FKBP5 intron 7 methylation is associated with higher anxiety proneness and smaller right thalamus volume in adolescents.

Dysregulation of stress response systems may mediate the detrimental effects of childhood trauma (CT) on mental health. FKBP5 regulates glucocorticoid receptor sensitivity and exerts pleiotropic effects on intracellular signaling, neurobiology and behavior. We investigated whether CT, alone and in combination with rs1360780 genotype, is associated with altered FKBP5 methylation and whether CT-associated methylation profiles are associated with anxiety proneness (AP) and structural brain volumes. Ninety-four adolescents completed the Childhood Trauma Questionnaire, and a composite AP score was generated from the Childhood Anxiety Sensitivity Index and the State-Trait Anxiety Inventory-Trait measure. Mean methylation values for 12 regulatory regions and 25 individual CpG sites were determined using high-accuracy measurement via targeted bisulfite sequencing. FKBP5 rs1360780 genotype and structural MRI data were available for a subset of participants (n = 71 and n = 75, respectively). Regression models revealed an inverse association between methylation of three intron 7 CpG sites (35558438, 35558566 and 35558710) and right thalamus volume. CpG35558438 methylation was positively associated with AP scores. Our data indicate that an intron 7 methylation profile, consistent with lower FKBP5 expression and elevated high sensitivity glucocorticoid receptor levels, is associated with higher AP and smaller right thalamus volume. Research into the mechanisms underlying the intron 7 methylation-thalamus volume relationship, and whether it confers increased risk for long-term psychopathology by altering the regulatory threshold of stress responding, is required.

Evaluating the Rising Incidence of Thyroid Cancer and Thyroid Nodule Detection Modes: A Multinational, Multi-institutional Analysis.

Importance: There is epidemiologic evidence that the increasing incidence of thyroid cancer is associated with subclinical disease detection. Evidence for a true increase in thyroid cancer incidence has also been identified. However, a true increase in disease would likely be heralded by an increased incidence of thyroid-referable symptoms in patients presenting with disease. Objectives: To evaluate whether modes of detection (MODs) used to identify thyroid nodules for surgical removal have changed compared with historic data and to determine if MODs vary by geographic location. Design, Setting, and Participants: This was a retrospective analysis of pathology and medical records of 1328 patients who underwent thyroid-directed surgery in 16 centers in 4 countries: 4 centers in Canada, 1 in Denmark, 1 in South Africa, and 12 in the US. The participants were the first 100 patients (or the largest number available) at each center who had thyroid surgery in 2019. The MOD of the thyroid finding that required surgery was classified using an updated version of a previously validated tool as endocrine condition, symptomatic thyroid, surveillance, or without thyroid-referable symptoms (asymptomatic). If asymptomatic, the MOD was further classified as clinician screening examination, patient-requested screening, radiologic serendipity, or diagnostic cascade. Main Outcomes and Measures: The MOD of thyroid nodules that were surgically removed, by geographic variation; and the proportion and size of thyroid cancers discovered in patients without thyroid-referable symptoms compared with symptomatic detection. Data analyses were performed from April 2021 to February 2022. Results: Of the 1328 patients (mean [SD] age, 52 [15] years; 993 [75%] women; race/ethnicity data were not collected) who underwent thyroid surgery that met inclusion criteria, 34% (448) of the surgeries were for patients with thyroid-related symptoms, 41% (542) for thyroid findings discovered without thyroid-referable symptoms, 14% (184) for endocrine conditions, and 12% (154) for nodules with original MOD unknown (under surveillance). Cancer was detected in 613 (46%) patients; of these, 30% (183 patients) were symptomatic and 51% (310 patients) had no thyroid-referable symptoms. The mean (SD) size of the cancers identified in the symptomatic group was 3.2 (2.1) cm (median [range] cm, 2.6 [0.2-10.5]; 95% CI, 2.91-3.52) and in the asymptomatic group, 2.1 (1.4) cm (median [range] cm, 1.7 [0.05-8.8]; 95% CI, 1.92-2.23). The MOD patterns were significantly different among all participating countries. Conclusions and Relevance: This retrospective analysis found that most thyroid cancers were discovered in patients who had no thyroid-referable symptoms; on average, these cancers were smaller than symptomatic thyroid cancers. Still, some asymptomatic cancers were large, consistent with historic data. The substantial difference in MOD patterns among the 4 countries suggests extensive variations in practice.

Genetic variation in neuropeptide Y interacts with childhood trauma to influence anxiety sensitivity.

BACKGROUND AND OBJECTIVES: Anxiety sensitivity (AS) refers to a fear of the negative implications of anxiety, and arises due to gene-environment interactions. We investigated whether genetic variation in two neuropeptides implicated in the stress response, neuropeptide Y (NPY) and pituitary adenylate cyclase-activating polypeptide receptor 1, interacted with childhood trauma (CT) to influence AS. DESIGN AND METHODS: This cross-sectional study examined the CT x genetic variant effects on AS in 951 adolescents who self-identified as Xhosa or South African Colored (SAC) ethnicity. RESULTS: In Xhosa females, the NPY rs5573 A allele and rs3037354 deletion variant were associated with increased (p = 0.035) and decreased (p = 0.034) AS, respectively. The interaction of CT and the NPY rs5574 A allele increased AS in SAC female participants (p = 0.043). The rs3037354 deletion variant protected against AS with increased CT in SAC male participants (p = 0.011). CONCLUSIONS: The NPY rs5574 A allele and rs3037354 deletion variant interact with CT to act as risk and protective factors, respectively, for AS in an ethnicity- and sex- differentiated manner. Our results reaffirm the role of NPY and gene-environment interactions in anxiety-related behaviors and reinforce the need for psychiatric genetics studies in diverse populations.

Anxiety: An overlooked confounder in the characterisation of chronic stress-related conditions?

Although anxiety disorders are among the most prevalent of psychiatric disorders, childhood trauma-related studies seldom consider anxiety proneness as distinct aetiological contributor. We aimed to distinguish between trauma- and anxiety-associated physiological profiles. South African adolescent volunteers were categorised for trauma exposure (CTQ, mean score 39±11) and anxiety proneness (AP)(CASI, mean score 37±7, STAI-T, mean score 41±8). Circulating hormone and leukocyte glucocorticoid receptor levels, as well as leukocyte functional capacity, were assessed. AP was associated with lower DHEAs (P<0.05) and higher leukocyte GR expression (P<0.05). DHEAs was also negatively correlated with anxiety sensitivity (CASI, P<0.05). In conclusion, AP may have more predictive power than trauma in terms of health profile. Increased glucocorticoid sensitivity previously reported after trauma, may be a unique function of anxiety and not trauma exposure per se. DHEAs concentration was identified as potentially useful marker for monitoring progressive changes in HPA-axis sensitivity and correlated with psychological measures of anxiety.

Differences in Abuse, Neglect, and Exposure to Community Violence in Adolescents With and Without PTSD and Depression.

South African adolescents are exposed to high levels of violence and trauma, including community violence, abuse, and neglect. Violence and trauma are associated with negative mental health outcomes, including posttraumatic stress disorder (PTSD) and depression. Demographic characteristics, additional exposure to trauma, community violence, and types of childhood abuse and neglect may place adolescents at greater risk of developing PTSD. This study aimed to first assess the weighted contribution of demographic factors, trauma load, community violence, and types of abuse and neglect in predicting PTSD symptom severity. Second, we aimed to determine group differences in demographic factors, trauma load, community violence, and types of abuse and neglect among participants with no disorder, PTSD only, PTSD and depression, and depression only. Participants were 215 adolescents identified with emotional and/or behavioral problems and referred to an adolescent trauma clinic from schools in the Western Cape region of South Africa. Clinical assessments were undertaken to assess community violence exposure; physical, sexual, and emotional abuse; physical and emotional neglect; and a clinical diagnosis of PTSD and comorbidity. Trauma-exposed adolescents with PTSD and depression reported significantly higher levels of emotional abuse and community violence exposure in comparison with trauma-exposed adolescents without a disorder. Emotional abuse, community violence exposure, and female gender were significant predictors of PTSD in regression analysis. These findings underscore the contribution of different types of trauma in the development of PTSD. Interventions focused on preventing trauma, PTSD, and depression should be multifaceted and be targeted at various levels, for example, individual/interpersonal level (reduce abuse in the household and immediate environment) and community/societal level (reduce crime rates in communities and strengthen conviction policies). Traumatized youth should routinely be screened for a history of abuse and particularly exposure to community violence, given their strong association with PTSD.

The effects of childhood maltreatment and anxiety proneness on neuropsychological test performance in non-clinical older adolescents.

BACKGROUND: The effect of childhood maltreatment (CM) on neuropsychological performance is well established, but the effect of anxiety proneness (AP) on such performance has been underexplored. We assessed the predictive ability of CM and AP, and their interaction, in non-clinical adolescents, for a range of previously documented neuropsychological deficits. METHODS: Multiple linear regression models were used to assess the unique and combined influences of CM and AP on neuropsychological performance in 104 non-clinical adolescents, who underwent both neuropsychiatric and neuropsychological assessment. RESULTS: The interaction of CM and AP was associated with poorer performance in executive functioning skills, processing speed, and estimated IQ. CM and AP were uniquely associated with verbal working memory performance, while verbal and visual memory performance and learning, and visuo-spatial ability, were not associated with either CM, AP or the interaction of CM and AP. LIMITATIONS: The use of self-report measures to determine participants' levels of CM, AP, and depression. The CTQ-SF, a retrospective self-report measure, may have introduced recall bias. The neuropsychological evaluation was not conducted in the Xhosa language, the first language of most African participants. Most instruments utilized have not been validated in a South African adolescent sample. The impact of important moderator variables (e.g., age of onset of maltreatment) was not assessed. CONCLUSIONS: Increased levels of CM and AP may be risk markers for poor performance in several key neuropsychological domains. Our findings underscore the importance of assessing the impact of both CM and anxiety-related temperamental traits on neuropsychological performance.

Relationship between childhood abuse and substance misuse problems is mediated by substance use coping motives, in school attending South African adolescents.

BACKGROUND: In adults, it has been shown that the relationship between childhood abuse and substance misuse problems is mediated by the belief that substance use helps cope with negative affective states. By contrast, in adolescents, it is unknown whether drug use coping motives play this same mediating role. METHODS: Secondary analysis of 1149 school attending adolescents in Cape Town, South Africa (average age = 16.24 years, range = 13-23; 60% female). Questionnaire measures obtained during a single test session (among a larger battery) assessed childhood trauma (CTQ), alcohol (AUDIT) and drug problems (DUDIT), and coping orientation (A-COPE) which contained three items assessing drug use to cope with negative affect. RESULTS: The three types of childhood abuse measured by the CTQ - emotional, physical and sexual - were positively associated with greater alcohol/drug problems, and drug use coping motives. Drug use coping motives mediated the relationships between childhood abuse types and alcohol/drug problems, and these mediational pathways remained significant when gender and other subscales of the A-COPE were included as covariates. CONCLUSIONS: These data are preliminary insofar as drug use coping motives were assessed with a non-validated subscale of the A-COPE. Nevertheless, drug use to cope with negative affect mediated the relationship between all three types of childhood abuse (emotional, physical, sexual) and alcohol/drug problems in school attending adolescents. The implication is that drug prevention programs for this risk group should seek to mitigate drug use coping motives.

No gene-by-environment interaction of BDNF Val66Met polymorphism and childhood maltreatment on anxiety sensitivity in a mixed race adolescent sample.

Background: Anxiety disorders in youth are attributable to multiple causal mechanisms, comprising biological vulnerabilities, such as genetics and temperament, and unfavourable environmental influences, such as childhood maltreatment (CM). Objective: A gene-environment (G x E) interaction study was conducted to determine the interactive effect of the BDNF Val66Met polymorphism and CM to increase susceptibility to anxiety sensitivity (AS) in a sample of mixed race adolescents. Method: Participants (n = 308, mean age = 15.8 years) who were all secondary school students and who completed measures for AS and CM were genotyped for the BDNF Val66Met polymorphism. Hierarchical multiple regression analysis was conducted to assess G x E influences on AS. Age and gender were included in the models as covariates as age was significantly associated with AS total score (p < .05), and females had significantly higher AS scores than males (p < .05). Results: A main effect of CM on AS was evident (p < .05), however, no main effect of BDNF genotype on AS was observed (p > .05). A non-significant G x E effect on AS was revealed (p < .05). Conclusions: Our results suggest that CM does not have a moderating role in the relationship between the BDNF Val66Met genotype and the increased risk of anxiety-related phenotypes, such as AS. Given the exploratory nature of this study, findings require replication in larger samples and adjustment for population stratification to further explore the role of BDNF Val66Met and CM on AS in mixed race adolescents.

Antecedentes: los trastornos de ansiedad en los jóvenes son atribuibles a múltiples mecanismos causales, que comprenden vulnerabilidades biológicas, como la genética y el temperamento; y las influencias ambientales desfavorables, como el maltrato infantil (MI). Objetivo: Se realizó un estudio interacción gen-ambiente (GxA) para determinar el efecto interactivo del polimorfismo Val66Met del BDNF y MI para aumentar la susceptibilidad para la sensibilidad a la ansiedad (SA) en una muestra de adolescentes de raza mixta.Método: los participantes (n=308, Edad Media:15.8 años) que fueron todos estudiantes de secundaria que completaron las medidas para SA y MI, fueron genotipificados para el polimorfismo Val66Met del BDNF. Se realizó un análisis de regresión múltiple jerárquica para evaluar las influencias GxA en SA. La edad y género se incluyeron como covariables en los modelos, ya que la edad se asoció significativamente con el puntuación total SA (p<0.05), y las mujeres tuvieron puntuaciones de SA significativamente mayores que los hombres (p<0.05).Resultados: Un efecto principal de MI en SA fue evidente (p<0.05), sin embargo, no se observó ningún efecto principal del genotipo BDNF en SA (p>0.05). Se reveló un efecto GxA No significativo sobre SA (p<0.05).Conclusiones: Nuestros resultados sugieren que MI no tiene un rol moderador en la relación entre el genotipo Val66Met del BDNF y el mayor riesgo de fenotipos relacionados con la ansiedad, como SA. Dada la naturaleza exploratoria de este estudio, los hallazgos requieren la replicación en muestras más grandes y el ajuste de la estratificación de la población para explorar más a fondo el rol de Val66Met del BDNF y MI en SA en adolescentes de raza mixta.

Hypothalamic-pituitary-adrenal axis variants and childhood trauma influence anxiety sensitivity in South African adolescents.

Anxiety sensitivity (AS) is characterised by the fear of anxiety-related symptoms and is a risk factor for the development of anxiety-related disorders. We examined whether genetic variation in three stress response genes, CRHR1, NR3C1, and FKBP5, interact with childhood trauma (CT) to predict AS in South African adolescents. Xhosa (n = 634) and Coloured (n = 317) students completed self-report measures of AS and CT, and a total of eighteen polymorphisms within CRHR1, NR3C1, and FKBP5 were genotyped. Differences in AS based on genetic variation and CT were analysed within population and gender groups using multiple linear regression. Associations were found between AS and FKBP5 rs9296158 (p = 0.025) and rs737054 (p = 0.045) in Coloured males. Analysis of gene x CT interactions indicated that NR3C1 rs190488 CC-genotype, NR3C1 rs10482605 G-allele addition, and FKBP5 rs3800373 C-allele addition protect against AS with increasing CT in Xhosa females (p = 0.009), Xhosa males (p = 0.036) and Coloured males (p = 0.049), respectively. We identified two different protective single nucleotide polymorphism (SNP) combinations in a four-SNP CRHR1 haplotype in Coloured males. An analysis of the interaction between CT and a six-SNP FKBP5 haplotype in Coloured males revealed both protective and risk allelic combinations. Our results provide evidence for the influence of both genetic variation in CRHR1, NR3C1 and FKBP5, as well as CT x SNP interactions, on AS in South African adolescents. This study reinforces the importance of examining the influence of gene-environment (G X E) interactions within gender and population groups.

Serotonin transporter variants play a role in anxiety sensitivity in South African adolescents.

OBJECTIVES: Anxiety sensitivity (AS) has predictive potential for the development of anxiety disorders. We investigated the role that gene-environment (G × E) interactions, focussing on childhood trauma (CT) and selected SLC6A4 variants, play in modulating levels of AS in a South African adolescent population. METHODS: All adolescents (n = 951) completed measures for AS and CT. Six SLC6A4 polymorphisms were genotyped. G × E influences on AS levels were assessed using multiple linear regression models. Relevant confounders were included in all analyses. RESULTS: Xhosa (n = 634) and Coloured (n = 317) participants were analysed independently of one another. The 5-HTTLPR-rs25531 L-G haplotype associated with reduced AS among Xhosa adolescents (P = 0.010). In addition, the rs1042173 CC-genotype protected against increased levels of AS in Xhosa participants who had experienced increased levels of CT (P = 0.038). Coloured males homozygous for the S-allele had significantly increased levels of AS compared to Coloured males with at least one L-allele (P = 0.016). CONCLUSIONS: This is the first study to be conducted on AS in adolescents from two ethnically diverse populations. Results indicate that the L-G haplotype confers protection against high AS levels in a Xhosa population. Furthermore, increased CT was found to protect against high levels of AS in Xhosa rs1042173 CC-carriers.

Neuropsychological manifestations in children with Sydenham's chorea after adjunct intravenous immunoglobulin and standard treatment.

This was an exploratory study comparing neuropsychological manifestations of Sydenham's chorea (SC), 6 months after initiation of treatment, in children who had received intravenous immunoglobulins as an adjunct to standard treatment, with those who had received standard treatment. We included a non-SC control group for comparison. We hypothesized that compared to controls, children with SC who had received prior intravenous immunoglobulins would demonstrate less pronounced impairments compared to those who had received standard care. We conducted a cross-sectional analysis of 17 children with -SC who had received treatment 6 months previously (9 treated with standard of care and 8 augmented with intravenous immunoglobulins) and 17 non-SC, medically well controls. The standard treatment group (n = 9) exhibited significant behavioral difficulties, including significantly poorer co-operation (p = 0.009) compared with the other augmented immunoglobulins and non-SC control groups, and increased impulsivity (p = 0.016) compared with non-SC controls. The standard treatment group scored significantly lower than the other two groups on a measure of executive functioning (p = 0.03). Children with SC may be more at risk for neuropsychological difficulties than non-SC, medically well children. Intravenous immunoglobulins may mitigate some of these impairments.

Traumatic dissociation as a predictor of posttraumatic stress disorder in South African female rape survivors.

Women survivors of rape are at an increased risk for posttraumatic stress disorder (PTSD). Traumatic dissociation has been identified as a precursor of PTSD. This study assessed the predictive potential of traumatic dissociation in PTSD and depression development.The study followed a longitudinal, prospective design. Ninety-seven female rape survivors were recruited from 2 clinics in Cape Town, South Africa. Clinical interviews and symptom status assessments of the participants were completed to measure dissociation, childhood traumas, resilience, depression, and PTSD.Traumatic dissociation was a significant predictor of PTSD and depression. The linear combination of prior dissociation, current dissociation, and resilience significantly explained 20.7% of the variance in PTSD. Dissociation mediated the relationship between resilience and PTSD.As traumatic dissociation significantly predicts PTSD, its early identification and management may reduce the risk of developing PTSD. Interventions focused on promoting resilience may also be successful in reducing the risk of dissociation following rape.

Anxiety Sensitivity in School Attending Youth: Exploratory and Confirmatory Factor Analysis of the 18-Item CASI in a Multicultural South African Sample.

Anxiety sensitivity (AS) is a risk factor for the development of anxiety disorders in youth. To date, the applicability of the Childhood Anxiety Sensitivity Index (CASI) in youth from a low or middle income country (LMIC) setting on the African continent has not been assessed. A representative sample of 1149 secondary school learners from 29 schools in Cape Town, South Africa, participated in the study. Participants completed the CASI on a single occasion. One-, two-, and four-factor models of the CASI were assessed. A one-factor solution that comprised items predominantly represented by physical concerns appeared to provide the best fit to our data, however, relatively low variance (26%) was explained. Subsequent item deletion resulted in a 9-item 'physical concerns' factor that showed good construct reliability (0.83) but also explained a low amount of variance (35%). In terms of gender, a one-factor model provided the best fit, however, low variance was explained (i.e., 25%). Configural, metric and scalar invariance of the CASI by gender was determined. Our results suggest that the 18-item CASI is not applicable to our target population and may require adaptation in this population; however, replication of this study in other multicultural adolescent samples in South Africa is first needed to further assess the validity of the AS construct as measured by the CASI.

Resilience and post-traumatic stress disorder in the acute aftermath of rape: a comparative analysis of adolescents versus adults.

BACKGROUND: Rape trauma contributes significantly to the mental burden of disease, affecting resilience and vulnerabilities at every developmental life stage. Appropriate resilience-promoting strategies could potentially buffer or protect trauma-exposed individuals from psychopathology. AIM: This study aimed to assess and compare (using validated measuring instruments) resilience, post-traumatic stress disorder (PTSD) and other variables in the acute aftermath of rape, between adolescent and adult females and to assess associations with these variables. METHOD: We conducted a comparative analysis of resilience, PTSD, prior trauma, demographic variables and psychiatric morbidity in 41 adolescent and 47 adult female rape survivors six weeks post-rape. We assessed the relationship of resilience to PTSD, demographic variables and prior trauma and investigated if resilience levels predicted PTSD after adjusting for prior trauma. RESULTS: We found no significant differences in resilience levels between the groups, but the adolescent PTSD rate (40%) was double that in adults (20%). In adults, a significant negative correlation was evident between resilience and PTSD symptoms scores. CONCLUSION: More knowledge of resilience versus stress susceptibility for PTSD throughout the lifespan is needed and can inform the development of more effective clinical assessment and resilience-promoting strategies.

Are childhood trauma exposures predictive of anxiety sensitivity in school attending youth?

BACKGROUND: Stressful life events in adolescents have been found to be longitudinally associated with higher anxiety sensitivity (AS). A question that has not been addressed is whether AS in adolescence is associated with different childhood adversity exposures. METHODS: School attending adolescents (n=1149) completed measures of anxiety sensitivity (CASI), trait anxiety (STAI-T), childhood trauma (CTQ), depression (CES-DC), alcohol (AUDIT) and drug use (DUDIT), and resilience (CD-RISC) and coping orientation (A-COPE). RESULTS: There was no significant gender difference in childhood trauma exposure, resilience levels or coping orientation. Gender differences were evident in terms of AS, trait anxiety, depression, alcohol and drug use. Depression, trait anxiety and alcohol use mediated the relationship between the amount of childhood trauma and AS and played a role in the relationship between certain childhood trauma types and AS. Neither resilience nor coping orientation had a moderating effect on the relationship between the amount of childhood trauma and AS. LIMITATIONS: Cross-sectional study, over- or under-reporting of data due to use of self-report instruments, and use of a retrospective measure of childhood trauma (CTQ) that is subject to recall bias. CONCLUSIONS: Girls are at greater risk than boys for early onset anxiety disorders as girls have higher rates of AS, trait anxiety and depression despite the same rates of childhood trauma, coping orientation and resilience. Our findings, in the context of childhood trauma, underscore the influence of depression, trait anxiety and alcohol use as risk factors for the development of AS in youth.

The 39-item Child Exposure to Community Violence (CECV) scale: exploratory factor analysis and relationship to PTSD symptomatology in trauma-exposed children and adolescents.

BACKGROUND: Exposure to multiple forms of community violence in youth is associated with a wide range of negative health outcomes. A number of scales measuring community violence exposure have been developed, including the Child Exposure to Community Violence Checklist (CECV). PURPOSE: This study examined the psychometric properties of an adapted version of the CECV in a South African sample of trauma-exposed youths. In addition, the study assessed the relationship between exposure to community violence and posttraumatic stress disorder (PTSD) symptomatology. METHODS: Trauma-exposed youth completed two self-report instruments, namely, the CECV and the Child PTSD Checklist (CPC), on a single occasion. Exploratory factor analysis (EFA) was used to investigate the factor structure of the CECV, and the association between CECV and CPC scores was also explored. RESULTS: EFA of the CECV revealed three factors that accounted for 38.66 % of variance in the model and consisted of 29 of the original 39 items. Reliability of the three factors ranged from moderate to excellent (α = 0.682 to α = 0.892). Exposure to community violence was positively correlated with posttraumatic stress symptomatology (r = 0.464, p < 0.001). Adolescents attending high school reported significantly higher levels of exposure to community violence than did children in primary school. CONCLUSION: Findings provide support for the conceptualization of exposure to community violence as comprising distinct, multiple factors. Levels of exposure to community violence and family violence were high. We found a highly significant, positive association between exposure to community violence and PTSD symptomatology, providing evidence for the convergent validity of the CECV.

BDNF Val66Met and DRD2 Taq1A polymorphisms interact to influence PTSD symptom severity: a preliminary investigation in a South African population.

BACKGROUND: We evaluated the role that selected variants in serotonin transporter (5-HTT), dopamine receptor 2 (DRD2) and brain-derived neurotrophic factor (BDNF) genes play in PTSD symptom severity in an at-risk population. We also investigated the interaction between the genetic variants to determine whether these variables and the interactions between the variables influenced the severity of PTSD symptoms. METHODS: PTSD symptoms were quantitatively assessed using the Davidson Trauma Scale (DTS) in 150 participants from an at-risk South African population. All participants were genotyped for the 5-HTTLPR, DRD2 Taq1A and BDNF Val66Met polymorphisms. Gene-gene interactions were investigated using various linear models. All analyses were adjusted for age, gender, major depressive disorder diagnosis, level of resilience, level of social support and alcohol dependence. RESULTS: A significant interaction effect between DRD2 Taq1A and BDNF Val66Met variants on DTS score was observed. On the background of the BDNF Val66Val genotype, DTS score increased significantly with the addition of a DRD2 Taq1A A1 allele. However, on the BDNF Met66 allele background, the addition of an A1 allele was found to reduce total DTS score. CONCLUSIONS: This study provides preliminary evidence for an epistatic interaction between BDNF Val66Met and DRD2 Taq1A polymorphisms on the severity of PTSD symptoms, where both too little and too much dopamine can result in increased PTSD symptom severity.

Investigation of telomere length and psychological stress in rape victims.

BACKGROUND: Women are at an increased risk of depression and other mental health problems following rape. Various etiological factors for depression, including predisposing genetic factors, have been identified. Telomeres are repetitive nucleoprotein structures located at chromosomal ends that protect them from premature degradation. Telomeres reduce in length with each cell division, resulting in cellular senescence and apoptosis. METHODS: Relative quantification of telomeric repeats using qPCR was performed to investigate whether shorter relative leukocyte telomere length (LTL) in a cohort of 64 rape victims was associated with resilience, the development of rape trauma-related major depressive disorder (MDD) or the development of posttraumatic stress disorder (PTSD) after 3 months. RESULTS: Out of the 64 participants, 23 participants were diagnosed with MDD at baseline and 31 after 3 months. Nine participants were diagnosed with PTSD (MDD and PTSD specifically related to the trauma). No significant associations were observed between relative LTL and resilience or the development of MDD at either baseline or after 3 months in this cohort. However, a marginally significant association was evident between relative LTL and PTSD status. CONCLUSIONS: The significant association between relative LTL and PTSD suggests that shorter relative LTL might have acted as a predisposing factor in the development of PTSD after a severely traumatic event. The results of this study indicate that telomere shortening may be an important marker of PTSD risk, with implications for early intervention and timely treatment, and as such warrant replication in a larger cohort.

Lifetime and HIV-related PTSD among persons recently diagnosed with HIV.

This cross-sectional study sought to determine the percentage of individuals who met criteria for lifetime PTSD and HIV-related PTSD among 85 recently diagnosed HIV-positive patients attending public health clinics in the Western Cape, South Africa. The PTSD module of the Composite International Diagnostic Interview (CIDI) was used to determine the percentage of those who met criteria for lifetime PTSD and HIV-related PTSD. The rate of lifetime PTSD and incidence of HIV-related PTSD was 54.1% (95% CI: 43.6-64.3%) and 40% (95% CI: 30.2-50.6%), respectively. Findings suggest that receiving an HIV-positive diagnosis and/or being HIV-positive may be considered a stressor that frequently results in HIV-related PTSD. Given the various barriers to efficient mental health interventions and services in South Africa, there are significant challenges that need to be addressed in order to ensure that the mental health of HIV-positive individuals is appropriately addressed.