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Abstract Background Depressive and anxiety disorders have shown to be associated to premature or advanced biological aging and consequently to adversely impact somatic health. Treatments with antidepressant medication or running therapy are both found to be effective for many but not all patients with mood and anxiety disorders. These interventions may, however, work through different pathophysiological mechanisms and could differ in their impact on biological aging and somatic health. This study protocol describes the design of an unique intervention study that examines whether both treatments are similarly effective in reducing or reversing biological aging (primary outcome), psychiatric status, metabolic stress and neurobiological indicators (secondary outcomes). Methods The MOod Treatment with Antidepressants or Running (MOTAR) study will recruit a total of 160 patients with a current major depressive and/or anxiety disorder in a mental health care setting. Patients will receive a 16-week treatment with either antidepressant medication or running therapy (3 times/week). Patients will undergo the treatment of their preference and a subsample will be randomized (1:1) to overcome preference bias. An additional no-disease-no-treatment group of 60 healthy controls without lifetime psychopathology, will be included as comparison group for primary and secondary outcomes at baseline. Assessments are done at week 0 for patients and controls, and at week 16 and week 52 for patients only, including written questionnaires, a psychiatric and medical examination, blood, urine and saliva collection and a cycle ergometer test, to gather information about biological aging (telomere length and telomerase activity), mental health (depression and anxiety disorder characteristics), general fitness, metabolic stress-related biomarkers (inflammation, metabolic syndrome, cortisol) and genetic determinants. In addition, neurobiological alterations in brain processes will be assessed using structural and functional Magnetic Resonance Imaging (MRI) in a subsample of at least 25 patients per treatment arm and in all controls. Discussion This intervention study aims to provide a better understanding of the impact of antidepressant medication and running therapy on biological aging, metabolic stress and neurobiological indicators in patients with depressive and anxiety disorders in order to guide a more personalized medicine treatment. Trial registration Trialregister.nl Number of identification: NTR3460, May 2012.

Abstract Background Only a minority of dialysis patients with depressive symptoms are diagnosed and receive treatment. Depressive symptoms are highly prevalent in this population and are associated with adverse clinical outcomes. Underlying factors for this undertreatment may be the lack of evidence for the safety and effectivity of antidepressant medication, the reluctance of patients to adhere to antidepressant medication, the lack of mental healthcare provision in somatic healthcare environments and end-stage renal disease (ESRD) related physical limitations that complicate face-to-face psychotherapy. Guided Internet-based self-help treatment has demonstrated to be effective for depressive symptoms in other chronic patient populations and may overcome these barriers. The aim of this study is to investigate the (cost) effectiveness of a guided Internet-based self-help intervention for symptoms of depression in dialysis patients. Methods This study is a cluster randomized controlled trial (RCT) that investigates the effectiveness of a 5-week Internet-based self-help Problem Solving Therapy (PST) for depressive symptoms in dialysis patients. Depressive symptoms will be measured using the Beck Depression Inventory – second edition (BDI-II), with a cut-off score of ≥10. We aim to include 206 dialysis patients with depressive symptoms who will be cluster randomized to the intervention or the Care as Usual (CAU) control group. Secondary outcomes will include anxiety symptoms, quality of life, economic costs and clinical outcomes, such as inflammatory factors and hair cortisol levels. Assessments will take place at baseline (T0), 2 weeks after intervention (T1) and 6 months (T2), 12 months (T3) and 18 months (T4) after intervention. The control group will be measured at the same time points. Analysis will be based on the intention-to-treat principle. Mixed models will be used to assess the changes within each condition between pre-treatment and post-treatment. Discussion If demonstrated to be (cost) effective, Internet-based PST will offer new possibilities to treat dialysis patients with depressive symptoms and to improve their quality of care. Trial registration Dutch Trial Register: Trial NL6648 (NTR6834) (prospectively registered 13th November 2017).

Abstract Background Selection of the optimal initial treatment in patients with major depressive disorder (MDD) in need of highly specialized care has the potential to benefit treatment outcomes and cost-effectiveness of treatment strategies. However, to date, there is a paucity of measures that could guide the selection of the initial treatment, in particular to indicate which patients with MDD are in need of highly specialized care. Recognizing this gap, this paper reports on the development and psychometric evaluation of the Decision Tool Unipolar Depression (DTUD), aimed to facilitate the early identification of patients with MDD in need of highly specialized care. Methods The DTUD was developed using a mixed-methods approach, consisting of a systematic review and a concept mapping study. To evaluate the psychometric features of the DTUD, a cross-sectional multicenter study was conducted. A total of 243 patients with MDD were evaluated with the DTUD. Feasibility was operationalized as the time required to complete the DTUD and the content clarity of the DTUD. Inter-rater reliability was evaluated using Krippendorf’s alpha. The Maudsley Staging Method (MSM) and the Dutch Measure for quantification of Treatment Resistance in Depression (DM-TRD) were administered to assess the convergent validity. A receiver operator characteristic curve was generated to evaluate the criterion validity and establish the optimal cut-off value. Results The mean administration time was 4.49 min (SD = 2.71), and the content of the total DTUD was judged as clear in 94.7% of the evaluations. Inter-rater reliability values ranged from 0.69 to 0.91. Higher scores on the DTUD were associated with higher scores on the MSM (rs = 0.47) and DM-TRD (rs = 0.53). Based on the maximum Youden index (0.494), maximum discrimination was reached at a cut-off score of ≥5 (sensitivity 67%, specificity 83%). Conclusion The DTUD demonstrated to be a tool with solid psychometric properties and, therefore, is a promising measure for the early identification of patients with MDD in need of highly specialized care. Use of the DTUD has the potential to facilitate the selection and initiation of the optimal initial treatment in patients with MDD, which in turn may improve the clinical effectiveness and cost-effectiveness of treatment strategies.

Abstract Background The aim of this study was to explore perceptions of free will in the repetitive behaviors of patients with obsessive-compulsive disorder (OCD) and to explore their relation with core clinical characteristics. Methods Experiences of free will were assessed with the Symptomatology And Perceived Free will rating scale (SAPF) in 295 subjects with a lifetime diagnosis of OCD. Patients’ scores on the SAPF were subjected to an explorative principal axis factor analysis (PAF). Factor scores were regressed on five OCD symptom dimensions and on seven clinical variables: illness duration, severity of OCD, insight, anxiety and depression, suicidal ideation and quality of life. Results The PAF revealed three factors: the perceived ability to control and change one’s course of action when faced with an obsession or compulsion (the “alternative possibilities” factor); the experience of obsessions or compulsions as intentional (the “intentionality” factor); and the experience of being the source or owner of the obsessions or compulsions (the “ownership” factor). Lower scores on the “alternative possibilities” factor were associated with lower scores on the washing dimension (β = 0.237, p = 0.004) and higher scores on the precision dimension (β = − 0.190, p = 0.025) and independently associated with longer illness duration (β = − 0.134, p = 0.039), higher illness severity (β = − 0.298, p