Hypothalamic -pituitary -adrenal axis -related genes and cognition in major mood disorders and schizophrenia: a systematic review

Hypothalamic-pituitary-adrenal (HPA) axis dysregulation and cognitive deficits are two well-characterized endophenotypes present in different serious mental illnesses (SMIs), including major depressive disorder, bipolar disorder and schizophrenia. Our aim was to study the influence of genetic and epigenetic variations in HPA axis-related genes on cognitive performance in clinical samples, including patients with major mood disorders and schizophrenia. A systematic search was performed using PubMed (Medline), PsycINFO and Scopus databases. The systematic review identified 12 studies dealing with HPA-related genes and cognition in samples including patients with SMIs, focusing on single nucleotide polymorphism (SNP) variants, while no studies analysing epigenetic variations were found. The results suggest different and specific effects on the cognitive performance of SNP variants in the HPA axis-related genes studied, as well as interactions with traumatic experiences. There was high heterogeneity in the studied samples, genes analysed, and cognitive tasks evaluated. The relationship between HPA-related genes and cognition in SMIs is still largely unknown, and further studies including larger samples and epigenetic variations are needed.