Genome-wide association (GWA) studies of psychiatric disorders have been criticized for their lack in explaining a considerable proportion of the heritability established in twin and family studies. GWA studies of Major Depressive Disorder (MDD) in particular have so far been unsuccessful in detecting genome-wide significant SNPs. Using two different recently proposed methods designed to estimate the heritability of a phenotype that is attributable to genome-wide SNPs, we show that SNPs on current platforms contain substantial information concerning the additive genetic variance of MDD. To assess the consistency of these two different methods we analyzed four other complex phenotypes from different domains. The pattern of results is consistent with estimates of heritability obtained in twin studies carried out in the same population.
Increased sympathetic activity has been hypothesized to have a role in the elevated somatic disease risk in persons with depressive or anxiety disorders. However, it remains unclear whether increased sympathetic activity reflects a direct effect of anxiety or depression or an indirect effect of antidepressant medication. The aim of this study was to test longitudinally whether cardiac sympathetic control, measured by pre-ejection period (PEP), was increased by depression/anxiety status and by antidepressant use. Cross-sectional and longitudinal data were from a depression and anxiety cohort: the Netherlands Study of Depression and Anxiety (NESDA). Baseline data of 2838 NESDA subjects (mean age 41.7 years, 66.7% female) and 2-year follow-up data of 2226 subjects were available for analyses. Included were subjects with and without depressive/anxiety disorders, using or not using different antidepressants at baseline or follow-up. The PEP was measured non-invasively by 1.5 h of ambulatory impedance cardiography. Cross-sectional analyses compared PEP across psychopathology and antidepressant groups. Longitudinal analyses compared 2-year changes in PEP in relation to changes in psychopathology and antidepressant use. Cross-sectional analyses showed that antidepressant-naïve depressive/anxious subjects had comparable PEP as controls, whereas subjects using tricyclic (TCA) or combined serotonergic/noradrenergic antidepressants (SNRI) had significantly shorter PEP compared with controls. In contrast, subjects using selective serotonin re-uptake inhibitors (SSRIs) had longer PEP than controls. Longitudinal results confirmed these findings: compared with 2-year change in PEP in continuous non-users (+2 ms), subjects who started TCA or SNRI treatment showed significantly shortened PEP (−11 ms, p=0.005 and p<0.001), whereas subjects who started SSRI treatment showed significant prolongation of PEP (+9 ms, p=0.002). Reversed findings were observed among those who stopped antidepressant use. These findings suggest that depressive and anxiety disorders are not associated with increased cardiac sympathetic control. However, results pose that TCA and SNRI use increases sympathetic control, whereas SSRI use decreases sympathetic control.
sympathetic nervous system; major depressive disorder; pre-ejection period; antidepressants; anxiety disorder; biological psychiatry; epidemiology; depression; unipolar/bipolar; psychopharmacology; antidepressants; autonomic nervous system; cardiac sympathetic effects
Personality can be thought of as a set of characteristics that influence people’s thoughts, feelings, and behaviour across a variety of settings. Variation in personality is predictive of many outcomes in life, including mental health. Here we report on a meta-analysis of genome-wide association (GWA) data for personality in ten discovery samples (17 375 adults) and five in-silico replication samples (3 294 adults). All participants were of European ancestry. Personality scores for Neuroticism, Extraversion, Openness to Experience, Agreeableness, and Conscientiousness were based on the NEO Five-Factor Inventory. Genotype data were available of ~2.4M Single Nucleotide Polymorphisms (SNPs; directly typed and imputed using HAPMAP data). In the discovery samples, classical association analyses were performed under an additive model followed by meta-analysis using the weighted inverse variance method. Results showed genome-wide significance for Openness to Experience near the RASA1 gene on 5q14.3 (rs1477268 and rs2032794, P = 2.8 × 10−8 and 3.1 × 10−8) and for Conscientiousness in the brain-expressed KATNAL2 gene on 18q21.1 (rs2576037, P = 4.9 × 10−8). We further conducted a gene-based test that confirmed the association of KATNAL2 to Conscientiousness. In-silico replication did not, however, show significant associations of the top SNPs with Openness and Conscientiousness, although the direction of effect of the KATNAL2 SNP on Conscientiousness was consistent in all replication samples. Larger scale GWA studies and alternative approaches are required for confirmation of KATNAL2 as a novel gene affecting Conscientiousness.
Personality; Five-Factor Model; Genome-wide association; Meta-analysis; Genetic variants
Cognitive reactivity to sad mood is a vulnerability marker of depression. Implicit self-depressed associations are related to depression status and reduced remission probability. It is unknown whether these cognitive vulnerabilities precede the first onset of depression.
To test the predictive value of cognitive reactivity and implicit self-depressed associations for the incidence of depressive disorders.
Prospective cohort study of 834 never-depressed individuals, followed over a two-year period. The predictive value of cognitive reactivity and implicit self-depressed associations for the onset of depressive disorders was assessed using binomial logistic regression. The multivariate model corrected for baseline levels of subclinical depressive symptoms, neuroticism, for the presence of a history of anxiety disorders, for family history of depressive or anxiety disorders, and for the incidence of negative life events.
As single predictors, both cognitive reactivity and implicit self-depressed associations were significantly associated with depression incidence. In the multivariate model, cognitive reactivity was significantly associated with depression incidence, together with baseline depressive symptoms and the number of negative life events, whereas implicit self-depressed associations were not.
Cognitive reactivity to sad mood is associated with the incidence of depressive disorders, also when various other depression-related variables are controlled for. Implicit self-depressed associations predicted depression incidence in a bivariate test, but not when controlling for other predictors.
A better understanding is needed about the role of depression and chronic pain, two related chronic conditions, as predictors of falls in older persons.
To examine whether overall depressive symptoms and symptom clusters are associated with fall risk, and to determine whether chronic pain mediates the relationship between depression and fall risk in aging.
Prospective cohort study.
City of Boston and surrounding communities.
Older community-dwelling adults (n=722,mean age 78.3y).
Depressive symptomatology was assessed at baseline by the CESDR as overall depression and two separate domains, cognitive or somatic symptoms. Chronic pain was examined at baseline as: number of pain sites (none, single site, or multisite/widespread), pain severity, and pain interference with daily life activities. Participants recorded falls on monthly postcards during a subsequent 18-month period.
By using negative binomial regression, the rate of incident falls was highest among those with highest burden of depressive symptoms (indicated by total CESDR, Cognitive or Somatic CESDR domains). After adjustment for multiple confounders and fall risk factors, fall rate ratios comparing the highest CESDR three quartiles to the lowest quartile were 1.91, 1.26, 1.11, respectively. Similarly graded associations were observed according to CESDR domains. Although pain location and interference were mediators of the relationship between depression and falls, adjustment for pain reduced fall risk estimates only modestly. There was no interaction between depression and pain in relation to fall risk.
Depressive symptoms are associated with fall risk in older adults and are mediated in part by chronic pain. Research is needed to determine effective strategies for reducing fall risk and related injuries in older people who have pain and depressive symptoms.
Depression; Falls; Pain; Aging
The authors tested for genetic linkage of DSM-IV-diagnosed major depressive disorder in families that were ascertained for cigarette smoking.
Within a study that targeted families characterized by a history of smoking, analyses derived a subset of 91 Australian families with two or more offspring with a history of DSM-IV major depressive disorder (affected sibling pairs, N=187) and 25 Finnish families (affected sibling pairs, N=33). Within this affected sibling pair design, the authors conducted nonparametric linkage analysis.
In the Australian heavy smoking families, the authors found a genome-wide significant multipoint LOD score of 4.14 for major depressive disorder on chromosome 3 at 24.9 cM (3p26-3p25).
Genome-wide significant linkage was detected for major depressive disorder on chromosome 3p in a sample ascertained for smoking. A linkage peak at this location was also observed in an independent study of major depressive disorder.
Sleep complaints increase profoundly with age; prevalence estimates of insomnia in the elderly reach up to 37%. The three major types of nocturnal complaints are difficulties initiating (DIS) and maintaining (DMS) sleep and early morning awakening (EMA), of which the latter appears most characteristic for aging. The neural correlates associated with these complaints have hardly been investigated, hampering the development of rational treatment and prevention. A recent study on structural brain correlates of insomnia showed that overall severity, but not duration, of insomnia complaints is associated with lower gray matter (GM) density in part of the left orbitofrontal cortex (OFC). Following up on this, we investigated, in an independent sample of people not diagnosed with insomnia, whether individual differences in GM density are associated with differences in DIS, DMS, and EMA. Sixty five healthy participants (mean age = 41 years, range 18–56) filled out questionnaires and underwent structural magnetic resonance imaging. Three compound Z-scores were computed for questionnaire items relating to DIS, DMS, and EMA. Whole-brain voxel-based morphometry was used to investigate their association with GM density. Results show that participants with lower GM density in a region where the left inferior OFC borders the insula report more EMA, but not DIS or DMS. This is the first study to investigate structural brain correlates of specific sleep characteristics that can translate into complaints in insomniacs. The selective association of EMA with orbitofrontal GM density makes our findings particularly relevant to elderly people, where EMA represents the most characteristic complaint. It is hypothesized that low GM density in aforementioned orbitofrontal area affects its role in sensing comfort. An intact ability to evaluate comfort may be crucial to maintain sleep, especially at the end of the night when sleep is vulnerable because homeostatic sleep propensity has dissipated.
insomnia; aging; early morning awakening; orbitofrontal cortex; voxel-based morphometry; structural magnetic resonance imaging
Depression is a common illness, often treated in primary care. Many studies have reported undertreatment with antidepressants in primary care. Recently, some studies also reported overtreatment with antidepressants. The present study was designed to assess whether treatment with antidepressants in primary care is in accordance with current guidelines, with a special focus on overtreatment.
We used baseline data of primary care respondents from the Netherlands Study of Depression and Anxiety (NESDA) (n = 1610). Seventy-nine patients with treatment in secondary care were excluded. We assessed justification for treatment with antidepressant according to the Dutch primary care guidelines for depression and for anxiety disorders. Use of antidepressants was based on drug-container inspection or, if unavailable, on self-report. Results were recalculated to the original population of primary care patients from which the participants in NESDA were selected (n = 10,677).
Of 1531 included primary care patients, 199 (13%) used an antidepressant, of whom 188 (94.5%) (possibly) justified. After recalculating these numbers to the original population (n = 10,677), we found 908 (95% CI 823 to 994) antidepressant users. Forty-nine (95% CI 20 to 78) of them (5.4%) had no current justification for an antidepressant, but 27 of them (54.5%) had a justified reason for an antidepressant at some earlier point in their life.
We found that overtreatment with antidepressants in primary care is not a frequent problem. Too long continuation of treatment seems to explain the largest proportion of overtreatment as opposed to inappropriate initiation of treatment.
Weight change may be considered an effect of depression. In turn, depression may follow weight change. Deteriorations in health may mediate these associations. The objective was to examine reciprocal associations between depressed mood and weight change, and the potentially mediating role of deteriorations in health (interim hospitalizations and incident mobility imitation) in these associations.
Prospective observational cohort study
Memphis, Tennessee and Pittsburgh, Pennsylvania
2406 black and white men and women, aged 70–79 participating in the Health, Aging and Body composition (Health ABC) study.
Depressed mood at baseline (T1) and 3-year follow-up (T4) was measured with the CES-D scale. Three weight change groups (T1–T4) were created: loss (≥5% loss), stable (within ±5% loss or gain), and weight gain (≥5% gain).
At T1 and T4, respectively 4.4% and 9.5% of the analysis sample had depressed mood. T1 depressed mood was associated with weight gain over the 3-year period (OR:1.91; 95%CI:1.13–3.22). Weight loss over the 3-year period was associated with T4 depressed mood (OR:1.51; 95%CI:1.05–2.16). Accounting for deteriorations in health in the reciprocal associations between weight change and depressed mood reduced effect sizes between 16–27%.
In this study, depressed mood predicted weight gain over three years, while weight loss over three years predicted depressed mood. These associations were partly mediated through deteriorations in health. Implications for clinical practice and prevention include increased awareness that depressed mood can cause weight change, but can also be preceded by deteriorations in health and weight change.
depression; weight change; aging
The purpose of this study was to conduct a pilot clinical trial to test the feasibility and efficacy of an exercise program and anti-depressant treatment compared with usual care in improving the emotional and physical functioning of older adults with minor depression. Participants were 37 older adults with minor depression who were randomized to exercise, sertraline, or usual care; 32 participants completed the 16 week study. Outcomes included measures of both emotional (clinician and self-report) and physical (observed and self-report) functioning. There were trends for the superiority of the exercise and sertraline conditions over usual care in improving SF-36 mental health scores and clinician-rated depression scores. Individuals in the exercise condition showed greater improvements in physical functioning than individuals in the usual care condition. Both sertraline and exercise show promise as treatments for late-life minor depression. However, exercise has the added benefit of improving physical functioning as well.
The authors examined the relationship between anxiety, depression, and physical disability, after controlling for demographic and health variables, in a sample of 374 adults ages 18-94. Results indicate that anxiety, depression, and comorbid anxiety and depression are associated with higher levels of disability, after controlling for factors such as age, gender, income, self-rated health, number of medical conditions, and number of physician visits in the past year. Furthermore, anxiety, depression, and comorbid anxiety and depression have a differential effect on disability according to age, with older adults with any of these symptoms reporting higher levels of disability than younger adults. These findings suggest that physicians working with older adults should assess for and treat anxiety as well as depressive symptoms.
The metabolic syndrome includes dyslipidemia, abdominal obesity, insulin resistance, and hypertension and is associated with an increased risk of diabetes and cerebrovascular disease (CVD), but consequences beyond these outcomes have not been examined extensively. We investigated whether metabolic abnormalities have independent consequences on loss of mobility function of older persons.
Data are from 2,920 men and women, 70–79 years, participating in the Health ABC study without mobility limitations at baseline. Metabolic syndrome was defined as ≥3 of the following: (a) waist circumference >102 (men) or >88 cm (women); (b) triglycerides ≥150 mg/dL; (c) high-density lipoprotein cholesterol <40 mg/dL (men) or <50 mg/dL (women); (d) blood pressure ≥130/85 mm Hg or antihypertensive medication; and (d) fasting glucose ≥110 mg/dL or antidiabetic medication. Mobility limitation was defined as difficulty or inability walking ¼ mile or climbing 10 steps during two consecutive semiannual assessments over 4.5 years.
The prevalence of metabolic syndrome was 38.6%. The metabolic syndrome was associated with an adjusted relative risk (RR) of 1.46 (95% confidence interval [CI] = 1.30–1.63) for developing mobility limitations. The risk increased when more metabolic syndrome components were present (p trend >.001). All metabolic syndrome components were significantly associated with incident mobility limitations with the highest RRs for abdominal obesity (RR = 1.54, 95% CI = 1.35–1.75) and hyperglycemia (RR = 1.44, 95% CI = 1.27–1.63). Findings were unchanged when persons with baseline, or incident, CVD, stroke, or diabetes were excluded.
Metabolic syndrome abnormalities, especially abdominal obesity and hyperglycemia, are predictive of mobility limitations in the elderly, independent of CVD or diabetes.
Metabolic syndrome; Obesity; Glucose; Mobility limitation; Older; Diabetes; Cerebrovascular disease
Dysfunctional self-schemas are assumed to play an important role in suicidal ideation. According to recent information-processing models, it is important to differentiate between ‘explicit’ beliefs and automatic associations. Explicit beliefs stem from the weighting of propositions and their corresponding ‘truth’ values, while automatic associations reflect more simple associations in memory. Both types of associations are assumed to have different functional properties and both may be involved in suicidal ideation. Thus far, studies into self-schemas and suicidal ideation focused on the more explicit, consciously accessible traces of self-schemas and predominantly relied on self-report questionnaires or interviews. To complement these ‘explicit’ findings and more directly tap into self-schemas, this study investigated automatic self-associations in a large scale community sample that was part of the Netherlands Study of Depression and Anxiety (NESDA). The results showed that automatic self-associations of depression and anxiety were indeed significantly related to suicidal ideation and past suicide attempt. Moreover, the interactions between automatic self-depressive (anxious) associations and explicit self-depressive (anxious) beliefs explained additional variance over and above explicit self-beliefs. Together these results provide an initial insight into one explanation of why suicidal patients might report difficulties in preventing and managing suicidal thoughts.
Suicidal ideation; Automatic associations; Implicit Association Test; Self-schemas
Recent genome-wide association (GWA) studies of lipids have been conducted in samples ascertained for other phenotypes, particularly diabetes. Here we report the first GWA analysis of loci affecting total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides sampled randomly from 16 population-based cohorts and genotyped using mainly the Illumina HumanHap300-Duo platform. Our study included a total of 17,797-22,562 persons, aged 18-104 years and from geographic regions spanning from the Nordic countries to Southern Europe. We established 22 loci associated with serum lipid levels at a genome-wide significance level (P < 5 × 10-8), including 16 loci that were identified by previous GWA studies. The six newly identified loci in our cohort samples are ABCG5 (TC, P = 1.5 × 10-11; LDL, P = 2.6 × 10-10), TMEM57 (TC, P = 5.4 × 10-10), CTCF-PRMT8 region (HDL, P = 8.3 × 10-16), DNAH11 (LDL, P = 6.1 × 10-9), FADS3-FADS2 (TC, P = 1.5 × 10-10; LDL, P = 4.4 × 10-13) and MADD-FOLH1 region (HDL, P = 6 × 10-11). For three loci, effect sizes differed significantly by sex. Genetic risk scores based on lipid loci explain up to 4.8% of variation in lipids and were also associated with increased intima media thickness (P = 0.001) and coronary heart disease incidence (P = 0.04). The genetic risk score improves the screening of high-risk groups of dyslipidemia over classical risk factors.
Northwestern Europeans are among the tallest of human populations. The increase in body height in these people appears to have reached a plateau, suggesting the ubiquitous presence of an optimal environment in which genetic factors may have exerted a particularly strong influence on human growth. Therefore, we performed a genome-wide association study (GWAS) of body height using 2.2 million markers in 10 074 individuals from three Dutch and one German population-based cohorts. Upon genotyping, the 12 most significantly height-associated single nucleotide polymorphisms (SNPs) from this GWAS in 6912 additional individuals of Dutch and Swedish origin, a genetic variant (rs6717918) on chromosome 2q37.1 was found to be associated with height at a genome-wide significance level (Pcombined = 3.4 × 10−9). Notably, a second SNP (rs6718438) located ∼450 bp away and in strong LD (r2 = 0.77) with rs6717918 was previously found to be suggestive of a height association in 29 820 individuals of mainly northwestern European ancestry, and the over-expression of a nearby natriuretic peptide precursor type C (NPPC) gene, has been associated with overgrowth and skeletal anomalies. We also found a SNP (rs10472828) located on 5p14 near the natriuretic peptide receptor 3 (NPR3) gene, encoding a receptor of the NPPC ligand, to be associated with body height (Pcombined = 2.1 × 10−7). Taken together, these results suggest that variation in the C-type natriuretic peptide signaling pathway, involving the NPPC and NPR3 genes, plays an important role in determining human body height.
The HapMap project has facilitated the selection of tagging single nucleotide polymorphisms (tagSNPs) for genome-wide association studies (GWAS) under the assumption that linkage disequilibrium (LD) in the HapMap populations is similar to the populations under investigation. Earlier reports support this assumption, although in most of these studies only a few loci were evaluated. We compared pair-wise LD and LD block structure across autosomes between the Dutch population and the CEU–HapMap reference panel. The impact of sampling distribution on the estimation of LD blocks was studied by bootstrapping. A high Pearson correlation (genome-wide; 0.93) between pair-wise r2 for the Dutch and the CEU populations was found, indicating that tagSNPs from the CEU–HapMap panel capture common variation in the Dutch population. However, some genomic regions exhibited, significantly lower correlation than the genome-wide estimate. This might decrease the validity of HapMap tagSNPs in these regions and the power of GWAS. The LD block structure differed considerably between the Dutch and CEU–HapMap populations. This was not explained by demographic differences between the CEU and Dutch samples, as testing for population stratification was not significant. We also found that sampling variation had a large effect on the estimation of LD blocks, as shown by the bootstrapping analysis. Thus, in small samples, most of the observed differences in LD blocks between populations are most likely the result of sampling variation. This poor concordance in LD block structure suggests that large samples are required for robust estimations of local LD block structure in populations.
Dutch population; HapMap–CEU; pair-wise LD; LD blocks; bootstrapping
Although depression has been associated with hyperactivity of the hypothalamo-pituitary-adrenal (HPA) axis, recent studies among depressed elderly have found decreased cortisol levels, which may be due to underlying physical frailty associated with HPA-axis hypoactivity. The authors examined the relationship between urinary cortisol level and late-life depressive symptoms. The authors also explored whether hypo- and hypercortisolemic depressive symptoms are qualitatively different.
Data are from 881 community-dwelling participants, average age 74.2 years, of the Aging in the Chianti Area Study. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D) scale and cortisol levels were determined in 24-hour urine samples.
Mean urinary cortisol level was 98.9 μg/24 hours (SD=47.8), and 31% of the sample had significant depressive symptoms (CES-D ≥16). There was no linear association between urinary cortisol level and depressive symptoms; however, there was a nonlinear association between urinary cortisol level and depressive symptoms. Older persons in the lowest and highest urinary cortisol deciles were 2.2 and 1.9 times more likely to have significant depressive symptoms than older persons in all other deciles. Depressed persons with low cortisol presented more physical frailty than depressed persons with high cortisol.
Late-life depressive symptoms are associated with both hyperactivity and hypoactivity of the HPA axis, which suggests distinct mechanisms for these associations.
Depressive symptoms; cortisol; hypothalamo-pituitary-adrenal axis; frailty; older persons
To determine whether benzodiazepine use is associated with incident disability in mobility and activities of daily living (ADLs) in older individuals.
A prospective cohort study.
Four sites of the Established Populations for Epidemiologic Studies of the Elderly.
This study included 9,093 subjects (aged ≥65) who were not disabled in mobility or ADLs at baseline.
Mobility disability was defined as inability to walk half a mile or climb one flight of stairs. ADL disability was defined as inability to perform one or more basic ADLs (bathing, eating, dressing, transferring from a bed to a chair, using the toilet, or walking across a small room). Trained interviewers assessed outcomes annually.
At baseline, 5.5% of subjects reported benzodiazepine use. In multivariable models, benzodiazepine users were 1.23 times as likely as nonusers (95% confidence interval (CI) = 1.09–1.39) to develop mobility disability and 1.28 times as likely (95% CI = 1.09–1.52) to develop ADL disability. Risk for incident mobility was increased with short- (hazard ratio (HR) = 1.27, 95% CI = 1.08–1.50) and long-acting benzodiazepines (HR = 1.20, 95% CI = 1.03–1.39) and no use. Risk for ADL disability was greater with short- (HR = 1.58, 95% CI = 1.25–2.01) but not long-acting (HR = 1.11, 95% CI = 0.89–1.39) agents than for no use.
Older adults taking benzodiazepines have a greater risk for incident mobility and ADL disability. Use of short-acting agents does not appear to confer any safety benefits over long-acting agents.
benzodiazepines; activities of daily living; disability; adverse drug event
To determine the influence of anxiety on the progression of disability and examine possible mediators of the relationship.
Community-based observational study.
Women’s Health and Aging Study I, a prospective observational study with assessments every 6 months over 3 years.
One thousand two functionally limited women aged 65 years and older.
Anxiety symptoms were assessed with 4 questions from the Hopkins Symptom Checklist (nervous or shaky, avoidance of certain things, tense or keyed up, fearful). Participants who reported experiencing 2 or more of these symptoms at baseline were considered anxious. Anxiety as a predictor of the onset of 4 types of disability was examined using Cox proportional hazard models. Three models were tested: an unadjusted model, a model adjusted for confounding variables (age, race, vision, number of diseases, physical performance, depressive symptoms), and a mediational model (benzodiazepine use, physical activity, emotional support).
Nineteen percent of women reported 2 or more symptoms of anxiety at baseline. Unadjusted models indicate that anxiety was associated with a greater risk of worsening disability: ADL disability (Hazard Risk = 1.40, 95% CI 1.10–1.79), mobility disability (HR = 1.41, 95% CI 1.06–1.86), lifting disability (HR = 1.54, 95% CI 1.20–1.97), and light housework disability (HR = 1.77, 95% CI 1.32–2.37). After adjusting for confounding variables, anxiety continued to predict the development of 2 types of disability: ADL disability (HR = 1.41, 95% CI 1.08–1.84) and light housework disability (HR = 1.56, 95% CI 1.14–2.14). Finally, benzodiazepine and psychotropic medication use, physical activity, and emotional support were not significant mediators of the effect of anxiety on the development of a disability.
Anxiety is a significant risk factor for the progression of disability among older women. Studies are needed to determine if treatment of anxiety delays or prevents disability.
anxiety symptoms; disability; aged (65+)
The authors describe characteristics that are associated with chronic anxiety symptoms and examine the use of anxiolytic and anti-depressant medications in physically disabled women with and without symptoms of anxiety.
Participants are 791 physically disabled women aged 65 years and older who participated in the Women’s Health and Aging Study for 2 to 3 years. Anxiety symptoms were measured with 4 questions from the Hopkins Symptom Checklist, and women were categorized as having no anxiety, intermittent anxiety, and chronic anxiety symptoms. Health-related characteristics, medications, physical functioning, physical activity, and psychosocial variables were also measured.
Forty-nine percent of women reported no anxiety symptoms, 41% reported intermittent symptoms, and 10% reported chronic symptoms of anxiety. Depressive symptoms and lack of emotional support were significant correlates of intermittent anxiety symptoms, while depressive symptoms, negative life events, and lack of emotional support were significant correlates of chronic anxiety symptoms. Over the course of 3 years, 20.3% of women with no anxiety, 33.0% of women with intermittent anxiety, and 48.7% of women with chronic anxiety symptoms took anxiolytic and/or anti-depressant medications.
Anxiety symptoms are common among disabled older women. Psychosocial variables were significantly different in women with intermittent or chronic anxiety symptoms compared with women without anxiety.
anxiety symptoms; chronic anxiety; aged (65+)
It has been hypothesized that cellular damage caused by oxidative stress is associated with late-life depression but epidemiological evidence is limited. In the present study we evaluated the association between urinary 8-iso-prostaglandin F2α (8-iso-PGF2α), a biomarker of lipid peroxidation, and depressed mood in a large sample of community-dwelling older adults. Participants were selected from the Health, Aging and Body Composition study, a community-based longitudinal study of older persons (aged 70–79 years). The present analyses was based on a subsample of 1027 men and 948 women free of mobility disability. Urinary concentration of 8-iso-PGF2α was measured by radioimmunoassay methods and adjusted for urinary creatinine. Depressed mood was defined as a score greater than 5 on the 15-item Geriatric Depression Scale and/or use of antidepressant medications. Depressed mood was present in 3.0% of men and 5.5% of women. Depressed men presented higher urinary concentrations of 8-iso-PGF2α than non-depressed men even after adjustment for multiple sociodemographic, lifestyle and health factors (p = 0.03, Cohen’s d = 0.30). This association was not present in women (depressed status-by-sex interaction p = 0.04). Our study showed that oxidative damage may be linked to depression in older men from a large sample of the general population. Further studies are needed to explore whether the modulation of oxidative stress may break down the link between late-life depression and its deleterious health consequences.
Depression in myocardial infarction patients is often a first episode with a late age of onset. Two studies that compared depressed myocardial infarction patients to psychiatric patients found similar levels of somatic symptoms, and one study reported lower levels of cognitive/affective symptoms in myocardial infarction patients. We hypothesized that myocardial infarction patients with first depression onset at a late age would experience fewer cognitive/affective symptoms than depressed patients without cardiovascular disease. Combined data from two large multicenter depression studies resulted in a sample of 734 depressed individuals (194 myocardial infarction, 214 primary care, and 326 mental health care patients). A structured clinical interview provided information about depression diagnosis. Summed cognitive/affective and somatic symptom levels were compared between groups using analysis of covariance, with and without adjusting for the effects of recurrence and age of onset. Depressed myocardial infarction and primary care patients reported significantly lower cognitive/affective symptom levels than mental health care patients (F (2,682) = 6.043, p = 0.003). Additional analyses showed that the difference between myocardial infarction and mental health care patients disappeared after adjusting for age of onset but not recurrence of depression. These group differences were also supported by data-driven latent class analyses. There were no significant group differences in somatic symptom levels. Depression after myocardial infarction appears to have a different phenomenology than depression observed in mental health care. Future studies should investigate the etiological factors predictive of symptom dimensions in myocardial infarction and late-onset depression patients.
Earlier findings show seasonality in processes and behaviors such as brain plasticity and depression that in part are regulated by Brain-Derived Neurotrophic Factor (BDNF). Based on this we investigated seasonal variation in serum BDNF concentrations in 2,851 persons who took part in the Netherlands Study of Depression and Anxiety (NESDA). Analyses by month of sampling (monthly n’s >196) showed pronounced seasonal variation in serum BDNF concentrations (P<.0001) with increasing concentrations in the spring-summer period (standardized regression weight (ß) = 0.19, P<.0001) and decreasing concentrations in the autumn-winter period (ß = −0.17, P<.0001). Effect sizes [Cohen’s d] ranged from 0.27 to 0.66 for monthly significant differences. We found similar seasonal variation for both sexes and for persons with a DSM-IV depression diagnosis and healthy control subjects. In explorative analyses we found that the number of sunshine hours (a major trigger to entrain seasonality) in the week of blood withdrawal and the 10 weeks prior to this event positively correlated with serum BDNF concentrations (Pearson’s correlation coefficients ranged: 0.05 – 0.18) and this could partly explain the observed monthly variation. These results provide strong evidence that serum BDNF concentrations systematically vary over the year. This finding is important for our understanding of those factors that regulate BDNF expression and may provide novel avenues to understand seasonal dependent changes in behavior and illness such as depression. Finally, the findings reported here should be taken into account when designing and interpreting studies on BDNF.
Dehydroepiandrosterone sulphate (DHEAS) is the most abundant circulating steroid secreted by adrenal glands—yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations. Genes at or near the identified loci include ZKSCAN5 (rs11761528; p = 3.15×10−36), SULT2A1 (rs2637125; p = 2.61×10−19), ARPC1A (rs740160; p = 1.56×10−16), TRIM4 (rs17277546; p = 4.50×10−11), BMF (rs7181230; p = 5.44×10−11), HHEX (rs2497306; p = 4.64×10−9), BCL2L11 (rs6738028; p = 1.72×10−8), and CYP2C9 (rs2185570; p = 2.29×10−8). These genes are associated with type 2 diabetes, lymphoma, actin filament assembly, drug and xenobiotic metabolism, and zinc finger proteins. Several SNPs were associated with changes in gene expression levels, and the related genes are connected to biological pathways linking DHEAS with ageing. This study provides much needed insight into the function of DHEAS.
Dehydroepiandrosterone sulphate (DHEAS), mainly secreted by the adrenal gland, is the most abundant circulating steroid in humans. It shows a significant physiological decline after the age of 25 and diminishes about 95% by the age of 85 years, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. Twin- and family-based studies have shown that there is a substantial genetic effect with heritability estimate of 60%, but no specific genes regulating serum DHEAS concentration have been identified to date. Here we take advantage of recent technical and methodological advances to examine the effects of common genetic variants on serum DHEAS concentrations. By examining 14,846 Caucasian individuals, we show that eight common genetic variants are associated with serum DHEAS concentrations. Genes at or near these genetic variants include BCL2L11, ARPC1A, ZKSCAN5, TRIM4, HHEX, CYP2C9, BMF, and SULT2A1. These genes have various associations with steroid hormone metabolism—co-morbidities of ageing including type 2 diabetes, lymphoma, actin filament assembly, drug and xenobiotic metabolism, and zinc finger proteins—suggesting a wider functional role for DHEAS than previously thought.
The purpose of this study is to determine if anxiety is associated with mortality and if race moderates and depression mediates this relationship.
Participants are 3,015 adults aged 70 to 79 years.
Anxiety symptoms were significant predictors of all-cause, cardiovascular, and noncardiovascular mortality among blacks but not whites. Depression was not related to mortality.
Although the mechanisms that underlie the relationship between anxiety and mortality are unknown, routine assessment of anxiety symptoms in clinical practice, particularly in black older adults, seems prudent.
anxiety; mortality; race; depression