The DOI matches its Crossref record, with a small difference in title or year; 66 of the 66 references it cites were found in a registry or an index.
Interaction Between <emph type="ital">FKBP5</emph> and Childhood Trauma and Risk of Aggressive Behavior
Open accessAbstract
CONTEXT: Childhood trauma may predispose individuals to aggressive behavior, and both childhood trauma and aggressive behavior are associated with hypothalamic-pituitary-adrenal axis dysregulation. OBJECTIVE: To determine whether there would be an interaction between genetic variation in FKBP5 and childhood trauma in predicting aggressive behavior. DESIGN: Cross-sectional study. Four FKBP5 single-nucleotide polymorphisms used in previous studies (rs3800373, rs9296158, rs1360780, and rs9470080) were genotyped. Three diplotypes were derived from 2 major putatively functional haplotypes regulating protein expression that were previously associated with glucocorticoid receptor sensitivity. SETTING: Penitentiary District of Abruzzo-Molise in central Italy. PARTICIPANTS: A population of 583 male Italian prisoners recruited between 2005 and 2008. MAIN OUTCOME MEASURES: A comprehensive analysis of aggression and impulsivity was undertaken using the Brown-Goodwin Lifetime History of Aggression (BGHA) questionnaire, the Buss-Durkee Hostility Inventory (BDHI), and the Barratt Impulsiveness Scale (BIS). A history of childhood trauma was investigated with the Childhood Trauma Questionnaire. The interaction between the FKBP5 diplotypes and childhood trauma on measures of aggression was analyzed. Analyses were replicated with a second behavioral measure of aggression: violent behavior in jail. Individual single-nucleotide polymorphism analysis was performed. RESULTS: Childhood trauma had a significant effect on BGHA and BDHI scores but not on BIS scores. We observed a significant influence of the FKBP5 high-expression diplotype on both a lifetime history of aggressive behavior (BGHA) (P = .012) and violent behavior in jail (P = .025) but only in individuals exposed to childhood trauma, in particular to physical abuse. No main effect of the FKBP5 diplotypes was observed. CONCLUSION: These data suggest that childhood trauma and variants in the FKBP5 gene may interact to increase the risk of overt aggressive behavior.
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“Further clinical studies confirm minor alleles of FKBP5 being particularly sensitive and interact with ELS/CT to increase aggressive behavior (387), suicide attempts (388), and depression (389).”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [387]
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“Sexual abuse was the least represented of the childhood traumas, which is consistent with previous reports by sex.(51,60,61) The interaction between FKBP5 and physical abuse in particular was strongly associated with both BGHA and violent behavior in jail, indicating that this type of childhood trauma in males may be…”
Initial reliability and validity of a new retrospective measure of child abuse and neglect
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“The CTQ has demonstrated high reliability and validity.(48,51,62) Because this is a male population, it was not possible to study potential sex differences.”
Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse
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“Genetic variation in FKBP5 may alter function of the stress-response pathway during development and thus alter CRH and AVP expression, predisposing those who had a significant history of child abuse to a higher risk of aggressive behavior through long-lasting traumainduced epigenetic changes.(59) Table 4.”
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The Biological Effects of Childhood Trauma
De Bellis, M. D., & Zisk, A. (2014) · Child and Adolescent Psychiatric Clinics of North America · doi:10.1016/j.chc.2014.01.002 · Cited by 892
“In a cross-sectional study, the less common FKBP5 haplotype (H2) was associated with an increased risk of overt aggressive behavior in adult male prisoners who had a history of physical abuse.(98) In an imaging study, healthy young adults were genotyped for 6 FKBP5 polymorphisms”
Paradise lost: the neurobiological and clinical consequences of child abuse and neglect
Nemeroff, C. B. (2016) · Neuron · doi:10.1016/j.neuron.2016.01.019 · Cited by 768
“…2010)—individuals homozygous for the minor alleles are particularly sensitive to the depressogenic effects of trauma (Zimmermann et al., 2011) and also interact with childhood trauma to increase suicide attempts (Roy et al., 2010), as well as increase aggressive behavior (Bevilacqua et al., 2012).”
BackgroundGene–Stress–Epigenetic regulation of FKBP5: clinical and translational implications
Zannas, A. S., Wiechmann, T., Gassen, N. C., & Binder, E. B. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.235 · Cited by 622
“…Klengel and Binder, 2013a; Koenen et al, 2005; Xie et al, 2010), suicidality (Roy et al, 2010; Roy et al, 2012), aggression and violent behaviors (Bevilacqua et al, 2012), psychosis (Collip et al, 2013), cognitive performance (Hernaus et al, 2014), and general physical illness (Lessard and…”
BackgroundInfluentialStress and the social brain: behavioural effects and neurobiological mechanisms
Sandi, C., & Haller, J. (2015) · Nature reviews. Neuroscience · doi:10.1038/nrn3918 · Cited by 657
Agorastos, A., Pervanidou, P., Chrousos, G. P., & Baker, D. G. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00118 · Cited by 385
“Further clinical studies confirm minor alleles of FKBP5 being particularly sensitive and interact with ELS/CT to increase aggressive behavior (387), suicide attempts (388), and depression (389).”
Background
Metadata
- Authors
- Bevilacqua, L.
- Affiliations
- University of Molise (IT)
- Corresponding author
- Bevilacqua, Laura
- ORCID
- Bevilacqua, Laura
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2012-01-01
- Volume
- 69
- Issue
- 1
- Pages
- 62
- ISSN
- 0003-990X (ISSN-L)
- PMC
- PMC3437943
- OpenAlex
- W2159672641
- Cited by
- 137
- References
- 66
- Citations by year
- 2025: 4 · 2024: 3 · 2023: 7 · 2022: 8 · 2021: 6 · 2020: 6 · 2019: 11 · 2018: 15 · 2017: 12 · 2016: 19 · 2015: 13 · 2014: 11 · 2013: 14 · 2012: 8
- FWCI
- 6.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi del Molise (submittedVersion)
- Funders
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (Z01AA000301)
- National Institute on Drug Abuse (R01DA010336, R01DA10336-02)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Social Sciences › Psychology › Clinical Psychology › Psychopathy, Forensic Psychiatry, Sexual Offending
- Keywords
- FKBP5, childhood trauma, aggression, impulsivity, gene-environment interaction, hypothalamic-pituitary-adrenal axis, glucocorticoid receptor sensitivity, physical abuse, prisoners, single nucleotide polymorphisms
- MeSH terms
- Tacrolimus Binding Protein 5, Adult, Aged, Aged, 80 and over, Aggression, Cross-Sectional Studies, Humans, Impulsive Behavior, Interview, Psychological, Italy, Male, Middle Aged, Prisoners, Risk Factors, Genetic Variation, Tacrolimus Binding Proteins, Adult Survivors of Child Abuse, Young Adult
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