A volumetric MRI study of limbic, associative and sensorimotor striatal subregions in schizophrenia

Introduction: Cognitive and emotional functioning is mediated by frontal-subcortical feedback loops. The striatum, a component of this circuitry, thus is a possible neural substrate of schizophrenia. Striatum volume, however, is believed to be differentially influenced by neuroleptic treatment due to an anterior-posterior D2 receptor density gradient. We thus rigorously parcellated it into subregions in order to assess whether neuroleptic effect on group differences is regionally specific. Methods: 29 chronic, male, schizophrenia patients and 28 male, normal controls (NCs), group-matched for handedness, age, and parental SES, underwent structural brain imaging on a 1.5. Tesla GE system. We manually measured the volume, normalized for intracranial contents, of the striatum parcellated into anatomic subregions and their corresponding limbic, associative and sensorimotor functional subregions and performed clinical correlations. Results: First, we found a localized bilateral enlargement of the posterior putamen in medicated chronic schizophrenia. Second, we showed associative striatal subregion volumes correlated with executive function in schizophrenia subjects and, to a lesser extent, in NCs. Third, we showed associative striatal subregions inversely correlated with negative symptoms but conversely, the ventral/limbic striatum did not correlate with positive or negative clinical symptoms. Discussion: Our novel parcellation strategy, based on rigorous delineation of the ventral striatum, allowed for the demonstration of localized volumetric differences between schizophrenia and NCs. Furthermore, by parcellating the striatum into functional subregions we demonstrated significant positive correlations between the volume of the associative striatum and executive functioning in schizophrenia, adding further support to the importance of its role in the pathophysiology of schizophrenia.