A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders

Abstract

Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation ( r g ≈ 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders ( n = 972), adults with major depressive disorder ( n = 832) and children with anxiety disorders ( n = 920; meta-analysis n = 2724). We estimated the variance in therapy outcomes that could be explained by common genetic variants ( h 2 SNP ) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h 2 SNP could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits.

Inclusion of genetic variants in an ensemble of gradient boosting decision trees does not improve the prediction of citalopram treatment response

“…Other work taking a candidate gene 6 , 7 , candidate system approach 5 , or polygenic risk scores 11 have generally found similarly disappointing results for the prediction of antidepressant treatment response. Thus, genetic variation may be most useful for investigating the etiology of treatment response between groups of patients (e.g., responders vs non-responders) but may currently not be useful for deriving personalized predictions of treatment response 34 . Other areas of research, such as educational attainment, have arrived at similar conclusions 35 .…”

The influence of common polygenic risk and gene sets on social skills group training response in autism spectrum disorder

“…Genome-wide association studies (GWAS) have been used to pinpoint common variants, with mostly small effects, associated with disorders or personality traits across the genome. For behavioral interventions, the size of available cohorts with detailed outcomes is limited, and to date, no significant variants have been associated with any specific intervention outcome using GWAS 2 . However, the use of polygenic risk score (PRS), an aggregate measure of the cumulative effects of single nucleotide polymorphisms (SNPs) derived from GWAS, has provided promising results in psychiatry both for behavioral and pharmacological treatments 3 – 7 .…”

Evidence for distinct genetic and environmental influences on fear acquisition and extinction

“…The modest but significant heritability of fear extinction (15%) suggests that a relatively small degree of variation in fear extinction in healthy individuals is influenced by genetic factors. There have been no twin studies of treatment response for anxiety, and two genome-wide meta analyses of Cognitive Behavioural Therapy (CBT) treatment response have failed to derive significant heritability estimates despite having statistical power to detect heritability of 30% or greater (Coleman et al, 2016; Rayner et al, 2019). This study thus adds to our limited knowledge about the relative role for genes and the environment in fear extinction, a mechanism underpinning exposure-based treatment, a core component of CBT for anxiety disorders.…”

“…These include specific life experiences, and individual characteristics such as unemployment, low educational attainment and poor interpersonal relationships that are also known to reduce treatment efficacy (DeRubeis et al, 2014;Mojtabai, 2017;Newman, Llera, Erickson, Przeworski, & Castonguay, 2013;Renaud, Russell, & Myhr, 2014). Specific disorder profiles, including greater symptom severity, comorbidity with other mental health disorders and poor treatment adherence are associated with poor treatment response in anxious adults and children (Hudson et al, 2013(Hudson et al, , 2015Rayner et al, 2019;Wergeland et al, 2016). Understanding modifiable personal risk factors may help identify areas for intervention that could serve as a precursor or adjunct to therapy to further enhance the effect of exposure within a personalised medicine framework.…”

“…Although there is evidence for familial clustering (Franchini, Serretti, Gasperini, & Smeraldi, 1998; O’Reilly, Bogue, & Singh, 1994) and influence of common genetic variants(Tansey et al, 2013) in response to antidepressant treatment for depression, the heritability of psychological treatment response is currently unknown. The largest studies in this field to date were insufficiently powered to draw strong conclusions (Coleman et al, 2016; Rayner et al, 2019).…”