Schizophrenia Bulletin Advance Access originally published online on June 12, 2008
Schizophrenia Bulletin 2009 35(6):1142-1162; doi:10.1093/schbul/sbn053
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Imaging Genetic Liability to Schizophrenia: Systematic Review of fMRI Studies of Patients’ Nonpsychotic Relatives
2 Department of Psychology
3 Department of Psychiatry, University of Minnesota
4 Department of Psychiatry, Harvard Medical School, Massachusetts Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center
5 Department of Psychiatry, Harvard Medical School, Massachusetts General Hospital
6 MGH/MIT/HMS Athinoula A. Martinos Center for Functional and Structural Biomedical Imaging
7 Department of Psychology
8 Department of Psychiatry
9 Department of Radiology, Washington University of St Louis
1 To whom correspondence should be addressed; Department of Psychology, University of Minnesota, N218 Elliott Hall, 75 East River Road, Minneapolis, MN 55455; tel: 612-624-3813; fax: 612-625-6668, e-mail: angus{at}umn.edu.
There is a growing literature on brain activity in the nonpsychotic first-degree relatives of patients with schizophrenia as measured using functional imaging. This systematic review examined 20 studies in 4 domains of cognition, including cognitive control (7 samples), working memory (5 samples), long-term memory (4 samples), and language (4 samples). While the literature was widely divergent, these studies did consistently find activation differences between patients’ relatives and controls. The most consistent increases in activation within hemisphere were found in right ventral prefrontal cortex (PFC) and right parietal cortex. Abnormal activity, defined as significant increases or decreases in activation relative to controls irrespective of hemisphere, was found in about two-thirds of contrasts in the cerebellum, dorsal prefrontal, lateral temporal, and parietal cortices, and thalamus, with basal ganglia and ventral PFC showing abnormalities in approximately half of those contrasts. Anterior cingulate was generally spared in patients’ relatives. The diversity of findings in studies of patients’ relatives may derive from differences between the cognitive demands across studies. We identify avenues for building a more accurate and cumulative literature, including symmetrical inclusion criteria for relatives and controls, recording in-scanner responses, using both a priori and whole-brain tests, explicitly reporting threshold values, reporting main effects of task, reporting effect sizes, and quantifying the risk of false negatives. While functional imaging in the relatives of schizophrenia patients remains a promising methodology for understanding the impact of the unexpressed genetic liability to schizophrenia, no single region or mechanism of abnormalities has yet emerged.
Keywords: schizophrenia / neuroimaging / fMRI / relatives / family study / cognitive control / working memory / memory / language / review