Genetic variation is associated with PTSD risk and aversive memory: Evidence from two trauma-Exposed African samples and one healthy European sample.

The probability to develop posttraumatic stress disorder (PTSD), characterized by vivid, intrusive emotional memories of the encountered traumatic events, depends - among other factors - on the number of previous traumatic experiences (traumatic load) and individual genetic vulnerability. So far, our knowledge regarding the biological underpinnings of PTSD is relatively sparse. Genome-wide association studies (GWAS) followed by independent replication might help to discover novel, so far unknown biological mechanisms associated with the development of traumatic memories. Here, a GWAS was conducted in N = 924 Northern Ugandan rebel war survivors and identified seven suggestively significant single nucleotide polymorphisms (SNPs; p ≤ 1 × 10-5) for lifetime PTSD risk. Of these seven SNPs, the association of rs3852144 on chromosome 5 was replicated in an independent sample of Rwandan genocide survivors (N = 370, p < .01). While PTSD risk increased with accumulating traumatic experiences, the vulnerability was reduced in carriers of the minor G-allele in an additive manner. Correspondingly, memory for aversive pictures decreased with higher number of the minor G-allele in a sample of N = 2698 healthy Swiss individuals. Finally, investigations on N = 90 PTSD patients treated with Narrative Exposure Therapy indicated an additive effect of genotype on PTSD symptom change from pre-treatment to four months after treatment, but not between pre-treatment and the 10-months follow-up. In conclusion, emotional memory formation seems to decline with increasing number of rs3852144 G-alleles, rendering individuals more resilient to PTSD development. However, the impact on therapy outcome remains preliminary and further research is needed to determine how this intronic marker may affect memory processes in detail.

Does trauma event type matter in the assessment of traumatic load?

Background: The likelihood of developing Posttraumatic Stress Disorder (PTSD) depends on the interaction of individual risk factors and cumulative traumatic experiences. Hence, the identification of individual susceptibility factors warrants precise quantification of trauma exposure. Previous research indicated that some traumatic events may have more severe influences on mental health than others; thus, the assessment of traumatic load may be improved by weighting event list items rather than calculating the simple sum score. Objective: We compared two statistical methods, Random Forests using Conditional Interference (RF-CI) and Least Absolute Shrinkage and Selection Operator (LASSO), based on their ability to rank traumatic experiences according to their importance for predicting lifetime PTSD. Methods: Statistical models were initially fitted in a sample of N1 = 441 survivors of the Northern Ugandan rebel war. The ability to correctly predict lifetime PTSD was then tested in an independent sample of N2 = 211, and subsequently compared with predictions by the simple sum score of different traumatic event types experienced. Results: Results indicate that RF-CI and LASSO allow for a ranking of traumatic events according to their predictive importance for lifetime PTSD. Moreover, RF-CI showed slightly better prediction accuracy than the simple sum score, followed by LASSO when comparing prediction results in the validation sample. Conclusion: Given the expense in time and calculation effort by RF-CI and LASSO, and the relatively low increase in prediction accuracy by RF-CI, we recommend using the simple sum score to measure the environmental factor traumatic load, e.g., in analyses of gene × environment interactions.

The role of memory-related gene WWC1 (KIBRA) in lifetime posttraumatic stress disorder: evidence from two independent samples from African conflict regions.

BACKGROUND: Posttraumatic stress disorder (PTSD) results from the formation of a strong memory for the sensory-perceptual and affective representations of traumatic experiences, which is detached from the corresponding autobiographical context information. Because WWC1, the gene encoding protein KIBRA, is associated with long-term memory performance, we hypothesized that common WWC1 alleles influence the risk for a lifetime diagnosis of PTSD. METHODS: Traumatic load and diagnosis of current and lifetime PTSD were assessed in two independent African samples of survivors from conflict zones who had faced severe trauma (n = 392, Rwanda, and n = 399, Northern Uganda, respectively). Array-based single nucleotide polymorphism (SNP) genotyping was performed. The influence of WWC1 tagging SNPs and traumatic load on lifetime PTSD was estimated by means of logistic regression models with correction for multiple comparisons in the Rwandan sample. Replication analysis was performed in the independent Ugandan sample. RESULTS: An association of two neighboring SNPs in almost complete linkage disequilibrium, rs10038727 and rs4576167, with lifetime PTSD was discovered in the Rwandan sample. Although each traumatic event added to the probability of lifetime PTSD in a dose-dependent manner in both genotype groups, carriers of the minor allele of both SNPs displayed a diminished risk (p = .007, odds ratio = .29 [95% confidence interval = .15-.54]). This effect was confirmed in the independent Ugandan sample. CONCLUSIONS: This study reveals an association between two WWC1 SNPs and the likelihood of PTSD development, indicating that this memory-related gene might be involved in processes that occur in response to traumatic stress and influence the strengthening of fear memories.

A pilot study on community-based outpatient treatment for patients with chronic psychotic disorders in Somalia: Change in symptoms, functioning and co-morbid khat use.

BACKGROUND: In Low and Middle Income Countries, mental health services are often poorly developed due to the lack of resources and trained personnel. In order to overcome these challenges, new ways of care have been suggested such as a focus on community-based services. In Somalia, the consumption of the natural stimulant khat is highly prevalent, aggravating mental illness. At the same time, mental health care is largely unavailable to the vast majority of the population. In a pilot project, we tested possibilities for effective measures in community-based out-patient mental health care. METHODS: Thirty-five male patients with chronic psychotic disorders and their carers were involved in a 10-months follow-up study. All of them abused khat. Seventeen outpatients experiencing acute psychotic episodes were recruited from the community and received an intensive six week home-based treatment package. Additionally eighteen patients with chronic psychotic disorders in remission were recruited either following hospital discharge or from the community. In a second phase of the study, both groups received community-based relapse prevention that differed in the degree of the family's responsibility for the treatment. The treatment package was comprised of psycho-education, low-dose neuroleptic treatment, monthly home visits and counseling. The Brief Psychiatric Rating Scale (BPRS) was applied three times. Additionally, we assessed functioning, khat use and other outcomes. RESULTS: Of the 35 patients enrolled in the study, 33 participated in the 10-month follow-up. Outpatients improved significantly in the first six weeks of treatment and did not differ from remitted patients at the start of the second treatment phase. In the preventive treatment phase, we find heterogeneous outcomes that diverge between symptom and functioning domains. With the exception of depressive symptoms, symptoms in all patients tended to worsen. The outpatient group had higher BPRS positive and negative symptom scores compared to the remitted group. Levels of functioning in 20 out of 33 patients significantly improved, with small differences between groups. Most patients experienced improvements in basic functioning, such as communication, self-care etc. Khat use could only be reduced in the group of outpatients. CONCLUSIONS: Community-based out-patient mental health treatment for chronic psychotic disorders has demonstrated positive effects in Somalia and is both feasible and practical, despite facing formidable challenges, e.g. controlling khat intake.

Screening for posttraumatic stress disorder among Somali ex-combatants: a validation study.

BACKGROUND: In Somalia, a large number of active and former combatants are affected by psychological problems such as Posttraumatic Stress Disorder (PTSD). This disorder impairs their ability to re-integrate into civilian life. However, many screening instruments for Posttraumatic Stress Disorder used in post-conflict settings have limited validity. Here we report on development and validation of a screening tool for PTSD in Somali language with a sample of ex-combatants. METHODS: We adapted the Posttraumatic Diagnostic Scale (PDS) to reflect linguistic and cultural differences within the Somali community so that local interviewers could be trained to administer the scale. For validation purposes, a randomly selected group of 135 Somali ex-combatants was screened by trained local interviewers; 64 of them were then re-assessed by trained clinical psychologists using the Composite International Diagnostic Interview (CIDI) and the Self-Report Questionnaire (SRQ-20). RESULTS: The screening instrument showed good internal consistency (Cronbach's alpha = .86), convergent validity with the CIDI (sensitivity = .90; specificity = .90) as well as concurrent validity: positive cases showed higher SRQ-20 scores, higher prevalence of psychotic symptoms, and higher levels of intake of the local stimulant drug khat. Compared to a single cut-off score, the multi-criteria scoring, in keeping with the DSM-IV, produced more diagnostic specificity. CONCLUSION: The results provide evidence that our screening instrument is a reliable and valid method to detect PTSD among Somali ex-combatants. A future Disarmament, Demobilization and Reintegration Program in Somalia is recommended to screen for PTSD in order to identify ex-combatants with special psycho-social needs.

Khat use as risk factor for psychotic disorders: a cross-sectional and case-control study in Somalia.

BACKGROUND: Little is known about the prevalence of khat-induced psychotic disorders in East African countries, where the chewing of khat leaves is common. Its main psycho-active component cathinone produces effects similar to those of amphetamine. We aimed to explore the prevalence of psychotic disorders among the general population and the association between khat use and psychotic symptoms. METHODS: In an epidemiological household assessment in the city of Hargeisa, North-West Somalia, trained local interviewers screened 4,854 randomly selected persons from among the general population for disability due to severe mental problems. The identified cases were interviewed based on a structured interview and compared to healthy matched controls. Psychotic symptoms were assessed using the items of the WHO Composite International Diagnostic Interview and quantified with the Positive and Negative Symptoms Scale. Statistical testing included Student's t-test and ANOVA. RESULTS: Local interviewers found that rates of severe disability due to mental disorders were 8.4% among males (above the age of 12) and differed according to war experiences (no war experience: 3.2%; civilian war survivors: 8.0%; ex-combatants: 15.9%). The clinical interview verified that in 83% of positive screening cases psychotic symptoms were the most prominent manifestations of psychiatric illness. On average, cases with psychotic symptoms had started to use khat earlier in life than matched controls and had been using khat 8.6 years before positive symptoms emerged. In most cases with psychotic symptoms, a pattern of binge use (> two 'bundles' per day) preceded the onset of psychotic symptoms, in contrast to controls of the same age. We found significant correlations between variables of khat consumption and clinical scales (0.35 to 0.50; p < 0.05), and between the age of onset of khat chewing and symptom onset (0.70; p <0.001). CONCLUSION: Evidence indicates a relationship between the consumption of khat and the onset of psychotic symptoms among the male population, whereby not the khat intake per se but rather early onset and excessive khat chewing seemed to be related to psychotic symptoms. The khat problem must be addressed by means other than prohibition, given the widespread use and its role in Somali culture.