Striatal dopamine in anhedonia: A simultaneous [11C]raclopride positron emission tomography and functional magnetic resonance imaging investigation.

BACKGROUND: Anhedonia is hypothesized to be associated with blunted mesocorticolimbic dopamine (DA) functioning in samples with major depressive disorder. The purpose of this study was to examine linkages between striatal DA, reward circuitry functioning, anhedonia, and, in an exploratory fashion, self-reported stress, in a transdiagnostic anhedonic sample. METHODS: Participants with (n = 25) and without (n = 12) clinically impairing anhedonia completed a reward-processing task during simultaneous positron emission tomography and magnetic resonance (PET-MR) imaging with [11C]raclopride, a DA D2/D3 receptor antagonist that selectively binds to striatal DA receptors. RESULTS: Relative to controls, the anhedonia group exhibited decreased task-related DA release in the left putamen, caudate, and nucleus accumbens and right putamen and pallidum. There were no group differences in task-related brain activation (fMRI) during reward processing after correcting for multiple comparisons. General functional connectivity (GFC) findings revealed blunted fMRI connectivity between PET-derived striatal seeds and target regions in the anhedonia group. Associations were identified between anhedonia severity and the magnitude of task-related DA release to rewards in the left putamen, but not mesocorticolimbic GFC. CONCLUSIONS: Results provide evidence for reduced striatal DA functioning during reward processing and blunted mesocorticolimbic network functional connectivity in a transdiagnostic sample with clinically significant anhedonia.

Parsing within & between-person dynamics of therapy homework completion and clinical symptoms in two cognitive behavioral treatments for adults with anhedonia.

OBJECTIVE: Homework is a key theoretical component of cognitive-behavioral therapies, however, the effects of homework on clinical outcomes have largely been evaluated between-persons rather than within-persons. METHODS: The effects of homework completion on treatment response were examined in a randomized trial comparing Behavioral Activation Treatment for Anhedonia (BATA, n = 38), a novel psychotherapy, to Mindfulness-Based Cognitive Therapy (MBCT, n=35). The primary endpoint was consummatory reward sensitivity, measured weekly by the Snaith Hamilton Pleasure Scale (SHAPS), up to 15 weeks. Multilevel models evaluated change in SHAPS scores over time and the effects of clinician-reported and participant-reported homework. RESULTS: BATA and MBCT resulted in significant, equivalent reductions in SHAPS scores. Unexpectedly, participants who completed greater mean total amounts of homework did not improve at a faster rate (i.e., no between-person effect). However, sessions with greater than average participant-reported homework completion were associated with greater than average reductions in SHAPS scores (i.e., a within-person effect). For clinician-reported homework, this effect was only evident within the BATA condition. CONCLUSION: This study shows psychotherapy homework completion relates to symptomatic improvement in cognitive-behavioral treatments for anhedonia when session-to-session changes are examined within-person. On the contrary, we found no evidence that total homework completion predicted greater improvements between-person. When possible, psychotherapy researchers should evaluate their constructs of interest across multiple sessions (not just pre/post) to allow more direct tests of hypotheses predicted by theoretical models of individual change processes.

The unified protocol for transdiagnostic treatment of emotional disorders for misophonia: a pilot trial exploring acceptability and efficacy.

Introduction: Misophonia is a recently defined disorder characterized by distressing responses to everyday sounds, such as chewing or sniffling. Individuals with misophonia experience significant functional impairment but have limited options for evidenced-based behavioral treatment. To address this gap in the literature, the current pilot trial explored the acceptability and efficacy of a transdiagnostic cognitive-behavioral approach to treating symptoms of misophonia. Methods: This trial was conducted in two studies: In Study 1, the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) was delivered to eight patients in order to receive feedback to guide revisions to the treatment to suit this population. In Study 2, ten patients received the revised UP treatment to explore its acceptability and preliminary efficacy. This study used a single-case experimental design with multiple baselines, randomizing patients to either a 2-week baseline or 4-week baseline prior to the 16 weeks of treatment, followed by four weeks of follow-up. Results: The findings from these studies suggested that patients found both the original and adapted versions of the UP to be acceptable and taught them skills for how to manage their misophonia symptoms. Importantly, the findings also suggested that the UP can help remediate symptoms of misophonia, particularly the emotional and behavioral responses. Discussion: These findings provide preliminary evidence that this transdiagnostic treatment for emotional disorders can improve symptoms of misophonia in adults.

Phenotyping misophonia: Psychiatric disorders and medical health correlates.

Misophonia is characterized by decreased tolerance to specific sounds and associated stimuli that causes significant psychological distress and impairment in daily functioning (Swedo et al., 2022). Aversive stimuli (often called "triggers") are commonly repetitive facial (e.g., nose whistling, sniffling, and throat clearing) or oral (e.g., eating, drinking, and mouth breathing) sounds produced by other humans. Few empirical studies examining the nature and features of misophonia have used clinician-rated structured diagnostic interviews, and none have examined the relationship between misophonia and psychiatric disorders in the Diagnostic and Statistical Manual-5th version (DSM-5; American Psychiatric Association, 2013). In addition, little is known about whether there are any medical health problems associated with misophonia. Accordingly, the purpose of the present study was to improve the phenotypic characterization of misophonia by investigating the psychiatric and medical health correlates of this newly defined disorder. Structured diagnostic interviews were used to assess rates of lifetime and current DSM-5 psychiatric disorders in a community sample of 207 adults. The three most commonly diagnosed current psychiatric disorders were: (1) social anxiety disorder, (2) generalized anxiety disorder, and (3) specific phobia. The three most common lifetime psychiatric disorders were major depressive disorder, social anxiety disorder, and generalized anxiety disorder. A series of multiple regression analyses indicated that, among psychiatric disorders that were correlated with misophonia, those that remained significant predictors of misophonia severity after controlling for age and sex were borderline personality disorder, obsessive compulsive disorder, and panic disorder. No medical health problems were significantly positively correlated with misophonia severity.

Development and Initial Validation of the Duke Misophonia Questionnaire.

Misophonia is characterized by decreased tolerance and accompanying defensive motivational system responding to certain aversive sounds and contextual cues associated with such stimuli, typically repetitive oral (e. g., eating sounds) or nasal (e.g., breathing sounds) stimuli. Responses elicit significant psychological distress and impairment in functioning, and include acute increases in (a) negative affect (e.g., anger, anxiety, and disgust), (b) physiological arousal (e.g., sympathetic nervous system activation), and (c) overt behavior (e.g., escape behavior and verbal aggression toward individuals generating triggers). A major barrier to research and treatment of misophonia is the lack of rigorously validated assessment measures. As such, the primary purpose of this study was to develop and psychometrically validate a self-report measure of misophonia, the Duke Misophonia Questionnaire (DMQ). There were two phases of measure development. In Phase 1, items were generated and iteratively refined from a combination of the scientific literature and qualitative feedback from misophonia sufferers, their family members, and professional experts. In Phase 2, a large community sample of adults (n = 424) completed DMQ candidate items and other measures needed for psychometric analyses. A series of iterative analytic procedures (e.g., factor analyses and IRT) were used to derive final DMQ items and scales. The final DMQ has 86 items and includes subscales: (1) Trigger frequency (16 items), (2) Affective Responses (5 items), (3) Physiological Responses (8 items), (4) Cognitive Responses (10 items), (5) Coping Before (6 items), (6) Coping During (10 items), (7) Coping After (5 items), (8) Impairment (12 items), and Beliefs (14 items). Composite scales were derived for overall Symptom Severity (combined Affective, Physiological, and Cognitive subscales) and Coping (combined the three Coping subscales). Depending on the needs of researchers or clinicians, the DMQ may be use in full form, individual subscales, or with the derived composite scales.

Multilevel growth curve analyses of behavioral activation for anhedonia (BATA) and mindfulness-based cognitive therapy effects on anhedonia and resting-state functional connectivity: Interim results of a randomized trial✰.

BACKGROUND: The neural mechanisms associated with anhedonia treatment response are poorly understood. Additionally, no study has investigated changes in resting-state functional connectivity (rsFC) accompanying psychosocial treatment for anhedonia. METHODS: We evaluated a novel psychotherapy, Behavioral Activation Therapy for Anhedonia (BATA, n = 38) relative to Mindfulness-Based Cognitive Therapy (MBCT, n = 35) in a medication-free, transdiagnostic, anhedonic sample in a parallel randomized controlled trial. Participants completed up to 15 sessions of therapy and up to four 7T MRI scans before, during, and after treatment (n = 185 scans). Growth curve models estimated change over time in anhedonia and in rsFC using average region-of-interest (ROI)-to-ROI connectivity within the default mode network (DMN), frontoparietal network (FPN), salience network, and reward network. Changes in rsFC from pre- to post-treatment were further evaluated using whole-network seed-to-voxel and ROI-to-ROI edgewise analyses. RESULTS: Growth curve models showed significant reductions in anhedonia symptoms and in average rsFC within the DMN and FPN over time, across BATA and MBCT. There were no differences in anhedonia reductions between treatments. Within-person, changes in average rsFC were unrelated to changes in anhedonia. Between-person, higher than average FPN rsFC was related to less anhedonia across timepoints. Seed-to-voxel and edgewise rsFC analyses corroborated reductions within the DMN and between the DMN and FPN over time, across the sample. CONCLUSIONS: Reductions in rsFC within the DMN, FPN, and between these networks co-occurred with anhedonia improvement across two psychosocial treatments for anhedonia. Future anhedonia clinical trials with a waitlist control group should disambiguate treatment versus time-related effects on rsFC.

The Mediating Role of Emotion Regulation Within the Relationship Between Neuroticism and Misophonia: A Preliminary Investigation.

Misophonia is a newly described condition characterized by heightened emotional reactivity (e.g., anger, anxiety, and disgust) to common repetitive sounds (e.g., oral or nasal sounds made by others), accompanied by difficulties responding to these sounds (e.g., intolerance, avoidance, and escape) and associated impairment in functioning. Although research indicates that problematic emotional responses are a key characteristic of misophonia, it is unknown whether individual differences in experiencing and regulating emotional responses influence severity of misophonia symptoms. Examination of individual differences in emotional functioning will help to guide treatment development for misophonia. Accordingly, the present study examined the associations among trait neuroticism, difficulties with emotion regulation, and symptoms of misophonia. For this study, a sample of 49 adults completed the Difficulties with Emotion Regulation Scale, the Misophonia Questionnaire, and the neuroticism subscale of the NEO-Personality inventory. Findings indicated that difficulties with emotion regulation and neuroticism were significantly positively correlated with symptoms of misophonia. Bootstrapped mediation analyses suggested that difficulties controlling impulsive behavior while experiencing intense negative emotions fully mediated the relationship between neuroticism and symptoms of misophonia. Results from this study suggest that neuroticism and difficulties with emotion regulation may be important risk factors and treatment targets for adults with misophonia, and difficulties controlling impulsive behavior when distressed may be an important individual difference accounting for the relationship between neuroticism and misophonia.

A Preliminary Investigation of the Association Between Misophonia and Symptoms of Psychopathology and Personality Disorders.

Misophonia is a condition characterized by defensive motivational system emotional responding to repetitive and personally relevant sounds (e.g., eating, sniffing). Preliminary research suggests misophonia may be associated with a range of psychiatric disorders, including personality disorders. However, very little research has used clinician-rated psychometrically validated diagnostic interviews when assessing the relationship between misophonia and psychopathology. The purpose of this study was to extend the early research in this area by examining the relationship between symptoms of misophonia and psychiatric diagnoses in a sample of community adults, using semi-structured diagnostic interviews. Results indicated higher misophonia symptoms were associated with more clinician-rated symptoms of personality disorders, but not other disorders. Anxiety partially mediated the relationship between personality disorder symptoms and misophonia. These results suggest misophonia may be associated with a range of psychiatric symptoms and highlight the role of anxiety in this poorly understood condition.

Applying the Stress Process Model to Stress-Burnout and Stress-Depression Relationships in Biomedical Doctoral Students: A Cross-Sectional Pilot Study.

Although doctoral students in the biomedical sciences have been recognized as a population at particular risk for mental health problems such as burnout and depression, little research has been conducted to identify candidate targets for intervention. To this end, we used the stress process model to evaluate potential mediators of stress-burnout and stress-depression relationships in biomedical doctoral students. A cross-sectional sample (n = 69) completed validated self-report measures of stress; symptoms of burnout and depression; and perceptions of mastery, social support, and advisor support. In linear regression models, we found that academic stressors were most predictive of burnout, whereas family/monetary stressors were most predictive of depression. In mediation models, we found that the relationship between stress and burnout was partially mediated by mastery and advisor support, while the stress-depression relationship was partially mediated by mastery. These findings represent a first step in identifying interventional targets to improve mental health in this at-risk population. Whereas certain stressors are inherent to the doctoral training environment, psychosocial interventions to enhance one's sense of mastery and/or to improve advisor relationships may mitigate the influence of such stressors on burnout and depression.

Meclizine enhancement of sensorimotor gating in healthy male subjects with high startle responses and low prepulse inhibition.

Histamine H1 receptor systems have been shown in animal studies to have important roles in the reversal of sensorimotor gating deficits, as measured by prepulse inhibition (PPI). H1-antagonist treatment attenuates the PPI impairments caused by either blockade of NMDA glutamate receptors or facilitation of dopamine transmission. The current experiment brought the investigation of H1 effects on sensorimotor gating to human studies. The effects of the histamine H1 antagonist meclizine on the startle response and PPI were investigated in healthy male subjects with high baseline startle responses and low PPI levels. Meclizine was administered to participants (n=24) using a within-subjects design with each participant receiving 0, 12.5, and 25 mg of meclizine in a counterbalanced order. Startle response, PPI, heart rate response, galvanic skin response, and changes in self-report ratings of alertness levels and affective states (arousal and valence) were assessed. When compared with the control (placebo) condition, the two doses of meclizine analyzed (12.5 and 25 mg) produced significant increases in PPI without affecting the magnitude of the startle response or other physiological variables. Meclizine also caused a significant increase in overall self-reported arousal levels, which was not correlated with the observed increase in PPI. These results are in agreement with previous reports in the animal literature and suggest that H1 antagonists may have beneficial effects in the treatment of subjects with compromised sensorimotor gating and enhanced motor responses to sensory stimuli.