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Bioinformatics psychiatry

María-Teresa Colomina, Fernando Sánchez-Santed, Nélida M Conejo, Paloma Collado, Alicia Salvador, Milagros Gallo, Helena Pinos, Cosme Salas, José F Navarro, Ana Adán, Arantza Azpiroz, Jorge L Arias
BACKGROUND: The concept of the exposome has emerged as a new strategy for studying all environmental exposures throughout an individual’s life and their impact on human health. Nowadays, electronic devices are available to collect data about an individual’s geolocation, biological function, or exposure biomarkers. The appearance of “omic” sciences and advances in bioinformatics have allowed massive data-gathering and analysis from various scientific fields...
February 2018: Psicothema
N Sun, C Nasello, L Deng, N Wang, Y Zhang, Z Xu, Z Song, K Kwan, R A King, Z P Pang, J Xing, G A Heiman, J A Tischfield
Tourette Disorder (TD) is a childhood-onset neuropsychiatric and neurodevelopmental disorder characterized by the presence of both motor and vocal tics. The genetic architecture of TD is believed to be complex and heterogeneous. Nevertheless, DNA sequence variants co-segregating with TD phenotypes within multiplex families have been identified. This report examines whole exomes of affected and unaffected individuals in a multiplex TD family to discover genes involved in the TD etiology. We performed whole exome sequencing on six out of nine members in a three-generation TD multiplex family...
September 12, 2017: Molecular Psychiatry
A B Niculescu, H Le-Niculescu, D F Levey, P L Phalen, H L Dainton, K Roseberry, E M Niculescu, J O Niezer, A Williams, D L Graham, T J Jones, V Venugopal, A Ballew, M Yard, T Gelbart, S M Kurian, A Shekhar, N J Schork, G E Sandusky, D R Salomon
Suicide remains a clear, present and increasing public health problem, despite being a potentially preventable tragedy. Its incidence is particularly high in people with overt or un(der)diagnosed psychiatric disorders. Objective and precise identification of individuals at risk, ways of monitoring response to treatments and novel preventive therapeutics need to be discovered, employed and widely deployed. We sought to investigate whether blood gene expression biomarkers for suicide (that is, a 'liquid biopsy' approach) can be identified that are more universal in nature, working across psychiatric diagnoses and genders, using larger cohorts than in previous studies...
September 2017: Molecular Psychiatry
B P F Rutten, E Vermetten, C H Vinkers, G Ursini, N P Daskalakis, E Pishva, L de Nijs, L C Houtepen, L Eijssen, A E Jaffe, G Kenis, W Viechtbauer, D van den Hove, K G Schraut, K-P Lesch, J E Kleinman, T M Hyde, D R Weinberger, L Schalkwyk, K Lunnon, J Mill, H Cohen, R Yehuda, D G Baker, A X Maihofer, C M Nievergelt, E Geuze, M P M Boks
In order to determine the impact of the epigenetic response to traumatic stress on post-traumatic stress disorder (PTSD), this study examined longitudinal changes of genome-wide blood DNA methylation profiles in relation to the development of PTSD symptoms in two prospective military cohorts (one discovery and one replication data set). In the first cohort consisting of male Dutch military servicemen (n=93), the emergence of PTSD symptoms over a deployment period to a combat zone was significantly associated with alterations in DNA methylation levels at 17 genomic positions and 12 genomic regions...
June 20, 2017: Molecular Psychiatry
X Xiao, H Chang, M Li
Recent large-scale genetic approaches such as genome-wide association studies have allowed the identification of common genetic variations that contribute to risk architectures of psychiatric disorders. However, most of these susceptibility variants are located in noncoding genomic regions that usually span multiple genes. As a result, pinpointing the precise variant(s) and biological mechanisms accounting for the risk remains challenging. By reviewing recent progresses in genetics, functional genomics and neurobiology of psychiatric disorders, as well as gene expression analyses of brain tissues, here we propose a roadmap to characterize the roles of noncoding risk loci in the pathogenesis of psychiatric illnesses (that is, identifying the underlying molecular mechanisms explaining the genetic risk conferred by those genomic loci, and recognizing putative functional causative variants)...
April 2017: 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
Intellectual disability (ID) is a clinically and genetically heterogeneous disorder, affecting 1-3% of the general population. Although research into the genetic causes of ID has recently gained momentum, identification of pathogenic mutations that cause autosomal recessive ID (ARID) has lagged behind, predominantly due to non-availability of sizeable families. Here we present the results of exome sequencing in 121 large consanguineous Pakistani ID families. In 60 families, we identified homozygous or compound heterozygous DNA variants in a single gene, 30 affecting reported ID genes and 30 affecting novel candidate ID genes...
November 2017: Molecular Psychiatry
S Rangaraju, D F Levey, K Nho, N Jain, K D Andrews, H Le-Niculescu, D R Salomon, A J Saykin, M Petrascheck, A B Niculescu
Antidepressants have been shown to improve longevity in C. elegans. It is plausible that orthologs of genes involved in mood regulation and stress response are involved in such an effect. We sought to understand the underlying biology. First, we analyzed the transcriptome from worms treated with the antidepressant mianserin, previously identified in a large-scale unbiased drug screen as promoting increased lifespan in worms. We identified the most robust treatment-related changes in gene expression, and identified the corresponding human orthologs...
August 2016: Molecular Psychiatry
J H S Tong, Z Hawi, C Dark, T D R Cummins, B P Johnson, D P Newman, R Lau, A Vance, H S Heussler, N Matthews, M A Bellgrove, K C Pang
Attention deficit hyperactivity disorder (ADHD) is a highly heritable psychiatric condition with negative lifetime outcomes. Uncovering its genetic architecture should yield important insights into the neurobiology of ADHD and assist development of novel treatment strategies. Twenty years of candidate gene investigations and more recently genome-wide association studies have identified an array of potential association signals. In this context, separating the likely true from false associations ('the wheat' from 'the chaff') will be crucial for uncovering the functional biology of ADHD...
November 2016: Molecular Psychiatry
F Z Marques, N Eikelis, R G Bayles, E A Lambert, N E Straznicky, D Hering, M D Esler, G A Head, D A Barton, M P Schlaich, G W Lambert
Norepinephrine released from sympathetic nerves is removed from the neuroeffector junction via the action of the norepinephrine transporter (NET). NET impairment is evident in several clinically important conditions including major depressive disorder (MDD), panic disorder (PD), essential hypertension and the postural orthostatic tachycardia syndrome (POTS). We aimed to determine whether a single nucleotide polymorphism (SNP) in the 3' untranslated region (UTR) of the NET gene is associated with NET impairment and to elucidate the mechanisms involved...
January 2017: Molecular Psychiatry
Aaron F Alexander-Bloch, Christopher J McDougle, Zhanna Ullman, David A Sweetser
Despite the recent acceleration in the discovery of genetic risk factors for intellectual disability (ID), the genetic etiology of ID is unknown in approximately half of cases and remains a major frontier of genetics in medicine and psychiatry. The distinction between syndromal and nonsyndromal forms of ID is of great clinical importance, but the boundary between these clinical entities is difficult to ascertain for many genes of interest. ID is more common in men than in women, but the genetic explanation of this sex asymmetry is incompletely understood...
June 2016: Psychiatric Genetics
Sophie Van der Sluis, Conor V Dolan, Jiang Li, Youqiang Song, Pak Sham, Danielle Posthuma, Miao-Xin Li
MOTIVATION: Standard genome-wide association studies, testing the association between one phenotype and a large number of single nucleotide polymorphisms (SNPs), are limited in two ways: (i) traits are often multivariate, and analysis of composite scores entails loss in statistical power and (ii) gene-based analyses may be preferred, e.g. to decrease the multiple testing problem. RESULTS: Here we present a new method, multivariate gene-based association test by extended Simes procedure (MGAS), that allows gene-based testing of multivariate phenotypes in unrelated individuals...
April 1, 2015: Bioinformatics
Ali Alawieh, Zahraa Sabra, Amaly Nokkari, Atlal El-Assaad, Stefania Mondello, Fadi Zaraket, Bilal Fadlallah, Firas H Kobeissy
Bioinformatics-based applications have been incorporated into several medical disciplines, including cancer, neuroscience, and recently psychiatry. Both the increasing interest in the molecular aspect of neuropsychiatry and the availability of high-throughput discovery and analysis tools have encouraged the incorporation of bioinformatics and neurosystems biology techniques into psychiatry and neuroscience research. As applied to neuropsychiatry, systems biology involves the acquisition and processing of high-throughput datasets to infer new information...
2014: Methods in Molecular Biology
Paul L Wood
Metabolomics research has the potential to provide biomarkers for the detection of disease, for subtyping complex disease populations, for monitoring disease progression and therapy, and for defining new molecular targets for therapeutic intervention. These potentials are far from being realized because of a number of technical, conceptual, financial, and bioinformatics issues. Mass spectrometry provides analytical platforms that address the technical barriers to success in metabolomics research; however, the limited commercial availability of analytical and stable isotope standards has created a bottleneck for the absolute quantitation of a number of metabolites...
January 2014: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Ali Alawieh, Fadi A Zaraket, Jian-Liang Li, Stefania Mondello, Amaly Nokkari, Mahdi Razafsha, Bilal Fadlallah, Rose-Mary Boustany, Firas H Kobeissy
Although neuropsychiatric (NP) disorders are among the top causes of disability worldwide with enormous financial costs, they can still be viewed as part of the most complex disorders that are of unknown etiology and incomprehensible pathophysiology. The complexity of NP disorders arises from their etiologic heterogeneity and the concurrent influence of environmental and genetic factors. In addition, the absence of rigid boundaries between the normal and diseased state, the remarkable overlap of symptoms among conditions, the high inter-individual and inter-population variations, and the absence of discriminative molecular and/or imaging biomarkers for these diseases makes difficult an accurate diagnosis...
2012: Frontiers in Neuroscience
Francesco Piva, Matteo Giulietti, Luisa Baldelli, Bernardo Nardi, Cesario Bellantuono, Tatiana Armeni, Franca Saccucci, Giovanni Principato
OBJECTIVE: Single nucleotide polymorphisms (SNPs) in serotonin related genes influence mental disorders, responses to pharmacological and psychotherapeutic treatments. In planning association studies, researchers that want to investigate new SNPs have to select some among a large number of candidates. Our aim is to guide researchers in the selection of the most likely phenotype affecting polymorphisms. Here, we studied serotonin receptor 2C (HTR2C) SNPs because, till now, only relatively few of about 2000 are investigated...
August 2011: Human Psychopharmacology
R H Perlis, D V Iosifescu, V M Castro, S N Murphy, V S Gainer, J Minnier, T Cai, S Goryachev, Q Zeng, P J Gallagher, M Fava, J B Weilburg, S E Churchill, I S Kohane, J W Smoller
BACKGROUND: Electronic medical records (EMR) provide a unique opportunity for efficient, large-scale clinical investigation in psychiatry. However, such studies will require development of tools to define treatment outcome. METHOD: Natural language processing (NLP) was applied to classify notes from 127 504 patients with a billing diagnosis of major depressive disorder, drawn from out-patient psychiatry practices affiliated with multiple, large New England hospitals...
January 2012: Psychological Medicine
Francesco Piva, Matteo Giulietti, Bernardo Nardi, Cesario Bellantuono, Giovanni Principato
OBJECTIVE: Among the experimentally assessed DNA variations in serotonin related genes, some influence physiological expression of personality and mental disorders, others alter the responses to pharmacological and/or psychotherapeutic treatments. Because of the huge number of polymorphisms lying in genes and of the great length of time necessary to perform association studies, a selection of the variations being studied is a necessary and crucial step. METHODS: In this work we used the most updated and assessed bioinformatic tools to predict the phenotype affecting polymorphisms of the human HTR1A, HTR2A and SLC6A4 serotonin related genes...
March 2010: Human Psychopharmacology
Hub Zwart
The genomics "revolution" is spreading. Originating in the molecular life sciences, it initially affected a number of biomedical research fields such as cancer genomics and clinical genetics. Now, however, a new "wave" of genomic bioinformation is transforming a widening array of disciplines, including those that address the social, historical and cultural dimensions of human life. Increasingly, bioinformation is affecting "human sciences" such as psychiatry, psychology, brain research, behavioural research ("behavioural genomics"), but also anthropology and archaeology ("bioarchaeology")...
June 2009: Medicine, Health Care, and Philosophy
Michele Ferrante, Kim T Blackwell, Michele Migliore, Giorgio A Ascoli
The identification and characterization of potential pharmacological targets in neurology and psychiatry is a fundamental problem at the intersection between medicinal chemistry and the neurosciences. Exciting new techniques in proteomics and genomics have fostered rapid progress, opening numerous questions as to the functional consequences of ligand binding at the systems level. Psycho- and neuro-active drugs typically work in nerve cells by affecting one or more aspects of electrophysiological activity. Thus, an integrated understanding of neuropharmacological agents requires bridging the gap between their molecular mechanisms and the biophysical determinants of neuronal function...
2008: Current Medicinal Chemistry
Lars Bertram
Genetically, schizophrenia is a complex disease whose pathogenesis is likely governed by a number of different risk factors. While substantial efforts have been made to identify the underlying susceptibility alleles over the past 2 decades, they have been of only limited success. Each year, the field is enriched with nearly 150 additional genetic association studies, each of which either proposes or refutes the existence of certain schizophrenia genes. To facilitate the evaluation and interpretation of these findings, we have recently created a database for genetic association studies in schizophrenia ("SzGene"; available at http://www...
September 2008: Schizophrenia Bulletin
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