Circadian markers as a predictor of response in the treatment of depression-A systematic review.

Despite many available treatment options for depression, response rates remain suboptimal. To improve outcome, circadian markers may be suitable as markers of treatment response. This systematic review provides an overview of circadian markers that have been studied as predictors of response in treatment of depression. A search was performed (EMBASE, PUBMED, PSYCHINFO) for research studies or articles, randomized controlled trials and case report/series with no time boundaries on March 2, 2024 (PROSPERO: CRD42021252333). Other criteria were; an antidepressant treatment as intervention, treatment response measured by depression symptom severity and/or occurrence of a clinical diagnosis of depression and assessment of a circadian marker at baseline. 44 articles, encompassing 8,772 participants were included in the analysis. Although additional research is needed with less variation in types of markers and treatments to provide definitive recommendations, circadian markers, especially diurnal mood variation and chronotype, show potential to implement as response markers in the clinic.

Increased fermentable carbohydrate intake alters colonic mucus barrier function through glycation processes and increased mast cell counts.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder for which dietary interventions can be a useful treatment. In recent years, the low-FODMAP approach is gaining traction in this regard. The fermentation of these non-absorbed carbohydrates by the gut microbiota can generate toxic glycating metabolites, such as methylglyoxal. These metabolites can have harmful effects by their role in the generation of advanced glycation end products (AGEs), which activates Receptor for AGEs (AGER). Mast cells can be stimulated by AGEs and play a role in IBS. We have treated mice with lactose or fructo-oligosaccharides (FOS), with or without co-administration of pyridoxamine and investigated the colonic mucus barrier. We have found that an increased intake of lactose and fructo-oligosaccharides induces a dysregulation of the colonic mucus barrier, increasing mucus discharge in empty colon, while increasing variability and decreasing average thickness mucus layer covering the fecal pellet. Changes were correlated with increased mast cell counts, pointing to a role for the crosstalk between these and goblet cells. Additionally, AGE levels in colonic epithelium were increased by treatment with the selected fermentable carbohydrates. Observed effects were prevented by co-treatment with anti-glycation agent pyridoxamine, implicating glycation processes in the negative impact of fermentable carbohydrate ingestion. This study shows that excessive intake of fermentable carbohydrates can cause colonic mucus barrier dysregulation in mice, by a process that involves glycating agents and increased mucosal mast cell counts.

Chronotype changes with age; seven-year follow-up from the Netherlands study of depression and anxiety cohort.

BACKGROUND: Chronotype reflects an individual's optimal daily timing of sleep, activity, and cognitive performance. Previous, cross-sectional, studies have suggested an age effect on chronotype with later chronotypes in adolescents and earlier chronotypes in children and elderly. Additionally, later chronotypes have been associated with more depressive symptoms. Few studies have been able to study longitudinal associations between chronotype and age, while adjusting for depressive symptoms. METHODS: Chronotype was assessed twice with the Munich Chronotype Questionnaire 7 years apart in the Netherlands Study of Depression and Anxiety (T1: N = 1842, mean age (SD): 42.63 years (12.66)) and T2: N = 1829, mean age (SD) 50.67 (13.11)). The longitudinal association between change in age and change in chronotype was tested using a generalized estimated equation analysis adjusted for covariates (including level of depressive symptoms). Using age-bins of 5 years (age at T2), change in chronotype between T1 and T2 was analyzed with Linear Mixed Models. RESULTS: We found a change towards an earlier chronotype with higher age (B (95% CI): -0.011 (-0.014-0.008), p < 0.001). For the age-bins, the difference in chronotype was significant for the 25-29 years age-bin. LIMITATIONS: The sample did not include individuals younger than 19 years or older than 68 years. CONCLUSIONS: In the whole sample chronotype changed towards becoming more morning-type over a period of 7 years, but this change was only significant for those aged 25-29 years. The study was performed in a large naturalistic cohort study with a wide age-range, including patients with a diagnosis of depressive and anxiety disorder and healthy controls.

Task-specific training for improving propulsion symmetry and gait speed in people in the chronic phase after stroke: a proof-of-concept study.

BACKGROUND: After stroke, some individuals have latent, propulsive capacity of the paretic leg, that can be elicited during task-specific gait training. The aim of this proof-of-concept study was to investigate the effect of five-week robotic gait training for improving propulsion symmetry by increasing paretic propulsion in chronic stroke survivors. METHODS: Twenty-nine individuals with chronic stroke and impaired paretic propulsion (≥ 8% difference in paretic vs. non-paretic propulsive impulse) were enrolled. Participants received ten 60-min sessions of individual robotic gait training targeting paretic propulsion (five weeks, twice a week), complemented with home exercises (15 min/day) focusing on increasing strength and practicing learned strategies in daily life. Propulsion measures, gait kinematics and kinetics, self-selected gait speed, performance of functional gait tasks, and daily-life mobility and physical activity were assessed five weeks (T0) and one week (T1) before the start of intervention, and one week (T2) and five weeks (T3) after the intervention period. RESULTS: Between T0 and T1, no significant differences in outcomes were observed, except for a marginal increase in gait speed (+ 2.9%). Following the intervention, propulsion symmetry (+ 7.9%) and paretic propulsive impulse had significantly improved (+ 8.1%), whereas non-paretic propulsive impulse remained unchanged. Larger gains in propulsion symmetry were associated with more asymmetrical propulsion at T0. In addition, following the intervention significantly greater paretic trailing limb angles (+ 6.6%) and ankle plantarflexion moments (+ 7.1%) were observed. Furthermore, gait speed (+ 7.2%), 6-Minute Walk Test (+ 6.4%), Functional Gait Assessment (+ 6.5%), and daily-life walking intensity (+ 6.9%) had increased following the intervention. At five-week follow-up (T3), gains in all outcomes were retained, and gait speed had further increased (+ 3.6%). CONCLUSIONS: The post-intervention gain in paretic propulsion did not only translate into improved propulsion symmetry and gait speed, but also pertained to performance of functional gait tasks and daily-life walking activity levels. These findings suggest that well-selected chronic stroke survivors may benefit from task-specific targeted training to utilize the residual propulsive capacity of the paretic leg. Future research is recommended to establish simple baseline measures for identification of individuals who may benefit from such training and confirm benefits of the used training concepts in a randomized controlled trial. TRIAL REGISTRATION: Registry number ClinicalTrials.gov ( www.clinicaltrials.gov ): NCT04650802, retrospectively registered 3 December 2020.

ONCOR: design of the Dutch cardio-oncology registry.

BACKGROUND: The relative new subspecialty 'cardio-oncology' was established to meet the growing demand for an interdisciplinary approach to the management of cancer therapy-related cardiovascular adverse events. In recent years, specialised cardio-oncology services have been implemented worldwide, which all strive to improve the cardiovascular health of cancer patients. However, limited data are currently available on the outcomes and experiences of these specialised services, and optimal strategies for cardio-oncological care have not been established. AIM: The ONCOR registry has been created for prospective data collection and evaluation of cardio-oncological care in daily practice. METHODS: Dutch hospitals using a standardised cardio-oncology care pathway are included in this national, multicentre, observational cohort study. All patients visiting these cardio-oncology services are eligible for study inclusion. Data collection at baseline consists of the (planned) cancer treatment and the cardiovascular risk profile, which are used to estimate the cardiotoxic risk. Information regarding invasive and noninvasive tests is collected during the time patients receive cardio-oncological care. Outcome data consist of the incidence of cardiovascular complications and major adverse cardiac events, and the impact of these events on the oncological treatment. DISCUSSION: Outcomes of the ONCOR registry may aid in gaining more insight into the incidence of cancer therapy-related cardiovascular complications. The registry facilitates research on mechanisms of cardiovascular complications and on diagnostic, prognostic and therapeutic strategies. In addition, it provides a platform for future (interventional) studies. Centres with cardio-oncology services that are interested in contributing to the ONCOR registry are hereby invited to participate.

[Ketamine as an anesthetic, analgesic and anti-depressant]. / Ketamine als anestheticum, analgeticum en als antidepressivum.

BACKGROUND: Treatment-resistance occurs in about 30% of patients with depression. Therefore, there is an urgent need to identify new treatment strategies. Ketamine, originally developed as an anesthetic, is studied and applied as treatment for patients with treatment-resistant depression.
AIM: A critical review of the current use of ketamine as an antidepressant.
METHOD: Literature study.
RESULTS: Ketamine is a proven effective acute antidepressant. However, limited information is available about maintenance of effect of ketamine, potential risks of repeated administration, and different routes of administration and treatment schedules.
CONCLUSION: Additional research on ketamine as an antidepressant is needed. Meanwhile, (off-label) treatment should only be applied after careful patient selection and under close monitoring.

[Housing, natural light and lighting, greenery and mental health]. / Huisvesting, lichtinval, groenvoorziening en geestelijke gezondheid.

BACKGROUND: Studies suggest that light and nature should be seriously considered when building new psychiatric clinics, because of their positive effects on psychiatric recovery.
AIM: To highlight positive and sustainable effects of light and greenery in mental health care.
METHOD: Literature study.
RESULTS: Daylight, artificial light and nature may have a positive influence on recovery and wellbeing of patients and employees in care institutions.
CONCLUSION: Taking light and nature into account in the design of a new psychiatric hospital is highly important. This can facilitate mental health of the users of the building.

Sleep restriction therapy may be effective for people with insomnia and depressive complaints: evidence from a case series.

BACKGROUND: Insomnia and depression are clearly interrelated. Several studies showed that treating insomnia with cognitive behavioural therapy positively affects concurrent depressive symptoms. However, it is unclear what treatment component is responsible for the change in depressive symptoms. AIMS: To develop the evidence base we employed a case series design in which we administered a single component sleep restriction treatment to individuals with both insomnia and depressive symptoms. METHOD: Seven patients were included, of whom six completed the intervention. Patients completed weekly assessments during the 4-week wait period and 6-week treatment phase. RESULTS: At the post-assessment, two out of six patients showed clinical improvement in depressive symptoms. All six patients showed clinically meaningful improvement at the 3-month follow-up assessment, and two patients had maintained gains at 6-month follow-up. CONCLUSIONS: This case series study shows that, especially at 3-month follow-up, sleep restriction therapy is associated with clinically relevant treatment gains in patients with both insomnia and depressive symptoms.

Cognitive processes mediate the effects of insomnia treatment: evidence from a randomized wait-list controlled trial.

INTRODUCTION: Both guided online and individual face-to-face cognitive behavioral therapy for insomnia (CBT-I) are effective in improving insomnia symptoms and sleep efficiency. Little is known about the underlying mechanisms generating this effect. The present study tests the assumption that pre-sleep arousal, sleep-related worry and dysfunctional beliefs about sleep are mediators in the effect of cognitive behavioral treatment for insomnia. METHODS: A secondary analysis was performed on data previously collected from a randomized controlled trial (N = 90). In this trial, participants were randomized to either a face-to-face CBT-I condition, an internet-delivered CBT-I condition, or a wait-list group. This article reports on the efficacy of these interventions on pre-sleep arousal, sleep-related worry, and dysfunctional beliefs. Furthermore, we investigated whether these measures mediated the treatment effect on insomnia severity and sleep efficiency. RESULTS: Both treatment modalities were efficacious for these cognitive measures; however, face-to-face treatment showed superiority over the online treatment. All three cognitive measures mediated the effect on insomnia severity. Sleep-related worry and pre-sleep arousal mediated the effect on sleep efficiency, but dysfunctional beliefs did not. CONCLUSION: Overall, these results point toward the importance of cognitive processes in the treatment of insomnia, implying that psychological treatments for insomnia may best be guided by (also) targeting these cognitive processes.

Cardio-oncology: an overview on outpatient management and future developments.

Recent advances in the early detection and treatment of cancer have led to increasing numbers of cancer survivors worldwide. Nonetheless, despite major improvements in the outcome of these patients, long-term side effects of radio- and chemotherapy affect both patient survival and quality of life, independent of the oncological prognosis. Chemotherapy-related cardiac dysfunction is one of the most notorious short-term side effects of anticancer treatment, occurring in ~10% of patients. Progression to overt heart failure carries a strikingly poor prognosis with a 2-year mortality rate of 60%. Early detection of left ventricular damage by periodic monitoring and prompt initiation of heart failure treatment is key in improving cardiovascular prognosis. To meet the growing demand for a specialised interdisciplinary approach for the prevention and management of cardiovascular complications induced by cancer treatment, a new discipline termed cardio-oncology has evolved. However, an uniform, multidisciplinary approach is currently lacking in the Netherlands. This overview provides an introduction and comprehensive summary of this emerging discipline and offers a practical strategy for the outpatient management of this specific patient population.

Mucus organisation is shaped by colonic content; a new view.

The colonic mucus barrier is commonly described as a continuous double layer covering the epithelium, separating the microbiota from the intestinal tissue. This model is currently considered valid throughout the colon. The colon is characterised by regional anatomo-functional specificities such as presence and consistency of contents and location. In this study, we characterised the organisation of the colonic mucus barrier in proximal and distal colon of rodents by histological and FISH staining, taking into account aforementioned specificities. By using longitudinal sections and imaging extensive areas of tissue with and without colonic contents, we have obtained a spatiotemporal overview of mucus organisation in the colon. We describe for the first time that the colonic mucus layer covers the faeces instead of the epithelium in the distal colon. This faecal mucus layer confines the microbiota to the faeces and prevents it from remaining in empty distal colon. In the proximal colon, the mucus did not form a separating layer between bacteria and epithelium. We conclude that the organisation of colonic mucus is reliant on the presence of the colonic content, and the location within the colon. Our findings reopen the discussion on the nature of the colonic mucus barrier.

A fresh look at IBS-opportunities for systems medicine approaches.

NeuroGUT is a EU-funded initial training network (ITN) of 14 research projects in neurogastroenterology that have employed an equal number of early-stage researchers. Neurogut trainees have-among other activities-attended an international conference on irritable bowel syndrome (IBS) in Bologna in 2016 and were asked to critically review and evaluate the current knowledge on IBS for their respective research activities, and to state what they were missing. Most appreciated were the topics brain imaging of gut activity, the role of the gut microbiota, the pharmacology of gut functions, the IBS-IBD interrelation, the new Rome IV criteria, the role of gas, and the placebo response in functional disorders. Missed were more detailed coverage of high-resolution manometry, functional brain imaging, advanced "systems medicine" approaches and bioinformatics technology, better sub-classification of IBS patients, and the development of disease biomarkers, extended at the molecular (genetic/epigenetic, proteonomic) level. They summarize that despite excellent specialized research, there is a gap open that should be filled with systems medicine. For this, it would be necessary that medical research learns even more from the data sciences and other basic disciplines, for example, information technology and system biology, and also welcomes a change in paradigm that enhances open sharing of data, information, and resources.

In search of patient characteristics that may guide empirically based treatment selection for personality disorder patients-a concept map approach.

Using the concept map method, this study aimed to summarize and describe patient characteristics pertinent to treatment selection for patients with personality disorders (PDs). Initial patient characteristics were derived from the research literature and a survey among Dutch expert clinicians. Concept mapping is a formalized conceptualization procedure that describes the underlying cognitive structures people use in complex tasks, such as treatment allocation. Based on expert opinions of 29 Dutch clinicians, a concept map was generated that yielded eight domains of patient characteristics, i.e., Severity of symptoms, Severity of personality pathology, Ego-adaptive capacities, Motivation and working alliance, Social context, Social demographic characteristics, Trauma, and Treatment history and medical condition. These domains can be ordered along two bipolar axes, running from internal to external concepts and from vulnerability to strength concepts, respectively. Our findings may serve as input for the delineation of algorithms for patient-treatment matching research in PD.

Be kind to your eating disorder patients: the impact of positive and negative feedback on the explicit and implicit self-esteem of female patients with eating disorders.

OBJECTIVE: Lack of self-esteem may play an important role in the development of eating disorders (ED). This study investigated the differential impact of positive and negative feedback on implicit and explicit self-esteem in women with an ED (N=25) as compared to women without an ED (N=29). METHOD: False feedback (positive or negative) was given on participant's performance on a specifically developed intellectual test. Before and after the performance, explicit and implicit self-esteem was measured. RESULTS: On the explicit measure ED patients reacted congruently with the nature of the feedback. On the implicit measure only ED patients responded to the positive feedback with an improvement of self-esteem, with no effect for negative feedback. The control group was unaffected by either feedback. Furthermore, no correlation was observed between the explicit and implicit measures, a finding suggesting that these measurements tap different constructs. CONCLUSION: Positive feedback affects implicit self-esteem of female patients with eating disorders. The results underline the importance of positively approaching women with ED.

Stress-induced muscle effort as a cause of repetitive strain injury?

The influence of stress-induced muscle effort during computer utilization was tested in patients with repetitive strain injury (RSI). Twenty academic researchers with a formal medical diagnosis of RSI and 20 matched controls, randomly selected from a sample of 71 colleagues with and without RSI, typed after stress (induced via an intelligence/skill task under social pressure) and after relaxation. Results indicated that both groups had more electromyography (EMG) activity in the shoulder muscles during typing after stress than after relaxation, but that patients started with higher baseline muscle activity. Furthermore, EMG activity of different muscle groups during typing after stress correlated among controls, but not among patients. Finally, analysis of intake forms showed that patients scored higher than controls on neuroticism and alexithymia, but not on extraversion, openness, agreeableness and conscientiousness. It was concluded that deviations in muscle activity during computer utilization, as well as neuroticism and alexithymia, may be risk factors for RSI.

The synergistic interaction of gemcitabine and cytosine arabinoside with the ribonucleotide reductase inhibitor triapine is schedule dependent.

Gemcitabine and ara-C have multiple mechanisms of action: DNA incorporation and for gemcitabine also ribonucleotide reductase (RNR) inhibition. Since dCTP competes with their incorporation into DNA, dCTP depletion can potentiate their cytotoxicity. We investigated whether additional RNR inhibition by Triapine (3-AP), a new potent RNR inhibitor, enhanced cytotoxicity of gemcitabine and ara-C in four non-small-cell-lung-cancer (NSCLC) cell lines, using the multiple-drug-effect analysis. Simultaneous and sequential exposure (preexposure to 3-AP for 24h) in a constant molar ratio of 3-AP and gemcitabine was antagonistic/additive in all cell lines. Preexposure to 3-AP at an IC(25) concentration for 24h before variable concentrations of gemcitabine was synergistic. RNR inhibition by 3-AP resulted in a more synergistic interaction in combination with ara-C, which does not inhibit RNR. Two cell lines with pronounced synergism (SW1573) or antagonism (H460) for gemcitabine/3-AP, were evaluated for accumulation of the active metabolites, dFdCTP and ara-CTP. Simultaneous exposure induced no or a small increase, but ara-CTP increased after pretreatment with 3-AP, 4-fold in SW1573 cells, but not in H460 (<1.5 fold). Ara-C and gemcitabine incorporation into DNA were more pronounced (about 2-fold increased) for sequential treatment in SW1573 compared to H460 cells (<1.5 fold). This was not related to the activity and expression of deoxycytidine kinase and the M2 subunit of RNR. In conclusion, RNR inhibition by 3-AP prior to gemcitabine or ara-C exposure stimulates accumulation of the active metabolites and incorporation into DNA. The combination 3-AP/Ara-C is more synergistic than 3-AP/gemcitabine possibly because gemcitabine already inhibits RNR, but ara-C does not.

Alexithymia, risk factor or consequence of work-related stress?

BACKGROUND: Primary alexithymia has been proposed as a trait-like risk factor for various psychiatric disorders. Alternatively, secondary alexithymia has been conceptualized as an inadequate coping reaction to a stressful situation. This study investigated the level and the type of alexithymia associated with occupational stress. METHOD: On 2 occasions, 69 patients with work-related stress and 62 healthy participants completed self-report instruments to measure alexithymia (20-item Toronto Alexithymia Scale), burnout complaints (Maslach Burnout Inventory) and general distress complaints (Depression Anxiety Stress Scales, Checklist Individual Strength). Group differences in alexithymia were analyzed using ANOVAs. The type of alexithymia was investigated by (a) determining absolute and relative stability, (b) exploring state dependence by adjusting alexithymia for burnout and distress complaints and (c) associating recovery of complaints with change in alexithymia. RESULTS: Alexithymia was significantly elevated among patients. In the patient group, absolute stability of two alexithymia dimensions (identifying feelings, describing feelings) and relative stability of one alexithymia dimension (identifying feelings) was lower than in the healthy group. Cross-sectional group differences became small and nonsignificant after adjustment for distress complaints. Among patients, change in alexithymia was moderately associated with symptom recovery. CONCLUSION: Elevated alexithymia among patients with occupational stress is highly state dependent, which indicates the presence of secondary alexithymia.

Psychometric evaluation of the Dutch version of the posttraumatic cognitions inventory (PTCI).

Trauma-related cognitions play an increasingly prominent role in research on trauma and in clinical practice. The present study investigated the psychometric characteristics of the Dutch version of the posttraumatic cognitions inventory (PTCI) and evaluated its potential as an outcome measure. Data were collected from a treatment-seeking sample of trauma victims (n=158) and a college sample (n=178). The PTCI's three-factor structure was retained in both samples. The PTCI demonstrated high internal consistency and two-week test-retest reliability. Convergent validity was evidenced by a pattern of correlations with instruments for trauma-related cognitions, posttraumatic stress disorder, and depressive symptoms that largely met a priori expectations. Reductions in self-reported and clinician-assessed posttraumatic stress disorder symptoms were positively associated with decreased PTCI scores, indicating that the PTCI could assist treatment evaluation. It is concluded that the Dutch version of the PTCI exhibits good psychometric characteristics and has the potential to contribute to trauma-related research.