There are multiple genetic links between
schizophrenia and a deficit of
proline dehydrogenase (PRODH)
enzyme activity. However, reports testing for an association of
schizophrenia with the resulting
proline elevation have been conflicting. The objectives of this study were to investigate whether hyperprolinemia is associated with
schizophrenia, and to measure the relationship between plasma
proline, and clinical features and symptoms of
schizophrenia. We performed a cross-sectional case-control study, comparing fasting plasma
proline in 90 control subjects and 64 schizophrenic patients and testing for association of mild to moderate hyperprolinemia with
schizophrenia. As secondary analyses, the relationship between hyperprolinemia and five measures of clinical onset, symptoms and outcome were investigated. Patients had significantly higher plasma
proline than matched controls (p<0.0001), and categorical analysis of gender adjusted hyperprolinemia showed a significant association with
schizophrenia (OR 6.15, p=0.0003). Hyperprolinemic patients were significantly older at their first hospitalization (p=0.015 following correction for multiple testing). While plasma
proline level was not related to total, positive or negative symptoms, hyperprolinemic status had a significant effect on length of
hospital stay (p=0.005), following adjustment for race, BPRS score, and cross-sectional time from admission to
proline measurement. Mild to moderate hyperprolinemia is a significant risk factor for
schizophrenia, and may represent an intermediate phenotype in the disease. Hyperprolinemic patients have a significantly later age of first psychiatric hospitalization, suggestive of later onset, and
hospital stays 46% longer than non-hyperprolinemic subjects. These findings have implications in the etiology of
schizophrenia, and for the clinical management of these patients.