Archival ReportEarly Life Stress Combined with Serotonin 3A Receptor and Brain-Derived Neurotrophic Factor Valine 66 to Methionine Genotypes Impacts Emotional Brain and Arousal Correlates of Risk for Depression
Section snippets
Negativity Bias and Susceptibility to Depression
The trait-like vulnerability to depression has been termed negativity bias, reflecting an inability to manage stress and associated attribution toward expecting negative outcomes (8, 9, 10). Negativity bias correlates with other constructs, such as neuroticism, which show a high heritability in risk for depression (9). Disposition to associated conditions of anxiety is also characterized by a negativity bias (11). Negativity bias reflects a complementary neglect of positive information (8). In
Emotional Brain and Arousal Correlates of Susceptibility to Depression
Asymmetry of brain activity, assessed by the EEG, is seen to reflect the regulation of negative versus positive emotion processing (7, 10). Variations in EEG asymmetry implicate asymmetrical activation of frontal brain circuitry and its limbic projections involved in regulating emotional reactions and the experience of emotion (or feelings). Right-sided activation has been linked to regulation of negative emotion and feelings, and left-sided activation has been linked to positive feeling states
Genotypes and Early Life Stress in Conferring Susceptibility to Depression
There is now overwhelming evidence regarding the importance of exposure to early life stress as a key environmental factor increasing susceptibility to depression and associated emotional disorders (21, 22). Self-reported negativity bias is heightened in otherwise healthy individuals with early life stressors (1). Exposure to stress is seen to exacerbate alterations in EEG asymmetry (13, 21).
Research on genetic susceptibility to depression has focused on monaminergic systems, particularly the
Participants
The sample comprised 363 healthy volunteers of European ancestry (53% male volunteers, mean age 36.4 ± 13 years, mean education 14.5 ± 2.6 years) from the Brain Research And Integrative Neuroscience Network (http://www.BRAINnet.net). The WebQ standardized battery of questionnaires was used to screen for exclusion criteria (for details, [1,4]). Questionnaires, including the Patient Health Questionnaire, items based on the Mental Status Examination, the World Health Organization Alcohol Use
Negativity Bias
Early life stress was a significant main predictor of negativity bias (R2 = .025). Individuals in the high (3+) ELS subgroup had greater negativity bias than the low (0–2) subgroup (b = −.277, SE = .116, t = −2.385, p = .018). The BDNF and HTR3A genotypes did interact with ELS to predict negativity bias in the total sample.
Heart Rate
Early life stress was a significant main effect predictor of emotion-elicited heart rate. The high (3+) ELS subgroup had higher heart rate than the low (0–2) ELS subgroup (R2
Discussion
Here, we examined if BDNF Val66Met and HTR3A genes interact with exposure to early life stress to impact brain, body arousal, and self-report correlates of susceptibility to depression, EEG asymmetry, emotion-elicited heart rate, and negativity bias. Drawing on previous findings, a priori hypotheses focused on BDNF methionine and HTR3A CC genotypes as risk variants. We tested the proposal that these genotypes would have a compound effect on EEG asymmetry, heart rate, and negativity bias that
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