The complexity of brain processes, genetic variability, and environmental factors all contribute to the challenge of understanding of the biological processes underlying psychiatric disorders (PsyDs). Environmental factors, such as trace elements (TrEs), are crucial for brain function, yet the relationship between TrEs and PsyDs remains underexplored and controversial. TrEs imbalance may serve as diagnostic or prognostic biomarkers for PsyDs and treatment response variability. According to this, the project aims to determinate if genetic alterations regulating TrEs levels are enriched in PsyDs, specifically Major Depression, Bipolar Disorder, and Schizophrenia, as well as related endophenotypes (EpMDs).

We compiled a list of genes involved in TrEs metabolism through literature mining and constructed a biological network using functional enrichment analysis in the Cytoscape environment with the String database. The RDoC framework, which assesses mental health in the context of fundamental human neurobehavioral domains, was employed to define EpMDs. To investigate the involvement of selected genes in MDs, we conducted a Gene Set Enrichment Analysis (GSEA), comparing our TrEs gene set with gene sets related to MDs and EpMDs. 

Our analyses evidenced an existing overlap between genes involved in metabolism and mental disorder, particularly with Schizophrenia risk-genes (ESR2, JUN, CASP3, IL6, CFH, CCL2, CD44, CRP, IGF1, APP, CYP2D6, LCN2, CXCL8, NLRP3, IL10, IL18, GSK3B, IL1B, HLA-DQB1, CYP2C19, PRNP, HLA-G, ICAM1, NFKB1, TP53, SPP1, HMGB1, IFNG, HFE, INS, LRRK2, TLR2, TGFB1, NOX4, HMOX1, SERPINE1, APOE, TNF, CD4, HIF1A, ALB, TLR4 – adj-pValue: 1.9×10-3).

The shared genes points to processes related to vesicle transport, immune regulation, synapses’ function and neurotransmitters regulation. This data highlights the importance of integrating genetic and neurochemical perspectives to better understand MDs.  Future research is necessary to elucidate how these shared genes and biological pathways between TrEs and MDs might serve as potential biomarkers for evaluating MDs risk and targets for personalized treatments.

The study was funded by: Bando Prin 2022 - DR n. 104 2/2/2022 - ERC LS2 - ID 2022YYXKF2 - CUP J53D23003310006 - “Clinical and molecular profiles of psychiatric endophenotypes in association with trace elements profiles: a model of precision medicine (PDoRiT).

Concetta Crisafulli was born in Messina (Italy), on June 09, 1975. She obtained her Biology Degree (2003), magna cum laude, at the Faculty of Science MM.FF.NN., University of Messina. She obtained PhD in “Experimental Medicine” (2008) at Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina. During her training she has been involved in national and international research and educational activities concerning Genetics and Molecular Biology. In 2010, she worked as visiting researcher at the Institute of Psychiatry “P. Ottonello”, University of Bologna.

Her recent research interests are focused on neuroscience, with particular attention to studies of genetic association in psychiatric disorders.

In this context, she has also conducted pharmacogenetics and pharmacogenomics studies. She is member of several organizations in the fields of pharmacology and genetics and molecular biology. In 2008 she won “Young Researcher” award at the University of Messina. She is author of more than 80 national and international scientific papers in the field of molecular pharmacology and psychiatric genetics. She is currently associate professor at the Department of Biomorphology and Biotecnologies, Division of Biology and Genetics, School of Medicine, University of Messina.