PATHOPHYSIOLOGY OF MOOD DISORDERS: PHARMACOGENETIC ASPECTS
Pp. 58-106 (49)
CHIARA FABBRI, STEFANO PORCELLI and ALESSANDRO SERRETTI
Major depressive disorder (MDD) is an emergent cause of personal and socioeconomic
burden, since its high lifetime prevalence (16.2%) and the unsatisfying response
rate of the available antidepressant drugs. Among modulators of treatment outcome, genetic
polymorphisms are thought to explain a significant share of the inter-individual variability,
according to a complex multi-loci model.
Given the described scenario, the present chapter aims to summarize and compare the main
pharmacogenetic findings regarding antidepressant treatment outcome, including both candidate
gene studies and genome-wide association studies.
The literature provided replicated evidence of association between several genes (in particular,
SLC6A4, HTR1A, HTR2A, COMT, MAOA, BDNF, GNB3, and MDR1) and antidepressant
efficacy, but findings were mainly contradictory. Despite the inconsistent pharmacongetic results
obtained so far, the increasing knowledge about MDD pathogenesis and antidepressant mechanisms
of action, together with better awareness of the limitations of previous pharmacogenetic studies,
may lead to the confirmations required to produce clinical applications. Technical improvement
in genotyping procedures may help to translate the increasing theoretic knowledge into practical
Serotonin (5-HT), norepinephrine (NE), dopamine (DA), glutamate, Brain derived
neurotrophic factor (BDNF), hypothalamic-pituitary-adrenal (HPA) axis, depression, antidepressant
drugs, selective serotonin reuptake inhibitors (SSRIs), copy number variants (CNV), single nucleotide
polymorphism (SNP), genome-wide association studies (GWAS)
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.