title: Targeting aggression in severe mental illness: The predictive role of genetic, epigenetic, and metabolomic markers.
abstract: Human aggression is a complex and widespread social behavior that is overrepresented in individuals affected by severe mental illness (SMI), such as schizophrenia (SCZ), bipolar disorder (BD), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). A substantial proportion of the liability threshold for aggressive behavior is determined by genetic factors, and environmental moderators might precipitate the manifestation of this behavioral phenotype through modification of gene expression via the epigenetic machinery. These specific alterations in the genetic and epigenetic make-up of aggressive individuals might determine distinct biochemical signatures detectable through metabolomics. An additional pathophysiological component playing a role in aggressive behavior might be determined by alterations of gut microbiota. Here, we present a selective review of human data on genetic, epigenetic, and metabolomic markers of aggressive behavior in SMI, discussing also the available evidence on the role of microbiome alterations. Clinical implication of these evidences, as well as future perspectives, will be discussed.
authors.affiliation: Section of Psychiatry, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy; Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Mirko
authors.initials: M
authors.lastname: Manchia
authors.affiliation: Department of Surgical Sciences, University of Cagliari and Neonatal Intensive Care Unit, Cagliari, Italy; Puericulture Institute and Neonatal Section, Azienda Ospedaliera Universitaria, Cagliari, Italy. Electronic address: vafanos@tin.it.
authors.forename: Vassilios
authors.initials: V
authors.lastname: Fanos
mesh_terms: D000374:Aggression; D015415:Biomarkers; D044127:Epigenesis, Genetic; D000069196:Gastrointestinal Microbiome; D006801:Humans; D001523:Mental Disorders / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology / Q000523:psychology*; D055442:Metabolome
chemical_list: D015415:Biomarkers
keywords: Attention-deficit/hyperactivity disorder; Autism; Bipolar disorder; Epigenetics; Gene-environment interaction; Metabolome; Microbiome; Schizophrenia