Publications by authors named "Ulrich Hegerl"

323 Publications

The Big Five Personality Traits and Brain Arousal in the Resting State.

Brain Sci 2021 Sep 26;11(10). Epub 2021 Sep 26.

LIFE-Leipzig Research Center for Civilization Diseases, University of Leipzig, 04103 Leipzig, Germany.

Based on Eysenck's biopsychological trait theory, brain arousal has long been considered to explain individual differences in human personality. Yet, results from empirical studies remained inconclusive. However, most published results have been derived from small samples and, despite inherent limitations, EEG alpha power has usually served as an exclusive indicator for brain arousal. To overcome these problems, we here selected N = 468 individuals of the LIFE-Adult cohort and investigated the associations between the Big Five personality traits and brain arousal by using the validated EEG- and EOG-based analysis tool VIGALL. Our analyses revealed that participants who reported higher levels of extraversion and openness to experience, respectively, exhibited lower levels of brain arousal in the resting state. Bayesian and frequentist analysis results were especially convincing for openness to experience. Among the lower-order personality traits, we obtained the strongest evidence for neuroticism facet 'impulsivity' and reduced brain arousal. In line with this, both impulsivity and openness have previously been conceptualized as aspects of extraversion. We regard our findings as well in line with the postulations of Eysenck and consistent with the recently proposed 'arousal regulation model'. Our results also agree with meta-analytically derived effect sizes in the field of individual differences research, highlighting the need for large (collaborative) studies.
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http://dx.doi.org/10.3390/brainsci11101272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533901PMC
September 2021

["iFightDepression" in inpatient treatment : Evaluation of a web-based, therapist-guided self-management program on a specialized ward for affective disorders].

Nervenarzt 2021 Oct 15. Epub 2021 Oct 15.

Department für Psychische Gesundheit, Klinik und Poliklinik für Psychiatrie und Psychotherapie, Universitätsklinikum Leipzig, AöR, Semmelweisstr. 10, 04103, Leipzig, Deutschland.

Background: E‑mental health mainly plays a role in the outpatient treatment of patients with depressive disorders. The goal of this study was to implement and evaluate the web-based, therapist-guided self-management tool "iFightDepression" (iFD) to clarify if there is a benefit for inpatient use.

Material And Methods: In this study 78 inpatients with affective disorders (ICD-10 F32.0‑3, F33.0-3) or dysthymia (F34) were recruited. The intervention duration with the iFD tool went from admission until discharge, therapeutic support was granted by the ward staff. Symptom severity, intervention expectations and experience with therapy were processed in an online questionnaire before the intervention (T0) while intervention satisfaction was captured after the intervention shortly before discharge (T1) in a paper-pencil questionnaire.

Results: Out of 78 participating inpatients 42 used the iFD tool at least once. Moderate to high levels of expectation regarding the iFD tool and mildly above-average level of satisfaction after the intervention were observed. Of the active users 67% indicated they would continue to use the iFD tool after discharge. The main reasons for not using the iFD tool were short duration of stay, severity of disease and lack of digital literacy.

Conclusion: An implementation of the iFD tool is feasible on principle. Active users gave positive feedback concerning the intervention and most participants claimed to continue using the iFD tool after discharge; however, low usage rates among study participants (42/78, 54%) showed barriers of implementation that have to be addressed and underline the importance of adaptations regarding the use of the intervention in a clinical setting.
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http://dx.doi.org/10.1007/s00115-021-01214-wDOI Listing
October 2021

Large-scale collaboration in ENIGMA-EEG: A perspective on the meta-analytic approach to link neurological and psychiatric liability genes to electrophysiological brain activity.

Brain Behav 2021 08 21;11(8):e02188. Epub 2021 Jul 21.

Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia.

Background And Purpose: The ENIGMA-EEG working group was established to enable large-scale international collaborations among cohorts that investigate the genetics of brain function measured with electroencephalography (EEG). In this perspective, we will discuss why analyzing the genetics of functional brain activity may be crucial for understanding how neurological and psychiatric liability genes affect the brain.

Methods: We summarize how we have performed our currently largest genome-wide association study of oscillatory brain activity in EEG recordings by meta-analyzing the results across five participating cohorts, resulting in the first genome-wide significant hits for oscillatory brain function located in/near genes that were previously associated with psychiatric disorders. We describe how we have tackled methodological issues surrounding genetic meta-analysis of EEG features. We discuss the importance of harmonizing EEG signal processing, cleaning, and feature extraction. Finally, we explain our selection of EEG features currently being investigated, including the temporal dynamics of oscillations and the connectivity network based on synchronization of oscillations.

Results: We present data that show how to perform systematic quality control and evaluate how choices in reference electrode and montage affect individual differences in EEG parameters.

Conclusion: The long list of potential challenges to our large-scale meta-analytic approach requires extensive effort and organization between participating cohorts; however, our perspective shows that these challenges are surmountable. Our perspective argues that elucidating the genetic of EEG oscillatory activity is a worthwhile effort in order to elucidate the pathway from gene to disease liability.
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http://dx.doi.org/10.1002/brb3.2188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413828PMC
August 2021

Large-scale collaboration in ENIGMA-EEG: A perspective on the meta-analytic approach to link neurological and psychiatric liability genes to electrophysiological brain activity.

Brain Behav 2021 08 21;11(8):e02188. Epub 2021 Jul 21.

Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia.

Background And Purpose: The ENIGMA-EEG working group was established to enable large-scale international collaborations among cohorts that investigate the genetics of brain function measured with electroencephalography (EEG). In this perspective, we will discuss why analyzing the genetics of functional brain activity may be crucial for understanding how neurological and psychiatric liability genes affect the brain.

Methods: We summarize how we have performed our currently largest genome-wide association study of oscillatory brain activity in EEG recordings by meta-analyzing the results across five participating cohorts, resulting in the first genome-wide significant hits for oscillatory brain function located in/near genes that were previously associated with psychiatric disorders. We describe how we have tackled methodological issues surrounding genetic meta-analysis of EEG features. We discuss the importance of harmonizing EEG signal processing, cleaning, and feature extraction. Finally, we explain our selection of EEG features currently being investigated, including the temporal dynamics of oscillations and the connectivity network based on synchronization of oscillations.

Results: We present data that show how to perform systematic quality control and evaluate how choices in reference electrode and montage affect individual differences in EEG parameters.

Conclusion: The long list of potential challenges to our large-scale meta-analytic approach requires extensive effort and organization between participating cohorts; however, our perspective shows that these challenges are surmountable. Our perspective argues that elucidating the genetic of EEG oscillatory activity is a worthwhile effort in order to elucidate the pathway from gene to disease liability.
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http://dx.doi.org/10.1002/brb3.2188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413828PMC
August 2021

Intervention Use and Symptom Change With Unguided Internet-Based Cognitive Behavioral Therapy for Depression During the COVID-19 Pandemic: Log Data Analysis of a Convenience Sample.

JMIR Ment Health 2021 Jul 16;8(7):e28321. Epub 2021 Jul 16.

Forschungszentrum Depression, Stiftung Deutsche Depressionshilfe, Frankfurt, Germany.

Background: Internet- and mobile-based interventions are most efficacious in the treatment of depression when they involve some form of guidance, but providing guidance requires resources such as trained personnel, who might not always be available (eg, during lockdowns to contain the COVID-19 pandemic).

Objective: The current analysis focuses on changes in symptoms of depression in a guided sample of patients with depression who registered for an internet-based intervention, the iFightDepression tool, as well as the extent of intervention use, compared to an unguided sample. The objective is to further understand the effects of guidance and adherence on the intervention's potential to induce symptom change.

Methods: Log data from two convenience samples in German routine care were used to assess symptom change after 6-9 weeks of intervention as well as minimal dose (finishing at least two workshops). A linear regression model with changes in Patient Health Questionnaire (PHQ-9) score as a dependent variable and guidance and minimal dose as well as their interaction as independent variables was specified.

Results: Data from 1423 people with symptoms of depression (n=940 unguided, 66.1%) were included in the current analysis. In the linear regression model predicting symptom change, a significant interaction of guidance and minimal dose revealed a specifically greater improvement for patients who received guidance and also worked with the intervention content (β=-1.75, t=-2.37, P=.02), while there was little difference in symptom change due to guidance in the group that did not use the intervention. In this model, the main effect of guidance was only marginally significant (β=-.53, t=-1.78, P=.08).

Conclusions: Guidance in internet-based interventions for depression is not only an important factor to facilitate adherence, but also seems to further improve results for patients adhering to the intervention compared to those who do the same but without guidance.
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http://dx.doi.org/10.2196/28321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288646PMC
July 2021

Intervention Use and Symptom Change With Unguided Internet-Based Cognitive Behavioral Therapy for Depression During the COVID-19 Pandemic: Log Data Analysis of a Convenience Sample.

JMIR Ment Health 2021 Jul 16;8(7):e28321. Epub 2021 Jul 16.

Forschungszentrum Depression, Stiftung Deutsche Depressionshilfe, Frankfurt, Germany.

Background: Internet- and mobile-based interventions are most efficacious in the treatment of depression when they involve some form of guidance, but providing guidance requires resources such as trained personnel, who might not always be available (eg, during lockdowns to contain the COVID-19 pandemic).

Objective: The current analysis focuses on changes in symptoms of depression in a guided sample of patients with depression who registered for an internet-based intervention, the iFightDepression tool, as well as the extent of intervention use, compared to an unguided sample. The objective is to further understand the effects of guidance and adherence on the intervention's potential to induce symptom change.

Methods: Log data from two convenience samples in German routine care were used to assess symptom change after 6-9 weeks of intervention as well as minimal dose (finishing at least two workshops). A linear regression model with changes in Patient Health Questionnaire (PHQ-9) score as a dependent variable and guidance and minimal dose as well as their interaction as independent variables was specified.

Results: Data from 1423 people with symptoms of depression (n=940 unguided, 66.1%) were included in the current analysis. In the linear regression model predicting symptom change, a significant interaction of guidance and minimal dose revealed a specifically greater improvement for patients who received guidance and also worked with the intervention content (β=-1.75, t=-2.37, P=.02), while there was little difference in symptom change due to guidance in the group that did not use the intervention. In this model, the main effect of guidance was only marginally significant (β=-.53, t=-1.78, P=.08).

Conclusions: Guidance in internet-based interventions for depression is not only an important factor to facilitate adherence, but also seems to further improve results for patients adhering to the intervention compared to those who do the same but without guidance.
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http://dx.doi.org/10.2196/28321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288646PMC
July 2021

Intervention Use and Symptom Change With Unguided Internet-Based Cognitive Behavioral Therapy for Depression During the COVID-19 Pandemic: Log Data Analysis of a Convenience Sample.

JMIR Ment Health 2021 Jul 16;8(7):e28321. Epub 2021 Jul 16.

Forschungszentrum Depression, Stiftung Deutsche Depressionshilfe, Frankfurt, Germany.

Background: Internet- and mobile-based interventions are most efficacious in the treatment of depression when they involve some form of guidance, but providing guidance requires resources such as trained personnel, who might not always be available (eg, during lockdowns to contain the COVID-19 pandemic).

Objective: The current analysis focuses on changes in symptoms of depression in a guided sample of patients with depression who registered for an internet-based intervention, the iFightDepression tool, as well as the extent of intervention use, compared to an unguided sample. The objective is to further understand the effects of guidance and adherence on the intervention's potential to induce symptom change.

Methods: Log data from two convenience samples in German routine care were used to assess symptom change after 6-9 weeks of intervention as well as minimal dose (finishing at least two workshops). A linear regression model with changes in Patient Health Questionnaire (PHQ-9) score as a dependent variable and guidance and minimal dose as well as their interaction as independent variables was specified.

Results: Data from 1423 people with symptoms of depression (n=940 unguided, 66.1%) were included in the current analysis. In the linear regression model predicting symptom change, a significant interaction of guidance and minimal dose revealed a specifically greater improvement for patients who received guidance and also worked with the intervention content (β=-1.75, t=-2.37, P=.02), while there was little difference in symptom change due to guidance in the group that did not use the intervention. In this model, the main effect of guidance was only marginally significant (β=-.53, t=-1.78, P=.08).

Conclusions: Guidance in internet-based interventions for depression is not only an important factor to facilitate adherence, but also seems to further improve results for patients adhering to the intervention compared to those who do the same but without guidance.
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http://dx.doi.org/10.2196/28321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288646PMC
July 2021

Effects of dietary interventions on depressive symptom profiles: results from the MooDFOOD depression prevention study.

Psychol Med 2021 Apr 7:1-10. Epub 2021 Apr 7.

Department of Psychiatry, Amsterdam UMC, Vrije Universiteit, Amsterdam Public Health Research Institute and Amsterdam Neuroscience, Amsterdam, The Netherlands.

Background: Dietary interventions did not prevent depression onset nor reduced depressive symptoms in a large multi-center randomized controlled depression prevention study (MooDFOOD) involving overweight adults with subsyndromal depressive symptoms. We conducted follow-up analyses to investigate whether dietary interventions differ in their effects on depressive symptom profiles (mood/cognition; somatic; atypical, energy-related).

Methods: Baseline, 3-, 6-, and 12-month follow-up data from MooDFOOD were used (n = 933). Participants received (1) placebo supplements, (2) food-related behavioral activation (F-BA) therapy with placebo supplements, (3) multi-nutrient supplements (omega-3 fatty acids and a multi-vitamin), or (4) F-BA therapy with multi-nutrient supplements. Depressive symptom profiles were based on the Inventory of Depressive Symptomatology.

Results: F-BA therapy was significantly associated with decreased severity of the somatic (B = -0.03, p = 0.014, d = -0.10) and energy-related (B = -0.08, p = 0.001, d = -0.13), but not with the mood/cognition symptom profile, whereas multi-nutrient supplementation was significantly associated with increased severity of the mood/cognition (B = 0.05, p = 0.022, d = 0.09) and the energy-related (B = 0.07, p = 0.002, d = 0.12) but not with the somatic symptom profile.

Conclusions: Differentiating depressive symptom profiles indicated that food-related behavioral interventions are most beneficial to alleviate somatic symptoms and symptoms of the atypical, energy-related profile linked to an immuno-metabolic form of depression, although effect sizes were small. Multi-nutrient supplements are not indicated to reduce depressive symptom profiles. These findings show that attention to clinical heterogeneity in depression is of importance when studying dietary interventions.
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http://dx.doi.org/10.1017/S0033291721000337DOI Listing
April 2021

The effect of depressive symptomatology on the association of vitamin D and sleep.

BMC Psychiatry 2021 04 6;21(1):178. Epub 2021 Apr 6.

Department of Psychiatry and Psychotherapy, University of Leipzig Medical Centre, Semmelweisstrasse 10, D-04103, Leipzig, Germany.

Background: Sleep disorders and vitamin D deficiency are highly prevalent health problems. Few studies examined the effect of vitamin D concentrations on objectively measured sleep with high methodological quality and temporal proximity. Previous analysis within the LIFE-Adult-Study suggested that a lower concentration of serum vitamin D was associated with both shorter and later night sleep. However, no conclusion about underlying mechanisms could be drawn. We addressed the question whether this relationship is explained by the presence of depressive syndromes, which are linked to both vitamin D deficiency and sleep disturbances.

Methods: It was investigated whether the association of vitamin D concentrations and night sleep parameters is mediated or moderated by depressive symptomatology. We investigated a subset (n = 1252) of the community sample from the LIFE-Adult-Study, in which sleep parameters had been objectively assessed using actigraphy, based on which two sleep parameters were calculated: night sleep duration and midsleep time. Serum 25(OH) D concentrations were measured using an electrochemiluminescence immunoassay. Depressive symptomatology was evaluated with the Centre for Epidemiological Studies Depression Scale. The mediation effect was analyzed by using Hayes' PROCESS macro tool for SPSS for Windows.

Results: The depressive symptomatology was neither significantly associated with night sleep duration nor midsleep time. The associations between vitamin D concentrations and night sleep duration/midsleep time through mediation by depressive symptomatology were not significant. Corresponding moderator analyses were also non-significant.

Conclusion: The associations between vitamin D concentrations and night sleep parameters (sleep duration and midsleep time) seem to be neither mediated nor moderated by depressive symptomatology.
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http://dx.doi.org/10.1186/s12888-021-03176-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025511PMC
April 2021

The "VIP-ADHD trial": Does brain arousal have prognostic value for predicting response to psychostimulants in adult ADHD patients?

Eur Neuropsychopharmacol 2021 Feb 31;43:116-128. Epub 2020 Dec 31.

Department of Psychiatry, Psychotherapy and Psychosomatic, University Hospital of Frankfurt.

EEG studies have shown that adult ADHD patients have less stable brain arousal regulation than age and gender matched controls. Psychostimulants have brain arousal stabilising properties evident in EEG patterns. The aim of this study was to investigate whether the stability of brain arousal regulation has prognostic value in predicting response to methylphenidate therapy in adult ADHD patients. In an open-label, single-arm, multi-centre, confirmatory trial, 121 adult ADHD patients were recruited and 112 qualified for the full analysis set. All participants received an initial dose of 20 mg extended release methylphenidate at baseline. After a titration phase of up to 4 weeks, patients remained on a weight-based target dose of extended release methylphenidate for 4 weeks. Using the Vigilance Algorithm Leipzig (VIGALL 2.1), we assessed brain arousal regulation before the treatment with methylphenidate, based on a 15-min EEG at quiet rest recorded at baseline. Using automatic stage-classification of 1 s segments, we computed the mean EEG-vigilance (indexing arousal level) and an arousal stability score (indexing arousal regulation). The primary endpoint was the association between successful therapy, defined by a 30% reduction in CAARS, and stable/unstable brain arousal. 52 patients (46%) showed an unstable brain arousal regulation of which 23% had therapy success. In the stable group, 35% had therapy success, implying an absolute difference of 12 percentage points (95% CI -5 to 29, p = 0.17) in the direction opposite to the hypothesized one. There were no new findings regarding the tolerability and safety of extended release methylphenidate therapy.
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http://dx.doi.org/10.1016/j.euroneuro.2020.12.003DOI Listing
February 2021

Fatigue and brain arousal in patients with major depressive disorder.

Eur Arch Psychiatry Clin Neurosci 2021 Apr 4;271(3):527-536. Epub 2020 Dec 4.

Depression Research Center, German Depression Foundation, Leipzig, Germany.

Fatigue is considered a key symptom of major depressive disorder (MDD), yet the term lacks specificity. It can denote a state of increased sleepiness and lack of drive (i.e., downregulated arousal) as well as a state of high inner tension and inhibition of drive with long sleep onset latencies (i.e., upregulated arousal), the latter typically found in depression. It has been proposed to differentiate fatigue along the dimension of brain arousal. We investigated whether such stratification within a group of MDD patients would reveal a subgroup with distinct clinical features. Using an automatic classification of EEG vigilance stages, an arousal stability score was calculated for 15-min resting EEGs of 102 MDD patients with fatigue. 23.5% of the patients showed signs of hypoarousal with EEG patterns indicating drowsiness or sleep; this hypoaroused subgroup was compared with remaining patients (non-hypoaroused subgroup) concerning self-rated measures of depressive symptoms, sleepiness, and sleep. The hypoaroused subgroup scored higher on the Beck Depression Inventory items "loss of energy" (Z = - 2.13, p = 0.033; ɳ = 0.044, 90% CI 0.003-0.128) and "concentration difficulty" (Z = - 2.40, p = 0.017; ɳ = 0.056, 90% CI 0.009-0.139), and reported higher trait and state sleepiness (p < 0.05) as compared to the non-hypoaroused group. The non-hypoaroused subgroup, in contrast, reported more frequently the presence of suicidal ideation (Chi = 3.81, p = 0.051; ɳ = 0.037, 90% CI 0.0008-0.126). In this study, we found some evidence that stratifying fatigued MDD patients by arousal may lead to subgroups that are pathophysiologically and clinically more homogeneous. Brain arousal may be a worth while target in clinical research for better understanding the mechanisms underlying suicidal tendencies and to improve treatment response.
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http://dx.doi.org/10.1007/s00406-020-01216-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981331PMC
April 2021

Simvastatin add-on to escitalopram in patients with comorbid obesity and major depression (SIMCODE): study protocol of a multicentre, randomised, double-blind, placebo-controlled trial.

BMJ Open 2020 12 1;10(12):e040119. Epub 2020 Dec 1.

Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Introduction: Major depressive disorder (MDD) and obesity are both common disorders associated with significant burden of disease worldwide. Importantly, MDD and obesity often co-occur, with each disorder increasing the risk for developing the other by about 50%-60%. Statins are among the most prescribed medications with well-established safety and efficacy. Statins are recommended in primary prevention of cardiovascular disease, which has been linked to both MDD and obesity. Moreover, statins are promising candidates to treat MDD because a meta-analysis of pilot randomised controlled trials has found antidepressive effects of statins as adjunct therapy to antidepressants. However, no study so far has tested the antidepressive potential of statins in patients with MDD and comorbid obesity. Importantly, this is a difficult-to-treat population that often exhibits a chronic course of MDD and is more likely to be treatment resistant. Thus, in this confirmatory randomised controlled trial, we will determine whether add-on simvastatin to standard antidepressant medication with escitalopram is more efficacious than add-on placebo over 12 weeks in 160 patients with MDD and comorbid obesity.

Methods And Analysis: This is a protocol for a randomised, placebo-controlled, double-blind multicentre trial with parallel-group design (phase II). One hundred and sixty patients with MDD and comorbid obesity will be randomised 1:1 to simvastatin or placebo as add-on to standard antidepressant medication with escitalopram. The primary outcome is change in the Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to week 12. Secondary outcomes include MADRS response (defined as 50% MADRS score reduction from baseline), MADRS remission (defined as MADRS score <10), mean change in patients' self-reported Beck Depression Inventory (BDI-II) and mean change in high-density lipoprotein, low-density lipoprotein and total cholesterol from baseline to week 12.

Ethics And Dissemination: This protocol has been approved by the ethics committee of the federal state of Berlin (Ethik-Kommission des Landes Berlin, reference: 19/0226-EK 11) and by the relevant federal authority (Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM), reference: 4043387). Study findings will be published in peer-reviewed journals and will be presented at (inter)national conferences.

Trial Registration Numbers: NCT04301271, DRKS00021119, EudraCT 2018-002947-27.
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http://dx.doi.org/10.1136/bmjopen-2020-040119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709515PMC
December 2020

Enhanced Vigilance Stability during Daytime in Insomnia Disorder.

Brain Sci 2020 Nov 7;10(11). Epub 2020 Nov 7.

Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Sleep laboratory, Medical Faculty Mannheim/Heidelberg University, 68159 Mannheim, Germany.

Central nervous hyperarousal is as a key component of current pathophysiological concepts of chronic insomnia disorder. However, there are still open questions regarding its exact nature and the mechanisms linking hyperarousal to sleep disturbance. Here, we aimed at studying waking state hyperarousal in insomnia by the perspective of resting-state vigilance dynamics. The VIGALL (Vigilance Algorithm Leipzig) algorithm has been developed to investigate resting-state vigilance dynamics, and it revealed, for example, enhanced vigilance stability in depressive patients. We hypothesized that patients with insomnia also show a more stable vigilance regulation. Thirty-four unmedicated patients with chronic insomnia and 25 healthy controls participated in a twenty-minute resting-state electroencephalography (EEG) measurement following a night of polysomnography. Insomnia patients showed enhanced EEG vigilance stability as compared to controls. The pattern of vigilance hyperstability differed from that reported previously in depressive patients. Vigilance hyperstability was also present in insomnia patients showing only mildly reduced sleep efficiency. In this subgroup, vigilance hyperstability correlated with measures of disturbed sleep continuity and arousal. Our data indicate that insomnia disorder is characterized by hyperarousal at night as well as during daytime.
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http://dx.doi.org/10.3390/brainsci10110830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695157PMC
November 2020

Tailored implementation of internet-based cognitive behavioural therapy in the multinational context of the ImpleMentAll project: a study protocol for a stepped wedge cluster randomized trial.

Trials 2020 Oct 28;21(1):893. Epub 2020 Oct 28.

University Medical Center Groningen, Interdisciplinary Center for Psychopathology and Emotion Regulation, University of Groningen, Groningen, The Netherlands.

Background: Internet-based Cognitive Behavioural Therapy (iCBT) is found effective in treating common mental disorders. However, the use of these interventions in routine care is limited. The international ImpleMentAll study is funded by the European Union's Horizon 2020 programme. It is concerned with studying and improving methods for implementing evidence-based iCBT services for common mental disorders in routine mental health care. A digitally accessible implementation toolkit (ItFits-toolkit) will be introduced to mental health care organizations with the aim to facilitate the ongoing implementation of iCBT services within local contexts. This study investigates the effectiveness of the ItFits-toolkit by comparing it to implementation-as-usual activities.

Methods: A stepped wedge cluster randomized controlled trial (SWT) design will be applied. Over a trial period of 30 months, the ItFits-toolkit will be introduced sequentially in twelve routine mental health care organizations in primary and specialist care across nine countries in Europe and Australia. Repeated measures are applied to assess change over time in the outcome variables. The effectiveness of the ItFits-toolkit will be assessed in terms of the degree of normalization of the use of the iCBT services. Several exploratory outcomes including uptake of the iCBT services will be measured to feed the interpretation of the primary outcome. Data will be collected via a centralized data collection system and analysed using generalized linear mixed modelling. A qualitative process evaluation of routine implementation activities and the use of the ItFits-toolkit will be conducted within this study.

Discussion: The ImpleMentAll study is a large-scale international research project designed to study the effectiveness of tailored implementation. Using a SWT design that allows to examine change over time, this study will investigate the effect of tailored implementation on the normalization of the use of iCBT services and their uptake. It will provide a better understanding of the process and methods of tailoring implementation strategies. If found effective, the ItFits-toolkit will be made accessible for mental health care service providers, to help them overcome their context-specific implementation challenges.

Trial Registration: ClinicalTrials.gov NCT03652883 . Retrospectively registered on 29 August 2018.
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http://dx.doi.org/10.1186/s13063-020-04686-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592568PMC
October 2020

Associations of Non-Alcoholic Beverages with Major Depressive Disorder History and Depressive Symptoms Clusters in a Sample of Overweight Adults.

Nutrients 2020 Oct 20;12(10). Epub 2020 Oct 20.

Institut Universitari d'Investigació en Ciències de la Salut, Idisba, Rediapp, University of Balearic Islands, 07122 Palma de Mallorca, Spain.

Background: Meta-analysis of observational studies concluded that soft drinks may increase the risk of depression, while high consumption of coffee and tea may reduce the risk. Objectives were to explore the associations between the consumption of soft drinks, coffee or tea and: (1) a history of major depressive disorder (MDD) and (2) the severity of depressive symptoms clusters (mood, cognitive and somatic/vegetative symptoms).

Methods: Cross-sectional and longitudinal analysis based on baseline and 12-month-follow-up data collected from four countries participating in the European MooDFOOD prevention trial. In total, 941 overweight adults with subsyndromal depressive symptoms aged 18 to 75 years were analyzed. History of MDD, depressive symptoms and beverages intake were assessed.

Results: Sugar-sweetened soft drinks were positively related to MDD history rates whereas soft drinks with non-nutritive sweeteners were inversely related for the high vs. low categories of intake. Longitudinal analysis showed no significant associations between beverages and mood, cognitive and somatic/vegetative clusters.

Conclusion: Our findings point toward a relationship between soft drinks and past MDD diagnoses depending on how they are sweetened while we found no association with coffee and tea. No significant effects were found between any studied beverages and the depressive symptoms clusters in a sample of overweight adults.
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http://dx.doi.org/10.3390/nu12103202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589496PMC
October 2020

Acceptability and feasibility of two interventions in the MooDFOOD Trial: a food-related depression prevention randomised controlled trial in overweight adults with subsyndromal symptoms of depression.

BMJ Open 2020 09 15;10(9):e034025. Epub 2020 Sep 15.

Department of Health Sciences, Faculty of Science and Amsterdam Public Health research institute, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Objectives: We report on the acceptability, feasibility, dose-response relationship and adherence of two nutritional strategies to improve mood (multinutrient supplements; food-related behavioural activation (F-BA)) studied in a randomised controlled depression prevention trial (the Multi-country cOllaborative project on the rOle of Diet, Food-related behaviour, and Obesity in the prevention of Depression (MooDFOOD) Trial). We also assessed baseline determinants of adherence and assessed whether better adherence resulted in lower depressive symptoms.

Design: Randomised controlled trial with a 2×2 factorial design conducted between 2015 and 2017.

Setting: Germany, the Netherlands, UK and Spain.

Participants: Community sample of 1025 overweight adults with elevated depressive symptoms without a current episode of major depressive disorder. Main eligibility criteria included age (18-75 years), being overweight or obese, and having at least mild depressive symptoms, shown by a Patient Health Questionnaire Score of ≥5. A total of 76% of the sample was retained at the 12-month follow-up.

Interventions: Daily nutritional supplements versus pill placebo or an F-BA therapy, delivered in individual and group sessions versus no behavioural intervention over a 1-year period.

Primary And Secondary Outcome Measures: Primary outcome: self-reported acceptability of the interventions.

Secondary Outcomes: adherence and self-reported depressive symptoms.

Results: Most participants reported that the F-BA was acceptable (83.61%), feasible to do (65.91%) and would recommend it to a friend (84.57%). Individual F-BA sessions (88.10%) were significantly more often rated as positive than group F-BA sessions (70.17%) and supplements (28.59%). There were statistically significant reductions in depressive symptoms for those who both adhered to the F-BA intervention and had a history of depression (B=-0.08, SE=0.03, p0.012) versus those who had no history of depression. Supplement intake had no effect on depressive symptoms irrespective of adherence.

Conclusions: F-BA may have scope for development as a depression prevention intervention and public health strategy but further refinement and testing are needed.

Trial Registration Number: NCT02529423.
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http://dx.doi.org/10.1136/bmjopen-2019-034025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493122PMC
September 2020

Supplementation-induced increase in circulating omega-3 serum levels is not associated with a reduction in depressive symptoms: Results from the MooDFOOD depression prevention trial.

Depress Anxiety 2020 11 26;37(11):1079-1088. Epub 2020 Aug 26.

Department of Psychiatry, Amsterdam Public Health Research Institute de Boelelaan, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Background: There is ambiguity on how omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are associated with depression, and what the temporality of the association might be. The present study aimed to examine whether (intervention-induced changes in) n-3 PUFA levels were associated with (changes in) depressive symptoms.

Methods: Baseline, 6- and 12-month follow-up data on 682 overweight and subclinically depressed persons from four European countries that participated in the MooDFOOD depression prevention randomized controlled trial were used. Participants were allocated to four intervention groups: (a) placebos, (b) placebos and food-related behavioral activation therapy (F-BA), (c) multinutrient supplements (fish oil and multivitamin), and (d) multinutrient supplements and F-BA. Depressive symptoms were measured using the inventory of depressive symptomatology. PUFA levels (µmol/L) were measured using gas chromatography. Analyses were adjusted for sociodemographics, lifestyle, and somatic health.

Results: Increases in n-3 PUFA, docosahexaenoic acid, and eicosapentaenoic acid levels over time were significantly larger in the supplement groups than in placebo groups. Change in PUFA levels was not significantly associated with the change in depressive symptoms (β = .002, SE = 0.003, p = .39; β = .003, SE = 0.005, p = .64; β = .005, SE = 0.005, p = .29; β = -.0002, SE = 0.0004, p = .69). Baseline PUFA levels did not modify the intervention effects on depressive symptoms.

Conclusions: In overweight and subclinical depressed persons, multinutrient supplements led to significant increases in n-3 PUFA levels over time, which were not associated with changes in depressive symptoms. Multinutrient supplements do not seem to be an effective preventive strategy in lowering depressive symptoms over time in these at-risk groups.
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http://dx.doi.org/10.1002/da.23092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693241PMC
November 2020

Fatigue in Cancer and Neuroinflammatory and Autoimmune Disease: CNS Arousal Matters.

Brain Sci 2020 Aug 19;10(9). Epub 2020 Aug 19.

Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe-Universität Frankfurt am Main, 60323 Frankfurt, Germany.

The term fatigue is not only used to describe a sleepy state with a lack of drive, as observed in patients with chronic physical illnesses, but also a state with an inhibition of drive and central nervous system (CNS) hyperarousal, as frequently observed in patients with major depression. An electroencephalogram (EEG)-based algorithm has been developed to objectively assess CNS arousal and to disentangle these pathophysiologically heterogeneous forms of fatigue. The aim of this study was to test the hypothesis that fatigued patients with CNS hyperarousal score higher on depressive symptoms than those without this neurophysiological pattern.

Methods: Subjects with fatigue (Multidimensional Fatigue Inventory sum-score > 40) in the context of cancer, neuroinflammatory, or autoimmune diseases were drawn from the 60+ cohort of the Leipzig Research Center for Civilization Diseases. CNS arousal was assessed by automatic EEG-vigilance stage classification using the Vigilance Algorithm Leipzig (VIGALL 2.1) based on 20 min EEG recordings at rest with eyes closed. Depression was assessed by the Inventory of Depressive Symptomatology (IDS-SR).

Results: Sixty participants (33 female; median age: 67.5 years) were included in the analysis. As hypothesized, fatigued patients with CNS hyperarousal had higher IDS-SR scores than those without hyperarousal (F = 18.34; < 0.0001, η = 0.240).

Conclusion: hyperaroused fatigue in patients with chronic physical illness may be a sign of comorbid depression.
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http://dx.doi.org/10.3390/brainsci10090569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564388PMC
August 2020

Effects of food-related behavioral activation therapy on eating styles, diet quality and body weight change: Results from the MooDFOOD Randomized Clinical Trial.

J Psychosom Res 2020 Jul 30;137:110206. Epub 2020 Jul 30.

Department of Psychiatry, Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands.

Objective: Depression and obesity are bi-directionally related, eating styles and diet quality are two important factors associated with both. It remains uncertain if and how these two factors can be modified. Therefore the current study aims to investigate whether food-related behavioral activation therapy (F-BA), targeting mood, dietary habits and food related behavior, can improve eating styles, and diet quality and reduce body weight in adults with overweight or obesity and subsyndromal depressive symptoms.

Methods: Data were derived from the MooDFOOD prevention trial, a 2x2 factorial RCT investigating the effect of nutritional strategies on prevention of depression. Changes in emotional, uncontrolled, and cognitive restrained eating (Three Factor Eating Questionnaire Revised), Mediterranean Diet Score (MDS), and body weight were analyzed among 1025 adults who either received F-BA or no intervention for 12 months. Intervention effect was tested by longitudinal analysis of covariance using mixed model analysis.

Results: The F-BA group showed a small decrease in emotional (β=-5.68, p<.001) and uncontrolled eating (β=-4.05, p=.03), and increase in cognitive restrained eating (β=5.53, p<.01), compared to no F-BA. The effect of the F-BA therapy on emotional and uncontrolled eating was stronger in those with higher baseline depressive symptoms (IDS-SR). The F-BA did also lead to small improvements in MDS (β=1.95, p<.001), but not to change in body weight.

Conclusion: Our trial showed no reduction in bodyweight, but provides support for the possibility to improve both unhealthy eating styles and diet quality using an intervention targeting these specifically, although effects were small [Trial registration: clinicaltrials.gov NCT02529423].
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http://dx.doi.org/10.1016/j.jpsychores.2020.110206DOI Listing
July 2020

Promises and risks of web-based interventions in the treatment of depression
.

Dialogues Clin Neurosci 2020 06;22(2):161-168

German Depression Foundation, Leipzig.

Major depression (MD) is a highly prevalent and severe disorder with many patients having no access to efficient treatments such as pharmaco- and psychotherapy. Web-based interventions promise to be a method to provide resource-efficient and widespread access to psychotherapeutic support. Meta-analyses summarizing studies that use face-to-face psychotherapy as a comparator provide evidence for equivalent antidepressant efficacy. Web-based interventions seem to be particularly efficacious when they are accompanied by some form of professional guidance. However, they are also associated with a variety of possible risks (eg, suicidal crises can be overlooked) and unwanted effects (eg, increase in rumination and somatization due to self-monitoring) that are so far under-studied. Although some naturalistic studies yield smaller effect sizes than randomized controlled trials (RCTs), well-designed interventions with adequate guidance have been shown to be successfully integrable into routine care.
.
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http://dx.doi.org/10.31887/DCNS.2020.22.2/uhegerlDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366945PMC
June 2020

Efficacy of a Guided Web-Based Self-Management Intervention for Depression or Dysthymia: Randomized Controlled Trial With a 12-Month Follow-Up Using an Active Control Condition.

J Med Internet Res 2020 07 14;22(7):e15361. Epub 2020 Jul 14.

Department of Psychiatry, Psychosomatics and Psychotherapy, Goethe-Universität Frankfurt, Frankfurt, Germany.

Background: An increasing number of studies suggest that web-based interventions for patients with depression can reduce their symptoms and are expected to fill currently existing treatment gaps. However, evidence for their efficacy has mainly been derived from comparisons with wait-list or treatment as usual controls. In particular, designs using wait-list controls are unlikely to induce hope and may even have nocebo effects, making it difficult to draw conclusions about the intervention's efficacy. Studies using active controls are rare and have not yielded conclusive results.

Objective: The main objective of this study is to assess the acute and long-term antidepressant efficacy of a 6-week, guided, web-based self-management intervention building on the principles of cognitive behavioral therapy (iFightDepression tool) for patients with depression compared with web-based progressive muscle relaxation as an active control condition.

Methods: A total of 348 patients with mild-to-moderate depressive symptoms or dysthymia (according to the Mini International Neuropsychiatric Interview) were recruited online and randomly assigned to 1 of the 2 intervention arms. Acute antidepressant effects after 6 weeks and long-term effects at 3-, 6-, and 12-month follow-up were studied using the Inventory of Depressive Symptomatology-self-rating as a primary outcome parameter and change in quality of life (Short Form 12) and user satisfaction (client satisfaction questionnaire) as secondary outcome parameters. Treatment effects were assessed using mixed model analyses.

Results: Over the entire observation period, a greater reduction in symptoms of depression (P=.01) and a greater improvement of life quality (P<.001) was found in the intervention group compared with the active control group. Separate tests for each time point revealed significant effects on depressive symptoms at the 3-month follow-up (d=0.281; 95% CI 0.069 to 0.493), but not after 6 weeks (main outcome:d=0.192; 95% CI -0.020 to 0.404) and 6 and 12 months. The intervention was significantly superior to the control condition with respect to user satisfaction (25.31 vs 21.97; t=5.804; P<.01).

Conclusions: The fact that antidepressant effects have been found for a guided self-management tool in comparison with an active control strengthens the evidence base for the efficacy of web-based interventions. The antidepressant effect became most prominent at the 3-month follow-up. After 6 weeks of intervention, significant positive effects were observed on life quality but not on depressive symptoms. Although the effect size of such web-based interventions on symptoms of depression might be smaller than that suggested by earlier studies using wait-list control conditions, they can be a cost-effective addition to antidepressants and face-to-face psychotherapy.

Trial Registration: International Clinical Trials Registry Platform ICTRP080-15-09032015; https://apps.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00009323.
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http://dx.doi.org/10.2196/15361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388040PMC
July 2020

Is There an Association or Not?-Investigating the Association of Depressiveness, Physical Activity, Body Composition and Sleep With Mediators of Inflammation.

Front Psychiatry 2020 25;11:563. Epub 2020 Jun 25.

Department of Psychiatry and Psychotherapy, University of Leipzig Medical Center, Leipzig, Germany.

Background: Cytokines are mediators of inflammation that contribute to a low-grade inflammation in different disorders like major depression and obesity. It still remains unclear which psychological and medical factors interact with cytokine regulation. In the current investigation, the association between levels of pro-and anti-inflammatory cytokines and anthropometrics, mood state (depressiveness), physical activity and sleep were investigated in a sample of community-dwelled adults.

Methods: Forty-nine subjects met the inclusion criteria for analyses and were assessed at two time-points (baseline (T1) and follow-up (T2), average T1-T2-interval = 215 days). Serum cytokine measures included the pro-inflammatory cytokines interleukin (IL)-2, IL-12, IFN-γ and TNF-α, the anti-inflammatory cytokines IL-4, IL-5, IL-10 and IL-13 and the granulocyte-macrophage colony-stimulating factor (GM-CSF); anthropometrics were assessed physical examination, depressiveness was assessed Beck Depression Inventory (BDI)2, parameters of physical activity (steps, METs) and sleep (night/total sleep duration) were measured a 1-week actigraphy.

Results: Correlation analyses showed low-to moderate significant relationships between the majority of cytokines and the BDI2 at T1, positive correlation with weight and BMI at T1 and T2, and negative correlations with the number of steps and METs at T2 and T2. Regression analyses for T1 revealed that the BDI2 score was the best positive predictor for the concentrations of all nine cytokines, followed by the number of steps and the nightsleep duration as negative predictors. At T2, the amount of steps was found to be negatively associated with IL-4, IL5, IL-10, GM-CSF, IFN-γ, and TNF-α, whereas the BMI could significantly predict IL-12 and IL-13. The BDI2-score was not significantly associated with any of the cytokines. No associations could be found between dynamics in cytokines from T1 and T2 and changes in any of the variables.

Discussion: The present results indicate an influence of physical activity, subjective well-being and body composition on inflammatory mediators. Since there was no standardized intervention targeting the independent variables between T1 and T2, no assumptions on causality can be drawn from the association results.
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http://dx.doi.org/10.3389/fpsyt.2020.00563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330708PMC
June 2020

Accuracy of the PHQ-2 Alone and in Combination With the PHQ-9 for Screening to Detect Major Depression: Systematic Review and Meta-analysis.

JAMA 2020 06;323(22):2290-2300

Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, Québec, Canada.

Importance: The Patient Health Questionnaire depression module (PHQ-9) is a 9-item self-administered instrument used for detecting depression and assessing severity of depression. The Patient Health Questionnaire-2 (PHQ-2) consists of the first 2 items of the PHQ-9 (which assess the frequency of depressed mood and anhedonia) and can be used as a first step to identify patients for evaluation with the full PHQ-9.

Objective: To estimate PHQ-2 accuracy alone and combined with the PHQ-9 for detecting major depression.

Data Sources: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, PsycINFO, and Web of Science (January 2000-May 2018).

Study Selection: Eligible data sets compared PHQ-2 scores with major depression diagnoses from a validated diagnostic interview.

Data Extraction And Synthesis: Individual participant data were synthesized with bivariate random-effects meta-analysis to estimate pooled sensitivity and specificity of the PHQ-2 alone among studies using semistructured, fully structured, or Mini International Neuropsychiatric Interview (MINI) diagnostic interviews separately and in combination with the PHQ-9 vs the PHQ-9 alone for studies that used semistructured interviews. The PHQ-2 score ranges from 0 to 6, and the PHQ-9 score ranges from 0 to 27.

Results: Individual participant data were obtained from 100 of 136 eligible studies (44 318 participants; 4572 with major depression [10%]; mean [SD] age, 49 [17] years; 59% female). Among studies that used semistructured interviews, PHQ-2 sensitivity and specificity (95% CI) were 0.91 (0.88-0.94) and 0.67 (0.64-0.71) for cutoff scores of 2 or greater and 0.72 (0.67-0.77) and 0.85 (0.83-0.87) for cutoff scores of 3 or greater. Sensitivity was significantly greater for semistructured vs fully structured interviews. Specificity was not significantly different across the types of interviews. The area under the receiver operating characteristic curve was 0.88 (0.86-0.89) for semistructured interviews, 0.82 (0.81-0.84) for fully structured interviews, and 0.87 (0.85-0.88) for the MINI. There were no significant subgroup differences. For semistructured interviews, sensitivity for PHQ-2 scores of 2 or greater followed by PHQ-9 scores of 10 or greater (0.82 [0.76-0.86]) was not significantly different than PHQ-9 scores of 10 or greater alone (0.86 [0.80-0.90]); specificity for the combination was significantly but minimally higher (0.87 [0.84-0.89] vs 0.85 [0.82-0.87]). The area under the curve was 0.90 (0.89-0.91). The combination was estimated to reduce the number of participants needing to complete the full PHQ-9 by 57% (56%-58%).

Conclusions And Relevance: In an individual participant data meta-analysis of studies that compared PHQ scores with major depression diagnoses, the combination of PHQ-2 (with cutoff ≥2) followed by PHQ-9 (with cutoff ≥10) had similar sensitivity but higher specificity compared with PHQ-9 cutoff scores of 10 or greater alone. Further research is needed to understand the clinical and research value of this combined approach to screening.
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http://dx.doi.org/10.1001/jama.2020.6504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284301PMC
June 2020

Temporal Associations of Daily Changes in Sleep and Depression Core Symptoms in Patients Suffering From Major Depressive Disorder: Idiographic Time-Series Analysis.

JMIR Ment Health 2020 Apr 23;7(4):e17071. Epub 2020 Apr 23.

Research Centre of the German Depression Foundation, Leipzig, Germany.

Background: There is a strong link between sleep and major depression; however, the causal relationship remains unclear. In particular, it is unknown whether changes in depression core symptoms precede or follow changes in sleep, and whether a longer or shorter sleep duration is related to improvements of depression core symptoms.

Objective: The aim of this study was to investigate temporal associations between sleep and depression in patients suffering from major depressive disorder using an idiographic research approach.

Methods: Time-series data of daily sleep assessments (time in bed and total sleep time) and self-rated depression core symptoms for an average of 173 days per patient were analyzed in 22 patients diagnosed with recurrent major depressive disorder using a vector autoregression model. Granger causality tests were conducted to test for possible causality. Impulse response analysis and forecast error variance decomposition were performed to quantify the temporal mutual impact of sleep and depression.

Results: Overall, 11 positive and 5 negative associations were identified between time in bed/total sleep time and depression core symptoms. Granger analysis showed that time in bed/total sleep time caused depression core symptoms in 9 associations, whereas this temporal order was reversed for the other 7 associations. Most of the variance (10%) concerning depression core symptoms could be explained by time in bed. Changes in sleep or depressive symptoms of 1 SD had the greatest impact on the other variable in the following 2 to 4 days.

Conclusions: Longer rather than shorter bedtimes were associated with more depression core symptoms. However, the temporal orders of the associations were heterogeneous.
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http://dx.doi.org/10.2196/17071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206522PMC
April 2020

Polymorphisms in CRYBB2 encoding βB2-crystallin are associated with antisaccade performance and memory function.

Transl Psychiatry 2020 04 21;10(1):113. Epub 2020 Apr 21.

Department of Psychiatry, Psychotherapy and Psychosomatics, Martin-Luther-University Halle-Wittenberg, Halle, Germany.

βB2-crystallin (gene symbol: Crybb2/CRYBB2) was first described as a structural protein of the ocular lens before it was detected in various brain regions of the mouse, including the hippocampus and the cerebral cortex. Mutations in the mouse Crybb2 gene lead to alterations of sensorimotor gating measured as prepulse inhibition (PPI) and reduced hippocampal size, combined with an altered number of parvalbumin-positive GABAergic interneurons. Decreased PPI and alterations of parvalbumin-positive interneurons are also endophenotypes that typically occur in schizophrenia. To verify the results found in mice, we genotyped 27 single nucleotide polymorphisms (SNPs) within the CRYBB2 gene and its flanking regions and investigated different schizophrenia typical endophenotypes in a sample of 510 schizophrenia patients and 1322 healthy controls. In the case-control study, no association with schizophrenia was found. However, 3 of the 4 investigated haplotype blocks indicated a decreased CRYBB2 mRNA expression. Two of these blocks were associated with poorer antisaccade task performance and altered working memory-linked functional magnetic resonance imaging signals. For the two haplotypes associated with antisaccade performance, suggestive evidence was found with visual memory and in addition, haplotype block 4 showed a nominally significant association with reduced sensorimotor gating, measured as P50 ratio. These results were not schizophrenia-specific, but could be detected in a combined sample of patients and healthy controls. This is the first study to demonstrate the importance of βB2-crystallin for antisaccade performance and memory function in humans and therefore provides implications for βB2-crystallin function in the human brain.
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http://dx.doi.org/10.1038/s41398-020-0791-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174396PMC
April 2020

Reported and Recorded Sleepiness in Obesity and Depression.

Front Psychiatry 2020 2;11:200. Epub 2020 Apr 2.

Institute for Statistics, Ludwig-Maximilians-Universität München, München, Germany.

Background: Obesity and depression are both associated with changes in sleep/wake regulation, with potential implications for individualized treatment especially in comorbid individuals suffering from both. However, the associations between obesity, depression, and subjective, questionnaire-based and objective, EEG-based measurements of sleepiness used to assess disturbed sleep/wake regulation in clinical practice are not well known.

Objectives: The study investigates associations between sleep/wake regulation measures based on self-reported subjective questionnaires and EEG-derived measurements of sleep/wake regulation patterns with depression and obesity and how/whether depression and/or obesity affect associations between such self-reported subjective questionnaires and EEG-derived measurements.

Methods: Healthy controls (HC, N = 66), normal-weighted depressed (DEP, N = 16), non-depressed obese (OB, N = 68), and obese depressed patients (OBDEP, N = 43) were included from the OBDEP (Obesity and Depression, University Leipzig, Germany) study. All subjects completed standardized questionnaires related to daytime sleepiness (ESS), sleep quality and sleep duration once as well as questionnaires related to situational sleepiness (KSS, SSS, VAS) before and after a 20 min resting state EEG in eyes-closed condition. EEG-based measurements of objective sleepiness were extracted by the VIGALL algorithm. Associations of subjective sleepiness with objective sleepiness and moderating effects of obesity, depression, and additional confounders were investigated by correlation analyses and regression analyses.

Results: Depressed and non-depressed subgroups differed significantly in most subjective sleepiness measures, while obese and non-obese subgroups only differed significantly in few. Objective sleepiness measures did not differ significantly between the subgroups. Moderating effects of obesity and/or depression on the associations between subjective and objective measures of sleepiness were rarely significant, but associations between subjective and objective measures of sleepiness in the depressed subgroup were systematically weaker when patients comorbidly suffered from obesity than when they did not.

Conclusion: This study provides some evidence that both depression and obesity can affect the association between objective and subjective sleepiness. If confirmed, this insight may have implications for individualized diagnosis and treatment approaches in comorbid depression and obesity.
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http://dx.doi.org/10.3389/fpsyt.2020.00200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144401PMC
April 2020

Reported and Recorded Sleepiness in Obesity and Depression.

Front Psychiatry 2020 2;11:200. Epub 2020 Apr 2.

Institute for Statistics, Ludwig-Maximilians-Universität München, München, Germany.

Background: Obesity and depression are both associated with changes in sleep/wake regulation, with potential implications for individualized treatment especially in comorbid individuals suffering from both. However, the associations between obesity, depression, and subjective, questionnaire-based and objective, EEG-based measurements of sleepiness used to assess disturbed sleep/wake regulation in clinical practice are not well known.

Objectives: The study investigates associations between sleep/wake regulation measures based on self-reported subjective questionnaires and EEG-derived measurements of sleep/wake regulation patterns with depression and obesity and how/whether depression and/or obesity affect associations between such self-reported subjective questionnaires and EEG-derived measurements.

Methods: Healthy controls (HC, N = 66), normal-weighted depressed (DEP, N = 16), non-depressed obese (OB, N = 68), and obese depressed patients (OBDEP, N = 43) were included from the OBDEP (Obesity and Depression, University Leipzig, Germany) study. All subjects completed standardized questionnaires related to daytime sleepiness (ESS), sleep quality and sleep duration once as well as questionnaires related to situational sleepiness (KSS, SSS, VAS) before and after a 20 min resting state EEG in eyes-closed condition. EEG-based measurements of objective sleepiness were extracted by the VIGALL algorithm. Associations of subjective sleepiness with objective sleepiness and moderating effects of obesity, depression, and additional confounders were investigated by correlation analyses and regression analyses.

Results: Depressed and non-depressed subgroups differed significantly in most subjective sleepiness measures, while obese and non-obese subgroups only differed significantly in few. Objective sleepiness measures did not differ significantly between the subgroups. Moderating effects of obesity and/or depression on the associations between subjective and objective measures of sleepiness were rarely significant, but associations between subjective and objective measures of sleepiness in the depressed subgroup were systematically weaker when patients comorbidly suffered from obesity than when they did not.

Conclusion: This study provides some evidence that both depression and obesity can affect the association between objective and subjective sleepiness. If confirmed, this insight may have implications for individualized diagnosis and treatment approaches in comorbid depression and obesity.
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http://dx.doi.org/10.3389/fpsyt.2020.00200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144401PMC
April 2020

Depressive Symptom Clusters in Relation to Body Weight Status: Results From Two Large European Multicenter Studies.

Front Psychiatry 2019 21;10:858. Epub 2019 Nov 21.

Department of Psychiatry and Psychotherapy, Medical Faculty, University Leipzig, Leipzig, Germany.

There is strong evidence for a bidirectional association between depression and obesity. Several biological, psychological, and behavior-related factors may influence this complex association. Clinical impression and preliminary evidence suggest that patients with a diagnosis of major depressive disorder may endorse very different depressive symptom patterns depending on their body weight status. Until now, little is known about potential differences in depressive symptoms in relation to body weight status. The aim of this analysis is the investigation of potential differences in depressive symptom clusters (mood symptoms, somatic/vegetative symptoms, and cognitive symptoms) in relation to body weight status. : Cross-sectional baseline data were derived from two large European multicenter studies: the MooDFOOD Trial and the NESDA cohort study, including persons with overweight and obesity and normal weight reporting subthreshold depressive symptoms (assessment Inventory of Depressive Symptomatology Self-Report, IDS-SR30). Different measures for body weight status [waist-to-hip ratio (WHR) and body mass index (BMI)] were examined. Propensity score matching was performed and multiple linear regression analyses were conducted. : A total of = 504 individuals (73.0% women) were analyzed. Results show that more somatic/vegetative depressive symptoms, such as pain, change in appetite and weight, gastrointestinal symptoms, and arousal-related symptoms, were significantly associated with both a higher BMI and higher WHR, respectively. In addition, being male and older age were significantly associated with higher WHR. Mood and cognitive depressive symptoms did not yield significant associations for both body weight status measures. Somatic/vegetative symptoms and not mood and cognitive symptoms of depression are associated with body weight status. Thus, the results support previous findings of heterogeneous depressive symptoms in relation to body weight status. In addition to BMI, other body weight status measures for obesity should be taken into account in future studies. www.ClinicalTrials.gov, identifier NCT02529423.
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http://dx.doi.org/10.3389/fpsyt.2019.00858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882291PMC
November 2019
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