Feasibility, Acceptability, and Preliminary Efficacy of a Smartphone App-Led Cognitive Behavioral Therapy for Depression Under Therapist Supervision: Open Trial.

BACKGROUND: Major depressive disorder affects approximately 1 in 5 adults during their lifetime and is the leading cause of disability worldwide. Yet, a minority receive adequate treatment due to person-level (eg, geographical distance to providers) and systems-level (eg, shortage of trained providers) barriers. Digital tools could improve this treatment gap by reducing the time and frequency of therapy sessions needed for effective treatment through the provision of flexible, automated support. OBJECTIVE: This study aimed to examine the feasibility, acceptability, and preliminary clinical effect of Mindset for Depression, a deployment-ready 8-week smartphone-based cognitive behavioral therapy (CBT) supported by brief teletherapy appointments with a therapist. METHODS: This 8-week, single-arm open trial tested the Mindset for Depression app when combined with 8 brief (16-25 minutes) video conferencing visits with a licensed doctoral-level CBT therapist (n=28 participants). The app offers flexible, accessible psychoeducation, CBT skills practice, and support to patients as well as clinician guidance to promote sustained engagement, monitor safety, and tailor treatment to individual patient needs. To increase accessibility and thus generalizability, all study procedures were conducted remotely. Feasibility and acceptability were assessed via attrition, patient expectations and feedback, and treatment utilization. The primary clinical outcome measure was the clinician-rated Hamilton Depression Rating Scale, administered at pretreatment, midpoint, and posttreatment. Secondary measures of functional impairment and quality of life as well as maintenance of gains (3-month follow-up) were also collected. RESULTS: Treatment credibility (week 4), expectancy (week 4), and satisfaction (week 8) were moderate to high, and attrition was low (n=2, 7%). Participants self-reported using the app or practicing (either on or off the app) the CBT skills taught in the app for a median of 50 (IQR 30-60; week 4) or 60 (IQR 30-90; week 8) minutes per week; participants accessed the app on an average 36.8 (SD 10.0) days and completed a median of 7 of 8 (IQR 6-8) steps by the week 8 assessment. The app was rated positively across domains of engagement, functionality, aesthetics, and information. Participants' depression severity scores decreased from an average Hamilton Depression Rating Scale score indicating moderate depression (mean 19.1, SD 5.0) at baseline to a week 8 mean score indicating mild depression (mean 10.8, SD 6.1; d=1.47; P<.001). Improvement was also observed for functional impairment and quality of life. Gains were maintained at 3-month follow-up. CONCLUSIONS: The results show that Mindset for Depression is a feasible and acceptable treatment option for individuals with major depressive disorder. This smartphone-led treatment holds promise to be an efficacious, scalable, and cost-effective treatment option. The next steps include testing Mindset for Depression in a fully powered randomized controlled trial and real-world clinical settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT05386329; https://clinicaltrials.gov/study/NCT05386329?term=NCT05386329.

Molecular basis underlying changes of brain entropy and functional connectivity in major depressive disorders after electroconvulsive therapy.

INTRODUCTION: Electroconvulsive therapy (ECT) is widely used for treatment-resistant depression. However, it is unclear whether/how ECT can be targeted to affect brain regions and circuits in the brain to dynamically regulate mood and cognition. METHODS: This study used brain entropy (BEN) to measure the irregular levels of brain systems in 46 major depressive disorder (MDD) patients before and after ECT treatment. Functional connectivity (FC) was further adopted to reveal changes of functional couplings. Moreover, transcriptomic and neurotransmitter receptor data were used to reveal genetic and molecular basis of the changes of BEN and functional connectivities. RESULTS: Compared to pretreatment, the BEN in the posterior cerebellar lobe (PCL) significantly decreased and FC between the PCL and the right temporal pole (TP) significantly increased in MDD patients after treatment. Moreover, we found that these changes of BEN and FC were closely associated with genes' expression profiles involved in MAPK signaling pathway, GABAergic synapse, and dopaminergic synapse and were significantly correlated with the receptor/transporter density of 5-HT, norepinephrine, glutamate, etc. CONCLUSION: These findings suggest that loops in the cerebellum and TP are crucial for ECT regulation of mood and cognition, which provides new evidence for the antidepressant effects of ECT and the potential molecular mechanism leading to cognitive impairment.

Long-term outcomes of physical activity counseling in in-patients with major depressive disorder: results from the PACINPAT randomized controlled trial.

Major depressive disorder (MDD) is an increasingly common psychiatric illness associated with a high risk of insufficient physical activity, which in turn is associated with negative mental and physical health outcomes. Theory-based, individually tailored, in-person and remote physical activity counseling has the potential to increase physical activity levels in various populations. Given this, the present study investigated the effect of such a physical activity intervention on the physical activity behavior of in-patients with MDD. This was a multi-center, two-arm randomized controlled trial including initially insufficiently physically active adult in-patients with MDD from four study sites in Switzerland. The sample consisted of 220 participants (Mage = 41 ± 12.6 years, 52% women), 113 of whom were randomized to the intervention group and 107 to the control group. The main outcome, moderate-to-vigorous physical activity (MVPA), was assessed at three time points via hip-worn accelerometer. According to accelerometer measures, there was no significant difference in minutes spent in MVPA over a 12-month intervention period when comparing the intervention with the control group (ß = -1.02, 95% CI = -10.68 to 8.64). Higher baseline physical activity significantly predicted physical activity at post and follow-up. This study showed that it is feasible to deliver an individually tailored, theory-based physical activity counseling intervention to in-patients with MDD, however yielding no significant effects on accelerometer-based MVPA levels. Further efforts are warranted to identify efficacious approaches.Trial registration: ISRCTN, ISRCTN10469580, registered on 3rd September 2018, https://www.isrctn.com/ISRCTN10469580 .

Just a gut feeling: Faecal microbiota transplant for treatment of depression - A mini-review.

BACKGROUND: The microbiota-gut-brain axis (MGBA) allows bidirectional crosstalk between the brain and gut microbiota (GM) and is believed to contribute to regulating mood/cognition/behaviour/metabolism/health and homeostasis. Manipulation of GM through faecal microbiota transplant (FMT) is a new, exciting and promising treatment for major depressive disorder (MDD). AIMS: This mini-review examines current research into GM and FMT as a therapy for depression. METHODS: Original research articles published in Medline/Cochrane Library/PubMed/EMBASE/PsycINFO databases/National Institute of Health website Clinicaltrials.gov/controlled-trials.com were searched. Full articles included in reference lists were evaluated. We summarise current data on GM and depression and discuss communication through the MGBA and the interaction of antidepressants and GM through this. We review compositions of dysbiosis in depressed cohorts, focusing on future directions in the treatment of MDD. RESULTS: Studies have demonstrated significant gut dysbiosis in depressed patients compared to healthy cohorts, with overgrowth of pro-inflammatory microbiota, reduction in anti-inflammatory species and reduced overall stability and taxonomic richness. FMT allows the introduction of healthy microbiota into the gastrointestinal tract, facilitating the restoration of eubiosis. CONCLUSION: The GM plays an integral role in human health and disease through its communication with the rest of the body via the MGBA. FMT may provide a means to transfer the healthy phenotype into the recipient and this concept in humans is attracting enormous attention as a prospective treatment for psychopathologies, such as MDD, in the future. It may be possible to manipulate the GM in a number of ways, but further research is needed to determine the exact likelihood and profiles involved in the development and amelioration of MDD in humans, as well as the long-term effects and potential risks of this procedure.

Examining the Efficacy of Extended Reality-Enhanced Behavioral Activation for Adults With Major Depressive Disorder: Randomized Controlled Trial.

BACKGROUND: Major depressive disorder (MDD) is a global concern with increasing prevalence. While many evidence-based psychotherapies (EBPs) have been identified to treat MDD, there are numerous barriers to patients accessing them. Virtual reality (VR) has been used as a treatment enhancement for a variety of mental health disorders, but few studies have examined its clinical use in treating MDD. Behavioral activation (BA) is a simple yet effective and established first-line EBP for MDD that has the potential to be easily enhanced and adapted with VR technology. A previous report by our group explored the feasibility and acceptability of VR-enhanced BA in a small clinical proof-of-concept pilot. This study examines the clinical efficacy of a more immersive extended reality (XR)-enhanced BA (XR-BA) prototype. This is the first clinical efficacy test of an XR-BA protocol. OBJECTIVE: This study examined whether XR-BA was feasible and efficacious in treating MDD in an ambulatory telemedicine clinic. METHODS: A nonblinded between-subject randomized controlled trial compared XR-BA to traditional BA delivered via telehealth. The study used a previously established, brief 3-week, 4-session BA EBP intervention. The experimental XR-BA participants were directed to use a Meta Quest 2 (Reality Labs) VR headset to engage in simulated pleasant or mastery activities and were compared to a control arm, which used only real-life mastery or pleasant activities as between-session homework. The Patient Health Questionnaire (PHQ)-9 was the primary outcome measure. Independent-sample and paired-sample t tests (2-tailed) were used to determine statistical significance and confirmed using structural equation modeling. RESULTS: Overall, 26 participants with MDD were randomized to receive either XR-BA (n=13, 50%) or traditional BA (n=13, 50%). The mean age of the 26 participants (n=6, 23% male; n=19, 73% female; n=1, 4% nonbinary or third gender) was 50.3 (SD 17.3) years. No adverse events were reported in either group, and no substantial differences in dropout rates or homework completion were observed. XR-BA was found to be statistically noninferior to traditional BA (t18.6=-0.28; P=.78). Both the XR-BA (t9=2.5; P=.04) and traditional BA (t10=2.3; P=.04) arms showed a statistically significant decrease in PHQ-9 and clinical severity from the beginning of session 1 to the beginning of session 4. There was a significant decrease in PHQ-8 to PHQ-9 scores between the phone intake and the beginning of session 1 for the XR-BA group (t11=2.6; P=.03) but not the traditional BA group (t11=1.4; P=.20). CONCLUSIONS: This study confirmed previous findings that XR-BA may be a feasible, non-inferior, and acceptable enhancement to traditional BA. Additionally, there was evidence that supports the potential of XR to enhance expectation or placebo effects. Further research is needed to examine the potential of XR to improve access, outcomes, and barriers to MDD care. TRIAL REGISTRATION: ClinicalTrials.gov NCT05525390; https://clinicaltrials.gov/study/NCT05525390.

Predictive modeling of antidepressant efficacy based on cognitive neuropsychological theory.

BACKGROUND: We aimed to develop a clinical predictive model based on the cognitive neuropsychological (CNP) theory and machine-learning to examine SSRI efficacy in the treatment of MDD. METHODS: Baseline assessments including clinical symptoms (HAMD, HAMA, BDI, and TEPS scores), negative biases (NEO-PI-R-N and NCPBQ scores), sociodemographic characteristics (social support and SES), and a 5-min eye-opening resting-state EEG were completed by 69 participants with first-episode major depressive disorder (MDD) and 36 healthy controls. The clinical symptoms and negative bias were again assessed after an 8-week treatment of depression with selective serotonin reuptake inhibitors (SSRIs). A multi-modality machine-learning model was developed to predict the effectiveness of SSRI antidepressants. RESULTS: At baseline, we observed significant differences between MDD patients and healthy controls in terms of social support, clinical symptoms, and negative bias characteristics (p < 0.001). A negative association was found (p < 0.05) between neuroticism and alpha asymmetry in both the central and central-parietal areas, as well as between negative cognitive processing bias and alpha asymmetry in the parietal region. Compared to responders, non-responders exhibited less negative cognitive processing bias and greater alpha asymmetry in both central and central-parietal regions. Importantly, we developed a multi-modality machine-learning model with 83 % specificity using the above salient features. CONCLUSIONS: Research results support the CNP theory of depression treatment. To some extent, the multimodal clinical model constructed based on the CNP theory effectively predicted the efficacy of this treatment in this population. LIMITATIONS: Small sample and only focus on the mechanisms of delayed-onset SSRI treatment.

Ventromedial prefrontal cortex activation and neurofeedback modulation during episodic future thinking for individuals with suicidal thoughts and behaviors.

Individuals experiencing suicidal thoughts and behaviors (STBs) show less specificity and positivity during episodic future thinking (EFT). Here, we present findings from two studies aiming to (1) further our understanding of how STBs may relate to neural responsivity during EFT and (2) examine the feasibility of modulating EFT-related activation using real-time fMRI neurofeedback (rtfMRI-nf). Study 1 involved 30 individuals with major depressive disorder (MDD; half with STBs) who performed an EFT task during fMRI, for which they imagined personally-relevant future positive, negative, or neutral events. Positive EFT elicited greater ventromedial prefrontal cortex (vmPFC) activation compared to negative EFT. Importantly, the MDD + STB group exhibited reduced vmPFC activation across all EFT conditions compared to MDD-STB; although EFT fluency and subjective experience remained consistent across groups. Study 2 included rtfMRI-nf focused on vmPFC modulation during positive EFT for six participants with MDD + STBs. Results support the feasibility and acceptability of the rtfMRI-nf protocol and quantitative and qualitative observations are provided to help inform future, larger studies aiming to examine similar neurofeedback protocols. Results implicate vmPFC blunting as a promising treatment target for MDD + STBs and suggest rtfMRI-nf as one potential technique to explore for enhancing vmPFC engagement.

Amygdala real-time fMRI neurofeedback upregulation in treatment resistant depression: Proof of concept and dose determination.

Previous work has shown that adults suffering from major depressive disorder (MDD) can increase their amygdala reactivity while recalling positive memories via real-time neurofeedback (rt-fMRI-nf) training, which is associated with reduction in depressive symptoms. This study investigated if this intervention could also be considered for patients suffering from MDD who do not respond to standard psychological and pharmacological interventions, i.e., treatment resistant (TR-MDD). 15 participants received 5 neurofeedback sessions. Outcome measures were depressive symptoms assessed by BDI scores up to 12 weeks following acute intervention, and amygdala activity changes from initial baseline to final transfer run during neurofeedback sessions (neurofeedback success). Participants succeeded in increasing their amygdala activity. A main effect of visit on BDI scores indicated a significant reduction in depressive symptomatology. Percent signal change in the amygdala showed a learning curve during the first session only. Neurofeedback success computed by session was significantly positive only during the second session. When examining the baseline amygdala response, baseline activity stabilized/asymptoted by session 3. This proof-of-concept study suggests that only two neurofeedback sessions are necessary to enable those patients to upregulate their amygdala activity, warranting a future RCT. Over the course of the rtfMRI-nf intervention, participants also reported reduced depressive symptomatology. Clinical trial registration number: NCT03428828 on ClinicalTrials.gov.

Lower odds of successful community discharge after medical hospitalization for Veterans with schizophrenia: A retrospective cohort study of national data.

Medical comorbidity, particularly cardiovascular diseases, contributes to high rates of hospital admission and early mortality in people with schizophrenia. The 30 days following hospital discharge represents a critical period for mitigating adverse outcomes. This study examined the odds of successful community discharge among Veterans with schizophrenia compared to those with major affective disorders and those without serious mental illness (SMI) after a heart failure hospital admission. Data for Veterans hospitalized for heart failure were obtained from the Veterans Health Administration (VHA) and Centers for Medicare & Medicaid Services between 2011 and 2019. Psychiatric diagnoses and medical comorbidities were assessed in the year prior to hospitalization. Successful community discharge was defined as remaining in the community without hospital readmission, death, or hospice for 30 days after hospital discharge. Logistic regression analyses adjusting for relevant factors were used to examine whether individuals with a schizophrenia diagnosis showed lower odds of successful community discharge versus both comparison groups. Out of 309,750 total Veterans in the sample, 7377 (2.4%) had schizophrenia or schizoaffective disorder and 32,472 (10.5%) had major affective disorders (bipolar disorder or recurrent major depressive disorder). Results from adjusted logistic regression analyses demonstrated significantly lower odds of successful community discharge for Veterans with schizophrenia compared to the non-SMI (Odds Ratio [OR]: 0.63; 95% Confidence Interval [CI]: 0.60, 0.66) and major affective disorders (OR: 0.65, 95%; CI: 0.62, 0.69) groups. Intervention efforts should target the transition from hospital to home in the subgroup of Veterans with schizophrenia.

A feasibility, randomised controlled trial of Club Connect: a group-based healthy brain ageing cognitive training program for older adults with major depression within an older people's mental health service.

BACKGROUND: Using the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework, we outline steps taken to implement an evidence-based cognitive training program, Club Connect, in older adults with major depressive disorder in an Older People's Mental Health Service in Sydney, Australia. The primary aim was to explore feasibility (or 'reach'), tolerability (or 'implementation'), and acceptability (or 'adoption'). The secondary aim was to explore the most sensitive clinical outcomes and measurement tools (i.e. 'effectiveness') to inform a formal randomised controlled trial, and to explore the healthcare resources used (i.e. costs) to assist decision-making by health care managers and policy-makers in relation to future resource allocation. METHODS: Using a single blinded feasibility design, 40 participants (mean age: 76.13 years, SD: 7.45, range: 65-95 years) were randomised to either (a) Club Connect, a 10-week group-based multifaceted program, comprising psychoeducation and computer-based cognitive training, or (b) a waitlist control group. RESULTS: Implementing group-based cognitive training within a clinical setting was feasible, well tolerated and accepted by participants. Further, cognitive training, in comparison to the waiting list control, was associated with moderate to very large effect size improvements in depression, stress and inhibition (ηp2 = 0.115-0.209). We also found moderate effect size improvements on measures of daily functioning, wellbeing and cognitive flexibility. Small effect size improvements for other cognitive and psychosocial outcomes were also observed. The average cost per person participating in in the intervention was AU$607.50. CONCLUSIONS: Our findings support the feasibility of implementing group-based cognitive training into a specialised clinical (public health) setting. This trial was registered on the Australian and New Zealand Clinical Trial Registry (ACTRN12619000195156, 12/02/2019).

The effect of the Yara smartphone application on anxiety, sleep quality, and suicidal thoughts in patients with major depressive disorder in Iran: a randomized controlled trial.

BACKGROUND: Depression is one of the most common mental disorders that leads to anxiety, sleep disturbances, and suicidal thoughts. Due to the high cost of treatment and the reluctance of many patients to seek medical help, major depressive disorder (MDD) is becoming more prevalent. Therefore, alternative methods like smartphone applications can help prevent and improve depression symptoms. The present study aimed to determine the effect of the newly developed Yara smartphone application on anxiety, sleep quality, and suicidal thoughts in patients with MDD. METHODS: This randomized controlled trial with a pretest-posttest design was conducted on Iranian patients with MDD in 2022. Sixty-four patients were recruited using convenience sampling and randomly assigned to two control and intervention groups. The intervention was conducted using the Yara smartphone application for three months. Data were collected using the Spielberger State-Trait Anxiety Inventory (STAI), Pittsburgh Sleep Quality Index (PSQI), and Beck Scale for Suicidal Ideation (BSSI). Data were first entered into IBM SPSS Statistics for Windows, version 22 (IBM Corp., Armonk, N.Y., USA) and then analyzed using descriptive and analytical statistics. RESULTS: There was no statistically significant difference in the mean score of anxiety and sleep quality between the intervention and control groups before the intervention (p ≥ .05). However, this difference in the mean score of anxiety and sleep quality was statistically significant in the two groups after the intervention (p < .05). The results showed no statistically significant difference in the mean score of suicidal thoughts between the two groups before and after the intervention (p ≥ .05). The use of the Yara smartphone application had a significant positive effect on anxiety and sleep quality in depressed patients (p < .001). At the same time, it had no significant effect on suicidal thoughts (p ≥ .05). CONCLUSION: Considering the positive effect of using the Yara smartphone application on reducing anxiety and improving sleep quality in depressed patients, this application can help alleviate the problems of depressed patients alongside existing treatment methods. Thus, this application is recommended for this group of patients in psychiatric clinics and departments. The Yara application's effectiveness was not approved on suicidal thoughts in this study so that further investigation would be necessary. TRIAL REGISTRATION: Iranian Registry of Clinical Trial approval code (IRCT# IRCT20131112015390N7).

Efficacy of transcranial photobiomodulation in the treatment for major depressive disorder: A TMS-EEG and pilot study.

BACKGROUND: Major depressive disorder (MDD) was a prevalent mental condition that may be accompanied by decreased excitability of left frontal pole (FP) and abnormal brain connections. An 820 nm tPBM can induce an increase in stimulated cortical excitability. The purpose of our study was to establish how clinical symptoms and time-varying brain network connectivity of MDD were affected by transcranial photobiomodulation (tPBM). METHODS: A total of 11 patients with MDD received 820 nm tPBM targeting the left FP for 14 consecutive days. The severity of symptoms was evaluated by neuropsychological assessments at baseline, after treatment, 4-week and 8-week follow-up; 8-min transcranial magnetic stimulation combined electroencephalography (TMS-EEG) was performed for five healthy controls and five patients with MDD before and after treatment, and time-varying EEG network was analyzed using the adaptive-directed transfer function. RESULTS: All of scales scores in the 11 patients decreased significantly after 14-day tPBM (p < .01) and remained at 8-week follow-up. The time-varying brain network analysis suggested that the brain regions with enhanced connection information outflow in MDD became gradually more similar to healthy controls after treatment. CONCLUSIONS: This study showed that tPBM of the left FP could improve symptoms of patients with MDD and normalize the abnormal network connections.

Imagery rescripting and cognitive restructuring for inpatients with moderate and severe depression - a controlled pilot study.

BACKGROUND: This controlled pilot study investigates the effect of the combined use of cognitive restructuring (CR) and imagery rescripting (IR) compared to treatment as usual among inpatients with moderate and severe depression. Alongside expert ratings and self-report tools, fitness wristbands were used as an assessment tool. METHODS: In addition to the standard inpatient care (SIC) program, 33 inpatients with moderate and severe depression were randomly assigned to an intervention group (two sessions of IR and CR) or an active treatment-as-usual (TAU) control group (two sessions of problem-solving and build-up of positive activity). Depression severity was assessed by the Hamilton Depression Rating Scale-21 (HDRS-21), the Beck Depression Inventory-II (BDI-II), and as a diagnostic adjunct daily step count via the Fitbit Charge 3™. We applied for analyses of HDRS-21 and BDI-II, 2 × 2 repeated-measures analysis of variance (ANOVA), and an asymptotic Wilcoxon test for step count. RESULTS: The main effect of time on both treatments was η2 = .402. Based on the data from the HDRS-21, patients in the intervention group achieved significantly greater improvements over time than the TAU group (η2 = .34). The BDI-II data did not demonstrate a significant interaction effect by group (η2 = .067). The daily hourly step count for participants of the intervention group was significantly higher (r = .67) than the step count for the control group. CONCLUSIONS: The findings support the utilization of imagery-based interventions for treating depression. They also provide insights into using fitness trackers as psychopathological assessment tools for depressed patients. TRIAL REGISTRATION: The trial is registered at the German Clinical Trials Register (Deutsches Register Klinischer Studien) under the registration number: DRKS00030809.

Gender Differences in Psychological Outcomes Following Surf versus Hike Therapy among U.S. Service Members.

BACKGROUND: Surf and hike therapies have demonstrated effectiveness as adjunct interventions for service members with major depressive disorder (MDD). This study explores gender differences in intervention outcomes following a pragmatic, randomized controlled trial of Surf and Hike Therapy for service members with MDD (N = 96; men, n = 46; women, n = 50). METHODS: Clinician-administered and self-report measures (depression, anxiety, positive affect, negative affect, resilience, and pain) were completed at preprogram, postprogram, and 3-month follow-up; brief measures (depression/anxiety and positive affect) were completed before and after each session. RESULTS: Multilevel modeling results showed that anxiety decreased from pre- to postprogram and significantly differed by gender (B = -2.26, p = 0.029), with women reporting greater reductions. The remaining outcomes from pre- to postprogram demonstrated significant improvements that did not differ by gender (ps = 0.218-0.733). There were no gender differences through follow-up (ps = 0.119-0.780). However, within sessions, women reported greater improvements in depression/anxiety (B = -0.93, p = 0.005) and positive affect (B = 3.73, p = 0.001). The change in positive affect scores within sessions was greater for women in Hike Therapy compared to men (p = 0.016). CONCLUSIONS: Overall, results demonstrate that both genders benefit from adjunctive Surf and Hike Therapies, but women exhibit a better response in terms of longer-term anxiety and immediate psychological outcomes.

Prevalence of suicidal ideation in German psychotherapy outpatients: A large multicenter assessment.

BACKGROUND: Suicidal ideation is a major concern in clinical practice. Yet, little is known about prevalence rates of suicidal ideation in patients undergoing outpatient psychotherapeutic treatment. Therefore, the aim of the current study is to assess the prevalence of suicidal ideation in a large sample of psychotherapy outpatients in Germany. The data analyzed in this study is taken from the KODAP-project on the coordination of data collection and analysis at German university-based research and training outpatient clinics for psychotherapy. METHODS: A total of N = 10,357 adult outpatients (64.4 % female; age: M(SD) = 35.94 (13.54), range: 18-92 years of age) starting cognitive-behavioral therapy at one of 27 outpatient clinics in Germany were included in the current study. Prevalence of suicidal ideation was assessed with the Suicide Item (Item 9) of the Beck-Depression Inventory II. RESULTS: Suicidal ideation was reported by 36.7 % (n = 3795) of the participants. Borderline Personality Disorder, Posttraumatic Stress Disorder, and recurrent Major Depression were the diagnoses most strongly associated with the presence and severity of suicidal ideation. LIMITATION: Suicide ideation was assessed only with the respective item of the Beck Depression Inventory II. CONCLUSION: Suicidal ideation is very common among adult patients who start psychotherapy in Germany. A well-founded knowledge of risk assessment in suicidal patients and suicide-specific treatment options is therefore highly relevant.

Effect of exercise for depression: systematic review and network meta-analysis of randomised controlled trials.

OBJECTIVE: To identify the optimal dose and modality of exercise for treating major depressive disorder, compared with psychotherapy, antidepressants, and control conditions. DESIGN: Systematic review and network meta-analysis. METHODS: Screening, data extraction, coding, and risk of bias assessment were performed independently and in duplicate. Bayesian arm based, multilevel network meta-analyses were performed for the primary analyses. Quality of the evidence for each arm was graded using the confidence in network meta-analysis (CINeMA) online tool. DATA SOURCES: Cochrane Library, Medline, Embase, SPORTDiscus, and PsycINFO databases. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Any randomised trial with exercise arms for participants meeting clinical cut-offs for major depression. RESULTS: 218 unique studies with a total of 495 arms and 14 170 participants were included. Compared with active controls (eg, usual care, placebo tablet), moderate reductions in depression were found for walking or jogging (n=1210, κ=51, Hedges' g -0.62, 95% credible interval -0.80 to -0.45), yoga (n=1047, κ=33, g -0.55, -0.73 to -0.36), strength training (n=643, κ=22, g -0.49, -0.69 to -0.29), mixed aerobic exercises (n=1286, κ=51, g -0.43, -0.61 to -0.24), and tai chi or qigong (n=343, κ=12, g -0.42, -0.65 to -0.21). The effects of exercise were proportional to the intensity prescribed. Strength training and yoga appeared to be the most acceptable modalities. Results appeared robust to publication bias, but only one study met the Cochrane criteria for low risk of bias. As a result, confidence in accordance with CINeMA was low for walking or jogging and very low for other treatments. CONCLUSIONS: Exercise is an effective treatment for depression, with walking or jogging, yoga, and strength training more effective than other exercises, particularly when intense. Yoga and strength training were well tolerated compared with other treatments. Exercise appeared equally effective for people with and without comorbidities and with different baseline levels of depression. To mitigate expectancy effects, future studies could aim to blind participants and staff. These forms of exercise could be considered alongside psychotherapy and antidepressants as core treatments for depression. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018118040.

Cortisol interdependence during psychotherapy in major depressive disorder.

The current study explored cortisol interdependence between patients and therapists during psychotherapy, the possible moderating effect of patient alliance ratings on this interdependence, and the associations between cortisol interdependence and treatment outcome. While cortisol interdependence was explored in other interpersonal contexts, its presence in psychotherapy has remained unexplored. We hypothesized that (a) patients' and therapists' cortisol levels at pre-session will predict their own and their partner's subsequent cortisol levels at post-session, (b) patient ratings of their relationship with their therapists will moderate these partner effects, and (c) cortisol interdependence will be associated with better treatment outcome. Fifty dyads undergoing 16 weeks of psychodynamic treatment for major depressive disorder participated in this study. Patient-therapist salivary cortisol samples were collected at eight time points, alongside a post-session patient-rated alliance questionnaire and a symptom severity interview. For analyses we employed the actor-partner interdependence model. Results revealed that (a) patients' and therapists' cortisol levels before sessions predicted their own post-session cortisol changes. However, significant cortisol interdependence was observed in patients' pre-session cortisol levels predicting therapists' post-session cortisol levels. Furthermore, (b) poorer alliance ratings associated with more pronounced cortisol interdependence, and (c) in dyads where patient pre-session cortisol predicted therapist's post-session cortisol, a better treatment outcome was found. This study found novel evidence of cortisol interdependence in psychotherapy and is partially in line with other studies inspecting cortisol interdependence in adjacent research fields. These findings emphasize the intricate psychophysiological interactions within therapeutic relationships and their associations with treatment outcome.

Cost-effectiveness of a mindful yoga intervention added to treatment as usual for young women with major depressive disorder versus treatment as usual only: Cost-effectiveness of yoga for young women with depression.

In a randomized controlled trial in the Netherlands, we studied the (cost)effectiveness of adding a mindful yoga intervention (MYI+TAU) to treatment as usual (TAU) for young women with major depressive disorder (MDD). In this paper, we present the results of the economic analyses. Societal costs and health outcomes were prospectively assessed during 15 months for all randomized participants (n = 171). Symptoms of depression (Depression Anxiety and Stress Scales; DASS) and quality adjusted life years (QALYs) were used as health outcomes in the economic analyses. Mean total societal costs during the 15 months of the study were €11.966 for the MYI+TAU group and €13.818 for the TAU group, differences in mean total societal costs were not statistically significant. Health outcomes (DASS and QALY) were slightly in favour of MYI+TAU, but differences between groups were not statistically significant. Combining costs and health outcomes in cost-effectiveness analyses indicated that MYI+TAU is likely to be cost-effective compared to TAU which was confirmed by sensitivity analyses. Although there were limitations in the cost-effectiveness analysis, findings from this study suggest that MYI+TAU warrants future attention for the potential to be cost-effective compared to TAU for young women with MDD.

Evaluation of the internet-based intervention "Selfapy" in participants with unipolar depression and the impact on quality of life: a randomized, parallel group study.

PURPOSE: Depressive disorders cause a major burden of disease worldwide and often lead to a loss of social functioning. Patients suffering from depressive disorders report a lower quality of life (QOL) than people without a history of mental health issues. Internet-based interventions (IBIs) based on cognitive behavioral therapy (CBT) are effective in reducing symptom severity but data on their impact on quality of life in clinically depressed patients so far is scarce. METHODS: Selfapy is a CBT-based IBI for depressive disorders. 401 participants (332 female, mean age 37 (SD = 11) with a diagnosis of major depressive disorder (MDD) or dysthymia were enrolled in a randomized, parallel, three-arm trial comparing a therapist-guided Selfapy intervention with an unguided Selfapy intervention and a waiting list control. QOL was measured using the WHOQOL-BREF at baseline, post-treatment (12 weeks) and at 24-week follow-up. The effects of the interventions on QOL were calculated using linear mixed effects models. RESULTS: At post-treatment (12 weeks) the guided and unguided intervention groups reported an increase in QOL on physical and psychological health domains compared to controls (significant group*time interaction). The gain in QOL was maintained over the follow-up period only for psychological health. QOL decreased in the social relationships and environment domains over the course of treatment and during the follow-up treatment for all participants. There were no differences between the guided and the unguided intervention. CONCLUSION: Selfapy proved to positively affect psychological and physical QOL in a sample of participants suffering from depressive disorders and can therefore be considered an effective and highly scalable therapeutic tool. The pattern of results might partly be attributable to effects of the COVID-19 pandemic and public health measures that coincided with the trial. TRIAL REGISTRATION: German Clinical Trials Register (DRKS): DRKS00017191. Registered June 14th, 2019, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00017191 .

Impact of comorbid opioid use disorder and major depressive disorder on healthcare utilization outcomes in patients with peripheral artery disease: A National Readmission Database analysis.

BACKGROUND: Prior research has demonstrated that individuals with peripheral artery disease (PAD) often have comorbid opioid use disorder (OUD) and major depressive disorder (MDD), with limited data regarding their impact on readmission outcomes, length of stay, and cost. This study aimed to investigate these healthcare utilization outcomes in patients with PAD who have comorbid OUD and MDD. METHODS: Data were obtained from the National Readmission Database from 2011 through 2018. The study population included all hospitalizations with PAD as the primary or secondary diagnosis, from which hospitalizations with OUD and MDD were extracted using appropriate ICD-9/10 diagnosis codes. Primary outcomes were 30-day and 90-day readmission, total cost, and total length of stay within the calendar year. We created hierarchical multivariable logistic regression models examining OUD with and without MDD, with a random effect for healthcare facility location. RESULTS: From 2011 to 2018, 13,265,817 weighted admissions with PAD were identified. These admissions were segmented into four categories: No OUD/No MDD (12,056,466), OUD/No MDD (323,762), No OUD/MDD (867,641), and OUD/MDD (17,948). The group with No OUD/No MDD was used as the reference group for all subsequent comparisons. Regarding 30-day and 90-day readmissions, patients with OUD/MDD had odds of 1.14 (95% CI 1.10, 1.18) and 1.09 (95% CI 1.06, 1.13), respectively. Patients with OUD/No MDD bore the highest median cost of $64,354 (IQR $30,797-137,074), and patients with OUD/MDD marked the lengthiest median stay of 6.01 days (IQR 2.01-13.30). CONCLUSION: This study found a significant association between these comorbidities and outcomes and therefore calls for targeted interventions and pain management strategies.