Apathy Is Associated With Ventral Striatum Volume in Schizophrenia Spectrum Disorder

Abstract

Apathy is prevalent in schizophrenia, but its etiology has received little investigation. The ventral striatum (VS), a key brain region involved in motivated behavior, has been implicated in studies of apathy. We therefore evaluated whether apathy is associated with volume of the VS on MRI in 23 patients with schizophrenia using voxel-based morphometry. Results indicated that greater self-reported apathy severity was associated with smaller volume of the right VS even when controlling for age, gender, depression, and total gray matter volume. The finding suggests that apathy is related to abnormality of brain circuitry subserving motivated behavior in patients with schizophrenia.

Amotivation is associated with smaller ventral striatum volumes in older patients with schizophrenia

“…This relationship persisted after considering several a priori variables often associated with amotivation and brain morphology. These findings are consistent with the theorized role of the VS in motivation and replicate and extend previous findings . Controlling for age, gender, depression (Beck Depression Inventory II scores), and total GM, Roth and colleagues found that amotivation, measured with the Apathy Evaluation Scale, was associated with smaller right VS volumes in schizophrenia patients.…”

“…These findings are consistent with the theorized role of the VS in motivation 16 and replicate and extend previous findings. 14 methods and a different measure of amotivation, we replicate these findings while additionally controlling for general positive symptoms and estimated antipsychotic D 2/3 R occupancy. Thus, our data suggest that amotivation is uniquely associated with reduced VS volumes, above and beyond striatal D 2/3 R blockade by antipsychotics.…”

“…Normality of variables was determined using the D'Agostino‐Pearson test. Our analyses focused on VS volumes as the main outcome variable for each hemisphere separately, as previous work found a specific relationship between amotivation and right VS volume . We constructed multivariate linear stepwise regression models with VS volumes as the dependent variable and various sociodemographic and clinical variables as the initial predictors.…”

“…Examination of the VS as a substrate for amotivation in schizophrenia is particularly relevant given its proposed role in regulating motivated behaviour . To our knowledge, only 1 study by Roth and colleagues has specifically explored this relationship . They observed that patients (n = 23) with more severe amotivation demonstrated reduced grey matter (GM) volumes in the right VS.…”

“…10,13 To our knowledge, only 1 study by Roth and colleagues has specifically explored this relationship. 14 They observed that patients (n = 23) with more severe amotivation demonstrated reduced grey matter (GM) volumes in the right VS. While several lines of preclinical evidence suggest that reduced dopamine (DA) functioning at D 2/3 receptors (D 2/3 Rs) in the VS increases amotivation, 7,15,16 there have been mixed observations in schizophrenia.…”