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Genetic testing depression bipolar affective disorder

Lynsey S Hall, Mark J Adams, Aleix Arnau-Soler, Toni-Kim Clarke, David M Howard, Yanni Zeng, Gail Davies, Saskia P Hagenaars, Ana Maria Fernandez-Pujals, Jude Gibson, Eleanor M Wigmore, Thibaud S Boutin, Caroline Hayward, Generation Scotland, David J Porteous, Ian J Deary, Pippa A Thomson, Chris S Haley, Andrew M McIntosh
Few replicable genetic associations for Major Depressive Disorder (MDD) have been identified. Recent studies of MDD have identified common risk variants by using a broader phenotype definition in very large samples, or by reducing phenotypic and ancestral heterogeneity. We sought to ascertain whether it is more informative to maximize the sample size using data from all available cases and controls, or to use a sex or recurrent stratified subset of affected individuals. To test this, we compared heritability estimates, genetic correlation with other traits, variance explained by MDD polygenic score, and variants identified by genome-wide meta-analysis for broad and narrow MDD classifications in two large British cohorts - Generation Scotland and UK Biobank...
January 10, 2018: Translational Psychiatry
S H Witt, F Streit, M Jungkunz, J Frank, S Awasthi, C S Reinbold, J Treutlein, F Degenhardt, A J Forstner, S Heilmann-Heimbach, L Dietl, C E Schwarze, D Schendel, J Strohmaier, A Abdellaoui, R Adolfsson, T M Air, H Akil, M Alda, N Alliey-Rodriguez, O A Andreassen, G Babadjanova, N J Bass, M Bauer, B T Baune, F Bellivier, S Bergen, A Bethell, J M Biernacka, D H R Blackwood, M P Boks, D I Boomsma, A D Børglum, M Borrmann-Hassenbach, P Brennan, M Budde, H N Buttenschøn, E M Byrne, P Cervantes, T-K Clarke, N Craddock, C Cruceanu, D Curtis, P M Czerski, U Dannlowski, T Davis, E J C de Geus, A Di Florio, S Djurovic, E Domenici, H J Edenberg, B Etain, S B Fischer, L Forty, C Fraser, M A Frye, J M Fullerton, K Gade, E S Gershon, I Giegling, S D Gordon, K Gordon-Smith, H J Grabe, E K Green, T A Greenwood, M Grigoroiu-Serbanescu, J Guzman-Parra, L S Hall, M Hamshere, J Hauser, M Hautzinger, U Heilbronner, S Herms, S Hitturlingappa, P Hoffmann, P Holmans, J-J Hottenga, S Jamain, I Jones, L A Jones, A Juréus, R S Kahn, J Kammerer-Ciernioch, G Kirov, S Kittel-Schneider, S Kloiber, S V Knott, M Kogevinas, M Landén, M Leber, M Leboyer, Q S Li, J Lissowska, S Lucae, N G Martin, F Mayoral-Cleries, S L McElroy, A M McIntosh, J D McKay, A McQuillin, S E Medland, C M Middeldorp, Y Milaneschi, P B Mitchell, G W Montgomery, G Morken, O Mors, T W Mühleisen, B Müller-Myhsok, R M Myers, C M Nievergelt, J I Nurnberger, M C O'Donovan, L M O Loohuis, R Ophoff, L Oruc, M J Owen, S A Paciga, B W J H Penninx, A Perry, A Pfennig, J B Potash, M Preisig, A Reif, F Rivas, G A Rouleau, P R Schofield, T G Schulze, M Schwarz, L Scott, G C B Sinnamon, E A Stahl, J Strauss, G Turecki, S Van der Auwera, H Vedder, J B Vincent, G Willemsen, C C Witt, N R Wray, H S Xi, A Tadic, N Dahmen, B H Schott, S Cichon, M M Nöthen, S Ripke, A Mobascher, D Rujescu, K Lieb, S Roepke, C Schmahl, M Bohus, M Rietschel
Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case-control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP...
June 20, 2017: Translational Psychiatry
V Deary, S P Hagenaars, S E Harris, W D Hill, G Davies, D C M Liewald, A M McIntosh, C R Gale, I J Deary
Self-reported tiredness and low energy, often called fatigue, are associated with poorer physical and mental health. Twin studies have indicated that this has a heritability between 6 and 50%. In the UK Biobank sample (N=108 976), we carried out a genome-wide association study (GWAS) of responses to the question, 'Over the last two weeks, how often have you felt tired or had little energy?' Univariate GCTA-GREML found that the proportion of variance explained by all common single-nucleotide polymorphisms for this tiredness question was 8...
February 14, 2017: Molecular Psychiatry
Masahiro Suzuki, Sara Dallaspezia, Clara Locatelli, Cristina Lorenzi, Makoto Uchiyama, Cristina Colombo, Francesco Benedetti
BACKGROUND: The discrepancy between subjective and objective severity of depressive syndromes has been proposed as a predictor of treatment outcome and suicidal risk in depression, and is associated with depressive cognitive distortions. A recent study reported that evening-type depressed patients showed higher depressive cognitions than morning-type patients. Therefore, it can be hypothesized that genetic factors affecting evening preference, such as carrying of the CLOCK rs1801260*C allele, may influence the discrepancy...
March 1, 2017: Journal of Affective Disorders
Pippa A Thomson, Barbara Duff, Douglas H R Blackwood, Liana Romaniuk, Andrew Watson, Heather C Whalley, Xiang Li, Maria R Dauvermann, T William J Moorhead, Catherine Bois, Niamh M Ryan, Holly Redpath, Lynsey Hall, Stewart W Morris, Edwin J R van Beek, Neil Roberts, David J Porteous, David St Clair, Brandon Whitcher, John Dunlop, Nicholas J Brandon, Zoë A Hughes, Jeremy Hall, Andrew McIntosh, Stephen M Lawrie
Rare genetic variants of large effect can help elucidate the pathophysiology of brain disorders. Here we expand the clinical and genetic analyses of a family with a (1;11)(q42;q14.3) translocation multiply affected by major psychiatric illness and test the effect of the translocation on the structure and function of prefrontal, and temporal brain regions. The translocation showed significant linkage (LOD score 6.1) with a clinical phenotype that included schizophrenia, schizoaffective disorder, bipolar disorder, and recurrent major depressive disorder...
2016: NPJ Schizophrenia
Eve S Fields, Raymond A Lorenz, Joel G Winner
This report describes two cases in which pharmacogenomic testing was utilized to guide medication selection for difficult to treat patients. The first patient is a 29-year old male with bipolar disorder who had severe akathisia due to his long acting injectable antipsychotic. The second patient is a 59-year old female with major depressive disorder who was not responding to her medication. In both cases, a proprietary combinatorial pharmacogenomic test was used to inform medication changes and improve patient outcomes...
2016: Pharmacogenomics and Personalized Medicine
C R Gale, S P Hagenaars, G Davies, W D Hill, D C M Liewald, B Cullen, B W Penninx, D I Boomsma, J Pell, A M McIntosh, D J Smith, I J Deary, S E Harris
People with higher levels of neuroticism have an increased risk of several types of mental disorder. Higher neuroticism has also been associated, less consistently, with increased risk of various physical health outcomes. We hypothesised that these associations may, in part, be due to shared genetic influences. We tested for pleiotropy between neuroticism and 17 mental and physical diseases or health traits using linkage disequilibrium regression and polygenic profile scoring. Genetic correlations were derived between neuroticism scores in 108 038 people in the UK Biobank and health-related measures from 14 large genome-wide association studies (GWASs)...
April 26, 2016: Translational Psychiatry
R G Fortgang, C M Hultman, T G M van Erp, T D Cannon
BACKGROUND: Impulsivity is associated with bipolar disorder as a clinical feature during and between manic episodes and is considered a potential endophenotype for the disorder. Schizophrenia and major depressive disorder share substantial genetic overlap with bipolar disorder, and these two disorders have also been associated with elevations in impulsivity. However, little is known about the degree of overlap among these disorders in discrete subfacets of impulsivity and whether any overlap is purely phenotypic or due to shared genetic diathesis...
May 2016: Psychological Medicine
Bernard Crespi, Emma Leach, Natalie Dinsdale, Mikael Mokkonen, Peter Hurd
Complex human social cognition has evolved in concert with risks for psychiatric disorders. Recently, autism and psychotic-affective conditions (mainly schizophrenia, bipolar disorder, and depression) have been posited as psychological 'opposites' with regard to social-cognitive phenotypes. Imagination, considered as 'forming new ideas, mental images, or concepts', represents a central facet of human social evolution and cognition. Previous studies have documented reduced imagination in autism, and increased imagination in association with psychotic-affective conditions, yet these sets of findings have yet to be considered together, or evaluated in the context of the diametric model...
May 2016: Cognition
Rosie May Walker, Andrea Nikie Christoforou, Daniel L McCartney, Stewart W Morris, Nicholas A Kennedy, Peter Morten, Susan Maguire Anderson, Helen Scott Torrance, Alix Macdonald, Jessika Elizabeth Sussmann, Heather Clare Whalley, Douglas H R Blackwood, Andrew Mark McIntosh, David John Porteous, Kathryn Louise Evans
BACKGROUND: Bipolar disorder (BD) is a severe, familial psychiatric condition. Progress in understanding the aetiology of BD has been hampered by substantial phenotypic and genetic heterogeneity. We sought to mitigate these confounders by studying a multi-generational family multiply affected by BD and major depressive disorder (MDD), who carry an illness-linked haplotype on chromosome 4p. Within a family, aetiological heterogeneity is likely to be reduced, thus conferring greater power to detect illness-related changes...
2016: Clinical Epigenetics
Christopher D Whelan, Derrek P Hibar, Laura S van Velzen, Anthony S Zannas, Tania Carrillo-Roa, Katie McMahon, Gautam Prasad, Sinéad Kelly, Joshua Faskowitz, Greig deZubiracay, Juan E Iglesias, Theo G M van Erp, Thomas Frodl, Nicholas G Martin, Margaret J Wright, Neda Jahanshad, Lianne Schmaal, Philipp G Sämann, Paul M Thompson
The human hippocampal formation can be divided into a set of cytoarchitecturally and functionally distinct subregions, involved in different aspects of memory formation. Neuroanatomical disruptions within these subregions are associated with several debilitating brain disorders including Alzheimer's disease, major depression, schizophrenia, and bipolar disorder. Multi-center brain imaging consortia, such as the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) consortium, are interested in studying disease effects on these subregions, and in the genetic factors that affect them...
March 2016: NeuroImage
Martin Johnsson, Michael J Williams, Per Jensen, Dominic Wright
The identification of genetic variants responsible for behavioral variation is an enduring goal in biology, with wide-scale ramifications, ranging from medical research to evolutionary theory on personality syndromes. Here, we use for the first time a large-scale genetical genomics analysis in the brains of chickens to identify genes affecting anxiety as measured by an open field test. We combine quantitative trait locus (QTL) analysis in 572 individuals and expression QTL (eQTL) analysis in 129 individuals from an advanced intercross between domestic chickens and Red Junglefowl...
January 2016: Genetics
Berit Kerner
Bipolar disorder is a common, complex psychiatric disorder characterized by mania and depression. The disease aggregates in families, but despite much effort, it has been difficult to delineate the basic genetic model or identify specific genetic risk factors. Not only single gene Mendelian transmission and common variant hypotheses but also multivariate threshold models and oligogenic quasi-Mendelian modes of inheritance have dominated the discussion at times. Almost complete sequence information of the human genome and falling sequencing costs now offer the opportunity to test these models in families in which the disorder is transmitted over several generations...
2015: Frontiers in Psychiatry
Leanne Stokes, Sarah J Spencer, Trisha A Jenkins
Pathophysiology associated with several psychiatric disorders has been linked to inflammatory biomarkers. This has generated a theory of major depressive disorders as an inflammatory disease. The idea of pro-inflammatory cytokines altering behavior is now well accepted however many questions remain. Microglia can produce a plethora of inflammatory cytokines and these cells appear to be critical in the link between inflammatory changes and depressive disorders. Microglia play a known role in sickness behavior which has many components of depressive-like behavior such as social withdrawal, sleep alterations, and anorexia...
2015: Frontiers in Cellular Neuroscience
K Ohi, G Ursini, M Li, J H Shin, T Ye, Q Chen, R Tao, J E Kleinman, T M Hyde, R Hashimoto, D R Weinberger
A genome-wide association study of cognitive deficits in patients with schizophrenia in Japan found association with a missense genetic variant (rs7157599, Asn8Ser) in the delta(4)-desaturase, sphingolipid 2 (DEGS2) gene. A replication analysis using Caucasian samples showed a directionally consistent trend for cognitive association of a proxy single-nucleotide polymorphism (SNP), rs3783332. Although the DEGS2 gene is expressed in human brain, it is unknown how DEGS2 expression varies during human life and whether it is affected by psychiatric disorders and genetic variants...
2015: Translational Psychiatry
A K Leonpacher, D Liebers, M Pirooznia, D Jancic, D F MacKinnon, F M Mondimore, B Schweizer, J B Potash, P P Zandi, F S Goes
BACKGROUND: Distinguishing bipolar disorder (BP) from major depressive disorder (MDD) has important relevance for prognosis and treatment. Prior studies have identified clinical features that differ between these two diseases but have been limited by heterogeneity and lack of replication. We sought to identify depression-related features that distinguish BP from MDD in large samples with replication. METHOD: Using a large, opportunistically ascertained collection of subjects with BP and MDD we selected 34 depression-related clinical features to test across the diagnostic categories in an initial discovery dataset consisting of 1228 subjects (386 BPI, 158 BPII and 684 MDD)...
August 2015: Psychological Medicine
S-Y Cheah, B R Lawford, R M Young, C P Morris, J Voisey
BACKGROUND: Dystrobrevin binding protein 1 (DTNBP1) is a schizophrenia susceptibility gene involved with neurotransmission regulation (especially dopamine and glutamate) and neurodevelopment. The gene is known to be associated with cognitive deficit phenotypes within schizophrenia. In our previous studies, DTNBP1 was found associated not only with schizophrenia but with other psychiatric disorders including psychotic depression, post-traumatic stress disorder, nicotine dependence and opiate dependence...
June 2015: European Psychiatry: the Journal of the Association of European Psychiatrists
Enda M Byrne, Uttam K Raheja, Sarah H Stephens, Andrew C Heath, Pamela A F Madden, Dipika Vaswani, Gagan V Nijjar, Kathleen A Ryan, Hassaan Youssufi, Philip R Gehrman, Alan R Shuldiner, Nicholas G Martin, Grant W Montgomery, Naomi R Wray, Elliot C Nelson, Braxton D Mitchell, Teodor T Postolache
OBJECTIVE: To test common genetic variants for association with seasonality (seasonal changes in mood and behavior) and to investigate whether there are shared genetic risk factors between psychiatric disorders and seasonality. METHOD: Genome-wide association studies (GWASs) were conducted in Australian (between 1988 and 1990 and between 2010 and 2013) and Amish (between May 2010 and December 2011) samples in whom the Seasonal Pattern Assessment Questionnaire (SPAQ) had been administered, and the results were meta-analyzed in a total sample of 4,156 individuals...
February 2015: Journal of Clinical Psychiatry
James Le Bas, Richard Newton, Rachel Sore, David Castle
Because affective pathogenesis is a hard problem for psychiatry, it behoves researchers to develop and test novel models of causality. We examine the notion that the adaptive drive to social investment - prestige - provides clues to the bipolar spectrum. A seven node bipolar spectrum is proposed, based on a putative gradient of "bipolarity". It is conceived that this gradient may correlate with the drive to social investment (prestige). In order to test this hypothesis with proof of concept data, a case control study categorised 228 subjects into a seven node bipolar spectrum...
February 2015: Medical Hypotheses
Diego Forni, Uberto Pozzoli, Rachele Cagliani, Claudia Tresoldi, Giorgia Menozzi, Stefania Riva, Franca R Guerini, Giacomo P Comi, Elisabetta Bolognesi, Nereo Bresolin, Mario Clerici, Manuela Sironi
BACKGROUND: The temporal coordination of biological processes into daily cycles is a common feature of most living organisms. In humans, disruption of circadian rhythms is commonly observed in psychiatric diseases,including schizophrenia, bipolar disorder, depression and autism. Light therapy is the most effective treatment for seasonal affective disorder and circadian-related treatments sustain antidepressant response in bipolar disorder patients. Day/night cycles represent a major circadian synchronizing signal and vary widely with latitude...
2014: Genome Biology
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