Fetal hypoxia and structural brain abnormalities in schizophrenic patients, their siblings, and controls.
BACKGROUND
Cortical gray matter reductions and cerebrospinal fluid (CSF) increases are robust correlates of schizophrenia, but their relationships to obstetric and other etiologic risk factors remain to be established.


METHODS
Structured diagnostic interviews, obstetric hospital records, and magnetic resonance imaging scans of the brain were obtained for 64 schizophrenic or schizoaffective patients (representative of all such probands in a Helsinki, Finland, birth cohort), along with 51 of their nonpsychotic full siblings and 54 demographically similar controls without family histories of psychosis.


RESULTS
Fetal hypoxia predicted reduced gray matter and increased CSF bilaterally throughout the cortex in patients (gray matter effect sizes, -0.31 to -0.56; CSF effect sizes, 0.25 to 0.47) and siblings (gray matter effect sizes, 0.33 to 0.47; CSF effect sizes, 0.17 to 0.33), most strongly in the temporal lobe. Effect sizes were 2 to 3 times greater among cases born small for their gestational age. Hypoxia also correlated significantly with ventricular enlargement, but only among patients (effect size, 0.31). In contrast, fetal hypoxia was not related to white matter among patients and siblings, nor to any tissue type in any region among controls. The associations were independent of family membership, overall brain volume, age, sex, substance abuse, and prenatal infection.


CONCLUSIONS
Fetal hypoxia is associated with greater structural brain abnormalities among schizophrenic patients and their nonschizophrenic siblings than among controls at low genetic risk for schizophrenia. This pattern of results points to a gene-environment interaction account of the disorder's neurodevelopmental pathogenesis.
Cannon
Tyrone D
TD
Department of Psychology, University of California, Los Angeles, 1285 Franz Hall, Los Angeles, CA 90095, USA. cannon@psych.ucla.edu
van Erp
Theo G M
TG
Rosso
Isabelle M
IM
Huttunen
Matti
M
Lönnqvist
Jouko
J
Pirkola
Tiia
T
Salonen
Oili
O
Valanne
Leena
L
Poutanen
Veli-Pekka
VP
Standertskjöld-Nordenstam
Carl-Gustav
CG
D000328:Adult; D001284:Atrophy; D001921:Brain / Q000002:abnormalities* / Q000473:pathology; D002540:Cerebral Cortex / Q000002:abnormalities / Q000473:pathology; D002555:Cerebrospinal Fluid / Q000502:physiology; D015331:Cohort Studies; D004292:Dominance, Cerebral / Q000502:physiology; D005260:Female; D005311:Fetal Hypoxia / Q000150:complications*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D012016:Reference Values; D012307:Risk Factors; D012559:Schizophrenia / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics