Are neurocognitive, clinical and social dysfunctions in schizotaxia reversible pharmacologically? Results from the Changsha study

The Changsha study identifies adult, non-psychotic relatives of patients with schizophrenia who show deficits in neurocognitive, social, clinical and other dimensions, and who meet provisional criteria for a liability syndrome for schizophrenia (‘schizotaxia’). In this study, we investigated whether negative symptoms, neurocognitive deficits, or other measures of clinical and social function in subjects who met our research criteria for schizotaxia were amenable to pharmacological remediation with a low dose (2.0 mg) of risperidone, a second generation antipsychotic medication. One hundred eighty nine relatives were assessed at the Mental Health Institute, Second Xiangya Hospital of Central South University, Changsha (Hunan Province, China), between 12/06 and 12/08. Eighty six of these individuals met modified criteria for schizotaxia, and 36 agreed to enter a 6-week, double-blind, placebo-controlled protocol. ANCOVAs using age and gender as covariates showed significant improvement in the risperidone group (n = 20) on neurocognitive function (Wisconsin Card Sorting Test Total Errors and Perseverative Errors) and on a self-report measure of social function (Social Adjustment Scale), compared to the placebo-control group (n = 16). Effect sizes were small to medium. Notably, risperidone effect sizes were larger (medium to large) in a subset of subjects (risperidone = 15; placebo = 10) whose membership in the schizotaxic group was supported empirically by cluster analysis. Negative symptoms did not change significantly in either analysis. The results are generally consistent with previous open-label investigations of risperidone administration in subjects with schizotaxia, and provide evidence that some neurocognitive and clinical problems are amenable to remediation in non-psychotic relatives of people with schizophrenia.