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Translational Psychiatry

Mark D Underwood, Suham A Kassir, Mihran J Bakalian, Hanga Galfalvy, Andrew J Dwork, J John Mann, Victoria Arango
Serotonin neurotransmitter deficits are reported in suicide, major depressive disorder (MDD) and alcohol use disorder (AUD). To compare pathophysiology in these disorders, we mapped brain serotonin transporter (SERT), 5-HT1A , and 5-HT2A receptor binding throughout prefrontal cortex and in anterior cingulate cortex postmortem. Cases and controls died suddenly minimizing agonal effects and had a postmortem interval ≤24 h to avoid compromised brain integrity. Neuropathology and toxicology confirmed absence of neuropathology and psychotropic medications...
December 14, 2018: Translational Psychiatry
Wei Guo, Rodrigo Machado-Vieira, Sanjay Mathew, James W Murrough, Dennis S Charney, Matthew Gruenbaum, 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
Growing evidence suggests that the glutamatergic modulator ketamine has rapid antidepressant effects in treatment-resistant depressed subjects. The anticholinergic agent scopolamine has also shown promise as a rapid-acting antidepressant. This study applied genome-wide markers to investigate the role of genetic variants in predicting acute antidepressant response to both agents. The ketamine-treated sample included 157 unrelated European subjects with major depressive disorder (MDD) or bipolar disorder (BD)...
December 14, 2018: Translational Psychiatry
Daniel Boloc, Anna Gortat, Jia Qi Cheng-Zhang, Susana García-Cerro, Natalia Rodríguez, Mara Parellada, Jeronimo Saiz-Ruiz, Manolo J Cuesta, Patricia Gassó, Amalia Lafuente, Miquel Bernardo, Sergi Mas
In previous work we developed a pharmacogenetic predictor of antipsychotic (AP) induced extrapyramidal symptoms (EPS) based on four genes involved in mTOR regulation. The main objective is to improve this predictor by increasing its biological plausibility and replication. We re-sequence the four genes using next-generation sequencing. We predict functionality "in silico" of all identified SNPs and test it using gene reporter assays. Using functional SNPs, we develop a new predictor utilizing machine learning algorithms (Discovery Cohort, N = 131) and replicate it in two independent cohorts (Replication Cohort 1, N = 113; Replication Cohort 2, N = 113)...
December 13, 2018: Translational Psychiatry
Gaia Olivo, Ingemar Swenne, Christina Zhukovsky, Anna-Kaisa Tuunainen, Helena Salonen-Ros, Elna-Marie Larsson, Santino Gaudio, Samantha J Brooks, Helgi B Schiöth
Atypical anorexia nervosa (AN) has a high incidence in adolescents and can result in significant morbidity and mortality. Neuroimaging could improve our knowledge regarding the pathogenesis of eating disorders (EDs), however research on adolescents with EDs is limited. To date no neuroimaging studies have been conducted to investigate brain functional connectivity in atypical AN. We investigated resting-state functional connectivity using 3 T MRI in 22 drug-naïve adolescent patients with atypical AN, and 24 healthy controls...
December 13, 2018: Translational Psychiatry
Simin Zhang, Weina Wang, Xiaorui Su, Graham J Kemp, Xibiao Yang, Jingkai Su, Qiaoyue Tan, Youjin Zhao, Huaiqiang Sun, Qiang Yue, Qiyong Gong
Anorexia nervosa (AN) is a severe psychiatric disorder with high mortality. The underlying neurobiological mechanisms are not well understood, and high-resolution structural magnetic resonance brain imaging studies have given inconsistent results. Here we aimed to psychoradiologically define the most prominent and replicable abnormalities of gray matter volume (GMV) in AN patients, and to examine their relationship to demographics and clinical characteristics, by means of a new coordinate-based meta-analytic technique called seed-based d mapping (SDM)...
December 13, 2018: Translational Psychiatry
Mark Z Kos, Jubao Duan, Alan R Sanders, Lucy Blondell, Eugene I Drigalenko, Melanie A Carless, Pablo V Gejman, Harald H H Göring
The dopaminergic hypothesis of schizophrenia (SZ) postulates that positive symptoms of SZ, in particular psychosis, are due to disturbed neurotransmission via the dopamine (DA) receptor D2 (DRD2). However, DA is a reactive molecule that yields various oxidative species, and thus has important non-receptor-mediated effects, with empirical evidence of cellular toxicity and neurodegeneration. Here we examine non-receptor-mediated effects of DA on gene co-expression networks and its potential role in SZ pathology...
December 13, 2018: Translational Psychiatry
Imanol Perez Arribas, Guy M Goodwin, John R Geddes, Terry Lyons, Kate E A Saunders
Mobile technologies offer new opportunities for prospective, high resolution monitoring of long-term health conditions. The opportunities seem of particular promise in psychiatry where diagnoses often rely on retrospective and subjective recall of mood states. However, deriving clinically meaningful information from the complex time series data these technologies present is challenging, and the current implications for patient care are uncertain. In this study, 130 participants with bipolar disorder (n = 48) or borderline personality disorder (n = 31) and healthy volunteers (n = 51) completed daily mood ratings using a bespoke smartphone app for up to 1 year...
December 13, 2018: Translational Psychiatry
Shan Jiang, Natalie Wen, Zeran Li, Umber Dube, Jorge Del Aguila, John Budde, Rita Martinez, Simon Hsu, Maria V Fernandez, Nigel J Cairns, Oscar Harari, Carlos Cruchaga, Celeste M Karch
Mutations in the microtubule-associated protein tau (MAPT) gene cause autosomal dominant frontotemporal lobar degeneration with tau inclusions (FTLD-tau). MAPT p.R406W carriers present clinically with progressive memory loss and neuropathologically with neuronal and glial tauopathy. However, the pathogenic events triggered by the expression of the mutant tau protein remain poorly understood. To identify the genes and pathways that are dysregulated in FTLD-tau, we performed transcriptomic analyses in induced pluripotent stem cell (iPSC)-derived neurons carrying MAPT p...
December 13, 2018: Translational Psychiatry
Karin Kucian, Ursina McCaskey, Ruth O'Gorman Tuura, Michael von Aster
Adequate mathematical competencies are currently indispensable in professional and social life. However, mathematics is often associated with stress and frustration and the confrontation with tasks that require mathematical knowledge triggers anxiety in many children. We examined if there is a relationship between math anxiety and changes in brain structure in children with and without developmental dyscalculia. Our findings showed that math anxiety is related to altered brain structure. In particular, the right amygdala volume was reduced in individuals with higher math anxiety...
December 10, 2018: Translational Psychiatry
Lhotse Hei Lui Ng, Yuhua Huang, Lei Han, Raymond Chuen-Chung Chang, Ying Shing Chan, Cora Sau Wan Lai
Stress is a major risk factor for the onset of many psychiatric diseases. In rodent models, chronic stress induces depression and impairs excitatory neurotransmission. However, little is known about the effect of stress on synaptic circuitry during the development of behavioral symptoms. Using two-photon transcranial imaging, we studied the effect of repeated restraint stress on dendritic spine plasticity in the frontal cortex in vivo. We found that restraint stress induced dendritic spine loss by decreasing the rate of spine formation and increasing the rate of spine elimination...
December 10, 2018: Translational Psychiatry
Nichola Marie Brydges, Anna Moon, Lowenna Rule, Holly Watkin, Kerrie L Thomas, Jeremy Hall
Experience of traumatic events in childhood is linked to an elevated risk of developing psychiatric disorders in adulthood. The neurobiological mechanisms underlying this phenomenon are not fully understood. The limbic system, particularly the hippocampus, is significantly impacted by childhood trauma. In particular, it has been hypothesised that childhood stress may impact adult hippocampal neurogenesis (AHN) and related behaviours, conferring increased risk for later mental illness. Stress in utero can lead to impaired hippocampal synaptic plasticity, and stress in the first 2-3 weeks of life reduces AHN in animal models...
December 10, 2018: Translational Psychiatry
Christopher T Smith, M Danica San Juan, Linh C Dang, Daniel T Katz, Scott F Perkins, Leah L Burgess, Ronald L Cowan, H Charles Manning, Michael L Nickels, Daniel O Claassen, Gregory R Samanez-Larkin, David H Zald
Impulsivity is a transdiagnostic feature of a range of externalizing psychiatric disorders. Preclinical work links reduced ventral striatal dopamine transporter (DAT) availability with heightened impulsivity and novelty seeking. However, there is a lack of human data investigating the relationship between DAT availability, particularly in subregions of the striatum, and the personality traits of impulsivity and novelty seeking. Here we collected PET measures of DAT availability (BPND ) using the tracer 18 F-FE-PE2I in 47 healthy adult subjects and examined relations between BPND in striatum, including its subregions: caudate, putamen, and ventral striatum (VS), and trait impulsivity (Barratt Impulsiveness Scale: BIS-11) and novelty seeking (Tridimensional Personality Questionnaire: TPQ-NS), controlling for age and sex...
December 7, 2018: Translational Psychiatry
Lijuan Zhao, Hong Chang, Dong-Sheng Zhou, Jun Cai, Weixing Fan, Wei Tang, Wenxin Tang, Xingxing Li, Weiqing Liu, Fang Liu, Yuanfang He, Yan Bai, Yan Sun, Jiapei Dai, Lingyi Li, Xiao Xiao, Chen Zhang, Ming Li
Genetic analyses of psychiatric illnesses, such as bipolar disorder (BPD), have revealed essential information regarding the underlying pathological mechanisms. While such studies in populations of European ancestry have achieved prominent success, understanding the genetic risk factors of these illnesses (especially BPD) in Chinese population remains an urgent task. Given the lack of genome-wide association study (GWAS) of BPD in Chinese population from Mainland China, replicating the previously reported GWAS hits in distinct populations will provide valuable information for future GWAS analysis in Han Chinese...
December 7, 2018: Translational Psychiatry
Michael S Breen, Sureyya Ozcan, Jordan M Ramsey, Zichen Wang, Avi Ma'ayan, Nitin Rustogi, Michael G Gottschalk, Maree J Webster, Cynthia Shannon Weickert, Joseph D Buxbaum, Sabine Bahn
Healthy cortical development depends on precise regulation of transcription and translation. However, the dynamics of how proteins are expressed, function and interact across postnatal human cortical development remain poorly understood. We surveyed the proteomic landscape of 69 dorsolateral prefrontal cortex samples across seven stages of postnatal life and integrated these data with paired transcriptome data. We detected 911 proteins by liquid chromatography-mass spectrometry, and 83 were significantly associated with postnatal age (FDR < 5%)...
December 5, 2018: Translational Psychiatry
Thomas Husson, Jean-Baptiste Duboc, Olivier Quenez, Camille Charbonnier, Maud Rotharmel, Macarena Cuenca, Xavier Jegouzo, Anne-Claire Richard, Thierry Frebourg, Jean-François Deleuze, Anne Boland, Emmanuelle Genin, Stéphanie Debette, Christophe Tzourio, Dominique Campion, Gaël Nicolas, Olivier Guillin
This study aims at assessing the burden of rare (minor allele frequency < 1%) predicted damaging variants in the whole exome of 92 bipolar I disorder (BD) patients and 1051 controls of French ancestry. Patients exhibiting an extreme phenotype (earlier onset and family history of mood disorder) were preferentially included to increase the power to detect an association. A collapsing strategy was used to test the overall burden of rare variants in cases versus controls at the gene level. Only protein-truncating and predicted damaging missense variants were included in the analysis...
December 5, 2018: Translational Psychiatry
Sara M Freeman, Michelle C Palumbo, Rebecca H Lawrence, Aaron L Smith, Mark M Goodman, Karen L Bales
The prosocial hormone oxytocin (OXT) has become a new target for research on the etiology and treatment of autism spectrum disorder (ASD), a condition characterized by deficits in social function. However, it remains unknown whether there are alterations in OXT receptor (OXTR) levels in the ASD brain. This study quantified the density of OXTR and of the structurally related vasopressin 1a receptor (AVPR1a) in postmortem brain tissue from individuals with ASD and typically developing individuals. We analyzed two regions known to contain OXTR across all primates studied to date: the nucleus basalis of Meynert (NBM), which mediates visual attention, and the superior colliculus, which controls gaze direction...
December 4, 2018: Translational Psychiatry
L C Houtepen, R Hardy, J Maddock, D Kuh, E L Anderson, C L Relton, M J Suderman, L D Howe
Childhood adversity affects later health, but the underlying molecular mechanisms are unclear. Although there is some evidence from animal models and case-control studies of a role for DNA methylation, evidence from human population-based studies is limited. In two cohorts (mothers from the Avon Longitudinal Study of Parents and Children, ALSPAC, n = 780 and women from the MRC National Survey of Health and Development, NSHD, n = 552), we assessed the association of seven adverse childhood experiences (ACEs: parental physical illness, parental mental illness, parental death, parental separation, suboptimal maternal bonding, childhood illness and child maltreatment) as well as their combination (ACE score) with genome-wide DNA methylation levels measured using the Illumina Infinium HumanMethylation450 BeadChip in peripheral blood at mean age 47 years (ALSPAC) and in buccal cells at age 53 years (NSHD)...
December 3, 2018: Translational Psychiatry
J Paul Hamilton, Matthew D Sacchet, Trine Hjørnevik, Frederick T Chin, Bin Shen, Robin Kämpe, Jun Hyung Park, Brian D Knutson, Leanne M Williams, Nicholas Borg, Greg Zaharchuk, M Catalina Camacho, Sean Mackey, Markus Heilig, Wayne C Drevets, Gary H Glover, Sanjiv S Gambhir, Ian H Gotlib
Major depressive disorder (MDD) is characterized by the altered integration of reward histories and reduced responding of the striatum. We have posited that this reduced striatal activation in MDD is due to tonically decreased stimulation of striatal dopamine synapses which results in decremented propagation of information along the cortico-striatal-pallido-thalamic (CSPT) spiral. In the present investigation, we tested predictions of this formulation by conducting concurrent functional magnetic resonance imaging (fMRI) and 11 C-raclopride positron emission tomography (PET) in depressed and control (CTL) participants...
November 30, 2018: Translational Psychiatry
Kennett D Radford, Thomas Y Park, Shalini Jaiswal, Hongna Pan, Andrew Knutsen, Michael Zhang, Mercedes Driscoll, Lisa A Osborne-Smith, Bernard J Dardzinski, Kwang H Choi
Ketamine is a multimodal dissociative anesthetic, which provides powerful analgesia for victims with traumatic injury. However, the impact of ketamine administration in the peri-trauma period on the development of post-traumatic stress disorder (PTSD) remains controversial. Moreover, there is a major gap between preclinical and clinical studies because they utilize different doses and routes of ketamine administration. Here, we investigated the effects of sub-anesthetic doses of intravenous (IV) ketamine infusion on fear memory and brain glucose metabolism (BGluM) in rats...
November 30, 2018: Translational Psychiatry
Doretta Caramaschi, Amy E Taylor, Rebecca C Richmond, Karoline Alexandra Havdahl, Jean Golding, Caroline L Relton, Marcus R Munafò, George Davey Smith, Dheeraj Rai
An association between maternal smoking in pregnancy and autism may be biologically plausible, but the evidence to date is inconsistent. We aimed to investigate the causal relationship between maternal smoking during pregnancy and offspring autism using conventional analysis and causal inference methods. In the Avon Longitudinal Study of Parents and Children we investigated the association of maternal smoking during pregnancy (exposure) with offspring autism spectrum disorder (ASD) or possible ASD diagnosis (n = 11,946) and high scores on four autism-related traits (outcomes) (n = 7402-9152)...
November 29, 2018: Translational Psychiatry
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