had

Molecular constraints on synaptic tagging and maintenance of long-term potentiation: a predictive model.

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Smolen, Paul; Baxter, Douglas A; Byrne, John H

2012-01-01

Protein synthesis-dependent, late long-term potentiation (LTP) and depression (LTD) at glutamatergic hippocampal synapses are well characterized examples of long-term synaptic plasticity. Persistent increased activity of protein kinase M ζ (PKMζ) is thought essential for maintaining LTP. Additional spatial and temporal features that govern LTP and LTD induction are embodied in the synaptic tagging and capture (STC) and cross capture hypotheses. Only synapses that have been "tagged" by a stimulus sufficient for LTP and learning can "capture" PKMζ. A model was developed to simulate the dynamics of key molecules required for LTP and LTD. The model concisely represents relationships between tagging, capture, LTD, and LTP maintenance. The model successfully simulated LTP maintained by persistent synaptic PKMζ, STC, LTD, and cross capture, and makes testable predictions concerning the dynamics of PKMζ. The maintenance of LTP, and consequently of at least some forms of long-term memory, is predicted to require continual positive feedback in which PKMζ enhances its own synthesis only at potentiated synapses. This feedback underlies bistability in the activity of PKMζ. Second, cross capture requires the induction of LTD to induce dendritic PKMζ synthesis, although this may require tagging of a nearby synapse for LTP. The model also simulates the effects of PKMζ inhibition, and makes additional predictions for the dynamics of CaM kinases. Experiments testing the above predictions would significantly advance the understanding of memory maintenance.

Impact of depression on long-term outcome after renal transplantation: a prospective cohort study.

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Zelle, Dorien M; Dorland, Heleen F; Rosmalen, Judith G M; Corpeleijn, Eva; Gans, Reinold O B; Homan van der Heide, Jaap J; van Son, Willem J; Navis, Gerjan; Bakker, Stephan J L

2012-11-27

Renal transplantation is the treatment of choice for end stage renal disease. Although there is more depression in wait-listed versus transplant patients, depression persists after transplantation. We investigated the determinants of depression in renal transplantation recipients (RTRs) and the association with cardiovascular (CV) and all-cause-mortality and graft failure. RTR were investigated between 2001 and 2003. Depression was assessed using the Depression Subscale of the Symptom Checklist (SCL-90). Mortality and graft failure were recorded until May 2009. A total of 527 RTR (age, 51±12 years; 55% men) were studied; 31% of the RTR were indicated with depression. Independent variables associated with depression were medically unfit for work, proteinuria, lower physical activity level, and longer dialysis duration. During follow-up for 7.0 (6.2-7.5) years, 114 RTR (59 CV) died. In Cox regression analyses, depression was strongly associated with increased risk for CV (HR=2.12 [1.27-3.53], P=0.004) and all-cause mortality (HR=1.96 [1.36-2.84], P<0.001). Adjustments for confounders did not materially change these associations. The association with graft failure (HR=1.77 [1.01-3.10]. P=0.047) disappeared after adjustment for kidney function (P=0.6). Although our study has several limitations, including the lack of pretransplant depression status, we identified medically unfit for work, proteinuria, lower physical activity level, and longer dialysis duration as independent variables associated with depression. We furthermore found that depression is associated with CV and all-cause mortality in RTR.

Self-reported immature defense style as a predictor of outcome in short-term and long-term psychotherapy.

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Laaksonen, Maarit A; Sirkiä, Carlos; Knekt, Paul; Lindfors, Olavi

2014-07-01

Identification of pretreatment patient characteristics predictive of psychotherapy outcome could help to guide treatment choices. This study evaluates patients' initial level of immature defense style as a predictor of the outcome of short-term versus long-term psychotherapy. In the Helsinki Psychotherapy Study, 326 adult outpatients with mood or anxiety disorder were randomized to individual short-term (psychodynamic or solution-focused) or long-term (psychodynamic) psychotherapy. Their defense style was assessed at baseline using the 88-item Defense Style Questionnaire and classified as low or high around the median value of the respective score. Both specific (Beck Depression Inventory [BDI], Hamilton Depression Rating Scale [HDRS], Symptom Check List Anxiety Scale [SCL-90-Anx], Hamilton Anxiety Rating Scale [HARS]) and global (Symptom Check List Global Severity Index [SCL-90-GSI], Global Assessment of Functioning Scale [GAF]) psychiatric symptoms were measured at baseline and 3-7 times during a 3-year follow-up. Patients with high use of immature defense style experienced greater symptom reduction in long-term than in short-term psychotherapy by the end of the 3-year follow-up (50% vs. 34%). Patients with low use of immature defense style experienced faster symptom reduction in short-term than in long-term psychotherapy during the first year of follow-up (34% vs. 19%). Knowledge of patients' initial level of immature defense style may potentially be utilized in tailoring treatments. Further research on defense styles as outcome predictors in psychotherapies of different types is needed.

An essential role for UBE2A/HR6A in learning and memory and mGLUR-dependent long-term depression.

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Bruinsma, Caroline F; Savelberg, Sanne M C; Kool, Martijn J; Jolfaei, Mehrnoush Aghadavoud; Van Woerden, Geeske M; Baarends, Willy M; Elgersma, Ype

2016-01-01

UBE2A deficiency syndrome (also known as X-linked intellectual disability type Nascimento) is an intellectual disability syndrome characterized by prominent dysmorphic features, impaired speech and often epilepsy. The syndrome is caused by Xq24 deletions encompassing the UBE2A (HR6A) gene or by intragenic UBE2A mutations. UBE2A encodes an E2 ubiquitin-conjugating enzyme involved in DNA repair and female fertility. A recent study in Drosophila showed that dUBE2A binds to the E3 ligase Parkin, which is required for mitochondrial function and responsible for juvenile Parkinson's disease. In addition, these studies showed impairments in synaptic transmission in dUBE2A mutant flies. However, a causal role of UBE2A in of cognitive deficits has not yet been established. Here, we show that Ube2a knockout mice have a major deficit in spatial learning tasks, whereas other tested phenotypes, including epilepsy and motor coordination, were normal. Results from electrophysiological measurements in the hippocampus showed no deficits in synaptic transmission nor in the ability to induce long-term synaptic potentiation. However, a small but significant deficit was observed in mGLUR-dependent long-term depression, a pathway previously implied in several other mouse models for neurodevelopmental disorders. Our results indicate a causal role of UBE2A in learning and mGLUR-dependent long-term depression, and further indicate that the Ube2a knockout mouse is a good model to study the molecular mechanisms underlying UBE2A deficiency syndrome. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Personality and the Long-Term Outcome of First-Episode Depression

DEFF Research Database (Denmark)

Bukh, Jens D.; Andersen, Per K.; Kessing, Lars V.

2016-01-01

or outpatients aged 18–70 years with a validated diagnosis of a single depressive episode according to ICD-10 were assessed by the Structured Clinical Interview for DSM-IV Axis II Personality Disorders and the Eysenck Personality Questionnaire from 2005 through 2007. At 5-year follow-up, 262 patients were...... disorder decreased the rate of remission by 30% (HR = 0.7; 95% CI, 0.5–0.9; P = .02) and increased the rate of recurrence after remission of the first depression by 80% (HR = 1.8; 95% CI, 1.0–3.0; P = .04). A higher neuroticism score at baseline decreased the rate of remission by 20% for each increase of 1...... SD (HR = 0.8; 95% CI, 0.7–0.9; P = .002), and a higher level of extraversion increased the rate of conversion to bipolar disorder by 60% for each increase of 1 SD (HR = 1.6; 95% CI, 1.0–2.5; P = .05). Conclusions: Comorbidity of cluster C personality disorders and the level of neuroticism...

Informing the Long-Term Learner Model: Motivating the Adult Learner (Phase 1)

Science.gov (United States)

2017-09-28

memory systems: 1) short - term memory , 2) working memory , and 3) long - term memory . The short - term memory stores the information for brief periods of...and the episodic buffer, which is linked to long - term memory . The visual working memory shares parts and interacts with attention (Gazzaley and...Nobre 2012; Zanto et al. 2011). Short - term memory is limited in its importance to

The requirement for enhanced CREB1 expression in consolidation of long-term synaptic facilitation and long-term excitability in sensory neurons of Aplysia

Science.gov (United States)

Liu, Rong-Yu; Cleary, Leonard J.; Byrne, John H.

2011-01-01

Accumulating evidence suggests that the transcriptional activator CREB1 is important for serotonin (5-HT)-induced long-term facilitation (LTF) of the sensorimotor synapse in Aplysia. Moreover, creb1 is among the genes activated by CREB1, suggesting a role for this protein beyond the induction phase of LTF. The time course of the requirement for CREB1 synthesis in the consolidation of long-term facilitation was examined using RNA interference (RNAi) techniques in sensorimotor co-cultures. Injection of CREB1 small-interfering RNA (siRNA) immediately or 10 h after 5-HT treatment blocked LTF when measured at 24 h and 48 h after treatment. In contrast, CREB1 siRNA did not block LTF when injected 16 h after 5-HT treatment. These results demonstrate that creb1 expression must be sustained for a relatively long time in order to support the consolidation of LTF. In addition, LTF is also accompanied by a long-term increase in the excitability (LTE) of sensory neurons (SNs). Because LTE was observed in the isolated SN after 5-HT treatment, this long-term change was intrinsic to that element of the circuit. LTE was blocked when CREB1 siRNA was injected into isolated SNs immediately after 5-HT treatment. These data suggest that 5-HT-induced CREB1 synthesis is required for consolidation of both LTF and LTE. PMID:21543617

Opening remarks for a panel discussion on short-term vs long-term procurement

International Nuclear Information System (INIS)

Courtenay, R.H.

1990-01-01

Long-term contracting in the late 1970's and early 1980's is blamed for some of the inequities that plague the uranium industry today. Utilities are obliged to pay prices far above prevailing levels and relatively low cost producers are forced to shut down while watching less efficient suppliers stay in business thanks to their long term supply agreements. Furthermore, it is argued that long-term contracts have contributed to supply instability by forcing the buildup of surplus inventories and by supporting excess incremental production by suppliers who have a baseload of long-term contracts. The depressed prices resulting from this oversupply are in turn jeopardizing future resource development and damaging supply reliability. In summary, the author's argument is that supply reliability will be greatly enhanced by the assurance of adequate primary supply from traditional sources such as Canada. This will not happen without long-term contracts. This conclusion may not be expected coming from a representative of Canada's largest uranium producer. But the final comment is less self serving. Many of the critics of long term contracts apparently expect a continuing and plentiful supply of East Bloc uranium to the spot market. A further question is to what extent East Bloc suppliers will eventually require long-term contracts in order to maintain production facilitates in economies that are no longer centrally planned, and where there is open competition for capital. Ultimately, reliability of supply from the non-traditional suppliers may also depend on long-term contracts

Trajectories of change and long-term outcomes in a randomised controlled trial of internet-based insomnia treatment to prevent depression.

Science.gov (United States)

Batterham, Philip J; Christensen, Helen; Mackinnon, Andrew J; Gosling, John A; Thorndike, Frances P; Ritterband, Lee M; Glozier, Nick; Griffiths, Kathleen M

2017-09-01

Insomnia treatment using an internet-based cognitive-behavioural therapy for insomnia (CBT-I) program reduces depression symptoms, anxiety symptoms and suicidal ideation. However, the speed, longevity and consistency of these effects are unknown. To test the following: whether the efficacy of online CBT-I was sustained over 18 months; how rapidly the effects of CBT-I emerged; evidence for distinct trajectories of change in depressive symptoms; and predictors of these trajectories. A randomised controlled trial compared the 6-week Sleep Healthy Using the Internet (SHUTi) CBT-I program to an attention control program. Adults ( N =1149) with clinical insomnia and subclinical depression symptoms were recruited online from the Australian community. Depression, anxiety and insomnia decreased significantly by week 4 of the intervention period and remained significantly lower relative to control for >18 months (between-group Cohen's d =0.63, 0.47, 0.55, respectively, at 18 months). Effects on suicidal ideation were only short term. Two depression trajectories were identified using growth mixture models: improving (95%) and stable/deteriorating (5%) symptoms. More severe baseline depression, younger age and limited comfort with the internet were associated with reduced odds of improvement. Online CBT-I produced rapid and long-term symptom reduction in people with subclinical depressive symptoms, although the initial effect on suicidal ideation was not sustained. P.J.B. has received grants from the National Health and Medical Research Council (NHMRC) during the conduct of the study. H.C. has received grants from the NHMRC and the Australian Research Council during the conduct of the study. L.M.R. receives research funding from the National Institutes of Health (NIH) that, in part, focuses on insomnia. F.P.T. and L.M.R. have equity ownership in BeHealth Solutions (Charlottesville, VA, USA), a company that develops and makes available products related to the research reported

DREAM (Downstream Regulatory Element Antagonist Modulator contributes to synaptic depression and contextual fear memory

Directory of Open Access Journals (Sweden)

Wu Long-Jun

2010-01-01

Full Text Available Abstract The downstream regulatory element antagonist modulator (DREAM, a multifunctional Ca2+-binding protein, binds specifically to DNA and several nucleoproteins regulating gene expression and with proteins outside the nucleus to regulate membrane excitability or calcium homeostasis. DREAM is highly expressed in the central nervous system including the hippocampus and cortex; however, the roles of DREAM in hippocampal synaptic transmission and plasticity have not been investigated. Taking advantage of transgenic mice overexpressing a Ca2+-insensitive DREAM mutant (TgDREAM, we used integrative methods including electrophysiology, biochemistry, immunostaining, and behavior tests to study the function of DREAM in synaptic transmission, long-term plasticity and fear memory in hippocampal CA1 region. We found that NMDA receptor but not AMPA receptor-mediated current was decreased in TgDREAM mice. Moreover, synaptic plasticity, such as long-term depression (LTD but not long-term potentiation (LTP, was impaired in TgDREAM mice. Biochemical experiments found that DREAM interacts with PSD-95 and may inhibit NMDA receptor function through this interaction. Contextual fear memory was significantly impaired in TgDREAM mice. By contrast, sensory responses to noxious stimuli were not affected. Our results demonstrate that DREAM plays a novel role in postsynaptic modulation of the NMDA receptor, and contributes to synaptic plasticity and behavioral memory.

Depression with melancholic features is associated with higher long-term risk for dementia.

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Simões do Couto, Frederico; Lunet, Nuno; Ginó, Sandra; Chester, Catarina; Freitas, Vanda; Maruta, Carolina; Figueira, Maria Luísa; de Mendonça, Alexandre

2016-09-15

Depression has been reported to increase the risk of subsequently developing dementia, but the nature of this relation remains to be elucidated. Depression can be a prodrome/manifestation of dementia or an early risk factor, and the effect may differ according to depression subtypes. Our aim was to study the association between early-onset depression and different depression subtypes, and the later occurrence of dementia. We conducted a cohort study including 322 subjects with depression, recruited between 1977 and 1984. A comparison cohort (non-exposed) was recruited retrospectively, to include 322 subjects admitted at the same hospital for routine surgery (appendicectomy or cholecystectomy), at the same period as the depressed cohort. Subjects were contacted again between 2009 and 2014, to assess their dementia status. We computed the risk for dementia in subjects with early onset depression and quantified the association between different depression subtypes (namely melancholic, anxious, and psychotic) and dementia. The odds of dementia were increased by 2.90 times (95% C.I. 1.61-5.21; pdepressed cohort when compared to the surgical cohort. When the analysis was restricted to patients younger than 45 years old at baseline, the odds for dementia in the depressed cohort were also significantly higher when compared to the surgical cohort (8.53; 95% C.I. 2.40-30.16). In the multivariate Cox analysis, subjects having depression with melancholic features had an increased risk for developing dementia compared to those without melancholic features (HR=3.64; 95% C.I. 1.78-11.26; p=0.025). About 59% of the participants with depression and 53% of those non-exposed were lost during follow up. The inclusion of biological biomarkers would strengthen the results. The sample included a low number of bipolar patients. These results support depression as an early risk factor for dementia. Depression with melancholic features was found as an important risk factor for dementia

Are female children more vulnerable to the long-term effects of maternal depression during pregnancy?

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Quarini, Catherine; Pearson, Rebecca M; Stein, Alan; Ramchandani, Paul G; Lewis, Glyn; Evans, Jonathan

2016-01-01

Female fetuses are more vulnerable to high levels of maternal glucocorticoids. We examined whether exposure to prenatal maternal depression, a condition associated with high glucocorticoids, carries greater risk for depression at 12 and 18 years in girls. Our sample comprised 7959 mothers and children from the Avon Longitudinal Study of Parents and Children following imputation for missing data. Maternal depression was assessed pre-and post-natally, and offspring depression at ages 12 and 18. We used logistic regression models to examine the relationship between exposure to prenatal and postnatal depression and offspring depression at 18 and 12 and interactions with gender. There was an interaction between prenatal depression and gender (P=0.027) and between postnatal depression and gender (P=0.027) for offspring depression at 18. Following adjustment in pre-natally depressed mothers, the odds ratio for offspring depression at 18 was 1.55 (95% c.i. 1.03-2.34) for girls and 0.54 (0.23-1.26) for boys. In post-natally depressed mothers, the odds ratio for offspring depression at 18 was 1.15 (0.70-1.89) in girls and 3.13 (1.52-6.45) in boys. However there was no evidence for interaction between prenatal or postnatal depression and gender (P=0.559 and 0.780 respectively) for offspring depression at 12. As expected with this large cohort spanning over 18 years, there was loss-to-follow-up. This is the first evidence in humans that increased vulnerability of female fetuses to maternal stress responses during pregnancy persists into adolescence. One explanation for gender differences emerging later is more depressive symptomatology is attributed to heritable risk at 12, whereas biological processes involved in brain development at 18 may be influenced by foetal programming. If replicated, this study has potential to help understand intergenerational transmission of depression, a leading cause of morbidity worldwide. Copyright © 2015 The Authors. Published by Elsevier B

Estradiol pretreatment ameliorates impaired synaptic plasticity at synapses of insulted CA1 neurons after transient global ischemia

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Takeuchi, Koichi; Yang, Yupeng; Takayasu, Yukihiro; Gertner, Michael; Hwang, Jee-Yeon; Aromolaran, Kelly; Bennett, Michael V.L.; Zukin, R. Suzanne

2015-01-01

Global ischemia in humans or induced experimentally in animals causes selective and delayed neuronal death in pyramidal neurons of the hippocampal CA1. The ovarian hormone estradiol administered before or immediately after insult affords histological protection in experimental models of focal and global ischemia and ameliorates the cognitive deficits associated with ischemic cell death. However, the impact of estradiol on the functional integrity of Schaffer collateral to CA1 (Sch-CA1) pyramidal cell synapses following global ischemia is not clear. Here we show that long term estradiol treatment initiated 14 days prior to global ischemia in ovariectomized female rats acts via the IGF-1 receptor to protect the functional integrity of CA1 neurons. Global ischemia impairs basal synaptic transmission, assessed by the input/output relation at Sch-CA1 synapses, and NMDA receptor (NMDAR)-dependent long term potentiation (LTP), assessed at 3 days after surgery. Presynaptic function, assessed by fiber volley and paired pulse facilitation, is unchanged. To our knowledge, our results are the first to demonstrate that estradiol at near physiological concentrations enhances basal excitatory synaptic transmission and ameliorates deficits in LTP at synapses onto CA1 neurons in a clinically-relevant model of global ischemia. Estradiol-induced rescue of LTP requires the IGF-1 receptor, but not the classical estrogen receptors (ER)-α or β. These findings support a model whereby estradiol acts via the IGF-1 receptor to maintain the functional integrity of hippocampal CA1 synapses in the face of global ischemia. PMID:25463028

In vivo studies of the long-term 51Cr red cell survival of serologically incompatible red cell units

International Nuclear Information System (INIS)

Baldwin, M.L.; Ness, P.M.; Barrasso, C.; Kickler, T.S.; Drew, H.; Tsan, M.F.; Shirey, R.S.

1985-01-01

The long-term survival of serologically incompatible red cell units was measured in five patients with antibodies to high-frequency antigens. Initially, the survival of 1 ml of 51 Cr-labeled incompatible red cells was measured over 1 hour. After demonstrating that the 1-hour survival times were successful (greater than 70%), each patient then received 5 ml of the same 51 Cr-labeled red cells followed by the transfusion of the remainder of the red cell unit. The long-term T 1/2Cr survival for each case was patient 1 (anti-McCa), 15 days; patient 2 (anti-JMH), 12 days; patient 3 (anti-Kna), 31 days; patient 4 (anti-McCa), 12 days; and patient 5 (anti-Hya), 14 days. Each antibody tested in an in vitro homologous macrophage assay showed less than 5 percent phagocytosis. Anti-JMH was the only antibody to react with IgG subclass antisera and was determined to be IgG4. The macrophage assay, IgG subclass testing, and short-term (1 hour, 1 ml) 51 Cr survival studies all indicated that the short-term survival was good. However, only the measurement of long-term survival with transfused units of serologically incompatible red cells was able to determine the actual survival, and clinical significance of the alloantibodies. Determining the actual long-term survival by the method described here can be of importance for patients requiring chronic red cell transfusion

Conditions of long-term success in a lifestyle intervention for overweight and obese youths.

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Fröhlich, Georg; Pott, Wilfried; Albayrak, Özgür; Hebebrand, Johannes; Pauli-Pott, Ursula

2011-10-01

Childhood lifestyle interventions usually involve the families. However, knowledge of family characteristics that promote or constrain a child's weight-reduction outcome is limited. Candidates for such factors might be family characteristics that have proven to be associated with social adjustment (development) in childhood. Thus, we analyzed whether family adversity, maternal depression, and attachment insecurity predict long-term success in children's weight reduction. Participants in the study were 111 parent-child dyads with overweight and obese children/adolescents (BMI mean: 29.07 [SD: 4.7] [range: 21.4-44.9]; BMI SD score mean: 2.43 [SD: 0.44] [range: 1.31-3.54]) aged between 7 and 15 years. The families took part in a best-practice lifestyle intervention of 1 year's duration. A longitudinal analysis with 3 assessment waves (baseline, conclusion, 1-year follow-up) was conducted. Hierarchical regression analyses revealed that long-term success (at least 5% weight reduction by the 1-year follow-up) versus failure (dropping out or less weight reduction) was significantly predicted by the set of psychosocial variables (family adversity, maternal depression, and attachment insecurity) when we controlled for familial obesity, preintervention overweight, age, and gender of the index child and parental educational level. Maternal depression proved to be the best predictor. Maintenance of weight reduction between the conclusion of the program and the 1-year-follow-up was also predicted by the set of psychosocial variables. Maternal insecure-anxious attachment attitudes best predicted this criterion. Although cross-validation is required, our results are the first evidence for proximal and distal family characteristics linked to long-term weight-reduction outcomes. The results suggest a need to create tailored intervention modules that address the difficulties of these families.

Chronic treatment with ginsenoside Rg1 promotes memory and hippocampal long-term potentiation in middle-aged mice.

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Zhu, G; Wang, Y; Li, J; Wang, J

2015-04-30

Ginseng serves as a potential candidate for the treatment of aging-related memory decline or memory loss. However, the related mechanism is not fully understood. In this study, we applied an intraperitoneal injection of ginsenoside Rg1, an active compound from ginseng in middle-aged mice and detected memory improvement and the underlying mechanisms. Our results showed that a period of 30-day administration of ginsenoside Rg1 enhanced long-term memory in the middle-aged animals. Consistent with the memory improvement, ginsenoside Rg1 administration facilitated weak theta-burst stimulation (TBS)-induced long-term potentiation (LTP) in acute hippocampal slices from middle-aged animals. Ginsenoside Rg1 administration increased the dendritic apical spine numbers and area in the CA1 region. In addition, ginsenoside Rg1 administration up-regulated the expression of hippocampal p-AKT, brain-derived neurotrophic factor (BDNF), proBDNF and glutamate receptor 1 (GluR1), but not p-ERK. Interestingly, the phosphatase and tensin homolog deleted on chromosome ten (PTEN) inhibitor (bpV) mimicked the ginsenoside Rg1 effects, including increasing p-AKT expression, promoting hippocampal basal synaptic transmission, LTP and memory. Taken together, our data suggest that ginsenoside Rg1 treatment improves memory in middle-aged mice possibly through regulating the PI3K/AKT pathway, altering apical spines and facilitating hippocampal LTP. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Long-term cost-effectiveness of collaborative care (vs usual care) for people with depression and comorbid diabetes or cardiovascular disease: a Markov model informed by the COINCIDE randomised controlled trial.

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Camacho, Elizabeth M; Ntais, Dionysios; Coventry, Peter; Bower, Peter; Lovell, Karina; Chew-Graham, Carolyn; Baguley, Clare; Gask, Linda; Dickens, Chris; Davies, Linda M

2016-10-07

To evaluate the long-term cost-effectiveness of collaborative care (vs usual care) for treating depression in patients with diabetes and/or coronary heart disease (CHD). 36 primary care general practices in North West England. 387 participants completed baseline assessment (collaborative care: 191; usual care: 196) and full or partial 4-month follow-up data were captured for 350 (collaborative care: 170; usual care: 180). 62% of participants were male, 14% were non-white. Participants were aged ≥18 years, listed on a Quality and Outcomes Framework register for CHD and/or type 1 or 2 diabetes mellitus, with persistent depressive symptoms. Patients with psychosis or type I/II bipolar disorder, actively suicidal, in receipt of services for substance misuse, or already in receipt of psychological therapy for depression were excluded. Collaborative care consisted of evidence-based low-intensity psychological treatments, delivered over 3 months and case management by a practice nurse and a Psychological Well Being Practitioner. As planned, the primary measure of cost-effectiveness was the incremental cost-effectiveness ratio (cost per quality-adjusted life year (QALY)). A Markov model was constructed to extrapolate the trial results from short-term to long-term (24 months). The mean cost per participant of collaborative care was £317 (95% CI 284 to 350). Over 24 months, it was estimated that collaborative care was associated with greater healthcare usage costs (net cost £674 (95% CI -30 953 to 38 853)) and QALYs (net QALY gain 0.04 (95% CI -0.46 to 0.54)) than usual care, resulting in a cost per QALY gained of £16 123, and a likelihood of being cost-effective of 0.54 (willingness to pay threshold of £20 000). Collaborative care is a potentially cost-effective long-term treatment for depression in patients with comorbid physical and mental illness. The estimated cost per QALY gained was below the threshold recommended by English decision

Long-term effects of intermittent equine parathyroid hormone fragment (ePTH-1-37) administration on bone metabolism in healthy horses.

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Weisrock, Katharina U; Winkelsett, Sarah; Martin-Rosset, William; Forssmann, Wolf-Georg; Parvizi, Nahid; Coenen, Manfred; Vervuert, Ingrid

2011-11-01

Intermittent administration of parathyroid hormone (PTH) is an anabolic therapy for osteoporotic conditions in humans. This study evaluated the effects of equine PTH fragment (ePTH-1-37) administration on bone metabolism in 12 healthy horses. Six horses each were treated once daily for 120days with subcutaneous injections of 0.5μg/kg ePTH-1-37 or placebo. Blood was collected to determine ionized calcium (Ca(++)), total Ca (Ca(T)), inorganic phosphorus, serum equine osteocalcin (eOC), carboxy-terminal telopeptide of type I collagen (ICTP), bone-specific alkaline phosphatase, and carboxy-terminal cross-linked telopeptide of type I collagen. Bone mineral density (BMD) was determined with dual X-ray absorptiometry of the metacarpus and calcaneus. Significantly higher blood Ca(++) and plasma Ca(T) concentrations were measured 5h after ePTH-1-37 administration compared to placebo. Higher serum eOC concentrations were found for ePTH-1-37 treatment at days 90 (P<0.05) and 120 (P=0.05). Significantly higher serum ICTP levels were observed with ePTH-1-37 treatment at days 60 and 90. For both study groups, BMD increased significantly in the calcaneus. Long-term use of ePTH-1-37 seemed to have no negative effects on bone metabolism in healthy horses. The absence of undesirable side effects is the premise to ensure safety for further clinical investigations in horses with increased bone resorption processes. Copyright © 2011 Elsevier Ltd. All rights reserved.

Toxicological effects of clofibric acid and diclofenac on plasma thyroid hormones of an Indian major carp, Cirrhinus mrigala during short and long-term exposures.

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Saravanan, Manoharan; Hur, Jang-Hyun; Arul, Narayanasamy; Ramesh, Mathan

2014-11-01

In the present investigation, the toxicity of most commonly detected pharmaceuticals in the aquatic environment namely clofibric acid (CA) and diclofenac (DCF) was investigated in an Indian major carp Cirrhinus mrigala. Fingerlings of C. mrigala were exposed to different concentrations (1, 10 and 100μgL(-1)) of CA and DCF for a period of 96h (short term) and 35 days (long term). The toxic effects of CA and DCF on thyroid hormones (THs) such as thyroid stimulating hormone (TSH), thyroxine (T4) and triiodothyronine (T3) levels were evaluated. During the short and long-term exposure period TSH level was found to be decreased at all concentrations of CA (except at the end of 14(th) day in 1 and 10μgL(-l) and 21(st) day in 1μgL(-l)) whereas in DCF exposed fish TSH level was found to be increased when compared to control groups. T4 level was found to be decreased at 1 and 100μgL(-l) of CA exposure at the end of 96h. However, T4 level was decreased at all concentrations of CA and DCF during long-term (35 days) exposure period. Fish exposed to all concentrations of CA and DCF had lower level of T3 in both the treatments. These results suggest that both CA and DCF drugs induced significant changes (P<0.01 and P<0.05) on thyroid hormonal levels of C. mrigala. The alterations of these hormonal levels can be used as potential biomarkers in monitoring of pharmaceutical drugs in aquatic organisms. Copyright © 2014 Elsevier B.V. All rights reserved.

Predictors and long-term health outcomes of eating disorders.

Directory of Open Access Journals (Sweden)

Katie M O'Brien

Full Text Available Anorexia and bulimia nervosa may have long-term effects on overall and reproductive health. We studied predictors of self-reported eating disorders and associations with later health events. We estimated odds ratios (ORs for these associations in 47,759 participants from the Sister Study. Two percent (n = 967 of participants reported a history of an eating disorder. Risk factors included being non-Hispanic white, having well-educated parents, recent birth cohort (OR = 2.16, 95% confidence interval [CI]: 2.01-2.32 per decade, and having a sister with an eating disorder (OR = 3.68, CI: 1.92-7.02. As adults, women who had experienced eating disorders were more likely to smoke, to be underweight, to have had depression, to have had a later first birth, to have experienced bleeding or nausea during pregnancy, or to have had a miscarriage or induced abortion. In this descriptive analysis, we identified predictors of and possible long-term health consequences of eating disorders. Eating disorders may have become more common over time. Interventions should focus on prevention and mitigation of long-term adverse health effects.

Long-term solar wind electron variations between 1971 and 1978

International Nuclear Information System (INIS)

Feldman, W.C.; Asbridge, J.R.; Bame, S.J.; Gosling, J.T.

1979-01-01

Imp solar wind electron data measured between 1971 and 1978 were studied with the aim of determining long-term variations near the earth. Two separate sets of parameter variations were observed: (1) in 1976--1977 the solar wind density, the electron temperature, and the interplanetary electrostatic potential were all enhanced, and (2) the halo density and associated electron parameters were all depressed during a 1 1/2-year period centered on the last 6 months of 1976. Although interpretation of these results in terms of corresponding coronal and interplanetary variations is not unique, it may be significant that measured solar wind parameters near the minimum of solar cycle 20 agree better with the Hartle-Sturrock model of the coronal expansion than they do during other epochs

Long-term product consistency test of simulated 90-19/Nd HLW glass

International Nuclear Information System (INIS)

Gan, X.Y.; Zhang, Z.T.; Yuan, W.Y.; Wang, L.; Bai, Y.; Ma, H.

2011-01-01

Chemical durability of 90-19/Nd glass, a simulated high-level waste (HLW) glass in contact with the groundwater was investigated with a long-term product consistency test (PCT). Generally, it is difficult to observe the long term property of HLW glass due to the slow corrosion rate in a mild condition. In order to overcome this problem, increased contacting surface (S/V = 6000 m -1 ) and elevated temperature (150 o C) were employed to accelerate the glass corrosion evolution. The micro-morphological characteristics of the glass surface and the secondary minerals formed after the glass alteration were analyzed by SEM-EDS and XRD, and concentrations of elements in the leaching solution were determined by ICP-AES. In our experiments, two types of minerals, which have great impact on glass dissolution, were found to form on 90-19/Nd HLW glass surface when it was subjected to a long-term leaching in the groundwater. One is Mg-Fe-rich phyllosilicates with honeycomb structure; the other is aluminosilicates (zeolites). Mg and Fe in the leaching solution participated in the formation of phyllosilicates. The main components of phyllosilicates in alteration products of 90-19/Nd HLW glass are nontronite (Na 0.3 Fe 2 Si 4 O 10 (OH) 2 .4H 2 O) and montmorillonite (Ca 0.2 (Al,Mg) 2 Si 4 O 10 (OH) 2 .4H 2 O), and those of aluminosilicates are mordenite ((Na 2 ,K 2 ,Ca)Al 2 Si 10 O 24 .7H 2 O)) and clinoptilolite ((Na,K,Ca) 5 Al 6 Si 30 O 72 .18H 2 O). Minerals like Ca(Mg)SO 4 and CaCO 3 with low solubility limits are prone to form precipitant on the glass surface. Appearance of the phyllosilicates and aluminosilicates result in the dissolution rate of 90-19/Nd HLW glass resumed, which is increased by several times over the stable rate. As further dissolution of the glass, both B and Na in the glass were found to leach out in borax form.

Depressing effect of phenoxyl acetic acids on flotation of minerals containing Ca2+/Mg2+ gangues

Institute of Scientific and Technical Information of China (English)

无

2007-01-01

Phenoxyl acetic acids were applied to determine their depressing effect on minerals containing Ca2+/Mg2+ gangues. Calcite,mixture of calcite and fluorite, and nickel ore were used in the flotation. And the depression mechanism was studied by the determination of contact angle, zeta potential, adsorptive capacity of collector, and IR analysis as well. It is found that 0.1 mmol/L of phenoxyl acetic acid derived from pyrogallol or gallic acid exhibits strong depressing ability on calcite in almost zero yields at pH value of 9.8, and calcite can be depressed in the flotation of calcite/fluorite mixture for approximate 87% yield of fluorite. The flotation result of practical nickel ore containing serpentine indicates that these two depressants may also show better depression performance to serpentine than traditional depressants such as sodium fluosilicate and carboxylmethyl cellulose. Analysis for the depression mechanism reveals that there exists strong chemical interaction between the depressants and minerals.

Molecular constraints on synaptic tagging and maintenance of long-term potentiation: a predictive model.

Directory of Open Access Journals (Sweden)

Paul Smolen

Full Text Available Protein synthesis-dependent, late long-term potentiation (LTP and depression (LTD at glutamatergic hippocampal synapses are well characterized examples of long-term synaptic plasticity. Persistent increased activity of protein kinase M ζ (PKMζ is thought essential for maintaining LTP. Additional spatial and temporal features that govern LTP and LTD induction are embodied in the synaptic tagging and capture (STC and cross capture hypotheses. Only synapses that have been "tagged" by a stimulus sufficient for LTP and learning can "capture" PKMζ. A model was developed to simulate the dynamics of key molecules required for LTP and LTD. The model concisely represents relationships between tagging, capture, LTD, and LTP maintenance. The model successfully simulated LTP maintained by persistent synaptic PKMζ, STC, LTD, and cross capture, and makes testable predictions concerning the dynamics of PKMζ. The maintenance of LTP, and consequently of at least some forms of long-term memory, is predicted to require continual positive feedback in which PKMζ enhances its own synthesis only at potentiated synapses. This feedback underlies bistability in the activity of PKMζ. Second, cross capture requires the induction of LTD to induce dendritic PKMζ synthesis, although this may require tagging of a nearby synapse for LTP. The model also simulates the effects of PKMζ inhibition, and makes additional predictions for the dynamics of CaM kinases. Experiments testing the above predictions would significantly advance the understanding of memory maintenance.

Effect of BRCA1/2 mutation on short-term and long-term breast cancer survival: a systematic review and meta-analysis.

Science.gov (United States)

Lee, Eun-Ha; Park, Sue K; Park, Boyoung; Kim, Sung-Won; Lee, Min Hyuk; Ahn, Sei Hyun; Son, Byung Ho; Yoo, Keun-Young; Kang, Daehee

2010-07-01

Reports of BRCA genetic mutations and risk of death or recurrence are inconsistent. This study aimed to compare overall and disease-free breast cancer survival rates between BRCA1/2 mutation carriers and non-carriers for short-term and long-term outcomes separately. We searched the PUBMED and EMBASE databases and retrieved 452 articles using keywords that included breast cancer, BRCA mutation, and survival. Seventeen articles were selected for systematic review and among them 11 were included in our meta-analysis. We used the random-effects model to calculate the summary hazard ratio and corresponding 95% confidence interval. BRCA1 mutation carriers had significantly lower short-term and long-term overall survival rates (OSR) relative to non-carriers (HR = 1.92 [95% CI = 1.45-2.53]; 1.33 [1.12-1.58], respectively), while both short-term and long-term OSR of BRCA2 carriers did not differ from non-carriers (HR = 1.30 [95% CI = 0.95-1.76]; 1.12 [95% CI = 0.86-1.45], respectively). For short-term progression-free survival rate (PFSR), BRCA1 mutation carriers had a significantly lower rate than non-carriers (HR = 1.54 [95% CI = 1.12-2.12]), while BRCA2 mutation carriers had a similar PFSR (HR = 1.23 [95% CI = 0.96-1.58]). For long-term PFSRs, we found no significant results. Our results suggest that BRCA1 mutation decreases short-term and long-term OSRs and short-term PFSR, however, BRCA2 mutation does not affect either short-term or long-term survival rate, which is attributed to the different carcinogenic pathways for BRCA1 and BRCA2.

A randomized controlled trial of combined exercise and psycho-education for low-SES women: short- and long-term outcomes in the reduction of stress and depressive symptoms.

Science.gov (United States)

van der Waerden, Judith E B; Hoefnagels, Cees; Hosman, Clemens M H; Souren, Pierre M; Jansen, Maria W J

2013-08-01

Exercise may have both a preventive and a therapeutic impact on mental health problems. The Exercise without Worries intervention aims to reduce stress and depressive symptoms in low-SES women by means of a group-based program combining physical exercise and psycho-education. Between September 2005 and May 2008, 161 Dutch low-SES women with elevated stress or depressive symptom levels were randomly assigned to the combined exercise/psycho-education intervention (EP), exercise only (E) or a waiting list control condition (WLC). The E condition provided low to moderate intensity stretching, strength, flexibility, and body focused training as well as relaxation, while the EP program integrated the exercise with cognitive-behavioral techniques. Depressive symptoms (CES-D) and perceived stress (PSS) were measured before and immediately after the intervention and at 2, 6 and 12 month follow-up. Multilevel linear mixed-effects models revealed no differential patterns in reduction of CES-D or PSS scores between the EP, E and WLC groups on the short (post-test and 2 month follow-up) or long term (6 and 12 months follow-up). Depressive symptom outcomes were moderated by initial depressive symptom scores: women from the EP and E groups with fewer initial symptoms benefited from participation on the short term. Further, women in the EP and E groups with the lowest educational level reported more stress reduction at post-test than women with higher educational levels. In the overall target population of low-SES women, no indications were found that the Exercise without Worries course reduced depressive symptom and stress levels on the short or long term. The findings do suggest, however, that exercise alone or in combination with psycho-education may be a viable prevention option for certain groups of disadvantaged women. Especially those low-SES women with less severe initial problems or those with low educational attainment should be targeted for future depression prevention

Long-term calcium addition increases growth release, wound closure, and health of sugar maple (Acer saccharum) trees at the Hubbard Brook Experimental Forest

Science.gov (United States)

Brett A. Huggett; Paul G. Schaberg; Gary J. Hawley; Christopher Eager

2007-01-01

We surveyed and wounded forest-grown sugar maple (Acer saccharum Marsh.) trees in a long-term, replicated Ca manipulation study at the Hubbard Brook Experimental Forest in New Hampshire, USA. Plots received applications of Ca (to boost Ca availability above depleted ambient levels) or A1 (to compete with Ca uptake and further reduce Ca availability...

Cholinergic induction of input-specific late-phase LTP via localized Ca2+ release in the visual cortex.

Science.gov (United States)

Cho, Kwang-Hyun; Jang, Hyun-Jong; Jo, Yang-Hyeok; Singer, Wolf; Rhie, Duck-Joo

2012-03-28

Acetylcholine facilitates long-term potentiation (LTP) and long-term depression (LTD), substrates of learning, memory, and sensory processing, in which acetylcholine also plays a crucial role. Ca(2+) ions serve as a canonical regulator of LTP/LTD but little is known about the effect of acetylcholine on intracellular Ca(2+) dynamics. Here, we investigated dendritic Ca(2+) dynamics evoked by synaptic stimulation and the resulting LTP/LTD in layer 2/3 pyramidal neurons of the rat visual cortex. Under muscarinic stimulation, single-shock electrical stimulation (SES) inducing ∼20 mV EPSP, applied via a glass electrode located ∼10 μm from the basal dendrite, evoked NMDA receptor-dependent fast Ca(2+) transients and the subsequent Ca(2+) release from the inositol 1,4,5-trisphosphate (IP(3))-sensitive stores. These secondary dendritic Ca(2+) transients were highly localized within 10 μm from the center (SD = 5.0 μm). The dendritic release of Ca(2+) was a prerequisite for input-specific muscarinic LTP (LTPm). Without the secondary Ca(2+) release, only muscarinic LTD (LTDm) was induced. D(-)-2-amino-5-phosphopentanoic acid and intracellular heparin blocked LTPm as well as dendritic Ca(2+) release. A single burst consisting of 3 EPSPs with weak stimulus intensities instead of the SES also induced secondary Ca(2+) release and LTPm. LTPm and LTDm were protein synthesis-dependent. Furthermore, LTPm was confined to specific dendritic compartments and not inducible in distal apical dendrites. Thus, cholinergic activation facilitated selectively compartment-specific induction of late-phase LTP through IP(3)-dependent Ca(2+) release.

Dimorphic changes of some features of loving relationships during long-term use of antidepressants in depressed outpatients.

Science.gov (United States)

Marazziti, Donatella; Akiskal, Hagop S; Udo, Mieko; Picchetti, Michela; Baroni, Stefano; Massimetti, Gabriele; Albanese, Francesco; Dell'Osso, Liliana

2014-09-01

The present study aimed at investigating the possible changes of some features of loving relationships during long-term treatment of depression with both selective serotonin reuptake inhibitors (SSRIs) and tricyclics (TCAs), by means of a specifically designed test, the so-called "Sex, Attachment, Love" (SALT) questionnaire. The sample was composed by 192 outpatients (123 women and 69 men, mean age±SD: 41.2±10.2 years), suffering from mild or moderate depression, according to DSM-IV-TR criteria, that were selected if they were treated with one antidepressant only for at least six months and were involved in a loving relationship. The results showed that SSRIs had a significant impact on the feelings of love and attachment towards the partner especially in men, while women taking TCAs complained of more sexual side effects than men. These data were supported also by the detection of a significant interaction between drug and sex on the "Love" and "Sex" domains. The present findings, while demonstrating a dimorphic effect of antidepressants on some component of loving relationships, need to be deepened in future studies. Copyright © 2014 Elsevier B.V. All rights reserved.

The self-management of longer-term depression: learning from the patient, a qualitative study.

Science.gov (United States)

Chambers, Eleni; Cook, Sarah; Thake, Anna; Foster, Alexis; Shaw, Sue; Hutten, Rebecca; Parry, Glenys; Ricketts, Tom

2015-07-24

Depression is a common mental health condition now viewed as chronic or long-term. More than 50 % of people will have at least one further episode of depression after their first, and therefore it requires long-term management. However, little is known about the effectiveness of self-management in depression, in particular from the patients' perspective. This study aimed to understand how people with longer-term depression manage the condition, how services can best support self-management and whether the principles and concepts of the recovery approach would be advantageous. Semi-structured in depth interviews were carried out with 21 participants, recruited from a range of sources using maximum variation sampling. Interpretative Phenomenological Analysis was used by a diverse team comprised of service users, practitioners and academics. Four super-ordinate themes were found: experience of depression, the self, the wider environment, self-management strategies. Within these, several prominent sub-themes emerged of importance to the participants. These included how aspects of themselves such as hope, confidence and motivation could be powerful agents; and how engaging in a wide range of chosen activities could contribute to their emotional, mental, physical, social, spiritual and creative wellbeing. Services in general were not perceived to be useful in specifically facilitating self-management. Increased choice and control were needed and a greater emphasis on an individualised holistic model. Improved information was needed about how to develop strategies and locate resources, especially during the first episode of depression. These concepts echoed those of the recovery approach, which could therefore be seen as valuable in aiding the self-management of depression.

Long-term athletic development- part 1: a pathway for all youth.

Science.gov (United States)

Lloyd, Rhodri S; Oliver, Jon L; Faigenbaum, Avery D; Howard, Rick; De Ste Croix, Mark B A; Williams, Craig A; Best, Thomas M; Alvar, Brent A; Micheli, Lyle J; Thomas, D Phillip; Hatfield, Disa L; Cronin, John B; Myer, Gregory D

2015-05-01

The concept of developing talent and athleticism in youth is the goal of many coaches and sports systems. Consequently, an increasing number of sporting organizations have adopted long-term athletic development models in an attempt to provide a structured approach to the training of youth. It is clear that maximizing sporting talent is an important goal of long-term athletic development models. However, ensuring that youth of all ages and abilities are provided with a strategic plan for the development of their health and physical fitness is also important to maximize physical activity participation rates, reduce the risk of sport- and activity-related injury, and to ensure long-term health and well-being. Critical reviews of independent models of long-term athletic development are already present within the literature; however, to the best of our knowledge, a comprehensive examination and review of the most prominent models does not exist. Additionally, considerations of modern day issues that may impact on the success of any long-term athletic development model are lacking, as are proposed solutions to address such issues. Therefore, within this 2-part commentary, Part 1 provides a critical review of existing models of practice for long-term athletic development and introduces a composite youth development model that includes the integration of talent, psychosocial and physical development across maturation. Part 2 identifies limiting factors that may restrict the success of such models and offers potential solutions.

Daily cognitive appraisals, daily affect, and long-term depressive symptoms: the role of self-esteem and self-concept clarity in the stress process.

Science.gov (United States)

Lee-Flynn, Sharon C; Pomaki, Georgia; Delongis, Anita; Biesanz, Jeremy C; Puterman, Eli

2011-02-01

The current study investigated how self-esteem and self-concept clarity are implicated in the stress process both in the short and long term. Initial and 2-year follow-up interviews were completed by 178 participants from stepfamily unions. In twice-daily structured diaries over 7 days, participants reported their main family stressor, cognitive appraisals (perceived stressor threat and stressor controllability), and negative affect. Results of multilevel modeling indicated that high self-esteem ameliorated the effect of daily negative cognitive appraisals on daily negative affect. Self-concept clarity also buffered the effect of low self-self-esteem on depressive symptoms 2 years later. Our findings point to the vulnerability of those having low self-esteem or low self-concept clarity in terms of both short- and long-term adaptation to stress. They indicate the need for the consideration of such individual differences in designing stress management interventions.

Serotonin-1A receptor imaging in recurrent depression: replication and literature review

Energy Technology Data Exchange (ETDEWEB)

Drevets, Wayne C. [Mood and Anxiety Disorders Program, MINH Molecular Imaging Branch, Bethesda, MD 20892 (United States); Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 19213 (United States); Department of Radiology, University of Pittsburgh, Pittsburgh, PA 19213 (United States)], E-mail: drevetsw@mail.nih.gov; Thase, Michael E. [Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 19213 (United States); Department of Psychiatry, University of Pennsylvania, School of Medicine and Philadelphia Veterans Affairs Medical Center, Philadelphia, PA 19104 (United States); Moses-Kolko, Eydie L. [Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 19213 (United States); Price, Julie [Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 19213 (United States); Department of Radiology, University of Pittsburgh, Pittsburgh, PA 19213 (United States); Frank, Ellen; Kupfer, David J. [Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 19213 (United States); Mathis, Chester [Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 19213 (United States); Department of Radiology, University of Pittsburgh, Pittsburgh, PA 19213 (United States)

2007-10-15

}R-binding capacity in the raphe in depressed suicide victims [Arango V, Underwood MD, Boldrini M, Tamir H, Kassir SA, Hsiung S, Chen JJ, Mann JJ. Serotonin 1A receptors, serotonin transporter binding and serotonin transporter mRNA expression in the brainstem of depressed suicide victims. Neuropsychopharmacology 2001;25(6):892-903]. There exists disagreement within the literature, however, regarding the presence and direction of 5-HT{sub 1A}R-binding abnormalities in depression, which may be explained in some cases by differences in anatomical location (e.g., [Stockmeier CA, Shapiro LA, Dilley GE, Kolli TN, Friedman L, Rajkowska G. Increase in serotonin-1A autoreceptors in the midbrain of suicide victims with major depression - postmortem evidence for decreased serotonin activity. J Neurosci 1998;18(18):7394-401]) and in other cases by pathophysiological heterogeneity within MDD (e.g., some depressives hypersecrete cortisol, which would be expected to down-regulate 5-HT{sub 1A}R expression [Lopez JF, Chalmers DT, Little KY, Watson SJ. Regulation of serotonin 1A, glucocorticoid, and mineralocorticoid receptor in rat and human hippocampus: implications for neurobiology of depression. Biol Psychiatry 1998;43:547-73]). Antidepressant drug treatment does not alter these abnormalities in 5-HT{sub 1A}R binding [Sargent PA, Kjaer KH, Bench CJ, Rabiner EA, Messa C, Meyer J, Gunn RN, Grasby PM, Cowen PJ. Brain serotonin{sub 1A} receptor binding measured by positron emission tomography with [{sup 11}C]WAY-100635: effects of depression and antidepressant treatment. Arch Gen Psychiatry 2000;57(2):174-80; Moses-Kolko EL, Price JC, Thase ME, Meltzer CC, Kupfer DJ, Mathis CA, Bogers WD, Berman SR, Houck PR, Schneider TN, Drevets WC. Measurement of 5-HT(1A) receptor binding in depressed adults before and after antidepressant drug treatment using positron emission tomography and [{sup 11}C]WAY-100635. Synapse 2007;61(7):523-30] but may compensate for blunted 5-HT{sub 1A}R function by increasing post

Long-term MRA follow-up after coiling of intracranial aneurysms: impact on mood and anxiety

International Nuclear Information System (INIS)

Ferns, Sandra P.; Nieuwkerk, Pythia T.; Majoie, Charles B.L.M.; Rooij, Willem Jan J. van; Rinkel, Gabriel J.E.

2011-01-01

Magnetic resonance angiography (MRA) screening for recurrence of a coiled intracranial aneurysm and formation of new aneurysms long-term after coiling may induce anxiety and depression. In coiled patients, we evaluated effects on mood and level of anxiety from long-term follow-up MRA in comparison to general population norms. Of 162 patients participating in a long-term (>4.5 years) MRA follow-up after coiling, 120 completed the EQ-5D questionnaire, a visual analog health scale and a self-developed screening related questionnaire at the time of MRA. Three months later, the same questionnaires were completed by 100 of these 120 patients. Results were compared to general population norms adjusted for gender and age. Any problem with anxiety or depression was reported in 56 of 120 patients (47%; 95%CI38 56%) at baseline and 42 of 100 patients (42%; 95%CI32 52%) at 3 months, equally for screen-positives and -negatives. Compared to the reference population, participants scored 38% (95%CI9 67%) and 27% (95%CI4 50%) more often any problem with anxiety or depression. Three months after screening, 21% (20 of 92) of screen-negatives and 13% (one of eight) of screen-positives reported to be less afraid of subarachnoid hemorrhage (SAH) compared to before screening. One of eight screen-positives reported increased fear of SAH. Patients with coiled intracranial aneurysms participating in long-term MRA screening reported significantly more often to be anxious or depressed than a reference group. Screening did not significantly increase anxiety or depression temporarily. However, subjectively, patients did report an increase in anxiety caused by screening, which decreased after 3 months. (orig.)

Long-term MRA follow-up after coiling of intracranial aneurysms: impact on mood and anxiety

Energy Technology Data Exchange (ETDEWEB)

Ferns, Sandra P.; Nieuwkerk, Pythia T.; Majoie, Charles B.L.M. [Academic Medical Center, Department of Radiology, Amsterdam (Netherlands); Rooij, Willem Jan J. van [St. Elisabeth Ziekenhuis, Department of Radiology, Tilburg (Netherlands); Rinkel, Gabriel J.E. [University Medical Center, Department of Neurology, Rudolf Magnus Institute of Neuroscience, Utrecht (Netherlands)

2011-05-15

Magnetic resonance angiography (MRA) screening for recurrence of a coiled intracranial aneurysm and formation of new aneurysms long-term after coiling may induce anxiety and depression. In coiled patients, we evaluated effects on mood and level of anxiety from long-term follow-up MRA in comparison to general population norms. Of 162 patients participating in a long-term (>4.5 years) MRA follow-up after coiling, 120 completed the EQ-5D questionnaire, a visual analog health scale and a self-developed screening related questionnaire at the time of MRA. Three months later, the same questionnaires were completed by 100 of these 120 patients. Results were compared to general population norms adjusted for gender and age. Any problem with anxiety or depression was reported in 56 of 120 patients (47%; 95%CI38<->56%) at baseline and 42 of 100 patients (42%; 95%CI32<->52%) at 3 months, equally for screen-positives and -negatives. Compared to the reference population, participants scored 38% (95%CI9<->67%) and 27% (95%CI4<->50%) more often any problem with anxiety or depression. Three months after screening, 21% (20 of 92) of screen-negatives and 13% (one of eight) of screen-positives reported to be less afraid of subarachnoid hemorrhage (SAH) compared to before screening. One of eight screen-positives reported increased fear of SAH. Patients with coiled intracranial aneurysms participating in long-term MRA screening reported significantly more often to be anxious or depressed than a reference group. Screening did not significantly increase anxiety or depression temporarily. However, subjectively, patients did report an increase in anxiety caused by screening, which decreased after 3 months. (orig.)

Psychological Distress, Anxiety, and Depression of Cancer-Affected BRCA1/2 Mutation Carriers: a Systematic Review.

Science.gov (United States)

Ringwald, Johanna; Wochnowski, Christina; Bosse, Kristin; Giel, Katrin Elisabeth; Schäffeler, Norbert; Zipfel, Stephan; Teufel, Martin

2016-10-01

Understanding the intermediate- and long-term psychological consequences of genetic testing for cancer patients has led to encouraging research, but a clear consensus of the psychosocial impact and clinical routine for cancer-affected BRCA1 and BRCA2 mutation carriers is still missing. We performed a systematic review of intermediate- and long-term studies investigating the psychological impact like psychological distress, anxiety, and depression in cancer-affected BRCA mutation carriers compared to unaffected mutation carriers. This review included the screening of 1243 studies. Eight intermediate- and long-term studies focusing on distress, anxiety, and depression symptoms among cancer-affected mutation carriers at least six months after the disclosure of genetic testing results were included. Studies reported a great variety of designs, methods, and patient outcomes. We found evidence indicating that cancer-affected mutation carriers experienced a negative effect in relation to psychological well-being in terms of an increase in symptoms of distress, anxiety, and depression in the first months after test disclosure. In the intermediate- and long-term, no significant clinical relevant symptoms occurred. However, none of the included studies used specific measurements, which can clearly identify psychological burdens of cancer-affected mutation carriers. We concluded that current well-implemented distress screening instruments are not sufficient for precisely identifying the psychological burden of genetic testing. Therefore, future studies should implement coping strategies, specific personality structures, the impact of genetic testing, supportive care needs and disease management behaviour to clearly screen for the possible intermediate- and long-term psychological impact of a positive test disclosure.

A systematic review on the long-term success of calcium phosphate plasma-spray-coated dental implants.

Science.gov (United States)

van Oirschot, B A J A; Bronkhorst, E M; van den Beucken, J J J P; Meijer, G J; Jansen, J A; Junker, R

2016-09-01

The objectives of the current review were (1) to systematically appraise, and (2) to evaluate long-term success data of calcium phosphate (CaP) plasma-spray-coated dental implants in clinical trials with at least 5 years of follow-up. To describe the long-term efficacy of functional implants, the outcome variables were (a) percentage annual complication rate (ACR) and (b) cumulative success rate (CSR), as presented in the selected articles. The electronic search yielded 645 titles. On the basis of the inclusion criteria, 8 studies were finally included. The percentage of implants in function after the first year was estimated to be 98.4 % in the maxilla and 99.2 % in the mandible. The estimates of the weighted mean ACR-percentage increased over the years up to 2.6 (SE 0.7) during the fifth year of function for the maxilla and to 9.4 (SE 8.4) for the mandible in the tenth year of function. After 10 years, the mean percentage of successful implants was estimated to be 71.1 % in the maxilla and 72.2 % in the mandible. The estimates seem to confirm the proposed, long-term progressive bone loss pattern of CaP-ceramic-coated dental implants. Within the limits of this meta-analytic approach to the literature, we conclude that: (1) published long-term success data for calcium phosphate plasma-spray-coated dental implants are limited, (2) comparison of the data is difficult due to differences in success criteria among the studies, and (3) long-term CSRs demonstrate very weak evidence for progressive complications around calcium phosphate plasma-spray-coated dental implants.

A single amino acid difference between the intracellular domains of amyloid precursor protein and amyloid-like precursor protein 2 enables induction of synaptic depression and block of long-term potentiation.

Science.gov (United States)

Trillaud-Doppia, Emilie; Paradis-Isler, Nicolas; Boehm, Jannic

2016-07-01

Alzheimer disease (AD) is initially characterized as a disease of the synapse that affects synaptic transmission and synaptic plasticity. While amyloid-beta and tau have been traditionally implicated in causing AD, recent studies suggest that other factors, such as the intracellular domain of the amyloid-precursor protein (APP-ICD), can also play a role in the development of AD. Here, we show that the expression of APP-ICD induces synaptic depression, while the intracellular domain of its homolog amyloid-like precursor protein 2 (APLP2-ICD) does not. We are able to show that this effect by APP-ICD is due to a single alanine vs. proline difference between APP-ICD and APLP2-ICD. The alanine in APP-ICD and the proline in APLP2-ICD lie directly behind a conserved caspase cleavage site. Inhibition of caspase cleavage of APP-ICD prevents the induction of synaptic depression. Finally, we show that the expression of APP-ICD increases and facilitates long-term depression and blocks induction of long-term potentiation. The block in long-term potentiation can be overcome by mutating the aforementioned alanine in APP-ICD to the proline of APLP2. Based on our results, we propose the emergence of a new APP critical domain for the regulation of synaptic plasticity and in consequence for the development of AD. Copyright © 2016 Elsevier Inc. All rights reserved.

Synaptic Transmission Optimization Predicts Expression Loci of Long-Term Plasticity.

Science.gov (United States)

Costa, Rui Ponte; Padamsey, Zahid; D'Amour, James A; Emptage, Nigel J; Froemke, Robert C; Vogels, Tim P

2017-09-27

Long-term modifications of neuronal connections are critical for reliable memory storage in the brain. However, their locus of expression-pre- or postsynaptic-is highly variable. Here we introduce a theoretical framework in which long-term plasticity performs an optimization of the postsynaptic response statistics toward a given mean with minimal variance. Consequently, the state of the synapse at the time of plasticity induction determines the ratio of pre- and postsynaptic modifications. Our theory explains the experimentally observed expression loci of the hippocampal and neocortical synaptic potentiation studies we examined. Moreover, the theory predicts presynaptic expression of long-term depression, consistent with experimental observations. At inhibitory synapses, the theory suggests a statistically efficient excitatory-inhibitory balance in which changes in inhibitory postsynaptic response statistics specifically target the mean excitation. Our results provide a unifying theory for understanding the expression mechanisms and functions of long-term synaptic transmission plasticity. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Roles of calcium/calmodulin-dependent kinase II in long-term memory formation in crickets.

Directory of Open Access Journals (Sweden)

Makoto Mizunami

Full Text Available Ca(2+/calmodulin (CaM-dependent protein kinase II (CaMKII is a key molecule in many systems of learning and memory in vertebrates, but roles of CaMKII in invertebrates have not been characterized in detail. We have suggested that serial activation of NO/cGMP signaling, cyclic nucleotide-gated channel, Ca(2+/CaM and cAMP signaling participates in long-term memory (LTM formation in olfactory conditioning in crickets, and here we show participation of CaMKII in LTM formation and propose its site of action in the biochemical cascades. Crickets subjected to 3-trial conditioning to associate an odor with reward exhibited memory that lasts for a few days, which is characterized as protein synthesis-dependent LTM. In contrast, animals subjected to 1-trial conditioning exhibited memory that lasts for only several hours (mid-term memory, MTM. Injection of a CaMKII inhibitor prior to 3-trial conditioning impaired 1-day memory retention but not 1-hour memory retention, suggesting that CaMKII participates in LTM formation but not in MTM formation. Animals injected with a cGMP analogue, calcium ionophore or cAMP analogue prior to 1-trial conditioning exhibited 1-day retention, and co-injection of a CaMKII inhibitor impaired induction of LTM by the cGMP analogue or that by the calcium ionophore but not that by the cAMP analogue, suggesting that CaMKII is downstream of cGMP production and Ca(2+ influx and upstream of cAMP production in biochemical cascades for LTM formation. Animals injected with an adenylyl cyclase (AC activator prior to 1-trial conditioning exhibited 1-day retention. Interestingly, a CaMKII inhibitor impaired LTM induction by the AC activator, although AC is expected to be a downstream target of CaMKII. The results suggest that CaMKII interacts with AC to facilitate cAMP production for LTM formation. We propose that CaMKII serves as a key molecule for interplay between Ca(2+ signaling and cAMP signaling for LTM formation, a new role of Ca

Eye Complications and Markers of Morbidity and Mortality in Long-term Type 1 Diabetes

DEFF Research Database (Denmark)

Grauslund, Jakob

2011-01-01

The incidence of type 1 diabetes is rising all over the world. Furthermore, the increased life-expectancy of type 1 diabetic patients is likely to cause a higher number of diabetes-related micro- and macrovascular complications in the years to come. In order to examine the level of long......-term complications in type 1 diabetes as well as potential markers of micro- and macroangiopathy, a population-based cohort of Danish type 1 diabetic patients was examined in order to achieve the following aims: 1  To evaluate diabetic retinopathy as a long-term marker of all-cause mortality in type 1 diabetes...... (Paper I). 2  To estimate the long-term incidence and associated risk factors of blindness (Paper II) and cataract surgery (Paper III) in type 1 diabetes. 3  To use retinal vascular analyses in order to investigate the associations of long-term micro- and macrovascular complications and retinal vascular...

Patterns of persistence with pharmacological treatment among patients with current depressive episode and their impact on long-term outcome: a naturalistic study with 5-year follow-up

Directory of Open Access Journals (Sweden)

Li K

2018-05-01

Full Text Available Kanglai Li,1,* Jiong Tao,2,* Yuemei Li,3 Minhua Chen,2 Xiuhua Wu,2 Yingtao Liao,2 Xiaolan Lin,4 Zhaoyu Gan2 1Department of Very Important Patient, the 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Psychiatry, the 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Department of Obstetrics, Wuzhou Gongren Hospital, Wuzhou, People’s Republic of China; 4Department of Infectious Diseases, the 3rd Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: The aim of the study was to describe and compare the patterns of medication persistence among patients with unipolar depression (UD or bipolar depression in a 5-year follow-up, and explore their impact on long-term outcome. Patients and methods: A total of 333 eligible patients with current major depressive episode were observed and followed up from the first index prescription for 5 years. Lack of persistence or treatment interruption was defined as a gap of at least 2 consecutive months without taking any medication. Time to lack of persistence in the first (TLP1 and the second (TLP2 episode of treatment, number of visits before the first treatment interruption (NV and number of treatment interruptions (NTI were measured. Results: During the 5-year follow-up, nearly 50% of patients experienced at least two times of treatment interruption. Pattern of medication persistence did not significantly differ between UD and bipolar disorder (BD patients. TLP1 was positively associated with TLP2. Shorter TLP1 predicted a higher possibility of subsequent visits because of recurrence or relapse and more NTI meant a lower likelihood of achieving full remission in the fifth year for both UD and BD patients. For UD patients, shorter TLP1 or less NV predicted a lower chance of achieving remission, while for BD patients

Long-Term Pain Treatment Did Not Improve Sleep in Nursing Home Patients with Comorbid Dementia and Depression: A 13-Week Randomized Placebo-Controlled Trial

Directory of Open Access Journals (Sweden)

Kjersti M. Blytt

2018-02-01

Full Text Available Objective: Previous research indicates that pain treatment may improve sleep among nursing home patients. We aimed to investigate the long-term effect of pain treatment on 24-h sleep patterns in patients with comorbid depression and dementia.Design: A 13-week, multicenter, parallel-group, double-blind, placebo-controlled randomized clinical trial conducted between August 2014 and September 2016.Setting: Long-term patients from 47 nursing homes in Norway.Participants: We included 106 patients with comorbid dementia and depression according to the Mini Mental Status Examination (MMSE and the Cornell Scale for Depression in Dementia (CSDD.Intervention: Patients who were not using analgesics were randomized to receive either paracetamol (3 g/day or placebo tablets. Those who already received pain treatment were randomized to buprenorphine transdermal system (maximum 10 μg/h/7 days or placebo transdermal patches.Measurements: Sleep was assessed continuously for 7 days by actigraphy, at baseline and in week 13. Total sleep time (TST, sleep efficiency (SE, sleep onset latency (SOL, wake after sleep onset (WASO, early morning awakening (EMA, and number of wake bouts (NoW were evaluated. In addition, daytime total sleep time (DTS was estimated. Pain was assessed with Mobilization-Observation-Behavior-Intensity-Dementia-2 Pain Scale (MOBID-2.Results: The linear mixed model analyses for TST, SE, SOL, WASO, EMA, NoW and DTS showed no statistically significant differences between patients who received active pain treatment and those who received placebo. Post hoc subgroup analyses showed that there were no statistically significant differences between active treatment and placebo from baseline to week 13 in patients who were in pain (MOBID-2 ≥ 3 at baseline, or in patients who had poor sleep (defined as SE < 85% at baseline. Patients who received active buprenorphine showed an increase in TST and SE compared to those who received active paracetamol

Psychometric analysis of common mental disorders -- Screening Questionnaire (CMD-SQ) in long-term sickness absence

DEFF Research Database (Denmark)

Søgaard, Hans Jørgen; Bech, Per

2009-01-01

and conviction), SCL-ANX4 (anxiety), SCL-DEP6 (depression), SCL-8 (emotional disorder), and CAGE (alcohol dependency). RESULTS: Of 2,414 incident persons on long-term sickness absence within one year, 1,121 participated in the study by filling in CMD-SQ and a subsample of 337 was diagnosed by a psychiatric...

Acute and long-term treatment of late-life major depressive disorder: duloxetine versus placebo.

Science.gov (United States)

Robinson, Michael; Oakes, Tina Myers; Raskin, Joel; Liu, Peng; Shoemaker, Scarlett; Nelson, J Craig

2014-01-01

To compare the efficacy of duloxetine with placebo on depression in elderly patients with major depressive disorder. Multicenter, 24-week (12-week short-term and 12-week continuation), randomized, placebo-controlled, double-blind trial. United States, France, Mexico, Puerto Rico. Age 65 years or more with major depressive disorder diagnosis (one or more previous episode); Mini-Mental State Examination score ≥20; Montgomery-Asberg Depression Rating Scale total score ≥20. Duloxetine 60 or 120 mg/day or placebo; placebo rescue possible. Primary-Maier subscale of the 17-item Hamilton Depression Rating Scale (HAMD-17) at week 12. Secondary-Geriatric Depression Scale, HAMD-17 total score, cognitive measures, Brief Pain Inventory (BPI), Numeric Rating Scales (NRS) for pain, Clinical Global Impression-Severity scale, Patient Global Impression of Improvement in acute phase and acute plus continuation phase of treatment. Compared with placebo, duloxetine did not show significantly greater improvement from baseline on Maier subscale at 12 weeks, but did show significantly greater improvement at weeks 4, 8, 16, and 20. Similar patterns for Geriatric Depression Scale and Clinical Global Impression-Severity scale emerged, with significance also seen at week 24. There was a significant treatment effect for all BPI items and 4 of 6 NRS pain measures in the acute phase, most BPI items and half of the NRS measures in the continuation phase. More duloxetine-treated patients completed the study (63% versus 55%). A significantly higher percentage of duloxetine-treated patients versus placebo discontinued due to adverse event (15.3% versus 5.8%). Although the antidepressant efficacy of duloxetine was not confirmed by the primary outcome, several secondary measures at multiple time points suggested efficacy. Duloxetine had significant and meaningful beneficial effects on pain. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights

Long-term functional, subjective and psychological results after single digit replantation.

Science.gov (United States)

Chen, Jing; Zhang, Ai Xian; Chen, Qing Zhong; Mu, Shuai; Tan, Jun

2018-03-01

The aim of this study was to analyse the long-term functional, subjective, and psychological results after single-digit replantation. Thirty cases of digital replantation (14 thumbs, 12 index fingers, 2 middle fingers, 1 ring finger, and 1 little finger) in 30 patients (7 females and 23 males) with a mean age of 44.2 years (20-65 years) were evaluated at the end of a mean follow-up time of 36 months (19-50 months). The active range of motion of joints, grip and pinch strength, cutaneous sensibility, upper-extremity functioning, and subjective satisfaction were determined using the Disability of Arm, Shoulder, and Hand (DASH) questionnaire and the Michigan Hand Outcomes questionnaire (MHQ). Psychological sequelae, including depression, anxiety, and posttraumatic stress disorder (PTSD), were assessed. A correlation analysis among variables was also performed. The mean score for the DASH questionnaire was 6.6 (range: 0-39.2). The symptom of cold intolerance occurred in 53% of the patients. Two patients were diagnosed with depression, and only one patient exhibited PTSD. The DASH score had a good statistical correlation with total grip strength, pinch grip strength, and static two-point discrimination (S-2PD) (P digit replantation are very low at long-term follow-up. Level IV, therapeutic study. Copyright © 2017 Turkish Association of Orthopaedics and Traumatology. Production and hosting by Elsevier B.V. All rights reserved.

26 CFR 1.460-1 - Long-term contracts.

Science.gov (United States)

2010-04-01

... the manufacture of personal property is a manufacturing contract. In contrast, a contract for the... performance of engineering and design services, and the production of components and subassemblies that are..., enters into a single long-term contract to design and manufacture a satellite and to develop computer...

Functional optical probing of the hippocampal trisynaptic circuit in vitro: network dynamics, filter properties, and polysynaptic induction of CA1 LTP.

Science.gov (United States)

Stepan, Jens; Dine, Julien; Eder, Matthias

2015-01-01

Decades of brain research have identified various parallel loops linking the hippocampus with neocortical areas, enabling the acquisition of spatial and episodic memories. Especially the hippocampal trisynaptic circuit [entorhinal cortex layer II → dentate gyrus (DG) → cornu ammonis (CA)-3 → CA1] was studied in great detail because of its seemingly simple connectivity and characteristic structures that are experimentally well accessible. While numerous researchers focused on functional aspects, obtained from a limited number of cells in distinct hippocampal subregions, little is known about the neuronal network dynamics which drive information across multiple synapses for subsequent long-term storage. Fast voltage-sensitive dye imaging in vitro allows real-time recording of activity patterns in large/meso-scale neuronal networks with high spatial resolution. In this way, we recently found that entorhinal theta-frequency input to the DG most effectively passes filter mechanisms of the trisynaptic circuit network, generating activity waves which propagate across the entire DG-CA axis. These "trisynaptic circuit waves" involve high-frequency firing of CA3 pyramidal neurons, leading to a rapid induction of classical NMDA receptor-dependent long-term potentiation (LTP) at CA3-CA1 synapses (CA1 LTP). CA1 LTP has been substantially evidenced to be essential for some forms of explicit learning in mammals. Here, we review data with particular reference to whole network-level approaches, illustrating how activity propagation can take place within the trisynaptic circuit to drive formation of CA1 LTP.

Short-term depression and transient memory in sensory cortex.

Science.gov (United States)

Gillary, Grant; Heydt, Rüdiger von der; Niebur, Ernst

2017-12-01

Persistent neuronal activity is usually studied in the context of short-term memory localized in central cortical areas. Recent studies show that early sensory areas also can have persistent representations of stimuli which emerge quickly (over tens of milliseconds) and decay slowly (over seconds). Traditional positive feedback models cannot explain sensory persistence for at least two reasons: (i) They show attractor dynamics, with transient perturbations resulting in a quasi-permanent change of system state, whereas sensory systems return to the original state after a transient. (ii) As we show, those positive feedback models which decay to baseline lose their persistence when their recurrent connections are subject to short-term depression, a common property of excitatory connections in early sensory areas. Dual time constant network behavior has also been implemented by nonlinear afferents producing a large transient input followed by much smaller steady state input. We show that such networks require unphysiologically large onset transients to produce the rise and decay observed in sensory areas. Our study explores how memory and persistence can be implemented in another model class, derivative feedback networks. We show that these networks can operate with two vastly different time courses, changing their state quickly when new information is coming in but retaining it for a long time, and that these capabilities are robust to short-term depression. Specifically, derivative feedback networks with short-term depression that acts differentially on positive and negative feedback projections are capable of dynamically changing their time constant, thus allowing fast onset and slow decay of responses without requiring unrealistically large input transients.

Learning, memory and long-term potentiation are altered in Nedd4 heterozygous mice.

Science.gov (United States)

Camera, Daria; Coleman, Harold A; Parkington, Helena C; Jenkins, Trisha A; Pow, David V; Boase, Natasha; Kumar, Sharad; Poronnik, Philip

2016-04-15

The consolidation of short-term memory into long-term memory involves changing protein level and activity for the synaptic plasticity required for long-term potentiation (LTP). AMPA receptor trafficking is a key determinant of LTP and recently ubiquitination by Nedd4 has been shown to play an important role via direct action on the GluA1 subunit, although the physiological relevance of these findings are yet to be determined. We therefore investigated learning and memory in Nedd4(+/-) mice that have a 50% reduction in levels of Nedd4. These mice showed decreased long-term spatial memory as evidenced by significant increases in the time taken to learn the location of and subsequently find a platform in the Morris water maze. In contrast, there were no significant differences between Nedd4(+/+) and Nedd4(+/-) mice in terms of short-term spatial memory in a Y-maze test. Nedd4(+/-) mice also displayed a significant reduction in post-synaptic LTP measured in hippocampal brain slices. Immunofluorescence of Nedd4 in the hippocampus confirmed its expression in hippocampal neurons of the CA1 region. These findings indicate that reducing Nedd4 protein by 50% significantly impairs LTP and long-term memory thereby demonstrating an important role for Nedd4 in these processes. Copyright © 2016 Elsevier B.V. All rights reserved.

A juvenile form of postsynaptic hippocampal long-term potentiation in mice deficient for the AMPA receptor subunit GluR-A

NARCIS (Netherlands)

Jensen, V.; Kaiser, K.M.M.; Borchardt, T.; Adelmann, G.; Rozov, A.; Burnashev, N.; Brix, C.; Frotscher, M.; Anderson, P.; Hvalby, O.; Sakmann, B.; Seeburg, P.H.; Sprengel, R.

2003-01-01

In adult mice, long-term potentiation (LTP) of synaptic transmission at CA3-to-CA1 synapses induced by tetanic stimulation requires L-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors containing GluR-A subunits. Here, we report a GluR-A-independent form of LTP, which is comparable in

Autosomal-dominant GTPCH1-deficient DRD: clinical characteristics and long-term outcome of 34 patients.

Science.gov (United States)

Trender-Gerhard, I; Sweeney, M G; Schwingenschuh, P; Mir, P; Edwards, M J; Gerhard, A; Polke, J M; Hanna, M G; Davis, M B; Wood, N W; Bhatia, K P

2009-08-01

An autosomal dominantly inherited defect in the GCH1 gene that encodes guanosine triphosphate cyclohydrolase 1 (GTPCH1) is the most common cause of dopa-responsive dystonia (DRD). A classic phenotype of young-onset lower-limb dystonia, diurnal fluctuations and excellent response to levodopa has been well recognised in association with GCH1 mutations, and rare atypical presentations have been reported. However, a number of clinical issues remain unresolved including phenotypic variability, long-term response to levodopa and associated non-motor symptoms, and there are limited data on long-term follow-up of genetically proven cases. A detailed clinical evaluation of 34 patients (19 women, 15 men), with confirmed mutations in the GCH1 gene, is presented. The classic phenotype was most frequent (n = 23), with female predominance (F:M = 16:7), and early onset (mean 4.5 years) with involvement of legs. However, a surprisingly large number of patients developed craniocervical dystonia, with spasmodic dysphonia being the predominant symptom in two subjects. A subset of patients, mainly men, presented with either a young-onset (mean 6.8 years) mild DRD variant not requiring treatment (n = 4), or with an adult-onset (mean 37 years) Parkinson disease-like phenotype (n = 4). Two siblings were severely affected with early hypotonia and delay in motor development, associated with compound heterozygous GCH1 gene mutations. The study also describes a number of supplementary features including restless-legs-like symptoms, influence of female sex hormones, predominance of tremor or parkinsonism in adult-onset cases, initial reverse reaction to levodopa, recurrent episodes of depressive disorder and specific levodopa-resistant symptoms (writer's cramp, dysphonia, truncal dystonia). Levodopa was used effectively and safely in 20 pregnancies, and did not cause any fetal abnormalities.

26 CFR 1.460-2 - Long-term manufacturing contracts.

Science.gov (United States)

2010-04-01

... time normally required to design and manufacture the first unit of an item for which the taxpayer... manufacture a new type of industrial equipment. C reasonably expects the normal production period for this... 26 Internal Revenue 6 2010-04-01 2010-04-01 false Long-term manufacturing contracts. 1.460-2...

Long-term associations between serum lipids and panretinal photocoagulation in type 1 diabetes

DEFF Research Database (Denmark)

Jørgensen, Jesper Skovlund; Mejnert Jørgensen, Trine; Green, Anders

2013-01-01

To examine the predictive value of serum lipids on the need for panretinal photocoagulation (PRP) treatment in a long-term follow-up of a cohort of Danish type 1 diabetic patients.......To examine the predictive value of serum lipids on the need for panretinal photocoagulation (PRP) treatment in a long-term follow-up of a cohort of Danish type 1 diabetic patients....

Long-term follow up of revascularization using platelet-rich fibrin.

Science.gov (United States)

Ray, Herbert L; Marcelino, Janel; Braga, Raquel; Horwat, Richard; Lisien, Michael; Khaliq, Shahryar

2016-02-01

Trauma is one of the primary causes of tooth loss and pulpal injury in adolescents and children. Prior to regenerative endodontics, treatment of necrotic, immature teeth with open apices was limited to long-term calcium hydroxide (Ca(OH)2 ) apexification and subsequent root canal therapy or extraction. Through revascularization, retention of these teeth can be achieved and the elimination of patient symptoms and the radiographic appearance of continued root development were obtained. This report illustrates a revascularization protocol through a case where platelet-rich fibrin (PRF) was utilized as an autologous scaffold for traumatized, necrotic, immature teeth with incomplete root development. Through consistent follow-up reports, comprising of both clinical examination and radiographs, marked improvement in the condition of the traumatized tooth was noted. This case demonstrates the feasibility of utilizing PRF as an effective treatment protocol for traumatized teeth in lieu of traditional treatment protocols, such as long-term calcium hydroxide (Ca(OH)2 ) apexification or extraction. The choice of utilizing PRF, as opposed to other platelet concentrates, such as platelet-rich plasma (PRP) or a blood clot, lies in PRF's ability to allow for a slow, long-term release of autologous growth factors. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Activation of CRH receptor type 1 expressed on glutamatergic neurons increases excitability of CA1 pyramidal neurons by the modulation of voltage-gated ion channels

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Stephan eKratzer

2013-07-01

Full Text Available Corticotropin-releasing hormone (CRH plays an important role in a substantial number of patients with stress-related mental disorders, such as anxiety disorders and depression. CRH has been shown to increase neuronal excitability in the hippocampus, but the underlying mechanisms are poorly understood. The effects of CRH on neuronal excitability were investigated in acute hippocampal brain slices. Population spikes (PS and field excitatory postsynaptic potentials (fEPSP were evoked by stimulating Schaffer-collaterals and recorded simultaneously from the somatic and dendritic region of CA1 pyramidal neurons. CRH was found to increase PS amplitudes (mean  Standard error of the mean; 231.8  31.2% of control; n=10 while neither affecting fEPSPs (104.3 ± 4.2%; n=10 nor long-term potentiation (LTP. However, when Schaffer-collaterals were excited via action potentials (APs generated by stimulation of CA3 pyramidal neurons, CRH increased fEPSP amplitudes (119.8 ± 3.6%; n=8 and the magnitude of LTP in the CA1 region. Experiments in slices from transgenic mice revealed that the effect on PS amplitude is mediated exclusively by CRH receptor 1 (CRHR1 expressed on glutamatergic neurons. The effects of CRH on PS were dependent on phosphatase-2B, L- and T-type calcium channels and voltage-gated potassium channels but independent on intracellular Ca2+-elevation. In patch-clamp experiments, CRH increased the frequency and decay times of APs and decreased currents through A-type and delayed-rectifier potassium channels. These results suggest that CRH does not affect synaptic transmission per se, but modulates voltage-gated ion currents important for the generation of APs and hence elevates by this route overall neuronal activity.

Factors Influencing Job Satisfaction Among Long-Term Care Staff.

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Doran, Kelly; Resnick, Barbara; Swanberg, Jennifer

2017-11-01

We assessed the intrapersonal, interpersonal, and organizational factors that predicted job satisfaction among long-term care employees. Baseline data were used to describe characteristics that influence job satisfaction. Using a forced linear regression model, while controlling for age and job title, we assessed if higher physical activity levels, fewer symptoms of depression, stress, and/or anxiety (ie, decreased mood), less back pain, stronger social support, and reports of low work demands were associated with higher job satisfaction. Mood (β = -0.412, P = 0.003) explained 17% of the variance in job satisfaction. This information can be used to guide facility wide programs and interventions aimed at increasing job satisfaction among all long-term care staff.

Relative Ease in Creating Detailed Orthographic Representations Contrasted with Severe Difficulties to Maintain Them in Long-term Memory Among Dyslexic Children.

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Binamé, Florence; Danzio, Sophie; Poncelet, Martine

2015-11-01

Most research into orthographic learning abilities has been conducted in English with typically developing children using reading-based tasks. In the present study, we examined the abilities of French-speaking children with dyslexia to create novel orthographic representations for subsequent use in spelling and to maintain them in long-term memory. Their performance was compared with that of chronological age (CA)-matched and reading age (RA)-matched control children. We used an experimental task designed to provide optimal learning conditions (i.e. 10 spelling practice trials) ensuring the short-term acquisition of the spelling of the target orthographic word forms. After a 1-week delay, the long-term retention of the targets was assessed by a spelling post-test. Analysis of the results revealed that, in the short term, children with dyslexia learned the novel orthographic word forms well, only differing from both CA and RA controls on the initial decoding of the targets and from CA controls on the first two practice trials. In contrast, a dramatic drop was observed in their long-term retention relative to CA and RA controls. These results support the suggestion of the self-teaching hypothesis (Share, 1995) that initial errors in the decoding and spelling of unfamiliar words may hinder the establishment of fully specified novel orthographic representations. Copyright © 2015 John Wiley & Sons, Ltd.

Health-related quality of life and self-reported long-term conditions: a population-based survey

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Ivan R. Zimmermann

Full Text Available Objective: To estimate and compare the effect of self-reported long-term health conditions and sociodemographic factors on perceived health-related quality of life (HRQoL. Methods: A population-based survey of adults (18 to 65 years living in Brasilia, Brazil, was conducted in 2012. Descriptive and multivariate analyses using a Tobit model were performed with data on sociodemographic variables, self-reported conditions, and the European Quality of Life-5 Dimensions (EQ-5D health states, providing utility scores (preferred health state between 0 and 1 for HRQoL estimates. Results: The mean utility of 1,820 adults interviewed (mean age: 38.4±12.6 years was 0.883 (95% confidence interval [95%CI] 0.874-0.892, with 76.2% in the highest utility range (0.8 to 1.0. EQ-5D dimensions with moderate problems were pain/discomfort (33.8% and anxiety/depression (20.5%. Serious problems were reported by only 0.3% of the sample in the mobility and self-care domain and by 3.1% in the pain/discomfort domain. Multivariate analysis revealed reduced HRQoL in individuals with depression, diabetes, and hypertension. Living in satellite towns (outside the city core, belonging to a lower economic class, or not being formally employed were also associated with decreased HRQoL. Beta coefficients for these impacts ranged from -0.033 (not formally employed to -0.141 (depression, reflecting the strongest impact. Conclusion: Of the long-term health conditions studied, depression had the greatest impact on HRQoL. Social class, employment status, and place of residence also affected HRQoL.

Removal of area CA3 from hippocampal slices induces postsynaptic plasticity at Schaffer collateral synapses that normalizes CA1 pyramidal cell discharge.

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Dumas, Theodore C; Uttaro, Michael R; Barriga, Carolina; Brinkley, Tiffany; Halavi, Maryam; Wright, Susan N; Ferrante, Michele; Evans, Rebekah C; Hawes, Sarah L; Sanders, Erin M

2018-05-05

Neural networks that undergo acute insults display remarkable reorganization. This injury related plasticity is thought to permit recovery of function in the face of damage that cannot be reversed. Previously, an increase in the transmission strength at Schaffer collateral to CA1 pyramidal cell synapses was observed after long-term activity reduction in organotypic hippocampal slices. Here we report that, following acute preparation of adult rat hippocampal slices and surgical removal of area CA3, input to area CA1 was reduced and Schaffer collateral synapses underwent functional strengthening. This increase in synaptic strength was limited to Schaffer collateral inputs (no alteration to temporoammonic synapses) and acted to normalize postsynaptic discharge, supporting a homeostatic or compensatory response. Short-term plasticity was not altered, but an increase in immunohistochemical labeling of GluA1 subunits was observed in the stratum radiatum (but not stratum moleculare), suggesting increased numbers of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors and a postsynaptic locus of expression. Combined, these data support the idea that, in response to the reduction in presynaptic activity caused by removal of area CA3, Schaffer collateral synapses undergo a relatively rapid increase in functional efficacy likely supported by insertion of more AMPARs, which maintains postsynaptic excitability in CA1 pyramidal neurons. This novel fast compensatory plasticity exhibits properties that would allow it to maintain optimal network activity levels in the hippocampus, a brain structure lauded for its ongoing experience-dependent malleability. Copyright © 2018 Elsevier B.V. All rights reserved.

Long Term Clinical Prognostic Factors in Relapsing-Remitting Multiple Sclerosis: Insights from a 10-Year Observational Study.

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Gabriel Bsteh

Full Text Available Multiple sclerosis (MS has a highly heterogenic course making prediction of long term outcome very difficult.The objective was to evaluate current and identify additional clinical factors that are linked to long term outcome of relapsing-remitting MS assessed by disability status 10 years after disease onset.This observational study included 793 patients with relapsing-remitting MS. Clinical factors hypothesized to influence long term outcome measured by EDSS scores 10 years after disease onset were analysed by Kaplan-Meier-estimates. Multinomial logistic regression models regarding mild (EDSS ≤2.5, moderate (EDSS 3.0-5.5 or severe (EDSS ≥6.0 disability were calculated to correct for confounders.Secondary progression was the strongest predictor of severe disability (Hazard ratio [HR] 503.8, 95% confidence interval [CI] 160.0-1580.1; p<0.001. Complete remission of neurological symptoms at onset reduced the risk of moderate disability (HR 0.42; CI 0.23-0.77; p = 0.005, while depression (HR 3.59; CI 1.14-11.24; p = 0.028 and cognitive dysfunction (HR 4.64; CI 1.11-19.50; p = 0.036 10 years after disease onset were associated with severe disability. Oligoclonal bands and pregnancy were not correlated with disability.We were able to identify clinically apparent chronic depression and cognitive dysfunction to be associated with adverse long term outcome in MS and to confirm that pregnancy has no negative impact. Additionally, we emphasize the positive predictive value of complete remission of initial symptoms.

Depressive symptoms and diabetes control in African Americans.

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Wagner, Julie A; Abbott, Gina L; Heapy, Alicia; Yong, Lynne

2009-02-01

This study of African Americans with diabetes investigated: (1) the relationship between depressive symptoms and glycemic control; (2) the relationship between depressive symptoms and long-term diabetes complications; (3) the relationship between depressive symptoms and medication usage; and (4) the effects of demographic and diabetes variables on these relationships. One-hundred twenty five African American diabetic adults who were attending health fairs reported demographic and medical history and provided blood samples for A1c assessment of glycemic control. They also completed the Centers for Epidemiological Studies Depression questionnaire, and the Diabetes Self-Care Inventory. After controlling for confounders, higher depressive symptoms were associated with higher A1c, more long-term diabetes complications, and more diabetes medications. Diabetes self-care did not fully account for these relationships. The relationship between depression and poor diabetes control exists in African Americans as it does in Whites. Providers are encouraged to attend to depression in their African American patients with diabetes.

Impact of a long-term fire retardant (Fire Trol 931) on the leaching of Ca, Mg, and K from a Mediterranean forest loamy soil.

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Michalopoulos, Charalampos; Koufopoulou, Sofia; Tzamtzis, Nikolaos; Pappa, Athina

2016-03-01

The present laboratory study was conducted in pot soil taken from forest. The leaching of calcium (Ca), magnesium (Mg), and potassium (K) (plant macronutrients) due to the application of a nitrogen phosphate-based long-term fire retardant (LTFR) (Fire Trol 931) was investigated. The concentrations of Ca(2+), Mg(2+), and K(+) were measured in the resulting leachates from pots with forest soil and pine tree alone and in combination with fire. Magnesium is a minor component of Fire Trol 931. The leaching of Ca(2+), Mg(2+), and K(+) from treated soils with the retardant pots was significantly greater than that from control pots. The leaching of Mg(2+) was found to be of small percentage of the initially applied Mg quantities. Fire Trol 931 application resulted in the leaching of Ca(2+), Mg(2+), and K(+) from a typical Mediterranean forest soil in pots, following the application of simulated annual precipitation probably due to ammonium (one of the major retardant components) soil deposition that mobilizes base cations from the soil. It seems that LTFR application may result in chemical leaching from the soil to the drainage water.

Calcium Input Frequency, Duration and Amplitude Differentially Modulate the Relative Activation of Calcineurin and CaMKII

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Li, Lu; Stefan, Melanie I.; Le Novère, Nicolas

2012-01-01

NMDA receptor dependent long-term potentiation (LTP) and long-term depression (LTD) are two prominent forms of synaptic plasticity, both of which are triggered by post-synaptic calcium elevation. To understand how calcium selectively stimulates two opposing processes, we developed a detailed computational model and performed simulations with different calcium input frequencies, amplitudes, and durations. We show that with a total amount of calcium ions kept constant, high frequencies of calcium pulses stimulate calmodulin more efficiently. Calcium input activates both calcineurin and Ca2+/calmodulin-dependent protein kinase II (CaMKII) at all frequencies, but increased frequencies shift the relative activation from calcineurin to CaMKII. Irrespective of amplitude and duration of the inputs, the total amount of calcium ions injected adjusts the sensitivity of the system to calcium input frequencies. At a given frequency, the quantity of CaMKII activated is proportional to the total amount of calcium. Thus, an input of a small amount of calcium at high frequencies can induce the same activation of CaMKII as a larger amount, at lower frequencies. Finally, the extent of activation of CaMKII signals with high calcium frequency is further controlled by other factors, including the availability of calmodulin, and by the potency of phosphatase inhibitors. PMID:22962589

The long-term psychiatric and medical prognosis of perinatal mental illness.

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Meltzer-Brody, Samantha; Stuebe, Alison

2014-01-01

The perinatal period provides an important window into a woman's long-term health. Perinatal mental illness is a common condition conferring potential serious long-term psychiatric and medical consequences for the mother and family. It is known that childbirth acts as a powerful trigger for depressive episodes in some women, and that women with histories of a mood disorder are particularly vulnerable. Some evidence links perinatal mental illness with obstetrical complications and reduced lactation initiation and duration. Therefore, perinatal mental illness may be a marker for long-term risk, and may contribute directly to subsequent cardiometabolic disease through both neuroendocrine mechanisms and the effects of mental illness on health behaviours. In clinical practice, these associations underscore the importance of screening and treating women with perinatal mental illness to ensure best possible long-term outcomes. Early screening and treatment may both mitigate the primary disease process and reduce the risk of comorbid medical conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Evidence for Long-Timescale Patterns of Synaptic Inputs in CA1 of Awake Behaving Mice.

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Kolb, Ilya; Talei Franzesi, Giovanni; Wang, Michael; Kodandaramaiah, Suhasa B; Forest, Craig R; Boyden, Edward S; Singer, Annabelle C

2018-02-14

Repeated sequences of neural activity are a pervasive feature of neural networks in vivo and in vitro In the hippocampus, sequential firing of many neurons over periods of 100-300 ms reoccurs during behavior and during periods of quiescence. However, it is not known whether the hippocampus produces longer sequences of activity or whether such sequences are restricted to specific network states. Furthermore, whether long repeated patterns of activity are transmitted to single cells downstream is unclear. To answer these questions, we recorded intracellularly from hippocampal CA1 of awake, behaving male mice to examine both subthreshold activity and spiking output in single neurons. In eight of nine recordings, we discovered long (900 ms) reoccurring subthreshold fluctuations or "repeats." Repeats generally were high-amplitude, nonoscillatory events reoccurring with 10 ms precision. Using statistical controls, we determined that repeats occurred more often than would be expected from unstructured network activity (e.g., by chance). Most spikes occurred during a repeat, and when a repeat contained a spike, the spike reoccurred with precision on the order of ≤20 ms, showing that long repeated patterns of subthreshold activity are strongly connected to spike output. Unexpectedly, we found that repeats occurred independently of classic hippocampal network states like theta oscillations or sharp-wave ripples. Together, these results reveal surprisingly long patterns of repeated activity in the hippocampal network that occur nonstochastically, are transmitted to single downstream neurons, and strongly shape their output. This suggests that the timescale of information transmission in the hippocampal network is much longer than previously thought. SIGNIFICANCE STATEMENT We found long (≥900 ms), repeated, subthreshold patterns of activity in CA1 of awake, behaving mice. These repeated patterns ("repeats") occurred more often than expected by chance and with 10 ms

Astrocyte IP3R2-dependent Ca2+ signaling is not a major modulator of neuronal pathways governing behavior.

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Jeremy ePetravicz

2014-11-01

Full Text Available Calcium-dependent release of gliotransmitters by astrocytes is reported to play a critical role in synaptic transmission and be necessary for long-term potentiation (LTP, long-term depression (LTD and other forms of synaptic modulation that are correlates of learning and memory . Further, physiological processes reported to be dependent on Ca2+ fluxes in astrocytes include functional hyperemia, sleep, and regulation of breathing. The preponderance of findings indicate that most, if not all, receptor dependent Ca2+ fluxes within astrocytes are due to release of Ca2+ through IP3 receptor/channels in the endoplasmic reticulum. Findings from several laboratories indicate that astrocytes only express IP3 receptor type 2 (IP3R2 and that a knockout of IP3R2 obliterates the GPCR-dependent astrocytic Ca2+ responses. Assuming that astrocytic Ca2+ fluxes play a critical role in synaptic physiology, it would be predicted that eliminating of astrocytic Ca2+ fluxes would lead to marked changes in behavioral tests. Here, we tested this hypothesis by conducting a broad series of behavioral tests that recruited multiple brain regions, on an IP3R2 conditional knockout mouse model. We present the novel finding that behavioral processes are unaffected by lack of astrocyte IP3R-mediated Ca2+ signals. IP3R2 cKO animals display no change in anxiety or depressive behaviors, and no alteration to motor and sensory function. Morris water maze testing, a behavioral correlate of learning and memory, was unaffected by lack of astrocyte IP3R2-mediated Ca2+-signaling. Therefore, in contrast to the prevailing literature, we find that neither receptor-driven astrocyte Ca2+ fluxes nor, by extension, gliotransmission is likely to be a major modulating force on the physiological processes underlying behavior.

0180 Does long-term stress cause depression?

DEFF Research Database (Denmark)

Raunkjaer, NM; Stokholm, Zara Ann; Willert, Morten Vejs

2014-01-01

OBJECTIVES: The aim is to examine occupational noise exposure as a risk factor for depression, utilising noise exposure as an objective measure of distressing working conditions that circumvents reporting bias. METHOD: In a 7-year cohort study we followed 109 378 industrial workers and 45 613 fin...

Long-Term Outcomes of Cognitive-Behavioral Therapy for Adolescent Body Dysmorphic Disorder.

Science.gov (United States)

Krebs, Georgina; de la Cruz, Lorena Fernández; Monzani, Benedetta; Bowyer, Laura; Anson, Martin; Cadman, Jacinda; Heyman, Isobel; Turner, Cynthia; Veale, David; Mataix-Cols, David

2017-07-01

Emerging evidence suggests that cognitive-behavioral therapy (CBT) is an efficacious treatment for adolescent body dysmorphic disorder (BDD) in the short term, but longer-term outcomes remain unknown. The current study aimed to follow up a group of adolescents who had originally participated in a randomized controlled trial of CBT for BDD to determine whether treatment gains were maintained. Twenty-six adolescents (mean age = 16.2, SD = 1.6) with a primary diagnosis of BDD received a course of developmentally tailored CBT and were followed up over 12 months. Participants were assessed at baseline, midtreatment, posttreatment, 2-, 6-, and 12-month follow-up. The primary outcome measure was the clinician-rated Yale-Brown Obsessive-Compulsive Scale Modified for BDD. Secondary outcomes included measures of insight, depression, quality of life, and global functioning. BDD symptoms decreased significantly from pre- to posttreatment and remained stable over the 12-month follow-up. At this time point, 50% of participants were classified as responders and 23% as remitters. Participants remained significantly improved on all secondary outcomes at 12-month follow-up. Neither baseline insight nor baseline depression predicted long-term outcomes. The positive effects of CBT appear to be durable up to 12-month follow-up. However, the majority of patients remained symptomatic and vulnerable to a range of risks at 12-month follow-up, indicating that longer-term monitoring is advisable in this population. Future research should focus on enhancing the efficacy of CBT in order to improve long-term outcomes. Copyright © 2017. Published by Elsevier Ltd.

Calcium/Calmodulin-dependent Protein Kinase II is a Ubiquitous Molecule in Human Long-term Memory Synaptic Plasticity: A Systematic Review

Science.gov (United States)

Ataei, Negar; Sabzghabaee, Ali Mohammad; Movahedian, Ahmad

2015-01-01

Background: Long-term memory is based on synaptic plasticity, a series of biochemical mechanisms include changes in structure and proteins of brain's neurons. In this article, we systematically reviewed the studies that indicate calcium/calmodulin kinase II (CaMKII) is a ubiquitous molecule among different enzymes involved in human long-term memory and the main downstream signaling pathway of long-term memory. Methods: All of the observational, case–control and review studies were considered and evaluated by the search engines PubMed, Cochrane Central Register of Controlled Trials and ScienceDirect Scopus between 1990 and February 2015. We did not carry out meta-analysis. Results: At the first search, it was fined 1015 articles which included “synaptic plasticity” OR “neuronal plasticity” OR “synaptic density” AND memory AND “molecular mechanism” AND “calcium/calmodulin-dependent protein kinase II” OR CaMKII as the keywords. A total of 335 articles were duplicates in the databases and eliminated. A total of 680 title articles were evaluated. Finally, 40 articles were selected as reference. Conclusions: The studies have shown the most important intracellular signal of long-term memory is calcium-dependent signals. Calcium linked calmodulin can activate CaMKII. After receiving information for learning and memory, CaMKII is activated by Glutamate, the most important neurotransmitter for memory-related plasticity. Glutamate activates CaMKII and it plays some important roles in synaptic plasticity modification and long-term memory. PMID:26445635

Long-term evolution of highly alkaline steel slag drainage waters.

Science.gov (United States)

Riley, Alex L; Mayes, William M

2015-07-01

The disposal of slag generated by the steel industry can have negative consequences upon the surrounding aquatic environment by the generation of high pH waters, leaching of potentially problematic trace metals, and rapid rates of calcite precipitation which smother benthic habitats. A 36-year dataset was collated from the long-term ambient monitoring of physicochemical parameters and elemental concentrations of samples from two steel slag leachate-affected watercourses in northern England. Waters were typified by elevated pH (>10), high alkalinity, and were rich in dissolved metals (e.g. calcium (Ca), aluminium (Al), and zinc (Zn)). Long-term trend analysis was performed upon pH, alkalinity, and Ca concentration which, in addition to Ca flux calculations, were used to highlight the longevity of pollution arising as a result of the dumping and subsequent leaching of steel slags. Declines in calcium and alkalinity have been modest over the monitoring period and not accompanied by significant declines in water pH. If the monotonic trends of decline in alkalinity and calcium continue in the largest of the receiving streams, it will be in the region of 50-80 years before calcite precipitation would be expected to be close to baseline levels, where ecological impacts would be negligible.

Lead (Pb+2) impairs long-term memory and blocks learning-induced increases in hippocampal protein kinase C activity

International Nuclear Information System (INIS)

Vazquez, Adrinel; Pena de Ortiz, Sandra

2004-01-01

The long-term storage of information in the brain known as long-term memory (LTM) depends on a variety of intracellular signaling cascades utilizing calcium (Ca 2+ ) and cyclic adenosine monophosphate as second messengers. In particular, Ca +2 /phospholipid-dependent protein kinase C (PKC) activity has been proposed to be necessary for the transition from short-term memory to LTM. Because the neurobehavioral toxicity of lead (Pb +2 ) has been associated to its interference with normal Ca +2 signaling in neurons, we studied its effects on spatial learning and memory using a hippocampal-dependent discrimination task. Adult rats received microinfusions of either Na + or Pb +2 acetate in the CA1 hippocampal subregion before each one of four training sessions. A retention test was given 7 days later to examine LTM. Results suggest that intrahippocampal Pb +2 did not affect learning of the task, but significantly impaired retention. The effects of Pb +2 selectively impaired reference memory measured in the retention test, but had no effect on the general performance because it did not affect the latency to complete the task during the test. Finally, we examined the effects of Pb +2 on the induction of hippocampal Ca +2 /phospholipid-dependent PKC activity during acquisition training. The results showed that Pb +2 interfered with the learning-induced activation of Ca +2 /phospholipid-dependent PKC on day 3 of acquisition. Overall, our results indicate that Pb +2 causes cognitive impairments in adult rats and that such effects might be subserved by interference with Ca +2 -related signaling mechanisms required for normal LTM

Exogenous hydrogen sulfide eliminates spatial memory retrieval impairment and hippocampal CA1 LTD enhancement caused by acute stress via promoting glutamate uptake.

Science.gov (United States)

He, Jin; Guo, Ruixian; Qiu, Pengxin; Su, Xingwen; Yan, Guangmei; Feng, Jianqiang

2017-05-14

Acute stress impairs the hippocampus-dependent spatial memory retrieval, and its synaptic mechanisms are associated with hippocampal CA1 long-term depression (LTD) enhancement in the adult rats. Endogenous hydrogen sulfide (H 2 S) is recognized as a novel gasotransmitter and has the neural protective roles. However, very little attention has been paid to understanding the effects of H 2 S on spatial memory retrieval impairment. We observed the protective effects of NaHS (a donor of H 2 S) against spatial memory retrieval impairment caused by acute stress and its synaptic mechanisms. Our results showed that NaHS abolished spatial memory retrieval impairment and hippocampal CA1 LTD enhancement caused by acute stress, but not by glutamate transporter inhibitor l-trans-pyrrolidine-2,4-dicarboxylic (tPDC), indicating that the activation of glutamate transporters is necessary for exogenous H 2 S to exert its roles. Moreover, NaHS restored the decreased glutamate uptake in the hippocampal CA1 synaptosomal fraction caused by acute stress. Dithiothreitol (DTT, a disulfide reducing agent) abolished a decrease in the glutamate uptake caused by acute stress, and NaHS eradicated the decreased glutamate uptake caused by 5,5'-dithio-bis(2-nitrobenzoic)acid (DTNB, a thiol oxidizing agent), collectively, revealing that exogenous H 2 S increases glutamate uptake by reducing disulfide bonds of the glutamate transporters. Additionally, NaHS inhibited the increased expression level of phosphorylated c-Jun-N-terminal kinase (JNK) in the hippocampal CA1 region caused by acute stress. The JNK inhibitor SP600125 eliminated spatial memory retrieval impairment, hippocampal CA1 LTD enhancement and the decreased glutamate uptake caused by acute stress, indicating that exogenous H 2 S exerts these roles by inhibiting the activation of JNK signaling pathway. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Long-term efficacy of a mini-course in radiation-reducing techniques in invasive cardiology

International Nuclear Information System (INIS)

Kuon, E.; Empen, K.; Hummel, A.; Doerr, M.; Reffelmann, T.; Felix, S.B.; Weitmann, K.; Hoffmann, W.; Staudt, A.

2013-01-01

Purpose: To validate the long-term efficacy of a 90-min. educational mini-course in less-irradiating cardiac interventional techniques. Materials and Methods: Before, two months after, and two years after the mini-course (periods I, II, and III), we analyzed the following radiation dose parameters for ten coronary angiographies (CA), performed by each of 7 cardiologists: total dose-area product (DAP), radiographic and fluoroscopic DAP fractions, number of radiographic frames and runs, and fluoroscopy time. Results: The median patient DAP for periods I, II and III was 31.4, 15.8 and 8.5 Gy x cm 2 , respectively. The long-term effect was related to shorter median fluoroscopy times (180, 172, and 120 s), shorter (57, 52, and 45) and fewer (12, 12, and 10) radiographic runs, consistent collimation and restriction to an adequate image quality. Both radiographic DAP/frame (28.7, 17.0, and 18.4 mGy x cm 2 ) and fluoroscopic DAP/second (45.7, 24.2, and 10.0 mGy x cm 2 ) decreased significantly. The multivariate linear regression analysis confirmed the increasing efficacy of the mini-course itself (-44.6 and -60.7 %), and revealed a decreasing influence of the interventionalist's experience (-8.6 % and -4.9 % per 1,000 CAs, lifelong performed until the mini-course). The number of CAs performed after the mini-course did not influence the long-term DAP results. Conclusion: The presented educational mini-course allows a significant, long-lasting, and apparently ongoing reduction of patient radiation exposure due to CA. A self-surveillant documentation of relevant radiation parameters is well suited to monitor and improve each operator's individual long-term radiation-reducing efforts. (orig.)

Longitudinal Changes in Psychological States in Online Health Community Members: Understanding the Long-Term Effects of Participating in an Online Depression Community.

Science.gov (United States)

Park, Albert; Conway, Mike

2017-03-20

significantly or at least as much as members of other online communities. On the basis of these findings, we contribute practical suggestions for designing online depression communities to enhance psychosocial benefit gains for members. We consider these results to be an important step toward a better understanding of the impact of prolonged participation in an online depression community, in addition to providing insights into the long-term psychosocial well-being of members. ©Albert Park, Mike Conway. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 20.03.2017.

Switching On Depression and Potentiation in the Cerebellum

Directory of Open Access Journals (Sweden)

Andrew R. Gallimore

2018-01-01

Full Text Available Long-term depression (LTD and long-term potentiation (LTP in the cerebellum are important for motor learning. However, the signaling mechanisms controlling whether LTD or LTP is induced in response to synaptic stimulation remain obscure. Using a unified model of LTD and LTP at the cerebellar parallel fiber-Purkinje cell (PF-PC synapse, we delineate the coordinated pre- and postsynaptic signaling that determines the direction of plasticity. We show that LTP is the default response to PF stimulation above a well-defined frequency threshold. However, if the calcium signal surpasses the threshold for CaMKII activation, then an ultrasensitive “on switch” activates an extracellular signal-regulated kinase (ERK-based positive feedback loop that triggers LTD instead. This postsynaptic feedback loop is sustained by another, trans-synaptic, feedback loop that maintains nitric oxide production throughout LTD induction. When full depression is achieved, an automatic “off switch” inactivates the feedback loops, returning the network to its basal state and demarcating the end of the early phase of LTD.

Patient-reported safety incidents in older patients with long-term conditions: a large cross-sectional study.

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Panagioti, Maria; Blakeman, Thomas; Hann, Mark; Bower, Peter

2017-05-30

Increasing evidence suggests that patient safety is a serious concern for older patients with long-term conditions. Despite this, there is a lack of research on safety incidents encountered by this patient group. In this study, we sought to examine patient reports of safety incidents and factors associated with reports of safety incidents in older patients with long-term conditions. The baseline cross-sectional data from a longitudinal cohort study were analysed. Older patients (n=3378 aged 65 years and over) with a long-term condition registered in general practices were included in the study. The main outcome was patient-reported safety incidents including availability and appropriateness of medical tests and prescription of wrong types or doses of medication. Binary univariate and multivariate logistic regression analyses were undertaken to examine factors associated with patient-reported safety incidents. Safety incidents were reported by 11% of the patients. Four factors were significantly associated with patient-reported safety incidents in multivariate analyses. The experience of multiple long-term conditions (OR=1.09, 95% CI 1.05 to 1.13), a probable diagnosis of depression (OR=1.36, 95% CI 1.06 to 1.74) and greater relational continuity of care (OR=1.28, 95% CI 1.08 to 1.52) were associated with increased odds for patient-reported safety incidents. Perceived greater support and involvement in self-management was associated with lower odds for patient-reported safety incidents (OR=0.95, 95% CI 0.93 to 0.97). We found that older patients with multimorbidity and depression are more likely to report experiences of patient safety incidents. Improving perceived support and involvement of patients in their care may help prevent patient-reported safety incidents. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

With long hours of work, might depression then lurk?

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Varma, Anshu; Marott, Jacob Louis; Stoltenberg, Christian Ditlev Gabriel

2012-01-01

The aim of this study was to examine depression as a potential negative health effect of long work hours, anticipating an exposure-response relationship.......The aim of this study was to examine depression as a potential negative health effect of long work hours, anticipating an exposure-response relationship....

Insomnia in long-term care facilities: a comparison of seven European countries and Israel: the Services and Health for Elderly in Long TERm care study.

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Gindin, Jacob; Shochat, Tamar; Chetrit, Angela; Epstein, Shulamit; Ben Israel, Yehoshua; Levi, Sarah; Onder, Graziano; Carpenter, Ian; Finne-Soveri, Harriet; van Hout, Hein; Henrard, Jean-Claude; Nikolaus, Thorsten; Topinkova, Eva; Fialová, Daniela; Bernabei, Roberto

2014-11-01

To assess insomnia and its correlates as part of the Services and Health for Elderly in Long TERm care (SHELTER) study, funded by the 7th Framework Programme of the European Union. Cross-cultural investigation. Long-term care facilities (LTCFs) in eight European countries (Czech Republic, France, Finland, Germany, England, the Netherlands, Italy) and one non-European country (Israel). Elderly residents (N = 4,156) of 57 LTCFs. Information on insomnia, age, sex, activities of daily living (ADLs), cognitive status, depression, major stressful life events, physical activity, fatigue, pain, and sleep medication use was extracted from the International Resident Assessment Instrument (interRAI)LTCF instrument. Rates of insomnia and its correlates were analyzed. Multivariate logistic regression was used to assess factors associated with insomnia, controlling for demographic variables. The prevalence of insomnia was 24% (range 13-30%), with significant differences between countries (P < .001). More insomnia complaints were reported in older than younger residents (P < .001). Higher rates of insomnia were associated with hypnosedatives and depression in all countries (P < .001) and with stressful life events, fatigue, and pain in most countries (P < .001). No associations were found between insomnia and ADLs, physical activity, or cognitive status. Age, depression, stressful life events, fatigue, pain and hypnosedatives were independent significant predictors of insomnia, controlling for all other variables and for country. Hypnosedatives and depression were strong predictors of insomnia beyond cultural differences. Overall, psychosocial variables were more strongly related to insomnia than functional and mental capacities. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

Novel nootropic drug sunifiram improves cognitive deficits via CaM kinase II and protein kinase C activation in olfactory bulbectomized mice.

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Moriguchi, Shigeki; Tanaka, Tomoya; Tagashira, Hideaki; Narahashi, Toshio; Fukunaga, Kohji

2013-04-01

Alzheimer's disease (AD) shows degeneration of the cholinergic system in the medial septum, thereby eliciting down-regulation of the olfactory function in patients. We have previously reported that olfactory bulbectomized (OBX) mice show hippocampus-dependent memory impairment as assessed by memory-related behavioral tasks and hippocampal long-term potentiation (LTP). In the present study, we focused whether novel pyrrolidone nootropic drug sunifiram improves both memory impairment and depression observed in OBX mice. OBX mice were administered once a day for 7-12 days with sunifiram (0.01-1.0mg/kg p.o.) from 10 days after operation with or without gavestinel (10mg/kg i.p.), which is glycine-binding site inhibitor of N-methyl-d-aspartate receptor (NMDAR). The spatial reference memory assessed by Y-maze and short-term memory assessed by novel object recognition task were significantly improved by sunifiram treatment in OBX mice. Sunifiram also restored hippocampal LTP injured in OBX mice without treatment with gavestinel. By contrast, sunifiram treatment did not ameliorate the depressive behaviors assessed by tail suspension task in OBX mice. Notably, sunifiram treatment restored CaMKIIα (Thr-286) autophosphorylation and GluR1 (Ser-831) phosphorylation in the hippocampal CA1 region from OBX mice to the levels of control mice. Likewise, sunifiram treatment improved PKCα (Ser-657) autophosphorylation and NR1 (Ser-896) phosphorylation to the control levels. Stimulation of CaMKII and PKC autophosphorylation by sunifiram was significantly inhibited by pre-treatment with gavestinel. However, sunifiram treatment did not affect the phosphorylation of CaMKIV (Thr-196) and ERK. Taken together, sunifiram ameliorates OBX-induced deficits of memory-related behaviors and impaired LTP in the hippocampal CA1 region via stimulation of glycine-binding site of NMDAR. Copyright © 2013 Elsevier B.V. All rights reserved.

Health-related quality of life in long-term survivors of testicular cancer

DEFF Research Database (Denmark)

Rossen, Philip Blach; Pedersen, Anette Fischer; Zachariae, Robert

2009-01-01

PURPOSE: A growing number of patients with testicular cancer (TC) become long-term survivors. As a consequence, quality-of-life (QOL) issues become increasingly important. The objective of this study was to investigate QOL among Danish TC survivors. METHODS: A long-term follow-up assessment of all...... patients with TC treated at Aarhus University Hospital in Denmark between 1990 and 2000 was conducted. A total of 401 survivors (response rate, 66%) completed questionnaires concerning QOL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30), depression (Beck...

Duration of unemployment and depression: a cross-sectional survey in Lithuania.

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Stankunas, Mindaugas; Kalediene, Ramune; Starkuviene, Skirmante; Kapustinskiene, Violeta

2006-07-05

In spite of a growing economy, unemployment is still a severe socio-economic problem in Lithuania. Nonetheless, no studies have been performed about the associations between unemployment and mental health in Lithuania. The aim of this study was to evaluate the associations between unemployment duration and depression in Lithuania. The data was collected in a cross-sectional study in 2005. There were 429 filled-in questionnaires received (53.6% response rate) from unemployed persons registered with the Kaunas Labour Market Office. The severity of depression symptoms was evaluated using the Beck Depression Inventory (BDI). Logistic regression was used to estimate the risk factors for occurrence of depression. Sex, age, place of residence, marital status, education, income and practiced religion were the independent variables. Long-term unemployment was defined as lasting a duration of 12 months or more. The findings showed that long-term unemployed persons had more episodes of a depressive mood in the past 12 months in comparison with the group of the short-term unemployed. In addition, the BDI score mean was higher among the long-term unemployed compared with the short-term unemployed (10.1 +/- 8.8 and 14.2 +/- 9.5 respectively, p unemployment and BDI score had a positive correlation (r = 0.1968, p unemployed, the risk of depression increased significantly when the person was female, had an older age and had experienced more episodes of unemployment. Among the long-term unemployed, an older age was the risk factor for development of depression. However, higher education and income were the factors that significantly decreased the risk of developing depression for-short term as well as for long-term unemployed. The results indicated that depression is a severe problem in the unemployed population. Depression is more elevated among the long-term unemployed. This leads to arguing for common efforts in providing needed social support and health care to reduce the

Long-term effects of psychotherapy on moderate depression: a comparative study of narrative therapy and cognitive-behavioral therapy.

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Lopes, Rodrigo T; Gonçalves, Miguel M; Fassnacht, Daniel B; Machado, Paulo P P; Sousa, Inês

2014-01-01

In a previous clinical controlled trial (Lopes et al., 2014), narrative therapy (NT) showed promising results in ameliorating depressive symptoms with comparable outcomes to cognitive-behavioral therapy (CBT) when patients completed treatment. This paper aims to assess depressive symptoms and interpersonal problems in this clinical sample at follow-up. Using the Beck Depression Inventory-II and Outcome Questionnaire-45.2 Interpersonal Relations Scale, naturalistic prospective follow-up assessment was conducted at 21 and 31 months after the last treatment session. At follow-up, patients kept improving in terms of depressive symptoms and interpersonal problems. The odds that a patient maintained recovery from depressive symptoms at follow-up were five times higher than the odds that a patient maintained recovery from interpersonal problems. In the same way, the odds of a patient never recovering from interpersonal problems were five times higher than the odds of never recovering from depressive symptoms. The study did not control for the natural course of depression or treatment continuation. For depressed patients with greater interpersonal disabilities, longer treatment plans and alternative continuation treatments should be considered. Copyright © 2014 Elsevier B.V. All rights reserved.

Short-term stress, but not mucosal healing nor depression was predictive for the risk of relapse in patients with ulcerative colitis: a prospective 12-month follow-up study.

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Langhorst, Jost; Hofstetter, Anna; Wolfe, Fred; Häuser, Winfried

2013-10-01

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease. Psychological factors such as depression and stress are under debate to contribute to the risk of relapse. The impact of mucosal healing to reduce the risk of relapse had not been studied prospectively. The aim of this study was to identify whether depression and stress increase and mucosal healing reduces the risk of clinical relapse in patients with UC in clinical remission. Patients in clinical remission were followed prospectively for 1 year, or less if they relapsed. Endoscopy and histology score and long-term perceived stress (Perceived Stress Questionnaire) were measured at baseline. Mucosal healing was defined by a Mayo Endoscopy score of 0-1. Depression (Hospital Anxiety and Depression Scale) and acute perceived stress (Cohen Perceived Stress Scale) were measured at baseline and after 1, 3, 6, 9, and 12 months. A time-dependent multivariate Cox regression model determined the predictors of time to relapse. Seventy-five patients were included into final analysis, of which 28 (37.3%) relapsed. Short-term stress at the last visit before relapse (hazard ratio [HR] = 1.05, 95% confidence interval [CI] = 1.01-1.10) and male gender (HR = 2.38, 95% CI = 1.01-5.61), but not baseline mucosal healing (HR = 0.86, 95% CI = 0.35-2.11), baseline long-term stress (HR = 0.20, 95% CI = 0.01-3.31), and depression at the last visit before relapse (HR = 1.08, 95% CI = 0.95-1.22) were predictive for a relapse. Short-term stress but not depression nor mucosal healing was predictive for the risk of relapse in patients with UC in clinical remission. Larger multicentre studies are necessary to confirm our findings.

Regulation of hippocampus-dependent memory by the zinc finger protein Zbtb20 in mature CA1 neurons.

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Ren, Anjing; Zhang, Huan; Xie, Zhifang; Ma, Xianhua; Ji, Wenli; He, David Z Z; Yuan, Wenjun; Ding, Yu-Qiang; Zhang, Xiao-Hui; Zhang, Weiping J

2012-10-01

The mammalian hippocampus harbours neural circuitry that is crucial for associative learning and memory. The mechanisms that underlie the development and regulation of this complex circuitry are not fully understood. Our previous study established an essential role for the zinc finger protein Zbtb20 in the specification of CA1 field identity in the developing hippocampus. Here, we show that conditionally deleting Zbtb20 specifically in mature CA1 pyramidal neurons impaired hippocampus-dependent memory formation, without affecting hippocampal architecture or the survival, identity and basal excitatory synaptic activity of CA1 pyramidal neurons. We demonstrate that mature CA1-specific Zbtb20 knockout mice exhibited reductions in long-term potentiation (LTP) and NMDA receptor (NMDAR)-mediated excitatory post-synaptic currents. Furthermore, we show that activity-induced phosphorylation of ERK and CREB is impaired in the hippocampal CA1 of Zbtb20 mutant mice. Collectively, these results indicate that Zbtb20 in mature CA1 plays an important role in LTP and memory by regulating NMDAR activity, and activation of ERK and CREB.

Long-term depression-like plasticity of the blink reflex for the treatment of blepharospasm.

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Kranz, Gottfried; Shamim, Ejaz A; Lin, Peter T; Kranz, George S; Hallett, Mark

2013-04-01

Our previous work showed a beneficial therapeutic effect on blepharospasm using slow repetitive transcranial magnetic stimulation, which produces a long-term depression (LTD)-like effect. High-frequency supraorbital electrical stimulation, asynchronous with the R2 component of the blink reflex, can also induce LTD-like effects on the blink reflex circuit in healthy subjects. Patients with blepharospasm have reduced inhibition of their blink recovery curves; therefore, a LTD-like intervention might normalize the blink reflex recovery (BRR) and have a favorable therapeutic effect. This is a randomized, sham-controlled, observer-blinded prospective study. In 14 blepharospasm patients, we evaluated the effects of high-frequency supraorbital stimulation on three separate treatment days. We applied 28 trains of nine stimuli, 400 Hz, either before or after the R2 or used sham stimulation. The primary outcome was the blink rate, number of spasms rated by a blinded physician and patient rating before, immediately after and 1 hour after stimulation while resting, reading, and talking; secondary outcome was the BRR. Stimulation "before" and "after" the R2 both showed a similar improvement as sham stimulation in physician rating, but patients felt significantly better with the before condition. Improvement in recovery of the blink reflex was noted only in the before condition. Clinical symptoms differed in the three baseline conditions (resting, reading, and talking). Stimulation before R2 increased inhibition in trigeminal blink reflex circuits in blepharospasm toward normal values and produced subjective, but not objective, improvement. Inhibition of the blink reflex pathway by itself appeared to be insufficient for a useful therapeutic effect. Copyright © 2013 Movement Disorder Society.

Maternal Beliefs as Long-Term Predictors of Mother-Child Interaction and Report.

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Kochanska, Grazyna

1990-01-01

Two kinds of parental beliefs, endorsed rearing philosophy (authoritative-authoritarian dimension) and affective attitude toward child (positive-negative affect dimension), were examined in 20 normal and 36 depressed mothers as long-term predictors of child rearing behaviors and interaction patterns with their children. (BC)

Relationship between long working hours and depression: a 3-year longitudinal study of clerical workers.

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Amagasa, Takashi; Nakayama, Takeo

2013-08-01

To clarify how long working hours affect the likelihood of current and future depression. Using data from four repeated measurements collected from 218 clerical workers, four models associating work-related factors to the depressive mood scale were established. The final model was constructed after comparing and testing the goodness-of-fit index using structural equation modeling. Multiple logistic regression analysis was also performed. The final model showed the best fit (normed fit index = 0.908; goodness-of-fit index = 0.936; root-mean-square error of approximation = 0.018). Its standardized total effect indicated that long working hours affected depression at the time of evaluation and 1 to 3 years later. The odds ratio for depression risk was 14.7 in employees who were not long-hours overworked according to the initial survey but who were long-hours overworked according to the second survey. Long working hours increase current and future risks of depression.

Short-Term Depression, Temporal Summation, and Onset Inhibition Shape Interval Tuning in Midbrain Neurons

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Baker, Christa A.

2014-01-01

A variety of synaptic mechanisms can contribute to single-neuron selectivity for temporal intervals in sensory stimuli. However, it remains unknown how these mechanisms interact to establish single-neuron sensitivity to temporal patterns of sensory stimulation in vivo. Here we address this question in a circuit that allows us to control the precise temporal patterns of synaptic input to interval-tuned neurons in behaviorally relevant ways. We obtained in vivo intracellular recordings under multiple levels of current clamp from midbrain neurons in the mormyrid weakly electric fish Brienomyrus brachyistius during stimulation with electrosensory pulse trains. To reveal the excitatory and inhibitory inputs onto interval-tuned neurons, we then estimated the synaptic conductances underlying responses. We found short-term depression in excitatory and inhibitory pathways onto all interval-tuned neurons. Short-interval selectivity was associated with excitation that depressed less than inhibition at short intervals, as well as temporally summating excitation. Long-interval selectivity was associated with long-lasting onset inhibition. We investigated tuning after separately nullifying the contributions of temporal summation and depression, and found the greatest diversity of interval selectivity among neurons when both mechanisms were at play. Furthermore, eliminating the effects of depression decreased sensitivity to directional changes in interval. These findings demonstrate that variation in depression and summation of excitation and inhibition helps to establish tuning to behaviorally relevant intervals in communication signals, and that depression contributes to neural coding of interval sequences. This work reveals for the first time how the interplay between short-term plasticity and temporal summation mediates the decoding of temporal sequences in awake, behaving animals. PMID:25339741

Adjuvant psychological therapy in long-term endocrine conditions.

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Daniels, J; Turner-Cobb, J M

2017-06-01

Consideration of psychological distress in long-term endocrine conditions is of vital importance given the prevalence of anxiety and depression in such disorders. Poor mental health can lead to compromised self-care, higher utilization of health services, lower rates of adherence, reduced quality of life and ultimately poorer outcomes. Adjuvant psychological therapy offers an effective resource to reduce distress in endocrine conditions. While the vast majority of work in this area has focused on psychological screening and intervention in diabetes, identification and recognition of psychological distress are equally important in other endocrinological conditions, with supportive evidence in polycystic ovary syndrome and Addison's disease. Referral pathways and recommendations set out by UK guidelines and the Department of Health mandate requires greater attention across a wider range of long-term endocrine conditions to facilitate improved quality of life and health outcome. © 2017 John Wiley & Sons Ltd.

Long-term efficacy of a mini-course in radiation-reducing techniques in invasive cardiology

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Kuon, E. [Klinik Fraenkische Schweiz, Ebermannstadt (Germany). Abt. fuer Kardiologie; Empen, K.; Hummel, A.; Doerr, M.; Reffelmann, T.; Felix, S.B. [Ernst-Moritz-Arndt-Universitaet, Greifswald (Germany). Abt. fuer Innere Medizin B; Weitmann, K.; Hoffmann, W. [Ernst-Moritz-Arndt-Universitaet, Greifswald (Germany). Inst. fuer Versorgungsmedizin; Staudt, A. [Helios Kliniken, Schwerin (Germany). Abt. fuer Kardiologie und Angiologie

2013-08-15

Purpose: To validate the long-term efficacy of a 90-min. educational mini-course in less-irradiating cardiac interventional techniques. Materials and Methods: Before, two months after, and two years after the mini-course (periods I, II, and III), we analyzed the following radiation dose parameters for ten coronary angiographies (CA), performed by each of 7 cardiologists: total dose-area product (DAP), radiographic and fluoroscopic DAP fractions, number of radiographic frames and runs, and fluoroscopy time. Results: The median patient DAP for periods I, II and III was 31.4, 15.8 and 8.5 Gy x cm{sup 2}, respectively. The long-term effect was related to shorter median fluoroscopy times (180, 172, and 120 s), shorter (57, 52, and 45) and fewer (12, 12, and 10) radiographic runs, consistent collimation and restriction to an adequate image quality. Both radiographic DAP/frame (28.7, 17.0, and 18.4 mGy x cm{sup 2}) and fluoroscopic DAP/second (45.7, 24.2, and 10.0 mGy x cm{sup 2}) decreased significantly. The multivariate linear regression analysis confirmed the increasing efficacy of the mini-course itself (-44.6 and -60.7 %), and revealed a decreasing influence of the interventionalist's experience (-8.6 % and -4.9 % per 1,000 CAs, lifelong performed until the mini-course). The number of CAs performed after the mini-course did not influence the long-term DAP results. Conclusion: The presented educational mini-course allows a significant, long-lasting, and apparently ongoing reduction of patient radiation exposure due to CA. A self-surveillant documentation of relevant radiation parameters is well suited to monitor and improve each operator's individual long-term radiation-reducing efforts. (orig.)

Long-term effects of low calcium dialysates on the serum calcium levels during maintenance hemodialysis treatments: A systematic review and meta-analysis.

Science.gov (United States)

Yoshikawa, Masahiro; Takase, Osamu; Tsujimura, Taro; Sano, Etsuko; Hayashi, Matsuhiko; Takato, Tsuyoshi; Hishikawa, Keiichi

2018-03-28

Hypercalcemia and hyperparathyroidism in patients receiving maintenance hemodialysis (MHD) can cause the progression of cardiovascular diseases (CVD) and mineral bone disorders (MBD). The KDIGO recommends the dialysates with a calcium (Ca) concentration of 1.25-1.5 mmol/L for MHD treatments, but the optimal concentration remains controversial. Here, we conducted a systematic review and a meta-analysis of seven randomized controlled trials examining a total of 622 patients to investigate the optimal concentration for MHD for 6 months or longer. The dialysates with a low Ca concentration (1.125 or 1.25 mmol/L) significantly lowered the serum Ca and raised the intact parathyroid hormone levels by 0.52 mg/dL (95% confidence interval, 0.20-0.85) and 39.59 pg/mL (14.80-64.38), respectively, compared with a high Ca concentration (1.50 or 1.75 mmol/L). Three studies showed that a low concentration was preferred for lowering arterial calcifications or atherosclerosis in different arteries, but one study showed that coronary arterial calcifications increased with a low concentration. Two studies showed contradictory outcomes in terms of MBD. Our meta-analysis showed that a dialysate with a low Ca concentration lowered the serum Ca levels in patients receiving long-term MHD, but further studies are needed to determine the optimal Ca concentration in terms of CVD and MBD.

Opposite effects of glucocorticoid receptor activation on hippocampal CA1 dendritic complexity in chronically stressed and handled animals

NARCIS (Netherlands)

Alfarez, D.N.; Karst, H.; Velzing, E.H.; Joëls, M.; Krugers, H.J.

2008-01-01

Remodeling of synaptic networks is believed to contribute to synaptic plasticity and long-term memory performance, both of which are modulated by chronic stress. We here examined whether chronic stress modulates dendritic complexity of hippocampal CA1 pyramidal cells, under conditions of basal as

Burst-induced anti-Hebbian depression acts through short-term synaptic dynamics to cancel redundant sensory signals.

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Harvey-Girard, Erik; Lewis, John; Maler, Leonard

2010-04-28

Weakly electric fish can enhance the detection and localization of important signals such as those of prey in part by cancellation of redundant spatially diffuse electric signals due to, e.g., their tail bending. The cancellation mechanism is based on descending input, conveyed by parallel fibers emanating from cerebellar granule cells, that produces a negative image of the global low-frequency signals in pyramidal cells within the first-order electrosensory region, the electrosensory lateral line lobe (ELL). Here we demonstrate that the parallel fiber synaptic input to ELL pyramidal cell undergoes long-term depression (LTD) whenever both parallel fiber afferents and their target cells are stimulated to produce paired burst discharges. Paired large bursts (4-4) induce robust LTD over pre-post delays of up to +/-50 ms, whereas smaller bursts (2-2) induce weaker LTD. Single spikes (either presynaptic or postsynaptic) paired with bursts did not induce LTD. Tetanic presynaptic stimulation was also ineffective in inducing LTD. Thus, we have demonstrated a form of anti-Hebbian LTD that depends on the temporal correlation of burst discharge. We then demonstrated that the burst-induced LTD is postsynaptic and requires the NR2B subunit of the NMDA receptor, elevation of postsynaptic Ca(2+), and activation of CaMKIIbeta. A model incorporating local inhibitory circuitry and previously identified short-term presynaptic potentiation of the parallel fiber synapses further suggests that the combination of burst-induced LTD, presynaptic potentiation, and local inhibition may be sufficient to explain the generation of the negative image and cancellation of redundant sensory input by ELL pyramidal cells.

Impaired fear memory specificity associated with deficient endocannabinoid-dependent long-term plasticity.

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Lovelace, Jonathan W; Vieira, Philip A; Corches, Alex; Mackie, Ken; Korzus, Edward

2014-06-01

In addition to its central role in learning and memory, N-methyl D-aspartate receptor (NMDAR)-dependent signaling regulates central glutamatergic synapse maturation and has been implicated in schizophrenia. We have transiently induced NMDAR hypofunction in infant mice during postnatal days 7-11, followed by testing fear memory specificity and presynaptic plasticity in the prefrontal cortex (PFC) in adult mice. We show that transient NMDAR hypofunction during early brain development, coinciding with the maturation of cortical plasticity results in a loss of an endocannabinoid (eCB)-mediated form of long-term depression (eCB-LTD) at adult central glutamatergic synapses, while another form of presynaptic long-term depression mediated by the metabotropic glutamate receptor 2/3 (mGluR2/3-LTD) remains intact. Mice with this selective impairment of presynaptic plasticity also showed deficits in fear memory specificity. The observed deficit in cortical presynaptic plasticity may represent a neural maladaptation contributing to network instability and abnormal cognitive functioning.

High somatic distress with high long-term stability in selected patients with chronic depression: a 3-year follow-up of ratings with Karolinska Scales of Personality (KSP).

Science.gov (United States)

Gardner, Ann; Hällström, Tore

2004-01-01

The main aim of the present study was to investigate mean levels and long-term stability of three scales from the Karolinska Scales of Personality (KSP), assessing somatic components of anxiety proneness in selected patients with chronic depressive symptoms. The KSP was filled in by 84 patients (26 men and 58 women) with a history of or ongoing major depression and audiological, or other comorbid somatic, symptoms. Mean scores for the Somatic Anxiety, Muscular Tension and Psychasthenia scales were above two standard deviations compared to a normative group sampled from the population. The KSP was filled in at follow-up by 65 patients. The mean interval between the ratings was 3.5 years. Comparisons between the ratings of the three scales revealed no significant mean score differences, and quite high individual stability. The mean scores were significantly increased in comparisons with depressed patients in primary care suggesting that these patients with chronic depression may comprise a depressive sub-type characterized by high "somatic distress". A putative origin for the high and stable scores in the presented sub-group of depressed patients, and the concept of "personality trait" in use even for pronounced symptoms, are discussed.

The long-term course of depressive disorders in the Lundby Study

DEFF Research Database (Denmark)

Mattisson, Cecilia; Bogren, Mats; Horstmann, Vibeke

2007-01-01

disorders in 7% and bipolar disorder in 2%. Five per cent committed suicide; male gender and severity of depression were significant risk factors. CONCLUSION: The low rates of recurrence and suicide suggest a better prognosis for community samples than for in- and out-patient samples. Udgivelsesdato: 2007...... who had experienced their first episode of depression were followed up. Their course was studied with regard to recurrence of depression related to duration of follow-up, transition to other psychiatric disorders including alcohol disorders, as well as incidence and risk factors of suicide. RESULTS...

The temporoammonic input to the hippocampal CA1 region displays distinctly different synaptic plasticity compared to the Schaffer collateral input in vivo: significance for synaptic information processing

Directory of Open Access Journals (Sweden)

Ayla eAksoy Aksel

2013-08-01

Full Text Available In terms of its sub-regional differentiation, the hippocampal CA1 region receives cortical information directly via the perforant (temporoammonic path (pp-CA1 synapse and indirectly via the tri-synaptic pathway where the last relay station is the Schaffer collateral-CA1 synapse (Sc-CA1 synapse. Research to date on pp-CA1 synapses has been conducted predominantly in vitro and never in awake animals, but these studies hint that information processing at this synapse might be distinct to processing at the Sc-CA1 synapse. Here, we characterized synaptic properties and synaptic plasticity at the pp-CA1 synapse of freely behaving adult rats. We established that field excitatory postsynaptic potentials at the pp-CA1 have longer onset latencies and a shorter time-to-peak compared to the Sc-CA1 synapse. LTP (> 24h was successfully evoked by tetanic afferent stimulation of pp-CA1 synapses. Low frequency stimulation evoked synaptic depression at Sc-CA1 synapses, but did not elicit LTD at pp-CA1 synapses unless the Schaffer collateral afferents to the CA1 region had been severed. Paired-pulse responses also showed significant differences. Our data suggest that synaptic plasticity at the pp-CA1 synapse is distinct from the Sc-CA1 synapse and that this may reflect its specific role in hippocampal information processing.

Case Reports Showing a Long-Term Effect of Subanesthetic Ketamine Infusion in Reducing L-DOPA-Induced Dyskinesias

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Scott J. Sherman

2016-02-01

Full Text Available Ketamine is an FDA-approved drug with a known safety profile. Low-dose subanesthetic intravenous ketamine infusion treatment has led to long-term reduction of treatment-resistant depression and of chronic pain states. We report on low-dose subanesthetic intravenous ketamine infusion treatment in Parkinson's disease (PD patients by 5 case studies and show a long-lasting therapeutic benefit to reduce L-DOPA-induced dyskinesia (LID, improve on time, and reduce depression. Based on the literature we hypothesize that low-dose ketamine may act as a ‘chemical deep brain stimulation', by desynchronizing hypersynchronous oscillatory brain activity, including in the basal ganglia and the motor cortex. The presented PD case reports indicate tolerability, safety and long-term beneficial effects of low-dose ketamine infusion that should be further investigated in a properly controlled prospective clinical trial for treatment of LID, as well as the prevalent nonmotor features pain and depression in PD patients.

Synaptic characteristics with strong analog potentiation, depression, and short-term to long-term memory transition in a Pt/CeO2/Pt crossbar array structure

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Kim, Hyung Jun; Park, Daehoon; Yang, Paul; Beom, Keonwon; Kim, Min Ju; Shin, Chansun; Kang, Chi Jung; Yoon, Tae-Sik

2018-06-01

A crossbar array of Pt/CeO2/Pt memristors exhibited the synaptic characteristics such as analog, reversible, and strong resistance change with a ratio of ∼103, corresponding to wide dynamic range of synaptic weight modulation as potentiation and depression with respect to the voltage polarity. In addition, it presented timing-dependent responses such as paired-pulse facilitation and the short-term to long-term memory transition by increasing amplitude, width, and repetition number of voltage pulse and reducing the interval time between pulses. The memory loss with a time was fitted with a stretched exponential relaxation model, revealing the relation of memory stability with the input stimuli strength. The resistance change was further enhanced but its stability got worse as increasing measurement temperature, indicating that the resistance was changed as a result of voltage- and temperature-dependent electrical charging and discharging to alter the energy barrier for charge transport. These detailed synaptic characteristics demonstrated the potential of crossbar array of Pt/CeO2/Pt memristors as artificial synapses in highly connected neuron-synapse network.

Long-term subregion-specific encoding of enhanced ethanol intake by D1DR medium spiny neurons of the nucleus accumbens.

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Renteria, Rafael; Buske, Tavanna R; Morrisett, Richard A

2018-03-01

The nucleus accumbens (NAc) is a critical component of the mesocorticolimbic system and is involved in mediating the motivational and reinforcing aspects of ethanol consumption. Chronic intermittent ethanol (CIE) exposure is a reliable model to induce ethanol dependence and increase volitional ethanol consumption in mice. Following a CIE-induced escalation of ethanol consumption, NMDAR (N-methyl-D-aspartate receptor)-dependent long-term depression in D1 dopamine receptor expressing medium spiny neurons of the NAc shell was markedly altered with no changes in plasticity in D1 dopamine receptor medium spiny neurons from the NAc core. This disruption of plasticity persisted for up to 2 weeks after cessation of ethanol access. To determine if changes in AMPA receptor (AMPAR) composition contribute to this ethanol-induced neuroadaptation, we monitored the rectification of AMPAR excitatory postsynaptic currents (EPSCs). We observed a marked decrease in the rectification index in the NAc shell, suggesting the presence of GluA2-lacking AMPARs. There was no change in the amplitude of spontaneous EPSCs (sEPSCs), but there was a transient increase in sEPSC frequency in the NAc shell. Using the paired pulse ratio, we detected a similar transient increase in the probability of neurotransmitter release. With no change in sEPSC amplitude, the change in the rectification index suggests that GluA2-containing AMPARs are removed and replaced with GluA2-lacking AMPARs in the NAc shell. This CIE-induced alteration in AMPAR subunit composition may contribute to the loss of NMDAR-dependent long-term depression in the NAc shell and therefore may constitute a critical neuroadaptive response underlying the escalation of ethanol intake in the CIE model. © 2017 Society for the Study of Addiction.

Metformin reduces serum CA199 levels in type 2 diabetes Chinese patients with time-effect and gender difference.

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Zhang, Dandan; Hou, Wolin; Liu, Fang; Yin, Jun; Lu, Wei; Li, Ming; Zheng, Taishan; Lu, Fengdi; Bao, Yuqian; Jia, Weiping

2015-02-01

This study was designed to clarify the influence of metformin on serum carbohydrate antigen 199 (CA199) levels and its associated factors in Chinese type 2 diabetes mellitus (T2DM) patients. In total, 1,253 T2DM patients were enrolled, including a non-metformin group (n = 616), a short-term metformin group (at least 1 week to 2 years; n=325), and a long-term metformin group (≥ 2 years; n = 312). Their clinical and biochemical characteristics were collected and compared. After 1 year, the biochemical parameters were re-examined in 296 patients. Sex hormones were determined, and associations between CA199 and other variables were assessed. At baseline, the incidence of abnormal CA199 levels was 14.7%, 8.9%, and 4.7% in the non-metformin, short-term metformin, and long-term metformin groups, respectively. CA199 levels in females were significantly higher than in males (P non-metformin controls vs. 17.62 ± 10.87 U/mL in the short-term group vs. 10.54 ± 8.14 U/mL in the long-term group; P = 0.000). The correlation and multiple stepwise regression analysis revealed that glycosylated hemoglobin, metformin, gender, total cholesterol, and follicle-stimulating hormone were independent impact factors on CA199 concentrations (all P Binary logistic regression revealed that the risk of abnormal CA199 concentrations of the total population with short-term metformin or long-term metformin treatment decreased 11% (odds ratio = 0.89; P = 0.001) and 30% (odds ratio = 0.70; P = 0.000), respectively, at baseline. After a 1-year follow-up, the incidence of high CA199 level decreased in both the short-term and the long-term metformin group compared with that of controls (P < 0.05). The extent of CA199 decrease in the long-term metformin group was the greatest (-17% vs. -4.9% in the short-term group vs. 3% in controls, P = 0.000), and the group's risk of high blood CA199 level was reduced 67% (odds ratio = 0.33; P = 0.023). The reduction in women was more apparent than that in men

Short-term memory and long-term memory are still different.

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Norris, Dennis

2017-09-01

A commonly expressed view is that short-term memory (STM) is nothing more than activated long-term memory. If true, this would overturn a central tenet of cognitive psychology-the idea that there are functionally and neurobiologically distinct short- and long-term stores. Here I present an updated case for a separation between short- and long-term stores, focusing on the computational demands placed on any STM system. STM must support memory for previously unencountered information, the storage of multiple tokens of the same type, and variable binding. None of these can be achieved simply by activating long-term memory. For example, even a simple sequence of digits such as "1, 3, 1" where there are 2 tokens of the digit "1" cannot be stored in the correct order simply by activating the representations of the digits "1" and "3" in LTM. I also review recent neuroimaging data that has been presented as evidence that STM is activated LTM and show that these data are exactly what one would expect to see based on a conventional 2-store view. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Brivaracetam augments short-term depression and slows vesicle recycling.

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Yang, Xiaofeng; Bognar, Joseph; He, Tianyu; Mohammed, Mouhari; Niespodziany, Isabelle; Wolff, Christian; Esguerra, Manuel; Rothman, Steven M; Dubinsky, Janet M

2015-12-01

Brivaracetam (BRV) decreases seizure activity in a number of epilepsy models and binds to the synaptic vesicle glycoprotein 2A (SV2A) with a higher affinity than the antiepileptic drug levetiracetam (LEV). Experiments were performed to determine if BRV acted similarly to LEV to induce or augment short-term depression (STD) under high-frequency neuronal stimulation and slow synaptic vesicle recycling. Electrophysiologic field excitatory postsynaptic potential (fEPSP) recordings were made from CA1 synapses in rat hippocampal slices loaded with BRV or LEV during intrinsic activity or with BRV actively loaded during hypertonic stimulation. STD was examined in response to 5 or 40 Hz stimulus trains. Presynaptic release of FM1-43 was visualized using two-photon microscopy to assess drug effects upon synaptic vesicle mobilization. When hippocampal slices were incubated in 0.1-30 μm BRV or 30 μm-1 mm LEV for 3 h, the relative CA1 field EPSPs decreased over the course of a high-frequency train of stimuli more than for control slices. This STD was frequency- and concentration-dependent, with BRV being 100-fold more potent than LEV. The extent of STD depended on the length of the incubation time for both drugs. Pretreatment with LEV occluded the effects of BRV. Repeated hypertonic sucrose treatments and train stimulation successfully unloaded BRV from recycling vesicles and reversed BRVs effects on STD, as previously reported for LEV. At their maximal concentrations, BRV slowed FM1-43 release to a greater extent than in slices loaded with LEV during prolonged stimulation. BRV, similar to LEV, entered into recycling synaptic vesicles and produced a frequency-dependent decrement of synaptic transmission at 100-fold lower concentrations than LEV. In addition, BRV slowed synaptic vesicle mobilization more effectively than LEV, suggesting that these drugs may modify multiple functions of the synaptic vesicle protein SV2A to curb synaptic transmission and limit epileptic activity

Long-term nonprogression and broad HIV-1-specific proliferative T-cell responses

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Nesrina eImami

2013-03-01

Full Text Available Complex mechanisms underlying the maintenance of fully functional, proliferative, HIV-1-specific T-cell responses involve processes from early T-cell development through to the final stages of T-cell differentiation and antigen recognition. Virus-specific proliferative CD4 and CD8 T-cell responses, important for the control of infection, are observed in some HIV-1+ patients during early stages of disease, and are maintained in long-term nonprogressing subjects. In the vast majority of HIV-1+ patients, full immune functionality is lost when proliferative HIV-1-specific T-cell responses undergo a variable progressive decline throughout the course of chronic infection. This appears irreparable despite administration of potent combination antiretroviral therapy, which to date is non-curative, necessitating life-long administration and the development of effective, novel, therapeutic interventions. While a sterilising cure, involving clearance of virus from the host, remains a primary aim, a functional cure may be a more feasible goal with considerable impact on worldwide HIV-1 infection. Such an approach would enable long-term co-existence of host and virus in the absence of toxic and costly drugs. Effective immune homeostasis coupled with a balanced response appropriately targeting conserved viral antigens, in a manner that avoids hyperactivation and exhaustion, may prove to be the strongest correlate of durable viral control. This review describes novel concepts underlying full immune functionality in the context of HIV-1 infection, which may be utilised in future strategies designed to improve upon existing therapy. The aim will be to induce long-term nonprogressor or elite controller status in every infected host, through immune-mediated control of viraemia and reduction of viral reservoirs, leading to lower HIV-1 transmission rates.

Self-concept and quality of object relations as predictors of outcome in short- and long-term psychotherapy.

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Lindfors, Olavi; Knekt, Paul; Heinonen, Erkki; Virtala, Esa

2014-01-01

Quality of object relations and self-concept reflect clinically relevant aspects of personality functioning, but their prediction as suitability factors for psychotherapies of different lengths has not been compared. This study compared their prediction on psychiatric symptoms and work ability in short- and long-term psychotherapy. Altogether 326 patients, 20-46 years of age, with mood and/or anxiety disorder, were randomized to short-term (solution-focused or short-term psychodynamic) psychotherapy and long-term psychodynamic psychotherapy. The Quality of Object Relations Scale (QORS) and the Structural Analysis of Social Behavior (SASB) self-concept questionnaire were measured at baseline, and their prediction on outcome during the 3-year follow-up was assessed by the Symptom Check List Global Severity Index and the Anxiety Scale, the Beck Depression Inventory and by the Work Ability Index, Social Adjustment Scale work subscale and the Perceived Psychological Functioning scale. Negative self-concept strongly and self-controlling characteristics modestly predicted better 3-year outcomes in long-term therapy, after faster early gains in short-term therapy. Patients with a more positive or self-emancipating self-concept, or more mature object relations, experienced more extensive benefits after long-term psychotherapy. The importance of length vs. long-term therapy technique on the differences found is not known. Patients with mild to moderate personality pathology, indicated by poor self-concept, seem to benefit more from long-term than short-term psychotherapy, in reducing risk of depression. Long-term therapy may also be indicated for patients with relatively good psychological functioning. More research is needed on the relative importance of these characteristics in comparison with other patient-related factors. © 2013 Published by Elsevier B.V.

Atomic structure of CaF2/MnF2-Si(1 1 1) superlattices from X-ray diffraction

International Nuclear Information System (INIS)

Alcock, Simon G.; Nicklin, C.L.; Howes, P.B.; Norris, C.A.; Kyutt, R.N.; Sokolov, N.S.; Yakovlev, N.L.

2007-01-01

X-ray reflectivity and non-specular crystal truncation rod scans have been used to determine the three-dimensional atomic structure of the buried CaF 2 -Si(1 1 1) interface and ultrathin films of MnF 2 and CaF 2 within a superlattice. We show that ultrathin films of MnF 2 , below a critical thickness of approximately four monolayers, are crystalline, pseudomorphic, and adopt the fluorite structure of CaF 2 . High temperature deposition of the CaF 2 buffer layer produces a fully reacted, CaF 2 -Si(1 1 1) type-B interface. The mature, 'long' interface is shown to consist of a partially occupied layer of CaF bonded to the Si substrate, followed by a distorted CaF layer. Our atomistic, semi-kinematical scattering method extends the slab reflectivity method by providing in-plane structural information

Carbon storage and long-term rate of accumulation in high-altitude Andean peatlands of Bolivia

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J.A. Hribljan

2015-11-01

Full Text Available (1 The high-altitude (4,500+ m Andean mountain range of north-western Bolivia contains many peatlands. Despite heavy grazing pressure and potential damage from climate change, little is known about these peatlands. Our objective was to quantify carbon pools, basal ages and long-term peat accumulation rates in peatlands in two areas of the arid puna ecoregion of Bolivia: near the village of Manasaya in the Sajama National Park (Cordillera Occidentale, and in the Tuni Condoriri National Park (Cordillera Real. (2 We cored to 5 m depth in the Manasaya peatland, whose age at 5 m was ca. 3,675 yr. BP with a LARCA of 47 g m-2 yr-1. However, probing indicated that the maximum depth was 7–10 m with a total estimated (by extrapolation carbon stock of 1,040 Mg ha-1. The Tuni peat body was 5.5 m thick and initiated ca. 2,560 cal. yr. BP. The peatland carbon stock was 572 Mg ha-1 with a long-term rate of carbon accumulation (LARCA of 37 g m-2 yr-1. (3 Despite the dry environment of the Bolivian puna, the region contains numerous peatlands with high carbon stocks and rapid carbon accumulation rates. These peatlands are heavily used for llama and alpaca grazing.

Upregulation of T-type Ca2+ channels in long-term diabetes determines increased excitability of a specific type of capsaicin-insensitive DRG neurons.

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Duzhyy, Dmytro E; Viatchenko-Karpinski, Viacheslav Y; Khomula, Eugen V; Voitenko, Nana V; Belan, Pavel V

2015-05-20

Previous studies have shown that increased excitability of capsaicin-sensitive DRG neurons and thermal hyperalgesia in rats with short-term (2-4 weeks) streptozotocin-induced diabetes is mediated by upregulation of T-type Ca(2+) current. In longer-term diabetes (after the 8th week) thermal hyperalgesia is changed to hypoalgesia that is accompanied by downregulation of T-type current in capsaicin-sensitive small-sized nociceptors. At the same time pain symptoms of diabetic neuropathy other than thermal persist in STZ-diabetic animals and patients during progression of diabetes into later stages suggesting that other types of DRG neurons may be sensitized and contribute to pain. In this study, we examined functional expression of T-type Ca(2+) channels in capsaicin-insensitive DRG neurons and excitability of these neurons in longer-term diabetic rats and in thermally hypoalgesic diabetic rats. Here we have demonstrated that in STZ-diabetes T-type current was upregulated in capsaicin-insensitive low-pH-sensitive small-sized nociceptive DRG neurons of longer-term diabetic rats and thermally hypoalgesic diabetic rats. This upregulation was not accompanied by significant changes in biophysical properties of T-type channels suggesting that a density of functionally active channels was increased. Sensitivity of T-type current to amiloride (1 mM) and low concentration of Ni(2+) (50 μM) implicates prevalence of Cav3.2 subtype of T-type channels in the capsaicin-insensitive low-pH-sensitive neurons of both naïve and diabetic rats. The upregulation of T-type channels resulted in the increased neuronal excitability of these nociceptive neurons revealed by a lower threshold for action potential initiation, prominent afterdepolarizing potentials and burst firing. Sodium current was not significantly changed in these neurons during long-term diabetes and could not contribute to the diabetes-induced increase of neuronal excitability. Capsaicin-insensitive low-pH-sensitive type

Immediate and Long-Term Mental Health Outcomes in Adolescent Female Rape Survivors.

Science.gov (United States)

Oshodi, Yewande; Macharia, Muiruri; Lachman, Anusha; Seedat, Soraya

2016-12-01

Rape is considered a stressful trauma and often has long-lasting health consequences. Compared with adult females, limited data exist on the psychological impact of rape in adolescents. The aim of this study was to assess the prevalence and associated factors of emotional distress in a cohort of adolescent rape survivors in Cape Town. Participants in this prospective longitudinal study were 31 adolescent female rape survivors recruited from a rape clinic in Cape Town and assessed within 2 weeks of the assault. Assessment measures included a sociodemographic questionnaire and initial screening with the Child and Adolescent Trauma Survey (CATS), the patient-rated Children's Depression Inventory (CDI), and the Multidimensional Anxiety Scale for Children (MASC). The CATS, CDI, and MASC were repeated at 1, 3, 6, 9, and 12 months post enrollment. Psychiatric diagnoses were made with the clinician-administered Mini International Neuropsychiatric Interview-Child and Adolescent version (MINI-Kid). At baseline, on the MINI-Kid, a definitive diagnosis of major depressive episode was endorsed in 22.6% of the participants. Stress-related disorders were found in 12.9%, whereas 16.1% had anxiety disorders. There was no diminution of symptoms on self-reported psychopathology measures at follow-up assessment over the five follow-up time points, suggesting persistent psychopathology over a 1-year period despite repeated clinical assessments and supportive counseling. Symptoms of anxiety, depression, and posttraumatic stress disorder in this sample of adolescent female rape survivors were high at enrollment and found to be persistent, underlining the need for long-term support, screening, and evidence-based follow-up care.

Persistent long-term facilitation at an identified synapse becomes labile with activation of short-term heterosynaptic plasticity.

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Hu, Jiang-Yuan; Schacher, Samuel

2014-04-02

Short-term and long-term synaptic plasticity are cellular correlates of learning and memory of different durations. Little is known, however, how these two forms of plasticity interact at the same synaptic connection. We examined the reciprocal impact of short-term heterosynaptic or homosynaptic plasticity at sensorimotor synapses of Aplysia in cell culture when expressing persistent long-term facilitation (P-LTF) evoked by serotonin [5-hydroxytryptamine (5-HT)]. Short-term heterosynaptic plasticity induced by 5-HT (facilitation) or the neuropeptide FMRFa (depression) and short-term homosynaptic plasticity induced by tetanus [post-tetanic potentiation (PTP)] or low-frequency stimulation [homosynaptic depression (HSD)] of the sensory neuron were expressed in both control synapses and synapses expressing P-LTF in the absence or presence of protein synthesis inhibitors. All forms of short-term plasticity failed to significantly affect ongoing P-LTF in the absence of protein synthesis inhibitors. However, P-LTF reversed to control levels when either 5-HT or FMRFa was applied in the presence of rapamycin. In contrast, P-LTF was unaffected when either PTP or HSD was evoked in the presence of either rapamycin or anisomycin. These results indicate that synapses expressing persistent plasticity acquire a "new" baseline and functionally express short-term changes as naive synapses, but the new baseline becomes labile following selective activations-heterosynaptic stimuli that evoke opposite forms of plasticity-such that when presented in the presence of protein synthesis inhibitors produce a rapid reversal of the persistent plasticity. Activity-selective induction of a labile state at synapses expressing persistent plasticity may facilitate the development of therapies for reversing inappropriate memories.

Long-term outcome in patients with Guillain-Barré syndrome requiring mechanical ventilation.

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Witsch, J; Galldiks, N; Bender, A; Kollmar, R; Bösel, J; Hobohm, C; Günther, A; Schirotzek, I; Fuchs, K; Jüttler, E

2013-05-01

We aimed to determine long-term disability and quality of life in patients with Guillain-Barré syndrome (GBS) who required mechanical ventilation (MV) in the acute phase. Our retrospective cohort study included 110 GBS patients admitted to an intensive care unit and requiring MV (01/1999-08/2010) in nine German tertiary academic medical centers. Outcome was determined 1 year or longer after hospital admission using the GBS disability scale, Barthel index (BI), EuroQuol-5D (EQ-5D) and Fatigue Severity Scale. Linear/multivariate regression analysis was used to analyze predicting factors for outcome. Mean time to follow up was 52.6 months. Hospital mortality was 5.5 % and long-term mortality 13.6 %. Overall 53.8 % had a favorable outcome (GBS disability score 0-1) and 73.7 % of survivors had no or mild disability (BI 90-100). In the five dimensions of the EQ-5D "mobility", "self-care", "usual activities", "pain" and "anxiety/depression" no impairments were stated by 50.6, 58.4, 36.4, 36.4 and 50.6 % of patients, respectively. A severe fatigue syndrome was present in 30.4 % of patients. Outcome was statistically significantly correlated with age, type of therapy and number of immunoglobulin courses. In GBS-patients requiring MV in the acute phase in-hospital, and long-term mortality are lower than that in previous studies, while long-term quality of life is compromised in a large fraction of patients, foremost by immobility and chronic pain. Efforts towards improved treatment approaches should address autonomic dysfunction to further reduce hospital mortality while improved rehabilitation concepts might ameliorate long-term disability.

Involvement of intracellular Zn2+ signaling in LTP at perforant pathway-CA1 pyramidal cell synapse.

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Tamano, Haruna; Nishio, Ryusuke; Takeda, Atsushi

2017-07-01

Physiological significance of synaptic Zn 2+ signaling was examined at perforant pathway-CA1 pyramidal cell synapses. In vivo long-term potentiation (LTP) at perforant pathway-CA1 pyramidal cell synapses was induced using a recording electrode attached to a microdialysis probe and the recording region was locally perfused with artificial cerebrospinal fluid (ACSF) via the microdialysis probe. Perforant pathway LTP was not attenuated under perfusion with CaEDTA (10 mM), an extracellular Zn 2+ chelator, but attenuated under perfusion with ZnAF-2DA (50 μM), an intracellular Zn 2+ chelator, suggesting that intracellular Zn 2+ signaling is required for perforant pathway LTP. Even in rat brain slices bathed in CaEDTA in ACSF, intracellular Zn 2+ level, which was measured with intracellular ZnAF-2, was increased in the stratum lacunosum-moleculare where perforant pathway-CA1 pyramidal cell synapses were contained after tetanic stimulation. These results suggest that intracellular Zn 2+ signaling, which originates in internal stores/proteins, is involved in LTP at perforant pathway-CA1 pyramidal cell synapses. Because the influx of extracellular Zn 2+ , which originates in presynaptic Zn 2+ release, is involved in LTP at Schaffer collateral-CA1 pyramidal cell synapses, synapse-dependent Zn 2+ dynamics may be involved in plasticity of postsynaptic CA1 pyramidal cells. © 2017 Wiley Periodicals, Inc.

Long lasting protein synthesis- and activity-dependent spine shrinkage and elimination after synaptic depression.

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Yazmín Ramiro-Cortés

Full Text Available Neuronal circuits modify their response to synaptic inputs in an experience-dependent fashion. Increases in synaptic weights are accompanied by structural modifications, and activity dependent, long lasting growth of dendritic spines requires new protein synthesis. When multiple spines are potentiated within a dendritic domain, they show dynamic structural plasticity changes, indicating that spines can undergo bidirectional physical modifications. However, it is unclear whether protein synthesis dependent synaptic depression leads to long lasting structural changes. Here, we investigate the structural correlates of protein synthesis dependent long-term depression (LTD mediated by metabotropic glutamate receptors (mGluRs through two-photon imaging of dendritic spines on hippocampal pyramidal neurons. We find that induction of mGluR-LTD leads to robust and long lasting spine shrinkage and elimination that lasts for up to 24 hours. These effects depend on signaling through group I mGluRs, require protein synthesis, and activity. These data reveal a mechanism for long lasting remodeling of synaptic inputs, and offer potential insights into mental retardation.

Effects of treadmill exercise intensity on spatial working memory and long-term memory in rats.

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Wang, Xiao-Qin; Wang, Gong-Wu

2016-03-15

Moderate exercise promotes learning and memory. Most studies mainly focused on memory exercise effects of in the ageing and patients. There is lack of quantitative research about effect of regular exercise intensity on different memory types in normal subjects. Present study investigated the effects of different intensities of treadmill exercise on working memory and long-term memory. Fifty female Wistar rats were trained by T-maze delayed spatial alternation (DSA) task with 3 delays (10s, 60s and 300s). Then they got a 30min treadmill exercise for 30days in 4 intensities (control, 0m/min; lower, 15m/min; middle, 20m/min, and higher, 30m/min). Then animals were tested in DSA, passive avoidance and Morris water maze tasks. 1. Exercise increased the neuronal density of hippocampal subregions (CA1, CA3 and dentate gyrus) vs. naïve/control. 2. In DSA task, all groups have similar baseline, lower intensity improved 10s delay accuracy vs. baseline/control; middle and higher intensities improved 300s delay accuracy vs. baseline/control. 3. In water maze learning, all groups successfully found the platform, but middle intensity improved platform field crossing times vs. control in test phase. Present results suggested that treadmill exercise can improve long-term spatial memory and working memory; lower intensity benefits to short-term delayed working memory, and middle or higher intensity benefits to long-term delayed working memory. There was an inverted U dose-effect relationship between exercise intensity and memory performance, but exercise -working memory effect was impacted by delay duration. Copyright © 2016 Elsevier Inc. All rights reserved.

Long-term leaching from MSWI air-pollution-control residues: Leaching characterization and modeling

DEFF Research Database (Denmark)

Hyks, Jiri; Astrup, Thomas; Christensen, Thomas Højlund

2009-01-01

Long-term leaching of Ca, Fe, Mg, K, Na, S, Al, As, Ba, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Zn, Mo, Sb, Si, Sri, Sr, Ti, V, P, Cl, and dissolved organic carbon from two different municipal solid waste incineration (MSWI) air-pollution-control residues was monitored during 24 months of column percolat......Long-term leaching of Ca, Fe, Mg, K, Na, S, Al, As, Ba, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Zn, Mo, Sb, Si, Sri, Sr, Ti, V, P, Cl, and dissolved organic carbon from two different municipal solid waste incineration (MSWI) air-pollution-control residues was monitored during 24 months of column...... percolation experiments; liquid-to-solid (L/S) ratios of 200-250 L/kg corresponding to more than 10,000 years in a conventional landfill were reached. Less than 2% of the initially present As, Cu, Pb, Zn, Cr, and Sb had leached during the Course of the experiments. Concentrations of Cd, Fe, Mg, Hg, Mn, Ni, Co......, Sn, Ti, and P were generally bellow 1 mu g/L; overall less than 1% of their mass leached. Column leaching data were further used in a two-step geochemical modeling in PHREEQC in order to (i) identify solubility controlling minerals and (ii) evaluate their interactions in a water-percolated column...

Long working hours and symptoms of anxiety and depression: a 5-year follow-up of the Whitehall II study

Science.gov (United States)

Virtanen, Marianna; Ferrie, Jane E.; Singh-Manoux, Archana; Shipley, Martin J.; Stansfeld, Stephen A.; Marmot, Michael G.; Ahola, Kirsi; Vahtera, Jussi; Kivimäki, Mika

2011-01-01

Background Although long working hours are common in working populations, little is known about the effect of long working hours on mental health. Method We examined the association between long working hours and onset of depressive and anxiety symptoms in middle-aged employees. Participants were 2960 full-time employees aged 44 to 66 (2248 men, 712 women) from the prospective Whitehall II cohort study of British civil servants. Working hours, anxiety and depressive symptoms, and covariates were measured at baseline (1997–1999) followed by two subsequent measurements of depressive and anxiety symptoms (2001 and 2002–2004). Results In prospective analysis of participants with no depressive symptoms (n=2549) or anxiety symptoms (n=2618) at baseline, Cox proportional hazard analysis adjusted for baseline covariates showed a 1.66-fold (95% CI 1.06–2.61) risk of depressive symptoms and a 1.74-fold (1.15–2.61) risk of anxiety symptoms among employees working more than 55 hours a week compared with employees working 35–40 hours a week. Sex-stratified analysis showed an excess risk of depression and anxiety associated with long working hours among women [hazard ratios 2.67 (1.07–6.68) and 2.84 (1.27–6.34)] but not men [1.30 (0.77–2.19) and 1.43 (0.89–2.30)]. Conclusions Working long hours is a risk factor for development of depressive and anxiety symptoms in women. PMID:21329557

Long working hours and symptoms of anxiety and depression: a 5-year follow-up of the Whitehall II study.

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Virtanen, M; Ferrie, J E; Singh-Manoux, A; Shipley, M J; Stansfeld, S A; Marmot, M G; Ahola, K; Vahtera, J; Kivimäki, M

2011-12-01

Although long working hours are common in working populations, little is known about the effect of long working hours on mental health. We examined the association between long working hours and the onset of depressive and anxiety symptoms in middle-aged employees. Participants were 2960 full-time employees aged 44 to 66 years (2248 men, 712 women) from the prospective Whitehall II cohort study of British civil servants. Working hours, anxiety and depressive symptoms, and covariates were measured at baseline (1997-1999) followed by two subsequent measurements of depressive and anxiety symptoms (2001 and 2002-2004). In a prospective analysis of participants with no depressive (n=2549) or anxiety symptoms (n=2618) at baseline, Cox proportional hazard analysis adjusted for baseline covariates showed a 1.66-fold [95% confidence interval (CI) 1.06-2.61] risk of depressive symptoms and a 1.74-fold (95% CI 1.15-2.61) risk of anxiety symptoms among employees working more than 55 h/week compared with employees working 35-40 h/week. Sex-stratified analysis showed an excess risk of depression and anxiety associated with long working hours among women [hazard ratios (HRs) 2.67 (95% CI 1.07-6.68) and 2.84 (95% CI 1.27-6.34) respectively] but not men [1.30 (0.77-2.19) and 1.43 (0.89-2.30)]. Working long hours is a risk factor for the development of depressive and anxiety symptoms in women.

Synaptic long-term potentiation and depression in the rat medial vestibular nuclei depend on neural activation of estrogenic and androgenic signals.

Directory of Open Access Journals (Sweden)

Mariangela Scarduzio

Full Text Available Estrogenic and androgenic steroids can be synthesised in the brain and rapidly modulate synaptic transmission and plasticity through direct interaction with membrane receptors for estrogens (ERs and androgens (ARs. We used whole cell patch clamp recordings in brainstem slices of male rats to explore the influence of ER and AR activation and local synthesis of 17β-estradiol (E2 and 5α-dihydrotestosterone (DHT on the long-term synaptic changes induced in the neurons of the medial vestibular nucleus (MVN. Long-term depression (LTD and long-term potentiation (LTP caused by different patterns of high frequency stimulation (HFS of the primary vestibular afferents were assayed under the blockade of ARs and ERs or in the presence of inhibitors for enzymes synthesizing DHT (5α-reductase and E2 (P450-aromatase from testosterone (T. We found that LTD is mediated by interaction of locally produced androgens with ARs and LTP by interaction of locally synthesized E2 with ERs. In fact, the AR block with flutamide prevented LTD while did not affect LTP, and the blockade of ERs with ICI 182,780 abolished LTP without influencing LTD. Moreover, the block of P450-aromatase with letrozole not only prevented the LTP induction, but inverted LTP into LTD. This LTD is likely due to the local activation of androgens, since it was abolished under blockade of ARs. Conversely, LTD was still induced in the presence of finasteride the inhibitor of 5α-reductase demonstrating that T is able to activate ARs and induce LTD even when DHT is not synthesized. This study demonstrates a key and opposite role of sex neurosteroids in the long-term synaptic changes of the MVN with a specific role of T-DHT for LTD and of E2 for LTP. Moreover, it suggests that different stimulation patterns can lead to LTD or LTP by specifically activating the enzymes involved in the synthesis of androgenic or estrogenic neurosteroids.

Synaptic long-term potentiation and depression in the rat medial vestibular nuclei depend on neural activation of estrogenic and androgenic signals.

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Scarduzio, Mariangela; Panichi, Roberto; Pettorossi, Vito Enrico; Grassi, Silvarosa

2013-01-01

Estrogenic and androgenic steroids can be synthesised in the brain and rapidly modulate synaptic transmission and plasticity through direct interaction with membrane receptors for estrogens (ERs) and androgens (ARs). We used whole cell patch clamp recordings in brainstem slices of male rats to explore the influence of ER and AR activation and local synthesis of 17β-estradiol (E2) and 5α-dihydrotestosterone (DHT) on the long-term synaptic changes induced in the neurons of the medial vestibular nucleus (MVN). Long-term depression (LTD) and long-term potentiation (LTP) caused by different patterns of high frequency stimulation (HFS) of the primary vestibular afferents were assayed under the blockade of ARs and ERs or in the presence of inhibitors for enzymes synthesizing DHT (5α-reductase) and E2 (P450-aromatase) from testosterone (T). We found that LTD is mediated by interaction of locally produced androgens with ARs and LTP by interaction of locally synthesized E2 with ERs. In fact, the AR block with flutamide prevented LTD while did not affect LTP, and the blockade of ERs with ICI 182,780 abolished LTP without influencing LTD. Moreover, the block of P450-aromatase with letrozole not only prevented the LTP induction, but inverted LTP into LTD. This LTD is likely due to the local activation of androgens, since it was abolished under blockade of ARs. Conversely, LTD was still induced in the presence of finasteride the inhibitor of 5α-reductase demonstrating that T is able to activate ARs and induce LTD even when DHT is not synthesized. This study demonstrates a key and opposite role of sex neurosteroids in the long-term synaptic changes of the MVN with a specific role of T-DHT for LTD and of E2 for LTP. Moreover, it suggests that different stimulation patterns can lead to LTD or LTP by specifically activating the enzymes involved in the synthesis of androgenic or estrogenic neurosteroids.

Explanatory factors for the association between depression and long-term physical disability after stroke.

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Ayerbe, Luis; Ayis, Salma A; Crichton, Siobhan; Rudd, Anthony G; Wolfe, Charles D A

2015-11-01

To identify explanatory factors for the association between depression at 3 months after stroke and physical disability at 3 years. Data from the South London Stroke Register (1998-2013) were used. Patients (n = 3,612) were assessed at stroke onset. Follow-up at 3 months included assessment for depression with the Hospital Anxiety and Depression scale (scores ≥ 7 = depression), physical disability (Barthel index) cognitive function, smoking habit, selective serotonin reuptake inhibitors (SSRIs) use, perception of recovery and social support. Physical disability was reassessed at 3 years. The associations between depression at 3 months and physical disability at 3 years were estimated with multinomial regression adjusting for age, gender, ethnicity, stroke severity and possible explanatory factors for the association (introduced in the models first individually and then sequentially): pre-stroke medical history and physical disability, cognitive function, smoking, SSRIs, perception of recovery and social support at 3 months. One thousand three hundred and seven survivors were assessed at 3 months, of which 418 (32.0%) had depression. Survivors with depression had a higher physical disability rate at 3 years. These associations remained significant after adjustment for individual explanatory factors but were not significant after adjustment for combined explanatory factors. Physical disability at 3 months was a relevant explanatory factor for this association. SSRIs were associated with severe, relative risk: 6.62 (2.92-15.02) P disability, relative risk: 3.45 (1.58-7.52) P = 0.002, at 3 years. The association between depression and physical disability appears to be multifactorial. The use of SSRIs after stroke requires further research. © The Author 2015. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Mice Overexpressing Type 1 Adenylyl Cyclase Show Enhanced Spatial Memory Flexibility in the Absence of Intact Synaptic Long-Term Depression

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Zhang, Ming; Wang, Hongbing

2013-01-01

There is significant interest in understanding the contribution of intracellular signaling and synaptic substrates to memory flexibility, which involves new learning and suppression of obsolete memory. Here, we report that enhancement of Ca[superscript 2+]-stimulated cAMP signaling by overexpressing type 1 adenylyl cyclase (AC1) facilitated…

Dispositional optimism as predictor of outcome in short- and long-term psychotherapy.

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Heinonen, Erkki; Heiskanen, Tiia; Lindfors, Olavi; Härkäpää, Kristiina; Knekt, Paul

2017-09-01

Dispositional optimism predicts various beneficial outcomes in somatic health and treatment, but has been little studied in psychotherapy. This study investigated whether an optimistic disposition differentially predicts patients' ability to benefit from short-term versus long-term psychotherapy. A total of 326 adult outpatients with mood and/or anxiety disorder were randomized into short-term (solution-focused or short-term psychodynamic) or long-term psychodynamic therapy and followed up for 3 years. Dispositional optimism was assessed by patients at baseline with the self-rated Life Orientation Test (LOT) questionnaire. Outcome was assessed at baseline and seven times during the follow-up, in terms of depressive (BDI, HDRS), anxiety (SCL-90-ANX, HARS), and general psychiatric symptoms (SCL-90-GSI), all seven follow-up points including patients' self-reports and three including interview-based measures. Lower dispositional optimism predicted faster symptom reduction in short-term than in long-term psychotherapy. Higher optimism predicted equally rapid and eventually greater benefits in long-term, as compared to short-term, psychotherapy. Weaker optimism appeared to predict sustenance of problems early in long-term therapy. Stronger optimism seems to best facilitate engaging in and benefiting from a long-term therapy process. Closer research might clarify the psychological processes responsible for these effects and help fine-tune both briefer and longer interventions to optimize treatment effectiveness for particular patients and their psychological qualities. Weaker dispositional optimism does not appear to inhibit brief therapy from effecting symptomatic recovery. Patients with weaker optimism do not seem to gain added benefits from long-term therapy, but instead may be susceptible to prolonged psychiatric symptoms in the early stages of long-term therapy. © 2016 The British Psychological Society.

Long-term impact of interferon beta-1b in patients with CIS

DEFF Research Database (Denmark)

Edan, G; Kappos, L; Montalbán, X

2014-01-01

OBJECTIVE: To examine the long-term impact of early treatment initiation of interferon beta-1b (IFNB1b, Betaferon/Betaseron) in patients with a first event suggestive of multiple sclerosis (MS). METHODS: In the original placebo-controlled phase of BENEFIT, patients were randomised to IFNB1b 250 μg...

Effects of fluoxetine on CRF and CRF1 expression in rats exposed to the learned helplessness paradigm.

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Fernández Macedo, Georgina Valeria; Cladouchos, María Laura; Sifonios, Laura; Cassanelli, Pablo Martín; Wikinski, Silvia

2013-02-01

Stress is a common antecedent reported by people suffering major depression. In these patients, extrahypothalamic brain areas, like the hippocampus and basolateral amygdala (BLA), have been found to be affected. The BLA synthesizes CRF, a mediator of the stress response, and projects to hippocampus. The main hippocampal target for this peptide is the CRF subtype 1 receptor (CRF1). Evidence points to a relationship between dysregulation of CRF/CRF1 extrahypothalamic signaling and depression. Because selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacological treatment for depression, we investigated the effect of chronic treatment with the SSRI fluoxetine on long-term changes in CRF/CRF1 signaling in animals showing a depressive-like behavior. Male Wistar rats were exposed to the learned helplessness paradigm (LH). After evaluation of behavioral impairment, the animals were treated with fluoxetine (10 mg/kg i.p.) or saline for 21 days. We measured BLA CRF expression with RT-PCR and CRF1 expression in CA3 and the dentate gyrus of the hippocampus with in situ hybridization. We also studied the activation of one of CRF1's major intracellular signaling targets, the extracellular signal-related kinases 1 and 2 (ERK1/2) in CA3. In saline-treated LH animals, CRF expression in the BLA increased, while hippocampal CRF1 expression and ERK1/2 activation decreased. Treatment with fluoxetine reversed the changes in CRF and CRF1 expressions, but not in ERK1/2 activation. In animals exposed to the learned helplessness paradigm, there are long-term changes in CRF and CRF1 expression that are restored with a behaviorally effective antidepressant treatment.

C-A4-01: Computerized Clinical Decision Support During Drug Ordering for Long-term Care Residents With Renal Insufficiency

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Field, Terry S; Rochon, Paula; Lee, Monica; Gavendo, Linda; Baril, Joann L; Gurwitz, Jerry H

2010-01-01

Objective: To determine whether a computerized clinical decision support system (CDSS) providing patient specific recommendations in real- time improves the quality of prescribing for long-term care residents with renal insufficiency. Design: A randomized trial within the long-stay units of a large long-term care facility. Randomization was within blocks by unit type. Alerts related to medication prescribing for residents with renal insufficiency were displayed to prescribers in the intervention units and hidden but tracked in control units. Measurement: The proportions of final drug orders that were appropriate were compared between intervention and control units within alert categories: recommended medication doses; recommended administration frequencies; recommendations to avoid the drug; 4) warnings of missing information. Results: The rates of alerts were nearly equal in the intervention and control units: 2.5 per 1000 resident days in the intervention units and 2.4 in the control units. The proportions of dose alerts for which the final drug orders were appropriate were similar between the intervention and control units (relative risk 0.95, 95% confidence interval 0.83, 1.1). For the remaining alert categories significantly higher proportions of final drug orders were appropriate in the intervention units: relative risk 2.4 for maximum frequency (1.4, 4.4); 2.6 for drugs that should be avoided (1.4, 5.0); and 1.8 for alerts to acquire missing information (1.1, 3.4). Overall, final drug orders were appropriate significantly more often than a relative risk 1.2 (1.0, 1.4). By tracking personnel time and expenditures, we estimated the cost of developing the CDSS as $48,668.57. Drug costs saved during the 12 months of the trial are estimated at $2,137. Conclusion: Clinical decision support for physicians prescribing medications for long-term care residents with renal insufficiency can improve the quality of prescribing decisions. However, patient well-being and

Risk factors and analysis of long-term headache in sporadic vestibular schwannoma: a multicenter cross-sectional study.

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Carlson, Matthew L; Tveiten, Øystein Vesterli; Driscoll, Colin L; Boes, Christopher J; Sullan, Molly J; Goplen, Frederik K; Lund-Johansen, Morten; Link, Michael J

2015-11-01

The primary goals of this study were: 1) to examine the influence of disease and treatment on headache in patients with sporadic vestibular schwannoma (VS); and 2) to identify clinical predictors of long-term headache disability. This was a cross-sectional observational study with international multicenter enrollment. Patients included those with primary sporadic Headache Disability Inventory (HDI), the Hospital Anxiety and Depression Scale, and a VS symptom questionnaire. The main outcome measures were univariate and multivariable associations with HDI total score. The overall survey response rate was 79%. Data from 538 patients with VS were analyzed. The mean age at time of survey was 64 years, 56% of patients were female, and the average duration between treatment and survey was 7.7 years. Twenty-seven percent of patients received microsurgery, 46% stereotactic radiosurgery, and 28% observation. Patients with VS who were managed with observation were more than twice as likely to have severe headache disability compared with 103 control subjects without VS. When accounting for baseline differences, there was no statistically significant difference in HDI outcome between treatment modalities at time of survey. Similarly, among the microsurgery cohort, the long-term risk of severe headache disability was not different between surgical approaches. Multivariable regression demonstrated that younger age, greater anxiety and depression, and a preexisting diagnosis of headache were the primary predictors of severe long-term headache disability, while tumor size and treatment modality had little influence. At a mean of almost 8 years following treatment, approximately half of patients with VS experience headaches of varying frequency and severity. Patient-driven factors including age, sex, mental health, and preexisting headache syndrome are the strongest predictors of long-term severe headache disability. Tumor size and treatment modality have less impact. These data

Enhanced AMPA receptor function promotes cerebellar long-term depression rather than potentiation

NARCIS (Netherlands)

van Beugen, Boeke J; Qiao, Xin; Simmons, Dana H; De Zeeuw, Chris I; Hansel, Christian

2014-01-01

Ampakines are allosteric modulators of AMPA receptors that facilitate hippocampal long-term potentiation (LTP) and learning, and have been considered for the treatment of cognition and memory deficits. Here, we show that the ampakine CX546 raises the amplitude and slows the decay time of excitatory

75 FR 81642 - Long-Term North to South Water Transfer Program, Sacramento County, CA

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2010-12-28

..., Sacramento County, CA AGENCY: Bureau of Reclamation, Interior. ACTION: Notice of intent to prepare an...., Chico, CA. Wednesday, January 12, 2011, 2-4 p.m., Sacramento, CA. Thursday, January 13, 2011, 6-8 p.m..., MP-410, Sacramento, CA 95825. Scoping meetings will be held at: Chico at the Chico Masonic Family...

Audit of long-term and short-term liabilities

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Korinko M.D.

2017-03-01

Full Text Available The article determines the importance of long-term and short-term liabilities for the management of financial and material resources of an enterprise. It reviews the aim, objects and information generators for realization of audit of short-term and long-term obligations. The organizing and methodical providing of audit of long-term and short-term liabilities of an enterprise are generalized. The authors distinguish the stages of realization of audit of long-term and short-term liabilities, the aim of audit on each of the presented stages, and recommend methodical techniques. It is fixed that it is necessary to conduct the estimation of the systems of internal control and record-keeping of an enterprise by implementation of public accountant procedures for determination of volume and maintenance of selection realization. After estimating the indicated systems, a public accountant determines the methodology for realization of public accountant verification of long-term and short-term liabilities. The analytical procedures that public accountants are expedient to use for realization of audit of short-term and long-term obligations are determined. The authors suggest the classification of the educed defects on the results of the conducted public accountant verification of short-term and long-term obligations.

Loss of FMRP Impaired Hippocampal Long-Term Plasticity and Spatial Learning in Rats

Directory of Open Access Journals (Sweden)

Yonglu Tian

2017-08-01

Full Text Available Fragile X syndrome (FXS is a neurodevelopmental disorder caused by mutations in the FMR1 gene that inactivate expression of the gene product, the fragile X mental retardation 1 protein (FMRP. In this study, we used clustered regularly interspaced short palindromic repeats (CRISPR/CRISPR-associated protein 9 (Cas9 technology to generate Fmr1 knockout (KO rats by disruption of the fourth exon of the Fmr1 gene. Western blotting analysis confirmed that the FMRP was absent from the brains of the Fmr1 KO rats (Fmr1exon4-KO. Electrophysiological analysis revealed that the theta-burst stimulation (TBS–induced long-term potentiation (LTP and the low-frequency stimulus (LFS–induced long-term depression (LTD were decreased in the hippocampal Schaffer collateral pathway of the Fmr1exon4-KO rats. Short-term plasticity, measured as the paired-pulse ratio, remained normal in the KO rats. The synaptic strength mediated by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR was also impaired. Consistent with previous reports, the Fmr1exon4-KO rats demonstrated an enhanced 3,5-dihydroxyphenylglycine (DHPG–induced LTD in the present study, and this enhancement is insensitive to protein translation. In addition, the Fmr1exon4-KO rats showed deficits in the probe trial in the Morris water maze test. These results demonstrate that deletion of the Fmr1 gene in rats specifically impairs long-term synaptic plasticity and hippocampus-dependent learning in a manner resembling the key symptoms of FXS. Furthermore, the Fmr1exon4-KO rats displayed impaired social interaction and macroorchidism, the results consistent with those observed in patients with FXS. Thus, Fmr1exon4-KO rats constitute a novel rat model of FXS that complements existing mouse models.

Evaluation of long-term interaction between cement and bentonite for geological disposal (1) - Project Overview

International Nuclear Information System (INIS)

Owada, Hitoshi; Hayashi, Daisuke; Yahagi, Ryoji; Ishii, Tomoko

2012-01-01

Document available in extended abstract form only. Bentonitic and cementitious materials are both planned for use as engineered barrier materials in the geological disposal of high level vitrified waste and TRU (transuranic) waste in Japan. As shown in Figure 1, bentonitic material will be placed around the waste packages as buffer material and a large amount of cementitious material is specified for use as filler, structure, support and grout. Cementitious material supplies an alkaline solution with high calcium concentration through reaction with groundwater. However, the alkaline solution will cause chemical and physical alteration of the bentonitic material. Since many important functions of an engineered barrier system (EBS), such as watertightness, chemical buffering, and sorption of radioactive nuclides, will be maintained by the properties of the buffer material, evaluation of long-term chemical or mechanical alteration of the buffer material is necessary to demonstrate the robustness of the EBS. Although many researches on chemical and mechanical alteration of bentonitic material, there was large uncertainty because the chemical alteration of bentonitic material is very slow and the altered region is very limited. In this project, the dissolution rate of montmorillonite under compaction and the spatial distribution of secondary C-S-H precipitation were obtained and mechanical and hydrological changes caused by the mineralogical change of bentonite material were modeled to reduce the uncertainty in the safety assessment of EBS performance. To improve the accuracy of the long term evaluation of the EBS performance, coupled analyses between hydraulic/mechanical calculations and geochemical-mass transport coupled calculations were performed. Alteration of mechanical properties caused by chemical degradation should be modeled for the coupled calculations. Because the mechanical properties of bentonitic material depend strongly on the montmorillonite content and

Gating of Long-Term Potentiation by Nicotinic Acetylcholine Receptors at the Cerebellum Input Stage

NARCIS (Netherlands)

F. Prestori (Francesca); C. Bonardi (Claudia); L. Mapelli (Lisa); P. Lombardo (Paola); R. Goselink (Rianne); M.E. de Stefano (Maria Egle); D. Gandolfi (Daniela); J. Mapelli (Jonathan); D. Bertrand (Daniel); M. Schonewille (Martijn); C.I. de Zeeuw (Chris); E. D'Angelo (Egidio)

2013-01-01

textabstractThe brain needs mechanisms able to correlate plastic changes with local circuit activity and internal functional states. At the cerebellum input stage, uncontrolled induction of long-term potentiation or depression (LTP or LTD) between mossy fibres and granule cells can saturate synaptic

Short- and long-term antidepressant effects of ketamine in a rat chronic unpredictable stress model.

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Jiang, Yinghong; Wang, Yiqiang; Sun, Xiaoran; Lian, Bo; Sun, Hongwei; Wang, Gang; Du, Zhongde; Li, Qi; Sun, Lin

2017-08-01

This research was aimed to evaluate the behaviors of short- or long-term antidepressant effects of ketamine in rats exposed to chronic unpredictable stress (CUS). Ketamine, a glutamate noncompetitive NMDA receptor antagonist, regulates excitatory amino acid functions, such as anxiety disorders and major depression, and plays an important role in synaptic plasticity and learning and memory. After 42 days of CUS model, male rats received either a single injection of ketamine (10 mg/kg; day 43) or 15 daily injections (days 43-75). The influence of ketamine on behavioral reactivity was assessed 24 hr (short-term) or 7 weeks after ketamine treatment (long-term). Behavioral tests used to assess the effects of these treatments included the sucrose preference (SP), open field (OF), elevated plus maze (EPM), forced swimming (FS), and water maze (WM) to detect anxiety-like behavior (OF and EPM), forced swimming (FS), and water maze (WM). Results: Short-term ketamine administration resulted in increases of body weight gain, higher sensitivity to sucrose, augmented locomotor activity in the OF, more entries into the open arms of the EPM, along increased activity in the FS test; all responses indicative of reductions in depression/despair in anxiety-eliciting situations. No significant differences in these behaviors were obtained under conditions of long-term ketamine administration ( p  > .05). The CUS + Ketamine group showed significantly increased activity as compared with the CUS + Vehicle group for analysis of the long-term effects of ketamine (* p   .05). Taken together these findings demonstrate that a short-term administration of ketamine induced rapid antidepressant-like effects in adult male rats exposed to CUS conditions, effects that were not observed in response to the long-term treatment regime.

Prevalence of Long-Term Opioid Use in Long-Stay Nursing Home Residents.

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Hunnicutt, Jacob N; Chrysanthopoulou, Stavroula A; Ulbricht, Christine M; Hume, Anne L; Tjia, Jennifer; Lapane, Kate L

2018-01-01

Overall and long-term opioid use among older adults have increased since 1999. Less is known about opioid use in older adults in nursing homes (NHs). Cross-sectional. U.S. NHs (N = 13,522). Long-stay NH resident Medicare beneficiaries with a Minimum Data Set 3.0 (MDS) assessment between April 1, 2012, and June 30, 2012, and 120 days of follow-up (N = 315,949). We used Medicare Part D claims to measure length of opioid use in the 120 days from the index assessment (short-term: ≤30 days, medium-term: >30-89 days, long-term: ≥90 days), adjuvants (e.g., anticonvulsants), and other pain medications (e.g., corticosteroids). MDS assessments in the follow-up period were used to measure nonpharmacological pain management use. Modified Poisson models were used to estimate adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) for age, gender, race and ethnicity, cognitive and physical impairment, and long-term opioid use. Of all long-stay residents, 32.4% were prescribed any opioid, and 15.5% were prescribed opioids long-term. Opioid users (versus nonusers) were more commonly prescribed pain adjuvants (32.9% vs 14.9%), other pain medications (25.5% vs 11.0%), and nonpharmacological pain management (24.5% vs 9.3%). Long-term opioid use was higher in women (aPR = 1.21, 95% CI = 1.18-1.23) and lower in racial and ethnic minorities (non-Hispanic blacks vs whites: APR = 0.93, 95% CI = 0.90-0.94) and those with severe cognitive impairment (vs no or mild impairment, aPR = 0.82, 95% CI = 0.79-0.83). One in seven NH residents was prescribed opioids long-term. Recent guidelines on opioid prescribing for pain recommend reducing long-term opioid use, but this is challenging in NHs because residents may not benefit from nonpharmacological and nonopioid interventions. Studies to address concerns about opioid safety and effectiveness (e.g., on pain and functional status) in NHs are needed. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics

Duration of unemployment and depression: a cross-sectional survey in Lithuania

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Starkuviene Skirmante

2006-07-01

Full Text Available Abstract Background In spite of a growing economy, unemployment is still a severe socio-economic problem in Lithuania. Nonetheless, no studies have been performed about the associations between unemployment and mental health in Lithuania. The aim of this study was to evaluate the associations between unemployment duration and depression in Lithuania. Methods The data was collected in a cross-sectional study in 2005. There were 429 filled-in questionnaires received (53.6% response rate from unemployed persons registered with the Kaunas Labour Market Office. The severity of depression symptoms was evaluated using the Beck Depression Inventory (BDI. Logistic regression was used to estimate the risk factors for occurrence of depression. Sex, age, place of residence, marital status, education, income and practiced religion were the independent variables. Long-term unemployment was defined as lasting a duration of 12 months or more. Results The findings showed that long-term unemployed persons had more episodes of a depressive mood in the past 12 months in comparison with the group of the short-term unemployed. In addition, the BDI score mean was higher among the long-term unemployed compared with the short-term unemployed (10.1 ± 8.8 and 14.2 ± 9.5 respectively, p Conclusion The results indicated that depression is a severe problem in the unemployed population. Depression is more elevated among the long-term unemployed. This leads to arguing for common efforts in providing needed social support and health care to reduce the effects of unemployment on mental health.

Long-term outcome in 324 polytrauma patients: what factors are associated with posttraumatic stress disorder and depressive disorder symptoms?

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Falkenberg, Lisa; Zeckey, Christian; Mommsen, Philipp; Winkelmann, Marcel; Zelle, Boris A; Panzica, Martin; Pape, Hans-Christoph; Krettek, Christian; Probst, Christian

2017-10-30

Physical impairment is well-known to last for many years after a severe injury, and there is a high impact on the quality of the survivor's life. The purpose of this study was to examine if this is also true for psychological impairment with symptoms of posttraumatic stress disorder or depression after polytrauma. Retrospective cohort outcome study. Level I trauma centre. 637 polytrauma trauma patients who were treated at our Level I trauma centre between 1973 and 1990. Minimum follow-up was 10 years after the injury. Patients were asked to fill in a questionnaire, including parts of the Posttraumatic Stress Diagnostic Scale, the Impact of Event Scale-Revised and the German Hospital Anxiety and Depression Scale, to evaluate mental health. Clinical outcome was assessed before by standardised scores. Three hundred and twenty-four questionnaires were evaluated. One hundred and forty-nine (45.9%) patients presented with symptoms of mental impairment. Quality of life was significantly higher in the mentally healthy group, while the impaired group achieved a lower rehabilitation status. Mental impairment can be found in multiple trauma victims, even after 10 years or more. Treating physicians should not only focus on early physical rehabilitation but also focus on early mental rehabilitation to prevent long-term problems in both physical and mental disability.

Estradiol attenuates ischemia-induced death of hippocampal neurons and enhances synaptic transmission in aged, long-term hormone-deprived female rats.

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Tomoko Inagaki

Full Text Available Transient global forebrain ischemia causes selective, delayed death of hippocampal CA1 pyramidal neurons, and the ovarian hormone 17β-estradiol (E2 reduces neuronal loss in young and middle-aged females. The neuroprotective efficacy of E2 after a prolonged period of hormone deprivation is controversial, and few studies examine this issue in aged animals given E2 treatment after induction of ischemia.The present study investigated the neuroprotective effects of E2 administered immediately after global ischemia in aged female rats (15-18 months after 6 months of hormone deprivation. We also used electrophysiological methods to assess whether CA1 synapses in the aging hippocampus remain responsive to E2 after prolonged hormone withdrawal. Animals were ovariohysterectomized and underwent 10 min global ischemia 6 months later. A single dose of E2 (2.25 µg infused intraventricularly after reperfusion significantly increased cell survival, with 45% of CA1 neurons surviving vs 15% in controls. Ischemia also induced moderate loss of CA3/CA4 pyramidal cells. Bath application of 1 nM E2 onto brain slices derived from non-ischemic aged females after 6 months of hormone withdrawal significantly enhanced excitatory transmission at CA1 synapses evoked by Schaffer collateral stimulation, and normal long-term potentiation (LTP was induced. The magnitude of LTP and of E2 enhancement of field excitatory postsynaptic potentials was indistinguishable from that recorded in slices from young rats.The data demonstrate that 1 acute post-ischemic infusion of E2 into the brain ventricles is neuroprotective in aged rats after 6 months of hormone deprivation; and 2 E2 enhances synaptic transmission in CA1 pyramidal neurons of aged long-term hormone deprived females. These findings provide evidence that the aging hippocampus remains responsive to E2 administered either in vivo or in vitro even after prolonged periods of hormone withdrawal.

What contributes to long-term quality of life in breast cancer patients who are undergoing surgery? Results of a multidimensional study.

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Wittmann, Victoria; Látos, Melinda; Horváth, Zoltán; Simonka, Zsolt; Paszt, Attila; Lázár, György; Csabai, Márta

2017-08-01

This study aims to examine the key determinants of long-term quality of life in breast cancer patients who are undergoing surgery using a multidimensional approach and taking into account preoperative and post-operative psychological characteristics such as anxiety, depression, posttraumatic growth, body image, and physical activity as well as medical parameters. The study involved 63 breast cancer patients from the Department of Surgery at the University of Szeged. Assessments occurred 1 day before surgery as well as 3 days and 18 months after surgery using the Spielberger State and Trait Anxiety Inventory (STAI), Beck's Depression Inventory (BDI), Functional Assessment of Cancer Therapy-Breast Cancer Scale (FACT-B), Posttraumatic Growth Inventory (PTGI) and Breast Impact of Treatment Scale (BITS). Data relating to physical activity, medical parameters and sociodemographic characteristics were also collected. The level of depression did not change over time. State anxiety decreased 18 months after the surgery compared to before the surgery; however, there was a greater decrease immediately after the surgery and then anxiety increased again 18 months later. Trait anxiety was associated with quality of life, posttraumatic growth and body image. Posttraumatic growth and the level of depression were found to be possible contributing factors to the increase in long-term quality of life. The results show that the timely detection and proper management of psychological distress and the enhancement of posttraumatic growth are of great value, as they might be important contributing factors to long-term quality of life in breast cancer patients.

Long-term breast-feeding in women with type 1 diabetes

DEFF Research Database (Denmark)

Stage, E; Nørgård, Hanne; Damm, Peter

2006-01-01

Breast-feeding may be more difficult in women with diabetes because of neonatal morbidity and fluctuating maternal blood glucose values. The frequency of long-term breast-feeding and the possible predictors for successful breast-feeding were investigated.......Breast-feeding may be more difficult in women with diabetes because of neonatal morbidity and fluctuating maternal blood glucose values. The frequency of long-term breast-feeding and the possible predictors for successful breast-feeding were investigated....

Persistent inhibition of hippocampal long-term potentiation in vivo by learned helplessness stress.

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Ryan, Benedict K; Vollmayr, Barbara; Klyubin, Igor; Gass, Peter; Rowan, Michael J

2010-06-01

The persistent cognitive disruptive effects of stress have been strongly implicated in the pathophysiology of depression and post-traumatic stress disorder. Here we examined factors influencing the time course of recovery from the inhibitory effect of acute inescapable stressors on the ability to induce long-term potentiation (LTP) in the dorsal hippocampus in vivo. We tested different forms of LTP, different stressors and different inbred strains of rats. Acute elevated platform stress completely, but transiently (learned helplessness, inhibited LTP for at least 4 weeks. Contrary to expectations, there was no clear relationship between the ability of the footshock to trigger helpless behavior, a model of stress-induced depression, and the magnitude of LTP inhibition. Moreover, LTP did not appear to be affected by genetic susceptibility to learned helplessness, a model of genetic vulnerability to depression. This long-lasting synaptic plasticity disruption may underlie persistent impairment of hippocampus-dependent cognition by excessive acute inescapable stress.

Long term variability of HDE 226868 = Cygnus X-1

International Nuclear Information System (INIS)

Liller, W.

1976-01-01

Investigation of blue-sensitive photographs of HDE 226868 = Cygnus X-1 reveal no (+-0.06 mag) long-term changes in brightness since the beginning of the century nor any abrupt intensity changes similar to what has been observed at x-ray and radio frequencies. From the double sinusoidal fluctuation with 5.6 day period, an attempt is made to derive a more precise value for the orbital period, but problems are encountered and discussed. There exists evidence that the amplitude of the orbital fluctuations is increasing slowly with time

Oral administration of fisetin promotes the induction of hippocampal long-term potentiation in vivo

OpenAIRE

Wen-bin He; Kazuho Abe; Tatsuhiro Akaishi

2018-01-01

To explore memory enhancing effect of the flavonoid fisetin, we investigated the effect of oral administration of flavonoids on the induction of long-term potentiation (LTP) at hippocampal CA1 synapses of anesthetized rats. Among four flavonoids (fisetin, quercetin, luteolin and myricetin) tested, only fisetin significantly facilitated the induction of hippocampal LTP. The effect of oral fisetin was abolished by intracerebroventricular injection of U0126, an agent that was previously found to...

Long-term follow-up study and long-term care of childhood cancer survivors

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Hyeon Jin Park

2010-04-01

Full Text Available The number of long-term survivors is increasing in the western countries due to remarkable improvements in the treatment of childhood cancer. The long-term complications of childhood cancer survivors in these countries were brought to light by the childhood cancer survivor studies. In Korea, the 5-year survival rate of childhood cancer patients is approaching 70%; therefore, it is extremely important to undertake similar long-term follow-up studies and comprehensive long-term care for our population. On the basis of the experiences of childhood cancer survivorship care of the western countries and the current Korean status of childhood cancer survivors, long-term follow-up study and long-term care systems need to be established in Korea in the near future. This system might contribute to the improvement of the quality of life of childhood cancer survivors through effective intervention strategies.

The effect of long-term acidifying feeding on digesta organic acids, mineral balance, and bone mineralization in growing pigs

DEFF Research Database (Denmark)

Nørgaard, Jan Værum; Højberg, Ole; Sørensen, Kristina Ulrich

2014-01-01

Acidification of slurry through dietary manipulation of urinary pH is a means of mitigating nitrogen emission from pig production, but long-term effects of diet acidification on bone mineralization and mineral balance is less investigated. The objective was therefore to study the long-term effects...... of feeding benzoic acid (BA) and calcium chloride (CaCl2) on the mineral balance and microbial activity in the gastrointestinal tract of pigs. Four diets containing the combinations of 0 or 10 g/kg BA and 0 or 20 g/kg CaCl2 were fed to 24 pigs in a factorial design. For the diets without CaCl2, calcium...... carbonate (CaCO3) was added to provide equimolar levels of Ca. The pigs were fed the diets from 36 kg until slaughter at 113 kg BW, and they were housed in balance cages for 12 d from 60 to 66 kg BW. Supplementation of BA and/or CaCl2 had only minor effect on accumulation of digesta organic acids (acetate...

Hippocampal long term memory: effect of the cholinergic system on local protein synthesis.

Science.gov (United States)

Lana, Daniele; Cerbai, Francesca; Di Russo, Jacopo; Boscaro, Francesca; Giannetti, Ambra; Petkova-Kirova, Polina; Pugliese, Anna Maria; Giovannini, Maria Grazia

2013-11-01

The present study was aimed at establishing a link between the cholinergic system and the pathway of mTOR and its downstream effector p70S6K, likely actors in long term memory encoding. We performed in vivo behavioral experiments using the step down inhibitory avoidance test (IA) in adult Wistar rats to evaluate memory formation under different conditions, and immunohistochemistry on hippocampal slices to evaluate the level and the time-course of mTOR and p70S6K activation. We also examined the effect of RAPA, inhibitor of mTORC1 formation, and of the acetylcholine (ACh) muscarinic receptor antagonist scopolamine (SCOP) or ACh nicotinic receptor antagonist mecamylamine (MECA) on short and long term memory formation and on the functionality of the mTOR pathway. Acquisition test was performed 30 min after i.c.v. injection of RAPA, a time sufficient for the drug to diffuse to CA1 pyramidal neurons, as demonstrated by MALDI-TOF-TOF imaging. Recall test was performed 1 h, 4 h or 24 h after acquisition. To confirm our results we performed in vitro experiments on live hippocampal slices: we evaluated whether stimulation of the cholinergic system with the cholinergic receptor agonist carbachol (CCh) activated the mTOR pathway and whether the administration of the above-mentioned antagonists together with CCh could revert this activation. We found that (1) mTOR and p70S6K activation in the hippocampus were involved in long term memory formation; (2) RAPA administration caused inhibition of mTOR activation at 1 h and 4 h and of p70S6K activation at 4 h, and long term memory impairment at 24 h after acquisition; (3) scopolamine treatment caused short but not long term memory impairment with an early increase of mTOR/p70S6K activation at 1 h followed by stabilization at longer times; (4) mecamylamine plus scopolamine treatment caused short term memory impairment at 1 h and 4 h and reduced the scopolamine-induced increase of mTOR/p70S6K activation at 1 h and 4 h; (5

Remaining authorized gas exports under long-term licences as of 1 November 1995

International Nuclear Information System (INIS)

1995-01-01

A statistical base of information on natural gas exports authorized under long-term licences to markets in the U.S. as of November 1, 1995, was provided. The first part of the report focused on the total licensed exports to the U.S. while the second part provided a breakdown of the licensed export volumes by U.S. market regions. The National Energy Board Act empowers the National Energy Board to issue licences and orders for the export of natural gas from Canada. Licences are issued for long-term periods (over 2 years) and orders for short-term periods (2 years or less). Each individual export licence contains terms and conditions including the duration of the licence, the point of export where the gas may leave Canada, and the maximum allowable volumes that may be exported daily, annually, and throughout the term of the licence. 17 figs

Long-term dentin remineralization by poly(amido amine) and rechargeable calcium phosphate nanocomposite after fluid challenges.

Science.gov (United States)

Liang, Kunneng; Xiao, Shimeng; Wu, Junling; Li, Jiyao; Weir, Michael D; Cheng, Lei; Reynolds, Mark A; Zhou, Xuedong; Xu, Hockin H K

2018-04-01

Previous studies investigated short-term dentin remineralization; studies on long-term dentin remineralization after fluid challenges mimicking fluids in oral environment are lacking. The objective of this study was to develop a long-term remineralization method to via poly(amido amine) (PAMAM) and rechargeable composite containing nanoparticles of amorphous calcium phosphate (NACP) after fluid challenges for the first time. NACP composite was immersed at pH 4 to exhaust its calcium (Ca) and phosphate (P) ions, and then recharged with Ca and P ions, to test the remineralization of the exhausted and recharged NACP composite. Dentin was acid-etched with 37% phosphoric acid. Four groups were prepared: (1) dentin control, (2) dentin with PAMAM, (3) dentin with the recharged NACP composite, and (4) dentin with PAMAM plus recharged NACP composite. PAMAM-coated dentin was immersed in phosphate-buffered saline with shaking for 72 days, because there is fluid flow in the mouth which could potentially detach the PAMAM from dentin. Specimens were treated with a cyclic artificial saliva/lactic acid regimen for 35 days. After 72days of immersion plus shaking, the PAMAM still successfully fulfilled its mineralization nucleation. The recharged NACP composite still provided acid-neutralization and ion re-release, which did not decrease with increasing the number of recharge cycles. The immersed-PAMAM plus NACP achieved complete dentin remineralization and restored the hardness to that of healthy dentin. In conclusion, superior long-term remineralization of the PAMAM plus NACP method was demonstrated for the first time. The immersed-PAMAM plus recharged NACP completely remineralized the pre-demineralized dentin, even after prolonged fluid-challenge similar to that in oral environment. The novel PAMAM plus NACP composite method is promising to provide long-term tooth protection and caries inhibition. Copyright © 2018 The Academy of Dental Materials. Published by Elsevier Ltd. All

Association between interpersonal trust, reciprocity, and depression in South Korea: a prospective analysis.

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Seung-Sup Kim

Full Text Available BACKGROUND: A growing body of empirical evidence indicates that low-level social capital is related to poor mental health outcomes. However, the prospective association between social capital and depression remains unclear, and no published studies have investigated the association with longitudinal data in East-Asian countries. METHODS: We analyzed data from the ongoing Korean Welfare Panel Study to prospectively investigate association between social capital and depression. Social capital was measured at the individual level by two items specific to interpersonal trust and reciprocity. Depression was annually assessed as a dichotomous variable using the Center for Epidemiologic Studies Depression Scale. After excluding participants who had depression in 2006, logistic regression models were applied to estimate the association between each social capital indicator and new-onset depression developed in 2007 or long-term depression in both 2007 and 2008. We also examined the association in a subpopulation restricted to healthy participants after excluding individuals with any pre-existing disability, chronic disease, or poor self-rated health condition. RESULTS: Compared to the high interpersonal trust group, the odds ratios of developing new-onset and long-term depression among the low interpersonal trust group were 1.22 (95% CI: 1.08∼1.38 and 1.23 (95% CI: 1.03∼1.50, respectively, and increased to 1.32 (95% CI: 1.10∼1.57 and 1.47 (95% CI: 1.05∼2.08 in the subpopulation analyses restricted to healthy individuals. Although the low and intermediate reciprocity group also had significantly higher odds of developing new-onset depression compared to the high reciprocity group, the effects were attenuated and statistically non-significant in the subpopulation analyses. CONCLUSION: Low interpersonal trust appears to be an independent risk factor for new-onset and long-term depression in South Korea.

Symptoms of Eating Disorders and Depression in Emerging Adults with Early-Onset, Long-Duration Type 1 Diabetes and Their Association with Metabolic Control.

Science.gov (United States)

Bächle, Christina; Lange, Karin; Stahl-Pehe, Anna; Castillo, Katty; Scheuing, Nicole; Holl, Reinhard W; Giani, Guido; Rosenbauer, Joachim

2015-01-01

This study analyzed the prevalence of and association between symptoms of eating disorders and depression in female and male emerging adults with early-onset, long-duration type 1 diabetes and investigated how these symptoms are associated with metabolic control. In a nationwide population-based survey, 211 type 1 diabetes patients aged 18-21 years completed standardized questionnaires, including the SCOFF questionnaire for eating disorder symptoms and the Patient Health Questionnaire (PHQ-9) for symptoms of depression and severity of depressive symptoms (PHQ-9 score). Multiple linear and logistic regression models were used to analyze the association between eating disorder and depressive symptoms and their associations with HbA1c. A total of 30.2% of the women and 9.5% of the men were screening positive for eating disorders. The mean PHQ-9 score (standard deviation) was 5.3 (4.4) among women and 3.9 (3.6) among men. Screening positive for an eating disorder was associated with more severe depressive symptoms among women (βwomen 3.8, peating disorder symptoms nor severity of depressive symptoms were associated with HbA1c among women, while HbA1c increased with the severity of depressive symptoms among men (βmen 0.14, p=0.006). Because of the high prevalence of eating disorder and depressive symptoms, their interrelationship, and their associations with metabolic control, particularly among men, regular mental health screening is recommended for young adults with type 1 diabetes.

Alteration in certain enzymological parameters of an Indian major carp, Cirrhinus mrigala exposed to short- and long-term exposure of clofibric acid and diclofenac.

Science.gov (United States)

Saravanan, Manoharan; Ramesh, Mathan; Petkam, Rakpong

2013-12-01

The extensive use of pharmaceuticals in human and veterinary medicine may enter the aquatic environment and pose a serious threat to non-target aquatic organisms like fish. In this study, Indian major carp Cirrhinus mrigala was exposed to different concentrations (1, 10 and 100 μg L⁻¹) of most commonly used pharmaceutical drugs clofibric acid (CA) and diclofenac (DCF) to evaluate its impacts on certain enzymological parameters during short- and long-term exposures. During short-term (96 h) exposure period, plasma glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and gill Na⁺/K⁺-ATPase activity were significantly altered at all concentrations of both the CA- and DCF-treated fish. In long-term exposure (35 days), gill Na⁺/K⁺-ATPase activity was found to be significantly increased at all concentration of CA and DCF exposures throughout the study period (except at the end of 7th day in 10 and 100 µg L⁻¹) . However, a biphasic trend was observed in plasma GOT and GPT activity when compared to the control groups. In both short- and long-term exposure, a significant (P < 0.01 and P < 0.05) changes were observed in all enzymological parameters of fish C. mrigala exposed to different concentrations of CA and DCF. The alterations of these enzymological parameters can be effectively used as potential biomarkers in monitoring of pharmaceutical toxicity in aquatic environment and organisms.

Long-term physical and psychological effects of the Vajont disaster

OpenAIRE

Zaetta, Cristina; Santonastaso, Paolo; Favaro, Angela

2011-01-01

Background: Few studies to date investigated the long-term consequences of disasters on physical health. Objective: The aim of the present report was to study the consequence on physical health of exposure to the Vajont disaster after 40 years. We also explored the effects of severity of trauma, posttraumatic stress disorder (PTSD), and major depression disorder on physical health and health-related quality of life. Method: Sixty survivors of the Vajont disaster and 48 control subjects of sim...

Surface coal mine land reclamation using a dry flue gas desulfurization product: Short-term and long-term water responses.

Science.gov (United States)

Chen, Liming; Stehouwer, Richard; Tong, Xiaogang; Kost, Dave; Bigham, Jerry M; Dick, Warren A

2015-09-01

Abandoned coal-mined lands are a worldwide concern due to their potential negative environmental impacts, including erosion and development of acid mine drainage. A field study investigated the use of a dry flue gas desulfurization product for reclamation of abandoned coal mined land in USA. Treatments included flue gas desulfurization product at a rate of 280 Mg ha(-1) (FGD), FGD at the same rate plus 112 Mg ha(-1) yard waste compost (FGD/C), and conventional reclamation that included 20 cm of re-soil material plus 157 Mg ha(-1) of agricultural limestone (SOIL). A grass-legume sward was planted after treatment applications. Chemical properties of surface runoff and tile water (collected from a depth of 1.2m below the ground surface) were measured over both short-term (1-4 yr) and long-term (14-20 yr) periods following reclamation. The pH of surface runoff water was increased from approximately 3, and then sustained at 7 or higher by all treatments for up to 20 yr, and the pH of tile flow water was also increased and sustained above 5 for 20 yr. Compared with SOIL, concentrations of Ca, S and B in surface runoff and tile flow water were generally increased by the treatments with FGD product in both short- and long-term measurements and concentrations of the trace elements were generally not statistically increased in surface runoff and tile flow water over the 20-yr period. However, concentrations of As, Ba, Cr and Hg were occasionally elevated. These results suggest the use of FGD product for remediating acidic surface coal mined sites can provide effective, long-term reclamation. Copyright © 2015. Published by Elsevier Ltd.

Transient increase in Zn2+ in hippocampal CA1 pyramidal neurons causes reversible memory deficit.

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Atsushi Takeda

Full Text Available The translocation of synaptic Zn(2+ to the cytosolic compartment has been studied to understand Zn(2+ neurotoxicity in neurological diseases. However, it is unknown whether the moderate increase in Zn(2+ in the cytosolic compartment affects memory processing in the hippocampus. In the present study, the moderate increase in cytosolic Zn(2+ in the hippocampus was induced with clioquinol (CQ, a zinc ionophore. Zn(2+ delivery by Zn-CQ transiently attenuated CA1 long-term potentiation (LTP in hippocampal slices prepared 2 h after i.p. injection of Zn-CQ into rats, when intracellular Zn(2+ levels was transiently increased in the CA1 pyramidal cell layer, followed by object recognition memory deficit. Object recognition memory was transiently impaired 30 min after injection of ZnCl(2 into the CA1, but not after injection into the dentate gyrus that did not significantly increase intracellular Zn(2+ in the granule cell layer of the dentate gyrus. Object recognition memory deficit may be linked to the preferential increase in Zn(2+ and/or the preferential vulnerability to Zn(2+ in CA1 pyramidal neurons. In the case of the cytosolic increase in endogenous Zn(2+ in the CA1 induced by 100 mM KCl, furthermore, object recognition memory was also transiently impaired, while ameliorated by co-injection of CaEDTA to block the increase in cytosolic Zn(2+. The present study indicates that the transient increase in cytosolic Zn(2+ in CA1 pyramidal neurons reversibly impairs object recognition memory.

Transient increase in Zn2+ in hippocampal CA1 pyramidal neurons causes reversible memory deficit.

Science.gov (United States)

Takeda, Atsushi; Takada, Shunsuke; Nakamura, Masatoshi; Suzuki, Miki; Tamano, Haruna; Ando, Masaki; Oku, Naoto

2011-01-01

The translocation of synaptic Zn(2+) to the cytosolic compartment has been studied to understand Zn(2+) neurotoxicity in neurological diseases. However, it is unknown whether the moderate increase in Zn(2+) in the cytosolic compartment affects memory processing in the hippocampus. In the present study, the moderate increase in cytosolic Zn(2+) in the hippocampus was induced with clioquinol (CQ), a zinc ionophore. Zn(2+) delivery by Zn-CQ transiently attenuated CA1 long-term potentiation (LTP) in hippocampal slices prepared 2 h after i.p. injection of Zn-CQ into rats, when intracellular Zn(2+) levels was transiently increased in the CA1 pyramidal cell layer, followed by object recognition memory deficit. Object recognition memory was transiently impaired 30 min after injection of ZnCl(2) into the CA1, but not after injection into the dentate gyrus that did not significantly increase intracellular Zn(2+) in the granule cell layer of the dentate gyrus. Object recognition memory deficit may be linked to the preferential increase in Zn(2+) and/or the preferential vulnerability to Zn(2+) in CA1 pyramidal neurons. In the case of the cytosolic increase in endogenous Zn(2+) in the CA1 induced by 100 mM KCl, furthermore, object recognition memory was also transiently impaired, while ameliorated by co-injection of CaEDTA to block the increase in cytosolic Zn(2+). The present study indicates that the transient increase in cytosolic Zn(2+) in CA1 pyramidal neurons reversibly impairs object recognition memory.

Enhanced long-term and impaired short-term spatial memory in GluA1 AMPA receptor subunit knockout mice: evidence for a dual-process memory model.

Science.gov (United States)

Sanderson, David J; Good, Mark A; Skelton, Kathryn; Sprengel, Rolf; Seeburg, Peter H; Rawlins, J Nicholas P; Bannerman, David M

2009-06-01

The GluA1 AMPA receptor subunit is a key mediator of hippocampal synaptic plasticity and is especially important for a rapidly-induced, short-lasting form of potentiation. GluA1 gene deletion impairs hippocampus-dependent, spatial working memory, but spares hippocampus-dependent spatial reference memory. These findings may reflect the necessity of GluA1-dependent synaptic plasticity for short-term memory of recently visited places, but not for the ability to form long-term associations between a particular spatial location and an outcome. This hypothesis is in concordance with the theory that short-term and long-term memory depend on dissociable psychological processes. In this study we tested GluA1-/- mice on both short-term and long-term spatial memory using a simple novelty preference task. Mice were given a series of repeated exposures to a particular spatial location (the arm of a Y-maze) before their preference for a novel spatial location (the unvisited arm of the maze) over the familiar spatial location was assessed. GluA1-/- mice were impaired if the interval between the trials was short (1 min), but showed enhanced spatial memory if the interval between the trials was long (24 h). This enhancement was caused by the interval between the exposure trials rather than the interval prior to the test, thus demonstrating enhanced learning and not simply enhanced performance or expression of memory. This seemingly paradoxical enhancement of hippocampus-dependent spatial learning may be caused by GluA1 gene deletion reducing the detrimental effects of short-term memory on subsequent long-term learning. Thus, these results support a dual-process model of memory in which short-term and long-term memory are separate and sometimes competitive processes.

Characteristics associated with the use of complementary health approaches among long-term cancer survivors.

Science.gov (United States)

Sohl, Stephanie J; Weaver, Kathryn E; Birdee, Gurjeet; Kent, Erin E; Danhauer, Suzanne C; Hamilton, Ann S

2014-04-01

This study aims to identify the prevalence and characteristics of long-term adult cancer survivors who use complementary health approaches (CHA). Participants completed the Follow-up Care Use Among Survivors (FOCUS) Survey, a cross-sectional investigation of long-term cancer survivors. The use of CHA and reasons for use were assessed. A multivariable logistic regression model was applied to identify if predisposing, enabling, and need characteristics described in the Complementary and Alternative Medicine Healthcare Model were associated with CHA use in the past year. Long-term cancer survivors in the study (N = 1,666) were predominately female (62%) and older (mean age = 69.5), with breast, prostate, colorectal, ovarian, and endometrial cancers. Thirty-three percent of survivors used CHA in the past year. Common reasons for CHA use were to relieve stress (28%), treat or prevent cancer (21%), relieve cancer-related symptoms (18%), and deal with another condition (18%). Predisposing (i.e., higher optimism) and need factors (i.e., experienced cancer-related symptoms, ever had depression/anxiety) were significantly associated with CHA (p-values financial resources) were not. Cancer survivors continue to report a high prevalence of recent CHA use more than 5 years after initial diagnosis. Healthcare providers should be aware of increased use of CHA among subgroups of long-term cancer survivors in order to guide safe and optimal use.

The Long-term Effects of Self-Esteem on Depression: The Roles of Alcohol and Substance Uses during Young Adulthood1

Science.gov (United States)

Park, Kiwoong; Yang, Tse-Chuan

2017-01-01

Using the National Longitudinal Surveys of Youth 1979, this study examines the roles of alcohol and substance use as mediators in the mechanism between self-esteem and depression, and investigates whether the mechanism works for both men and women. Results demonstrate that alcohol and substance use during young adulthood mediates the effect of self-esteem on depression among men. Furthermore, self-esteem during young adulthood remains a determinant of high depression in middle adulthood. However, we did not find evidence to support that same mechanism among women. Our findings provide insight into how self-esteem affects depression over the transition from young to middle adulthood, and elucidate potential gendered responsivity to low self-esteem. PMID:28936002

Factors associated with long-term use of hypnotics among patients with chronic insomnia.

Directory of Open Access Journals (Sweden)

Yoshikazu Takaesu

Full Text Available This study investigated factors associated with long-term use of benzodiazepines (BZDs or benzodiazepine receptor agonists (BzRAs as hypnotics in patients with chronic insomnia. Consecutive patients (n = 140 with chronic insomnia were enrolled in this study (68 men and 72 women; mean age, 53.8 ± 10.8 years. All patients filled out a self-assessment questionnaire asking clinical descriptive variables at the baseline of the treatment period; patients received the usual dose of a single type of BZD or BzRA. The Pittsburgh Sleep Quality Index (PSQI and the Zung Self-Rating Depression Scale were self-assessed at the baseline, and the former was re-evaluated at the time of cessation of medication or at the end of the 6-month treatment period. The PSQI included the following sub-items: evaluating sleep quality (C1, sleep latency (C2, sleep duration (C3, habitual sleep efficiency (C4, frequency of sleep disturbance (C5, use of sleeping medication (C6, and daytime dysfunction (C7. Among the patients, 54.6% needed to continue hypnotics for a 6-month treatment period. Logistic regression analysis revealed that, among descriptive variables, only the PSQI score appeared as a significant factor associated with long-term use {odds ratio (OR = 2.8, 95% confidence interval (CI = 2.0-4.0}. The receiver operating curve (ROC analysis identified that the cut-off PSQI total score at the baseline for predicting long-term use was estimated at 13.5 points (area under the curve = 0.86, 95% CI = 0.8-0.92. Among the sub-items of PSQI, the increases in C1: (OR = 8.4, 95% CI = 2.4-30.0, C3: (OR = 3.6, 95% CI = 1.1-11.5, C4: (OR = 11.1, 95% CI = 3.6-33.9, and C6: (OR = 3.4, 95% CI = 1.9-6.2 scores were associated with long-term use. This study revealed that a high PSQI score at the baseline, particularly in the sub-items relating to sleep maintenance disturbance, is predictive of long-term hypnotic treatment. Our results imply the limitation of the effectiveness of