Structural variation, including CNVs, are also a potential source of depression risk loci. CNVs can be inherited or spontaneous, also referred to as de novo. De novo CNVs—those that are present in offspring but not in either parent, have been shown to be important risk factors for several neuropsychiatric disorders, namely autism,117,118 schizophrenia119,120 and bipolar disorder.121 After conducting a systematic literature search of PubMed for papers published by December 2013 using the MESH terms for depression described previously and the phrase “Copy Number Var*,” we identified four studies, which provide preliminary evidence implicating CNVs in depression.124-127 In the largest of these studies, Glessner and colleagues found 12 CNV regions that were exclusive to cases with MDD. The region with the highest frequency in cases was a locus on chromosome 5 (5q35.1) that overlapped the genes SLIT3, CCDC99, and DOCK2. The finding of a CNV overlapping the gene SLIT3 is interesting, as SLIT3 is known to play a role in axon development and neurodevelopmental disorders.
