The effects of psychotherapy for anhedonia on subcortical brain volumes measured with ultra-high field MRI.

Anhedonia is a transdiagnostic symptom often resistant to treatment. The identification of biomarkers sensitive to anhedonia treatment will aid in the evaluation of novel anhedonia interventions. This is an exploratory analysis of changes in subcortical brain volumes accompanying psychotherapy in a transdiagnostic anhedonic sample using ultra-high field (7-Tesla) MRI. Outpatients with clinically impairing anhedonia (n = 116) received Behavioral Activation Treatment for Anhedonia, a novel psychotherapy, or Mindfulness-Based Cognitive Therapy (ClinicalTrials.gov Identifiers NCT02874534 and NCT04036136). Subcortical brain volumes were estimated via the MultisegPipeline, and regions of interest were the amygdala, caudate nucleus, hippocampus, pallidum, putamen, and thalamus. Bivariate mixed effects models estimated pre-treatment relations between anhedonia severity and subcortical brain volumes, change over time in subcortical brain volumes, and associations between changes in subcortical brain volumes and changes in anhedonia symptoms. As reported previously (Cernasov et al., 2023), both forms of psychotherapy resulted in equivalent and significant reductions in anhedonia symptoms. Pre-treatment anhedonia severity and subcortical brain volumes were not related. No changes in subcortical brain volumes were observed over the course of treatment. Additionally, no relations were observed between changes in subcortical brain volumes and changes in anhedonia severity over the course of treatment. This trial included a modest sample size and did not have a waitlist-control condition or a non-anhedonic comparison group. In this exploratory analysis, psychotherapy for anhedonia was not accompanied by changes in subcortical brain volumes, suggesting that subcortical brain volumes may not be a candidate biomarker sensitive to response to psychotherapy.

Gibson K ，Cernasov P ，Styner M ，Walsh EC ，Kinard JL ，Kelley L ，Bizzell J ，Phillips R ，Pfister C ，Scott M ，Freeman L ，Pisoni A ，Nagy GA ，Oliver JA ，Smoski MJ ，Dichter GS ... -  《-》

Longitudinal associations between perceived stress and anhedonia during psychotherapy.

Chronic stress alters reward sensitivity and contributes to the emergence of anhedonia. In clinical samples, the perception of stress is a strong predictor of anhedonia. While there is substantial evidence demonstrating psychotherapy reduces perceived stress, little is known regarding the effects of treatment-related decreases in perceived stress on anhedonia. The current study investigated reciprocal relations between perceived stress and anhedonia using a cross-lagged panel model approach in a 15-week clinical trial examining the effects of Behavioral Activation Treatment for Anhedonia (BATA), a novel psychotherapy to treat anhedonia, compared to a Mindfulness-Based Cognitive Therapy (MBCT) comparison intervention (ClinicalTrials.gov Identifiers NCT02874534 and NCT04036136). Treatment completers (n = 72) experienced significant reductions in anhedonia (M = -8.94, SD = 5.66) on the Snaith-Hamilton Pleasure Scale (t(71) = 13.39, p < .0001), and significant reductions in perceived stress (M = -3.71, SD = 3.88) on the Perceived Stress Scale (t(71) = 8.11, p < .0001) following treatment. Across all treatment-seeking participants (n = 87), a longitudinal autoregressive cross-lagged model revealed significant paths showing that higher levels of perceived stress at treatment Week 1 predicted reductions in anhedonia at treatment Week 4; lower levels of perceived stress at Week 8 predicted reductions in anhedonia at Week 12. Anhedonia did not significantly predict perceived stress at any stage of treatment. This study showed specific timing and directional effects of perceived stress on anhedonia during psychotherapy treatment. Individuals with relatively high perceived stress at the start of treatment were more likely to report relatively lower anhedonia a few weeks into treatment. At mid-treatment, individuals with low perceived stress were more likely to report lower anhedonia towards the end of treatment. These results demonstrate that early treatment components reduce perceived stress, thus allowing for downstream changes in hedonic functioning during mid-late treatment. The findings presented here suggest it will be critically important for future clinical trials evaluating novel interventions for anhedonia to measure stress levels repeatedly, as an important mechanism of change. Development of a Novel Transdiagnostic Intervention for Anhedonia - R61 Phase. TRIAL URL: https://clinicaltrials.gov/ct2/show/NCT02874534. NCT02874534.

Phillips R ，Walsh E ，Jensen T ，Nagy G ，Kinard J ，Cernasov P ，Smoski M ，Dichter G ... -  《-》

A parallel-arm, randomized trial of Behavioral Activation Therapy for anhedonia versus mindfulness-based cognitive therapy for adults with anhedonia.

Anhedonia, deficits in motivation and pleasure, is a transdiagnostic symptom of psychopathology and negative prognostic marker. 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. 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 included a modest sample size, lack of longer-term follow up data, and non-preregistered analytic plan. 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.

Cernasov PM ，Walsh EC ，Nagy GA ，Kinard JL ，Kelley L ，Phillips RD ，Pisoni A ，Diehl J ，Haworth K ，West J ，Freeman L ，Pfister C ，Scott M ，Daughters SB ，Gaylord S ，Dichter GS ，Smoski MJ ... -  《-》

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(✰).

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. 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. 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. 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.

Cernasov P ，Walsh EC ，Kinard JL ，Kelley L ，Phillips R ，Pisoni A ，Eisenlohr-Moul TA ，Arnold M ，Lowery SC ，Ammirato M ，Truong K ，Nagy GA ，Oliver JA ，Haworth K ，Smoski M ，Dichter GS ... -  《-》

Developmentally stable whole-brain volume reductions and developmentally sensitive caudate and putamen volume alterations in those with attention-deficit/hyperactivity disorder and their unaffected siblings.

Greven CU ，Bralten J ，Mennes M ，O'Dwyer L ，van Hulzen KJ ，Rommelse N ，Schweren LJ ，Hoekstra PJ ，Hartman CA ，Heslenfeld D ，Oosterlaan J ，Faraone SV ，Franke B ，Zwiers MP ，Arias-Vasquez A ，Buitelaar JK ... -  《-》