Understanding the neurobiological basis of anhedonia in major depressive disorder — evidence for reduced neural activation during reward and loss processing

Abstract

Background: Anhedonia is a key symptom of major depressive disorder (MDD). Anhedonia is associated with aberrant reward processing, but whether it might interfere similarly with the neural processing of aversive stimuli, such as monetary loss, remains unknown. We aimed to investigate potential associations between anhedonia and neural response during reward and loss processing in patients with MDD. Methods: We investigated blood-oxygen-level-dependent response in the orbitofrontal cortex, cingulate cortex, insula and basal ganglia during monetary reward and loss processing in 182 patients with MDD, using a card-guessing paradigm. We measured anhedonia with the Social and Physical Anhedonia Scale (SASPAS), and we tested for the main and interaction effects of SASPAS scores and the experimental condition (reward or loss) in a full factorial model. Results: We detected a negative main effect of anhedonia, as well as a significant interaction effect of anhedonia and the experimental condition, on orbitofrontal and insular neural response. Post hoc analyses revealed that the interaction was driven by a significant association between higher anhedonia scores and hypoactivation during loss processing. We observed no significant association between anhedonia and neural response during reward processing. Limitations: This study had a cross-sectional design. Conclusion: Our findings confirmed that altered neural processing in the orbitofrontal cortex and insula is a neurobiological feature of anhedonic symptomatology in people with MDD. The pronounced association between anhedonia and blunted neural response during loss processing supports a broader concept for the neurobiological basis of anhedonia. Hence, MDD with anhedonic features might be characterized by reduced neural response to external stimuli, potentially because of amotivation.

Optogenetic hedonic hotspots in orbitofrontal cortex and insula: causing enhancement of sweetness ‘liking’

“…Some individuals with major depression or schizophrenia are reported to have symptoms of consummatory or true anhedonia, meaning inability to experience pleasure, while others may have a more selective avolition or anticipatory anhedonia, meaning loss of motivational 'wanting' for life rewards even if hedonic reactivity remains intact (70)(71)(72)(73). A recent study in humans found that patients with major depressive disorder with anhedonia had blunted fMRI BOLD responses in OFC and insula during a monetary gain/ loss task, suggesting that in humans these cortical regions may contribute to hedonic dysfunction (74). Whether activation of the cortical suppressive 'hedonic coldstrip' described here contributes to reduced pleasure in true anhedonia, or whether promoting activity in hedonic hotspots could reverse such hedonic deficits remain open questions that could be addressed by future clinical research.…”