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Fetal hypoxia and structural brain abnormalities in schizophrenic patients, their siblings, and controls
Tyrone D Cannon1, Theo G M van Erp, Isabelle M Rosso
1Department of Psychology, University of California, Los Angeles, 1285 Franz Hall, Los Angeles, CA 90095, USA. cannon@psych.ucla.edu
Insights
Fetal hypoxia is linked to brain abnormalities in schizophrenia patients and their siblings. This suggests a gene-environment interaction in schizophrenia development, impacting cortical gray matter and cerebrospinal fluid.
Area of Science:
- Neuroscience
- Psychiatry
- Genetics
Background:
- Schizophrenia is associated with reduced gray matter and increased cerebrospinal fluid (CSF).
- The link between obstetric risk factors and these brain changes is not well understood.
Purpose of the Study:
- To investigate the relationship between fetal hypoxia and structural brain abnormalities in schizophrenia.
- To explore potential gene-environment interactions in schizophrenia pathogenesis.
Main Methods:
- Utilized brain MRI scans, diagnostic interviews, and obstetric records from a Helsinki birth cohort.
- Included patients with schizophrenia/schizoaffective disorder, their nonpsychotic siblings, and controls without family history of psychosis.
Main Results:
- Fetal hypoxia predicted reduced gray matter and increased CSF in patients and siblings, particularly in the temporal lobe.
- These associations were stronger in patients born small for gestational age and were independent of genetic risk and other factors.
- Hypoxia correlated with ventricular enlargement only in patients.
Conclusions:
- Fetal hypoxia is associated with greater structural brain abnormalities in individuals at risk for schizophrenia.
- Findings support a gene-environment interaction model for schizophrenia's neurodevelopmental origins.
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.