Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders.
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ABSTRACT:
SUBMITTER: Eijsbouts C
PROVIDER: S-EPMC8571093 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:AIM:To assess the association of six polymorphisms in serotonin-related genes with depressive or anxiety disorders in patients with irritable bowel syndrome (IBS). METHODS:The lifetime prevalence of depressive and anxiety disorders was assessed in 95 IBS patients (85% women) using the Munich version of the Composite International Diagnostic Interview (CIDI). IBS was diagnosed according to the Rome III criteria. SCL6A4 HTTLPR polymorphism (rs4795541) was determined using PCR-based method. Single-nucleotide polymorphisms in HTR1A (rs6295), HTR2A (rs6313 and rs6311), HTR2C (rs6318), and TPH1 (rs1800532) were detected by minisequencing method. RESULTS:IBS patients with depressive disorders were characterized by higher frequency of 5-HTTLPR L allele in comparison to IBS patients with anxiety disorders. The lower frequency of 1438 A allele in HTR2A was found in IBS patients with depressive disorders in comparison to IBS patients without mental disorders. The lower G allele frequency in HTR2C rs6318 polymorphism among IBS patients with anxiety disorders was also observed. CONCLUSIONS:Our results provide further evidence for the involvement of SLC6A4 rs4795541 and HTR2A rs6311 polymorphisms in the pathophysiology of depressive disorders in IBS patients. The new findings indicate that HTR2C rs6318 polymorphism may be associated with the susceptibility to anxiety disorders in IBS patients.
| S-EPMC5603736 | biostudies-literature
Project description:Anxiety disorders (ANX), namely generalized anxiety, panic disorder, and phobias, are common, etiologically complex syndromes that show increasing prevalence and comorbidity throughout adolescence and beyond. Few genome-wide association studies (GWAS) examining ANX risk have been published and almost exclusively in individuals of European ancestry. In this study, we phenotyped participants from the Army Study To Assess Risk and Resilience in Servicemembers (STARRS) to approximate DSM-based ANX diagnoses. We factor-analyzed those to create a single dimensional anxiety score for each subject. GWAS were conducted using that score within each of three ancestral groups (EUR, AFR, LAT) and then meta-analyzed across ancestries (NTotal = 16,510). We sought to (a) replicate prior ANX GWAS findings in ANGST; (b) determine whether results extended to other ancestry groups; and (c) meta-analyze with ANGST for increased power to identify novel susceptibility loci. No reliable genome-wide significant SNP associations were detected in STARRS. However, SNPs within the CAMKMT gene located in region 2p21 associated with shared ANX risk in ANGST were replicated in EUR soldiers but not other ancestry groups. Combining EUR STARRS and ANGST (N = 28,950) yielded a more robust 2p21 association signal (p = 9.08x10-11 ). Gene-based analyses supported three genes within 2p21 and LBX1 on chromosome 10. More powerful ANX genetic studies will be required to identify further loci.
| S-EPMC7210051 | biostudies-literature
Project description:Differential gene expression profiling in peripheral blood mononuclear cells (PBMCs) was performed using Human Transcriptome Array 2 (HTA2)
2016-12-31 | GSE63379 | GEO
Project description:ImportanceMajor depressive disorder, bipolar disorder, posttraumatic stress disorder, and anxiety disorders are highly comorbid and have shared clinical features. It is not yet known whether their clinical overlap is reflected at the neurobiological level.ObjectiveTo detect transdiagnostic convergence in abnormalities in task-related brain activation.Data sourceTask-related functional magnetic resonance imaging articles published in PubMed, Web of Science, and Google Scholar during the last decade comparing control individuals with patients with mood, posttraumatic stress, and anxiety disorders were examined.Study selectionFollowing Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines, articles were selected if they reported stereotactic coordinates of whole-brain-based activation differences between adult patients and control individuals.Data extraction and synthesisCoordinates of case-control differences coded by diagnosis and by cognitive domain based on the research domain criteria were analyzed using activation likelihood estimation.Main outcomes and measuresIdentification of transdiagnostic clusters of aberrant activation and quantification of the contribution of diagnosis and cognitive domain to each cluster.ResultsA total of 367 experiments (major depressive disorder, 149; bipolar disorder, 103; posttraumatic stress disorder, 55; and anxiety disorders, 60) were included comprising observations from 4507 patients and 4755 control individuals. Three right-sided clusters of hypoactivation were identified centered in the inferior prefrontal cortex/insula (volume, 2120 mm3), the inferior parietal lobule (volume, 1224 mm3), and the putamen (volume, 888 mm3); diagnostic differences were noted only in the putamen (χ23 = 8.66; P = .03), where hypoactivation was more likely in bipolar disorder (percentage contribution = 72.17%). Tasks associated with cognitive systems made the largest contribution to each cluster (percentage contributions >29%). Clusters of hyperactivation could only be detected using a less stringent threshold. These were centered in the perigenual/dorsal anterior cingulate cortex (volume, 2208 mm3), the left amygdala/parahippocampal gyrus (volume, 2008 mm3), and the left thalamus (volume, 1904 mm3). No diagnostic differences were observed (χ23 < 3.06; P > .38), while tasks associated with negative valence systems made the largest contribution to each cluster (percentage contributions >49%). All findings were robust to the moderator effects of age, sex, and magnetic field strength of the scanner and medication.Conclusions and relevanceIn mood disorders, posttraumatic stress disorder, and anxiety disorders, the most consistent transdiagnostic abnormalities in task-related brain activity converge in regions that are primarily associated with inhibitory control and salience processing. Targeting these shared neural phenotypes could potentially mitigate the risk of affective morbidity in the general population and improve outcomes in clinical populations.
| S-EPMC6822098 | biostudies-literature
Project description:OBJECTIVE:Mood disorders are the most common comorbid conditions in epilepsy, but the cause remains unclear. One possible explanation is a shared genetic susceptibility to epilepsy and mood disorders. We tested this hypothesis by evaluating lifetime prevalence of mood disorders in relatives with and without epilepsy in families containing multiple individuals with epilepsy, and comparing the findings with rates from a general population sample. METHODS:The Composite International Diagnostic Interview was administered to 192 individuals from 60 families, including 110 participants with epilepsy of unknown cause (50 focal epilepsy [FE], 42 generalized epilepsy [GE], 6 FE and GE, 12 unclassifiable) and 82 relatives without epilepsy (RWOE). Odds ratios (ORs) for lifetime prevalence of mood disorders in participants with versus without epilepsy were computed through logistic regression, using generalized estimation equations to account for familial clustering. Standardized prevalence ratios (SPRs) were used to compare prevalence in family members with general population rates. RESULTS:Compared with RWOE, ORs for mood disorders were significantly increased in participants with FE (OR = 2.4, 95% confidence interval [CI] = 1.1-5.2) but not in those with GE (OR = 1.0, 95% CI = 0.4-2.2). In addition, prevalence of mood disorders was increased in individuals with epilepsy who had ?1 relative with FE. Compared with general population rates, mood disorders were significantly increased in individuals with FE but not in those with GE. Rates were also increased in RWOE, but not significantly so (SPR = 1.4, P = .14). SIGNIFICANCE:These findings are consistent with the hypothesis of shared genetic susceptibility to epilepsy and mood disorders, but suggest (1) the effect may be restricted to FE, and (2) the shared genetic effect on risk of mood disorders and epilepsy may be restricted to individuals with epilepsy, that is, to those in whom the genetic risk for epilepsy is "penetrant."
| S-EPMC5803440 | biostudies-literature
Project description:BACKGROUND:Mood and anxiety disorders are leading causes of disability and mortality, due largely to their onset during adolescence and young adulthood and broader impact on functioning. Key factors that are associated with disability and these disorders in young people are social and economic participation (e.g. education, employment), physical health, suicide and self-harm behaviours, and alcohol and substance use. A better understanding of the objective markers (i.e. neurobiological parameters) associated with these factors is important for the development of effective early interventions that reduce the impact of disability and illness persistence. METHODS:We systematically reviewed the literature for neurobiological parameters (i.e. neuropsychology, neuroimaging, sleep-wake and circadian biology, neurophysiology and metabolic measures) associated with functional domains in young people (12 to 30 years) with mood and/or anxiety disorders. RESULTS:Of the one hundred and thirty-four studies selected, 7.6 % investigated social and economic participation, 2.1 % physical health, 15.3 % suicide and self-harm behaviours, 6.9 % alcohol and substance use, whereas the majority (68.1 %) focussed on clinical syndrome. CONCLUSIONS:Despite the predominance of studies that solely examine the clinical syndrome of young people the literature also provides evidence of distinct associations among objective measures (indexing various aspects of brain circuitry) and other functional domains. We suggest that a shift in focus towards characterising the mechanisms that underlie and/or mediate multiple functional domains will optimise personalised interventions and improve illness trajectories.
| S-EPMC4878058 | biostudies-literature
Project description:We examined the association between regular cigarette smoking and new onset of mood and anxiety disorders.We used logistic regression analysis to detect associations between regular smoking and new-onset disorders during the 3-year follow-up among 34 653 participants in the longitudinal US National Epidemiologic Survey on Alcohol and Related Conditions (2001-2005). We used instrumental variable methods to assess the appropriateness of these models.Regular smoking was associated with an increased risk of new onset of mood and anxiety disorders in multivariable analyses (Fdf = 5,61 = 11.73; P < .001). Participants who smoked a larger number of cigarettes daily displayed a trend toward greater likelihood of new-onset disorders. Age moderated the association of smoking with most new-onset disorders. The association was mostly statistically significant and generally stronger in participants aged 18 to 49 years but was smaller and mostly nonsignificant in older adults.Our finding of a stronger association between regular cigarette smoking and increased risk of new-onset mood and anxiety disorders among younger adults suggest the need for vigorous antismoking campaigns and policy initiatives targeting this age group.
| S-EPMC3726564 | biostudies-literature
Project description:Anxiety is characterized by altered responses under uncertain conditions, but the precise mechanism by which uncertainty changes the behaviour of anxious individuals is unclear. Here we probe the computational basis of learning under uncertainty in healthy individuals and individuals suffering from a mix of mood and anxiety disorders. Participants were asked to choose between four competing slot machines with fluctuating reward and punishment outcomes during safety and stress. We predicted that anxious individuals under stress would learn faster about punishments and exhibit choices that were more affected by those punishments, thus formalizing our predictions as parameters in reinforcement learning accounts of behaviour. Overall, the data suggest that anxious individuals are quicker to update their behaviour in response to negative outcomes (increased punishment learning rates). When treating anxiety, it may therefore be more fruitful to encourage anxious individuals to integrate information over longer horizons when bad things happen, rather than try to blunt their responses to negative outcomes.
| S-EPMC6790140 | biostudies-literature
Project description:BackgroundSerious and debilitating symptoms of anxiety are the most common mental health problem worldwide, accounting for around 5% of all adult years lived with disability in the developed world. Avoidance behavior-avoiding social situations for fear of embarrassment, for instance-is a core feature of such anxiety. However, as for many other psychiatric symptoms the biological mechanisms underlying avoidance remain unclear.MethodsReinforcement learning models provide formal and testable characterizations of the mechanisms of decision making; here, we examine avoidance in these terms. A total of 101 healthy participants and individuals with mood and anxiety disorders completed an approach-avoidance go/no-go task under stress induced by threat of unpredictable shock.ResultsWe show an increased reliance in the mood and anxiety group on a parameter of our reinforcement learning model that characterizes a prepotent (pavlovian) bias to withhold responding in the face of negative outcomes. This was particularly the case when the mood and anxiety group was under stress.ConclusionsThis formal description of avoidance within the reinforcement learning framework provides a new means of linking clinical symptoms with biophysically plausible models of neural circuitry and, as such, takes us closer to a mechanistic understanding of mood and anxiety disorders.
| S-EPMC5598542 | biostudies-literature
Project description:Irritable bowel syndrome (IBS) is a common abdominal pain disorder without an organic explanation. Abuse histories (physical, sexual, emotional) are prevalent in IBS. While abuse relates to mood disorders (depression and anxiety) also common in IBS, the influence of abuse on gastrointestinal (GI) symptoms and health-related quality of life (HRQOL) and its independence from psychological symptom comorbidity has not been studied.Consecutive GI outpatients completed the ROME III Research Diagnostic Questionnaire and questionnaires on trauma (Life-Stress Questionnaire), mood (Beck Depression/Anxiety Inventories), somatic symptoms (PHQ-12), and HRQOL (SF-36). Current GI symptom severity and bother were assessed using 10-cm Visual Analog Scales.272 ROME-defined IBS (47.6 ± 0.9 years, 81% female) and 246 non-FGID (51.6 ± 1.0 years, 65% female) subjects participated. IBS patients reported greater rates of physical, sexual, and emotional abuse (p < 0.006 each), and higher depression, anxiety, and somatic symptoms (p < 0.001). Greater bowel symptom bother (7.4 ± 0.2 vs 6.7 ± 0.2, p = 0.040), severity (7.7 ± 0.2 vs 6.5 ± 0.2, p < 0.001), recent symptomatic days (9.8 ± 0.4 vs 8.5 ± 0.3, p = 0.02), and poorer HRQOL (40.9 ± 2.3 vs 55.5 ± 1.7, p < 0.001) were noted in IBS with abuse. Abuse effects were additive, with greater IBS symptom severity and poorer HRQOL noted in cases with multiple forms of abuse. Mediation analyses suggested that abuse effects on GI symptoms and HRQOL were partially mediated by mood.Abuse experiences common among IBS sufferers are associated with reports of greater GI symptoms and poorer HRQOL, particularly in those with multiple forms of abuse; this relationship may be partially mediated by concomitant mood disturbances.
| S-EPMC5042818 | biostudies-literature