Cited by 527Child Abuse and TraumaChild Welfare and AdoptionChild and Adolescent Psychosocial and Emotional Development

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The Devastating Clinical Consequences of Child Abuse and Neglect: Increased Disease Vulnerability and Poor Treatment Response in Mood Disorders

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Lippard, Elizabeth T.C., Nemeroff, Charles B.·2020·American Journal of Psychiatry

DOI 10.1176/appi.ajp.2019.19010020PMC PMC6939135

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Abstract

A large body of evidence has demonstrated that exposure to childhood maltreatment at any stage of development can have long-lasting consequences. It is associated with a marked increase in risk for psychiatric and medical disorders. This review summarizes the literature investigating the effects of childhood maltreatment on disease vulnerability for mood disorders, specifically summarizing cross-sectional and more recent longitudinal studies demonstrating that childhood maltreatment is more prevalent and is associated with increased risk for first mood episode, episode recurrence, greater comorbidities, and increased risk for suicidal ideation and attempts in individuals with mood disorders. It summarizes the persistent alterations associated with childhood maltreatment, including alterations in the hypothalamic-pituitary-adrenal axis and inflammatory cytokines, which may contribute to disease vulnerability and a more pernicious disease course. The authors discuss several candidate genes and environmental factors (for example, substance use) that may alter disease vulnerability and illness course and neurobiological associations that may mediate these relationships following childhood maltreatment. Studies provide insight into modifiable mechanisms and provide direction to improve both treatment and prevention strategies.

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SLC6A4 methylation as an epigenetic marker of life adversity exposures in humans: A systematic review of literature
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Child maltreatment as a risk factor for opioid dependence: Comparison of family characteristics and type and severity of child maltreatment with a matched control group
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Prevalence and correlates of physical and sexual abuse in children and adolescents with bipolar disorder
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Homelessness, Mental Health and Suicidality Among LGBTQ Youth Accessing Crisis Services
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Childhood trauma, family history, and their association with mood disorders in early adulthood
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Psychosocial stressors and the prognosis of major depression: a test of Axis IV
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Reduced gray matter volume in psychotic disorder patients with a history of childhood sexual abuse
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Variation in the oxytocin receptor gene is associated with increased risk for anxiety, stress and depression in individuals with a history of exposure to early life stress
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Amygdala and hippocampus volumes are differently affected by childhood trauma in patients with bipolar disorders and healthy controls
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Neuroimmune Interface in the Comorbidity between Alcohol Use Disorder and Major Depression
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Childhood adversity, adult stress, and the risk of major depression or generalized anxiety disorder in US soldiers: a test of the stress sensitization hypothesis
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“Soldiers exposed to childhood maltreatment have a greater risk for depression or anxiety following recent life stressors (94).”
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A cognitive vulnerability–stress perspective on bipolar spectrum disorders in a normative adolescent brain, cognitive, and emotional development context
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The Behavioral and Immunological Impact of Maternal Separation: A Matter of Timing
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Microglia and alcohol meet at the crossroads: Microglia as critical modulators of alcohol neurotoxicity
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Examining perceived stress, childhood trauma and interpersonal trauma in individuals with drug addiction
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Childhood maltreatment severity is associated with elevated C-reactive protein and body mass index in adults with schizophrenia and bipolar diagnoses
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Are there sensitive periods when child maltreatment substantially elevates suicide risk? Results from a nationally representative sample of adolescents: G omez et al.
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Hypothalamic-pituitary-adrenal axis genetic variation and early stress moderates amygdala function
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Childhood trauma and treatment outcome in bipolar disorder
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Childhood maltreatment preceding depressive disorder at age 18 years: A prospective Brazilian birth cohort study
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BDNFVal66Met genotype interacts with childhood adversity and influences the formation of hippocampal subfields
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Genotype and Childhood Sexual Trauma Moderate Neurocognitive Performance: A Possible Role for Brain-Derived Neurotrophic Factor and Apolipoprotein E Variants
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Grey matter volume and thickness abnormalities in young people with a history of childhood abuse
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Adverse childhood experiences influence white matter microstructure in patients with bipolar disorder
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Interactive Effects of Childhood Maltreatment and Recent Stressful Life Events on Alcohol Consumption in Adulthood
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The Association Between Moderate Alcohol Use and Illness Severity in Bipolar Disorder
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Altered brain network integrity after childhood maltreatment: A structural connectomic DTI-study
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Prenatal stress-immune programming of sex differences in comorbidity of depression and obesity/metabolic syndrome
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Childhood Emotional Maltreatment as a Robust Predictor of Suicidal Ideation: A 3-Year Multi-Wave, Prospective Investigation
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Childhood trauma and the limbic network: a multimodal MRI study in patients with bipolar disorder and controls
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Childhood trauma, dimensions of psychopathology and the clinical expression of bipolar disorders: A pathway analysis
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Prevalence of child sexual abuse among adults and youths with bipolar disorder: A systematic review
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Authors: Lippard, E. T. C., & Nemeroff, C. B.
Affiliations: The University of Texas at Austin (US)
ORCID: Lippard, Elizabeth T.C.
Nemeroff, Charles B.
Venue: American Journal of Psychiatry
Publisher: American Psychiatric Association Publishing
Published: 2020-01-01
Volume: 177
Issue: 1
Pages: 20-36
ISSN: 0002-953X (ISSN-L)
1535-7228
DOI: 10.1176/appi.ajp.2019.19010020
PMC: PMC6939135
OpenAlex: W2973818823
Cited by: 527
References: 230
Citations by year: 2026: 60 · 2025: 88 · 2024: 91 · 2023: 96 · 2022: 104 · 2021: 58 · 2020: 25
FWCI: 7.44
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: American Journal of Psychiatry (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Brain and Behavior Research Foundation
American Foundation for Suicide Prevention
American Psychiatric Publishing
Celgene
Sunovion
OPKO Health
National Institutes of Health (AA024933)
Department of Mechanical Engineering, University of Texas at Austin
Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin
Dell Medical School, University of Texas at Austin
Laureate Institute for Brain Research, University of Tulsa
National Institute on Alcohol Abuse and Alcoholism (K01AA027573, R01AA024933)
National Institute of Mental Health (R01MH117293)
Janssen Research and Development
Topics: Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
Social Sciences › Sociology and Political Science › Child Welfare and Adoption
Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
Keywords: child abuse, mood disorders, bipolar disorder, depression, disease susceptibility, treatment response, suicidal ideation, suicide attempts, episode recurrence, comorbidities, hypothalamic-pituitary-adrenal axis, inflammatory cytokines, candidate genes, substance use, neurobiology of depression, prevention
MeSH terms: Child, Child Abuse, Disease Susceptibility, Humans, Risk Factors, Comorbidity, Mood Disorders

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The Devastating Clinical Consequences of Child Abuse and Neglect: Increased Disease Vulnerability and Poor Treatment Response in Mood Disorders

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