Search

BackgroundThe use of ketamine for depression has increased rapidly in the past decades. Ketamine is often prescribed as an add-on to other drugs used in psychiatric patients, but clear information on drug-drug interactions is lacking. With this review, we aim to provide an overview of the pharmacodynamic interactions between ketamine and mood stabilizers, benzodiazepines, monoamine oxidase-inhibitors, antipsychotics, and psychostimulants.MethodsMEDLINE and Web of Science were searched.ResultsTwenty-four studies were included. For lithium, no significant interactions with ketamine were reported. Two out of 5 studies on lamotrigine indicated that the effects of ketamine were attenuated. Benzodiazepines were repeatedly shown to reduce the duration of ketamine’s antidepressant effect. For the monoamine oxidase-inhibitor tranylcypromine, case reports showed no relevant changes in vital signs during concurrent S-ketamine use. One paper indicated an interaction between ketamine and haloperidol, 2 other studies did not. Four papers investigated risperidone, including 3 neuroimaging studies showing an attenuating effect of risperidone on ketamine-induced brain perfusion changes. Clozapine significantly blunted ketamine-induced positive symptoms in patients with schizophrenia but not in healthy participants. One paper reported no effect of olanzapine on ketamine’s acute psychotomimetic effects.ConclusionCurrent literature shows that benzodiazepines and probably lamotrigine reduce ketamine’s treatment outcome, which should be taken into account when considering ketamine treatment. There is evidence for an interaction between ketamine and clozapine, haloperidol, and risperidone. Due to small sample sizes, different subject groups and various outcome parameters, the evidence is of low quality. More studies are needed to provide insight into pharmacodynamic interactions with ketamine.

OBJECTIVE: Studies on the course of depression often ignore comorbid anxiety disorders or anxiety symptoms. We explored predictors of complete remission (no depression nor anxiety diagnoses at follow-up) and of the course of comorbid anxiety symptoms. We additionally tested the hypothesis that the course of anxiety disorders and symptoms in depressed patients is explained by negative life-events in the presence of high neuroticism or a low sense of mastery.METHODS: An observational study of 270 patients (≥60 years) diagnosed with major depressive disorder and 2-year follow-up data, who participated in the Netherlands Study of Depression in Older persons (NESDO). Sociodemographic, somatic, psychiatric, and treatment variables were first explored as possible predictors. A multiple logistic regression analysis was used to examine their predictive value concerning complete remission. Subsequently, negative life-events, personality and their interaction were tested as potential predictors. Linear Mixed Models were used to assess whether the personality traits modified the effect of early and recent life-events, and time and their interactions on the course of the anxiety symptoms.RESULTS: A total of 135 of 270 patients achieved complete remission. Depressed patients with a comorbid anxiety disorder at baseline less often achieved complete remission: 38 of 103 (37.0%) versus 97 of 167 (58.1%). The severity of depressive and anxiety symptomatology, the presence of a comorbid anxiety disorder, and a poorer physical health at baseline predicted nonremission. In line with our hypothesis, a less favorable course of self-reported anxiety symptoms was associated with more recent negative life-events, but only among patients with a high level of neuroticism or a low level of mastery.CONCLUSION: Comorbid anxiety in depression as a negative impact on complete remission at 2-year follow-up. The course of anxiety severity seems dependent on the interaction of personality traits and life-events.

Background With increasing age, symptoms of depression may increasingly overlap with age-related physical frailty and cognitive decline. We aim to identify late-life-related subtypes of depression based on measures of depressive symptom dimensions, cognitive performance, and physical frailty. Methods A clinical cohort study of 375 depressed older patients with a DSM-IV depressive disorder (acronym NESDO). A latent profile analysis was applied on the three subscales of the Inventory of Depressive Symptomatology, as well as performance in five cognitive domains and two proxies for physical frailty. For each class, we investigated remission, dropout, and mortality at 2-year follow-up as well as change over time of depressive symptom severity, cognitive performance, and physical frailty. Results A latent profile analysis model with five classes best described the data, yielding two subgroups suffering from pure depression (“mild” and “severe” depression, 55% of all patients) and three subgroups characterized by a specific profile of cognitive and physical frailty features, labeled as “amnestic depression,” “frail-depressed, physically dominated,” and “frail-depressed, cognitively dominated.” The prospective analyses showed that patients in the subgroup of “mild depression” and “amnestic depression” had the highest remission rates, whereas patients in both frail-depressed subgroups had the highest mortality rates. Conclusions Late-life depression can be subtyped by specific combinations of age-related clinical features, which seems to have prospective relevance. Subtyping according to the cognitive profile and physical frailty may be relevant for studies examining underlying disease processes as well as to stratify treatment studies on the effectiveness of antidepressants, psychotherapy, and augmentation with geriatric rehabilitation.

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.

We compared the presence of autistic and comorbid psychopathology and functional impairments in young adults who received a clinical diagnosis of Pervasive Developmental Disorders Not Otherwise Specified or Asperger’s Disorder during childhood to that of a referred comparison group. While the Autism Spectrum Disorder group on average scored higher on a dimensional ASD self- and other-report measure than clinical controls, the majority did not exceed the ASD cutoff according to the Autism Diagnostic Observation Schedule. Part of the individuals with an ASD diagnosis in their youth no longer show behaviors that underscribe a clinical ASD diagnosis in adulthood, but have subtle difficulties in social functioning and a vulnerability for a range of other psychiatric disorders.

BACKGROUND: Testosterone has been implicated in suicidality in cross-sectional studies. Stress that coincides with a suicide attempt may alter androgen levels, so prospective studies are needed to exclude reverse causation. We aimed to examine the associations of plasma androgens with concurrent and future suicidality, and if present, whether these associations were mediated by a behavioral trait like reactive aggression.METHODS: Baseline plasma levels of total testosterone, 5α-dihydrotestosterone, and androstenedione were determined with liquid chromatography-tandem mass spectrometry, and dehydroepiandrosterone-sulphate with a radioimmunoassay. Suicidality was assessed using the Suicidal Ideation Scale at baseline and after 2-, 4-, 6-, and 9-year follow-up. Men and women were analyzed separately, and potential confounders were considered.RESULTS: Participants (N = 2861; 66.3% women) had a mean age of 42.0 years (range 18-65) and almost half (46.9%) fulfilled criteria for a major depressive or anxiety disorder. At baseline 13.2% of men and 11.2% of women reported current suicidal ideation. In participants who were non-suicidal at baseline, slightly more men than women reported suicidal ideation during follow-up (14.7% vs. 12.5%), whereas the reverse pattern was observed for suicide attempts (3.6% vs. 4.2%). None of the associations between androgens and current and future suicidality were significant.LIMITATIONS: Androgens were determined once, which may have been insufficient to predict suicidality over longer periods.DISCUSSION: The lack of associations between plasma levels of androgens determined by 'gold-standard' laboratory methods with suicidality do not support previous cross-sectional and smaller studies in adult men and women with values within the physiological range.

Background: Chronotype is an individual's preferred timing of sleep and activity, and is often referred to as a later chronotype (or evening-type) or an earlier chronotype (or morning-type). Having an evening chronotype is associated with more severe depressive and anxiety symptoms. Based on these findings it is has been suggested that chronotype is a stable construct associated with vulnerability to develop depressive or anxiety disorders. To examine this, we test the stability of chronotype over 7 years, and its longitudinal association with the change in severity of depressive and anxiety symptoms. Methods: Data of 1,417 participants with a depressive and/or anxiety disorder diagnosis and healthy controls assessed at the 2 and 9-year follow-up waves of the Netherlands Study of depression and anxiety were used. Chronotype was assessed with the Munich chronotype questionnaire. Severity of depressive and anxiety symptoms were assessed with the inventory of depressive symptomatology and Beck anxiety inventory. Results: Chronotype was found to be moderately stable (r = 0.53) and on average advanced (i.e., became earlier) with 10.8 min over 7 years (p

Background A substantial percentage of depressed patients do not respond satisfactorily to conventional antidepressant treatment. This treatment resistant depression (TRD) may be partly related to inflammatory processes in the central nervous system. Accordingly, peripheral inflammatory markers might serve to predict treatment response with novel but still experimental forms of antidepressant treatment. Methods A literature search on treatment of TRD and inflammatory markers was performed using the PubMed/Medline database on November 8th 2018, and 95 articles were retrieved initially, which were subsequently screened and selected only when the inclusion and exclusion criteria were met. Results Ten studies were recruited. In five studies higher baseline interleukin-6 (IL-6) or C-reactive protein (CRP)/high-sensitivity-CRP (hsCRP) in blood predicted better response to medication with anti-inflammatory characteristics, such as ketamine and infliximab. One study found that higher IL-6 predicted worse response to antidepressant treatment in patients with TRD. No evidence was found for the predictive value of other inflammatory markers (e.g., Tumor Necrosis Factor-α, Interferon-γ). Limitations The number of available studies was limited; included studies showed considerable methodological variation and used different definitions for TRD. Conclusion The inflammatory markers IL-6 and CRP/hsCRP could hold promise as markers for the prediction of treatment response in TRD. Clearly, this field of research is still far from mature but it could pave the way for novel and efficacious treatments for at least the inflammatory type of TRD with more well-designed studies and more convincing results.

Objective Combined oral contraceptives are often considered a treatment option for women with premenstrual syndrome or premenstrual dysphoric disorder also seeking contraception, but evidence for this treatment is scarce. We aimed to determine (1) the level of evidence for the efficacy of combined oral contraceptives in managing premenstrual depressive symptoms and overall premenstrual symptomatology and (2) the comparative efficacy of combined oral contraceptives (the International Prospective Register of Systematic Reviews registration number CRD42020205510). Data Sources We searched Cochrane Central Register of Controlled Trials, PubMed, Web of Science, PsycINFO, EMCare, and Embase from inception to June 3, 2021. Study Eligibility Criteria All randomized clinical trials that evaluated the efficacy of combined oral contraceptives in women with premenstrual syndrome or premenstrual dysphoric disorder were considered eligible for inclusion in this meta-analysis. Study Appraisal and Synthesis Methods A random effect Bayesian pairwise and network meta-analysis was conducted with change in premenstrual depressive symptoms and overall premenstrual symptomatology between baseline and 3 cycles as outcome. Certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Results Of 3664 records, 9 eligible trials were included that studied 1205 women with premenstrual syndrome or premenstrual dysphoric disorder (mean age per study range, 24.6–36.5 years). The pairwise meta-analysis revealed that combined oral contraceptives were more efficacious than placebo in treating overall premenstrual symptomatology (standardized mean difference, 0.41; 95% credible interval, 0.17–0.67), but not premenstrual depressive symptoms specifically (standardized mean difference, 0.22; 95% credible interval, −0.06 to 0.47). However, none of the combined oral contraceptives were more effective than each other in reducing premenstrual depressive symptoms and overall premenstrual symptomatology. Conclusion Combined oral contraceptives may improve overall premenstrual symptomatology in women with premenstrual syndrome or premenstrual dysphoric disorder, but not premenstrual depressive symptoms. There is no evidence for one combined oral contraceptive being more efficacious than any other.

BackgroundThe output of many healthy physiological systems displays fractal fluctuations with self-similar temporal structures. Altered fractal patterns are associated with pathological conditions. There is evidence that patients with bipolar disorder have altered daily behaviors.MethodsTo test whether fractal patterns in motor activity are altered in patients with bipolar disorder, we analyzed 2-week actigraphy data collected from 106 patients with bipolar disorder type I in a euthymic state, 73 unaffected siblings of patients, and 76 controls. To examine the link between fractal patterns and symptoms, we analyzed 180-day actigraphy and mood symptom data that were simultaneously collected from 14 patients.ResultsCompared to controls, patients showed excessive regularity in motor activity fluctuations at small time scales (α1 > 1), indicating a more rigid motor control system. α1 values of siblings were between those of patients and controls. Further examinations revealed that the group differences in α1 were only significant in females. Sex also affected the group differences in fractal patterns at larger time scales (>2 h) as quantified by scaling exponent α2. Specifically, female patients and siblings had a smaller α2 compared to female controls, indicating more random activity fluctuations; while male patients had a larger α2 compared to male controls. Interestingly, a higher weekly depression score was associated with a lower α1 in the subsequent week.ConclusionsOur results show sex- and scale-dependent alterations in fractal activity regulation in patients with bipolar disorder. The mechanisms underlying the alterations are yet to be determined.

Contains fulltext : 207225.pdf (Publisher’s version ) (Open Access) 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. 12 p.

Background: While cross-sectional associations of inflammatory markers interleukin-6 (IL-6) and C-reactive protein with major depressive disorder are well established, evidence for longitudinal associations mostly comes from studies on depression symptoms, not diagnoses. This study examined cross-sectional and bidirectional longitudinal associations between depression diagnosis and symptoms in an adult sample over a 6-year period. Methods: Data were obtained from the baseline (n = 2416) and 2- and 6-year follow-up assessments (n = 1925 and n = 1924, respectively) of the Netherlands Study of Depression and Anxiety. C-reactive protein and IL-6 were assessed at each wave, as were the Composite International Diagnostic Interview and Inventory of Depressive Symptomatology. Linear mixed models and generalized estimating equation models with a binomial distribution were used to study longitudinal associations between depression and inflammation and vice versa. Results: There was a consistent cross-sectional association between current depressive disorder (vs. no current disorder) and symptoms with IL-6 across all follow-up measurements (Cohen's d depression diagnosis = 0.06, p =.017; B standardized Inventory of Depressive Symptomatology = 0.029, SE = 0.011, p =.008). In longitudinal analyses, higher IL-6 levels predicted subsequent chronic course in those with a diagnosis at baseline in women but not in men (odds ratio women = 1.13, 95% confidence interval = 1.04–1.23), and both depressive disorder and high severity predicted higher IL-6 levels at the subsequent follow-up (p values

BACKGROUND: Neuromodulation is nowadays investigated as a promising method for pain relief. Research indicates that a single 30-minute stimulation with transcranial pulsed electromagnetic fields (tPEMF) can induce analgesic effects. However, it is unknown whether tPEMF can induce analgesia in neuropathic pain patients.OBJECTIVE: To evaluate the effect of tPEMF on spontaneous pain and heat pain in neuropathic pain patients.METHODS: This study had a randomized double-blind crossover design. Twenty neuropathic pain patients received 30-minutes of tPEMF and 30-minutes sham stimulation. Primary outcomes were pain intensity, pain aversion and heat pain. Secondary outcomes included affect, cognition, and motor function, to investigate safety, tolerability and putative working mechanisms of tPEMF. Outcomes were assessed before, during and after stimulation.RESULTS: No differences in analgesic affects between tPEMF and sham stimulation were found for pain intensity, pain aversion or heat pain. No differences between tPEMF and sham stimulation were observed for affect, motor, and cognitive outcomes.CONCLUSION: A single 30-minute tPEMF stimulation did not induce analgesic effects in neuropathic pain patients, compared to sham. Further study is needed to determine whether prolonged stimulation is necessary for analgesic effects.

Research into major depressive disorder (MDD) is complicated by population heterogeneity, which has motivated the search for more homogeneous subtypes through data-driven computational methods to identify patterns in data. In addition, data on biological differences could play an important role in identifying clinically useful subtypes. This systematic review aimed to summarize evidence for biological subtypes of MDD from data-driven studies. We undertook a systematic literature search of PubMed, PsycINFO, and Embase (December 2018). We included studies that identified (1) data-driven subtypes of MDD based on biological variables, or (2) data-driven subtypes based on clinical features (e.g., symptom patterns) and validated these with biological variables post-hoc. Twenty-nine publications including 24 separate analyses in 20 unique samples were identified, including a total of similar to 4000 subjects. Five out of six biochemical studies indicated that there might be depression subtypes with and without disturbed neurotransmitter levels, and one indicated there might be an inflammatory subtype. Seven symptom-based studies identified subtypes, which were mainly determined by severity and by weight gain vs. loss. Two studies compared subtypes based on medication response. These symptom-based subtypes were associated with differences in biomarker profiles and functional connectivity, but results have not sufficiently been replicated. Four out of five neuroimaging studies found evidence for groups with structural and connectivity differences, but results were inconsistent. The single genetic study found a subtype with a distinct pattern of SNPs, but this subtype has not been replicated in an independent test sample. One study combining all aforementioned types of data discovered a subtypes with different levels of functional connectivity, childhood abuse, and treatment response, but the sample size was small. Although the reviewed work provides many leads for future research, the methodological differences across studies and lack of replication preclude definitive conclusions about the existence of clinically useful and generalizable biological subtypes.

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.

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.

After a cessation of almost 40 years, there is renewed interest into therapeutic applicationsof the serotonergic psychedelic psilocybin for the treatment of patients with various psychiatric disorders. PubMed was searched for clinical trials into "psilocybin" between 2000 and 2020, complemented by handsearching. Articles were also screened for explanatory models and working mechanisms. Psilocybin has been studied in 9 clinical trials: for the treatment of substance use disorders, depression, end-of-life anxiety, demoralization, and obsessive-compulsive disorder. Results show that psilocybin is well tolerated, with only limited side-effects, while even patients with treatment-resistant disorders sometimes show marked, long-term improvements after one or a few sessions. Initial results are encouraging, but there are several limitations. More research is needed to determine which patient populations can benefit, what role setting and the placebo response play, and how these novel treatments can be optimized.

This case report describes successful maintenance treatment with oral S-ketamine in a patient with severe depression, who previously was resistant to electroconvulsive therapy and deep brain stimulation, and who also had comorbid psychotic and obsessive compulsive symptoms.

BackgroundStudies investigating the link between depressive symptoms and inflammation have yielded inconsistent results, which may be due to two factors. First, studies differed regarding the specific inflammatory markers studied and covariates accounted for. Second, specific depressive symptoms may be differentially related to inflammation. We address both challenges using network psychometrics.MethodsWe estimated seven regularized Mixed Graphical Models in the Netherlands Study of Depression and Anxiety (NESDA) data (N = 2321) to explore shared variances among (1) depression severity, modeled via depression sum-score, nine DSM-5 symptoms, or 28 individual depressive symptoms; (2) inflammatory markers C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α); (3) before and after adjusting for sex, age, body mass index (BMI), exercise, smoking, alcohol, and chronic diseases.ResultsThe depression sum-score was related to both IL-6 and CRP before, and only to IL-6 after covariate adjustment. When modeling the DSM-5 symptoms and CRP in a conceptual replication of Jokela et al., CRP was associated with ‘sleep problems’, ‘energy level’, and ‘weight/appetite changes’; only the first two links survived covariate adjustment. In a conservative model with all 38 variables, symptoms and markers were unrelated. Following recent psychometric work, we re-estimated the full model without regularization: the depressive symptoms ‘insomnia’, ‘hypersomnia’, and ‘aches and pain’ showed unique positive relations to all inflammatory markers.ConclusionsWe found evidence for differential relations between markers, depressive symptoms, and covariates. Associations between symptoms and markers were attenuated after covariate adjustment; BMI and sex consistently showed strong relations with inflammatory markers.

Multiple studies show an association between inflammatory markers and major depressive disorder (MDD). People with chronic low-grade inflammation may be at an increased risk of MDD, often in the form of sickness behaviors. We hypothesized that inflammation is predictive of the severity and the course of a subset of MDD symptoms, especially symptoms that overlap with sickness behavior, such as anhedonia, anorexia, low concentration, low energy, loss of libido, psychomotor slowness, irritability, and malaise. We tested the association between basal and lipopolysaccharide (LPS)-induced inflammatory markers with individual MDD symptoms (measured using the Inventory of Depressive Symptomatology Self-Report) over a period of up to 9 years using multivariate-adjusted mixed models in 1147–2872 Netherlands Study of Depression and Anxiety (NESDA) participants. At baseline, participants were on average 42.2 years old, 66.5% were women and 53.9% had a current mood or anxiety disorder. We found that basal and LPS-stimulated inflammatory markers were more strongly associated with sickness behavior symptoms at up to 9-year follow-up compared with non-sickness behavior symptoms of depression. However, we also found significant associations with some symptoms that are not typical of sickness behavior (e.g., sympathetic arousal among others). Inflammation was not related to depression as a unified syndrome but rather to the presence and the course of specific MDD symptoms, of which the majority were related to sickness behavior. Anti-inflammatory strategies should be tested in the subgroup of MDD patients who report depressive symptoms related to sickness behavior.

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.

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.

BACKGROUND: Patients with substance use disorder (SUD) or Attention Deficit Hyperactivity Disorder (ADHD) have a high risk of drop out from treatment. Few studies have investigated predictors of therapy drop out and outcome in SUD patients with comorbid ADHD. Recently, integrated cognitive behavioral therapy (CBT/Integrated) was shown to be more effective than standard CBT (CBT/SUD) in the treatment of SUD + ADHD.OBJECTIVE: To investigate the association of demographic, clinical and neurocognitive variables with drop-out and treatment outcome, and to examine which of these variables are suitable for patient-treatment matching.METHODS: We performed an RCT in which 119 patients were allocated to CBT/Integrated (n = 60) or CBT/SUD (n = 59). In addition, 55 patients had dropped out before randomization. Demographic variables, clinical characteristics and measures of cognitive functioning (Stroop, Tower of London (ToL) and Balloon Analogue Risk Task (BART)) were included as predictors. Outcome measures were: early treatment drop-out, ADHD symptom severity, and substance use severity at end of treatment and follow up.RESULTS: Primary substance of abuse (drugs as opposed to alcohol only) and lower accuracy scores on the ToL were significant predictors of early treatment drop-out. Having more depression and anxiety symptoms and using ADHD medication at baseline significantly predicted more ADHD symptoms at end of treatment, and higher accuracy scores on the ToL significantly predicted higher substance use at end of treatment. No significant predictor-by-treatment interactions were found.CONCLUSION: The results add to the existing realization that also relatively mild cognitive deficits are a risk factor for treatment drop-out in these patients.

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.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.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.Dutch Trial Register, NTR6161. Registered 21 October 2016.

Large studies investigating the psychosocial effects of lifestyle interventions in patients with a severe mental illness (SMI) are scarce, especially in residential patients. This large, randomized controlled, multicentre pragmatic trial assessed the psychosocial effects of a combined diet-and-exercise lifestyle intervention targeting the obesogenic environment of SMI residential patients. Twenty-nine sheltered and clinical care teams were randomized into intervention (n = 15) or control (n = 14) arm. Team tailored diet-and-exercise lifestyle plans were set up to change the obesogenic environment into a healthier setting, and team members were trained in supporting patients to make healthier choices. The control group received care-as-usual. The Calgary Depression Scale for Schizophrenia (CDSS), Positive and Negative Syndrome Scale (PANSS), Health of the Nation Outcome Scales (HoNOS) and the Manchester Short Assessment of Quality of Life (MANSA) were assessed at baseline and after three and twelve months. Data were available for 384 intervention and 386 control patients (48.6 +/- 12.5 years old, 62.7% males, 73.7% psychotic disorder). Linear mixed model analysis showed no psychosocial improvements in the intervention group compared to care-as-usual; the intervention group showed a slightly reduced quality of life (overall) and a small increase in depressive symptoms (clinical care facilities) and psychotic symptoms (sheltered facilities). This may be due to difficulties with implementation, the intervention not being specifically designed for improvements in mental well-being, or the small change approach, which may take longer to reach an effect. Further research might elucidate what type of lifestyle intervention under what circumstances positively affects psychosocial outcomes in this population. (c) 2018 Elsevier B.V. All rights reserved.

Objective Clinical characteristics appear limited in their ability to predict course of anxiety disorders, therefore we explored the predictive value of biological parameters on course of anxiety disorders. Methods 907 persons with an anxiety (panic, social phobia, generalised anxiety) disorder with a baseline and two-year follow-up measure were selected from the Netherlands Study of Depression and Anxiety (NESDA). Previously, three course trajectories were distinguished which vary in terms of symptom severity and chronicity. Baseline clinical parameters like anxiety severity, anxiety duration, and disability were limited in their ability to predict the two-year course. This study explored whether metabolic syndrome, hypothalamic-pituitary-adrenal-axis functioning, inflammation markers, and neuroplasticity were indicators of two-year course and whether these parameters improved the model containing the most predictive clinical parameters only. Results Baseline diastolic blood pressure of persons with chronic moderate symptoms was significantly higher than of persons with non-chronic mild symptoms (odds ratio [OR] = 1.18, 95% confidence interval [CI95%] 1.01 to 1.38). Baseline high-density lipid cholesterol of persons with severe chronic symptoms was significantly lower than of persons with non-chronic mild symptoms (OR = 0.77, CI95% 0.62 to 0.96). The predictive ability of both parameters was however low with concordance statistics of 0.55 and 0.57 respectively. Addition of biological parameters did not improve the predictive ability of the model containing the clinical parameters. Conclusions In addition to clinical characteristics, biological parameters did not improve the predictive ability of the model for course trajectory of anxiety disorders. Prediction of course trajectory in anxiety disorders remains difficult and warrants further research.

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.

BackgroundUnhealthy 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.MethodsThis 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.ResultsGeneral 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.ConclusionA 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 registrationDutch Trial Registry,www.trialregister.nl, NTR3765, 21 December 2012.

Major Depressive Disorder (MDD) is a heterogeneous disorder with a considerable symptomatic overlap with other psychiatric and somatic disorders. This study aims at providing evidence for association of a set of serum and urine biomarkers with MDD. We analyzed urine and serum samples of 40 MDD patients and 47 age- and sex-matched controls using 40 potential MDD biomarkers (21 serum biomarkers and 19 urine biomarkers). All participants were of Caucasian origin. We developed an algorithm to combine the heterogeneity at biomarker level. This method enabled the identification of correlating biomarkers based on differences in variation and distribution between groups, combined the outcome of the selected biomarkers, and calculated depression probability scores (the "bio depression score"). Phenotype permutation analysis showed a significant discrimination between MDD and euthymic (control) subjects for biomarkers in urine (P

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.

Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened\ud risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified\ud 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and\ud implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved\ud in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression\ud with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were\ud putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry\ud lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression\ud and imply that a continuous measure of risk underlies the clinical phenotype.

BackgroundTo effectively shape mental healthcare policy in modern-day China, up-to-date epidemiological data on mental disorders is needed. The objective was to estimate the prevalence, age-of-onset (AOO) and sociodemographic correlates of mental disorders in a representative household sample of the general population (age ⩾ 18) in the Tianjin Municipality in China.MethodsData came from the Tianjin Mental health Survey (TJMHS), which was conducted between July 2011 and March 2012 using a two-phase design. 11 748 individuals were screened with an expanded version of the General Health Questionnaire and 4438 subjects were selected for a diagnostic interview by a psychiatrist, using the Structured Clinical Interview for the Diagnostic and Statistical Manual – fourth edition (SCID).ResultsThe lifetime and 1-month prevalence of any mental disorder were 23.6% and 12.8%, respectively. Mood disorders (lifetime: 9.3%; 1-month: 3.9%), anxiety disorders (lifetime: 4.5% 1-month: 3.1%) and substance-use disorders (lifetime: 8.8%; 1-month: 3.5%) were most prevalent. The median AOO ranged from 25 years [interquartile range (IQR): 23–32] for substance-use disorders to 36 years (IQR: 24–50) for mood disorders. Not being married, non-immigrant status (i.e. local ‘Hukou’), being a farmer, having ConclusionResults from the current survey indicate that mental disorders are steadily reported more commonly in rapidly-developing urban China. Several interesting sociodemographic correlates were observed (e.g. male gender and non-immigrant status) that warrant further investigation and could be used to profile persons in need of preventive intervention.

BACKGROUND: Offspring of patients with depressive and/or anxiety disorders are at high risk of developing a similar disorder themselves. Early recognition and treatment may have substantial effects on prognosis. The main aim of this study was to examine the time to initial help-seeking and its determinants in offspring after the first onset of a mood and/or anxiety disorder.METHODS: Data are presented of 215 offspring with a mood and/or anxiety disorder participating in a cohort study with 10 year follow-up. We determined age of disorder onset and age of initial help-seeking. Offspring characteristics (gender, IQ, age of onset, disorder type, suicidal ideation) and family characteristics (socioeconomic status, family functioning) were investigated as potential predictors of the time to initial help-seeking.RESULTS: The estimated overall proportion of offspring of depressed/anxious patients who eventually seek help after onset of a mood and/or anxiety disorder was 91.9%. The time to initial help-seeking was more than two years in 39.6% of the offspring. Being female, having a mood disorder or comorbid mood and anxiety disorder (relative to anxiety) and a disorder onset in adolescence or adulthood (relative to childhood) predicted a shorter time to initial help-seeking.LIMITATIONS: Baseline information relied on retrospective reports. Age of onsets and age of initial help-seeking may therefore be subject to recall bias.CONCLUSION: Although most offspring eventually seek help after onset of a mood/anxiety disorder, delays in help-seeking were common, especially in specific subgroups of patients. This information may help to develop targeted strategies to reduce help-seeking delays.

Background: Evidence lacks on whether obesity along with major depression (MD)/anxiety leads to higher health care use (HCU) and health care-related costs (HCC) compared with either condition alone. The objective of the study was to examine the longitudinal associations of obesity, MD/anxiety, and their combination with HCU and HCC.Methods: Longitudinal data (2004-2013) among N = 2706 persons at baseline and 2-,4-, and 6-year follow-up were collected on obesity, MD/anxiety and HCU.Results: The combination of obesity and MD/anxiety was associated with an increased risk of primary and specialty care visits, and of hospitalizations, odds ratios (95%-confidence intervals): 1.83 (1.44; 2.34), 1.31 (1.06; 1.61) and 1.79 (1.40; 2.29) compared to non-obese and non-depressed individuals. The primary and specialty care costs were higher in persons with obesity and MD/anxiety than in persons without these conditions, but the relative excess risk due to interactions between obesity and MD/anxiety regarding HCU and HCC were not statistically significant (i.e. no synergistic effect).Conclusions: Obesity along with MD/anxiety leads to higher HCU and HCC over time. However, the HCC associated with the joint presence of both conditions are not higher than the sum of the HCC due to each condition independently.

Contains fulltext : 178015.pdf (Publisher’s version ) (Closed access) Background: depression is associated with worse executive function, but underlying mechanisms might differ by age. Aims: to investigate whether vascular disease burden affects the association between depression and executive dysfunction differentially by age. Method: among 83,613 participants of Lifelines (population-based cohort study), linear regression analyses were applied to examine the association between executive function (Ruff Figural Fluency test, dependent variable) and depression according to DSM-IV criteria (Mini International Neuropsychiatric Interview, independent variable). Results: adjusted for demographic characteristics, major depressive disorder was associated with a lower level of executive function in both younger and older adults. Minor depressive disorder was only associated with worse executive function in younger adults. Adding vascular disease burden to the final model with major depressive disorder, reduced this strength of this association by 5.9% in younger and 5.0% in older adults. Conclusions: major depression was associated with worse executive function across the lifespan, but minor depression only in younger adults. The impact of vascular burden on the association did not differ between younger and older adults. Therefore, vascular risk reduction is important in both age groups.

Objective: Despite the increasing recognition in clinical practice of body image problems in other than appearance related mental disorders, the question remains how aspects of body image are affected in different disorders. The aim of this study was to measure body image in patients with a variety of mental disorders and to compare scores with those in the general population in order to obtain more insight in the relative disturbance of body image in the patients group compared to healthy controls. In a further exploration associations with self-reported mental health, quality of life and empowerment were established as well as the changes in body image in patients over time.Methods: 176 women and 91 men in regular psychiatric treatment completed the Dresden Body Image Questionnaire, the Outcome Questionnaire, the Manchester Short Assessment of Quality of Life and the Mental Health Confidence Scale. Measurements were repeated after four months.Results: Patients with mental disorders, especially those with post-traumatic stress disorder (PTSD), scored significantly lower on body image, with large effect sizes, in comparison with the healthy controls. Scores of patients from different diagnostic groups varied across domains of body image, with body acceptance lowest in the group with eating disorders, and sexual fulfillment extremely low in PTSD. Vitality did not differ significantly between the various disorders. Gender differences were large for body acceptance and sexual fulfillment and small for vitality. Associations of body image with self-reported mental health, quality of life and empowerment were moderate to strong. After four months of treatment positive changes in body image were observed.Conclusions: Negative body image is a common problem occurring in most patients with mental disorders. Diagnosis-specific profiles emerge, with PTSD being the most affected disorder. Body acceptance and sexual fulfillment were the most differentiating aspects of body image between diagnoses. Changes in body image occur over the course of treatment. (C) 2017 Elsevier Inc. All rights reserved.

Objectives: Disturbances in sleep and waking patterns are highly prevalent during mood episodes in bipolar disorder. The question remains whether these disturbances persist during phases of euthymia and whether they are heritable traits of bipolar disorder. The current study investigates objective sleep measures in a large sample of bipolar I patients, non-affected siblings and controls.Methods: A total of 107 bipolar disorder I patients, 74 non-affected siblings, and 80 controls were included. Sleep was measured with actigraphy over the course of 14 days. Seven sleep parameters were analyzed for group differences and their relationship with age at onset, number of episodes and psychotic symptoms using linear mixed model analysis to account for family dependencies.Results: Patients had a longer sleep duration and later time of sleep offset compared to the non-affected siblings but these differences were entirely attributable to differences in mood symptoms. We found no difference between patients and controls or siblings and controls when the analyses were restricted to euthymic patients. None of the bipolar illness characteristics were associated with sleep.Limitations: Medication use was not taken into account which may have influenced our findings and controls were younger compared to non-affected siblings.Conclusions: In the largest study to date, our findings suggest that recovered bipolar I patients and their siblings do not experience clinically significant sleep disturbances. Sleep disturbances are primarily a reflection of current mood state, but are unrelated to the course of the disorder.

BackgroundIn search of empirical classifications of depression and anxiety, most subtyping studies focus solely on symptoms and do so within a single disorder. This study aimed to identify and validate cross-diagnostic subtypes by simultaneously considering symptoms of depression and anxiety, and disability measures.MethodA large cohort of adults (Lifelines, n = 73 403) had a full assessment of 16 symptoms of mood and anxiety disorders, and measurement of physical, social and occupational disability. The best-fitting subtyping model was identified by comparing different hybrid mixture models with and without disability covariates on fit criteria in an independent test sample. The best model's classes were compared across a range of external variables.ResultsThe best-fitting Mixed Measurement Item Response Theory model with disability covariates identified five classes. Accounting for disability improved differentiation between people reporting isolated non-specific symptoms [‘Somatic’ (13.0%), and ‘Worried’ (14.0%)] and psychopathological symptoms [‘Subclinical’ (8.8%), and ‘Clinical’ (3.3%)]. Classes showed distinct associations with clinically relevant external variables [e.g. somatization: odds ratio (OR) 8.1–12.3, and chronic stress: OR 3.7–4.4]. The Subclinical class reported symptomatology at subthreshold levels while experiencing disability. No pure depression or anxiety, but only mixed classes were found.ConclusionsAn empirical classification model, incorporating both symptoms and disability identified clearly distinct cross-diagnostic subtypes, indicating that diagnostic nets should be cast wider than current phenomenology-based categorical systems.

OBJECTIVE: Somatic symptoms have been suggested to negatively affect the course of major depressive disorder (MDD). Mechanisms behind this association, however, remain elusive. This study examines the impact of somatic symptoms on MDD prognosis and aims to determine whether this effect can be explained by psychiatric characteristics, somatic diseases, lifestyle factors, and disability.METHODS: In 463 MDD patients (mean age=44.9 years, 69.8% female) from the Netherlands Study of Depression and Anxiety (NESDA), we examined whether the type and number of somatic symptom clusters predicted the two-year persistence of MDD. Diagnoses of MDD were established with the Composite International Diagnostic Interview (CIDI) and somatic symptom clusters were assessed with the Four-Dimensional Symptom Questionnaire (4DSQ) somatization scale. Psychiatric characteristics, somatic diseases, lifestyle factors, and disability were taken into account as factors potentially underlying the association.RESULTS: The cardiopulmonary, gastrointestinal, and general cluster significantly predicted the two-year persistence of MDD, but only when two or more of these clusters were present (OR=2.32, 95% CI=1.51-3.57, p=CONCLUSIONS: Somatic symptoms are predictors of a worse prognosis of MDD independent of psychiatric characteristics, somatic diseases, lifestyle factors, and disability. These results stress the importance of considering somatic symptoms in the diagnostic and treatment trajectory of patients with MDD. Future research should focus on identifying treatment modalities targeting depressive as well as somatic symptoms.

Background: The locus of control (LOC) construct has been associated with onset, course, and severity of anxiety and depression. We investigated the stability of LOC, the bidirectional relationships between LOC and symptom severity of anxiety and depression over nine years, and the influence of intermediate positive and negative life-events on these associations.Methods: Data came from five assessment waves over nine years of 2052 subjects with an anxiety or depressive disorder or healthy controls. First, the stability of LOC (assessed with 5-item Mastery Scale) was tested. Next, associations between LOC, anxiety severity (Beck Anxiety Inventory), depression severity (Inventory of Depressive Symptomatology), and intermediate positive and negative life-events (20-item List of Threatening Experience Questionnaire) were determined with structural equation modeling.Results: LOC was rather stable over nine years (r = 0.62), and scores increased slightly with age (i.e. became more internal). LOC yielded equal stability estimates as symptom levels of anxiety and depression did over nine years. A more external LOC predicted higher anxiety and depression severity, but did not influence the incidence of positive and negative life-events. Higher depression severity and more negative life-events predicted the development of a more external LOC, whereas more positive life-events predicted a more internal LOC. Anxiety severity had no effect on LOC.Limitations: Life-events were assessed with self-report measures.Conclusions: The prospective associations between LOC and meaningful changes in anxiety and depressive symptom severity and experienced life-events may yield important new insights for clinical interventions.

BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) frequently co-occurs with Substance Use Disorders (SUDs). Standard ADHD pharmacotherapies are not effective in patients with this comorbidity and cognitive behavioral therapy (CBT) has not been tested in this population. This RCT aimed to compare the efficacy of Integrated CBT (CBT/Integrated) directed at adult ADHD and SUD with CBT directed at SUD only (CBT/SUD) in patients with SUD and ADHD (SUD + ADHD).METHODS: Randomized clinical trial among 119 SUD + ADHD patients in a SUD treatment center. CBT/Integrated consisted of 15 individual sessions of motivational therapy, coping skills training and relapse prevention for SUD, and training of planning skills, problem-solving skills and dealing with emotions for ADHD. CBT/SUD consisted of 10 individual SUD treatment sessions only. Primary outcome was ADHD symptom severity according to the ADHD rating scale (ARS) at post-treatment. Secondary outcomes included ADHD symptom severity after two-month follow-up, and treatment response (≥30% ADHD symptom reduction), substance use, depressive or anxiety symptoms, and quality of life at post-treatment and follow-up.RESULTS: CBT/Integrated was more effective than CBT/SUD in the reduction of ADHD symptoms post-treatment: ARS = 28.1 (SD 9.0) vs. 31.5 (SD 11.4) (F = 4.739, df = 1, 282, p = .030; d = 0.34). At follow-up, CBT/Integrated still resulted in lower ARS scores than CBT/SUD, but the difference was not significant at the 0.05 level. For other secondary outcomes, including substance use, no significant between-group differences were present.CONCLUSIONS: Compared to regular SUD cognitive behavioral therapy, integrated cognitive behavioral therapy resulted in a significant extra improvement in ADHD symptoms in SUD + ADHD patients.

OBJECTIVES: Older age and Major depressive disorder (MDD) are both risk factors for the development of cardiovascular diseases. Testosterone has been associated with MDD and Metabolic Syndrome (MetS) in men, though associations in women are less clear. Therefore, we investigated whether testosterone is associated with MetS and whether this association is different for depressed and non-depressed older men and women.METHODS: In this prospective cohort study, 478 participants (349 patients with MDD and 129 controls) aged between 60 and 93 years from the Netherlands Study of Depression in Older Persons (NESDO) were included. Total testosterone (TT) and sex-hormone binding globulin (SHBG) levels were measured using a second generation radioimmune assay. Free testosterone (FT) was calculated based on TT. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria.RESULTS: A higher risk for MetS was found in men with low FT and TT (Odds Ratio [OR]: 0.67, 95% confidence interval [95%CI]: 0.47-0.95 and OR: 0.51, 95%CI: 0.34-0.75), and in women with high FT (OR: 1.41, 95%CI: 1.08-1.82). Strong associations in the same direction were found with adiposity, glucose and plasma lipid MetS components at baseline, but not with changes in these components at two-year follow-up. The associations did not significantly differ between MDD patients and controls.CONCLUSIONS: Independently of having MDD, low testosterone levels in men, and in contrast, high testosterone levels in women were significantly associated with MetS and its components.

Highlights • Connectivity analyses complemented with a metric exploring switching in brain activity. • Lower insula-salience connectivity predicts insufficient antidepressant response. • This same insula region is activated less when switching from task to a rest. • This could be a potential biomarkers for predicting future antidepressant response., Insufficient response to treatment is the main cause of prolonged suffering from major depressive disorder (MDD). Early identification of insufficient response could result in faster and more targeted treatment strategies to reduce suffering. We therefore explored whether baseline alterations within and between resting state functional connectivity networks could serve as markers of insufficient response to antidepressant treatment in two years of follow-up. We selected MDD patients (N = 17) from the NEtherlands Study of Depression and Anxiety (NESDA), who received ≥ two antidepressants, indicative for insufficient response, during the two year follow-up, a group of MDD patients who received only one antidepressant (N = 32) and a healthy control group (N = 19) matched on clinical characteristics and demographics. An independent component analysis (ICA) of baseline resting-state scans was conducted after which functional connectivity within the components was compared between groups. We observed lower connectivity of the right insula within the salience network in the group with ≥ two antidepressants compared to the group with one antidepressant. No difference in connectivity was found between the patient groups and healthy control group. Given the suggested role of the right insula in switching between task-positive mode (activation during attention-demanding tasks) and task-negative mode (activation during the absence of any task), we explored whether right insula activation differed during switching between these two modes. We observed that in the ≥2 antidepressant group, the right insula was less active compared to the group with one antidepressant, when switching from task-positive to task-negative mode than the other way around. These findings imply that lower right insula connectivity within the salience network may serve as an indicator for prospective insufficient response to antidepressants. This result, supplemented by the diminished insula activation when switching between task and rest related networks, could indicate an underlying mechanism that, if not sufficiently targeted by current antidepressants, could lead to insufficient response. When replicated, these findings may contribute to the identification of biomarkers for early detection of insufficient response.

BackgroundRoutine outcome monitoring (ROM) may enhance individual treatment and is also advocated as a means to compare the outcome of different treatment programs or providers. There is debate on the optimal instruments to be used for these separate tasks.MethodsThree sets with longitudinal data from ROM were analyzed with correlational analysis and repeated measures ANOVAs, allowing for a head-to-head comparison of measures regarding their sensitivity to detect change. The responsiveness of three disorder-specific instruments, the Beck Depression Inventory, the Inventory of Depressive Symptoms, and the Mood and Anxiety Symptoms Questionnaire, was compared to three generic instruments, the Symptom Checklist (SCL-90), the Outcome Questionnaire (OQ-45), and the Brief Symptom Inventory, respectively.ResultsIn two of the three datasets, disorder-specific measures were more responsive compared to the total score on generic instruments. Subscale scores for depression embedded within generic instruments are second best and almost match disorder-specific scales in responsiveness. No evidence of a desynchronous response on outcome measures was found.LimitationsThe present study compares measures head-to-had, and responsiveness is not assessed against an external criterion, such as clinical recovery.DiscussionDisorder-specific measures yield the most precise assessment for individual treatment and are recommended for clinical use. Generic measures may allow for comparisons across diagnostic groups and their embedded subscales approach the responsiveness of disorder-specific measures.

BackgroundThere is increasing interest in day-to-day affect fluctuations of patients with depressive and anxiety disorders. Few studies have compared repeated assessments of positive affect (PA) and negative affect (NA) across diagnostic groups, and fluctuation patterns were not uniformly defined. The aim of this study is to compare affect fluctuations in patients with a current episode of depressive or anxiety disorder, in remitted patients and in controls, using affect instability as a core concept but also describing other measures of variability and adjusting for possible confounders.MethodsEcological momentary assessment (EMA) data were obtained from 365 participants of the Netherlands Study of Depression and Anxiety with current (n = 95), remitted (n = 178) or no (n = 92) DSM-IV defined depression/anxiety disorder. For 2 weeks, five times per day, participants filled-out items on PA and NA. Affect instability was calculated as the root mean square of successive differences (RMSSD). Tests on group differences in RMSSD, within-person variance, and autocorrelation were performed, controlling for mean affect levels.ResultsCurrent depression/anxiety patients had the highest affect instability in both PA and NA, followed by remitters and then controls. Instability differences between groups remained significant when controlling for mean affect levels, but differences between current and remitted were no longer significant.ConclusionsPatients with a current disorder have higher instability of NA and PA than remitted patients and controls. Especially with regard to NA, this could be interpreted as patients with a current disorder being more sensitive to internal and external stressors and having suboptimal affect regulation.

Background: Despite increasing evidence for the diagnostic instability between and within depressive and anxiety disorders, most studies report solely on the recurrence rates of the specific index disorders. Neglecting this evidence has an inherent risk of underestimating recurrence rates of depressive and anxiety disorders. This study investigates the impact of diagnostic instability of recurrence rates in depression and anxiety.Methods: Data were derived from the Netherlands Study of Depression and Anxiety (NESDA). The sample of 656 participants had a panic disorder with or without agoraphobia, agoraphobia, social phobia, generalized anxiety disorder, major depressive disorder or dysthymia, and a subsequent remission. Recurrence rates of index disorders (diagnostically stable recurrence) and newly arisen anxiety or depressive disorders (diagnostically unstable recurrence), were calculated over a 4-year follow-up period.Results: In anxiety disorders (n=281), the recurrence rate is more than doubled, from 23.8% with a stable recurrence, to 54.8%, when diagnostically unstable recurrences are included. In depressive disorders (N=173) the recurrence rate increases from 37.6% to 49.7%, and in comorbid anxiety and depressive disorders (N=202) the diagnostically unstable recurrences increase from 54.0% to 66.3%.Limitations: Attrition during follow up may have biased the results; remission was defined as absence of symptoms for 1 month; very short-term remission and recurrence patterns were not assessed.Conclusions: Diagnostically unstable recurrences have a significant impact on recurrence rates, with the greatest instability for anxiety disorders. When only diagnostically stable recurrences are assessed, recurrence rates are highly underrated and provide biased estimates of the true course of these disorders. (C) 2016 Elsevier B.V. All rights reserved.

Contains fulltext : 156142.pdf (Publisher’s version ) (Closed access) Major depressive disorder (MDD) has been associated with abnormalities in speech and behavioural mimicry. These abnormalities may contribute to the impairments in interpersonal functioning that are often seen in MDD patients. MDD has also been associated with disturbances in the brain serotonin system, but the extent to which serotonin regulates speech and behavioural mimicry remains unclear. In a randomized, double-blind, crossover study, we induced acute tryptophan depletion (ATD) in individuals with or without a family history of MDD. Five hours afterwards, participants engaged in two behavioural-mimicry experiments in which speech and behaviour were recorded. ATD reduced the time participants waited before speaking, which might indicate increased impulsivity. However, ATD did not significantly alter speech otherwise, nor did it affect mimicry. This suggests that a brief lowering of brain serotonin has limited effects on verbal and non-verbal social behaviour. The null findings may be due to low test sensitivity, but they otherwise suggest that low serotonin has little effect on social interaction quality in never-depressed individuals. It remains possible that recovered MDD patients are more strongly affected. 9 p.

Heterogeneity of major depressive disorder (MDD) illness course complicates clinical decision-making. Although efforts to use symptom profiles or biomarkers to develop clinically useful prognostic subtypes have had limited success, a recent report showed that machine-learning (ML) models developed from self-reports about incident episode characteristics and comorbidities among respondents with lifetime MDD in the World Health Organization World Mental Health (WMH) Surveys predicted MDD persistence, chronicity and severity with good accuracy. We report results of model validation in an independent prospective national household sample of 1056 respondents with lifetime MDD at baseline. The WMH ML models were applied to these baseline data to generate predicted outcome scores that were compared with observed scores assessed 10-12 years after baseline. ML model prediction accuracy was also compared with that of conventional logistic regression models. Area under the receiver operating characteristic curve based on ML (0.63 for high chronicity and 0.71-0.76 for the other prospective outcomes) was consistently higher than for the logistic models (0.62-0.70) despite the latter models including more predictors. A total of 34.6-38.1% of respondents with subsequent high persistence chronicity and 40.8-55.8% with the severity indicators were in the top 20% of the baseline ML-predicted risk distribution, while only 0.9% of respondents with subsequent hospitalizations and 1.5% with suicide attempts were in the lowest 20% of the ML-predicted risk distribution. These results confirm that clinically useful MDD risk-stratification models can be generated from baseline patient self-reports and that ML methods improve on conventional methods in developing such models.

Rationale Major depressive disorder (MDD) has been associated with disturbances in social functioning and in the brain serotonin system. Reduced levels of serotonin may negatively influence social functioning, for example by impairing the recognition of facial emotion expressions. Objectives The present study investigated the effect of acute tryptophan depletion (ATD), which reduces brain serotonin, on a related component of social functioning, empathic accuracy (EA), and oxytocin levels. Methods Individuals with (FH+) and without (FH−) a family history of MDD participated in a randomized, double-blind, crossover study. On two separate test days, participants ingested tryptophan-deficient and nutritionally balanced amino acid mixtures. Six hours later, they performed an EA task, which involved watching videos of people recounting autobiographical emotional events. While watching, participants continuously rated how these people felt during the recounting. Mood state was repeatedly assessed using the Positive Affect and Negative Affect Schedule and a series of visual analogue scales. Blood samples obtained at baseline and 5 h after mixture ingestion were assessed for tryptophan and oxytocin levels. Results ATD decreased circulating levels of tryptophan and oxytocin. Nevertheless, there were no significant effects of ATD on EA or mood in either FH group. Conclusions While previous studies have shown that acute reductions in brain serotonin alter the recognition of facial emotion expressions in never-depressed individuals, the present study suggests that empathic abilities may remain unaffected. Electronic supplementary material The online version of this article (doi:10.1007/s00213-015-4093-9) contains supplementary material, which is available to authorized users.