Childhood maltreatment and internalizing/externalizing disorders in trauma-exposed adolescents: Does posttraumatic stress disorder (PTSD) severity have a mediating role?

Childhood maltreatment is associated with wide-ranging psychopathology at all stages of life. In the current study, we investigated whether posttraumatic stress disorder (PTSD) severity mediated the association between childhood maltreatment and internalizing and externalizing disorders among 262 South African trauma-exposed adolescents (aged 12-18 years). Childhood maltreatment and PTSD symptom severity were assessed using the Childhood Trauma Questionnaire and the Child PTSD Checklist, respectively. Psychiatric disorders were assessed utilizing the Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime version and were grouped into internalizing or externalizing disorders. Hierarchal logistic regression was used to assess the association of childhood maltreatment subtype with internalizing and externalizing disorders, controlling for age and gender, with PTSD symptom severity added to the final model. We found that sexual abuse was significantly associated with internalizing disorders, although this effect was no longer significant when PTSD was added to the model demonstrating that PTSD mediated the association between sexual abuse and internalizing disorders. Physical abuse, but not PTSD, was associated with externalizing disorders. Physical abuse, emotional neglect, and PTSD were associated with comorbid internalizing and externalizing disorders. These findings have implications for intervention and prevention strategies targeted at trauma-exposed adolescents with a history of childhood maltreatment.

Childhood trauma exposure and reward processing in healthy adults: A functional neuroimaging study.

The association between childhood trauma exposure and risk of developing psychopathology may in part be mediated by the effects of chronic stress on dopaminergic neurotransmission. However, little is known about the differential effects of distinct trauma types on reward processing, particularly in adults without concurrent medical or psychiatric disorders. We examined the association of childhood trauma exposure, including the differential effects of abuse and neglect, with reward processing in healthy adults (n = 114). Functional magnetic resonance imaging during a monetary incentive delay task was used to assess neural activity in the ventral striatum and orbitofrontal cortex in relation to reward anticipation and reward outcome, respectively. Exposure to childhood trauma, including abuse and neglect, was assessed using the Childhood Trauma Questionnaire-Short Form. We found a significant effect for abuse on ventral striatal activation during reward anticipation, adjusting for age, sex, scanner site, educational level, and household monthly income. There were no effects for abuse or neglect, independently or combined, on orbitofrontal cortex activation during reward outcome. Our findings suggest differential effects of childhood abuse on ventral striatum activation during reward anticipation in healthy adults.

Hair cortisol levels in posttraumatic stress disorder and metabolic syndrome.

Individuals with post-traumatic stress disorder (PTSD) evidence increased rates of metabolic syndrome (MetS), and both PTSD and MetS are associated with alterations in hypothalamic-pituitary-adrenal (HPA) axis function. Few investigations have examined the possible role of HPA-axis dysfunction in the co-occurrence of PTSD and MetS. In a case-control study, we aimed to determine whether hair cortisol concentrations (HCC) were associated with (i) PTSD caseness and severity and (ii) PTSD and MetS co-occurrence. We used the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) to determine PTSD diagnoses and severity scores in 216 females of mixed ancestry aged between 20 and 79 years (M = 43.8, SD =13.3). Hair samples, representing a three-month retrospective window of cortisol levels, were obtained and analyzed utilizing liquid chromatography-tandem mass spectrometry. We constructed multivariate linear regression models to evaluate whether PTSD diagnosis, PTSD severity, and MetS comorbidity were associated with HCC, controlling for potential confounders. HCC were significantly higher (adj ß = 0.154, p = .033; Cohen's d = 0.44) in PTSD patients (n = 110) than trauma-exposed controls (n = 106) and CAPS severity scores (adj ß = 0.207, p = .005) were significantly associated with HCC. MetS was not associated with HCC and there were no significant interactions between PTSD and MetS on HCC. This study provides evidence of a chronically dysregulated neuroendocrine mediated stress response in PTSD, with a clear dose-response relationship. HCC do not, however, appear to have specificity for the comorbidity of PTSD and MetS in this sample.LAY SUMMARYWe found that levels of the stress hormone, cortisol, measured in hair samples were significantly higher in South African women with post-traumatic stress disorder (PTSD) than in women who had also experienced trauma but did not have PTSD. Hair cortisol levels were, however, not associated with metabolic syndrome, a cluster of risk factors for heart disease, in the women studied. We thus show that South African women with PTSD have elevated long-term stress hormone levels and that this effect is related to PTSD and not solely due to trauma exposure.

The relationship between nutrient intake and executive function in adults with post-traumatic stress disorder.

BACKGROUND: Executive function (EF) deficits are common in adults with post-traumatic stress disorder (PTSD). Macro- and micronutrient intake are potential modifiable factors that may influence EF in PTSD. OBJECTIVES: To explore the relationship between the daily dietary intake of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs), vitamin C, vitamin E, vitamin D, vitamin B12 and folate, and EF in adults with PTSD. METHODS: This was a cross-sectional observational study of adults with PTSD who completed neurocognitive assessments (n = 201). Digit span backwards, spatial span backwards, Stroop test and the Ruff Figural Fluency Task were used to assess EF. FoodFinder nutrient intake based on 24-h dietary recalls was used to calculate average daily nutrient intake. Multivariable linear regression models were used to regress EF on the nutrient variables. RESULTS: Intake of vitamin E, ω-3 PUFAs, and ω-6 PUFAs were all positively associated with planning and set-shifting, with vitamin E (adjusted ß = 0.20, p = 0.004) and ω-6 (adjusted ß = 0.17, p = 0.01) remaining significant after adjustment for age; sex; education and body mass index. Vitamin D intake was negatively associated with interference (adjusted ß = -0.21, p = 0.01). Vitamin C, vitamin B12 and folate intake were not associated with EF. LIMITATIONS: 24-h dietary recall data is limited by recall bias. Circulating nutrient levels were not measured. CONCLUSIONS: Dietary intake of vitamins E, ω-3 and ω-6 may be important modifiable factors affecting EF in adults with PTSD. Randomised controlled trials are needed to investigate whether micro- and macronutrient interventions can improve EF and other outcomes in PTSD.

Feasibility, acceptability and preliminary efficacy of a mental health self-management app in clinicians working during the COVID-19 pandemic: A pilot randomised controlled trial.

COVID-19 affected the well-being of healthcare workers (HCWs) globally. Mental health app interventions (MHAIs) may offer appropriate and accessible means to support HCWs' mental health. We conducted a pilot randomised controlled crossover trial involving 34 clinicians randomised to either a MHAI or a waitlisted group. After one month, outcome assessments were repeated and the waitlisted group then crossed over to the MHAI; they again completed outcome assessments after a month. The primary outcomes were feasibility, assessed with the Systems Usability Scale (SUS), and acceptability, assessed with the Client Satisfaction Questionnaire (CSQ). Secondary outcomes included efficacy for various mental health parameters. The SUS and CSQ scores indicated above average feasibility and acceptability. There was a significant difference in anxiety from baseline to 1-month follow-up between the groups, with greater improvement in the MHAI group. The groups differed in resilience and patient-related burnout from baseline to 1-month follow-up, with a trend towards significance, with greater improvements in the MHAI group. Anxiety and acute stress disorder severity improved significantly from pre- to post-intervention. We demonstrated that MHAIs hold potential for improving well-being of HCWs, although these findings will need to be replicated in adequately powered trials.

The impact of childhood maltreatment on women's reproductive health, with a focus on symptoms of polycystic ovary syndrome.

BACKGROUND: Childhood maltreatment leads to lifelong health risks, particularly in women. Although reproductive health has been linked to such maltreatment, limited literature exists on its association with polycystic ovary syndrome (PCOS). OBJECTIVES: In a sample of psychiatrically healthy women, we evaluated the impact of child maltreatment (subtypes of abuse and neglect) on women's reproductive health outcomes, specifically PCOS. PARTICIPANTS AND SETTING: The 237 psychiatrically healthy women, aged between 18 and 79 years, were control participants in a case-control study (SHARED ROOTS), conducted in Cape Town, South Africa, between May 2014 and June 2017. METHODS: Probable PCOS was based on a history of symptoms of ovulatory dysfunction and hyperandrogenism or a diagnosis of PCOS. We conducted hierarchical logistic regression models to assess which child maltreatment subtypes (emotional, physical and sexual abuse and emotional and physical neglect) were significantly associated with PCOS, controlling for sociodemographic and clinical factors. RESULTS: Probable PCOS was present in 29 (12.2 %) women. Emotional abuse (31.6 %) was the most frequent type of child maltreatment and was significantly associated with PCOS (OR = 5.11, CI 1.87; 13.98), including when other maltreatment types were accounted for (OR = 3.90, CI 1.27; 12.02). Physical abuse was associated with PCOS (OR = 4.21, CI 1.43; 12.38), but was not significant when other maltreatment types were factored in. CONCLUSIONS: Child maltreatment is independently associated with PCOS in women without psychiatric disorders. In the context of all maltreatment subtypes, emotional abuse remained associated with PCOS, suggesting its unique effect on this endocrinopathy.

Hair cortisol levels in schizophrenia and metabolic syndrome.

AIM: Individuals with schizophrenia demonstrate higher rates of metabolic syndrome (MetS) than the general population. Hair cortisol concentrations (HCC) reflect longer-term cortisol secretion and can provide additional insights into the role of the hypothalamic pituitary adrenal (HPA) axis in schizophrenia and co-occurring MetS. METHODS: In a case-control study of 16 patients with schizophrenia (11 first episode psychosis [FEP] and 5 chronic) and 21 controls hair samples, representing a 3-month retrospective window of cortisol, were collected and analysed utilizing liquid chromatography tandem mass spectrometry. We investigated whether schizophrenia and MetS co-occurrence were associated with HCC utilizing multivariate regression models. We also explored the longitudinal trajectory of HCC in FEP patients by conducting a mixed models analysis. RESULTS: At baseline HCC were significantly lower (Cohen's d = 0.88) in patients with schizophrenia than in controls (p = .014). HCC increased from baseline to month-12 in FEP patients compared to controls, demonstrating a trend towards significance (p = .097). MetS was not associated with HCC at baseline, but HCC increased significantly from baseline to month-12 in relation to MetS (p = .037). CONCLUSIONS: In a subgroup of schizophrenia patients, psychosis may be associated with a blunted HPA axis with lower long-term cortisol output. MetS was associated with an increase in HCC and elevated cortisol levels observed in schizophrenia may be related to increased rates of MetS in schizophrenia patients.

The association between hair cortisol levels, inflammation and cognitive functioning in females.

Glucocorticoids and inflammatory markers can influence cognitive function. Hair cortisol concentrations (HCC) reflect longer-term hypothalamic pituitary adrenal (HPA) axis function and combined with immune markers can provide insights into how HPA-axis and immune pathways interact to influence cognition. We examined the association between HCC and high sensitivity c-reactive protein (hsCRP) levels, as well as the interaction between HCC and hsCRP, and cognitive function in a sample of 153 females, aged between 18 and 79 years, from a cross-sectional case-control study (SHARED ROOTS), conducted in Cape Town, South Africa from May 2014 until June 2017. We examined whether HCC and hsCRP levels were associated with performance on neurocognitive tests in both unadjusted and adjusted linear regression models. HCC demonstrated a significant inverse association with verbal working memory in both unadjusted (p = 0.010) and adjusted (p = 0.016) analyses. There were significant interactions between HCC and hsCRP on verbal intelligence (p = 0.016), language (p = 0.023) and executive function (p = 0.008) scores, such that at low HCC hsCRP levels were positively associated with language (p = 0.020) and executive function (p = 0.006) scores and at high HCC hsCRP levels were inversely associated with verbal intelligence (p = 0.034) scores. Though the results did not survive correction for multiple comparisons, they suggest stress-related neuroendocrine effects on working memory impairment. Furthermore, under physiological conditions and low long-term HCC, there may be positive effects of peripheral inflammatory markers on cognitive performance, whereas there may be detrimental effects when the HPA-axis is dysregulated as reflected by high long-term cortisol output.

Cut it out or wait it out? Case series of middle fossa arachnoid cysts presenting with psychiatric symptoms and a discussion of the ethics of neurosurgical management.

Arachnoid cysts have been linked to neuropsychiatric morbidity. We describe two patients presenting with dissociative and manic symptoms believed to be associated with middle fossa arachnoid cysts. They were managed medically and remitted eventually, but symptoms were resistant. We briefly review the literature to discuss mechanisms by which cysts could cause symptoms and consider whether neurosurgical management would be appropriate. Although neurosurgery can be considered, its role is currently limited by practical and ethical considerations.

Examining Individual and Synergistic Contributions of PTSD and Genetics to Blood Pressure: A Trans-Ethnic Meta-Analysis.

Growing research suggests that posttraumatic stress disorder (PTSD) may be a risk factor for poor cardiovascular health, and yet our understanding of who might be at greatest risk of adverse cardiovascular outcomes after trauma is limited. In this study, we conducted the first examination of the individual and synergistic contributions of PTSD symptoms and blood pressure genetics to continuous blood pressure levels. We harnessed the power of the Psychiatric Genomics Consortium-PTSD Physical Health Working Group and investigated these associations across 11 studies of 72,224 trauma-exposed individuals of European (n = 70,870) and African (n = 1,354) ancestry. Genetic contributions to blood pressure were modeled via polygenic scores (PGS) for systolic blood pressure (SBP) and diastolic blood pressure (DBP) that were derived from a prior trans-ethnic blood pressure genome-wide association study (GWAS). Results of trans-ethnic meta-analyses revealed significant main effects of the PGS on blood pressure levels [SBP: ß = 2.83, standard error (SE) = 0.06, p < 1E-20; DBP: ß = 1.32, SE = 0.04, p < 1E-20]. Significant main effects of PTSD symptoms were also detected for SBP and DBP in trans-ethnic meta-analyses, though there was significant heterogeneity in these results. When including data from the largest contributing study - United Kingdom Biobank - PTSD symptoms were negatively associated with SBP levels (ß = -1.46, SE = 0.44, p = 9.8E-4) and positively associated with DBP levels (ß = 0.70, SE = 0.26, p = 8.1E-3). However, when excluding the United Kingdom Biobank cohort in trans-ethnic meta-analyses, there was a nominally significant positive association between PTSD symptoms and SBP levels (ß = 2.81, SE = 1.13, p = 0.01); no significant association was observed for DBP (ß = 0.43, SE = 0.78, p = 0.58). Blood pressure PGS did not significantly moderate the associations between PTSD symptoms and blood pressure levels in meta-analyses. Additional research is needed to better understand the extent to which PTSD is associated with high blood pressure and how genetic as well as contextual factors may play a role in influencing cardiovascular risk.

Hair glucocorticoid levels in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) and metabolic syndrome (MetS) share certain pathophysiological pathways, including hypothalamic pituitary adrenal (HPA) axis dysfunction. Hair glucocorticoid (GC) levels reflect longer-term HPA-axis function and can provide additional insights into the role of a dysregulated HPA-axis in PD and co-occurring cardiovascular disease (CVD) risk. OBJECTIVES: In a case-control study we examined the association of PD diagnosis, clinical features and PD-CVD risk (as defined by the MetS) co-occurrence with hair GC (cortisol and cortisone) levels. METHODS: Hair samples, representing a three-month retrospective window of GC levels, were collected and analysed utilizing liquid chromatography tandem mass spectrometry in 56 females (25 PD patients and 31 controls) of mixed ancestry, aged between 45 and 78 years (PD patients, M = 64.5, SD = 8.4; controls, M = 55.7, SD = 6.9). Multivariate regression models were constructed with PD diagnostic status, clinical features and MetS comorbidity regressed on hair GC levels, adjusting for potential confounders. RESULTS: The prevalence of MetS was 56.0 % in PD patients and 25.8 % in controls. Hair cortisone (adj B = 5.44, 95 % CI 2.05; 8.83, p =  0.002), but not hair cortisol levels (adj B = 0.05, 95 % CI -0.12; 0.22, p =  0.539), were significantly higher (Cohen's d = 0.87) in PD patients than in controls. Non-motor symptoms of PD (e.g., mood and anxiety) were significantly associated with hair cortisone levels (adj B = 0.29, 95 % CI 0.07; 0.51, p =  0.014). MetS was not associated with hair GC levels and there were no significant interactions between PD and MetS on hair GC levels. CONCLUSIONS: This study is the first study reporting on hair GC levels in PD. We found chronically increased cortisone, but not cortisol, levels in PD patients compared to controls. Furthermore, hair cortisone levels were significantly positively associated with PD symptoms related to mood, anhedonia, and anxiety. Hair GC levels were not associated with PD-MetS comorbidity in this sample. Hair cortisone levels may provide additional insights into HPA-axis dysfunction in PD.

Hair cortisol as a biomarker of stress and resilience in South African mixed ancestry females.

BACKGROUND: Hair cortisol concentrations (HCC) are increasingly used as a biomarker of stress, however limited research exists regarding the relationship between HCC and protective factors, such as resilience. Additionally, studies measuring HCC need to account for possible confounders, and these factors have not been examined in sufficiently diverse settings. OBJECTIVES: Our objectives were to identify determinants of HCC in a sample of mixed ancestry adults and investigate the association of HCC with measures of self-perceived stress and resilience. METHODS: Our sample comprised 164 females (mean age 46.5 years, SD = 15.0), self-identifying as mixed ancestry, who were control participants in a case-control study (SHARED ROOTS), conducted in Cape Town, South Africa from May 2014 until June 2017. We examined which socio-demographic, hair related, clinical and behavioural factors were associated with HCC in both unadjusted and adjusted linear regression models. Furthermore, the relationship of HCC with self-perceived stress and resilience scores were also examined. RESULTS: HCC (Mdn 4.4 pg/ml; IQR 2.8; 11.4) were significantly positively associated with hair product use and breastfeeding, and significantly negatively associated with age, level of education, duration of sun exposure, duration of storage, and demonstrated a trend towards significance with frequency of hair washing, in adjusted models. HCC were inversely associated with CD-RISC scores (adj ß = -0.179, p =  0.012) but were not significantly associated with PSS scores (adj ß = -0.001, p =  0.989). CONCLUSIONS: We identified specific determinants of HCC in our sample, including the first indication that sun exposure has an effect on HCC under naturalistic conditions. These potential confounders need to be controlled for in the design and analysis of future studies. HCC may be a biomarker of resilience to stress, rather than perceived stress. Further research measuring HCC in more diverse settings and populations and including constructs related to resilience are needed.

Excess mortality associated with mental illness in people living with HIV in Cape Town, South Africa: a cohort study using linked electronic health records.

BACKGROUND: Mental disorders can adversely affect HIV treatment outcomes and survival. Data are scarce on premature deaths in people with mental disorders in HIV-positive populations, particularly in low-income and middle-income countries. In this study, we quantified excess mortality associated with mental disorders in HIV-positive people in South Africa, adjusting for HIV treatment outcomes. METHODS: For this cohort study, we analysed routinely collected data on HIV-positive adults receiving antiretroviral therapy (ART) in Cape Town, South Africa between Jan 1, 2004, to Dec 31, 2017. Data from three ART programmes were linked with routine medical records on mental health treatment from Jan 1, 2010, to Dec 31, 2017, and mortality surveillance data from the South African National Population Register up to Dec 31, 2017. People living with HIV aged 15 years or older who initiated ART at a programme site were eligible for analysis. We followed up patients from ART initiation or Jan 1, 2010, whichever occurred later, to transfer, death, or Dec 31, 2017. Patients were considered as having a history of mental illness if they had ever received psychiatric medication or been hospitalised for a mental disorder. We calculated adjusted hazard ratios (aHRs) with 95% CIs for associations between history of mental illness, mortality, and HIV treatment outcomes (retention in care with viral load suppression [VLS; viral load <1000 copies per mL], retention in care with non-suppressed viral load [NVL; viral load ≥1000 copies per mL], and loss to follow-up [LTFU; >180 days late for a clinic visit at closure of the database]) using Cox proportional hazard regression and multistate models. RESULTS: 58 664 patients were followed up for a median of 4·3 years (IQR 2·1-6·4), 2927 (5·0%) of whom had a history of mental illness. After adjustment for age, sex, treatment programme, and year of ART initiation, history of mental illness was associated with increased risk of mortality from all causes (aHR 2·98 [95% CI 2·69-3·30]), natural causes (3·00 [2·69-3·36]), and unnatural causes (2·10 [1·27-3·49]), compared with no history of mental illness. Risk of all-cause mortality in people with a history of mental illness remained increased in multivariable analysis adjusted for age, sex, treatment programme, year of ART initiation, CD4 count and WHO clinical stage at ART initiation, retention in HIV care with or without VLS, and LTFU (2·73 [2·46-3·02]). In our multistate model, adjusted for age, sex, year of ART initiation, cumulative time with NVL, and WHO clinical stage and CD4 cell count at ART initiation, rates of excess all-cause mortality in people with history of mental illness were greatest in patients retained in care with VLS (aHR 3·43 [95% CI 2·83-4·15]), followed by patients retained in care with NVL (2·74 [2·32-3·24]), and smallest in those LTFU (2·12 [1·78-2·53]). History of mental illness was also associated with increased risk of HIV viral rebound (transitioning from VLS to NVL; 1·50 [1·32-1·69]) and LTFU in people with VLS (1·19 [1·06-1·34]). INTERPRETATION: Mental illness was associated with substantial excess mortality in HIV-positive adults in Cape Town. Excess mortality among people with a history of mental illness occurred independently of HIV treatment success. Interventions to reduce excess mortality should address the complex physical and mental health-care needs of people living with HIV and mental illness. FUNDING: National Institutes of Health, Swiss National Science Foundation, South African Medical Research Council.

Cortisol levels in different tissue samples in posttraumatic stress disorder patients versus controls: a systematic review and meta-analysis protocol.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a disorder that develops following exposure to severely stressful events. Altered cortisol secretion has been reported in PTSD; however, results have been inconsistent. Previous meta-analyses of cortisol levels in PTSD have combined results of studies that have used different tissue samples (blood, saliva, urine) for cortisol measurement and have not included newer methods of determining cortisol levels (e.g. hair samples). In this systematic review, we will synthesise evidence from studies evaluating basal cortisol levels in PTSD patients versus controls and stratify studies according to tissue type used for cortisol measurement. We will also determine whether results from different tissue types can be pooled and if any specific tissue samples have better utility in research studies on PTSD. METHODS: We will perform a systematic review of the scientific literature including all studies that have evaluated basal or baseline cortisol levels in adults with current PTSD versus controls, with and without trauma exposure. Independent reviewers will conduct searches in electronic databases (Medline, CINAHL, PTSDpubs, Web of Science, Scopus, ProQuest Dissertations & Theses A&I, ClinicalTrials.gov, and ICTRP), and additional studies will be obtained by searching the reference lists of articles. Two reviewers (LLvdH and SW) will independently conduct standardised screening, eligibility assessments, data extraction, and quality assessments before qualitative and, if appropriate, quantitative (meta-analysis and meta-regression) synthesis. Disagreements that arise at any stage will be resolved by a third reviewer (ShS). DISCUSSION: In line with previous reviews, we expect that cortisol levels will be lower in PTSD patients than in controls, but that patterns may vary somewhat according to the tissue sample in which cortisol is measured. This systematic review will assist in developing a better understanding of the acute and chronic patterns of basal cortisol secretion in PTSD and will inform future research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018091874.