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Overview of the five identified glucocorticoid receptor haplotypes based on the four investigated common single nucleotide polymorphisms (SNPs) within this gene, and their respective frequencies within the cohort (based on two estimated haplotypes per participant).
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Background: Exposure to adversity in utero is thought to increase susceptibility to develop posttraumatic stress disorder (PTSD) following later life trauma, due to neurobiological programming effects during critical developmental periods. It remains unknown whether effects of prenatal adversity on PTSD susceptibility are modulated by genetic varia...
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Context 1
... confidence interval was also used in the exploratory analyses. As the haplotypes consisted of SNPs within the same gene and are therefore not independent, no multiple testing correction was applied to account for the separate haplotype models (Castro-Vale et al., 2021). ...
Context 2
... SNPs conformed to HWE (all p-values > 0.6). Five haplotypes were found, with the most frequent haplotype (41.9%) consisting of the common major alleles of the four SNPs as reported in the general population (Figure 1). Other identified haplotypes were: the BclI haplotype, containing the minor allele of the BclI SNP and the major alleles for all other three SNPs (frequency: 35.9%); the exon 9β haplotype, containing the minor allele of the exon 9β SNP and the major alleles for all other three SNPs (frequency: 15.2%), the N363S haplotype, containing the minor allele of the N363S SNP and the major alleles for all other three SNPs (frequency: 3.8%), and finally the ER22/23K + exon 9β haplotype, containing the minor alleles for these two SNPs and the major alleles for the two remaining SNPs (frequency: 3.2%). ...
Citations
... Finally, in a study using the Dutch famine birth cohort, a historical birth cohort of individuals born around the time of the Dutch famine of 1944-1945, by Gultig et al. (2023), exploratory sex-specific analyses were performed to evaluate whether prenatal famine exposure and genetic variation in the glucocorticoid receptor (GR) moderated the associations between childhood trauma or adulthood trauma and PTSD symptoms severity later in life. The authors found that participants exposed to famine during early gestation, but only those not carrying the GR Bcll haplotype, showed a significantly stronger association between adulthood trauma and PTSD symptoms severity compared to non-exposed controls. ...
Background: Posttraumatic stress disorder (PTSD) is two to three times more common in women than in men. To better understand this phenomenon, we need to know why men, women, and possibly individuals with other sex/gender identities respond differently to trauma. To stimulate sex and gender sensitive research, the European Journal of Psychotraumatology (EJPT) was the first journal to adopt a gender policy. In addition, a call for papers entitled Integrating and Evaluating Sex and Gender in Psychotrauma Research was announced.
Objective: This special issue synthesizes the past five years of psychotrauma research with regard to sex/gender differences.
Method: Seventy-seven articles were identified from EJPT archives, including five systematic reviews. These articles examined sex differences and/or gender differences in exposure to trauma, posttraumatic stress responses, or how sex and gender impacts (mental) health outcomes or treatment responses.
Results: Findings from these studies outlined that: 1. sex and gender still need to be more clearly defined, also in relation to the context that codetermine trauma responses, like other ‘diversity’ variables; 2. in most studies, sex and gender are measured or reported as binary variables; 3. sex and gender are important variables when examining trauma exposure, responses to these events, symptoms trajectories, and mental and physical health outcomes across the life span; and 4. in PTSD treatment studies, including a meta-analysis and a systematic review, sex and gender were not significant predictors of treatment outcome.
Conclusion: Future research must focus on sex and gender as important and distinct variables; they should include sex and gender in their statistical analyses plan to better clarify associations between these variables and (responses to) psychotrauma. To enhance reporting of comparable data across studies, we provide suggestions for future research, including how to assess sex and gender.
... The glucocorticoid-induced tumor necrosis factor receptor family-related protein is implicated in atherosclerosis progression in mice and correlates with unstable plaque characteristics and abnormalities in the human cerebrovascular system (Shami et al. , 2020). Studies exploring genetic variations in GR highlight a link between GR alterations and the intensity of PTSD symptoms, suggesting that glucocorticoid signaling may be disrupted in PTSD patients even before encountering stress (Danan et al. , 2021;Gultig et al. , 2023). The heightened arousal from trauma triggers activation of the HPA axis, resulting in elevated cortisol production that typically serves to dampen the stress response. ...
Post-traumatic stress disorder (PTSD) is a complex psychological disorder provoked by distressing experiences, and it remains without highly effective intervention strategies. The exploration of PTSD’s underlying mechanisms is crucial for advancing diagnostic and therapeutic approaches. Current studies primarily explore PTSD through the lens of the CNS, investigating concrete molecular alterations in the cerebral area and neural circuit irregularities. However, the body’s response to external stressors, particularly the changes in cardiovascular function, is often pronounced, evidenced by notable cardiac dysfunction. Consequently, examining PTSD with a focus on cardiac function is vital for the early prevention and targeted management of the disorder. This review undertakes a comprehensive literature analysis to detail the alterations in brain and heart structures and functions associated with PTSD. It also synthesizes potential mechanisms of heart-brain axis interactions relevant to PTSD’s development. Ultimately, by considering cardiac function, this review proposes novel perspectives for PTSD’s prophylaxis and therapy.
Post‐traumatic stress disorder (PTSD) is a complex psychological disorder provoked by distressing experiences, and it remains without highly effective intervention strategies. The exploration of PTSD's underlying mechanisms is crucial for advancing diagnostic and therapeutic approaches. Current studies primarily explore PTSD through the lens of the central nervous system, investigating concrete molecular alterations in the cerebral area and neural circuit irregularities. However, the body's response to external stressors, particularly the changes in cardiovascular function, is often pronounced, evidenced by notable cardiac dysfunction. Consequently, examining PTSD with a focus on cardiac function is vital for the early prevention and targeted management of the disorder. This review undertakes a comprehensive literature analysis to detail the alterations in brain and heart structures and functions associated with PTSD. It also synthesizes potential mechanisms of heart–brain axis interactions relevant to the development of PTSD. Ultimately, by considering cardiac function, this review proposes novel perspectives for PTSD's prophylaxis and therapy.