scholarly journals Genome wide meta-analysis identifies genomic relationships, novel loci, and pleiotropic mechanisms across eight psychiatric disorders

2019 ◽  
Author(s):  
◽  
Phil H. Lee ◽  
Verneri Anttila ◽  
Hyejung Won ◽  
Yen-Chen A. Feng ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Meta Analysis ◽  
Autism Spectrum ◽  
Pleiotropic Effects ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Hyperactivity Disorder ◽  
Genome Wide ◽  
Genomic Relationships ◽  
The Brain

SummaryGenetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed a meta-analysis of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders identifying three groups of inter-related disorders. We detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning in the second trimester prenatally, and play prominent roles in a suite of neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.

scholarly journals Comprehensive exploration of the genetic contribution of the dopaminergic and serotonergic pathways to psychiatric disorders

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Judit Cabana-Domínguez ◽  
Bàrbara Torrico ◽  
Andreas Reif ◽  
Noèlia Fernàndez-Castillo ◽  
Bru Cormand
Keyword(s):  
Psychiatric Disorders ◽  
Meta Analysis ◽  
Autism Spectrum ◽  
Genetic Contribution ◽  
Obsessive Compulsive ◽  
Gene Set ◽  
Compulsive Disorder ◽  
Kegg Pathways ◽  
Gene Sets ◽  
Psychiatric Conditions

AbstractPsychiatric disorders are highly prevalent and display considerable clinical and genetic overlap. Dopaminergic and serotonergic neurotransmission have been shown to play an important role in many psychiatric disorders. Here we aim to assess the genetic contribution of these systems to eight psychiatric disorders (attention-deficit hyperactivity disorder (ADHD), anorexia nervosa (ANO), autism spectrum disorder (ASD), bipolar disorder (BIP), major depression (MD), obsessive-compulsive disorder (OCD), schizophrenia (SCZ) and Tourette’s syndrome (TS)) using publicly available GWAS analyses performed by the Psychiatric Genomics Consortium that include more than 160,000 cases and 275,000 controls. To do so, we elaborated four different gene sets: two ‘wide’ selections for dopamine (DA) and for serotonin (SERT) using the Gene Ontology and KEGG pathways tools, and two’core’ selections for the same systems, manually curated. At the gene level, we found 67 genes from the DA and/or SERT gene sets significantly associated with one of the studied disorders, and 12 of them were associated with two different disorders. Gene-set analysis revealed significant associations for ADHD and ASD with the wide DA gene set, for BIP with the wide SERT gene set, and for MD with the core SERT set. Interestingly, interrogation of a cross-disorder GWAS meta-analysis of the eight psychiatric conditions displayed association with the wide DA gene set. To our knowledge, this is the first systematic examination of genes encoding proteins essential to the function of these two neurotransmitter systems in these disorders. Our results support a pleiotropic contribution of the dopaminergic and serotonergic systems in several psychiatric conditions.

scholarly journals Genetic influences on eight psychiatric disorders based on family data of 4 408 646 full and half-siblings, and genetic data of 333 748 cases and controls

2018 ◽  
Vol 49 (07) ◽  
pp. 1166-1173 ◽  
Author(s):  
E. Pettersson ◽  
P. Lichtenstein ◽  
H. Larsson ◽  
J. Song ◽  
A. Agrawal ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Autism Spectrum ◽  
Psychiatric Research ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Hyperactivity Disorder ◽  
Unique Character ◽  
Psychiatric Conditions ◽  
Heritability Estimates ◽  
Study Designs

AbstractBackgroundMost studies underline the contribution of heritable factors for psychiatric disorders. However, heritability estimates depend on the population under study, diagnostic instruments, and study designs that each has its inherent assumptions, strengths, and biases. We aim to test the homogeneity in heritability estimates between two powerful, and state of the art study designs for eight psychiatric disorders.MethodsWe assessed heritability based on data of Swedish siblings (N = 4 408 646 full and maternal half-siblings), and based on summary data of eight samples with measured genotypes (N = 125 533 cases and 208 215 controls). All data were based on standard diagnostic criteria. Eight psychiatric disorders were studied: (1) alcohol dependence (AD), (2) anorexia nervosa, (3) attention deficit/hyperactivity disorder (ADHD), (4) autism spectrum disorder, (5) bipolar disorder, (6) major depressive disorder, (7) obsessive-compulsive disorder (OCD), and (8) schizophrenia.ResultsHeritability estimates from sibling data varied from 0.30 for Major Depression to 0.80 for ADHD. The estimates based on the measured genotypes were lower, ranging from 0.10 for AD to 0.28 for OCD, but were significant, and correlated positively (0.19) with national sibling-based estimates. When removing OCD from the data the correlation increased to 0.50.ConclusionsGiven the unique character of each study design, the convergent findings for these eight psychiatric conditions suggest that heritability estimates are robust across different methods. The findings also highlight large differences in genetic and environmental influences between psychiatric disorders, providing future directions for etiological psychiatric research.

Mindfulness-Based Interventions for Psychiatric Disorders

2018 ◽  
Author(s):  
Aleeze Moss ◽  
Diane Reibel
Keyword(s):  
Psychiatric Disorders ◽  
Dialectical Behavior Therapy ◽  
Stress Reduction ◽  
Anxiety And Depression ◽  
Obsessive Compulsive ◽  
Functional Changes ◽  
Compulsive Disorder ◽  
Hyperactivity Disorder ◽  
Acceptance And Commitment ◽  
The Brain

Mindfulness-Based Interventions (MBIs) are nonpharmacological interventions that show promise for the treatment of a number of mental health conditions. This chapter describes several MBIs, specifically Mindfulness-Based Stress Reduction (MBSR), Mindfulness-Based Cognitive Therapy (MBCT), Dialectical Behavior Therapy (DBT) and Acceptance and Commitment Therapy (ACT) and the research that supports the efficacy of these interventions in the treatment of psychiatric disorders. MBSR and MBCT have been shown to be effective in the treatment of anxiety and depression. DBT has been shown to be effective in the treatment of borderline personality disorder and ACT effective in the treatment of obsessive-compulsive disorder. New MBIs are being developed to work specifically with populations suffering with posttraumatic stress disorder, eating disorders, addictions, and attention deficit hyperactivity disorder. Current research on neural mechanisms associated with mindfulness training and its benefits are demonstrating structural and functional changes in the brain.

scholarly journals Cross-disorder GWAS meta-analysis for Attention Deficit/Hyperactivity Disorder, Autism Spectrum Disorder, Obsessive Compulsive Disorder, and Tourette Syndrome

2019 ◽  
Author(s):  
Zhiyu Yang ◽  
Hanrui Wu ◽  
Phil H. Lee ◽  
Fotis Tsetsos ◽  
Lea K. Davis ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Attention Deficit Hyperactivity Disorder ◽  
Obsessive Compulsive Disorder ◽  
Tourette Syndrome ◽  
Attention Deficit ◽  
Meta Analysis ◽  
Autism Spectrum ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Hyperactivity Disorder

AbstractAttention Deficit/Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), Obsessive-Compulsive Disorder (OCD), and Tourette Syndrome (TS) are among the most prevalent neurodevelopmental psychiatric disorders of childhood and adolescence. High comorbidity rates across these four disorders point toward a common etiological thread that could be connecting them across the repetitive behaviors-impulsivity-compulsivity continuum. Aiming to uncover the shared genetic basis across ADHD, ASD, OCD, and TS, we undertake a systematic cross-disorder meta-analysis, integrating summary statistics from all currently available genome-wide association studies (GWAS) for these disorders, as made available by the Psychiatric Genomics Consortium (PGC) and the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH). We present analysis of a combined dataset of 93,294 individuals, across 6,788,510 markers and investigate associations on the single-nucleotide polymorphism (SNP), gene and pathway levels across all four disorders but also pairwise. In the ADHD-ASD-OCD-TS cross disorder GWAS meta-analysis, we uncover in total 297 genomewide significant variants from six LD (linkage disequilibrium) -independent genomic risk regions. Out of these genomewide significant association results, 199 SNPs, that map onto four genomic regions, show high posterior probability for association with at least three of the studied disorders (m-value>0.9). Gene-based GWAS meta-analysis across ADHD, ASD, OCD, and TS identified 21 genes significantly associated under Bonferroni correction. Out of those, 15 could not be identified as significantly associated based on the individual disorder GWAS dataset, indicating increased power in the cross-disorder comparisons. Cross-disorder tissue-specificity analysis implicates the Hypothalamus-Pituitary-Adrenal axis (stress response) as possibly underlying shared pathophysiology across ADHD, ASD, OCD, and TS. Our work highlights genetic variants and genes that may contribute to overlapping neurobiology across the four studied disorders and highlights the value of re-defining the framework for the study across this spectrum of highly comorbid disorders, by using transdiagnostic approaches.

scholarly journals Association between polygenic propensity for psychiatric disorders and nutrient intake

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Avina K. Hunjan ◽  
Christopher Hübel ◽  
Yuhao Lin ◽  
Thalia C. Eley ◽  
Gerome Breen
Keyword(s):  
Psychiatric Disorders ◽  
Nutrient Intake ◽  
Autism Spectrum ◽  
Dietary Behaviour ◽  
Obsessive Compulsive ◽  
Higher Alcohol ◽  
Polygenic Score ◽  
Compulsive Disorder ◽  
Genome Wide ◽  
Polygenic Scores

AbstractDespite the observed associations between psychiatric disorders and nutrient intake, genetic studies are limited. We examined whether polygenic scores for psychiatric disorders are associated with nutrient intake in UK Biobank (N = 163,619) using linear mixed models. We found polygenic scores for attention-deficit/hyperactivity disorder, bipolar disorder, and schizophrenia showed the highest number of associations, while a polygenic score for autism spectrum disorder showed no association. The relatively weaker obsessive-compulsive disorder polygenic score showed the greatest effect sizes suggesting its association with diet traits may become more apparent with larger genome-wide analyses. A higher alcohol dependence polygenic score was associated with higher alcohol intake and individuals with higher persistent thinness polygenic scores reported their food to weigh less, both independent of socioeconomic status. Our findings suggest that polygenic propensity for a psychiatric disorder is associated with dietary behaviour. Note, nutrient intake was self-reported and findings must therefore be interpreted mindfully.

scholarly journals Genome-wide association meta-analysis of childhood and adolescent internalising symptoms

2020 ◽  
Author(s):  
Eshim S Jami ◽  
Anke R Hammerschlag ◽  
Hill F Ip ◽  
Andrea G Allegrini ◽  
Beben Benyamin ◽  
...  
Keyword(s):  
Confidence Intervals ◽  
Meta Analysis ◽  
Genetic Correlations ◽  
Genetic Effects ◽  
Childhood Aggression ◽  
Genome Wide Association ◽  
Childhood And Adolescence ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Genome Wide

Internalising symptoms in childhood and adolescence are as heritable as adult depression and anxiety, yet little is known of their molecular basis. This genome-wide association meta-analysis of internalising symptoms included repeated observations from 64,641 individuals, aged between 3 and 18. The N-weighted meta-analysis of overall internalising symptoms (INToverall) detected no genome-wide significant hits and showed low SNP heritability (1.66%, 95% confidence intervals 0.84-2.48%, Neffective=132,260). Stratified analyses showed rater-based heterogeneity in genetic effects, with self-reported internalising symptoms showing the highest heritability (5.63%, 95% confidence intervals 3.08-8.18%). Additive genetic effects on internalising symptoms appeared stable over age, with overlapping estimates of SNP heritability from early-childhood to adolescence. Gene-based analyses showed significant associations with three genes: WNT3 (p=1.13×10-06), CCL26 (p=1.88×10-06), and CENPO (p=2.54×10-06). Of these, WNT3 was previously associated with neuroticism, with which INToverall also shared a strong genetic correlation (rg=0.76). Genetic correlations were also observed with adult anxiety, depression, and the wellbeing spectrum (|rg|> 0.70), as well as with insomnia, loneliness, attention-deficit hyperactivity disorder, autism, and childhood aggression (range |rg|=0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa. Overall, childhood and adolescent internalising symptoms share substantial genetic vulnerabilities with adult internalising disorders and other childhood psychiatric traits, which could explain both the persistence of internalising symptoms over time, and the high comorbidity amongst childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.

Dysfunctional meta-cognitive beliefs across psychopathology: A meta-analytic review

2016 ◽  
Vol 33 (S1) ◽  
pp. s225-s225 ◽  
Author(s):  
X. Sun ◽  
S.H.W. So ◽  
C. Zhu ◽  
P.W.L. Leung
Keyword(s):  
Psychiatric Disorders ◽  
Meta Analysis ◽  
Effect Sizes ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Analytic Review ◽  
Cognitive Beliefs ◽  
Patient Groups ◽  
Competing Interest ◽  
And Coping

IntroductionIt is assumed that dysfunctional meta-cognitive beliefs about one's thoughts increase problematic appraisals and coping behaviors, which further contribute to the development of mental disorders (Wells and Matthews, 1994; Wells, 2000). Although this research interest originated around generalized anxiety disorder (GAD), recent studies have begun to examine similar meta-cognitive processes in other disorders. The majority of studies using Meta-cognitions Questionnaire (MCQ; Cartwright-Hatton & Wells, 1997) and its variants to assess meta-cognitive beliefs.ObjectivesWe conducted a meta-analysis to integrate empirical findings on group differences in meta-cognitive beliefs between healthy individuals and patients with various psychiatric disorders.MethodsWe followed the PRISMA guideline (Liberati et al., 2009). A systematic literature search was conducted. We included studies that involved a diagnosed psychiatric group and healthy controls (aged 18 or above), reported group comparisons of metacognition, and were published during the period of 1990–27 August 2015. Effect sizes were computed.ResultsA final set of 43 studies was included. Large combined effect sizes were found on each subdomain of the MCQ, indicating increased levels of dysfunctional meta-cognitive beliefs in patients. Subgroup analyses were carried out based on psychiatric diagnosis (i.e. psychosis, n = 10; GAD, n = 7; obsessive-compulsive disorder, OCD, n = 15; anorexia nervosa, n = 5). All patient groups were more dysfunctional on each subtype of meta-cognitive beliefs than controls. Effect size of U/D was particularly large for GAD, and that of CSC was particularly large for OCD.ConclusionsDysfunctional meta-cognitive beliefs are evident across several psychiatric disorders, with specific types of beliefs being more marked in certain diagnoses.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Methylphenidate-induced Obsessive Compulsive Disorder in Attention Deficit Hyperactivity Disorder

2016 ◽  
Vol 2 (1) ◽  
pp. 21-22
Author(s):  
Sharath Vishwaraj
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Complete Remission ◽  
Psychiatric Disorders ◽  
Obsessive Compulsive Disorder ◽  
Attention Deficit ◽  
Specific Treatment ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Hyperactivity Disorder ◽  
Childhood Psychiatric Disorders

ABSTRACT Introduction Attention deficit hyperactivity disorder (ADHD) is one of the most common childhood psychiatric disorders. It is most often treated with methylphenidate (MPH). A 6-year-old male with ADHD was started on MPH. He developed severe obsessive-compulsive disorder (OCD), which lasted for 1 day and was self-limiting. There was complete remission on stopping MPH, without any specific treatment for OCD. How to cite this article Bavle A, Vishwaraj S. Methylphenidate- induced Obsessive Compulsive Disorder in Attention Deficit Hyperactivity Disorder. J Med Sci 2016;2(1):21-22.

scholarly journals Novel genome-wide associations for anhedonia, genetic correlation with psychiatric disorders, and polygenic association with brain structure

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Joey Ward ◽  
Laura M. Lyall ◽  
Richard A. I. Bethlehem ◽  
Amy Ferguson ◽  
Rona J. Strawbridge ◽  
...  
Keyword(s):  
White Matter ◽  
Psychiatric Disorders ◽  
Brain Structure ◽  
Genetic Correlations ◽  
Grey Matter Volume ◽  
Obsessive Compulsive ◽  
Major Depressive ◽  
Compulsive Disorder ◽  
Matter Volume ◽  
Genome Wide

AbstractAnhedonia is a core symptom of several psychiatric disorders but its biological underpinnings are poorly understood. We performed a genome-wide association study of state anhedonia in 375,275 UK Biobank participants and assessed for genetic correlation between anhedonia and neuropsychiatric conditions (major depressive disorder, schizophrenia, bipolar disorder, obsessive compulsive disorder and Parkinson’s Disease). We then used a polygenic risk score approach to test for association between genetic loading for anhedonia and both brain structure and brain function. This included: magnetic resonance imaging (MRI) assessments of total grey matter volume, white matter volume, cerebrospinal fluid volume, and 15 cortical/subcortical regions of interest; diffusion tensor imaging (DTI) measures of white matter tract integrity; and functional MRI activity during an emotion processing task. We identified 11 novel loci associated at genome-wide significance with anhedonia, with a SNP heritability estimate (h2SNP) of 5.6%. Strong positive genetic correlations were found between anhedonia and major depressive disorder, schizophrenia and bipolar disorder; but not with obsessive compulsive disorder or Parkinson’s Disease. Polygenic risk for anhedonia was associated with poorer brain white matter integrity, smaller total grey matter volume, and smaller volumes of brain regions linked to reward and pleasure processing, including orbito-frontal cortex. In summary, the identification of novel anhedonia-associated loci substantially expands our current understanding of the biological basis of state anhedonia and genetic correlations with several psychiatric disorders confirm the utility of this phenotype as a transdiagnostic marker of vulnerability to mental illness. We also provide the first evidence that genetic risk for state anhedonia influences brain structure, including in regions associated with reward and pleasure processing.

Inhibitory control and psychopathology: A meta-analysis of studies using the stop signal task

2010 ◽  
Vol 16 (6) ◽  
pp. 1064-1076 ◽  
Author(s):  
JONATHAN LIPSZYC ◽  
RUSSELL SCHACHAR
Keyword(s):  
Substance Dependence ◽  
Meta Analysis ◽  
Stop Signal ◽  
Stop Signal Task ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Hyperactivity Disorder ◽  
Oppositional Defiant ◽  
Stop Signal Reaction Time ◽  
Comorbid Adhd

AbstractThe Stop Signal Task (SST) is a measure that has been used widely to assess response inhibition. We conducted a meta-analysis of studies that examined SST performance in patients with various psychiatric disorders to determine the magnitude and generality of deficient inhibition. A five-item instrument was used to assess the methodological quality of studies. We found medium deficits in stop signal reaction time (SSRT), reflecting the speed of the inhibitory process, for attention-deficit hyperactivity disorder (ADHD) (g = 0.62), obsessive compulsive disorder (OCD) (g = 0.77) and schizophrenia (SCZ) (g = 0.69). SSRT was less impaired or normal for anxiety disorder (ANX), autism, major depressive disorder (MDD), oppositional defiant disorder/conduct disorder (ODD/CD), pathological gambling, reading disability (RD), substance dependence, and Tourette syndrome. We observed a large SSRT deficit for comorbid ADHD + RD (g = 0.82). SSRT was less than moderately impaired for ADHD + ANX and ADHD + ODD/CD. Study quality did not significantly affect SSRT across ADHD studies. This confirms an inhibition deficit in ADHD, and suggests that comorbid ADHD has different effects on inhibition in patients with ANX, ODD/CD, and RD. Further studies are needed to firmly establish an inhibition deficit in OCD and SCZ. (JINS, 2010, 16, 1064–1076.)

Sign in / Sign up

Export Citation Format

Share Document