Dataset Information

Maternal posttraumatic stress and FKBP5 Genotype interact to predict trauma-related symptoms in preschool-age offspring.

ABSTRACT:

Background

Children of parents with posttraumatic stress (PTS) face heightened risk for developing emotional and behavioral problems, regardless of whether they experience a traumatic event themselves. The current study investigates whether child FKBP5, a stress relevant gene shown to interact with child trauma exposure to increase risk for PTS, also moderates the well-established link between maternal PTS and child symptoms.

Methods

Data are derived from a longitudinal lab-based study for which 205 dyads of trauma-exposed mothers and their preschool-age children from a sample enriched for violence exposure provided DNA samples and completed measures of maternal and child trauma-related symptoms. Hypotheses tested whether child FKBP5 rs1360780 SNP genotype interacts with child trauma exposure and maternal PTS to predict child trauma-related symptoms.

Results

Hypotheses were partially supported, with maternal PTS predicting increased child symptoms for children carrying the minor T-allele (CT/TT), but not those homozygous for the major C-allele.

Limitations

Study results may not generalize to lower-risk or non-clinical populations, did not assess between-group differences in race/ethnicity, and do not consider other genes that may interact with FKBP5 or contribute to genetic risk for trauma-related impairment.

Conclusions

These findings provide the first evidence that the robust gene x environment interaction involving FKBP5 and child trauma exposure extends to other environmental perturbations, including maternal PTS. Our results highlight the importance of efforts to address trauma-related psychopathology in caregivers, which may disrupt intergenerational risk processes and improve outcomes for children.

SUBMITTER: Pereira DMBP

PROVIDER: S-EPMC10112507 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Publications

Maternal posttraumatic stress and FKBP5 Genotype interact to predict trauma-related symptoms in preschool-age offspring.

Pereira Destiny M B Printz DMBP Grasso Damion J DJ Hodgkinson Colin A CA McCarthy Kimberly J KJ Wakschlag Lauren S LS Briggs-Gowan Margaret J MJ

Journal of affective disorders 20210526

<h4>Background</h4>Children of parents with posttraumatic stress (PTS) face heightened risk for developing emotional and behavioral problems, regardless of whether they experience a traumatic event themselves. The current study investigates whether child FKBP5, a stress relevant gene shown to interact with child trauma exposure to increase risk for PTS, also moderates the well-established link between maternal PTS and child symptoms.<h4>Methods</h4>Data are derived from a longitudinal lab-based ...[more]

PMID: 34130185

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Project description:ContextIn addition to trauma exposure, other factors contribute to risk for development of posttraumatic stress disorder (PTSD) in adulthood. Both genetic and environmental factors are contributory, with child abuse providing significant risk liability.ObjectiveTo increase understanding of genetic and environmental risk factors as well as their interaction in the development of PTSD by gene x environment interactions of child abuse, level of non-child abuse trauma exposure, and genetic polymorphisms at the stress-related gene FKBP5.Design, setting, and participantsA cross-sectional study examining genetic and psychological risk factors in 900 nonpsychiatric clinic patients (762 included for all genotype studies) with significant levels of childhood abuse as well as non-child abuse trauma using a verbally presented survey combined with single-nucleotide polymorphism (SNP) genotyping. Participants were primarily urban, low-income, black (>95%) men and women seeking care in the general medical care and obstetrics-gynecology clinics of an urban public hospital in Atlanta, Georgia, between 2005 and 2007.Main outcome measuresSeverity of adult PTSD symptomatology, measured with the modified PTSD Symptom Scale, non-child abuse (primarily adult) trauma exposure and child abuse measured using the traumatic events inventory and 8 SNPs spanning the FKBP5 locus.ResultsLevel of child abuse and non-child abuse trauma each separately predicted level of adult PTSD symptomatology (mean [SD], PTSD Symptom Scale for no child abuse, 8.03 [10.48] vs > or =2 types of abuse, 20.93 [14.32]; and for no non-child abuse trauma, 3.58 [6.27] vs > or =4 types, 16.74 [12.90]; P < .001). Although FKBP5 SNPs did not directly predict PTSD symptom outcome or interact with level of non-child abuse trauma to predict PTSD symptom severity, 4 SNPs in the FKBP5 locus significantly interacted (rs9296158, rs3800373, rs1360780, and rs9470080; minimum P = .0004) with the severity of child abuse to predict level of adult PTSD symptoms after correcting for multiple testing. This gene x environment interaction remained significant when controlling for depression severity scores, age, sex, levels of non-child abuse trauma exposure, and genetic ancestry. This genetic interaction was also paralleled by FKBP5 genotype-dependent and PTSD-dependent effects on glucocorticoid receptor sensitivity, measured by the dexamethasone suppression test.ConclusionsFour SNPs of the FKBP5 gene interacted with severity of child abuse as a predictor of adult PTSD symptoms. There were no main effects of the SNPs on PTSD symptoms and no significant genetic interactions with level of non-child abuse trauma as predictor of adult PTSD symptoms, suggesting a potential gene-childhood environment interaction for adult PTSD.

Project description:BackgroundScientific enthusiasm about gene × environment interactions, spurred by the 5-HTTLPR (serotonin transporter-linked polymorphic region) × SLEs (stressful life events) interaction predicting depression, have recently been tempered by sober realizations of small effects and meta-analyses reaching opposing conclusions. These mixed findings highlight the need for further research. Converging evidence suggests that the effects of 5-HTTLPR genotype may be neurodevelopmental in origin, but we are not aware of empirical studies that have investigated whether the 5-HTTLPR genotype × SLE interaction predicts preschool-onset depression (PO-MDD), the earliest validated form of depression.MethodsChildren (n = 234) aged 3-5 were recruited for a longitudinal study designed to examine PO-MDD. In a comprehensive baseline assessment, the child's primary caregivers completed questionnaires and were interviewed about their child's behaviors, psychiatric symptoms, and exposure to SLEs.ResultsA 5-HTTLPR × SLEs interaction emerged, such that children homozygous for the short allele were more susceptible to depression in the context of elevated SLE than long allele carriers. In contrast, at low SLE exposure, short allele homozygotes had fewer depressive symptoms. The data were best fit by a plasticity model with a substantial reduction in fit by diathesis-stress models.ConclusionsExtending studies in adult and adolescent populations, these data suggest that 5-HTTLPR genotype may provide plasticity to environmental influence, for better or worse. Specifically, children homozygous for the short allele were more susceptible to the depressogenic effects of SLEs but benefitted, in the form of reduced depressive symptoms, in the context of relatively benign environmental conditions (i.e. relatively low SLE exposure). These data highlight the importance of examining gene × environment interactions across development, environment, and outcome but should be interpreted cautiously given the small sample size.

Dataset Information

Maternal posttraumatic stress and FKBP5 Genotype interact to predict trauma-related symptoms in preschool-age offspring.

Background

Methods

Results

Limitations

Conclusions

Publications

Maternal posttraumatic stress and FKBP5 Genotype interact to predict trauma-related symptoms in preschool-age offspring.

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