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Translational Psychiatry

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https://www.readbyqxmd.com/read/28994820/sexual-dimorphism-of-ambra1-related-autistic-features-in-human-and-mouse
#1
M Mitjans, M Begemann, A Ju, E Dere, L Wüstefeld, S Hofer, I Hassouna, J Balkenhol, B Oliveira, S van der Auwera, R Tammer, K Hammerschmidt, H Völzke, G Homuth, F Cecconi, K Chowdhury, H Grabe, J Frahm, S Boretius, T Dandekar, H Ehrenreich
Ambra1 is linked to autophagy and neurodevelopment. Heterozygous Ambra1 deficiency induces autism-like behavior in a sexually dimorphic manner. Extraordinarily, autistic features are seen in female mice only, combined with stronger Ambra1 protein reduction in brain compared to males. However, significance of AMBRA1 for autistic phenotypes in humans and, apart from behavior, for other autism-typical features, namely early brain enlargement or increased seizure propensity, has remained unexplored. Here we show in two independent human samples that a single normal AMBRA1 genotype, the intronic SNP rs3802890-AA, is associated with autistic features in women, who also display lower AMBRA1 mRNA expression in peripheral blood mononuclear cells relative to female GG carriers...
October 10, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28972592/genetically-driven-brain-serotonin-deficiency-facilitates-panic-like-escape-behavior-in-mice
#2
J Waider, S Popp, M D Lange, R Kern, J F Kolter, J Kobler, N C Donner, K R Lowe, J H Malzbender, C J Brazell, M R Arnold, B Aboagye, A Schmitt-Böhrer, C A Lowry, H C Pape, K P Lesch
Multiple lines of evidence implicate brain serotonin (5-hydroxytryptamine; 5-HT) system dysfunction in the pathophysiology of stressor-related and anxiety disorders. Here we investigate the influence of constitutively deficient 5-HT synthesis on stressor-related anxiety-like behaviors using Tryptophan hydroxylase 2 (Tph2) mutant mice. Functional assessment of c-Fos after associated foot shock, electrophysiological recordings of GABAergic synaptic transmission, differential expression of the Slc6a4 gene in serotonergic neurons were combined with locomotor and anxiety-like measurements in different contextual settings...
October 3, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28972591/altered-activation-and-connectivity-in-a-hippocampal-basal-ganglia-midbrain-circuit-during-salience-processing-in-subjects-at-ultra-high-risk-for-psychosis
#3
T Winton-Brown, A Schmidt, J P Roiser, O D Howes, A Egerton, P Fusar-Poli, N Bunzeck, A A Grace, E Duzel, S Kapur, P McGuire
Animal models of psychosis propose that abnormal hippocampal activity drives increased subcortical dopamine function, which is thought to contribute to aberrant salience processing and psychotic symptoms. These effects appear to be mediated through connections between the hippocampus, ventral striatum/pallidum and the midbrain. The aim of the present study was to examine the activity and connectivity in this pathway in people at ultra high risk (UHR) for psychosis. Functional magnetic resonance imaging was used to compare neural responses in a hippocampal-basal ganglia-midbrain network during reward, novelty and aversion processing between 29 UHR subjects and 32 healthy controls...
October 3, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28949340/dietary-fish-n-3-polyunsaturated-fatty-acid-consumption-and-depression-risk-in-japan-a-population-based-prospective-cohort-study
#4
Y J Matsuoka, N Sawada, M Mimura, R Shikimoto, S Nozaki, K Hamazaki, Y Uchitomi, S Tsugane
Systematic review of observational studies has revealed that fish consumption and levels of n-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid are associated with a reduced risk of depression. A reverse J-shaped effect of n-3 PUFAs was suggested. However, there is limited evidence from populations with high fish consumption and no studies have used a standard psychiatrist-based diagnosis of major depressive disorder (MDD). Therefore, this population-based, prospective study investigated the association of dietary fish, n-3 PUFA, and n-6 PUFA consumption with risk of psychiatrist-diagnosed MDD in Japan...
September 26, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28949339/identification-of-a-plasma-signature-of-psychotic-disorder-in-children-and-adolescents-from-the-avon-longitudinal-study-of-parents-and-children-alspac-cohort
#5
A O'Gorman, T Suvitaival, L Ahonen, M Cannon, S Zammit, G Lewis, H M Roche, I Mattila, T Hyotylainen, M Oresic, L Brennan, D R Cotter
The identification of an early biomarker of psychotic disorder is important as early treatment is associated with improved patient outcome. Metabolomic and lipidomic approaches in combination with multivariate statistical analysis were applied to identify plasma alterations in children (age 11) (38 cases vs 67 controls) and adolescents (age 18) (36 cases vs 117 controls) preceeding or coincident with the development of psychotic disorder (PD) at age 18 in the Avon Longitudinal Study of Parents and Children (ALSPAC)...
September 26, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28949338/in-the-grip-of-worry-cerebral-blood-flow-changes-during-worry-induction-and-reappraisal-in-late-life-generalized-anxiety-disorder
#6
H T Karim, D L Tudorascu, M A Butters, S Walker, H J Aizenstein, C Andreescu
This corrects the article DOI: 10.1038/tp.2017.180.
September 26, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28949337/investigating-the-genetic-underpinnings-of-early-life-irritability
#7
L Riglin, O Eyre, M Cooper, S Collishaw, J Martin, K Langley, E Leibenluft, A Stringaris, A K Thapar, B Maughan, M C O'Donovan, A Thapar
Severe irritability is one of the commonest reasons prompting referral to mental health services. It is frequently seen in neurodevelopmental disorders that manifest early in development, especially attention-deficit/hyperactivity disorder (ADHD). However, irritability can also be conceptualized as a mood problem because of its links with anxiety/depressive disorders; notably DSM-5 currently classifies severe, childhood-onset irritability as a mood disorder. Investigations into the genetic nature of irritability are lacking although twin studies suggest it shares genetic risks with both ADHD and depression...
September 26, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28949336/disrupted-hippocampal-neuregulin-1-erbb3-signaling-and-dentate-gyrus-granule-cell-alterations-in-suicide
#8
I Mahar, B Labonte, S Yogendran, E Isingrini, L Perret, M A Davoli, A Rachalski, B Giros, G Turecki, N Mechawar
This corrects the article DOI: 10.1038/tp.2017.132.
September 26, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28949335/the-bet-brd-inhibitor-jq1-improves-brain-plasticity-in-wt-and-app-mice
#9
E Benito, B Ramachandran, H Schroeder, G Schmidt, H Urbanke, S Burkhardt, V Capece, C Dean, A Fischer
Histone acetylation is essential for memory formation and its deregulation contributes to the pathogenesis of Alzheimer's disease. Thus, targeting histone acetylation is discussed as a novel approach to treat dementia. The histone acetylation landscape is shaped by chromatin writer and eraser proteins, while readers link chromatin state to cellular function. Chromatin readers emerged novel drug targets in cancer research but little is known about the manipulation of readers in the adult brain. Here we tested the effect of JQ1-a small-molecule inhibitor of the chromatin readers BRD2, BRD3, BRD4 and BRDT-on brain function and show that JQ1 is able to enhance cognitive performance and long-term potentiation in wild-type animals and in a mouse model for Alzheimer's disease...
September 26, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28926003/age-of-first-exposure-to-american-football-and-long-term-neuropsychiatric-and-cognitive-outcomes
#10
M L Alosco, A B Kasimis, J M Stamm, A S Chua, C M Baugh, D H Daneshvar, C A Robbins, M Mariani, J Hayden, S Conneely, R Au, A Torres, M D McClean, A C McKee, R C Cantu, J Mez, C J Nowinski, B M Martin, C E Chaisson, Y Tripodis, R A Stern
Previous research suggests that age of first exposure (AFE) to football before age 12 may have long-term clinical implications; however, this relationship has only been examined in small samples of former professional football players. We examined the association between AFE to football and behavior, mood and cognition in a large cohort of former amateur and professional football players. The sample included 214 former football players without other contact sport history. Participants completed the Brief Test of Adult Cognition by Telephone (BTACT), and self-reported measures of executive function and behavioral regulation (Behavior Rating Inventory of Executive Function-Adult Version Metacognition Index (MI), Behavioral Regulation Index (BRI)), depression (Center for Epidemiologic Studies Depression Scale (CES-D)) and apathy (Apathy Evaluation Scale (AES))...
September 19, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28926002/polygenic-loading-for-major-depression-is-associated-with-specific-medical-comorbidity
#11
T H McCoy, V M Castro, L Snapper, K Hart, J L Januzzi, J C Huffman, R H Perlis
Major depressive disorder frequently co-occurs with medical disorders, raising the possibility of shared genetic liability. Recent identification of 15 novel genetic loci associated with depression allows direct investigation of this question. In cohorts of individuals participating in biobanks at two academic medical centers, we calculated polygenic loading for risk loci reported to be associated with depression. We then examined the association between such loading and 50 groups of clinical diagnoses, or topics, drawn from these patients' electronic health records, determined using a novel application of latent Dirichilet allocation...
September 19, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28926001/ketamine-differential-neurophysiological-dynamics-in-functional-networks-in-the-rat-brain
#12
A Ahnaou, H Huysmans, R Biermans, N V Manyakov, W H I M Drinkenburg
Recently, the N-methyl-d-aspartate-receptor (NMDAR) antagonist ketamine has emerged as a fast-onset mechanism to achieve antidepressant activity, whereas its psychomimetic, dissociative and amnestic effects have been well documented to pharmacologically model schizophrenia features in rodents. Sleep-wake architecture, neuronal oscillations and network connectivity are key mechanisms supporting brain plasticity and cognition, which are disrupted in mood disorders such as depression and schizophrenia. In rats, we investigated the dynamic effects of acute and chronic subcutaneous administration of ketamine (2...
September 19, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28926000/the-bdnf-val66met-polymorphism-regulates-glucocorticoid-induced-corticohippocampal-remodeling-and-behavioral-despair
#13
M Notaras, X Du, J Gogos, M van den Buuse, R A Hill
The BDNF Val66Met polymorphism has been associated with sensitivity to stress and affective disorders. We therefore sought to model the inter-causality of these relationships under controlled laboratory conditions. We subjected humanized BDNF Val66Met (hBDNF(Val66Met)) transgenic mice to a history of stress, modeled by chronic late-adolescent corticosterone (CORT) exposure, before evaluating affective-related behavior using the forced-swim test (FST) in adulthood. While hBDNF(Met/Met) mice had a depression-like phenotype in the FST irrespective of CORT, hBDNF(Val/Val) wildtype mice had a resilient phenotype but developed an equally robust depressive-like phenotype following CORT...
September 19, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28925999/an-evaluation-of-the-effects-of-intensity-and-duration-on-outcomes-across-treatment-domains-for-children-with-autism-spectrum-disorder
#14
E Linstead, D R Dixon, E Hong, C O Burns, R French, M N Novack, D Granpeesheh
Applied behavior analysis (ABA) is considered an effective treatment for individuals with autism spectrum disorder (ASD), and many researchers have further investigated factors associated with treatment outcomes. However, few studies have focused on whether treatment intensity and duration have differential influences on separate skills. The aim of the current study was to investigate how treatment intensity and duration impact learning across different treatment domains, including academic, adaptive, cognitive, executive function, language, motor, play, and social...
September 19, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28925998/a-critical-period-for-antidepressant-induced-acceleration-of-neuronal-maturation-in-adult-dentate-gyrus
#15
I Åmellem, S Suresh, C C Chang, S S L Tok, A Tashiro
Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used medications for mood and anxiety disorders, and adult neurogenesis in the dentate gyrus has been shown to be involved in the behavioral effects of SSRIs in mice. Studies have shown the varied effects of chronic treatment with SSRIs on adult neurogenesis. One such effect is the acceleration of neuronal maturation, which affects the functional integration of new neurons into existing neuronal circuitry. In this study, we labeled new neurons by using GFP-expressing retroviral vectors in mice and investigated the effect of an SSRI, fluoxetine, on these neurons at different time points after neuronal birth...
September 19, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28895942/disrupted-cortical-brain-network-in-post-traumatic-stress-disorder-patients-a-resting-state-electroencephalographic-study
#16
M Shim, C-H Im, S-H Lee
This study aimed to examine the source-level cortical brain networks of post-traumatic stress disorder (PTSD) based on the graph theory using electroencephalography (EEG). Sixty-six cortical source signals were estimated from 78 PTSD and 58 healthy controls (HCs) of resting-state EEG. Four global indices (strength, clustering coefficient (CC), path length (PL) and efficiency) and one nodal index (CC) were evaluated in six frequency bands (delta, theta, alpha, low beta, high beta and gamma). PTSD showed decreased global strength, CC and efficiency, in delta, theta, and low beta band and enhanced PL in theta and low beta band...
September 12, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28895941/outcome-reporting-bias-in-randomized-controlled-trials-investigating-antipsychotic-drugs
#17
M Lancee, C M C Lemmens, R S Kahn, C H Vinkers, J J Luykx
Recent literature hints that outcomes of clinical trials in medicine are selectively reported. If applicable to psychotic disorders, such bias would jeopardize the reliability of randomized clinical trials (RCTs) investigating antipsychotics and thus their extrapolation to clinical practice. We therefore comprehensively examined outcome reporting bias in RCTs of antipsychotic drugs by a systematic review of prespecified outcomes on ClinicalTrials.gov records of RCTs investigating antipsychotic drugs in schizophrenia and schizoaffective disorder between 1 January 2006 and 31 December 2013...
September 12, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28872641/polyunsaturated-fatty-acid-deficiency-during-neurodevelopment-in-mice-models-the-prodromal-state-of-schizophrenia-through-epigenetic-changes-in-nuclear-receptor-genes
#18
M Maekawa, A Watanabe, Y Iwayama, T Kimura, K Hamazaki, S Balan, H Ohba, Y Hisano, Y Nozaki, T Ohnishi, M Toyoshima, C Shimamoto, K Iwamoto, M Bundo, N Osumi, E Takahashi, A Takashima, T Yoshikawa
The risk of schizophrenia is increased in offspring whose mothers experience malnutrition during pregnancy. Polyunsaturated fatty acids (PUFAs) are dietary components that are crucial for the structural and functional integrity of neural cells, and PUFA deficiency has been shown to be a risk factor for schizophrenia. Here, we show that gestational and early postnatal dietary deprivation of two PUFAs-arachidonic acid (AA) and docosahexaenoic acid (DHA)-elicited schizophrenia-like phenotypes in mouse offspring at adulthood...
September 5, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28872640/nectin-3-modulates-the-structural-plasticity-of-dentate-granule-cells-and-long-term-memory
#19
X-X Wang, J-T Li, X-M Xie, Y Gu, T-M Si, M V Schmidt, X-D Wang
Nectin-3, a cell adhesion molecule enriched in hippocampal neurons, has been implicated in stress-related cognitive disorders. Nectin-3 is expressed by granule cells in the dentate gyrus (DG), but it remains unclear whether nectin-3 in DG modulates the structural plasticity of dentate granule cells and hippocampus-dependent memory. In this study, we found that DG nectin-3 expression levels were developmentally regulated and reduced by early postnatal stress exposure in adult mice. Most importantly, knockdown of nectin-3 levels in all DG neuron populations by adeno-associated virus (AAV) mimicked the cognitive effects of early-life stress, and impaired long-term spatial memory and temporal order memory...
September 5, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28872639/gene-expression-associated-with-suicide-attempts-in-us-veterans
#20
J D Flory, D Donohue, S Muhie, R Yang, S A Miller, R Hammamieh, K Ryberg, R Yehuda
According to a recent report from the Office of Suicide Prevention in the US Department of Veterans Affairs, veterans represent 8.5% of the US population, but account for 18% of all deaths from suicide. The aim of this study of psychiatric patients (n=39; 87% male) was to compare blood gene expression data from veterans with a history of one or more suicide attempts to veterans who had never attempted suicide. The attempter and non-attempter groups were matched for age and race/ethnicity, and both groups included veterans with a diverse psychiatric history that included posttraumatic stress disorder (PTSD) and substance-use disorders...
September 5, 2017: Translational Psychiatry
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