# Peripheral blood RNA-seq analysis in bipolar and schizophrenia spectrum disorders: modest influence of antipsychotic treatment

**Authors:** Yosra Bejaoui, Suhaila Ghuloum, Teena John, Gaurav Thareja, Tanwir Habib, Karsten Suhre, Hassen Al-Amin

PMC · DOI: 10.3389/fphar.2026.1745052 · Frontiers in Pharmacology · 2026-02-18

## TL;DR

This study finds shared gene expression patterns in bipolar and schizophrenia disorders, with immune and metabolic changes that are not strongly affected by antipsychotic treatment.

## Contribution

The study identifies a core set of differentially expressed genes shared between bipolar and schizophrenia disorders, independent of antipsychotic treatment.

## Key findings

- Patients with bipolar and schizophrenia disorders share 1,278 differentially expressed genes, regardless of antipsychotic use.
- These genes are enriched in immune processes, metabolic pathways, and cellular homeostasis.
- A co-expression module was strongly linked to mental illness status, not metabolic traits.

## Abstract

Bipolar disorder (BP) and schizophrenia spectrum disorders (SSD) are chronic mental health conditions that share genetic risks. Despite extensive research, the biological mechanisms underlying these disorders are still not fully understood.

In this study, we analyzed peripheral blood RNA-seq data from 64 patients with BP and SSD, both on and off antipsychotic treatment, and 92 healthy controls. We conducted differential gene expression analyses, pathway enrichment analyses, weighted gene co-expression network analysis (WGCNA), and clinical trait association analyses.

Patients showed distinct blood transcriptomic profiles compared to controls, with a core set of 1,278 differentially expressed genes shared between individuals with mental illness, both on and off antipsychotics. These common DEGs were enriched in immune processes, metabolic pathways, and cellular homeostasis functions. WGCNA identified a co-expression module that was strongly associated with mental illness status and not with metabolic traits. We also observed a significant group effect for total cholesterol, LDL cholesterol, systolic blood pressure, and diastolic blood pressure when comparing metabolic clinical features among MD, MD + APs, and HC.

This transcriptomic study of BP and SSD in a Qatar-based cohort highlights dysregulated immune and metabolic pathways.

## Linked entities

- **Diseases:** bipolar disorder (MONDO:0004985)

## Full-text entities

- **Genes:** SPON2 (spondin 2) [NCBI Gene 10417] {aka DIL-1, DIL1, M-SPONDIN, MINDIN}, XIST (X inactive specific transcript) [NCBI Gene 7503] {aka DXS1089, DXS399E, LINC00001, NCRNA00001, SXI1, swd66}, PLXNC1 (plexin C1) [NCBI Gene 10154] {aka CD232, PLXN-C1, VESPR}, OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) [NCBI Gene 8473] {aka HINCUT-1, HRNT1, MRX106, O-GLCNAC, OGT1, XLID106}, MIB2 (MIB E3 ubiquitin protein ligase 2) [NCBI Gene 142678] {aka ZZANK1, ZZZ5}, DNAJB1 (DnaJ heat shock protein family (Hsp40) member B1) [NCBI Gene 3337] {aka HSPF1, Hdj1, Hsp40, RSPH16B, Sis1}, ROBO2 (roundabout guidance receptor 2) [NCBI Gene 6092] {aka SAX3}, CNTN1 (contactin 1) [NCBI Gene 1272] {aka CMYO12, CMYP12, F3, GP135, MYPCN}, TSIX (TSIX transcript, XIST antisense RNA) [NCBI Gene 9383] {aka LINC00013, NCRNA00013, XIST-AS, XIST-AS1, XISTAS}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, SLC33A2 (solute carrier family 33 member 2) [NCBI Gene 113655] {aka MFSD3}, LIM2 (lens intrinsic membrane protein 2) [NCBI Gene 3982] {aka CTRCT19, MP17, MP19}, GPR152 (G protein-coupled receptor 152) [NCBI Gene 390212] {aka PGR5}, RHOD (ras homolog family member D) [NCBI Gene 29984] {aka ARHD, RHOHP1, RHOM, Rho}, MATN1 (matrilin 1) [NCBI Gene 4146] {aka CMP, CRTM}, TMEM238 (transmembrane protein 238) [NCBI Gene 388564], CYRIA (CYFIP related Rac1 interactor A) [NCBI Gene 81553] {aka CYRI-A, FAM49A}, NTRK2 (neurotrophic receptor tyrosine kinase 2) [NCBI Gene 4915] {aka DEE58, EIEE58, GP145-TrkB, OBHD, TRKB, trk-B}, FRS2 (fibroblast growth factor receptor substrate 2) [NCBI Gene 10818] {aka FRS1A, FRS2A, FRS2alpha, SNT, SNT-1, SNT1}, ATR (ATR checkpoint kinase) [NCBI Gene 545] {aka FCTCS, FRP1, MEC1, SCKL, SCKL1}, PLIN4 (perilipin 4) [NCBI Gene 729359] {aka KIAA1881, MDRV, MRUPAV, S3-12}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, SLC22A4 (solute carrier family 22 member 4) [NCBI Gene 6583] {aka DFNB60, ETTh, OCTN1}, CRYZ (crystallin zeta) [NCBI Gene 1429], HRNR (hornerin) [NCBI Gene 388697] {aka FLG3, S100A16, S100a18}, CSNK1D (casein kinase 1 delta) [NCBI Gene 1453] {aka ASPS, CKI-delta, CKId, CKIdelta, FASPS2, HCKID}
- **Diseases:** lymphomas (MESH:D008223), female breast carcinoma (MESH:D001943), Bipolar disorder (MESH:D001714), cutaneous melanoma (MESH:C562393), HIV-1 infection (MESH:D015658), primary biliary cirrhosis (MESH:D008105), autoimmune hepatitis (MESH:D019693), infectious diseases (MESH:D003141), encephalopathy (MESH:D001927), connective tissue diseases (MESH:D003240), encephalitis (MESH:D004660), infection (MESH:D007239), cardiovascular disease (MESH:D002318), neuropsychiatric (MESH:C000631768), retinitis (MESH:D012173), immune- (MESH:D007154), psychosis (MESH:D011618), spinocerebellar ataxia (MESH:D020754), benign prostatic hyperplasia (MESH:D011470), health (OMIM:603663), BD (MESH:D001528), autoimmune diseases (MESH:D001327), obesity (MESH:D009765), classical Hodgkin's lymphoma (MESH:D006689), APs (MESH:D018420), MD (MESH:C535955), systemic lupus erythematosus (MESH:D008180), neurodegenerative disorders (MESH:D019636), pancreatic ductal carcinoma (MESH:D021441), inflammatory (MESH:D007249), metabolic syndrome (MESH:D024821), HC (MESH:D000067329), acute coronary syndrome (MESH:D054058), pancreatic carcinoma (MESH:D010190), SSD (MESH:D019967), mental disorder (MESH:D001523), , and neoplastic disorders (MESH:D009369), schizophrenia (MESH:D012559)
- **Chemicals:** APs (MESH:D000250), AP (MESH:D000667), chlorpromazine (MESH:D002746), lipopolysaccharide (MESH:D008070), lipid (MESH:D008055), purine (MESH:C030985), sphingolipid (MESH:D013107), glucose (MESH:D005947), quetiapine (MESH:D000069348), folate (MESH:D005492), FGA (-), MD (MESH:D008573), olanzapine (MESH:D000077152), TCA (MESH:D014238), cholesterol (MESH:D002784), risperidone (MESH:D018967), ceramide (MESH:D002518), haloperidol (MESH:D006220), pyruvate (MESH:D019289), clozapine (MESH:D003024), hexose (MESH:D006601), phosphatidylinositol phosphate (MESH:D018129), aripiprazole (MESH:D000068180), triglyceride (MESH:D014280)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12957230/full.md

## References

45 references — full list in the complete paper: https://tomesphere.com/paper/PMC12957230/full.md

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Source: https://tomesphere.com/paper/PMC12957230