Greater Reductions In Depressive Symptoms Research Articles

Intravenous ketamine versus electroconvulsive therapy for major depressive disorder or bipolar depression: A meta-analysis of randomized controlled trials.

Intravenous (IV) ketamine has been evaluated alongside electroconvulsive therapy (ECT) in addressing major depressive disorder (MDD) or bipolar depression (BD), though the comparative outcomes remain inconclusive. This meta-analysis aimed to provide a systematic assessment of the efficacy, safety, and tolerability of IV ketamine relative to ECT for treating MDD or BD. Randomized controlled trials (RCTs) comparing IV ketamine and ECT in terms of efficacy, safety, and tolerability for MDD or BD were identified and reviewed. Three independent investigators extracted relevant data, which was synthesized using RevMan 5.3 software under a random effects model. Five RCTs encompassing 664 patients diagnosed with MDD or BD were analyzed. At 24 h post-initial treatment, IV ketamine demonstrated a statistically greater reduction in depressive symptoms compared to ECT (standardized mean difference (SMD) = -0.53; 95 % CI = -1.03 to -0.04; P = 0.04; I2 = 80 %). However, no significant differences were observed between groups in terms of the study-defined response (risk ratio (RR) = 1.49; 95 % CI = 0.08 to 28.42; P = 0.79; I2 = 0 %) at 24 h. Similarly, no notable differences were found for depressive symptom improvement (SMD = -0.48; 95 % CI = -2.41 to 1.45; P = 0.63; I2 = 99 %), the study-defined response (RR: 0.96, 95 % CI: 0.70 to 1.31; P = 0.79; I2 = 75 %) or remission (RR: 0.91, 95 % CI: 0.45 to 1.82; P = 0.78; I2 = 90 %) at the end-of-treatment visit. Among the three RCTs (60 %) comparing the neurocognitive outcomes of IV ketamine and ECT through varying test batteries, results were inconsistent. IV ketamine was associated with marked increases in dissociation, blurred vision, dizziness, and diplopia, while ECT led to a significant rise in muscle pain (all Ps < 0.05). Discontinuation rates due to any cause were comparable between both groups (P > 0.05). IV ketamine demonstrates a faster onset of antidepressant effects compared to ECT, despite both treatments yielding comparable outcomes at the end-of-treatment visit for patients with MDD or BD. However, large-scale RCTs are required to thoroughly evaluate the long-term efficacy and safety of IV ketamine relative to ECT in these populations.

Telehealth-delivered depression prevention: Short-term outcomes from a school-based randomized controlled trial.

To examine short-term (i.e., postintervention) outcomes from a randomized controlled trial comparing a school-based telehealth-delivered depression prevention program, Interpersonal Psychotherapy-Adolescent Skills Training (IPT-AST), to services as usual (SAU). We expected IPT-AST would be acceptable and feasible and that IPT-AST adolescents would experience greater reductions in depression symptoms, anxiety symptoms, and impairment compared with SAU. Adolescents (N = 242; Mage = 14.80 years, SD = 0.70; 65% female; 21% Black; 13% Hispanic/Latinx) with elevated scores on the Center for Epidemiologic Studies Depression Scale (Radloff, 1977) at screening provided data at baseline, 2-month (midpoint of IPT-AST), and 3-month (postintervention) assessments. They reported depression symptoms on the Center for Epidemiologic Studies Depression Scale, anxiety symptoms on the Screen for Child Anxiety Related Emotional Disorders (Birmaher et al., 1997), and impairment on the Columbia Impairment Scale (Bird et al., 1993). Baseline depression diagnosis was examined as a moderator. Hierarchical linear models showed that adolescents reported significant reductions in depression symptoms and impairment across conditions. IPT-AST adolescents reported significantly greater reductions in anxiety symptoms than SAU adolescents, d = .39, 95% CI [.05, .72], p = .003. Depression diagnosis moderated outcomes (ds = .33-.34, ps ≤ .05), such that IPT-AST adolescents without a diagnosis at baseline showed greater improvements in depression and anxiety symptoms than SAU adolescents. Adolescents in SAU with a depression diagnosis at baseline showed greater improvements in impairment compared with IPT-AST. Attendance and satisfaction data demonstrated the feasibility and acceptability of telehealth-delivered IPT-AST. Results support telehealth-delivered IPT-AST as a promising intervention for improving short-term outcomes among adolescents with depression symptoms but without a depression diagnosis. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Electroconvulsive Therapy Changes Immunological Markers in Patients With Major Depressive Disorder: A Scoping Review.

Major depressive disorder (MDD) is a highly prevalent and disabling condition. As such, understanding the causes of and treatment options for MDD is critical. Electroconvulsive therapy (ECT) remains the gold standard depression treatment, but the molecular mechanisms that underlie its effects are still largely unknown. One such explanation hinges on the immuno-inflammatory correlates of ECT treatment, given mounting evidence supporting the inflammatory hypothesis of depression. This review aims to provide an overview of the suggested immunomodulatory effects of ECT and the predictive value of immune biomarkers in relation to treatment outcomes and side effects. We conducted a preregistered, systematic literature search utilizing MEDLINE (PubMed), Embase (Elsevier), and PsycINFO (EBSCO) databases. We employed keywords related to MDD, ECT, gut microbiome, and the immune system. We only included human subjects research published between 1985 and January 13, 2021. Twenty-six unique studies were included in our analyses. Findings indicate a proinflammatory profile associated with MDD, with immune biomarkers exhibiting acute and chronic changes following ECT. Consistently, lower baseline interleukin 6 levels and higher C-reactive protein levels are correlated with a greater reduction in depressive symptoms following ECT. Furthermore, included studies emphasize the predictive value of peripheral immune changes, specifically interleukin 6 and tumor necrosis factor α, on cognitive outcomes following ECT. Given these results, further exploration of the potential roles of immunomodulatory effects on ECT treatment outcomes, as well as adverse cognitive side effects, is indicated.

Comparison of changes in stress coping strategies between cognitive behavioral therapy and pharmacotherapy.

Coping refers to conscious responses to negative circumstances, with the intention of ameliorating these situations. Few studies have compared the differences between psychotherapy and medication treatment for coping strategies for depression. In this study, we investigated the differences in coping strategies between cognitive behavioral therapy (CBT) combined with medication (CBT group) and medication alone (pharmacotherapy group) among outpatients with depression. A prospective observational study was conducted among 50 patients with major depression (24 and 26 in the CBT and pharmacotherapy groups, respectively). Stress coping strategies (Coping Inventory for Stressful Situations [CISS]) and depression severity (Beck Depression Inventory-Second Edition [BDI-II]) were assessed at baseline and 16 weeks later. Changes in the CISS and BDI-II scores in both groups were tested using repeated analysis of variance. Inverse probability weighting with propensity score analysis was applied to address potential selection bias. At 16 weeks, the CBT group exhibited increased CISS task-oriented coping, distraction, and social diversion scores, which differed from those of the pharmacotherapy group. The CBT group exhibited a significantly greater reduction in depressive symptoms than the pharmacotherapy group. This study was not a randomized controlled trial and thus may have selection bias. Gaining adaptive coping skills, including task-oriented coping, distraction, and social diversion skills, by combining CBT with medication may lead to greater improvement in depression symptoms. These findings suggest that clinicians should evaluate coping strategies and facilitate the acquisition of adaptive coping strategies in patients with depression to reduce their symptoms.

Efficacy and acceptability of S-adenosyl-L-methionine (SAMe) for depressed patients: a systematic review and meta-analysis of randomized controlled trials

IntroductionCurrent treatment options for depression remain unsatisfactory. SAMe, a naturally occurring body chemical available as a dietary supplement, was discovered in the 1950s. SAMe deficiency is associated with depression.ObjectivesThis systematic review and meta-analysis aimed to investigate the efficacy and acceptability of SAMe in treating patients with depression. The primary efficacy outcome was measured through the reduction in depression severity scores. All-cause dropout rates were assessed as indicators of treatment acceptability.MethodsTo include the randomized trials comparing SAMe with other agents, we conducted a search on PubMed, Embase, and the Cochrane Library from their inceptions until April 27, 2023. The quality of trials was assessed using version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). Depression severity and overall dropout rates were synthesized using a random-effect model for frequentist pairwise meta-analysis.ResultsWe categorized 23 trials (N = 2,234) into 11 trials comparing SAMe vs. placebo, 5 trials comparing SAMe + antidepressant vs. placebo + antidepressants, and 7 trials comparing SAMe vs. antidepressants. SAMe demonstrated a significantly greater reduction in depressive symptoms compared to placebo (SMD = -0.58, 95%CI [-0.93; -0.23], I2 = 68%), as can be seen in Figure 1. A trend was observed wherein SAMe showed a lesser reduction in depressive symptoms compared to antidepressants (SMD = 0.06, 95%CI [-0.06; 0.18], I2 = 49%). When administered alongside ongoing antidepressant treatment, SAMe did not significantly differ from placebo in reducing depressive symptoms (SMD = -0.16, 95%CI [-0.44; 0.13], I2 = 57%). In the subgroup analysis of 11 trials comparing SAMe and placebo, it was found that while the intramuscular (SMD = -0.92, 95%CI [-1.39; -0.44]) and oral routes (SMD = -0.66, 95%CI [-1.24; -0.08]) revealed the efficacy of SAMe, the intravenous route did not exhibit the same efficacy (SMD = -0.16, 95%CI [-0.47; 0.14]). The efficacy of SAMe was not influenced by factors such as physical illness, history of antidepressant nonresponse, proportion of females, age, duration and dosage of SAMe supplementation, publication year, and baseline depression severity. There was no significant difference in dropout rates between SAMe and controls.Image:ConclusionsLimited evidence suggests that SAMe is well accepted and effective in reducing depressive symptoms. However, its antidepressant effect may not be as strong as that of traditional antidepressants. Randomized-controlled trials comparing SAMe to antidepressants in depressed patients, both with and without ongoing antidepressant use, are still necessary.Disclosure of InterestNone Declared

Sex differences in response to cognitive behavioural therapy for insomnia: A chart review of 455 patients with chronic insomnia

BackgroundInsomnia is more prevalent in females, however studies examining sex differences in response to insomnia treatment are scarce. This study assessed sex-specific differences in cognitive behavioural therapy for insomnia (CBT-I)-related changes in insomnia symptoms in a large clinical cohort. MethodsA chart review was conducted of a clinical cohort (females n = 305, males n = 150) referred to a sleep clinic. Participants had a registered psychologist confirm diagnosis of chronic insomnia according to DSM-IV/V criteria and a Level 1 or 2 sleep study. Daily sleep diaries and questionnaires including the Insomnia Severity Index (ISI), Flinders Fatigue Scale (FFS), the Daytime Feelings and Functioning Scale (DFFS), and the Depression, Anxiety and Stress Scale-21 items (DASS), were administered at baseline, post-treatment, and three-month follow-up. Linear mixed models determined interactions between sex and timepoint on symptoms. ResultsMean (SD) age was 51.7 yrs (15.7, range = 18-90 yrs), and mean BMI was 26.3 kg/m2 (4.9), neither of which differed by sex. At pre-treatment, females demonstrated higher objective total sleep time (min) [343.5 (97.6) vs 323.8 min (92.1), p = 0.044], ISI [19.7 (4.2) vs 18.6 (4.4), p = 0.033], and FFS scores [19.2 (6.0) vs 16.9 (7.2), p = 0.003]. Compared to males, females experienced a greater reduction in FFS and DFFS scores and DASS depressive symptoms (p for interaction: 0.017, 0.043, 0.016 respectively) from baseline to follow-up. The greater reduction in depressive symptoms did not persist after controlling for age, BMI, and sleep apnea severity. Subjective total sleep time similarly increased across treatment for both males [baseline: 335.7 (15.1), post: 357.9 (15.5)] and females [baseline: 318.3 (10.4), post: 354.4 (10.7)], p for interaction: 0.22. ConclusionFemales and males experience similar, substantial benefits from CBT-I after accounting for comorbidities, suggesting the same treatment can resolve insomnia in both sexes.

A WHO digital intervention to address depression among young Chinese adults: a type 1 effectiveness-implementation randomized controlled trial

Common mental disorders among young people are rising globally. Current university-based interventions are inadequate to address the need for evidence-based interventions. We investigated the effectiveness and implementation of Step-by-Step (SbS), a WHO digital intervention to address depression, among Chinese university students with depressive symptoms. In this paper, we report a type 1 hybrid effectiveness-implementation randomized controlled trial conducted between September 2021 and September 2022. The control condition was enhanced treatment as usual (ETAU, psychoeducation). The primary outcome was improvement in depression symptoms. Secondary outcomes were improvements in psychological well-being, anxiety symptoms, and self-identified psychosocial problems. Effectiveness of the intervention was evaluated using generalized linear mixed models. Implementation outcomes were evaluated by thematic analysis of participant interviews. A total of 371 participants were enrolled to two treatment conditions in a 1:1 ratio. SbS resulted in a greater reduction in depressive symptoms at posttreatment (p = 0.004, Hedges’ g = 0.35), but no significant difference between SbS and ETAU was observed at three-month follow-up (p = 0.179, Hedges’ g = 0.16). The treatment effect was larger among those who adhered to the treatment (Hedges’ gs = 0.59 and 0.30). Subjective well-being also improved for SbS at both time points (Hedges’ gs = 0.31 and 0.30). In addition, SbS resulted in more improvement in anxiety symptoms at posttreatment (p = 0.029, Hedges’ g = 0.26), but not at three-month follow-up (p = 0.265, Hedges’ g = 0.13). The qualitative results demonstrated that the intervention was well-implemented as a self-help mental health service, with minimal support from peer supporters. In conclusion, Step-by-Step, a digital intervention developed by WHO, was effective in reducing depressive symptoms in the short term and improving psychological well-being in a longer term. The sustained effect on depression needs further investigation. Improving uptake and engagement in the program is needed for its scale-up implementation as a university-based mental health service for Chinese young adults. Trial registration: ChiCTR2100050214.

Comparable Efficacy of Repeated Transcranial Direct Current Stimulation, Cognitive Behavioral Therapy, and Their Combination in Improvement of Cold and Hot Cognitive Functions and Amelioration of Depressive Symptoms.

This study aimed to evaluate the effectiveness of repeated transcranial direct current stimulation (rtDCS), cognitive behavioral therapy (CBT), and their combination (rtDCS-CBT) in the treatment of cognitive dysfunction, social cognition, and depressive symptoms in women diagnosed with major depressive disorder (MDD). A total of 40 female participants with MDD were randomly assigned to one of four groups: rtDCS, CBT, rtDCS-CBT, and a control group. The participants' depressive symptoms, executive functions, and social cognition were assessed at baseline, preintervention, postintervention, and during a 1-month follow-up. The rtDCS group received 10 sessions of anodal dorsolateral and cathodal ventromedial prefrontal cortex (2 mA for 20 minutes). The CBT group received 10 sessions of traditional CBT, whereas the combined group received CBT after the tDCS sessions. The results of the analysis of variance indicated that all intervention groups demonstrated significant improvements in depressive symptoms, cognitive dysfunction, and social cognition compared with the control group (all p < 0.001). Furthermore, the rtDCS-CBT group exhibited significantly greater reductions in depressive symptoms when compared with each intervention alone (all p < 0.001). Notably, working memory improvements were observed only in the rtDCS group ( p < 0.001). In conclusion, this study suggests that both CBT and tDCS, either individually or in combination, have a positive therapeutic impact on enhancing executive functions, theory of mind, and depressive symptoms in women with MDD.

Reduced reward responsiveness and depression vulnerability: Consideration of social contexts and implications for intervention.

Depression is a prevalent, heterogeneous, and debilitating disorder that often emerges in adolescence, and there is a need to better understand vulnerability processes to inform more targeted intervention efforts. Psychophysiological methods, like event-related potentials (ERPs), can offer unique insights into the cognitive and emotional processes underlying depression vulnerability. I review my and others' research examining ERP measures of reward responsiveness in youth depression and present a conceptual model of the development of low reward responsiveness, its role in depression vulnerability, and potential windows for targeted intervention. There is evidence that ablunted reward positivity (RewP) is observable in children at risk for depression, appears to be shaped in part by early social experiences, and predicts later depressive symptoms in combination with other risk factors like stress exposure. Further, a component consistent with RewP is reliably elicited in response to social acceptance feedback in computerized peer interaction tasks and demonstrates unique associations with social contextual factors and depressive symptoms, supporting the utility of developing psychophysiological tasks that may better capture youths' real-world experiences and social risk processes. In addition, I address the translational implications of clinical psychophysiological research and describe a series of studies showing that a reduced RewP predicts greater reductions in depressive symptoms with treatment but is not modifiable by current treatments like cognitive behavioral therapy. Finally, I describe our preliminary efforts to develop a positive emotion-focused intervention for the offspring of depressed mothers, informed by the RewP literature, and describe future directions for translating psychophysiological research to intervention and prevention.

Assessing the Scalability of a Community-Based Self-Management Intervention for Older Adults with Diabetes and other Chronic Conditions – The Aging, Community and Health Research Unit Community Partnership Program (ACHRU-CPP)

Background: A multi-pronged approach was undertaken to assess the scalability of the Aging, Community and Health Research Unit – Community Partnership Program (ACHRU-CPP), a complex, integrated 6-month self-management program for community-living older adults with diabetes and multimorbidity and their caregivers, in two Canadian provinces. The ACHRU-CPP was co-designed by patients, caregivers, home and community-care providers, and researchers, in response to a gap identified by older adults in the self-management of their diabetes and other conditions. The intervention was tested in a feasibility study and an earlier pragmatic trial found that older adults who received the ACHRU-CPP experienced greater improvements in quality of life and self-management, and greater reduction in depressive symptoms, compared to those who received usual diabetes care, at no additional cost to society. Delivered by a collaborative team of primary care providers (registered nurses, registered dietitians) and a community program coordinator, key components include home visits, group wellness sessions, team-based case conferences, caregiver support, interprofessional collaboration, and nurse-led care coordination. Scalability assessment is an integral phase of the current research program, which evaluated the effectiveness and implementation of the ACHRU-CPP in four settings in Ontario (ON) and Prince Edward Island (PEI).&#x0D; Methods: Multiple methods were used to assess scalability of the ACHRU-CPP in ON and PEI: an environmental scan, individual key informant interviews, and qualitative and quantitative data from both the foundational studies and the current trial of ACHRU-CPP implementation and effectiveness. The Intervention Scalability Assessment Tool (ISAT) guided data collection and analysis. The environmental scan was conducted with strategic input from Scalability Working Groups in ON and PEI. These groups were comprised of members of the program’s governance structure, including patient and public research partners, researchers, primary care and community service providers and administrators, and policy- and decision-makers. These partners advised on relevant research and policy documents, identified potential key informants (i.e., policy- and decision-makers at the local, provincial, and national levels), and will participate in scalability assessment workshops in ON and PEI in late 2022, to finalize the scalability assessment, and identify components of the intervention to be strengthened, and barriers to be addressed to enhance the scalability of the program, in each province.&#x0D; &#x0D; Results: To date, the results of the scalability assessment have identified areas of strength and limitations within the program, most notably issues with health human resources, mixed results regarding the effectiveness of the program, and other resource gaps.&#x0D; Conclusion: This study has evaluated the scalability of a community-based program for older adults with diabetes and multiple chronic conditions that integrates primary and community care. It also provides valuable insight on the usefulness and feasibility of the ISAT for assessing scalability, as well as strategies to engage strategic practice, policy, and public partners in the process. &#x0D; Next steps: While scale-up of the ACHRU-CPP may be merited due to the prevalence of diabetes and multimorbidity among older adults, and alignment of this program with health policy, several barriers need to be addressed before scale-up can be recommended.&#x0D;

Examining a Fully Automated Mobile-Based Behavioral Activation Intervention in Depression: Randomized Controlled Trial.

Despite significant progress in our understanding of depression, prevalence rates have substantially increased in recent years. Thus, there is an imperative need for more cost-effective and scalable mental health treatment options, including digital interventions that minimize therapist burden. This study focuses on a fully automated digital implementation of behavioral activation (BA)-a core behavioral component of cognitive behavioral therapy for depression. We examine the efficacy of a 1-month fully automated SMS text message-based BA intervention for reducing depressive symptoms and anhedonia. To this end, adults reporting at least moderate current depressive symptoms (8-item Patient Health Questionnaire score ≥10) were recruited online across the United States and randomized to one of three conditions: enjoyable activities (ie, BA), healthy activities (ie, an active control condition), and passive control (ie, no contact). Participants randomized to enjoyable and healthy activities received daily SMS text messages prompting them to complete 2 activities per day; participants also provided a daily report on the number and enjoyment of activities completed the prior day. A total of 126 adults (mean age 32.46, SD 7.41 years) with current moderate depressive symptoms (mean score 16.53, SD 3.90) were recruited. Participants in the enjoyable activities condition (BA; n=39) experienced significantly greater reductions in depressive symptoms compared to participants in the passive condition (n=46). Participants in both active conditions-enjoyable activities and healthy activities (n=41)-reported reduced symptoms of anxiety compared to those in the control condition. These findings provide preliminary evidence regarding the efficacy of a fully automated digital BA intervention for depression and anxiety symptoms. Moreover, reminders to complete healthy activities may be a promising intervention for reducing anxiety symptoms.

Home-administered transcranial direct current stimulation with asynchronous remote supervision in the treatment of depression: feasibility, tolerability, and clinical effectiveness.

Depression is an often chronic condition, characterized by wide-ranging physical, cognitive and psychosocial symptoms that can lead to disability, premature mortality or suicide. It affects 350 million people globally, yet up to 30% do not respond to traditional treatment, creating an urgent need for novel non-pharmacological treatments. This open-label naturalistic study assesses the practical feasibility, tolerability, and clinical effectiveness of home-administered transcranial direct current stimulation (tDCS) with asynchronous remote supervision, in the treatment of depression. Over the course of 3 weeks, 40 patients with depression received psychotherapy and half of this group also received daily bi-frontal tDCS stimulation of the dorsolateral prefrontal cortex. These patients received tDCS for 30 min per session with the anode placed over F3 and the cathode over F4, at an intensity of 2 mA for 21 consecutive days. We measured patients' level of depression symptoms at four time points using the Beck Depression Inventory, before treatment and at 1-week intervals throughout the treatment period. We monitored practical feasibility such as daily protocol compliance and tolerability including side effects, with the PlatoScience cloud-based remote supervision platform. Of the 20 patients in the tDCS group, 90% were able to comply with the protocol by not missing more than three of their assigned sessions, and none dropped out of the study. No serious adverse events were reported, with only 14 instances of mild to moderate side effects and two instances of scalp pain rated as severe, out of a total of 420 stimulation sessions. Patients in the tDCS group showed a significantly greater reduction in depression symptoms after 3 weeks of treatment, compared to the treatment as usual (TAU) group [t(57.2) = 2.268, p = 0.027]. The tDCS group also showed greater treatment response (50%) and depression remission rates (75%) compared to the TAU group (5 and 30%, respectively). These findings provide a possible indication of the clinical effectiveness of home-administered tDCS for the treatment of depression, and its feasibility and tolerability in combination with asynchronous supervision.

24 Mindfulness-based cognitive therapy enhances executive control in recurrent depression in a randomized wait-list controlled trial

Objective:Adults with recurrent depression have been shown to have cognitive deficits also while in remission. Thus, it has been suggested that with a chronic course of depression, poorer executive control can be a vulnerability factor for depressive relapse. This has led to research on how cognitive remediation training can protect against recurrent depressive episodes. Findings indicate that such training has short term effects on cognitive functioning, and small effect on depression symptoms. Less focus has been on how “standard” psychotherapy can have positive effects on executive and attentional control. Mindfulness-based cognitive therapy (MBCT) has been shown to be as effective as antidepressant medication in preventing relapses of depressive episodes. Mindfulness training in healthy samples seems to improve executive and attentional control. However, the few studies of MBCT in recurrent depression show mixed effects on executive and attentional control. As far as we know, no prior study has investigated the effect of MBCT in recurrent depression with the revised version of the attention network test (ANT-R). In a randomized controlled trial, we expected that the MBCT group would show enhanced executive control and lower levels of attentional fluctuations than the wait-list controls (WLC) from pre (T0) to post (T1) treatment. We further investigated if positive effects of MBCT on executive and attentional control were associated with reduction in depression symptoms.Participants and Methods:Adults with recurrent depression in partial or full remission (N = 64) were randomized to MBCT or WLC. In the MBCT and WLC groups, 25 and 29, respectively, performed the ANT-R at T0 and T1. The attention network reaction time scores of executive control, alerting, and orienting were calculated in addition to attention fluctuations scores of intra-individual reaction time variability (IIVRT) and exgaussian-mean of longer reaction times (TAU). Self-reported depression symptoms were measured with BDI-II. The two groups were compared at baseline on full-scale IQ (WASI), executive control (D-KEFS Stroop), and processing speed (D-KEFS TMT).Results:The MBCT and WCL groups did not differ significantly in age or gender distribution, education, full-scale IQ or in baseline executive and attentional control as measured with the ANT-R, Stroop and TMT. The MBCT group showed a higher efficiency in conflict detection as measured with the executive control score from T0 to T1 compared to the WLC. This positive effect of MBCT on executive control was independent from the greater reductions in depression symptoms in the MBCT group compared to in the WLCs. However, reduction in depression symptoms at T1 was associated with enhanced efficiency in responding to alerting cues in conflict detection. No effects of MBCT compared to WLC were found at T1 on the attention fluctuation measures (IIVRT and TAU).Conclusions:The findings from the current study indicates that MBCT enhances executive control in adults with recurrent depression. As such, MBCT may target an important cognitive vulnerability factor in the chronic course of recurrent depression that may contribute to its efficacy in preventing depressive relapses. It was also observed that reductions in depression symptoms led to higher alertness in conflict detection.

Evaluating a Peer-Support Mobile App for Mental Health and Substance Use Among Adolescents Over 12 Months During the COVID-19 Pandemic: Randomized Controlled Trial.

Although it is well known that adolescents frequently turn to their friends for support around mental health and substance use problems, there are currently no evidence-based digital programs to support them to do this. The aim of this study was to evaluate the efficacy of the Mind your Mate program, a digital peer-support program, in improving mental health symptoms, reducing the uptake of substance use, and increasing help seeking. The Mind your Mate program consists of a 40-minute web-based classroom lesson and a companion smartphone mobile app. The active control group received school-based health education as usual. A cluster randomized controlled trial was conducted with 12 secondary schools and 166 students (mean age 15.3, SD 0.41 years; 72/166, 43.4% female; and 133/166, 80.1% born in Australia). Participants completed self-reported questionnaires assessing symptoms of mental health (depression, anxiety, and psychological distress), substance use (alcohol and other drug use), and help-seeking measures at baseline and at 6-month and 12-month follow-ups. Students who received the Mind your Mate program had greater reductions in depressive symptoms over a 12-month period than controls (b=-1.86, 95% CI -3.73 to 0.02; Cohen d=-0.31). Anxiety symptoms decreased among students in the intervention group; however, these reductions did not meet statistical significance thresholds. No differences were observed in relation to psychological distress or help-seeking. Small to moderate reductions in depression symptoms were observed among students allocated to receive the Mind your Mate intervention. Although the current results are encouraging, there is a need to continue to refine, develop, and evaluate innovative applied approaches for the prevention of mental disorders in real-world settings. Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12620000753954; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12620000753954. RR2-10.2196/26796.

Connecting Through Caregiving: Reappraising Intergeneration Relationship in Dementia Caregiving

PurposeDementia caregiving presents a challenge in life transition wherein the adult child is caring for his or her parents. The study examined the effects of a telephone-administered perspective-taking intervention for adult child caregivers of persons with Alzheimer’s Disease and Dementia to reduce levels of depressive symptoms as well as presence and reaction to behavioral problems and also to enhance social support. The mediation effect of perspective-taking on depressive symptoms was also examined.MethodA two-arm cluster randomized controlled trial was conducted for 176 participants with 24 clusters for the 12-week Connecting Through Caregiving (CTC) intervention and Basic Skill Training (BSB). The CTC intervention integrated perspective taking with basic skill training. The primary outcome was depressive symptoms. The first secondary outcome was the presence and reaction to behavioral problems in the care-recipients. The second secondary outcome was social support. The trial also examined whether intervention effects were mediated by perspective-taking. Measures were obtained at baseline Week 1 (pre-intervention), Week 12 (post-intervention) and Week 24 (three-month follow up).ResultsData was collected from 2018 to 2021. Ninety-one participants completed the intervention for CTC and eighty-five completed BSB. In terms of the primary outcome, as compared to the BSB group, the CTC group reported significantly greater reductions in depressive symptoms. For the secondary outcomes, the CTC group also reported reduced perceived presence and reaction to behavioral and memory problems of the care recipient as well as increased social support. Perspective-taking was found to mediate between intervention and reduction of depressive symptoms of the caregiver. No moderation effect on the intervention was found for the presence of COVID-19.ConclusionThe results provided support for the efficacy of the CTC telephone intervention. Findings have implications for enhancing sustainable care for non-digitalized older adults in the wider society.Trial RegistrationClinicalTrial.gov NCT03030027

Stress system concordance as a predictor of longitudinal patterns of resilience in adolescence.

Resilience promotes positive adaptation to challenges and may facilitate recovery for adolescents experiencing psychopathology. This work examined concordance across the experience, expression, and physiological response to stress as a protective factor that may predict longitudinal patterns of psychopathology and well-being that mark resilience. Adolescents aged 14-17 at recruitment (oversampled for histories of non-suicidal self-injury; NSSI) were part of a three-wave (T1, T2, T3) longitudinal study. Multi-trajectory modeling produced four distinct profiles of stress experience, expression, and physiology at T1 (High-High-High, Low-Low-Low, High-Low-Moderate, and High-High-Low, respectively). Linear mixed-effect regressions modeled whether the profiles predicted depressive symptoms, suicide ideation, NSSI engagement, positive affect, satisfaction with life, and self-worth over time. Broadly, concordant stress response profiles (Low-Low-Low, High-High-High) were associated with resilient-like patterns of psychopathology and well-being over time. Adolescents with a concordant High-High-High stress response profile showed a trend of greater reduction in depressive symptoms (B = 0.71, p = 0.052), as well as increased global self-worth (B = -0.88, p = 0.055), from T2 to T3 compared to the discordant High-High-Low profile. Concordance across multi-level stress responses may be protective and promote future resilience, whereas blunted physiological responses in the presence of high perceived and expressed stress may indicate poorer outcomes over time.

The effects of ketamine on symptoms of depression and anxiety in real-world care settings: A retrospective controlled analysis

IntroductionKetamine intravenous therapy (KIT) appears effective for treating depression in controlled trials testing a short series of infusions. A rapidly proliferating number of clinics offer KIT for depression and anxiety, using protocols without a strong evidence basis. Controlled comparison of mood and anxiety from real-world KIT clinics, and the stability of outcomes, is lacking. MethodsWe performed a retrospective controlled analysis on patients treated with KIT in ten community clinics across the US, between 08/2017‐03/2020. Depression and anxiety symptoms were evaluated using the Quick Inventory of Depressive Symptomatology-Self Report 16-item (QIDS) and the Generalized Anxiety Disorder 7-item (GAD-7) scales, respectively. Comparison data sets from patients who did not undergo KIT were obtained from previously published real-world studies. ResultsOf 2758 patients treated, 714 and 836 met criteria for analysis of KIT induction and maintenance outcomes, respectively. Patients exhibited significant and concordant reduction in both anxiety and depression symptoms after induction (Cohen's d = -1.17 and d = -1.56, respectively). Compared to two external datasets of KIT-naive depressed patients or patients starting standard antidepressant therapy, KIT patients experienced a significantly greater reduction in depression symptoms at eight weeks (Cohen's d = -1.03 and d = -0.62 respectively). Furthermore, we identified a subpopulation of late-responders. During maintenance, up to a year post-induction, increases in symptoms were minimal. LimitationsDue to the retrospective nature of the analyses, interpreting this dataset is limited by incomplete patient information and sample attrition. ConclusionsKIT treatment elicited robust symptomatic relief that remained stable up to one year of follow-up.

Right dorsolateral prefrontal cortex volumetric reduction is associated with antidepressant effect of low-dose ketamine infusion: A randomized, double-blind, midazolam-controlled PET-MRI clinical trial

BackgroundEvidence has shown a rapid antidepressant and antisuicidal effects of low-dose ketamine infusion among patients with treatment-resistant depression (TRD) and prominent suicidal ideation (SI). The dorsolateral prefrontal cortex (DLPFC) plays a crucial role in the TRD pathomechanisms. ObjectiveWhether the structural and functional changes of the DLPFC, particularly Brodmann area 46, are associated with the antidepressant and antisuicidal effects of ketamine infusion among such patients is unknown. MethodsWe randomized 48 patients with TRD and SI into groups receiving a single infusion of 0.5 mg/kg ketamine or 0.045 mg/kg midazolam. The Hamilton Depression Rating Scale and the Montgomery–Asberg Depression Rating Scale were used to assess symptoms. Positron emission tomography (PET)–magnetic resonance imaging was conducted prior to infusion and on Day 3 postinfusion. We performed longitudinal voxel-based morphometry (VBM) analysis to evaluate the gray matter (GM) volume changes of the DLPFC. The standardized uptake value ratio (SUVr) of 18F-fluorodeoxyglucose PET images was calculated using the SUV of the cerebellum as a reference region. ResultsThe VBM analysis revealed a small but significant volumetric reduction in the right DLPFC in the ketamine group compared with that in the midazolam group. A greater reduction in depressive symptoms was associated with a smaller decrease in right DLPFC volumes (p = 0.025). However, we found no SUVr changes of the DLPFC between baseline and post-Day 3 ketamine infusion. DiscussionThe optimal modulation of the right DLPFC GM volumes may play an essential role in the antidepressant neuromechanisms of low-dose ketamine.

Considering depression as a secondary outcome in the optimization of physical activity interventions for breast cancer survivors in the PACES trial: a factorial randomized controlled trial

BackgroundDepressive symptoms result in considerable burden for breast cancer survivors. Increased physical activity may reduce these burdens but existing evidence from physical activity interventions in equivocal. Furthermore, physical activity intervention strategies may differentially impact depressive symptoms, which should be considered in designing and optimizing behavioral interventions for breast cancer survivors.MethodsThe Physical Activity for Cancer Survivors (PACES) trial enrolled 336 participants breast cancer survivors, who were 3 months to 10 years post-treatment, and insufficiently active (< 150 min of moderate-to-vigorous physical activity per week). Participants were randomly assigned to a combination of 4 intervention strategies in a full-factorial design: 1) supervised exercise sessions, 2) facility access, 3) Active Living Every Day, and 4) Fitbit self-monitoring. Depressive symptoms were assessed at baseline, mid-intervention (3 months), and post-intervention (6 months) using the Quick Inventory for Depressive Symptoms. Change in depressive symptoms were analyzed using a linear mixed-effects model.ResultsResults from the linear mixed-effects model indicated that depressive symptoms decreased significantly across the entire study sample over the 6-month intervention (F = 4.09, p = 0.044). A significant ALED x time interaction indicated participants who received the ALED intervention experienced greater reductions in depressive symptoms (F = 5.29, p = 0.022). No other intervention strategy significantly impacted depressive symptoms.ConclusionsThe ALED intervention consists of strategies (i.e., goal setting, social support) that may have a beneficial impact on depressive symptoms above and beyond the effect of increased physical activity. Our findings highlight the need to consider secondary outcomes when designing and optimizing physical activity interventions.Trial registrationClinicalTrials.gov NCT03060941. Posted February 23, 2017.

The effects of a sleep-focused smartphone application on insomnia and depressive symptoms: a randomised controlled trial and mediation analysis.

Rates of depression are increasing among adolescents. A novel way to reduce depression is by improving sleep. We evaluated whether an app-based intervention for insomnia improved sleep and depression, and whether changes in insomnia mediated changes in depression. We conducted a 2-arm single-blind randomised controlled trial at the Black Dog Institute in Australia. Adolescents 12-16 years experiencing insomnia symptoms were randomly allocated to receive Sleep Ninja, an app-delivered cognitive behavioural therapy program for insomnia, or to an active control group involving weekly text message sleep tips. Assessments took place at baseline, 6 weeks (post-intervention) and 14 weeks (post-baseline). Co-primary outcomes were symptoms of insomnia and depression at post-intervention (primary endpoint). Intent-to-treat analyses were conducted. The trial is registered with the Australian and New Zealand Clinical Trials Registry, number ACTRN12619001462178. Between October 25, 2019, and September 6, 2020, 264 participants were randomised to receive Sleep Ninja (n = 131) or to the control group (n = 133). Relative to the control group, those allocated to the intervention reported a greater reduction in insomnia symptoms at 6 weeks (95% CI: -2.96 to -0.41, d = .41) and 14 weeks (95% CI: -3.34 to -0.19, d = .39), and a greater reduction in depression symptoms at 6 weeks (95% CI: -3.46 to -0.56, d = .28) but not 14 weeks (p < 1). Change in insomnia mediated change in depression. No adverse events were reported. An app-delivered program for insomnia could be a practical, non-stigmatising and scalable way to reduce symptoms of insomnia and depression among adolescents experiencing difficulties getting enough good quality sleep.