[Psychosomatic health inventory: Basic psychosomatic documentation for quality assurance inpatient care]. / Gesundheitsinventar Psychosomatik: Psychosomatische Basisdokumentation zur Qualitätssicherung im stationären Alltag.

Objectives: As part of the quality assurance of inpatient treatment, the severity of the disease and the course of therapy must be mapped. However, there is a high degree of heterogeneity in the implementation of basic diagnostics in psychosomatic facilities.There is a lack of scientifically based standardisation in determining the quality of outcomes. Methods: With the help of scientifically established test instruments, a resource-saving basic documentation instrument was developed. Many existing psychometric instruments were checked for test quality, costs and computer-supported application. Results: The Psychosomatic Health Inventory (gi-ps) consists of three basic modules with a total of 63 items: sociodemography, screening and psychosomatic health status.The latter is represented bymeans of construct-based recording on eight scales. Its collection at admission and discharge allows the presentation of the quality of outcomes.The development of a proprietary software solution with LimeSurvey enables the computer-based collection, evaluation, and storage of data. A list of test inventories for confirming diagnoses and predictors has been compiled, which are recommended for use in clinical routine. Discussion: With the gi-ps, a modular basic documentation instrument including the software solution is available to all interested institutions free of charge.

Serotonin transporter gene methylation predicts long-term cortisol concentrations in hair.

Epigenetic signatures, such as DNA methylation (DNAM), have been implicated in long-term dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis and related health risks. Based on a wealth of neuroendocrine studies on genetic polymorphisms in the serotonin transporter gene (SLC6A4), this locus constitutes a key candidate to explore associations of DNAM patterns and HPA-axis functioning. The few studies addressing this link so far exclusively relied on spot measurements of HPA-axis activity, which may not adequately reflect cortisol output over prolonged periods of time. To address this gap, hair cortisol concentrations (HCC), a valid measure of integrated long-term cortisol levels, were utilized to investigate endocrine correlates of SLC6A4 DNAM in 183 adults. Whole blood samples were drawn for DNAM analyses of 83 CpG sites within a 799-bp promoter-associated CpG island of SLC6A4 via bisulfite pyrosequencing. In addition, all participants were genotyped for the serotonin transporter polymorphism (5-HTTLPR). First, results revealed a significant negative association of SLC6A4 DNAM and HCC. Second, there was no significant main effect of 5-HTTLPR genotype on HCC when analyses were conducted on the basis of both bi-allelic classification and the 5-HTTLPR/rs25531 mini-haplotype. Third, the current data revealed a significant interaction of SLC6A4 DNAM and 5-HTTLPR genotype on HCC. Comparable to the pattern we had previously observed concerning cortisol stress reactivity, the S allele relates to increased HCC in individuals displaying low levels of SLC6A4 DNAM. By contrast, no such effect occurred under conditions of high SLC6A4 DNAM, indicating that epigenetic changes may compensate for genotype-dependent differences in long-term cortisol output. Together, respective findings support the idea of an epigenetic contribution to long-term HPA-axis activity and further highlight the usefulness of combining genetic and epigenetic information in future neuroendocrine studies.

Glucocorticoid receptor gene methylation moderates the association of childhood trauma and cortisol stress reactivity.

Exposure to childhood trauma (CT) has been linked to sustained dysregulations of major stress response systems, including findings of both exaggerated and attenuated hypothalamus-pituitary-adrenal (HPA) axis activity. Likewise, CT constitutes a common risk factor for a broad range of psychiatric conditions that involve distinct neuroendocrine profiles. In this study, we investigated the role of epigenetic variability in a stress-related gene as a potential mediator or moderator of such differential trajectories in CT survivors. For this, we screened adult volunteers for CT and recruited a healthy sample of 98 exposed (67 with mild-moderate, 31 with moderate-severe exposure) and 102 control individuals, with an equal number of males and females in each group. DNA methylation (DNAM) levels of the glucocorticoid receptor exon 1F promoter (NR3C1-1F) at functionally relevant sites were analyzed via bisulfite pyrosequencing from whole blood samples. Participants were exposed to a laboratory stressor (Trier Social Stress Test) to assess salivary cortisol stress responses. The major finding of this study indicates that DNAM in a biologically relevant region of NR3C1-1F moderates the specific direction of HPA-axis dysregulation (hypo- vs. hyperreactivity) in adults exposed to moderate-severe CT. Those trauma survivors with increased NR3C1-1F DNAM displayed, on average, 10.4 nmol/l (62.3%) higher peak cortisol levels in response to the TSST compared to those with low DNAM. In contrast, unexposed and mildly-moderately exposed individuals displayed moderately sized cortisol stress responses irrespective of NR3C1-1F DNAM. Contrary to some prior work, however, our data provides no evidence for a direct association of CT and NR3C1-1F DNAM status. According to this study, epigenetic changes of NR3C1-1F may provide a more in-depth understanding of the highly variable neuroendocrine and pathological sequelae of CT.

Current developments and controversies: does the serotonin transporter gene-linked polymorphic region (5-HTTLPR) modulate the association between stress and depression?

PURPOSE OF REVIEW: Human observational studies have shown that, in interaction with life stress, the short or S-allele of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) is associated with an enhanced risk for depression. However, this gene-by-environment interaction (G×E) has recently been questioned by two meta-analyses. We aim to provide an overview and appraisal of recent developments and controversies. RECENT FINDINGS: The statistical approach of the meta-analyses aimed at a very strict replication of the initial finding and, accordingly, included only a minority of all available studies. Furthermore, the negative results of the meta-analyses appear to be predominantly driven by a few large studies that used retrospective, self-report measures of life stress. In contrast, among 19 studies using interview-based or more objective measures of stress, there were 13 replications, five part-replications and only one nonreplication. Finally, a broader approach based on evidence from different research fields and methodologies supports a 5-HTTLPR by stress interaction. SUMMARY: Whereas there is no doubt that the meta-analyses are methodologically sound, it appears that this technique is only in part suitable for appraising all of the available evidence. Furthermore, convergent evidence is accumulating from different research fields that 5-HTTLPR is indeed closely associated with different biological pathways associated with stress regulation and depression.

Serotonin transporter gene-linked polymorphic region (5-HTTLPR) and diurnal cortisol: A sex by genotype interaction.

In interaction with stressful life events, the serotonin transporter gene-linked polymorphic region (5-HTTLPR) is associated with depression. In response to stress, the hypothalamic-pituitary-adrenal (HPA) axis is activated. HPA activity is often increased in depression. Thus, one potential mechanism by which 5-HTTLPR might increase risk for depression is by its impact on HPA activity. We examined the effects of 5-HTTLPR on diurnal saliva cortisol secretion (0800 h, 1200 h, 1600 h, 2200 h) in 130 healthy adults (66 men, 64 women) equally distributed across four age groups (30-70 years) using the tri-allelic classification [high-expressing (LA/LA), intermediate-expressing (LG/LA, LA/S), low-expressing (S/S, S/LG)]. We found a significant sex by 5-HTTLPR interaction on cortisol secretion. In men, higher cortisol levels were associated with lower transcriptional activity of 5-HTTLPR, whereas no such trend was observed in women. Our results suggest that men and women differ in serotonergic mediation of HPA-axis activity. This might contribute to sex-specific risk for depression.