In this review, we considered affective cognition, its disruption in depression, and the possible modulatory role of 5-HT. Given the large and ever-increasing literature in this area, we had to be selective but the evidence that we reviewed leads to certain important conclusions.
The neuronal basis of affective cognition depends on a network of brain regions. Neuropsychological studies highlight roles of the amygdala (particularly in the recognition of emotion and emotional memory) and VMPFC (particularly in social and moral emotions). The neuroimaging literature in healthy volunteers confirms the importance of these regions as part of a wider network also including the hippocampus, parahippocampal gyrus, temporal cortices, insula, ACC, and other medial and ventral prefrontal regions. The pattern of responses within these networks is dependent on specific emotions, with more emphasis on limbic regions for basic emotions, such as fear, and with more emphasis on medial prefrontal regions for complex emotions, such as guilt. The pattern also depends on task demands, with emotion perception tasks preferentially engaging posterior and subcortical components of the network and prefrontal regions becoming more involved as more integration with cognitive processes is required. Influential models of affective processing have been proposed, involving a posterior/subcortical system for emotion perception and a prefrontal system exerting regulatory control (Ochsner and Gross, 2005
; Phillips et al, 2003
). Although we have not discussed reward learning or emotional decision making in this study, similar models can be derived to describe these processes (Dolan, 2007
). Such interconnected models of affective cognition allow for both top-down control of emotional response by cognitive mechanisms and bottom-up biases of cognitive processing by emotional appraisal; however, affective cognition may ultimately be better explained by a more integrative model. Inconsistencies and gaps in the current literature must be addressed before a comprehensive model can be confidently proposed.
The interface between emotion and cognition is fundamentally important in understanding mood disorder. We have described the clinical relevance of cognitive emotions such as guilt and shame and also the possible specificity of deficits in affective cognition to depression. In broad terms, depressed patients show biases toward negative material and/or away from positive material relative to controls. These biases cut across cognitive domains, being observed for recognition, attention, and memory. Neuroimaging studies suggest that these biases have an identifiable neuronal basis. Although the pattern of results is complex, there is general support for the view that disturbances of affective cognition are associated with imbalances in limbic-cortical circuitry. Phillips et al (2003
) argued that emotional stimuli elicit heightened responses in limbic regions including the amygdala and that hypo-response in prefrontal regions reflects a failure of cortical systems to regulate emotional responses. Various iterations of Helen Mayberg's influential model emphasize enhanced amygdala response to emotional stimuli in the depressed state that normalizes on recovery. Critically, she places the subgenual ACC at the epicenter of the dysfunctional network, hypothesizing a critical role for this region in emotion regulation (Ressler and Mayberg, 2007
) and demonstrates that in treatment-resistant patients, deep brain stimulation in this region causes dramatic symptom improvement (Mayberg et al, 2005
; Mayberg, 2009
). A central role for the subgenual ACC is interesting in the context of the moral emotion literature we have reviewed, suggesting that this region mediates self-blame, which is an important symptom of depression. Exciting recent research suggests that connectivity between the amygdala and ventral ACC, as well as the OFC, may be a critical substrate of disrupted affective cognition in depression.
We explored the possible role of 5-HT in modulating affective cognition and its disruption in depression. The results are complex and equivocal at times. Both behavioral and neuronal effects in controls are subtle and inconsistent, whereas in depressed patients, results are difficult to interpret in the context of effects of 5-HT manipulation on depressed mood. Overall, the evidence offers some support for serotonergic modulation of affective cognition. However, a number of intervening factors may be critical, including current mood, personality traits, gender, and genotype, all of which have been shown to interact with 5-HT effects. Task selection may also be crucial; eg, we reviewed 5-HT effects on long-term forgetting of emotional material rather than short-term recall, and effects on reaction times rather than response accuracy. Improved understanding of the complex relationships between 5-HT, mood, and affective cognition is critical for developing effective therapies for depression.