Childhood maltreatment as predictor and moderator for treatment outcome in patients with major depressive disorders treated with metacognitive therapy or behavioral activation.

BACKGROUND: Childhood maltreatment (CM) is a risk factor for developing and maintaining depression. It is unclear whether CM influences the effect of treatments for depression. This study examined CM's predictor and moderator effect in Behavioral Activation (BA) and Metacognitive Therapy (MCT). METHOD: CM was analyzed in a trial comparing a six months treatment program of either BA or MCT for 122 outpatients with major depressive disorder (MDD). Depression was assessed by the Hamilton Rating Scale for Depression (HRSD-24). CM was assessed using the Childhood Trauma Questionnaire (CTQ). RESULTS: Linear mixed models showed no predictor or moderator effects for the CTQ total score (all p > .58) but revealed a moderator effect for 'sexual abuse' on the reduction of depressive symptoms (ß = 10.98, SE = 4.48, p = .015) indicating that patients with experiences of childhood sexual abuse benefited more from BA. There also was a predictor effect for 'physical neglect' (ß = -3.35, SE = 1.70, p = .049): patients without the experience of physical neglect benefited more from treatment regardless of condition. Exploratory analyses indicated no predictor or moderator effects for the onset or persistence of depression, comorbid anxiety disorders or Cluster-C PDs (all p > .28). LIMITATIONS: Limitations include small sample sizes for some of the subsamples. CONCLUSION: Childhood sexual abuse seems to moderate treatment effectiveness in a sample of severely affected outpatients with MDD treated with MCT or BA. If confirmed in further trials, a history of sexual abuse might guide the choice between MCT and BA. TRIAL REGISTRATION: German Clinical Trials Register DRKS-ID: DRKS00011536 (retrospectively registered on February 13, 2017, without changes to the study protocol).

The Effectiveness of Dialectical Behavior Therapy Compared to Schema Therapy for Borderline Personality Disorder: A Randomized Clinical Trial.

INTRODUCTION: In the treatment of borderline personality disorder (BPD), there is empirical support for both dialectical behavior therapy (DBT) and schema therapy (ST); these treatments have never been compared directly. This study examines whether either of them is more effective than the other in treating patients with BPD. METHODS: In this randomized, parallel-group, rater-blind clinical trial, outpatients aged between 18 and 65 years with a primary diagnosis of BPD were recruited in a tertiary outpatient treatment center (Lübeck, Germany). Participants were randomized to DBT or ST with one individual and one group session per week over 1.5 years. The primary outcome was the BPD symptom severity assessed with the mean score of the Borderline Personality Disorder Severity Index at 1-year naturalistic follow-up. RESULTS: Between November 26, 2014, and December 14, 2018, we enrolled 164 patients (mean age = 33.7 [SD = 10.61] years). Of these, 81 (49.4%) were treated with ST and 83 (50.6%) with DBT, overall, 130 (79.3%) were female. Intention-to-treat analysis with generalized linear mixed models did not show a significant difference at 1-year naturalistic follow-up between DBT and ST for the BPDSI total score (mean difference 3.32 [95% CI: -0.58-7.22], p = 0.094, d = -24 [-0.69; 0.20]) with lower scores for DBT. Pre-to-follow-up effect sizes were large in both groups (DBT: d = 2.45 [1.88-3.02], ST: d = 1.78 [1.26-2.29]). CONCLUSION: Patients in both treatment groups showed substantial improvements indicating that even severely affected patients with BPD and various comorbid disorders can be treated successfully with DBT and ST. An additional non-inferiority trial is needed to show if both treatments are equally effective. The trial was retrospectively registered on the German Clinical Trials Register, DRKS00011534 without protocol changes.

Imagery rescripting and cognitive restructuring for inpatients with moderate and severe depression - a controlled pilot study.

BACKGROUND: This controlled pilot study investigates the effect of the combined use of cognitive restructuring (CR) and imagery rescripting (IR) compared to treatment as usual among inpatients with moderate and severe depression. Alongside expert ratings and self-report tools, fitness wristbands were used as an assessment tool. METHODS: In addition to the standard inpatient care (SIC) program, 33 inpatients with moderate and severe depression were randomly assigned to an intervention group (two sessions of IR and CR) or an active treatment-as-usual (TAU) control group (two sessions of problem-solving and build-up of positive activity). Depression severity was assessed by the Hamilton Depression Rating Scale-21 (HDRS-21), the Beck Depression Inventory-II (BDI-II), and as a diagnostic adjunct daily step count via the Fitbit Charge 3™. We applied for analyses of HDRS-21 and BDI-II, 2 × 2 repeated-measures analysis of variance (ANOVA), and an asymptotic Wilcoxon test for step count. RESULTS: The main effect of time on both treatments was η2 = .402. Based on the data from the HDRS-21, patients in the intervention group achieved significantly greater improvements over time than the TAU group (η2 = .34). The BDI-II data did not demonstrate a significant interaction effect by group (η2 = .067). The daily hourly step count for participants of the intervention group was significantly higher (r = .67) than the step count for the control group. CONCLUSIONS: The findings support the utilization of imagery-based interventions for treating depression. They also provide insights into using fitness trackers as psychopathological assessment tools for depressed patients. TRIAL REGISTRATION: The trial is registered at the German Clinical Trials Register (Deutsches Register Klinischer Studien) under the registration number: DRKS00030809.

Depression and fatigue six months post-COVID-19 disease are associated with overlapping symptom constellations: A prospective, multi-center, population-based cohort study.

BACKGROUND: Depression and fatigue are commonly observed sequelae following viral diseases such as COVID-19. Identifying symptom constellations that differentially classify post-COVID depression and fatigue may be helpful to individualize treatment strategies. Here, we investigated whether self-reported post-COVID depression and post-COVID fatigue are associated with the same or different symptom constellations. METHODS: To address this question, we used data from COVIDOM, a population-based cohort study conducted as part of the NAPKON-POP platform. Data were collected in three different German regions (Kiel, Berlin, Würzburg). We analyzed data from >2000 individuals at least six months past a PCR-confirmed COVID-19 disease, using elastic net regression and cluster analysis. The regression model was developed in the Kiel data set, and externally validated using data sets from Berlin and Würzburg. RESULTS: Our results revealed that post-COVID depression and fatigue are associated with overlapping symptom constellations consisting of difficulties with daily activities, perceived health-related quality of life, chronic exhaustion, unrestful sleep, and impaired concentration. Confirming the overlap in symptom constellations, a follow-up cluster analysis could categorize individuals as scoring high or low on depression and fatigue but could not differentiate between both dimensions. LIMITATIONS: The data presented are cross-sectional, consisting primarily of self-reported questionnaire or medical records rather than biometric data. CONCLUSIONS: In summary, our results suggest a strong link between post-COVID depression and fatigue, highlighting the need for integrative treatment approaches.

Chairwork in schema therapy for patients with borderline personality disorder-A qualitative study of patients' perceptions.

Objective: Chairwork is one of the core experiential techniques of Schema Therapy (ST) which is used in the treatment of patients with borderline personality disorder (BPD). However, little is known about how people with BPD experience chairwork. The aim of this study was to explore the experiences of patients with BPD with chairwork in ST. Method: Qualitative data were collected through semi-structured interviews with 29 participants with a primary diagnosis of BPD who experienced chairwork as part of their ST treatment. The interview data were analyzed using qualitative content analysis. Findings: Many participants reported initial skepticism, and difficulties with engaging in chairwork. Specific therapist behaviors as well as some external (e.g., restricted facilities, noise) and internal factors (especially feeling ashamed or ridiculous) were named as hindering factors. Participants described several therapist behaviors facilitating chairwork such as providing safety, clear guidance through the process as well as flexible application of the technique according to their needs, and sufficient time for debriefing. Participants experienced emotional pain and exhaustion as short-term effects of the technique. All participants reported positive long-term effects including an improved understanding of their mode model as well as positive mode changes (e.g., less Punitive Parent and more Healthy Adult Mode), greater self-acceptance, improvements in coping with emotions and needs as well as improvements in interpersonal relationships. Conclusions: Chairwork is experienced as an emotionally demanding but valuable technique. Based on the participants' statements, the delivery of chairwork can be optimized which can help to improve treatment outcome.

The Effectiveness of Metacognitive Therapy Compared to Behavioral Activation for Severely Depressed Outpatients: A Single-Center Randomized Trial.

INTRODUCTION: Major depressive disorder (MDD) is a highly prevalent and disabling disorder. This study examines two psychotherapy methods for MDD, behavioral activation (BA), and metacognitive therapy (MCT), when applied as outpatient treatments to severely affected patients. METHODS: The study was conducted in a tertiary outpatient treatment center. Patients with a primary diagnosis of MDD (N = 122) were included in the intention-to-treat sample (55.7% female, mean age 41.9 years). Participants received one individual and one group session weekly for 6 months (M). Assessments took place at baseline, pretreatment, mid-treatment (3 M), post-treatment (6 M), and follow-up (12 M). The primary outcome was depressive symptomatology assessed by the Hamilton Rating Scale for Depression at 12 M follow-up. Secondary outcomes included general symptom severity, psychosocial functioning, and quality of life. RESULTS: Linear mixed models indicated a change in depressive symptoms (F(2, 83.495) = 12.253, p < 0.001) but no between-group effect (F(1, 97.352) = 0.183, p = 0.670). Within-group effect sizes were medium for MCT (post-treatment: d = 0.610; follow-up: d = 0.692) and small to medium for BA (post-treatment: d = 0.636, follow-up: d = 0.326). In secondary outcomes, there were improvements (p ≤ 0.040) with medium to large within-group effect sizes (d ≥ 0.501) but no between-group effects (p ≥ 0.304). Response and remission rates did not differ between conditions at follow-up (response MCT: 12.9%, BA: 13.3%, remission MCT: 9.7%, BA: 10.0%). The deterioration rate was lower in MCT than in BA (χ21 = 5.466, p = 0.019, NTT = 7.4). DISCUSSION: Both MCT and BA showed symptom reductions. Remission and response rates were lower than in previous studies, highlighting the need for further improvements in adapting/implementing treatments for severely affected patients with MDD.

Reply to Witthöft et al. Comment on "Wardzinski et al. Mobile Phone Radiation Deflects Brain Energy Homeostasis and Prompts Human Food Ingestion. Nutrients 2022, 14, 339".

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Mobile Phone Radiation Deflects Brain Energy Homeostasis and Prompts Human Food Ingestion.

Obesity and mobile phone usage have simultaneously spread worldwide. Radio frequency-modulated electromagnetic fields (RF-EMFs) emitted by mobile phones are largely absorbed by the head of the user, influence cerebral glucose metabolism, and modulate neuronal excitability. Body weight adjustment, in turn, is one of the main brain functions as food intake behavior and appetite perception underlie hypothalamic regulation. Against this background, we questioned if mobile phone radiation and food intake may be related. In a single-blind, sham-controlled, randomized crossover comparison, 15 normal-weight young men (23.47 ± 0.68 years) were exposed to 25 min of RF-EMFs emitted by two different mobile phone types vs. sham radiation under fasting conditions. Spontaneous food intake was assessed by an ad libitum standard buffet test and cerebral energy homeostasis was monitored by 31phosphorus-magnetic resonance spectroscopy measurements. Exposure to both mobile phones strikingly increased overall caloric intake by 22-27% compared with the sham condition. Differential analyses of macronutrient ingestion revealed that higher calorie consumption was mainly due to enhanced carbohydrate intake. Measurements of the cerebral energy content, i.e., adenosine triphosphate and phosphocreatine ratios to inorganic phosphate, displayed an increase upon mobile phone radiation. Our results identify RF-EMFs as a potential contributing factor to overeating, which underlies the obesity epidemic. Beyond that, the observed RF-EMFs-induced alterations of the brain energy homeostasis may put our data into a broader context because a balanced brain energy homeostasis is of fundamental importance for all brain functions. Potential disturbances by electromagnetic fields may therefore exert some generalized neurobiological effects, which are not yet foreseeable.

Hypocaloric Dieting Unsettles the Neuroenergetic Homeostasis in Humans.

BACKGROUND: The effects of low-calorie dieting in obesity are disappointing in the long run. The brain's energy homeostasis plays a key role in the regulation of body weight. We hypothesized that the cerebral energy status underlies an adaptation process upon body weight loss due to hypocaloric dieting in humans. OBJECTIVE: We instructed 26 healthy obese participants to reduce body weight via replacement of meals by a commercial diet product for two weeks. The cerebral energy status was assessed by 31 phosphorus magnetic resonance spectroscopy (31 PMRS) before and after low-caloric dieting as well as at follow-up. A standardized test buffet was quantified after body weight loss and at follow-up. Blood glucose metabolism and neurohormonal stress axis activity were monitored. RESULTS: Weight loss induced a decline in blood concentrations of insulin (p = 0.002), C-peptide (p = 0.005), ACTH (p = 0.006), and norepinephrine (p = 0.012). ATP/Pi (p = 0.003) and PCr/Pi ratios (p = 0.012) were increased and NADH levels reduced (p = 0.041) after hypocaloric dieting. At follow-up, weight loss persisted (p < 0.001), while insulin, C-peptide, and ACTH increased (p < 0.005 for all) corresponding to baseline levels again. Despite repealed hormonal alterations, ratios of PCr/Pi remained higher (p = 0.039) and NADH levels lower (p = 0.007) 6 weeks after ending the diet. ATP/Pi ratios returned to baseline levels again (p = 0.168). CONCLUSION: Low-calorie dieting reduces neurohormonal stress axis activity and increases the neuroenergetic status in obesity. This effect was of a transient nature in terms of stress hormonal measures. In contrast, PCr/Pi ratios remained increased after dieting and at follow-up while NADH levels were still reduced, which indicates a persistently unsettled neuroenergetic homeostasis upon diet-induced rapid body weight loss.

Brain activations show association with subsequent endocrine responses to oral glucose challenge in a satiation-level dependent manner.

Aims: The communication between brain and peripheral homeostatic systems is a central element of ingestive control. We set out to explore which parts of the brain have strong functional connections to peripheral signalling molecules in a physiological context. It was hypothesised that associations can be found between endocrine response to glucose ingestion and preceding brain activity in dependence of the nutritional status of the body. Materials and methods: Young, healthy male participants underwent both a 38 â€‹h fasting and a control condition with standardized meals. On the second day of the experiment, participants underwent fMRI scanning followed by ingestion of glucose solution in both conditions. Subsequent endocrine responses relevant to energy metabolism were assessed. Associations between preceding brain activation and endocrine responses were examined. Results: In both fasting and non-fasting conditions, brain activity was associated with subsequent endocrine responses after glucose administration, but relevant brain areas differed substantially between the conditions. In the fasting condition relations between the caudate nucleus and the orbitofrontal regions with insulin and C-peptide were prevailing, whereas in the non-fasting condition associations between various brain regions and adiponectin and cortisol were the predominant significant outcome. Conclusion: Connections between endocrine response following a glucose challenge and prior brain activity suggests that the brain is playing an active role in the networks regulating food intake and associated endocrine signals. Further studies are needed to demonstrate causation.

Psychotic-like experiences in patients with insomnia or sleep apnea: associations with sleep parameters.

OBJECTIVES: There are strong links between sleep and psychotic-like experiences (PLE), such as magical ideations or persecutory ideas. Sleep disturbances seem to play an important role in the occurrence of such symptoms, but studies investigating PLE in patients with sleep disorders are lacking. METHODS: We studied 24 subjects with insomnia disorder (41 ± 13 years) and 47 participants with obstructive sleep apnea (OSA, 47 ± 11 years) in the sleep laboratory and 33 healthy controls. Sleep in patients with sleep disorders was recorded and scored according to standard criteria of the American Academy of Sleep Medicine. PLE were measured by the Magical Ideation Scale (MIS, short form with 10 items) and by the Peters et al., Delusions Inventory (PDI, 21 items). Additionally, cognitive tests and further psychological self-rating tests such as the Beck Depression Inventory (BDI) and the Pittsburgh Sleep Quality Index (PSQI) were administered. RESULTS: Patients with insomnia had significantly higher scores of magical and delusional ideations compared to healthy controls. Sleep apnea patients showed a tendency of a higher score of delusional beliefs in comparison to controls. Magical ideations in insomnia subjects were significantly negatively correlated with the number of sleep spindles. In a subgroup of insomnia patients without antidepressants, delusional beliefs were negatively associated with rapid eye movement (REM)-sleep. CONCLUSIONS: As there are indications that diminutions of sleep spindles are a biomarker for dysfunctional thalamo-cortical circuits underlying the neuropathology of psychosis, we conclude that there might be a sub-group of insomnia patients with fewer sleep spindles which is more vulnerable to developing a psychotic disorder in the future.

Effects of hunger, satiety and oral glucose on effective connectivity between hypothalamus and insular cortex.

The hypothalamus and insular cortex play an essential role in the integration of endocrine and homeostatic signals and their impact on food intake. Resting-state functional connectivity alterations of the hypothalamus, posterior insula (PINS) and anterior insula (AINS) are modulated by metabolic states and caloric intake. Nevertheless, a deeper understanding of how these factors affect the strength of connectivity between hypothalamus, PINS and AINS is missing. This study investigated whether effective (directed) connectivity within this network varies as a function of prandial states (hunger vs. satiety) and energy availability (glucose levels and/or hormonal modulation). To address this question, we measured twenty healthy male participants of normal weight twice: once after 36 â€‹h of fasting (except water consumption) and once under satiated conditions. During each session, resting-state functional MRI (rs-fMRI) and hormone concentrations were recorded before and after glucose administration. Spectral dynamic causal modeling (spDCM) was used to assess the effective connectivity between the hypothalamus and anterior and posterior insula. Using Bayesian model selection, we observed that the same model was identified as the most likely model for each rs-fMRI recording. Compared to satiety, the hunger condition enhanced the strength of the forward connections from PINS to AINS and reduced the strength of backward connections from AINS to PINS. Furthermore, the strength of connectivity from PINS to AINS was positively related to plasma cortisol levels in the hunger condition, mainly before glucose administration. However, there was no direct relationship between glucose treatment and effective connectivity. Our findings suggest that prandial states modulate connectivity between PINS and AINS and relate to theories of interoception and homeostatic regulation that invoke hierarchical relations between posterior and anterior insula.

Endocrine profile dataset of fasting and normally eating young, healthy men and following activation of brain areas involved in ingestive behaviour.

Data includes endocrine data (adiponectin, ACTH, cortisol, C-peptide, insulin and glucose) of a 38 hour fasting intervention and a control condition with standardised meals in young healthy male subjects. The data was collected using a within-design approach. The data of ten common bilateral regions of interest (ROIs) involved in ingestive behaviour are included as fMRI percent signal change measurements of the amygdala, caudate nucleus, insula (classified into three regions), nucleus accumbens (NAcc), orbitofrontal cortex (OFC, classified into two different regions), pallidum, and lastly, the putamen. These measurements were performed whilst images of food were shown to participants during fMRI who would rate them on a scale from 1 to 8. Reaction times as well as each image's score are also included in the dataset. Endocrine data is especially useful as it is a well-controlled dataset of healthy young males in fasting and satiated conditions. Furthermore, this data can provide a physiological reference for experiments in patients with impaired glucose tolerance or metabolic syndrome. fMRI data may be useful as an extension of an existing dataset or for replication of the collected data.

Modulation of brain activity by hormonal factors in the context of ingestive behaviour.

INTRODUCTION: Metabolic and hormonal signals have been shown to be associated with brain activity in the context of ingestive behaviour. However, this has mostly been seen in studies using external administration of hormones or glucose. We therefore studied endocrine-brain interaction in a physiological setting with hormone levels determined by metabolic conditions such as normal food intake vs. prolonged fasting. METHODS: 24 healthy, normal weight men participated in two sessions, one involving a 38-hour fasting period and one a non-fasting control condition with standardized meals. Functional magnetic resonance imaging was performed at the end of the experiment with participants being required to rate pictures of food. Brain activation was compared between conditions in predefined regions of interest (ROIs). Multiple blood samples were taken to determine levels of insulin, C-peptide, cortisol, ACTH, glucose and adiponectin. These were used as a predictor variable in a regression analysis on brain activations in the different ROIs. RESULTS: Food pictures were rated as more desirable in the fasting condition. Univariate analysis of ROI activations revealed mainly effects of food rating and no significant effects of the metabolic state. Multiple regression analysis revealed associations between orbitofrontal cortex activation and blood glucose in the non-fasting condition. In the fasting condition adiponectin was associated with the signal from the caudate nucleus and insulin and C-peptide were associated with functional activity of orbitofrontal regions. DISCUSSION: Associations of endocrine signals and functional neural regions could be demonstrated in a realistic setting without external administration of hormones. As the current approach was correlational, further studies need to address the causal role of hormonal signals.

Machine Learning Based Classification of Resting-State fMRI Features Exemplified by Metabolic State (Hunger/Satiety).

OBJECTIVE: Resting-state functional magnetic resonance imaging (rs-fMRI) has become an essential measure to investigate the human brain's spontaneous activity and intrinsic functional connectivity. Several studies including our own previous work have shown that the brain controls the regulation of energy expenditure and food intake behavior. Accordingly, we expected different metabolic states to influence connectivity and activity patterns in neuronal networks. METHODS: The influence of hunger and satiety on rs-fMRI was investigated using three connectivity models (local connectivity, global connectivity and amplitude rs-fMRI signals). After extracting the connectivity parameters of 90 brain regions for each model, we used sequential forward floating selection strategy in conjunction with a linear support vector machine classifier and permutation tests to reveal which connectivity model differentiates best between metabolic states (hunger vs. satiety). RESULTS: We found that the amplitude of rs-fMRI signals is slightly more precise than local and global connectivity models in order to detect resting brain changes during hunger and satiety with a classification accuracy of 81%. CONCLUSION: The amplitude of rs-fMRI signals serves as a suitable basis for machine learning based classification of brain activity. This opens up the possibility to apply this combination of algorithms to similar research questions, such as the characterization of brain states (e.g., sleep stages) or disease conditions (e.g., Alzheimer's disease, minimal cognitive impairment).

Impact of Hunger, Satiety, and Oral Glucose on the Association Between Insulin and Resting-State Human Brain Activity.

To study the interplay of metabolic state (hungry vs. satiated) and glucose administration (including hormonal modulation) on brain function, resting-state functional magnetic resonance imaging (rs-fMRI) and blood samples were obtained in 24 healthy normal-weight men in a repeated measurement design. Participants were measured twice: once after a 36 h fast (except water) and once under satiation (three meals/day for 36 h). During each session, rs-fMRI and hormone concentrations were recorded before and after a 75 g oral dose of glucose. We calculated the amplitude map from blood-oxygen-level-dependent (BOLD) signals by using the fractional amplitude of low-frequency fluctuation (fALFF) approach for each volunteer per condition. Using multiple linear regression analysis (MLRA) the interdependence of brain activity, plasma insulin and blood glucose was investigated. We observed a modulatory impact of fasting state on intrinsic brain activity in the posterior cingulate cortex (PCC). Strikingly, differences in plasma insulin levels between hunger and satiety states after glucose administration at the time of the scan were negatively related to brain activity in the posterior insula and superior frontal gyrus (SFG), while plasma glucose levels were positively associated with activity changes in the fusiform gyrus. Furthermore, we could show that changes in plasma insulin enhanced the connectivity between the posterior insula and SFG. Our results indicate that hormonal signals like insulin alleviate an acute hemostatic energy deficit by modifying the homeostatic and frontal circuitry of the human brain.

Endocrine responses and food intake in fasted individuals under the influence of glucose ingestion.

INTRODUCTION: Different metabolic conditions can affect what and how much we eat. Hormones of glucose metabolism and adipokines such as adiponectin take part in the control of these decisions and energy balance of the body. However, a comprehensive understanding of how these endocrine and metabolic factors influence food intake has not been reached. We hypothesised that the amount of food a person consumes differs substantially after a fasting period even after the energy deficit was partially removed by glucose ingestion and endocrine signals like insulin and C-peptide indicated a high glucose metabolic status. Furthermore, the macronutrient composition of the consumed food and a possible association with adiponectin under the influence of glucose ingestion was assessed. METHODS: In a within-subject design, 24 healthy males participated in both a fasting (42 h) and control (non-fasting) condition. A total of 20 blood samples from each subject were collected during each condition to assess serum levels of adiponectin, insulin, C-peptide, cortisol and ACTH. At the end of each condition food intake was measured with an ad libitum buffet after the acute energy deficit was compensated using a carbohydrate-rich drink. RESULTS: The total amount of caloric intake and single macronutrients was higher after the fasting intervention after replenishment with glucose. All recorded hormone levels, except for adiponectin, were significantly different for at least one of the study intervals. The relative proportions of the macronutrient composition of the consumed food were stable in both conditions under the influence of glucose ingestion. In the non-fasting condition, the relative amount of protein intake correlated with adiponectin levels during the experiment. DISCUSSION AND CONCLUSION: An anabolic glucose metabolism after glucose ingestion following a fasting intervention did not even out energy ingestion compared to a control group with regular food intake and glucose ingestion. Anorexigenic hormones like insulin in this context were not able despite higher levels than in the control condition to ameliorate the drive for food intake to normal or near normal levels. Relative macronutrient intake remains stable under these varying metabolic conditions and glucose influence. Serum adiponectin levels showed a positive association with the relative protein intake in the non-fasting condition under the influence of glucose although adiponectin levels overall did not differ in between the conditions.

Double transcranial direct current stimulation of the brain increases cerebral energy levels and systemic glucose tolerance in men.

Transcranial direct current stimulation (tDCS) is a neuromodulatory method that has been tested experimentally and has already been used as an adjuvant therapeutic option to treat a number of neurological disorders and neuropsychiatric diseases. Beyond its well known local effects within the brain, tDCS also transiently promotes systemic glucose uptake and reduces the activity of the neurohormonal stress axes. We aimed to test whether the effects of a single tDCS application could be replicated upon double stimulation to persistently improve systemic glucose tolerance and stress axes activity in humans. In a single-blinded cross-over study, we examined 15 healthy male volunteers. Anodal tDCS vs sham was applied twice in series. Systemic glucose tolerance was investigated by the standard hyperinsulinaemic-euglycaemic glucose clamp procedure, and parameters of neurohormonal stress axes activity were measured. Because tDCS-induced brain energy consumption has been shown to be part of the mechanism underlying the assumed effects, we monitored the cerebral high-energy phosphates ATP and phosphocreatine by 31 phosphorus magnetic resonance spectroscopy. As hypothesised, analyses revealed that double anodal tDCS persistently increases glucose tolerance compared to sham. Moreover, we observed a significant rise in cerebral high-energy phosphate content upon double tDCS. Accordingly, the activity of the neurohormonal stress axes was reduced upon tDCS compared to sham. Our data demonstrate that double tDCS promotes systemic glucose uptake and reduces stress axes activity in healthy humans. These effects suggest that repetitive tDCS may be a future non-pharmacological option for combating glucose intolerance in type 2 diabetes patients.

PRO*MDD Study Protocol: Effectiveness of Outpatient Treatment Programs for Major Depressive Disorder: Metacognitive Therapy vs. Behavioral Activation a Single-Center Randomized Clinical Trial.

Background: Major depressive Disorder (MDD) is a severe mental disorder associated with considerable disability and high costs. Over the last decades, various psychotherapies for MDD have been developed and researched, among others Behavioral Activation (BA) and Metacognitive Therapy (MCT). MCT and BA target different maintaining factors of MDD and have not been compared to date. The PRO*MDD randomized controlled trial will compare MCT and BA in the routine clinical setting of an outpatient clinic. Methods and Design: We aim to recruit 128 MDD patients, who will be randomly assigned to either MCT or BA. In both conditions, patients will receive one individual therapy session and one group therapy session per week for a maximum of 6 months. Assessments will take place at baseline, pre-treatment, mid-treatment, post-treatment as well as at 12, 18, and 30 months after start of treatment as follow-up. The primary outcome is reduction of depression severity assessed with the Hamilton Rating Scale for Depression; secondary outcomes address quality of life, psychosocial functioning and participation as well as comorbidity. Discussion: The PRO*MDD study is the first randomized controlled trial to compare the effectiveness of MCT and BA. The outcome of this trial will increase our knowledge on the effectiveness and applicability of both treatment modalities and therefore contribute to the improvement of treatment for depressive patients. Ethics and dissemination: The study has been reviewed and approved on 11 August 2016 by the Ethics Committee of the Lübeck University (reference number: 16-176). The results will be discussed through peer-reviewed publications. Trial registration: German Clinical Trials Register DRKS-ID: DRKS00011536 (retrospectively registered).

PRO*BPD: effectiveness of outpatient treatment programs for borderline personality disorder: a comparison of Schema therapy and dialectical behavior therapy: study protocol for a randomized trial.

BACKGROUND: Borderline Personality Disorder (BPD) is a severe mental illness that is associated with low quality of life, low psychosocial functioning, and high societal costs. Treatments for BPD have improved in the last decades. Dialectical behavior therapy (DBT) and Schema therapy (ST) have demonstrated efficacy in reducing BPD symptoms and costs. However, research has not compared these two treatment approaches. In addition, there is a lack of 'real world studies' that replicate positive findings in regular mental healthcare settings. Thus, the PROgrams for Borderline Personality Disorder (PRO*BPD) study will compare the (cost-) effectiveness of DBT and ST in structured outpatient treatment programs in the routine clinical setting of an outpatient clinic. METHODS/DESIGN: We aim to recruit 160 BPD patients, who will be randomly assigned to either DBT or ST. In both conditions, patients receive one group therapy and one individual therapy session/week for a maximum of 18 months. Both treatment programs have similar frameworks, which guarantee clinical equipoise. The primary outcome is a reduction of BPD-symptoms. Also, the costs related to BPD are assessed and an economic evaluation is performed from a societal perspective. Secondary outcomes examine other measures of BPD-typical and general psychopathology, comorbidity, quality of life, psychosocial functioning and participation. Data are collected prior to the beginning therapy and every six months until the end of therapy, as well as at six months, one year and two years of follow-up after the end of therapy. Finally, we conduct a qualitative study to understand patients' experiences with the two methods. DISCUSSION: The PRO*BPD study is the first randomized trial to compare the (cost-) effectiveness of DBT and ST. By examining the clinical effectiveness of a broad spectrum of outcome parameters, conducting an economic evaluation and assessing patients' experiences, this study will significantly advance our knowledge on psychotherapy for BPD and will provide insight into the treatment approaches that should be offered to different BPD patients from clinical, economic and stakeholder's perspectives. TRIAL REGISTRATION: German Clinical Trial Register, DRKS00011534 , Date of registration: 11/01/2017, retrospectively registered.