Cited by 137Stress Responses and CortisolChild Abuse and TraumaPsychopathy, Forensic Psychiatry, Sexual Offending

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Interaction Between <emph type="ital">FKBP5</emph> and Childhood Trauma and Risk of Aggressive Behavior

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Bevilacqua, Laura·2012·Archives of General Psychiatry

DOI 10.1001/archgenpsychiatry.2011.152PMC PMC3437943

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Abstract

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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Klengel, T., & Binder, E. B. (2012) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145712001459 · Cited by 35
“, 2010), aggression (Bevilacqua et al., 2012) and suicide attempts (Roy et al.”
Do common genotypes of FK506 binding protein 5 (FKBP5) moderate the effects of childhood maltreatment on cognition in schizophrenia and healthy controls?
Green, M. J., Raudino, A., Cairns, M. J., Wu, J. Q., Tooney, P. A., Scott, R. J., & Carr, V. J. (2015) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2015.07.019 · Cited by 32
“, 2010), aggression (Bevilacqua et al., 2012) and psychosis (Collip et al.”
Background
Trauma exposure interacts with impulsivity in predicting emotion regulation and depressive mood
Ceschi, G., Billieux, J., Hearn, M., Fürst, G., & der Linden, M. V. (2014) · European Journal of Psychotraumatology · doi:10.3402/ejpt.v5.24104 · Cited by 31
“Although contradictory findings have also been published (Bevilacqua et al., 2012), together, these results suggest that trauma and impulsivity may indeed exert a multiplier effect on interindividual cognitive emotion regulation differences.”
Result
Monitoring and predicting the risk of violence in residential facilities. No difference between patients with history or with no history of violence
de Girolamo, G., Buizza, C., Sisti, D., Ferrari, C., Bulgari, V., Iozzino, L., Boero, M. E., Cristiano, G., Francesco, A. D., Giobbio, G. M., et al. (2016) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2016.05.010 · Cited by 31
The emerging role of the FKBP5 gene polymorphisms in vulnerability–stress model of schizophrenia: further evidence from a Serbian population
Mihaljevic, M. M., Zeljić, K., Soldatović, I., Petrović, S. A., Mirjanić, T., Richards, A. L., Mantripragada, K. K., Pekmezovic, T. D., Novaković, I. V., & Marić, N. P. (2016) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-016-0720-7 · Cited by 30
“Genotypes of these functional SNPs with minor (risk) allele have been consistently associated with broad range of stress-related psychiatric disorders such as PTSD, depression, bipolar disorder, borderline personality disorder [16–21] and pathological conditions (suicide, aggressive behavior) following trauma exposure…”
BackgroundInfluential
Long-term programing of psychopathology-like behaviors in male rats by peripubertal stress depends on individual’s glucocorticoid responsiveness to stress
Walker, S. E., & Sandi, C. (2018) · Stress · doi:10.1080/10253890.2018.1435639 · Cited by 30
“A growing number of findings indicate that having a differential physiological sensitivity to stress may be a factor that modulates the outcome of early life stress exposure (Bevilacqua et al., 2012; Binder et al., 2008; Bryushkova et al., 2016; Klengel et al., 2013).”
Background
FKBP5 is associated with amygdala volume in the human brain and mood state: A voxel-based morphometry (VBM) study
Hirakawa, H., Akiyoshi, J., Muronaga, M., Tanaka, Y., Ishitobi, Y., Inoue, A., Oshita, H., Aizawa, S., Masuda, K., Higuma, H., et al. (2016) · International Journal of Psychiatry in Clinical Practice · doi:10.3109/13651501.2016.1144772 · Cited by 30
The effects of early trauma and the FKBP5 gene on PTSD and the HPA axis in a clinical sample of Gulf War veterans
Young, D. A., Inslicht, S. S., Metzler, T. J., Neylan, T. C., & Ross, J. A. (2018) · Psychiatry Research · doi:10.1016/j.psychres.2018.03.037 · Cited by 30
Genomic updates in understanding PTSD
Sharma, S. K., & Ressler, K. J. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2018.11.010 · Cited by 29
“(Bevilacqua et al., 2012; Binder et al., 2004; Roy et al., 2010) FKBP5 biology has also been covered extensively elsewhere.”
Background
Allostatic Load and Biomarkers of Stress in the Preterm Infant: An Integrative Review
Casavant, S. G., Cong, X. S., FITCH, R. H., Moore, J., Rosenkrantz, T. S., & Starkweather, A. R. (2019) · Biological Research For Nursing · doi:10.1177/1099800418824415 · Cited by 29
Examining the factors associated with impulsivity in forensic populations: A systematic review
Alford, M., O'Rourke, S., Doyle, P., & Todd, L. (2020) · Aggression and Violent Behavior · doi:10.1016/j.avb.2020.101409 · Cited by 23
Differential Susceptibility to Environmental Influences
Belsky, J., & Pluess, M. (2016) · Wiley eBooks · doi:10.1002/9781119125556.devpsy202 · Cited by 29
Psychopathological consequences of maltreatment among children and adolescents: A systematic review of the GxE literature
Maglione, D., Caputi, M., Moretti, B., & Scaini, S. (2018) · Research in Developmental Disabilities · doi:10.1016/j.ridd.2018.06.005 · Cited by 34
Predictors for self‐directed aggression in Italian prisoners include externalizing behaviors, childhood trauma and the serotonin transporter gene polymorphism 5‐ HTTLPR
Gorodetsky, E. K., Carli, V., Sarchiapone, M., Roy, A., Goldman, D. A., & Enoch, M. (2016) · Genes Brain & Behavior · doi:10.1111/gbb.12293 · Cited by 27
“Full details of the dataset are provided in Bevilacqua et al. (2012).”
Background
FKBP5 genotype interacts with early life trauma to predict heavy drinking in college students
Lieberman, R., Armeli, S., Scott, D. M., Kranzler, H. R., Tennen, H. A., & Covault, J. (2016) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32460 · Cited by 26
“…conditions, including post-traumatic stress disorder (PTSD) [Binder et al., 2008], anxiety, depression [Binder et al., 2004; Lavebratt et al., 2010], addictive disorders [Huang et al., 2014; Levran et al., 2014; Jensen et al., 2015], and aggressive or violent behavior [Bevilacqua et al., 2012].”
Background
From child maltreatment to emerging adult problem drinking: Identification of a multilevel internalizing pathway among African American youth
Handley, E. D., Rogosch, F. A., & Cicchetti, D. (2017) · Development and Psychopathology · doi:10.1017/s0954579417001419 · Cited by 25
“…attempts (Roy, Gorodetsky, Yuan, Goldman, & Enoch, 2010; Roy, Hodgkinson, DeLuca, Goldman, & Enoch, 2012), posttraumatic stress disorder and dissociative symptoms (Xie et al., 2010; Yaylaci, Cicchetti, Rogosch, Bulut, & Hetzel, 2016), and aggressive and violent behaviors (Bevilacqua et al., 2012).”
The interactive effects of child maltreatment and the FK506 binding protein 5 gene (FKBP5) on dissociative symptoms in adolescence
Yaylaci, F. T., Cicchetti, D., Rogosch, F. A., Bulut, O., & Hetzel, S. (2016) · Development and Psychopathology · doi:10.1017/s095457941600105x · Cited by 26
“Only three studies to date have examined the haplotype that comprises the four SNPs we examined in the FKBP5 locus to find significant G E interactions (Bevilacqua et al., 2012; Dackis et al., 2012; Roy et al., 2010).”
Background
FKBP5 genotype and early life stress exposure predict neurobehavioral outcomes for preterm infants
D’Agata, A. L., Walsh, S. J., Vittner, D. J., Cong, X. S., McGrath, J. M., & Young, E. E. (2017) · Developmental Psychobiology · doi:10.1002/dev.21507 · Cited by 24
Moderators and mediators of a maternal depression treatment study: Impact of maternal trauma and parenting on child outcomes
Swartz, H. A., Cyranowski, J. M., Cheng, Y., & Amole, M. C. (2018) · Comprehensive Psychiatry · doi:10.1016/j.comppsych.2018.08.001 · Cited by 23
“Using previously validated cutpoints [49, 50], threshold scores were used to create five Swartz et al.”
Method
Vulnerability to inflammation-related depressive symptoms: Moderation by stress in women with breast cancer
Manigault, A. W., Kuhlman, K. R., Irwin, M. R., Cole, S. W., Ganz, P. A., Crespi, C. M., & Bower, J. E. (2021) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2021.03.004 · Cited by 22
Traumatic experiences and PTSD symptoms in substance use disorder: A comparison of recovered versus current users
Belfrage, A., Njå, A. L. M., Lunde, S., Årstad, J., Fodstad, E. C., Lid, T. G., & Erga, A. H. (2022) · Nordic Studies on Alcohol and Drugs · doi:10.1177/14550725221122222 · Cited by 22
“neglect (Bevilacqua et al., 2012; Erfanian, 2018; Walker et al., 1999).”
Method
Examining gene–environment interactions in comorbid depressive and disruptive behavior disorders using a Bayesian approach
Adrian, M. C., Kiff, C. J., Glazner, C., Kohen, R., Tracy, J. H., Zhou, C., McCauley, E., & Stoep, A. V. (2015) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2015.06.004 · Cited by 22
Co-occurring tobacco use and posttraumatic stress disorder: Smoking cessation treatment implications: Tobacco Use in Posttraumatic Stress Disorder
Kelly, M. M., Jensen, K. P., & Sofuoglu, M. (2015) · The American Journal on Addictions · doi:10.1111/ajad.12304 · Cited by 23
Childhood parenting and adolescent internalizing and externalizing symptoms: Moderation by multilocus hypothalamic–pituitary–adrenal axis-related genetic variation
Cao, C., & Rijlaarsdam, J. (2022) · Development and Psychopathology · doi:10.1017/s0954579421001620 · Cited by 19
FKBP5 variation is associated with the acute and chronic effects of nicotine
Jensen, K. P., Herman, A. I., Morean, M. E., Kranzler, H. R., Gelernter, J. E., & Sofuoglu, M. (2014) · The Pharmacogenomics Journal · doi:10.1038/tpj.2014.76 · Cited by 19
Childhood Abuse and Suicidal Behaviors Among Chinese Migrant Workers: The Mediating Role of Alexithymia and Social Support
Chen, L., Ngoubene-Atioky, A. J., Zanardelli, G., Deng, Y., & Yu, L. (2020) · Archives of Suicide Research · doi:10.1080/13811118.2019.1658142 · Cited by 17
What can HPA axis-linked genes tell us about anxiety disorders in adolescents?
Bortoluzzi, A., Blaya, C., da Rosa, E. D., Paim, M. F., Rosa, V. D. O., Leistner‐Segal, S., & Manfro, G. G. (2015) · Trends in Psychiatry and Psychotherapy · doi:10.1590/2237-6089-2015-0035 · Cited by 20
Gene–Environment Interactions in the Etiology of Human Violence
Laucht, M., Brandeis, D., & Zohsel, K. (2013) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2013_260 · Cited by 18
Interaction between FKBP5 variability and recent life events in the anxiety spectrum: Evidence for the differential susceptibility model
Pérez, B. P., Cristóbal-Narváez, P., Sheinbaum, T., Kwapil, T. R., Ballespí, S., Peña, E., de Castro-Català, M., Riba, M. D., Rosa, A., & Neus Barrantes-vidal, A. (2018) · PLoS ONE · doi:10.1371/journal.pone.0193044 · Cited by 18
Physiological Genomics Plays a Crucial Role in Response to Stressful Life Events, the Development of Aggressive Behaviours, and Post-Traumatic Stress Disorder (PTSD)
Magwai, T., & Xulu, K. R. (2022) · Genes · doi:10.3390/genes13020300 · Cited by 20
DNA polymorphism in the FKBP5 gene affects impulsivity in intertemporal choice
Kawamura, Y., Takahashi, T., Liu, X., Nishida, N., Tokunaga, K., Ukawa, K., Noda, Y., Yoshikawa, A., Shimada, T., Umekage, T., et al. (2013) · Asia-Pacific Psychiatry · doi:10.1111/appy.12009 · Cited by 15
“Furthermore, rs1360780 has been implicated in the relationship between childhood trauma and aggressive behavior (Bevilacqua et al., 2012).”
Background
Genetic and Psychosocial Predictors of Aggression: Variable Selection and Model Building With Component-Wise Gradient Boosting
Suchting, R., Gowin, J. L., Green, C. E., Walss‐Bass, C., & Lane, S. D. (2018) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2018.00089 · Cited by 16
“…(Gao et al., 2015; Coccaro et al., 2016; Hsieh and Chen, 2017); biological factors, including genetic variation (Tuvblad and Baker, 2011; Bevilacqua et al., 2012; Takahashi et al., 2012; Dorfman et al., 2014); and contextual/situational factors such as substance use and provocation…”
Background
Potential role of FKBP5 single‐nucleotide polymorphisms in functional seizures
Asadi‐Pooya, A. A., Simani, L., Asadollahi, M., Rashidi, F. S., Ahmadipour, E., Alavi, A., Roozbeh, M., Akbari, N., & Firouzabadi, N. (2023) · Epilepsia Open · doi:10.1002/epi4.12716 · Cited by 14
A Prospective Cohort Study of Influences on Externalizing Behaviors Across Childhood: Results From a Nurse Home Visiting Randomized Controlled Trial
Enoch, M., Kitzman, H. J., Smith, J. A. V. D. L., Anson, E. A., Hodgkinson, C. A., Goldman, D. A., & Olds, D. L. (2016) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2016.02.007 · Cited by 15
Childhood trauma: a risk for major depression in patients with psoriasis
Erfanian, M. (2018) · Psychiatry and Clinical Psychopharmacology · doi:10.1080/24750573.2018.1452521 · Cited by 15
“[36], the cut-off scores for each subscale were for sexual abuse ≥8, physical abuse ≥8, emotional abuse ≥10, physical neglect ≥8, and emotional neglect ≥15.”
Background
Developmental pathways from child maltreatment to adolescent marijuana dependence: Examining moderation by FK506 binding protein 5 gene (FKBP5)
Handley, E. D., Rogosch, F. A., & Cicchetti, D. (2015) · Development and Psychopathology · doi:10.1017/s0954579415000899 · Cited by 15
“Although the majority of this prior work has identified FKBP5 minor alleles as conferring risk in interaction with childhood adversity (e.g., Bevilacqua et al., 2012; Binder et al., 2008; Dackis et al., 2012; Xie et al., 2010), there are a few studies that have demonstrated interactive risk…”
BackgroundInfluential
Childhood Adversity and the Association Between Stress Sensitivity and Problematic Alcohol Use in Adults
Hall, O. T., Phan, K. L., & Gorka, S. M. (2021) · Journal of Traumatic Stress · doi:10.1002/jts.22709 · Cited by 17
FKBP5 interacts with maltreatment in children with extreme, pervasive, and persistent aggression
Bryushkova, L., Zai, C., Chen, S., Pappa, I., Mileva, V., Tiemeier, H., Bakermans-Kranenburg, M., Kennedy, J. L., & Beitchman, J. H. (2016) · Psychiatry Research · doi:10.1016/j.psychres.2015.09.052 · Cited by 13
Childhood abuse history and attention bias in adults
Letkiewicz, A. M., Silton, R. L., Mimnaugh, K. J., Miller, G. A., Heller, W., Fisher, J. E., & Sass, S. M. (2020) · Psychophysiology · doi:10.1111/psyp.13627 · Cited by 16
The Role of Cognitive Deficits in Borderline Personality Disorder with Early Traumas: A Mediation Analysis
Bozzatello, P., Blua, C., Brasso, C., Rocca, P., & Bellino, S. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12030787 · Cited by 16
Resolution of remitting seronegative symmetrical synovitis with pitting edema (RS3PE) during Nivolumab therapy for non-small cell lung cancer: a case report.
Filetti, M., Anselmi, E., Macrini, S., Rizzo, F., Iacono, D., Giusti, R., & Marchetti, P. (2018) · Seminars in Arthritis and Rheumatism · doi:10.1016/j.semarthrit.2017.12.013 · Cited by 12
FKBP5 haplotypes and PTSD modulate the resting-state brain activity in Han Chinese adults who lost their only child
Qi, R., Luo, Y., Zhang, L., Weng, Y., Surento, W., Jahanshad, N., Xu, Q., Yin, Y., Li, L., Cao, Z., et al. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-0770-5 · Cited by 10
Omics Approaches to Investigate the Pathogenesis of Suicide
Boldrini, M., Xiao, Y., Singh, T., Zhu, C., Jabbi, M., Pantazopoulos, H., Gürsoy, G., Martinowich, K., Punzi, G., Vallender, E. J., et al. (2024) · Biological Psychiatry · doi:10.1016/j.biopsych.2024.05.017 · Cited by 13
“Other useful measures include the Global Assessment Scale to assess individual level of functioning (22), recent stressful life events quanti ﬁ cation with the St. Paul Ramsey scale (23), early-life adversity history using data from a psychological autopsy (20) that parallels the Childhood Trauma Questionnaire (24), a…”
Method
Interaction between Sirtuin 1 (SIRT1) polymorphisms and childhood maltreatment on aggression risk in Chinese male adolescents
Wang, M., Peng, C., Chang, H., Yu, M., Rong, F., & Yu, Y. (2022) · Journal of Affective Disorders · doi:10.1016/j.jad.2022.04.063 · Cited by 10
Saliva as a Blood Alternative for Genome-Wide DNA Methylation Profiling by Methylated DNA Immunoprecipitation (MeDIP) Sequencing
Staunstrup, N. H., Starnawska, A., Nyegaard, M., Nielsen, A. L., Børglum, A. D., & Mors, O. N. (2017) · Epigenomes · doi:10.3390/epigenomes1030014 · Cited by 10
“As an example to the latter, childhood maltreatment has shown to be associated with FKBP5 gene promoter hypomethylation in both brain and blood tissues [13,14].”
Background

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)
DOI: 10.1001/archgenpsychiatry.2011.152
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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Interaction Between <emph type="ital">FKBP5</emph> and Childhood Trauma and Risk of Aggressive Behavior

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