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Translational Psychiatry

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https://www.readbyqxmd.com/read/28440817/effects-of-dopamine-d2-d3-receptor-antagonism-on-human-planning-and-spatial-working-memory
#1
M Naef, U Müller, A Linssen, L Clark, T W Robbins, C Eisenegger
Psychopharmacological studies in humans suggest important roles for dopamine (DA) D2 receptors in human executive functions, such as cognitive planning and spatial working memory (SWM). However, studies that investigate an impairment of such functions using the selective DA D2/3 receptor antagonist sulpiride have yielded inconsistent results, perhaps because relatively low doses were used. We believe we report for the first time, the effects of a higher (800 mg p.o.) single dose of sulpiride as well as of genetic variation in the DA receptor D2 gene (DA receptor D2 Taq1A polymorphism), on planning and working memory...
April 25, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28440816/influences-of-prenatal-and-postnatal-maternal-depression-on-amygdala-volume-and-microstructure-in-young-children
#2
D J Wen, J S Poh, S N Ni, Y-S Chong, H Chen, K Kwek, L P Shek, P D Gluckman, M V Fortier, M J Meaney, A Qiu
Maternal depressive symptoms influence neurodevelopment in the offspring. Such effects may appear to be gender-dependent. The present study examined contributions of prenatal and postnatal maternal depressive symptoms to the volume and microstructure of the amygdala in 4.5-year-old boys and girls. Prenatal maternal depressive symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS) at 26 weeks of gestation. Postnatal maternal depression was assessed at 3 months using the EPDS and at 1, 2, 3 and 4...
April 25, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28440815/15q11-2-cnv-affects-cognitive-structural-and-functional-correlates-of-dyslexia-and-dyscalculia
#3
M O Ulfarsson, G B Walters, O Gustafsson, S Steinberg, A Silva, O M Doyle, M Brammer, D F Gudbjartsson, S Arnarsdottir, G A Jonsdottir, R S Gisladottir, G Bjornsdottir, H Helgason, L M Ellingsen, J G Halldorsson, E Saemundsen, B Stefansdottir, L Jonsson, V K Eiriksdottir, G R Eiriksdottir, G H Johannesdottir, U Unnsteinsdottir, B Jonsdottir, B B Magnusdottir, P Sulem, U Thorsteinsdottir, E Sigurdsson, D Brandeis, A Meyer-Lindenberg, H Stefansson, K Stefansson
Several copy number variants have been associated with neuropsychiatric disorders and these variants have been shown to also influence cognitive abilities in carriers unaffected by psychiatric disorders. Previously, we associated the 15q11.2(BP1-BP2) deletion with specific learning disabilities and a larger corpus callosum. Here we investigate, in a much larger sample, the effect of the 15q11.2(BP1-BP2) deletion on cognitive, structural and functional correlates of dyslexia and dyscalculia. We report that the deletion confers greatest risk of the combined phenotype of dyslexia and dyscalculia...
April 25, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28440814/depletion-of-adult-neurogenesis-using-the-chemotherapy-drug-temozolomide-in-mice-induces-behavioural-and-biological-changes-relevant-to-depression
#4
M Egeland, C Guinaudie, A Du Preez, K Musaelyan, P A Zunszain, C Fernandes, C M Pariante, S Thuret
Numerous studies have examined links between postnatal neurogenesis and depression using a range of experimental methods to deplete neurogenesis. The antimitotic drug temozolomide (TMZ) has previously been used successfully as an experimental tool in animals to deplete adult neurogenesis and is used regularly on human patients as a standard chemotherapy for brain cancer. In this study, we wanted to evaluate whether TMZ as a model for chemotherapy treatment could affect parameters related to depression in an animal model...
April 25, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28440813/instability-of-default-mode-network-connectivity-in-major-depression-a-two-sample-confirmation-study
#5
T Wise, L Marwood, A M Perkins, A Herane-Vives, R Joules, D J Lythgoe, W-M Luh, S C R Williams, A H Young, A J Cleare, D Arnone
Major depression is associated with altered static functional connectivity in various brain networks, particularly the default mode network (DMN). Dynamic functional connectivity is a novel tool with little application in affective disorders to date, and holds the potential to unravel fluctuations in connectivity strength over time in major depression. We assessed stability of connectivity in major depression between the medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC), key nodes in the DMN that are implicated in ruminative cognitions...
April 25, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28440812/biobehavioral-effects-of-baclofen-in-anxious-alcohol-dependent-individuals-a-randomized-double-blind-placebo-controlled-laboratory-study
#6
M Farokhnia, M L Schwandt, M R Lee, J W Bollinger, L A Farinelli, J P Amodio, L Sewell, T A Lionetti, D E Spero, L Leggio
Baclofen has been suggested as a potential pharmacotherapy for alcohol use disorder, but the clinical data are conflicting. Here we investigated the biobehavioral effects of baclofen in a sample of anxious alcohol-dependent individuals. This was a randomized, double-blind, placebo-controlled, human laboratory study in non-treatment seeking alcohol-dependent individuals with high trait anxiety (N=34). Participants received baclofen (30 mg per day) or placebo for at least 8 days, then performed an experimental session consisting of alcohol cue-reactivity followed by alcohol administration procedure (alcohol priming, then alcohol self-administration)...
April 25, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28440811/evaluation-of-circadian-phenotypes-utilizing-fibroblasts-from-patients-with-circadian-rhythm-sleep-disorders
#7
A Hida, Y Ohsawa, S Kitamura, K Nakazaki, N Ayabe, Y Motomura, K Matsui, M Kobayashi, A Usui, Y Inoue, H Kusanagi, Y Kamei, K Mishima
We evaluated the circadian phenotypes of patients with delayed sleep-wake phase disorder (DSWPD) and non-24-hour sleep-wake rhythm disorder (N24SWD), two different circadian rhythm sleep disorders (CRSDs) by measuring clock gene expression rhythms in fibroblast cells derived from individual patients. Bmal1-luciferase (Bmal1-luc) expression rhythms were measured in the primary fibroblast cells derived from skin biopsy samples of patients with DSWPD and N24SWD, as well as control subjects. The period length of the Bmal1-luc rhythm (in vitro period) was distributed normally and was 22...
April 25, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28440810/naltrexone-modulates-dopamine-release-following-chronic-but-not-acute-amphetamine-administration-a-translational-study
#8
N Jayaram-Lindström, J Guterstam, J Häggkvist, M Ericson, T Malmlöf, B Schilström, C Halldin, S Cervenka, T Saijo, A-L Nordström, J Franck
The opioid antagonist naltrexone has been shown to attenuate the subjective effects of amphetamine. However, the mechanisms behind this modulatory effect are currently unknown. We hypothesized that naltrexone would diminish the striatal dopamine release induced by amphetamine, which is considered an important mechanism behind many of its stimulant properties. We used positron emission tomography and the dopamine D2-receptor radioligand [(11)C]raclopride in healthy subjects to study the dopaminergic effects of an amphetamine injection after pretreatment with naltrexone or placebo...
April 25, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28440809/a-missense-polymorphism-in-the-putative-pheromone-receptor-gene-vn1r1-is-associated-with-sociosexual-behavior
#9
S Henningsson, D Hovey, K Vass, H Walum, K Sandnabba, P Santtila, P Jern, L Westberg
Pheromones regulate social and reproductive behavior in most mammalian species. These effects are mediated by the vomeronasal and main olfactory systems. Effects of putative pheromones on human neuroendocrine activity, brain activity and attractiveness ratings suggest that humans may communicate via similar chemosignaling. Here we studied two samples of younger and older individuals, respectively, with respect to one nonsynonymous polymorphism in the gene encoding the human vomeronasal type-1 receptor 1, VN1R1, and one nonsynonymous polymorphism in the gene encoding the olfactory receptor OR7D4...
April 25, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28418405/adenosine-a2a-receptor-and-erk-driven-impulsivity-potentiates-hippocampal-neuroblast-proliferation
#10
A Oliveros, C H Cho, A Cui, S Choi, D Lindberg, D Hinton, M-H Jang, D-S Choi
Dampened adenosine A2A receptor (A2AR) function has been implicated in addiction through enhancement of goal-directed behaviors. However, the contribution of the A2AR to the control of impulsive reward seeking remains unknown. Using mice that were exposed to differential reward of low rate (DRL) schedules during Pavlovian-conditioning, second-order schedule discrimination, and the 5-choice serial reaction time task (5-CSRTT), we demonstrate that deficits of A2AR function promote impulsive responses. Antagonism of the A2AR lowered ERK1 and ERK2 phosphorylation in the dorsal hippocampus (dHip) and potentiated impulsivity during Pavlovian-conditioning and the 5-CSRTT...
April 18, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28418404/a-pathway-linking-reward-circuitry-impulsive-sensation-seeking-and-risky-decision-making-in-young-adults-identifying-neural-markers-for-new-interventions
#11
H W Chase, J C Fournier, M A Bertocci, T Greenberg, H Aslam, R Stiffler, J Lockovich, S Graur, G Bebko, E E Forbes, M L Phillips
High trait impulsive sensation seeking (ISS) is common in 18-25-year olds, and is associated with risky decision-making and deleterious outcomes. We examined relationships among: activity in reward regions previously associated with ISS during an ISS-relevant context, uncertain reward expectancy (RE), using fMRI; ISS impulsivity and sensation-seeking subcomponents; and risky decision-making in 100, transdiagnostically recruited 18-25-year olds. ISS, anhedonia, anxiety, depression and mania were measured using self-report scales; clinician-administered scales also assessed the latter four...
April 18, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28418403/assessing-the-presence-of-shared-genetic-architecture-between-alzheimer-s-disease-and-major-depressive-disorder-using-genome-wide-association-data
#12
J Gibson, T C Russ, M J Adams, T-K Clarke, D M Howard, L S Hall, A M Fernandez-Pujals, E M Wigmore, C Hayward, G Davies, A D Murray, B H Smith, D J Porteous, I J Deary, A M McIntosh
Major depressive disorder (MDD) and Alzheimer's disease (AD) are both common in older age and frequently co-occur. Numerous phenotypic studies based on clinical diagnoses suggest that a history of depression increases risk of subsequent AD, although the basis of this relationship is uncertain. Both illnesses are polygenic, and shared genetic risk factors could explain some of the observed association. We used genotype data to test whether MDD and AD have an overlapping polygenic architecture in two large population-based cohorts, Generation Scotland's Scottish Family Health Study (GS:SFHS; N=19 889) and UK Biobank (N=25 118), and whether age of depression onset influences any relationship...
April 18, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28418402/transcriptome-sequencing-study-implicates-immune-related-genes-differentially-expressed-in-schizophrenia-new-data-and-a-meta-analysis
#13
A R Sanders, E I Drigalenko, J Duan, W Moy, J Freda, H H H Göring, P V Gejman
We undertook an RNA sequencing (RNAseq)-based transcriptomic profiling study on lymphoblastoid cell lines of a European ancestry sample of 529 schizophrenia cases and 660 controls, and found 1058 genes to be differentially expressed by affection status. These differentially expressed genes were enriched for involvement in immunity, especially the 697 genes with higher expression in cases. Comparing the current RNAseq transcriptomic profiling to our previous findings in an array-based study of 268 schizophrenia cases and 446 controls showed a highly significant positive correlation over all genes...
April 18, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28418401/weak-associations-between-pubertal-development-and-psychiatric-and-behavioral-problems
#14
E Smith-Woolley, K Rimfeld, R Plomin
Pubertal development has been associated with adverse outcomes throughout adolescence and adulthood. However, much of the previous literature has categorized outcome variables and pubertal timing measures for ease of mean difference or odds ratio interpretation. We use a UK-representative sample of over 5000 individuals drawn from the Twins Early Development Study to extend this literature by adopting an individual differences approach and emphasizing effect sizes. We investigate a variety of psychiatric and behavioral measures collected longitudinally at ages 11, 14 and 16, for multiple raters and for males and females separately...
April 18, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28418400/short-telomere-length-is-associated-with-impaired-cognitive-performance-in-european-ancestry-cohorts
#15
S Hägg, Y Zhan, R Karlsson, L Gerritsen, A Ploner, S J van der Lee, L Broer, J Deelen, R E Marioni, A Wong, A Lundquist, G Zhu, N K Hansell, E Sillanpää, I O Fedko, N A Amin, M Beekman, A J M de Craen, S Degerman, S E Harris, K-J Kan, C M Martin-Ruiz, G W Montgomery, A N Adolfsson, C A Reynolds, N J Samani, H E D Suchiman, A Viljanen, T von Zglinicki, M J Wright, J-J Hottenga, D I Boomsma, T Rantanen, J A Kaprio, D R Nyholt, N G Martin, L Nyberg, R Adolfsson, D Kuh, J M Starr, I J Deary, P E Slagboom, C M van Duijn, V Codd, N L Pedersen
The association between telomere length (TL) dynamics on cognitive performance over the life-course is not well understood. This study meta-analyses observational and causal associations between TL and six cognitive traits, with stratifications on APOE genotype, in a Mendelian Randomization (MR) framework. Twelve European cohorts (N=17 052; mean age=59.2±8.8 years) provided results for associations between qPCR-measured TL (T/S-ratio scale) and general cognitive function, mini-mental state exam (MMSE), processing speed by digit symbol substitution test (DSST), visuospatial functioning, memory and executive functioning (STROOP)...
April 18, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28418399/restoring-effects-of-oxytocin-on-the-attentional-preference-for-faces-in-autism
#16
M Kanat, I Spenthof, A Riedel, L T van Elst, M Heinrichs, G Domes
Reduced attentional preference for faces and symptoms of social anxiety are common in autism spectrum disorders (ASDs). The neuropeptide oxytocin triggers anxiolytic functions and enhances eye gaze, facial emotion recognition and neural correlates of face processing in ASD. Here we investigated whether a single dose of oxytocin increases attention to faces in ASD. As a secondary question, we explored the influence of social anxiety on these effects. We tested for oxytocin's effects on attention to neutral faces as compared to houses in a sample of 29 autistic individuals and 30 control participants using a dot-probe paradigm with two different presentation times (100 or 500 ms)...
April 18, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28418398/intranasal-oxytocin-enhances-intrinsic-corticostriatal-functional-connectivity-in-women
#17
R A I Bethlehem, M V Lombardo, M-C Lai, B Auyeung, S K Crockford, J Deakin, S Soubramanian, A Sule, P Kundu, V Voon, S Baron-Cohen
Oxytocin may influence various human behaviors and the connectivity across subcortical and cortical networks. Previous oxytocin studies are male biased and often constrained by task-based inferences. Here, we investigate the impact of oxytocin on resting-state connectivity between subcortical and cortical networks in women. We collected resting-state functional magnetic resonance imaging (fMRI) data on 26 typically developing women 40 min following intranasal oxytocin administration using a double-blind placebo-controlled crossover design...
April 18, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28398343/large-scale-interaction-effects-reveal-missing-heritability-in-schizophrenia-bipolar-disorder-and-posttraumatic-stress-disorder
#18
H J Woo, C Yu, K Kumar, J Reifman
Genetic susceptibility factors behind psychiatric disorders typically contribute small effects individually. A possible explanation for the missing heritability is that the effects of common variants are not only polygenic but also non-additive, appearing only when interactions within large groups are taken into account. Here, we tested this hypothesis for schizophrenia (SZ) and bipolar disorder (BP) disease risks, and identified genetic factors shared with posttraumatic stress disorder (PTSD). When considered independently, few single-nucleotide polymorphisms (SNPs) reached genome-wide significance...
April 11, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28398342/two-subgroups-of-antipsychotic-naive-first-episode-schizophrenia-patients-identified-with-a-gaussian-mixture-model-on-cognition-and-electrophysiology
#19
N Bak, B H Ebdrup, B Oranje, B Fagerlund, M H Jensen, S W Düring, M Ø Nielsen, B Y Glenthøj, L K Hansen
Deficits in information processing and cognition are among the most robust findings in schizophrenia patients. Previous efforts to translate group-level deficits into clinically relevant and individualized information have, however, been non-successful, which is possibly explained by biologically different disease subgroups. We applied machine learning algorithms on measures of electrophysiology and cognition to identify potential subgroups of schizophrenia. Next, we explored subgroup differences regarding treatment response...
April 11, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28398341/the-cacna1c-risk-allele-rs1006737-is-associated-with-age-related-prefrontal-cortical-thinning-in-bipolar-i-disorder
#20
M G Soeiro-de-Souza, B Lafer, R A Moreno, F G Nery, T Chile, K Chaim, C da Costa Leite, R Machado-Vieira, M C G Otaduy, H Vallada
Calcium channels control the inflow of calcium ions into cells and are involved in diverse cellular functions. The CACNA1C gene polymorphism rs1006737 A allele has been strongly associated with increased risk for bipolar disorder (BD) and with modulation of brain morphology. The medial prefrontal cortex (mPFC) has been widely associated with mood regulation in BD, but the role of this CACNA1C polymorphism in mPFC morphology and brain aging has yet to be elucidated. One hundred seventeen euthymic BD type I subjects were genotyped for CACNA1C rs1006737 and underwent 3 T three-dimensional structural magnetic resonance imaging scans to determine cortical thickness of mPFC components (superior frontal cortex (sFC), medial orbitofrontal cortex (mOFC), caudal anterior cingulate cortex (cACC) and rostral anterior cingulate cortex (rACC))...
April 11, 2017: Translational Psychiatry
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