TY - JOUR
T1 - Heritability of Brain Morphology Related to Schizophrenia
T2 - A Large-Scale Automated Magnetic Resonance Imaging Segmentation Study
AU - Goldman, Aaron L.
AU - Pezawas, Lukas
AU - Mattay, Venkata S.
AU - Fischl, Bruce
AU - Verchinski, Beth A.
AU - Zoltick, Brad
AU - Weinberger, Daniel R.
AU - Meyer-Lindenberg, Andreas
N1 - Funding Information:
This work was supported by the National Institute of Mental Health Intramural Research Program. Support for this research was also provided in part by the National Center for Research Resources (P41-RR14075, R01 RR16594-01A1 and the NCRR BIRN Morphometric Project BIRN002, U24 RR021382), the National Institute for Biomedical Imaging and Bioengineering (R01 EB001550), the National Institute for Neurological Disorders and Stroke (R01 NS052585-01), as well as the Mental Illness and Neuroscience Discovery (MIND) Institute and is part of the National Alliance for Medical Image Computing (NAMIC), funded by the National Institutes of Health (NIH) through the NIH Roadmap for Medical Research, Grant U54 EB005149. Information on the National Centers for Biomedical Computing can be obtained from http://nihroadmap.nih.gov/bioinformatics .
PY - 2008/3/1
Y1 - 2008/3/1
N2 - 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 λ (λs), 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.
AB - 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 λ (λs), 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.
KW - Brain volume
KW - MRI
KW - heritability
KW - phenotypes
KW - schizophrenia
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U2 - 10.1016/j.biopsych.2007.06.006
DO - 10.1016/j.biopsych.2007.06.006
M3 - Article
C2 - 17727823
AN - SCOPUS:38949151125
SN - 0006-3223
VL - 63
SP - 475
EP - 483
JO - Biological psychiatry
JF - Biological psychiatry
IS - 5
ER -