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.

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.

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 VO2 max (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.

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.

Estimating the risk of PTSD in recent trauma survivors: results of the International Consortium to Predict PTSD (ICPP).

A timely determination of the risk of post-traumatic stress disorder (PTSD) is a prerequisite for efficient service delivery and prevention. We provide a risk estimate tool allowing a calculation of individuals' PTSD likelihood from early predictors. Members of the International Consortium to Predict PTSD (ICPP) shared individual participants' item-level data from ten longitudinal studies of civilian trauma survivors admitted to acute care centers in six countries. Eligible participants (N=2,473) completed an initial clinical assessment within 60 days of trauma exposure, and at least one follow-up assessment 4-15 months later. The Clinician-Administered PTSD Scale for DSM-IV (CAPS) evaluated PTSD symptom severity and diagnostic status at each assessment. Participants' education, prior lifetime trauma exposure, marital status and socio-economic status were assessed and harmonized across studies. The study's main outcome was the likelihood of a follow-up PTSD given early predictors. The prevalence of follow-up PTSD was 11.8% (9.2% for male participants and 16.4% for females). A logistic model using early PTSD symptom severity (initial CAPS total score) as a predictor produced remarkably accurate estimates of follow-up PTSD (predicted vs. raw probabilities: r=0.976). Adding respondents' female gender, lower education, and exposure to prior interpersonal trauma to the model yielded higher PTSD likelihood estimates, with similar model accuracy (predicted vs. raw probabilities: r=0.941). The current model could be adjusted for other traumatic circumstances and accommodate risk factors not captured by the ICPP (e.g., biological, social). In line with their use in general medicine, risk estimate models can inform clinical choices in psychiatry. It is hoped that quantifying individuals' PTSD risk will be a first step towards systematic prevention of the disorder.

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

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.

Antecedentes: Comprender el desarrollo del trastorno de estrés postraumático (TEPT) es una condición previa para una evaluación de riesgos y una planificación de prevención eficientes. Los estudios hasta la fecha han sido específicos del sitio y de la muestra. Hacia el desarrollo de modelos generalizables de desarrollo y predicción de TEPT, el Consorcio Internacional para Predecir el TEPT (ICPP) recopiló datos de 13 estudios de TEPT longitudinales basados en la atención aguda realizados en seis países diferentes.Objetivo: describir el enfoque del ICPP para la combinación de datos y la armonización, y presentar los resultados descriptivos entre estudios que informan el curso longitudinal del trastorno de estrés postraumático después del trauma agudo.Métodos: se recogieron datos a nivel de ítem de 13 estudios longitudinales de adultos sobrevivientes de trauma civil. Se identificaron y armonizaron constructos (por ejemplo, trastorno de estrés postraumático, depresión), medidas (preguntas o escalas) y variables de tiempo (días desde el trauma) y se recodificaron aquellas con codificación inconsistente (por ejemplo, educación, exposición de trauma a lo largo de la vida). Administrado en 11 estudios, la Escala de TEPT Administrada por el Clínico (CAPS) surgió como la principal medida del diagnóstico y la gravedad del TEPT.Resultados: el conjunto de datos agrupado incluyó 6254 sujetos (39,9% mujeres). La tasa promedio de retención de estudios fue 87.0% (rango: 49.1% a 93.5%). Las evaluaciones iniciales de los participantes se realizaron dentro de los dos meses posteriores a la exposición al trauma. Las duraciones de seguimiento variaron de 188 a 1110 días. Reflejando los criterios de inclusión de los estudios, la prevalencia de TEPT basal difirió significativamente entre los estudios (rango: 3,1% a 61,6%), y se observaron diferencias similares en las evaluaciones posteriores (respectivamente, 4,3% a 38,2% y 3,8% a 27,0% para la segunda y tercera evaluaciones).Conclusión: la agrupación de datos de los estudios recopilados de forma independiente requiere una cuidadosa conservación de los conjuntos de datos individuales para extraer y optimizar las comunalidades informativas. Sin embargo, es un paso importante hacia el desarrollo de un modelo de predicción robusto y generalizable para el TEPT y poder superar los hallazgos de estudios únicos. Las grandes diferencias en la prevalencia de TEPT advierten longitudinalmente contra el uso de cualquier estudio individual para inferir el resultado del trauma. La multiplicidad de instrumentos utilizados en estudios individuales enfatiza la necesidad de elementos de datos comunes en estudios futuros.

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.

Reactivity to social stress in ethnic minority men.

Repeated exposures to social exclusion, through a process of sensitization, may result in larger responses to experiences of social stress. The current study tested the hypothesis that healthy Moroccan-Dutch men respond stronger to social stress than Dutch controls 1) in daily life, and 2) in an experimental set-up. A general population sample of 50 Moroccan-Dutch and 50 Dutch young adult males were tested with 1) the Experience Sampling Method, a structured diary technique, assessing reactivity to social stress in daily life, and 2) an experimental exposure to social peer evaluation. No group differences were found in affective or psychotic reactivity to daily social stress. When exposed to a negative social evaluation in the lab, a blunted affective response was found in the Moroccan-Dutch compared to the Dutch group, whereas the psychotic response did not differ significantly between groups. In conclusion, healthy Moroccan-Dutch men are not more sensitive to social stress than healthy Dutch men. Instead, the blunted affective response of Moroccan-Dutch men to peer evaluation may signify habituation rather than sensitization.

Prevention of Post-Traumatic Stress Disorder After Trauma: Current Evidence and Future Directions.

Post-traumatic stress disorder (PTSD) is a frequent, tenacious, and disabling consequence of traumatic events. The disorder's identifiable onset and early symptoms provide opportunities for early detection and prevention. Empirical findings and theoretical models have outlined specific risk factors and pathogenic processes leading to PTSD. Controlled studies have shown that theory-driven preventive interventions, such as cognitive behavioral therapy (CBT), or stress hormone-targeted pharmacological interventions, are efficacious in selected samples of survivors. However, the effectiveness of early clinical interventions remains unknown, and results obtained in aggregates (large groups) overlook individual heterogeneity in PTSD pathogenesis. We review current evidence of PTSD prevention and outline the need to improve the disorder's early detection and intervention in individual-specific paths to chronic PTSD.

Increased release of dopamine in the striata of young adults with hearing impairment and its relevance for the social defeat hypothesis of schizophrenia.

IMPORTANCE: An increased risk for psychosis is observed in people with hearing impairment. According to the social defeat hypothesis, the long-term experience of exclusion leads to enhanced baseline activity and/or sensitization of the dopamine system and puts the individual at increased risk for psychosis. OBJECTIVE: To investigate whether young adults with severe hearing impairment (SHI) experience more feelings of social defeat, show greater dopamine release in response to dexamphetamine, and report a stronger subjective reaction to this substance than normal-hearing young adults and to examine whether dopamine release is associated with both self-reported social exclusion and dexamphetamine-induced psychotic experiences. DESIGN, SETTING, AND PARTICIPANTS: A sample of 19 participants with SHI and 19 smoking-, age-, and sex-matched healthy controls underwent single-photon emission computed tomography with iodine 123-labeled iodobenzamide as a radiotracer before and after an amphetamine challenge at an academic hospital. EXPOSURES: Dexamphetamine sulfate (0.3 mg/kg) administered intravenously. MAIN OUTCOMES AND MEASURES: Baseline D2/3 receptor binding and endogenous dopamine release. RESULTS: The participants with SHI reported experiencing more feelings of social defeat (U=109, z=-2.09, P=.04) and loneliness (U=87.5, z=-2.72, P=<.001) than did healthy controls, but they did not differ from healthy controls with regard to baseline psychotic symptoms (U=156.5, z=-0.70, P=.48). There were no significant group differences in baseline D2/3 receptor binding. However, repeated-measures multivariate analysis of covariance with age (in months) and tobacco smoking (in pack-years) as covariates showed that there was a greater amphetamine-induced striatal dopamine release among the participants with SHI than among the healthy controls (F1,34=4.55, P=.04). After amphetamine administration, the participants with SHI reported more changes in affect than the healthy controls, but not a greater increase in psychotic symptoms. Likewise, reports of social exclusion and an increase in psychotic symptoms were not associated with dopamine release. CONCLUSIONS AND RELEVANCE: Our study presents preliminary evidence of dopamine sensitization in a socially excluded group of people with hearing impairment. If replicated by future studies in other excluded groups, this finding may have major implications for our understanding of the underlying mechanism and for prevention of psychotic disorders.