Review ArticleGenetics of nonpharmacological treatments of depressionZanardi, Raffaellaa,b; Carminati, Matteob; Attanasio, Francescob; Fabbri, Chiarac,d; Serretti, Alessandroc Author Information aDepartment of Clinical Neurosciences, Mood Disorder Unit, IRCCS San Raffaele Institute, Milan bDepartment of Clinical Neurosciences, University Vita-Salute San Raffaele, Milan cDepartment of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy dSocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK Received 27 May 2022 Accepted 27 October 2022. Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.psychgenetics.com. Correspondence to Raffaella Zanardi, MD, Department of Clinical Neurosciences, Mood Disorder Unit, IRCCS San Raffaele Institute, Via Stamira d'Ancona, 20, 20127 Milan, Italy, Tel: +390226433250; e-mail: [email protected] Psychiatric Genetics 33(1):p 1-7, February 2023. | DOI: 10.1097/YPG.0000000000000332 Buy SDC Metrics Abstract Nonpharmacological antidepressant treatments are effective and well tolerated in selected patients. However, response is heterogeneous and validated biomarkers would be precious to aid treatment choice. We searched Pubmed, Scopus, and Google Scholar until May 2022 for original articles evaluating the association of genetic variables with the efficacy of nonpharmacological treatments for major depressive episodes. Most studies analyzed small sample sizes using the candidate gene approach, leading to poorly replicated findings that need to be interpreted cautiously. The few available methylome-wide and genome-wide association studies (GWASs) considered only electroconvulsive therapy (ECT) and cognitive-behavioral therapy in small samples, providing interesting findings by using polygenic risk scores. A deeper knowledge of the genetic factors implicated in treatment response may lead to a better understanding of the neurobiological mechanisms of nonpharmacological therapies for depression, and depression itself. Future GWAS are going to expand their sample size, thanks to consortia such as the gen-ECT-ic consortium. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.