Resting state connectivity predictors of symptom change during gaze-contingent music reward therapy of social anxiety disorder.

BACKGROUND: Social anxiety disorder (SAD) is common, first-line treatments are often only partially effective, and reliable predictors of treatment response are lacking. Here, we assessed resting state functional connectivity (rsFC) at pre-treatment and during early treatment as a potential predictor of response to a novel attention bias modification procedure, gaze-contingent music reward therapy (GC-MRT). METHODS: Thirty-two adults with SAD were treated with GC-MRT. rsFC was assessed with multi-voxel pattern analysis of fMRI at pre-treatment and after 2-3 weeks. For comparison, 20 healthy control (HC) participants without treatment were assessed twice for rsFC over the same time period. All SAD participants underwent clinical evaluation at pre-treatment, early-treatment (week 2-3), and post-treatment. RESULTS: SAD and depressive symptoms improved significantly from pre-treatment to post-treatment. After 2-3 weeks of treatment, decreased connectivity between the executive control network (ECN) and salience network (SN), and increased connectivity within the ECN predicted improvement in SAD and depressive symptoms at week 8. Increased connectivity between the ECN and default mode network (DMN) predicted greater improvement in SAD but not depressive symptoms at week 8. Connectivity within the DMN decreased significantly after 2-3 weeks of treatment in the SAD group, while no changes were found in HC over the same time interval. CONCLUSION: We identified early changes in rsFC during a course of GC-MRT for SAD that predicted symptom change. Connectivity changes within the ECN, ECN-DMN, and ECN-SN may be related to mechanisms underlying the clinical effects of GC-MRT and warrant further study in controlled trials.

Changes in anhedonia over the course of eating disorder treatment.

OBJECTIVE: Anhedonia, a transdiagnostic symptom referring to the loss of ability to experience pleasure, is heightened across eating disorder (ED) diagnoses. This study aimed to assess whether anhedonia changes during ED treatment and explore how changes in anhedonia relate to treatment outcome. METHOD: Adults and adolescents in a partial hospitalization program for EDs (N = 499) completed the Eating Disorders Examination Questionnaire (EDE-Q) and the anhedonia subscale of the Beck Depression Inventory (BDI) at admission and discharge. RESULTS: Anhedonia scores significantly decreased from admission to discharge. Anhedonia at admission was also significantly different across ED diagnostic groups. To examine how study variables related to discharge EDE-Q scores, a hierarchical linear regression was conducted with demographic, diagnostic, and medication variables in the first step, anhedonia and EDE-Q scores at admission added to the second step, and anhedonia at discharge added to the final step. Greater anhedonia at discharge was related to higher EDE-Q scores at discharge. DISCUSSION: Our findings suggest that anhedonia changes significantly over the course of intensive treatment and changes in anhedonia relate to ED symptoms at discharge. Future research is needed to determine whether specifically targeting anhedonia in ED treatment may influence treatment outcomes. PUBLIC SIGNIFICANCE: The findings from this study suggest that anhedonia may decrease during eating disorder (ED) treatment, and greater anhedonia may relate to elevated ED symptoms. These results provide support for the continued study of anhedonia in ED samples and indicate that anhedonia should be explored as a potential target for novel ED treatments.

Anhedonia in eating disorders: A meta-analysis and systematic review.

OBJECTIVE: Anhedonia, or loss of pleasure, is related to deficits in reward processing across a variety of psychiatric disorders. In light of research suggesting abnormal reward processing in eating disorders (EDs), the study of anhedonia in EDs may yield important insights into the role of reward in eating pathology. This meta-analysis and review aimed to provide both a quantitative and qualitative synthesis of the existing literature on this topic. METHOD: We conducted this research (or these meta-analyses) according to PRISMA guidelines. We searched four databases for both peer-reviewed and unpublished literature, and included studies only if a self-report or clinical interview measure of anhedonia was administered to a sample with an ED diagnosis. RESULTS: We included 21 studies in the systematic review, and 10 studies in two meta-analyses that compared anhedonia between ED and control samples (n = 9 studies) and within different ED diagnoses (n = 5 studies). Meta-analyses revealed that anhedonia was significantly higher in ED groups compared to healthy controls, but there was no significant difference in anhedonia between ED diagnostic groups. A qualitative review of the literature also suggested that anhedonia may be correlated with increased ED symptom severity. DISCUSSION: Findings indicated that anhedonia is elevated in EDs and may be a relevant treatment target. Future research should examine how self-reported anhedonia may correlate with components of reward processing in EDs in order to improve theoretical models as well as targeted interventions.

OBJETIVO: La anhedonia, o pérdida de placer, está relacionada con déficits en el procesamiento de recompensas en una variedad de trastornos psiquiátricos. A la luz de la investigación que sugiere una anormalidad en el proceso de la recompensa en los trastornos de la conducta alimentaria (TCA), el estudio de la anhedonia en los TCA puede producir información importante sobre el papel de la recompensa en la patología alimentaria. Este metanálisis y revisión tuvo como objetivo proporcionar una síntesis cuantitativa y cualitativa de la literatura existente sobre este tema. MÉTODO: Se realizó esta investigación (o estos metanálisis) de acuerdo con las guías PRISMA. Se realizaron búsquedas en cuatro bases de datos de literatura revisada por pares y no publicada, y se incluyeron estudios solo si se administró una medida de anhedonia en el autoreporte o en una entrevista clínica a una muestra con un diagnóstico de TCA. RESULTADOS: Se incluyeron 21 estudios en la revisión sistemática y 10 estudios en dos metanálisis que compararon la anhedonia entre TCA y las muestras de control (n = 9 estudios) y dentro de diferentes diagnósticos de TCA (n = 5 estudios). Los metanálisis revelaron que la anhedonia fue significativamente mayor en los grupos de TCA en comparación con los controles sanos, pero no hubo diferencias significativas en la anhedonia entre los grupos de diagnóstico de TCA. Una revisión cualitativa de la literatura también sugirió que la anhedonia puede estar correlacionada con una mayor gravedad de los síntomas de TCA. DISCUSIÓN: Los hallazgos indicaron que la anhedonia está elevada en los TCA y puede ser un objetivo de tratamiento relevante. La investigación futura debe examinar cómo la anhedonia autoreportada puede correlacionarse con los componentes del procesamiento de recompensas en los TCA para mejorar los modelos teóricos, así como las intervenciones dirigidas.

Exploring the contributions of affective constructs and interoceptive awareness to feeling fat.

PURPOSE: Feeling fat, a subjective feeling of being overweight that does not always correspond to actual body weight, is commonly reported in patients with an eating disorder. Research suggests that feeling fat relates to deficits in interoceptive awareness, the perception and integration of signals related to body states. Relatedly, recent work has linked feeling fat to affective constructs, such as depressive symptoms and guilt. The current study explores the unique relationships between feeling fat, self-reported, and objective IA, guilt, alexithymia, and depressive symptoms. METHOD: Female undergraduates (N = 128) completed the 11th item of the Eating Disorder Examination Questionnaire, the Toronto Alexithymia Scale, the Guilt subscale of the Positive and Negative Affect Schedule, and the Beck Depression Inventory-II. Participants also completed two IA measures: a heartbeat perception task and the Multidimensional Assessment of Interoceptive Awareness. RESULTS: All collected measures explained 56% of the variability in feeling fat. Depressive symptoms, self-reported IA, and BMI accounted for significant variability in feeling fat. Relative weights analyses revealed that depressive symptoms accounted for the most variability in feeling fat (19%). This finding remained significant after controlling for BMI, which also accounted for significant variability in feeling fat (25%). CONCLUSIONS: Our results replicate previous findings that depressive symptoms relate significantly to feeling fat and extend this work by incorporating the role of interoceptive awareness, guilt, and alexithymia. Endorsement of feeling fat during an intake assessment may alert clinicians to assess for depressive symptoms, and focusing on depressive symptoms in treatment may improve feeling fat. LEVEL OF EVIDENCE: Level I Evidence obtained from an experimental study.

RIP2 enhances cell survival by activation of NF-ĸB in triple negative breast cancer cells.

Receptor-interacting protein 2 (RIP2) is an essential mediator of inflammation and innate immunity, but little is known about its role outside the immune system. Recently, RIP2 has been linked to chemoresistance of triple negative breast cancer (TNBC), the most aggressive breast cancer subtype for which there is an urgent need for targeted therapies. In this study we show that high expression of RIP2 in breast tumors correlates with a worse prognosis and a higher risk of recurrence. We also demonstrate that RIP2 confers TNBC cell resistance against paclitaxel and ceramide-induced apoptosis. Overexpression of RIP2 lead to NF-κB activation, which contributed to higher expression of pro-survival proteins and cell survival. Conversely, RIP2 knockdown inhibited NF-κB signaling, reduced levels of anti-apoptotic proteins and sensitized cells to drug treatment. Together, these data show that RIP2 promotes survival of breast cancer cells through NF-κB activation and that targeting RIP2 may be therapeutically beneficial for treatment of TNBC.

Anticipatory and consummatory pleasure in avoidant/restrictive food intake disorder.

BACKGROUND: Recent research suggests that individuals with eating disorders (EDs) report elevated anhedonia, or loss of pleasure. Although individuals with avoidant/restrictive food intake disorder (ARFID) often express that they do not look forward to eating, it is unclear whether they experience lower pleasure than those without EDs. Thus, identifying whether individuals with ARFID experience anhedonia may yield important insights that inform clinical conceptualization and treatment. METHODS: A sample of 71 participants ages 10-23 with full and subthreshold ARFID and 33 healthy controls (HCs) completed the Pica, ARFID, and Rumination Disorder Interview, a diagnostic interview to assess ARFID profile severity (lack of interest in food, sensory sensitivity, fear of aversive consequences) and the Temporal Experience of Pleasure Scale (TEPS), a self-report measure of consummatory and anticipatory pleasure. Statistical analyses were performed using the full TEPS and also the TEPS with food-related items removed. RESULTS: The ARFID group reported significantly lower anticipatory and consummatory pleasure compared to HCs, but these differences were no longer significant after controlling for depression, nor after removing food items from the TEPS. Within the ARFID sample, greater ARFID severity was associated with lower anticipatory pleasure across analyses, and greater endorsement of the lack of interest in food profile was related to lower anticipatory pleasure. ARFID severity was also associated with lower consummatory pleasure using the full TEPS, but this relationship was no longer significant with food items removed. CONCLUSIONS: These results provide initial evidence for lower pleasure before potentially pleasurable events in individuals with more severe ARFID, particularly those with the lack of interest phenotype. Our findings also suggest that depression is likely to contribute low pleasure in this population. Future research should seek to further characterize how dimensions of pleasure relate to the maintenance and treatment of ARFID symptoms.

Individuals with eating disorders often report elevated anhedonia, or an inability to experience pleasure. Past research on pleasure in eating disorders has focused primarily on individuals with anorexia nervosa and bulimia nervosa, and it is unclear whether people with other eating disorders also experience lower pleasure than healthy individuals. In the current study, we measured anticipatory pleasure (looking forward to something enjoyable) and consummatory pleasure (enjoying a pleasant stimulus) in a sample with avoidant/restrictive food intake disorder (ARFID) and healthy controls. We also repeated our analyses after removing food-related items from the scale assessing pleasure. The ARFID group scored lower on both dimensions of pleasure than controls, but this difference was primarily due to greater depression symptoms and the presence of food-related items in the pleasure questionnaire. Within the ARFID sample, individuals with more severe ARFID reported less anticipatory pleasure, even after removing questions about enjoyment of food. Lower anticipatory pleasure was especially characteristic of the lack of interest in eating phenotype of ARFID. These results suggest that ARFID severity, lack of interest in eating, and depression contribute to low pleasure in this population.

Fast evidence accumulation in social anxiety disorder enhances decision making in a probabilistic reward task.

Choices and response times in two-alternative decision-making tasks can be modeled by assuming that individuals steadily accrue evidence in favor of each alternative until a response boundary for one of them is crossed, at which point that alternative is chosen. Prior studies have reported that evidence accumulation during decision-making tasks takes longer in adults with psychopathology than in healthy controls, indicating that slow evidence accumulation may be transdiagnostic. However, few studies have examined perceptual decision making in anxiety disorders, where hypervigilance might enhance performance. Therefore, this study used the Hierarchical Drift Diffusion model to investigate evidence accumulation in adults with social anxiety disorder (SAD) and healthy controls as they performed a probabilistic reward task (PRT), in which social rewards were delivered for correct perceptual judgments. Adults with SAD completed the PRT before and after gaze-contingent music reward therapy (GCMRT), which trains attention allocation and has shown efficacy for SAD. Healthy controls also completed the PRT twice. Results revealed excellent performance in adults with SAD, especially after GCMRT: relative to controls, they showed faster evidence accumulation, better discriminability, and earned more rewards. These data highlight a positive effect of attention training on performance in anxious adults and show how a behavioral trait that is typically problematic-hypervigilance in SAD-can nevertheless confer advantages in certain contexts. The data also indicate that, in contrast to other forms of psychopathology, SAD is not characterized by slow evidence accumulation, at least in the context of the social PRT. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Anticipatory and consummatory pleasure in eating disorders.

BACKGROUND: Recent research suggests that anhedonia, or the inability to experience pleasure, is elevated in individuals with eating disorders (EDs). However, past literature has only studied anhedonia in EDs as a unidimensional construct rather than separately examining anticipatory (i.e., prediction of pleasure for a future event) and consummatory (i.e., enjoyment of a present event) pleasure. Given that these subcomponents of pleasure have distinct neurobiological correlates, studying pleasure as a multifaceted construct may yield important insights into the underlying mechanisms of binge eating or food restriction. METHODS: A sample of 124 women with anorexia nervosa, bulimia nervosa, or other specified feeding or eating disorder and 84 control women (CW) completed self-report measures of anticipatory pleasure, consummatory pleasure, ED symptoms, depression, harm avoidance, and anxiety. RESULTS: Individuals with EDs endorsed significantly lower anticipatory pleasure than CW, but there were no significant group differences in consummatory pleasure. Further, there were no significant differences in self-reported pleasure among ED diagnostic groups. Within the ED sample, anticipatory pleasure but not consummatory pleasure was positively related to binge eating frequency and significantly negatively correlated with cognitive ED symptoms, state and trait anxiety, and harm avoidance. Both anticipatory and consummatory pleasure was negatively associated with depression. CONCLUSION: The results of the current study suggest that lower pleasure across the ED spectrum may be due to deficits in anticipatory, but not consummatory, pleasure. Future research should continue to explore the behavioral, affective, and neural correlates of anticipatory pleasure in EDs to characterize better how it relates to the onset and maintenance of binge eating and other eating disorder pathology.

Anhedonia, or the inability to experience pleasure, has been observed in individuals with eating disorders. Neuroscience research suggests that pleasure may be separated into two distinct components: anticipatory pleasure (how much someone predicts they will enjoy a future experience) and consummatory pleasure (how much someone enjoys a present experience). In the current study, individuals with eating disorders and healthy controls completed questionnaires assessing anticipatory and consummatory pleasure, binge eating, other eating disorder behaviors, depression, anxiety, and constructs associated with reward and punishment sensitivity. The sample with eating disorders reported significantly lower anticipatory but not consummatory pleasure than the control sample. Within the eating disorder sample, greater anticipatory pleasure was also related to higher binge eating frequency but lower depression, anxiety, and weight and shape concerns. These results suggest that anticipatory pleasure may be particularly important in future research on the etiology and treatment of eating disorders.

Increased attention allocation to socially threatening faces in social anxiety disorder: A replication study.

BACKGROUND: Threat-related attention bias has been implicated in the etiology and maintenance of social anxiety disorder (SAD), with attentional research increasingly using eye-tracking methodology to overcome the poor psychometric properties of response-time-based tasks and measures. Yet, extant eye-tracking research in social anxiety has mostly failed to report on psychometrics and attempts to replicate past results are rare. Therefore, we attempted to replicate a previously published eye-tracking study of gaze patterns in socially anxious and nonanxious participants as they viewed social threatening and neutral faces, while also exploring the psychometric properties of the attentional measures used. METHODS: Gaze was monitored as participants freely viewed 60 different matrices comprised of eight socially-threatening and eight neutral faces, presented for 6000 ms each. Gaze patterns directed at threat and neutral areas of interest (AOIs) were compared by group. Internal consistency and test-retest reliability were also evaluated. RESULTS: Relative to healthy controls, socially anxious patients dwelled significantly longer on threat faces, replicating prior findings with the same task. Internal consistency of total dwell time on threat and neutral AOIs was high, and two-week test-retest reliability was acceptable. LIMITATIONS: Test-retest reliability was only examined for the control group, which had a small sample size. CONCLUSION: Increased dwell time on socially threatening stimuli is a reliable, stable, and generalizable measure of attentional bias in adults with social anxiety.

Neurophysiological predictors of gaze-contingent music reward therapy among adults with social anxiety disorder.

Social anxiety disorder (SAD) is associated with fear of negative evaluation and heightened performance monitoring. The best-established treatments help only a subset of patients, and there are no well-established predictors of treatment response. The current study investigated whether individual differences in processing errors might predict response to gaze-contingent music reward therapy (GC-MRT). At baseline, healthy control subjects (HC; n = 20) and adults with SAD (n = 29), ages 19-43 years, completed the Flanker Task while electroencephalography (EEG) data were recorded. SAD participants then received up to 12 sessions over 8 weeks of GC-MRT, designed to train participants' attention away from threatening and toward neutral faces. Clinical assessments were completed 9- (post-treatment) and 20-weeks (follow-up) after initiating the treatment. At baseline, compared to HC, SAD performed the task more accurately and exhibited increased error-related negativity (ERN) and delta power to error commission. After controlling for age and baseline symptoms, more negative ERN and increased frontal midline theta (FMT) predicted reduced self-reported social anxiety symptoms at post-treatment, and FMT also predicted clinician-rated and self-reported symptom reduction at the follow-up assessment. Hypervigilance to error is characteristic of SAD and warrants further research as a predictor of treatment response for GC-MRT.

How Supraphysiological Oxygen Levels in Standard Cell Culture Affect Oxygen-Consuming Reactions.

Most mammalian tissue cells experience oxygen partial pressures in vivo equivalent to 1-6% O2 (i.e., physioxia). In standard cell culture, however, headspace O2 levels are usually not actively regulated and under these conditions are ~18%. This drives hyperoxia in cell culture media that can affect a wide variety of cellular activities and may compromise the ability of in vitro models to reproduce in vivo biology. Here, we review and discuss some specific O2-consuming organelles and enzymes, including mitochondria, NADPH oxidases, the transplasma membrane redox system, nitric oxide synthases, xanthine oxidase, and monoamine oxidase with respect to their sensitivities to O2 levels. Many of these produce reactive oxygen and/or nitrogen species (ROS/RNS) as either primary end products or byproducts and are acutely sensitive to O2 levels in the range from 1% to 18%. Interestingly, many of them are also transcriptional targets of hypoxia-inducible factors (HIFs) and chronic cell growth at physioxia versus 18% O2 may alter their expression. Aquaporins, which facilitate hydrogen peroxide diffusion into and out of cells, are also regulated by HIFs, indicating that O2 levels may affect intercellular communication via hydrogen peroxide. The O2 sensitivities of these important activities emphasize the importance of maintaining physioxia in culture.

Aripiprazole and impulse-control disorders in high-risk patients.

A case study demonstrating the association between aripiprazole and impulse-control disorders and a call for caution when prescribing aripiprazole to high-risk patients.

Regulation of photoperiodic flowering by Arabidopsis photoreceptors.

Photoperiodism is a day-length-dependent seasonal change of physiological or developmental activities that is widely found in plants and animals. Photoperiodic flowering in plants is regulated by photosensory receptors including the red/far-red light-receptor phytochromes and the blue/UV-A light-receptor cryptochromes. However, the molecular mechanisms underlying the specific roles of individual photoreceptors have remained poorly understood. Here, we report a study of the day-length-dependent response of cryptochrome 2 (cry2) and phytochrome A (phyA) and their role as day-length sensors in Arabidopsis. The protein abundance of cry2 and phyA showed a diurnal rhythm in plants grown in short-day but not in plants grown in long-day. The short-day-specific diurnal rhythm of cry2 is determined primarily by blue light-dependent cry2 turnover. Consistent with a proposition that cry2 and phyA are the major day-length sensors in Arabidopsis, we show that phyA mediates far-red light promotion of flowering with modes of action similar to that of cry2. Based on these results and a finding that the photoperiodic responsiveness of plants depends on light quality, a model is proposed to explain how individual phytochromes and cryptochromes work together to confer photoperiodic responsiveness in Arabidopsis.