Examining processes of change for acceptance and commitment therapy and cognitive behavioral therapy self-help books with depressed college students.

Given the prevalence of depression, it is worthwhile to consider a variety of treatment approaches to reach as many sufferers as possible, including highly accessible formats such as self-help books. Books based in acceptance and commitment therapy (ACT) and cognitive behavioral therapy (CBT) propose to treat depression through distinct processes of change, though the degree to which these treatments are distinguishable in this format is unclear. Furthermore, it is possible that some individuals may respond better to therapeutic processes from one approach over the other based on personal preferences. We tested the effects of ACT and CBT self-help books on processes of change in a sample of 139 depressed college students in which some participants were given a choice of treatment and others were randomized. Cognitive fusion, which improved better in the ACT group, was the only process of change that distinguished the two treatments. Additionally, early improvements in cognitive fusion were associated with less depression-related stigma at posttreatment. Lastly, randomization, instead of choosing a treatment, led to greater improvements in almost all processes of change. We discuss how these findings inform personalized care, tangible differences between ACT and CBT, and effective practices for treating depression at large scale.

Predictors of adherence to a publicly available self-guided digital mental health intervention.

Low adherence to self-guided digital mental health interventions (DMHIs) have raised concerns about their real-world effectiveness. Naturalistic data from self-guided DMHIs are often not available, hindering our ability to assess adherence among real-world users. This study aimed to analyze 3 years of user data from the public launch of an empirically supported 12-session self-guided DMHI, to assess overall program adherence rates and explore predictors of adherence. Data from 984 registered users were analyzed. Results showed that only 14.8% of users completed all 12 modules and 68.6% completed less than half of the modules. Users who were younger, had milder depression, had never seen a mental health provider, and who rejected signing-up for weekly program emails completed significantly more modules. Results add to concerns about the generalizability of controlled research on DMHIs due to lower adherence outside of research trials. This study highlights the potential of user data in identifying key factors that may be related to adherence. By examining adherence patterns among different sub-sets of users, we can pinpoint and focus on individuals who may adhere and benefit more from self-guided programs. Findings could also have implications for guiding intervention personalization for individuals who struggle to complete DMHIs.

Adding online storytelling-based acceptance and commitment therapy to antidepressant treatment for primary care patients: a randomized clinical trial.

Depression is most often treated in primary care, where the prevailing treatment is antidepressant medication. Primary care patients with depression are less likely to be exposed to psychosocial interventions, despite evidence suggesting many of these treatments are effective. An example is acceptance and commitment therapy (ACT), a behavioral treatment for depression with a growing evidence base. A self-guided ACT intervention with a peer narrative (i.e. storytelling) format was developed with the intention of creating a treatment option for primary care patients that was more accessible than traditional psychotherapy. Titled LifeStories, the online program features videos of real individuals sharing coping skills for depression based on lived experiences and key ACT principles. A total of 93 primary care patients taking antidepressants were randomized to either continued antidepressant treatment alone or antidepressant treatment plus LifeStories for 4 weeks. There were no differences over time on depression severity and psychological inflexibility. However, LifeStories led to greater improvements in quality of life and increased patients' interest in additional treatment compared to antidepressant medication alone.Clinical trial pre-registration: ClinicalTrials.gov (NCT04757961).

Evaluating the effects of guided coaching calls on engagement and outcomes for online acceptance and commitment therapy.

Previous research indicates mixed results for guided support with online interventions. The current secondary analysis evaluated the effects of phone coaching from a dismantling trial of online acceptance and commitment therapy (ACT) in a sample of 136 distressed college students randomized to one of three versions of an ACT website. Participants were randomized to receive email prompts alone (non-coaching condition) or email plus phone coaching (coaching condition). Results indicated no differences between the coaching and non-coaching conditions on program engagement, program satisfaction, mental health outcomes, and almost all psychological flexibility processes. However, participants in the coaching condition reported stronger pre- to posttreatment improvements in psychological inflexibility than the non-coaching condition. This effect was moderated by ACT component condition, with larger pre- to posttreatment effects from coaching on psychological inflexibility in the values/committed action condition and weaker improvements from coaching in the acceptance/defusion condition. Overall, results indicate online self-guided ACT interventions with email prompts are sufficient for addressing college student mental health and that phone coaching provided minimal additional benefit.

Pilot randomized controlled trial of a video self-help intervention for depression based on acceptance and commitment therapy: Feasibility and acceptability.

A common setting where depression is identified and treated is in primary care, where there is a need for low-intensity and cost-effective interventions to be used as part of a stepped-care model. The current study involved a pilot, parallel-group, randomized controlled trial of a video self-help intervention for primary care patients based on acceptance and commitment therapy (ACT). The intervention, called LifeStories, consisted of storytelling vignettes of patients describing their use of ACT-consistent coping skills for depression. Primary care patients were recruited to determine feasibility, acceptability, and potential clinical effects of the intervention. Twenty-one participants were assigned to use LifeStories over a period of 4 weeks, and 19 participants were assigned to an attention-matched comparison group. Qualitative feedback indicated that participants using LifeStories found the intervention to be engaging and useful in transmitting key ACT principles. Furthermore, those receiving LifeStories rated their level of "transportation" or immersion in the videos higher than the control group. Both conditions showed large improvements in levels of depression at a 12-week follow-up. There were no significant differences in symptom outcomes between groups; however, because this was a pilot study, it was not powered to detect differences between interventions. Both conditions additionally showed smaller effect size changes in psychological flexibility, a key ACT mechanism. The results suggest LifeStories to be a feasible and acceptable psychological intervention that may improve depression, and further research is warranted to determine its effectiveness as part of a stepped-care approach to treating depression in primary care.

SET alpha and SET beta mRNA isoforms in chronic lymphocytic leukaemia.

Alteration in RNA splicing is implicated in carcinogenesis and progression. Mutations in spliceosome genes and alternative splicing of other genes have been noted in chronic lymphocytic leukaemia (CLL), a common B cell malignancy with heterogeneous outcomes. We previously demonstrated that differences in the amount of SET oncoprotein (a physiological inhibitor of the serine/threonine phosphatase, PP2A) is associated with clinical aggressiveness in patients with CLL. It is unknown if alternative splicing of gene transcripts regulating kinases and phosphatases affects disease pathobiology and CLL progression. We show here for the first time that mRNA levels of the alternatively spliced SET isoforms, SETA and SETB (SETα and SETß), significantly correlate with disease severity (overall survival and time-to-first-treatment) in CLL patients. In addition, we demonstrate that relative increase of SETA to SETB mRNA can discriminate patients with a more aggressive disease course within the otherwise favourable CLL risk classifications of IGHV mutated and favourable hierarchical fluorescence in situ hybridisation groups. We validate our finding by showing comparable relationships of SET mRNA with disease outcomes using samples from an independent CLL cohort from a separate institution. These findings indicate that alternative splicing of SET, and potentially other signalling cascade molecules, influences CLL biology and patient outcomes.

Feasibility and acceptability of post-hospitalization ecological momentary assessment in patients with psychotic-spectrum disorders.

BACKGROUND: Up to 50% of patients with psychotic-spectrum disorders are medication nonadherent. The use of real-time assessment via ecological momentary assessment (EMA) on mobile devices might offer important insights into adherence behaviors that cannot be measured in the clinic. However, existing EMA studies have only studied acutely ill patients during hospitalization or more stable patients in the community. METHODS: Feasibility and acceptability of EMA in 65 patients with psychotic-spectrum disorders who were recently discharged from the hospital were assessed. EMA was administered for four weeks via study-provided mobile devices. Feasibility was measured by study recruitment/retention rates, patients' connectivity, and completion rates. Quantitative and qualitative acceptability data were collected. RESULTS: Participants completed 28-31% of offered EMA assessments. The only significant predictor of reduced EMA completion was recent cannabis use. EMA completion was maintained from weeks 1 to 3 but significantly dropped at the fourth week. Patient acceptability feedback was generally positive; negative comments related primarily to technological problems. CONCLUSIONS: This was the first study to use EMA in recently discharged patients with psychotic-spectrum disorders. EMA is feasible and acceptable in this population, but completion rates were lower than in more stable samples. Future research should consider limiting the assessment period, screening for substance use, and integrating assessment with intervention elements to increase EMA engagement.

Reach, adoption, and maintenance of online acceptance and commitment therapy at a university: An implementation case study.

College students are undergoing a mental health crisis and existing clinical resources at universities may be inadequate to meet their needs. One solution to this problem could be the use of self-guided, online programs for mental health that can be easily distributed to students. A persistent issue, however, is the transition from program development to implementation of a self-guided program at campus-wide scale. We describe, in a self-narrative format, the steps taken to translate an online program we developed based in acceptance and commitment therapy, called Acceptance and Commitment Therapy Guide, from a research context to a campus-wide service at our university. We also present demographic, previous treatment, and referral data of over 1,500 student sign-ups to describe the reach of our program, how it was adopted into existing university services and systems, and how we maintained the program long term. Findings from these implementation efforts are discussed in the context of suggestions for using self-guided programs for students to fill gaps in mental health service provision in university settings. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Choosing ACT or CBT: A preliminary test of incorporating client preferences for depression treatment with college students.

BACKGROUND: Depression is a significant concern among college students, who suffer at higher rates and with greater severity than the general population. Online self-help could reduce the burden currently placed on college counseling centers, and programs based in cognitive behavioral therapies (CBTs) have a strong evidence base. However, online CBTs for depression often suffer from low adherence rates. An understudied method for improving adherence in this population is offering students a choice between various CBTs. METHODS: We conducted a randomized trial with 142 students with high levels of depression, with a subset of participants randomly receiving either traditional cognitive behavioral therapy (tCBT) or acceptance and commitment therapy (ACT) and an additional arm who could choose between the two. RESULTS: Both treatments effectively reduced depression over 10 weeks, with ACT showing a slight advantage over tCBT. Surprisingly, students who were randomized to their treatment saw greater reductions in anxiety, and higher adherence to the program, than those who chose between the two. LIMITATIONS: Our study suffered from a notable amount of dropout and our results should be considered preliminary. Our sample size was relatively small at posttreatment, limiting our ability to make strong conclusions about group differences. Additionally, further steps could have been taken to minimize the risk of bias when presenting treatment options to the choice group. CONCLUSIONS: Our preliminary results suggest that simply providing students with an evidence-based resource may be more important than providing options and raise additional questions about the function of client preference in self-help dissemination.

Dynamic regulation of ROCK in tumor cells controls CXCR4-driven adhesion events.

CXCR4 is a chemokine receptor often found aberrantly expressed on metastatic tumor cells. To investigate CXCR4 signaling in tumor cell adhesion, we stably overexpressed CXCR4 in MCF7 breast tumor cells. Cell attachment assays demonstrate that stimulation of the receptor with its ligand, CXCL12, promotes adhesion of MCF7-CXCR4 cells to both extracellular matrix and endothelial ligands. To more closely mimic the conditions experienced by a circulating tumor cell, we performed the attachment assays under shear stress conditions. We found that CXCL12-induced tumor cell attachment is much more pronounced under flow. ROCK is a serine/threonine kinase associated with adhesion and metastasis, which is regulated by CXCR4 signaling. Thus, we investigated the contribution of ROCK activity during CXC12-induced adhesion events. Our results demonstrate a biphasic regulation of ROCK in response to adhesion. During the initial attachment, inhibition of ROCK activity is required. Subsequently, re-activation of ROCK activity is required for maturation of adhesion complexes and enhanced tumor cell migration. Interestingly, CXCL12 partially reduces the level of ROCK activity generated by attachment, which supports a model in which stimulation with CXCL12 regulates tumor cell adhesion events by providing an optimal level of ROCK activity for effective migration.

Utilizing ACT daily as a self-guided app for clients waiting for services at a college counseling center: A pilot study.

ObjectiveConsidering increasing demands for mental health services at college counseling centers (CCCs), there is a need for cost-effective solutions that avoid depleting stressed CCC resources. This study examined if ACT Daily, a mobile application based on acceptance and commitment therapy (ACT), could serve as an effective self-guided intervention. Participants: 11 individuals on a CCC waitlist suffering from anxiety/depression participated in the study over 2 weeks. Methods: This study implemented a pre-post, open trial design of ACT Daily. Assessments were completed at baseline and 2-week post assessment. Results: Results indicated that ACT Daily was acceptable and that participants improved on depression and anxiety symptoms as well as psychological inflexibility processes over the 2 weeks. App data further indicated significant in-the-moment improvements on depression, anxiety and psychological inflexibility immediately following skill coaching, with these effects becoming larger over time. Conclusions: Mobile apps like ACT Daily could serve as an effective, pre-therapy tool for depressed/anxious students.

Development of a Storytelling Video Self-Help Intervention Based on Acceptance and Commitment Therapy for Major Depression: Open Trial Results.

This study involved the initial development and testing of a video self-help intervention called LifeStories, which features real patients describing their use of coping strategies for depression based on Acceptance and Commitment Therapy. We conducted a baseline-controlled open trial (AB design) of 11 individuals diagnosed with major depressive disorder. Participants reported high levels of satisfaction and transportation (i.e., engagement) after watching LifeStories. No significant changes were observed during the 4-week baseline period in terms of interviewer-rated depression severity (primary outcome), but a significant and large effect size improvement was observed at Week 8 postintervention. The majority of participants (54.5%) showed a reliable and clinically significant posttreatment response. Significant improvements also were observed during the intervention period only for self-reported depressive symptoms and aspects of mindfulness (nonreactivity). Qualitative data analysis of participant interviews identified additional areas for improvement and refinement. Future testing in a randomized trial is warranted based on these encouraging results.

Subcellular localization of ammonium transporters in Dictyostelium discoideum.

BACKGROUND: With the exception of vertebrates, most organisms have plasma membrane associated ammonium transporters which primarily serve to import a source of nitrogen for nutritional purposes. Dictyostelium discoideum has three ammonium transporters, Amts A, B and C. Our present work used fluorescent fusion proteins to determine the cellular localization of the Amts and tested the hypothesis that the transporters mediate removal of ammonia generated endogenously from the elevated protein catabolism common to many protists. RESULTS: Using RFP and YFP fusion constructs driven by the actin 15 promoter, we found that the three ammonium transporters were localized on the plasma membrane and on the membranes of subcellular organelles. AmtA and AmtB were localized on the membranes of endolysosomes and phagosomes, with AmtB further localized on the membranes of contractile vacuoles. AmtC also was localized on subcellular organelles when it was stabilized by coexpression with either the AmtA or AmtB fusion transporter. The three ammonium transporters exported ammonia linearly with regard to time during the first 18 hours of the developmental program as revealed by reduced export in the null strains. The fluorescently tagged transporters rescued export when expressed in the null strains, and thus they were functional transporters. CONCLUSION: Unlike ammonium transporters in most organisms, which import NH3/NH4+ as a nitrogen source, those of Dictyostelium export ammonia/ammonium as a waste product from extensive catabolism of exogenously derived and endogenous proteins. Localization on proteolytic organelles and on the neutral contractile vacuole suggests that Dictyostelium ammonium transporters may have unique subcellular functions and play a role in the maintenance of intracellular ammonium distribution. A lack of correlation between the null strain phenotypes and ammonia excretion properties of the ammonium transporters suggests that it is not the excretion function that is important for coupling ammonia levels to the slug versus culmination choice, but rather a sensor and/or signaling function of these proteins that is important.

Acceptance and Commitment Therapy for Inpatients with Psychosis (the REACH Study): Protocol for Treatment Development and Pilot Testing.

Patients with schizophrenia-spectrum disorders frequently require treatment at inpatient hospitals during periods of acute illness for crisis management and stabilization. Acceptance and Commitment Therapy (ACT), a "third wave" cognitive-behavioral intervention that employs innovative mindfulness-based strategies, has shown initial efficacy in randomized controlled trials for improving acute and post-discharge outcomes in patients with psychosis when studied in acute-care psychiatric hospitals in the U.S. However, the intervention has not been widely adopted in its current form because of its use of an individual-only format and delivery by doctoral-level research therapists with extensive prior experience using ACT. The aim of the Researching the Effectiveness of Acceptance-based Coping during Hospitalization (REACH) Study is to adapt a promising acute-care psychosocial treatment for inpatients with psychosis, and to pilot test its effectiveness in a routine inpatient setting. More specifically, we describe our plans to: (a) further develop and refine the treatment and training protocols, (b) conduct an open trial and make further modifications based on the experience gained, and

A role for the androgen receptor in the treatment of male breast cancer.

Male breast cancer (BC) is relatively rare, making up less than 1% of all breast cancer cases in the United States. Treatment guidelines for male BC are derived from studies on the treatment of female BC, and are based molecular and clinical characteristics, such as hormone receptor positivity. For female estrogen receptor positive (ER+) breast cancers, the standard of care includes three classes of endocrine therapies: selective estrogen receptor modulators, aromatase inhibitors, and pure anti-estrogens. In contrast to female ER+ breast cancers, there is less known about the optimal treatment for male ER+ BC. Furthermore, in contrast to ER, less is known about the role of the androgen receptor (AR) in male and female BC. We report here the treatment of a 28-year-old man with metastatic AR+, ER+ breast cancer otherwise refractory to chemotherapy, who has had a durable clinical response to hormonal suppression with the combination of aromatase inhibition (Letrozole) in conjunction with a GnRH agonist (Leuprolide).

Immunotherapeutic applications of NK cells.

Natural Killer (NK) cells are lymphoid cells that exhibit an innate response against virus-infected cells. These cells are also capable of mounting an immune response against tumor cells after education through major histocompatibility complex (MHC) class I molecules. NK cell regulation is mediated through IFN-gamma and IL-15, important cytokines which can drive NK cell expansion in vivo. Previous studies have shown effective infusion of allogeneic NK cells after lymphodepleting regimens with induction of remission of poor prognosis acute myeloid leukemia (AML). Challenges remain in the expansion of these NK cells once infused and in their education to recognize tumor targets. A principal mechanism of tumor recognition is through KIR mismatch in cells lacking self MHC I molecules. Activating KIRs exist, though their ligands are unknown at this time. Impacting NK cell expansion and education in vivo has been challenging, and thus far clinical applications of NK cells have shown promise in helping to maintain remission in humans, though this remission has not been maintained. Future efforts to utilize NK cells clinically are focusing on developing more consistency in successful expansion of NK cell and educating them to recognize their tumor targets. Additional efforts to utilize novel antibody-based therapy to engage NK cells to their tumor targets are also in development.