Regional gray matter, white matter, and cerebrospinal fluid distributions in schizophrenic patients, their siblings, and controls

Background: Cortical gray matter volume reductions and cerebrospinal fluid (CSF) volume increases are robust correlates of schizophrenia, but their so urces have not been established conclusively. Methods: Structured diagnostic interviews and magnetic resonance imaging sc ans of the brain were obtained on 75 psychotic probands (63 with schizophre nia and 12 with schizoaffective disorder), ascertained so as to be represen tative of all such probands in a Helsinki, Finland, birth cohort; 60 of the ir nonpsychotic full siblings; and 56 demographically similar control subje cts without a personal or family history of treated psychiatric morbidity. Results: Patients with schizophrenia and their siblings exhibited significa nt reductions in cortical gray matter volume and significant increases in s ulcal CSF volume compared with controls. The patients, but not their siblin gs, also exhibited significant reductions in white matter volume and signif icant increases in ventricular CSF volume. Regional effects were most robus t when component volumes were expressed as percentages of overall regional volumes; in this case, for patient and sibling groups, gray matter volume r eductions and sulcal CSF volume increases were significantly more pronounce d in the frontal and temporal lobes than in the remainder of the brain. Non e of the group differences varied significantly by sex or hemisphere. Conclusions: Structural alterations of the cerebral cortex, particularly in the frontal and temporal lobes, are present in patients with schizophrenia and in some of their siblings without schizophrenia; such changes are thus likely to reflect genetic (or shared environmental) effects. Ventricular e nlargement is unique to the clinical phenotype and is thus likely to be aff ected primarily by nonshared causative factors.