The origin of sex differences in prevalence and presentation of neuropsychiatric and behavioral traits is largely unknown. Given established genetic contributions and correlations, we tested for a ...sex-differentiated genetic architecture within and between traits.
Using European ancestry genome-wide association summary statistics for 20 neuropsychiatric and behavioral traits, we tested for sex differences in single nucleotide polymorphism (SNP)-based heritability and genetic correlation (rg < 1). For each trait, we computed per-SNP z scores from sex-stratified regression coefficients and identified genes with sex-differentiated effects using a gene-based approach. We calculated correlation coefficients between z scores to test for shared sex-differentiated effects. Finally, we tested for sex differences in across-trait genetic correlations.
We observed no consistent sex differences in SNP-based heritability. Between-sex, within-trait genetic correlations were high, although <1 for educational attainment and risk-taking behavior. We identified 4 genes with significant sex-differentiated effects across 3 traits. Several trait pairs shared sex-differentiated effects. The top genes with sex-differentiated effects were enriched for multiple gene sets, including neuron- and synapse-related sets. Most between-trait genetic correlation estimates were not significantly different between sexes, with exceptions (educational attainment and risk-taking behavior).
Sex differences in the common autosomal genetic architecture of neuropsychiatric and behavioral phenotypes are small and polygenic and unlikely to fully account for observed sex-differentiated attributes. Larger sample sizes are needed to identify sex-differentiated effects for most traits. For well-powered studies, we identified genes with sex-differentiated effects that were enriched for neuron-related and other biological functions. This work motivates further investigation of genetic and environmental influences on sex differences.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Clinical, epidemiological, and genetic findings support an overlap between eating disorders, obsessive-compulsive disorder (OCD), and anxiety symptoms. However, little research has examined the role ...of genetics in the expression of underlying phenotypes. We investigated whether the anorexia nervosa (AN), OCD, or AN/OCD transdiagnostic polygenic scores (PGS) predict eating disorder, OCD, and anxiety symptoms in a large developmental cohort in a sex-specific manner.
Using summary statistics from Psychiatric Genomics Consortium AN and OCD genome-wide association studies, we conducted an AN/OCD transdiagnostic genome-wide association meta-analysis. We then calculated AN, OCD, and AN/OCD PGS in participants from the Avon Longitudinal Study of Parents and Children to predict eating disorder, OCD, and anxiety symptoms, stratified by sex (combined
= 3212-5369 per phenotype).
The PGS prediction of eating disorder, OCD, and anxiety phenotypes differed between sexes, although effect sizes were small. AN and AN/OCD PGS played a more prominent role in predicting eating disorder and anxiety risk than OCD PGS, especially in girls. AN/OCD PGS provided a small boost over AN PGS in the prediction of some anxiety symptoms. All three PGS predicted higher compulsive exercise across different developmental timepoints
0.03 (s.e. = 0.01) for AN and AN/OCD PGS at age 14;
0.05 (s.e. = 0.02) for OCD PGS at age 16 in girls.
Compulsive exercise may have a transdiagnostic genetic etiology, and AN genetic risk may play a role in the presence of anxiety symptoms. Converging with prior twin literature, our results also suggest that some of the contribution of genetic risk may be sex-specific.
The University of Florida (UF) Health Personalized Medicine Program launched in 2012 with
genotyping for clopidogrel response at UF Health Shands Hospital. We have since expanded
genotyping to UF ...Health Jacksonville and established the infrastructure at UF Health to support clinical implementation for five additional gene-drug pairs:
-thiopurines,
(
)-PEG IFN-α-based regimens,
-opioids,
-antidepressants and
-proton pump inhibitors. We are contributing to the evidence based on outcomes with genotype-guided therapy through pragmatic studies of our clinical implementations. In addition, we have developed a broad array of educational programs for providers, trainees and students that incorporate personal genotype evaluation to enhance participant learning.
Healthcare workers (HCWs) experienced high levels of stress and mental health consequences associated with the COVID-19 pandemic, which may have contributed to unhealthy coping behaviors, such as ...substance use coping (SUC). This study aimed to understand the extent of and predictors of SUC.
The sample consisted of 263 HCWs in North Central Florida. Univariable and multivariable logistic regression analyses investigated whether moral injury and other work risk factors, protective factors, and clinically relevant symptoms (i.e., work exhaustion, interpersonal disengagement, depression, anxiety, and/or PTSD) were associated with likelihood of SUC.
Clinically relevant levels of interpersonal disengagement and anxiety increased the likelihood of SUC. Mediational analyses found that interpersonal disengagement and anxiety explained 54.3% of the relationship between Self Moral Injury and SUC and explained 80.4% of the relationship between professional fulfillment and SUC.
Healthcare supervisors should be aware that providers who are experiencing moral injury and less professional fulfillment may be experiencing significant interpersonal disengagement and anxiety, which could lead to SUC. Future studies should examine the effects of implementing targeted prevention and treatment interventions, along with longitudinal outcomes related to SUC behaviors.
•Individuals with HD had hypoactive responses to errors.•Individuals with HD self-reports were opposite of their facial responses to errors.•Individuals with HD exhibit dissociation between ...perception and emotional reactions.
Hoarding disorder (HD) has been hypothesized to arise from deficits in error monitoring and abnormalities in emotional processing, but the relationship between error monitoring and emotional processing has not been examined. We examined measures of self-report, as well as behavioral, physiological, and facial responses to errors during a Stop-Change Task. 25 participants with HD and 32 healthy controls (HC) were recruited. Participants reported on number of errors committed and pre/post emotional response to errors. Skin conductance response (SCR) during correct and error commission trials was examined. Facial expression during task performance was coded for self-conscious and negative emotions. HD and HC participants had significantly different error rates but comparable error correction and post-error slowing. SCR was significantly lower for HD during error commission than for HC. During error trials, HD participants showed a significant deficit in displays of self-conscious emotions compared to HC. Self-reported emotions were increased in HD, with more negative and self-conscious emotion reported than was reported for HC participants. These findings suggest that hypoactive emotional responding at a physiological level may play a role in how errors are processed in individuals with HD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Childhood adversity is associated with the development or expression of many neuropsychiatric disorders, including those with strong genetic underpinnings. Despite reported associations between ...perceived stress and tic severity, the relationship between potentially traumatic events in childhood and Tourette Syndrome (TS), a highly heritable neuropsychiatric disorder, is unknown. This study aimed to assess whether exposure to eight categories of adverse childhood experiences (ACEs) is associated with TS severity and impairment, and whether TS genetic risk modifies this association. Online survey data were collected from 351 adult males with TS who previously participated in genetic studies. Participants completed the ACE questionnaire and a lifetime version of the Yale Global Tic Severity Scale (YGTSS). Demographic and relevant health data were assessed; polygenic risk scores (PRS) measuring aggregated TS genetic risk were derived using genome-wide association data. Univariable and multivariable linear regressions examined the relationships between childhood adversity and retrospectively recalled worst-ever tic severity and impairment, adjusting for covariates. Potential gene-by-environment (GxE) interactions between ACE and PRS were estimated. After covariate adjustment, there was a significant graded dose-response relationship between ACE Scores and increases in lifetime worst-ever tic severity and impairment. There was some evidence that TS genetic risk moderated the relationship between ACE Score and tic impairment, but not tic severity, particularly for individuals with higher TS polygenic risk. We provide evidence that childhood adversity is associated with higher lifetime TS severity and impairment, although future longitudinal studies with genetically-sensitive designs are needed to determine whether these relationships are causal and/or directional.
•Tourette syndrome has genetic and environmental influences on severity/impairment.•Adverse childhood experiences associated with higher tic severity and impairment.•Complex gene-by-environment relationship between TS genetic risk and adversity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background Although susceptibility loci exist for Gilles de la Tourette syndrome (GTS), no causative gene has been identified, perhaps in part because of phenotypic heterogeneity. This study used ...latent class analyses (LCA) to identify GTS subphenotypes and assess characteristics and heritability of the classes. Methods The study included 952 individuals from 222 GTS families recruited for genetic studies. LCA identified a best-fit model for combinations of the diagnoses of GTS, obsessive-compulsive disorder (OCD), OC symptoms and behaviors (OCS/OCB), and attention-deficit/hyperactivity disorder (ADHD) in a random sample of one sibling from each family ( n = 197), a replication sample randomly chosen from the remaining siblings ( n = 203), and in the entire sample (all siblings and parents, N = 952). Heritabilities were assessed for all categoric diagnoses and LCA classes using a variance components approach. Results In this large sample of GTS sib pairs and their parents, three GTS-affected groups were identified—GTS + OCS/OCB (Class III), GTS + OCD (Class IV), and GTS + OCD + ADHD (Class V)—in addition to a minimally affected class (I) and a small chronic tics + OCD class (II). A preponderance of males and younger age at onset was found in more comorbidly affected classes. Only the GTS + OCD + ADHD class was highly heritable. Conclusions Our data suggest that GTS classes may represent distinct entities, with both shared and unique etiologies. In particular, GTS + OCD + ADHD may represent a separate, heritable phenotype that can be used to further inform genetic studies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Hoarding disorder often results in debilitating functional impairment and may also compromise health-related quality of life (QoL). This study investigated the association between hoarding behavior ...and QoL relative to six highly impairing medical and psychiatric disorders in a sample of 20,722 participants enrolled in the internet-based Brain Health Registry. Nearly 1 in 8 participants (12.2%) endorsed clinically relevant hoarding symptoms (CHS). In separate multivariable linear regression models, hoarding was more strongly associated with mental QoL than diabetes (Standardizedβ = −0.21, 95% CI: -0.22, −0.20 vs. −0.01 -0.02, 0.0), heart disease (−0.22 -0.23, −0.20 vs. 0.00 -0.02, 0.01), chronic pain (−0.18 -0.19, −0.16 vs. −0.12 -0.13, −0.10), post-traumatic stress disorder (PTSD; −0.20 -0.22, −0.19 vs. −0.07 -0.09, −0.06), and substance use disorder (SUD; −0.21 -0.23, −0.20 vs. −0.04 -0.05, −0.03). Similarly, CHS was more strongly negatively associated with physical QoL than diabetes (−0.11 -0.10, −0.12 vs. −0.08 -0.06, −0.09), major depressive disorder (−0.09 -0.10, −0.08 vs. −0.05 -0.06, 0.03), PTSD (−0.11 -0.12, −0.10 vs. −0.08 -0.09, −0.07), and SUD (−0.12 -0.13, −0.09 vs. −0.01 -0.02, 0.00). Higher hoarding severity was associated with reductions in both mental (Standardizedβ = −0.28, ΔR2 = 0.08, p < 0.0001) and physical (β = −0.12, ΔR2 = 0.02, p < 0.0001) QoL, though the strength of the relationship between hoarding symptoms and QoL varied with depression severity. Efforts to improve the overall QoL and well-being of those with CHS are needed.
•Self-reported QoL impairment increases with the severity of hoarding symptomatology.•Hoarding symptom severity is negatively associated with QoL even at low levels.•Hoarding is more associated with QoL than most health conditions assessed.•The association between hoarding and QoL varies with depression symptom severity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•There was no association found between subjective memory complaints and objective memory performances (either visual or verbal) in individuals with hoarding disorder.•While there was initially an ...association between subjective attentional complaints and objective attention performance, this association was completely accounted for by self-reported anxiety symptoms.•Following treatment, reductions subjective memory complaints occurred in conjunction with parallel reductions in hoarding dysfunction.
Individuals with Hoarding Disorder (HD) frequently complain of problems with attention and memory. These self-identified difficulties are often used as justification for saving and acquiring behaviors. Research using neuropsychological measures to examine verbal and visual memory performance and sustained attention have reported contradictory findings. Here we aim to determine the relationship between self-reported problems with memory and attention, objective memory and attention performance, and self-reported depression and anxiety symptoms in HD. Data was available for 319 individuals who participated in a treatment study of HD. Multiple regression was used to assess the relationship between self-reported complaints and objective measures, with age, education, and measures of depression and anxiety included as covariates. We found no association between self-reported memory difficulties and objective verbal or visual memory performance. Self-reported problems with attention were associated with objective attentional performance, although this relationship was partially accounted for by anxiety symptom severity. There was a small association between visual memory performance at baseline and improvements in hoardingrelated functional abilities following treatment. Improvements in subjective memory complaints pre-to-post treatment were associated with improvements in hoarding symptom severity and hoarding-related functioning. These results demonstrate a dissociation between perceived and objective functioning in HD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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