The circuitry of depression:fMRI profile differences as a function of life stress

The main purpose of the present project was to examine the manner in which the brain activity of depressed individuals differs as a function of the presence or absence of severe life stressors in the three months preceding the onset of major depression. Two hypotheses were presented. The first, fueled by research on the impact of life events on depression, proposed that individuals with a severe life stress (stress group) would be characterized by more dysregulated prefrontal cortical, anterior cingulated cortical, hippocampal, and amygdalar activation compared to individuals without a severe life stress (no-stress group) when presented with stimuli from an emotion-face paradigm. The second hypothesis, stimulated by research on the increased biological vulnerability of individuals whose depression onset is less stress related, proposed that the same brain areas would be more dysregulated in individuals without prior stress.; The correlates of severe life stress, assessed with the Life Events and Difficulties Schedule (LEDS), on relative differences in functional brain activation was analyzed for 12 individuals with or without stress preceding onset. When presented with Fearful faces, the stress group showed bilateral activation in the right superior frontal gyrus and the left frontal lobe as well as bilateral parietal activity. The no-stress group, however, demonstrated right superior frontal activation only. When presented with Sad faces, the stress group again showed bilateral activation in the frontal lobes, but also in the right temporal gyrus, the left occipital lobe, and the precuneus of the left parietal lobe. The no-stress group showed left temporal lobe and parahippocampal gyrus activation in this condition. Then, when presented with Angry faces, the stress group only showed left middle frontal activation while the no-stress group showed bilateral superior frontal gyrus activity. When presented with Happy faces the no-stress group showed no activation but the stress group demonstrated left parietal and superior temporal activation. These results, which are interpreted as evidence in support of both hypotheses, help refine the current understanding of the neurological correlates of depression by highlighting the central role played by the presence or absence of severe life events in shaping the functional signature of the depressed brain.