Hippocampal Volume Development in Healthy Siblings of Childhood-Onset Schizophrenia Patients

Objective: Previous anatomic studies have established a reduction in hippocampal volume in schizophrenia, but few have investigated the progressive course of these changes and whether they are trait markers. In the present study, the authors examined hippocampal volumes in relation to age for patients with childhood-onset schizophrenia, their nonpsychotic healthy siblings, and healthy comparison subjects. Method: Anatomic brain magnetic resonance scans were obtained in childhood-onset schizophrenia probands (N= 89, 198 scans), their nonpsychotic full siblings (N= 78, 172 scans), and matched healthy comparison subjects (N= 79, 198 scans) between the ages of 10 and 29 years. Total, left, and right hippocampal volumes were measured using FreeSurfer software and analyzed using a linear mixed-model regression covarying for sex and intracranial volume. Results: Childhood-onset schizophrenia probands had a fixed reduction in hippocampal volumes (total, left, and right) relative to both nonpsychotic siblings and healthy comparison subjects, whereas there were no significant volumetric or trajectory differences between non-psychotic siblings and healthy comparison subjects. Conclusions: Fixed hippocampal volume loss seen in childhood-onset schizophrenia, which is not shared by healthy siblings, appears to be related to the illness. De-creased hippocampal volume is not strongly genetically related but represents an important intermediate disease phenotype.