Altered levels of circulating insulin and other neuroendocrine hormones associated with the onset of schizophrenia

doi:10.1016/j.psyneuen.2010.12.018

Psychoneuroendocrinology

Volume 36, Issue 7, August 2011, Pages 1092-1096

https://doi.org/10.1016/j.psyneuen.2010.12.018 Get rights and content

Summary

Recently, we showed that the circulating levels of insulin-related peptides and the secretory granule protein chromogranin A were increased in small cohorts of first onset schizophrenia patients. Assuming that this effect was associated with impaired insulin signalling, we investigated the possibility that secretion of other hormones is also affected in schizophrenia. Multiplex immunoassay analysis of 21 hormones and hormone-related molecules was carried out using sera from 236 first and recent onset schizophrenia patients and 230 matched controls. Serum concentrations of insulin and chromogranin A were increased in schizophrenia subjects, consistent with our previous study. In addition, we found elevated concentrations of pancreatic polypeptide, prolactin, progesterone and cortisol, and decreased levels of growth hormone. We also found that growth hormone levels were decreased in post-mortem pituitaries obtained from chronic schizophrenia patients. It will be important to determine whether any of these molecules are involved in the pathosphysiology of schizophrenia or if they reflect the associated insulin resistance. We conclude that function of multiple components of the hypothalamic-pituitary-adrenal-gonadal axis may be affected in schizophrenia. This could have important implications for future biomarker discovery efforts and personalized medicine strategies based on patient stratification for the treatment of this debilitating disorder.

Introduction

Schizophrenia patients have a decreased life expectancy due to increased incidence of co-morbidities such as metabolic syndrome, insulin resistance, cardiovascular disorders and type II diabetes (Ryan and Thakore, 2002). Some of these effects are known to be induced by antipsychotic treatment (Meyer et al., 2008). However, there is also evidence of metabolic syndrome in schizophrenia subjects which predates the original development and availability of antipsychotics, and recent studies have shown that first onset antipsychotic-naïve patients exhibit metabolic abnormalities including insulin resistance (Spelman et al., 2007).

Recently, we showed that the circulating levels of insulin-related peptides and the secretory protein chromogranin A were significantly elevated in small cohorts of first onset antipsychotic-naïve schizophrenia subjects (Guest et al., 2010). As insulin signalling regulates other neuroendocrine cells, it is possible that secretion of hormones from other cell types of the diffuse neuroendocrine system is also affected in schizophrenia. We tested this hypothesis by performing multiplex immunoassay analysis of 21 hormones and hormone-associated molecules representing diverse neuroendocrine and gonadal systems in sera obtained from a large combined cohort comprised of 236 first and recent onset schizophrenia and 230 control subjects. Our aims were to validate our previous findings regarding the increased levels of circulating insulin and chromogranin A, and to determine if additional neuroendocrine secreted molecules are also altered in this larger cohort of subjects.

Section snippets

Subjects

Ethical committees from the Universities of Cologne (cohort 1), Muenster (cohort 2) and Magdeburg (cohorts 3 and 5) in Germany, and that from Erasmus University (cohort 4) in the Netherlands, approved the protocols of the study as described previously (Schwarz et al., 2010). Essentially, informed written consent was obtained for all participants, diagnoses were carried out using the Diagnosis and Statistical Manual (DSM)-IV and clinical tests performed by psychiatrists under Good Clinical

Results

Using the multiplex immunoassay method, we found that the circulating levels of 7 analytes showed significant differences in schizophrenia compared to control subjects (Table 1B). The levels of insulin and chromogranin A were increased in this larger combined set of cohorts (n = 466 subjects), consistent with the findings of our previous targeted immunoassay study (Guest et al., 2010) which analyzed a subset of subjects (n = 134) from the same cohorts. In addition, we found that the circulating

Discussion

The current study has confirmed our previous findings which showed that the circulating levels of insulin and chromogranin A were increased in first onset anti-psychotic naïve schizophrenia subjects (Guest et al., 2010). High levels of insulin are associated with metabolic conditions such as insulin resistance and recent studies have shown that altered expression of chromogranin A may have a similar association (Friese et al., 2010). Based on the hypothesis that some schizophrenia subjects are

Role of the funding source

Funding for the study was by the Stanley Medical Research Institute and the European Union FP7 SchizDX research programme (grant reference 223427). These funding sources had no further role: in the study design; in the collection, analysis and interpretation of the data; in the report writing; and in the decision to submit the paper for publication.

Conflict of interest

ES is a consultant for Rules Based Medicine. PG and HR are consultants for Psynova Neurotech.

Acknowledgements

We are grateful for all patients and control subjects who contributed to the study.

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Short communicationAltered levels of circulating insulin and other neuroendocrine hormones associated with the onset of schizophrenia

Summary

Introduction

Section snippets

Subjects

Results

Discussion

Role of the funding source

Conflict of interest

Acknowledgements

Gastroenterology

Trends Endocrinol. Metab.

Mol. Cell. Proteomics

Horm. Behav.

Psychiatry Res.

Am. J. Obstet. Gynecol.

Neuropsychopharmacology

Schizophr. Res.

Prostaglandins Leukot. Essent. Fatty Acids

Life Sci.

Obesity induced by high-fat diet promotes insulin resistance in the ovary

J. Endocrinol.

Short communication
Altered levels of circulating insulin and other neuroendocrine hormones associated with the onset of schizophrenia