Gene_Fkbp5_and_Its_Affect_on_Child_Abuse_and_Risks_of_Posttraumatic_Stress_Disorder_in_Adults

RUNNING HEAD: Association of FKBP5 and Childhood Abuse Research Analysis Paper Association of FKBP5 Polymorphisms and Childhood Abuse with Risk of Posttraumatic Stress Disorder Symptoms in Adults Angela Whitmore April 13, 2008 HLTH 401 Abstract A traumatic event such as child-abuse, witnessing a crime and/or serving time in combat all can lead to PTSD (Posttraumatic Stress Disorder). Even though, each individual may handle the event differently PTSD can still develop as a result. Posttraumatic Stress Disorder is an anxiety disorder, which can develop after you have experienced a traumatizing event. (National Center for Posttraumatic Stress Disorder 2008). A research study was conducted to measure gene variation due to childhood abuse, resulting in PTSD. The participants included 900 African Americans 18-81 years old, from poor urban neighborhoods. Studies were based on childhood abuse and non-childhood abuse. Studies will show that a genetic variation in gene FKBP5 due to childhood abuse pose a risk and the potential for developing PTSD. Summary We relate PTSD to the FKBP5 gene because they both relate directly to stress levels. The gene FKBP5 produces a protein that helps regulate binding among stress hormones and their receptors on cells. When stress hormones and their receptors do not bind it could cause gene variation, this gene being FKBP5. Other terms used in this study are HPA (hypothalamic-pituitary-adrenal axis which is also called the reproductive axis. HPA is a major part of the neuro-endocrine system that controls reactions to stress and regulates various body processes, including digestion and the immune system. GR receptor (Glucocorticoid receptor), expressed in almost every cell of the body and regulates either directly or indirectly genes controlling a wide variety of processes, including the development, metabolism an immune response of the organism. DST (Dexamethasone suppression test), measures the response of the adrenal glands to ACTH (Acetycholemine). Dexamethasone is given and levels of cortisol are measured. Cortisol levels should decrease in response to the administration of dexamethasone. And last, a term that will be used a lot is SNP, which stands for Single-nucleotide polymorphisms. This research study is based on a naturalistic type design. “In a naturalistic design the researcher examines data, records observations, and transcriptions of interviews to obtain initial descriptions, impressions and haunches. (Depoy pg 243). Qualitative data was used to conduct research and began with a screen interview of 900 participants. The participants filled out a battery self-report describing trauma history and symptoms. A modified PTSD symptom scale was used to asses PTSD over a 2 weeks time period. These are just a few of many testing procedures done to conclude if the gene FKBP5 had a relation to childhood abuse and PTSD in adults. Is there a relation between gene FKBP5 and childhood abuse with risk of PTSD in adults' It is hypothesized that the functional SNP in FKBP5 moderates the development of PTSD in adults. The Null hypothesis: there is no relationship between the functional SNP in FKBP5 moderate and the development of PTSD in adults. The alternative hypothesis states there is a relationship between the functional SNP in FKBP5 moderate and the development of PTSD in adults. A directional hypothesis states, early trauma, PTSD and FKBP5 have all shown to influence GR resistance, therefore variants in this gene may alter the impact of early trauma or PTSD on GR sensitivity. A variable is a concept or construct to which a numerical value is assigned. (Depoy pg. 325). In this study the dependent variable is variations in the gene FKBP5. An increase in the gene FKBP5 depends on whether or not certain variations in the stress-related gene were also present. The independent variable is based on the environmental factors such as child abuse, non-child abuse, sexual/physical abuse and traumatic experiences. There is a theoretical approach to this study and it is based on inductive reasoning. Inductive reasoning is based on human reasoning that involves a process in which general rules evolve or develop from individual cases or from observation of a phenomenon. (Depoy pg 320). The 900 African American participants were observed based on interviews, surveys and clinical tests. Participants were selected based on systemic sampling. In systemic sampling interval width is determined an individuals are selected for a study. (Depoy pg. 148). Data was collected to investigate the roles of genetic an environmental factors in predicting the development of PTSD in a population of urban, low-income, predominately black men and women. The participants were also chosen based on purposive sampling. Purposive sampling involves the deliberate selection of individuals by the researcher based on predefined criteria. (Depoy pg 153). Participants were asked to self-identify their race/ethnicity based on common categories such as black, white, Hispanic/Latino, Asian, mixed or other. The data collected in this study was based on screen interviews. Screen interviews were given to the 900 participants while they sat in a waiting room at a hospital. Approximately 58% of those approached to participate in the study agreed to do so. (JAMA 2008) Participants completed a battery self-report which measured trauma history and symptoms. They were paid $15 for participating in the study and providing a saliva sample for DNA extraction. Written and verbal consent was obtained for all participants, and all procedures were approved by review boards of Emory University. The rights of the participants were protected and all information was kept private in concordance with health laws and practices. Findings in this research study include that levels of child abuse and non-child abuse trauma each independently predicted the level of adult PTSD systemically. FKBP5 did not directly predict the level of PTSD symptoms or interact with the level of non-child abuse trauma to predict PTSD symptoms. SNP within the FKBP5 locus greatly interacted with the level of child abuse to predict the level of adult PTSD symptoms. The most important finding was the interaction between FKBP5 and child abuse history to predict the levels of adult PTSD symptoms. The findings were adequate to accept the hypothesis that FKBP5 may enhance the effects of Cortisol, following child abuse on FKBP5. Meaning alterations of HPA axis responsiveness has been identified as risk factors for PTSD. Descriptive analysis and statistics were used; they include analyzing non child abuse trauma exposure and PTSD symptoms. This was done by using general linear models using PSS (PTSD Symptom Scale) total scores as a dependent variable and the TEI (Traumatic events inventory) categorical variable representing number of types of non-child abuse/traumatic experience as the independent variable. The linear model showed the presence of type 1 (non-abuse) increased the PSS score at each non-child abuse trauma level by 4.58 pts on average of (2.05-6.51). The presence of type 2 child abuse (physical and sexual) increased the PSS score to 9.04 on average of (7.79-10.20). Findings were not surprising; children who were not abused had lower trauma levels than those who did experience abuse. There were limitations and weaknesses in this study. 1.) Researchers could not present an independent replication so the level of validation could only be considered hypothesis generating. This s called construct validity, where a researcher has developed a theoretical rationale underlying the test instrument. The researcher attempted to construct validity based on the effects of polymorphisms in the DST (Dexamethasone suppression test) to strengthen their findings. 2.) History was affected based on external events on the study outcome. The lack of ancestry informative marker data on the complete sample was a limitation to the study. The results are not likely due to the population structure since ancestry is not known. Researchers should make their focus more broad when basing it on abuse. Abuse is a worldwide epidemic and should be looked at from a universal standpoint and not just based on one culture. 3.) Testing was also a limitation. Testing is the effect of being observed or tested on the study outcome. (Depoy pg 83). DNA was available for 762 individuals, of the 762; there were 138 with no genotype information. Eleven of the participants did not have any DNA collected, 88 attempted to collect using spit samples but DNA extraction failed completely in 2. Testing sites should have been set up along with days and times for participants to sign up. This method would have allowed for all participants to be evaluated on an equal basis. 4.) The PSS test is a self-report, over a two week period, where participants were asked a series of questions on abuse. This test is not valid because participants may not provide valid events and/ or may not recall them. Also, not all events may have been reported due to embarrassment if it was too traumatic. “We examined 8 SNPs spanning 120 of the FKBP5 locus but found no significant main effect of FKBP5 genotypes on PSS total score.” (JAMA 2008.) There were threats to external validity in this study. The ability to generalize from a study sample to the population from which the sample was derived is referred to as external validity. (Depoy pg 130). The researchers here bound their study to low-income, urban black families instead of families in general, and not dependent on race. “The sample derived from primarily impoverished, inner-city outpatient, primary care clinics and participants were not presenting for treatment for PTSD so that researchers can not directly generalize their findings to a clinical or epidemiological setting. There were strengths in this research study as well. 1.) The level of knowledge was impressive in evaluating association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. The research method used was accurate for the population. The intent of ethnography is to understand the underlying patterns of behavior and the meanings of culture. Through extended observation of African Americans 18-81 years of age, on child abuse and its effect on FKBP5 and PTSD, the ethnographer seeks to understand rules of behavior and pattern within this community. 2.) Data was credible and collected on many different levels by interviewing participants using: ∙ Screen interviews ∙ Self-reports ∙ DNA extractions, PSS Scale, Beck depression used for depressive symptoms ∙ Childhood trauma questionnaire ∙ Dexamethasone Suppression test ∙ SNP genotyping ∙ Ancestry Information markers There were many different analysis types used in this study to see if FKBP5 varied. 3.) In the discussion, researchers efficiently translated meanings and terminology. They were also careful to represent the meanings and intent of expression accurately in translating data. For example, the reader may not have known that stress gene FKBP5 and high expressions of it associate with GR resistance. GR resistance was explained to be a receptor that binds to cells that controls a wide variety of processes, including development. Implications/Conclusions The implications of this study were to increase understanding of genetic and environmental risk factors and their interaction in the development of PTSD. Results supported the hypothesis that Glucocorticoid Response system moderates the effects of early lifestyles on adult PTSD symptoms. The GR hypersensitivity may be important in the pathophysiology of PTSD. The results were determined from a clinical sense, according to box 10-3 on pg 119 Depoy. Jargon was avoided, and the purpose was specified. The purpose was to measure gene variation of FKBP5 due to child abuse and its relation to PTSD. Results The results show that genes can be influenced by environmental factors such as child abuse, trauma and serving time in combat. These environmental factors can have a negative effect on a child into adulthood resulting in PTSD. Conducting research on genetics based on environmental factors is not easy; everyone has their own unique DNA and handles traumatizing events differently. The research process and results of this study helps to predict who is at risk of developing PTSD based on variations in the gene FKBP5 along with other assays and tests. Understanding how genes and their environment interact affects mental health and can help researchers to develop more accurate methods to cope with or rehabilitate those suffering from PTSD. PTSD is not a cultural dilemma but a quiet and well-known disorder many suffer with. References Binder, B. Elisabeth MD, PhD and Rebekah, D. Bradley PhD. “Association of FKBP5 Polymorphisms and Childhood Abuse with Risk of Posttraumatic Stress Disorder.” (2008) Vol. 299 No. 11 Retrieved April 8, 2008 from: jamaabuse1.doc Depoy, Elizabeth. & Laura N. Gitlin. Introduction to Research: “Understanding and Applying Multiple Strategies.” (2005). Elsevier Mosby Pub St. Louis, MI pgs. 83-325 Port, Tami. Genetics of Anxiety Disorder: “Post Stress-Related Gene May Help explain Traumatic Stress.” (2008). Retrieved April 11, 2008 from: http://geneticsrevolution.suite101.com/article.cfm/genetics_of_anxiety_disorder_ptsd National Center for Post Traumatic Stress Disorder (2008). “What is Posttraumatic Stress Disorder'” Retrieved April 11, 2008 from: http://www.ncptsva.gov/ncmain/ncdocs/fact_shts/fs_what_is_ptsd.htm Internet web address for research article: jamaabuse1.doc