The authors declared that they have no financial disclosures or conflicts of interest.
A review of neuroimaging studies of young relatives of individuals with schizophrenia: A developmental perspective from schizotaxia to schizophrenia
Article first published online: 17 OCT 2013
Copyright © 2013 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Special Issue: Identifying the Origins of Mental Illness: A Festschrift in Honor of Ming T. Tsuang
Volume 162, Issue 7, pages 604–635, October 2013
How to Cite
2013. A Review of Neuroimaging Studies of Young Relatives of Individuals With Schizophrenia: A Developmental Perspective From Schizotaxia to Schizophrenia. Am J Med Genet Part B 162B:604–635., , , , , , , .
- Issue published online: 17 OCT 2013
- Article first published online: 17 OCT 2013
- Manuscript Accepted: 24 APR 2013
- Manuscript Received: 30 JAN 2013
- NIMH. Grant Numbers: MH081928, MH065571, MH092840, RO1 MH064023, MH078113, KO2 01180
- Commonwealth Research Center of the Massachusetts Department of Mental Health. Grant Number: SCDMH82101008006
In an effort to identify the developing abnormalities preceding psychosis, Dr. Ming T. Tsuang and colleagues at Harvard expanded Meehl's concept of “schizotaxia,” and examined brain structure and function in families affected by schizophrenia (SZ). Here, we systematically review genetic (familial) high-risk (HR) studies of SZ using magnetic resonance imaging (MRI), examine how findings inform models of SZ etiology, and suggest directions for future research. Neuroimaging studies of youth at HR for SZ through the age of 30 were identified through a MEDLINE (PubMed) search. There is substantial evidence of gray matter volume abnormalities in youth at HR compared to controls, with an accelerated volume reduction over time in association with symptoms and cognitive deficits. In structural neuroimaging studies, prefrontal cortex (PFC) alterations were the most consistently reported finding in HR. There was also consistent evidence of smaller hippocampal volume. In functional studies, hyperactivity of the right PFC during performance of diverse tasks with common executive demands was consistently reported. The only longitudinal fMRI study to date revealed increasing left middle temporal activity in association with the emergence of psychotic symptoms. There was preliminary evidence of cerebellar and default mode network alterations in association with symptoms. Brain abnormalities in structure, function and neurochemistry are observed in the premorbid period in youth at HR for SZ. Future research should focus on the genetic and environmental contributions to these alterations, determine how early they emerge, and determine whether they can be partially or fully remediated by innovative treatments. © 2013 Wiley Periodicals, Inc.