Polyunsaturated fatty acids changes during electroconvulsive therapy in major depressive disorder.

Polyunsaturated fatty acids (PUFAs) have important electrochemical properties and have been implicated in the pathophysiology of major depressive disorder (MDD) and its treatment. However, the relation of PUFAs with electroconvulsive therapy (ECT) has never been investigated. Therefore, we aimed to explore the associations between PUFA concentrations and response to ECT in patients with MDD. We included 45 patients with unipolar MDD in a multicentre study. To determine PUFA concentrations, we collected blood samples at the first (T0) and twelfth (T12) ECT-session. We assessed depression severity using the Hamilton Rating Scale for Depression (HAM-D) at T0, T12 and at the end of the ECT-course. ECT-response was defined as 'early response' (at T12), 'late response' (after ECT-course) and 'no' response (after the ECT-course). The PUFA chain length index (CLI), unsaturation index (UI) and peroxidation index (PI) and three individual PUFAs (eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA] and nervonic acid [NA]) were associated with response to ECT using linear mixed models. Results showed a significant higher CLI in 'late responders' compared to 'non responders'. For NA, 'late responders' showed significantly higher concentrations compared to 'early'- and 'non responders'. In conclusion, this study provides the first indication that PUFAs are associated with the efficacy of ECT. This indicates that PUFAs' influence on neuronal electrochemical properties and neurogenesis may affect ECT outcomes. Thereby, PUFAs form a potentially modifiable factor predicting ECT outcomes, that warrants further investigation in other ECT-cohorts.

Anhedonia as a transdiagnostic symptom across psychological disorders: a network approach.

BACKGROUND: Anhedonia is apparent in different mental disorders and is suggested to be related to dysfunctions in the reward system and/or affect regulation. It may hence be a common underlying feature associated with symptom severity of mental disorders. METHODS: We constructed a cross-sectional graphical Least Absolute Shrinkage and Selection Operator (LASSO) network and a relative importance network to estimate the relationships between anhedonia severity and the severity of symptom clusters of major depressive disorder (MDD), anxiety sensitivity (AS), attention-deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD) in a sample of Dutch adult psychiatric patients (N = 557). RESULTS: Both these networks revealed anhedonia severity and depression symptom severity as central to the network. Results suggest that anhedonia severity may be predictive of the severity of symptom clusters of MDD, AS, ADHD, and ASD. MDD symptom severity may be predictive of AS and ADHD symptom severity. CONCLUSIONS: The results suggest that anhedonia may serve as a common underlying transdiagnostic psychopathology feature, predictive of the severity of symptom clusters of depression, AS, ADHD, and ASD. Thus, anhedonia may be associated with the high comorbidity between these symptom clusters and disorders. If our results will be replicated in future studies, it is recommended for clinicians to be more vigilant about screening for anhedonia and/or depression severity in individuals diagnosed with an anxiety disorder, ADHD and/or ASD.

Negative memory bias as a transdiagnostic cognitive marker for depression symptom severity.

BACKGROUND: Negative memory bias is a strong risk factor for the development and maintenance of depression. Recent evidence also found negative memory bias in other mental disorders. Here, we aim to: 1) assess the presence and strength of negative memory bias in a range of (comorbid) mental disorders, 2) investigate which disorder-specific symptoms are associated with negative memory bias, and 3) test whether negative memory bias might be a transdiagnostic mechanism. METHODS: Negative memory bias was measured in patients with at least one diagnosis of a stress-related disorder (n = 86), a neurodevelopmental disorder (n = 53), or both (n = 68), and 51 controls. Depression, anxiety, attention-deficit/hyperactivity disorder, and autism spectrum disorder symptom severity was assessed using questionnaires. Groups were compared on negative memory bias and the associations between negative memory bias and symptom severity were made using linear regression models. RESULTS: All patient groups showed stronger negative memory bias than the controls. Negative memory bias was individually associated with all symptom severity indices, but when added into a single model, only the association with depressive symptom severity remained. This persisted after controlling for diagnostic group. LIMITATIONS: Due to the cross-sectional sectional study design, we could only look at the associations between negative memory bias and disorder-specific symptoms and not at the direction of the effects. CONCLUSIONS: Negative memory bias is characteristic of a depressotypic processing style and present in different mental disorders. It might play a mechanistic role in the development of (subclinical) co-occurrence between mental disorders.

A randomized controlled trial of a standard 4-week protocol of repetitive transcranial magnetic stimulation in severe treatment resistant depression.

BACKGROUND: Treatment options for major depressive disorder (MDD) in individuals who are depressed for at least 2 years and failed two or more different types of therapeutic intervention, remain scarce. Being less invasive than electroconvulsive therapy, repetitive transcranial magnetic stimulation (rTMS) might be an alternative treatment option. RESEARCH QUESTION: Does high frequency rTMS applied over the left prefrontal cortex ameliorate depressive symptoms in patients with treatment resistant major depressive disorder and is the efficacy dependent on treatment resistance? METHOD: We performed a randomized controlled trial investigating the effect of twenty sessions of real or sham-rTMS, during 4 consecutive weeks. Efficacy was blindly rated with the Hamilton depression rating scale (HDRS-17) at baseline and 1 week after end of treatment, and the Dutch method for quantification of treatment resistance in Depression (DM-TRD) was assessed at baseline. RESULTS: An interim analysis showed no differences in antidepressant response between real and sham rTMS and we therefore discontinued the RCT after 31 patients. The mean difference of the HDRS score between baseline and post-treatment was 3.7 (± 4.0; change 16%), indicating a small but significant improvement across time (F(1,30)=25.4;p < 0.01). There were no differences however between the treatment arms (F(1.30) = 1.5;p = 0.23). We did find a negative correlation between the change in HDRS score and DM-TRD in the active rTMS group, but this correlation was not significantly different from the sham group. CONCLUSION: "Standard" 4-week rTMS treatment is not effective in chronic, severe treatment-resistant depressed patients. While a replication of our data in this patient group may be ethically difficult, further research with less treatment resistant patients might help in positioning rTMS within the current stepped care approach to depression.

[Antidepressants are frequently prescribed but still critized; a perspective on causes and solutions]. / Antidepressiva: al decennia voor­geschreven én toch nog steeds bekritiseerd; een perspectief op oorzaken en oplossingen.

BACKGROUND: From around 1980, antidepressants (ad) have increasingly been prescribed, for longer periods of time, especially selective serotonin reuptake inhibitors (ssris). Paradoxically, their effectiveness is still doubted, especially outside the psychiatric profession.
AIM: To explain increase and offer a perspective on causes and solutions, and to indicate how to reach consensus.
METHOD: Position paper with critical analysis and synthesis of relevant literature.
RESULTS: The rise in AD prescriptions results from: 1. increased safety and ease of prescribing, 2. increased presentation and recognition of depression in primary care, 3. extension of indication criteria, 4. effective marketing strategies, and 5. effectiveness in acute phase (aad) and of relapse/recurrence prevention in continuation/maintenance phases (coad).Critics point to: 1. low added value of aad relative to placebo, 2. many drop-outs and non-responders, 3. relapse/recurrence prevention with coad works only for responders to aad, 4. relapse/recurrence after AD discontinuation often involves withdrawal symptoms, and 5. publication bias, selective reporting, selective patient selection, and suboptimal blinding, resulting in overestimated effectiveness and underestimated disadvantages.Factors that keep fueling the controversy are: 1. critics stress the net effectiveness of AD whereas proponents point at gross effectiveness which includes spontaneous recovery and placebo effect; 2. persistence of distrust in industry-funded rcts; 3. ideological positions, reinforced by conflicts of interest and selective citations; 4. lack of rcts with relevant long-term outcome measurements.
CONCLUSION: Although consensus is difficult to achieve given the ideological component, there are options. Three factors are critically important: confer to establish which data convince the opposition, response prediction (what works for whom), and rcts with long-term functional outcomes.

Absence of default mode downregulation in response to a mild psychological stressor marks stress-vulnerability across diverse psychiatric disorders.

Clinically, it is well-established that vulnerability to stress is a common feature across a broad spectrum of psychiatric disorders. However, this link has been mechanistically studied almost exclusively in patients with so-called stress-related disorders such as depression and anxiety. To probe transdiagnostic mechanisms, we set out to study the acute stress response across a broader range of psychiatric disorders taking a large-scale brain network perspective. We investigated the brain's response to a mild, experimentally well-controlled psychological stressor in the form of an aversive movie. We studied 168 patients with stress-related and/or neurodevelopmental disorders (including comorbidity) and 46 control subjects. We focused on three networks that have a central role in the brain's stress response and are affected in a wide range of psychiatric disorders: the salience network (SN), default mode network (DMN) and frontoparietal network (FPN). Our results support an increased vulnerability to stress across all patients, indicated by a higher subjective stress level at baseline and follow-up compared to matched controls. At the brain systems level, the stress response was characterized by a relatively decreased FPN connectivity and an absence of a decrease in the within DMN connectivity across all disorders compared to controls. At the neurocognitive level, these findings may reflect a diminished top-down control and a tendency to more pronounced (negative) self-referential processing. Besides these shared aspects of the maladaptive stress response, we also discuss indications for disorder-specific aspects. Taken together, our results emphasize the importance of investigating the mechanistic underpinnings of psychiatric disorders transdiagnostically as recently done in neurogenetics.

Fatty acids and recurrence of major depressive disorder: combined analysis of two Dutch clinical cohorts.

OBJECTIVE: Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acid (PUFA) alterations in patients with major depressive disorder (MDD) have been shown to persist after remission. Whether these alterations are risk factors for MDD recurrence remains unknown. Here, we examined whether fatty acids predict time until MDD recurrence in remitted MDD patients. METHODS: Data were used from remitted MDD patients of the Netherlands Study of Depression and Anxiety (n = 356) and the Depression Evaluation Longitudinal Therapy Assessment studies (n = 118). Associations of FAs with time until MDD recurrence up to 8-year follow-up were analyzed using Cox regression analyses. Study-specific estimates were pooled using mega- and meta-analysis techniques. RESULTS: 27.5% (NESDA) and 56.8% (DELTA) participants had an MDD recurrence. Pooled results showed that no FA was significantly associated with time until MDD recurrence (n-3 PUFAs: hazard ratio (HR) = 1.17, 95% confidence interval (CI) = 0.98-1.41, P = 0.082; n-6 PUFAs: HR = 1.08, 95% CI = 0.84-1.38, P = 0.55). CONCLUSION: In remitted MDD patients, circulating PUFAs were not associated with prospective risk of MDD recurrence. Consequently, circulating PUFAs are unlikely to reflect a vulnerability marker for recurrence, so correcting n-3 PUFA 'deficits' through supplementation does not seem a promising option to prevent MDD recurrence.

Iatrogenic opioid use disorder, chronic pain and psychiatric comorbidity: A systematic review.

OBJECTIVE: A systematic review of the literature on the risks of developing iatrogenic opioid use disorders in chronic pain patients with psychiatric comorbidity. METHODS: We conducted literature searches on Pubmed with key subjects: "chronic pain", "psychiatry", "opioids" and "opioid use disorder" and for original, English written articles published from 2000 until the first of September 2017. Final selection of the articles for review was made in a consensus between three reviewers. RESULTS: Longitudinal studies showed a significant association between psychiatric comorbidity, especially depression and anxiety disorders and the development of problematic opioid use, more severe opioid craving and poor opioid treatment outcome (analgesia and side effects) in chronic pain patients. Cross-sectional studies showed a similar association between psychiatric disorders and problematic opioid use, where studies in specialized pain settings showed a higher prevalence of psychiatric disorders, compared to non-specialized settings. CONCLUSIONS: This systematic review showed a significant association between psychiatric comorbidity, especially depression and anxiety disorders and the development of problematic opioid use in chronic pain patients. We therefore recommend psychiatric screening in chronic pain management. Chronic pain patients with comorbid psychiatric disorders need a multidisciplinary approach and monitoring opioid use is warranted in these patients.

Cortisol, dehydroepiandrosterone sulfate, fatty acids, and their relation in recurrent depression.

BACKGROUND: Alterations in hypothalamic-pituitary-adrenal (HPA)-axis activity, fatty acid metabolism, and their relation have been associated with (recurrent) major depressive disorder (MDD), although conflicting findings exist. AIMS: To determine whether alterations in HPA-axis activity and fatty acids in recurrent MDD remain during remission (i.e. reflect a potential trait factor). Furthermore, to test the association between HPA-axis activity and fatty acids in patients versus controls. METHODS: We cross-sectionally compared 73 remitted unmedicated recurrent MDD patients with 46 matched never-depressed controls. Measurements included salivary cortisol and dehydroepiandrosterone sulfate (DHEAS) (awakening, evening, and after sad mood induction) and erythrocyte fatty acid parameters: (I) three main fatty acids [omega-3 docosahexaenoic acid (DHA), and the omega-3 eicosapentaenoic acid/omega-6 arachidonic acid (EPA/AA)-ratio], and (II) structural fatty acid indices [chain length, unsaturation and peroxidation]. RESULTS: Patients showed higher cortisol awakening responses (p = 0.006) and lower evening cortisol/DHEAS ratios (p = 0.044) compared to matched controls. Fatty acids did not differ between patients and controls, but HPA-axis indicators were significantly associated with fatty acid parameters in both groups (0.001 ≤ p ≤ 0.043). Patients and controls significantly differed in the relations between awakening DHEAS or cortisol/DHEAS ratios and fatty acid parameters, including unsaturation and peroxidation indices (0.001≤ p ≤ 0.034). Significance remained after correction for confounders. CONCLUSIONS: Our results further support alterations in HPA-axis activity, i.e. a lower baseline, but higher responsiveness of awakening cortisol, in remitted medication-free recurrent MDD patients. Furthermore, the relationship between HPA-axis and fatty acids showed significant differences in recurrent MDD patients versus controls. Prospective research is needed to determine the predictive value of this relationship for MDD recurrence.

[The patient's perspective on the self-management and professional treatment of depression]. / Zelfmanagement bij en behandeling van depressie; het patiëntenperspectief.

BACKGROUND: More than two-thirds of all patients suffering from depression experience insufficient improvement despite treatment. Self-management strategies and treatment objectives should be more in line with what patients consider to be helpful. This would improve the treatment efficacy of domains relevant to patients and allow for self-management of depression where possible.
AIM: To explore the patient's perspective on self-management and professional treatment for depression.
METHOD: Predominantly qualitative methods: in-depth individual interviews, concept mapping (mixed method) and a nationwide self-report survey.
RESULTS: Participants generated 50 self-management strategies addressing themes such as engaging in activities (e.g. 'leaving the house regularly'), focus on the diagnosis depression (e.g. 'acceptation') and treatment (e.g. 'trusting the therapist'), remaining socially engaged (e.g. 'informing family about the depression') and good structure and self-care (e.g. 'setting realistic goals'). A lack of clarity and consensus about either the nature of the depression or the content of treatment and a precarious relationship with the professional were perceived as impeding characteristics of treatment.
CONCLUSION: Patients appear to be able to contribute actively and in various ways when managing their own mental health. By exploring the patient's perspectives, professionals could offer treatment established through shared goals.

[The diagnosis of unipolar versus bipolar disorders using neuroimaging]. / Diagnostiek van uni- versus bipolaire stoornissen middels neuro-imaging.

BACKGROUND: Clinical differentiation between unipolar and bipolar depression can be a challenge. Additional diagnostic tools based on biomarkers could help resolve ambiguous cases. In this article we discuss studies from the dissertation 'Bipolar or unipolar? A brain teasing question', investigating to which extent neuroimaging could contribute to such detection.
AIM: To investigate whether neuroimaging can aid in differentiating between uni- and bipolar disorder.
METHOD: An analysis of the brain anatomy and functioning in medication-free uni- and bipolar participants and healthy controls using magnetic resonance imaging (MRI).
RESULTS: The results indicate that there are differences regarding both brain structure and functioning when comparing unipolar and bipolar patients. The nature of these differences corresponded with the present mood state. Diagnosis could also be predicted on an individual level. However, direct implementation during clinical practice is currently not possible, in part due to the heterogeneity of the findings and the limitations inherent to MRI-research.
CONCLUSION: Neuroimaging may be a promising technique for development of additional diagnostic tools to differentiate between unipolar and bipolar disorder.

Focus on fatty acids in the neurometabolic pathophysiology of psychiatric disorders.

Continuous research into the pathophysiology of psychiatric disorders, such as major depressive disorder (MDD), posttraumatic stress disorder (PTSD), and schizophrenia, suggests an important role for metabolism. This narrative review will provide an up-to-date summary of how metabolism is thought to be involved in the pathophysiology of these psychiatric disorders. We will focus on (I) the important role of fatty acids in these metabolic alterations, (II) whether fatty acid alterations represent epiphenomena or risk factors, and (III) similarities and dissociations in fatty acid alterations between different psychiatric disorders. (Historical) epidemiological evidence links fatty acid intake to psychiatric disorder prevalence, corroborated by altered fatty acid concentrations measured in psychiatric patients. These fatty acid alterations are connected with other concomitant pathophysiological mechanisms, including biological stress (hypothalamic-pituitary-adrenal (HPA)-axis and oxidative stress), inflammation, and brain network structure and function. Metabolomics and lipidomics studies are underway to more deeply investigate this complex network of associated neurometabolic alterations. Supplementation of fatty acids as disease-modifying nutraceuticals has clinical potential, particularly add-on eicosapentaenoic acid (EPA) in depressed patients with markers of increased inflammation. However, by interpreting the observed fatty acid alterations as partly (mal)adaptive phenomena, we attempt to nuance translational expectations and provide new clinical applications for these novel neurometabolic insights, e.g., to predict treatment response or depression recurrence. In conclusion, placing fatty acids in context can contribute to further understanding and optimized treatment of psychiatric disorders, in order to diminish their overwhelming burden of disease.

Cortical abnormalities in bipolar disorder: an MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group.

Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d=-0.293; P=1.71 × 10-21), left fusiform gyrus (d=-0.288; P=8.25 × 10-21) and left rostral middle frontal cortex (d=-0.276; P=2.99 × 10-19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.

How the brain connects in response to acute stress: A review at the human brain systems level.

The brain's response to stress is a matter of extensive neurocognitive research in an attempt to unravel the mechanistic underpinnings of neural adaptation. In line with the broadly defined concept of acute stress, a wide variety of induction procedures are used to mimic stress experimentally. We set out to review commonalities and diversities of the stress-related functional activity and connectivity changes of functional brain networks in healthy adults across procedures. The acute stress response is consistently associated with both increased activity and connectivity in the salience network (SN) and surprisingly also with increased activity in the default mode network (DMN), while most studies show no changes in the central executive network. These results confirm earlier findings of an essential, coordinating role of the SN in the acute stress response and indicate a dynamic role of the DMN whose function is less clear. Moreover, paradigm specific brain responses have to be taken into account when investigating the role and the within and between network connectivity of these three networks.

Dietary pattern derived by reduced rank regression and depressive symptoms in a multi-ethnic population: the HELIUS study.

BACKGROUND/OBJECTIVES: To investigate the association of dietary patterns derived by reduced rank regression (RRR) with depressive symptoms in a multi-ethnic population. SUBJECTS/METHODS: Cross-sectional data from the HELIUS study were used. In total, 4967 men and women (18-70 years) of Dutch, South-Asian Surinamese, African Surinamese, Turkish and Moroccan origin living in the Netherlands were included. Diet was measured using ethnic-specific food frequency questionnaires. Depressive symptoms were measured with the nine-item patient health questionnaire. RESULTS: By performing RRR in the whole population and per ethnic group, comparable dietary patterns were identified and therefore the dietary pattern for the whole population was used for subsequent analyses. We identified a dietary pattern that was strongly related to eicosapentaenoic acid+docosahexaenoic acid, folate, magnesium and zinc (response variables) and which was characterized by milk products, cheese, whole grains, vegetables, legumes, nuts, potatoes and red meat. After adjustment for confounders, a statistically significant inverse association was observed in the whole population (B: -0.03, 95% CI: -0.06, -0.00, P=0.046) and among Moroccan (B: -0.09, 95% CI: -0.13, -0.04, P=0.027) and South-Asian Surinamese participants (B: -0.05, 95% CI: -0.09, -0.01, P=<0.001), whereas no statistically significant association was found in the remaining ethnic groups. No statistically significant associations were found between the dietary pattern and significant depressed mood in any of the ethnic groups. CONCLUSIONS: No consistent evidence was found that consumption of a dietary pattern, high in nutrients that are hypothesized to protect against depression, was associated with lower depressive symptoms across different ethnic groups.

The impact of frailty on depressive disorder in later life: Findings from the Netherlands Study of depression in older persons.

BACKGROUND: Physical frailty and depressive symptoms are reciprocally related in community-based studies, but its prognostic impact on depressive disorder remains unknown. METHODS: A cohort of 378 older persons (≥60 years) suffering from a depressive disorder (DSM-IV criteria) was reassessed at two-year follow-up. Depressive symptom severity was assessed every six months with the Inventory of Depressive Symptomatology, including a mood, motivational, and somatic subscale. Frailty was assessed according to the physical frailty phenotype at the baseline examination. RESULTS: For each additional frailty component, the odds of non-remission was 1.24 [95% CI=1.01-1.52] (P=040). Linear mixed models showed that only improvement of the motivational (P<001) subscale and the somatic subscale (P=003) of the IDS over time were dependent on the frailty severity. CONCLUSIONS: Physical frailty negatively impacts the course of late-life depression. Since only improvement of mood symptoms was independent of frailty severity, one may hypothesize that frailty and residual depression are easily mixed-up in psychiatric treatment.

Biological profiling of prospective antidepressant response in major depressive disorder: Associations with (neuro)inflammation, fatty acid metabolism, and amygdala-reactivity.

BACKGROUND: A better understanding of factors underlying antidepressant non-response may improve the prediction of which patients will respond to what treatment. Major depressive disorder (MDD) is associated with alterations in fatty acid metabolism, (neuro)inflammation and amygdala-reactivity. However, their mutual relations, and the extent to which they are associated with prospective antidepressant-response, remain unknown. PURPOSE: To test (I) alterations in (neuro)inflammation and its associations with fatty acid metabolism and amygdala-reactivity in MDD-patients compared to controls, and (II) whether these alterations are associated with prospective paroxetine response. METHODS: We compared 70 unmedicated MDD-patients with 51 matched healthy controls at baseline, regarding erythrocyte membrane omega-6 arachidonic acid (AA), inflammation [serum (high-sensitivity) C-reactive protein (CRP)], and in a subgroup amygdala-reactivity to emotional faces using functional magnetic resonance imaging (fMRI) (N=42). Subsequently, we treated patients with 12 weeks paroxetine, and repeated baseline measures after 6 and 12 weeks to compare non-responders, early-responders (response at 6 weeks), and late-responders (response at 12 weeks). RESULTS: Compared to controls, MDD-patients showed higher CRP (p=0.016) and AA (p=0.019) after adjustment for confounders at baseline. AA and CRP were mutually correlated (p=0.043). In addition, patients showed a more negative relation between AA and left amygdala-reactivity (p=0.014). Moreover, AA and CRP were associated with antidepressant-response: early responders showed lower AA (p=0.018) and higher CRP-concentrations (p=0.008) than non-responders throughout the study. CONCLUSION: Higher observed CRP and AA, their mutual association, and relation with amygdala-reactivity, are corroborative with a role for (neuro)inflammation in MDD. In addition, observed associations of these factors with prospective antidepressant-response suggest a potential role as biomarkers. Future studies in independent samples are needed to replicate and test the clinical applicability of these biological predictors for treatment response to result in a precision/personalized medicine approach for treatment.

[Behavioural activation as a first-line treatment for depression]. / Gedragsactivatie als eerstelijnsbehandeling voor depressie.

Psychological treatments are important to reduce the global burden of depression; however, cognitive behavioural therapy (CBT), which is considered the gold-standard treatment, is costly and sparsely available. Behavioural activation (BA) is a psychological treatment aimed at overcoming depression by increasing positive activities, with the help of registration and activity scheduling. It is a simpler and less costly alternative to CBT, and is no less effective in the treatment of moderate to severe depression. Two-thirds of depressed patients can be effectively treated with BA, providing evidence for it being an important extension of the therapeutic arsenal for depression; this will quite probably be reflected by a more prominent place for this treatment in upcoming guidelines.

[Does less seclusion create a safer environment? An attempt to map the concept of 'feeling safe']. / Minder separeren, veiligheid creëren; het concept 'veiligheidsgevoel' in beeld gebracht.

BACKGROUND: The degree of restraint imposed by a psychiatrist seems to be influenced by the safety of the team. So far, there have been few attempts to map the concept of 'feeling safe'.
AIM: To analyse, define and quantify the concept of 'feeling safe'.
METHOD: Concept mapping involves combining, in a structured way, qualitative (item collection) and quantitative methods (multi-dimensional scaling and hierarchical clusteranalysis) with the knowledge of professionals from psychiatric practice (N=24), first on an individual basis and then as a group (N=8).
RESULTS: The participants generated and prioritised a total of 97 different items. These were then divided into six clusters: organisational structure, professionalism of team members, increased expertise, marginal conditions, internal and external features of the hospital building, views on mental health care and policy. Group members gave almost equal priority to the clusters, but they assigned different degrees of importance to separate items (ranging from 4.63 to 2.38 on a five-point scale).
CONCLUSION: Concept mapping is an adequate method of defining the concept of 'feeling safe'. Professionalism of the team and qualities such as openness and ability to communicate, expertise and trusting one's colleagues and having an adequate alarm system available are all important factors that help to make employees 'feel safe' in their respective departments.

[Tailored pharmacotherapy. Consultations about medication in a care programme for depression]. / Farmacotherapie op maat; medicatieconsulten in een zorgprogramma voor depressie.

BACKGROUND: Despite the increasing rationalisation of mental health care, there are no specific recommendations regarding the number of contacts between a patient and a psychiatrist for the pharmacotherapy that forms part of the combined outpatient treatment (antidepressants and psychotherapy) of depression. AIM: To consider the possibility of drawing up an advisory document regarding frequency, number and duration of consultations about medication in combined treatment for depression. METHOD: We reviewed the literature and had qualitative interviews with psychiatrists and trainees in psychiatric residency. RESULTS: The literature focuses predominantly on diagnostics and patient characteristics that determine the amount of care required. Advice on medication and pharmacotherapy is provided only by experts. According to the interviews, in psychiatric practice many factors influence the number and duration of consultations. Nevertheless, a distinctive pattern emerged. CONCLUSION: Regarding medication in the acute treatment phase, five or six visits to a psychiatrist are sufficient for most patients. Extra consultations have to be arranged for smaller groups of less stable patients and for crisis-prone patients.