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Translational Psychiatry

Johan Ormel, Catharina A Hartman, Harold Snieder
The recent successful genome-wide association studies (GWASs) for depression have yielded more than 80 replicated loci and brought back the excitement that had evaporated during the years of negative GWAS findings. The identified loci provide anchors to explore their relevance for depression, but this comes with new challenges. Using the watershed model of genotype-phenotype relationships as a conceptual aid and recent genetic findings on other complex phenotypes, we discuss why it took so long and identify seven future challenges...
March 15, 2019: Translational Psychiatry
Arpan Dutta, Shane McKie, Darragh Downey, Emma Thomas, Gabriella Juhasz, Danilo Arnone, Rebecca Elliott, Steve Williams, J F William Deakin, Ian M Anderson
The relationship between altered default mode network (DMN) connectivity and abnormal serotonin function in major depressive disorder (MDD) has not been investigated. Using intravenous citalopram and resting-state fMRI, we investigated DMN intra-network connectivity and serotonin function in 77 healthy controls and patients with MDD. There were no significant main effects of MDD or citalopram on DMN intra-network connectivity; however, significant interactions indicated that group differences under saline were modified by citalopram...
March 15, 2019: Translational Psychiatry
Héléna A Gaspar, Zachary Gerring, Christopher Hübel, Christel M Middeldorp, Eske M Derks, Gerome Breen
The major depressive disorder (MDD) working group of the Psychiatric Genomics Consortium (PGC) has published a genome-wide association study (GWAS) for MDD in 130,664 cases, identifying 44 risk variants. We used these results to investigate potential drug targets and repurposing opportunities. We built easily interpretable bipartite drug-target networks integrating interactions between drugs and their targets, genome-wide association statistics, and genetically predicted expression levels in different tissues, using the online tool Drug Targetor ( drugtargetor...
March 15, 2019: Translational Psychiatry
Mina Fukai, Tomoyasu Bunai, Tetsu Hirosawa, Mitsuru Kikuchi, Shigeru Ito, Yoshio Minabe, Yasuomi Ouchi
Transcranial direct-current stimulation (tDCS) to the dorsolateral prefrontal cortex (DLPFC) has been established as an effective and noninvasive method to modulate cognitive function. Nevertheless, the mechanisms causing those cognitive changes under the tDCS remain largely unknown. We strove to elucidate the cognito-biological relation under the tDCS condition by examining whether the dopamine system activated by tDCS is involved in cognitive changes in human participants, or not. To evaluate the dopamine system, we used [11 C]-raclopride positron emission tomography (PET) scanning: 20 healthy men underwent two [11 C]-raclopride PET scans and subsequent neuropsychological tests...
March 15, 2019: Translational Psychiatry
Adam J Walker, J Blair Price, Kristin Borreggine, Shari L Sutor, Andrea Gogos, Jane A McGillivray, Mark A Frye, Susannah J Tye
Lithium has been shown to have some therapeutic efficacy as an adjunctive treatment for intractable forms of major depression. Activation of mammalian target of rapamycin (mTOR) and inhibition of glycogen synthase kinase-3β (GSK3β) have been implicated in its putative mechanisms of action. These proteins are integral components of the insulin signaling pathway, which may serve as a critical co-regulator of drug action. Utilizing an animal model of tricyclic antidepressant resistance, we investigated the relationship between insulin signaling and antidepressant response to lithium augmentation...
March 15, 2019: Translational Psychiatry
Fabrice Chimienti, Laurent Cavarec, Laurent Vincent, Nicolas Salvetat, Victoria Arango, Mark D Underwood, J John Mann, Jean-François Pujol, Dinah Weissmann
Author forgot to attach a supplementary doc file which includes the supplementary methods and supplementary figure legends.
March 14, 2019: Translational Psychiatry
Kevin P Jensen, Richard Lieberman, Henry R Kranzler, Joel Gelernter, Kaitlin Clinton, Jonathan Covault
Alcohol use contributes to numerous diseases and injuries. The nervous system is affected by alcohol in diverse ways, though the molecular mechanisms of these effects are not clearly understood. Using human-induced pluripotent stem cells (iPSCs), we developed a neural cell culture model to identify the mechanisms of alcohol's effects. iPSCs were generated from fibroblasts and differentiated into forebrain neural cells cultures that were treated with 50 mM alcohol or sham conditions (same media lacking alcohol) for 7 days...
March 12, 2019: Translational Psychiatry
Changhong Li, Yanjun Hou, Jia Zhang, Guangzhi Sui, Xueliang Du, Julio Licinio, Ma-Li Wong, Yunlei Yang
Recent studies indicate that activation of hypothalamic Agouti-related protein (Agrp) neurons can increase forage-related/repetitive behavior and decrease anxiety levels. However, the impact of physiological hunger states and food deprivation on anxiety-related behaviors have not been clarified. In the present study, we evaluated changes in anxiety levels induced by physiological hunger states and food deprivation, and identified the neuron population involved. Ad libitum fed and fasted mice were tested in the open field and elevated plus-maze behavioral tests...
March 8, 2019: Translational Psychiatry
Fumi Masuda, Shinichiro Nakajima, Takahiro Miyazaki, Kazunari Yoshida, Sakiko Tsugawa, Masataka Wada, Kamiyu Ogyu, Paul E Croarkin, Daniel M Blumberger, Zafiris J Daskalakis, Masaru Mimura, Yoshihiro Noda
Cortical excitation/inhibition (E/I) imbalances contribute to various clinical symptoms observed in autism spectrum disorder (ASD). However, the detailed pathophysiologic underpinning of E/I imbalance remains uncertain. Transcranial magnetic stimulation (TMS) motor-evoked potentials (MEP) are a non-invasive tool for examining cortical inhibition in ASD. Here, we conducted a systematic review on TMS neurophysiology in motor cortex (M1) such as MEPs and short-interval intracortical inhibition (SICI) between individuals with ASD and controls...
March 7, 2019: Translational Psychiatry
Youna Vandaele, Caroline Vouillac-Mendoza, Serge H Ahmed
The concept of compulsive cocaine-seeking habits is difficult to reconcile with other evidence showing that humans and even rats remain able to shift their choice away from the drug and toward an alternative nondrug reward, when available. This paradox could dissolve if preference for the nondrug option reflected in fact inflexible habitual decision-making (i.e., fixed in a habitual control mode, with no return to a goal-directed control mode). Previous research in rats has shown that prior drug use can favor habit formation, but whether the resulting habits are inflexible or not is largely unknown...
March 6, 2019: Translational Psychiatry
Wei Guo, Rodrigo Machado-Vieira, Sanjay Mathew, James W Murrough, Dennis S Charney, Matthew Grunebaum, Maria A Oquendo, Bashkim Kadriu, Nirmala Akula, Ioline Henter, Peixiong Yuan, Kathleen Merikangas, Wayne Drevets, Maura Furey, J John Mann, Francis J McMahon, Carlos A Zarate, Yin Yao Shugart
Michael F. Grunebaum's name was misspelled/misstated as "Gruenbaum M.F." in the original Article. This has now been updated in the HTML and PDF versions of this Article.
March 5, 2019: Translational Psychiatry
Morgan L Alexander, Sankaraleengam Alagapan, Courtney E Lugo, Juliann M Mellin, Caroline Lustenberger, David R Rubinow, Flavio Fröhlich
Major depressive disorder (MDD) is one of the most common psychiatric disorders, but pharmacological treatments are ineffective in a substantial fraction of patients and are accompanied by unwanted side effects. Here we evaluated the feasibility and efficacy of transcranial alternating current stimulation (tACS) at 10 Hz, which we hypothesized would improve clinical symptoms by renormalizing alpha oscillations in the left dorsolateral prefrontal cortex (dlPFC). To this end, 32 participants with MDD were randomized to 1 of 3 arms and received daily 40 min sessions of either 10 Hz-tACS, 40 Hz-tACS, or active sham stimulation for 5 consecutive days...
March 5, 2019: Translational Psychiatry
Maria Niarchou, Samuel J R A Chawner, Joanne L Doherty, Anne M Maillard, Sébastien Jacquemont, Wendy K Chung, LeeAnne Green-Snyder, Raphael A Bernier, Robin P Goin-Kochel, Ellen Hanson, David E J Linden, Stefanie C Linden, F Lucy Raymond, David Skuse, Jeremy Hall, Michael J Owen, Marianne B M van den Bree
One of the co-authors, Marianne B.M. van den Bree has had her name incorrectly abbreviated by citation manager. It was stated as "Bree MBMVD14", but has been updated to "van den Bree, M.B.M." in the HTML, PDF, and XML versions of this article.
March 5, 2019: Translational Psychiatry
Charlie Hatcher, Caroline L Relton, Tom R Gaunt, Tom G Richardson
Integrative approaches that harness large-scale molecular datasets can help develop mechanistic insight into findings from genome-wide association studies (GWAS). We have performed extensive analyses to uncover transcriptional and epigenetic processes which may play a role in complex trait variation. This was undertaken by applying Bayesian multiple-trait colocalization systematically across the genome to identify genetic variants responsible for influencing intermediate molecular phenotypes as well as complex traits...
February 28, 2019: Translational Psychiatry
Laura Ponson, Marie Gomot, Romuald Blanc, Catherine Barthelemy, Sylvie Roux, Arnold Munnich, Serge Romana, Nadia Aguillon-Hernandez, Valérie Malan, Frédérique Bonnet-Brilhault
Since the online publication of the above article, the authors have noted errors with the author list. The author names were listed as '(last name)(first name)' instead of '(first name)(last name)'.
February 28, 2019: Translational Psychiatry
Kate Porcheret, Dalena van Heugten-van der Kloet, Guy M Goodwin, Russell G Foster, Katharina Wulff, Emily A Holmes
Sleep enhances the consolidation of memory; however, this property of sleep may be detrimental in situations where memories of an event can lead to psychopathology, such as following a traumatic event. Intrusive memories of trauma are emotional memories that spring to mind involuntarily and are a core feature of post-traumatic stress disorder. Total sleep deprivation in a hospital setting on the first night after an analogue trauma (a trauma film) led to fewer intrusive memories compared to sleep as usual in one study...
February 27, 2019: Translational Psychiatry
Mark Drakesmith, Greg D Parker, Jacqueline Smith, Stefanie C Linden, Elliott Rees, Nigel Williams, Michael J Owen, Marianne van den Bree, Jeremy Hall, Derek K Jones, David E J Linden
Genomic copy number variants (CNVs) are amongst the most highly penetrant genetic risk factors for neuropsychiatric disorders. The scarcity of carriers of individual CNVs and their phenotypical heterogeneity limits investigations of the associated neural mechanisms and endophenotypes. We applied a novel design based on CNV penetrance for schizophrenia (Sz) and developmental delay (DD) that allows us to identify structural sequelae that are most relevant to neuropsychiatric disorders. Our focus on brain structural abnormalities was based on the hypothesis that convergent mechanisms contributing to neurodevelopmental disorders would likely manifest in the macro- and microstructure of white matter and cortical and subcortical grey matter...
February 25, 2019: Translational Psychiatry
Monique Ernst, Brenda Benson, Eric Artiges, Adam X Gorka, Herve Lemaitre, Tiffany Lago, Ruben Miranda, Tobias Banaschewski, Arun L W Bokde, Uli Bromberg, Rüdiger Brühl, Christian Büchel, Anna Cattrell, Patricia Conrod, Sylvane Desrivières, Tahmine Fadai, Herta Flor, Antoine Grigis, Juergen Gallinat, Hugh Garavan, Penny Gowland, Yvonne Grimmer, Andreas Heinz, Viola Kappel, Frauke Nees, Dimitri Papadopoulos-Orfanos, Jani Penttilä, Luise Poustka, Michael N Smolka, Argyris Stringaris, Maren Struve, Betteke M van Noort, Henrik Walter, Robert Whelan, Gunter Schumann, Christian Grillon, Marie-Laure Paillère Martinot, Jean-Luc Martinot
This study examines the effects of puberty and sex on the intrinsic functional connectivity (iFC) of brain networks, with a focus on the default-mode network (DMN). Consistently implicated in depressive disorders, the DMN's function may interact with puberty and sex in the development of these disorders, whose onsets peak in adolescence, and which show strong sex disproportionality (females > males). The main question concerns how the DMN evolves with puberty as a function of sex. These effects are expected to involve within- and between-network iFC, particularly, the salience and the central-executive networks, consistent with the Triple-Network Model...
February 25, 2019: Translational Psychiatry
Seena Fazel, Achim Wolf, Henrik Larsson, Susan Mallett, Thomas R Fanshawe
Assessment of suicide risk in individuals with severe mental illness is currently inconsistent, and based on clinical decision-making with or without tools developed for other purposes. We aimed to develop and validate a predictive model for suicide using data from linked population-based registers in individuals with severe mental illness. A national cohort of 75,158 Swedish individuals aged 15-65 with a diagnosis of severe mental illness (schizophrenia-spectrum disorders, and bipolar disorder) with 574,018 clinical patient episodes between 2001 and 2008, split into development (58,771 patients, 494 suicides) and external validation (16,387 patients, 139 suicides) samples...
February 25, 2019: Translational Psychiatry
Mathilde Règue, Corinne Poilbout, Vincent Martin, Bernard Franc, Laurence Lanfumey, Raymond Mongeau
Post-traumatic stress disorder (PTSD) is a trauma- and stress-related disorder with dysregulated fear responses and neurobiological impairments, notably at neurotrophic and inflammation levels. Understanding the mechanisms underlying this disease is crucial to develop PTSD models that meet behavioral and neurobiological validity criteria as well as innovative therapeutic approaches. Serotonin 2C receptors (5-HT2CR) are known for their important role in anxiety, and mice having only the fully edited VGV isoform of 5-HT2CR, which thereby overexpressed brain 5-HT2CR, are of special interest to study PTSD predisposition...
February 21, 2019: Translational Psychiatry
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