Brain Mapping in Adolescents With Very Early Onset Schizophrenia
By Paul Thompson, Ph.D.
March 1, 2003
Dr. Thompson has developed several neuroimaging approaches for investigating brain changes in schizophrenia, childhood development and Alzheimer's disease. He is assistant professor of neurology at the David Geffen School of Medicine at UCLA.
Two final studies illustrate the usefulness of neuroimaging as a biomarker in schizophrenia. In a recent twin study (Cannon et al., 2002a), we detected frontal and temporal cortical deficits (around 5% to 8%) in healthy relatives of patients who are at increased genetic risk for developing the disease. These deficits were correlated with the degree of genetic affinity to a patient (i.e., worse deficits in identical twins of patients than fraternal twins, for example, as the latter share fewer genes with a patient). Patients' siblings and children have a 10% lifetime risk of developing schizophrenia, much greater than the 1% risk in the general population.
Isolation of a brain deficit that is an index of liability for schizophrenia is important for two reasons. First, a heritable biomarker, found in at-risk relatives, can be used in genetic association and linkage studies. Differences between MRIs of relatives can be covaried with the number of alleles they share with a patient at a candidate marker locus, to see if particular genetic loci play a role in increasing liability. The notion of genetic linkage (which links trait variation with allelic variation at a marker locus) can be generalized to the notion of a brain map of linkage, showing brain deficits that are linked with allelic variations (e.g., Thompson et al., 2003). As neuroimaging and genetic databases increase in size and content, the merger of genetics and neuroimaging will empower the search for (and characterization of) susceptibility genes. This is likely to clarify their effects on brain phenotype and disease progression in human populations.
Secondly, analysis of brain changes in those at genetic risk may help identify relatives who are in the prodromal (i.e., pre-symptomatic) phase of the disease. Since individual outcomes depend heavily on how early the disease process is detected, relatives with both genetic and neuroimaging risk markers may be able to use this information proactively. Armed with this knowledge, they may in the future opt for early interventions and drug treatment before the ravages of the disease have set in.
Special thanks go to the members of the NIMH Child Psychiatry Branch, the University of California, Los Angeles, Laboratory of Neuroimaging, and the Queensland Center for Magnetic Resonance, for their key role in the studies summarized here.
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