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Objective Depression has been associated with metabolomic alterations. Depressive and anxiety disorders are often comorbid diagnoses and are suggested to share etiology. We investigated whether differential metabolomic alterations are present between anxiety and depressive disorders and which clinical characteristics of these disorders are related to metabolomic alterations.Methods Data were from the Netherlands Study of Depression and Anxiety (NESDA), including individuals with current comorbid anxiety and depressive disorders (N = 531), only a current depression (N = 304), only a current anxiety disorder (N = 548), remitted depressive and/or anxiety disorders (N = 897), and healthy controls (N = 634). Forty metabolites from a proton nuclear magnetic resonance lipid-based metabolomics panel were analyzed. First, we examined differences in metabolites between disorder groups and healthy controls. Next, we assessed whether depression or anxiety clinical characteristics (severity and symptom duration) were associated with metabolites.Results As compared to healthy controls, seven metabolomic alterations were found in the group with only depression, reflecting an inflammatory (glycoprotein acetyls; Cohen's d = 0.12, p = 0.002) and atherogenic-lipoprotein-related (e.g., apolipoprotein B: Cohen's d = 0.08, p = 0.03, and VLDL cholesterol: Cohen's d = 0.08, p = 0.04) profile. The comorbid group showed an attenuated but similar pattern of deviations. No metabolomic alterations were found in the group with only anxiety disorders. The majority of metabolites associated with depression diagnosis were also associated with depression severity; no associations were found with anxiety severity or disease duration.Conclusion While substantial clinical overlap exists between depressive and anxiety disorders, this study suggests that altered inflammatory and atherogenic-lipoprotein-related metabolomic profiles are uniquely associated with depression rather than anxiety disorders.

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: Cognitive behavioural analysis system of psychotherapy (CBASP) is an effective individual treatment for persistent depressive disorder (PDD), but evidence on group treatment (Group-CBASP) is limited. Our aim was to review the effect of Group-CBASP on self-report depression severity in outpatients with PDD, overall and by age of depression-onset.METHODS: A retrospective chart review study (November 2011-March 2017) in 54 patients with PDD (29 late-onset, 25 early-onset). Patients were previously treated by pharmacotherapy (92.6%), psychotherapy (98.1%) and/or electroconvulsive therapy (11.1%). Group-CBASP involved 24 weekly sessions during 6 months, followed by individual appointments over 6 months. The Inventory of Depressive Symptoms -self rating(IDS-SR) was used at baseline and after 3, 6, 9 and 12 months, computing mean differences and response rates.RESULTS: The mean IDS-SR score decreased significantly from 39.83 at baseline to 33.78 at 6 months: a decrease from severe to moderate depression after 24 weeks of Group-CBASP, with a medium effect size (Cohen's d = .49). At 12 months, the mean IDS-SR score was 32.81, indicating moderate symptom levels remained. At 6 and 12 months, mean IDS-SR scores were similar among late- versus early-onset patients, but at 12 months response rates were higher among late-onset patients.LIMITATIONS: Although results of our study provide valuable input for future prospective studies, limitations were the use of a retrospective design and the small group size.CONCLUSION: Group-CBASP offered to an outpatient population with PDD was associated with clinically relevant decrease in self-reported symptom severity, and with sustained response particularly in patients with late onset of depression.PRACTITIONER POINTS: Group-CBASP seems to be a good alternative for CBASP in individual setting. Patients with late age of depression-onset seem to benefit more from Group-CBASP. This study shows that clinical relevant effects of Group-CBASP, followed by individual contacts, remain at least for 6 months. Research on personalizing treatment strategies is needed to improve patient assignment for Group-CBASP.

A recent individual patient data meta-analysis showed that antidepressant medication is slightly more efficacious than cognitive behavioral therapy (CBT) in reducing overall depression severity in patients with a DSM-defined depressive disorder. We used an update of that dataset, based on seventeen randomized clinical trials, to examine the comparative efficacy of antidepressant medication vs. CBT in more detail by focusing on individual depressive symptoms as assessed with the 17-item Hamilton Rating Scale for Depression. Five symptoms (i.e., "depressed mood" , "feelings of guilt" , "suicidal thoughts" , "psychic anxiety" and "general somatic symptoms") showed larger improvements in the medication compared to the CBT condition (effect sizes ranging from .13 to .16), whereas no differences were found for the twelve other symptoms. In addition, network estimation techniques revealed that all effects, except that on "depressed mood" , were direct and could not be explained by any of the other direct or indirect treatment effects. Exploratory analyses showed that information about the symptom-specific efficacy could help in identifying those patients who, based on their pre-treatment symptomatology, are likely to benefit more from antidepressant medication than from CBT (effect size of .30) versus those for whom both treatments are likely to be equally efficacious. Overall, our symptom-oriented approach results in a more thorough evaluation of the efficacy of antidepressant medication over CBT and shows potential in "precision psychiatry" .

Electroconvulsive therapy (ECT) is the treatment of choice for severe and treatment-resistant\ud depression; disorder severity and unfavorable treatment outcomes are shown to be influenced\ud by an increased genetic burden for major depression (MD). Here, we tested whether ECT assignment\ud and response/nonresponse are associated with an increased genetic burden for major\ud depression (MD) using polygenic risk score (PRS), which summarize the contribution of diseaserelated\ud common risk variants. Fifty-one psychiatric inpatients suffering from a major depressive\ud episode underwent ECT. MD-PRS were calculated for these inpatients and a separate\ud population-based sample (n = 3,547 healthy; n = 426 self-reported depression) based on summary\ud statistics from the Psychiatric Genomics Consortium MDD-working group (Cases:\ud n = 59,851; Controls: n = 113,154). MD-PRS explained a significant proportion of disease status\ud between ECT patients and healthy controls (p = .022, R2 = 1.173%); patients showed higher\ud MD-PRS. MD-PRS in population-based depression self-reporters were intermediate between\ud ECT patients and controls (n.s.). Significant associations between MD-PRS and ECT response\ud (50% reduction in Hamilton depression rating scale scores) were not observed. Our findings indicate\ud that ECT cohorts show an increased genetic burden for MD and are consistent with the\ud hypothesis that treatment-resistant MD patients represent a subgroup with an increased genetic\ud risk for MD. Larger samples are needed to better substantiate these findings.

BACKGROUND: Actigraphy may provide a more valid assessment of sleep, circadian rhythm (CR), and physical activity (PA) than self-reported questionnaires, but has not been used widely to study the association with depression/anxiety and their clinical characteristics.METHODS: Fourteen-day actigraphy data of 359 participants with current (n = 93), remitted (n = 176), or no (n = 90) composite international diagnostic interview depression/anxiety diagnoses were obtained from the Netherlands Study of Depression and Anxiety. Objective estimates included sleep duration (SD), sleep efficiency, relative amplitude (RA) between day-time and night-time activity, mid sleep on free days (MSF), gross motor activity (GMA), and moderate-to-vigorous PA (MVPA). Self-reported measures included insomnia rating scale, SD, MSF, metabolic equivalent total, and MVPA.RESULTS: Compared to controls, individuals with current depression/anxiety had a significantly different objective, but not self-reported, PA and CR: lower GMA (23.83 vs. 27.4 milli-gravity/day, p = .022), lower MVPA (35.32 vs. 47.64 min/day, p = .023), lower RA (0.82 vs. 0.83, p = .033). In contrast, self-reported, but not objective, sleep differed between people with current depression/anxiety compared to those without current disorders; people with current depression/anxiety reported both shorter and longer SD and more insomnia. More depressive/anxiety symptoms and number of depressive/anxiety diagnoses were associated with larger disturbances of the actigraphy measures.CONCLUSION: Actigraphy provides ecologically valid information on sleep, CR, and PA that enhances data from self-reported questionnaires. As those with more severe or comorbid forms showed the lowest PA and most CR disruptions, the potential for adjunctive behavioral and chronotherapy interventions should be explored, as well as the potential of actigraphy to monitor treatment response to such interventions.

Aims To determine comorbidity patterns in treatment-seeking substance use disorder (SUD) patients with and without adult attention deficit hyperactivity disorder (ADHD), with an emphasis on subgroups defined by ADHD subtype, taking into account differences related to gender and primary substance of abuse. Design Data were obtained from the cross-sectional International ADHD in Substance use disorder Prevalence (IASP) study. Setting Forty-seven centres of SUD treatment in 10 countries. Participants A total of 1205 treatment-seeking SUD patients. Measurements Structured diagnostic assessments were used for all disorders: presence of ADHD was assessed with the Conners' Adult ADHD Diagnostic Interview for DSM-IV (CAADID), the presence of antisocial personality disorder (ASPD), major depression (MD) and (hypo)manic episode (HME) was assessed with the Mini International Neuropsychiatric Interview-Plus (MINI Plus), and the presence of borderline personality disorder (BPD) was assessed with the Structured Clinical Interview for DSM-IV Axis II (SCID II). Findings The prevalence of DSM-IV adult ADHD in this SUD sample was 13.9%. ASPD [odds ratio (OR) = 2.8, 95% confidence interval (CI) = 1.8–4.2], BPD (OR = 7.0, 95% CI = 3.1–15.6 for alcohol; OR = 3.4, 95% CI = 1.8–6.4 for drugs), MD in patients with alcohol as primary substance of abuse (OR = 4.1, 95% CI = 2.1–7.8) and HME (OR = 4.3, 95% CI = 2.1–8.7) were all more prevalent in ADHD+ compared with ADHD− patients (P

Attention deficit/hyperactivity disorder (ADHD) is an increasingly recognized comorbid condition in subjects with substance use disorders (SUDs). This paper describes the methods and study population of the International ADHD in Substance Use Disorders Prevalence (IASP) study. Objectives of the IASP are to determine the prevalence of ADHD in adult treatment seeking patients with SUD in different countries and SUD populations, determine the reliability and validity of the Adult ADHD Self-report Scale V 1.1 (ASRS) as ADHD screening instrument in SUD populations, investigate the comorbidity profile of SUD patients with and without ADHD, compare risk factors and protective factors in SUD patients with and without a comorbid diagnosis of ADHD, and increase our knowledge about the relationship between ADHD and the onset and course of SUD. In this cross-sectional, multi-centre two stage study, subjects were screened for ADHD with the ASRS, diagnosed with the Conner's Adult ADHD Diagnostic Interview for DSM-IV (CAADID), and evaluated for SUD, major depression, bipolar disorder, anti social personality disorder and borderline personality disorder. Three thousand five hundred and fifty-eight subjects from 10 countries were included. Of these 40.9% screened positive for ADHD. This is the largest international study on this population evaluating ADHD and comorbid disorders.

OBJECTIVES AND DESIGN This study describes a randomized controlled trial which aimed to evaluate whether 16 sessions of psychotherapy combined with pharmacotherapy is more effective in relieving depression and improving social functioning than 8 sessions of psychotherapy combined with pharmacotherapy. METHODS. Randomized controlled trial comparing two treatment conditions with different psychotherapy dosages in out-patients with major depression. All patients studied had a baseline score of at least 14 points on the 17-item Hamilton Depression Rating Scale (HDRS). The two conditions consisted of 8- or 16-session short psychodynamic supportive psychotherapy, both in combination with pharmacotherapy. Efficacy was assessed using the 17-item HDRS, the clinical global impression of severity and of improvement, the depression subscale of the Ninety Symptom Checklist, the Quality of Life Depression Scale, and the Groningen Social Disability Schedule. RESULTS. Social functioning improved significantly in both groups. No significant differences were found between 8 and 16 sessions with regard to social functioning. A significant advantage is found for patients in remission on 5 of the 11 dimensions in social functioning over patients not in remission. CONCLUSIONS. At the end of treatment, no clear differences are found between 8 or 16 sessions of psychotherapy - both combined with pharmacotherapy - with regard to severity of depression and social functioning. It is thus still unknown if patients with major depression show more improvement in social functioning and less symptoms of depression after 16 sessions of combined therapy than after 8 sessions. Currently, it seems that for major depression 8 sessions of combined therapy are equally effective as 16 sessions.