Abnormalities in metabolism and hypothalamic-pituitary-adrenal axis function in schizophrenia.

For decades, evidence has been emerging that the pathogenesis of schizophrenia can involve perturbations in metabolic and hypothalamic-pituitary-adrenal (HPA) axis pathways. Variations in manifestation of these effects could be related to the differences in clinical symptoms between affected individuals as well as to differences in treatment response, including the finding that a high proportion of subjects fail to respond to current antipsychotic medications. Here, we review the evidence for abnormalities in metabolism and HPA axis regulation in schizophrenia. Such studies may prove critical for increasing our understanding of the multidimensional nature of psychiatric illnesses and for improving the timeliness and accuracy of diagnosis. Stratification of subjects according to molecular phenotype reflecting the disease state or trait could help to improve existing treatments through application of novel personalized medicine strategies and by the development of much-needed novel antipsychotic agents.