Tracing neurodiverse disruptions underlying emotional episodic memory to diagnosis-specific network of emotional regulation in psychiatric disorders

Abstract

AbstractObjectiveEmotional dysfunctions are prevalent across various psychiatric disorders, leading to diverse emotional problems. Disrupted emotional episodic memory is a prominent deficit and may underlie various affective symptoms in clinical phenotypes. However, diagnosis-specific of neurodiverse disruptions remain elusive.MethodsWe used task-based functional magnetic resonance imaging (fMRI) and a normative modelling framework to establish a reference for functional activation during emotional episodic memory, drawing from a large dataset of healthy individuals (n = 409). Individualized deviations from this reference were evaluated using a clinical dataset of 328 participants, which included 168 healthy controls and patients with major depressive disorder (MDD, n = 56), bipolar disorder (BD, n = 31), and schizophrenia (SZ, n = 73). Regional deviations were mapped to four large-scale emotional regulation networks and used to predict affective symptoms across different mental disorders.ResultsWe constructed a verifiable normative model of functional activation during emotional episodic memory to parse clinical heterogeneity. Diagnosis-specific regional deviations were enriched in the non-overlapping large-scale emotional regulation networks: MDD showed enrichment in emotion regulation network related to emotion perception and generation, BD in cognitive appraisal and emotional reactivity, and SZ in working memory and response inhibition. Individualized deviations significantly predicted affective symptom in distinct disorder, and specific emotional regulation network showed maximum feature weight.ConclusionsThese findings have potential implications for the understanding of dissociable neuropathological patterns of affective symptoms and improving individualized clinical diagnosis and treatment in psychiatric disorders.