Peripheral blood correlates of negative symptom severity in schizophrenia: exploratory findings from an Indian cohort
6 affiliations
- 1Symbiosis School of Biological Sciences (SSBS), Symbiosis International (Deemed University), Pune, Maharashtra, India
- 2Psychiatry Unit, K.E.M. Hospital and Research Centre (KEMHRC), Pune, India
- 3Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India
- 4AMCHSS, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India
- 5Symbiosis Medical College for Women (SMCW), Symbiosis International (Deemed University), Pune, Maharashtra, India
- 6Grampians Health Ballarat, Mental Health Services, Ballarat, VIC, Australia
Abstract
BackgroundSchizophrenia (SCZ) is characterized by positive and negative symptoms, with the latter often poorly responsive to treatment. Negative symptoms are associated with increased cardiovascular risk and metabolic syndrome. Investigation of the cellular and molecular alterations associated with negative symptom severity may provide insights into disease mechanisms and aid in the identification of novel therapeutic targets.MethodologyA multi-center case-control study was conducted using peripheral blood as a surrogate tissue. Peripheral blood mononuclear cells were subjected to RNA sequencing. Cellular compositional changes were estimated by digital deconvolution using CIBERSORTx. Transcriptomic correlates of negative symptom severity were identified using weighted gene co-expression network analysis (WGCNA).ResultsDigital deconvolution of the peripheral blood mononuclear cell transcriptome of 47 participants (25 SCZ and 22 healthy controls) uncovered a nominal inverse association between activated CD4+ memory T-cell proportions and negative symptom severity (p = 0.016). WGCNA revealed modules showing a trend toward positive correlation with negative symptom severity (r = 0.35) that were enriched for genes involved in cytotoxic immune responses. Hub genes identified from these modules included GZMH, NKG7, GZMM, TBX21, CTSW, CST7, FCRL6, ADGRG1, and HOPX.ConclusionThe nominal inverse association of activated CD4+ memory T-cells with negative symptom severity, together with the enrichment of cytotoxic immune response genes, is consistent with immune remodeling toward terminally differentiated cytotoxic lymphocyte phenotypes in schizophrenia. These novel findings provide preliminary evidence for cellular and molecular immune correlates associated with negative symptom severity in SCZ but warrant validation in larger cohorts.
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BibTeX
@article{kamble2026peripheral,
title = {{Peripheral blood correlates of negative symptom severity in schizophrenia: exploratory findings from an Indian cohort}},
author = {Vinesh S. Kamble and Vipul V. Wagh and Soumya Yadav and Sukeshini B. Khandagale and Aditi Agnihotri and Shruti Purohit and Suchita Agrawal and Pavithra Jayasankar and Swarna Buddha Nayok and Biju Viswanath and Srikant Ambatipudi and Gaurav Pawar and Vasudeo Paralikar and Ajit Naik and Ajit Naik and Satyajeet P. Khare},
journal = {Frontiers in Genetics},
year = {2026},
month = nov,
doi = {10.3389/fgene.2026.1918773},
url = {https://doi.org/10.3389/fgene.2026.1918773},
note = {CC BY},
}
RIS
TY - JOUR
TI - Peripheral blood correlates of negative symptom severity in schizophrenia: exploratory findings from an Indian cohort
AU - Vinesh S. Kamble
AU - Vipul V. Wagh
AU - Soumya Yadav
AU - Sukeshini B. Khandagale
AU - Aditi Agnihotri
AU - Shruti Purohit
AU - Suchita Agrawal
AU - Pavithra Jayasankar
AU - Swarna Buddha Nayok
AU - Biju Viswanath
AU - Srikant Ambatipudi
AU - Gaurav Pawar
AU - Vasudeo Paralikar
AU - Ajit Naik
AU - Ajit Naik
AU - Satyajeet P. Khare
PY - 2026
DA - 2026/11/04
JO - Frontiers in Genetics
DO - 10.3389/fgene.2026.1918773
UR - https://doi.org/10.3389/fgene.2026.1918773
AB - BackgroundSchizophrenia (SCZ) is characterized by positive and negative symptoms, with the latter often poorly responsive to treatment. Negative symptoms are associated with increased cardiovascular risk and metabolic syndrome. Investigation of the cellular and molecular alterations associated with negative symptom severity may provide insights into disease mechanisms and aid in the identification of novel therapeutic targets.MethodologyA multi-center case-control study was conducted using peripheral blood as a surrogate tissue. Peripheral blood mononuclear cells were subjected to RNA sequencing. Cellular compositional changes were estimated by digital deconvolution using CIBERSORTx. Transcriptomic correlates of negative symptom severity were identified using weighted gene co-expression network analysis (WGCNA).ResultsDigital deconvolution of the peripheral blood mononuclear cell transcriptome of 47 participants (25 SCZ and 22 healthy controls) uncovered a nominal inverse association between activated CD4+ memory T-cell proportions and negative symptom severity (p = 0.016). WGCNA revealed modules showing a trend toward positive correlation with negative symptom severity (r = 0.35) that were enriched for genes involved in cytotoxic immune responses. Hub genes identified from these modules included GZMH, NKG7, GZMM, TBX21, CTSW, CST7, FCRL6, ADGRG1, and HOPX.ConclusionThe nominal inverse association of activated CD4+ memory T-cells with negative symptom severity, together with the enrichment of cytotoxic immune response genes, is consistent with immune remodeling toward terminally differentiated cytotoxic lymphocyte phenotypes in schizophrenia. These novel findings provide preliminary evidence for cellular and molecular immune correlates associated with negative symptom severity in SCZ but warrant validation in larger cohorts.
SN - 1664-8021
ER -