Mediators Of Intervention Effects Research Articles

The researcher's guide to selecting biomarkers in mental health studies.

Clinical mental health researchers may understandably struggle with how to incorporate biological assessments in clinical research. The options are numerous and are described in a vast and complex body of literature. Here we provide guidelines to assist mental health researchers seeking to include biological measures in their studies. Apart from a focus on behavioral outcomes as measured via interviews or questionnaires, we advocate for a focus on biological pathways in clinical trials and epidemiological studies that may help clarify pathophysiology and mechanisms of action, delineate biological subgroups of participants, mediate treatment effects, and inform personalized treatment strategies. With this paper we aim to bridge the gap between clinical and biological mental health research by (1) discussing the clinical relevance, measurement reliability, and feasibility of relevant peripheral biomarkers; (2) addressing five types of biological tissues, namely blood, saliva, urine, stool and hair; and (3) providing information on how to control sources of measurement variability.

Optimizing Individual HIV Testing and Counseling for Emerging Adult Sexual Minority Men (Aged 18 to 24) in Relationships: A Pilot Randomized Controlled Trial of Adjunct Communication Components.

The majority of new HIV infections in the US occur among sexual minority men (SMM) with older adolescent and emerging adult SMM at the highest risk. Those in relationships face unique HIV prevention challenges. Existing sexual HIV transmission risk interventions for male couples often encounter implementation challenges and engaging younger SMM early in relationships may be particularly difficult. This pilot randomized controlled trial evaluated the acceptibility and feasibility of We Test HIV testing - a behavioral health intervention tailored for younger SMM in realtionships - and generated preliminary estimates of effect size. The intervention comprises two adjunct moduls - video-based communication skills training as well as communication goal setting and planning - delivered in conjunction with routine HIV testing and counseling in individual or dyadic formats. A sample of 69 SMM aged 17 to 24 were recruited online. Following baseline assessment, youth were randomized to receive either the experimental, We Test, intervention or routine HIV testing (the control condition). Follow-up assessments were completed 3 and 6 months post-baseline. Results suggested the study was feasible and the individually delivered format was acceptible. We Test HIV testing was associated with significant improvements in communication skills. In addition, youth who remained in a relationship experienced an increase in communal coping to reduce HIV infection risk and relationship power. While groups did not differ with respect to condomless anal sex with casual partners, these psycho-social constructs (communication, communal coping with HIV prevention, and relationship power) may serve as mediators of intervention effects on sexual risk reduction in a larger study.

1825-LB: Reproductive Health (RH) and Gestational Diabetes (GDM) Knowledge Mediates the Intervention Effect on the Intention to Communicate in Dyads of American Indian and Alaska Native (AIAN) Female Adolescents and Young Adults (FAYA) at Risk for GDM and their Adult Female Caregivers

AIAN women are unduly impacted by GDM. This secondary analysis of Stopping GDM trial data explored possible mechanisms of action of a psycho-behavioral educational intervention targeting healthy behaviors to reduce GDM risk from pre- to post-test among AIAN FAYA. Dyads of FAYA and their adult female caregivers were recruited from 5 sites. Each dyad member independently completed questionnaires regarding RH and GDM knowledge, health beliefs, and intention to initiate discussion with healthcare providers (HCPs) and their corresponding dyad member. Between assessments intervention participants viewed a 45-minute video, the initial component of the intervention. Dyadic mediation analysis was conducted using the Actor-Partner Interdependence Model extended to Mediation (APIMeM) assuming distinguishable dyad members. The sample (N=149 dyads; intervention; n=79; control: n=70) included FAYA (mean age 16.7±3.0 years) and adult female caregivers (mean age 44.1±9.3 years; 81.0% being mothers of FAYA). APIMeM revealed a positive actor indirect effect of the intervention for improvement in the FAYA’s intention to initiate discussion through increases in FAYA’s RH and GDM knowledge (1.53, 95%CI=[0.27, 2.98]). A positive partner indirect effect was also observed for the intervention on the improvement in the FAYA’s intention to initiate discussion through increases in the adult caregiver’s RH and GDM knowledge (0.61, 95%CI=[0.042, 1.42]). No effects were found for changes in health beliefs of FAYA or adult caregivers as mediators of intervention effects on FAYA’s and adult caregiver’s intention to initiate discussion. These results suggest that enhancing RH and GDM knowledge may improve key downstream outcomes such as communication between FAYA, adult caregivers and HCPs for AIAN FAYA at risk for GDM. Disclosure S.M. Sereika: None. K.R. Moore: None. S.A. Stotz: None. X. Pei: None. Y. Wang: None. D. Charron-Prochownik: None. Funding National Institutes of Health (R01-NR014831)

Does intervention engagement mediate physical activity change in a web-based computer-tailored physical activity intervention?-Secondary outcomes from a randomised controlled trial.

The relationship between intervention engagement and behaviour change may vary depending on the specific engagement metric being examined. To counter this composite engagement measures may provide a deeper understanding of the relationship between engagement and behaviour change, though few studies have applied such multidimensional engagement metrics. The aim of this secondary analysis of RCT data was to examine how a composite engagement score mediates the effect of a web-based computer-tailored physical activity intervention. 501 inactive Australian adults were randomised to a no-treatment control or intervention group. Intervention participants received 8 sessions of web-based personalised physical activity advice over a 12-week intervention period and the ability to complete action plans. Change in physical activity was assessed using Actigraph accelerometers at baseline, 3-months and 9-months. Engagement with the intervention (i.e., a composite score including frequency, intensity, duration and type) was continuously assessed during the intervention period using website tracking software and database metrics. Generalised structural equation models were used to examine how a composite engagement score mediated intervention effects at 3 months and 9 months. At 3 months, mediation analysis revealed that the intervention group had significantly higher engagement scores than the control group [a-path exp(b) = 6.462, 95% CI = 5.121-7.804, p < 0.001]. Further, increased engagement with the intervention platform was associated with an increased time spent in moderate-to-vigorous physical activity [ab-coefficient exp(b) = 1.008, 95% CI = 1.004-1.014, P < 0.001]; however, the magnitude of this effect was small. There were no significant mediation effects at the 9-month time point. The findings suggest that a composite intervention engagement score has a small positive influence on physical activity changes and that other factors (e.g., behaviour change techniques) are likely to be more important drivers of behaviour change.

Improved quality of life and psychological symptoms following mindfulness and cognitive rehabilitation in multiple sclerosis and their mediating role for cognition: a randomized controlled trial

BackgroundMultiple sclerosis (MS) frequently gives rise to depressive and anxiety symptoms, but these are often undertreated. This study investigated the effect of mindfulness-based cognitive therapy (MBCT) and cognitive rehabilitation therapy (CRT) on psychological outcomes and quality of life (QoL), and whether they mediate treatment effects on MS-related cognitive problems.MethodsThis randomized controlled trial included MS patients with cognitive complaints (n = 99) and compared MBCT (n = 32) and CRT (n = 32) to enhanced treatment as usual (n = 35). Baseline, post-treatment and 6-months follow-up assessments included patient-reported outcome measures (PROMS) and cognitive outcomes (self-reported and neuropsychological assessment). PROMS concerned psychological symptoms, well-being, QoL, and daily life function. Linear mixed models indicated intervention effects on PROMS and mediation effects of PROMS on cognitive outcomes.ResultsMBCT positively affected depressive symptoms (Cohen’s d (d) = −0.46), fatigue (d = −0.39), brooding (d = −0.34), mindfulness skills (d = 0.49), and mental QoL (d = −0.73) at post-treatment. Effects on mindfulness skills remained significant 6 months later (d = 0.42). CRT positively affected depressive symptoms (d = −0.46), mindfulness skills (d = 0.37), and mental QoL (d = −0.45) at post-treatment, but not at 6-month follow-up. No effects on anxiety, well-being, self-compassion, physical QoL, and daily life function were found. Treatment effects on self-reported, but not objective, cognition were mediated by psychological symptoms and mindfulness skills.ConclusionsMBCT and CRT reduced a wide array of psychological symptoms and improved mental QoL. These improvements seemed to impact self-reported cognitive problems after both treatments, whereas objective cognitive improvements after MBCT seemed independent of improvement in psychological symptoms. Future studies should investigate long-term sustainability of these beneficial effects.Trial registrationThe trial was prospectively registered in the Dutch Trial registry on 31 May 2017 (NL6285; https://trialsearch.who.int/Trial2.aspx?TrialID=NTR6459).

Peer-Led Symptom Management Intervention to Enhance Resilience in People With Systemic Sclerosis: Mediation Analysis From a Randomized Clinical Trial.

Facilitated self-management interventions have the potential to enhance resilience and well-being. We examined whether resilience is a mediator of improving physical and psychological symptoms for people with systemic sclerosis (SSc) who participated in a 12-week online peer-led symptom management intervention. We conducted a secondary data analysis from a randomized control trial comparing a peer health-coached intervention to a waitlist control. Participants completed the Connor-Davidson Resilience Scale, the Functional Assessment of Chronic Illness Therapy-Fatigue scale, and the Patient Reported Outcomes Measurement Information System measures of pain interference and depressive symptoms at the baseline and at weeks 6 and 12. Linear mixed effect regression models were used to assess the effect of intervention on changes in resilience. Causal mediation analyses were conducted to examine whether changes in resilience at week 12 mediated intervention effects on changes in fatigue, pain interference, and depressive symptoms at week 12. One hundred and seventy-three eligible participants were enrolled. Participants in the intervention group reported improvements in resilience (P < 0.001). These changes in resilience mediated the intervention effects on fatigue with indirect effect of -1.41 (95% confidence interval [CI] -2.41 to -0.41), pain interference of -0.86 (95% CI -1.65 to -0.08), and depressive symptoms of -1.99 (95% CI -3.16 to -0.81). For participants in the intervention who had positive improvements in their physical and psychological symptoms, increased resilience was a mechanism for these improvements. These findings support the importance of addressing resilience to improve symptoms in similar SSc interventions.

The Impact of Monetary Incentives on Delay Discounting Within a Year-Long Physical Activity Intervention.

Delay discounting is the depreciation in a reward's perceived value as a function of the time until receipt. Monetary incentive programs that provide rewards contingent on meeting daily physical activity (PA) goals may change participants' delay discounting preferences. Determine if monetary incentives provided in close temporal proximity to meeting PA goals changed delay discounting, and if such changes mediated intervention effects. Inactive adults (n = 512) wore accelerometers during a 12-month intervention where they received proximal monetary incentives for meeting daily moderate-to-vigorous PA (MVPA) goals or delayed incentives for study participation. Delay discount rate and average MVPA were assessed at baseline, end of intervention, and a 24-month follow-up. Using structural equation modeling, we tested effects of proximal versus delayed rewards on delay discounting and whether any changes mediated intervention effects on MVPA. PA self-efficacy was also evaluated as a potential mediator, and both self-efficacy and delay discounting were assessed as potential moderators of intervention effects. Proximal rewards significantly increased participants' delay discounting (β = 0.238, confidence interval [CI]: -0.078, 0.380), indicating greater sensitivity to reinforcement timing. This change did not mediate incentive-associated increases in MVPA at the end of the 12-month intervention (β = -0.016, CI: -0.053, 0.019) or at a 24-month follow-up (β = -0.020, CI: -0.059, 0.018). Moderation effects were not found. Incentive-induced increases in delay discounting did not deleteriously impact MVPA. This finding may help assuage concerns about using monetary incentives for PA promotion, but further research regarding the consequences of changes in delay discounting is warranted.

Online behavioural interventions for children and young people with eczema: a quantitative evaluation.

Two online behavioural interventions (one website for parents/carers of children with eczema; and one for young people with eczema) have been shown in randomised controlled trials to facilitate a sustained improvement in eczema severity. To describe intervention use and examine potential mediators of intervention outcomes and contextual factors that may influence intervention delivery and outcomes. Quantitative process evaluation in UK primary care. Parents/carers and young people were recruited through primary care. Intervention use was recorded and summarised descriptively. Logistic regression explored sociodemographic and other factors associated with intervention engagement. Mediation analysis investigated whether patient enablement (ability to understand and cope with health issues), treatment use, and barriers to adherence were mediators of intervention effect. Subgroup analysis compared intervention effects among pre-specified participant subsets. A total of 340 parents/carers and 337 young people were recruited. Most parents/carers (87%, n = 148/171) and young people (91%, n = 153/168) in the intervention group viewed the core introduction by 24 weeks. At 24 weeks, users had spent approximately 20 minutes on average on the interventions. Among parents/carers, greater intervention engagement was associated with higher education levels, uncertainty about carrying out treatments, and doubts about treatment efficacy at baseline. Among young people, higher intervention use was associated with higher baseline eczema severity. Patient enablement (the ability to understand and cope with health issues) accounted for approximately 30% of the intervention effect among parents/carers and 50% among young people. This study demonstrated that positive intervention outcomes depended on a modest time commitment from users. This provides further support that the wider implementation of Eczema Care Online is justified.

Effect of modernized collaborative care for depression on brain-derived neurotrophic factor (BDNF) and depressive symptom clusters: Data from the eIMPACT trial

Brain-derived neurotrophic factor (BDNF) levels are lower in people with depression and are normalized following pharmacological treatment. However, it is unknown if psychological treatments for depression improve BDNF and if change in BDNF is a mediator of intervention effects on depressive symptoms. Therefore, using data from the eIMPACT trial, we sought to determine the effect of modernized collaborative care for depression on 12-month changes in BDNF and cognitive/affective and somatic depressive symptom clusters and to examine whether BDNF changes mediate intervention effects on depressive symptoms. 216 primary care patients with depression from a safety net healthcare system were randomized to 12 months of the eIMPACT intervention (internet cognitive-behavioral therapy [CBT], telephonic CBT, and select antidepressant medications) or usual primary care. Plasma BDNF was measured with commercially available kits, and depressive symptom clusters were assessed by the Patient Health Questionnaire-9. The intervention did not influence BDNF but did improve both the cognitive/affective and somatic clusters over 12 months. Changes in BDNF did not mediate the intervention effect on either cluster. Our findings suggest that modernized collaborative care is an effective treatment for both the cognitive/affective and somatic symptoms of depression and that the mechanism of action is not improvements in BDNF. Trial registrationClinicalTrials.gov Identifier: NCT02458690

How do cognitive behavioral therapy and interpersonal psychotherapy improve youth depression? Applying meta-analytic structural equation modeling to three decades of randomized trials.

Investigating the mechanisms through which psychotherapy brings about desired change can inform efforts to improve therapies. We applied meta-analytic structural equation modeling (MASEM) to assess putative change mechanisms for cognitive behavioral therapy (CBT) as mediators of youth depression treatment outcome. Then, we tested whether candidate mediators (CMs) showed evidence of treatment-specificity to CBT versus interpersonal psychotherapy (IPT). Literature searches identified 34 randomized trials (27 CBT, 6 IPT, 1 CBT/IPT, 3,868 participants, published 1982-2020) that measured seven CMs: negative cognition, social engagement, family functioning, pleasant activity engagement, problem solving, reframing, or avoidance. We assessed mediational pathways and whether posttreatment CMs mediated treatment effects on posttreatment depression symptoms, covarying pretreatment CMs, and symptoms. Treatment type was tested as a moderator of mediational pathways. Results show that negative cognition (24 trials) and pleasant activities (3 trials) mediated depression symptom outcome in CBT. Social engagement and family functioning showed stronger mediation in IPT (5 and 6 trials) than in CBT (14 and 13 trials). We conclude that negative cognition is a robust mediator of CBT but may not be treatment-specific; pleasant activities may also be a mediator of CBT. However, the lack of treatment or mediation effects involving problem solving and reframing contradicts CBT theory. In contrast, social and family mechanisms appear to be IPT-specific mediators. These conclusions are provisional due to small samples examining IPT and several CMs, limitations in CM measurement (i.e., posttreatment retrospective report), and assumptions of MASEM-and will need to be confirmed when more and better evidence accumulates. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The increase in vagally-mediated heart rate variability mediates treatment effects of exercise on global symptom severity across diagnostically heterogenous mental disorders: A secondary analysis of the ImPuls trial

BackgroundThe reduced ability to adaptively respond to stressors (coping) has been proposed as an underlying mechanism across psychopathology. It is associated with a reduced vagally-mediated heart rate variability (vmHRV) at rest and increased perceived stress. The present study investigated the increase in vmHRV and the reduction in perceived stress as potential mediators of the previously demonstrated intervention effect of exercise on global symptom severity across diagnostically heterogeneous mental disorders. MethodsSedentary outpatients with depressive disorders, anxiety disorders, insomnia and attention deficit hyperactivity disorder were randomly assigned to a 12-week standardized exercise intervention (n = 38) or passive control condition (n = 36). Baseline and post-treatment assessments included measures of global symptom severity (Symptom Checklist-90), resting vmHRV (root mean square of successive differences between normal heartbeats), and perceived stress (Perceived Stress Scale). Intention-to-treat analyses were conducted using linear mixed models and structural equations modeling. ResultsAmong the intervention group, resting vmHRV increased significantly (d = 0.87, p = .003) but perceived stress did not show a significant reduction (d = −0.32, p = .267) compared to the control group. The increase in vmHRV partially mediated the intervention effect on global symptom severity (ß = −0.05, p = .013). ConclusionThe study results provide evidence that an increase in vmHRV potentially acts as a partial mediator for the beneficial effects of exercise interventions on symptoms across individuals with mental disorders who may have a diminished ability to cope with stressors.

Cardiorenal protective effects of canagliflozin in CREDENCE according to glucose lowering

IntroductionRelationships between glycemic-lowering effects of sodium glucose co-transporter 2 inhibitors and impact on kidney and cardiovascular outcomes are uncertain.Research design and methodsWe analyzed 4395 individuals with prebaseline and postbaseline hemoglobin...

Early Family Intervention for Youth at Risk for Bipolar Disorder: Psychosocial and Neural Mediators of Outcome.

The impairing neurodevelopmental course of bipolar disorder (BD) suggests the importance of early intervention for youth in the beginning phases of the illness. We report the results of a 3-site randomized trial of family-focused therapy for youth at high-risk (FFT-HR) for BD, and explore psychosocial and neuroimaging variables as mediators of treatment effects. High-risk youth (<18 years) with major depressive disorder or other specified BD, active mood symptoms, and a family history of BD were randomly assigned to 4 months of FFT-HR (psychoeducation, communication and problem-solving skills training) or 4 months of enhanced care psychoeducation. Adjunctive pharmacotherapy was provided by study psychiatrists. Neuroimaging scans were conducted before and after psychosocial treatments in eligible participants. Independent evaluators interviewed participants every 4-6 months over 1-4 years regarding symptomatic outcomes. Among 127 youth (mean 13.2 ± 2.6 years) over a median of 98 weeks, FFT-HR was associated with longer intervals prior to new mood episodes and lower levels of suicidal ideation than enhanced care. Reductions in perceived family conflict mediated the effects of psychosocial interventions on the course of mood symptoms. Among 34 participants with pre-/post-treatment fMRI scans, youth in FFT-HR had (a) stronger resting state connectivity between ventrolateral PFC and anterior default mode network, and (b) increased activity of dorsolateral and medial PFC in emotion processing and problem-solving tasks, compared to youth in enhanced care. FFT-HR may delay new mood episodes in symptomatic youth with familial liability to BD. Putative treatment mechanisms include neural adaptations suggestive of improved emotion regulation.

0397 Efficacy of second-stage clinician-led CBTI in non-responders to digital CBTI: Is alleviation of cognitive arousal a mechanism?

Abstract Introduction Cognitive-behavioral therapy for insomnia (CBTI) is first-line treatment for insomnia, but a provider shortage limits access. eHealth technology can increase access to behavioral interventions, and digital CBTI (fully automated programs) are effective. However, &amp;gt;50% of digital CBTI patients do not remit, and non-remission is linked to undertreated cognitive arousal, a central feature of insomnia. In a randomized controlled trial, we randomized digital CBTI non-remitters to second-stage clinician-led CBTI or control. We evaluated whether second-stage CBTI effectively reduced insomnia and depression, and tested whether reductions in cognitive arousal mediated these effects. Methods 207 patients whose insomnia did not remit with digital CBTI presented to second-stage therapy. Patients were randomized to clinician-led CBTI or sleep education control via telemedicine. Study outcomes included insomnia (insomnia severity index, ISI), depression (quick inventory of depressive symptomatology self-report 16-item survey, QIDS-SR16), and three indices of cognitive arousal (pre-sleep arousal scale’s cognitive factor [PSASC], perseverative thinking questionnaire [PTQ], and daytime insomnia symptoms response scale [DISRS]). Results Before second-stage therapy, all patients reported clinically significant insomnia (ISI≥10), 13.0% reported moderate depression, and 69.5% reported high cognitive arousal. Step 2 CBTI patients, relative to Controls, reported larger decreases in ISI (-6.43±4.31 vs -2.58±4.83, t=6.05, p&amp;lt;.001, Cohen’s d=.84). At posttreatment, 56.3% of Step 2 CBTI patients remitted (ISI≤7) relative to just 16.3% of Controls (Χ2=35.77, p&amp;lt;.001, RR=3.45). CBTI patients reported larger reductions in depression relative to control, which was a small-to-medium effect (-2.63±3.11 vs -1.11, t=3.15, p=.002, Cohen’s d=.44). Contrary to hypotheses, Step 2 CBTI did not reduce cognitive arousal relative to Control as measured by the PSASC (p=.195), PTQ (p=.840), and DISRS (p=.643). Conclusion Clinician-led CBTI is effective for alleviating symptoms of insomnia and comorbid depression in insomnia patients who do not initially remit with digital CBTI. Contrary to hypotheses, reducing cognitive arousal did not mediate treatment effects. As most insomnia non-remitters present to second-stage therapy with high cognitive arousal, alternative approaches that better target cognitive arousal symptoms may represent viable second-stage therapy options for insomnia. Support (if any) This RCT (NCT03322774) was supported by NIMH R01-MH122636.

0325 Reducing nocturnal cognitive arousal and rumination mediate treatment effects of digital cognitive behavioral therapy for insomnia

Abstract Introduction High cognitive arousal—i.e., heightened cognitive activity often in the form of perseverative thinking—is a central feature insomnia. Emerging evidence from randomized controlled trials (RCTs) support alleviating cognitive arousal as a mechanism by which cognitive behavioral therapy for insomnia (CBTI) reduces symptoms of insomnia and depression. However, few RCTs have published CBTI data on cognitive arousal outcomes. The present study tested whether CBTI alleviates cognitive arousal symptoms, and whether reducing cognitive arousal symptoms mediate CBTI effects on insomnia and depression. Methods 434 patients with clinical insomnia symptoms (Insomnia Severity Index [ISI] ≥ 15) were randomized to digital CBTI or digital sleep education control. Study outcomes included insomnia (ISI), depression (quick inventory of depressive symptomatology self-report 16-item survey, QIDS-SR16), and two indices of cognitive arousal (pre-sleep arousal scale’s cognitive factor [PSASC] and daytime insomnia symptoms response scale [DISRS]). Treatment effects and mediation analyses were conducted using multivariate linear regression. Results While controlling for baseline symptoms, CBTI patients, relative to controls, reported lower levels of insomnia (b=-2.45, p&amp;lt;.001), depression (b=-1.13, p&amp;lt;.001), nocturnal cognitive arousal (b=-2.37, p&amp;lt;.001) and insomnia-focused rumination (b=-3.43, p&amp;lt;.001) after treatment. Posthoc independent samples t-tests showed that CBTI produced small-medium effects on nocturnal cognitive arousal (Cohen’s d=.40) and insomnia-focused rumination (Cohen’s d=.31). Mediation analyses showed that reducing nocturnal cognitive arousal (PSASCT2-T1) mediated 29.0% of CBTI effects on insomnia (αβ=-.709, 95%CI=-1.09, -0.38), and 35.1% of CBTI effects on depression (αβ=-.397, 95%CI=-0.65, -0.19). Mediation analyses showed that reducing insomnia-focused rumination (DISRST2-T1) mediated 10.6% of CBTI on insomnia (αβ=-.261, 95%CI=-0.50, -0.08), but did not mediate antidepressant effects (αβ=-.300, 95%CI=-1.46, 0.72). Conclusion Digital CBTI effectively alleviated nocturnal cognitive arousal and insomnia-focused rumination. Moreover, alleviating nocturnal cognitive arousal was a mechanism by which CBTI reduced symptoms of insomnia and depression. By comparison, reducing insomnia-focused rumination mediated a small proportion of CBTI effects on insomnia and was uninvolved in depression effects. Although reducing cognitive arousal facilitated insomnia and depression outcomes, CBTI is likely limited by its modest effects on cognitive arousal symptoms. Improving insomnia therapy benefits for cognitive arousal may enhance patient outcomes. Support (if any) This RCT (NCT03322774) was supported by NIMH R01-MH122636.

Relation of serum BDNF to major depression and exploration of mechanistic roles of serum BDNF in a study of vitamin D3 and omega-3 supplements for late-life depression prevention

This study: 1) examined cross-sectional and longitudinal relations of serum brain-derived neurotrophic factor (BDNF) to late-life depression (LLD); 2) tested effects of vitamin D3 and omega-3s on change in BDNF; 3) explored modifying or mediating roles of BDNF on effects of vitamin D3 and omega-3s for LLD. We selected 400 adults from a completed trial of vitamin D3 and omega-3 supplements for LLD prevention. BDNF was measured using an enzyme-linked immunosorbent assay. We administered semi-structured diagnostic interviews and Patient Health Questionnaire [PHQ]-9 to ascertain outcomes at baseline (depression caseness vs. non-caseness; PHQ-9) and at 2-year follow-up among baseline non-depressed individuals (incident vs. no incident MDD; change in PHQ-9). At baseline, while there were no significant differences in mean serum BDNF comparing depression cases and non-cases, being in the lowest vs. highest serum BDNF quartile was significantly associated with worse depressive symptoms. There were no significant longitudinal associations between serum BDNF and LLD. Neither supplement significantly affected change in BDNF; serum BDNF did not appear to modify or mediate treatment effects on LLD. In conclusion, we observed significant cross-sectional but not longitudinal associations between serum BDNF levels and LLD. Vitamin D3 or omega-3s did not alter serum BDNF over 2 years.

Potential moderators and mediators of intervention effects in a sport-based mental health literacy and resilience program for adolescent men

Engaging young men in mental health promotion initiatives is important given the negative attitudes toward mental health and increased suicide rates, reported by young men. Ahead of the Game (AOTG) is a sport-based, psychoeducational initiative which uses sports as a mental health and resilience promotional medium. This study sought contribute to the literature on the effectiveness of the AOTG program by exploring for whom, and through what mechanisms, the intervention works. A secondary analysis of the AOTG randomized controlled trial was conducted, which comprised a sample of 350 adolescent male sport-playing participants (M = 14.53 years, SD = 1.19 years) and control group of 466 sport participants (M = 14.66 years, SD = 1.39), various mental health related measures were taken at baseline and at approximately 8 weeks follow-up. Moderation analyses were conducted to examine age, socioeconomic status, and baseline measures of mental health as potential moderators of program effects. Mediation analyses were run to explore whether changes in psychological distress and wellbeing were mediated by changes in AOTG’s various primary mental health related outcomes. Results indicated age did not moderate any effects of AOTG. Meanwhile, socioeconomic status and baseline help seeking, implicit beliefs, and psychological distress all showed signs of moderating main effects of AOTG. Mediation analyses revealed that changes in resilience and implicit beliefs partially mediated changes in psychological distress. Further, increased resilience had an indirect effect of on athletes’ wellbeing. The implications and future directions, in light of these findings, are explored. Lay summary: Ahead of the Game was shown to be effective regardless of age and particularly beneficial for those in low socioeconomic, displaying low levels of help seeking, and those with higher psychological distress. Increasing resilience was also shown to be an important pathway for increasing wellbeing and reducing distress.

Reduction in avoidance mediates effects of brief behavioral therapy for pediatric anxiety and depression

Brief behavioral therapy (BBT) is an efficacious transdiagnostic intervention for pediatric anxiety and depression that targets behavioral avoidance as a key mechanism. It is unknown if change in avoidance mediates treatment effects, as theorized. Data on avoidance at baseline and Week 16 were available on 52 youth (ages 8–16 years) from a randomized controlled trial (Weersing, Jeffreys, et al., 2017) comparing BBT and assisted referral to community care (ARC). BBT had significant effects on youth-reported behavioral avoidance, and significant indirect effects on functioning and anxiety, statistically mediated through changes in youth-reported behavioral avoidance. Change in youth-reported avoidance was not a significant mediator of depression. Parent-report of avoidance was not impacted by treatment and was not a significant mediator. Overall, BBT appears to be an effective treatment for targeting behavioral avoidance, which in turn, may improve functioning and lessen anxiety. Clinical trial registration informationhttps://clinicaltrials.gov; NCT01147614.

When depressed—be mindful of and kind to yourself: Self-compassion as mediator of change in a mindful depression treatment

Objective Self-compassion as an outcome and potential mediator in mindfulness-based interventions has gained increased attention in the last years. However, most mediation studies had several methodological shortcomings which precluded robust conclusions regarding its mediating role. This randomized controlled study aimed to address these issues by assessing self-compassion, as proposed mediator and outcome, in a temporal sequence. Method Eighty-one patients with current depression and work-related conflicts were randomly assigned to either an eight-week mindfulness-based day hospital treatment (MDT-DH; n = 47; including psychopharmacological treatment if necessary) or a waitlist control condition including a psychopharmacological consultation (PCC; n = 34). The outcome, depression severity, was assessed before, at mid-treatment and after the treatment while the proposed mediator, self-compassion, was measured at two week-intervals from before treatment until directly after treatment. Within-person and between-person mediation effects were analysed using multilevel structural equation modelling. Results The results from the mediation models show that self-compassion (as a general factor) and two of its components (mindfulness of personal suffering and common humanity) increased and mediated the change in depressive symptoms over time. Conclusion This study provides preliminary support for self-compassion as a mediator of treatment effects on depression in a mindful depression treatment.

Long-term efficacy of exercise across diagnostically heterogenous mental disorders and the mediating role of affect regulation skills

BackgroundExercise interventions are efficacious in reducing disorder-specific symptoms in various mental disorders. However, little is known about long-term transdiagnostic efficacy of exercise across heterogenous mental disorders and the potential mechanisms underlying treatment effects. MethodsPhysically inactive outpatients, with depressive disorders, anxiety disorders, insomnia or attention deficit hyperactivity disorder were randomized to a standardized 12-week exercise intervention, combining moderate exercise with behavior change techniques (BCTs) (n = 38), or a passive control group (n = 36). Primary outcome was global symptom severity (Symptom Checklist-90, SCL-90-R) and secondary outcomes were self-reported exercise (Physical Activity, Exercise, and Sport Questionnaire), exercise-specific affect regulation (Physical Activity-related Health Competence Questionnaire) and depression (SCL-90-R) assessed at baseline (T1), post-treatment (T2) and one year after post-treatment (T3). Intention-to-treat analyses were conducted using linear mixed models and structural equations modeling. ResultsFrom T1 to T3, the intervention group significantly improved on global symptom severity (d = −0.43, p = .031), depression among a depressed subsample (d = −0.62, p = .014), exercise (d = 0.45, p = .011) and exercise-specific affect regulation (d = 0.44, p = .028) relative to the control group. The intervention group was more likely to reveal clinically significant changes from T1 to T3 (p = .033). Increases in exercise-specific affect regulation mediated intervention effects on global symptom severity (ß = −0.28, p = .037) and clinically significant changes (ß = −0.24, p = .042). ConclusionsThe exercise intervention showed long-term efficacy among a diagnostically heterogeneous outpatient sample and led to long-lasting exercise behavior change. Long-term increases in exercise-specific affect regulation within exercise interventions seem to be essential for long-lasting symptom reduction.