Hippocampal shape abnormalities of patients with childhood-onset schizophrenia and their unaffected siblings.

OBJECTIVE: The hippocampus has been implicated in the pathogenesis of schizophrenia, and hippocampal volume deficits have been a consistently reported abnormality, but the subregional specificity of the deficits remains unknown. The authors explored the nature and developmental trajectory of subregional shape abnormalities of the hippocampus in patients with childhood-onset schizophrenia (COS), their healthy siblings, and healthy volunteers. METHOD: Two hundred twenty-five anatomic brain magnetic resonance images were obtained from 103 patients with COS, 169 from their 79 healthy siblings, and 255 from 101 age- and sex-matched healthy volunteers (age range = 9-29 years). The hippocampus was segmented using FreeSurfer automated image analysis software, and hippocampal shape was evaluated by comparing subjects at more than 6,000 vertices on the left and right hippocampal surfaces. Longitudinal data were examined using mixed model regression analysis. RESULTS: Patients with COS showed significant bilateral inward deformation in the anterior hippocampus. Healthy siblings also showed a trend for anterior inward deformation. However, the trajectory of shape change did not differ significantly between the groups. Inward deformations in the anterior hippocampus were positively related to positive symptom severity, whereas outward surface displacement was positively related to overall functioning. CONCLUSION: This is the first and largest longitudinal three-way analysis of subregional hippocampal shape abnormalities in patients with COS and their healthy siblings compared with healthy controls. The anterior hippocampal abnormalities in COS suggest the pathophysiologic importance of this subregion in schizophrenia. The trend level and overlapping shape abnormalities in the healthy siblings suggest a more subtle, subregionally specific neuroanatomic endophenotype.

Absence of anatomic corpus callosal abnormalities in childhood-onset schizophrenia patients and healthy siblings.

The corpus callosum (CC) has been implicated in the pathogenesis of schizophrenia, and CC deficits have been reported in adults with schizophrenia. We explored the developmental trajectory of the corpus callosum in childhood-onset schizophrenia (COS) patients, their healthy siblings (SIB) and healthy volunteers. We obtained 235 anatomic brain magnetic resonance imaging (MRI) scans from 98 COS patients, 153 scans from 71 of their healthy siblings, and 253 scans from 100 age- and gender-matched healthy volunteers, across ages 9-30 years. The volumes of five sub-regions of the CC were calculated using FreeSurfer, and summed to give the total volume. Longitudinal data were examined using mixed model regression analysis. There were no significant differences for the total or sub-regional CC volumes between the three groups. There were also no significant differences between the groups for developmental trajectory (slope) of the CC. This is the largest longitudinal study of CC development in schizophrenia and the first COS study of the CC to include healthy siblings. Overall, CC volume and growth trajectory did not differ between COS patients, healthy siblings, or healthy volunteers. These results suggest that CC development, at least at a macroscopic level, may not be a salient feature of schizophrenia.