Forget me not: The effect of doxycycline on human declarative memory.

Investigations into neuroprotective drugs are in high demand for the treatment of neurodegenerative diseases, such as multiple sclerosis or Alzheimer's disease, but also psychiatric disorders, such as depression, trauma, and substance use. One potential drug class being investigated are tetracyclines impacting on a variety of neuroprotective mechanisms. At the same time, tetracyclines like doxycycline have been suggested to affect human fear and spatial memory as well as reducing declarative memory retention. Based on the assumed necessity for synaptic consolidation in hippocampus-dependent learning, we hypothesised declarative memory may be similarly impaired by doxycycline as fear and spatial memory. Therefore, in this study we investigate the potential diminishing effects of doxycycline on consolidation of declarative memory in healthy humans. Additionally, to test for effect specificity we assessed motor memory, sustained attention, and processing speed. We administered a neuropsychological test battery in three independent randomized placebo-controlled double-blind trials (RCTs), in which healthy young volunteers (total N = 252) either received a single oral dose doxycycline (200 mg, n = 126) or placebo (n = 126) in a between-subject design. We found no evidence for a detrimental effect of doxycycline on declarative memory; instead, doxycycline improved declarative learning (p-value=0.022, Cohen's d=0.15) and memory consolidation (p=0.040, d=0.26). Contrarily, doxycycline slightly reduced motor learning (p=0.001, d=0.10) but subtly strengthened long-term motor memory (p=0.001, d=0.10). These results suggest that doxycycline can improve declarative learning and memory without having long term negative effects on other cognitive domains in healthy humans. Our results give hope to further investigate doxycycline in neuroprotective treatment applications.

Combined Effects of Nasal Ketamine and Trauma-Focused Psychotherapy in Treatment-Resistant Post-Traumatic Stress Disorder: A Pilot Case Series.

OBJECTIVE: This pilot case series investigated the feasibility and efficacy of an eight-week therapy program, combining nasally administered ketamine (0.5 mg/kg) with trauma-focused psychotherapy, for individuals with chronic, treatment-resistant post-traumatic stress disorder (PTSD). METHOD: Three patients with chronic, treatment-resistant PTSD underwent the eight-week therapy program. Clinical assessments included the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and the Hamilton Depression Rating Scale (HAMD) at baseline, post-assessment, and follow-up assessment, along with additional measures assessing other relevant symptoms and side effects. RESULTS: The results demonstrated clinically relevant reductions in PTSD symptoms, indicated by a change in the CAPS-5 score at post-assessment (M = -18.00; SE = 6.48) and follow-up assessment (M = -25.33, SE = 5.58). Additionally, depressive symptoms showed notable improvement, with changes in HAMD scores at post-assessment (M = -8.33, SE = 3.07) and follow-up assessment (M = -9.00, SE = 3.77). Positive effects were also observed in anxiety reduction, decreased dissociations, and improvements in emotion regulation and disturbances of self-organization. CONCLUSIONS: Despite potential variations in clinical profiles among the patients, the therapy program demonstrated positive outcomes for all participants. Nasally administered ketamine was well tolerated and resulted in immediate symptom reduction in tension, anxiety, and common PTSD symptoms. However, to validate these findings and compare treatment efficacy, future randomized controlled trials are warranted, especially in comparison with trauma-focused therapy alone.

Network analyses of ecological momentary emotion and avoidance assessments before and after cognitive behavioral therapy for anxiety disorders.

Negative emotions and associated avoidance behaviors are core symptoms of anxiety. Current treatments aim to resolve dysfunctional coupling between them. However, precise interactions between emotions and avoidance in patients' everyday lives and changes from pre- to post-treatment remain unclear. We analyzed data from a randomized controlled trial where patients with anxiety disorders underwent 16 sessions of cognitive behavioral therapy (CBT). Fifty-six patients (68 % female, age: M = 33.31, SD = 12.45) completed ecological momentary assessments five times a day on 14 consecutive days before and after treatment, rating negative emotions and avoidance behaviors experienced within the past 30 min. We computed multilevel vector autoregressive models to investigate contemporaneous and time-lagged associations between anxiety, depression, anger, and avoidance behaviors within patients, separately at pre- and post-treatment. We examined pre-post changes in network density and avoidance centrality, and related these metrics to changes in symptom severity. Network density significantly decreased from pre- to post-treatment, indicating that after therapy, mutual interactions between negative emotions and avoidance were attenuated. Specifically, contemporaneous associations between anxiety and avoidance observed before CBT were no longer significant at post-treatment. Effects of negative emotions on avoidance assessed at a later time point (avoidance instrength) decreased, but not significantly. Reduction in avoidance instrength positively correlated with reduction in depressive symptom severity, meaning that as patients improved, they were less likely to avoid situations after experiencing negative emotions. Our results elucidate mechanisms of successful CBT observed in patients' daily lives and may help improve and personalize CBT to increase its effectiveness.

Examining bi-directional links between loneliness, social connectedness and sleep from a trait and state perspective.

Greater loneliness as well as a lack of social connectedness have often been associated with poorer sleep. However, the temporal dynamics and direction of these associations remain unclear. Aim of the current study was to examine bi-directional associations between loneliness/social connectedness and sleep in 48 stress-exposed medical students during their first medical internship, considered a period of heightened stress. We obtained trait-level questionnaire data on loneliness and global sleep completed before and during the internship as well as state-level diary- and wearable-based data on daily changes in social connectedness and sleep collected twice over the period of seven consecutive days, once before and once during the internship. Bi-directional associations among greater loneliness and higher daytime dysfunction on trait-level were identified. In addition, several uni-directional associations between loneliness/social connectedness and sleep were found on trait- and state-level. In sum, findings of this study point at a bi-directional relation among loneliness/social connectedness and sleep, in which variables seem to reciprocally influence each other across longer-term periods as well as on a day-to-day basis.

Positive autobiographical memories to counteract low mood in remitted depression: A longitudinal daily-life investigation.

Positive autobiographical memories (AMs) have the potential to repair low mood, but previously depressed individuals have difficulty leveraging their positive AMs for emotion regulation purposes. We examined whether previously depressed individuals benefit from guided, deliberate recollection of preselected AMs to counteract low mood in daily life, utilizing individuals' smartphones to facilitate recollection. Sixty participants enrolled in 2020 were randomly allocated to retrieval of positive or everyday activity AMs and completed ecological momentary assessment of emotional experience for 3 weeks. Participants first created a pool of six memories for the digital AM diary. This was followed by a training week with two recollection tasks daily and a 2-week follow-up period where the diary could be used spontaneously. The positive condition experienced a greater increase in feelings of happiness and a greater decrease in feelings of sadness from pre- to post-AM recollection. While participants in the positive condition used the AM technique more frequently overall during the 2-week follow-up, the effect of condition was moderated by changes in feelings of sadness. The more participants experienced an emotional benefit during the training week, the more they used it spontaneously. Emotional vividness of untrained positive AMs at the 2-week follow-up differed depending on whether they were assessed before or after the first pandemic lockdown. Residual depressive symptoms decreased in both conditions over the study course, while mental well-being remained unchanged. Strengthening positive, self-affirming AMs in daily life may provide a tool to support regulation of transient low mood in those remitted from depression. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Perceived responsiveness in suicidal ideation: An experience sampling study in psychiatric patients.

INTRODUCTION: Perceived responsiveness, or the extent to which one feels understood, validated and cared for by close others, plays a crucial role in people's well-being. Can this interpersonal process also protect people at risk? We assessed whether fluctuations in suicidal ideation were associated with fluctuations in the degree of perceived responsiveness that psychiatric patients (admitted in the context of suicide or indicating suicidal ideation) experienced in daily interactions immediately after discharge. METHODS: Fifty-seven patients reported on suicidal ideation (5 times a day) and perceived responsiveness (daily) for four consecutive weeks. The effects of established risk factors-thwarted belongingness, perceived burdensomeness, and hopelessness-were assessed as well. RESULTS: The more patients felt that close others had been responsive to them, the less suicidal ideation they reported. At low levels of thwarted belongingness, perceived burdensomeness, or hopelessness, perceived responsiveness seemed to play a protective role, negatively co-occurring with suicidal ideation. When thwarted belongingness, perceived burdensomeness, and hopelessness were high, perceived responsiveness did not have an effect. CONCLUSION: Perceived responsiveness could be a protective factor for suicidal ideation for people at risk only when they are experiencing low levels of negative perceptions. When experiencing highly negative perceptions, however, perceived responsiveness seems to matter less.

Optimizing Outcomes in Psychotherapy for Anxiety Disorders Using Smartphone-Based and Passive Sensing Features: Protocol for a Randomized Controlled Trial.

BACKGROUND: Psychotherapies, such as cognitive behavioral therapy (CBT), currently have the strongest evidence of durable symptom changes for most psychological disorders, such as anxiety disorders. Nevertheless, only about half of individuals treated with CBT benefit from it. Predictive algorithms, including digital assessments and passive sensing features, could better identify patients who would benefit from CBT, and thus, improve treatment choices. OBJECTIVE: This study aims to establish predictive features that forecast responses to transdiagnostic CBT in anxiety disorders and to investigate key mechanisms underlying treatment responses. METHODS: This study is a 2-armed randomized controlled clinical trial. We include patients with anxiety disorders who are randomized to either a transdiagnostic CBT group or a waitlist (referred to as WAIT). We index key features to predict responses prior to starting treatment using subjective self-report questionnaires, experimental tasks, biological samples, ecological momentary assessments, activity tracking, and smartphone-based passive sensing to derive a multimodal feature set for predictive modeling. Additional assessments take place weekly at mid- and posttreatment and at 6- and 12-month follow-ups to index anxiety and depression symptom severity. We aim to include 150 patients, randomized to CBT versus WAIT at a 3:1 ratio. The data set will be subject to full feature and important features selected by minimal redundancy and maximal relevance feature selection and then fed into machine leaning models, including eXtreme gradient boosting, pattern recognition network, and k-nearest neighbors to forecast treatment response. The performance of the developed models will be evaluated. In addition to predictive modeling, we will test specific mechanistic hypotheses (eg, association between self-efficacy, daily symptoms obtained using ecological momentary assessments, and treatment response) to elucidate mechanisms underlying treatment response. RESULTS: The trial is now completed. It was approved by the Cantonal Ethics Committee, Zurich. The results will be disseminated through publications in scientific peer-reviewed journals and conference presentations. CONCLUSIONS: The aim of this trial is to improve current CBT treatment by precise forecasting of treatment response and by understanding and potentially augmenting underpinning mechanisms and personalizing treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT03945617; https://clinicaltrials.gov/ct2/show/results/NCT03945617. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/42547.

Burst versus continuous delivery design in digital mental health interventions: Evidence from a randomized clinical trial.

Objective: Digital mental health interventions delivered via smartphone-based apps effectively treat various conditions; however, optimizing their efficacy while minimizing participant burden remains a key challenge. In this study, we investigated the potential benefits of a burst delivery design (i.e. interventions delivered only in pre-defined time intervals) in comparison to the continuous delivery of interventions. Methods: We randomly assigned 93 participants to the continuous delivery (CD) or burst delivery (BD) group. The CD group engaged in ReApp, a mobile app that increases positive cognitive reappraisal with a consistent delivery schedule that provides five prompts per day throughout the 3-week-long study, while the BD group received five daily prompts only in the first and third weeks of the study. Results: No significant differences were found between the groups in terms of adherence, mental health outcomes (specifically depressive and anxiety symptoms), level of perceived stress, and perceived helpfulness of intervention. The BD group showed a significantly decreased perceived difficulty of intervention over time. Conclusions: The results suggest that the burst delivery may be as suitable for digital mental health interventions as the continuous delivery. The perceived difficulty of the intervention declined more steeply for the BD group, indicating that it improved the feasibility of the positive cognitive reappraisal intervention without hurting its efficacy. This outcome may inform the design of less burdensome interventions with improved outcomes in future research.

The impact of doxycycline on human contextual fear memory.

RATIONALE:  Previous work identified an attenuating effect of the matrix metalloproteinase (MMP) inhibitor doxycycline on fear memory consolidation. This may present a new mechanistic approach for the prevention of trauma-related disorders. However, so far, this has only been unambiguously demonstrated in a cued delay fear conditioning paradigm, in which a simple geometric cue predicted a temporally overlapping aversive outcome. This form of learning is mainly amygdala dependent. Psychological trauma often involves the encoding of contextual cues, which putatively necessitates partly different neural circuits including the hippocampus. The role of MMP signalling in the underlying neural pathways in humans is unknown. METHODS: Here, we investigated the effect of doxycycline on configural fear conditioning in a double-blind placebo-controlled randomised trial with 100 (50 females) healthy human participants. RESULTS: Our results show that participants successfully learned and retained, after 1 week, the context-shock association in both groups. We find no group difference in fear memory retention in either of our pre-registered outcome measures, startle eye-blink responses and pupil dilation. Contrary to expectations, we identified elevated fear-potentiated startle in the doxycycline group early in the recall test, compared to the placebo group. CONCLUSION: Our results suggest that doxycycline does not substantially attenuate contextual fear memory. This might limit its potential for clinical application.

A systematic review and meta-analysis of transdiagnostic cognitive behavioural therapies for emotional disorders.

Transdiagnostic cognitive behavioural psychotherapy (TD-CBT) may facilitate the treatment of emotional disorders. Here we investigate short- and long-term efficacy of TD-CBT for emotional disorders in individual, group and internet-based settings in randomized controlled trials (PROSPERO CRD42019141512). Two independent reviewers screened results from PubMed, MEDLINE, PsycINFO, Google Scholar, medRxiv and OSF Preprints published between January 2000 and June 2023, selected studies for inclusion, extracted data and evaluated risk of bias (Cochrane risk-of-bias tool 2.0). Absolute efficacy from pre- to posttreatment and relative efficacy between TD-CBT and control treatments were investigated with random-effects models. Of 56 identified studies, 53 (6,705 participants) were included in the meta-analysis. TD-CBT had larger effects on depression (g = 0.74, 95% CI = 0.57-0.92, P < 0.001) and anxiety (g = 0.77, 95% CI = 0.56-0.97, P < 0.001) than did controls. Across treatment formats, TD-CBT was superior to waitlist and treatment-as-usual. TD-CBT showed comparable effects to disorder-specific CBT and was superior to other active treatments for depression but not for anxiety. Different treatment formats showed comparable effects. TD-CBT was superior to controls at 3, 6 and 12 months but not at 24 months follow-up. Studies were heterogeneous in design and methodological quality. This review and meta-analysis strengthens the evidence for TD-CBT as an efficacious treatment for emotional disorders in different settings.

Attenuating human fear memory retention with minocycline: a randomized placebo-controlled trial.

Pavlovian fear conditioning is widely used as a pre-clinical model to investigate methods for prevention and treatment of anxiety and stress-related disorders. In this model, fear memory consolidation is thought to require synaptic remodeling, which is induced by signaling cascades involving matrix metalloproteinase 9 (MMP-9). Here we investigated the effect of the tetracycline antibiotic minocycline, an inhibitor of MMP-9, on fear memory retention. We conducted a pre-registered, randomized, double-blind, placebo-controlled trial in N = 105 healthy humans (N = 70 female), using a configural fear conditioning paradigm. We administered a single dose of minocycline before configural fear memory acquisition and assessed fear memory retention seven days later in a recall test. To index memory retention, we pre-registered fear-potentially startle (FPS) as our primary outcome, and pupil dilation as the secondary outcome. As control indices of memory acquisition, we analyzed skin conductance responses (SCR) and pupil dilation. We observed attenuated retention of configural fear memory in individuals treated with minocycline compared to placebo, as measured by our primary outcome. In contrast, minocycline did not affect fear memory acquisition or declarative contingency memory. Our findings provide in-vivo evidence for the inhibition of fear memory consolidation by minocycline. This could motivate further research into primary prevention, and given the short uptake time of minocycline, potentially also secondary prevention of PTSD after trauma.

Feasibility, Adherence, and Effectiveness of Blended Psychotherapy for Severe Mental Illnesses: Scoping Review.

BACKGROUND: Blended psychotherapy (bPT) combines face-to-face psychotherapy with digital interventions to enhance the effectiveness of mental health treatment. The feasibility and effectiveness of bPT have been demonstrated for various mental health issues, although primarily for patients with higher levels of functioning. OBJECTIVE: This scoping review aims to investigate the feasibility, adherence, and effectiveness of bPT for the treatment of patients with severe mental illnesses (SMIs). METHODS: Following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines, we conducted searches in PubMed, MEDLINE, Embase, PsycINFO, and PsycArticles for studies published until March 23, 2023. RESULTS: Out of 587 screened papers, we incorporated 25 studies encompassing 23 bPT interventions, involving a total of 2554 patients with SMI. The intervention formats and research designs exhibited significant variation. Our findings offer preliminary evidence supporting the feasibility of bPT for SMI, although there is limited research on adherence. Nevertheless, the summarized studies indicated promising attrition rates, spanning from 0% to 37%, implying a potential beneficial impact of bPT on adherence to SMI treatment. The quantity of evidence on the effects of bPT for SMI was limited and challenging to generalize. Among the 15 controlled trials, 4 concluded that bPT interventions were effective compared with controls. However, it is noteworthy that 2 of these studies used the same study population, and the control groups exhibited significant variations. CONCLUSIONS: Overall, our review suggests that while bPT appears promising as a treatment method, further research is necessary to establish its effectiveness for SMI. We discuss considerations for clinical implementation, directions, and future research.

German Version of the Mobile Agnew Relationship Measure: Translation and Validation Study.

BACKGROUND: The mobile Agnew Relationship Measure (mARM) is a self-report questionnaire for the evaluation of digital mental health interventions and their interactions with users. With the global increase in digital mental health intervention research, translated measures are required to conduct research with local populations. OBJECTIVE: The aim of this study was to translate and validate the original English version of the mARM into a German version (mARM-G). METHODS: A total of 2 native German speakers who spoke English as their second language conducted forward translation of the original items. This version was then back translated by 2 native German speakers with a fluent knowledge of English. An independent bilingual reviewer then compared these drafts and created a final German version. The mARM-G was validated by 15 experts in the field of mobile app development and 15 nonexperts for content validity and face validity; 144 participants were recruited to conduct reliability testing as well as confirmatory factor analysis. RESULTS: The content validity index of the mARM-G was 0.90 (expert ratings) and 0.79 (nonexperts). The face validity index was 0.89 (experts) and 0.86 (nonexperts). Internal consistency for the entire scale was Cronbach α=.91. Confirmatory factor analysis results were as follows: the chi-square statistic to df ratio was 1.66. Comparative Fit Index was 0.87 and the Tucker-Lewis Index was 0.86. The root mean square error of approximation was 0.07. CONCLUSIONS: The mARM-G is a valid and reliable tool that can be used for future studies in German-speaking countries.

Imager-A mobile health mental imagery-based ecological momentary intervention targeting reward sensitivity: A randomized controlled trial.

Robust reward sensitivity may help preserve mental well-being in the face of adversity and has been proposed as a key stress resilience factor. Here, we present a mobile health application, "Imager," which targets reward sensitivity by training individuals to create mental images of future rewarding experiences. We conducted a two-arm randomized controlled trial with 95 participants screened for reward sensitivity. Participants in the intervention group received an ecological momentary intervention-Imager, which encouraged participants to create mental images of rewarding events for 1 week. The control group participants received only ecological momentary assessment, without the instruction to generate mental images. Adherence to Imager was high; participants in the intervention group engaged in 88% of the planned activities. In the follow-up assessment, the intervention group reported less mental health symptoms, mainly in depression (ß = -0.34, df = 93, p = .004) and less perceived stress (ß = -0.18, df = 93, p = .035), than control group participants and compared with the baseline assessment. Our results show the positive effects of Imager on mental health symptoms. The encouraging effects of the app on mental health outcomes may lead to greater use of ecological momentary interventions in the clinical preventive practice of affective disorders.

Psychological Resilience Factors and Their Association With Weekly Stressor Reactivity During the COVID-19 Outbreak in Europe: Prospective Longitudinal Study.

BACKGROUND: Cross-sectional relationships between psychosocial resilience factors (RFs) and resilience, operationalized as the outcome of low mental health reactivity to stressor exposure (low "stressor reactivity" [SR]), were reported during the first wave of the COVID-19 pandemic in 2020. OBJECTIVE: Extending these findings, we here examined prospective relationships and weekly dynamics between the same RFs and SR in a longitudinal sample during the aftermath of the first wave in several European countries. METHODS: Over 5 weeks of app-based assessments, participants reported weekly stressor exposure, mental health problems, RFs, and demographic data in 1 of 6 different languages. As (partly) preregistered, hypotheses were tested cross-sectionally at baseline (N=558), and longitudinally (n=200), using mixed effects models and mediation analyses. RESULTS: RFs at baseline, including positive appraisal style (PAS), optimism (OPT), general self-efficacy (GSE), perceived good stress recovery (REC), and perceived social support (PSS), were negatively associated with SR scores, not only cross-sectionally (baseline SR scores; all P<.001) but also prospectively (average SR scores across subsequent weeks; positive appraisal (PA), P=.008; OPT, P<.001; GSE, P=.01; REC, P<.001; and PSS, P=.002). In both associations, PAS mediated the effects of PSS on SR (cross-sectionally: 95% CI -0.064 to -0.013; prospectively: 95% CI -0.074 to -0.0008). In the analyses of weekly RF-SR dynamics, the RFs PA of stressors generally and specifically related to the COVID-19 pandemic, and GSE were negatively associated with SR in a contemporaneous fashion (PA, P<.001; PAC,P=.03; and GSE, P<.001), but not in a lagged fashion (PA, P=.36; PAC, P=.52; and GSE, P=.06). CONCLUSIONS: We identified psychological RFs that prospectively predict resilience and cofluctuate with weekly SR within individuals. These prospective results endorse that the previously reported RF-SR associations do not exclusively reflect mood congruency or other temporal bias effects. We further confirm the important role of PA in resilience.

EEG wakefulness regulation in transdiagnostic patients after a recent suicide attempt.

OBJECTIVE: Decades of research have not yet produced statistically reliable predictors of preparatory behavior eventually leading to suicide attempts or deaths by suicide. As the nature of suicidal behavior is complex, it is best investigated in a transdiagnostic approach, while assessing objective markers, as proposed by the Research Domain Criteria (Cuthbert, 2013). METHODS: A 15-min resting-state EEG was recorded in 45 healthy controls, and 49 transdiagnostic in-patients with a recent (<6 months) suicide attempt. Brain arousal regulation in eyes-closed condition was assessed with the Vigilance Algorithm Leipzig (VIGALL) (Sander et al., 2015). RESULTS: A significant incline of median vigilance and vigilance slope was observed in patients within the first 3-min of the EEG recording. Additionally, a significant positive correlation of self-reported suicidal ideation with the vigilance slope over 15-min recording time, as well as a significant negative correlation with EEG vigilance stage A1 during the first 3-min was found. CONCLUSIONS: Transdiagnostic patients with a recent suicide attempt show a distinct vigilance regulation pattern. Further studies including a control group consisting of patients without life-time suicide attempts are needed to increase the clinical utility of the findings. SIGNIFICANCE: These findings might serve as potential objective markers of suicidal behavior.

EEG source functional connectivity in patients after a recent suicide attempt.

OBJECTIVE: Electroencephalogram (EEG) based frequency measures within the alpha frequency range (AFR), including functional connectivity, show potential in assessing the underlying pathophysiology of depression and suicide-related outcomes. We investigated the association between AFR connectivity, suicidal thoughts and behaviors, and depression in a transdiagnostic sample of patients after a recent suicide attempt (SA). METHODS: Lagged source-based measures of linear and nonlinear whole-brain connectivity within the standard AFR ([sAFR], 8-12 Hz) and the individually referenced AFR (iAFR) were applied to 70 15-minute resting-state EEGs from patients after a SA and 70 age- and gender-matched healthy controls (HC). Hypotheses were tested using network-based statistics and multiple regression models. RESULTS: Results showed no significant differences between patients after a SA and HC in any of the assessed connectivity modalities. However, a subgroup analysis revealed significantly increased nonlinear connectivity within the sAFR for patients after a SA with a depressive disorder or episode ([DD], n = 53) compared to matched HC. Furthermore, a multiple regression model, including significant main effects for group and global nonlinear connectivity within the sAFR outperformed all other models in explaining variance in depressive symptom severity. CONCLUSIONS: Our study further supports the importance of the AFR in pathomechanisms of suicidality and depression. The iAFR does not seem to improve validity of phase-based connectivity. SIGNIFICANCE: Our results implicate distinct neurophysiological patterns in suicidal subgroups. Exploring the potential of these patterns for treatment stratification might advance targeted interventions for suicidal thoughts and behaviors.

Investigating Relationships Among Self-Efficacy, Mood, and Anxiety Using Digital Technologies: Randomized Controlled Trial.

BACKGROUND: Digital tools assessing momentary parameters and offering interventions in people's daily lives play an increasingly important role in mental health research and treatment. Ecological momentary assessment (EMA) makes it possible to assess transient mental health states and their parameters. Ecological momentary interventions (EMIs) offer mental health interventions that fit well into individuals' daily lives and routines. Self-efficacy is a transdiagnostic construct that is commonly associated with positive mental health outcomes. OBJECTIVE: The aim of our study assessing mood, specific self-efficacy, and other parameters using EMA was 2-fold. First, we wanted to determine the effects of daily assessed moods and dissatisfaction with social contacts as well as the effects of baseline variables, such as depression, on specific self-efficacy in the training group (TG). Second, we aimed to explore which variables influenced both groups' positive and negative moods during the 7-day study period. METHODS: In this randomized controlled trial, we applied digital self-efficacy training (EMI) to 93 university students with elevated self-reported stress levels and daily collected different parameters, such as mood, dissatisfaction with social contacts, and specific self-efficacy, using EMA. Participants were randomized to either the TG, where they completed the self-efficacy training combined with EMA, or the control group, where they completed EMA only. RESULTS: In total, 93 university students participated in the trial. Positive momentary mood was associated with higher specific self-efficacy in the evening of the same day (b=0.15, SE 0.05, P=.005). Higher self-efficacy at baseline was associated with reduced negative mood during study participation (b=-0.61, SE 0.30, P=.04), while we could not determine an effect on positive mood. Baseline depression severity was significantly associated with lower specific self-efficacy over the week of the training (b=-0.92, SE 0.35, P=.004). Associations between higher baseline anxiety with higher mean negative mood (state anxiety: b=0.78, SE 0.38, P=.04; trait anxiety: b=0.73, SE 0.33, P=.03) and lower mean positive mood (b=-0.64, SE 0.28, P=.02) during study participation were found. Emotional flexibility was significantly enhanced in the TG. Additionally, dissatisfaction with social contacts was associated with both a decreased positive mood (b=-0.56, SE 0.15, P<.001) and an increased negative mood (b=0.45, SE 0.12, P<.001). CONCLUSIONS: This study showed several significant associations between mood and self-efficacy as well as those between mood and anxiety in students with elevated stress levels, for example, suggesting that improving mood in people with low mood could enhance the effects of digital self-efficacy training. In addition, engaging in 1-week self-efficacy training was associated with increased emotional flexibility. Future work is needed to replicate and investigate the training's effects in other groups and settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT05617248; https://clinicaltrials.gov/study/NCT05617248.

Dynamic Modelling of Mental Resilience in Young Adults: Protocol for a Longitudinal Observational Study (DynaM-OBS).

BACKGROUND: Stress-related mental disorders are highly prevalent and pose a substantial burden on individuals and society. Improving strategies for the prevention and treatment of mental disorders requires a better understanding of their risk and resilience factors. This multicenter study aims to contribute to this endeavor by investigating psychological resilience in healthy but susceptible young adults over 9 months. Resilience is conceptualized in this study as the maintenance of mental health or quick recovery from mental health perturbations upon exposure to stressors, assessed longitudinally via frequent monitoring of stressors and mental health. OBJECTIVE: This study aims to investigate the factors predicting mental resilience and adaptive processes and mechanisms contributing to mental resilience and to provide a methodological and evidence-based framework for later intervention studies. METHODS: In a multicenter setting, across 5 research sites, a sample with a total target size of 250 young male and female adults was assessed longitudinally over 9 months. Participants were included if they reported at least 3 past stressful life events and an elevated level of (internalizing) mental health problems but were not presently affected by any mental disorder other than mild depression. At baseline, sociodemographic, psychological, neuropsychological, structural, and functional brain imaging; salivary cortisol and α-amylase levels; and cardiovascular data were acquired. In a 6-month longitudinal phase 1, stressor exposure, mental health problems, and perceived positive appraisal were monitored biweekly in a web-based environment, while ecological momentary assessments and ecological physiological assessments took place once per month for 1 week, using mobile phones and wristbands. In a subsequent 3-month longitudinal phase 2, web-based monitoring was reduced to once a month, and psychological resilience and risk factors were assessed again at the end of the 9-month period. In addition, samples for genetic, epigenetic, and microbiome analyses were collected at baseline and at months 3 and 6. As an approximation of resilience, an individual stressor reactivity score will be calculated. Using regularized regression methods, network modeling, ordinary differential equations, landmarking methods, and neural net-based methods for imputation and dimension reduction, we will identify the predictors and mechanisms of stressor reactivity and thus be able to identify resilience factors and mechanisms that facilitate adaptation to stressors. RESULTS: Participant inclusion began in October 2020, and data acquisition was completed in June 2022. A total of 249 participants were assessed at baseline, 209 finished longitudinal phase 1, and 153 finished longitudinal phase 2. CONCLUSIONS: The Dynamic Modelling of Resilience-Observational Study provides a methodological framework and data set to identify predictors and mechanisms of mental resilience, which are intended to serve as an empirical foundation for future intervention studies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/39817.