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Genetic psychiatry

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https://www.readbyqxmd.com/read/29021832/pharmacogenomics-in-the-treatment-of-mood-disorders-strategies-and-opportunities-for-personalized-psychiatry
#1
REVIEW
Azmeraw T Amare, Klaus Oliver Schubert, Bernhard T Baune
Personalized medicine (personalized psychiatry in a specific setting) is a new model towards individualized care, in which knowledge from genomics and other omic pillars (microbiome, epigenomes, proteome, and metabolome) will be combined with clinical data to guide efforts to new drug development and targeted prescription of the existing treatment options. In this review, we summarize pharmacogenomic studies in mood disorders that may lay the foundation towards personalized psychiatry. In addition, we have discussed the possible strategies to integrate data from omic pillars as a future path to personalized psychiatry...
September 2017: EPMA Journal
https://www.readbyqxmd.com/read/28992526/improved-efficacy-with-targeted-pharmacogenetic-guided-treatment-of-patients-with-depression-and-anxiety-a-randomized-clinical-trial-demonstrating-clinical-utility
#2
Paul Bradley, Michael Shiekh, Vishaal Mehra, Keith Vrbicky, Stacey Layle, Marilyn C Olson, Alejandra Maciel, Ali Cullors, Jorge A Garces, Andrew A Lukowiak
The objective of this study was to evaluate the effect of pharmacogenetics-guided treatment on patients diagnosed with depression and/or anxiety, in a diverse set of clinical settings, as compared to the standard of care. The trial design followed a prospective, randomized, subject- and rater-blinded approach enrolling 685 patients from clinical providers specializing in Psychiatry, Internal Medicine, Obstetrics & Gynecology, and Family Medicine. The NeuroIDgenetix(®) test uses a genetic variant panel of ten genes, along with concomitant medications, to make medication management recommendations based on gene-drug and drug-drug interactions for over 40 medications used in the treatment of depression and anxiety...
September 23, 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28991256/genome-wide-association-analysis-identifies-30-new-susceptibility-loci-for-schizophrenia
#3
Zhiqiang Li, Jianhua Chen, Hao Yu, Lin He, Yifeng Xu, Dai Zhang, Qizhong Yi, Changgui Li, Xingwang Li, Jiawei Shen, Zhijian Song, Weidong Ji, Meng Wang, Juan Zhou, Boyu Chen, Yahui Liu, Jiqiang Wang, Peng Wang, Ping Yang, Qingzhong Wang, Guoyin Feng, Benxiu Liu, Wensheng Sun, Baojie Li, Guang He, Weidong Li, Chunling Wan, Qi Xu, Wenjin Li, Zujia Wen, Ke Liu, Fang Huang, Jue Ji, Stephan Ripke, Weihua Yue, Patrick F Sullivan, Michael C O'Donovan, Yongyong Shi
We conducted a genome-wide association study (GWAS) with replication in 36,180 Chinese individuals and performed further transancestry meta-analyses with data from the Psychiatry Genomics Consortium (PGC2). Approximately 95% of the genome-wide significant (GWS) index alleles (or their proxies) from the PGC2 study were overrepresented in Chinese schizophrenia cases, including ∼50% that achieved nominal significance and ∼75% that continued to be GWS in the transancestry analysis. The Chinese-only analysis identified seven GWS loci; three of these also were GWS in the transancestry analyses, which identified 109 GWS loci, thus yielding a total of 113 GWS loci (30 novel) in at least one of these analyses...
October 9, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28977440/advancing-psychiatric-genetics-through-dissecting-heterogeneity
#4
Karen Hodgson, Peter McGuffin, Cathryn M Lewis
There has been substantial progress in psychiatric genetics in recent years, through collaborative efforts to build large samples sizes for case/control analyses for a number of psychiatric disorders. The identification of replicated trait-associated genomic loci represents a large stride forward in a field where little is known about the biological processes involved in disorder. As researchers build on this early foundation, they are beginning to advance the field towards more fine-grained approaches that interrogate the many sources of heterogeneity within psychiatric genetics that can obscure the identification of genotypic influences on disorder...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28972577/genome-wide-association-study-across-european-and-african-american-ancestries-identifies-a-snp-in-dnmt3b-contributing-to-nicotine-dependence
#5
D B Hancock, Y Guo, G W Reginsson, N C Gaddis, S M Lutz, R Sherva, A Loukola, C C Minica, C A Markunas, Y Han, K A Young, D F Gudbjartsson, F Gu, D W McNeil, B Qaiser, C Glasheen, S Olson, M T Landi, P A F Madden, L A Farrer, J Vink, N L Saccone, M C Neale, H R Kranzler, J McKay, R J Hung, C I Amos, M L Marazita, D I Boomsma, T B Baker, J Gelernter, J Kaprio, N E Caporaso, T E Thorgeirsson, J E Hokanson, L J Bierut, K Stefansson, E O Johnson
Cigarette smoking is a leading cause of preventable mortality worldwide. Nicotine dependence, which reduces the likelihood of quitting smoking, is a heritable trait with firmly established associations with sequence variants in nicotine acetylcholine receptor genes and at other loci. To search for additional loci, we conducted a genome-wide association study (GWAS) meta-analysis of nicotine dependence, totaling 38,602 smokers (28,677 Europeans/European Americans and 9925 African Americans) across 15 studies...
October 3, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28969442/psychiatric-genomics-an-update-and-an-agenda
#6
Patrick F Sullivan, Arpana Agrawal, Cynthia M Bulik, Ole A Andreassen, Anders D Børglum, Gerome Breen, Sven Cichon, Howard J Edenberg, Stephen V Faraone, Joel Gelernter, Carol A Mathews, Caroline M Nievergelt, Jordan W Smoller, Michael C O'Donovan
The Psychiatric Genomics Consortium (PGC) is the largest consortium in the history of psychiatry. This global effort is dedicated to rapid progress and open science, and in the past decade it has delivered an increasing flow of new knowledge about the fundamental basis of common psychiatric disorders. The PGC has recently commenced a program of research designed to deliver "actionable" findings-genomic results that 1) reveal fundamental biology, 2) inform clinical practice, and 3) deliver new therapeutic targets...
October 3, 2017: American Journal of Psychiatry
https://www.readbyqxmd.com/read/28963561/drug-enrichment-and-discovery-from-schizophrenia-genome-wide-association-results-an-analysis-and-visualisation-approach
#7
H A Gaspar, G Breen
Using successful genome-wide association results in psychiatry for drug repurposing is an ongoing challenge. Databases collecting drug targets and gene annotations are growing and can be harnessed to shed a new light on psychiatric disorders. We used genome-wide association study (GWAS) summary statistics from the Psychiatric Genetics Consortium (PGC) Schizophrenia working group to build a drug repositioning model for schizophrenia. As sample size increases, schizophrenia GWAS results show increasing enrichment for known antipsychotic drugs, selective calcium channel blockers, and antiepileptics...
September 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28953811/genetics-and-psychiatry-myth-or-reality
#8
Giada Juli, Rebecca Juli, Luigi Juli
Greek mythology and philosophical speculations were the first human productions on madness and psychiatry. Likewise, the origins of genetics sink their roots in a very remote and difficult time. This work tries to give an idea of the relationship between genetics and psychiatry through the myth and reality.
September 2017: Psychiatria Danubina
https://www.readbyqxmd.com/read/28948971/purinergic-system-in-psychiatric-diseases
#9
REVIEW
A Cheffer, A R G Castillo, J Corrêa-Velloso, M C B Gonçalves, Y Naaldijk, I C Nascimento, G Burnstock, H Ulrich
Psychiatric disorders are debilitating diseases, affecting >80 million people worldwide. There are no causal cures for psychiatric disorders and available therapies only treat the symptoms. The etiology of psychiatric disorders is unknown, although it has been speculated to be a combination of environmental, stress and genetic factors. One of the neurotransmitter systems implicated in the biology of psychiatric disorders is the purinergic system. In this review, we performed a comprehensive search of the literature about the role and function of the purinergic system in the development and predisposition to psychiatric disorders, with a focus on depression, schizophrenia, bipolar disorder, autism, anxiety and attention deficit/hyperactivity disorder...
September 26, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28945215/influence-of-polygenic-risk-scores-on-lipid-levels-and-dyslipidemia-in-a-psychiatric-population-receiving-weight-gain-inducing-psychotropic-drugs
#10
Aurélie Delacrétaz, Patricia Lagares Santos, Nuria Saigi Morgui, Frederik Vandenberghe, Anaïs Glatard, Mehdi Gholam-Rezaee, Armin von Gunten, Philippe Conus, Chin B Eap
OBJECTIVES: Dyslipidemia represents a major health issue in psychiatry. We determined whether weighted polygenic risk scores (wPRSs) combining multiple single-nucleotide polymorphisms (SNPs) associated with lipid levels in the general population are associated with lipid levels [high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (TC), and triglycerides] and/or dyslipidemia in patients receiving weight gain-inducing psychotropic drugs. We also determined whether genetics improve the predictive power of dyslipidemia...
September 21, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28942195/short-overview-on-metabolomic-approach-and-redox-changes-in-psychiatric-disorders
#11
REVIEW
Gordana Nedic Erjavec, Marcela Konjevod, Matea Nikolac Perkovic, Dubravka Svob Strac, Lucija Tudor, Coral Barbas, Tilman Grune, Neven Zarkovic, Nela Pivac
Schizophrenia, depression and posttraumatic stress disorder (PTSD) are severe mental disorders and complicated diagnostic entities, due to their phenotypic, biological and genetic heterogeneity, unknown etiology, and poorly understood alterations in biological pathways and biological mechanisms. Disturbed homeostasis between overproduction of oxidant species, overcoming redox regulation and a lack of cellular antioxidant defenses, resulting in free radical-mediated pathology and subsequent neurotoxicity contributes to development of depression, schizophrenia and PTSD, their heterogeneous clinical presentation and resistance to treatment...
September 6, 2017: Redox Biology
https://www.readbyqxmd.com/read/28941093/staging-in-bipolar-disorder-from-theoretical-framework-to-clinical-utility
#12
Michael Berk, Robert Post, Aswin Ratheesh, Emma Gliddon, Ajeet Singh, Eduard Vieta, Andre F Carvalho, Melanie M Ashton, Lesley Berk, Susan M Cotton, Patrick D McGorry, Brisa S Fernandes, Lakshmi N Yatham, Seetal Dodd
Illness staging is widely utilized in several medical disciplines to help predict course or prognosis, and optimize treatment. Staging models in psychiatry in general, and bipolar disorder in particular, depend on the premise that psychopathology moves along a predictable path: an at-risk or latency stage, a prodrome progressing to a first clinical threshold episode, and one or more recurrences with the potential to revert or progress to late or end-stage manifestations. The utility and validity of a staging model for bipolar disorder depend on its linking to clinical outcome, treatment response and neurobiological measures...
October 2017: World Psychiatry: Official Journal of the World Psychiatric Association (WPA)
https://www.readbyqxmd.com/read/28936814/-the-role-of-molecular-karyotyping-in-the-genetic-etiology-of-autism
#13
Burcu Özbaran, Bilçağ Akgün, Duygu Kaçamak, Sezen Köse, Ayşenur Kavasoğlu, Hüseyin Onay
OBJECTIVE: The aim of this study was to investigate the deletions and duplications with a molecular karyotyping technique and to elucidate the etiology of autism. METHOD: A total of 31 patients (20 boys and 11 girls) between 4 to 18 years old with normal chromosomal analysis and no Fragile X mutation were diagnosed in the Ege University Child and Adolescent Psychiatry Clinic with autism (according to DSM-IV-TR criteria) and were enrolled in the study. Symptom severity of the patients was evaluated with a Childhood Autism Rating Scale...
2017: Türk Psikiyatri Dergisi, Turkish Journal of Psychiatry
https://www.readbyqxmd.com/read/28929285/genomic-disorders-in-psychiatry-what-does-the-clinician-need-to-know
#14
REVIEW
Chelsea Lowther, Gregory Costain, Danielle A Baribeau, Anne S Bassett
PURPOSE OF REVIEW: The purpose of this review is to summarize the role of genomic disorders in various psychiatric conditions and to highlight important recent advances in the field that are of potential clinical relevance. RECENT FINDINGS: Genomic disorders are caused by large rare recurrent deletions and duplications at certain chromosomal "hotspots" (e.g., 22q11.2, 16p11.2, 15q11-q13, 1q21.1, 15q13.3) across the genome. Most overlap multiple genes, affect development, and are associated with variable cognitive and other neuropsychiatric expression...
September 20, 2017: Current Psychiatry Reports
https://www.readbyqxmd.com/read/28924187/the-ipsych2012-case-cohort-sample-new-directions-for-unravelling-genetic-and-environmental-architectures-of-severe-mental-disorders
#15
C B Pedersen, J Bybjerg-Grauholm, M G Pedersen, J Grove, E Agerbo, M Bækvad-Hansen, J B Poulsen, C S Hansen, J J McGrath, T D Als, J I Goldstein, B M Neale, M J Daly, D M Hougaard, O Mors, M Nordentoft, A D Børglum, T Werge, P B Mortensen
The Integrative Psychiatric Research (iPSYCH) consortium has established a large Danish population-based Case-Cohort sample (iPSYCH2012) aimed at unravelling the genetic and environmental architecture of severe mental disorders. The iPSYCH2012 sample is nested within the entire Danish population born between 1981 and 2005, including 1 472 762 persons. This paper introduces the iPSYCH2012 sample and outlines key future research directions. Cases were identified as persons with schizophrenia (N=3540), autism (N=16 146), attention-deficit/hyperactivity disorder (N=18 726) and affective disorder (N=26 380), of which 1928 had bipolar affective disorder...
September 19, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28924186/interactome-analysis-reveals-znf804a-a-schizophrenia-risk-gene-as-a-novel-component-of-protein-translational-machinery-critical-for-embryonic-neurodevelopment
#16
Y Zhou, F Dong, T A Lanz, V Reinhart, M Li, L Liu, J Zou, H S Xi, Y Mao
Recent genome-wide association studies identified over 100 genetic loci that significantly associate with schizophrenia (SZ). A top candidate gene, ZNF804A, was robustly replicated in different populations. However, its neural functions are largely unknown. Here we show in mouse that ZFP804A, the homolog of ZNF804A, is required for normal progenitor proliferation and neuronal migration. Using a yeast two-hybrid genome-wide screen, we identified novel interacting proteins of ZNF804A. Rather than transcriptional factors, genes involved in mRNA translation are highly represented in our interactome result...
September 19, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28924184/genetic-contributions-to-trail-making-test-performance-in-uk-biobank
#17
S P Hagenaars, S R Cox, W D Hill, G Davies, D C M Liewald, S E Harris, A M McIntosh, C R Gale, I J Deary
The Trail Making Test (TMT) is a widely used test of executive function and has been thought to be strongly associated with general cognitive function. We examined the genetic architecture of the TMT and its shared genetic aetiology with other tests of cognitive function in 23 821 participants from UK Biobank. The single-nucleotide polymorphism-based heritability estimates for trail-making measures were 7.9% (part A), 22.4% (part B) and 17.6% (part B-part A). Significant genetic correlations were identified between trail-making measures and verbal-numerical reasoning (rg>0...
September 19, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28894301/lateral-hypothalamic-glp-1-receptors-are-critical-for-the-control-of-food-reinforcement-ingestive-behavior-and-body-weight
#18
L López-Ferreras, J E Richard, E E Noble, K Eerola, R H Anderberg, K Olandersson, L Taing, S E Kanoski, M R Hayes, K P Skibicka
Increased motivation for highly rewarding food is a major contributing factor to obesity. Most of the literature focuses on the mesolimbic nuclei as the core of reward behavior regulation. However, the lateral hypothalamus (LH) is also a key reward-control locus in the brain. Here we hypothesize that manipulating glucagon-like peptide-1 receptor (GLP-1R) activity selectively in the LH can profoundly affect food reward behavior, ultimately leading to obesity. Progressive ratio operant responding for sucrose was examined in male and female rats, following GLP-1R activation and pharmacological or genetic GLP-1R blockade in the LH...
September 12, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28894298/molecular-basis-of-dendritic-atrophy-and-activity-in-stress-susceptibility
#19
T C Francis, R Chandra, A Gaynor, P Konkalmatt, S R Metzbower, B Evans, M Engeln, T A Blanpied, M K Lobo
Molecular and cellular adaptations in nucleus accumbens (NAc) medium spiny neurons (MSNs) underlie stress-induced depression-like behavior, but the molecular substrates mediating cellular plasticity and activity in MSN subtypes in stress susceptibility are poorly understood. We find the transcription factor early growth response 3 (EGR3) is increased in D1 receptor containing MSNs of mice susceptible to social defeat stress. Genetic reduction of Egr3 levels in D1-MSNs prevented depression-like outcomes in stress susceptible mice by preventing D1-MSN dendritic atrophy, reduced frequency of excitatory input and altered in vivo activity...
September 12, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28894297/the-pnkd-gene-is-associated-with-tourette-disorder-or-tic-disorder-in-a-multiplex-family
#20
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
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