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OBJECTIVE: Our objective is to evaluate the mental status of primary early breast cancer survivors according to DSM-IV criteria, distinguishing new psychiatric diagnosis, which started after the cancer diagnosis from relapse. METHODS: A comparative study of 144 breast cancer survivors and 125 women without previous history of cancer was carried out. Neuropsychiatric symptomatology was assessed retrospectively using standardized psychiatric examinations (Mini International Neuropsychiatric Interview, Watson's Post-Traumatic Stress Disorder Inventory) over three successive periods, 'before cancer' (from childhood to 3 years before the interview), 'around the cancer event' (the last 3 years including the time of diagnosis and treatment), and 'currently' (the last 2 weeks). RESULTS: Increased rates of anxiety and mood disorders were observed following a diagnosis of breast cancer compared with controls (generalized anxiety disorder (GAD) and major depressive disorder (MDD); 10.4 vs 1.6% and 19.4 vs 8.8%, respectively). The cancer disease promoted the development of dysthymia (n=4 new cases/6 two-year prevalent cases) and PTSD (7/7) and the re-emergence of MDD (n=21 relapses/28 three-year prevalent cases) and GAD (10/15). No improvement in serious mood disorders such as MDD (16.0 vs 7.2%) and dysthymia (4.2 vs 0%) was reported at the time of interview, more than 1.75 years (median time) after the cancer surgery, the prevalence being 2-4 times greater in breast cancer survivors than in controls. CONCLUSION: Despite significant advances in treatment, a diagnosis of breast cancer is highly associated with various forms of psychopathology, regardless of psychiatric history, with symptoms persisting after treatment. These results may assist clinicians in planning mental healthcare for women with breast cancer. [ABSTRACT FROM AUTHOR]

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., (Copyright © 2023 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

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., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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.

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., Competing Interests: None declared, (© 2020 Joule Inc. or its licensors.)

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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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., (Copyright © 2020 Alacreu-Crespo, Olié, Guillaume, Girod, Cazals, Chaudieu and Courtet.)

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., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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., Competing Interests: None declared., (© 2019 Joule Inc. or its licensors)

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.

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., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.

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.

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., (Copyright © 2014 Elsevier B.V. All rights reserved.)

C-reactive protein (CRP) is a heritable biomarker of systemic inflammation that is commonly elevated in depressed patients. Variants in the CRP gene that influence protein levels could thus be associated with depression but this has seldom been examined, especially in the elderly. Depression was assessed in 990 people aged at least 65 years as part of the ESPRIT study. A clinical level of depression (DEP) was defined as having a score of ⩾16 on The Center for Epidemiologic Studies Depression scale or a diagnosis of current major depression based on the Mini-International Neuropsychiatric Interview and according to Diagnostic and Statistical Manual of Mental Disorders-IV criteria. Five single-nucleotide polymorphisms spanning the CRP gene were genotyped, and circulating levels of high-sensitivity CRP were determined. Multivariable analyses adjusted for socio-demographic characteristics, smoking, ischemic pathologies, cognitive impairment and inflammation-related chronic pathologies. The minor alleles of rs1130864 and rs1417938 were associated with a decreased risk of depression in women at Bonferroni-corrected significance levels (P=0.002). CRP gene variants were associated with serum levels in a gender-specific manner, but only rs1205 was found to be nominally associated with both an increased risk of DEP and lower circulating CRP levels in women. Variants of the CRP gene thus influence circulating CRP levels and appear as independent susceptibility factors for late-life depression.

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 β-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.

The aim of this study was to evaluate the effects of anti-inflammatory intake on cognitive function in 7234 community-dwelling elderly persons. Cognitive performance, clinical diagnosis of dementia, and anti-inflammatory use were evaluated at baseline, and 2, 4, and 7 years later. Multivariate logistic regression analyses were adjusted for sociodemographic, behavioral, physical, mental health variables, and genetic vulnerability (apolipoprotein E ε4). Elderly women taking inhaled corticosteroids were at increased risk for cognitive decline over 7 years in executive functioning (odds ratio, 1.76; 95% confidence interval, 1.14-2.71; p = 0.04); the effect being increased after continuous use (odds ratio, 3.15; 95% confidence interval, 1.29-7.68; p = 0.01) and not found after discontinuation of treatment. In men, no significant associations were observed. Corticosteroid use was not significantly associated with an increase risk of incident dementia over 7 years. Nonsteroidal anti-inflammatory drug use was not significantly associated with either dementia incidence or cognitive decline in both sexes. The association may be related to hypothalamic-pituitary-adrenal corticotropic axis dysfunctioning rather than a direct anti-inflammatory mechanism. Long-term use of inhaled corticosteroids may constitute a form of reversible cognitive disorder in elderly women. Physicians should check this possibility before assuming neurodegenerative changes., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Road Traffic Accidents (RTA) are most probably the leading cause of post traumatic stress disorder (PTSD) in developed countries. The autonomic nervous system (ANS) disturbances, due to psychological trauma, are part of the pathophysiology of PTSD. The aim of the present study was to determine whether early heart rate variability (HRV) measurement, a biomarker of the ANS function, could act as a predictor of PTSD development after a RTA., Methods: We prospectively investigated 35 survivors of RTA with both physical injury and psychological trauma. HRV data were obtained from 24-h Holter ECG monitoring, which was performed on the second day after the accident. Time domain analysis was applied to the inter-beat (RR) interval time series to calculate the various parameters of HRV. PTSD status was assessed 2 and 6 months after RTA., Results: There was a global diminution of HRV measurements in the PTSD group at both 2 and 6 months. The variability index was the best predictor of PTSD with the area under the receiveroperating curve for discriminating PTSD at 6 months at 0.92 (95% CI: 0.785; 1.046). A cut-off at 2.19% yielded a sensitivity of 85.7% and a specificity of 81.8% for PTSD. Positive and negative predictive values were respectively 75% and 90%. However, initial heart rate (HR) data were relevant at 2 months but not at 6 months., Conclusion: RTA survivors exhibiting lower parasympathetic modulation of HR, indexed by temporal analysis of HRV, are more susceptible to developing PTSD as a short and long-term outcome., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

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.

Objective: A history of trauma is associated with poor mental and physical health, but the specific impact of posttraumatic stress disorder (PTSD) symptoms on physical health using objective indicators of health status has rarely been evaluated in elderly civilians. This study investigates the long-term consequences of a lifetime exposure to trauma on health in a French elderly general population., Method: Data from this retrospective study were derived from a longitudinal study (the Enquête de Santé Psychologique-Risques, Incidence et Traitement [ESPRIT]) of community-dwelling participants. Psychiatric health, medical history, and clinical examination (ICD-10 criteria) were assessed in 1,662 subjects (mean [SD] age = 72.5 [5.2] years). Lifetime traumatic exposure, PTSD, and psychiatric diagnoses were obtained using the Watson PTSD Inventory and the Mini-International Neuropsychiatric Interview. The outcome measures used were the Mini-International Neuropsychiatric Interview, Center for Epidemiologic Studies Depression Scale, Mini-Mental State Examination, and measures of physical health., Results: We observed an increase in the number and severity of health-related outcomes between groups, with nontraumatized subjects having the lowest risk and those with trauma leading to recurrent reexperiencing of events (nonresilient subjects) having the highest risk. Traumatized persons who did not report reexperiencing symptoms (resilient subjects) showed better current mental health than traumatized subjects who did and nontraumatized subjects. Nonresilient subjects were more likely to have current depressive symptoms (P = .003), current major depression (P < .0001), current anxiety disorder (P = .032), and psychiatric comorbidity (P = .002) than nontraumatized subjects. Resilient subjects differed from nontraumatized subjects in having significantly less current suicidal ideation (P = .054) and psychiatric comorbidity (P = .035). Both groups of traumatized subjects showed a higher rate of cardio-ischemic diseases, notably current angina pectoris (multivariate, adjusted OR = 2.27; 95% CI, 1.31-3.91; and OR = 2.34; 95% CI, 1.22-4.49; for resilient and nonresilient groups, respectively). Traumatized persons, specifically those nonresilient, showed a higher waist-hip ratio, higher triglyceride levels, and a greater frequency of hypertension., Conclusions: Our findings suggest that trauma could be associated with cardio-ischemic diseases independently of PTSD symptoms expression. However, the presence of these symptoms appears associated with additional metabolic risk factors., (© Copyright 2011 Physicians Postgraduate Press, Inc.)

Background: Lipids appear to mediate depressive vulnerability in the elderly; however, sex differences and genetic vulnerability have not been taken into account in previous prospective studies., Methods: Depression was assessed in a population of 1040 women and 752 men aged 65 years and older at baseline and after 7-year follow-up. Clinical level of depression (DEP) was defined as having either a score of 16 or higher on the Centre for Epidemiology Studies Depression scale or a diagnosis of current major depression on the Mini-International Neuropsychiatric Interview. Lipid levels, apolipoprotein E, and serotonin transporter linked promoter region (5-serotonin transporter gene linked promoter region) genotypes were evaluated at baseline., Results: Multivariate analyses adjusted by sociodemographic and behavioral variables, measures of physical health including ischemic pathologies, and genetic vulnerability indicated gender-specific associations between dyslipidemia and DEP, independent of the use of lipid-lowering agents or apolipoprotein E status. Men with low low-density lipoprotein cholesterol levels had twice the risk of prevalent and incident DEP, whereas in women low high-density lipoprotein cholesterol levels were found to be significantly associated with increased prevalent DEP (odds ratio = 1.5) only. A significant interaction was observed between low low-density lipoprotein-cholesterol and 5-serotonin transporter gene linked promoter region genotype, men with s/s or s/l genotype being at increased risk of DEP (odds ratio = 6.0 and 2.7, respectively). No significant gene-environment interaction was observed for women., Conclusions: DEP is associated with higher atherogenic risk in women (low high-density lipoprotein cholesterol), whereas the reverse is observed in men (low low-density lipoprotein cholesterol). Late-life depression may have a complex gender-specific etiology involving genetic vulnerability in men., (Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

The relationship between disease and good health has received relatively little attention in mental health. Resilience can be viewed as a defence mechanism, which enables people to thrive in the face of adversity and improving resilience may be an important target for treatment and prophylaxis. Though resilience is a widely-used concept, studies vary substantially in their definition, and measurement. Above all, there is no common underlying theoretical construct to this very heterogeneous research which makes the evaluation and comparison of findings extremely difficult. Furthermore, the varying multi-disciplinary approaches preclude meta-analysis, so that clarification of research in this area must proceed firstly by conceptual unification. We attempt to collate and classify the available research around a multi-level biopsychosocial model, theoretically and semiotically comparable to that used in describing the complex chain of events related to host resistance in infectious disease. Using this underlying construct we attempt to reorganize current knowledge around a unitary concept in order to clarify and indicate potential intervention points for increasing resilience and positive mental health., (2010 Elsevier Ltd. All rights reserved.)