Endophenotypes in schizophrenia: A selective review

BackgroundGiven 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.MethodsWe 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.ResultsCombined, 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.ConclusionsThese 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.