No association between ADCYAP1R1 and post-traumatic stress disorder in two independent samples

Department of Society, Human Development and Health, Harvard School of Public Health, Boston, MA, USA.
Molecular Psychiatry (Impact Factor: 14.5). 09/2011; 17(3):239-41. DOI: 10.1038/mp.2011.118
Source: PubMed


Molecular Psychiatry publishes work aimed at elucidating biological mechanisms underlying psychiatric disorders and their treatment

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Available from: Andrea L Roberts, Jul 18, 2014
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    • "Further, PTSD associates with alterations in peripheral blood DNA methylation and mRNA expression of the ADCYAP1R1 transcript (Ressler et al., 2011). Although the association Genetics, epigenetics, and neuroimaging genetics of PTSD 3 with the ADCYAP1R1 variant was not replicated among presumably less traumatized, African American and Caucasian populations (Chang et al., 2012b), an interaction between ADCYAP1R1 genotype and childhood maltreatment may predict PTSD in females (Uddin et al., 2012). The neurobiology of stress regulation, particularly with regard to the HPA axis and the regulation of CRH production and cortisol feedback, may underlie many of the symptoms of PTSD. "
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    ABSTRACT: Post-traumatic stress disorder (PTSD) is increasingly recognized as both a disorder of enormous mental health and societal burden, but also as an anxiety disorder that may be particularly understandable from a scientific perspective. Specifically, PTSD can be conceptualized as a disorder of fear and stress dysregulation, and the neural circuitry underlying these pathways in both animals and humans are becoming increasingly well understood. Furthermore, PTSD is the only disorder in psychiatry in which the initiating factor, the trauma exposure, can be identified. Thus, the pathophysiology of the fear and stress response underlying PTSD can be examined and potentially interrupted. Twin studies have shown that the development of PTSD following a trauma is heritable, and that genetic risk factors may account for up to 30-40% of this heritability. A current goal is to understand the gene pathways that are associated with PTSD, and how those genes act on the fear/stress circuitry to mediate risk vs. resilience for PTSD. This review will examine gene pathways that have recently been analysed, primarily through candidate gene studies (including neuroimaging studies of candidate genes), in addition to genome-wide associations and the epigenetic regulation of PTSD. Future and on-going studies are utilizing larger and collaborative cohorts to identify novel gene candidates through genome-wide association and other powerful genomic approaches. Identification of PTSD biological pathways strengthens the hope of progress in the mechanistic understanding of a model psychiatric disorder and allows for the development of targeted treatments and interventions.
    Full-text · Article · Oct 2013 · The International Journal of Neuropsychopharmacology
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    • "For example, Ressler and colleagues reported a sex-specific association of SNP rs2267735 mapping to a putative estrogen response element within the gene PACAPR1 (encoded by ADCYAP1R1) with PTSD in females only (Ressler et al., 2011) which has been replicated in several studies (Almli et al., 2013; Uddin et al., 2013; Wang et al., 2013). However, Chang and colleagues were unable to replicate the association between rs2267735 and PTSD in either AA or EA females in these two large independent samples (Chang et al., 2012). Taken together, these findings support the importance of investigating the genetic risk factors that specifically increase vulnerability in women. "
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    ABSTRACT: Posttraumatic stress disorder (PTSD) is a common and debilitating mental disorder with a particularly high burden for women. Emerging evidence suggests PTSD may be more heritable among women and evidence from animal models and human correlational studies suggest connections between sex-linked biology and PTSD vulnerability, which may extend to the disorder's genetic architecture. We conducted a genome-wide association study (GWAS) of PTSD in a primarily African American sample of women from the Detroit Neighborhood Health Study (DNHS) and tested for replication in an independent cohort of primarily European American women from the Nurses Health Study II (NHSII). We genotyped 413 DNHS women - 94 PTSD cases and 319 controls exposed to at least one traumatic event - on the Illumina HumanOmniExpress BeadChip for >700,000 markers and tested 578 PTSD cases and 1963 controls from NHSII for replication. We performed a network-based analysis integrating data from GWAS-derived independent regions of association and the Reactome database of functional interactions. We found genome-wide significant association for one marker mapping to a novel RNA gene, lincRNA AC068718.1, for which we found suggestive evidence of replication in NHSII. Our network-based analysis indicates that our top GWAS results were enriched for pathways related to telomere maintenance and immune function. Our findings implicate a novel RNA gene, lincRNA AC068718.1, as risk factor for PTSD in women and add to emerging evidence that non-coding RNA genes may play a crucial role in shaping the landscape of gene regulation with putative pathological effects that lead to phenotypic differences.
    Full-text · Article · Sep 2013 · Psychoneuroendocrinology
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    • "Chang et al. (2012) failed to replicate the findings of Ressler et al. (2011). However, the first precondition for PTSD is exposure to a traumatic stressor, and a substantial proportion of Chang et al. (2012) samples were not trauma exposed and therefore may carry an unexpressed genetic vulnerability for PTSD. Therefore, additional studies to examine the association between PTSD and ADCYAP1R1 are needed; especially those with a highly trauma exposed sample. "
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    ABSTRACT: BACKGROUND: Genetic factors are important in the development of posttraumatic stress disorder (PTSD) following exposure to traumatic events. However, the molecular genetic underpinnings of this disorder remain largely unresolved. The present study investigated the association between ADCYAP1R1 rs2267735 genotype and PTSD symptoms in a highly traumatized sample of Chinese adults. METHODS: Participants included 326 victims who experienced 2008 Wenchuan earthquake and lost their children during the disaster. PTSD symptoms were assessed with the PTSD Checklist (PCL). The ADCYAP1R1 rs2267735 SNP was genotyped with the Sequenom iPlex chemistries and the MassARRAY system. RESULTS: The results indicated that although the rs2267735 'CC' genotype was not associated with total PTSD symptoms, it could significantly predict severity of PTSD's emotional numbing symptoms inwomen. LIMITATIONS: A relatively small sample exposed to specific traumatic events was used, and PTSD was assessed using a self-reported instrument. CONCLUSIONS: The findings suggest that the PACAP-PAC1 receptor pathway may play an important role in female human responses to traumatic stress, and carry implications for better understanding and treating of posttraumatic psychopathology.
    Full-text · Article · Feb 2013 · Journal of Affective Disorders
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