PTSD+and+genetic+inheritance

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=What is the connection between genetic inheritance and PTSD in child abuse sufferers?=

The data suggest that some functions of the serotonin transporter gene may mitigate or accentuate response to a severe trauma. According to the authors, this is consistent with current pharmacological treatment of PTSD with selective serotonin reuptake inhibitors (SSRIs). Additionally, variants in the gene have previously been shown to be associated with different risk for depression following life stress. The researchers concluded that when examined in a relatively homogenous sample with shared trauma and known prior levels of child and adult trauma, this serotonin transporter genotype may serve as a useful predictor of risk for PTSD related symptoms in the weeks and months following trauma.

http://psychcentral.com/news/2011/09/07/ptsd-risk-may-depend-on-genetics/29222.html

From the vantage point of genetics research, PTSD is considered a complex or polygenetic disorder. Unlike Huntington's disease and other disorders where there is a single gene that is necessary and sufficient for the development of the disorder, there is likely no PTSD gene. Instead, there are probably many genes that contribute additively, in a probabilistic fashion, to the inherited liability for PTSD. http://www.psychiatrictimes.com/display/article/10168/52511

http://web.ebscohost.com/ehost/detail?vid=6&hid=17&sid=aa35a36b-b16f-4ad8-9fbd-dd4ea500227e%40sessionmgr4&bdata=JnNpdGU9ZWhvc3QtbGl2ZQ%3d%3d#db=pbh&AN=35417133

//In female children, there is a more likelihood of developing PTSD due to a gene// An enzyme called pituitary adenylate cyclase–activating polypeptide (PACAP) may play a role in posttraumatic stress disorder (PTSD ) in women but not men, according to new research from the Emory University School of Medicine in Atlanta, the University of Vermont in Burlington, and other institutions (Ressler KJ et al. // Nature //. 2011;470[7335]:492-497). PACAP and its receptor (PAC1) are known to regulate the response of cells to stress. To assess whether these proteins are associated with PTSD, investigators analyzed blood levels of PACAP as well as variation and modification of the gene s encoding PACAP and PAC1 in a cohort of more than 1200 highly traumatized individuals with and without PTSD. The researchers found a sex-specific association of PACAP blood levels with fear physiology, PTSD diagnosis, and symptoms in females. Also, a gene tic variant in a putative estrogen response element within the gene encoding the receptor predicted PTSD diagnosis and symptoms in females … http://jama.ama-assn.org/content/305/13/1290.4.extract?sid=6d9754b3-5f50-4fac-b99f-738f566194d2

http://jama.ama-assn.org/content/299/11/1291.full?sid=1b7ffec8-7b35-4d15-984f-ad443325ab45
 * Four 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.
 * A recent review[|12] covering candidate genes in the serotonin, dopamine, glucocorticoid receptor (GR), γ-aminobutyric acid, apolipoprotein E, brain-derived neurotrophic factor, and the neuropeptide Y system finds that (1) the support for a relationship between the serotonin transporter gene and PTSD exists only in research on the interaction of this system with stressful life events in predicting depressive symptoms; (2) results on the dopamine system are inconsistent; (3) there is a lack of evidence for relationships with brain-derived neurotrophic factor, neuropeptide Y, or GR polymorphisms and PTSD with the exception of a finding between GR genotype and basal cortisol levels in a subgroup of patients with PTSD[|30]​ ; and finally, (4) limited evidence for the γ-aminobutyric acid system and the apolipoprotein E system.
 * One of the first studies finding an interaction between a genetic polymorphism and child abuse in predicting psychopathology was the study by Caspi et al,[|31] which found that maltreated children with a monoamine oxidase A (// MAOA //) genotype conferring low levels of // MAOA // expression were more likely to develop conduct disorder and antisocial-personality disorder and to commit violent crimes as adults compared with those children with the high-activity // MAOA //genotype.
 * The largest group of genotype × environment studies has examined the interaction between variation at the // 5HTTLPR // (a complex-repeat polymorphism in the 5′ upstream region of // SLC6A4 //, which encodes the serotonin transporter the// 5HTTLPR //) and stressful life events, including child abuse, in predicting depression.
 * From a developmental perspective, HPA axis genes are strong candidates with respect to altering susceptibility to PTSD. Exposure to trauma and stress increase HPA axis activity, and PTSD has been associated with long-lasting alterations in HPA axis reactivity [|42] ​,[|43] and specifically higher GR sensitivity. Polymorphisms in genes regulating GR activity may impact the acute effects of trauma on the HPA axis and thereby possibly impact long-term HPA axis regulation affecting the development of PTSD.
 * Several studies suggest that the depression-related HPA axis hyperactivity may be related to early life stress. For example, plasma corticotropin and cortisol, as well as cerebrospinal fluid corticotropin-releasing hormone (CRH) concentrations, correlate with perceived early life stress more than with current depression. [|47] ,[|48] ​ Preclinical studies indicate that the persistent hyperactivity of the HPA axis associated with early life stress is mediated by a hyperactive CRH receptor 1 (CRHR1) system, with chronic overactivity of CRHR1 in limbic brain regions.

Behavioral genetics research, based on twin studies, has demonstrated an important genetic contribution to the predisposition to develop PTSD (Kendler, Neale, Kessler, & Heath, 1993; True, Rice, Eisen, & Heath, 1993). However, it is important to view this in the context of two other findings. First, the same behavioral genetics research shows that this genetic disposition is not specific but pertains to a spectrum of diagnoses rather than to one particular diagnosis such as PTSD http://www.psychoanalysis.ugent.be/pages/nl/artikels/artikels%20Paul%20Verhaeghe/Actual%20neurosis%201.pdf