Endophenotypes in schizophrenia: A selective review

Background: Given the wealth of data in the literature on schizophrenia endophenotypes, it is useful to have one source to reference their frequency data. We reviewed the literature on disease-liability associated variants in structural and functional magnetic resonance images (MRI), sensory processing measures, neuromotor abilities, neuropsychological measures, and physical characteristics in schizophrenia patients (SCZ), their first-degree relatives (REL), and healthy controls (HC). The purpose of this review was to provide a summary of the existing data on the most extensively published endophenotypes for schizophrenia. Methods: We searched PubMed and MedLine for all studies on schizophrenia endophenotypes comparing SCZ to HC and/or REL to HC groups. Percent abnormal values, generally defined as > 2 SD from the mean (in the direction of abnormality) and/or associated effect sizes (Cohen's d) were calculated for each study. Results: Combined, the articles reported an average 39.4% (SD = 20.7%; range = 2.2-100%) of abnormal values in SCZ, 28.1% (SD = 16.6%; range = 1.6-67.0%) abnormal values in REL, and 10.2% (SD = 6.7%; range = 0.0-34.6%) in HC groups. Conclusions: These findings are reviewed in the context of emerging hypotheses on schizophrenia endophenotypes, as well as a discussion of clustering trends among the various intermediate phenotypes. In addition, programs for future research are discussed, as instantiated in a few recent large-scale studies on multiple endophenotypes across patients, relatives, and healthy controls.