Genetic, Hemodynamic, and Electrophysiological Correlates of Cortico-Limbic Function in Clinically Depressed Individuals

Abstract

Resting frontal electroencephalographic (EEG) asymmetry has been hypothesized to be a biological marker of clinical depression but may reflect an endophenotype specific to women. Frontal EEG asymmetry was assessed in individuals (22% male) with (n = 12) and without (n = 21) a DSM-IV diagnosis of lifetime Major Depressive Disorder (MDD) or Dysthmic Disorder on 4 occasions within a two-week period. Depressed women exhibited greater relative right frontal activity at rest than never-depressed women across occasions. In contrast, depressed men displayed greater relative left frontal activity than never-depressed men. The same participants engaged in a Passive Viewing Face task while undergoing functional magnetic resonance imaging (fMRI). The present study did not replicate previous findings which show a hyperactive hemodynamic response in the amygdalae among depressed individuals. Mixed linear models indicated a lifetime depression by biological sex by amygdala activation interaction. For never-depressed control participants, frontal asymmetry is unrelated to the level of emotion-related amygdalae activation, but for lifetime depression spectrum participants, in both men and women, relatively greater amygdalae activation to emotional faces is associated with less left frontal activity as compared to those with less amygdalae activation to emotional faces. Also, when activation to emotionally expressive faces was closer to the levels of activation observed in the neutral face condition, the predicted pattern of association between frontal EEG asymmetry and depression based on the above findings was disrupted in men, but preserved in women. When levels of activation to emotion faces was considerably lower than that to neutral faces, the pattern was generally preserved for men, but not for women. Preliminary tests were also conducted in an attempt to replicate previous reports that document a positive correlation between the risk allele of the serotonin transporter gene and amygdalae activation. The present study failed to replicate this pattern, perhaps on account of the relatively small sample size available when non-Caucasian participants were excluded from the analysis.