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Molecular Psychiatry

Roy H Perlis, Maurizio Fava, Thomas H McCoy
No abstract text is available yet for this article.
November 14, 2018: Molecular Psychiatry
Yuan Zhang, Longfei Du, Ying Bai, Bing Han, Cancan He, Liang Gong, Rongrong Huang, Ling Shen, Jie Chao, Pei Liu, Hongxing Zhang, Haisan Zhang, Ling Gu, Junxu Li, Gang Hu, Chunming Xie, Zhijun Zhang, Honghong Yao
Circular RNAs (circRNAs), highly expressed in the central nervous system, are involved in various regulatory processes and implicated in some pathophysiology. However, the potential role of circRNAs in psychiatric diseases, particularly major depressive disorder (MDD), remains largely unknown. Here, we demonstrated that circular RNA DYM (circDYM) levels were significantly decreased both in the peripheral blood of patients with MDD and in the two depressive-like mouse models: the chronic unpredictable stress (CUS) and lipopolysaccharide (LPS) models...
November 9, 2018: Molecular Psychiatry
Preben Bo Mortensen
No abstract text is available yet for this article.
November 9, 2018: Molecular Psychiatry
Evelyn Andersson, James J Crowley, Nils Lindefors, Brjánn Ljótsson, Erik Hedman-Lagerlöf, Julia Boberg, Samir El Alaoui, Robert Karlsson, Yi Lu, Manuel Mattheisen, Anna K Kähler, Cecilia Svanborg, David Mataix-Cols, Simon Mattsson, Erik Forsell, Viktor Kaldo, Martin Schalling, Catharina Lavebratt, Patrick F Sullivan, Christian Rück
No abstract text is available yet for this article.
November 8, 2018: Molecular Psychiatry
Guusje Collin, Larry J Seidman, Matcheri S Keshavan, William S Stone, Zhenghan Qi, Tianhong Zhang, Yingying Tang, Huijun Li, Sheeba Arnold Anteraper, Margaret A Niznikiewicz, Robert W McCarley, Martha E Shenton, Jijun Wang, Susan Whitfield-Gabrieli
The emergence of prodromal symptoms of schizophrenia and their evolution into overt psychosis may stem from an aberrant functional reorganization of the brain during adolescence. To examine whether abnormalities in connectome organization precede psychosis onset, we performed a functional connectome analysis in a large cohort of medication-naive youth at risk for psychosis from the Shanghai At Risk for Psychosis (SHARP) study. The SHARP program is a longitudinal study of adolescents and young adults at Clinical High Risk (CHR) for psychosis, conducted at the Shanghai Mental Health Center in collaboration with neuroimaging laboratories at Harvard and MIT...
November 8, 2018: Molecular Psychiatry
Mandy Johnstone, Navneet A Vasistha, Miruna C Barbu, Owen Dando, Karen Burr, Edward Christopher, Sophie Glen, Christelle Robert, Rana Fetit, Kenneth G Macleod, Matthew R Livesey, David St Clair, Douglas H R Blackwood, Kirsty Millar, Neil O Carragher, Giles E Hardingham, David J A Wyllie, Eve C Johnstone, Heather C Whalley, Andrew M McIntosh, Stephen M Lawrie, Siddharthan Chandran
The molecular basis of how chromosome 16p13.11 microduplication leads to major psychiatric disorders is unknown. Here we have undertaken brain imaging of patients carrying microduplications in chromosome 16p13.11 and unaffected family controls, in parallel with iPS cell-derived cerebral organoid studies of the same patients. Patient MRI revealed reduced cortical volume, and corresponding iPSC studies showed neural precursor cell (NPC) proliferation abnormalities and reduced organoid size, with the NPCs therein displaying altered planes of cell division...
November 6, 2018: Molecular Psychiatry
Aaron Tan, Sara Costi, Laurel S Morris, Nicholas T Van Dam, Marin Kautz, Alexis E Whitton, Allyson K Friedman, Katherine A Collins, Gabriella Ahle, Nisha Chadha, Brian Do, Diego A Pizzagalli, Dan V Iosifescu, Eric J Nestler, Ming-Hu Han, James W Murrough
Major depressive disorder (MDD) is a leading cause of disability worldwide, yet current treatment strategies remain limited in their mechanistic diversity. Recent evidence has highlighted a promising novel pharmaceutical target-the KCNQ-type potassium channel-for the treatment of depressive disorders, which may exert a therapeutic effect via functional changes within the brain reward system, including the ventral striatum. The current study assessed the effects of the KCNQ channel opener ezogabine (also known as retigabine) on reward circuitry and clinical symptoms in patients with MDD...
November 1, 2018: Molecular Psychiatry
Mehdi Farokhnia, Sara L Deschaine, Armin Sadighi, Lisa A Farinelli, Mary R Lee, Fatemeh Akhlaghi, Lorenzo Leggio
Previous studies suggest that GABA-B receptor agonism may represent an effective pharmacological approach to treat addictive disorders. Baclofen is a selective GABA-B receptor agonist which has been investigated as a potential treatment for alcohol use disorder. However, research is needed to understand the biobehavioral mechanisms underlying baclofen's effect on alcohol use. In the present randomized, double-blind, placebo-controlled study, thirty-four alcohol-dependent individuals were randomized to receive baclofen (30 mg/d) or placebo for a week, and then participated in a laboratory experiment consisting of three procedures: alcohol cue-reactivity, priming, and self-administration...
October 31, 2018: Molecular Psychiatry
Zhentao Zhang, Xiao-Guang Li, Zhi-Hao Wang, Mingke Song, Shan Ping Yu, Seong Su Kang, Xia Liu, Zhaohui Zhang, Manling Xie, Gong-Ping Liu, Jian-Zhi Wang, Keqiang Ye
δ-Secretase, an age-dependent asparagine protease, cleaves both amyloid precursor protein (APP) and Tau and is required for amyloid plaque and neurofibrillary tangle pathologies in Alzheimer's disease (AD). However, whether δ-secretase activation is sufficient to trigger AD pathogenesis remains unknown. Here we show that the fragments of δ-secretase-cleavage, APP (586-695) and Tau(1-368), additively drive AD pathogenesis and cognitive dysfunctions. Tau(1-368) strongly augments BACE1 expression and Aβ generation in the presence of APP...
October 31, 2018: Molecular Psychiatry
Jun Oh, Cathrine Petersen, Christine M Walsh, Jackson C Bittencourt, Thomas C Neylan, Lea T Grinberg
Sleep and wakefulness control in the mammalian brain requires the coordination of various discrete interconnected neurons. According to the most conventional sleep model, wake-promoting neurons (WPNs) and sleep-promoting neurons (SPNs) compete for network dominance, creating a systematic "switch" that results in either the sleep or awake state. WPNs and SPNs are ubiquitous in the brainstem and diencephalon, areas that together contain <1% of the neurons in the human brain. Interestingly, many of these WPNs and SPNs co-express and co-release various types of the neurotransmitters that often have opposing modulatory effects on the network...
October 30, 2018: Molecular Psychiatry
K Gapp, G van Steenwyk, P L Germain, W Matsushima, K L M Rudolph, F Manuella, M Roszkowski, G Vernaz, T Ghosh, P Pelczar, I M Mansuy, E A Miska
Psychiatric diseases have a strong heritable component known to not be restricted to DNA sequence-based genetic inheritance alone but to also involve epigenetic factors in germ cells. Initial evidence suggested that sperm RNA is causally linked to the transmission of symptoms induced by traumatic experiences. Here, we show that alterations in long RNA in sperm contribute to the inheritance of specific trauma symptoms. Injection of long RNA fraction from sperm of males exposed to postnatal trauma recapitulates the effects on food intake, glucose response to insulin and risk-taking in adulthood whereas the small RNA fraction alters body weight and behavioural despair...
October 30, 2018: Molecular Psychiatry
Maurizio Fava, Michael E Thase, Madhukar H Trivedi, Elliot Ehrich, William F Martin, Asli Memisoglu, Narinder Nangia, Arielle D Stanford, Miao Yu, Sanjeev Pathak
No abstract text is available yet for this article.
October 29, 2018: Molecular Psychiatry
Qi Yan, Kwangsik Nho, Jorge L Del-Aguila, Xingbin Wang, Shannon L Risacher, Kang-Hsien Fan, Beth E Snitz, Howard J Aizenstein, Chester A Mathis, Oscar L Lopez, F Yesim Demirci, Eleanor Feingold, William E Klunk, Andrew J Saykin, Carlos Cruchaga, M Ilyas Kamboh
Deposition of amyloid plaques in the brain is one of the two main pathological hallmarks of Alzheimer's disease (AD). Amyloid positron emission tomography (PET) is a neuroimaging tool that selectively detects in vivo amyloid deposition in the brain and is a reliable endophenotype for AD that complements cerebrospinal fluid biomarkers with regional information. We measured in vivo amyloid deposition in the brains of ~1000 subjects from three collaborative AD centers and ADNI using 11 C-labeled Pittsburgh Compound-B (PiB)-PET imaging followed by meta-analysis of genome-wide association studies, first to our knowledge for PiB-PET, to identify novel genetic loci for this endophenotype...
October 25, 2018: Molecular Psychiatry
Jordan Marrocco, Nathan R Einhorn, Gordon H Petty, Howard Li, Neelima Dubey, Jessica Hoffman, Karen F Berman, David Goldman, Francis S Lee, Peter J Schmidt, Bruce S McEwen
Premenstrual dysphoric disorder (PMDD) affects over 5% of women, with symptoms similar to anxiety and major depression, and is associated with differential sensitivity to circulating ovarian hormones. Little is known about the genetic and epigenetic factors that increase the risk to develop PMDD. We report that 17β-estradiol (E2) affects the behavior and the epigenome in a mouse model carrying a single-nucleotide polymorphism of the brain-derived neurotrophic factor gene (BDNF Val66Met), in a way that recapitulates the hallmarks of PMDD...
October 24, 2018: Molecular Psychiatry
M Elena Martinez, Christine W Duarte, J Patrizia Stohn, Aldona Karaczyn, Zhaofei Wu, Victoria E DeMambro, Arturo Hernandez
Genetic factors do not fully account for the relatively high heritability of neurodevelopmental conditions, suggesting that non-genetic heritable factors contribute to their etiology. To evaluate the potential contribution of aberrant thyroid hormone status to the epigenetic inheritance of neurological phenotypes, we examined genetically normal F2 generation descendants of mice that were developmentally overexposed to thyroid hormone due to a Dio3 mutation. Hypothalamic gene expression profiling in postnatal day 15 F2 descendants on the paternal lineage of ancestral male and female T3-overexposed mice revealed, respectively, 1089 and 1549 differentially expressed genes...
October 24, 2018: Molecular Psychiatry
Tadafumi Kato, Mie Kubota-Sakashita, Tomoaki M Kato
No abstract text is available yet for this article.
October 23, 2018: Molecular Psychiatry
Christopher Hübel, Sarah J Marzi, Gerome Breen, Cynthia M Bulik
Eating disorders are complex heritable conditions influenced by both genetic and environmental factors. Given the progress of genomic discovery in anorexia nervosa, with the identification of the first genome-wide significant locus, as well as animated discussion of epigenetic mechanisms in linking environmental factors with disease onset, our goal was to conduct a systematic review of the current body of evidence on epigenetic factors in eating disorders to inform future directions in this area. Following PRISMA guidelines, two independent authors conducted a search within PubMed and Web of Science and identified 18 journal articles and conference abstracts addressing anorexia nervosa (n = 13), bulimia nervosa (n = 6), and binge-eating disorder (n = 1), published between January 2003 and October 2017...
October 23, 2018: Molecular Psychiatry
Hilary Coon, Todd M Darlington, Emily DiBlasi, W Brandon Callor, Elliott Ferris, Alison Fraser, Zhe Yu, Nancy William, Sujan C Das, Sheila E Crowell, Danli Chen, John S Anderson, Michael Klein, Leslie Jerominski, Dale Cannon, Andrey Shabalin, Anna Docherty, Megan Williams, Ken R Smith, Brooks Keeshin, Amanda V Bakian, Erik Christensen, Qingqin S Li, Nicola J Camp, Douglas Gray
Suicide is the 10th leading cause of death in the United States. Although environment has undeniable impact, evidence suggests that genetic factors play a significant role in completed suicide. We linked a resource of ~ 4500 DNA samples from completed suicides obtained from the Utah Medical Examiner to genealogical records and medical records data available on over eight million individuals. This linking has resulted in the identification of high-risk extended families (7-9 generations) with significant familial risk of completed suicide...
October 23, 2018: Molecular Psychiatry
Toby Pillinger, Enrico D'Ambrosio, Robert McCutcheon, Oliver D Howes
Updated online [insert date]: This article was originally published under standard licence, but has now been made available under a [CC BY 4.0] license. The PDF and HTML versions of the paper have been modified accordingly.
October 18, 2018: Molecular Psychiatry
Ralf Kuja-Halkola, Kristina Lind Juto, Charlotte Skoglund, Christian Rück, David Mataix-Cols, Ana Pérez-Vigil, Johan Larsson, Clara Hellner, Niklas Långström, Predrag Petrovic, Paul Lichtenstein, Henrik Larsson
Large-scale family studies on the co-occurrence of attention-deficit/hyperactivity disorder (ADHD) and borderline personality disorder (BPD) are lacking. Thus, we aimed to estimate the co-occurrence and familial co-aggregation of clinically ascertained ADHD and BPD diagnoses using the entire Swedish population. In a register-based cohort design we included individuals born in Sweden 1979-2001, and identified their diagnoses during 1997-2013; in total, 2,113,902 individuals were included in the analyses. We obtained clinical diagnoses of ADHD and BPD from inpatient and outpatient care...
October 15, 2018: Molecular Psychiatry
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