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Molecular Psychiatry

Matthew Ii Timberlake, Yogesh Dwivedi
Depression is a devastating mental disorder that affects millions of people worldwide. Inflammation has been shown to be a key factor involved in the underlying pathophysiology of depression and has been shown in a substantial proportion of cases of depression. Changes attributed with morphological deformities and immunomodulation in susceptible regions of the depressed brain raised the possibility of altered cellular homeostasis transduced by the intracellular stress response. How emotional stressors can lead to an inflamed brain that directly affects physiology and activity is yet to be fully understood...
September 13, 2018: Molecular Psychiatry
Christos Chinopoulos
No abstract text is available yet for this article.
September 13, 2018: Molecular Psychiatry
Yu-Wei Chen, Manasmita Das, Esteban A Oyarzabal, Qing Cheng, Nicholas W Plummer, Kathleen G Smith, Grace K Jones, Daniel Malawsky, Jerrel L Yakel, Yen-Yu Ian Shih, Patricia Jensen
Noradrenergic signaling plays a well-established role in promoting the stress response. Here we identify a subpopulation of noradrenergic neurons, defined by developmental expression of Hoxb1, that has a unique role in modulating stress-related behavior. Using an intersectional chemogenetic strategy, in combination with behavioral and physiological analyses, we show that activation of Hoxb1-noradrenergic (Hoxb1-NE) neurons decreases anxiety-like behavior and promotes an active coping strategy in response to acute stressors...
September 13, 2018: Molecular Psychiatry
Jennifer L McGuire, Laura B Ngwenya, Robert E McCullumsmith
Traumatic brain injury (TBI) is a pervasive problem in the United States and worldwide, as the number of diagnosed individuals is increasing yearly and there are no efficacious therapeutic interventions. A large number of patients suffer with cognitive disabilities and psychiatric conditions after TBI, especially anxiety and depression. The constellation of post-injury cognitive and behavioral symptoms suggest permanent effects of injury on neurotransmission. Guided in part by preclinical studies, clinical trials have focused on high-yield pathophysiologic mechanisms, including protein aggregation, inflammation, metabolic disruption, cell generation, physiology, and alterations in neurotransmitter signaling...
September 13, 2018: Molecular Psychiatry
Luke Clark, Isabelle Boileau, Martin Zack
Gambling disorder (GD) was reclassified as a behavioral addiction in the DSM-5 and shares clinical and behavioral features with substance use disorders (SUDs). Neuroimaging studies of GD hold promise in isolating core features of the addiction syndrome, avoiding confounding effects of drug neurotoxicity. At the same time, a neurobiologically-grounded theory of how behaviors like gambling can become addictive remains lacking, posing a significant hurdle for ongoing decisions in addiction nosology. This article integrates research on reward-related brain activity (functional MRI) and neurotransmitter function (PET) in GD, alongside the consideration of structural MRI data as to whether these signals more likely reflect pre-existing vulnerability or neuroadaptive change...
September 13, 2018: Molecular Psychiatry
Hoau-Yan Wang, Mathew L MacDonald, Karin E Borgmann-Winter, Anamika Banerjee, Patrick Sleiman, Andrew Tom, Amber Khan, Kuo-Chieh Lee, Panos Roussos, Steven J Siegel, Scott E Hemby, Warren B Bilker, Raquel E Gur, Chang-Gyu Hahn
Multiple lines of evidence point to glutamatergic signaling in the postsynaptic density (PSD) as a pathophysiologic mechanism in schizophrenia. Integral to PSD glutamatergic signaling is reciprocal interplay between GluN and mGluR5 signaling. We examined agonist-induced mGluR5 signaling in the postmortem dorsolateral prefrontal cortex (DLPFC) derived from 17 patients and age-matched and sex-matched controls. The patient group showed a striking reduction in mGluR5 signaling, manifested by decreases in Gq/11 coupling and association with PI3K and Homer compared to controls (p < 0...
September 13, 2018: Molecular Psychiatry
Helen Q Cai, Vibeke S Catts, Maree J Webster, Cherrie Galletly, Dennis Liu, Maryanne O'Donnell, Thomas W Weickert, Cynthia Shannon Weickert
Elevated pro-inflammatory cytokines exist in both blood and brain of people with schizophrenia but how this affects molecular indices of the blood-brain barrier (BBB) is unclear. Eight mRNAs relating to BBB function, a microglia and three immune cell markers were measured by qPCR in the prefrontal cortex from 37 people with schizophrenia/schizoaffective disorder and 37 matched controls. This cohort was previously grouped into "high inflammation" and "low inflammation" subgroups based on cortical inflammatory-related transcripts...
September 13, 2018: Molecular Psychiatry
Nils Opel, Azmeraw T Amare, Ronny Redlich, Jonathan Repple, Claas Kaehler, Dominik Grotegerd, Katharina Dohm, Dario Zaremba, Elisabeth J Leehr, Joscha Böhnlein, Katharina Förster, Christian Bürger, Susanne Meinert, Verena Enneking, Daniel Emden, Ramona Leenings, Nils Winter, Tim Hahn, Walter Heindel, Jochen Bauer, David Wilhelms, Simon Schmitt, Andreas Jansen, Axel Krug, Igor Nenadic, Marcella Rietschel, Stephanie Witt, Andreas J Forstner, Markus M Nöthen, Tilo Kircher, Volker Arolt, Bernhard T Baune, Udo Dannlowski
Neuroticism has been shown to act as an important risk factor for major depressive disorder (MDD). Genetic and neuroimaging research has independently revealed biological correlates of neurotic personality including cortical alterations in brain regions of high relevance for affective disorders. Here we investigated the influence of a polygenic score for neuroticism (PGS) on cortical brain structure in a joint discovery sample of n = 746 healthy controls (HC) and n = 268 MDD patients. Findings were validated in an independent replication sample (n = 341 HC and n = 263 MDD)...
September 5, 2018: Molecular Psychiatry
Cesar Gonzalez, Enrique Armijo, Javiera Bravo-Alegria, Andrea Becerra-Calixto, Charles E Mays, Claudio Soto
The typical abnormalities observed in the brain of Alzheimer's disease (AD) patients include synaptic alterations, neuronal death, brain inflammation, and the accumulation of protein aggregates in the form of amyloid plaques and neurofibrillary tangles. Despite the development of many animal and in vitro models for AD, there is a lack of an experimental approach that fully recapitulates essential aspects of the disease in human cells. Here, we report the generation of a new model to study AD, consisting of cerebral organoids (COs) produced from human-induced pluripotent stem cells (iPSCs)...
August 31, 2018: Molecular Psychiatry
Abraham Nunes, Hugo G Schnack, Christopher R K Ching, Ingrid Agartz, Theophilus N Akudjedu, Martin Alda, Dag Alnæs, Silvia Alonso-Lana, Jochen Bauer, Bernhard T Baune, Erlend Bøen, Caterina Del Mar Bonnin, Geraldo F Busatto, Erick J Canales-Rodríguez, Dara M Cannon, Xavier Caseras, Tiffany M Chaim-Avancini, Udo Dannlowski, Ana M Díaz-Zuluaga, Bruno Dietsche, Nhat Trung Doan, Edouard Duchesnay, Torbjørn Elvsåshagen, Daniel Emden, Lisa T Eyler, Mar Fatjó-Vilas, Pauline Favre, Sonya F Foley, Janice M Fullerton, David C Glahn, Jose M Goikolea, Dominik Grotegerd, Tim Hahn, Chantal Henry, Derrek P Hibar, Josselin Houenou, Fleur M Howells, Neda Jahanshad, Tobias Kaufmann, Joanne Kenney, Tilo T J Kircher, Axel Krug, Trine V Lagerberg, Rhoshel K Lenroot, Carlos López-Jaramillo, Rodrigo Machado-Vieira, Ulrik F Malt, Colm McDonald, Philip B Mitchell, Benson Mwangi, Leila Nabulsi, Nils Opel, Bronwyn J Overs, Julian A Pineda-Zapata, Edith Pomarol-Clotet, Ronny Redlich, Gloria Roberts, Pedro G Rosa, Raymond Salvador, Theodore D Satterthwaite, Jair C Soares, Dan J Stein, Henk S Temmingh, Thomas Trappenberg, Anne Uhlmann, Neeltje E M van Haren, Eduard Vieta, Lars T Westlye, Daniel H Wolf, Dilara Yüksel, Marcus V Zanetti, Ole A Andreassen, Paul M Thompson, Tomas Hajek
Bipolar disorders (BDs) are among the leading causes of morbidity and disability. Objective biological markers, such as those based on brain imaging, could aid in clinical management of BD. Machine learning (ML) brings neuroimaging analyses to individual subject level and may potentially allow for their diagnostic use. However, fair and optimal application of ML requires large, multi-site datasets. We applied ML (support vector machines) to MRI data (regional cortical thickness, surface area, subcortical volumes) from 853 BD and 2167 control participants from 13 cohorts in the ENIGMA consortium...
August 31, 2018: Molecular Psychiatry
Martino Belvederi Murri, Mario Amore, Matteo Respino, George S Alexopoulos
The network theory conceptualizes mental disorders as complex networks of symptoms influencing each other by creating feedback loops, leading to a self-sustained syndromic constellation. Symptoms central to the network have the greatest impact in sustaining the rest of symptoms. This analysis focused on the network structure of depressive symptoms in late-life because of their distinct etiologic factors, clinical presentation, and outcomes. We analyzed cross-sectional data from wave 2 of the 19 country Survey of Health, Ageing, and Retirement in Europe (SHARE) and included non-institutionalized adults aged 65 years or older (mean age 74 years, 59% females) endorsing at least one depressive symptom on the EURO-D scale for depression (N =8,557)...
August 31, 2018: Molecular Psychiatry
S Riazuddin, M Hussain, A Razzaq, Z Iqbal, M Shahzad, D L Polla, Y Song, E van Beusekom, A A Khan, L Tomas-Roca, M Rashid, M Y Zahoor, W M Wissink-Lindhout, M A R Basra, M Ansar, Z Agha, K van Heeswijk, F Rasheed, M Van de Vorst, J A Veltman, C Gilissen, J Akram, T Kleefstra, M Z Assir, D Grozeva, K Carss, F L Raymond, T D O'Connor, S A Riazuddin, S N Khan, Z M Ahmed, A P M de Brouwer, H van Bokhoven, S Riazuddin
This Article was originally published under a CC BY-NC-SA 4.0 license, but has now been made available under a CC BY 4.0 license. The PDF and HTML versions of the Article have been modified accordingly.
August 31, 2018: Molecular Psychiatry
Xueying Jiang, Sevilla D Detera-Wadleigh, Nirmala Akula, Barbara S Mallon, Liping Hou, Tiaojiang Xiao, Gary Felsenfeld, Xinglong Gu, Francis J McMahon
Biological characterization of genetic variants identified in genome-wide association studies (GWAS) remains a substantial challenge. Here we used human-induced pluripotent stem cells (iPSC) and their neural derivatives to characterize common variants on chromosome 3p22 that have been associated by GWAS with major mental illnesses. IPSC-derived neural progenitor cells carrying the risk allele of the single nucleotide polymorphism (SNP), rs9834970, displayed lower baseline TRANK1 expression that was rescued by chronic treatment with therapeutic dosages of valproic acid (VPA)...
August 22, 2018: Molecular Psychiatry
Stephen A Semick, Leonardo Collado-Torres, Christina A Markunas, Joo Heon Shin, Amy Deep-Soboslay, Ran Tao, Marilyn A Huestis, Laura J Bierut, Brion S Maher, Eric O Johnson, Thomas M Hyde, Daniel R Weinberger, Dana B Hancock, Joel E Kleinman, Andrew E Jaffe
Cigarette smoking during pregnancy is a major public health concern. While there are well-described consequences in early child development, there is very little known about the effects of maternal smoking on human cortical biology during prenatal life. We therefore performed a genome-wide differential gene expression analysis using RNA sequencing (RNA-seq) on prenatal (N = 33; 16 smoking-exposed) as well as adult (N = 207; 57 active smokers) human postmortem prefrontal cortices. Smoking exposure during the prenatal period was directly associated with differential expression of 14 genes; in contrast, during adulthood, despite a much larger sample size, only two genes showed significant differential expression (FDR < 10%)...
August 21, 2018: Molecular Psychiatry
Marie Rieux, Melanie Alpaugh, Francesca Cicchetti
No abstract text is available yet for this article.
August 20, 2018: Molecular Psychiatry
Shin-Ichi Kano, Colin A Hodgkinson, Lorraine Jones-Brando, Sharon Eastwood, Koko Ishizuka, Minae Niwa, Eric Y Choi, Daniel J Chang, Yian Chen, Swetha D Velivela, Flora Leister, Joel Wood, Kodavali Chowdari, Francesca Ducci, Daniel A Caycedo, Elizabeth Heinz, Emily R Newman, Nicola Cascella, Preben B Mortensen, Peter P Zandi, Faith Dickerson, Vishwajit Nimgaonkar, David Goldman, Paul J Harrison, Robert H Yolken, Akira Sawa
Clinical studies frequently report that patients with major mental illness such as schizophrenia and bipolar disorder have co-morbid physical conditions, suggesting that systemic alterations affecting both brain and peripheral tissues might underlie the disorders. Numerous studies have reported elevated levels of anti-Toxoplasma gondii (T. gondii) antibodies in patients with major mental illnesses, but the underlying mechanism was unclear. Using multidisciplinary epidemiological, cell biological, and gene expression profiling approaches, we report here multiple lines of evidence suggesting that a major mental illness-related susceptibility factor, Disrupted in schizophrenia (DISC1), is involved in host immune responses against T...
August 20, 2018: Molecular Psychiatry
Francesco Petrelli, Glenn Dallérac, Luca Pucci, Corrado Calì, Tamara Zehnder, Sébastien Sultan, Salvatore Lecca, Andrea Chicca, Andrei Ivanov, Cédric S Asensio, Vidar Gundersen, Nicolas Toni, Graham William Knott, Fulvio Magara, Jürg Gertsch, Frank Kirchhoff, Nicole Déglon, Bruno Giros, Robert H Edwards, Jean-Pierre Mothet, Paola Bezzi
Astrocytes orchestrate neural development by powerfully coordinating synapse formation and function and, as such, may be critically involved in the pathogenesis of neurodevelopmental abnormalities and cognitive deficits commonly observed in psychiatric disorders. Here, we report the identification of a subset of cortical astrocytes that are competent for regulating dopamine (DA) homeostasis during postnatal development of the prefrontal cortex (PFC), allowing for optimal DA-mediated maturation of excitatory circuits...
August 20, 2018: Molecular Psychiatry
Paul J Harrison, Lucy Colbourne, Charlotte H Harrison
Various neuropathological findings have been reported in bipolar disorder (BD). However, it is unclear which findings are well established. To address this gap, we carried out a systematic review of the literature. We searched over 5000 publications, identifying 103 data papers, of which 81 were eligible for inclusion. Our main findings can be summarised as follows. First, most studies have relied on a limited number of brain collections, and have used relatively small sample sizes (averaging 12 BD cases and 15 controls)...
August 20, 2018: Molecular Psychiatry
Leah M Mayo, Anna Asratian, Johan Lindé, Lovisa Holm, Daniel Nätt, Gaëlle Augier, Niclas Stensson, Haley A Vecchiarelli, Georgia Balsevich, Robert J Aukema, Bijar Ghafouri, Primavera A Spagnolo, Francis S Lee, Matthew N Hill, Markus Heilig
Post-traumatic stress disorder (PTSD) is a common, debilitating condition with limited treatment options. Extinction of fear memories through prolonged exposure therapy, the primary evidence-based behavioral treatment for PTSD, has only partial efficacy. In mice, pharmacological inhibition of fatty acid amide hydrolase (FAAH) produces elevated levels of anandamide (AEA) and promotes fear extinction, suggesting that FAAH inhibitors may aid fear extinction-based treatments. A human FAAH 385C->A substitution encodes an FAAH enzyme with reduced catabolic efficacy...
August 17, 2018: Molecular Psychiatry
Ryan Sun, Zhaoxi Wang, Birgit Claus Henn, Li Su, Quan Lu, Xihong Lin, Robert O Wright, David C Bellinger, Molly Kile, Maitreyi Mazumdar, Martha Maria Tellez-Rojo, Lourdes Schnaas, David C Christiani
It is believed that genetic factors play a large role in the development of many cognitive and neurological processes; however, epidemiological evidence for the genetic basis of childhood neurodevelopment is very limited. Identification of the genetic polymorphisms associated with early-stage neurodevelopment will help elucidate biological mechanisms involved in neuro-behavior and provide a better understanding of the developing brain. To search for such variants, we performed a genome-wide association study (GWAS) for infant mental and motor ability at two years of age with mothers and children recruited from cohorts in Bangladesh and Mexico...
August 17, 2018: Molecular Psychiatry
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