Psychobiological mechanisms underlying the association between early life stress and depression in adolescence

Early life stress (ELS), or exposure to adverse experiences before the age of 18 years, is alarmingly prevalent and is a strong risk factor for the development of depression in adolescence. Despite the consistency of this association, we do not fully understand how, or for whom, ELS gets 'under the skin' to increase adolescents' risk for experiencing depression. In this context, researchers have identified psychobiological characteristics that may serve to link early adversity to risk for adolescent depression. In this paper we discuss four of these characteristics: stress reactivity, reward processing, inflammation, and biological aging. For each of these putative mechanisms we describe the nature of their associations with both ELS and depression, focusing when possible on these relations during adolescence. In addition to being a vulnerable period for the emergence of depression, adolescence is also characterized by developmental shifts in critical domains of psychobiological functioning that add nuance to the associations with early life stress and depression. Following this presentation, we discuss how these constructs likely co-occur and interact in ways that alter the relation between early adversity and risk for adolescent depression; we also consider factors that might serve to moderate this association. We conclude by describing unresolved issues and suggesting directions for future research concerning the ways that ELS increases adolescents' risk for the development of depression. Specifically, we discuss how researchers might address the lack of consistency in findings examining associations among ELS, biological functioning, and depression in adolescent samples by examining systematically the types of stress experienced, the biological functioning and specific aspects of depression that are assessed in each study, and moderators such as participants' sex, developmental stage, and family history. We seek to stimulate researchers to examine other mechanisms that might underlie the association of early adversity with depression in order to inform the development of more effective approaches to the prevention and treatment of this debilitating disorder.

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Publication Details

Journal
Molecular Psychiatry
Published
2025-11-16
DOI
https://doi.org/10.1038/s41380-025-03348-8
Citations
1
Primary Topic
Stress Responses and Cortisol
Type
article
Field-Weighted Citation Impact
1.11

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article

Psychobiological mechanisms underlying the association between early life stress and depression in adolescence

Jessica L. Buthmann, Ian H. Gotlib, Jessica P. Uy, Daniel Pine
1 citations
Molecular Psychiatry
Stress Responses and Cortisol
1.11
article

Psychobiological mechanisms underlying the association between early life stress and depression in adolescence

Jessica L. Buthmann, Ian H. Gotlib, Jessica P. Uy, Daniel Pine
article en
1 citations

Abstract

Early life stress (ELS), or exposure to adverse experiences before the age of 18 years, is alarmingly prevalent and is a strong risk factor for the development of depression in adolescence. Despite the consistency of this association, we do not fully understand how, or for whom, ELS gets 'under the skin' to increase adolescents' risk for experiencing depression. In this context, researchers have identified psychobiological characteristics that may serve to link early adversity to risk for adolescent depression. In this paper we discuss four of these characteristics: stress reactivity, reward processing, inflammation, and biological aging. For each of these putative mechanisms we describe the nature of their associations with both ELS and depression, focusing when possible on these relations during adolescence. In addition to being a vulnerable period for the emergence of depression, adolescence is also characterized by developmental shifts in critical domains of psychobiological functioning that add nuance to the associations with early life stress and depression. Following this presentation, we discuss how these constructs likely co-occur and interact in ways that alter the relation between early adversity and risk for adolescent depression; we also consider factors that might serve to moderate this association. We conclude by describing unresolved issues and suggesting directions for future research concerning the ways that ELS increases adolescents' risk for the development of depression. Specifically, we discuss how researchers might address the lack of consistency in findings examining associations among ELS, biological functioning, and depression in adolescent samples by examining systematically the types of stress experienced, the biological functioning and specific aspects of depression that are assessed in each study, and moderators such as participants' sex, developmental stage, and family history. We seek to stimulate researchers to examine other mechanisms that might underlie the association of early adversity with depression in order to inform the development of more effective approaches to the prevention and treatment of this debilitating disorder.

Molecular PsychiatryVol. 31(2)
National Institute of Mental Health (US), Stanford University (US)
U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Mental Health
Openalex Percentile: Top 18%
Stress Responses and Cortisol
1.11
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