Additive genetic contribution to symptom dimensions in major depressive disorder

• Type of Material: Article
• Authors: Rahel Pearson, University of Texas, Austin; Rohan H. Palmer, Emory University; Leslie Brick, Emory University; John E. McGeary, Providence Veterans Affairs Medical Center; Valerie S. Knopik, Brown University; Christopher G. Beevers, University of Texas, Austin
• Language: English
• Date: 2016-05-01
• Publisher: American Psychological Association
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 American Psychological Association.
• Final Published Version (URL): http://dx.doi.org/10.1037/abn0000161
• Title of Journal or Parent Work: Journal of Abnormal Psychology
• ISSN: 0021-843X
• Volume: 125
• Issue: 4
• Start Page: 495
• End Page: 501
• Grant/Funding Information: Dr. Rohan Palmer is supported by K01AA021113 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA).; The study was supported by NIMH Contract # N01MH90003 to the University of Texas Southwestern Medical Center.
• Keywords: Polymorphism, Single Nucleotide; Middle Aged; Male; Depressive Disorder, Major; Mental Status Schedule; Adult; Psychiatric Status Rating Scales; Depression; Genotype; Humans; Likelihood Functions; Female; Genetic Predisposition to Disease
• Research Categories: Psychology, Clinical; Health Sciences, Mental Health; Biology, Genetics

Abstract

Major depressive disorder (MDD) is a phenotypically heterogeneous disorder with a complex genetic architecture. In this study, genomic-relatedness-matrix restricted maximum-likelihood analysis (GREML) was used to investigate the extent to which variance in depression symptoms/symptom dimensions can be explained by variation in common single nucleotide polymorphisms (SNPs) in a sample of individuals with MDD (N = 1,558) who participated in the National Institute of Mental Health Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. A principal components analysis of items from the Hamilton Rating Scale for Depression (HRSD) obtained prior to treatment revealed 4 depression symptom components: (a) appetite, (b) core depression symptoms (e.g., depressed mood, anhedonia), (c) insomnia, and (d) anxiety. These symptom dimensions were associated with SNP-based heritability (h2SNP) estimates of 30%, 14%, 30%, and 5%, respectively. Results indicated that the genetic contribution of common SNPs to depression symptom dimensions were not uniform. Appetite and insomnia symptoms in MDD had a relatively strong genetic contribution whereas the genetic contribution was relatively small for core depression and anxiety symptoms. While in need of replication, these results suggest that future gene discovery efforts may strongly benefit from parsing depression into its constituent parts.