Vulnerability markers in the schizophrenia spectrum: implications for phenomenology, genetics, and the identification of the schizophrenia prodrome.

A continuum of symptoms between "normality" and overt psychosis has been documented in relatives of schizophrenia patients, SPD, and individuals who may be in the early stages of a psychotic illness with "subsyndromal" symptoms. The empirically derived criteria for SPD have been refined to define a clinical phenotype that is linked to schizophrenia. The clinical SPD symptoms define a heterogeneous group of individuals who are often comorbid for Axis I and II disorders, may or may not have a family history of schizophrenia, and are at risk for developing schizophrenia themselves. SPD subjects have similar abnormalities to those observed in schizophrenia patients on various psychophysiologic paradigms designed to study central inhibition, including P50 event-related potential suppression, PPI of the startle response, and the antisaccade task. Because SPD subjects do not have many of the confounding variables observed in schizophrenia patients (i.e., medication effects), these paradigms might represent vulnerability markers that are possible endophenotypes for schizophrenia spectrum illness. Questions still remain as to whether SPD is genotypically linked to schizophrenia but has genes of lesser penetrance, fewer affected genes, lack of a second hit, or perhaps protective factors. It is also possible that SPD, like schizophrenia, is a common final pathway that can come about because of several etiologic factors that affect crucial neurodevelopmental periods. Future directions in SPD work might include the use of vulnerability markers to essentially subtype schizophrenia spectrum patients and create simpler endophenotypes to understand the phenomenologic and neurobiologic substrate. The use of vulnerability markers along with clinical symptoms may help to improve the predictive power for identifying individuals at risk for schizophrenia for early intervention. Finally, genetic studies have yet to be performed in SPD.