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.

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.

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.

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.

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.

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.

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.

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.

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.

A call to experimentally study acute affect-regulation mechanisms specific to driven exercise in eating disorders.

Driven exercise (i.e., feeling compelled to exercise to control one's weight or shape, to obtain other positive consequences of exercising, or to avoid other negative consequences of not exercising) is a common phenomenon in individuals with eating disorders (EDs), typically associated with negative clinical outcomes. Current theoretical models of driven exercise highlight the short-term affect-regulating outcome of acute driven exercise, which is implicated to maintain this symptom either by positive or negative reinforcement. However, few studies have actually investigated cognitive, affective, and psychobiological mechanisms related to acute driven exercise. In particular, experimental studies that directly test mechanisms leading to the short-term affective improvement after acute driven exercise are scarce. In this article, we therefore propose potential cognitive, affective, and psychobiological mechanisms that could explain the affect-regulating function of driven exercise in individuals with EDs. In addition, we suggest examples of experimental studies that could directly test these mechanisms in individuals with EDs, as recent studies have demonstrated the safety of supervised exercise in EDs research. Our aim of stimulating research on the underlying causes and maintenance factors of driven exercise in EDs has the potential to critically inform treatment development for this high-risk population.

Body image avoidance affects interpersonal distance perception: A virtual environment experiment.

OBJECTIVE: Eating disorders have a considerable influence on social contacts. The avoidance towards the own body may result in the avoidance of others. Previous research has found a preference for larger interaction distances in individuals with eating disorders (ED) as compared to control participants (CG). We aimed to replicate these findings and to investigate whether the body weight of the interactant moderates the effect. METHOD: We recruited a female sample with mixed ED subtypes (n = 21) and a female CG (n = 28). Participants were immersed in a virtual environment and engaged in a number of fictitious social interactions. They approached a virtual person until a comfortable distance for interaction was reached. The approached virtual persons differed with respect to body weight in five levels (underweight to obese). RESULTS: Our results indicate that interpersonal distance varies as a U-shaped function of the avatar's body weight, and that higher levels of body avoidance, present in ED individuals, magnify this effect. CONCLUSIONS: We discuss our results with regard to the role of perspective and disgust to provide a useful framework and to motivate future studies in the domain of body avoidance in social interactions.

Testing an emotion regulation model of physical activity in adolescents with anorexia nervosa: A pilot ecological momentary assessment.

OBJECTIVE: Adolescents with anorexia nervosa (AN) often show increased levels of exercise and physical activity. Psychological models suggest that physical activity in AN might attenuate momentary negative affect. However, this has not been directly tested in adolescents with AN, and it remains unclear whether this is a distinct mechanism of physical activity in AN compared with healthy controls (HCs). METHOD: In a 1-day ecological momentary assessment, 32 adolescent inpatients with AN and 30 HCs responded to hourly questions on momentary affect while wearing an actigraph to objectively assess physical activity. RESULTS: Linear mixed models identified that adolescents with AN experienced more aversive tension, more negative affect, and less positive affect throughout the day than HCs. Preliminary evidence for a momentary association of higher levels of physical activity with positive affect were found for both groups, whereas higher levels of physical activity were associated with less negative affect in adolescents with AN only. When correcting for multiple testing, interactions did not hold statistical significance. DISCUSSION: Our results indicate a down-regulation effect of physical activity on negative affect for AN and a more general up-regulation effect of positive affect. However, our sample size was small, and replication of our findings is needed.

Mitochondrial genome modulates myocardial Akt/Glut/HK salvage pathway in spontaneously hypertensive rats adapted to chronic hypoxia.

Recently we have shown that adaptation to continuous normobaric hypoxia (CNH) decreases myocardial ischemia/reperfusion injury in spontaneously hypertensive rats (SHR) and in a conplastic strain (SHR-mtBN). The protective effect was stronger in the latter group characterized by a selective replacement of the SHR mitochondrial genome with that of a more ischemia-resistant Brown Norway strain. The aim of the present study was to examine the possible involvement of the hypoxia inducible factor (HIF)-dependent pathway of the protein kinase B/glucose transporters/hexokinase (Akt/GLUT/HK) in this mitochondrial genome-related difference of the cardioprotective phenotype. Adult male rats were exposed for 3 wk to CNH ([Formula: see text] 0.1). The expression of dominant isoforms of Akt, GLUT, and HK in left ventricular myocardium was determined by real-time RT-PCR and Western blotting. Subcellular localization of GLUTs was assessed by quantitative immunofluorescence. Whereas adaptation to hypoxia markedly upregulated protein expression of HK2, GLUT1, and GLUT4 in both rat strains, Akt2 protein level was significantly increased in SHR-mtBN only. Interestingly, a higher content of HK2 was revealed in the sarcoplasmic reticulum-enriched fraction in SHR-mtBN after CNH. The increased activity of HK determined in the mitochondrial fraction after CNH in both strains suggested an increase of HK association with mitochondria. Interestingly, HIF1a mRNA increased and HIF2a mRNA decreased after CNH, the former effect being more pronounced in SHR-mtBN than in SHR. Pleiotropic effects of upregulated Akt2 along with HK translocation to mitochondria and mitochondria-associated membranes can potentially contribute to a stronger CNH-afforded cardioprotection in SHR-mtBN compared with progenitor SHR.

Selective replacement of mitochondrial DNA increases the cardioprotective effect of chronic continuous hypoxia in spontaneously hypertensive rats.

Mitochondria play an essential role in improved cardiac ischaemic tolerance conferred by adaptation to chronic hypoxia. In the present study, we analysed the effects of continuous normobaric hypoxia (CNH) on mitochondrial functions, including the sensitivity of the mitochondrial permeability transition pore (MPTP) to opening, and infarct size (IS) in hearts of spontaneously hypertensive rats (SHR) and the conplastic SHR-mtBN strain, characterized by the selective replacement of the mitochondrial genome of SHR with that of the more ischaemia-resistant brown Norway (BN) strain. Rats were adapted to CNH (10% O2, 3 weeks) or kept at room air as normoxic controls. In the left ventricular mitochondria, respiration and cytochrome c oxidase (COX) activity were measured using an Oxygraph-2k and the sensitivity of MPTP opening was assessed spectrophotometrically as Ca2+-induced swelling. Myocardial infarction was analysed in anaesthetized open-chest rats subjected to 20 min of coronary artery occlusion and 3 h of reperfusion. The IS reached 68±3.0% and 65±5% of the area at risk in normoxic SHR and SHR-mtBN strains, respectively. CNH significantly decreased myocardial infarction to 46±3% in SHR. In hypoxic SHR-mtBN strain, IS reached 33±2% and was significantly smaller compared with hypoxic SHR. Mitochondria isolated from hypoxic hearts of both strains had increased detergent-stimulated COX activity and were less sensitive to MPTP opening. The maximum swelling rate was significantly lower in hypoxic SHR-mtBN strain compared with hypoxic SHR, and positively correlated with myocardial infarction in all experimental groups. In conclusion, the mitochondrial genome of SHR modulates the IS-limiting effect of adaptation to CNH by affecting mitochondrial energetics and MPTP sensitivity to opening.

Adaptation to chronic continuous hypoxia potentiates Akt/HK2 anti-apoptotic pathway during brief myocardial ischemia/reperfusion insult.

Adaptation to chronic hypoxia represents a potential cardioprotective intervention reducing the extent of acute ischemia/reperfusion (I/R) injury, which is a major cause of death worldwide. The main objective of this study was to investigate the anti-apoptotic Akt/hexokinase 2 (HK2) pathway in hypoxic hearts subjected to I/R insult. Hearts isolated from male Wistar rats exposed either to continuous normobaric hypoxia (CNH; 10% O2) or to room air for 3 weeks were perfused according to Langendorff and subjected to 10 min of no-flow ischemia and 10 min of reperfusion. The hearts were collected either after ischemia or after reperfusion and used for protein analyses and quantitative fluorescence microscopy. The CNH resulted in increased levels of HK1 and HK2 proteins and the total HK activity after ischemia compared to corresponding normoxic group. Similarly, CNH hearts exhibited increased ischemic level of Akt protein phosphorylated on Ser473. The CNH also strengthened the interaction of HK2 with mitochondria and prevented downregulation of mitochondrial creatine kinase after reperfusion. The Bax/Bcl-2 ratio was significantly lower after I/R in CNH hearts than in normoxic ones, suggesting a lower probability of apoptosis. In conclusion, the Akt/HK2 pathway is likely to play a role in the development of a cardioprotective phenotype of CNH by preventing the detachment of HK2 from mitochondria at reperfusion period and decreases the Bax/Bcl-2 ratio during I/R insult, thereby lowering the probability of apoptosis activation in the mitochondrial compartment.

Aversive tension in female adolescents with Anorexia Nervosa: a controlled ecological momentary assessment using smartphones.

BACKGROUND: Current models of Anorexia Nervosa (AN) emphasize the role of emotion regulation. Aversive tension, described as a state of intense arousal and negative valence, is considered to be a link between emotional events and disordered eating. Recent research focused only on adult patients, and mainly general emotion regulation traits were studied. However, the momentary occurrence of aversive tension, particularly in adolescents with AN, has not been previously studied. METHOD: 20 female adolescents with AN in outpatient treatment and 20 healthy adolescents aged 12 to 19 years participated in an ecological momentary assessment using their smartphones. Current states of aversive tension and events were assessed hourly for two consecutive weekdays. Mean and maximum values of aversive tension were compared. Multilevel analyses were computed to test the influence of time and reported events on aversive tension. The effect of reported events on subsequent changes of aversive tension in patients with AN were additionally tested in a multilevel model. RESULTS: AN patients showed higher mean and maximum levels of aversive tension. In a multilevel model, reported food intake was associated with higher levels of aversive tension in the AN group, whereas reported school or sport-related events were not linked to specific states of aversive tension. After food intake, subsequent increases of aversive tension were diminished and decreases of aversive tension were induced in adolescents with AN. CONCLUSIONS: Aversive tension may play a substantial role in the psychopathology of AN, particular in relation with food intake. Therefore, treatment should consider aversive tension as a possible intervening variable during refeeding. Our findings encourage further research on aversive tension and its link to disordered eating. TRIAL REGISTRATION: German register of clinical trials (DRKS): DRKS00005228 (Date of registration: September 2, 2013).

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.

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.

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.