Transdiagnostic Neural Markers of Emotion–Cognition Interaction in Psychotic Disorders

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Abstract

Deficits in working memory (WM) and emotion processing are prominent impairments in psychotic disorders, and have been linked to reduced quality of life and real-world functioning. Translation of knowledge regarding the neural circuitry implementing these deficits into improved diagnosis and targeted treatments has been slow, possibly because of categorical definitions of disorders. Using the dimensional Research Domain Criteria (RDoC) framework, we investigated the clinical and practical utility of transdiagnostic behavioral and neural measures of emotion-related WM disruption across psychotic disorders. Behavioral and functional MRI data were recorded while 53 participants with psychotic disorders and 29 participants with no history of psychosis performed a modified n-back task with fear and neutral distractors. Hierarchical regression analyses showed that psychotic symptoms entered after diagnosis accounted for unique variance in fear versus neutral accuracy and activation in the ventrolateral, dorsolateral, and dorsomedial prefrontal cortex, but diagnostic group entered after psychotic symptoms did not. These results remained even after controlling for negative symptoms, disorganized symptoms, and dysphoria. Finally, worse accuracy and greater prefrontal activity were associated with poorer social functioning and unemployment across diagnostic groups. Present results support the transdiagnostic nature of behavioral and neuroimaging measures of emotion-related WM disruption as they relate to psychotic symptoms, irrespective of diagnosis. They also provide support for the practical utility of these markers in explaining real-world functioning. Overall, these results elucidate key aspects of the RDoC construct of WM maintenance by clarifying its transdiagnostic importance and clinical utility in psychotic disorders.

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