TY - JOUR
T1 - Convergent Functional Genomics approach to prioritize molecular targets of risk in early life stress-related psychiatric disorders
AU - Cattaneo, Annamaria
AU - Cattane, Nadia
AU - Scassellati, Catia
AU - D'Aprile, Ilari
AU - Riva, Marco Andrea
AU - Pariante, Carmine Maria
N1 - Publisher Copyright:
© 2020
PY - 2020/10
Y1 - 2020/10
N2 - There is an overwhelming evidence proving that mental disorders are not the product of a single risk factor – i.e. genetic variants or environmental factors, including exposure to maternal perinatal mental health problems or childhood adverse events - rather the product of a trajectory of cumulative and multifactorial insults occurring during development, such as exposures during the foetal life to adverse mental condition in the mother, or exposures to adverse traumatic events during childhood or adolescence. In this review, we aim to highlight the potential utility of a Convergent Functional Genomics (CFG) approach to clarify the complex brain-relevant molecular mechanisms and alterations induced by early life stress (ELS). We describe different studies based on CFG in psychiatry and neuroscience, and we show how this ‘hypothesis-free’ tool can prioritize a stringent number of genes modulated by ELS, that can be tested as potential candidates for Gene x Environment (GxE) interaction studies. We discuss the results obtained by using a CFG approach identifying FoxO1 as a gene where genetic variability can mediate the effect of an adverse environment on the development of depression. Moreover, we also demonstrate that FoxO1 has a functional relevance in stress-induced reduction of neurogenesis, and can be a potential target for the prevention or treatment of stress-related psychiatric disorders. Overall, we suggest that CFG approach could include trans-species and tissues data integration and we also propose the application of CFG to examine in depth and to prioritize top candidate genes that are affected by ELS across lifespan and generations.
AB - There is an overwhelming evidence proving that mental disorders are not the product of a single risk factor – i.e. genetic variants or environmental factors, including exposure to maternal perinatal mental health problems or childhood adverse events - rather the product of a trajectory of cumulative and multifactorial insults occurring during development, such as exposures during the foetal life to adverse mental condition in the mother, or exposures to adverse traumatic events during childhood or adolescence. In this review, we aim to highlight the potential utility of a Convergent Functional Genomics (CFG) approach to clarify the complex brain-relevant molecular mechanisms and alterations induced by early life stress (ELS). We describe different studies based on CFG in psychiatry and neuroscience, and we show how this ‘hypothesis-free’ tool can prioritize a stringent number of genes modulated by ELS, that can be tested as potential candidates for Gene x Environment (GxE) interaction studies. We discuss the results obtained by using a CFG approach identifying FoxO1 as a gene where genetic variability can mediate the effect of an adverse environment on the development of depression. Moreover, we also demonstrate that FoxO1 has a functional relevance in stress-induced reduction of neurogenesis, and can be a potential target for the prevention or treatment of stress-related psychiatric disorders. Overall, we suggest that CFG approach could include trans-species and tissues data integration and we also propose the application of CFG to examine in depth and to prioritize top candidate genes that are affected by ELS across lifespan and generations.
KW - Convergent functional genomics
KW - Depression
KW - Early life stress
KW - FoxO1
KW - Gene X Environment
KW - Psychiatric disorders
UR - http://www.scopus.com/inward/record.url?scp=85102603631&partnerID=8YFLogxK
U2 - 10.1016/j.bbih.2020.100120
DO - 10.1016/j.bbih.2020.100120
M3 - Review article
AN - SCOPUS:85102603631
SN - 2666-3546
VL - 8
JO - Brain, Behavior, and Immunity - Health
JF - Brain, Behavior, and Immunity - Health
M1 - 100120
ER -