Distinct molecular phenotypes in male and female schizophrenia patients.
BACKGROUND
In 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.


RESULTS
Here, 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
We 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.
Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom.
Jordan M
JM
Ramsey
Emanuel
E
Schwarz
Paul C
PC
Guest
Nico J M
NJ
van Beveren
F Markus
FM
Leweke
Matthias
M
Rothermundt
Bernhard
B
Bogerts
Johann
J
Steiner
Sabine
S
Bahn
D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood; D054382:Chemokine CXCL13 / Q000097:blood; D005260:Female; D006801:Humans; D018793:Interleukin-13 / Q000097:blood; D019409:Interleukin-15 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011388:Prolactin / Q000097:blood; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy; D012727:Sex Characteristics; D013739:Testosterone / Q000097:blood; D000514:alpha 1-Antichymotrypsin / Q000097:blood
D014150:Antipsychotic Agents; D015415:Biomarkers; C110663:CXCL13 protein, human; D054382:Chemokine CXCL13; C569274:IL15 protein, human; D018793:Interleukin-13; D019409:Interleukin-15; D000514:alpha 1-Antichymotrypsin; D013739:Testosterone; D011388:Prolactin