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.

Longitudinal associations between perceived stress and anhedonia during psychotherapy.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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. TRIAL NAME: Development of a Novel Transdiagnostic Intervention for Anhedonia - R61 Phase. TRIAL URL: https://clinicaltrials.gov/ct2/show/NCT02874534. TRIAL REGISTRATION NUMBER: NCT02874534.

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.

Ultra high-field (7tesla) magnetic resonance spectroscopy in Amyotrophic Lateral Sclerosis.

The main objective of this study was to utilize high field (7T) in vivo proton magnetic resonance imaging to increase the ability to detect metabolite changes in people with ALS, specifically, to quantify levels of glutamine and glutamine separately. The second objective of this study was to correlate metabolic markers with clinical outcomes of disease progression. 13 ALS participants and 12 age-matched healthy controls (HC) underwent 7 Tesla MRI and MRS. Single voxel MR spectra were acquired from the left precentral gyrus using a very short echo time (TE = 5 ms) STEAM sequence. MRS data was quantified using LCModel and correlated to clinical outcome markers. N-acetylaspartate (NAA) and total NAA (tNA, NAA + NAAG) were decreased by 17% in people with ALS compared to HC (P = 0.004 and P = 0.005, respectively) indicating neuronal injury and/or loss in the precentral gyrus. tNA correlated with disease progression as measured by forced vital capacity (FVC) (P = 0.014; Rρ = 0.66) and tNA/tCr correlated with overall functional decline as measured by worsening of the ALS Functional Rating Scale-Revised (ALSFRS-R) (P = 0.004; Rρ = -0.74). These findings underscore the importance of NAA as a reliable biomarker for neuronal injury and disease progression in ALS. Glutamate (Glu) was 15% decreased in people with ALS compared to HC (P = 0.02) while glutamine (Gln) concentrations were similar between the two groups. Furthermore, the decrease in Glu correlated with the decrease in FVC (P = 0.013; Rρ = 0.66), a clinical marker of disease progression. The decrease in Glu is most likely driven by intracellular Glu loss due to neuronal loss and degeneration. Neither choline containing components (Cho), a marker for cell membrane turnover, nor myo-Inositol (mI), a suspected marker for neuroinflammation, showed significant differences between the two groups. However, mI/tNA was correlated with upper motor neuron burden (P = 0.004, Rρ = 0.74), which may reflect a relative increase of activated microglia around motor neurons. In summary, 7T 1H MRS is a powerful non-invasive imaging technique to study molecular changes related to neuronal injury and/or loss in people with ALS.