Predicting eating disorder and anxiety symptoms using disorder-specific and transdiagnostic polygenic scores for anorexia nervosa and obsessive-compulsive disorder

BACKGROUND: 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. METHODS: 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 N = 3212-5369 per phenotype). RESULTS: 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 [β = 0.03 (s.e. = 0.01) for AN and AN/OCD PGS at age 14; β = 0.05 (s.e. = 0.02) for OCD PGS at age 16] in girls. CONCLUSIONS: 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 relationship between perfectionism and psychopathology: a meta-analysis

Objective: The clinical significance of 2 main dimensions of perfectionism (perfectionistic strivings and perfectionistic concerns) was examined via a meta-analysis of studies investigating perfectionism in the psychopathology literature. Method: We investigated relationships between psychopathology outcomes (clinical diagnoses of depression, anxiety disorders, obsessive-compulsive disorder, and eating disorders; symptoms of these disorders; and outcomes related to psychopathology, such as deliberate self-harm, suicidal ideation, and general distress) and each perfectionism dimension. The relationships were examined by evaluating (a) differences in the magnitude of association of the 2 perfectionism dimensions with psychopathology outcomes and (b) subscales of 2 common measures of perfectionism. Results: A systematic literature search retrieved 284 relevant studies, resulting in 2,047 effect sizes that were analysed with meta-analysis and meta-regression while accounting for data dependencies. Conclusion: Findings support the notion of perfectionism as a transdiagnostic factor by demonstrating that both dimensions are associated with various forms of psychopathology

Examination of the shared genetic basis of anorexia nervosa and obsessive–compulsive disorder

Anorexia nervosa (AN) and obsessive–compulsive disorder (OCD) are often comorbid and likely to share genetic risk factors. Hence, we examine their shared genetic background using a cross-disorder GWAS meta-analysis of 3495 AN cases, 2688 OCD cases, and 18,013 controls. We confirmed a high genetic correlation between AN and OCD (rg = 0.49 ± 0.13, p = 9.07 × 10−7) and a sizable SNP heritability (SNP h2 = 0.21 ± 0.02) for the cross-disorder phenotype. Although no individual loci reached genome-wide significance, the cross-disorder phenotype showed strong positive genetic correlations with other psychiatric phenotypes (e.g., rg = 0.36 with bipolar disorder and 0.34 with neuroticism) and negative genetic correlations with metabolic phenotypes (e.g., rg = −0.25 with body mass index and −0.20 with triglycerides). Follow-up analyses revealed that although AN and OCD overlap heavily in their shared risk with other psychiatric phenotypes, the relationship with metabolic and anthropometric traits is markedly stronger for AN than for OCD. We further tested whether shared genetic risk for AN/OCD was associated with particular tissue or cell-type gene expression patterns and found that the basal ganglia and medium spiny neurons were most enriched for AN–OCD risk, consistent with neurobiological findings for both disorders. Our results confirm and extend genetic epidemiological findings of shared risk between AN and OCD and suggest that larger GWASs are warranted

Intrusive Uncertainty in Obsessive Compulsive Disorder

In this article we examine obsessive compulsive disorder (OCD). We examine and reject two existing models of this disorder: the Dysfunctional Belief Model and the Inference-Based Approach. Instead, we propose that the main distinctive characteristic of OCD is a hyperactive sub-personal signal of being in error, experienced by the individual as uncertainty about his or her intentional actions (including mental actions). This signalling interacts with the anxiety sensitivities of the individual to trigger conscious checking processes, including speculations about possible harms. We examine the implications of this model for the individual’s capacity to control his or her thoughts

Stepped care treatment for depression and anxiety in primary care. a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Depressive and anxiety disorders are common in general practice but not always treated adequately. Introducing stepped care might improve this. In this randomized trial we examined the effectiveness of such a stepped care model.</p> <p>Methods</p> <p>The study population consisted of primary care attendees aged 18-65 years with minor or major DSM-IV depressive and/or anxiety disorders, recruited through screening. We randomized 120 patients to either stepped care or care as usual. The stepped care program consisted of (1) <it>watchful waiting</it>, (2) <it>guided self-help</it>, (3) short face-to-face <it>Problem Solving Treatment </it>and (4) <it>pharmacotherapy and/or specialized mental health care</it>. Patients were assessed at baseline and after 8, 16 and 24 weeks.</p> <p>Results</p> <p>Symptoms of depression and anxiety decreased significantly over time for both groups. However, there was no statistically significant difference between the two groups (IDS: <it>P </it>= 0.35 and HADS: <it>P </it>= 0.64). The largest, but not significant, effect (<it>d </it>= -0.21) was found for anxiety on T3. In both groups approximately 48% of the patients were recovered from their DSM-IV diagnosis at the final 6 months assessment.</p> <p>Conclusions</p> <p>In summary we could not demonstrate that stepped care for depression and anxiety in general practice was more effective than care as usual. Possible reasons are discussed.</p> <p>Trial Registration</p> <p>Current Controlled Trails: <a href="http://www.controlled-trials.com/ISRCTN17831610">ISRCTN17831610</a>.</p

A systematic review of the clinical effectiveness and cost-effectiveness of pharmacological and psychological interventions for the management of obsessive–compulsive disorder in children/adolescents and adults

Background: Obsessive–compulsive disorder (OCD) is a relatively common and disabling condition. Objectives: To determine the clinical effectiveness, acceptability and cost-effectiveness of pharmacological and psychological interventions for the treatment of OCD in children, adolescents and adults. Data sources: We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Trials Registers, which includes trials from routine searches of all the major databases. Searches were conducted from inception to 31 December 2014. Review methods: We undertook a systematic review and network meta-analysis (NMA) of the clinical effectiveness and acceptability of available treatments. Outcomes for effectiveness included mean differences in the total scores of the Yale–Brown Obsessive–Compulsive Scale or its children’s version and total dropouts for acceptability. For the cost-effectiveness analysis, we developed a probabilistic model informed by the results of the NMA. All analyses were performed using OpenBUGS version 3.2.3 (members of OpenBUGS Project Management Group; see www.openbugs.net). Results: We included 86 randomised controlled trials (RCTs) in our systematic review. In the NMA we included 71 RCTs (54 in adults and 17 in children and adolescents) for effectiveness and 71 for acceptability (53 in adults and 18 in children and adolescents), comprising 7643 and 7942 randomised patients available for analysis, respectively. In general, the studies were of medium quality. The results of the NMA showed that in adults all selective serotonin reuptake inhibitors (SSRIs) and clomipramine had greater effects than drug placebo. There were no differences between SSRIs, and a trend for clomipramine to be more effective did not reach statistical significance. All active psychological therapies had greater effects than drug placebo. Behavioural therapy (BT) and cognitive therapy (CT) had greater effects than psychological placebo, but cognitive–behavioural therapy (CBT) did not. BT and CT, but not CBT, had greater effects than medications, but there are considerable uncertainty and methodological limitations that should be taken into account. In children and adolescents, CBT and BT had greater effects than drug placebo, but differences compared with psychological placebo did not reach statistical significance. SSRIs as a class showed a trend for superiority over drug placebo, but the difference did not reach statistical significance. However, the superiority of some individual drugs (fluoxetine, sertraline) was marginally statistically significant. Regarding acceptability, all interventions except clomipramine had good tolerability. In adults, CT and BT had the highest probability of being most cost-effective at conventional National Institute for Health and Care Excellence thresholds. In children and adolescents, CBT or CBT combined with a SSRI were more likely to be cost-effective. The results are uncertain and sensitive to assumptions about treatment effect and the exclusion of trials at high risk of bias. Limitations: The majority of psychological trials included patients who were taking medications. There were few studies in children and adolescents. Conclusions: In adults, psychological interventions, clomipramine, SSRIs or combinations of these are all effective, whereas in children and adolescents, psychological interventions, either as monotherapy or combined with specific SSRIs, were more likely to be effective. Future RCTs should improve their design, in particular for psychotherapy or combined interventions. Study registration: The study is registered as PROSPERO CRD42012002441. Funding details: The National Institute for Health Research Health Technology Assessment programme