Amygdala hyperactivation and prefrontal hypoactivation in subjects with cognitive vulnerability to depression.

The hopelessness theory (HT) of depression is a diathesis-stress theory which construes cognitive vulnerability (CV) to depression. Neuroimaging studies examining depression have implicated the amygdala as an important potential locus of dysfunction in the processing of salient threatening stimuli. However, little is known about neural activation in the brain of subjects with CV to depression. Medication-free major depressive disorder (MDD) subjects (N=29), never depressed subjects with CV (N=26), and demographically matched never depressed healthy control (HC) subjects (N=31) were scanned using functional magnetic resonance imaging (fMRI) while performing an emotional matching task. The MDD subjects showed elevated left amygdala responses and reduced left dorsolateral prefrontal cortex (dlPFC) activation levels relative to HC subjects. Similarly, CV subjects had greater activity in the amygdala bilaterally and lesser activation in the dlPFC bilaterally, relative to HC subjects. The present findings raise the possibility that cognitive vulnerability to depression might be characterized by hypoactivation of the prefrontal cortex and hyperactivation of the amygdala in response to emotional stimuli; our observations might provide a potential interpretation to explain the abnormalities in neural networks mediating cognitive modulation of emotions in individuals with cognitive vulnerability to depression.