Genes -- later trauma response --- elusive search for link
Jan 3, 2013
It has long, and naturally, been thought that the reason individuals differ in their response to potentially traumatising experiences lies in different individuals different genetic makeup. However, the search continues for what precise mechanisms are involved in this process, exemplified by recent studies discussed in this post.
Firstly, in the attached brief article [LINK] John Pearson, of the Biostatistics and Computational Biology Unit, University of Otago, Christchurch, New Zealand, discusses how one possible "candidate" for the gene involved has surprisingly, at least in the sample studied, NOT been found to be involved:
From the paper: "we do not find strong evidence in support of the reported GE (Gene by Environment interaction) effect of rs1049353 (a formerly proposed gene responsible for the effect) and childhood physical abuse on MDD in CNR1 (genetic sub-set of the overall sample group),either in the CHDS (Christchurch Health Sample) or in the combined datasets. The equivalent result for lifetime depression with anhedonia also requires replication and examination in a genome wide context." At least on the basis of this study: "the hunt continues!" In this study the effect being looked at was the contribution of childhood physical abuse on increasing the chances of later-age depression.
The complex interplay of the three factors: genetic vulnerability, life event, and disorder-specific dynamics is further examined in a study by Uddin and colleagues from the Center for Molecular Medicine and Genetics, at Wayne State University School of Medicine, in Detroit, Michigan, USA. A growing literature indicates that genetic variation, in combination with adverse early life experiences, shapes risk for later mental illness. Recent work also suggests that molecular variation at the ADCYAP1R1 locus is associated with posttraumatic stress disorder (PTSD) in women. Uddin et al sought to test whether childhood maltreatment (CM) interacts with ADCYAP1R1 genotype to predict PTSD in women. Data were obtained from 495 adult female participants from the Detroit Neighborhood Health Study. Genotyping of rs2267735, an ADCYAP1R1 variant, was conducted via TaqMan assay. PTSD, depression, and CM exposure were assessed via structured interviews. Main and interacting effects of ADCYAP1R1 and CM levels on past month PTSD and post-traumatic stress (PTS) severity were examined using logistic regression and a general linear model, respectively. As a secondary analysis, the researchers also assessed main and interacting effects of ADCYAP1R1 and CM variation on risk of past-month depression diagnosis and symptom severity. No significant main effects were observed for ADCYAP1R1 genotype on either PTSD/PTS severity. In contrast, a significant ADCYAP1R1 × CM interaction was observed for both past month PTSD and PTS severity, with carriers of the “C” allele showing enhanced risk for these outcomes among women exposed to CM. No significant main or interaction effects were observed for past month depression/depression severity. Uddin et al conclude: Genetic variation at the ADCYAP1R1 locus interacts with CM to shape risk of later PTSD, but not depression, among women.
Another study (brief overview attached [LINK], this time by Wichers, of the Department of Psychiatry and Psychology, South Limberg Mental Health Research and Teaching Network, EURON, Maastricht University, The Netherlands, looks at how statistical model-fitting suggests reciprocal causation and shared influences between depressive symptoms and negative life events. Not surprisingly, but "refreshingly" (from my viewpoint) this study came to the conclusion: "The inter-relationship between depressive symptoms and negative life events is complex and varies across genetic, environmental and individual specific effects. Both reciprocal causation and shared latent influences contribute to the relationship".
I'd be amongst the first to say that I don't understand the finer points of these studies, and say I cannot comment on any methodological strengths or weaknesses they may have. However, I would caution against the simplistic drawing of conclusions that any particular genetic makeup "causes" specific pathology, and encourage people to be aware of the fallacies inherent in "Biologism" [LINK] but with the sorts of theoretical caveats Hayes talks about in mind, I admire this sort of research -- it seeks after all, to make the best use of the latest advances in science to improving the human condition; so long as human beings are not "mechanised" in the process, and so long as other "softer" sciences are enabled to play their role.
The sorts of research being carried out by Pearson, Uddin, and Wichers can be considered as part of "pharmacogenomics" -- the study of how an individual's genetic inheritance affects the body's response to drugs (both existing and new drugs based on the sorts of research understandings made by possible by the studies of Pearson and others). The term comes from the words pharmacology and genomics and is thus the intersection of pharmaceuticals and genetics. See here [LINK] and for a guide to local research (in New Zealand) here [LINK]