Social influences on the relationship between dissociation and psychotic-like experiences.

BACKGROUND: Shame is experienced as a threat to social self, and so activates threat-protective responses. There is evidence that shame has trauma-like characteristics, suggesting it can be understood within the same conceptual framework as trauma and dissociation. Evidence for causal links among trauma, dissociation, and psychosis thus warrant the investigation of how shame may influence causal mechanisms for psychosis symptoms. METHODS: This study tested the interaction between dissociation and shame, specifically external shame (feeling shamed by others), in predicting psychotic-like experiences (PLEs) six months later in a general population sample (N = 314). It also tested if social safeness moderates these effects. A longitudinal, online questionnaire design tested a moderation model (dissociation-shame) and a moderated moderation model (adding social safeness), using multiple regressions with bootstrap procedures. RESULTS: Although there was no direct effect of dissociation on PLEs six months later, there was a significant interaction effect with shame, controlling for PLEs at baseline. There were complex patterns in the directions of effects: For high-shame-scorers, higher dissociation predicted higher PLE scores, but for low-shame-scorers, higher dissociation predicted lower PLE scores. Social safeness was found to significantly moderate these interaction effects, which were unexpectedly more pronounced in the context of higher social safeness. CONCLUSIONS: The results demonstrate evidence for an interaction between dissociation and shame on its impact on PLEs, which manifests particularly for those experiencing higher social safeness. This suggests a potential role of social mechanisms in both the etiology and treatment of psychosis, which warrants further testing in clinical populations.

Longitudinal Assessment of Seasonal Impacts and Depression Associations on Circadian Rhythm Using Multimodal Wearable Sensing: Retrospective Analysis.

BACKGROUND: Previous mobile health (mHealth) studies have revealed significant links between depression and circadian rhythm features measured via wearables. However, the comprehensive impact of seasonal variations was not fully considered in these studies, potentially biasing interpretations in real-world settings. OBJECTIVE: This study aims to explore the associations between depression severity and wearable-measured circadian rhythms while accounting for seasonal impacts. METHODS: Data were sourced from a large longitudinal mHealth study, wherein participants' depression severity was assessed biweekly using the 8-item Patient Health Questionnaire (PHQ-8), and participants' behaviors, including sleep, step count, and heart rate (HR), were tracked via Fitbit devices for up to 2 years. We extracted 12 circadian rhythm features from the 14-day Fitbit data preceding each PHQ-8 assessment, including cosinor variables, such as HR peak timing (HR acrophase), and nonparametric features, such as the onset of the most active continuous 10-hour period (M10 onset). To investigate the association between depression severity and circadian rhythms while also assessing the seasonal impacts, we used three nested linear mixed-effects models for each circadian rhythm feature: (1) incorporating the PHQ-8 score as an independent variable, (2) adding seasonality, and (3) adding an interaction term between season and the PHQ-8 score. RESULTS: Analyzing 10,018 PHQ-8 records alongside Fitbit data from 543 participants (n=414, 76.2% female; median age 48, IQR 32-58 years), we found that after adjusting for seasonal effects, higher PHQ-8 scores were associated with reduced daily steps (ß=-93.61, P<.001), increased sleep variability (ß=0.96, P<.001), and delayed circadian rhythms (ie, sleep onset: ß=0.55, P=.001; sleep offset: ß=1.12, P<.001; M10 onset: ß=0.73, P=.003; HR acrophase: ß=0.71, P=.001). Notably, the negative association with daily steps was more pronounced in spring (ß of PHQ-8 × spring = -31.51, P=.002) and summer (ß of PHQ-8 × summer = -42.61, P<.001) compared with winter. Additionally, the significant correlation with delayed M10 onset was observed solely in summer (ß of PHQ-8 × summer = 1.06, P=.008). Moreover, compared with winter, participants experienced a shorter sleep duration by 16.6 minutes, an increase in daily steps by 394.5, a delay in M10 onset by 20.5 minutes, and a delay in HR peak time by 67.9 minutes during summer. CONCLUSIONS: Our findings highlight significant seasonal influences on human circadian rhythms and their associations with depression, underscoring the importance of considering seasonal variations in mHealth research for real-world applications. This study also indicates the potential of wearable-measured circadian rhythms as digital biomarkers for depression.

Thinking About the Future of Cognitive Remediation Therapy Revisited: What Is Left to Solve Before Patients Have Access?

In our previous paper on the Future of Cognitive Remediation published more than 10 years ago, we envisaged an imminent and wide implementation of cognitive remediation therapies into mental health services. This optimism was misplaced. Despite evidence of the benefits, costs, and savings of this intervention, access is still sparse. The therapy has made its way into some treatment guidance, but these documents weight the same evidence very differently, causing confusion, and do not consider barriers to implementation. This paper revisits our previous agenda and describes how some challenges were overcome but some remain. The scientific community, with its commitment to Open Science, has produced promising sets of empirical data to explore the mechanisms of treatment action. This same community needs to understand the specific and nonspecific effects of cognitive remediation if we are to provide a formulation-based approach that can be widely implemented. In the last 10 years we have learned that cognitive remediation is not "brain training" but is a holistic therapy that involves an active therapist providing motivation support, and who helps to mitigate the impact of cognitive difficulties through metacognition to develop awareness of cognitive approaches to problems. We conclude that, of course, more research is needed but, in addition and perhaps more importantly at this stage, we need more public and health professionals' understanding of the benefits of this therapy to inform and include this approach as part of treatment regimens.

Evaluating remote delivery of cognitive remediation in people with psychosis.

BACKGROUND: Cognitive Remediation (CR) is an evidence-based therapy targeting cognitive difficulties in people with psychosis to promote functional recovery, but it is rarely implemented routinely. To reach more individuals, CR is beginning to be delivered remotely, but there is limited evidence to support the acceptability of this method. AIMS: To evaluate the acceptability and feasibility of remote therapist-supported CR in people with psychosis and estimate its cost and potential benefits. METHODS: A case-series with all participants assessed before and after therapy with measures of personal goal attainment (main outcome), cognition, functioning and symptoms. Acceptability was assessed with post-therapy interviews. Feasibility was assessed using proportions and confidence intervals on pre-specified parameters. Indication of benefits was assessed with exploratory analyses comparing baseline and post-therapy scores on the pre-specified outcomes. The cost of providing remote CR was assessed from both healthcare and societal perspectives. RESULTS: Twenty-nine participants started therapy with two dropping out; on average participants attended 25.5 sessions. Interviews suggested that remote CR had good acceptability and led to perceived benefits. Significant and large improvements were observed on goal attainment. Cost analyses suggest that remote CR has the same health care cost as face-to-face therapy but a lower societal cost. CONCLUSIONS: Our results support the use of remote CR in psychosis services as an alternative delivery modality. This method may improve adherence, attendance and be more convenient for service users. Possible barriers such as poor digital literacy or appropriate device ownership should be addressed before starting therapy.

Understanding the Mechanisms of Cognitive Remediation on Recovery in People With Early Psychosis: A Mediation and Moderation Analysis.

BACKGROUND: To provide precision cognitive remediation therapy (CR) for schizophrenia, we need to understand whether the mechanism for improved functioning is via cognition improvements. This mechanism has not been rigorously tested for potential moderator effects. STUDY DESIGN: We used data (n = 377) from a randomized controlled trial using CIRCuiTS, a therapist-supported CR, with participants from first-episode psychosis services. We applied structured equation modeling to test whether: (1) CR hours explain the goal attainment functional outcome (GAS) at posttreatment, (2) global cognitive improvement mediates GAS, and if (3) total symptoms moderate the CR hours to cognitive improvement pathway, and/or negative symptoms moderate the cognition to functioning pathway, testing moderator effects via the mediator or directly on CR hours to functioning path. STUDY RESULTS: CR produced significant functioning benefit for each therapy hour (Coeff = 0.203, 95% CI 0.101-0.304, P < .001). The mediated path from CR hours to cognition and cognition to functioning was small and nonsignificant (Coeff = 0.014, 95% CI = -0.010, 0.037, P = .256). Total symptoms did not moderate the path to cognition (P = .211) or the direct path to outcome (P = .896). However, negative symptoms significantly moderated the effect of cognitive improvements on functioning (P = .015) with high negative symptoms reducing the functional gains of improved cognition. CONCLUSIONS: Although cognitive improvements were correlated with functioning benefit, they did not fully explain the positive effect of increased therapy hours on functioning, suggesting additional CR factors also contribute to therapy benefit. Negative symptoms interfere with the translation of cognitive improvements into functional gains so need consideration.

Changes in BDNF methylation patterns after cognitive remediation therapy in schizophrenia: A randomized and controlled trial.

Although cognitive remediation therapy (CRT) produces cognitive benefits in schizophrenia, we do not yet understand whether molecular changes are associated with this cognitive improvement. A gene central to synaptic plasticity, the BDNF, has been proposed as one potential route. This study assesses whether BDNF methylation changes following CRT-produced cognitive improvement are detected. A randomized and controlled trial was performed with two groups (CRT, n = 40; TAU: Treatment as Usual, n = 20) on a sample of participants with schizophrenia. CRT was delivered by trained therapists using a web-based computerized program. Mixed Models, where the interaction of treatment (CRT, TAU) by time (T0: 0 weeks, T1: 16 weeks) was the main effect were used. Then, we tested the association between the treatment and methylation changes in three CpG islands of the BDNF gene. CRT group showed significant improvements in some cognitive domains. Between-groups differential changes in 5 CpG units over time were found, 4 in island 1 (CpG1.2, CpG1.7, CpG1.10, CpG1.17) and 1 in island 3 (CpG3.2). CRT group showed increases in methylation in CpG1.2, CpG1.7 and decreases in pG1.10, CpG1.17, and CpG3.2. Differences in the degree of methylation were associated with changes in Speed of Processing, Working Memory, and Verbal Learning within the CRT group. Those findings provide new data on the relationship between cognitive improvement and changes in peripheral methylation levels of BDNF gene, a key factor involved in neuroplasticity regulation. Trial Registration: NCT04278027.

Identifying depression-related topics in smartphone-collected free-response speech recordings using an automatic speech recognition system and a deep learning topic model.

BACKGROUND: Prior research has associated spoken language use with depression, yet studies often involve small or non-clinical samples and face challenges in the manual transcription of speech. This paper aimed to automatically identify depression-related topics in speech recordings collected from clinical samples. METHODS: The data included 3919 English free-response speech recordings collected via smartphones from 265 participants with a depression history. We transcribed speech recordings via automatic speech recognition (Whisper tool, OpenAI) and identified principal topics from transcriptions using a deep learning topic model (BERTopic). To identify depression risk topics and understand the context, we compared participants' depression severity and behavioral (extracted from wearable devices) and linguistic (extracted from transcribed texts) characteristics across identified topics. RESULTS: From the 29 topics identified, we identified 6 risk topics for depression: 'No Expectations', 'Sleep', 'Mental Therapy', 'Haircut', 'Studying', and 'Coursework'. Participants mentioning depression risk topics exhibited higher sleep variability, later sleep onset, and fewer daily steps and used fewer words, more negative language, and fewer leisure-related words in their speech recordings. LIMITATIONS: Our findings were derived from a depressed cohort with a specific speech task, potentially limiting the generalizability to non-clinical populations or other speech tasks. Additionally, some topics had small sample sizes, necessitating further validation in larger datasets. CONCLUSION: This study demonstrates that specific speech topics can indicate depression severity. The employed data-driven workflow provides a practical approach for analyzing large-scale speech data collected from real-world settings.

Durability of Effects of Cognitive Remediation on Cognition and Psychosocial Functioning in Schizophrenia: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

OBJECTIVE: Cognitive remediation provides substantial improvements in cognitive performance and real-world functioning for people living with schizophrenia, but the durability of these benefits needs to be reassessed and better defined. The aims of this study were to provide a comprehensive assessment of the durability of the benefits of cognitive remediation for cognition and functioning in people living with schizophrenia and evaluating potential moderators of effects. METHODS: A systematic search was conducted in PubMed, Scopus, and PsycINFO, and reference lists of included articles and Google Scholar were inspected. Eligible studies were randomized clinical trials of cognitive remediation in patients diagnosed with schizophrenia spectrum disorders in which follow-up assessments were included. Screening and data extraction were performed by at least two independent reviewers. Cohen's d was used to measure outcomes. Primary outcomes were changes in cognition and functioning from baseline to conclusion of follow-up. Moderators of the durability of effects were assessed. RESULTS: Of 2,840 identified reports, 281 full texts were assessed and 130 reports on 67 studies with 5,334 participants were included. Cognitive remediation produced statistically significant positive effects that persisted at the end of follow-up in global cognition (d=0.23) and in global functioning (d=0.26). Smaller study samples and single-center studies were associated with better cognitive outcomes; longer treatment and follow-up duration, techniques for transferring cognitive gains to the real world, integration with psychiatric rehabilitation, group format of delivery, and more female participants in the sample were associated with better functional outcomes. CONCLUSIONS: Cognitive remediation provides durable improvements in cognition and functioning in schizophrenia. This finding corroborates the notion that cognitive remediation should be implemented more widely in clinical and rehabilitation practice.

Evaluating the acceptability of remote cognitive remediation from the perspective of psychosis service users.

OBJECTIVES: Cognitive remediation (CR) can reduce the cognitive difficulties experienced by people with psychosis. Adapting CR to be delivered remotely provides new opportunities for extending its use. However, doing so requires further evaluation of its acceptability from service users' views. We evaluate the acceptability of therapist-supported remote CR from the perspectives of service users using participatory service user-centred methods. METHOD: After receiving 12 weeks of therapist-supported remote CR, service users were interviewed by a service user researcher following a semi-structured 18-question interview guide. Transcripts were analysed using reflexive thematic analysis with themes and codes further validated by a Lived Experience Advisory Panel and member checking. RESULTS: The study recruited 26 participants, almost all of whom reported high acceptability of remote CR, and some suggested improvements. Four themes emerged: (1) perceived treatment benefits, (2) remote versus in-person therapy, (3) the therapist's role, and (4) how it could be better. CONCLUSIONS: This study used comprehensive service user involvement methods. For some participants, technology use remained a challenge and addressing these difficulties detracted from the therapy experience. These outcomes align with existing research on remote therapy, suggesting that remote CR can expand choice and improve access to treatment for psychosis service users once barriers are addressed. Future use of remote CR should consider technology training and equipment provision to facilitate therapy for service users and therapists.

Experiencing hallucinations in daily life: The role of metacognition.

BACKGROUND: Hallucinations have been linked to failures in metacognitive reflection suggesting an association between hallucinations and overestimation of performance, although the cross-sectional findings are inconsistent. This inconsistency may relate to the fluctuating hallucinatory experiences that are not captured in cross-sectional studies. Ecological Momentary Assessment (EMA) captures in-the-moment experiences over time so can identify causal relationships between variables such as the associations between metacognition and hallucinatory experience in daily life and overcome problems in cross-sectional designs. METHODS: Participants (N = 41) experiencing daily hallucinations completed baseline questionnaires and smartphone surveys 7 times per day for 14 days. They were prompted to identify a task they would complete in the next 4 h and to make metacognitive predictions around the likelihood of completing the task, the difficulty of the task, and how well they would complete it (standard of completion). RESULTS: 76 % finished the 14-days of assessment with an average of 42.2 % survey completion. Less accurate metacognition was associated with more hallucinations, but less accurate likelihood and standard of completion was associated with fewer hallucinations. Using a cross-lagged analysis, metacognitive predictions around the likelihood of completion (p < .001) and standard of completion (p = .01) predicted hallucination intensity at the following timepoint, and metacognitive predictions regarding likelihood of completion (p = .02) predicted hallucination control at the following timepoint. DISCUSSION: Interventions that aim to improve metacognitive ability in-the-moment may serve to reduce the intensity and increase the control of hallucinations.

Participant perspectives on cognitive remediation and social recovery in early psychosis (CReSt-R): An acceptability study.

AIM: Psychosis spectrum disorders continue to rank highly among causes of disability. This has resulted in efforts to expand the range of treatment targets beyond symptom remission to include other recovery markers, including social and occupational function and quality of life. Although the efficacy of psychosocial interventions in early psychosis has been widely reported, the acceptability of these interventions is less well-known. This study explores the participant perspective on a novel, psychosocial intervention combining cognitive remediation and social recovery therapy. METHODS: We employed a qualitative research design, based on semi-structured interviews and reflexive thematic analysis. Six participants with early psychosis were recruited from the intervention arm of a randomized pilot study, three women and three men, aged between 22 and 27 years. RESULTS: Four themes were developed through the analytical process, namely, (1) a solid therapeutic foundation, (2) multi-directional flow of knowledge, (3) a tailored toolset, and (4) an individual pathway to recovery. Participants also provided pragmatic feedback about how to improve the delivery of the therapy assessments and intervention. Both the themes and pragmatic feedback are described. CONCLUSIONS: People with early psychosis described the intervention as acceptable, engaging, helpful and person-centred, suggesting its potential role in a multicomponent therapy model of early intervention in psychosis services. Participants in this study also highlight the importance of an individualized approach to therapy, the vital role of the therapeutic relationship and the ecological validity and value of adopting an assertive outreach delivery, providing therapy outside a conventional clinic setting.

Measures of Social and Occupational Function in Early Psychosis: A Systematic Review and Meta-analysis.

Deficits in social and occupational function are widely reported in psychosis, yet no one measure of function is currently agreed upon as a gold standard in psychosis research. The aim of this study was to carry out a systematic review and meta-analysis of functioning measures to determine what measures were associated with largest effect sizes when measuring between-group differences, changes over time, or response to treatment. Literature searches were conducted based on PsycINFO and PubMed to identify studies for inclusion. Cross-sectional and longitudinal observational and intervention studies of early psychosis (≤5 years since diagnosis) that included social and occupational functioning as an outcome measure were considered. A series of meta-analyses were conducted to determine effect size differences for between-group differences, changes over time, or response to treatment. Subgroup analyses and meta-regression were carried out to account for variability in study and participant characteristics. One hundred and sixteen studies were included, 46 studies provided data (N = 13 261) relevant to our meta-analysis. Smallest effect sizes for changes in function over time and in response to treatment were observed for global measures, while more specific measures of social and occupational function showed the largest effect sizes. Differences in effect sizes between functioning measures remained significant after variability in study and participant characteristics were accounted for. Findings suggest that more specific measures of social function are better able to detect changes in function over time and in response to treatment.

Cognitive Remediation in Bipolar (CRiB2): study protocol for a randomised controlled trial assessing efficacy and mechanisms of cognitive remediation therapy compared to treatment as usual.

BACKGROUND: A substantial proportion of people with bipolar disorder (BD) experience persistent cognitive difficulties associated with impairments in psychosocial functioning and a poorer disorder course. Emerging evidence suggests that cognitive remediation (CR), a psychological intervention with established efficacy in people with schizophrenia, can also benefit people with BD. Following a proof-of-concept trial showing that CR is feasible and potentially beneficial for people with BD, we are conducting an adequately powered trial in euthymic people with BD to 1) determine whether an individual, therapist-supported, computerised CR can reduce cognitive difficulties and improve functional outcomes; and 2) explore how CR exerts its effects. METHODS: CRiB2 is a two-arm, assessor-blind, multi-site, randomised controlled trial (RCT) comparing CR to treatment-as-usual (TAU). Participants are people with a diagnosis of BD, aged between 18 and 65, with no neurological or current substance use disorder, and currently euthymic. 250 participants will be recruited through primary, secondary, tertiary care, and the community. Participants will be block-randomised (1:1 ratio, stratified by site) to continue with their usual care (TAU) or receive a 12-week course of therapy and usual care (CR + TAU). The intervention comprises one-on-one CR sessions with a therapist supplemented with independent cognitive training for 30-40 h in total. Outcomes will be assessed at 13- and 25-weeks post-randomisation. Efficacy will be examined by intention-to-treat analyses estimating between-group differences in primary (i.e., psychosocial functioning at week 25 measured with the Functional Assessment Short Test) and secondary outcomes (i.e., measures of cognition, mood, patient-defined goals, and quality of life). Global cognition, metacognitive skills, affect fluctuation, and salivary cortisol levels will be evaluated as putative mechanisms of CR through mediation models. DISCUSSION: This study will provide a robust evaluation of efficacy of CR in people with BD and examine the putative mechanisms by which this therapy works. The findings will contribute to determining the clinical utility of CR and potential mechanisms of action. TRIAL REGISTRATION: Cognitive Remediation in Bipolar 2 (CRiB2): ISRCTN registry: https://www.isrctn.com/ISRCTN10362331 . Registered 04 May 2022. Overall trial status: Ongoing; Recruitment status: Recruiting.

Evaluation of a new online cognitive remediation therapy (CIRCuiTSTM ) training for mental health professionals.

OBJECTIVE: Cognitive remediation (CR) improves cognition and aids recovery in people with psychosis. An active therapist provides increased benefit, but CR training for therapists is not routinely available, so CR has limited scalability. This study describes the development and evaluation of the first online CR therapist training programme. METHODS: An online CR training, based on expert and novice therapist consultations, was developed, and then pilot tested with novice trainees and changes made to produce the evaluation version. Feasibility, acceptability, and training benefits were assessed in a group of naïve UK NHS mental health professionals. Training engagement with a group of clinicians who accessed the programme for professional development was compared to those who paid fees. RESULTS: Most mental health professionals finished training and passed the knowledge test, indicating that training enhanced clinicians' knowledge. Fee-paying trainees had significantly faster completion times and a higher proportion finished in the recommended time. Those who were successful at passing the knowledge questionnaire had significantly fewer years in practice. The majority were satisfied with the programme, felt they had made considerable progress and that training would allow them to begin practicing CR, and would recommend the training to colleagues. CONCLUSIONS: This online CR training programme was feasible, acceptable to participants and showed benefits for clinicians. It improved knowledge even in the most junior of staff who have had less time to develop clinical know-how.

Satisfaction with cognitive remediation therapy: its effects on implementation and outcomes using the cognitive remediation satisfaction scale.

Cognitive Remediation (CR) improves cognition and functioning but is implemented in a variety of ways (independent, group and one-to-one). There is no information on whether service users find these implementation methods acceptable or if their satisfaction influences CR outcomes. We used mixed participatory methods, including focus groups, to co-develop a CR satisfaction scale. This was refined using three psychometric criteria (Cronbach's alpha, item discrimination, test-retest agreement) to select items. Factor analysis explored potential substructures. The refined measure was used in structural equation joint modelling to evaluate whether satisfaction with CR is affected by implementation method and treatment engagement or influences recovery outcome, using data from a randomised controlled trial. Four themes (therapy hours, therapist, treatment effects, computer use) generated a 31-item Cognitive Remediation Satisfaction scale (CRS) that reduced to 18 Likert items, 2 binary and 2 open-ended questions following psychometric assessment. CRS had good internal consistency (Alpha = 0.814), test-retest reliability (r= 0.763), and concurrent validity using the Working Alliance Inventory (r = 0.56). A 2-factor solution divided items into therapy engagement and therapy effects. Satisfaction was not related to implementation method but was significantly associated with CR engagement. Therapy hours were significantly associated with recovery, but there was no direct effect of satisfaction on outcome. Although satisfaction is important to therapy engagement, it has no direct effect on outcome. CR therapy hours directly affect outcome irrespective of which implementation model is used, so measuring satisfaction early might help to identify those who are likely to disengage. The study has mixed methods design.

A case series study of compassion-focused therapy for distressing experiences in psychosis.

OBJECTIVES: Compassion-focused therapy (CFT) is an evolution-informed biopsychosocial approach that seeks to cultivate attachment and care motivational systems and their psychophysiological regulators. These can counteract some of the harmful effects of social threat, inferiority, shame, self-criticism and depression, which are common in people with psychosis and undermine their well-being, social trust and ability to feel safe. This study aimed to test the acceptability of a novel manualized individual CFT intervention for psychosis (CFTp). DESIGN: A non-concurrent, multiple-baseline, case series design, with three phases: baseline, intervention and follow-up. METHODS: The 26-session CFTp intervention was provided for a sample of eight people with distressing psychotic experiences and a psychosis-related diagnosis. The study aimed to assess acceptability of CFTp and to test clinically reliable improvements while receiving the intervention, compared to a baseline period. RESULTS: Seven of eight participants completed the therapy, and clinically reliable improvements were found at both the single-case and group level of analysis. At the single-case level, over half the participants showed improvements in depression (5/7), stress (5/7), distress (5/7), anxiety (4/7) and voices (3/5). One participant showed a deterioration in anxiety (1/7) and dissociation (1/7). At the group level (n = 7), there were significant improvements in depression, stress, distress, voices and delusions. The improvements in voices, delusions and distress were sustained at 6- to 8-week follow-up, but depression and stress dropped slightly to trend-level improvements. CONCLUSIONS: CFTp is a feasible and acceptable intervention for psychosis, and further investigation is warranted with a randomized controlled trial.

Multilingual markers of depression in remotely collected speech samples: A preliminary analysis.

BACKGROUND: Speech contains neuromuscular, physiological and cognitive components, and so is a potential biomarker of mental disorders. Previous studies indicate that speaking rate and pausing are associated with major depressive disorder (MDD). However, results are inconclusive as many studies are small and underpowered and do not include clinical samples. These studies have also been unilingual and use speech collected in controlled settings. If speech markers are to help understand the onset and progress of MDD, we need to uncover markers that are robust to language and establish the strength of associations in real-world data. METHODS: We collected speech data in 585 participants with a history of MDD in the United Kingdom, Spain, and Netherlands as part of the RADAR-MDD study. Participants recorded their speech via smartphones every two weeks for 18 months. Linear mixed models were used to estimate the strength of specific markers of depression from a set of 28 speech features. RESULTS: Increased depressive symptoms were associated with speech rate, articulation rate and intensity of speech elicited from a scripted task. These features had consistently stronger effect sizes than pauses. LIMITATIONS: Our findings are derived at the cohort level so may have limited impact on identifying intra-individual speech changes associated with changes in symptom severity. The analysis of features averaged over the entire recording may have underestimated the importance of some features. CONCLUSIONS: Participants with more severe depressive symptoms spoke more slowly and quietly. Our findings are from a real-world, multilingual, clinical dataset so represent a step-change in the usefulness of speech as a digital phenotype of MDD.

Challenges in Using mHealth Data From Smartphones and Wearable Devices to Predict Depression Symptom Severity: Retrospective Analysis.

BACKGROUND: Major depressive disorder (MDD) affects millions of people worldwide, but timely treatment is not often received owing in part to inaccurate subjective recall and variability in the symptom course. Objective and frequent MDD monitoring can improve subjective recall and help to guide treatment selection. Attempts have been made, with varying degrees of success, to explore the relationship between the measures of depression and passive digital phenotypes (features) extracted from smartphones and wearables devices to remotely and continuously monitor changes in symptomatology. However, a number of challenges exist for the analysis of these data. These include maintaining participant engagement over extended time periods and therefore understanding what constitutes an acceptable threshold of missing data; distinguishing between the cross-sectional and longitudinal relationships for different features to determine their utility in tracking within-individual longitudinal variation or screening individuals at high risk; and understanding the heterogeneity with which depression manifests itself in behavioral patterns quantified by the passive features. OBJECTIVE: We aimed to address these 3 challenges to inform future work in stratified analyses. METHODS: Using smartphone and wearable data collected from 479 participants with MDD, we extracted 21 features capturing mobility, sleep, and smartphone use. We investigated the impact of the number of days of available data on feature quality using the intraclass correlation coefficient and Bland-Altman analysis. We then examined the nature of the correlation between the 8-item Patient Health Questionnaire (PHQ-8) depression scale (measured every 14 days) and the features using the individual-mean correlation, repeated measures correlation, and linear mixed effects model. Furthermore, we stratified the participants based on their behavioral difference, quantified by the features, between periods of high (depression) and low (no depression) PHQ-8 scores using the Gaussian mixture model. RESULTS: We demonstrated that at least 8 (range 2-12) days were needed for reliable calculation of most of the features in the 14-day time window. We observed that features such as sleep onset time correlated better with PHQ-8 scores cross-sectionally than longitudinally, whereas features such as wakefulness after sleep onset correlated well with PHQ-8 longitudinally but worse cross-sectionally. Finally, we found that participants could be separated into 3 distinct clusters according to their behavioral difference between periods of depression and periods of no depression. CONCLUSIONS: This work contributes to our understanding of how these mobile health-derived features are associated with depression symptom severity to inform future work in stratified analyses.