Differential impact of preventive cognitive therapy while tapering antidepressants versus maintenance antidepressant treatment on affect fluctuations and individual affect networks and impact on relapse: a secondary analysis of a randomised controlled trial.

Background: There is an urgent need to better understand and prevent relapse in major depressive disorder (MDD). We explored the differential impact of various MDD relapse prevention strategies (pharmacological and/or psychological) on affect fluctuations and individual affect networks in a randomised setting, and their predictive value for relapse. Methods: We did a secondary analysis using experience sampling methodology (ESM) data from individuals with remitted recurrent depression that was collected alongside a randomised controlled trial that ran in the Netherlands, comparing: (I) tapering antidepressants while receiving preventive cognitive therapy (PCT), (II) combining antidepressants with PCT, or (III) continuing antidepressants without PCT, for the prevention of depressive relapse, as well as ESM data from 11 healthy controls. Participants had multiple past depressive episodes, but were remitted for at least 8 weeks and on antidepressants for at least six months. Exclusion criteria were: current (hypo)mania, current alcohol or drug abuse, anxiety disorder that required treatment, psychological treatment more than twice per month, a diagnosis of organic brain damage, or a history of bipolar disorder or psychosis. Fluctuations (within-person variance, root mean square of successive differences, autocorrelation) in negative and positive affect were calculated. Changes in individual affect networks during treatment were modelled using time-varying vector autoregression, both with and without applying regularisation. We explored whether affect fluctuations or changes in affect networks over time differed between treatment conditions or relapse outcomes, and predicted relapse during 2-year follow-up. This ESM study was registered at ISRCTN registry, ISRCTN15472145. Findings: Between Jan 1, 2014, and Jan 31, 2015, 72 study participants were recruited, 42 of whom were included in the analyses. We found no indication that affect fluctuations differed between treatment groups, nor that they predicted relapse. We observed large individual differences in affect network structure across participants (irrespective of treatment or relapse status) and in healthy controls. We found no indication of group-level differences in how much networks changed over time, nor that changes in networks over time predicted time to relapse (regularised models: hazard ratios [HR] 1063, 95% CI <0.0001->10 000, p = 0.65; non-regularised models: HR 2.54, 95% CI 0.23-28.7, p = 0.45) or occurrence of relapse (regularised models: odds ratios [OR] 22.84, 95% CI <0.0001->10 000, p = 0.90; non-regularised models: OR 7.57, 95% CI 0.07-3709.54, p = 0.44) during complete follow-up. Interpretation: Our findings should be interpreted with caution, given the exploratory nature of this study and wide confidence intervals. While group-level differences in affect dynamics cannot be ruled out due to low statistical power, visual inspection of individual affect networks also revealed no meaningful patterns in relation to MDD relapse. More studies are needed to assess whether affect dynamics as informed by ESM may predict relapse or guide personalisation of MDD relapse prevention in daily practice. Funding: The Netherlands Organisation for Health Research and Development, Dutch Research Council, University of Amsterdam.

Advancing urban mental health research: from complexity science to actionable targets for intervention.

Urbanisation and common mental disorders (CMDs; ie, depressive, anxiety, and substance use disorders) are increasing worldwide. In this Review, we discuss how urbanicity and risk of CMDs relate to each other and call for a complexity science approach to advance understanding of this interrelationship. We did an ecological analysis using data on urbanicity and CMD burden in 191 countries. We found a positive, non-linear relationship with a higher CMD prevalence in more urbanised countries, particularly for anxiety disorders. We also did a review of meta-analytic studies on the association between urban factors and CMD risk. We identified factors relating to the ambient, physical, and social urban environment and showed differences per diagnosis of CMDs. We argue that factors in the urban environment are likely to operate as a complex system and interact with each other and with individual city inhabitants (including their psychological and neurobiological characteristics) to shape mental health in an urban context. These interactions operate on various timescales and show feedback loop mechanisms, rendering system behaviour characterised by non-linearity that is hard to predict over time. We present a conceptual framework for future urban mental health research that uses a complexity science approach. We conclude by discussing how complexity science methodology (eg, network analyses, system-dynamic modelling, and agent-based modelling) could enable identification of actionable targets for treatment and policy, aimed at decreasing CMD burdens in an urban context.

Guided internet interventions for depression: impact of sociodemographic factors on treatment outcome in Indonesia.

Depression is the leading cause of disability worldwide, but an alarming treatment gap exists, especially in lower- and middle income countries (LMIC), where people are exposed to many societal and sociodemographic risk factors. As internet access increases in LMIC, online interventions could decrease this gap, especially when shown suitable for all demographics, including vulnerable groups with low socioeconomic status (SES). We used mixed-model analysis to explore moderating effects of sociodemographic factors (age, sex, education level, SES and urbanicity) on treatment effect in a recent trial in Indonesia, comparing guided online behavioral activation versus online psychoeducation only for depression, in 313 participants from (sub)urban areas. Outcome measures were self-reported Patient Health Questionnaire 9 (PHQ-9) and Inventory of Depressive Symptomatology (IDS-SR). Without correction for multiple testing, we found urbanicity to moderate treatment effect, with stronger treatment effect in suburban relative to urban participants (IDS-SR 24 weeks past baseline, p = 0.04) and a trend towards moderation by SES, with stronger treatment effect in low SES groups (PHQ-9 10 weeks past baseline, p = 0.07). These exploratory results suggest online treatments are a promising mental health intervention for all demographics in a (sub)urban LMIC setting, but hypothesis-testing studies including rural participants are warranted.

Long-term deep brain stimulation of the ventral anterior limb of the internal capsule for treatment-resistant depression.

OBJECTIVE: Deep brain stimulation (DBS) reduces depressive symptoms in approximately 40%-60% of patients with treatment-resistant depression (TRD), but data on long-term efficacy and safety are scarce. Our objective was to assess the efficacy and safety of DBS targeted at the ventral anterior limb of the internal capsule (vALIC) in 25 patients with TRD during a 1-year, open-label, maintenance period, which followed a 1-year optimisation period. METHODS: Depression severity was measured using the 17-item Hamilton Depression Rating Scale (HAM-D-17), Montgomery-Asberg Depression Rating Scale (MADRS) and self-reported Inventory of Depressive Symptomatology (IDS-SR). Primary outcomes were response rate (≥50% HAM-D-17 score reduction) after the maintenance phase, approximately 2 years after DBS surgery, and changes in depression scores and occurrence of adverse events during the maintenance phase. RESULTS: Of 25 operated patients, 21 entered and 18 completed the maintenance phase. After the maintenance phase, eight patients were classified as responder (observed response rate: 44.4%; intention-to-treat: 32.0%). During the maintenance phase, HAM-D-17 and MADRS scores did not change, but the mean IDS-SR score decreased from 38.8 (95% CI 31.2 to 46.5) to 35.0 (95% CI 26.1 to 43.8) (p=0.008). Non-responders after optimisation did not improve during the maintenance phase. Four non-DBS-related serious adverse events occurred, including one suicide attempt. CONCLUSIONS: vALIC DBS for TRD showed continued efficacy 2 years after surgery, with symptoms remaining stable after optimisation as rated by clinicians and with patient ratings improving. This supports DBS as a viable treatment option for patients with TRD. TRIAL REGISTRATION NUMBER: NTR2118.

A population-based retrospective study comparing cancer mortality between Moluccan migrants and the general Dutch population: equal risk 65 years after immigration?

OBJECTIVE: To test the hypothesis that cancer mortality rates among the Moluccan-Dutch, the oldest non-Western migrant group to arrive in the Netherlands after the Second World War, are similar to those in the general Dutch population. DESIGN: Population-based retrospective study. SETTING: Data from the national cause of death registry in the Netherlands and municipal registries. PARTICIPANTS: Using historic records containing family names of all Moluccan-Dutch who arrived in the Netherlands in 1951, we identified 81 591 Moluccan-Dutch persons in the national cause of death registry of the Netherlands. The reference group consisted of 15 866 538 persons of the general Dutch population. OUTCOME MEASURES: Mortality data were linked to demographic data from municipal registries. We calculated all-cancer and cancer-specific mortality and measured differences between the two groups using Poisson regression, adjusting for sex, age and area socioeconomic status. We conducted a sub-analysis for the first-generation and second-generation Moluccan-Dutch. RESULTS: There was no difference in all-cancer mortality between Moluccan-Dutch and the general Dutch population. Mortality was higher among Moluccan-Dutch for liver, cervix and corpus uteri cancers, but lower for stomach, oesophagus, kidney and nervous system cancers. For most cancers, mortality risk as compared with the general Dutch population varied between different generations of Moluccan-Dutch. CONCLUSIONS: Several decades after migration, the Moluccan-Dutch show similar all-cancer mortality, but different cancer-specific mortality rates, when compared with the general Dutch population.

Higher self-reported prevalence of hypertension among Moluccan-Dutch than among the general population of The Netherlands: results from a cross-sectional survey.

BACKGROUND: Several studies in The Netherlands revealed ethnic disparities in hypertension prevalence, but none have focused on the Moluccan-Dutch, a migrant group from Indonesia that settled in The Netherlands in 1951. The Moluccan-Dutch are considered to be fairly well integrated in Dutch society. The aim of this study was to compare hypertension prevalence among the Moluccan-Dutch to the native Dutch and to explore the contribution of known risk factors. METHODS: A health interview survey was conducted from August 2012 till March 2013 among nineteen Moluccan neighborhoods, resulting in the inclusion of 708 participants. The primary outcome variable was self-reported prevalence of hypertension. Explanatory variables were BMI, exercise, smoking, alcohol intake and mental health status. Data on the control group was extracted from the Dutch National Health Survey 2011, using a similar questionnaire. Differences in risk factor exposure were explored using Chi-square tests and the contribution of risk factors, separately and combined, was explored using multivariate logistic regression analysis. RESULTS: Moluccan-Dutch showed higher odds for reporting hypertension when compared to native Dutch, after adjusting for age and level of education (OR = 1.38; 95% CI = 1.13-1.69) and additional risk factors (OR = 1.49; 95% CI = 1.19-1.88). A higher prevalence of hypertension was found in both Moluccan-Dutch men (26.4% vs. 16.7%; p < 0.001) and women (26.7% vs. 17.9%; p < 0.001), when compared to the control group. Not only middle-aged, but also young Moluccan-Dutch men showed higher prevalence of hypertension. CONCLUSION: The Moluccan-Dutch may be at increased risk for reporting hypertension. These results suggest that long-term stay over several generations does not necessarily result in similar levels of hypertension prevalence as the host population.