Alterations in rhythmic and non-rhythmic resting-state EEG activity and their link to cognition in older age.

While many structural and biochemical changes in the brain have previously been associated with older age, findings concerning functional properties of neuronal networks, as reflected in their electrophysiological signatures, remain rather controversial. These discrepancies might arise due to several reasons, including diverse factors determining general spectral slowing in the alpha frequency range as well as amplitude mixing between the rhythmic and non-rhythmic parameters. We used a large dataset (N = 1703, mean age 70) to comprehensively investigate age-related alterations in multiple EEG biomarkers taking into account rhythmic and non-rhythmic activity and their individual contributions to cognitive performance. While we found strong evidence for an individual alpha peak frequency (IAF) decline in older age, we did not observe a significant relationship between theta power and age while controlling for IAF. Not only did IAF decline with age, but it was also positively associated with interference resolution in a working memory task primarily in the right and left temporal lobes suggesting its functional role in information sampling. Critically, we did not detect a significant relationship between alpha power and age when controlling for the 1/f spectral slope, while the latter one showed age-related alterations. These findings thus suggest that the entanglement of IAF slowing and power in the theta frequency range, as well as 1/f slope and alpha power measures, might explain inconsistencies reported previously in the literature. Finally, despite the absence of age-related alterations, alpha power was negatively associated with the speed of processing in the right frontal lobe while 1/f slope showed no consistent relationship to cognitive performance. Our results thus demonstrate that multiple electrophysiological features, as well as their interplay, should be considered for the comprehensive assessment of association between age, neuronal activity, and cognitive performance.

A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials.

Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD.

Lifestyle causal beliefs are associated with higher personal and perceived stigma regarding depressive disorders: results from a representative population survey.

BACKGROUND: Depression is a prevalent and severe disorder associated with considerable stigma. This stigma contributes to the suffering and impedes help seeking behaviour of those affected. Stigma can be influenced by causal beliefs about depression and personal contact with people suffering from depression. The aim of this study was to investigate (1) the associations between beliefs about the aetiology of depression and personal / perceived stigma, as well as (2) a possible moderating effect of personal contact with people with depression on these associations. METHODS: Stigma, causal beliefs, and contact with depression were assessed in a representative online survey among German adults (N = 5,000). Multiple regression analyses were performed with contact levels (unaffected vs. personally affected (diagnosed) vs. personally affected (undiagnosed) vs. affected by relatives with depression vs. persons who treat depression) and causal beliefs (biogenetic vs. psychosocial vs. lifestyle) as predictor variables for personal and perceived stigma as dependent variables. RESULTS: Higher personal stigma was associated with lifestyle causal beliefs (p < .001, f² = 0.07), lower personal stigma with biogenetic (p = .006, f² = 0.01) and psychosocial (p < .001, f² = 0.02) causal beliefs. A positive interaction between psychosocial beliefs and the contact group "relatives" (p = .039) further suggests that this contact group does not benefit so strongly from psychosocial causal beliefs regarding personal stigma. Higher perceived stigma was associated with psychosocial (p < .001, f² = 0.01) and lifestyle (p < .011, f² = 0.01) causal beliefs. Regarding contact levels, the "unaffected" had significantly higher personal stigma scores than each of the other contact groups (p < .001). The contact group "affected (diagnosed)" had significantly higher perceived stigma scores than "unaffected". CONCLUSIONS: The available data show that anti-stigma campaigns should clearly communicate, that depression is not caused by an unfavorable lifestyle. In general, psychosocial or biological explanatory models should be explained. Especially for the target group "relatives of depressive patients", who can be an important support for patients, education about biogenetic explanatory models should be provided. However, it is important to note that causal beliefs are only one of many factors that impact on stigma.

Outcome assessment of a complex mental health intervention in the workplace. Results from the MENTUPP pilot study.

OBJECTIVE: Multicomponent interventions are recommendable to achieve the greatest mental health benefits, but are difficult to evaluate due to their complexity. Defining long-term outcomes, arising from a Theory of Change (ToC) and testing them in a pilot phase, is a useful approach to plan a comprehensive and meaningful evaluation later on. This article reports on the pilot results of an outcome evaluation of a complex mental health intervention and examines whether appropriate evaluation measures and indicators have been selected ahead of a clustered randomised control trial (cRCT). METHODS: The MENTUPP pilot is an evidence-based intervention for Small and Medium Enterprises (SMEs) active in three work sectors and nine countries. Based on our ToC, we selected the MENTUPP long-term outcomes, which are reported in this article, are measured with seven validated scales assessing mental wellbeing, burnout, depression, anxiety, stigma towards depression and anxiety, absenteeism and presenteeism. The pilot MENTUPP intervention assessment took place at baseline and at 6 months follow-up. RESULTS: In total, 25 SMEs were recruited in the MENTUPP pilot and 346 participants completed the validated scales at baseline and 96 at follow-up. Three long-term outcomes significantly improved at follow-up (p < 0.05): mental wellbeing, symptoms of anxiety, and personal stigmatising attitudes towards depression and anxiety. CONCLUSIONS: The results of this outcome evaluation suggest that MENTUPP has the potential to strengthen employees' wellbeing and decrease anxiety symptoms and stigmatising attitudes. Additionally, this study demonstrates the utility of conducting pilot workplace interventions to assess whether appropriate measures and indicators have been selected. Based on the results, the intervention and the evaluation strategy have been optimised.

Effectiveness of Self-guided Tailored Implementation Strategies in Integrating and Embedding Internet-Based Cognitive Behavioral Therapy in Routine Mental Health Care: Results of a Multicenter Stepped-Wedge Cluster Randomized Trial.

BACKGROUND: Internet-based cognitive behavioral therapy (iCBT) services for common mental health disorders have been found to be effective. There is a need for strategies that improve implementation in routine practice. One-size-fits-all strategies are likely to be ineffective. Tailored implementation is considered as a promising approach. The self-guided integrated theory-based Framework for intervention tailoring strategies toolkit (ItFits-toolkit) supports local implementers in developing tailored implementation strategies. Tailoring involves identifying local barriers; matching selected barriers to implementation strategies; developing an actionable work plan; and applying, monitoring, and adapting where necessary. OBJECTIVE: This study aimed to compare the effectiveness of the ItFits-toolkit with implementation-as-usual (IAU) in implementing iCBT services in 12 routine mental health care organizations in 9 countries in Europe and Australia. METHODS: A stepped-wedge cluster randomized trial design with repeated measures was applied. The trial period lasted 30 months. The primary outcome was the normalization of iCBT delivery by service providers (therapists, referrers, IT developers, and administrators), which was measured with the Normalization Measure Development as a proxy for implementation success. A 3-level linear mixed-effects modeling was applied to estimate the effects. iCBT service uptake (referral and treatment completion rates) and implementation effort (hours) were used as secondary outcomes. The perceived satisfaction (Client Satisfaction Questionnaire), usability (System Usability Scale), and impact of the ItFits-toolkit by implementers were used to assess the acceptability of the ItFits-toolkit. RESULTS: In total, 456 mental health service providers were included in this study. Compared with IAU, the ItFits-toolkit had a small positive statistically significant effect on normalization levels in service providers (mean 0.09, SD 0.04; P=.02; Cohen d=0.12). The uptake of iCBT by patients was similar to that of IAU. Implementers did not spend more time on implementation work when using the ItFits-toolkit and generally regarded the ItFits-toolkit as usable and were satisfied with it. CONCLUSIONS: The ItFits-toolkit performed better than the usual implementation activities in implementing iCBT services in routine practice. There is practical utility in the ItFits-toolkit for supporting implementers in developing and applying effective tailored implementation strategies. However, the effect on normalization levels among mental health service providers was small. These findings warrant modesty regarding the effectiveness of self-guided tailored implementation of iCBT services in routine practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT03652883; https://clinicaltrials.gov/ct2/show/NCT03652883. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-020-04686-4.

Is unemployment associated with inefficient sleep habits? A cohort study using objective sleep measurements.

Unemployed people could be at risk of developing inefficient sleep habits by spending excessive time in bed, as they lack a structuring activity. This could impact their mental health and reintegration into labour. This study aims to analyse possible associations between employment status and sleep parameters using actigraphy. Subjects (148 employed and 50 unemployed) were drawn from a German population-based cohort. Sleep parameters were measured with the SenseWear Bodymedia Pro 3 armband. Comparison of means concerning sleep duration, sleep efficiency, time of sleep and sleep fragmentation was performed separately for week days and weekends. Multiple linear regression analysis was performed to analyse group differences controlling for covariates. Finally, we defined cut-off scores for each sleep variable, and analysed the distribution of subjects above and below these values. Unemployed people did not sleep significantly longer than employed people. However, on week days, they displayed night sleep efficiency reduced by on average > 5% points, they lay down for 28 min longer, had later mid sleep time (38 min) and sleep offset (55 min), as well as more frequent awakenings after sleep onset accounting for being awake 28 min longer (all p ≤ 0.005). Sleep in unemployed subjects compared with employed subjects aged 41-64 years was less efficient, more fragmented and shifted to a later point of the night. Results support prior findings that unemployment has a negative influence on sleep quality. Unemployed individuals could benefit from intervention programmes aiming at the adoption of healthier sleep habits.

Psychometric properties of the Depression Stigma Scale in the Portuguese population and its association with gender and depressive symptomatology.

BACKGROUND: Stigma is one of the most significant constraints on people living with depression. There is a lack of validated scales in Portugal to measure depression stigma; therefore, the Depression Stigma Scale (DSS) is essential to the depression stigma research in Portugal. METHODS: We developed the adaptation process with the ITC Guidelines for Translation and Adapting Tests taken into consideration. We collected the sample as part of the OSPI program-Optimizing suicide prevention programs and their implementation in Europe, specifically within the application in Portugal, and included 1693 participants. Floor-ceiling effects and response ranges were analyzed, and we calculated Cronbach alphas, and Confirmatory Analysis. Validity evidence was tested with two well-documented hypotheses, using data on gender and depression symptoms. RESULTS: The sample was well comparable with the general Portuguese population, indicating its representativeness. We identified a three-factor structure in each subscale (personal and perceived stigma): weak-not-sick, discrimination, and dangerous/unpredictable, with good model fit results. The Cronbach's alphas were satisfactory, and validity was confirmed. CONCLUSIONS: This study established the validity and demonstrated good psychometric properties of the DSS in the Portuguese population. The validation of the DSS can be beneficial in exploring stigma predictors and evaluating the effectiveness of stigma reduction interventions.

The role of comorbid depressive symptoms on long-range temporal correlations in resting EEG in adults with ADHD.

Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder, characterized by core symptoms of inattention, hyperactivity and impulsivity. Comorbid depression is commonly observed in ADHD-patients. Psychostimulants are recommended as first-line treatment for ADHD. Aberrant long-range temporal correlations (LRTCs) of neuronal activities in resting-state are known to be associated with disorganized thinking and concentrating difficulties (typical in ADHD) and with maladaptive thinking (typical in depression). It has yet to be examined whether (1) LRTC occur in ADHD-patients, and if so, (2) whether LRTC might be a competent biomarker in ADHD comorbid with current depression and (3) how depression affects psychostimulant therapy of ADHD symptoms. The present study registered and compared LRTCs in different EEG frequency bands in 85 adults with ADHD between groups with (n = 28) and without (n = 57) additional depressive symptoms at baseline. Treatment-related changes in ADHD, depressive symptoms and LRTC were investigated in the whole population and within each group. Our results revealed significant LRTCs existed in all investigated frequency bands. There were, however, no significant LRTC-differences between ADHD-patients with and without depressive symptoms at baseline and no LRTC-changes following treatment. However, depressed ADHD patients did seem to benefit more from the therapy with psychostimulant based on self-report.

An online program with individualized vs automated support for significant others of depressed individuals - study protocol of a randomized controlled trial.

BACKGROUND: Due to budget restrictions in mental health care, non-professional caregivers are increasingly burdened with the emotional and practical care for their depressed relatives. However, informal family caregiving is mostly a stressful role with negative consequences on the physical and mental health of the caretakers to the extent that they have an elevated risk of experiencing psychiatric disorders themselves. While psychoeducation for relatives of depressed individuals showed positive results both in terms of the caretakers' strain and the depressive symptoms of the affected person, there are major barriers to participate in presence in those programs. Digital programs might be a viable alternative. We found no empirically evaluated digital program available for informal caregivers of depressed patients. METHODS: An online program for relatives of depressed individuals has been developed including four interactive modules on 1) psychoeducation, 2) how to strengthen the relationship with the depressed person, 3) how to deal with the depressive symptoms of the patient, and 4) find the right balance between caring for the depressed person and self-care. We investigate if this self-help program is more effective when used with individualized versus automated e-mail support, and if both supported conditions are more effective than treatment-as-usual (TAU in form of written information material) in terms of the risk of mental diseases in caregivers. The primary outcome is the reduction of the caregiver's nonspecific mental distress as measured by the change of the Kessler Psychological Distress Scale score from baseline to four weeks after randomization. Caregivers (n = 500:500:250) will be randomized to one of the three conditions. DISCUSSION: Psychological support for caregivers of individuals with mental disorders such as depression should be offered as part of integrated services. There is a huge potential to develop and implement interactive online approaches to support informal caregivers of patients with depression to function in their multiple roles and to help them to remain healthy. TRIAL REGISTRATION: DRKS, DRKS00025241 . Registered 5 Mai 2021.

["iFightDepression" in inpatient treatment : Evaluation of a web-based, therapist-guided self-management program on a specialized ward for affective disorders]. / "iFightDepression" im stationären Setting : Evaluation eines internetbasierten, therapeutenbegleiteten Selbstmanagementprogramms auf einer Spezialstation für affektive Störungen.

BACKGROUND: E­mental health mainly plays a role in the outpatient treatment of patients with depressive disorders. The goal of this study was to implement and evaluate the web-based, therapist-guided self-management tool "iFightDepression" (iFD) to clarify if there is a benefit for inpatient use. MATERIAL AND METHODS: In this study 78 inpatients with affective disorders (ICD-10 F32.0­3, F33.0-3) or dysthymia (F34) were recruited. The intervention duration with the iFD tool went from admission until discharge, therapeutic support was granted by the ward staff. Symptom severity, intervention expectations and experience with therapy were processed in an online questionnaire before the intervention (T0) while intervention satisfaction was captured after the intervention shortly before discharge (T1) in a paper-pencil questionnaire. RESULTS: Out of 78 participating inpatients 42 used the iFD tool at least once. Moderate to high levels of expectation regarding the iFD tool and mildly above-average level of satisfaction after the intervention were observed. Of the active users 67% indicated they would continue to use the iFD tool after discharge. The main reasons for not using the iFD tool were short duration of stay, severity of disease and lack of digital literacy. CONCLUSION: An implementation of the iFD tool is feasible on principle. Active users gave positive feedback concerning the intervention and most participants claimed to continue using the iFD tool after discharge; however, low usage rates among study participants (42/78, 54%) showed barriers of implementation that have to be addressed and underline the importance of adaptations regarding the use of the intervention in a clinical setting.

Effects of dietary interventions on depressive symptom profiles: results from the MooDFOOD depression prevention study.

BACKGROUND: Dietary interventions did not prevent depression onset nor reduced depressive symptoms in a large multi-center randomized controlled depression prevention study (MooDFOOD) involving overweight adults with subsyndromal depressive symptoms. We conducted follow-up analyses to investigate whether dietary interventions differ in their effects on depressive symptom profiles (mood/cognition; somatic; atypical, energy-related). METHODS: Baseline, 3-, 6-, and 12-month follow-up data from MooDFOOD were used (n = 933). Participants received (1) placebo supplements, (2) food-related behavioral activation (F-BA) therapy with placebo supplements, (3) multi-nutrient supplements (omega-3 fatty acids and a multi-vitamin), or (4) F-BA therapy with multi-nutrient supplements. Depressive symptom profiles were based on the Inventory of Depressive Symptomatology. RESULTS: F-BA therapy was significantly associated with decreased severity of the somatic (B = -0.03, p = 0.014, d = -0.10) and energy-related (B = -0.08, p = 0.001, d = -0.13), but not with the mood/cognition symptom profile, whereas multi-nutrient supplementation was significantly associated with increased severity of the mood/cognition (B = 0.05, p = 0.022, d = 0.09) and the energy-related (B = 0.07, p = 0.002, d = 0.12) but not with the somatic symptom profile. CONCLUSIONS: Differentiating depressive symptom profiles indicated that food-related behavioral interventions are most beneficial to alleviate somatic symptoms and symptoms of the atypical, energy-related profile linked to an immuno-metabolic form of depression, although effect sizes were small. Multi-nutrient supplements are not indicated to reduce depressive symptom profiles. These findings show that attention to clinical heterogeneity in depression is of importance when studying dietary interventions.

Fatigue and brain arousal in patients with major depressive disorder.

Fatigue is considered a key symptom of major depressive disorder (MDD), yet the term lacks specificity. It can denote a state of increased sleepiness and lack of drive (i.e., downregulated arousal) as well as a state of high inner tension and inhibition of drive with long sleep onset latencies (i.e., upregulated arousal), the latter typically found in depression. It has been proposed to differentiate fatigue along the dimension of brain arousal. We investigated whether such stratification within a group of MDD patients would reveal a subgroup with distinct clinical features. Using an automatic classification of EEG vigilance stages, an arousal stability score was calculated for 15-min resting EEGs of 102 MDD patients with fatigue. 23.5% of the patients showed signs of hypoarousal with EEG patterns indicating drowsiness or sleep; this hypoaroused subgroup was compared with remaining patients (non-hypoaroused subgroup) concerning self-rated measures of depressive symptoms, sleepiness, and sleep. The hypoaroused subgroup scored higher on the Beck Depression Inventory items "loss of energy" (Z = - 2.13, p = 0.033; ɳ2 = 0.044, 90% CI 0.003-0.128) and "concentration difficulty" (Z = - 2.40, p = 0.017; ɳ2 = 0.056, 90% CI 0.009-0.139), and reported higher trait and state sleepiness (p < 0.05) as compared to the non-hypoaroused group. The non-hypoaroused subgroup, in contrast, reported more frequently the presence of suicidal ideation (Chi2 = 3.81, p = 0.051; ɳ2 = 0.037, 90% CI 0.0008-0.126). In this study, we found some evidence that stratifying fatigued MDD patients by arousal may lead to subgroups that are pathophysiologically and clinically more homogeneous. Brain arousal may be a worth while target in clinical research for better understanding the mechanisms underlying suicidal tendencies and to improve treatment response.

The effect of depressive symptomatology on the association of vitamin D and sleep.

BACKGROUND: Sleep disorders and vitamin D deficiency are highly prevalent health problems. Few studies examined the effect of vitamin D concentrations on objectively measured sleep with high methodological quality and temporal proximity. Previous analysis within the LIFE-Adult-Study suggested that a lower concentration of serum vitamin D was associated with both shorter and later night sleep. However, no conclusion about underlying mechanisms could be drawn. We addressed the question whether this relationship is explained by the presence of depressive syndromes, which are linked to both vitamin D deficiency and sleep disturbances. METHODS: It was investigated whether the association of vitamin D concentrations and night sleep parameters is mediated or moderated by depressive symptomatology. We investigated a subset (n = 1252) of the community sample from the LIFE-Adult-Study, in which sleep parameters had been objectively assessed using actigraphy, based on which two sleep parameters were calculated: night sleep duration and midsleep time. Serum 25(OH) D concentrations were measured using an electrochemiluminescence immunoassay. Depressive symptomatology was evaluated with the Centre for Epidemiological Studies Depression Scale. The mediation effect was analyzed by using Hayes' PROCESS macro tool for SPSS for Windows. RESULTS: The depressive symptomatology was neither significantly associated with night sleep duration nor midsleep time. The associations between vitamin D concentrations and night sleep duration/midsleep time through mediation by depressive symptomatology were not significant. Corresponding moderator analyses were also non-significant. CONCLUSION: The associations between vitamin D concentrations and night sleep parameters (sleep duration and midsleep time) seem to be neither mediated nor moderated by depressive symptomatology.

Equivalency of the diagnostic accuracy of the PHQ-8 and PHQ-9: a systematic review and individual participant data meta-analysis.

BACKGROUND: Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9. METHODS: We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy. RESULTS: 16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (-0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01). CONCLUSIONS: PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.

Human brain arousal in the resting state: a genome-wide association study.

Arousal affects cognition, emotion, and behavior and has been implicated in the etiology of psychiatric disorders. Although environmental conditions substantially contribute to the level of arousal, stable interindividual characteristics are well-established and a genetic basis has been suggested. Here we investigated the molecular genetics of brain arousal in the resting state by conducting a genome-wide association study (GWAS). We selected N = 1877 participants from the population-based LIFE-Adult cohort. Participants underwent a 20-min eyes-closed resting state EEG, which was analyzed using the computerized VIGALL 2.1 (Vigilance Algorithm Leipzig). At the SNP-level, GWAS analyses revealed no genome-wide significant locus (p < 5E-8), although seven loci were suggestive (p < 1E-6). The strongest hit was an expression quantitative trait locus (eQTL) of TMEM159 (lead-SNP: rs79472635, p = 5.49E-8). Importantly, at the gene-level, GWAS analyses revealed significant evidence for TMEM159 (p = 0.013, Bonferroni-corrected). By mapping our SNPs to the GWAS results from the Psychiatric Genomics Consortium, we found that all corresponding markers of TMEM159 showed nominally significant associations with Major Depressive Disorder (MDD; 0.006 ≤ p ≤ 0.011). More specifically, variants associated with high arousal levels have previously been linked to an increased risk for MDD. In line with this, the MetaXcan database suggests increased expression levels of TMEM159 in MDD, as well as Autism Spectrum Disorder, and Alzheimer's Disease. Furthermore, our pathway analyses provided evidence for a role of sodium/calcium exchangers in resting state arousal. In conclusion, the present GWAS identifies TMEM159 as a novel candidate gene which may modulate the risk for psychiatric disorders through arousal mechanisms. Our results also encourage the elaboration of the previously reported interrelations between ion-channel modulators, sleep-wake behavior, and psychiatric disorders.

The Accuracy of the Patient Health Questionnaire-9 Algorithm for Screening to Detect Major Depression: An Individual Participant Data Meta-Analysis.

BACKGROUND: Screening for major depression with the Patient Health Questionnaire-9 (PHQ-9) can be done using a cutoff or the PHQ-9 diagnostic algorithm. Many primary studies publish results for only one approach, and previous meta-analyses of the algorithm approach included only a subset of primary studies that collected data and could have published results. OBJECTIVE: To use an individual participant data meta-analysis to evaluate the accuracy of two PHQ-9 diagnostic algorithms for detecting major depression and compare accuracy between the algorithms and the standard PHQ-9 cutoff score of ≥10. METHODS: Medline, Medline In-Process and Other Non-Indexed Citations, PsycINFO, Web of Science (January 1, 2000, to February 7, 2015). Eligible studies that classified current major depression status using a validated diagnostic interview. RESULTS: Data were included for 54 of 72 identified eligible studies (n participants = 16,688, n cases = 2,091). Among studies that used a semi-structured interview, pooled sensitivity and specificity (95% confidence interval) were 0.57 (0.49, 0.64) and 0.95 (0.94, 0.97) for the original algorithm and 0.61 (0.54, 0.68) and 0.95 (0.93, 0.96) for a modified algorithm. Algorithm sensitivity was 0.22-0.24 lower compared to fully structured interviews and 0.06-0.07 lower compared to the Mini International Neuropsychiatric Interview. Specificity was similar across reference standards. For PHQ-9 cutoff of ≥10 compared to semi-structured interviews, sensitivity and specificity (95% confidence interval) were 0.88 (0.82-0.92) and 0.86 (0.82-0.88). CONCLUSIONS: The cutoff score approach appears to be a better option than a PHQ-9 algorithm for detecting major depression.

Supplementation-induced increase in circulating omega-3 serum levels is not associated with a reduction in depressive symptoms: Results from the MooDFOOD depression prevention trial.

BACKGROUND: There is ambiguity on how omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are associated with depression, and what the temporality of the association might be. The present study aimed to examine whether (intervention-induced changes in) n-3 PUFA levels were associated with (changes in) depressive symptoms. METHODS: Baseline, 6- and 12-month follow-up data on 682 overweight and subclinically depressed persons from four European countries that participated in the MooDFOOD depression prevention randomized controlled trial were used. Participants were allocated to four intervention groups: (a) placebos, (b) placebos and food-related behavioral activation therapy (F-BA), (c) multinutrient supplements (fish oil and multivitamin), and (d) multinutrient supplements and F-BA. Depressive symptoms were measured using the inventory of depressive symptomatology. PUFA levels (µmol/L) were measured using gas chromatography. Analyses were adjusted for sociodemographics, lifestyle, and somatic health. RESULTS: Increases in n-3 PUFA, docosahexaenoic acid, and eicosapentaenoic acid levels over time were significantly larger in the supplement groups than in placebo groups. Change in PUFA levels was not significantly associated with the change in depressive symptoms (ß = .002, SE = 0.003, p = .39; ß = .003, SE = 0.005, p = .64; ß = .005, SE = 0.005, p = .29; ß = -.0002, SE = 0.0004, p = .69). Baseline PUFA levels did not modify the intervention effects on depressive symptoms. CONCLUSIONS: In overweight and subclinical depressed persons, multinutrient supplements led to significant increases in n-3 PUFA levels over time, which were not associated with changes in depressive symptoms. Multinutrient supplements do not seem to be an effective preventive strategy in lowering depressive symptoms over time in these at-risk groups.

Effect of food-related behavioral activation therapy on food intake and the environmental impact of the diet: results from the MooDFOOD prevention trial.

PURPOSE: Food-based dietary guidelines are proposed to not only improve diet quality, but to also reduce the environmental impact of diets. The aim of our study was to investigate whether food-related behavioral activation therapy (F-BA) applying Mediterranean-style dietary guidelines altered food intake and the environmental impact of the diet in overweight adults with subsyndromal symptoms of depression. METHODS: In total 744 adults who either received the F-BA intervention (F-BA group) or no intervention (control group) for 12 months were included in this analysis. Food intake data were collected through a food frequency questionnaire at baseline and after 6 and 12 months. Greenhouse gas emissions (GHGE), land use (LU), and fossil energy use (FEU) estimates from life-cycle assessments and a weighted score of the three (pReCiPe score) were used to estimate the environmental impact of each individual diet at each timepoint. RESULTS: The F-BA group reported increased intakes of vegetables (19.7 g/day; 95% CI 7.8-31.6), fruit (23.0 g/day; 9.4-36.6), fish (7.6 g/day; 4.6-10.6), pulses/legumes (4.0 g/day; 1.6-6.5) and whole grains (12.7 g/day; 8.0-17.5), and decreased intake of sweets/extras (- 6.8 g/day; - 10.9 to - 2.8) relative to control group. This effect on food intake resulted in no change in GHGE, LU, and pReCiPe score, but a relative increase in FEU by 1.6 MJ/day (0.8, 2.4). CONCLUSIONS: A shift towards a healthier Mediterranean-style diet does not necessarily result in a diet with reduced environmental impact in a real-life setting. TRIAL REGISTRATION: ClinicalTrials.gov. Number of identification: NCT02529423. August 2015.

Is brain arousal regulation a predictor of response to psychostimulant therapy in adult ADHD patients?

We investigated whether baseline brain arousal instability during resting state EEG, using the Vigilance Algorithm Leipzig (VIGALL 2.1), can predict response to methylphenidate therapy in adult ADHD patients. An arousal stability score of the EEGs of 28 adult ADHD patients was calculated quantifying the extent of arousal decline. In logistic regression analysis, arousal stability score predicted response to MPH [odds ratio 1.28 (95% CI 1.0-1.65); p = 0.027]. In this pilot study, we demonstrated that arousal stability at baseline predicted methylphenidate treatment response, indicating that less stable arousal regulation during a 15-min EEG at rest increases the chance of treatment response.

Efficacy of a Guided Web-Based Self-Management Intervention for Depression or Dysthymia: Randomized Controlled Trial With a 12-Month Follow-Up Using an Active Control Condition.

BACKGROUND: An increasing number of studies suggest that web-based interventions for patients with depression can reduce their symptoms and are expected to fill currently existing treatment gaps. However, evidence for their efficacy has mainly been derived from comparisons with wait-list or treatment as usual controls. In particular, designs using wait-list controls are unlikely to induce hope and may even have nocebo effects, making it difficult to draw conclusions about the intervention's efficacy. Studies using active controls are rare and have not yielded conclusive results. OBJECTIVE: The main objective of this study is to assess the acute and long-term antidepressant efficacy of a 6-week, guided, web-based self-management intervention building on the principles of cognitive behavioral therapy (iFightDepression tool) for patients with depression compared with web-based progressive muscle relaxation as an active control condition. METHODS: A total of 348 patients with mild-to-moderate depressive symptoms or dysthymia (according to the Mini International Neuropsychiatric Interview) were recruited online and randomly assigned to 1 of the 2 intervention arms. Acute antidepressant effects after 6 weeks and long-term effects at 3-, 6-, and 12-month follow-up were studied using the Inventory of Depressive Symptomatology-self-rating as a primary outcome parameter and change in quality of life (Short Form 12) and user satisfaction (client satisfaction questionnaire) as secondary outcome parameters. Treatment effects were assessed using mixed model analyses. RESULTS: Over the entire observation period, a greater reduction in symptoms of depression (P=.01) and a greater improvement of life quality (P<.001) was found in the intervention group compared with the active control group. Separate tests for each time point revealed significant effects on depressive symptoms at the 3-month follow-up (d=0.281; 95% CI 0.069 to 0.493), but not after 6 weeks (main outcome:d=0.192; 95% CI -0.020 to 0.404) and 6 and 12 months. The intervention was significantly superior to the control condition with respect to user satisfaction (25.31 vs 21.97; t259=5.804; P<.01). CONCLUSIONS: The fact that antidepressant effects have been found for a guided self-management tool in comparison with an active control strengthens the evidence base for the efficacy of web-based interventions. The antidepressant effect became most prominent at the 3-month follow-up. After 6 weeks of intervention, significant positive effects were observed on life quality but not on depressive symptoms. Although the effect size of such web-based interventions on symptoms of depression might be smaller than that suggested by earlier studies using wait-list control conditions, they can be a cost-effective addition to antidepressants and face-to-face psychotherapy. TRIAL REGISTRATION: International Clinical Trials Registry Platform ICTRP080-15-09032015; https://apps.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00009323.