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 sources have not been established conclusively.


METHODS
Structured diagnostic interviews and magnetic resonance imaging scans of the brain were obtained on 75 psychotic probands (63 with schizophrenia and 12 with schizoaffective disorder), ascertained so as to be representative of all such probands in a Helsinki, Finland, birth cohort; 60 of their nonpsychotic full siblings; and 56 demographically similar control subjects without a personal or family history of treated psychiatric morbidity.


RESULTS
Patients with schizophrenia and their siblings exhibited significant reductions in cortical gray matter volume and significant increases in sulcal CSF volume compared with controls. The patients, but not their siblings, also exhibited significant reductions in white matter volume and significant increases in ventricular CSF volume. Regional effects were most robust when component volumes were expressed as percentages of overall regional volumes; in this case, for patient and sibling groups, gray matter volume reductions and sulcal CSF volume increases were significantly more pronounced in the frontal and temporal lobes than in the remainder of the brain. None 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 enlargement is unique to the clinical phenotype and is thus likely to be affected primarily by nonshared causative factors.
Cannon
T D
TD
Department of Psychology, University of Pennsylvania, Philadelphia 19104-6196, USA. cannon@hirisk.psych.upenn.edu
van Erp
T G
TG
Huttunen
M
M
Lönnqvist
J
J
Salonen
O
O
Valanne
L
L
Poutanen
V P
VP
Standertskjöld-Nordenstam
C G
CG
Gur
R E
RE
Yan
M
M
D000328:Adult; D001921:Brain / Q000033:anatomy & histology*; D002552:Cerebral Ventricles / Q000033:anatomy & histology; D002555:Cerebrospinal Fluid / Q000502:physiology*; D005190:Family; D005260:Female; D005387:Finland / Q000453:epidemiology; D005625:Frontal Lobe / Q000033:anatomy & histology; D007839:Functional Laterality; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011618:Psychotic Disorders / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000235:genetics; D012494:Sampling Studies; D012559:Schizophrenia / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000235:genetics; D012737:Sex Factors; D013702:Temporal Lobe / Q000033:anatomy & histology