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.

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.

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.

Psychosocial stress promotes food intake and enhances the neuroenergetic level in men.

Psychosocial stress may lead to increased food consumption and overweight. In turn, obesity is related to reduced brain energy content. We hypothesized that psychosocial stress influencing food intake may alter the neuroenergetic status in the human brain. We tested 14 healthy normal weight men in a randomized crossover design. A modified version of the Trier Social Stress Test (TSST) was carried out to induce psychosocial stress vs. control in a neuroimaging setting. Cerebral energy content, i.e. high energy phosphates adenosine triphosphate (ATP) and phosphocreatine (PCr), was measured by 31phosphorus magnetic resonance spectroscopy. Food intake was quantified by an ad libitum buffet test. Stress hormonal response and alterations in glucose metabolism were monitored by blood sampling. Before data collection, we mainly expected a stress-induced reduction in cerebral high energy phosphates, followed by higher food intake. Psychosocial stress increased serum cortisol concentrations (p = .003) and fat intake of all participants by 25% (p = .043), as well as food intake of "stress-eaters" by 41.1% (p = .003) compared with controls. Blood glucose and insulin concentrations were not affected (p > .174 for both). Cerebral ATP and PCr levels generally increased upon stress-induction (p > = .022 and p = .037, respectively). Our data confirm that psychosocial stress may enhance food intake. Contrary to our expectations, stress induces a distinct increase in the neuroenergetic status. This insight suggests that the underlying central nervous mechanisms of stress-induced overeating may involve the regulation of the brain energy homeostasis.

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.

[Treatment of Eating Disorders by Emotion Regulation]. / Therapie der Essstörung durch Emotionsregulation.

Patients with an eating disorder have difficulties perceiving emotions. They have skills deficits in the acceptance, modification and opposite action to emotion driven behavior. They use disturbed eating behavior (restrained eating, binge eating and purging), but also situational avoidance, dissociation and substance use as an instrument for emotional avoidance. This constitutes an innovative starting point for therapy.

Glycemic increase induced by intravenous glucose infusion fails to affect hunger, appetite, or satiety following breakfast in healthy men.

Meal-dependent fluctuations of blood glucose and corresponding endocrine signals such as insulin are thought to provide important regulatory input for central nervous processing of hunger and satiety. Since food intake also triggers the release of numerous gastrointestinal signals, the specific contribution of changes in blood glucose to appetite regulation in humans has remained unclear. Here we tested the hypothesis that inducing glycemic fluctuations by intravenous glucose infusion is associated with concurrent changes in hunger, appetite, and satiety. In a single blind, counter-balanced crossover study 15 healthy young men participated in two experimental conditions on two separate days. 500 ml of a solution containing 50 g glucose or 0.9% saline, respectively, was intravenously infused over a 1-h period followed by a 1-h observation period. One hour before start of the respective infusion subjects had a light breakfast (284 kcal). Blood glucose and serum insulin concentrations as well as self-rated feelings of hunger, appetite, satiety, and fullness were assessed during the entire experiment. Glucose as compared to saline infusion markedly increased glucose and insulin concentrations (peak glucose level: 9.7 ± 0.8 vs. 5.3 ± 0.3 mmol/l; t(14) = -5.159, p < 0.001; peak insulin level: 370.4 ± 66.5 vs. 109.6 ± 21.5 pmol/l; t(14) = 4.563, p < 0.001) followed by a sharp decline in glycaemia to a nadir of 3.0 ± 0.2 mmol/l (vs. 3.9 ± 0.1 mmol/l at the corresponding time in the control condition; t(14) = -3.972, p = 0.001) after stopping the infusion. Despite this wide glycemic fluctuation in the glucose infusion condition subjective feelings of hunger, appetite satiety, and fullness did not differ from the control condition throughout the experiment. These findings clearly speak against the notion that fluctuations in glycemia and also insulinemia represent major signals in the short-term regulation of hunger and satiety.

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).

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.

Partial sleep restriction modulates secretory activity of thyrotropic axis in healthy men.

Sleep and endocrine function are known to be closely related, but studies on the effect of moderate sleep loss on endocrine axes are still sparse. We examined the influence of partial sleep restriction for 2 days on the secretory activity of the thyrotropic axis. Fifteen healthy, normal-weight men were tested in a balanced, cross-over study. Serum concentrations of thyrotrophin (TSH), free triiodothyronine (fT3) and free thyroxine (fT4) were monitored at 1-h intervals during a 15-h daytime period (08:00-23:00 h) following two nights of restricted sleep (bedtime 02:45-07:00 h) and two nights of regular sleep (bedtime 22:45-07:00 h), respectively. Serum concentrations of fT3 (P < 0.026) and fT4 (P = 0.089) were higher after sleep restriction than regular sleep, with a subsequent blunting of TSH concentrations in the evening hours of the sleep restriction condition (P = 0.008). These results indicate profound alterations in the secretory activity of the thyrotropic axis after 2 days of sleep restriction to ~4 h, suggesting that acute partial sleep loss impacts endocrine homeostasis, with potential consequences for health and wellbeing.

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.

Sleep timing may modulate the effect of sleep loss on testosterone.

BACKGROUND: Sleep loss has been shown to reduce secretory activity of the pituitary-gonadal axis in men, but the determinants of this effect are unknown. OBJECTIVE: To discriminate the effects of sleep duration and sleep timing on serum concentrations of luteinizing hormone (LH), testosterone (T) and prolactin (PRL). METHODS: Fifteen young, healthy men (27·1 ± 1·3 years; BMI, 22·9 ± 0·3 kg/m(2) ) were examined in a condition of sleep time restriction to 4 h (bedtime, 02:45 -07:00 h) for two consecutive nights and in a control condition of 8 h regular sleep (bedtime, 22:45-07:00 h). After the second night, serum concentrations of LH, T and PRL were monitored over a 15-h period. In addition, these hormones were measured in serum samples obtained in a further experiment in eight healthy men (24·5 ± 1·1 years; BMI, 23·7 ± 0·6 kg/m(2) ) in the morning after one night of total sleep deprivation, of 4·5 h sleep (bedtime, 22:30-03:30 h), and of regular 7 h sleep (bedtime, 22:30-06:00 h). RESULTS: Serum LH, T and PRL concentrations showed characteristic diurnal variations across the 15-h period without any differences between the 4- and 8-h sleep conditions. However, total sleep deprivation and 4·5 h of sleep restricted to the first night-half markedly decreased morning T and PRL concentrations (both P ≤ 0·05). CONCLUSION: Collectively, our data suggest that the effect of sleep restriction on pituitary-gonadal secretory activity may be modulated by sleep timing. While sleep loss in the early part of the night does not affect T and PRL, early awakening and wakefulness during the second part of the night reduces morning circulating T and PRL concentrations.

Lactate infusion during euglycemia but not hypoglycemia reduces subsequent food intake in healthy men.

Considering that lactate is known to interact with central glucose-sensing networks, we tested whether hyperlactatemia affects food intake in humans. According to a balanced within-subject 2×2 design, 12 healthy, fasted men (age: 20-40 years; BMI: 20-26 kg/m(2)) were intravenously infused lactate and saline, respectively, for 105 min during concomitant euglycemic and hypoglycemic, respectively, insulin infusion of 75 min. Ten minutes after the simultaneous end of infusions, free-choice food intake was assessed at 10:25 h. Lactate decreased food intake following euglycemia as compared to the other three conditions in which food intake did not differ. Results point to an anorexigenic effect of lactate under euglycemic conditions.

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.

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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Impaired glucose tolerance in healthy men with low body weight.

BACKGROUND: Impaired glucose tolerance (IGT) and high body mass index (BMI) are recognized risk factors for type 2 diabetes mellitus (T2DM). However, data suggest that also underweight predisposes people to develop T2DM. Here, we experimentally tested if already moderate underweight is associated with impaired glucose tolerance as compared to normal weight controls. Obese subjects were included as additional reference group. METHOD: We included three groups of low weight, normal weight, and obese subjects comprising 15 healthy male participants each. All participants underwent a standardized hyperinsulinemic-euglycemic glucose clamp intervention to determine glucose tolerance. In addition, insulin sensitivity index (ISI) was calculated by established equation. RESULTS: ISI values were higher in low and normal weight than in obese subjects (P < 0.010) without any difference between low and normal weight groups (P = 0.303). Comparable to obese participants (P = 0.178), glucose tolerance was found decreased in low weight as compared with normal weight subjects (P = 0.007). Pearson's correlation analysis revealed a positive relationship between glucose tolerance and BMI in low (P = 0.043) and normal weight subjects (P = 0.021), an effect that was found inverse in obese participants (P = 0.028). CONCLUSION: Our study demonstrates that not only obese but also healthy people with moderate underweight display glucose intolerance. It is therefore suggested that all deviations from normal BMI may be accompanied by an increased risk of developing T2DM in later life indicating that the maintenance of body weight within the normal range has first priority in the prevention of this disease.

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.

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.

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.