title: Brain volumes in familial and non-familial schizophrenic probands and their unaffected relatives.
abstract: Structural brain abnormalities are consistently reported in schizophrenic subjects but the etiology of these abnormalities remains unclear. We tested the contribution of genetic predisposition and obstetric complications to the structural brain abnormalities found in schizophrenic probands and their relatives. MRI scans were carried out on 35 schizophrenic probands from families multiply affected with the disorder, and 63 of their unaffected relatives, including 10 parents who appeared to transmit genetic risk to their children; as well as 31 schizophrenic probands from families with no other affected members, 33 of their unaffected relatives; and finally 68 controls. Volumetric measurements of whole brain, lateral ventricles, third ventricle, cerebellum, and temporal lobes were completed for each subject. The impact of obstetric complications on brain structure was assessed across the gradient of presumed genetic predisposition. Both groups of schizophrenic probands displayed enlargement of the lateral and third ventricles, and there was a gradient of ventricular enlargement amongst the unaffected relatives in proportion to their likelihood of carrying schizophrenic genes. Ventricular enlargement was largely confined to males in both probands and unaffected relatives. Obstetric complications were associated with ventricular enlargement only in the familial probands. Non-familial probands displayed reduced volume of the temporal lobes bilaterally. In families with several schizophrenic members, ventricular enlargement is a marker for genetic liability, particularly in males. Individuals inheriting the susceptibility to schizophrenia appear particularly prone to develop ventricular enlargement in response to obstetric complications.
authors.affiliation: Division of Psychological Medicine, Institute of Psychiatry, de Crespigny Park, London, United Kingdom. c.mcdonald@iop.kcl.AC.uk
authors.forename: Colm
authors.initials: C
authors.lastname: McDonald
authors.forename: Anton
authors.initials: A
authors.lastname: Grech
authors.forename: Timothea
authors.initials: T
authors.lastname: Toulopoulou
authors.forename: Katja
authors.initials: K
authors.lastname: Schulze
authors.forename: Ben
authors.initials: B
authors.lastname: Chapple
authors.forename: Pak
authors.initials: P
authors.lastname: Sham
authors.forename: Muriel
authors.initials: M
authors.lastname: Walshe
authors.forename: Tonmoy
authors.initials: T
authors.lastname: Sharma
authors.forename: Thordur
authors.initials: T
authors.lastname: Sigmundsson
authors.forename: Xavier
authors.initials: X
authors.lastname: Chitnis
authors.forename: Robin M
authors.initials: RM
authors.lastname: Murray
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology*; D001927:Brain Diseases / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D011248:Pregnancy Complications; D012559:Schizophrenia / Q000150:complications / Q000235:genetics*