The Involvement of the Hypothalamic-pituitary-gonadal, Hypothalamic-pituitary-adrenal and Somatotrophic Axes in the Development and Treatment of Schizophrenia

In the present review, organizational and activational hormonal effects are proposed to be dysfunctional in schizophrenia and psychosis. Specifically, organizational effects are held responsible for the long-lasting anatomical and functional changes in brain development associated with the disease. Later in life, activational effects may be superimposed and may interact with the earlier induced biological vulnerabilities, eventually triggering the first psychotic episode in schizophrenia. In parallel, it is known that schizophrenia follows a different course in male and female patients and that the first psychotic episode frequently occurs shortly before or during puberty. The different course of schizophrenia in male and female patients seems to be related to digressions in hormonal secretion between the genders. Further the excessive change of hormonal secretion during puberty suggests a relationship between hormonal secretion and the development of schizophrenia, possibly mediated by epigenetic regulation of neuroendocrine systems. We discuss the Hypothalamic-Pituitary-Gonadal (HPG), the Hypothalamic-Pituitary-Adrenal (HPA) and the Somatotropic axes and further present evidence for positive treatment effects in schizophrenia by hormonal agents. We conclude that organizational as well as activational effects of hormones may attribute to the development of schizophrenia. Research on hormonal factors in schizophrenia might therefore enhance the general understanding of the disease in regard to its neurobiology and treatment options.