Fuente: PubMed "nature biotechnology" J Affect Disord. 2026 May 29:122049. doi: 10.1016/j.jad.2026.122049. Online ahead of print.ABSTRACTMajor depressive disorder (MDD) is characterized by core anhedonic symptoms, including pervasive dampening of positive responsiveness and social interactions mediated by the habitual avoidance of strategies involving engagement with positive emotions. Current MDD treatments primarily aim at rebalancing the regulation of negative emotions and at modulating limbic activity. Understanding neural deficits in positive social regulation is critical for developing therapeutic interventions for MDD and social anhedonia symptoms. We used fMRI to assess positive social emotion upregulation in 40 women, comprising 20 medicated patients with MDD and matched healthy controls. Ecologically valid conditions with robust activation patterns were designed to investigate disruptions within prefrontal emotion regulation circuits by contrasting active upregulation of positive social situations with passive viewing of neutral social situations. We assessed connectivity network models using a probabilistic empirical Bayes approach. Although patients rated positive social pictures lower in valence and had greater social anhedonia scores, we identified similar activity in bilateral amygdala and ventromedial prefrontal cortex (vmPFC) during upregulation. However, superior frontal gyrus (SFG) and posterior right ventrolateral PFC (prvlPFC) were hypoactive, while dorsolateral PFC and anterior right vlPFC (arvlPFC) were hyperactive. We unveiled impaired cognitive control pathways from SFG and dorsolateral PFC to arvlPFC, between functional subdivisions of vlPFC, and contextual modulation by social appraisal. Our preliminary findings indicate that despite medicated patients having proper evaluation of sociality and stabilized limbic responses, their positive social responsiveness, top-down upregulation and appraisal efficacy remained deficient. These findings complement neurobiological bases underlying aberrant positive social emotion upregulation and appraisal processes.PMID:42217637 | DOI:10.1016/j.jad.2026.122049