Differences in subcortical brain volumes among patients with schizophrenia and bipolar disorder and healthy controls

Patients with schizophrenia and bipolar disorder have an overlapping polygenic architecture and clinical similarities, although the 2 disorders are distinct diagnoses with clinical dissimilarities. It remains unclear whether there are specific differences in subcortical volumes between schizophrenia and bipolar disorder, and whether the subcortical differences are affected by any clinical characteristics. We investigated differences in subcortical volumes bilaterally among patients with schizophrenia, patients with bipolar disorder and healthy controls. We also investigated the influences of clinical characteristics on specific subcortical volumes in these patient groups.

We collected 3 T T ₁-weighted MRI brain scans from 413 participants (157 with schizophrenia, 51 with bipolar disorder and 205 controls) with a single scanner at a single institute. We used FreeSurfer version 6.0 for processing the T ₁-weighted images to segment the following subcortical brain volumes: thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala and nucleus accumbens. Differences in the 7 subcortical volumes were investigated among the groups. We also evaluated correlations between subcortical volumes and clinical variables in these patient groups.

Of 7 subcortical regions, patients with schizophrenia had significantly smaller volumes in the left thalamus (Cohen d = -0.29, p = 5.83 × 10^-3), bilateral hippocampi (left, d = -0.36, p = 8.85 × 10^-4; right, d = -0.41, p = 1.15 × 10^-4) and left amygdala (d = -0.31, p = 4.02 × 10^-3) than controls. Compared with controls, patients with bipolar disorder had bilateral reductions only in the hippocampal volumes (left, d = -0.52, p = 1.12 × 10^-3; right, d = -0.58, p = 0.30 × 10^-4). We also found that patients with schizophrenia had significantly smaller volumes in the bilateral amygdalae (left, d = -0.43, p = 4.22 × 10^-3; right, d = -0.45, p = 4.56 × 10^-3) than patients with bipolar disorder. We did not find any significant volumetric differences in the other 6 subcortical structures between patient groups (p > 0.05). Smaller left amygdalar volumes were significantly correlated with younger onset age only in patients with schizophrenia (r = 0.22, p = 5.78 × 10^-3).

We did not evaluate the differences in subcortical volumes between patients stratified based on clinical bipolar disorder subtype and a history of psychotic episodes because our sample size of patients with bipolar disorder was limited.

Our findings suggest that volumetric differences in the amygdala between patients with schizophrenia and those with bipolar disorder may be a putative biomarker for distinguishing 2 clinically similar diagnoses.