The neural basis of hot and cold cognition in depressed patients, unaffected relatives, and low-risk healthy controls: An fMRI investigation

Modern cognitive neuropsychological models of depression posit that negatively biased emotional ("hot") processing confers risk for depression, while preserved executive function ("cold") cognition promotes resilience.We compared neural responses during hot and cold cognitive tasks in 99 individuals: those at familial risk for depression (N = 30 unaffected first-degree relatives of depressed individuals) and those currently experiencing a major depressive episode (N = 39 unmedicated depressed patients) with low-risk healthy controls (N = 30). Primary analyses assessed neural activation on two functional magnetic resonance imaging tasks previously associated with depression: dorsolateral prefrontal cortex (DLPFC) responsivity during the n-back working memory task; and amygdala and subgenual anterior cingulate cortex (sgACC) responsivity during incidental emotional face processing.Depressed patients exhibited significantly attenuated working memory-related DLPFC activation, compared to low-risk controls and unaffected relatives; unaffected relatives did not differ from low-risk controls. We did not observe a complementary pattern during emotion processing. However, we found preliminary support that greater DLPFC activation was associated with lower amygdala response during emotion processing.These findings require confirmation in a longitudinal study to observe each individual's risk of developing depression; without this, we cannot identify the true risk level of the first-degree relative or low-risk control group.These findings have implications for understanding the neural mechanisms of risk and resilience in depression: they are consistent with the suggestion that preserved executive function might confer resilience to developing depression in first-degree relatives of depressed patients.