Brain-derived neurotrophic factor val66met genotype and early life stress effects upon bipolar course

Abstract

Background: Gene-environment interactions may contribute to bipolar disorder (BD) clinical course variability. We examined effects of brain-derived neurotrophic factor (BDNF) val66met genotype and early life stress (ELS) upon illness severity and chronicity in adult BD patients.

Methods: 80 patients (43 BD I, 33 BD II, 4 BD not otherwise specified, mean ± SD age 46.4 ± 14.0 years, 63.7% female) receiving open evidence-based and measurement-based care in the Stanford Bipolar Disorders Clinic for at least 12 months underwent BDNF val66met genotyping and completed the Childhood Trauma Questionnaire. BDNF met allele carrier genotype and history of childhood sexual and physical abuse were evaluated in relation to mean prior-year Clinical Global Impressions-Bipolar Version-Overall Severity of Illness (MPY-CGI-BP-OS) score and clinical and demographic characteristics.

Results: BDNF met allele carriers (but not non-met allele carriers) with compared to without childhood sexual abuse had 21% higher MPY-CGI-BP-OS scores (3.5 ± 0.7 versus 2.9 ± 0.7, respectively, t = -2.4, df = 28, p = 0.025) and 35% earlier BD onset age (14.6 ± 5.7 versus 22.8 ± 7.9 years, respectively, t = 3.0, df = 27, p = 0.006). Regression analysis, however, was non-significant for a BDNF-childhood sexual abuse interaction.

Limitations: small sample of predominantly female Caucasian insured outpatients taking complex medication regimens; only one gene polymorphism considered.

Conclusions: Between group comparisons suggested BDNF met allele carrier genotype might amplify negative effects of ELS upon BD illness severity/chronicity, although with regression analysis, there was not a significant gene-environment interaction. Further studies with larger samples are warranted to assess whether BDNF met allele carriers with ELS are at risk for more severe/chronic BD illness course.

Figure 1. Childhood Sexual Abuse Associated with Greater Bipolar Illness Severity and Chronicity in BDNF Met Allele Carriers

MPY-CGI-BP-OS indicates mean prior-year Clinical Global Impressions-Bipolar Version-Overall Severity of Illness, and results are shown as mean ± standard deviation. BDNF indicates brain-derived neurotrophic factor. CTQ-sexual indicates childhood sexual abuse history reported on Childhood Trauma Questionnaire.

Figure 2. Childhood Sexual Abuse Associated with Earlier Bipolar Onset Age in BDNF Met Allele Carriers

Onset age is shown as mean ± standard deviation. BDNF indicates brain-derived neurotrophic factor. CTQ-sexual indicates childhood sexual abuse history reported on Childhood Trauma Questionnaire.