Heritability of brain morphology related to schizophrenia: a large-scale automated magnetic resonance imaging segmentation study.
BACKGROUND
Schizophrenia is a devastating psychiatric disorder with a strong genetic component that has been related to a number of structural brain alterations. Currently available data on the heritability of these structural changes are inconsistent.


METHODS
To examine heritability of morphological alterations in a large sample, we used a novel and validated fully-automated whole brain segmentation technique to study disease-related variability and heritability in anatomically defined regions of interest in 221 healthy control subjects, 169 patients with schizophrenia, and 183 unaffected siblings.


RESULTS
Compared with healthy control subjects, patients showed a bilateral decrease in hippocampal and cortical gray matter volume and increases in bilateral dorsal striatum and right lateral ventricle. No significant volumetric differences were found in unaffected siblings compared with normal control subjects in any structure. Post hoc analysis of the dorsal striatum showed the volumetric increase to be widespread, including caudate, putamen, and globus pallidus. With Risch's lambda (lambda(s)), we found strong evidence for heritability of reduced cortical volume and moderate evidence for hippocampal volume, whereas abnormal striatal and ventricle volumes showed no sign of heritability. Additional exploratory analyses were performed on amygdala, thalamus, nucleus accumbens, ventral diencephalon, and cerebral and cerebellar cortex and white matter. Of these regions, patients showed increased volume in ventral diencephalon and cerebellum.


CONCLUSIONS
These findings support evidence of genetic control of brain volume even in adults, particularly of hippocampal and neocortical volume and of cortical volumetric reductions being familial, but do not support measures of subcortical volumes per se as representing intermediate biologic phenotypes.
Goldman
Aaron L
AL
Neuroimaging Core Facility, Genes, Cognition and Psychosis Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA.
Pezawas
Lukas
L
Mattay
Venkata S
VS
Fischl
Bruce
B
Verchinski
Beth A
BA
Zoltick
Brad
B
Weinberger
Daniel R
DR
Meyer-Lindenberg
Andreas
A
D000293:Adolescent; D000328:Adult; D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics; D001921:Brain / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology*; D015897:Comorbidity; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000235:genetics; D004292:Dominance, Cerebral / Q000235:genetics; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D008297:Male; D001523:Mental Disorders / Q000175:diagnosis / Q000235:genetics; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000175:diagnosis / Q000235:genetics*; D012016:Reference Values; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics*; D012569:Schizotypal Personality Disorder / Q000175:diagnosis / Q000235:genetics; D035781:Siblings; D012984:Software