# Exploration of Early-Treatment-Associated Changes in Metabolic and Inflammatory Biomarkers in First-Episode Psychosis in Italian Patients

**Authors:** Elisabetta Maffioletti, Clarissa Ferrari, Roberta Zanardini, Roberta Rossi, Sarah Tosato, Chiara Bonetto, Mario Ballarin, Antonio Lasalvia, Mirella Ruggeri, Massimo Gennarelli, Andrea Geviti, Luisella Bocchio-Chiavetto

PMC · DOI: 10.3390/ijms27042065 · International Journal of Molecular Sciences · 2026-02-23

## TL;DR

The study explores how early treatment affects metabolic and inflammatory biomarkers in first-episode psychosis patients in Italy.

## Contribution

It identifies treatment-related changes in leptin, GLP-1, and ghrelin levels in psychosis patients.

## Key findings

- Leptin levels increased significantly during treatment.
- GLP-1 levels decreased significantly during treatment.
- Ghrelin levels decreased only in the experimental treatment group.

## Abstract

Studies conducted in first-episode psychosis (FEP) patients have shown alterations in inflammation and metabolism. Our objective was to investigate potential treatment-related effects on these systems in Italian FEP patients undergoing either an experimental treatment consisting of a multi-element psychosocial intervention (EXP), including cognitive–behavioural therapy, or treatment as usual (TAU). A total of 191 FEP patients with first contact between April 2010 and March 2011 were clinically assessed at baseline and after 9 months of treatment, and the serum levels of 19 analytes were determined through single or multiplex enzyme-linked immunosorbent assays (ELISAs). A significant increase was observed in leptin levels and a significant decrease in Glucagon-Like Peptide-1 (GLP-1) levels during the treatment (time effect, p < 0.001 for both), with no significant interaction between time and treatment type. Although ghrelin levels changed significantly over time in the whole cohort (p = 0.008), a significant decrease was observed only in the EXP group (post hoc test: p = 0.001). None of the biomarkers measured at baseline showed a predictive effect on treatment efficacy, and no significant associations were identified between changes in clinical scores and changes in biomarker levels. These results suggest that early-phase psychosis treatments are associated with possible effects on metabolic regulation.

## Linked entities

- **Proteins:** lepa (leptin a), GHRL (ghrelin and obestatin prepropeptide)
- **Diseases:** psychosis (MONDO:0005485)

## Full-text entities

- **Genes:** GCG (glucagon) [NCBI Gene 2641] {aka GLP-1, GLP1, GLP2, GRPP}, GLP1R (glucagon like peptide 1 receptor) [NCBI Gene 2740] {aka GLP-1, GLP-1-R, GLP-1R}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, IL1RN (interleukin 1 receptor antagonist) [NCBI Gene 3557] {aka CRMO2, DIRA, ICIL-1RA, IL-1RN, IL-1ra, IL-1ra3}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, RETN (resistin) [NCBI Gene 56729] {aka ADSF, FIZZ3, RENT, RETN1, RSTN, XCP1}, NAMPT (nicotinamide phosphoribosyltransferase) [NCBI Gene 10135] {aka 1110035O14Rik, PBEF, PBEF1, VF, VISFATIN}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, GIP (gastric inhibitory polypeptide) [NCBI Gene 2695], LEP (leptin) [NCBI Gene 3952] {aka LEPD, OB, OBS}, SERPINE1 (serpin family E member 1) [NCBI Gene 5054] {aka PAI, PAI-1, PAI1, PLANH1}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, CCL5 (C-C motif chemokine ligand 5) [NCBI Gene 6352] {aka D17S136E, RANTES, SCYA5, SIS-delta, SISd, TCP228}, Bdnf (brain derived neurotrophic factor) [NCBI Gene 12064], CCL4 (C-C motif chemokine ligand 4) [NCBI Gene 6351] {aka ACT2, AT744.1, G-26, HC21, LAG-1, LAG1}, BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}, JAK2 (Janus kinase 2) [NCBI Gene 3717] {aka JTK10}, MSH3 (mutS homolog 3) [NCBI Gene 4437] {aka DUP, FAP4, MRP1}, Lep (leptin) [NCBI Gene 16846] {aka ob, obese}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}
- **Diseases:** insulin resistance (MESH:D007333), anxiety (MESH:D001007), schizophrenia (MESH:D012559), neuroinflammation (MESH:D000090862), mental disorder (MESH:D001523), cardiovascular diseases (MESH:D002318), inflammatory syndrome (MESH:D018746), FEP (MESH:D011618), affective psychosis (MESH:D000341), intellectual disability (MESH:D008607), delusions (MESH:D063726), abnormal glucose and lipid metabolism (MESH:D052439), psychomotor disorder (MESH:D011596), injury to (MESH:D014947), Inflammatory (MESH:D007249), hallucinations (MESH:D006212), loss (MESH:D016388), metabolic syndrome (MESH:D024821), emotional disorders (MESH:D009358), chronic (MESH:D002908), abdominal obesity (MESH:D056128), impaired glucose tolerance (MESH:D018149), self-neglect (MESH:D058069), first (MESH:D061219), eating disorders (MESH:D001068), type 2 diabetes (MESH:D003924), speech disorder (MESH:D013064), weight gain (MESH:D015430), language deficits (MESH:D007806), obese (MESH:D009765), Depression (MESH:D003866)
- **Chemicals:** triglycerides (MESH:D014280), appetite-regulating hormones (MESH:D054439), olanzapine (MESH:D000077152), haloperidol (MESH:D006220), EXP (-), clozapine (MESH:D003024), serotonin (MESH:D012701), glucose (MESH:D005947), quetiapine (MESH:D000069348), risperidone (MESH:D018967), blood glucose (MESH:D001786), norepinephrine (MESH:D009638), dopamine (MESH:D004298), lipid (MESH:D008055)
- **Species:** Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## References

99 references — full list in the complete paper: https://tomesphere.com/paper/PMC12940655/full.md

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Source: https://tomesphere.com/paper/PMC12940655