Thalamic white matter macrostructure and subnuclei volumes in Parkinson’s disease depression

Depression is a common non-motor feature of Parkinson’s disease (PD) which confers significant morbidity and is challenging to treat. The thalamus is a key component in the basal ganglia-thalamocortical network critical to the pathogenesis of PD and depression but the precise thalamic subnuclei involved in PD depression have not been identified. We performed structural and diffusion-weighted imaging (DWI) on 76 participants with PD to evaluate the relationship between PD depression and grey and white matter thalamic subnuclear changes. We used a thalamic segmentation method to divide the thalamus into its 50 constituent subnuclei (25 each hemisphere). Fixel-based analysis was used to calculate mean fibre cross-section (FC) for white matter tracts connected to each subnucleus. We assessed volume and FC at baseline and 14–20 months follow-up. A generalised linear mixed model was used to evaluate the relationship between depression, subnuclei volume and mean FC for each thalamic subnucleus. We found that depression scores in PD were associated with lower right pulvinar anterior (PuA) subnucleus volume. Antidepressant use was associated with higher right PuA volume suggesting a possible protective effect of treatment. After follow-up, depression scores were associated with reduced white matter tract macrostructure across almost all tracts connected to thalamic subnuclei. In conclusion, our work implicates the right PuA as a relevant neural structure in PD depression and future work should evaluate its potential as a therapeutic target for PD depression.

Newer generation antidepressants and withdrawal effects: reconsidering the role of antidepressants and helping patients to stop

In England, the prescribing of antidepressants, primarily the newer generation antidepressant classes, has steadily increased over recent years. There is ongoing debate about how the efficacy of these drugs is viewed, their place in therapy and the harms associated with stopping them. Much of the evidence of their efficacy comes from short-term placebo-controlled trials which tend not to include outcomes that are of greatest relevance to patients, such as social functioning or quality of life, but rather restrict outcomes narrowly to symptom measures. On such measures these studies do not demonstrate clinically significant differences from placebo for depression. A range of adverse effects are also recognised, often greater in naturalistic studies of long-term antidepressants users than those measured in short-term efficacy studies, including emotional numbing, sexual difficulties, fatigue and weight gain. There is increasing recognition that withdrawal symptoms from antidepressants are common and that these symptoms can be severe and long-lasting in some patients. Recent guidance on how to stop antidepressants in a tolerable way has been presented by the Royal College of Psychiatrists. We believe that increasing awareness about the difficulty that some patients have in stopping antidepressants should lead to more cautious prescribing practice, with antidepressants given to fewer patients and for shorter periods of time. This article discusses the perceived benefits and harms of antidepressant use.

Low vitamin B12 but not folate is associated with incident depressive symptoms in community-dwelling older adults: a 4 year longitudinal study

The objective was to examine the prospective relationship between folate and vitamin B12 (B12) status and incident depressive symptoms in a representative cohort of community-dwelling older people. This was a longitudinal study utilising the Irish Longitudinal Study on Aging (n =3,849 aged ≥50 years) and investigated the relationship between blood plasma folate and B12 levels at baseline (wave 1) and incident depressive symptoms at 2 and 4 years (waves 2 and 3). Participants with depression at wave 1 were excluded. A score ≥9 on the Center for Epidemiologic Studies Depression Scale-8 at wave 2 or 3 was indicative of incident depressive symptoms. Plasma B12 and folate concentrations were determined by microbiological assay. B12 status profiles (pmol/l) were defined as: <185, deficient-low; 185 - <258, low normal; >258 - 601, normal and >601 high. Folate status profiles (nmol/l) were defined as: ≤10.0, deficient-low; >10 - 23.0, low normal; >23.0 - 45.0, normal; >45.0, high. Logistic regression models reporting odds ratios were used to analyse the longitudinal association of B-vitamin categories with incident depression. Both B12 and folate plasma concentrations were lower in the group with incident depressive symptoms vs. non depressed (folate: 21.4 vs. 25.1 nmol/L; P=0.0003); (B12: 315.7 vs. 335.9 pmol/L; P=0.0148). Regression models demonstrated that participants with deficient-low B12 status at baseline had a significantly higher likelihood of incident depression four years later (odds ratio 1.51, 95% CI 1.01-2.27, P=0.043). This finding remained robust after controlling for relevant covariates including physical activity, chronic disease burden, vitamin D status. cardiovascular disease and antidepressant use. No associations of folate status with incident depression were observed. Older adults with deficient-low B12 status had a 51% increased likelihood of developing depressive symptoms over 4 years. Given the high rates of B12 deficiency, these findings are important and highlight the need to further explore the low cost benefits of optimising vitamin B12 status for depression in older adults.

Prevalence of common mental disorders and treatment receipt for people from ethnic minority backgrounds in England: repeated cross-sectional surveys of the general population in 2007 and 2014

Background Concerns persist that some ethnic minority groups experience longstanding mental health inequalities in England. It is unclear if these have changed over time. Aims To assess the prevalence of common mental disorders (CMDs) and treatment receipt by ethnicity, and changes over time, using data from the nationally representative probability sample in the Adult Psychiatric Morbidity Surveys. Method We used survey data from 2007 (n = 7187) and 2014 (n = 7413). A Clinical Interview Schedule – Revised score of ≥12 indicated presence of a CMD. Treatment receipt included current antidepressant use; any counselling or therapy; seeing a general practitioner about mental health; or seeing a community psychiatrist, psychologist or psychiatric nurse, in the past 12 months. Multivariable logistic regression assessed CMD prevalence and treatment receipt by ethnicity. Results CMD prevalence was highest in the Black group; ethnic variation was explained by demographic and socioeconomic factors. After adjustment for these factors and CMDs, odds ratios for treatment receipt were lower for the Asian (0.62, 95% CI 0.39−1.00) and White Other (0.58, 95% CI 0.38–0.87) groups in 2014, compared with the White British group; for the Black group, this inequality appeared to be widening over time (2007 treatment receipt odds ratio 0.68, 95% CI 0.38−1.23; 2014 treatment receipt odds ratio 0.23, 95% CI 0.13−0.40; survey year interaction P < 0.0001). Conclusions Treatment receipt was lower for all ethnic minority groups compared with the White British group, and lowest among Black people, for whom inequalities appear to be widening over time. Addressing socioeconomic inequality could reduce ethnic inequalities in mental health problems, but this does not explain pronounced treatment inequalities.

Methylome-wide association study of antidepressant use in Generation Scotland and the Netherlands Twin Register implicates the innate immune system

Antidepressants are an effective treatment for major depressive disorder (MDD), although individual response is unpredictable and highly variable. Whilst the mode of action of antidepressants is incompletely understood, many medications are associated with changes in DNA methylation in genes that are plausibly linked to their mechanisms. Studies of DNA methylation may therefore reveal the biological processes underpinning the efficacy and side effects of antidepressants. We performed a methylome-wide association study (MWAS) of self-reported antidepressant use accounting for lifestyle factors and MDD in Generation Scotland (GS:SFHS, N = 6428, EPIC array) and the Netherlands Twin Register (NTR, N = 2449, 450 K array) and ran a meta-analysis of antidepressant use across these two cohorts. We found ten CpG sites significantly associated with self-reported antidepressant use in GS:SFHS, with the top CpG located within a gene previously associated with mental health disorders, ATP6V1B2 (β = −0.055, pcorrected = 0.005). Other top loci were annotated to genes including CASP10, TMBIM1, MAPKAPK3, and HEBP2, which have previously been implicated in the innate immune response. Next, using penalised regression, we trained a methylation-based score of self-reported antidepressant use in a subset of 3799 GS:SFHS individuals that predicted antidepressant use in a second subset of GS:SFHS (N = 3360, β = 0.377, p = 3.12 × 10−11, R2 = 2.12%). In an MWAS analysis of prescribed selective serotonin reuptake inhibitors, we showed convergent findings with those based on self-report. In NTR, we did not find any CpGs significantly associated with antidepressant use. The meta-analysis identified the two CpGs of the ten above that were common to the two arrays used as being significantly associated with antidepressant use, although the effect was in the opposite direction for one of them. Antidepressants were associated with epigenetic alterations in loci previously associated with mental health disorders and the innate immune system. These changes predicted self-reported antidepressant use in a subset of GS:SFHS and identified processes that may be relevant to our mechanistic understanding of clinically relevant antidepressant drug actions and side effects.

Anxiolytic and Antidepressant Use and Burnout: Optimism as a Mediator in Spanish Nurses

The aim of this study was to analyze the relationship between burnout, the use of drugs (anxiolytics and antidepressants) and optimism in nurses. At the end of 2018, a cross-sectional descriptive study was carried out with a sample of actively employed nurses recruited by snowball sampling. The sample consisted of 1432 nurses in Andalusia (Spain), aged 22–58, who were working at the time of data collection, 83.2% of whom were women. Data were collected anonymously in an ad hoc questionnaire about sociodemographic information and use of anxiolytics and/or antidepressives: the Brief Burnout Questionnaire—Revised for Nurses (CBB-R) and the Life Orientation Test—Revised (LOT-R). Descriptive, mediation and moderation analyses were performed, with significant results having a p-value less than 0.05. The results on burnout showed significant relationships with use of the drugs. In particular, personal impact, job dissatisfaction and motivational abandonment were positively related to use of certain of the anxiolytics and antidepressants presented, while the correlation with the social climate was negative. Furthermore, optimism correlated negatively with drug use. Knowing that optimism can alleviate the repercussions of the use of drugs opens up new lines of research and the possibility of developing programs aimed at promoting a positive disposition in the face of complicated events.

A Patient Stratification Approach to Identifying the Likelihood of Continued Chronic Depression and Relapse Following Treatment for Depression

Background: Subgrouping methods have the potential to support treatment decision making for patients with depression. Such approaches have not been used to study the continued course of depression or likelihood of relapse following treatment. Method: Data from individual participants of seven randomised controlled trials were analysed. Latent profile analysis was used to identify subgroups based on baseline characteristics. Associations between profiles and odds of both continued chronic depression and relapse up to one year post-treatment were explored. Differences in outcomes were investigated within profiles for those treated with antidepressants, psychological therapy, and usual care. Results: Seven profiles were identified; profiles with higher symptom severity and long durations of both anxiety and depression at baseline were at higher risk of relapse and of chronic depression. Members of profile five (likely long durations of depression and anxiety, moderately-severe symptoms, and past antidepressant use) appeared to have better outcomes with psychological therapies: antidepressants vs. psychological therapies (OR (95% CI) for relapse = 2.92 (1.24–6.87), chronic course = 2.27 (1.27–4.06)) and usual care vs. psychological therapies (relapse = 2.51 (1.16–5.40), chronic course = 1.98 (1.16–3.37)). Conclusions: Profiles at greater risk of poor outcomes could benefit from more intensive treatment and frequent monitoring. Patients in profile five may benefit more from psychological therapies than other treatments.