Pro-cognitive effects of dual tacrine derivatives acting as cholinesterase inhibitors and NMDA receptor antagonists.

Therapeutic options for Alzheimer's disease are limited. Dual compounds targeting two pathways concurrently may enable enhanced effect. The study focuses on tacrine derivatives inhibiting acetylcholinesterase (AChE) and simultaneously N-methyl-D-aspartate (NMDA) receptors. Compounds with balanced inhibitory potencies for the target proteins (K1578 and K1599) or increased potency for AChE (K1592 and K1594) were studied to identify the most promising pro-cognitive compound. Their effects were studied in cholinergic (scopolamine-induced) and glutamatergic (MK-801-induced) rat models of cognitive deficits in the Morris water maze. Moreover, the impacts on locomotion in the open field and AChE activity in relevant brain structures were investigated. The effect of the most promising compound on NMDA receptors was explored by in vitro electrophysiology. The cholinergic antagonist scopolamine induced a deficit in memory acquisition, however, it was unaffected by the compounds, and a deficit in reversal learning that was alleviated by K1578 and K1599. K1578 and K1599 significantly inhibited AChE in the striatum, potentially explaining the behavioral observations. The glutamatergic antagonist dizocilpine (MK-801) induced a deficit in memory acquisition, which was alleviated by K1599. K1599 also mitigated the MK-801-induced hyperlocomotion in the open field. In vitro patch-clamp corroborated the K1599-associated NMDA receptor inhibitory effect. K1599 emerged as the most promising compound, demonstrating pro-cognitive efficacy in both models, consistent with intended dual effect. We conclude that tacrine has the potential for development of derivatives with dual in vivo effects. Our findings contributed to the elucidation of the structural and functional properties of tacrine derivatives associated with optimal in vivo pro-cognitive efficacy.

Working out measurement overlap in the assessment of maladaptive exercise.

OBJECTIVE: Although exercise is generally considered healthy, many individuals engage in maladaptive exercise (e.g., compulsive in nature). Several definitions of maladaptive exercise exist, leading to multiple, varied assessment tools; assuming homogeneity across these assessments contributes to low consensus in etiological models. METHOD: We used a Jaccard Index to quantify content overlap among 15 commonly-used self-report instruments measuring maladaptive exercise, with 31 features identified across 224 items. RESULTS: The most common features were exercise to control weight/shape and to avoid negative affect (both included in 9/15 instruments), or compensate for calories consumed (8/15 instruments). Overlap among instruments was low (.206) and no features were common across all instruments. CONCLUSIONS: Findings generally support theoretical models of exercise in eating pathology. However, instruments most commonly used to assess maladaptive exercise measure heterogenous content. Careful consideration should be taken when comparing findings derived from differing instruments, when synthesizing literature on maladaptive exercise, and when selecting instruments to measure specific maladaptive exercise features. PUBLIC SIGNIFICANCE: Many, varied, tools exist for the assessment of maladaptive exercise (e.g., compulsive or compensatory) in the context of eating disorders. Assuming homogeneity across tools contributes to low consensus in the field. We used a Jaccard Index to quantify content overlap among 15 self-report instruments measuring maladaptive exercise. The most commonly used instruments measure heterogenous content. Careful consideration should be taken when synthesizing literature and selecting instruments to use in research.

Pathways between Child Maltreatment, Psychological Symptoms, and Life Satisfaction: A Network Analysis in Adolescent Inpatients.

Child maltreatment is a risk factor for mental disorders and decreased life satisfaction during adolescence. We investigated whether child maltreatment would link to life satisfaction both directly and through psychological symptoms, whether these relations would change from admission to discharge after treatment, and which types of maltreatment, symptoms and facets of life satisfaction would be most influential in adolescent inpatients with internalizing mental disorders. N = 896 adolescent receiving inpatient psychotherapeutic treatment completed questionnaires on child maltreatment experiences, current psychopathology and subjective life satisfaction at admission and discharge (n = 765). Main diagnoses were affective (n = 322), eating (n = 447), obsessive-compulsive (n = 70) and anxiety disorders (n = 57). Network models of child maltreatment, psychopathology and life satisfaction nodes were estimated at admission and discharge and compared using network comparison tests. Potential causal shortest pathways were investigated using directed acyclic graphs.Network models were stable with no significant differences between admission and discharge. Strongest nodes of each cluster were "emotional abuse" (child maltreatment), "worthlessness", "thinking about dying" and "feeling lonely" (psychopathology) and "satisfied with life" (life satisfaction) at both admission and discharge. Emotional neglect showed direct connections to life satisfaction, indicating its relevance for therapeutic interventions. At both admission and discharge, "sexual abuse" indirectly predicted lower life satisfaction through psychological symptoms. In conclusion, child maltreatment is directly and indirectly connected to life satisfaction in adolescents with mental disorders. Emotional abuse and neglect were especially important in linking child maltreatment to life satisfaction and psychopathology.

Validation of a Latin-American Spanish version of the Body Esteem Scale for Adolescents and Adults (BESAA-LA) in Colombian and Nicaraguan adults.

BACKGROUND: Body dissatisfaction (BD) is a growing concern in Latin America; reliable and culturally appropriate scales are necessary to support body image research in Spanish speaking Latin American countries. We sought to validate a Latin-American Spanish version of the Body Esteem Scale for Adolescents and Adults (BESAA; Mendelson et al. 2001). METHODS: The BESAA was translated, culturally adapted, and validated in a sample of adults in Colombia (N = 525, 65% women, Mage 24.4, SD = 9.28). We assessed factor structure (using confirmatory factor analysis (CFA), exploratory factor analysis (EFA) and exploratory structural equation model (ESEM)), internal reliability (using Cronbach's alpha and omega), validity (using the Body Appreciation Scale BAS and Sociocultural Attitudes Towards Appearance Questionnaire SATAQ), test-retest stability in a small subsample (N = 84, using Intraclass correlations ICC) and measurement invariance across gender. To evaluate the generalizability of the scale, we assessed reliability, validity, and factor structure in a second sample from rural Nicaragua (N = 102, 73% women, Mage 22.2, SD = 4.72), and assessed measurement invariance across Nicaraguan and Colombian participants. RESULTS: The scale showed good internal reliability and validity in both samples, and there was evidence of adequate test-retest stability in the Colombian sample. EFA showed a three-factor structure with subscales we labelled 'appearance-positive', 'appearance-negative' and 'weight', that was confirmed using CFA and ESEM in the Colombian sample. Measurement invariance was confirmed across the Colombian and Nicaraguan samples, and across gender within the Colombian sample. CONCLUSION: The Latin-American Spanish version of the BESAA (BESAA-LA) appears to be a psychometrically sound measure with good reliability, validity and invariance across gender and countries. These results support the use of this scale to measure body satisfaction/dissatisfaction in Latin American adult populations.

Effects of 36 hours of sleep deprivation on military-related tasks: Can ammonium inhalants maintain performance?

INTRODUCTION: A lack of sleep can pose a risk during military operations due to the associated decreases in physical and cognitive performance. However, fast-acting ergogenic aids, such as ammonia inhalants (AI), may temporarily mitigate those adverse effects of total sleep deprivation (TSD). Therefore, the present study aimed to investigate the acute effect of AI on cognitive and physical performance throughout 36 hours of TSD in military personnel. METHODS: Eighteen male military cadets (24.1 ± 3.0 y; 79.3 ± 8.3 kg) performed 5 identical testing sessions during 36 hours of TSD (after 0 [0], 12 [-12], 24 [-24], and 36 [-36] hours of TSD), and after 8 [+8] hours of recovery sleep. During each testing session, the following assessments were conducted: Epworth sleepiness scale (ESS), simple reaction time (SRT), shooting accuracy (SA), rifle disassembling and reassembling (DAS), and countermovement jump height (JH). Heart rate (HR) was continuously monitored during the SA task, and a rating of perceived exertion (RPE) was obtained during the JH task. At each time point, tests were performed twice, either with AI or without AI as control (CON), in a counterbalanced order. RESULTS: There was faster SRT (1.6%; p < 0.01) without increasing the number of errors, higher JH (1.5%; p < 0.01), lower RPE (9.4%; p < 0.001), and higher HR (5.0%; p < 0.001) after using AI compared to CON regardless of TSD. However, neither SA nor DAS were affected by AI or TSD (p > 0.05). Independent of AI, the SRT was slower (3.2-9.3%; p < 0.001) in the mornings (-24, +8) than in the evening (-12), JH was higher (3.0-4.7%, p < 0.001) in the evenings (-12, -36) than in the mornings (0, -24, +8), and RPE was higher (20.0-40.1%; p < 0.001) in the sleep-deprived morning (-24) than all other timepoints (0, -12, -36, +8). Furthermore, higher ESS (59.5-193.4%; p < 0.001) was reported at -24 and -36 than the rest of the time points (0, -12, and + 8). CONCLUSION: Although there were detrimental effects of TSD, the usage of AI did not reduce those adverse effects. However, regardless of TSD, AI did result in a short-term increase in HR, improved SRT without affecting the number of errors, and improved JH while concurrently decreasing the RPE. No changes, yet, were observed in SA and DAS. These results suggest that AI could potentially be useful in some military scenarios, regardless of sleep deprivation.

Effects of acceptance-based strategies on psychological responses to disorder-relevant stimuli in inpatients with obsessive-compulsive disorder: An experimental study.

BACKGROUND AND OBJECTIVES: Preliminary findings suggest that acceptance and commitment therapy-informed exposure therapy may be an effective treatment for obsessive-compulsive disorder (OCD). However, there is a lack of experimental studies that have examined immediate effects of acceptance-based strategies during exposure to disorder-relevant stimuli in persons with OCD. METHODS: Fifty-three inpatients (64% female) with OCD participated in an experimental study during which they were exposed to obsessive-compulsive washing-relevant pictures and were instructed to either passively view these pictures for 5 s (neutral condition), to accept their feelings (acceptance condition) or to intensify their feelings (exposure condition) for 90 s each. RESULTS: The acceptance condition led to higher acceptance and lower unpleasantness of patients' current feelings compared to the neutral condition and to lower strength of obsessions and urge to perform compulsions but only when compared to the exposure condition. Higher self-reported OCD symptom severity related to higher unpleasantness and strength of obsessions, particularly in the neutral condition. LIMITATIONS: Future studies need to test whether the current findings translate to other stimuli and other forms of obsessions and compulsions. Due to the short duration, the exposure condition might have only mimicked the early phase of exposure and response prevention. CONCLUSIONS: Acceptance-based strategies during cue exposure immediately increase acceptance of and reduce unpleasant feelings. In line with the rationale of acceptance-based treatment approaches, which do not aim at immediate disorder-specific symptom reductions, effects on obsessions and compulsions may be more delayed or require repeated training sessions.

Review: Genes Involved in Mitochondrial Physiology Within 22q11.2 Deleted Region and Their Relevance to Schizophrenia.

BACKGROUND AND HYPOTHESIS: Schizophrenia is associated with altered energy metabolism, but the cause and potential impact of these metabolic changes remain unknown. 22q11.2 deletion syndrome (22q11.2DS) represents a genetic risk factor for schizophrenia, which is associated with the loss of several genes involved in mitochondrial physiology. Here we examine how the haploinsufficiency of these genes could contribute to the emergence of schizophrenia in 22q11.2DS. STUDY DESIGN: We characterize changes in neuronal mitochondrial function caused by haploinsufficiency of mitochondria-associated genes within the 22q11.2 region (PRODH, MRPL40, TANGO2, ZDHHC8, SLC25A1, TXNRD2, UFD1, and DGCR8). For that purpose, we combine data from 22q11.2DS carriers and schizophrenia patients, in vivo (animal models) and in vitro (induced pluripotent stem cells, IPSCs) studies. We also review the current knowledge about seven non-coding microRNA molecules located in the 22q11.2 region that may be indirectly involved in energy metabolism by acting as regulatory factors. STUDY RESULTS: We found that the haploinsufficiency of genes of interest is mainly associated with increased oxidative stress, altered energy metabolism, and calcium homeostasis in animal models. Studies on IPSCs from 22q11.2DS carriers corroborate findings of deficits in the brain energy metabolism, implying a causal role between impaired mitochondrial function and the development of schizophrenia in 22q11.2DS. CONCLUSIONS: The haploinsufficiency of genes within the 22q11.2 region leads to multifaceted mitochondrial dysfunction with consequences to neuronal function, viability, and wiring. Overlap between in vitro and in vivo studies implies a causal role between impaired mitochondrial function and the development of schizophrenia in 22q11.2DS.

Pathways between childhood maltreatment and life satisfaction in adolescents with eating disorders: A network analysis.

OBJECTIVE: This study explored the association between Childhood maltreatment (CM) experiences and life satisfaction in adolescents with eating disorders (EDs). METHODS: Adolescent inpatients with EDs completed the Childhood Trauma Questionnaire, the Satisfaction With Life Scale, the Brief Symptom Inventory and the Eating Disorder Inventory-2 at admission (n = 361) and discharge (n = 354). A network analysis was conducted to identify the shortest pathways between different types of CM and life satisfaction at admission and discharge. RESULTS: General psychopathology, life satisfaction, and ED symptoms improved from admission to discharge. At admission, emotional abuse and emotional neglect were included in the pathway between sexual/physical abuse and life satisfaction. Emotional neglect was directly connected with life satisfaction while emotional abuse was connected through feeling disliked by others, feelings of inferiority and worthlessness. At discharge, only the direct negative connection between emotional neglect and perception of excellent conditions in the life persisted. CONCLUSIONS: Emotional maltreatment experiences and general psychopathology, but not disordered eating symptoms, are involved in the association between sexual/physical CM and life satisfaction in adolescents with EDs. Emotional neglect may affect life satisfaction regardless of symptoms severity. These findings inform clinicians for assessment and treatment of maltreated adolescents with EDs.

Depressive symptoms and weight change in inpatients with anorexia nervosa: A cross-lagged panel model.

OBJECTIVE: Anorexia nervosa (AN) is marked by a high rate of comorbid depression, which raises the question whether depressive symptoms may adversely affect treatment outcome. Thus, we examined whether depressive symptoms at admission would predict weight change from admission to discharge in a large sample of inpatients with AN. In addition, we also explored the reverse direction, that is, whether body mass index (BMI) at admission would predict changes in depressive symptoms. METHODS: A sample of 3011 adolescents and adults with AN (4% male) who received inpatient treatment at four Schoen Clinics was analyzed. Depressive symptoms were measured with the Patient Health Questionnaire-9. RESULTS: BMI significantly increased and depressive symptoms significantly decreased from admission to discharge. BMI and depressive symptoms were unrelated at admission and discharge. Higher BMI at admission predicted smaller decreases in depressive symptoms and higher depressive symptoms at admission predicted larger weight gain. The latter effect, however, was mediated by longer length of stay. CONCLUSION: Results indicate that depressive symptoms do not adversely affect weight gain during inpatient treatment in persons with AN. Instead, higher BMI at admission is predictive of smaller improvements in depressive symptoms but this effect seems to be negligible in terms of clinical relevance.

Distance to home does not influence treatment success during and after inpatient treatment in adolescents with anorexia nervosa.

Current treatment guidelines recommend that inpatients with eating disorders-particularly adolescents with anorexia nervosa-should receive treatment at facilities within close distance to their home. However, whether distance to home actually influences short- and long-term treatment outcome in adolescents with anorexia nervosa has not been investigated yet. We re-analyzed data at admission, discharge, and 1-year follow up from a recent study with N = 142 female, adolescent inpatients with anorexia nervosa. Distance to home did not moderate changes in body weight, eating disorder symptoms, depressive symptoms, compulsive exercise, and life satisfaction. This is the first analysis that indicates that specialized inpatient treatment for adolescents with anorexia nervosa is effective both close to and away from home.

Comparing illness duration and age as predictors of treatment outcome in female inpatients with anorexia nervosa.

It has been widely assumed that longer illness duration predicts poorer treatment outcome in persons with anorexia nervosa (AN). However, studies on the prognostic effects of illness duration have produced mixed results. Thus, the aim of the current study was to examine the relationship between illness duration and short-term treatment outcome in a large sample of female inpatients with AN (n = 902, aged 12-73 years). Treatment outcome variables included body mass index, therapist-rated global functioning (Global Assessment of Functioning scale and Clinical Global Impression-Improvement scale) and subscales of the Eating Disorder Inventory-2. Longer illness duration predicted smaller weight gain, smaller improvements in global functioning, and smaller decreases in self-reported eating disorder symptoms. However, illness duration was almost perfectly correlated with patients' age (r = .81, 95% CI [.76, .85]), and comparing regression models revealed that models using either illness duration or age were indistinguishable. Results suggest that longer illness duration does indeed relate to worse short-term treatment outcome in inpatients with AN. This effect, however, does not add significant information above and beyond patients' age and, thus, the importance of illness duration for anticipating treatment outcome both in research and in clinical practice must be critically examined.

Desmin Knock-Out Cardiomyopathy: A Heart on the Verge of Metabolic Crisis.

Desmin mutations cause familial and sporadic cardiomyopathies. In addition to perturbing the contractile apparatus, both desmin deficiency and mutated desmin negatively impact mitochondria. Impaired myocardial metabolism secondary to mitochondrial defects could conceivably exacerbate cardiac contractile dysfunction. We performed metabolic myocardial phenotyping in left ventricular cardiac muscle tissue in desmin knock-out mice. Our analyses revealed decreased mitochondrial number, ultrastructural mitochondrial defects, and impaired mitochondria-related metabolic pathways including fatty acid transport, activation, and catabolism. Glucose transporter 1 and hexokinase-1 expression and hexokinase activity were increased. While mitochondrial creatine kinase expression was reduced, fetal creatine kinase expression was increased. Proteomic analysis revealed reduced expression of proteins involved in electron transport mainly of complexes I and II, oxidative phosphorylation, citrate cycle, beta-oxidation including auxiliary pathways, amino acid catabolism, and redox reactions and oxidative stress. Thus, desmin deficiency elicits a secondary cardiac mitochondriopathy with severely impaired oxidative phosphorylation and fatty and amino acid metabolism. Increased glucose utilization and fetal creatine kinase upregulation likely portray attempts to maintain myocardial energy supply. It may be prudent to avoid medications worsening mitochondrial function and other metabolic stressors. Therapeutic interventions for mitochondriopathies might also improve the metabolic condition in desmin deficient hearts.

An update on the epidemiology of eating disorders in Latin America: current findings and future challenges.

PURPOSE OF REVIEW: We systematically reviewed the recent literature on the epidemiology of eating disorders in Latin America. RECENT FINDINGS: Most screened articles only investigated risk for eating disorders or disordered eating behaviors. Four studies reported prevalence for eating disorders. One study reported age-standardized prevalence ranging from 0.04% [95% confidence interval, CI (0.03, 0.06)] to 0.09% [95% CI (0.07, 0.13)] for anorexia nervosa and from 0.13% [95% CI (0.08, 0.17)] to 0.27% [95% CI (0.18, 0.37)] for bulimia nervosa. Three additional studies conducted in Brazil identified a general eating disorder point-prevalence of 0.40% in children aged 6--14 years and a point-prevalence of 0.7 % [95% CI (0.34, 1.55)] for bulimia nervosa, 1.4% [95% CI (0.81, 2.43)] for binge-eating disorder and 6.2% [95% CI (3.10, 5.27)] for recurrent binge eating. SUMMARY: Since 2020, only few studies were published on the epidemiology of full-threshold eating disorders in Latin America. Prevalence was in a comparable range to previous findings. No studies regarding new DSM-5 eating disorder diagnoses were identified, and studies investigating the impact of the COVID-19 pandemic on prevalence or incidence of eating disorders in these countries are needed.

Weight suppression and body mass index at admission interactively predict weight trajectories during inpatient treatment of anorexia nervosa.

OBJECTIVE: Weight suppression refers to the difference between an individual's current and highest body weight at their current height. Higher weight suppression has been found to predict weight gain in both non-clinical samples and patients with eating disorders. Few studies also have reported interactive effects between weight suppression and current body mass index when predicting weight gain. METHODS: In this retrospective study, we analyzed clinical records of inpatients with anorexia nervosa (N = 2191, 97% female) and tested whether weight suppression and body mass index at admission would interactively predict different weight trajectories during treatment. RESULTS: Body weight increased non-linearly during treatment. Higher weight suppression predicted larger weight gain but the nature of this effect depended on body mass index at admission. In patients with a relatively low body weight at admission, those with high weight suppression started at a lower weight and showed a nearly linear and steeper weight gain than those with low weight suppression. In patients with a relatively high body weight at admission, those with high weight suppression started at a similar weight and showed a non-linear and larger weight gain than those with low weight suppression. CONCLUSION: Findings further support that weight suppression is a robust predictor of weight gain in addition to-and in interaction with-current body weight. As weight suppression can easily be assessed at admission, it may help to anticipate treatment course and outcome in patients with anorexia nervosa.

Early within-person weight gain and variability during inpatient treatment for anorexia nervosa: Age-dependent effects on treatment outcome.

OBJECTIVE: Early weight gain during inpatient treatment for anorexia nervosa (AN) is a dynamic process characterised by within-person variability that may be age-dependent. We examined whether age moderates the effect of within-person weight gain and variability on treatment outcome. METHOD: Within-person level estimates of N = 2881 underweight adolescents and adults with AN for daily average weight gain (linear slope) and variability (root mean squared errors) were obtained using random-effects modelling. Between-person level regression analyses were calculated to assess effects on weight, eating disorder psychopathology and attaining normal body weight (body mass index [BMI]: 18.5-25 kg/m2 ). RESULTS: Higher weight gain during first 2 weeks of inpatient treatment predicted higher weight, lower drive for thinness and lower body dissatisfaction at discharge, but not lower bulimic symptoms. Moreover, it predicted a higher probability of discharge weight within normal range. Younger age was associated with stronger effects of early weight gain on weight, drive for thinness and body dissatisfaction at discharge. Weight variability was not associated with any outcome. CONCLUSIONS: Age moderated effects of early weight gain on treatment outcomes, with larger effects for younger patients. Weight variability alone did not influence treatment across age and should be of lesser clinical concern during early inpatient treatment.

Psychometric properties of the Compulsive Exercise Test in a large sample of female adolescent and adult inpatients with anorexia nervosa and bulimia nervosa.

OBJECTIVE: The Compulsive Exercise Test (CET) was developed to assess compulsive exercise in patients with eating disorders (EDs), but originally validated in a nonclinical sample, and psychometric properties were only investigated in small clinical samples. Therefore, the aim of this study was to examine its psychometric properties in a large clinical sample of adolescent and adult inpatients with anorexia nervosa and bulimia nervosa. METHOD: A sample of 2,535 German female inpatients with EDs completed the CET and other instruments at admission and discharge. Factor structure (confirmatory [CFA] and exploratory factor analyses [EFA]), internal consistency and construct validity, measurement invariance across age and diagnostic groups, group comparisons of means, as well as sensitivity to change during treatment were assessed. RESULTS: The CET showed high internal consistency, very good construct validity, and sensitivity to change. CFA indicated a better fit of four-factor and three-factor solutions compared to the original five-factor model. However, subsequent EFA identified an optimum for a five-factor model. Only three subscales were satisfactorily invariant to measurement, but not the CET total score. Only small differences in scores between patient groups were observed. DISCUSSION: Results support internal consistency, construct validity, and sensitivity to change, whereas factor structure remains inconclusive, questioning the theoretical basis of the CET. There is limited support for using the lack of enjoyment subscale, and only moderate support for using the rigidity subscale in patients with EDs. It is recommended to further explore and/or revise the original CET, including investigation in other samples, for example, male samples.

Glycolytic and Krebs cycle enzymes activity in rat prefrontal cortex, hippocampus, and striatum after single and repeated NMDA inhibition by MK-801.

Psychosis is a state of altered thoughts which often accompanies schizophrenia. It was suggested that changes in energetic metabolism accompany psychosis and post-psychosis states. Here, we use the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 to experimentally induce psychosis-like behavior in rats. We addressed an effect of single and repeated (5×) MK-801 application (0.3 mg/kg; i.p.) on the energy metabolism in homogenates and crude mitochondrial fraction (CMF) of the striatum (STR), prefrontal cortex (PFC), and the hippocampus (HIP) of the adult male Wistar rat (n = 39). In each brain region, we assessed activity of glycolytic (hexokinase (HK) and lactate dehydrogenase (LDH)) and Krebs cycle enzymes (citrate synthase (CS) and malate dehydrogenase (MDH)) 2 h and 3 days (3d) after the last MK-801 application together with relative respiratory rates assessment in tissue homogenate. In STR, a single MK-801 application led to a decrease in the LDH (p = 0.0035) and the increase of the MDH (p = 0.0043) activities following 3d. Therein, repeated MK-801 doses evoked increased LDH (p = 0.0204) and CS (p = 0.0019) activities in the homogenate 2 h and increased HK (p = 0.0007) 3d after the last application. Elevated HK activity within CMF was observed after 3d (p = 0.0054). In PFC, repeated MK-801 application decreased HK activity in the homogenate 3d after the final application (p = 0.0234). Correspondingly, PFC HK activity in CMF of repeated administration samples dropped (p = 0.003). In HIP, repeated MK-801 administration led to increased respiration of SDH (p = 0.0475) only 2 h after the last application and decreased CS activity (p = 0.0160) was observed 3d after the last application. Our results indicate a progressive metabolic dysregulation of glycolytic and Krebs cycle enzymes following repeated inhibition of NMDA receptors activity in a region-specific manner. Energetic alterations may form a basis for persisting cognitive problems during and following a psychosis in schizophrenia patients.

Exercise Satiation: A novel theoretical conceptualization for problematic exercise observed in eating disorders.

Exercise Satiation is a novel theoretical conceptualization for problematic exercise often observed in eating disorders. Problematic exercise is present across the spectrum of eating disorder presentations and is a cardinal symptom of eating disorders that has been difficult to treat historically. Conceptualizing exercise in the context of Reward Satiation similar to other biological drives such as eating could provide new insights into the etiology, maintenance, and treatment of problematic exercise in eating disorders. Through this understanding, we may be able to provide and increase adherence to interventions that target these mechanisms and as such, reduce impairment associated with problematic exercise for those with eating disorders. Using the Research Domain Criteria (RDoC) framework, we propose and discuss potential research avenues to explore Exercise Satiation in the context of eating disorders.

Reasons for admission and variance of body weight at referral in female inpatients with anorexia nervosa in Germany.

BACKGROUND: Body mass index (BMI) at hospital admission in patients with anorexia nervosa (AN) represents a prognostic marker for mortality, chronicity and future body weight. The current study focused on the associations between BMI standard deviation score (BMI-SDS) at admission and reasons for seeking inpatient treatment. Further interest was given to the relationship between premorbid weight and weight at admission, as well as the effect of both weight at referral and reasons for admission on treatment outcome. METHODS: Data ascertained in the German Register of Children and Adolescents with AN were analysed to assess the parental and patient overlap for 23 predefined reasons for admission, using factor analyses and regressions models. RESULTS: Complete parent-patient data sets were available for 360 patients out of 769. The highest consensus rates between parents and patients were obtained for weight and eating behavior related reasons and hyperactivity. Based on factor analysis, four factors emerged. Premorbid BMI-SDS, age and 'low body weight' as stated by patients or parents explained almost 40% of the variance of the BMI-SDS at admission. CONCLUSIONS: Results underscore the relevance of age and premorbid BMI for BMI at admission. Only single reasons for admission explained further variance, with 'low body weight' having the largest effect. Approximately 40% of the variance of BMI-SDS was explained. For the first time, the effect of premorbid BMI for BMI at admission was robustly demonstrated in a multicenter study. Of the variance in BMI-SDS at discharge, our model could explain 37%, with reasons for admission having a small effect. Further investigation of the reasons for admission would be worthwhile to improve treatment and prognosis.

Emotion regulation in adolescents with anorexia and bulimia nervosa: Differential use of adaptive and maladaptive strategies compared to healthy adolescents.

OBJECTIVE: Adolescents with anorexia (AN) and bulimia nervosa (BN) often struggle with emotion regulation (ER). These difficulties have predominantly been assessed across emotions, without considering adaptive and maladaptive ER separately. We compared adolescents with AN or BN to healthy adolescents (HCs) regarding the adaptive and maladaptive ER of three emotions. METHOD: A treatment-seeking sample of 197 adolescents (atypical/full-threshold AN: N = 118, atypical/full-threshold BN: N = 32; HC: N = 47) reported emotion-specific ER with the FEEL-KJ questionnaire. Mixed models were calculated for adaptive and maladaptive ER to assess differences between emotions (anxiety, anger, and sadness) and groups (AN, BN, and HC). RESULTS: Main effects of emotion (p < .001) and group (p < .001) were found, but no interaction effects were found (p > .05). Post hoc tests showed lower maladaptive and higher adaptive ER for anxiety than anger or sadness (p < .001). AN and BN reported lower adaptive (p < .001) and higher maladaptive ER than HCs (p < .001). BN showed the highest levels of maladaptive ER (p = .009). DISCUSSION: The differences between AN and BN in adaptive and maladaptive ER should be considered. Furthermore, investigating differences in ER of other emotions in eating disorders might be promising.