Volumes of brain structures in twins discordant for schizophrenia

Background: The study was designed to examine the relative contributions of genetic and nongeneric factors to structural brain abnormalities in schizo phrenia and subjects at risk to develop the disorder. Methods: The brains of 15 monozygotic and 14 same-sex dizygotic twins disco rdant for schizophrenia (patients) and 29 healthy twins pair-wise matched f or zygosity, sex, age, and birth order were st studied using high-resolutio n magnetic resonance imaging scans. Results: Intracranial and whole-brain corrected frontal lobe volumes were s maller (4.6% and 2.7%, respectively) in discordant monozygotic twins as com pared with healthy monozygotic twins. Irrespective of zygosity, discordant twins had smaller whole-brain (2%), parahippocampal (9%), and hippocampal ( 8%) volumes than healthy twins. Moreover, patients had smaller whole-brain volumes (2.2%) than their nonschizophrenic cotwins, who in turn had smaller brains (1%) than healthy twins. Lateral and third-ventricle volumes were i ncreased in discordant dizygotic twins as compared with healthy dizygotic t wins (60.6% and 56.6%, respectively). Finally, within discordant twins, lat eral ventricles were larger (14.4%) in patients than in their nonschizophre nic cotwins. Conclusions: Smaller intracranial volumes in the monozygotic patients and t heir cotwins suggest that increased genetic risk to develop schizophrenia i s related to reduced brain growth early in life. The additional reduction i n whole-brain Volume found in the patients suggests that the manifestation of the disorder is related to (neurodegenerative) processes that are most l ikely nongenetic in origin.