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Translational Psychiatry

T Zayats, K K Jacobsen, R Kleppe, C P Jacob, S Kittel-Schneider, M Ribasés, J A Ramos-Quiroga, V Richarte, M Casas, N R Mota, E H Grevet, M Klein, J Corominas, J Bralten, T Galesloot, A A Vasquez, S Herms, A J Forstner, H Larsson, G Breen, P Asherson, S Gross-Lesch, K P Lesch, S Cichon, M B Gabrielsen, O L Holmen, C H D Bau, J Buitelaar, L Kiemeney, S V Faraone, B Cormand, B Franke, A Reif, J Haavik, S Johansson
Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable childhood-onset neuropsychiatric condition, often persisting into adulthood. The genetic architecture of ADHD, particularly in adults, is largely unknown. We performed an exome-wide scan of adult ADHD using the Illumina Human Exome Bead Chip, which interrogates over 250 000 common and rare variants. Participants were recruited by the International Multicenter persistent ADHD CollaboraTion (IMpACT). Statistical analyses were divided into 3 steps: (1) gene-level analysis of rare variants (minor allele frequency (MAF)<1%); (2) single marker association tests of common variants (MAF⩾1%), with replication of the top signals; and (3) pathway analyses...
October 18, 2016: Translational Psychiatry
R A Bryant, K L Felmingham, B Liddell, P Das, G S Malhi
The FKBP5 polymorphism is a key regulator of the glucocorticoid system underpinning stress responsivity, and risk alleles can increase vulnerability for developing posttraumatic stress disorder. To delineate the specific role of FKBP5 risk alleles unencumbered by the confounds of psychopathology, this study investigated whether high-risk alleles of the FKBP5 polymorphism are characterized by distinctive neural activity during resting state. Thirty-seven healthy participants were selected on the basis of four SNPs in the FKBP5 gene region (rs3800373, rs9296158, rs1360780 and rs9470080) to determine participants who were carriers of the FKBP5 high- and low-risk alleles...
October 18, 2016: Translational Psychiatry
T Munk-Olsen, M L Maegbaek, B M Johannsen, X Liu, L M Howard, A di Florio, V Bergink, S Meltzer-Brody
Perinatal psychiatric episodes comprise various disorders and symptom severity, which are diagnosed and treated in multiple treatment settings. To date, no studies have quantified the incidence and prevalence of perinatal psychiatric episodes treated in primary and secondary care, which we aimed to do in the present study. We designed a descriptive prospective study and included information from Danish population registers to study first-time ever and recurrent psychiatric episodes during the perinatal period, including treatment at psychiatric facilities and general practitioners (GPs)...
October 18, 2016: Translational Psychiatry
A Kibleur, G Gras-Combe, D Benis, J Bastin, T Bougerol, S Chabardès, M Polosan, O David
High-frequency deep brain stimulation of the subthalamic nucleus can be used to treat severe obsessive-compulsive disorders that are refractory to conventional treatments. The mechanisms of action of this approach possibly rely on the modulation of associative-limbic subcortical-cortical loops, but remain to be fully elucidated. Here in 12 patients, we report the effects of high-frequency stimulation of the subthalamic nucleus on behavior, and on electroencephalographic responses and inferred effective connectivity during motor inhibition processes involved in the stop signal task...
October 18, 2016: Translational Psychiatry
L Germine, E B Robinson, J W Smoller, M E Calkins, T M Moore, H Hakonarson, M J Daly, P H Lee, A J Holmes, R L Buckner, R C Gur, R E Gur
Breakthroughs in genomics have begun to unravel the genetic architecture of schizophrenia risk, providing methods for quantifying schizophrenia polygenic risk based on common genetic variants. Our objective in the current study was to understand the relationship between schizophrenia genetic risk variants and neurocognitive development in healthy individuals. We first used combined genomic and neurocognitive data from the Philadelphia Neurodevelopmental Cohort (4303 participants ages 8-21 years) to screen 26 neurocognitive phenotypes for their association with schizophrenia polygenic risk...
October 18, 2016: Translational Psychiatry
A Rumshisky, M Ghassemi, T Naumann, P Szolovits, V M Castro, T H McCoy, R H Perlis
The ability to predict psychiatric readmission would facilitate the development of interventions to reduce this risk, a major driver of psychiatric health-care costs. The symptoms or characteristics of illness course necessary to develop reliable predictors are not available in coded billing data, but may be present in narrative electronic health record (EHR) discharge summaries. We identified a cohort of individuals admitted to a psychiatric inpatient unit between 1994 and 2012 with a principal diagnosis of major depressive disorder, and extracted inpatient psychiatric discharge narrative notes...
October 18, 2016: Translational Psychiatry
J M Parrott, L Redus, D Santana-Coelho, J Morales, X Gao, J C O'Connor
The kynurenine pathway of tryptophan metabolism has an important role in mediating the behavioral effects of inflammation, which has implications in understanding neuropsychiatric comorbidity and for the development of novel therapies. Inhibition of the rate-limiting enzyme, indoleamine 2,3-dioxygenase (IDO), prevents the development of many of these inflammation-induced preclinical behaviors. However, dysregulation in the balance of downstream metabolism, where neuroactive kynurenines are generated, is hypothesized to be a functionally important pathogenic feature of inflammation-induced depression...
October 18, 2016: Translational Psychiatry
P Seeman
Although all current antipsychotics act by interfering with the action of dopamine at dopamine D2 receptors, two recent reports showed that 800 to 1000 mg of cannabidiol per day alleviated the signs and symptoms of schizophrenia, although cannabidiol is not known to act on dopamine receptors. Because these recent clinical findings may indicate an important exception to the general rule that all antipsychotics interfere with dopamine at dopamine D2 receptors, the present study examined whether cannabidiol acted directly on D2 receptors, using tritiated domperidone to label rat brain striatal D2 receptors...
October 18, 2016: Translational Psychiatry
S Cohen, G Ifergane, E Vainer, M A Matar, Z Kaplan, J Zohar, A A Mathé, H Cohen
Pharmacotherapeutic intervention during traumatic memory consolidation has been suggested to alleviate or even prevent the development of posttraumatic stress disorder (PTSD). We recently reported that, in a controlled, prospective animal model, depriving rats of sleep following stress exposure prevents the development of a PTSD-like phenotype. Here, we report that administering the wake-promoting drug modafinil to rats in the aftermath of a stressogenic experience has a similar prophylactic effect, as it significantly reduces the prevalence of PTSD-like phenotype...
October 11, 2016: Translational Psychiatry
Y Horiuchi, M A Kondo, K Okada, Y Takayanagi, T Tanaka, T Ho, M Varvaris, K Tajinda, H Hiyama, K Ni, C Colantuoni, D Schretlen, N G Cascella, J Pevsner, K Ishizuka, A Sawa
Cognitive impairment is a key feature of schizophrenia (SZ) and determines functional outcome. Nonetheless, molecular signatures in neuronal tissues that associate with deficits are not well understood. We conducted nasal biopsy to obtain olfactory epithelium from patients with SZ and control subjects. The neural layers from the biopsied epithelium were enriched by laser-captured microdissection. We then performed an unbiased microarray expression study and implemented a systematic neuropsychological assessment on the same participants...
October 11, 2016: Translational Psychiatry
A-M D'Cruz, M W Mosconi, M E Ragozzino, E H Cook, J A Sweeney
Restricted and repetitive behaviors, and a pronounced preference for behavioral and environmental consistency, are distinctive characteristics of autism spectrum disorder (ASD). Alterations in frontostriatal circuitry that supports flexible behavior might underlie this behavioral impairment. In an functional magnetic resonance imaging study of 17 individuals with ASD, and 23 age-, gender- and IQ-matched typically developing control participants, reversal learning tasks were used to assess behavioral flexibility as participants switched from one learned response choice to a different response choice when task contingencies changed...
October 11, 2016: Translational Psychiatry
A L Cochran, M G McInnis, D B Forger
The Diagnostic and Statistical Manual of Mental Disorder (DSM) classification of bipolar disorder defines categories to reflect common understanding of mood symptoms rather than scientific evidence. This work aimed to determine whether bipolar I can be objectively classified from longitudinal mood data and whether resulting classes have clinical associations. Bayesian nonparametric hierarchical models with latent classes and patient-specific models of mood are fit to data from Longitudinal Interval Follow-up Evaluations (LIFE) of bipolar I patients (N=209)...
October 11, 2016: Translational Psychiatry
R Abend, I Jalon, G Gurevitch, R Sar-El, T Shechner, D S Pine, T Hendler, Y Bar-Haim
Research associates processes of fear conditioning and extinction with treatment of anxiety and stress-related disorders. Manipulation of these processes may therefore be beneficial for such treatment. The current study examines the effects of electrical brain stimulation on fear extinction processes in healthy humans in order to assess its potential relevance for treatment enhancement. Forty-five participants underwent a 3-day fear conditioning and extinction paradigm. Electrical stimulation targeting the medial prefrontal cortex was applied during the extinction-learning phase (Day 2)...
October 11, 2016: Translational Psychiatry
L S Resende, C E Amaral, R B S Soares, A S Alves, L Alves-Dos-Santos, L R G Britto, S Chiavegatto
MAX is a conserved constitutive small phosphoprotein from a network of transcription factors that are extensively studied in tumorigenesis and whose functions affect cell proliferation, differentiation and death. Inspired by its higher expression during development and in regions involved in emotional behaviors, we hypothesized its involvement in cerebral changes caused by early-life stress. We studied the effects of repeated social stress during adolescence on behaviors and on MAX and its putative partner MYC...
October 11, 2016: Translational Psychiatry
S-S Jiao, L-L Shen, C Zhu, X-L Bu, Y-H Liu, C-H Liu, X-Q Yao, L-L Zhang, H-D Zhou, D G Walker, J Tan, J Götz, X-F Zhou, Y-J Wang
Reduced expression of brain-derived neurotrophic factor (BDNF) has a crucial role in the pathogenesis of Alzheimer's disease (AD), which is characterized with the formation of neuritic plaques consisting of amyloid-beta (Aβ) and neurofibrillary tangles composed of hyperphosphorylated tau protein. A growing body of evidence indicates a potential protective effect of BDNF against Aβ-induced neurotoxicity in AD mouse models. However, the direct therapeutic effect of BDNF supplement on tauopathy in AD remains to be established...
October 4, 2016: Translational Psychiatry
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
Alzheimer's disease (AD) is the most frequent cause of dementia. Misfolded protein pathological hallmarks of AD are brain deposits of amyloid-β (Aβ) plaques and phosphorylated tau neurofibrillary tangles. However, doubts about the role of Aβ in AD pathology have been raised as Aβ is a common component of extracellular brain deposits found, also by in vivo imaging, in non-demented aged individuals. It has been suggested that some individuals are more prone to Aβ neurotoxicity and hence more likely to develop AD when aging brains start accumulating Aβ plaques...
October 4, 2016: Translational Psychiatry
D Peleg-Raibstein, G Sarker, K Litwan, S D Krämer, S M Ametamey, R Schibli, C Wolfrum
Epidemiological studies have shown an association between maternal overnutrition and increased risk of the progeny for the development of obesity as well as psychiatric disorders. Animal studies have shown results regarding maternal high-fat diet (HFD) and a greater risk of the offspring to develop obesity. However, it still remains unknown whether maternal HFD can program the central reward system in such a way that it will imprint long-term changes that will predispose the offspring to addictive-like behaviors that may lead to obesity...
October 4, 2016: Translational Psychiatry
E S Gouvea, V K Ota, C Noto, M L Santoro, L M Spindola, P N Moretti, C M Carvalho, G Xavier, A C Rios, J R Sato, M A F Hayashi, E Brietzke, A Gadelha, R A Bressan, Q Cordeiro, S I Belangero
Psychotic disorders affect ~3% of the general population and are among the most severe forms of mental diseases. In early stages of psychosis, clinical aspects may be difficult to distinguish from one another. Undifferentiated psychopathology at the first-episode of psychosis (FEP) highlights the need for biomarkers that can improve and refine differential diagnosis. We investigated gene expression differences between patients with FEP-schizophrenia spectrum (SCZ; N=53) or FEP-Mania (BD; N=16) and healthy controls (N=73)...
October 4, 2016: Translational Psychiatry
K Ma, A Xu, S Cui, M-R Sun, Y-C Xue, J-H Wang
Major depression is a prevalent emotion disorder. Chronic stressful life in genetically susceptible individuals is presumably a major etiology that leads to neuron and synapse atrophy in the limbic system. Molecular mechanisms underlying the pathological changes remain elusive. Mice were treated by chronic unpredictable mild stress (CUMS) until they demonstrated depression-like behavior. GABA release in the medial prefrontal cortex was evaluated by cell electrophysiology and imaging. Molecular profiles related to GABA synthesis and uptake were investigated by the high-throughput sequencings of microRNAs and mRNAs as well as western blot analysis in this cortical area...
October 4, 2016: Translational Psychiatry
C Tessier, K Sweers, A Frajerman, H Bergaoui, F Ferreri, C Delva, N Lapidus, A Lamaziere, J P Roiser, M De Hert, P Nuss
Schizophrenia is a severe mental condition in which several lipid abnormalities-either structural or metabolic-have been described. We tested the hypothesis that an abnormality in membrane lipid composition may contribute to aberrant dopamine signaling, and thereby symptoms and cognitive impairment, in schizophrenia (SCZ) patients. Antipsychotic-medicated and clinically stable SCZ outpatients (n=74) were compared with matched healthy subjects (HC, n=40). A lipidomic analysis was performed in red blood cell (RBC) membranes examining the major phospholipid (PL) classes and their associated fatty acids (FAs)...
October 4, 2016: Translational Psychiatry
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