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Abstract Background Despite the availability of a wide variety of evidence-based treatments for major depressive disorder (MDD), many patients still experience impairments in their lives after remission. Programs are needed that effectively support patients in coping with these impairments. The program Storytelling and Training to Advance Individual Recovery Skills (STAIRS) was developed to address this need and combines the use of peer contact, expert-by-experience guidance, family support and professional blended care. The aim of the planned study is (1) to assess the efficacy of the STAIRS program in patients with remitted MDD, (2) to investigate patients’ subjective experiences with STAIRS, and (3) to evaluate the program’s cost-effectiveness. Methods A concurrent mixed-methods randomized controlled trial design will be used. Patients aged between 18 and 65 years with remitted MDD (N = 140) will be randomized to either a group receiving care as usual (CAU) + the STAIRS-program or a control group receiving CAU + some basic psychoeducation. Quantitative efficacy data on functional and personal recovery and associated aspects will be collected using self-report questionnaires at the start of the intervention, immediately following the intervention, and at the six-month follow-up. Insights into patients’ experiences on perceived effects and the way in which different program elements contribute to this effect, as well as the usability and acceptability of the program, will be gained by conducting qualitative interviews with patients from the experimental group, who are selected using maximum variation sampling. Finally, data on healthcare resource use, productivity loss and quality of life will be collected and analysed to assess the cost-effectiveness and cost-utility of the STAIRS-program. Discussion Well-designed recovery-oriented programs for patients suffering from MDD are scarce. If efficacy and cost-effectiveness are demonstrated with this study and patients experience the STAIRS program as usable and acceptable, this program can be a valuable addition to CAU. The qualitative interviews may give insights into what works for whom, which can be used to promote implementation. Trial registration This trial was registered at ClinicalTrials.gov on 1 July 2021, registration number NCT05440812.

Abstract Depression shows a metabolomic signature overlapping with that of cardiometabolic conditions. Whether this signature is linked to specific depression profiles remains undetermined. Previous research suggested that metabolic alterations cluster more consistently with depressive symptoms of the atypical spectrum related to energy alterations, such as hyperphagia, weight gain, hypersomnia, fatigue and leaden paralysis. We characterized the metabolomic signature of an “atypical/energy-related” symptom (AES) profile and evaluated its specificity and consistency. Fifty-one metabolites measured using the Nightingale platform in 2876 participants from the Netherlands Study of Depression and Anxiety were analyzed. An ‘AES profile’ score was based on five items of the Inventory of Depressive Symptomatology (IDS) questionnaire. The AES profile was significantly associated with 31 metabolites including higher glycoprotein acetyls (β = 0.13, p = 1.35*10-12), isoleucine (β = 0.13, p = 1.45*10-10), very-low-density lipoproteins cholesterol (β = 0.11, p = 6.19*10-9) and saturated fatty acid levels (β = 0.09, p = 3.68*10-10), and lower high-density lipoproteins cholesterol (β = −0.07, p = 1.14*10-4). The metabolites were not significantly associated with a summary score of all other IDS items not included in the AES profile. Twenty-five AES-metabolites associations were internally replicated using data from the same subjects (N = 2015) collected at 6-year follow-up. We identified a specific metabolomic signature—commonly linked to cardiometabolic disorders—associated with a depression profile characterized by atypical, energy-related symptoms. The specific clustering of a metabolomic signature with a clinical profile identifies a more homogenous subgroup of depressed patients at higher cardiometabolic risk, and may represent a valuable target for interventions aiming at reducing depression’s detrimental impact on health.

Background: The experience sampling methodology (ESM) is increasingly being suggested as a clinical tool in mental health care, as it offers ecologically valid, microlevel information on psychopathological processes. Patients and clinicians have recommended that applications of ESM should be personalized and integrated into the existing clinical process, but there is still much uncertainty about how implementation may look like. Objective: To provide an example of personalized ESM assessment and feedback being integrated into psychotherapy for depression, specifically looking at the collaborative use of ESM in case conceptualization. Methods: George, a 27-year-old man diagnosed with depression, and his therapist participated in the Therap-i randomized controlled trial, which investigates the efficacy of a personalized ESM module added to psychotherapy. Together, they created a personalized ESM questionnaire, aiming to capture their hypotheses and questions regarding George’s case conceptualization. George then filled out his ESM questionnaire five times per day, for 8 weeks. During this period, ESM data were discussed and interpreted by George, his therapist, and a researcher, in three feedback sessions. In these sessions, data were visualized in a flexible feedback interface that allowed for collaborative exploration of George’s data. Both patient and therapist evaluated the module through questionnaires and George also participated in a semi-structured evaluation interview. Results: George’s ESM questionnaire included personalized items on the topics of self-esteem and open versus withdrawn behavior. He completed 241 (89.3%) assessments. Discussions during the feedback sessions focused on two core themes: First, George’s low energy level, which was further explored with regard to his sleep, medication, and activity patterns. Second, his low sense of self-esteem, which led to an in-depth exploration of his thinking patterns and social interactions. The ESM module was seen as useful and insightful by both George and therapist. Conclusions: This case shows how ESM and ESM-based feedback can stimulate the collaborative exploration of the patient’s complaints, and how it can provide useful insights for treatment. We discuss how our personalized ESM module relates to current clinical principles and practices, and make suggestions for further implementation.

Abstract Background Apart from cost‐effectiveness, considerations like equity and acceptability may affect health‐care priority setting. Preferably, priority setting combines evidence evaluation with an appraisal procedure, to elicit and weigh these considerations. Objective To demonstrate a structured approach for eliciting and evaluating a broad range of assessment criteria, including key stakeholders’ values, aiming to support decision makers in priority setting. Methods For a set of cost‐effective substitute interventions for depression care, the appraisal criteria were adopted from the Australian Assessing Cost‐Effectiveness initiative. All substitute interventions were assessed in an appraisal, using focus group discussions and semi‐structured interviews conducted among key stakeholders. Results Appraisal of the substitute cost‐effective interventions yielded an overview of considerations and an overall recommendation for decision makers. Two out of the thirteen pairs were deemed acceptable and realistic, that is investment in therapist‐guided and Internet‐based cognitive behavioural therapy instead of cognitive behavioural therapy in mild depression, and investment in combination therapy rather than individual psychotherapy in severe depression. In the remaining substitution pairs, substantive issues affected acceptability. The key issues identified were as follows: workforce capacity, lack of stakeholder support and the need for change in clinicians’ attitude. Conclusions Systematic identification of stakeholders’ considerations allows decision makers to prioritize among cost‐effective policy options. Moreover, this approach entails an explicit and transparent priority‐setting procedure and provides insights into the intended and unintended consequences of using a certain health technology. Patient contribution Patients were involved in the conduct of the study for instance, by sharing their values regarding considerations relevant for priority setting.

Background Mental health was only modestly affected in adults during the early months of the COVID-19 pandemic on the group level, but interpersonal variation was large. Aims We aim to investigate potential predictors of the differences in changes in mental health. Method Data were aggregated from three Dutch ongoing prospective cohorts with similar methodology for data collection. We included participants with pre-pandemic data gathered during 2006–2016, and who completed online questionnaires at least once during lockdown in The Netherlands between 1 April and 15 May 2020. Sociodemographic, clinical (number of mental health disorders and personality factors) and COVID-19-related variables were analysed as predictors of relative changes in four mental health outcomes (depressive symptoms, anxiety and worry symptoms, and loneliness), using multivariate linear regression analyses. Results We included 1517 participants with (n = 1181) and without (n = 336) mental health disorders. Mean age was 56.1 years (s.d. 13.2), and 64.3% were women. Higher neuroticism predicted increases in all four mental health outcomes, especially for worry (β = 0.172, P = 0.003). Living alone and female gender predicted increases in depressive symptoms and loneliness (β = 0.05–0.08), whereas quarantine and strict adherence with COVID-19 restrictions predicted increases in anxiety and worry symptoms (β = 0.07–0.11).Teleworking predicted a decrease in anxiety symptoms (β = −0.07) and higher age predicted a decrease in anxiety (β = −0.08) and worry symptoms (β = −0.10). Conclusions Our study showed neuroticism as a robust predictor of adverse changes in mental health, and identified additional sociodemographic and COVID-19-related predictors that explain longitudinal variability in mental health during the COVID-19 pandemic.

Because major depressive disorder (MDD) has a strong negative impact on patients' lives, well–designed treatment programs are needed that address the lasting effects of MDD. Previous work has shown that such programs should not only focus on symptomatic recovery, but also on the subsequent personal recovery process. Currently, few programs with this specific focus exist. Therefore, this study aimed to assess the feasibility of a newly developed blended program to support the personal recovery process of MDD patients: Storytelling and Training to Advance Individual Recovery Skills (STAIRS). STAIRS is a program using peer support and guidance by experts by experience and clinicians, which can be added to regular depression treatment when symptomatic recovery is almost reached. Topics addressed in this program are: (1) effects of depression and treatment; (2) structure; (3) (self) stigma; (4) self-image; (5) meaning of life; (6) connection to others; (7) physical health; (8) relaxation; and (9) preventing relapse. Experiences with the STAIRS program were collected from five participating patients with questionnaires and a focus-group interview, as well as from four trainers using semi-structured interviews. Participants valued the topics addressed in STAIRS, the used working methods, the presence of an expert by experience and the ability to share experiences with peers. The use of an online platform and the involvement of others is seen as potentially supportive but turned out to be more challenging. Perceived effects of STAIRS include positive changes in participants' daily lives and their contacts with others. Overall, the results indicate that when implemented accessibly, STAIRS is a promising and feasible program to foster personal recovery among patients recovering from MDD.

Insomnia exhibits a clinically relevant relationship with major depressive disorder (MDD). Increasing evidence suggests that insomnia is associated with neurobiological alterations that resemble the pathophysiology of MDD. However, research in a clinical population is limited. The present study, therefore, aimed to investigate the relationship between insomnia and the main pathophysiological mechanisms of MDD in a clinical sample of individuals with MDD. Data were extracted from three cohorts (N = 227) and included an evaluation of depression severity (Quick Inventory of Depressive Symptomatology, QIDS-SR16) and insomnia severity (QIDS-SR16 insomnia items) as well as serum and urine assessments of 24 immunologic (e.g., tumour necrosis factor α receptor 2 and calprotectin), neurotrophic (e.g., brain-derived neurotrophic factor and epidermal growth factor), neuroendocrine (e.g., cortisol and aldosterone), neuropeptide (i.e., substance P), and metabolic (e.g., leptin and acetyl-L-carnitine) biomarkers. Linear regression analyses evaluating the association between insomnia severity and biomarker levels were conducted with and without controlling for depression severity (M = 17.32), antidepressant use (18.9%), gender (59.0% female; 40.5% male), age (M = 42.04), and the cohort of origin. The results demonstrated no significant associations between insomnia severity and biomarker levels. In conclusion, for the included biomarkers, current findings reveal no contribution of insomnia to the clinical pathophysiology of MDD.

Abstract Early-warning signals (EWS) have been successfully employed to predict transitions in research fields such as biology, ecology, and psychiatry. The predictive properties of EWS might aid in foreseeing transitions in mood episodes (i.e. recurrent episodes of mania and depression) in bipolar disorder (BD) patients. We analyzed actigraphy data assessed during normal daily life to investigate the feasibility of using EWS to predict mood transitions in bipolar patients. Actigraphy data of 15 patients diagnosed with BD Type I collected continuously for 180 days were used. Our final sample included eight patients that experienced a mood episode, three manic episodes and five depressed episodes. Actigraphy data derived generic EWS (variance and kurtosis) and context-driven EWS (autocorrelation at lag-720) were used to determine if these were associated to upcoming bipolar episodes. Spectral analysis was used to predict changes in the periodicity of the sleep/wake cycle. The study procedures were pre-registered. Results indicated that in seven out of eight patients at least one of the EWS did show a significant change-up till four weeks before episode onset. For the generic EWS the direction of change was always in the expected direction, whereas for the context-driven EWS the observed effect was often in the direction opposite of what was expected. The actigraphy data derived EWS and spectral analysis showed promise for the prediction of upcoming transitions in mood episodes in bipolar patients. Further studies into false positive rates are suggested to improve effectiveness for EWS to identify upcoming bipolar episode onsets.

Abstract Background Sleep traits are associated with cardiometabolic disease risk, with evidence from Mendelian randomization (MR) suggesting that insomnia symptoms and shorter sleep duration increase coronary artery disease risk. We combined adjusted multivariable regression (AMV) and MR analyses of phenotypes of unfavourable sleep on 113 metabolomic traits to investigate possible biochemical mechanisms linking sleep to cardiovascular disease. Methods We used AMV (N = 17,368) combined with two-sample MR (N = 38,618) to examine effects of self-reported insomnia symptoms, total habitual sleep duration, and chronotype on 113 metabolomic traits. The AMV analyses were conducted on data from 10 cohorts of mostly Europeans, adjusted for age, sex, and body mass index. For the MR analyses, we used summary results from published European-ancestry genome-wide association studies of self-reported sleep traits and of nuclear magnetic resonance (NMR) serum metabolites. We used the inverse-variance weighted (IVW) method and complemented this with sensitivity analyses to assess MR assumptions. Results We found consistent evidence from AMV and MR analyses for associations of usual vs. sometimes/rare/never insomnia symptoms with lower citrate (− 0.08 standard deviation (SD)[95% confidence interval (CI) − 0.12, − 0.03] in AMV and − 0.03SD [− 0.07, − 0.003] in MR), higher glycoprotein acetyls (0.08SD [95% CI 0.03, 0.12] in AMV and 0.06SD [0.03, 0.10) in MR]), lower total very large HDL particles (− 0.04SD [− 0.08, 0.00] in AMV and − 0.05SD [− 0.09, − 0.02] in MR), and lower phospholipids in very large HDL particles (− 0.04SD [− 0.08, 0.002] in AMV and − 0.05SD [− 0.08, − 0.02] in MR). Longer total sleep duration associated with higher creatinine concentrations using both methods (0.02SD per 1 h [0.01, 0.03] in AMV and 0.15SD [0.02, 0.29] in MR) and with isoleucine in MR analyses (0.22SD [0.08, 0.35]). No consistent evidence was observed for effects of chronotype on metabolomic measures. Conclusions Whilst our results suggested that unfavourable sleep traits may not cause widespread metabolic disruption, some notable effects were observed. The evidence for possible effects of insomnia symptoms on glycoprotein acetyls and citrate and longer total sleep duration on creatinine and isoleucine might explain some of the effects, found in MR analyses of these sleep traits on coronary heart disease, which warrant further investigation.

Abstract Major depressive disorder (MDD) has a higher prevalence in women with supraphysiologic androgen levels. Whether there is also an association between depression and androgen levels in the physiological range, is unknown. This study examined if women with current MDD have higher androgen levels compared to women who have never had MDD, and if androgen levels are associated with onset and remission of MDD. In 1659 women (513 current MDD, 754 remitted MDD, and 392 never MDD), baseline plasma levels of total testosterone, 5α-dihydrotestosterone, and androstenedione were determined with liquid chromatography-tandem mass spectrometry, and dehydroepiandrosterone-sulfate and sex hormone binding globulin (SHBG) with radioimmunoassays. Free testosterone was calculated. MDD status was assessed at baseline, and at 2 and 4 years follow-up. Women were aged between 18 and 65 years (mean age 41) with total testosterone levels in the physiological range (geometric mean 0.72 nmol/L [95% CI 0.27–1.93]). After adjusting for covariates and multiple testing, women with current MDD had a higher mean free testosterone than women who never had MDD (adjusted geometric mean 8.50 vs. 7.55 pmol/L, p = 0.0005), but this difference was not large enough to be considered clinically meaningful as it was consistent with statistical equivalence. Levels of other androgens and SHBG did not differ and were also statistically equivalent between the groups. None of the androgens or SHBG levels predicted onset or remission of MDD. Our findings support the idea that plasma androgens within the physiological range have no or only limited effects on depressive disorders in women.

Recently, the abuse of ketamine has soared. Therefore, it is of great importance to study its potential risks. The effects of prolonged ketamine on the brain can be observationally studied in chronic recreational users. We performed a systematic review of studies reporting functional and structural brain changes after repeated ketamine abuse. We searched the following electronic databases: Medline, Embase and PsycINFO We screened 11,438 records and 16 met inclusion criteria, totaling 440 chronic recreational ketamine users (2–9.7 years; mean use 2.4 g/day), 259 drug-free controls and 44 poly-drug controls. Long-term recreational ketamine use was associated with lower gray matter volume and less white matter integrity, lower functional thalamocortical and corticocortical connectivity. The observed differences in both structural and functional neuroanatomy between ketamine users and controls may explain some of its long-term cognitive and psychiatric side effects, such as memory impairment and executive functioning. Given the effect that long-term ketamine exposure may yield, an effort should be made to curb its abuse.

Background Intravenous infusion of ketamine can produce rapid and large symptom reduction in patients with treatment-resistant depression (TRD) but presents major obstacles to clinical applicability, especially in community settings. Oral esketamine may be a promising addition to our TRD treatment armamentarium. Aims To explore the safety, tolerability and potential clinical effectiveness of a 3-week treatment with repeated, low-dose oral esketamine. Method Seven patients with chronic and severe TRD received 1.25 mg/kg generic oral esketamine daily, over 21 consecutive days. Scores on the Systematic Assessment for Treatment Emergent Events (SAFTEE), Community Assessment of Psychic Experiences (CAPE), Clinician Administered Dissociative States Scale (CADSS) and Hamilton Rating Scale for Depression (HRSD) instruments, as well as blood pressure and heart rate, were repeatedly assessed. Results Treatment with oral esketamine was well-tolerated. No serious side-effects occurred, and none of the participants discontinued treatment prematurely. Psychotomimetic effects were the most frequently reported adverse events. Mean HDRS score decreased by 16.5%, from 23.6 to 19.7. Three participants showed reductions in HDRS scores above the minimum clinically important difference (eight-point change), of whom two showed partial response. No participants showed full response or remission. Conclusions These results strengthen the idea that oral esketamine is a safe and well-tolerated treatment for patients with chronic and severe TRD, but therapeutic effects were modest. Results were used to design a randomised controlled trial that is currently in progress.

Abstract Background Little is known about the public stigma on mental illness and mental health knowledge (MHK) in China, public stigma and low MHK can negatively affect patients’ health and increase the burden of mental disorders on society. This study aimed at investigating the rates of stigma and MHK, the correlates of stigma and MHK, and the association between MHK and stigma among a Chinese population. Methods The data is from the Tianjin Mental Health Survey (TJMHS), which involved a large and a representative sample of adult community residents in the Chinese municipality of Tianjin (n = 11,748). In a 12% random subsample (n = 1775) the Perceived Discrimination and Devaluation scale (PDD) and a Mental Health Knowledge Questionnaire (MHKQ) were administered. First, percentages of the responses to the individual items of the PDD and MHKQ were investigated. Second, sociodemographic correlates of PDD and MHK, and the association between stigma and MHK were investigated. Results We found that a sizable proportion of participants responded that others would hold a negative attitude towards (former) mental patients, especially with regard to engaging in closer personal relationships. Most people were not familiar about the causes, treatments and prevention of mental illness. Resident area, age, education level, Per capita family income and employment status were related to devaluation score and MHKQ score. MHK was negatively associated with public stigma. Conclusions There is room for improvement with regard to levels of public stigma and MHK in China. Providing psychoeducation to improve public MHK could also contribute to reduction of public stigma.

Abstract Background The past decades of research have seen an increase in statistical tools to explore the complex dynamics of mental health from patient data, yet the application of these tools in clinical practice remains uncommon. This is surprising, given that clinical reasoning, e.g., case conceptualizations, largely coincides with the dynamical system approach. We argue that the gap between statistical tools and clinical practice can partly be explained by the fact that current estimation techniques disregard theoretical and practical considerations relevant to psychotherapy. To address this issue, we propose that case conceptualizations should be formalized. We illustrate this approach by introducing a computational model of functional analysis, a framework commonly used by practitioners to formulate case conceptualizations and design patient-tailored treatment. Methods We outline the general approach of formalizing idiographic theories, drawing on the example of a functional analysis for a patient suffering from panic disorder. We specified the system using a series of differential equations and simulated different scenarios; first, we simulated data without intervening in the system to examine the effects of avoidant coping on the development of panic symptomatic. Second, we formalized two interventions commonly used in cognitive behavioral therapy (CBT; exposure and cognitive reappraisal) and subsequently simulated their effects on the system. Results The first simulation showed that the specified system could recover several aspects of the phenomenon (panic disorder), however, also showed some incongruency with the nature of panic attacks (e.g., rapid decreases were not observed). The second simulation study illustrated differential effects of CBT interventions for this patient. All tested interventions could decrease panic levels in the system. Conclusions Formalizing idiographic theories is promising in bridging the gap between complexity science and clinical practice and can help foster more rigorous scientific practices in psychotherapy, through enhancing theory development. More precise case conceptualizations could potentially improve intervention planning and treatment outcomes. We discuss applications in psychotherapy and future directions, amongst others barriers for systematic theory evaluation and extending the framework to incorporate interactions between individual systems, relevant for modeling social learning processes. With this report, we hope to stimulate future efforts in formalizing clinical frameworks.

Abstract Background Failure to seek treatment for mental health disorders is a serious public health concern. Unfortunately, there is little insight into help-seeking and its associated factors in China which has undergone rapid economic development in the past 30 years and has an increasing prevalence of mental disorder. Therefore, this study aimed to (1) investigate help-seeking rates in healthcare and non-healthcare settings and (2) investigate the correlates of help-seeking behavior in a large Chinese survey. Methods Data came from the Tianjin Mental Health Survey (TJMHS), a representative sample of adult community residents in the Chinese municipality of Tianjin (n = 11,748). Of these, 1759 individuals had ≥1 axis-I diagnosis according to the Diagnostic and Statistical manual– fourth edition (DSM-IV) and were administered a Help-Seeking Questionnaire. Results 15.7% of patients reported that they had ever sought help during their entire lifetime before the interview, with 4.5% seeking help in mental healthcare, 3.2% in other healthcare and 8.1% in non-healthcare settings (e.g., family, friends, and spiritual advisor). Among help-seekers, the first help was mostly sought in non-healthcare settings (58.4%), followed by healthcare (27.5%) and mental healthcare settings (24.5%). Female gender, younger age, having 7–9 years vs 0–6 years of education, a low income, a psychotic disorder and having ≥2 disorders were associated with increased help-seeking. Older age, being married and having a psychotic or organic disorder were associated with increased help-seeking in healthcare vs. non-healthcare settings. Conclusion A small percentage of persons with mental disorders in the Tianjin region seek help and among those who do, variations in the types of help-seeking may be partially explained by demographic and clinical characteristics.

Abstract Background There is an urgent need to develop additional treatment strategies for patients with treatment-resistant depression (TRD). The rapid but short-lived antidepressant effects of intravenous (IV) ketamine as a racemic mixture have been shown repeatedly in this population, but there is still a paucity of data on the efficacy and safety of (a) different routes of administration, and (b) ketamine’s enantiomers esketamine and arketamine. Given practical advantages of oral over IV administration and pharmacodynamic arguments for better antidepressant efficacy of esketamine over arketamine, we designed a study to investigate repeated administration of oral esketamine in patients with TRD. Methods This study features a triple-blind randomized placebo-controlled trial (RCT) comparing daily oral esketamine versus placebo as add-on to regular antidepressant medications for a period of 6 weeks, succeeded by a follow-up of 4 weeks. The methods support examination of the efficacy, safety, tolerability, mechanisms of action, and economic impact of oral esketamine in patients with TRD. Discussion This is the first RCT investigating repeated oral esketamine administration in patients with TRD. If shown to be effective and tolerated, oral esketamine administration poses important advantages over IV administration. Trial registration Dutch Trial Register, NTR6161. Registered 21 October 2016.

Abstract Background Unhealthy lifestyle behaviours contribute to alarming cardiometabolic risk in patients with serious mental illness (SMI). Evidence-based practical lifestyle tools supporting patients and staff in improving patient lifestyle are lacking. Methods This multi-site randomized controlled pragmatic trial determined the effectiveness of a twelve-month multimodal lifestyle approach, including a web-based tool to improve patients’ cardiometabolic health, versus care-as-usual. Using the web tool, nurses (trained in motivational interviewing) assisted patients in assessing their lifestyle behaviours, creating a risk profile and constructing lifestyle goals, which were discussed during fortnightly regular care visits. Twenty-seven community-care and sheltered-living teams were randomized into intervention (N = 17) or control (N = 10) groups, including 244 patients (140 intervention/104 control, 49.2% male, 46.1 ± 10.8 years) with increased waist circumference (WC), BMI or fasting glucose. The primary outcomes concerned differences in WC after six and twelve months intervention, while BMI and metabolic syndrome Z-score were secondary outcome measures. Results General multilevel linear mixed models adjusted for antipsychotic medication showed that differences in WC change between intervention and control were − 0.15 cm (95%CI: − 2.49; 2.19) after six and − 1.03 cm (95%CI: − 3.42; 1.35) after twelve months intervention; however, the differences were not statistically significant. No intervention effects were found for secondary outcome measures. The intervention increased patients’ readiness to change dietary behaviour. Conclusion A multimodal web-based intervention facilitating nurses to address lifestyle changes in SMI patients did not improve patient cardiometabolic health. Web-tool use was lower than expected and nurses need more lifestyle coaching knowledge and skills. The type of intervention and delivery mode need optimization to realize effective lifestyle care for SMI patients. Trial registration Dutch Trial Registry, www.trialregister.nl, NTR3765, 21 December 2012.

Abstract Objectives Psychosocial factors have been hypothesized to increase the risk of cancer. This study aims (1) to test whether psychosocial factors (depression, anxiety, recent loss events, subjective social support, relationship status, general distress, and neuroticism) are associated with the incidence of any cancer (any, breast, lung, prostate, colorectal, smoking‐related, and alcohol‐related); (2) to test the interaction between psychosocial factors and factors related to cancer risk (smoking, alcohol use, weight, physical activity, sedentary behavior, sleep, age, sex, education, hormone replacement therapy, and menopausal status) with regard to the incidence of cancer; and (3) to test the mediating role of health behaviors (smoking, alcohol use, weight, physical activity, sedentary behavior, and sleep) in the relationship between psychosocial factors and the incidence of cancer. Methods The psychosocial factors and cancer incidence (PSY‐CA) consortium was established involving experts in the field of (psycho‐)oncology, methodology, and epidemiology. Using data collected in 18 cohorts (N = 617,355), a preplanned two‐stage individual participant data (IPD) meta‐analysis is proposed. Standardized analyses will be conducted on harmonized datasets for each cohort (stage 1), and meta‐analyses will be performed on the risk estimates (stage 2). Conclusion PSY‐CA aims to elucidate the relationship between psychosocial factors and cancer risk by addressing several shortcomings of prior meta‐analyses.

Background Observational studies suggest that hormonal contraceptive use may increase depressive symptoms in women, but it is unclear whether the effect is causal. Aims To quantitatively examine the evidence from randomised clinical trials for the link between hormonal contraceptive use and depressive symptoms. Method We performed a systematic review and network meta-analysis of randomised clinical trials comparing women randomised to any form of a hormonal contraceptive with women randomised to any other form of a (non-)hormonal contraceptive or placebo. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Web of Science, PsycINFO, EMCare and EMBASE, from inception to 1 May 2020. Certainty of the evidence was assessed with the Grading of Recommendations Assessment, Development and Evaluation approach. A random-effect Bayesian network meta-analysis was conducted, with change in depressive symptoms between baseline and three cycles as outcome. Results This review identified 3492 records, of which 14 trials were eligible and 12 could be included in the network meta-analysis. These trials included 5833 participants (mean age per study range: 16.8–32.4 years) and compared 10 different interventions. Compared with placebo, hormonal contraceptive use did not cause worsening of depressive symptoms (standardised mean difference: median, −0.04; range, −0.17 [95% credible interval −0.46 to 0.13] to 0.13 [95% credible interval −0.28 to 0.56]). Conclusions This study suggests that hormonal contraceptive use does not lead to an increase in depressive symptoms in adult women. Future studies should include first-time users, to confirm the results in young women.

Abstract Background Affective disorders, encompassing depressive-, anxiety-, and somatic symptom disorders, are the most prevalent mental disorders in later life. Treatment protocols and guidelines largely rely on evidence from RCTs conducted in younger age samples and ignore comorbidity between these disorders. Moreover, studies in geriatric psychiatry are often limited to the “younger old” and rarely include the most frail. Therefore, the effectiveness of treatment in routine clinical care for older patients and impact of ageing characteristics is largely unknown. Objective The primary aim of the Routine Outcome Monitoring for Geriatric Psychiatry & Science (ROM-GPS) – project is to examine the impact of ageing characteristics on the effectiveness of treatment for affective disorders in specialised geriatric mental health care. Methods ROM-GPS is a two-stage, multicentre project. In stage one, all patients aged ≥60 years referred to participating outpatient clinics for specialised geriatric mental health care will be routinely screened with a semi-structured psychiatric interview, the Mini International Neuropsychiatric Interview and self-report symptom severity scales assessing depression, generalized anxiety, hypochondria, and alcohol use. Patients with a unipolar depressive, anxiety or somatic symptom disorder will be asked informed consent to participate in a second (research) stage to be extensively phenotyped at baseline and closely monitored during their first year of treatment with remission at one-year follow-up as the primary outcome parameter. In addition to a large test battery of potential confounders, specific attention is paid to cognitive functioning (including computerized tests with the Cogstate test battery as well as paper and pencil tests) and physical functioning (including multimorbidity, polypharmacy, and different frailty indicators). The study is designed as an ongoing project, enabling minor adaptations once a year (change of instruments). Discussion Although effectiveness studies using observational data can easily be biased, potential selection bias can be quantified and potentially corrected (e.g. by propensity scoring). Knowledge of age-related determinants of treatment effectiveness, may stimulate the development of new interventions. Moreover, studying late-life depressive, anxiety and somatic symptom disorders jointly enables data-driven studies for more optimal classification of these disorders in later life. Trial registration Dutch Trial Register: NL6704 (www.trialregister.nl). Retrospectively registered on 2017-12-05.

Abstract Background At many outpatient departments for psychiatry worldwide, standardized monitoring of the safety of prescribed psychotropic drugs is not routinely performed in daily clinical practice. Therefore it is unclear to which extent the drugs used by psychiatric outpatients are prescribed effectively and safely. These issues warrant structured monitoring of medication use, (pre-existing) co-morbidities, effectiveness and side effects during psychiatric outpatient treatment. Improvement of monitoring practices provides an opportunity to ensure that somatic complications and adverse drug effects are detected and dealt with in a timely manner. Structural support for data collection and follow-up tests seems essential for improvement of monitoring practices in psychiatric outpatients. The implementation of a structured somatic monitoring program as part of routine clinical practice, as we describe in this study protocol, may be a solution. Methods In order to address these issues, we developed the innovative program ‘Monitoring Outcomes of Psychiatric Pharmacotherapy (MOPHAR)’. MOPHAR is an infrastructure for implementation of standardized routine outcome monitoring (ROM; including standardized monitoring of treatment effect), monitoring of adverse psychotropic medication effects in psychiatric outpatients, encompassing both somatic adverse effects (e.g. metabolic disturbances) and subjective adverse effects (e.g. sedation or sexual side effects) and medication reconciliation. Discussion In the MOPHAR monitoring program, a nurse performs general and psychotropic drug-specific somatic screenings and provides the treating mental health care providers with more and better information on somatic monitoring for treatment decisions. Given our experience regarding implementation of the MOPHAR program, we expect that the MOPHAR program is feasible and beneficial for patients in any MHS organisation. This paper describes the objectives, target population, setting and the composition and roles of the treatment team. It also indicates what measurements are performed at which time points during outpatient treatment in the MOPHAR monitoring program, as well as the research aspects of this project. Trial registration MOPHAR research has been prospectively registered with the Netherlands Trial Register on 19th of November 2014. (NL4779).

Introduction: Toxoplasma gondii (T. gondii) is an obligate intracellular parasite that is estimated to be carried by one-third of the world population. Latent T. gondii infection has been linked to several neuropsychiatric mood disorders and behaviors. The aim of the present study was to examine whether T. gondii seropositivity is associated with affective disorders, as well as with aggression reactivity and suicidal thoughts. Methods: In the Netherlands Study of Depression and Anxiety (NESDA), T. gondii antibodies were assessed in patients with current depressive (n ​= ​133), anxiety (n ​= ​188), comorbid depressive and anxiety (n ​= ​148), and remitted disorders (n ​= ​889), as well as in healthy controls (n ​= ​373) based on DSM-IV criteria. Seropositivity was analyzed in relation to disorder status, aggression reactivity and suicidal thoughts using multivariate analyses of covariance and regression analyses. Results: Participants were on average 51.2 years (SD ​= ​13.2), and 64.4% were female. Seropositivity was found in 673 participants (38.9%). A strong positive association between T. gondii seropositivity and age was observed. No significant associations were found between T. gondii seropositivity and disorder status, aggression reactivity and suicidal thoughts. The adjusted odds ratio (OR) for any remitted disorder versus controls was 1.13 (95% CI: 0.87-1.49), and for any current disorder versus controls was 0.94 (95% CI: 0.69-1.28). Conclusions: No evidence was found for a relationship between affective disorders and T. gondii infection in the current sample.

Methods: Patients (n = 244) were randomized to receive either care-as-usual or a lifestyle intervention in which mental health nurses coached patients in changing their lifestyle by using a web tool. Costs and quality of life were assessed at baseline and at 6 and 12 months. Incremental costs per centimeter waist circumference (WC) lost and per Quality-Adjusted Life Year (QALY) gained were assessed. Budget impact was estimated based on three intervention-uptake scenarios using a societal and a third-party payer perspective. Results: Costs and reduction in WC were higher in the intervention (n = 114) than in the control (n = 94) group after 12 months, although not statistically significant, resulting in €1,370 per cm WC lost. QALYs did not differ between the groups, resulting in a low probability of the intervention being cost-effective in cost/QALY gained. The budget impact analysis showed that for a reasonable participation of 43%, total costs were around €81 million over 5 years, or on average €16 million annually (societal perspective). Conclusions: The intervention is not cost-effective at 12 months and the budget impact over 5 years is substantial. Possibly, 12 months was too short to implement the intervention, improve cardiometabolic health, and reduce care costs. Therefore, the incentive for this intervention cannot be found in short-term financial advantages. However, there may be benefits associated with lifestyle interventions in the long term that remain unclear.

BackgroundAlthough symptomatic remission is considered the optimal outcome in depression, this is not always achieved. Furthermore, symptom indicators do not fully capture patients’ and clinicians’ perspectives on remission. Broader indicators of (partial) remission from depression should be considered.AimsTo investigate relevant outcomes of depression treatment in specialist care from patients’ and clinicians’ perspectives and to investigate whether these perspectives differ from each other.MethodThree focus groups with 11 patients with depression and seven semi-structured interviews with clinicians were conducted exploring their perspectives on remission. All interviews were audio-recorded and transcribed verbatim. We analysed the transcripts thematically using the phenomenologist approach.ResultsIndependently, both patients and clinicians perceived the following outcomes relevant: restoring social functioning and interpersonal relations, regaining quality of life and achieving personal goals. All clinicians emphasised symptom reduction and satisfaction with treatment as relevant outcomes, whereas the former was not an obvious theme in patients. Unlike clinicians, patients made a clear distinction between treatment outcomes in first versus recurrent/chronic depression.ConclusionsClassically defined study outcomes based on symptom resolution only partly reflect issues considered important by patients and clinicians in specialist depression treatment. Incorporating patients’ and clinicians’ perspectives in the development of measurable end-points makes them more suitable for use in trials and subsequent translation to clinical practice. Furthermore, evaluating patients’ perspectives on treatment outcomes helps in the development of tailored interventions according to patients’ needs.

Functional Somatic Symptoms (FSS) are somatic symptoms for which no somatic cause can be identified despite adequate diagnostic testing. FSS are common, costly, and disabling, and treatment options are limited.Psychotherapy is one of few evidence-based treatments for FSS. Yet, this form of therapy is not widely used, since it is usually reserved for severe symptoms, requires a highly trained therapist, and is not well accepted by patients.The current paper describes the development of the online intervention ‘Grip self-help’ and provides a description of the intervention itself. Grip self-help is an early intervention for mild to moderate FSS in primary care, which aims to reduce somatic symptoms and improve quality of life.In the Grip self-help intervention, patients fill out a set of online questionnaires exploring unhelpful cognitions, emotions, behaviors, and social factors associated with the symptoms. Using this information, a personal profile is generated, identifying factors that might maintain FSS in that individual. As a next step, patients are offered online self-help exercises that are tailored to these factors. Guidance is offered by a primary care professional. The intervention will ultimately result in a personalized self-help guide, composed of texts that are extracted from the exercises patients found useful during the intervention.Grip self-help is the first intervention for FSS combining the concepts of e-health, self-help, and personalized medicine. Guided by a primary care professional, patients are offered an easily accessible, yet highly personalized treatment. Grip self-help thus has the potential to meet the needs of the large group of patients with mild to moderate FSS. Keywords: Functional somatic symptoms, Medically unexplained symptoms, Somatoform disorders, Somatic symptom disorder, Self-help, E-health, Patient-tailored

BackgroundOff-label ketamine treatment has shown acute antidepressant effects that offer hope for patients with therapy-resistant depression. However, its potential for integration into treatment algorithms is controversial, not least because the evidence base for maintenance treatment with repeated ketamine administration is currently weak. Ketamine is also a drug of misuse, which has raised concerns regarding the target population. Little is known about which patients would seek ketamine treatment if it were more widely available.AimsTo explore some of the characteristics of the patients actively seeking ketamine treatment.MethodAn online survey containing questions about duration of current depressive episode, number of antidepressants used and other comments was completed by patients who were exploring the internet regarding the possibility of ketamine for depression.ResultsOf the 1088 people who registered their interest, 93.3% reported depression, 64.3% reported a chronic course of their symptoms and in the past 10 years, 86.3% had tried at least two antidepressants. Desperation was a common theme, but this appeared to be competently expressed. A small minority (

Abstract Background A subgroup of depressed patients with increased inflammatory activity was shown to be more susceptible to develop Treatment Resistant Depression (TRD). Earlier studies with anti-inflammatory drugs have shown benefits in the treatment of major depressive disorder (MDD), but the effects are expected to be higher in patients with increased inflammatory activity. Supplementation of N-acetylcysteine (NAC) to ongoing antidepressant therapy may positively influence outcome of depression treatment in these patients. Therefore, this study aims to investigate the efficacy of NAC supplementation in patients with insufficient response to standard antidepressant treatment, and to explore potential roles of inflammation and oxidative stress involved in the alleged pathophysiological processes of TRD. Methods/design A double-blind randomized placebo-controlled study comparing NAC versus placebo as add-on medication to antidepressant treatment with 12-week treatment and 8-week follow up in patients with TRD and increased inflammatory activity. Apart from clinical efficacy defined as the change in Hamilton Depression Rating Scale (HAMD)-17 score, secondary outcomes include changes in pathophysiological mechanisms related to depression as well as changes in local brain activity (functional Magnetic Resonance Imaging, fMRI) and white matter integrity (Diffusion Tensor Imaging, DTI). Importantly, sole patients with CRP levels with values between 0.85 and 10 mg/L will be included. Discussion This is the first clinical trial taking both TRD and increased inflammatory activity as inclusion criteria. This study will provide reliable evidence for the efficacy of NAC in patients with TRD displaying increased inflammatory activity. And this study also will help explore further the roles of inflammation and oxidative stress involved in the alleged pathophysiological processes of TRD. Trial registration The trial protocol has been registered on “ClinicalTrials.gov“with protocol ID “NAC-2015-TJAH” and ClinicalTrials.gov ID “NCT02972398”.

Abstract Background Depression is a leading cause of disability worldwide. To reduce the societal burden and improve quality of life for individual patients, treatments for depression need to be optimized. There is a particular need for person-tailored interventions that reinforce self-management of patients. Systematic self-monitoring and personalized feedback through the Experience Sampling Method (ESM) could provide such a person-tailored, empowering intervention that enhances treatment outcomes. The primary aim of this study is to investigate the efficacy of self-monitoring and personalized feedback as an add-on tool in the treatment of depressive complaints in a natural setting. Methods The ZELF-i study is a pragmatic multi-site randomized controlled trial (RCT). We aim to recruit 150 individuals with depressive symptoms aged between 18 and 65 years, who have an intake for outpatient basic or specialized treatment at a mental health care organization in the North of the Netherlands. After the intake, participants will be randomly allocated to one of three study arms: two experimental groups engaging in 28 days of systematic self-monitoring (5 times per day) and receiving weekly personalized feedback on positive affect and activities (“Do”-module) or on negative affect and thinking patterns (“Think”-module), and a control group receiving no additional intervention. Self-report inventories of depressive symptoms, psychosocial functioning and feelings of empowerment will be administered before and after the intervention period, and at follow-up measurements at 1, 2, 3 and 6 months. The patient-experienced utility of the intervention will be investigated by a combination of quantitative and qualitative research methods. Discussion The present study is the first to examine the effects of add-on self-monitoring and personalized feedback on depressive complaints in clinical practice. It is also the first to evaluate two different ESM modules targeted at both of depression’s core symptoms. Lastly, it is the first study that uses a combination of qualitative and quantitative methods to evaluate the patient-experienced utility of ESM with personalized feedback as an intervention for depression. Results of the present study may improve treatment for depression, if the intervention is found to be effective. Trial registration Dutch Trial Register, NTR5707, registered prospectively 1 February 2016.

Abstract Background Major depressive disorder (MDD) is often handled as an episodic and isolated disorder, resulting in an optimistic view about its prognosis. Herein, we test the idea that the prognosis of MDD changes if we vary the perspective in terms of (1) a longer time frame and (2) a broader diagnostic conceptualisation including dysthymia, (hypo)mania and anxiety disorders as relevant outcomes. Methods Patients with current MDD at baseline (n = 903) and available 2-, 4-, and/or 6-year follow-up assessments were selected from the Netherlands Study of Depression and Anxiety, a psychiatric cohort study. Combining psychiatric DSM-IV-based diagnoses and life-chart data, patient course trajectories were classified as (1) recovered (no diagnoses at 2-year follow-up or thereafter), (2) recurrent without chronic episodes, (3) recurrent with chronic episodes or (4) consistently chronic since baseline. A chronic episode was defined as having a current diagnosis at the follow-up assessment and consistent symptoms over 2 years. Proportions of course trajectories were provided moving from a short, narrow perspective (2-year follow-up, considering only MDD diagnosis) to a long, broad perspective (6-year follow-up, including MDD, dysthymia, (hypo)mania and anxiety diagnoses). Results With the short, narrow perspective, the recovery rate was 58% and 21% had a chronic episode. However, in the long, broad perspective the recovery rate was reduced to 17%, while 55% of the patients experienced chronic episodes. Conclusions Results from a long and rigorous follow-up in a large cohort suggests that most MDD patients have an unfavourable prognosis. Longer follow-up and broader diagnostic conceptualisation show that the majority of patients have a disabling and chronic disorder. Conceptualising and handling MDD as a narrowly defined and episodic disorder may underestimate the prognosis of the majority of depressed patients and, consequently, the type of care that is appropriate.

Depressive and anxiety disorders are highly prevalent and form a substantial burden for individuals and their family members. A recent study showed that approximately two-thirds of the children of patients with severe depressive and/or anxiety disorders develop one of these disorders themselves before 35 years of age. In the Netherlands, various preventive interventions are available for children of parents with mental illnesses. However, the actual reach of interventions is small (< 1% of all children participate). A major barrier appeared to be parents' hesitancy to let children participate in preventive programs. In order to address this barrier, we designed a pilot study to implement a psychoeducation program on parenting and mental illnesses. The main aim of this study was to investigate how a preventive family-focused approach can be embedded in routine adult psychiatric care. The pilot started in April 2017 and has ended in September 2018. It was conducted in the University Center Psychiatry (UCP) in Groningen, The Netherlands. This article describes the implementation process so far. The main intervention was a monthly organized group-psychoeducation called “parenting and a mental illness,” which could be attended by parents currently treated in the UCP. In 18 months, implementation activities were divided in four phases; (1) Creating awareness, (2) Adoption of the intervention, (3) Implementation and evaluation, and (4) Continuation phase. The program development process was evaluated using both qualitative and quantitative data. Based on the pilot study we were able to make recommendations for the further implementation of this approach so that more parents can be reached in future. Further study with follow-up activities is needed to measure the effects of the psychoeducation, for instance on parenting functioning and the quality of the parent-child interaction.

Introduction: The prevalence of ADHD among patients with substance use disorder (SUD) is substantial. This study addressed the following research questions: Are early developmental, temperamental and educational problems overrepresented among SUD patients with ADHD compared to SUD patients without ADHD? Do this comorbid group receive early help for their ADHD, and are there signs of self-medicating with illicit central stimulants? Method: An international, multi-centre cross-sectional study was carried out involving seven European countries, with 1205 patients in treatment for SUD. The mean age was 40 years and 27% of the sample was female. All participants were interviewed with the Mini International Neuropsychiatric Interview Plus and the Conners' Adult ADHD Diagnostic Interview for DSM-IV. Results: SUD patients with ADHD (n = 196; 16.3% of the total sample) had a significantly slower infant development than SUD patients without ADHD (n = 1,009; 83.4%), had greater problems controlling their temperament, and had lower educational attainment. Only 24 (12%) of the current ADHD positive patients had been diagnosed and treated during childhood and/or adolescence. Finally, SUD patients with ADHD were more likely to have central stimulants or cannabis as their primary substance of abuse, whereas alcohol use was more likely to be the primary substance of abuse in SUD patients without ADHD. Conclusion: The results emphasize the importance of early identification of ADHD and targeted interventions in the health and school system, as well as in the addiction field.

The identification of biomarkers associated with major depressive disorder (MDD) holds great promise to develop an objective laboratory test. However, current biomarkers lack discriminative power due to the complex biological background, and not much is known about the influence of potential modifiers such as gender. We first performed a cross-sectional study on the discriminative power of biomarkers for MDD by investigating gender differences in biomarker levels. Out of 28 biomarkers, 21 biomarkers were significantly different between genders. Second, a novel statistical approach was applied to investigate the effect of gender on MDD disease classification using a panel of biomarkers. Eleven biomarkers were identified in men and eight in women, three of which were active in both genders. Gender stratification caused a (non-significant) increase of Area Under Curve (AUC) for men (AUC = 0.806) and women (AUC = 0.807) compared to non-stratification (AUC = 0.739). In conclusion, we have shown that there are differences in biomarker levels between men and women which may impact accurate disease classification of MDD when gender is not taken into account.

After publication of our article [1] we were notified that Figure 1 was wrongly presented.

(1) Background: The use of smartphone-based ecological momentary assessment (EMA) questionnaires in affective disorder research has rapidly increased. Though, a thorough understanding of experienced burden of and adherence to EMA is crucial in determining the usefulness of EMA. (2) Methods: Persons with current affective disorders (n = 100), remitted persons (n = 190), and healthy controls (n = 94) participated in a smartphone-based EMA two-week monitoring period. Our primary outcomes were (momentary) perceived burden of and adherence to EMA. (3) Results: In the whole sample, lower positive and higher negative affect were associated with slightly higher levels of perceived momentary burden (B = −0.23 [95%CI = −0.27−0.19], B = 0.30 [95%CI = 0.24−0.37], respectively). The persons with current affective disorders reported slightly higher levels of experienced momentary burden (Mdn = 1.98 [IQR = 1.28−2.57]), than the remitted persons (Mdn = 1.64 [IQR = 1.11−2.24]) and healthy controls (Mdn = 1.28 [IQR = 1.04−1.92]). Nevertheless, the persons with current affective disorders still showed very high adherence rates (Mdn = 94.3% [IQR = 87.9−97.1]), at rates on a par with the remitted persons (Mdn = 94.3% [IQR = 90.0−97.1]) and healthy controls (Mdn = 94.3% [IQR = 90.0−98.6]). (4) Discussion: Frequent momentary questionnaires of mental well-being are slightly more burdensome to the persons with current affective disorders, but this does not seem to have a negative impact on adherence. Their high rate of adherence to EMA—which was similar to that in remitted persons and healthy controls —suggests that it is feasible to apply (short-duration) EMA.

Background and Objectives. In the proposed symptom network approach to psychopathology, psychiatric disorders are assumed to result from the (causal) interplay between symptoms. By implementing this approach we explored whether individual feedback on symptom dynamics complements current categorical classification and treatment. The aim of this proof-of-principle case-study was to explore the feasibility, acceptability and usability of this transdiagnostic approach. Methods. A female patient, aged 67, suffering from treatment resistant anxious and depressive symptoms was treated in our tertiary outpatient clinic for old age psychiatry. She participated in ecological momentary assessments (EMA), which in-volved intensive repeated measurements of mood and context-related items during two weeks. Visualizations of the interplay between the items were provided by network graphs and were discussed with the patient. Results. Network graphs were discussed with the patient. For example, it was hypothesized and discussed with the patient that feeling relaxed increased physical activity, causing physical discomfort in the following hours. Physical discomfort caused stress as its symptoms resembled her feared somatic anxiety symptoms. This increased the patient’s insight that stress, expressed as somatic symptoms, played a central role in her panic disorder. This started a dialogue on how to cope with stress caused by somatic (anxiety) symptoms and provided a rationale for the patient to start an interoceptive exposure intervention she had repeatedly refused before. Limitations. The observed symptom dynamics may not be generalizable to any other random two weeks. Conclusions. Personalized diagnosis of psychopathology incorporating complex symptom dynamics is feasible and a promising addition to current categorical diagnostic systems and could guide intervention selection. This merits further exploration.

Background: A crucial but often overlooked impact of early life exposure to trauma is its far-reaching effect on a person’s relationship with their body. Several domains of body experience may be negatively influenced or damaged as a result of early childhood trauma. Objective: The aim of this study was to investigate disturbances in three domains of body experience: body attitude, body satisfaction, and body awareness. Furthermore, associations between domains of body experience and severity of trauma symptoms as well as frequency of dissociation were evaluated. Method: Body attitude was measured with the Dresden Body Image Questionnaire, body satisfaction with the Body Cathexis Scale, and body awareness with the Somatic Awareness Questionnaire in 50 female patients with complex trauma and compared with scores in a non-clinical female sample (n = 216). Patients in the clinical sample also filled out the Davidson Trauma Scale and the Dissociation Experience Scale. Results: In all measured domains, body experience was severely affected in patients with early childhood trauma. Compared with scores in the non-clinical group, effect sizes in Cohen’s d were 2.7 for body attitude, 1.7 for body satisfaction, and 0.8 for body awareness. Associations between domains of body experience and severity of trauma symptoms were low, as were the associations with frequency of dissociative symptoms. Conclusions: Early childhood trauma in women is associated with impairments in self-reported body experience that warrant careful assessment in the treatment of women with psychiatric disorders.

Background: Although complete nonresponse in depression treatment is considered to be a major problem in clinical practice, research in this area is very limited. The objective of this preliminary study was to determine the frequency and predictors of complete nonresponse in different treatments for depression. Methods: Post hocanalysis of the pooled data of 3 consecutive randomized controlled trials of outpatient depression treatment was conducted. The subjects were 313 patients with major depressive disorder and 17-item Hamilton Rating Scale for Depression (HAM-D-17) scores between 14 and 25 who were treated for 6 months with either pharmacotherapy, short-term psychodynamic supportive psychotherapy or combined therapy. Complete nonresponse was defined as a <25 response according to the HAM-D-17. Sociodemographic factors, depression features and adherence were investigated as predictors in a multivariate stepwise logistic regression analysis. Results: Overall, nonresponse occurred in 34 of the patients. In pharmacotherapy this was 46, in psychotherapy 39 and in combined therapy 28. The severity of somatic symptoms was associated with nonresponse in both combined therapy and psychotherapy. No predictive factors were found in the case of pharmacotherapy. In psychotherapy, nonresponse was related to age above 40 years, chronic depression and nonadherence by the patient. In the case of combined therapy, younger age, previous use of an antidepressant and having a previous depressive episode were associated with nonresponse. Conclusion: Easily measurable patient characteristics may help to identify patients at risk of complete nonresponse to treatment. It is suggested that predictors may differ across treatment modalities. However, head-to-head comparisons are required before it can be recommended to take this into account when selecting the most appropriate treatment for individual depressed patients. [ABSTRACT FROM AUTHOR]

Background. Vascular depression is regarded as a subtype of depression, especially in, but not entirely restricted to, the elderly, characterized by a specific clinical presentation and an association with (cerebro)vascular risk and disease. It could have major implications for treatment if subjects at risk for such a depression could be easily identified by their clinical presentation in general practice.Method. We studied the symptom profile of depression in subjects with and without vascular risk factors in two large Dutch community-based studies, the Rotterdam Study and the Amsterdam Study of the Elderly (AMSTEL).Results. We could not confirm the specific symptom profile in depressed subjects with vascular risk factors in either of the two cohorts. Depressed subjects with vascular risk factors showed more loss of energy and more physical disability than those without vascular risk factors. However, presumed specific symptoms of vascular depression, namely psychomotor retardation and anhedonia, were not significantly associated with any of the vascular risk indicators. Loss of energy was significantly associated with myocardial infarction and peripheral arterial disease.Conclusions. In these two large community-based studies we identified some differences between vascular and non-vascular depressed subjects but found no evidence for a specific symptom profile of vascular depression as previously defined. [ABSTRACT FROM AUTHOR]

INTRODUCTION:Somatic complications account for the majority of the 13-30 years shortened life expectancy in psychiatric patients compared to the general population. The study aim was to assess to which extent patients visiting outpatient departments for mood and anxiety disorders were monitored for relevant somatic comorbidities and (adverse) effects of psychotropic drugs-more specifically a) metabolic parameters, b) lithium safety and c) ECGs-during their treatment. METHODS:We performed a retrospective clinical records review and cross-sectional analysis to assess the extent of somatic monitoring at four outpatient departments for mood and anxiety disorders in The Netherlands. We consecutively recruited adult patients visiting a participating outpatient department between March and November 2014. The primary outcome was percentage of patients without monitoring measurements. Secondary outcomes were number of measurements per parameter per patient per year and time from start of treatment to first measurement. RESULTS:We included 324 outpatients, of whom 60.2% were female. Most patients were treated for depressive disorders (39.8%), anxiety disorders (16.7%) or bipolar or related disorders (11.7%) and 198 patients (61.1%) used at least one psychotropic drug. For 186 patients (57.4%), no monitoring records were recorded (median treatment period 7.3 months, range 0-55.6). The median number of measurements per parameter per year since the start of outpatient treatment for patients with monitoring measurements was 0.31 (range 0.0-12.9). The median time to first monitoring measurement per parameter for patients with monitoring measurements was 3.8 months (range 0.0-50.7). DISCUSSION:Somatic monitoring in outpatients with mood and anxiety disorders is not routine clinical practice. Monitoring practices need to be improved to prevent psychiatric outpatients from undetected somatic complications.

Migration is seen as a risk factor for developing psychiatric symptoms and experiencing social exclusion. In the Netherlands, the Moroccan-Dutch population is the second largest migrant group. 70% of all young Moroccan-Dutch people meet each other in the online community www.marokko.nl. Within this community, we investigated the association between experiences of social exclusion and self-reported depressive symptoms and psychotic experiences.Participants were recruited via the website www.marokko.nl. They completed an online survey, with screening instruments for depressive symptoms (K10) and psychotic experiences (PQ-16), measures of social exclusion (perceived discrimination, social defeat and social support), and questions about demographical information. With regression analysis the association between social exclusion and psychiatric symptoms was investigated.We included 267 participants; 87% were female. 27% of the sample has received mental healthcare in the past. Over 50% of these people screened positive for depressive symptoms and psychotic experiences. Perceived discrimination and social defeat were significantly associated with psychotic experiences and social defeat was associated with depressive symptoms. Social support and higher education were associated with less depressive symptoms and psychotic experiences.Our findings suggest that the online environment allows for epidemiological research and early symptom detection. Levels of psychopathology were high in our sample. This suggests that a part of this young ethnic minority population might not get adequate mental healthcare. Since this population can be reached through Internet, the online environment may therefore also offer an appropriate setting for intervention, to increase resilience towards social exclusion.

Body image has implications for psychosocial functioning and quality of life and its disturbance is reported in a broad range of psychiatric disorders. In view of the lack of instruments in Dutch measuring body image as a broad concept, we set out to make an instrument available that reflects the multidimensional character of this construct by including more dimensions than physical appearance. The Dresden Körperbildfragebogen (DBIQ, Dresden Body Image Questionnaire) particularly served this purpose. The DBIQ consists of 35 items and five subscales: body acceptance, sexual fulfillment, physical contact, vitality, and self-aggrandizement. The main objective of the present study was to evaluate the psychometric properties of the Dutch translation of the Dresden Body Image Questionnaire (DBIQ-NL) in a non-clinical sample.The psychometric properties of the DBIQ-NL were examined in a non-clinical sample of 988 respondents aged between 18 and 65. We investigated the subscales' internal consistency and test-retest reliability. In order to establish construct validity we evaluated the association with a related construct, body cathexis, and with indices of self-esteem and psychological wellbeing. The factor structure of the DBIQ-NL was examined via confirmatory factor analysis (CFA). The equivalence of the measurement model across sex and age was evaluated by multiplegroup confirmatory factor analyses.Confirmatory factor analyses showed a structure in accordance with the original scale, where model fit was improved significantly by moving one item to another subscale. Multiple group confirmatory factor analysis across sex and age demonstrated partial strong invariance. Internal consistency was good with little overlap between the subscales. Temporal reliability and construct validity were satisfactory.Results indicate that the DBIQ-NL is a reliable and valid instrument for non-clinical subjects. This provides a sound basis for further investigation of the DBIQ-NL in a clinical sample.

Electroconvulsive therapy (ECT) is an effective treatment for depression, but can have negative side effects including amnesia. The mechanisms of action underlying both the antidepressant and side effects of ECT are not well understood. An equivalent manipulation that is conducted in experimental animals is electroconvulsive seizure (ECS). Rodent studies have provided valuable insights into potential mechanisms underlying the antidepressant and side effects of ECT. However, relatively few studies have investigated the effects of ECS in animal models with a depression-relevant manipulation such as chronic stress. In the present study, mice were first exposed to chronic social stress (CSS) or a control procedure for 15 days followed by ECS or a sham procedure for 10 days. Behavioral effects were investigated using an auditory fear conditioning (learning) and expression (memory) test and a treadmill-running fatigue test. Thereafter, immunohistochemistry was conducted on brain material using the microglial marker Iba-1 and the cholinergic fibre marker ChAT. CSS did not increase fear learning and memory in the present experimental design; in both the control and CSS mice ECS reduced fear learning and fear memory expression. CSS induced the expected fatigue-like effect in the treadmill-running test; ECS induced increased fatigue in CSS and control mice. In CSS and control mice ECS induced inflammation in hippocampus in terms of increased expression of Iba-1 in radiatum of CA1 and CA3. CSS and ECS both reduced acetylcholine function in hippocampus as indicated by decreased expression of ChAT in several hippocampal sub-regions. Therefore, CSS increased fatigue and reduced hippocampal ChAT activity and, rather than reversing these effects, a repeated ECS regimen resulted in impaired fear learning-memory, increased fatigue, increased hippocampal Iba-1 expression, and decreased hippocampal ChAT expression. As such, the current model does not provide insights into the mechanism of ECT antidepressant function but does provide evidence for pathophysiological mechanisms that might contribute to important ECT side-effects.

IntroductionDifferentiating bipolar depression (BD) from unipolar depression (UD) is difficult in clinical practice and, consequently, accurate recognition of BD can take as long as nine years. Research has therefore focused on the discriminatory capacities of biomarkers, such as markers of the hypothalamic-pituitary-adrenal (HPA) axis or immunological activity. However, no previous study included assessments of both systems, which is problematic as they may influence each other. Therefore, this study aimed to explore whether cortisol indicators and inflammatory markers were a) independently associated with and/or b) showed effect modification in relation to a lifetime (hypo)manic episode in a large sample of depressed patients.MethodsData were derived from the Netherlands Study of Depression and Anxiety and comprised 764 patients with a DSM-IV depressive disorder at baseline, of which 124 (16.2%) had a lifetime (hypo)manic episode at the 2-year assessment, or a more recent episode at the 4-year or 6-year assessment. Baseline cortisol awakening response, evening cortisol and diurnal cortisol slope were considered as cortisol indicators, while baseline C-reactive Protein (CRP), Interleukin-6 (IL-6), and Tumor Necrosis Factor Alpha (TNF-α) were included as inflammatory markers.ResultsIn depressed men and women, none of the cortisol indicators and inflammatory markers were (independently) associated with a (hypo)manic episode. However, effect modification was found of diurnal cortisol slope and CRP in relation to a (hypo)manic episode. Further analyses showed that depressed men with high levels of diurnal cortisol slope and CRP had an increased odds (OR=10.99, p=.001) of having a (hypo)manic episode. No significant differences were found in women.ConclusionOur findings suggest that the combination of high diurnal cortisol slope and high CRP may differentiate between UD and BD. This stresses the importance of considering HPA-axis and immunological activity simultaneously, but more research is needed to unravel their interrelatedness.

BackgroundCrime victimisation is a serious problem in psychiatric patients. However, research has focused on patients with severe mental illness and few studies exist that address victimisation in other outpatient groups, such as patients with depression. Due to large differences in methodology of the studies that address crime victimisation, a comparison of prevalence between psychiatric diagnostic groups is hard to make. Objectives of this study were to determine and compare one-year prevalence of violent and non-violent criminal victimisation among outpatients from different diagnostic psychiatric groups and to examine prevalence differences with the general population.MethodCriminal victimisation prevalence was measured in 300 outpatients living in Amsterdam, The Netherlands. Face-to-face interviews were conducted with outpatients with depressive disorder (n = 102), substance use disorder (SUD, n = 106) and severe mental illness (SMI, n = 92) using a National Crime Victimisation Survey, and compared with a matched general population sample (n = 10865).ResultsOf all outpatients, 61% reported experiencing some kind of victimisation over the past year; 33% reported violent victimisation (3.5 times more than the general population) and 36% reported property crimes (1.2 times more than the general population). Outpatients with depression (67%) and SUD (76%) were victimised more often than SMI outpatients (39%). Younger age and hostile behaviour were associated with violent victimisation, while being male and living alone were associated with non-violent victimisation. Moreover, SUD was associated with both violent and non-violent victimisation.ConclusionOutpatients with depression, SUD, and SMI are at increased risk of victimisation compared to the general population. Furthermore, our results indicate that victimisation of violent and non-violent crimes is more common in outpatients with depression and SUD than in outpatients with SMI living independently in the community.

Although current classification systems have greatly contributed to the reliability of psychiatric diagnoses, they ignore the unique role of individual symptoms and, consequently, potentially important information is lost. The network approach, in contrast, assumes that psychopathology results from the causal interplay between psychiatric symptoms and focuses specifically on these symptoms and their complex associations. By using a sophisticated network analysis technique, this study constructed an empirically based network structure of 120 psychiatric symptoms of twelve major DSM-IV diagnoses using cross-sectional data of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC, second wave; N = 34,653). The resulting network demonstrated that symptoms within the same diagnosis showed differential associations and indicated that the strategy of summing symptoms, as in current classification systems, leads to loss of information. In addition, some symptoms showed strong connections with symptoms of other diagnoses, and these specific symptom pairs, which both concerned overlapping and non-overlapping symptoms, may help to explain the comorbidity across diagnoses. Taken together, our findings indicated that psychopathology is very complex and can be more adequately captured by sophisticated network models than current classification systems. The network approach is, therefore, promising in improving our understanding of psychopathology and moving our field forward.

OBJECTIVE: One third of patients with a major depressive episode also experience manic symptoms or, even, a (hypo)manic episode. Retrospective studies on the temporal sequencing of symptomatology suggest that the majority of these patients report depressive symptoms before the onset of manic symptoms. However, prospective studies are scarce and this study will, therefore, prospectively examine the onset of either manic symptoms or a (hypo)manic episode in patients with a major depressive disorder. In addition, we will consider the impact of a large set of potential risk factors on both outcomes. METHODOLOGY: Four-year follow-up data were used to determine the onset of manic symptoms as well as a CIDI-based (hypo)manic episode in a large sample (n = 889, age: 18-65 years) of outpatients with a major depressive disorder and without manic symptoms at baseline. Baseline vulnerability (i.e., sociodemographics, family history of depression, childhood trauma, life-events) and clinical (i.e., isolated manic symptoms, depression characteristics, and psychiatric comorbidity) factors were considered as potential risk factors. RESULTS: In our sample of depressed patients, 15.9% developed manic symptoms and an additional 4.7% developed a (hypo)manic episode during four years. Baseline isolated manic symptoms and comorbid alcohol dependence predicted both the onset of manic symptoms and a (hypo)manic episode. Low education only predicted the onset of manic symptoms, whereas male gender, childhood trauma and severity of depressive symptoms showed strong associations with, especially, the onset of (hypo)manic episodes. CONCLUSIONS: A substantial proportion (20.6%) of patients with a major depressive disorder later developed manic symptoms or a (hypo)manic episode. Interestingly, some identified risk factors differed for the two outcomes, which may indicate that pathways leading to the onset of manic symptoms or a (hypo)manic episode might be different. Our findings indirectly support a clinical staging model.

Infections with different herpes viruses have been associated with cognitive functioning in psychiatric patients and healthy adults. The aim of this study was to find out whether antibodies to different herpes viruses are prospectively associated with cognitive functioning in a general adolescent population.This study was performed in TRAILS, a large prospective general population cohort (N = 1084, 54% female, mean age 16.2 years (SD 0.6)). At age 16, immunoglobulin G antibodies against HSV1, HSV2, CMV and EBV were measured next to high sensitive C-Reactive Protein (hsCRP). Two years later, immediate memory and executive functioning were assessed using the 15 words task and the self ordered pointing task. Multiple linear regression analysis with bootstrapping was performed to study the association between viral infections and cognitive function, adjusting for gender, socioeconomic status, ethnicity, and cannabis use.Presence of HSV1 antibodies was associated with memory function ((B = -0.272, 95% CI = -0.556 to -0.016, p = 0.047)), while the association with executive functioning did not reach statistical significance (B = 0.560, 95% CI is -0.053 to 1.184, p = 0.075). The level of HSV1 antibodies was associated with both memory function (B = -0.160, 95% CI = -0.280 to -0.039, p = 0.014) and executive functioning (B = 0.296, 95% CI = 0.011 to 0.578, p = 0.046). Other herpes viruses and hsCRP were not associated with cognitive functioning.Both presence and level of HSV1 antibodies are prospectively associated with reduced cognitive performance in a large cohort of adolescents.