White matter microstructural associates of apathy-avolition in schizophrenia

Apathy is present at the onset in nearly half the patients with schizophrenia. Current therapies lack the efficiency to improve apathy in patients. The presence of apathy is also associated with poorer outcomes. Despite its clinical importance, the underlying mechanism of apathy in schizophrenia is unclear, but it seems frontostriatal connections play a role. In this study, we investigated whole-brain white matter microstructural properties associated with the severity of apathy-avolition in schizophrenia. We included 80 schizophrenia patients (60 Male, 20 Female) from the Mind Clinical Imaging Consortium database and associated Apathy-Avolition score of "Scale for Assessment of Negative Symptoms" with fiber integrity measures derived from diffusion-weighted imaging using Tract-Based Spatial Statistics (TBSS). We also did tractography on eight tracts, including bilateral superior longitudinal fasciculus, uncinate fasciculus, cingulum, genu and splenium of the corpus callosum. Age, gender, years of education, chlorpromazine equivalent cumulative dose, and acquisition site were inserted as covariates. We showed a widespread association between lower fiber integrity (by measures of increased mean diffusivity and decreased fractional anisotropy) and increased apathy-avolition in TBSS, which we also validated in tractography. Moreover, mean diffusivity, and not fractional anisotropy, was associated with apathy independent of disease severity. In conclusion, we propose diffuse white-matter pathology, within the corpus callosum, limbic system, and the frontostriatal circuit is involved in apathy-avolition in schizophrenia. Also, we suggest that diffuse neuroinflammatory processes may play a part in apathy-avolition, independent of disease severity.