Subtyping late-life depression according to inflammatory and metabolic dysregulation: a prospective study.

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.

Cerebellar Grey Matter Volume in Older Persons Is Associated with Worse Cognitive Functioning.

The cerebellum is increasingly recognised for its role in modulation of cognition, behaviour, and affect. The present study examined the relation between structural cerebellar damage (grey matter volume (GMV), white matter hyperintensities (WMHs), lacunar infarcts (LIs) and microbleeds (MBs)) and measures of cognitive, psychological (i.e. symptoms of depression and apathy) and general daily functioning in a population of community-dwelling older persons with mild cognitive deficits, but without dementia. In 194 participants of the Discontinuation of Antihypertensive Treatment in Elderly People (DANTE) Study Leiden, the association between cerebellar GMV, WMHs, LIs and MBs and measures of cognitive, psychological and general daily functioning was analysed with linear regression analysis, adjusted for age, sex, education and cerebral volume. Cerebellar GMV was associated with the overall cognition score (standardised beta 0.20 [95% CI, 0.06-0.33]). Specifically, posterior cerebellar GMV was associated with executive function (standardised beta 0.18 [95% CI, 0.03-0.16]). No relation was found between vascular pathology and cognition. Also, no consistent associations were found on the cerebellar GMV and vascular pathology measures and psychological and general daily functioning. In this population of community-dwelling elderly, less posterior cerebellar GMV but not vascular pathology was associated with worse cognitive function, specifically with poorer executive function. No relation was found between cerebellar pathology and psychological and general daily functioning.

Impaired cognition is associated with adverse outcome in older patients in the Emergency Department; the Acutely Presenting Older Patients (APOP) study.

Objective: to investigate whether cognitive impairment, measured early after Emergency Department (ED) arrival and irrespective of its cause, is independently associated with functional decline or mortality after 3 and 12 months in older ED patients. Design and setting: a prospective multi-centre cohort study in all Acutely Presenting Older Patients visiting the Emergency Department (APOP study) of three hospitals in the Netherlands. Participants: 2,130 patients, ≥70 years. Measurements: data on demographics, disease severity and geriatric characteristics were collected during the first hour of the ED visit. Cognition was measured using the 6-Item-Cognitive-Impairment-Test ('6CIT'). Cognitive impairment was defined as 6CIT ≥11, self-reported dementia or the inability to perform the cognition test. The composite adverse outcome after 3 and 12 months was defined as a 1-point decrease in Katz Activities of Daily Living (ADL), new institutionalisation or mortality. Multivariable regression analysis was used to assess whether cognitive impairment independently associates with adverse outcome. Results: of 2,130 included patients, 588 (27.6%) had cognitive impairment at baseline and 654 patients (30.7%) suffered from adverse outcome after 3 months. Cognitive impairment associated with increased risk for adverse outcome (adjusted odds ratio (OR) 1.72, 95%CI 1.37-2.17). After 12 months, 787 patients (36.9%) suffered from adverse outcome. Again, cognitive impairment independently associated with increased risk for adverse outcome (adjusted OR 1.89, 95%CI 1.46-2.46). ORs were similar for patients who were discharged home versus hospitalised patients. Conclusion: cognitive impairment measured during the early stages of ED visit, irrespective of the cause, is independently associated with adverse outcome after 3 and 12 months in older patients.

Big Five personality characteristics are associated with depression subtypes and symptom dimensions of depression in older adults.

OBJECTIVE: This study examined the associations of personality characteristics with both subtypes and symptom dimensions of depression in older adults. METHODS: Three hundred and seventy-eight depressed older adults participated in the Netherlands Study of Depression in Older Persons. Personality characteristics were assessed by the NEO-Five Factor Inventory. Subtypes and symptom dimensions of depression were determined using the Composite International Diagnostic Interview and the Inventory of Depressive Symptomatology (IDS). Multinomial logistic regression analyses were performed to examine the associations between personality and atypical, melancholic, and unspecified subtypes of major depression. Linear regression analyses examined the associations between personality and the IDS mood, somatic, and motivation symptom dimensions. The analyses were adjusted for confounders and additionally adjusted for depression severity. RESULTS: Neuroticism, Extraversion, Conscientiousness, and Agreeableness were associated with specified (atypical or melancholic) major depression compared with unspecified major depression in the bivariate analyses but lost their significance after adjustments for functional limitations and severity of depression. Neuroticism was positively associated with the IDS mood and motivation symptom dimensions, also in the adjusted models. Further, Extraversion and Agreeableness were negatively associated with the IDS mood symptom dimension, and Extraversion and Conscientiousness were negatively associated with the IDS motivation symptom dimension. None was associated with the IDS somatic symptom dimension. CONCLUSIONS: This study demonstrated the association of personality characteristics with mood and motivational symptoms of late-life depression. The lacking ability of personality to differentiate between melancholic and atypical depression seems to be largely explained by severity of depressive symptoms. Copyright © 2017 John Wiley & Sons, Ltd.

Cerebrovascular involvement and clinical presentation of late-life depression, findings from the NESDO study.

OBJECTIVES: The vascular depression hypothesis, which supposes a causal relation of vascular risk factors and vascular disease with depression, has not been definitively accepted. Inconsistent findings may be due to different clinical presentations of depression in older people with and without a clear history of stroke. We therefore aimed to investigate the association between vascular pathology, with and without previous stroke, and different symptom domains of depression. METHOD: For our study, we used baseline data of 378 people aged 60 years and older with a current depression who participated in the Netherlands Study of Depression in Older persons (NESDO), an observational (multicentre) cohort study. Using all information on vascular pathology and risk factors, three classes were operationalized: a first class of depressed older people with previous stroke; a second class of depressed older people with cardiovascular and peripheral arterial diseases, but without stroke; and a third class of depressed older people with no vascular disease. RESULTS: The depressed older people with previous stroke were characterized by more 'motivational' symptoms, which distinguished them from other depressed older people. Inclusion in this stroke group was also associated with having increased prevalence of hypertension, smoking more cigarettes, and lower alcohol consumption. CONCLUSIONS: Our findings suggest that the 'vascular depression' connotation should be reserved for depressed (older) patients with vascular pathology and evident cerebral involvement.

In depressed older persons higher blood pressure is associated with symptoms of apathy. The NESDO study.

BACKGROUND: In older persons, a relationship between both higher and lower blood pressure and depression has inconsistently been reported. Blood pressure may be differentially associated with distinct symptom domains of depression. We examined the cross-sectional relation of current systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) with different depressive symptom domains among depressed older persons. METHODS: In the Netherlands Study of Depression in Older Persons (NESDO), 270 participants aged 60 years and above were diagnosed with depression in the past month. Using the three corresponding subscales of the Inventory of Depressive Symptoms-Self Report (IDS-SR), motivational, mood and somatic symptom domains were assessed. Additionally, symptoms of apathy were determined with the Apathy Scale. Multiple linear regression was used to examine the cross-sectional relationship between current SBP, DBP and MAP with both IDS-SR subscale and Apathy Scale scores. Unstandardized betas were calculated per 10 mmHg increase in blood pressure measures. RESULTS: Mean age of participants was 70.4 years (standard deviation 7.3). Higher SBP (Beta 0.33, t (254) = 2.01, p = 0.045), higher DBP (Beta 0.68, t (254) = 2.15, p = 0.03) and higher MAP (Beta 0.63, t (254) = 2.33, p = 0.02) were associated with higher Apathy Scale scores in the fully adjusted model. Furthermore, a higher SBP was associated with higher IDS-SR mood subscale scores (Beta 0.25, t (254) = 2.13, p = 0.03). CONCLUSIONS: Depressed older people with higher blood pressure measures had particularly more symptoms of apathy. To disentangle the relationship of blood pressure with late-life depression, it is important to pay attention to the role of apathy symptoms.

Phenomenology of depression in older compared with younger adults: meta-analysis.

BACKGROUND: Late-life depression may differ from early-life depression in its phenomenology. AIMS: To investigate the effect of age on the phenomenology of major depression. METHOD: A systematic search was conducted in PubMed, Embase and PsycINFO for all studies examining the relation between age and phenomenology of major depression according to RDC, DSM and ICD criteria. Studies were included only if the age groups were compared at the single-item level using the 17-, 21- or 24-item versions of the Hamilton Rating Scale for Depression; a meta-analysis was done for each item of the 17-item scale. RESULTS: Eleven papers met the inclusion criteria. Older depressed adults, compared with younger depressed adults, demonstrated more agitation, hypochondriasis and general as well as gastrointestinal somatic symptoms, but less guilt and loss of sexual interest. CONCLUSIONS: The phenomenology of late-life depression differs only in part from that of early-life depression. Major depression in older people may have a more somatic presentation, whereas feelings of guilt and loss of sexual function may be more prevalent in younger people.

Psychiatric disorders in Huntington's disease: a 2-year follow-up study.

OBJECTIVE: This study investigates the presence and course of formal psychiatric disorders according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) in 142 Huntington's disease (HD) mutation carriers in a two-year follow-up design. METHOD: Of the 142 mutation carriers, 106 (75%) participated in the second measurement of an ongoing cohort study on psychopathology in HD. Presence of psychiatric disorders was assessed using the Composite International Diagnostic Interview. RESULTS: Of the 91 patients without a formal psychiatric disorder at baseline, 14 (15%) had a psychiatric disorder after 2 years, mostly a major depressive disorder (MDD) (64%). The baseline characteristics of lower education, having no children, a lower level of global daily functioning, a lifetime psychiatric diagnosis, and the use of psychotropic medication were predictive of incident psychiatric disorders after 2 years. Of the 15 patients with a psychiatric diagnosis at baseline, eight (53%) no longer had a psychiatric disorder at follow-up. All seven patients (47%) with a persistent psychiatric disorder were female and their most prevalent diagnosis was generalized anxiety disorder. CONCLUSION: This cohort study confirms that psychiatric disorders, in particular MDD, frequently occur in patients with HD. Professionals working with HD patients should therefore be aware of the high risk of psychopathology in HD because early diagnosis and treatment of psychiatric disorders may improve the quality of life of patients and their caregivers.

Correlates of apathy in Huntington's disease.

The authors aim to study prevalence and clinical correlates of apathy in Huntington's disease. Apathy was defined as an Apathy Scale score > or =14 points in 152 Huntington's disease mutation carriers and 56 noncarriers. Correlates of apathy were analyzed cross-sectionally in mutation carriers using multivariable logistic regression analysis. Forty-nine (32%) Huntington's disease mutation carriers showed apathy compared to none of the noncarriers. After exclusion of 10 depressed patients, apathy was independently associated with male sex, worse global functioning, and higher use of neuroleptics and benzodiazepines.

Hair cortisol in patients with a depressive episode treated with electroconvulsive therapy.

BACKGROUND: There is substantial evidence showing changes in hypothalamic pituitary adrenal (HPA)-axis activity in patients with major depressive disorder (MDD). Also, there seem to be differences in HPA-axis functioning between MDD subgroups. It is however unclear whether hair cortisol concentrations (HCC), which are a stable marker of long-term cortisol levels, are suitable as a biomarker for identifying subgroups in MDD. METHODS: We were able to attain valid HCC from a scalp hair sample of sixty-two patients with a major depressive episode right before electroconvulsive therapy (ECT). HCC were our main biological outcome measure. We created subgroups using depression severity as defined by the Hamilton Depression Rating Scale, the presence/absence of psychotic symptoms, the presence of melancholia as defined by the CORE and catatonia as defined by the Bush-Francis Catatonia Rating Scale. RESULTS: Our analyses of the total group showed a median HCC of 4.4 pg/mg. We found patients with catatonia (N = 10) to have substantially higher median HCC (8.3 pg/mg) than patients without catatonia (3.8 pg/mg). Although presence of melancholia and depression severity were not significantly associated with HCC, more severe psychomotor agitation was associated with higher HCC. Pre-treatment HCC was not associated with ECT outcome. STRENGTHS AND LIMITATIONS: A complicating factor in interpretation of our results was the large variability in HCC. This could be related to potential confounders such as cardiometabolic and other comorbidities, that were however addressed to the extent possible. CONCLUSIONS: HCC is a potential biomarker for MDD patients with severe agitation and/or catatonia. CLINICALTRIALS.GOV: Identifier: NCT02562846.

Increased C-reactive protein is not associated with apathy: the Leiden 85-Plus Study.

BACKGROUND: Apathy has recently been recognized as a distinct clinical syndrome although it is difficult to differentiate from late life depression. In old age, apathy as a syndrome in itself and depression may have different etiologies. Inflammatory markers have been associated with depression in the elderly, but the relation with apathy is unknown. OBJECTIVE: To assess the relation between C-reactive protein (CRP) and apathy as a syndrome in itself, apart from depression, in subjects aged 85 and older. METHODS: All data come from the Leiden 85-Plus Study, a prospective, population-based study of 599 elderly subjects. CRP was measured at baseline. In all subjects with a Mini Mental State Examination (MMSE) > or = 19 points (n = 500), apathy and depression were assessed annually from age 85 to 90 using the three apathy and twelve depression questions of the 15-item Geriatric Depression Scale (GDS-15). The association between CRP and apathy or depressive symptoms was assessed both at baseline and longitudinally. RESULTS: At baseline, no association was found between CRP-concentration and apathy or depression. In subjects free of apathy and depression at baseline, subjects in the highest CRP-tertile at baseline had significantly more increase in depressive symptoms but not in apathy symptoms during follow-up. CONCLUSION: Higher CRP concentrations increased the risk of depression but not apathy in a community-based cohort of 85 years old subjects. This suggests that apathy and depression in old age have different etiologies.

[Psychiatric symptoms in systemic lupus erythematosus]. / Psychiatrische symptomen bij systemische lupus erythematosus.

BACKGROUND: This article focuses on two patients with psychiatric symptoms arising from systemic lupus erythematosus (SLE). Affective and psychotic symptoms frequently occur in SLE, often in combination with cognitive disturbances, and can be a first manifestation of the disorder. The diagnosis and treatment of a possible case of neuropsychiatric SLE should preferably take place in a multidisciplinary setting.

[Immune activation and depression in the elderly]. / Immuunactivatie en depressie bij ouderen.

Besides the monoamine hypothesis, the stress hypothesis and the vascular hypothesis, the inflammatory hypothesis might be an etiological explanation for late-life depression. There is a growing amount of evidence to support this hypothesis. In animal studies, injection with cytokines was shown to cause behavioural changes ('sickness behaviour') similar to depressive symptoms in humans. Cytokine treatment of certain tumours and chronic hepatitis can also cause depressive symptoms. The prevalence of depression in patients with autoimmune diseases is higher than in the general population. Etanercept had a favourable effect on the depressive symptoms in patients with psoriasis, independent of improvement of physical symptoms. Cytokines affect the hypothalamus-pituitary-adrenal axis and cerebral neurotransmitter systems, both of which are thought to be involved in depression. Immune activation has been associated with depression, and several anti-depressive treatments affect immune parameters, although inconsistently. Since the aging process is associated with a dysregulation of the immune system, the inflammation hypothesis might be particularly true in late-life depression.

[Delirium in the intensive care unit]. / Delirium op de intensive care.

Delirium is a common condition in the intensive care unit (ICU). Between 16-89% of all ICU patients experience an episode of delirium during admission. Several detection tools have been developed for use specifically in the ICU. The Confusion Assessment Method for the intensive care unit (CAM-ICU) and the Intensive Care Delirium Screening Checklist (ICDSC) combine high sensitivity with high specificity. Treatment consists of treatment of underlying disorders, nonpharmacological measures and symptomatic drug therapy. The prognosis for ICU patients who experience delirium is worse than for those who do not. Delirious patients are more likely to develop complications, spend longer in hospital and have a higher mortality rate. In view of the high frequency, poor prognosis, high costs and lack of studies into the treatment of ICU delirium, research into the possibilities for prevention, early detection and treatment of the condition is essential.

Inflammatory markers and cortisol parameters across depressive subtypes in an older cohort.

BACKGROUND: There is growing evidence that inflammatory and cortisol dysregulation are underlying pathophysiological mechanisms in the aetiology of major depressive disorder, particularly in younger adults. However, findings of biological disturbances in late-life depression have been divergent, probably due to the even greater heterogeneity of depression in older adults with aging processes influencing biological factors. Using empirically derived subtypes may enable the identification of biological disturbances underlying depression in older adults. METHODS: Data were used from the Netherlands Study of Depression in Older Persons (NESDO) of 359 persons aged 60 years or older, with a current diagnosis of major depressive disorder (MDD). Depressive subtypes (severe atypical, severe melancholic, and moderate severe subtype) that were previously identified through latent class analysis (LCA), were examined on differences in inflammatory markers including C-reactive protein (CRP), interleukin-6 (IL-6), and neutrophil gelatinase-associated lipocalin (NGAL), as well as cortisol parameters. RESULTS: No differences in measures for inflammation and cortisol across subtypes were observed in uncorrected or for putative confounders corrected models. LIMITATIONS: Several subjects had missing cortisol and inflammatory data, decreasing the power. However, results did not change after imputation analysis. DISCUSSION: In this cohort of depressed older adults, no differences in inflammation and cortisol measures between depression subtypes were observed. This is probably due to the many (patho)physiological processes that are involved in aging, thereby clouding the results.

Suicidal ideation and subsequent completed suicide in both psychiatric and non-psychiatric populations: a meta-analysis.

AIMS: Several authors claimed that expression of suicidal ideation is one of the most important predictors of completed suicide. However, the strength of the association between suicidal ideation and subsequent completed suicide has not been firmly established in different populations. Furthermore, the absolute suicide risk after expression of suicidal ideation is unknown. In this meta-analysis, we examined whether the expression of suicidal ideation predicted subsequent completed suicide in various populations, including both psychiatric and non-psychiatric populations. METHODS: A meta-analysis of cohort and case-control studies that assessed suicidal ideation as determinant for completed suicide in adults. Two independent reviewers screened 5726 articles for eligibility and extracted data of the 81 included studies. Pooled risk ratios were estimated in a random effects model stratified for different populations. Meta-regression analysis was used to determine suicide risk during the first year of follow-up. RESULTS: The risk for completed suicide was clearly higher in people who had expressed suicidal ideation compared with people who had not, with substantial variation between the different populations: risk ratio ranging from 2.35 (95% confidence interval (CI) 1.43-3.87) in affective disorder populations to 8.00 (95% CI 5.46-11.7) in non-psychiatric populations. In contrast, the suicide risk after expression of suicidal ideation in the first year of follow-up was higher in psychiatric patients (risk 1.40%, 95% CI 0.74-2.64) than in non-psychiatric participants (risk 0.23%, 95% CI 0.10-0.54). Past suicide attempt-adjusted risk ratios were not pooled due to large underreporting. CONCLUSIONS: Assessment of suicidal ideation is of priority in psychiatric patients. Expression of suicidal ideation in psychiatric patients should prompt secondary prevention strategies to reduce their substantial increased risk of suicide.

[Chronic low back pain: the failure of organic medicine]. / Chronische lage rugpijn: het falen van de orgaangeneeskunde.

In this issue of the journal, a series of 67 patients is presented with persistent or recurrent chronic low back pain and leg pain after insertion of a lumbar-disc prosthesis in a private hospital in Germany. A relationship between degenerative changes in the vertebral column and chronic low back pain is often assumed but lacks a scientific basis. Psychosocial factors are much more important than biomechanical factors in determining the outcome, but the interaction between these determinants is far more complicated than just 'having problems'. Accordingly, a multidisciplinary approach is the most successful mode of treatment, while local measures aimed at the vertebral column are generally ineffective or of unproven value. Patients will continue to seek magic cures from 'quacks with a knife' as long as medical specialists are insufficiently trained to deal with unexplained somatic symptoms.