Strengthening self-regulation and reducing poverty to prevent adolescent depression and anxiety: Rationale, approach and methods of the ALIVE interdisciplinary research collaboration in Colombia, Nepal and South Africa.

This is the final version. Available from Cambridge University Press via the DOI in this record. Availability of data and materials: Data and materials from this study are not yet available for sharing as the study is still in the data collection phase.AIMS: Depression and anxiety are the leading contributors to the global burden of disease among young people, accounting for over a third (34.8%) of years lived with disability. Yet there is limited evidence for interventions that prevent adolescent depression and anxiety in low- and middle-income countries (LMICs), where 90% of adolescents live. This article introduces the 'Improving Adolescent mentaL health by reducing the Impact of poVErty (ALIVE)' study, its conceptual framework, objectives, methods and expected outcomes. The aim of the ALIVE study is to develop and pilot-test an intervention that combines poverty reduction with strengthening self-regulation to prevent depression and anxiety among adolescents living in urban poverty in Colombia, Nepal and South Africa. METHODS: This aim will be achieved by addressing four objectives: (1) develop a conceptual framework that identifies the causal mechanisms linking poverty, self-regulation and depression and anxiety; (2) develop a multi-component selective prevention intervention targeting self-regulation and poverty among adolescents at high risk of developing depression or anxiety; (3) adapt and validate instruments to measure incidence of depression and anxiety, mediators and implementation parameters of the prevention intervention; and (4) undertake a four-arm pilot cluster randomised controlled trial to assess the feasibility, acceptability and cost of the selective prevention intervention in the three study sites. RESULTS: The contributions of this study include the active engagement and participation of adolescents in the research process; a focus on the causal mechanisms of the intervention; building an evidence base for prevention interventions in LMICs; and the use of an interdisciplinary approach. CONCLUSIONS: By developing and evaluating an intervention that addresses multidimensional poverty and self-regulation, ALIVE can make contributions to evidence on the integration of mental health into broader development policy and practice.Wellcome TrustUK Research and InnovationNational Institute for Health Researc

Efficacy and Tolerability of High-Dose Escitalopram in Posttraumatic Stress Disorder.

Background Open-label trials suggest that escitalopram (up to 20 mg/d) is an effective treatment for some, but not all posttraumatic stress disorder (PTSD) patients. Higher doses of escitalopram effectively reduced major depression symptoms in patients who had not responded to regular doses. The current study examines the efficacy, tolerability, and adherence to high-dose escitalopram in PTSD. Methods Forty-five PTSD patients received 12 weeks of gradually increasing doses of escitalopram reaching 40 mg daily at 4 weeks. Among those, 12 participants received regular doses of antidepressants at study onset including escitalopram (n = 7). The Clinician-Administered PTSD Scale (CAPS) evaluated PTSD symptoms severity before treatment, at 3 months (upon treatment termination), and at 6 months (maintenance effect). A 20% reduction in CAPS scores was deemed clinically significant. Results Adverse events and medication adherence were monitored at each clinical session. Linear mixed-models analysis showed a significant reduction of mean CAPS scores (11.5 ± 18.1 points) at 3 months and maintenance of gains by 6 months (F2,34.56 = 8.15, P = 0.001). Eleven participants (34.3%) showed clinically significant improvement at 3 months. Only 9 participants (20%) left the study. There were no serious adverse events and few mild ones with only 2 adverse events (diarrhea, 11.1%; drowsiness, 11.1%) reported by more than 10% of participants. Conclusion High doses of escitalopram are tolerable and well adhered to in PTSD. Their beneficial effect at a group level is due to a particularly good response in a subset of patients.Variability in prior pharmacological treatment precludes a definite attribution of the results to high doses of escitalopram

A Virtual Reality Game to Assess OCD Symptoms

Background: Symptoms of obsessive-compulsive disorder (OCD) are often underreported by patients and mainly triggered in the patients private domain, making it harder for clinicians to recognize OCD. Virtual reality (VR) can be used to assess OCD symptoms in the clinician's office. We developed a VR game in order to provoke subjective and physiological OCD symptoms. We hypothesize that (1) the VR game provokes more OCD symptoms in patients compared to healthy controls, (2) performing virtual compulsions leads to a reduction in emotional responses in OCD patients and that (3) the severity of VR game provoked symptoms correlates with severity of OCD symptoms. Methods: Participants played the VR game on a laptop while physiological measures were recorded simultaneously. We measured emotional responses, virtual compulsions and physiological arousal in response to our VR game in 26 OCD patients and 26 healthy controls. We determined correlations between emotional responses, virtual compulsions and OCD severity. Results: We found higher levels of VR-provoked anxiety (U = 179.5, p = 0.004) and virtual compulsions in OCD patients compared to healthy controls (p = 0.001). There was a significant reduction in emotional responses after performing virtual compulsions in the OCD patients. The emotional responses and virtual compulsions did not correlate significantly with Y-BOCS scores. A baseline difference between patients and healthy controls was found in heart rate variability (HRV), but no significant change in HRV, heartrate and skin conductance was found during the VR game Conclusions: Our study clearly shows our OCD VR game is capable of provoking more anxiety and virtual compulsions in patients with OCD compared to healthy controls. Providing a direct patient-rated measurement in the clinicians room, the VR game could help in assessing core OCD symptoms and recognizing OCD. Clinical Trial Registry Number: Netherlands Trial Register NTR5935

Cardiorespiratory fitness, regular physical activity, and autonomic nervous system reactivity to laboratory and daily life stress

The cross-stressor adaptation hypothesis—which posits that adjustment to physical stress as a result of regular physical activity and its effects on fitness crosses over to psychological stress reactivity—has been around for over four decades. However, the literature has been plagued by heterogeneities preventing definitive conclusions. We address these heterogeneity issues in a combined laboratory and daily life study of 116 young adults (M = 22.48 SD = 3.56, 57.76% female). The exposure, i.e., the potential driver of adaptation, was defined in three ways. First, a submaximal test was performed to obtain aerobic fitness measured as the VO2max (kg/ml/min). Second, leisure time exercise behavior, and third, overall moderate-to-vigorous physical activity (MVPA), were obtained from a structured interview. Outcomes were autonomic nervous system (ANS) reactivity and affective responsiveness to stressors. ANS activity was measured continuously and expressed as inter-beat-interval (IBI), pre-ejection-period (PEP), respiratory sinus arrythmia (RSA), and non-specific Skin Conductance Responses (ns.SCR). Negative and positive affect were recorded after each experimental condition in the laboratory and hourly in daily life with a nine-item digital questionnaire. Linear regressions were performed between the three exposure measures as predictors and the various laboratory and daily life stress measurements as outcomes. Our results support the resting heart rate reducing effect of aerobic fitness and total MVPA in both the laboratory and daily life. We did not find evidence for the cross-stressor adaptation hypothesis, irrespective of ANS or affective outcome measure or whether the exposure was defined as exercise/MVPA or aerobic fitness

Psychotic reactions to daily life stress and dopamine function in people with severe hearing impairment

Minor stresses measured in daily life have repeatedly been associated with increased momentary psychotic experiences, both in individuals with psychotic disorders and in persons who are genetically at an increased risk for these disorders. Severe hearing impairment (SHI) is an environmental risk factor for psychotic disorder, possibly due to the experience of social exclusion. The aim of the current study is to investigate whether people with SHI exhibit higher levels of psychotic reactivity to social stressors in daily life than normal-hearing controls and whether this reactivity is associated with decreased baseline dopamine (DA) D2/3 receptor availability and/or elevated DA release following a dexamphetamine challenge. We conducted an experience sampling study in 15 young adults with SHI and 19 matched normal-hearing controls who had previously participated in a single photon emission computed tomography study measuring DA D2/3 receptor availability and DA release in response to dexamphetamine. The association between social stress and momentary psychotic experiences in daily life was stronger among SHI participants than among normal-hearing controls. Interactions between social stress and baseline striatal DA D2/3 receptor availability or DA release were not significant in multilevel models of momentary psychotic experiences including age, sex and tobacco use. While both elevated striatal DA release and elevated psychotic stress reactivity have been found in the same population defined by an environmental risk factor, SHI, their inter-relationship cannot be established. Further research is warranted to clarify the association between biological and psychological endophenotypes and psychosis ris

Sexual minority status and psychotic symptoms: findings from the Netherlands Mental Health Survey and Incidence Studies (NEMESIS)

Ethnic minority position is associated with increased risk for psychotic outcomes, which may be mediated by experiences of social exclusion, defeat and discrimination. Sexual minorities are subject to similar stressors. The aim of this study is to examine whether sexual minorities are at increased risk for psychotic symptoms and to explore mediating pathways.status: publishe

Sexual minority status and psychotic symptoms: findings from the Netherlands Mental Health Survey and Incidence Studies (NEMESIS)

BACKGROUND: Ethnic minority position is associated with increased risk for psychotic outcomes, which may be mediated by experiences of social exclusion, defeat and discrimination. Sexual minorities are subject to similar stressors. The aim of this study is to examine whether sexual minorities are at increased risk for psychotic symptoms and to explore mediating pathways. METHOD: A cross-sectional survey was performed assessing cumulative incidence of psychotic symptoms with the Composite International Diagnostic Interview in two separate random general population samples (NEMESIS-1 and NEMESIS-2). Participants were sexually active and aged 18-64 years (n = 5927, n = 5308). Being lesbian, gay or bisexual (LGB) was defined as having sexual relations with at least one same-sex partner during the past year. Lifetime experience of any psychotic symptom was analysed using logistic regression, adjusted for gender, educational level, urbanicity, foreign-born parents, living without a partner, cannabis use and other drug use. RESULTS: The rate of any psychotic symptom was elevated in the LGB population as compared with the heterosexual population both in NEMESIS-1 [odds ratio (OR) 2.56, 95% confidence interval (CI) 1.71-3.84] and NEMESIS-2 (OR 2.30, 95% CI 1.42-3.71). Childhood trauma, bullying and experience of discrimination partly mediated the association. CONCLUSIONS: The finding that LGB orientation is associated with psychotic symptoms adds to the growing body of literature linking minority status with psychosis and other mental health problems, and suggests that exposure to minority stress represents an important mechanism

Application of data pooling to longitudinal studies of early post-traumatic stress disorder (PTSD): the International Consortium to Predict PTSD (ICPP) project

ABSTRACT Background:: Understanding the development of post-traumatic stress disorder (PTSD) is a precondition for efficient risk assessment and prevention planning. Studies to date have been site and sample specific. Towards developing generalizable models of PTSD development and prediction, the International Consortium to Predict PTSD (ICPP) compiled data from 13 longitudinal, acute-care based PTSD studies performed in six different countries. Objective:: The objectives of this study were to describe the ICPP’s approach to data pooling and harmonization, and present cross-study descriptive results informing the longitudinal course of PTSD after acute trauma. Methods:: Item-level data from 13 longitudinal studies of adult civilian trauma survivors were collected. Constructs (e.g. PTSD, depression), measures (questions or scales), and time variables (days from trauma) were identified and harmonized, and those with inconsistent coding (e.g. education, lifetime trauma exposure) were recoded. Administered in 11 studies, the Clinician Administered PTSD Scale (CAPS) emerged as the main measure of PTSD diagnosis and severity. Results:: The pooled data set included 6254 subjects (39.9% female). Studies’ average retention rate was 87.0% (range 49.1–93.5%). Participants’ baseline assessments took place within 2 months of trauma exposure. Follow-up durations ranged from 188 to 1110 days. Reflecting studies’ inclusion criteria, the prevalence of baseline PTSD differed significantly between studies (range 3.1–61.6%), and similar differences were observed in subsequent assessments (4.3–38.2% and 3.8–27.0% for second and third assessments, respectively). Conclusion:: Pooling data from independently collected studies requires careful curation of individual data sets for extracting and optimizing informative commonalities. However, it is an important step towards developing robust and generalizable prediction models for PTSD and can exceed findings of single studies. The large differences in prevalence of PTSD longitudinally cautions against using any individual study to infer trauma outcome. The multiplicity of instruments used in individual studies emphasizes the need for common data elements in future studies