The Involvement of Genes in Adolescent Depression: A Systematic Review

Abstract

Numerous studies have reported on the roles of genetic factors in the development of depression in adolescents and young adults. However, there are few systematic reviews that update our understanding of adolescent depression with the biological findings identifying the roles of gene expression and/or polymorphism(s). This review systematically summarized the findings that clearly identified the contribution of a gene to the risk of depression in adolescents between the ages of 10 and 19 years old and young adults between the ages of 20 and 25 years old. Data were obtained through searching PubMed, Embase, and Web of Science. A total of 47 studies on early adolescence and three studies on young adults were included in the current review. Most articles studied genes in the serotonergic system (n = 26), dopaminergic system (n = 3), and the Brain-derived neurotropic factor (BDNF) gene (n = 12). 92.3% of studies (24/26) identified positive associations of 5-HTTLPR polymorphism with depressive illness or depressive symptoms. 83.3% of studies (10/12) found positive association between BDNF Val66Met genotype and adolescent depressive symptoms. More studies should be conducted on the 18 genes reported in a few studies to clarify their roles in the risk for adolescent depression.

Depression in Adolescence and Brain-Derived Neurotrophic Factor

“…More interestingly, the first-degree relatives of depressed adolescents who were also suicidal had increased lifetime rates of suicidal behavior, which significantly co-segregated with MDD, providing evidence for the familial aggregation of depression in adolescent-onset MDD. Twin studies also confirmed the association of genetic factors in adolescent depression, although there are very few longitudinal twin studies of adolescent depression ( Rice, 2009 ; Xia and Yao, 2015 ). Although this study was conducted in adolescent females, the only twin study reported to date confirmed that the prevalence of MDD in adolescent co-twins was much higher (up to 36%) in monozygotic twins than in dizygotic twins.…”

Association Between BDNF Gene Variant Rs6265 and the Severity of Depression in Antidepressant Treatment-Free Depressed Patients

“…However, in spite of these functional consequences, systematic reviews of the results of association studies suggest that this BDNF genotype does neither exert a major influence on the development of depression (7)(8)(9), nor on the serum BDNF levels (10). However, the influence of the Val66Met BDNF (rs6265) polymorphism may depend on age group, gender, and ethnicity (7,(11)(12)(13)(14). Moreover, according to other meta-analyses interesting results were obtained concerning an association with the results of drug treatment (more specifically in Asian gender and when treated with selective serotonin reuptake inhibitors; SSRIs) (15,16) and vulnerability with life stress (17).…”

Association of Serotonin Transporter Gene AluJb Methylation with Major Depression, Amygdala Responsiveness, 5-HTTLPR/rs25531 Polymorphism, and Stress

“…The main target of SSRIs, the serotonin transporter (5-HTT, SERT), broadly influences serotonergic neurotransmission and is encoded by the SLC6A4 gene. In a polymorphic SLC6A4 promoter region, the functional insertion/deletion polymorphism 5-HTTLPR and the functionally related single nucleotide polymorphism rs25531 are discussed as risk factors for the psychopathology of MDD (Xia and Yao, 2015) and frequently associated with robust neural correlates of MDD, like reduced hippocampal volumes (eg, Frodl et al, 2008). Starting with the seminal study of Hariri and colleagues (Hariri et al, 2002), numerous imaging genetic studies also investigated the association of the 5-HTTLPR region and amygdala activity, with several replications (eg, Dannlowski et al, 2010) but, however, also controversially discussed results (cf.…”