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CHRFAM7A gene expression in schizophrenia: clinical correlates and the effect of antipsychotic treatment

  • Psychiatry and Preclinical Psychiatric Studies - Original Article
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Abstract

Earlier studies have implicated CHRNA7, coding α-7 nicotinic acetylcholine receptor (α7 nAChR), and its partially duplicated chimeric gene CHRFAM7A in schizophrenia. However, the relationship between the alterations in peripheral gene expression of CHRFAM7A and severity of clinical symptoms has not been examined. Furthermore, potential influence of the antipsychotic medication on CHRFAM7A expression in drug-naive or drug-free schizophrenia is an unexplored area. CHRFAM7A gene expression in lymphocytes was analyzed in 90 antipsychotic-naïve or free schizophrenia patients using TaqMan-based quantitative RT-PCR. Psychotic symptoms were assessed using Scale for Assessment of Positive Symptoms and Scale for Assessment of Negative Symptoms (SANS). The relationship between psychopathology and CHRFAM7A expression was examined. In addition, measurement of CHRFAM7A gene expression was repeated during follow-up after short-term antipsychotic treatment in 38 patients. There was significant inverse correlation between CHRFAM7A expression and total negative psychopathology score—SANS, and this relationship persisted after accounting for possible confounders such as age, sex and smoking. On exploration of the factor structure of psychopathology using principal component analysis, all the negative symptoms—affective flattening, alogia, apathy, anhedonia and inattention were found to be inversely associated with CHRFAM7A expression. Furthermore, analysis of repeated measures revealed a significant increase in CHRFAM7A expression in patients after short-term administration of antipsychotic medication. Our study observations support the role for CHRFAM7A gene in schizophrenia pathogenesis and suggest a potential novel link between deficient CHRFAM7A expression and negative psychopathology. Furthermore, up-regulation of CHRFAM7A gene expression by antipsychotics suggests that it could be a potential state marker for clinical severity.

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Acknowledgements

This work is supported by the CEIB Programme Support Grant to GV (BT/PR5322/COE/34/8/2012) as well as by the Wellcome Trust/DBT India Alliance Senior Fellowship research grant to GV (500236/Z/11/Z). SVK, SMA and ACA are supported by the Wellcome Trust/DBT India Alliance. VS is supported by the Indian Council of Medical Research (DHR/HRD/Young Scientist/Type-VI-(2)/2015). AR is supported by the DST-INSPIRE (IF-120727). RA is supported by the CEIB Programme Support Grant. MS is supported by the UGC-RGNF & DV is supported by the UGC-NET-JRF. We sincerely acknowledge the reviewers inputs during the revision of the manuscript.

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  1. Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, 560029, India

    Sunil V. Kalmady, Rimjhim Agrawal, Venkataram Shivakumar, Sri Mahavir Agarwal, Janardhanan C. Narayanaswamy & Ganesan Venkatasubramanian

  2. Department of Human Genetics, National Institute of Mental Health and Neurosciences, Bangalore, India

    Deepthi Venugopal, Manjula Subbanna, Ashwini Rajasekaran & Monojit Debnath

  3. Department of Psychiatric Social Work, National Institute of Mental Health and Neurosciences, Bangalore, India

    Anekal C. Amaresha

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  1. Sunil V. Kalmady
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Kalmady, S.V., Agrawal, R., Venugopal, D. et al. CHRFAM7A gene expression in schizophrenia: clinical correlates and the effect of antipsychotic treatment. J Neural Transm 125, 741–748 (2018). https://doi.org/10.1007/s00702-017-1833-5

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