Distinct Molecular Phenotypes in Male and Female Schizophrenia Patients

Abstract

BackgroundIn schizophrenia, sex specific dimorphisms related to age of onset, course of illness and response to antipsychotic treatment may be mirrored by sex-related differences in the underlying molecular pathways.Methodology/Principal FindingsHere, we have carried out multiplex immunoassay profiling of sera from 4 independent cohorts of first episode antipsychotic naive schizophrenia patients (n = 133) and controls (n = 133) to identify such sex-specific illness processes in the periphery. The concentrations of 16 molecules associated with hormonal, inflammation and growth factor pathways showed significant sex differences in schizophrenia patients compared with controls. In female patients, the inflammation-related analytes alpha-1-antitrypsin, B lymphocyte chemoattractant BLC and interleukin-15 showed negative associations with positive and negative syndrome scale (PANSS) scores. In male patients, the hormones prolactin and testosterone were negatively associated with PANSS ratings. In addition, we investigated molecular changes in a subset of 33 patients before and after 6 weeks of treatment with antipsychotics and found that treatment induced sex-specific changes in the levels of testosterone, serum glutamic oxaloacetic transaminase, follicle stimulating hormone, interleukin-13 and macrophage-derived chemokine. Finally, we evaluated overlapping and distinct biomarkers in the sex-specific molecular signatures in schizophrenia, major depressive disorder and bipolar disorder.Conclusions/SignificanceWe propose that future studies should investigate the common and sex-specific aetiologies of schizophrenia, as the current findings suggest that different therapeutic strategies may be required for male and female patients.

Potential Biomarkers Selection for Bipolar Disorder Identification

“…We found that prolactin is inversely related (0.83) with BD in males which is the opposite effect we found in a schizophrenia study (Ramsey et al, 2013). Further study of the gender effect of PRL on BD.…”

Leukocyte telomere length: Effects of schizophrenia, age, and gender

“…Because numerous studies have shown that the onset of schizophrenia tends to be later in life in women than in men (Howard et al, 2000), and the present results indicate that the separation between women with schizophrenia and HC women might differ from that between men with schizophrenia and HC men at various ages, understanding the effects of aging in schizophrenia will likely require studying LTL (and other aging parameters) separately in men and women (Ramsey et al, 2013).…”

“…These factors may be increased in schizophrenia compared to HCs (Emiliani et al, 2014;Muller et al, 2015;Shivakumar et al, 2014). This could, in theory, result in shortened LTL, but there is only mixed evidence that these factors are differentially prevalent in men vs women with schizophrenia (Joseph et al, 2015;Kunz et al, 2011;Lee et al, 2016;Ramsey et al, 2013;Reyazuddin et al, 2014).…”

Macrophage-Derived Chemokine: A Putative Marker of Pharmacological Therapy Response in Major Depression?

“…With regard to psychiatric disorders, alterations in MDC levels have been found in patients suffering from schizophrenia [27,28] . Ramsey et al [27] compared untreated schizophrenic patients with healthy subjects and found sex-specific differences in the serum MDC levels of patients compared to in controls.…”

“…Ramsey et al [27] compared untreated schizophrenic patients with healthy subjects and found sex-specific differences in the serum MDC levels of patients compared to in controls. No such differences could be found for patients suffering from MDD or bipolar disorder (BP).…”