Neural and Behavioral Markers of Negative Symptoms and Cognitive Impairment in Patients with Psychosis

Abstract

Negative and cognitive symptoms impair functioning in patients with psychotic illnesses [i.e., schizophrenia spectrum disorders (SZ) and bipolar I disorder with psychotic features (BD)]. Disruptions in mesocorticolimbic circuitry are hypothesized to underpin negative symptoms and cognitive impairment in patients with psychosis and may also facilitate reward-motivational deficits. In male and female patients with psychosis ( N  = 44) and healthy controls (HC = 27), we used neuroimaging to define gray matter morphology and white matter microstructure. We examined negative symptom severity with the Clinical Assessment Interview for Negative Symptoms (CAINS), effort allocation during reward processing with the Effort Expenditure for Rewards Task (EEfRT), and cognitive performance with the MATRICS cognitive consensus battery (MCCB). Reduced nucleus accumbens volumes in patients with psychosis were associated with higher CAINS total and motivation and pleasure subscale scores as well as lower effort expenditure for medium (50%) and high (88%) reward probability conditions during EEfRT. The fornix showed reduced fractional anisotropy in patients with psychosis. Negative associations were present between CAINS motivation and pleasure subscores and MCCB composite and subscale scores. Lower gray matter volume in cerebellar Lobule IV corresponded with impaired effort allocation during medium and high reward probability conditions and lower cognitive performance. However, Lobule IV was not correlated with CAINS scores. While nucleus accumbens volume may serve as a marker of negative symptoms in psychotic illnesses, cerebellar Lobule IV morphology may inform on cognitive impairment in patients with SZ and BD. The nucleus accumbens and Lobule IV may each contribute to reduced effort allocation during reward processing.