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BACKGROUND: Anhedonia, deficits in motivation and pleasure, is a transdiagnostic symptom of psychopathology and negative prognostic marker. METHODS: In this randomized, parallel-arm clinical trial, a novel intervention, Behavioral Activation Treatment for Anhedonia (BATA), was compared to an individually administered Mindfulness-Based Cognitive Therapy (MBCT) in a transdiagnostic cohort of adults with clinically significant anhedonia (ClinicalTrials.gov Identifiers NCT02874534 and NCT04036136). Participants received 8-15 individual psychotherapy sessions, once weekly, with either BATA (n = 61) or MBCT (n = 55) and completed repeated self-report assessment of anhedonia and other internalizing symptoms. RESULTS: Indicators of treatment feasibility were similar across conditions, though MBCT showed a trend towards greater attrition rates than BATA, with an adjusted odd's ratio of 2.04 [0.88, 4.73]. Treatment effects on the primary clinical endpoint of anhedonia symptoms did not significantly differ, with a 14-week estimated difference on the Snaith Hamilton Pleasure Scale (SHAPS) of -0.20 [-2.25, 1.84] points in BATA compared to MBCT (z = 0.19, p = 0.845, d = 0.05). The expected 14-week change in SHAPS scores across conditions was -7.18 [-8.22, -6.15] points (z = 13.6, p < 0.001, d = 1.69). There were no significant differences in the proportion of participants demonstrating reliable and clinically significant improvements in SHAPS scores, or in the magnitude of internalizing symptom reductions. LIMITATIONS: Limitations included a modest sample size, lack of longer-term follow up data, and non-preregistered analytic plan. DISCUSSION: There was no evidence to support superior clinical efficacy of BATA over MBCT in a transdiagnostic cohort of adults with elevated anhedonia. Both interventions reduced anhedonia symptoms to a comparable magnitude of other existing treatments.
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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.
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Terapia Cognitivo-Conductual , Atención Plena , Adulto , Humanos , Anhedonia/fisiología , Cognición , Terapia Cognitivo-Conductual/métodos , Placer/fisiologíaRESUMEN
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.
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Trastorno Depresivo Mayor , Dopamina , Humanos , Racloprida , Dopamina/metabolismo , Anhedonia , Tomografía de Emisión de Positrones , Imagen por Resonancia MagnéticaRESUMEN
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the central nervous system that results in a progressive loss of motor function and ultimately death. It is critical, yet also challenging, to develop non-invasive biomarkers to identify, localize, measure and/or track biological mechanisms implicated in ALS. Such biomarkers may also provide clues to identify potential molecular targets for future therapeutic trials. Herein we report on a pilot study involving twelve participants with ALS and nine age-matched healthy controls who underwent high-resolution resting state functional magnetic resonance imaging at an ultra-high field of 7 Tesla. A group-level whole-brain analysis revealed a disruption in long-range functional connectivity between the superior sensorimotor cortex (in the precentral gyrus) and bilateral cerebellar lobule VI. Post hoc analyses using atlas-derived left and right cerebellar lobule VI revealed decreased functional connectivity in ALS participants that predominantly mapped to bilateral postcentral and precentral gyri. Cerebellar lobule VI is a transition zone between anterior motor networks and posterior non-motor networks in the cerebellum, and is associated with a wide range of key functions including complex motor and cognitive processing tasks. Our observation of the involvement of cerebellar lobule VI adds to the growing number of studies implicating the cerebellum in ALS. Future avenues of scientific investigation should consider how high-resolution imaging at 7T may be leveraged to visualize differences in functional connectivity disturbances in various genotypes and phenotypes of ALS along the ALS-frontotemporal dementia spectrum.
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Esclerosis Amiotrófica Lateral , Enfermedades Neurodegenerativas , Esclerosis Amiotrófica Lateral/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Proyectos PilotoRESUMEN
The social motivation hypothesis of autism posits that autism spectrum disorder (ASD) is characterized by impaired motivation to seek out social experience early in life that interferes with the development of social functioning. This framework suggests that impaired mesolimbic dopamine function underlies compromised responses to social rewards in ASD. Although this hypothesis is supported by functional magnetic resonance imaging (fMRI) studies, no molecular imaging study has evaluated striatal dopamine functioning in response to rewards in ASD. Here, we examined striatal functioning during monetary incentive processing in ASD and controls using simultaneous positron emission tomography (PET) and fMRI. Using a bolus + infusion protocol with the D2/D3 dopamine receptor antagonist [11C]raclopride, voxel-wise binding potential (BPND) was compared between groups (controls = 12, ASD = 10) in the striatum. Striatal clusters showing significant between-group BPND differences were used as seeds in whole-brain fMRI general functional connectivity analyses. Relative to controls, the ASD group demonstrated decreased phasic dopamine release to incentives in the bilateral putamen and left caudate, as well as increased functional connectivity between a PET-derived right putamen seed and the precuneus and insula. Within the ASD group, decreased phasic dopamine release in the putamen was related to poorer theory-of-mind skills. Our findings that ASD is characterized by impaired striatal phasic dopamine release to incentives provide support for the social motivation hypothesis of autism. PET-fMRI may be a suitable tool to evaluate novel ASD therapeutics targeting the striatal dopamine system.
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Trastorno del Espectro Autista , Trastorno Autístico , Trastorno del Espectro Autista/diagnóstico por imagen , Trastorno Autístico/diagnóstico por imagen , Cuerpo Estriado/diagnóstico por imagen , Cuerpo Estriado/metabolismo , Dopamina , Humanos , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Racloprida , Receptores de Dopamina D2/metabolismoRESUMEN
Few studies have explored neural mechanisms of reward learning in ASD despite evidence of behavioral impairments of predictive abilities in ASD. To investigate the neural correlates of reward prediction errors in ASD, 16 adults with ASD and 14 typically developing controls performed a prediction error task during fMRI scanning. Results revealed greater activation in the ASD group in the left paracingulate gyrus during signed prediction errors and the left insula and right frontal pole during thresholded unsigned prediction errors. Findings support atypical neural processing of reward prediction errors in ASD in frontostriatal regions critical for prediction coding and reward learning. Results provide a neural basis for impairments in reward learning that may contribute to traits common in ASD (e.g., intolerance of unpredictability).
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Research has consistently demonstrated that testing prior to the presentation of misleading post-event information, within the context of a standard eyewitness misinformation paradigm, results in an increase in the misinformation effect. The present study investigated whether changes in misinformation susceptibility in the context of interim testing are affected by retention interval differences between misinformation presentation and final testing. Further, this study tested possible divergences in original and post-event learning between conditions where elaboration in processing of critical details was encouraged either indirectly, via interim testing, or directly, by visually emphasizing critical details. In two experiments, we compared three groups of participants. All participants were exposed to an event, presented with misleading post-event misinformation, and then given a final test on the original event. One group was given an interim test between the original event and the post-event synopsis. A second was presented with a post-event synopsis in which critical details were visually emphasized. A third group served as a baseline comparison group for which synopsis processing was not manipulated. All experimental phases occurred in a single session in Experiment 1. A 48-hour retention interval was inserted between the post-event synopsis and final test in Experiment 2. In Experiment 1, we found that interim testing and emphasizing critical details increased misinformation susceptibility as compared to that found in the standard misinformation group. In Experiment 2, misinformation susceptibility was reduced in the interim testing group. These results suggest that interim testing and emphasizing critical details influence the rate of original detail forgetting. At a longer retention interval, the benefits of testing in learning emerged.