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.

[Aftershocks; about the psychological consequences of gas extraction in Groningen]. / Naschokken; over de psychische gevolgen van de gaswinning in Groningen.

BACKGROUND: In recent decades, gas extraction in Groningen has led to a lot of material and immaterial damage, including much psychological suffering, which was ignored by policymakers for years. With the publication of the report of the Parliamentary Inquiry into Natural Gas Extraction in Groningen, this is recognized and suggestions are made to repair the damage caused in the broadest sense. AIM: Description of current and expected psychological consequences, and research and treatment to be conducted focused on this specific regional phenomenon. METHOD: Describing the Groningen situation based on various sources, and identifying current and expected mental consequences based on currently available data and scientific literature. RESULTS: Psychological consequences are largely known and identified, but not yet quantified. It is most important for the well-being of inhabitants that the government takes its care task seriously and supports victims in a practical sense. Subsequently, a targeted treatment offer must be developed. CONCLUSION: The knowledge available within psychiatry and psychology about the development and treatment of psychological complaints should play a role in researching and improving the well-being and the mental health of those affected by the gas extraction problem, now and in the future.

[About quakes and biorhythms; sleeping problems in the Groningen earthquake area]. / Over bevingen en bioritme; slaapproblemen in het Groninger aardbevingsgebied.

BACKGROUND: Gas extraction-induced earthquakes have been taking place in the province of Groningen , the Netherlands, for many years. These lead to damage to homes and other buildings. This damage, and the way in which claims are handled, leads to physical and mental health problems, including sleeping problems. AIM: Drawing attention to the regional problems related to gas-extraction and, in particular, sleeping problems. METHOD: To describe of the background situation based on available sources and naming the mental consequences, especially sleep complaints. Also to calculate patterns in the course of the earthquakes related to the time of day and the season based on the KNMI (The Royal Netherlands Meteorological Institute) registrations since 12-8-2012. RESULTS: Most serious earthquakes in the last decade have occurred at night and when the sun has set. CONCLUSION: Because the most serious quakes take place during the period when it is dark during the day, this will influence sleeping behavior. Mental health care could play a role by stimulating research and treatment of these sleep complaints in order to prevent more serious complaints. Some possible suggestions are described.

Repeated oral esketamine in patients with treatment resistant depression and comorbid posttraumatic stress disorder.

Introduction: Ketamine and its S-enantiomer esketamine are novel pharmacotherapeutic options for treatment resistant depression (TRD). There is growing evidence on the efficacy for other psychiatric disorders, including posttraumatic stress disorder (PTSD). It is hypothesized that psychotherapy may further potentiate the effects of (es)ketamine in psychiatric disorders. Methods: Repeated oral esketamine was prescribed once or twice weekly in five patients suffering from TRD and comorbid PTSD. We describe the clinical effects of esketamine and report data from psychometric instruments and patients' perspectives. Results: Esketamine treatment duration ranged from six weeks to a year. In four patients, we observed improvement in depressive symptoms, increased resilience and more receptiveness to psychotherapy. One patient experienced symptom worsening in response to a threatening situation during esketamine treatment, highlighting the need for a safe setting. Discussion: (Es)ketamine treatment within a psychotherapeutic framework appears promising in patients with treatment resistant symptoms of depression and PTSD. Controlled trials are warranted to validate these results and to elucidate the optimal treatment methods.

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.

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.

[Neuropsychiatric manifestations of COVID-19 in intensive care unit patients]. / Neuropsychiatrische verschijnselen bij patiënten met COVID-19 op de ic.

It has become clear that COVID-19 can lead to neuropsychiatric complications. In this article, three cases are discussed that illustrate how neuropsychiatric complications can manifest within the COVID-19 disease course. Patients are at risk to develop a severe, hyperactive delirium, which is often accompanied by anxiety and sometimes neurological symptoms. The treatment of the neuropsychiatric complications is characterized by unusually high doses of antipsychotics and sedatives. Timely psychiatric consultation is advised for adequate recognition and effective treatment of delirium and other neuropsychiatric symptoms.

Personalized ESM monitoring and feedback to support psychological treatment for depression: a pragmatic randomized controlled trial (Therap-i).

BACKGROUND: Major depressive disorder (MDD) is a highly prevalent mental disorder with large disease burden, high levels of relapse or persistence, and overall suboptimal outcomes of protocolized pharmacological and psychotherapeutic treatments. There is an urgent need to improve treatment effectiveness, possibly through systematic treatment personalization. In psychotherapeutic treatments this can be achieved by case conceptualization. To support this process, we developed the Therap-i module, which consists of personalized Experienced Sampling Methodology (ESM) and feedback. The Therap-i module is integrated into outpatient psychotherapeutic treatment as usual (TAU) for depression. The study aim is to investigate the efficacy of the Therap-i module in decreasing symptomatology in unresponsive or relapsing patients diagnosed with MDD. We hypothesize that the Therap-i module will contribute to TAU by i) decreasing depressive symptoms, and ii) improving general functioning, therapeutic working alliance, and illness perception. This paper provides details of the study rationale, aims, procedures, and a discussion on potential pitfalls and promises of the module. METHODS: Patients diagnosed with MDD (n = 100) will enrol in a pragmatic two-armed randomized controlled trial. Randomization is stratified according to the patient's treatment resistance level assessed with the Dutch Method for quantification of Treatment Resistance in Depression (DM-TRD). All fill-out the Inventory of Depressive Symptomatology Self Report (IDS-SR), Outcome Questionnaire (OQ-45), Illness Perception Questionnaire Mental Health (IPQ-MH), and Work Alliance Inventory Self Report (WAI-SR). In the intervention arm, through close collaboration between patient, clinician, and researcher, a personalized ESM diary is developed based on the patient's case conceptualization. During the ESM monitoring period (8 weeks, 5 assessments/day), patients receive feedback three times, which is discussed among the abovementioned three parties. Both patients and clinicians will evaluate the Therap-i module. RESULTS: Data collection is ongoing. DISCUSSION: This is the first study in which personalized ESM and feedback is integrated in outpatient psychotherapeutic TAU for depression. The labour intensive procedure and methodological pitfalls are anticipated challenges and were taken into account when designing the study. When hypotheses are confirmed, the Therap-i module may advance treatment for depression by providing insights into personalized patterns driving or perpetuating depressive complaints. TRIAL REGISTRATION: Trial NL7190 (NTR7381) , registered prospectively 03-08-2018.

Affect fluctuations examined with ecological momentary assessment in patients with current or remitted depression and anxiety disorders.

BACKGROUND: There 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. METHODS: Ecological 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. RESULTS: Current 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. CONCLUSIONS: Patients 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.

Towards precision medicine: What are the stratification hypotheses to identify homogeneous inflammatory subgroups.

Diverse lines of research testify a link, presumably causal, between immune dysregulation and the development, course and clinical outcome of psychiatric disorders. However, there is a large heterogeneity among the patients' individual immune profile and this heterogeneity prevents the development of precise diagnostic tools and the identification of therapeutic targets. The aim of this review was to delineate possible subgroups of patients on the basis of clinical dimensions, investigating whether they could lead to particular immune signatures and tailored treatments. We discuss six clinical entry points; genetic liability to immune dysregulation, childhood maltreatment, metabolic syndrome, cognitive dysfunction, negative symptoms and treatment resistance. We describe the associated immune signature and outline the effects of anti-inflammatory drugs so far. Finally, we discuss advantages of this approach, challenges and future research directions.

[Psychedelics in the treatment of depression, anxiety, and obsessive-compulsive disorder]. / Psychedelica bij de behandeling van depressie, angst en obsessieve-compulsieve stoornis.

BACKGROUND: There is a need for new, effective treatments for patients with (treatment-resistant) depressive disorders, anxiety disorders and obsessive-compulsive disorder (ocd). At the same time, there is renewed interest in psychedelics for the treatment of psychiatric disorders.
AIM: To provide an overview of results from past and current research into psychedelics in the treatment of depression, anxiety disorders and ocd.
METHOD: Literature search in Medline and PubMed databases, supplemented with cross-references and results from recent studies.
RESULTS: There is a considerable evidence base for the atypical psychedelic ketamine. Ketamine has a rapid, beneficial effect on depression and suicidality; longer-term effects are less clear. Research into classical psychedelics for the treatment of depression and anxiety disorders is currently limited to a few small (open label) studies, although positive outcomes are reported even after a single administration, with potentially longer lasting benefits. Studies must be repeated in larger and more diverse groups of patients.
CONCLUSION: Further research into efficacy, therapeutic mechanisms and intervention models is very worthwhile; for the benefit of patients, but also to provide a deeper insight into the psychotherapeutic and neurobiological mechanisms that play a role in (the treatment of) common mental disorders.

[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.

[Psychedelics in the treatment of PTSD]. / Psychedelica bij de behandeling van PTSS.

BACKGROUND: Posttraumatic stress disorder (PTSD) is often a chronic condition, despite the availability of various evidence-based treatment options. Psychedelics offer new treatment opportunities.
AIM: An overview of the current evidence, therapeutic context, and possible mechanisms of action of different types of psychedelics in the treatment of PTSD.
METHOD: A scoping review of the available literature.
RESULTS: MDMA-assisted psychotherapy has shown to produce lasting reductions in PTSD symptoms in multiple RCTs. Based on a small number of studies, ketamine administration appears to lead to temporary symptom relief. Current studies are investigating whether the use of ketamine in combination with psychotherapy can lead to lasting reductions in PTSD symptoms. Classical psychedelics (such as psilocybin and LSD) induce psychoactive effects (on behavior or experience) that could contribute to the psychotherapeutic treatment of PTSD but have not yet been investigated in controlled studies. Reported positive effects extend beyond PTSD symptoms only.
CONCLUSION: Psychedelics may have potential to serve as a catalyst for the psychotherapeutic treatment of PTSD. Most evidence exists for MDMA-supported psychotherapy; relatively little research is available on ketamine and classical psychedelics. Future research needs to show whether the use of psychedelics can be integrated into available treatment options for PTSD.

[Psychedelics in the treatment of substance use disorders and psychosis]. / Psychedelica bij de behandeling van verslaving en psychose.

BACKGROUND: After psychedelics were banned in 1968, the flourishing research on the use of psychedelics in patients with a mental disorder stopped abruptly. Recently, we see a renaissance of this research.
AIM: To present an overview of what is known about the treatment of addiction and psychosis with psychedelics.
METHOD: Literature study based on Medline en PubMed publications till December 2019.
RESULTS: Studies on the effectiveness of psychedelics in the treatment of addiction and psychosis is still very limited in size and methodological quality. Nevertheless, most studies show positive effects of both classical and atypical psychedelics in a variety of addictions on motivation, craving, reduced consumption, and abstinence often following a single dose and with long-lasting benefits (3-24 months). Use of ketamine in patients with a psychosis stabilized on an antipsychotic might reduce negative symptoms.
CONCLUSION: Before psychedelics can be used in standard clinical practice for the treatment of patients with an addiction or a psychosis, larger and methodologically better studies are needed. The use of psychedelics also creates an opportunity to better understand the shared underlying pathology of many different mental disorders.

[Psychedelics for existential distress in terminally ill patients]. / Psychedelica bij existentieel lijden bij patiënten met een terminale ziekte.

BACKGROUND: Existential distress in patients with a terminal illness is often associated with (symptoms of) anxiety and depression. Psychotherapeutic interventions seem effective but effects are short-lived. There are no proven effective pharmacological interventions.
AIM: To present an overview of literature on psychedelic treatment of existential distress in patients with terminal illness.
METHOD: Literature research in PubMed/Medline databases, supplemented with cross-references.
RESULTS: 14 clinical studies have been conducted: 6 with classic psychedelics between 1960 and 1980, and 8 with classic psychedelics and ketamine after 2000. Results of early pre-post studies are promising but have serious methodological limitations. Recent clinical research with LSD, psilocybin and ketamine are also promising although limited in terms of research design and generalizability. Overall, studies show a positive effect on existential and spiritual well-being, quality of life, acceptance and (symptoms of) anxiety and depression. Mystical experiences are correlated with positive outcomes. Few adverse effects are reported.
CONCLUSION: Treatment of existential distress using classical psychedelics or ketamine in patients with terminal illness seems auspicious. Larger clinical studies in a more diverse patient population with fewer methodological limitations are needed to draw conclusions about efficacy and generalizability.

Predicting the course of anxiety disorders: The role of biological parameters.

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.

Associations of plasma androgens with suicidality among men and women: A 9-year longitudinal cohort study.

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.