Lipidomics and genomics in mental health: insights into major depressive disorder, bipolar disorder, schizophrenia, and obsessive-compulsive disorder

Martina Nicole Modesti; Jan Francesco Arena; Antonio Del Casale; Giovanna Gentile; Marina Borro; Giovanna Parmigiani; Maurizio Simmaco; Cecilia Guariglia; Stefano Ferracuti

doi:10.1186/s12944-025-02512-x

Lipidomics and genomics in mental health: insights into major depressive disorder, bipolar disorder, schizophrenia, and obsessive-compulsive disorder

Lipids Health Dis. 2025 Mar 11;24(1):89. doi: 10.1186/s12944-025-02512-x.

Authors

Martina Nicole Modesti¹, Jan Francesco Arena², Antonio Del Casale², Giovanna Gentile^{3

4}, Marina Borro^{3

4}, Giovanna Parmigiani⁵, Maurizio Simmaco^{3

4}, Cecilia Guariglia^{6

7}, Stefano Ferracuti⁸

Affiliations

¹ Department of Psychology, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy. martinanicole.modesti@uniroma1.it.
² Department of Dynamic and Clinical Psychology and Health Studies, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.
³ Department of Neuroscience, Mental Health, and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.
⁴ Laboratory of Clinical Biochemistry, Advanced Molecular Diagnostic Unit, Sant 'Andrea University Hospital, Rome, Italy.
⁵ Department of Law, University of Modena and Reggio Emilia, Modena, Italy.
⁶ Department of Psychology, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy.
⁷ Cognitive and Motor Rehabilitation and Neuroimaging Unit, "Santa Lucia" Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), Rome, Italy.
⁸ Department of Human Neuroscience, Faculty of Medicine and Dentistry, Sapienza, University of Rome, Rome, Italy.

Abstract

Introduction: This systematic review explores the hypothesis that various lipid categories and lipid metabolism-related genomic variations link to mental disorders, seeking potential clinically useful markers.

Methods: We searched PubMed, Scopus, and PsycInfo databases until October 12th, 2024, using terms related to lipidomics, lipid-related genomics, and different mental disorders, i.e., Major Depressive Disorder (MDD), Bipolar Disorder (BD), Schizophrenia (SCZ), and Obsessive-Compulsive Disorder (OCD). Eligible studies were assessed. Extracted data included author, year, methodology, outcomes, genes, and lipids linked to disorders. Bias and evidence certainty were evaluated. The systematic review adhered to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and a registered protocol (PROSPERO: CRD42023438862).

Results: A total of 27 studies were included. SCZ showed alterations in 77 lipids, including triglycerides (TG), ceramides, and phosphatidylcholine, while MDD and BD exhibited 97 and 47 altered lipids, respectively, with overlap among disorders. Shared genes, such as ABCA13, DGKZ, and FADS, and pathways involving inflammation, lipid metabolism, and mitochondrial function were identified. OCD was associated with sphingolipid signaling and peroxisomal metabolism.

Discussion: Lipid signatures in MDD, BD, and SCZ shed light on underlying processes. Further research is needed to validate biomarkers and refine their clinical applications in precision psychiatry.

Keywords: Bipolar Disorder; Genomics; Lipid Metabolism; Major Depressive Disorder; Metabolomics; Obsessive–Compulsive Disorder; Precision Medicine; Schizophrenia.

Publication types

Systematic Review

MeSH terms

Bipolar Disorder* / genetics
Bipolar Disorder* / metabolism
Genomics*
Humans
Lipid Metabolism / genetics
Lipidomics*
Major Depressive Disorder* / genetics
Major Depressive Disorder* / metabolism
Mental Health
Obsessive-Compulsive Disorder* / genetics
Obsessive-Compulsive Disorder* / metabolism
Schizophrenia* / genetics
Schizophrenia* / metabolism