RT Journal Article
SR Electronic
T1 The D2R-DISC1 protein complex and associated proteins are altered in schizophrenia and normalized with antipsychotic treatment
JF Journal of Psychiatry and Neuroscience
JO JPN
FD Canadian Medical Association
SP E134
OP E147
DO 10.1503/jpn.210145
VO 47
IS 2
A1 Jijun Wang
A1 Ping Su
A1 Jian Yang
A1 Lihua Xu
A1 Aihua Yuan
A1 Chunbo Li
A1 Tianhong Zhang
A1 Fang Dong
A1 Jingjing Zhou
A1 James Samsom
A1 Albert H.C. Wong
A1 Fang Liu
YR 2022
UL http://jpn.ca/content/47/2/E134.abstract
AB Background For decades, the dopamine D2 receptor (D2R) has been known as the main target of antipsychotic medications, but the mechanism for antipsychotic effects beyond this pharmacological target remains unclear. Disrupted-in-schizophrenia 1 (DISC1) is a gene implicated in the etiology of schizophrenia, and we have found elevated levels of the D2R-DISC1 complex in the postmortem brain tissue of patients with schizophrenia.Methods We used coimmunoprecipitation to measure D2R-DISC1 complex levels in peripheral blood samples from patients with schizophrenia and unaffected controls in 3 cohorts (including males and females) from different hospitals. We also used label-free mass spectrometry to conduct proteomic analysis of these samples.Results Levels of the D2R-DISC1 complex were elevated in the peripheral blood samples of patients with schizophrenia from 3 independent cohorts, and were normalized with antipsychotic treatment. Proteomic analysis of the blood samples from patients with high D2R-DISC1 complex levels that were normalized with antipsychotic treatment revealed a number of altered proteins and pathways associated with D2R, DISC1 and the D2R-DISC1 complex. We identified additional proteins and pathways that were associated with antipsychotic treatment in schizophrenia, and that may also be novel targets for schizophrenia treatment.Limitations Sample sizes were relatively small, but were sufficient to detect associations between D2R-DISC1 levels, schizophrenia and treatment response. The relevance of leukocyte changes to the symptoms of schizophrenia is unknown. The coimmunoprecipitation lanes included several nonspecific bands.Conclusion Levels of the D2R-DISC1 complex were elevated in patients with schizophrenia and reduced with antipsychotic treatment. This finding reinforces the independent role of each protein in schizophrenia. Our results enhanced our understanding of the molecular pathways involved in schizophrenia and in antipsychotic medications, and identified novel potential molecular targets for treating schizophrenia.