Basal ganglia volumetric changes in psychotic spectrum disorders

Background: Basal ganglia are particularly important for understanding the pathobiology of psychosis given their key roles in dopaminergic neurotransmission which are associated with psychotic symptoms and one of the target sites of antipsychotic drugs. Psychotic symptoms are prevalent in both schizophrenia (SZ) and bipolar disorder (BD). Although the components of basal ganglia are implicated in psychosis, comparative structural changes of components of the basal ganglia between SZ and BD are less clear after disentanglement of clinical effects of antipsychotic dose, duration and severity of illness. Methods: In this study, we examined the morphology of the basal ganglia in 326 subjects comprising of 45 patients of BD type I with psychotic symptoms, 97 first-episode SZ (FE-SZ) patients, 86 non-first-episode chronic SZ (NFE-SZ) patients, in comparison with 98 healthy controls (HC). Results: Results showed increased volumes in subregions of caudate, putamen, and pallidum in chronic SZ patients compared with HC after controlling for age, gender, and total intracranial volume. No change was found between FE-SZ patients, psychotic BD patients, and HC. Furthermore, hierarchical regressions showed that the dosage of antipsychotics had a significant contribution to basal ganglia volumetric enlargement in NFE-SZ after controlling for the effects of age, gender, total intracranial volume, age at illness onset, as well as illness duration and severity. Limitations: Lack of information about the cumulative history of exposure to medication for all the three groups of patients is a major limitation in our study. Conclusions: There are distinct basal ganglia structural changes in SZ and psychotic BD. Basal ganglia are enlarged in chronic SZ but not in FE-SZ and BD and this enlargement is significantly associated with antipsychotic dosage over and beyond the effects of illness duration and severity.