Genetic Influences on the Neural and Physiological Bases of Acute Threat: A Research Domain Criteria (RDoC) Perspective

The NIMH Research Domain Criteria (RDoC) initiative aims to describe key dimensional constructs underlying mental function across multiple units of analysis—from genes to observable behaviors—in order to better understand psychopathology. The acute threat (“fear”) construct of the RDoC Negative Valence System has been studied extensively from a translational perspective, and is highly pertinent to numerous psychiatric conditions, including anxiety and trauma-related disorders. We examined genetic contributions to the construct of acute threat at two units of analysis within the RDoC framework: (1) neural circuits and (2) physiology. Specifically, we focused on genetic influences on activation patterns of frontolimbic neural circuitry and on startle, skin conductance, and heart rate responses. Research on the heritability of activation in threat-related frontolimbic neural circuitry is lacking, but physiological indicators of acute threat have been found to be moderately heritable (35–50%). Genetic studies of the neural circuitry and physiology of acute threat have almost exclusively relied on the candidate gene method and, as in the broader psychiatric genetics literature, most findings have failed to replicate. The most robust support has been demonstrated for associations between variation in the serotonin transporter (SLC6A4) and catechol-O-methyltransferase (COMT) genes with threat-related neural activation and physiological responses. However, unbiased genome-wide approaches using very large samples are needed for gene discovery, and these can be accomplished with collaborative consortium-based research efforts, such as those of the Psychiatric Genomics Consortium (PGC) and Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium. © 2015 Wiley Periodicals, Inc

Caregiving and 5-HTTLPR Genotype Predict Adolescent Physiological Stress Reactivity: Confirmatory Tests of Gene × Environment Interactions

A theory-driven confirmatory approach comparing diathesis–stress and differential susceptibility models of Gene × Environment (G × E) interactions was applied to examine whether 5-HTTLPR genotype moderated the effect of early maternal caregiving on autonomic nervous system (ANS) stress reactivity in 113 adolescents aged 13–17 years. Findings supported a differential susceptibility, rather than diathesis–stress, framework. Carriers of one or more 5-HTTLPR short alleles (SS/SL carriers) reporting higher quality caregiving exhibited approach ANS responses to a speech task, whereas those reporting lower quality caregiving exhibited withdrawal ANS responses. Carriers of two 5-HTTLPR long alleles (LL carriers) were unaffected by caregiving. Findings suggest that 5-HTTLPR genotype and early caregiving in interaction are associated with ANS stress reactivity in adolescents in a “for better and for worse” fashion, and they demonstrate the promise of confirmatory methods for testing G × E interactions

Association of sexual harassment and sexual assault with midlife women’s mental and physical health

Importance: Sexual harassment and sexual assault are prevalent experiences among women. However, their association with health indices is less well understood. Objective: To investigate the association of history of sexual harassment and sexual assault with blood pressure, mood, anxiety, and sleep among midlife women. Design, setting, and participants: Nonsmoking women without cardiovascular disease were recruited from the community to undergo physical measurements (blood pressure, height, weight), medical history, and questionnaire psychosocial assessments (workplace sexual harassment, sexual assault, depression, anxiety, sleep). Exposures: Sexual harassment and sexual assault. Main outcomes and measures: Blood pressure, depressive symptoms, anxiety, and sleep characteristics. Results: Among the 304 nonsmoking women aged 40 to 60 years who participated in the study, all were free of clinical cardiovascular disease, and the mean (SD) age was 54.05 (3.99) years. A total of 19% reported a history of workplace sexual harassment (n = 58), and 22% reported a history of sexual assault (n = 67). Sexual harassment was related to significantly greater odds of stage 1 or 2 hypertension among women not taking antihypertensives (odds ratio [OR], 2.36; 95% CI, 1.10-5.06; P = .03) as well as clinically poor sleep (OR, 1.89; 95% CI, 1.05-3.42; P = .03), after adjusting for covariates. Sexual assault was associated with significantly greater odds of clinically elevated depressive symptoms (OR, 2.86; 95% CI, 1.42-5.77; multivariable P = .003), clinically relevant anxiety (OR, 2.26; 95% CI, 1.26-4.06; P = .006), and clinically poor sleep (OR, 2.15; 95% CI, 1.23-3.77; multivariable P = .007), after adjusting for covariates. Conclusions and relevance: Sexual harassment and sexual assault are prevalent experiences among midlife women. Sexual harassment was associated with higher blood pressure and poorer sleep. Sexual assault was associated with poorer mental health and sleep. Efforts to improve women's health should target sexual harassment and assault prevention

Geriatrisch spreekuur door een specialist ouderengeneeskunde in de huisartspraktijk

Beschreven wordt een innovatief project waarin huisartsen, een specialist ouderengeneeskunde en een thuiszorgorganisatie samenwerken. Doel was kwetsbare ouderen op te sporen, adequaat te behandelen en te ondersteunen, zodat ze zolang mogelijk in hun vertrouwde omgeving kunnen blijven wonen. Opsporing van kwetsbare ouderen vond plaats met het Easycare instrument. De resultaten, verzameld tussen 1 oktober 2007 en 1 juli 2009, tonen dat vooral mensen met dementieverschijnselen zijn opgespoord en behandeld. Bij hen lag het accent op het verlenen van zorgplangestuurde zorg, het geven van adviezen met betrekking tot de psychogeriatrische zorgverlening en de inzet van thuiszorg op maat. Bij ouderen met somatische problematiek vonden vooral eenmalige consulten door de specialist ouderengeneeskunde plaats. De tevredenheid over de geboden zorg bij ouderen zelf en ook de betrokken professionals was groot. In de pilot werd voorts een tendens gevonden van minder verwijzingen naar de 2elijn en een reductie van het aantal acute opnames in het verpleeghuis

Maternal Depressive Symptoms Not Associated with Reduced Height in Young Children in a US Prospective Cohort Study

Background: Shorter stature is associated with greater all cause and heart disease mortality, but taller stature with increased risk of cancer mortality. Though childhood environment is important in determining height, limited data address how maternal depression affects linear growth in children. We examined the relationships between antenatal and postpartum depressive symptoms and child height and linear growth from birth to age 3 years in a U.S. sample. Methods: Subjects were 872 mother-child pairs in Project Viva, a prospective pre-birth cohort study. The study population is relatively advantaged with high levels of income and education and low risk of food insecurity. We assessed maternal depression at mid-pregnancy (mean 28 weeks' gestation) and 6 months postpartum with the Edinburgh Postnatal Depression Scale (score > = 13 on 0–30 scale indicating probable depression). Child outcomes at age 3 were height-for-age z-score (HAZ) and leg length. HAZ was also available at birth and ages 6 months, 1, 2, and 3 years. Findings: Seventy (8.0%) women experienced antenatal depression and 64 (7.3%) experienced postpartum depression. The mean (SD) height for children age 3 was 97.2 cm (4.2), with leg length of 41.6 cm (2.6). In multivariable linear regression models, exposure to postpartum depression was associated with greater HAZ (0.37 [95% confidence interval: 0.16, 0.58]) and longer leg length (0.88 cm [0.35, 1.41]). The relationship between postpartum depression and greater HAZ was evident starting at 6 months and continued to age 3. We found minimal relationships between antenatal depression and child height outcomes. Conclusion: Our findings do not support the hypothesis that maternal depression is associated with reduced height in children in this relatively advantaged sample in a high-income country

Posttraumatic stress disorder in the World Mental Health Surveys

Background: Traumatic events are common globally; however, comprehensive population-based cross-national data on the epidemiology of posttraumatic stress disorder (PTSD), the paradigmatic trauma-related mental disorder, are lacking. Methods: Data were analyzed from 26 population surveys in the World Health Organization World Mental Health Surveys. A total of 71 083 respondents ages 18+ participated. The Composite International Diagnostic Interview assessed exposure to traumatic events as well as 30-day, 12-month, and lifetime PTSD. Respondents were also assessed for treatment in the 12 months preceding the survey. Age of onset distributions were examined by country income level. Associations of PTSD were examined with country income, world region, and respondent demographics. Results: The cross-national lifetime prevalence of PTSD was 3.9% in the total sample and 5.6% among the trauma exposed. Half of respondents with PTSD reported persistent symptoms. Treatment seeking in high-income countries (53.5%) was roughly double that in low-lower middle income (22.8%) and upper-middle income (28.7%) countries. Social disadvantage, including younger age, female sex, being unmarried, being less educated, having lower household income, and being unemployed, was associated with increased risk of lifetime PTSD among the trauma exposed. Conclusions: PTSD is prevalent cross-nationally, with half of all global cases being persistent. Only half of those with severe PTSD report receiving any treatment and only a minority receive specialty mental health care. Striking disparities in PTSD treatment exist by country income level. Increasing access to effective treatment, especially in low- and middle-income countries, remains critical for reducing the population burden of PTSD

Применение метода долгосрочного прогнозирования водонефтяного фактора для определения максимально возможного расчётного объёма добычи нефти месторождения "Чёрный Дракон", Вьетнам

Objective - Although junctional adhesion molecule-A (JAM-A) has recently been implicated in leukocyte recruitment on early atherosclerotic endothelium and after reperfusion injury, its role in neointima formation after arterial injury remains to be elucidated. Methods and Results - Here we show that the genetic deletion of JAM-A in apolipoprotein E - deficient (apoE(-/-)) mice significantly reduced neointimal hyperplasia after wire injury of carotid arteries without altering medial area. This was associated with a significant decrease in neointimal macrophage content, whereas the relative content of smooth muscle cells and endothelial recovery was unaltered in JAM-A(-/-) apoE(-/-) compared with JAM-A(-/-) apoE(-/-) lesions. In carotid arteries perfused ex vivo, deficiency in JAM-A significantly impaired the recruitment of monocytes 1 week, but not 1 day, after injury. These effects were paralleled by an attenuation of monocyte arrest and transmigration on activated JAM-A(-/-) apoE(-/-) versus JAM-A(-/-) apoE(-/-) endothelial cells under flow conditions in vitro. A mechanism underlying reduced recruitment was implied by findings that the luminal expression of the arrest chemokine RANTES in injured arteries and its endothelial deposition by activated platelets in vitro were diminished by JAM-A deficiency. Conclusions - Our data provide the first evidence to our knowledge for a crucial role of JAM-A in accelerated lesion formation and monocyte infiltration in atherosclerosis-prone mice

Trauma and posttraumatic stress disorder in South Africa: analysis from the South African Stress and Health Study

Background: South Africa’s unique history, characterised by apartheid, a form of constitutional racial segregation and exploitation, and a long period of political violence and state-sponsored oppression ending only in 1994, suggests a high level of trauma exposure in the general population. The aim of this study was to document the epidemiology of trauma and posttraumatic stress disorder (PTSD) in the South African general population. Methods: The South African Stress and Health Study is a nationally representative survey of South African adults using the WHO’s Composite International Diagnostic Interview (CIDI) to assess exposure to trauma and presence of DSM-IV mental disorders. Results: The most common traumatic events were the unexpected death of a loved one and witnessing trauma occurring to others. Lifetime and 12-month prevalence rates of PTSD were 2.3% and 0.7% respectively, while the conditional prevalence of PTSD after trauma exposure was 3.5%. PTSD conditional risk after trauma exposure and probability of chronicity after PTSD onset were both highest for witnessing trauma. Socio-demographic factors such as sex, age and education were largely unrelated to PTSD risk. Conclusions: The occurrence of trauma and PTSD in South Africa is not distributed according to the sociodemographic factors or trauma types observed in other countries. The dominant role of witnessing in contributing to PTSD may reflect the public settings of trauma exposure in South Africa and highlight the importance of political and social context in shaping the epidemiology of PTSD

Association of the rs2242446 polymorphism in the norepinephrine transporter gene SLC6A2 and anxious arousal symptoms of posttraumatic stress disorder

To the Editor: Recently, we found that greater norepinephrine transporter (NET) availability in the locus ceruleus of trauma survivors with posttraumatic stress disorder (PTSD) was associated with increased severity of anxious arousal (ie, hypervigilance and exaggerated startle) symptoms, but not any of the other empirically derived symptom clusters that characterize this disorder.1 This finding suggests that greater NET availability in the locus ceruleus may serve a compensatory function of clearing elevated synaptic norepinephrine and maintaining anxious arousal symptoms in persons with PTSD