Trauma and mental health in young adults who arrived in France as unaccompanied and separated migrant children.

OBJECTIVES: The mental health of unaccompanied and separated minors (UASC) has been widely studied but not their first years of adulthood, often characterised by uncertainty after leaving child protection. The aim of this study was to estimate the prevalence of psychiatric disorders using standardised and validated research instruments and examine the effect of exposure to trauma. METHODS: One hundred and ten youth (92.7% male, median age 19.7 [18.1-22.8]) from Chambery, Montpellier and La Rochelle were recruited to a cross-sectional exploratory study. During a face-to-face interview, somatoform disorder, anxiety, and depression were assessed using the Patient Health Questionnaire (score≥10) and post-traumatic stress disorder (PTSD) with the PTSD Checklist for DSM-5 (score≥33). Traumatic life events were assessed using the Life Events Checklist. RESULTS: Of the youth, 19.3% had a probable somatoform disorder, 17.6% anxiety, 28.7% depression, and 20% PTSD. The number of traumatic life events increased the risk of depression (multi-adjusted OR (95%CI): 1.56 (1.25-1.96)), PTSD (1.60 (1.23-2.08)), somatoform disorder (1.41 (1.10-1.82), and anxiety (1.33 (1.02-1.72)). Physical assault was the type of event positively associated with the most disorders (P≤0.01, except for anxiety), followed by witnessing sudden and violent death (P≤0.01 for depression and PTSD) and sexual assault (P=0.002 for PTSD). CONCLUSION: Our study highlights the high prevalence of psychiatric disorders in young adults who arrived as UASC and the impact on their mental health of cumulative trauma and exposure to interpersonal and violent traumatic life events. A greater focus on their mental health with regular assessments is needed in order to provide rapid and adapted care.

Association between uncertainty regarding right-to-stay and mental health in unaccompanied and separated migrant children (UASC) reaching adulthood: findings from France.

PURPOSE: There is substantial evidence suggesting high levels of mental health problems in unaccompanied and separated children (UASC). However, there is less focus on the first years of adulthood characterised by increased vulnerability and fear of expulsion. We aimed to describe the mental health of UASC on reaching adulthood, and how this was affected by uncertainty regarding their right-to-stay in France. METHODS: One hundred and ten youth aged 18-22 were recruited via child protection reception centres. We administered the Patient Health Questionnaire somatic (PHQ-15), anxiety (GAD-7) and depression (PHQ-9) modules, the Post-Traumatic Stress Disorder Checklist (PCL-5) and Connor-Davidson Resilience Scale (CD-RISC-10). Logistic regression analysis was performed with the dependent variable, a secure (versus uncertain) situation, defined as (1) detaining a residence permit and being in school, an apprenticeship or a salaried job, or (2) waiting for residence permit whilst occupying a salaried job. RESULTS: Of the sample, 19.3% reached criteria for a probable somatic disorder, 17.6% for anxiety and 28.7% for depression (score  ≥ 10); 41.8% were in an uncertain situation regarding their right-to-stay. Uncertainty was associated with higher anxiety ((OR per Interquartile range (95% CI), 1.77 (1.05-2.98)) and post-traumatic stress symptoms (2.05 (1.06-4.00)), lower resilience (0.50 (0.27-0.91)), and participants rating their anxiety (p = 0.02) and depressive symptoms (p = 0.003) as more severe since reaching adulthood. CONCLUSIONS: Our findings suggest uncertainty regarding right-to-stay is associated with increased mental health symptoms, specifically anxiety and trauma-induced stress, thereby highlighting the vulnerability of UASC in their first years of adulthood. This calls for greater support during this transition period with regular symptom monitoring for timely psychological interventions.

The association between adverse childhood events and later-life cognitive function and dementia risk.

BACKGROUND: Considerable work exists in the literature to describe the negative impacts of early-life stress exposures on health in adulthood. This study investigated whether the accumulation of adverse childhood events is associated with later-life cognitive function and incident dementia. METHODS: Participants were 1562 community-dwelling older adults, who were enrolled in the ESPRIT cohort in France. Adverse childhood events were measured using a modified version of the Childhood Trauma Questionnaire. Cognition was measured using tests of global cognition, visual memory, verbal fluency, psychomotor speed and executive function. Fourteen-year incident dementia was diagnosed using DSM-IV criteria. RESULTS: In comparison to participants with two or less adverse childhood events, increased risk of poor psychomotor speed at baseline was observed in individuals with multiple adverse childhood events (3-4 events OR: 1.39, 95% CI: 1.00-1.93); ≥5 events (OR: 1.52, 95% CI: 1.07-2.17), particularly in women but not in men. Worse verbal fluency was also observed in individuals who experienced between three and four adverse childhood events (OR: 1.34, 95% CI: 1.00-1.78). Amongst the individual factors investigated, early-life abuse/maltreatment (OR: 1.47, 95% CI: 1.02-2.14) and poverty/financial difficulties (OR: 1.53, 95% CI: 1.12-2.08) was associated with worse psychomotor speed. No associations were observed with incident dementia. LIMITATIONS: Participants most at risk (those with baseline dementia) were excluded. CONCLUSION: Multiple adverse childhood events are associated with worse psychomotor speed, and verbal fluency in later-life, however further research is needed to determine the mechanisms underlying this association and whether it results from unmeasured confounding, including social disadvantage.

A Prospective Study of Diurnal Cortisol and Incident Dementia in Community-Dwelling Older Adults.

Diurnal salivary cortisol was measured in 334 older adults without dementia, at four times on two separate days, under quiet and stressful conditions. In multivariate Cox proportional hazard models, higher global diurnal cortisol secretion was associated with incident dementia (HR = 1.09 [1.02-1.15] per one-unit increase in cortisol measure, p = 0.007) and Alzheimer's disease (HR = 1.12 [1.04-1.21], p = 0.003) over a mean (SD) of 8.1 (4.0) years, independent of potential confounders and stressful conditions. Individuals with incident dementia had a slower rate of cortisol elimination under non-stressful conditions, reflected by higher cortisol levels in the evening, and an abnormal response to stress (blunted evening stress response).

Steroid 21-hydroxylase gene variants and late-life depression.

OBJECTIVES: A feature of late-life depression is alterations of the stress hormone system. The CYP21A2 gene encodes for the steroid 21-hydroxylase enzyme which is required for the biosynthesis of mineralocorticoids and glucocorticoids, two main components of the stress response in humans. Variants in the CYP21A2 gene could influence risk of late-life depression, but this has not been examined. This study investigated possible associations between five variants in the CYP21A2 gene and late-life depression in 1007 older community-dwelling men and women. RESULTS: In multivariate logistic regression model, significant associations were found between three single-nucleotide polymorphisms (rs389883, rs437179, and rs630379) and depression in women specifically (OR ranging from 1.51 to 1.68, p-values 0.025 to 0.0045), and the two latter remained significant after correction for multiple testing. Variants of the CYP21A2 gene appear as susceptibility factors for late-life depression in a sex-specific manner, independently of somatic and neuropsychiatric comorbidity.

Structural brain alterations in older adults exposed to early-life adversity.

BACKGROUND: Adverse childhood events may have differential effects on the brain that persist into adulthood. Findings on structural brain alterations in older adults exposed to early-life adversity are inconsistent notably due to heterogeneity in imaging studies, population, psychiatric comorbidities, nature of adverse events, and genetic vulnerability. This study examines whether exposure related to physical or sexual maltreatment, emotional maltreatment, and global adverse environment during childhood are associated with specific alterations in grey matter volumes and if this varies according to sex and serotonin transporter-linked promoter region (5-HTTLPR) genotype. METHOD: Structural MRI was used to acquire anatomical scans from 398 community-dwelling older adults. Quantitative regional estimates of 23 subregional volumes were derived using FreeSurfer software. Retrospective reporting of childhood adversity was collected using structured self-reported questionnaire. Analyses adjusted for age, sex, brain volume, head injury, lifetime depression and anxiety disorder, psychiatric medication, and cardiovascular ischemic pathologies. RESULTS: Exposure to adverse family environment was associated with smaller volumes of several frontal, cingulate, and parietal subregions and larger amygdala in the 5-HTTLPR SS genotype participants specifically but larger volumes of caudate, putamen, pallidum, and nucleus accumbens in the SL genotype participants. Highly significant differences were found with excessive sharing of parent problems with children, associated with larger grey-matter volumes in the thalamus and several frontal and parietal regions in 5-HTTLPR SL male participants specifically. CONCLUSIONS: Early-life adversity is associated with grey-matter volume alterations in older adults and this varies according to the type of adversity experienced, sex, and serotonergic genetic vulnerability; 5-HTTLPR SS participants appearing most vulnerable and SL individuals most resilient.

11ß-Hydroxylase (CYP11B1) gene variants and new-onset depression in later life.

Background: Cumulative exposure to high glucocorticoid levels is detrimental for the brain and may have particular implications in later life. A feature of late-life depression is increased cortisol secretion. Variants in the CYP11B1 gene, which codes for the enzyme responsible for cortisol synthesis, could influence risk of late-life depression, but this hypothesis has not been examined. We investigated the associations between variants in the CYP11B1 gene and late-life depression, taking into account history of depression and potential sex-specific effects. Methods: We assessed depression in 1007 community-dwellers aged 65 years or older (60% women) at baseline and over a 14-year follow-up. A clinical level of depression was defined as a score of ≥ 16 on the Centre for Epidemiology Studies Depression scale or a diagnosis of current major depression based on the Mini-International Neuropsychiatric Interview and according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV). We examined incident and recurrent depression in participants without or with a history of major depression, respectively. We genotyped 5 single-nucleotide polymorphisms (SNPs) spanning CYP11B1. We used multivariable analyses to adjust for age, body mass index, cardiovascular ischemic pathologies, hypertension, cognitive impairment and anxiety. Results: In women, rs6471580 and rs7016924 were associated with a 50% lower rate of incident (new-onset) late-life depression, and rs11783855 was associated with a 2.4-fold higher rate of late-life depression. These associations remained after correction for multiple testing, but we found no associations for recurrent depression in women or men. Limitations: This study focused on the major gene involved in corticosteroid biosynthesis, but other genes may also be implicated in this pathway. Conclusion: Variants of the CYP11B1 gene appear to be susceptibility factors for late-life depression in a sex-specific manner.

The long-term consequences of trauma and posttraumatic stress disorder symptoms on later life cognitive function and dementia risk.

Stress may be a risk factor for dementia, however it is unknown whether post-traumatic stress disorder (PTSD) symptoms are associated with incident dementia in community-dwelling older individuals. The aim was to determine whether lifetime major trauma with and without re-experiencing of PTSD symptoms is associated with later-life cognition and dementia risk. Participants were 1,700 community-dwelling older adults (65+) in the longitudinal ESPRIT study followed over 14 years. Lifetime major traumatic exposure and PTSD were assessed using Watson's PTSD Inventory. Cognitive tests assessed global cognition, visual memory, verbal fluency, psychomotor speed and executive function. Incident dementia was diagnosed according to DSM-IV criteria. Lifetime major trauma (versus no trauma) was associated with significantly increased executive function and increased global function in men, however women with lifetime trauma and re-experiencing symptoms had a significantly increased risk of low global cognition. Over 14 years, lifetime trauma without re-experiencing symptoms was associated with a significantly decreased risk of incident dementia, particularly for women. Lifetime major trauma without re-experiencing symptoms (but not with) may be protective for later life cognitive function. However, the mechanisms and moderating factors underlying these association requires further investigation.

Dexamethasone Suppression Test May Predict More Severe/Violent Suicidal Behavior.

INTRODUCTION: Several studies demonstrated that the hypothalamic-pituitary-adrenal (HPA) axis is dysregulated in suicide attempters. Prospective studies found that people with an abnormal response at the dexamethasone suppression test (DST) are more likely to commit suicide. However, whether DST may predict suicide attempts remains less clear. A possible strategy to address this question is to consider the suicide attempt lethality. OBJECTIVES: (1) To compare the pre- and post-DST cortisol levels in serious/violent suicide attempters and in non-serious/non-violent suicide attempters, and (2) to investigate whether cortisol level can predict new suicide attempts or their lethality. METHODS: The study included 70 recent suicide attempters (25 with a serious or violent attempt) who were followed for two years. Three saliva samples for cortisol measurement were obtained at 8a.m., 3p.m., and 9p.m. before the DST (pre-DST). Then, at 11 p.m., 1 mg of dexamethasone was given orally. The following day (post-DST), three saliva samples were collected at the same hours as before. The post-DST-pre-DST salivary cortisol Δ index was calculated for each collection time. The Risk-Rescue Ratio Scale (RRRS) and the Suicidal Intent Scale (SIS) were used to characterize the suicide attempt at inclusion and those occurring during the follow-up. RESULTS: Post-DST cortisol level at 9 p.m. was higher in patients with an initial violent or serious suicide attempt than in non-violent/non-serious attempters (p < .010). Higher post-DST cortisol at 9p.m. was associated with lower RRRS rescue score and higher clinical impression of suicide severity at inclusion. Among the 66 patients who completed the follow-up, 26 attempted suicide again at least once. Higher pre-DST cortisol at 8a.m. predicted new suicide attempts during the follow-up (OR = 2.15 [1.11, 4.15]), and higher cortisol Δ index at 9p.m. was associated with higher suicide intent during the follow-up. CONCLUSIONS: Our results suggest that HPA axis hyper-reactivity monitored with the DST is a marker of violent/serious suicide attempt with lower rescue possibility. Furthermore, higher changes between pre-DST and post-DST cortisol levels may predict higher suicide intent. These findings might help to characterize the biological features of nearest suicide phenotypes.

Structural brain changes with lifetime trauma and re-experiencing symptoms is 5-HTTLPR genotype-dependent.

Background: Findings on structural brain alterations following trauma are inconsistent due probably to heterogeneity in imaging studies and population, clinical presentations, genetic vulnerability, and selection of controls. This study examines whether trauma and re-experiencing symptoms are associated with specific alterations in grey matter volumes and if this varies according to 5-HTTLPR genotype. Methods: Structural MRI was used to acquire anatomical scans from 377 community-dwelling older adults. Quantitative regional estimates of 22 subregional volumes were derived using FreeSurfer software. Lifetime trauma was assessed using the validated Watson's PTSD inventory, which evaluates the most severe trauma experienced according to DSM criteria. Analyses adjusted for age, sex, total brain volume, head injury, and comorbidities. Results: Of the 212 participants reporting lifetime trauma, 35.4% reported re-experiencing symptoms and for 1.9%, this was severe enough to meet criteria for full threshold PTSD. In participants with the SS 5-HTTLPR genotype only, re-experiencing symptoms were associated with smaller volumes in middle and superior temporal, frontal (lateral orbital, rostral and caudal middle) and parietal (precuneus, inferior and superior) regions. The trauma-exposed participants without re-experiencing symptoms were not significantly different from the non-trauma-exposed participants except for smaller precuneus and superior parietal region in traumatized participants and a larger amygdala in traumatized women specifically. Conclusions: In the non-clinical sample, lifetime trauma and re-experiencing symptoms were associated with smaller volume in prefrontal, temporal and parietal cortex subregions, and this varied according to serotonergic genetic vulnerability, 5-HTTLPR SS individuals being most susceptible.

Antecedentes: Los hallazgos sobre las alteraciones estructurales cerebrales luego del trauma son inconsistentes debido probablemente a heterogeneidad en los estudios de imagen y población, presentaciones clínicas, vulnerabilidad genética y selección de los controles. Este estudio examina si el trauma y los síntomas de reexperimentación están asociados con alteraciones específicas en los volúmenes de materia gris y si esto varía de acuerdo al genotipo 5-HTTLPR.Métodos: Se utilizó IMR estructural para adquirir mapeos anatómicos de 377 adultos mayores residentes en viviendas comunitarias. Se derivaron estimados regionales cuantitativos de 22 volúmenes sub-regionales usando el software FreeSurfer. Se evaluó trauma a través de la vida utilizando el inventario para TEPT validado de Watson, que evalúa el trauma más severo experimentado de acuerdo a criterios DSM. Se ajustaron los análisis por edad, sexo, volumen cerebral total, trauma encefálico y comorbilidades.Resultados: De los 212 participantes que reportaron trauma en la vida, un 35.4% reportó síntomas de reexperimentación y para el 1,9% fueron lo suficientemente severos para cumplir los criterios para el umbral completo del TEPT. Sólo en los participantes con el genotipo SS 5-HTTLPR, los síntomas de reexperimentación se asociaron con menores volúmenes en las regiones temporal media y superior, frontal (orbitolateral, rostral y caudal medial) y parietal (precúneo, inferior y superior). Los participantes expuestos a trauma sin síntomas de reexperimentación no variaron significativamente respecto a los no expuestos a trauma excepto por menor tamaño del precúneo y región superior parietal en los participantes traumatizados y un mayor tamaño de la amígdala específicamente en mujeres traumatizadas.Conclusiones: En una muestra no-clínica, el trauma a través de la vida y los síntomas de reexperimentación se asociaron con menor tamaño en sub-regiones corticales prefrontales, temporales y parietales, y esto varía de acuerdo a la vulnerabilidad genética serotoninérgica, siendo más susceptibles los individuos 5-HTTLPR SS.

The extent to which childhood adversity and recent stress influence all-cause mortality risk in older adults.

BACKGROUND: Psychological stress is recognized as a major risk factor for a range of non-communicable diseases and possibly mortality. The extent to which the type and timing of stress exposure influences mortality, and potential differences between genders, remains unknown. OBJECTIVE: To examine the association between early-life and recent stressful experiences and mortality risk in later life, and to determine possible gender differences in these associations. METHOD: Data were obtained from 2152 French community-dwelling participants (aged ≥65). Questionnaires were used to evaluate recent stress, as well as retrospective reporting of childhood adversity. Mortality status was determined through death registries. Adjusted Cox proportional hazards models were used to determine the association between stress and 16-year mortality risk. RESULTS: Over a mean 12.9 years, 850 people died. Having a childhood home environment with very serious conflicts was associated with a 54% increased mortality risk (95%CI:1.21-1.96), and childhood abuse/maltreatment with a 34% increased risk (95% CI:1.05-1.70). For females, specific childhood events (serious illness HR:1.91, 95%CI:1.40-2.60; war/natural disaster HR:1.47, 95%CI:1.14-1.88) and the number of events (≥5 adverse events HR:1.91, 95%CI:1.25-2.32), also increased mortality risk. In terms of recent events, mortality risk increased by 66% (95%CI:1.39-2.00) in participants reporting a recent serious illness or physical trauma and by 86% for those reporting problems with the police/justice (95%CI:1.05-3.30). Among males specifically, mortality risk also increased with major financial problems (HR:1.92, 95%CI:1.14-3.21), and when they had a relative with a serious illness (HR:1.26, 95%CI:1.01-1.55). CONCLUSIONS: Stressful life experiences are associated with all-cause mortality however the associations varied between early-life adversities and recent stress, and were different across the genders. Among females, certain types of childhood adversity continue to predict mortality risk in later life, while in males specific recent stress significantly increased mortality risk.

Lifetime major depression and grey-matter volume

Background: There is evidence of structural brain alterations in major depressive disorder (MDD), but little is known about how these alterations might be affected by age at onset or genetic vulnerability. This study examines whether lifetime episodes of MDD are associated with specific alterations in grey-matter volume, and whether those alterations vary according to sex or serotonin transporter-linked promoter region (5-HTTLPR) genotype (LL, SL or SS). Methods: We used structural MRI to acquire anatomic scans from 610 community-dwelling participants. We derived quantitative regional estimates of grey-matter volume in 16 subregions using FreeSurfer software. We diagnosed MDD according to DSM-IV criteria. We adjusted analyses for age, sex, total brain volume, education level, head injury and comorbidities. Results: Lifetime MDD was associated with a smaller insula, thalamus, ventral diencephalon, pallidum and nucleus accumbens and with a larger pericalcarine region in both men and women. These associations remained after adjustment for false discovery rate. Lifetime MDD was also associated with a smaller caudate nucleus and amygdala in men and with a larger rostral anterior cingulate cortex in women. Late-onset first episodes of MDD (after age 50 years) were associated with a larger rostral anterior cingulate cortex and lingual and pericalcarine regions; early-onset MDD was associated with a smaller ventral diencephalon and nucleus accumbens. Some associations differed according to 5-HTTLPR genotype: the thalamus was smaller in participants with MDD and the LL genotype; pericalcarine and lingual volumes were higher in those with the SL genotype. Limitations: This study was limited by its cross-sectional design. Conclusion: Major depressive disorder was associated with persistent volume reductions in the deep nuclei and insula and with enlargements in visual cortex subregions; alterations varied according to age of onset and genotype.

The effect of an adverse psychological environment on salivary cortisol levels in the elderly differs by 5-HTTLPR genotype.

BACKGROUND: An adverse psychological environment (e.g. stressful events or depression) has been shown to influence basal cortisol levels and cortisol response to stress. This differs depending on the adverse stimuli, but also varies across individuals and may be influenced by genetic predisposition. An insertion/deletion polymorphism in the serotonin transporter gene (5-HTTLPR) is a strong candidate in this regard. OBJECTIVE: To investigate how stressful life events and depression are associated with diurnal cortisol levels in community-dwelling elderly and determine whether this varies according to genetic variability in the 5-HTTLPR. METHODS: This population-based study included 334 subjects aged 65 and older (mean (SD) = 76.5 (6.3)). Diurnal cortisol was measured on two separate days, under quiet (basal) and stressful conditions. The number of recent major stressful events experienced during the past year was assessed from a 12-item validated questionnaire as an index of cumulative recent stressful events. Lifetime trauma was evaluated using the validated Watson's PTSD inventory, which evaluates the most severe traumatic or frightening experience according to DSM criteria. Depression was defined as having a Mini-International Neuropsychiatric Interview (MINI) diagnosis of current major depressive disorder or high levels of depressive symptoms (Center for Epidemiologic Studies-Depression Scale ≥16). 5-HTTLPR genotyping was performed on blood samples. RESULTS: Exposure to stressful life events was associated with lower basal evening cortisol levels overall, and in the participants with the 5-HTTLPR L allele but not the SS genotype. The greatest effects (over 50% decrease, p < 0.001) were observed for the LL participants having experienced multiple recent stressful events or severe lifetime traumas. Participants with the L allele also had higher evening cortisol stress response. Conversely, depression tended to be associated with a 42% higher basal morning cortisol in the SS participants specifically, but did not modify the association between stressful events and cortisol levels. CONCLUSION: An adverse psychological environment is associated with basal cortisol levels and cortisol stress response, but this differs according to 5-HTTLPR genotype.

Preliminary evidence for a role of the adrenergic nervous system in generalized anxiety disorder.

Generalized anxiety disorder (GAD) is a common chronic condition that is understudied compared to other psychiatric disorders. An altered adrenergic function has been reported in GAD, however direct evidence for genetic susceptibility is missing. This study evaluated the associations of gene variants in adrenergic receptors (ADRs) with GAD, with the involvement of stressful events. Data were obtained from 844 French community-dwelling elderly aged 65 or over. Anxiety disorders were assessed using the Mini-International Neuropsychiatry Interview, according to DSM-IV criteria. Eight single-nucleotide polymorphisms (SNPs) involved with adrenergic function were genotyped; adrenergic receptors alpha(1A) (ADRA1A), alpha(2A) (ADRA2A), and beta2 (ADRB2) and transcription factor TCF7L2. Questionnaires evaluated recent stressful life events as well as early environment during childhood and adolescence. Using multivariate logistic regression analyses four SNPs were significantly associated with GAD. A 4-fold modified risk was found with ADRA1A rs17426222 and rs573514, and ADRB2 rs1042713 which remained significant after Bonferroni correction. Certain variants may moderate the effect of adverse life events on the risk of GAD. Replication in larger samples is needed due to the small case number. This is the first study showing that ADR variants are susceptibility factors for GAD, further highlighting the critical role of the adrenergic nervous system in this disorder.

Heterogeneity in HPA axis dysregulation and serotonergic vulnerability to depression.

Variability in the serotonin transporter (5-HTTLPR) gene can influence the risk of depression associated with adversity, as well as cortisol stress reactivity, although not consistently. No study has examined the impact of both a stressful environment and corticotropic-axis dysfunction on depression, as a function of 5-HTTLPR. This population-based study included 334 subjects aged 65 and older. Depression was measured at both diagnostic (major depression according to DSM-IV) and symptomatic (subthreshold depression) levels of caseness, in addition to 5-HTTLPR and rs25531 genotyping and diurnal cortisol measures. For participants with the SS genotype, higher morning cortisol levels were associated with a 4-fold increased risk of depression. Among LL participants, both evening cortisol levels and recent stressful events increased depression risk, although only the latter remained significant after multivariable adjustment. Conversely, SL individuals appeared somewhat resilient to depression in terms of cortisol and recent stress. These findings indicate that 5-HTTLPR genetic variability appears to influence the association between stress-related factors and late-life depression, although the gene-environment interactions failed to reach statistical significance levels. Participants homozygous for the short allele appeared to have a cortisol-related neuroendocrine vulnerability to depression, while long allele homozygotes were more reactive to stressful events in terms of depression risk.

Biological underpinnings of trauma and post-traumatic stress disorder: focusing on genetics and epigenetics.

Certain individuals are more susceptible to stress and trauma, as well as the physical and mental health consequences following such exposure, including risk for post-traumatic stress disorder (PTSD). This differing vulnerability is likely to be influenced by genetic predisposition and specific characteristics of the stress itself (nature, intensity and duration), as well as epigenetic mechanisms. In this review we provide an overview of research findings in this field. We highlight some of the key genetic risk factors identified for PTSD, and the evidence that epigenetic processes might play a role in the biological response to trauma, as well as being potential biomarkers of PTSD risk. We also discuss important considerations for future research in this area.

Generalized anxiety in community-dwelling elderly: Prevalence and clinical characteristics.

BACKGROUND: Generalized anxiety disorder (GAD) is a chronic and disabling disorder with a low rate of full remission. As it is commonly assumed that cases in the elderly principally represent the continuing chronic course of early onset illness, there has been little research into the clinical characteristics, including comorbid psychiatric and physical conditions, which may be specific to older people. METHODS: Lifetime GAD and psychiatric comorbidity were diagnosed in 1974 community-dwelling elderly people aged 65 or over using a standardized psychiatric examination, the MINI, based on DSM-IV criteria. Multivariate regression analyses were adjusted for socio-demographic, lifestyle, biological, and clinical variables, as well as adverse life events. RESULTS: The lifetime prevalence of GAD was 11% (95% CI=9.6-12.4%) of whom 24.6% reported a late onset with a first episode after 50 years of age. The 6-month current prevalence was 4.6% (95% CI=3.7-5.5%). Most of the prevalent cases were recurrent but only 36.3% were receiving treatment. Fourteen percent were comorbid with major depression and 34% with phobia but their associated factors differed. The factors associated with pure GAD were being female, having cognitive impairment, lower body mass index, reporting low affective support during childhood, taking a high number of somatic medications independently of other mental health factors, e.g. psychotropic medication use, major depression, and phobia. LIMITATIONS: The study is limited by cross-sectional design. CONCLUSIONS: Our data indicate that GAD prevalence is high in elderly people with a late-life onset of GAD in 25% of cases. GAD in the elderly is not just a severity marker of depression and is clinically distinct from phobia, the other major anxiety disorder of the elderly.

Glycemia, insulin resistance, insulin secretion, and risk of depressive symptoms in middle age.

OBJECTIVE: The extent to which abnormal glucose metabolism increases the risk of depression remains unclear. In this study, we investigated prospective associations of levels of fasting glucose and fasting insulin and indices of insulin resistance and secretion with subsequent new-onset depressive symptoms (DepS). RESEARCH DESIGN AND METHODS: In this prospective cohort study of 3,145 adults from the Whitehall II Study (23.5% women, aged 60.6 ± 5.9 years), baseline examination included fasting glucose and insulin level, the homeostasis model assessment of insulin resistance (HOMA2-%IR), and the homeostasis model assessment of ß-cell insulin secretion (HOMA2-%B). DepS (Center for Epidemiologic Studies Depression Scale ≥16 or use of antidepressive drugs) were assessed at baseline and at 5-year follow-up. RESULTS: Over the 5-year follow-up, DepS developed in 142 men and 84 women. Women in the lowest quintile of insulin secretion (HOMA2-%B ≤55.3%) had 2.18 (95% CI 1.25-3.78) times higher odds of developing DepS than those with higher insulin secretion. This association was not accounted for by inflammatory markers, cortisol secretion, or menopausal status and hormone replacement therapy. Fasting insulin measures were not associated with DepS in men, and fasting glucose measures were not associated with new-onset DepS in either sex. CONCLUSIONS: Low insulin secretion appears to be a risk factor for DepS in middle-aged women, although further work is required to confirm this finding.

Measuring resilience in adult women using the 10-items Connor-Davidson Resilience Scale (CD-RISC). Role of trauma exposure and anxiety disorders.

PURPOSE: Resilience is the ability of individuals to adapt positively in the face of trauma. Little is known, however, about lifetime factors affecting resilience. METHODS: We assessed the effects of psychiatric disorder and lifetime trauma history on the resilience self-evaluation using the Connor-Davidson Resilience Scale (CD-RISC-10) in a high-risk-women sample. Two hundred and thirty eight community-dwelling women, including 122 participants in a study of breast cancer survivors and 116 participants without previous history of cancer completed the CD-RISC-10. Lifetime psychiatric symptoms were assessed retrospectively using two standardized psychiatric examinations (Mini International Neuropsychiatric Interview and Watson's Post-Traumatic Stress Disorder Inventory). RESULTS: Multivariate logistic regression adjusted for age, education, trauma history, cancer, current psychiatric diagnoses, and psychoactive treatment indicated a negative association between current psychiatric disorder and high resilience compared to low resilience level (OR = 0.44, 95% CI [0.21-0.93]). This was related to anxiety and not mood disorder. A positive and independent association with a trauma history was also observed (OR = 3.18, 95% CI [1.44-7.01]). CONCLUSION: Self-evaluation of resilience is influenced by both current anxiety disorder and trauma history. The independent positive association between resilience and trauma exposure may indicate a "vaccination" effect. This finding need to be taken into account in future studies evaluating resilience in general or clinical populations.

Depressed mood and blood pressure: the moderating effect of situation-specific arousal levels.

Previous studies are inconclusive with regard to the relationship between variations in blood pressure (BP) and affect. In the present study we evaluated the hypothesis that inconsistencies in previous findings may be attributed to the moderating role of variations in psychological or physical conditions during BP measurement. Change in depressive symptoms was examined in 1046 individuals at two points in time, at inclusion into the study, when BP was measured repeatedly under higher (standing posture or anticipation of interview) and lower (supine posture or recovery after interview) arousal conditions, and at 4year follow-up. We observed that higher systolic BP levels measured under high arousal conditions and lower systolic BP levels measured under low arousal conditions at inclusion were both associated with a decrease in depressive mood across time in the study sample. The results suggest that higher or lower cardiovascular activity as indexed by systolic BP corresponds with higher or lower negative mood as a function of situation-specific arousal levels. This biobehavioural association between mood and BP might be related to the moderating effect of adaptive processes on physiological activity in different situations, which may in turn be associated with resilience to adversity.