The Role of Midbrain Dopaminergic Nuclei in Anhedonia and Real-Life Social Anhedonia: A Task-Based fMRI and Ecological Momentary Assessment Study

Background: Anhedonia – the reduction of interest and pleasure in response to rewarding stimuli – is critically linked to the dopaminergic system. While animal studies have extensively demonstrated a role of the midbrain dopaminergic nuclei (mDA) in anhedonia-like behaviour, human neuroimaging research has primarily focused on downstream target regions. Here, we investigated whether mDA functional activity is associated with subclinical anhedonic symptoms, real-life social anhedonia, vulnerability factors, and overt psychopathology across different populations. Methods: We employed a multimodal approach combining fMRI during a reward-processing task, ecological momentary assessment, and psychometric measures across multiple samples from two independent cohorts (total N = 516). Results: In healthy controls (HCs; N = 144), anhedonic symptoms were predicted by reduced activity in two peaks within the mDA (pFWE = 0.021 and pFWE = 0.028). This finding was replicated in an independent community-based sample (N = 331, pFWE = 0.006). The dopaminergic nature of the involved nuclei was supported by the spatial correlation between their functional connectivity maps and PET-based maps of dopamine receptor availability. Blunted mDA activity also predicted diminished real-life hedonic responses to social stimuli and mediated the effect of early life stressors (ELSs) on anhedonic symptoms. Finally, we compared patients with schizophrenia (SCZ) to HCs (total N = 185), showing that patients exhibited reduced mDA activity, which was associated with greater anhedonia severity. Conclusions: These findings provide robust evidence for the involvement of mDA functional activity in anhedonia across both general population and SCZ. Moreover, we showed that mDA activity modulates real-life social anhedonia and is shaped by exposure to ELSs.