Convergent Functional Genomics approach to prioritize molecular targets of risk in early life stress-related psychiatric disorders

Annamaria Cattaneo; Nadia Cattane; Catia Scassellati; Ilari D'Aprile; Marco Andrea Riva; Carmine Maria Pariante

doi:10.1016/j.bbih.2020.100120

Convergent Functional Genomics approach to prioritize molecular targets of risk in early life stress-related psychiatric disorders

Annamaria Cattaneo^*, Nadia Cattane, Catia Scassellati, Ilari D'Aprile, Marco Andrea Riva, Carmine Maria Pariante

^*Corresponding author for this work

Research output: Contribution to journal › Review article › peer-review

3 Citations (Scopus)

Abstract

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.

Original language	English
Article number	100120
Journal	Brain, Behavior, and Immunity - Health
Volume	8
DOIs	https://doi.org/10.1016/j.bbih.2020.100120
Publication status	Published - Oct 2020

Keywords

Convergent functional genomics
Depression
Early life stress
FoxO1
Gene X Environment
Psychiatric disorders

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10.1016/j.bbih.2020.100120

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title = "Convergent Functional Genomics approach to prioritize molecular targets of risk in early life stress-related psychiatric disorders",

abstract = "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 {\textquoteleft}hypothesis-free{\textquoteright} 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.",

keywords = "Convergent functional genomics, Depression, Early life stress, FoxO1, Gene X Environment, Psychiatric disorders",

author = "Annamaria Cattaneo and Nadia Cattane and Catia Scassellati and Ilari D'Aprile and Riva, {Marco Andrea} and Pariante, {Carmine Maria}",

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year = "2020",

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AU - Cattaneo, Annamaria

AU - Cattane, Nadia

AU - Scassellati, Catia

AU - D'Aprile, Ilari

AU - Riva, Marco Andrea

AU - Pariante, Carmine Maria

PY - 2020/10

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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.

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KW - Depression

KW - Early life stress

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KW - Gene X Environment

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Convergent Functional Genomics approach to prioritize molecular targets of risk in early life stress-related psychiatric disorders

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Keywords

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