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Enduring effects of early-life adversity on reward processes: A systematic review and meta-analysis of animal studies.

ABSTRACT: Two-thirds of individuals experience adversity during childhood such as neglect, abuse or highly-stressful events. Early-life adversity (ELA) increases the life-long risk of developing mood and substance use disorders. Reward-related deficits has emerged as a key endophenotype of such psychiatric disorders. Animal models are invaluable for studying how ELA leads to reward deficits. However, the existing literature is heterogenous with difficult to reconcile findings. To create an overview, we conducted a systematic review containing multiple meta-analyses regarding the effects of ELA on reward processes overall and on specific aspects of reward processing in animal models. A comprehensive search identified 120 studies. Most studies omitted key details resulting in unclear risk of bias. Overall meta-analysis showed that ELA significantly reduced reward behaviors (SMD: -0.42 [-0.60; -0.24]). The magnitude of ELA effects significantly increased with longer exposure. When reward domains were analyzed separately, ELA only significantly dampened reward responsiveness (SMD: -0.525[-0.786; -0.264]) and social reward processing (SMD: -0.374 [-0.663; -0.084]), suggesting that ELA might lead to deficits in specific reward domains.

SUBMITTER: Duque-Quintero M

PROVIDER: S-EPMC10729999 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Enduring effects of early-life adversity on reward processes: A systematic review and meta-analysis of animal studies.

Duque-Quintero Mariana M Hooijmans Carlijn R CR Hurowitz Alexander A Ahmed Afsana A Barris Ben B Homberg Judith R JR Hen Rene R Harris Alexander Z AZ Balsam Peter P Atsak Piray P

Neuroscience and biobehavioral reviews 20220915

Two-thirds of individuals experience adversity during childhood such as neglect, abuse or highly-stressful events. Early-life adversity (ELA) increases the life-long risk of developing mood and substance use disorders. Reward-related deficits has emerged as a key endophenotype of such psychiatric disorders. Animal models are invaluable for studying how ELA leads to reward deficits. However, the existing literature is heterogenous with difficult to reconcile findings. To create an overview, we co ...[more]

PMID: 36116576

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Project description:BackgroundGlobally, early-life adversity (ELA) is linked to an increased risk of developing depression in adulthood; however, only a few studies have examined the specific effects of various types of ELA on depression in children and adolescents. This meta-analysis explores the association between the subtypes of ELA and the risk for youth-onset depression.MethodsWe searched three electronic databases for reporting types of ELA, namely, emotional abuse, physical abuse, sexual abuse, emotional neglect, physical neglect, family conflict/violence, divorce, low socioeconomic status, and left-behind experience, associated with depression before the age of 18 years. Our meta-analysis utilized the odds ratio (OR) and relied on a random effects model. Large heterogeneous effects were detected. Some factors moderated the association between ELA and depression in youths. The homogeneity of variance test and meta-regression analysis were used to detect these relationships.ResultsA total of 87 studies with 213,006 participants were ultimately identified via several strategies in this meta-analysis. Individuals who experienced ELA were more likely to develop depression before the age of 18 years old than those without a history of ELA (OR=2.14; 95% CI [1.93, 2.37]). The results of the subgroup analysis revealed a strong association between ELA and depression in youth, both in terms of specific types and dimensions. Specifically, emotional abuse (OR = 4.25, 95% CI [3.04, 5.94]) was more strongly related to depression in children and adolescents than other forms of ELA were. For both dimensions, threat (OR = 2.60, 95% CI [2.23, 3.02]) was more closely related to depression than deprivation was (OR = 1.76, 95% CI [1.55, 1.99]).ConclusionThis meta-analysis revealed that the adverse effects of a broader consideration of ELA on the risk of youth-onset depression vary according to the subtypes of ELA.Systematic review registationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023405803, identifier 42023405803.

Project description:BackgroundMental health and vulnerabilities to neuropsychiatric disorders involve the interplay of genes and environment, particularly during sensitive developmental periods. Early-life adversity (ELA) and stress promote vulnerabilities to stress-related affective disorders, yet it is unknown how transient ELA dictates lifelong neuroendocrine and behavioral reactions to stress. The population of hypothalamic corticotropin-releasing factor (CRF)-expressing neurons that regulate stress responses is a promising candidate to mediate the long-lasting influences of ELA on stress-related behavioral and hormonal responses via enduring transcriptional and epigenetic mechanisms.MethodsCapitalizing on a well-characterized model of ELA, we examined ELA-induced changes in gene expression profiles of CRF-expressing neurons in the hypothalamic paraventricular nucleus of developing male mice. We used single-cell RNA sequencing on isolated CRF-expressing neurons. We determined the enduring functional consequences of transcriptional changes on stress reactivity in adult ELA mice, including hormonal responses to acute stress, adrenal weights as a measure of chronic stress, and behaviors in the looming shadow threat task.ResultsSingle-cell transcriptomics identified distinct and novel CRF-expressing neuronal populations, characterized by both their gene expression repertoire and their neurotransmitter profiles. ELA-provoked expression changes were selective to specific subpopulations and affected genes involved in neuronal differentiation, synapse formation, energy metabolism, and cellular responses to stress and injury. Importantly, these expression changes were impactful, apparent from adrenal hypertrophy and augmented behavioral responses to stress in adulthood.ConclusionsWe uncover a novel repertoire of stress-regulating CRF cell types differentially affected by ELA and resulting in augmented stress vulnerability, with relevance to the origins of stress-related affective disorders.

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Enduring effects of early-life adversity on reward processes: A systematic review and meta-analysis of animal studies.

Publications

Enduring effects of early-life adversity on reward processes: A systematic review and meta-analysis of animal studies.

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