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Randomized Controlled Trial
. 2024 Dec 23;24(1):946.
doi: 10.1186/s12888-024-06413-8.

Identification of serum metabolic traits of AIWG in first-episode schizophrenia patients

Suzhen Zhang #  1   2 , Zhaolin Zhai #  1   2   3 , Tianhao Gao  1   2   3 , Xinping Kuai  1   2 , Xuan Li  1   2 , Yuke Dong  1   2   3 , Chang Lu  1   2   3 , Kaiming Zhuo  1   2 , Qiong Xiang  4   5 , Dengtang Liu  6   7   8   9   10
Affiliations
Randomized Controlled Trial

Identification of serum metabolic traits of AIWG in first-episode schizophrenia patients

Suzhen Zhang et al. BMC Psychiatry. .

Abstract

Background: Antipsychotic-induced weight gain (AIWG) is a common side effect of antipsychotic drugs and may lead to cardiometabolic comorbidities. There is an urgent public health need to identify patients at high risk of AIWG and determine potential biomarkers for AIWG.

Methods: In the Sequential Multiple-Assignment Randomized Trials to Compare Antipsychotic Treatments (SMART-CAT) trail, first-episode schizophrenia patients were randomly assigned to olanzapine, risperidone, perphenazine, amisulpride or aripiprazole for 8 weeks. We applied absolute quantitative lipidomics at baseline and after 8 weeks of antipsychotic treatment in 80 patients. To evaluate the effects of AIWG on lipid profile, 25 patients with ≥ 7% weight changes (weight gain, WG) and 28 patients with <|3|% weight changes (weight stable, WS) were investigated, separately.

Results: We found that baseline CerP(d40:3) and PC(20:1_22:6) were positively associated with weight changes at follow-up (r > 0.4, pFDR < 0.05). Additionally, baseline CerP(d40:3) and PC(20:1_22:6) independently predicted rapid weight gain, with receiver operating curve (ROC) of 0.76 (95% CI: 0.63-0.90), and 0.75 (95% CI: 0.62-0.88), respectively. Compared with baseline, levels of 45 differential lipid metabolites (fold change > 1.2, VIP > 1 and pFDR < 0.05) were significantly higher in the WG group. Interestingly, no differential lipid metabolites were identified in the WS group. The LASSO regression model identified 18 AIWG lipid signatures, including 2 cholesterol esters (ChEs), 1 diglyceride (DG), 12 phosphatidylcholines (PCs), 1 phosphatidylglycerol (PG), 1 phosphatidylinositol (PI), and 1 sphingomyelin (SM), with the ChE(16:1) contributing the most. Furthermore, the level changes of ChE(16:1) were positively associated with weight gain(r = 0.67, pFDR < 0.05).

Conclusion: Our findings indicate that lipid profile may serve as predictors of rapid weight gain in schizophrenia and provide useful markers for AIWG intervention.

Keywords: Antipsychotic; Lipid; Schizophrenia; Weight gain.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was approved by the Institutional Review Board of Shanghai Mental Health Center. All participants provided written informed consents. All procedures carried out in the study comply with the Declaration of Helsinki for experiments involving humans. Consent for publication: No individual data is presented, and consent to publication is therefore not applicable. Competing interests: The authors declare no competing interests. Conflict of interest: All authors have no competing interest to disclose, financial or otherwise.

Figures

Fig. 1
Fig. 1
(a) Study setting. (b) Lipid class. (c) (d) (e) Correlation of pre-therapeutic lipid metabolites with weight change (%) (8-week follow-up vs. baseline) in the FES. (f) (g) (h) Difference in pre-therapeutic lipid levels between WG and NON-WG. (i) Pre-therapeutic lipid metabolites serve as predictors for rapid weight gain in the FES. WG, weight gain; NON-WG, non-weight gain; WS, weight stable
Fig. 2
Fig. 2
(a) (b) OPLS-DA scores plots distinguishing patients before (Blue dots) and after (Green square) treatments of the WG group and the WS group. (c) (d) Heatmap and lipid class of the 59 differential metabolites of the WG group. (e) Regression coefficient of the LASSO model. WG, weight gain; WS, weight stable
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