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Background: Inflammation and metabolic dysregulation are age-related physiological changes and are associated with depressive disorder. We tried to identify subgroups of depressed older patients based on their metabolic-inflammatory profile and examined the course of depression for these subgroups. Methods: This clinical cohort study was conducted in a sample of 364 depressed older (⩾60 years) patients according to DSM-IV criteria. Severity of depressive symptoms was monitored every 6 months and a formal diagnostic interview repeated at 2-year follow-up. Latent class analyses based on baseline metabolic and inflammatory biomarkers were performed. Adjusted for confounders, we compared remission of depression at 2-year follow-up between the metabolic-inflammatory subgroups with logistic regression and the course of depression severity over 2-years by linear mixed models. Results: We identified a 'healthy' subgroup (n = 181, 49.7%) and five subgroups characterized by different profiles of metabolic-inflammatory dysregulation. Compared to the healthy subgroup, patients in the subgroup with mild 'metabolic and inflammatory dysregulation' (n = 137, 37.6%) had higher depressive symptom scores, a lower rate of improvement in the first year, and were less likely to be remitted after 2-years [OR 0.49 (95% CI 0.26–0.91)]. The four smaller subgroups characterized by a more specific immune-inflammatory dysregulation profile did not differ from the two main subgroups regarding the course of depression. Conclusions: Nearly half of the patients with late-life depressions suffer from metabolic-inflammatory dysregulation, which is also associated with more severe depression and a worse prognosis. Future studies should examine whether these depressed older patients benefit from a metabolic-inflammatory targeted treatment. [ABSTRACT FROM AUTHOR]

The assessment of medically unexplained symptoms and “somatic symptom disorders” in older adults is challenging due to somatic multimorbidity, which threatens the validity of somatization questionnaires. In a systematic review study, the Patient Health Questionnaire–15 (PHQ-15) and the somatization subscale of the Symptom Checklist 90-item version (SCL-90 SOM) are recommended out of 40 questionnaires for usage in large-scale studies. While both scales measure physical symptoms which in younger persons often refer to unexplained symptoms, in older persons, these symptoms may originate from somatic diseases. Using empirical data, we show that PHQ-15 and SCL-90 SOM among older patients correlate with proxies of somatization as with somatic disease burden. Updating the previous systematic review, revealed six additional questionnaires. Cross-validation studies are needed as none of 46 identified scales met the criteria of suitability for an older population. Nonetheless, specific recommendations can be made for studying older persons, namely the SCL-90 SOM and PHQ-15 for population-based studies, the Freiburg Complaint List and somatization subscale of the Brief Symptom Inventory 53-item version for studies in primary care, and finally the Schedule for Evaluating Persistent Symptoms and Somatic Symptom Experiences Questionnaire for monitoring treatment studies. [ABSTRACT FROM AUTHOR]

Objective: First, to evaluate the outcome of 2 transdiagnostic day treatment programs. A 20-week psychotherapeutic day treatment (PDT) and an activating day treatment (ADT) program delivered in blocks of 4 weeks with a maximum of 24 weeks with respect to depression, anxiety, and hypochondriasis. Second, to explore the impact of cognitive impairment and personality pathology on treatment outcome.Methods: The course of depression (Inventory of Depressive Symptoms), anxiety (Geriatric Anxiety Inventory), and hypochondriasis (Whitley Index) were evaluated by linear mixed models adjusted for age, sex, level of education, and alcohol usage among 49 patients (mean age 65 years, 67% females) receiving PDT and among 61 patients (mean age 67.1, 61% females) receiving ADT. Pre-post effect-sizes were expressed as Cohen's d. Subsequently, cognitive impairment (no, suspected, established) and personality pathology (DSM-IV criteria as well as the Big Five personality traits) were examined as potential moderators of treatment outcome.Results: Among patients receiving PDT, large improvements were found for depression (d = 1.1) and anxiety (d = 1.2) but not for hypochondriasis (d = 0.0). Patients receiving ADT showed moderate treatment effects for depression (d = 0.6), anxiety (d = 0.6), as well as hypochondriasis (d = 0.6). Personality pathology moderates treatment outcome of neither PDT nor ADT. Cognitive impairment negatively interfered with the course of depressive symptoms among patients receiving PDT.Conclusions: Transdiagnostic day treatment is promising for older adults with affective disorders with high feasibility. [ABSTRACT FROM AUTHOR]

BackgroundDepression is associated with the metabolic syndrome (MS). We examined whether metabolic dysregulation predicted the 2-year course of clinical depression.MethodA total of 285 older persons (⩾60 years) suffering from depressive disorder according to DSM-IV-TR criteria was followed up for 2 years. Severity of depression was assessed with the Inventory of Depressive Symptomatology (IDS) at 6-month intervals. Metabolic syndrome was defined according the National Cholesterol Education Programme (NCEP-ATP III). We applied logistic regression and linear mixed models adjusted for age, sex, years of education, smoking, alcohol use, physical activity, somatic co-morbidity, cognitive functioning and drug use (antidepressants, anti-inflammatory drugs) and severity of depression at baseline.ResultsMS predicted non-remission at 2 years (odds ratioper component = 1.26, 95% confidence interval 1.00–1.58), p = 0.047), which was driven by the waist circumference and HDL cholesterol. MS was not associated with IDS sum score. Subsequent analyses on its subscales, however, identified an association with the somatic symptom subscale score over time (interaction time × somatic subscale, p = 0.005), driven by higher waist circumference and elevated fasting glucose level.ConclusionsMetabolic dysregulation predicts a poor course of late-life depression. This finding supports the concept of ‘metabolic depression’, recently proposed on population-based findings of a protracted course of depressive symptoms in the presence of metabolic dysregulation. Our findings seem to be driven by abdominal obesity (as indicated by the waist circumference) and HDL cholesterol dysregulation. [ABSTRACT FROM PUBLISHER]

Background:Anxiety disorders are assumed to increase suicide risk, although confounding by comorbid psychiatric disorders may be one explanation. This study describes the characteristics of older patients with an anxiety disorder who died by suicide in comparison to younger patients.Method:A 15-year national clinical survey of all suicides in the UK (n = 25,128). Among the 4,481 older patients who died by suicide (≥ 60 years), 209 (4.7%) suffered from a primary anxiety disorder, and 533 (11.9%) from a comorbid anxiety disorder. Characteristics of older (n = 209) and younger (n = 773) patients with a primary anxiety disorder were compared by logistic regression adjusted for sex and living arrangement.Results:Compared to younger patients, older patients with a primary anxiety disorder were more often males and more often lived alone. Although 60% of older patients had a history of psychiatric admissions and 50% of deliberate self-harm, a history of self-harm, violence, and substance misuse was significantly less frequent compared to younger patients, whereas physical health problems and comorbid depressive illness were more common. Older patients were prescribed significantly more psychotropic drugs and received less psychotherapy compared to younger patients.Conclusion:Anxiety disorders are involved in one of every six older patients who died by suicide. Characteristics among patients who died by suicide show severe psychopathology, with a more prominent role for physical decline and social isolation compared to their younger counterparts. Moreover, treatment was less optimal in the elderly, suggesting ageism. These results shed light on the phenomenon of suicide in late-life anxiety disorder and suggest areas where prevention efforts might be focused. [ABSTRACT FROM PUBLISHER]

Objective: Physical activity is inversely associated with depression in adolescents, but the overall associations are fairly weak, suggesting individual differences in the strength of the associations. The aim of this study was to investigate whether plasticity genes modify the reciprocal prospective associations between physical activity and depressive symptoms found previously. Methods: In a prospective population-based study {N = 1,196), physical activity and depressive symptoms were assessed three times, around the ages of 11, 13.5, and 16. Structural Equation Modeling was used to examine reciprocal effects of physical activity and depressive symptoms over time. The plasticity genes examined were 5-HTTLPR, DRD2, DRD4, MAOA, TPH1, 5-HTR2A, COMT, and BDNF . A cumulative gene plasticity index consisting of three groups (low, intermediate, and high) according to the number of plasticity alleles carried by the adolescents was created. Using a multigroup approach, we examined whether the associations between physical activity and depressive symptoms differed between the three cumulative plasticity groups, as well as between the individual polymorphisms. Results: We found significant cross-sectional and cross-lagged paths from physical activity to depressive symptoms and vice versa. Neither the cumulative plasticity index nor the individual polymorphisms modified the strengths of these associations. Conclusion: Associations between adolescents' physical activity and depressive symptoms are not modified by plasticity genes. [ABSTRACT FROM AUTHOR]

The study aimed to examine the relationship between spontaneous cerebral emboli (SCE), patent foramen ovale (PFO) and white matter hyperintensities (WMH) on cerebral MRI in patients with Alzheimer's disease (AD) and vascular dementia (VaD). SCE were identified by transcranial Doppler of the middle cerebral artery for 1 h. A "significant" v-aCS (venous-to-arterial circulation shunt indicative of PFO; ⩾15 embolic signals within 12 cardiac cycles) was detected by intravenous injection of "air in saline" ultrasound contrast. Deep white matter hyperintensities (DWMH) and periventricular hyperintensities (PVH) were assessed using Schelten's scale. After correction for cardiovascular risk factors, both DWMH and PVH were significantly associated with the presence of a PFO in AD (β=0.31, p=0.02 for DWMH, odds ratio 8.7, p=0.011 for PVH) but not in VaD. No consistent relationship was found between SCE and WMH in AD. In VaD, the severity of DWMH was negatively correlated with SCE (β=-0.55; p=0.001). In conclusion, the presence of a significant venous-to-arterial shunt is associated with more severe DWMH in AD, and may play a part in the aetiology of the disorder. In addition, there is a significant negative correlation between SCE and DWMH in VaD, which supports the hypothesis that VaD may be the result of ischaemic injury, predominantly reflecting embolic aetiology. [ABSTRACT FROM AUTHOR]

Background: There are considerable overlaps between vascular dementia and Alzheimer's disease (AD), with a suggestion that cerebrovascular disease (CVD) contributes to the neurodegenerative pathology of AD. Paradoxical embolization of venous emboli into the systemic circulation through a venous to arterial circulation shunt (v-aCS), the most commonly a patent foramen ovale (PFO), is known to cause cryptogenic stroke in younger people. We reviewed the potential role of paradoxical embolization in AD. Methods: A review of the literature on paradoxical embolization in neurological disorders and techniques to detect v-aCS and PFO, supplemented by data from our own studies. Results: Before our research, the role of paradoxical embolism in dementia had not been studied. The potential role of embolization in cerebral damage was highlighted by studies in patients undergoing coronary artery bypass or carotid surgery. Paradoxical embolization was found to occur in patients with cryptogenic stroke, migraine, decompression sickles and during hip surgery. The methods for detecting v-aCS or PFO had not been standardized. We found 'significant' v-aCS (equivalent to PFO) in 32% of AD patients compared with 22% of controls, but the study was not sufficiently powered to test the statistic significance of this difference. In AD, there was evidence of an association between 'significant' v-aCS and the severity of white matter hyperintensities on magnetic resonance imaging (MRI). Conclusion: Paradoxical embolization through a v-aCS may be a potentially preventable or treatable cause of CVD in AD. [ABSTRACT FROM AUTHOR]

Autism spectrum disorders (ASDs) in older adults have been neglected for a long time. As far as we know only five papers have been published. No empirical research in this area was found. Four papers were case studies of men diagnosed with an ASD (James et al., 2006; Naidu et al., 2006; van Alphen and Heijnen-Kohl, 2009; van Niekerk et al., 2011), and the fifth one was an opinion paper concerning the diagnosis of ASD in the elderly and the difficulties arising in this (Heijnen-Kohl and van Alphen, 2009). [ABSTRACT FROM AUTHOR]

About two-thirds of long-term users of benzodiazepines in the population are able to discontinue this drug with the aid of supervised programmes for tapering off. Little is known about the long-term outcome of such programmes, and they have never been compared with usual care. After a 15-month follow-up of a randomised controlled trial comparing such a programme with and without psychotherapy with usual care, we found significantly higher longitudinal abstinence rates in long-term benzodiazepine users who received a benzodiazepine tapering-off programme without psychotherapy (25 out of 69, 36%) compared with those who received usual care (5 out of 33,15%; P=0.03). [ABSTRACT FROM AUTHOR]

Objectives: Growth differentiation factor-15 (GDF-15) is an inflammatory molecule that reacts to cell stress. Since major depression is associated with inflammation, we examined whether GDF-15 levels are elevated in patients with late-life depression.Methods: Plasma GDF-15 levels were analyzed in 350 patients diagnosed with major depressive disorder in the last six months and 128 non-depressed controls from the Netherlands Study of Depression in Older persons (age ≥ 60 years). Major depressive disorder and age of onset were assessed with the Composite International Diagnostic Interview. Severity of depressive symptoms was measured with the Inventory of Depressive Symptoms (IDS-30). Multiple linear regression models were applied to study depression (diagnosis, onset age, severity, antidepressant drug use) as determinant of GDF-15 level, adjusted for demographic and clinical variables.Results: Plasma GDF-15 levels were 22% higher in patients with major depression compared to controls. Within the depressed group, levels were higher in patients with older age of onset. GDF-15 levels showed a small, positive correlation to the levels of the inflammatory mediators IL-6 and C-reactive protein (r=0.23, and 0.24, p<0.05). This increase was independent from comorbidities, such as cardiovascular disease, rheumatism and diabetes, and anti-inflammatory drugs. However, this increase was dependent on lifestyle factors as smoking, physical activity and alcohol use. Within the depressed subgroup, neither depression severity or antidepressant drug use was associated with GDF-15 levels in the fully adjusted models.Conclusion: The inflammatory factor GDF-15 does not seem to be an independent inflammatory marker for late-life major depressive disorder. [ABSTRACT FROM AUTHOR]

Background Although it is well established that late-life depression is associated with both systemic low-graded inflammation and cognitive impairment, the relation between inflammation and cognition in depressed older persons is still equivocal. The objective of this study is to examine the association between plasma Neutrophil Gelatinase-Associated Lipocalin (NGAL) concentrations and cognitive functioning in late-life depression, including the potentially moderating role of sex. Methods A total of 369 depressed older persons (=60 years) from The Netherlands study of Depression in Older persons (NESDO) were included. Four cognitive domains, i.e. verbal memory, processing speed, interference control and attention were assessed with three cognitive tests (Stroop test, Wais Digit span test, and Rey's verbal learning test). Multiple linear regression analyses were applied with the four cognitive domains as dependent variables adjusted for confounders. Results The association between NGAL levels and specific cognitive domains were sex-specific. In women, higher NGAL levels were associated with impaired verbal memory and lower processing speed. In men, higher NGAL levels were associated with worse interference control. Higher NGAL levels were not associated with attention. No sex-specific associations of either high sensitivity C-reactive protein (hsCRP) or interleukin-6 (IL-6) with cognitive functioning were found. Conclusion This study shows sex-specific association of NGAL with cognitive functioning in late-life depression. [ABSTRACT FROM AUTHOR]

Objectives: Frailty marks an increased risk for adverse health outcomes. Since childhood trauma is associated with the onset of physical and mental health diseases during the lifespan, we examined the link between childhood trauma and multidimensional frailty., Method: A cross-sectional study embedded in a clinical cohort study (ROM-GPS) of older (≥60 years) patients (n=182) with a unipolar depressive-, anxiety- and/or somatic symptom disorder according to DSM-criteria referred to specialized geriatric mental health care. Frailty was assessed with the Tilburg Frailty Indicator (TFI), comprising a physical, psychological, and social dimension. Physical, sexual and psychological abuse and emotional neglect before the age of 16 years was measured with a structured interview., Results: Of 182 patients, 103 (56.6%) had experienced any childhood trauma and 154 (84.6%) were frail (TFI sum score ≥5). Linear regression analyses, adjusted for lifestyle, psychological and physical-health factors, showed that the presence of any type of childhood trauma was not associated with the TFI sum score, however when considered separately, physical abuse was (ß=0.16, p=.037). Regarding the specific frailty dimensions, any childhood trauma was associated with social frailty (ß=0.18, p=.019), with emotional neglect as main contributor., Conclusion: These findings demonstrate a complex link between different types of childhood trauma and multidimensional frailty among older psychiatric patients. Regarding the three dimensions of frailty, social frailty seems most affected by childhood trauma. This may have been underestimated until now and should receive more attention in clinical care and future research., (Copyright © 2021. Published by Elsevier B.V.)

Background: To examine the mortality risk of current and life-time depressive as well as anxiety disorders, whether this risk is moderated by sex or age, and whether this risk can be explained by lifestyle and/or somatic health status., Methods: A cohort study (Lifelines) including 141,377 participants (18-93 years) which were followed-up regarding mortality for 8.6 years (range 3.0-13.7). Baseline depressive and anxiety disorders according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria were assessed with the Mini International Neuropsychiatric Interview and lifetime diagnoses by self-report. All-cause mortality was retrieved from Statistics Netherlands. Cox-regression was applied to calculate proportional hazard ratios, adjusted for lifestyle (physical activity, alcohol use, smoking, and body mass index) and somatic health status (multimorbidity and frailty) in different models., Results: The mortality rate of depressive and anxiety disorders was conditional upon age but not on sex. Only in people below 60 years, current depressive and anxiety disorders were associated with mortality. Only depressive disorder and panic disorder independently predicted mortality when all mental disorders were included simultaneously in one overall model (hazard ratio [HR] = 2.18 [95% confidence intervals (CI): 1.56-3.05], p < 0.001 and HR = 2.39 [95% CI: 1.15-4.98], p = 0.020). Life-time depressive and anxiety disorders, however, were independent of each other associated with mortality. Associations hardly changed when adjusted for lifestyle characteristics but decreased substantially when adjusted for somatic health status (in particular physical frailty)., Conclusions: In particular, depressive disorder is associated with excess mortality in people below 60 years, independent of their lifestyle. This effect seems partly explained by multimorbidity and frailty, which suggest that chronic disease management of depression-associated somatic morbidity needs to be (further) improved.

Background: Increasing age as well as borderline personality pathology are associated with a lower level of health-related quality of life (HR-QoL). Our objective was to investigate whether the presence of borderline personality traits modifies the association between age and HR-QoL in the general population., Methods: Cross-sectional data from 5,303 respondents (aged 21-72 years) of the Netherlands Mental Health Survey and Incidence Study-2 were analyzed. Borderline personality traits were assessed with the International Personality Disorder Examination questionnaire. Mental and physical HR-QoL were measured with the Medical Outcomes Study Short Form Health Survey. Multiple linear regression analysis was used to examine the association of borderline personality traits, age and their interaction on mental as well as physical HR-QoL, adjusted for demographic variables as well as somatic and mental disorders., Results: A total of 1,520 (28.7%) respondents reported one or more borderline personality traits of which 58 (1.1%) reported five or more indicative of a borderline personality disorder. A higher age was associated with lower physical HR-QoL. This negative association became significantly stronger in the presence of borderline personality traits. The association between increasing age and mental HR-QoL was positive in the absence of borderline personality traits and negative in the presence of borderline personality traits., Conclusion: Borderline personality traits negatively interfere with the association between age and HR-QoL irrespective of somatic and mental disorders. Attention of clinicians and researchers for subthreshold borderline personality pathology is needed in middle-aged and older persons.

The COVID-19 pandemic has changed everyday life tremendously in a short period of time. After a brief timeline of the Dutch situation and our management strategy to adapt geriatric mental health care, we present a case-series to illustrate the specific challenges for geriatric psychiatrists., (Copyright © 2020. Published by Elsevier Inc.)

Background: Empirical studies on the clinical characteristics of older persons with medically unexplained symptoms are limited to uncontrolled pilot studies. Therefore, we aim to examine the psychiatric characteristics of older patients with medically unexplained symptoms (MUS) compared to older patients with medically explained symptoms (MES), also across healthcare settings., Methods: A case-control study including 118 older patients with MUS and 154 older patients with MES. To include patients with various developmental and severity stages, patients with MUS were recruited in the community (n = 12), primary care (n = 77), and specialized healthcare (n = 29). Psychopathology was assessed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria (Mini-International Neuropsychiatric Interview) and by dimensional measures (e.g., psychological distress, hypochondriasis, and depressive symptoms)., Results: A total of 69/118 (58.5%) patients with MUS met the criteria for a somatoform disorder according to DSM-IV-TR criteria, with the highest proportion among patients recruited in specialized healthcare settings (p = 0.008). Patients with MUS had a higher level of psychological distress and hypochondriasis compared to patients with MES. Although psychiatric disorders (beyond somatoform disorders) were more frequently found among patients with MUS compared to patients with MES (42.4 vs. 24.8%, p = 0.008), this difference disappeared when adjusted for age, sex, and level of education (odds ratio = 1.7 [95% confidence interval: 1.0-3.0], p = 0.070)., Conclusions: Although psychological distress is significantly higher among older patients with MUS compared to those with MES, psychiatric comorbidity rates hardly differ between both patient groups. Therefore, treatment of MUS in later life should primarily focus on reducing psychological distress, irrespective of the healthcare setting patients are treated in.

Background: Brain-derived neurotrophic factor (BDNF) levels decline during depression and normalise after remission, although studies in older patient samples are inconsistent. Whether BDNF serum levels predict depression remission is unclear. We hypothesize that the predictive value of serum BDNF levels in late-life depression is moderated by selective serotonin reuptake inhibitors (SSRI) usage and early traumatization., Methods: Our study sample was a subset of the Netherlands Study of Depression in Older persons (NESDO), a prospective cohort study. It consisted of 267 older persons with a diagnosis of depression, for which follow-up data were available. Depression diagnosis was assessed at baseline and follow up using a structured diagnostic interview (Composite International Diagnostic Interview (CIDI), volume2.1). Logistic regression was performed (adjusted for covariates) with remission of depression after two years as the dependent variable and baseline BDNF serum levels, childhood traumatization and SSRI use as independent variables. Results - The mean age of the subjects was 70.7 years, 65.6% of them were female, their mean BDNF level was 7.7 ng/ml, 80 (30.0%) of them were traumatised in their childhood,71 (26.6%) used SSRIs and 136 (50.9%) no longer had a depressive disorder at the two year follow up. The predictive value of BDNF serum levels was conditional on traumatization and SSRI usage (threeway interaction p = .010). Higher BDNF serum levels predicted remission in traumatized depressed patients without SSRI usage (OR = 1.17, 95% C.I.: 1.00-1.36; p = .048) and in non-traumatized depressed patients who used SSRIs (OR = 1.17, 95% C.I.: 1.00-1.36; p = .052), but not in the other two subgroups., Conclusion: The association between BDNF serum levels and the course of late-life depression seems to depend on SSRI use and childhood trauma. Based on these results, we hypothesize that childhood trauma may permanently reduce ('blunt') the responsiveness of the neurotrophic system to SSRI usage, and that this responsiveness might be more important for depression course than the actual BDNF serum levels., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Different biological mechanisms may underlie depression beginning in early life (early-onset) and depression beginning later in life (late-onset). Although the relation between inflammation and depression has been studied extensively, the distinct role of inflammation in early and late-onset depression in older patients has not been addressed before. In the cross-sectional part of this study, we explored differences in levels of circulating inflammatory markers and cytokine levels in lipopolysaccharide (LPS) stimulated whole blood between older subjects with a late-life onset depression (≥60 years) and older subjects with an early-onset depression (<60 years). Secondly, in a 2-year follow-up study, we examined if circulating and stimulated inflammatory markers influenced the change in Inventory of Depressive Symptomatology (IDS) scores, and if this relation was different for early- and late-onset depression., Methods: The study was part of the Netherlands Study of Depression in Older Persons (NESDO). We included 350 patients, all aged 60 and older, with a depressive episode in the previous 6 months: 119 with a late-onset depression and 231 with an early-onset depression. Blood samples were collected and CRP, IL-6, NGAL, GDF15, and, LPS plasma levels were determined and whole blood was LPS stimulated and cytokine levels IL-1β, IL-6, TNFα, IFNγ, IL-10, and IL-1 receptor antagonist (IL-1ra) were determined., Results: After adjustment for demographics, health indicators, and medication use, increased plasma CRP levels were more strongly associated with late-onset depression than early-onset depression (OR [95% CI]: 1.43 [1.05-1.94]). In the longitudinal analyses, higher circulating IL-6 levels were associated with a significantly slower decline in IDS scores in the crude and the adjusted models (p ≤ 0.027). This relation was not different between late- and early-onset depression. Other circulating and stimulated inflammatory markers were not associated with late- and/or early-onset depression., Conclusions: This study provides preliminary evidence that low-grade inflammation is more strongly associated with late-onset than early-onset depression in older adults, suggesting a distinct inflammatory etiology for late-onset depression. Cytokine production capacity did not distinguish between early- and late-onset depression., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The level of physical activity (PA) and the prevalence of depression both change across the lifespan. We examined whether the association between PA and depression is moderated by age. As sense of mastery and functional limitations have been previously associated with low PA and depression in older adults, we also examined whether these are determinants of the differential effect of age on PA and depression., Methods: 1079 patients with major depressive disorder (aged 18-88 years) were followed-up after two-years; depression diagnosis and severity as well as PA were re-assessed. Linear and logistic regression analyses were used to test reciprocal prospective associations between PA and depression outcomes. In all models the interaction with age was tested., Results: PA at baseline predicted remission of depressive disorder at follow-up (OR = 1.43 [95% CI: 1.07-1.93], p = .018). This effect was not moderated by age. PA predicted improvement of depression symptom severity in younger (B = -2.03; SE = .88; p = .022), but not in older adults (B = 2.24; SE = 1.48; p = .128) (p = .015 for the interaction PA by age in the whole sample). The level of PA was relatively stable over time. Depression, sense of mastery and functional limitation were for all ages not associated with PA at follow-up., Conclusions: Age did not moderate the impact of PA on depressive disorder remission. Only in younger adults, sufficient PA independently predicts improvement of depressive symptom severity after two-year follow-up. Level of PA rarely changed over time, and none of the determinants tested predicted change in PA, independent of age., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Depression is one of the most prevalent and debilitating psychiatric disorders worldwide. Recently, we showed that both relatively short and relatively long cytosine-adenine-guanine (CAG) repeats in the huntingtin gene (HTT) are associated with an increased risk of lifetime depression. However, to what extent the variations in CAG repeat length in the other eight polyglutamine disease-associated genes (PDAGs) are associated with depression is still unknown. We determined the CAG repeat sizes of ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7, TBP, ATN1 and AR in two well-characterized Dutch cohorts-the Netherlands Study of Depression and Anxiety and the Netherlands Study of Depression in Older Persons-including 2165 depressed and 1058 non-depressed individuals-aged 18-93 years. The association between PDAG CAG repeat size and the risk for depression was assessed via binary logistic regression. We found that the odds ratio (OR) for lifetime depression was significantly higher for individuals with >10, compared with subjects with ≤10, CAG repeats in both ATXN7 alleles (OR=1.90, confidence interval (CI) 1.26-2.85). For TBP we found a similar association: A CAG repeat length exceeding the median in both alleles was associated with an increased risk for lifetime depression (OR=1.33, CI 1.00-1.76). In conclusion, we observed that carriers of either ATXN7 or TBP alleles with relatively large CAG repeat sizes in both alleles had a substantially increased risk of lifetime depression. Our findings provide critical evidence for the notion that repeat polymorphisms can act as complex genetic modifiers of depression.

Background: Physical frailty and depressive symptoms are reciprocally related in community-based studies, but its prognostic impact on depressive disorder remains unknown., Methods: A cohort of 378 older persons (≥60 years) suffering from a depressive disorder (DSM-IV criteria) was reassessed at two-year follow-up. Depressive symptom severity was assessed every six months with the Inventory of Depressive Symptomatology, including a mood, motivational, and somatic subscale. Frailty was assessed according to the physical frailty phenotype at the baseline examination., Results: For each additional frailty component, the odds of non-remission was 1.24 [95% CI=1.01-1.52] (P=040). Linear mixed models showed that only improvement of the motivational (P<001) subscale and the somatic subscale (P=003) of the IDS over time were dependent on the frailty severity., Conclusions: Physical frailty negatively impacts the course of late-life depression. Since only improvement of mood symptoms was independent of frailty severity, one may hypothesize that frailty and residual depression are easily mixed-up in psychiatric treatment., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

A low plasma 25-OH vitamin D3 level is a universal risk factor for a wide range of diseases and has also been implicated in late-life depression. It is currently unknown whether the biologically active form of vitamin D, that is, 1,25-(OH)2 vitamin D3, is also decreased in late-life depression, or whether vitamin D levels correlate with specific depression characteristics. We determined plasma 25-OH vitamin D3, 1,25-(OH)2 vitamin D3 and parathormone levels in 355 depressed older persons and 124 non-depressed comparison subjects (age 60 years). Psychopathology was established with the Composite International Diagnostic Interview 2.1, together with potential confounders and depression characteristics (severity, symptom profile, age of onset, recurrence, chronicity and antidepressant drug use). Adjusted for confounders, depressed patients had significantly lower levels of 25-OH vitamin D33 (Cohen's d =0.28 (95% confidence interval: 0.07-0.49), P=0.033) as well as 1,25-(OH)2 vitamin D3 (Cohen's d =0.48 (95% confidence interval: 0.27-0.70), P<0.001) than comparison subjects. Of all depression characteristics tested, only the use of tricyclic antidepressants (TCAs) was significantly correlated with lower 1,25-(OH)2 vitamin D3 levels (Cohen's d =0.86 (95% confidence interval: 0.53-1.19), P<0.001), but not its often measured precursor 25-OH vitamin D3. As vitamin D levels were significantly lower after adjustment for confounders, vitamin D might have an aetiological role in late-life depression. Differences between depressed and non-depressed subjects were largest for the biologically active form of vitamin D. The differential impact of TCAs on 25-OH vitamin D3 and 1,25-(OH)2 vitamin D3 levels suggests modulation of 1-α-hydroxylase and/or 24-hydroxylase, which may in turn have clinical implications for biological ageing mechanisms in late-life depression.

Objective: Systemic low graded inflammation has been identified as a possible biological pathway in late-life depression. Identification of inflammatory markers and their association with characteristics of depression is essential with the aim to improve diagnosis and therapeutic approaches. This study examines the determinants of plasma Neutrophil Gelatinase-Associated Lipocalin (NGAL), which is selectively triggered by TNFα receptor 1 signaling within the central nervous system, and its association with late-life depressive disorder., Methods: Baseline data were obtained from a well-characterized prospective cohort study of 350 depressed and 129 non-depressed older persons (≥60years). Past 6month diagnosis of major depressive disorder (MDD) according to DSM-IV-TR criteria was assessed with the Composite International Diagnostic Interview (CIDI 2.0). Potential determinants of plasma NGAL included sociodemographic characteristics, lifestyle and psychiatric and physical comorbidity., Results: Plasma NGAL concentrations were significantly associated with age, male gender, smoking and waist circumference. Adjusted for these determinants, depressed patients had significantly higher NGAL plasma levels compared to non-depressed comparison group. Depressed patients who did not meet full criteria for MDD in the month before sampling (partially remitted) had lower plasma NGAL levels compared with those who did. Subjects with a recurrent depression had higher plasma NGAL levels compared to those with a first episode. NGAL levels were neither related with specific symptom profiles of depression nor with antidepressant drug use., Conclusion: Adjusted for confounders, NGAL plasma levels are increased in depressed older persons, without any effect of antidepressant medication and age of onset., (© 2013.)

Background: Personality may play an important role in late-life depression. The aim of this study is to examine the association between the Big Five personality domains and the diagnosis, severity and age of onset of late-life depression., Methods: The NEO-Five Factor Inventory (NEO-FFI) was cross-sectionally used in 352 depressed and 125 non-depressed older adults participating in the Netherlands Study of Depression in Older Persons (NESDO). Depression diagnosis was determined by the Composite International Diagnostic Interview (CIDI). Severity of depression was assessed by the Inventory of Depressive Symptomatology (IDS). Logistic and linear regression analyses were applied. Adjustments were made for sociodemographic, cognitive, health and psychosocial variables., Results: Both the presence of a depression diagnosis and severity of depression were significantly associated with higher Neuroticism (OR=1.35, 95% CI=1.28-1.43 and B=1.06, p<.001, respectively) and lower Extraversion (OR=.79, 95% CI=.75-.83; B=-.85, p<.001) and Conscientiousness (OR=.86, 95% CI=.81.-.90; B=-.86, p<.001). Earlier onset of depression was significantly associated with higher Openness (B=-.49, p=.026)., Limitations: Due to the cross-sectional design, no causal inferences can be drawn. Further, current depression may have influenced personality measures., Conclusions: This study confirms an association between personality and late-life depression. Remarkable is the association found between high Openness and earlier age of depression onset., (© 2013 Elsevier B.V. All rights reserved.)

Objective: To review current knowledge regarding the prevalence of somatization problems in later life by level of caseness (somatoform disorders and medically unexplained symptoms, MUS) and to compare these rates with those in middle-aged and younger age groups., Method: A systematic search of the literature published from 1966 onwards was conducted in the Pubmed and EMBASE databases., Results: Overall 8 articles, describing a total of 7 cohorts, provided data of at least one prevalence rate for somatoform disorders or MUS for the middle-aged (50-65 years) or older age (≥65 years) group. Prevalence rates for somatoform disorders in the general population range from 11 to 21% in younger, 10 to 20% in the middle-aged, and 1.5 to 13% in the older age groups. Prevalence rates for MUS show wider ranges, of respectively 1.6-70%, 2.4-87%, and 4.6-18%, in the younger, middle, and older age groups, which could be explained by the use of different instruments as well as lack of consensus in defining MUS., Conclusion: Somatoform disorders and MUS are common in later life, although the available data suggest that prevalence rates decline after the age of 65 years. More systematic research with special focus on the older population is needed to understand this age-related decline in prevalence rates., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: Vascular disease and neuroticism are both risk factors for late-life depression. In this study we examined the interaction between vascular disease and neuroticism as determinants of clinically relevant depressive symptoms (CRDS) in late-life., Methods: Multivariate logistic regression in a survey of 1396 population-dwelling people aged ≥70 years. CRDS were defined as scoring ≥16 on the CES-D. Vascular disease was categorised into four levels: none, ≥2 vascular risk factors, cardiac disease or stroke., Results: Neuroticism was strongly associated with CRDS in women (OR: 1.6, 95% CI: 1.4-1.8). In men vascular disease interacted negatively but significantly with neuroticism (cardiac disease by neuroticism: OR: 0.8, 95% CI: 0.6-0.9; stroke by neuroticism: OR: 0.8, 95% CI: 0.6-0.96) when predicting CRDS., Conclusions: In men vascular disease attenuates the predictive value of neuroticism in CRDS, which might be mediated by apathy caused by cerebrovascular disease., (Copyright © 2010 John Wiley & Sons, Ltd.)

Background: Research examining the course of depressive symptoms during electroconvulsive therapy (ECT) is relatively scarce., Objective: To classify patients according to the course of their depressive symptoms while receiving ECT., Methods: The sample consisted of 156 consecutive patients receiving ECT for unipolar depressive disorder. Depressive symptoms were measured weekly with the Montgomery-Asberg Depression Rating Scale. Latent class analysis was applied to identify distinct trajectories of symptom improvement., Results: We identified five classes of different trajectories (improvement rates) of depressive symptoms, i.e. fast improvement (39 patients), intermediate improvement (47 patients), slow improvement (30 patients), slow improvement with delayed onset (18 patients), and finally a trajectory with no improvement (20 patients). The course of depressive symptoms at the end of the treatment within the trajectories of intermediate improvement, slow improvement and slow improvement with delayed onset, was still improving and did not achieve a plateau., Conclusion: The different courses of depressive symptoms during ECT probably contribute to mixed results of prediction studies of ECT outcome. Data suggest that for a large group of patients no optimal clinical endpoint can be identified, other than full remission or no improvement at all, to discontinue ECT.

Background: Whether long-term benzodiazepine users who participate in a family practice-based benzodiazepine discontinuation programme substitute benzodiazepines by other psychotropics is not clear., Objective: To evaluate the impact of a benzodiazepine discontinuation programme on non-benzodiazepine psychotropic prescription in family practice., Methods: In family practices in the Netherlands, 2425 long-term benzodiazepine users participated in a two-step benzodiazepine discontinuation programme. The programme started with a discontinuation letter (Step 1). Subjects unable to stop (N = 1707) were offered participation in Step 2, a three-group randomized trial with a taper procedure with group psychotherapy, a taper without psychotherapy and usual care. Only 156 subjects agreed to participate. The comparison group consisted of 1821 long-term users from family practices not participating in the programme. The main outcome was the change in prescription of non-benzodiazepine psychotropic medication from baseline (3 months before the start of the programme) till 21 months after the start of the programme. Four logistic regression models were performed concerning antidepressant prescription in the follow-up., Results: Only antidepressants were prescribed in relevant numbers. The prescription of antidepressants was not related to the programme. (P-value of experimental versus control group varied between 0.18 and 0.85 in the four models). The most important predictor of antidepressant prescription in follow-up was baseline antidepressant prescription [odds ratio (OR): 67.2; 95% confidence interval (95% CI): 49.8-90.7]. Subjects, of whom the prescription of benzodiazepines had been discontinued completely, had been prescribed less antidepressants (OR: 0.8; 95% CI: 0.6-1.0)., Conclusion: An effective benzodiazepine reduction programme was not accompanied by a substitute use of other psychotropics.

Background: Predictors of benzodiazepine discontinuation after sending a discontinuation letter by the family practitioner have not been established sufficiently., Objective: To identify predictors of short- and long-term discontinuation of benzodiazepine use and relapse in use after a minimal intervention with a discontinuation letter followed by an offer for an evaluation consultation., Methods: Predictors of benzodiazepine discontinuation and relapse in use were studied by logistic regression analysis and survival analysis within a family practice population of long-term benzodiazepine users (n = 1707) addressed by a discontinuation letter and followed for 21 months., Results: A lower baseline prescription, a shorter duration of use, male gender and use of an agent with a half-life time <24 hours were predictive of complete discontinuation in the short (6 months) and long term (21 months). Multiple agent use at baseline, use of antidepressants at 6 months and benzodiazepine type (anxiolytic/hypnotic) at baseline predicted relapse. Attendance at an evaluation consultation 3 months after the letter was sent was not predictive of discontinuation or relapse., Conclusions: Amount of baseline use and duration of use are the main determinative characteristics of successful discontinuation. The discontinuation letter intervention is suitable for use with a broad group of long-term benzodiazepine users in family practice and can be used as a first step within a stepped care approach to decrease long-term benzodiazepine use.

This study aimed to assess benzodiazepine craving longitudinally and to describe its time course by means of the Benzodiazepine Craving Questionnaire (BCQ). Subjects were long-term benzodiazepine users participating in a two-part treatment intervention aimed to reduce long-term benzodiazepine use in general practice in The Netherlands. Four repeated measurements of benzodiazepine craving were taken over a 21-month follow-up period. Results indicated that (1) benzodiazepine craving severity decreased over time, (2) patients still using benzodiazepines experienced significantly more severe craving than patients who had quit their use after one of the two interventions, and (3) the way in which patients had attempted to quit did not influence the experienced craving severity over time, however, (4) patients who had received additional tapering off, on average, reported significantly more severe craving than patients who had only received a letter as an incentive to quit. Although benzodiazepine craving is prevalent among (former) long-term benzodiazepine users during and after discontinuation, craving severity decreases over time to negligible proportions. Self-reported craving can be longitudinally monitored and quantified by means of the BCQ.