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Translational Psychiatry

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https://www.readbyqxmd.com/read/28195573/whole-exome-sequencing-of-individuals-from-an-isolated-population-implicates-rare-risk-variants-in-bipolar-disorder
#1
F Lescai, T D Als, Q Li, M Nyegaard, G Andorsdottir, M Biskopstø, A Hedemand, A Fiorentino, N O'Brien, A Jarram, J Liang, J Grove, J Pallesen, E Eickhardt, M Mattheisen, L Bolund, D Demontis, A G Wang, A McQuillin, O Mors, J Wang, A D Børglum
Bipolar disorder affects about 1% of the world's population, and its estimated heritability is about 75%. Only few whole genome or whole-exome sequencing studies in bipolar disorder have been reported, and no rare coding variants have yet been robustly identified. The use of isolated populations might help finding variants with a recent origin, more likely to have drifted to higher frequency by chance. Following this approach, we investigated 28 bipolar cases and 214 controls from the Faroe Islands by whole exome sequencing, and the results were followed-up in a British sample of 2025 cases and 1358 controls...
February 14, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28195572/dna-methylation-as-a-putative-mechanism-for-reduced-dendritic-spine-density-in-the-superior-temporal-gyrus-of-subjects-with-schizophrenia
#2
B McKinney, Y Ding, D A Lewis, R A Sweet
Reduced dendritic spine density (DSD) in cortical layer 3 of the superior temporal gyrus (STG), and multiple other brain regions, is consistently observed in postmortem studies of schizophrenia (SZ). Elucidating the molecular mechanisms of this intermediate phenotype holds promise for understanding SZ pathophysiology, identifying SZ treatment targets and developing animal models. DNA methylation (DNAm), the addition of a methyl group to a cytosine nucleotide, regulates gene transcription and is a strong candidate for such a mechanism...
February 14, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28195571/electrical-stimulation-of-the-bed-nucleus-of-the-stria-terminalis-reduces-anxiety-in-a-rat-model
#3
K Luyck, T Tambuyzer, M Deprez, J Rangarajan, B Nuttin, L Luyten
We recently showed that deep brain stimulation (DBS) in the bed nucleus of the stria terminalis (BST) reduces obsessions, compulsions and associated anxiety in patients suffering from severe, treatment-refractory obsessive-compulsive disorder. Here, we investigated the anxiolytic effects of electrical BST stimulation in a rat model of conditioned anxiety, unrelated to obsessions or compulsions. Two sets of stimulation parameters were evaluated. Using fixed settings at 100 Hz, 40 μs and 300 μA (Set A), we observed elevated freezing and startle levels, whereas stimulation at 130 Hz, 220 μs and individually tailored amplitudes (Set B) appeared to reduce freezing...
February 14, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28195570/to-use-or-not-to-use-compulsive-behavior-and-its-role-in-smartphone-addiction
#4
Y-H Lin, Y-C Lin, S-H Lin, Y-H Lee, P-H Lin, C-L Chiang, L-R Chang, C C H Yang, T B J Kuo
Global smartphone penetration has led to unprecedented addictive behaviors. To develop a smartphone use/non-use pattern by mobile application (App) in order to identify problematic smartphone use, a total of 79 college students were monitored by the App for 1 month. The App-generated parameters included the daily use/non-use frequency, the total duration and the daily median of the duration per epoch. We introduced two other parameters, the root mean square of the successive differences (RMSSD) and the Similarity Index, in order to explore the similarity in use and non-use between participants...
February 14, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28195569/rare-damaging-variants-in-dna-repair-and-cell-cycle-pathways-are-associated-with-hippocampal-and-cognitive-dysfunction-a-combined-genetic-imaging-study-in-first-episode-treatment-naive-patients-with-schizophrenia
#5
Z Yang, M Li, X Hu, B Xiang, W Deng, Q Wang, Y Wang, L Zhao, X Ma, P C Sham, G Northoff, T Li
Schizophrenia is a complex neurodevelopmental disorder where changes in both hippocampus and memory-related cognitive functions are central. However, the exact relationship between neurodevelopmental-genetic factors and hippocampal-cognitive dysfunction remains unclear. The general aim of our study is to link the occurrence of rare damaging mutations involved in susceptibility gene pathways to the structure and function of hippocampus in order to define genetically and phenotypically based subgroups in schizophrenia...
February 14, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28195568/military-deployment-correlates-with-smaller-prefrontal-gray-matter-volume-and-psychological-symptoms-in-a-subclinical-population
#6
O Butler, J Adolf, T Gleich, G Willmund, P Zimmermann, U Lindenberger, J Gallinat, S Kühn
Research investigating the effects of trauma exposure on brain structure and function in adults has mainly focused on post-traumatic stress disorder (PTSD), whereas trauma-exposed individuals without a clinical diagnoses often serve as controls. However, this assumes a dichotomy between clinical and subclinical populations that may not be supported at the neural level. In the current study we investigate whether the effects of repeated or long-term stress exposure on brain structure in a subclinical sample are similar to previous PTSD neuroimaging findings...
February 14, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28195567/bdnf-val66met-association-with-serotonin-transporter-binding-in-healthy-humans
#7
P M Fisher, B Ozenne, C Svarer, D Adamsen, S Lehel, W F C Baaré, P S Jensen, G M Knudsen
The serotonin transporter (5-HTT) is a key feature of the serotonin system, which is involved in behavior, cognition and personality and implicated in neuropsychiatric illnesses including depression. The brain-derived neurotrophic factor (BDNF) val66met and 5-HTTLPR polymorphisms have predicted differences in 5-HTT levels in humans but with equivocal results, possibly due to limited sample sizes. Within the current study we evaluated these genetic predictors of 5-HTT binding with [(11)C]DASB positron emission tomography (PET) in a comparatively large cohort of 144 healthy individuals...
February 14, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28195566/rgs2-expression-predicts-amyloid-%C3%AE-sensitivity-mci-and-alzheimer-s-disease-genome-wide-transcriptomic-profiling-and-bioinformatics-data-mining
#8
A Hadar, E Milanesi, A Squassina, P Niola, C Chillotti, M Pasmanik-Chor, O Yaron, P Martásek, M Rehavi, D Weissglas-Volkov, N Shomron, I Gozes, D Gurwitz
No abstract text is available yet for this article.
February 14, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28170005/recurrence-of-depressive-disorders-after-interferon-induced-depression
#9
W-C Chiu, Y-P Su, K-P Su, P-C Chen
Interferon alpha (IFN-α)-treated patients commonly develop depression during the therapy period. Although most IFN-α-induced depressive disorders achieve remission after IFN-α therapy, no studies have examined the long-term mood effects of IFN-α treatment. We conducted a 12-year population-based cohort study of hepatitis C virus (HCV)-infected patients who were older than 20 years and had received IFN-α therapy. The sample was obtained from the Taiwan National Health Insurance Research Database. The cohort included patients with and without IFN-α-induced depression, matched randomly by age, sex and depression history, at a ratio of 1:10...
February 7, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28170004/inflammation-and-the-neural-diathesis-stress-hypothesis-of-schizophrenia-a-reconceptualization
#10
REVIEW
O D Howes, R McCutcheon
An interaction between external stressors and intrinsic vulnerability is one of the longest standing pathoaetiological explanations for schizophrenia. However, novel lines of evidence from genetics, preclinical studies, epidemiology and imaging have shed new light on the mechanisms that may underlie this, implicating microglia as a key potential mediator. Microglia are the primary immune cells of the central nervous system. They have a central role in the inflammatory response, and are also involved in synaptic pruning and neuronal remodeling...
February 7, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28170003/brain-volumetric-and-metabolic-correlates-of-electroconvulsive-therapy-for-treatment-resistant-depression-a-longitudinal-neuroimaging-study
#11
M Cano, I Martínez-Zalacaín, Á Bernabéu-Sanz, O Contreras-Rodríguez, R Hernández-Ribas, E Via, A de Arriba-Arnau, V Gálvez, M Urretavizcaya, J Pujol, J M Menchón, N Cardoner, C Soriano-Mas
Recent research suggests that neuroplastic and neuroinflammatory changes may account for the mode of action of electroconvulsive therapy (ECT), although extant data do not allow for a clear disambiguation between these two hypotheses. Multimodal neuroimaging approaches (for example, combining structural and metabolic information) may help in clarifying this issue. Here we aimed to assess longitudinal changes in (i) regional gray matter (GM) volumes and (ii) hippocampal metabolite concentrations throughout an acute course of bitemporal ECT, as well as (iii) to determine the association between imaging changes and clinical improvement...
February 7, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28170002/regulation-of-dopaminergic-function-an-18-f-dopa-pet-apomorphine-challenge-study-in-humans
#12
S Jauhar, M Veronese, M Rogdaki, M Bloomfield, S Natesan, F Turkheimer, S Kapur, O D Howes
Dopaminergic function has a key role in normal brain function, dopaminergic dysfunction being implicated in numerous neuropsychiatric disorders. Animal studies show that dopaminergic stimulation regulates dopaminergic function, but it is not known whether this exists in humans. In the first study (study 1), we measured dopamine synthesis capacity (indexed as Ki(cer)) to identify the relationship between baseline and change in Ki(cer) under resting conditions for comparison with effects of dopaminergic stimulation...
February 7, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28170001/the-mcp-4-mcp-1-ratio-in-plasma-is-a-candidate-circadian-biomarker-for-chronic-post-traumatic-stress-disorder
#13
C Dalgard, O Eidelman, C Jozwik, C H Olsen, M Srivastava, R Biswas, Y Eudy, S W Rothwell, G P Mueller, P Yuan, W C Drevets, H K Manji, M Vythlingam, D S Charney, A Neumeister, R J Ursano, D M Jacobowitz, H B Pollard, O Bonne
Post-traumatic stress disorder (PTSD) is psychiatric disease, which can occur following exposure to traumatic events. PTSD may be acute or chronic, and can have a waxing and waning course of symptoms. It has been hypothesized that proinflammatory cytokines and chemokines in the cerebrospinal fluid (CSF) or plasma might be mediators of the psychophysiological mechanisms relating a history of trauma exposure to changes in behavior and mental health disorders, and medical morbidity. Here we test the cytokine/chemokine hypothesis for PTSD by examining levels of 17 classical cytokines and chemokines in CSF, sampled at 0900 hours, and in plasma sampled hourly for 24 h...
February 7, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28140406/control-of-chronic-excessive-alcohol-drinking-by-genetic-manipulation-of-the-edinger-westphal-nucleus-urocortin-1-neuropeptide-system
#14
W J Giardino, E D Rodriguez, M L Smith, M M Ford, D Galili, S H Mitchell, A Chen, A E Ryabinin
Midbrain neurons of the centrally projecting Edinger-Westphal nucleus (EWcp) are activated by alcohol, and enriched with stress-responsive neuropeptide modulators (including the paralog of corticotropin-releasing factor, urocortin-1). Evidence suggests that EWcp neurons promote behavioral processes for alcohol-seeking and consumption, but a definitive role for these cells remains elusive. Here we combined targeted viral manipulations and gene array profiling of EWcp neurons with mass behavioral phenotyping in C57BL/6 J mice to directly define the links between EWcp-specific urocortin-1 expression and voluntary binge alcohol intake, demonstrating a specific importance for EWcp urocortin-1 activity in escalation of alcohol intake...
January 31, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28140405/the-impact-of-disrupted-in-schizophrenia-1-disc1-on-the-dopaminergic-system-a-systematic-review
#15
REVIEW
T Dahoun, S V Trossbach, N J Brandon, C Korth, O D Howes
Disrupted-in-Schizophrenia 1 (DISC1) is a gene known as a risk factor for mental illnesses possibly associated with dopamine impairments. DISC1 is a scaffold protein interacting with proteins involved in the dopamine system. Here we summarise the impact of DISC1 disruption on the dopamine system in animal models, considering its effects on presynaptic dopaminergic function (tyrosine hydroxylase levels, dopamine transporter levels, dopamine levels at baseline and after amphetamine administration) and postsynaptic dopaminergic function (dopamine D1 and D2 receptor levels, dopamine receptor-binding potential and locomotor activity after amphetamine administration)...
January 31, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28140404/particulate-air-pollutants-apoe-alleles-and-their-contributions-to-cognitive-impairment-in-older-women-and-to-amyloidogenesis-in-experimental-models
#16
M Cacciottolo, X Wang, I Driscoll, N Woodward, A Saffari, J Reyes, M L Serre, W Vizuete, C Sioutas, T E Morgan, M Gatz, H C Chui, S A Shumaker, S M Resnick, M A Espeland, C E Finch, J C Chen
Exposure to particulate matter (PM) in the ambient air and its interactions with APOE alleles may contribute to the acceleration of brain aging and the pathogenesis of Alzheimer's disease (AD). Neurodegenerative effects of particulate air pollutants were examined in a US-wide cohort of older women from the Women's Health Initiative Memory Study (WHIMS) and in experimental mouse models. Residing in places with fine PM exceeding EPA standards increased the risks for global cognitive decline and all-cause dementia respectively by 81 and 92%, with stronger adverse effects in APOE ɛ4/4 carriers...
January 31, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28140403/medical-history-of-discordant-twins-and-environmental-etiologies-of-autism
#17
C Willfors, T Carlsson, B-M Anderlid, A Nordgren, E Kostrzewa, S Berggren, A Ronald, R Kuja-Halkola, K Tammimies, S Bölte
The environmental contributions to autism spectrum disorder (ASD) and their informative content for diagnosing the condition are still largely unknown. The objective of this study was to investigate associations between early medical events and ASD, as well as autistic traits, in twins, to test the hypothesis of a cumulative environmental effect on ASD risk. A total of 80 monozygotic (MZ) twin pairs (including a rare sample of 13 twin pairs discordant for clinical ASD) and 46 dizygotic (DZ) twin pairs with varying autistic traits, were examined for intra-pair differences in early medical events (for example, obstetric and neonatal factors, first year infections)...
January 31, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28140402/glucose-deficit-triggers-tau-pathology-and-synaptic-dysfunction-in-a-tauopathy-mouse-model
#18
E Lauretti, J-G Li, A Di Meco, D Praticò
Clinical investigations have highlighted a biological link between reduced brain glucose metabolism and Alzheimer's disease (AD). Previous studies showed that glucose deprivation may influence amyloid beta formation in vivo but no data are available on the effect that this condition might have on tau protein metabolism. In the current paper, we investigated the effect of glucose deficit on tau phosphorylation, memory and learning, and synaptic function in a transgenic mouse model of tauopathy, the h-tau mice...
January 31, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28140401/advanced-paternal-age-effects-in-neurodevelopmental-disorders-review-of-potential-underlying-mechanisms
#19
REVIEW
M Janecka, J Mill, M A Basson, A Goriely, H Spiers, A Reichenberg, L Schalkwyk, C Fernandes
Multiple epidemiological studies suggest a relationship between advanced paternal age (APA) at conception and adverse neurodevelopmental outcomes in offspring, particularly with regard to increased risk for autism and schizophrenia. Conclusive evidence about how age-related changes in paternal gametes, or age-independent behavioral traits affect neural development is still lacking. Recent evidence suggests that the origins of APA effects are likely to be multidimensional, involving both inherited predisposition and de novo events...
January 31, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28140400/further-support-for-association-between-gwas-variant-for-positive-emotion-and-reward-systems
#20
T M Lancaster, N Ihssen, L M Brindley, D E J Linden
A recent genome-wide association study (GWAS) identified a significant single-nucleotide polymorphism (SNP) for trait-positive emotion at rs322931 on chromosome 1, which was also associated with brain activation in the reward system of healthy individuals when observing positive stimuli in a functional magnetic resonance imaging (fMRI) study. In the current study, we aimed to further validate the role of variation at rs322931 in reward processing. Using a similar fMRI approach, we use two paradigms that elicit a strong ventral striatum (VS) blood oxygen-level dependency (BOLD) response in a sample of young, healthy individuals (N=82)...
January 31, 2017: Translational Psychiatry
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