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

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 to 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 the 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 VI corresponded with impaired effort allocation during medium and high reward probability conditions and lower cognitive performance. However, lobule VI was not correlated with CAINS scores. While nucleus accumbens volume may serve as marker of negative symptoms in psychotic illnesses, cerebellar lobule VI morphology may inform on cognitive impairment in patients with SZ and BD. The nucleus accumbens and lobule VI may each contribute to reduced effort allocation during reward processing.Significance Statement Improving negative symptoms and cognitive impairment in SZ and BD remains an unmet clinical need. This study reveals that, in SZ and BD, structural changes in the nucleus accumbens and cerebellar lobule VI are associated with negative symptoms and cognitive impairments, respectively. The current findings also suggest that reductions in nucleus accumbens and cerebellar lobule VI volume may also underpin impaired reduced effort allocation during reward processing. This study provides impetus for further probing supratentorial and cerebellar circuitry to further understand negative and cognitive symptoms experienced by patients with psychotic illness and their associations with reward-motivational deficits.