Genetics of response to cognitive behavior therapy in adults with major depression: a preliminary report

Abstract

Major depressive disorder is heritable and a leading cause of disability. Cognitive behavior therapy is an effective treatment for major depression. By quantifying genetic risk scores based on common genetic variants, the aim of this report was to explore the utility of psychiatric and cognitive trait genetic risk scores, for predicting the response of 894 adults with major depressive disorder to cognitive behavior therapy. The participants were recruited in a psychiatric setting, and the primary outcome score was measured using the Montgomery Åsberg Depression Rating Scale-Self Rated. Single-nucleotide polymorphism genotyping arrays were used to calculate the genomic risk scores based on large genetic studies of six phenotypes: major depressive disorder, bipolar disorder, attention-deficit/hyperactivity disorder, autism spectrum disorder, intelligence, and educational attainment. Linear mixed-effect models were used to test the relationships between the six genetic risk scores and cognitive behavior therapy outcome. Our analyses yielded one significant interaction effect (B = 0.09, p < 0.001): the autism spectrum disorder genetic risk score correlated with Montgomery Åsberg Depression Rating Scale-Self Rated changes during treatment, and the higher the autism spectrum disorder genetic load, the less the depressive symptoms decreased over time. The genetic risk scores for the other psychiatric and cognitive traits were not related to depressive symptom severity or change over time. Our preliminary results indicated, as expected, that the genomics of the response of patients with major depression to cognitive behavior therapy were complex and that future efforts should aim to maximize sample size and limit subject heterogeneity in order to gain a better understanding of the use of genetic risk factors to predict treatment outcome.

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

“…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][4][5][6][7] . For instance, PRS has been studied to predict the response to cognitive behavior therapy in major depressive disorder (MDD) 4 .…”

“…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 . For instance, PRS has been studied to predict the response to cognitive behavior therapy in major depressive disorder (MDD) 4 . In addition to PRS, gene-set analysis can be utilized to group multiple genetic variants in genes and further to related gene sets to unravel biological processes and cellular functions related to intervention responses 8 .…”

Autism spectrum disorder polygenic scores are associated with every day executive function in children admitted for clinical assessment

“…However, identifying those with particularly low or high risk may be of some value. A viable approach is to look at “extreme” PGS, as done by others [Andersson et al, ; Khera et al, ; Schizophrenia Working Group of the Psychiatric Genomics Consortium, ]. Individuals with high PGS for a given disorder might also be at increased risk for known comorbid traits and disorders.…”

Is digital cognitive behavioural therapy for insomnia effective in treating sub-threshold insomnia: a pilot RCT

“…Moderators of improvement in insomnia symptoms following CBT-I are still relatively unexplored (Luik, Kyle, & Espie, 2017). Accumulating evidence of genetic predictors of CBT outcome in a range of anxiety disorders and depression have been reported (Andersson et al, 2013(Andersson et al, , 2019Bryant et al, 2010;Hudson et al, 2013;Lonsdorf et al, 2010), and holds promise for delivering a fuller understanding of psychopathology and the ability to tailor treatments to individuals (Beevers & McGeary, 2012).…”