Who benefits from digital interventions for bipolar disorder? Stage of illness characteristics as predictors of changes in quality of life.

OBJECTIVES: This study explored the potential role of stage-related variables in intervention outcomes in bipolar disorder (BD). Specifically, we aimed to identify which subgroups of individuals were most likely to experience improved quality of life following digitally delivered psychosocial interventions for BD. METHODS: The study involved a secondary analysis of combined data from two randomised control trials (RCTs). Each trial assessed the effectiveness of digitally delivered interventions for improving quality of life, in late-stage (ORBIT RCT) or early-stage (BETTER RCT) BD. Three iterations of cluster analyses were performed, identifying subgroups of individuals based on (i) current phenomenology, (ii) course of illness and (iii) medication response. The resultant subgroups were compared with regard to changes in quality of life pre-post intervention, via repeated measures ANOVAs. RESULTS: In each cluster analysis, two clusters were found. The current phenomenology clusters reflected two impairment levels, 'moderate impairment' and 'low impairment'. The course of illness clusters reflected 'more chronicity' and 'less chronicity' and the medication response clusters reflected 'good medication response' and 'poor medication response'. Differences in changes in quality of life over time were observed between the two current phenomenology clusters and between the medication response clusters, while the course of illness subgroups did not respond differently. CONCLUSIONS: There are at least two distinct groups of treatment-seeking individuals with established BD, based on illness features with previously established links to different illness stages. Clusters within the current phenomenology and medication response domains demonstrated significantly different trajectories of QoL change over time in the context of our interventions, highlighting potential implications for treatment selection aligned with precision psychiatry.

Active components and mechanisms of action of psychological interventions in bipolar disorder: A systematic literature review.

OBJECTIVE: The efficacy of psychological interventions for bipolar disorder (BD) is well established, but much remains unknown about how change occurs. The primary objective of this exploratory study was to audit what is known about active components and mechanisms of action of psychological interventions for BD. METHOD: We conducted a systematic review (PROSPERO CRD42022323276). Two independent reviewers screened references from four databases and extracted data from eligible studies. RESULTS: We included four component studies, six studies with mediation analyses and 26 studies presenting subjective experiences of how psychological interventions bring change. Ten mediators were examined across six studies, with only one putative mediator, medication adherence, tested in more than one study. Some initial support for mediation of varied outcomes by control over thoughts, positive non-verbal behaviour, self-esteem, post-trauma growth and medication adherence. Some preliminary support was found in two components, human support and IPT. Studies exploring participant experiences of therapeutic change enumerated a range of potential active components, mechanisms of action and contextual factors potentially warranting investigation in future research. However, the evidence base for active components and mechanisms of action in psychological interventions for BD is unsatisfactory. Findings were inconsistent, studies homogenous with significant methodological limitations and statistical approaches failed to meet quality criteria. CONCLUSIONS: Preliminary identification of potential components and mechanisms via qualitative analyses and the insights emerging from this review will inform future research aimed at investigating how psychological interventions work in BD.

Conceptualizing the later stage of bipolar disorder: Descriptive analyses from the ORBIT trial.

OBJECTIVES: This study aimed to investigate the features of later stage bipolar disorder (BD) and specifically, factors underlying later stage BD and potential subgroups within this stage, to understand more about the later stage group and contribute to the measurement of stage. METHODS: An exploratory factor analysis was conducted using variables relating to current phenomenological aspects of illness, followed by cluster analyses based on the identified factors. Finally, the resultant clusters were compared based on course of illness variables. RESULTS: Fourteen extracted factors explained 57 percent of the variance. Latent structures aligned with current depressive symptoms, energy and interest, independence, occupational functioning, symptoms of anxiety, pain, elevated symptoms, interpersonal functioning, anger, perceptions of social connections, and perceptions of current medication effectiveness, cognitive issues, sleep issues, and sense of isolation. Two clusters were identified which differed significantly on each of these factors, and on a range of course of illness features including lifetime number of episodes, duration of illness and number of depressive hospitalizations. CONCLUSIONS: Latent phenomenological features relevant to individuals in the later stage of BD were identified. Two clusters of individuals in later stage BD differ based on these features as well as course of illness, suggesting that there are distinct subgroups of individuals in the later stage of BD, distinguishable based on current phenomenology and illness history. However, findings are exploratory and therefore require confirmation before they can be applied clinically.

Consensus on nomenclature for clinical staging models in bipolar disorder: A narrative review from the International Society for Bipolar Disorders (ISBD) Staging Task Force.

OBJECTIVES: Clinical staging is widely used in medicine to map disease progression, inform prognosis, and guide treatment decisions; in psychiatry, however, staging remains a hypothetical construct. To facilitate future research in bipolar disorders (BD), a well-defined nomenclature is needed, especially since diagnosis is often imprecise with blurred boundaries, and a full understanding of pathophysiology is lacking. METHODS: Under the auspices of the International Society of Bipolar Disorders, a Task Force of international experts was convened to review, discuss, and integrate findings from the scientific literature relevant to the development of a consensus staging model and standardize a terminology that could be used to advance future research including staging of BD and related disorders. RESULTS: Consensus opinion and areas of uncertainty or difference were identified in regard to terms referring to staging as it may apply to BD, to at-risk status and subthreshold stages, and to various clinical stages of BD as it is currently diagnosed. CONCLUSION: The use of a standardized nomenclature about the clinical stages of BD will facilitate communication about research on clinical and pathological components of this heterogeneous group of disorders. The concepts presented are based on current evidence, but the template provided allows for further refinements as etiological advances come to light.

Number of episodes in bipolar disorder: The case for more thoughtful conceptualization and measurement.

OBJECTIVES: Number of mood episodes (NoE) may be an important prognostic indicator in bipolar disorder, with implications for treatment. However, NoE has been conceptualized and measured inconsistently throughout the literature. This review examines the construct of NoE in bipolar disorder, with the aim of enhancing its conceptualization and measurement. METHODS: A critical evaluation of literatures on important correlates of NoE, conceptually and phenomenologically overlapping features, and previous studies considering and measuring this construct was undertaken. RESULTS: The literature indicates that despite frequent use, NoE has been inconsistently defined and measured. Multiple studies have linked NoE with important clinical factors, including relapse, functioning, cognitive impairment and the effectiveness of both pharmacological and psychosocial interventions, yet conclusions are limited by its inconsistent treatment. Additionally, it seems evident that that NoE may best be treated as a fuzzy construct (rather than precise figure), with yet to be defined overlaps with clinical variables such as age at onset and severity. Attempts to measure this construct have varied in comprehensiveness and structure. CONCLUSIONS: The NoE construct may have important implications for individuals with bipolar disorders. However, more consistent and systematic definition and assessment of NoE is required to advance this literature and clarify its role. Recommendations aimed at advancing the conceptualization and the measurement of NoE are provided. Conceptualization may be advanced by considering and exploring relationships between NoE and factors with which it overlaps, while measurement may best be improved with increased consistency and balancing accuracy with feasibility.

The influence of stage of illness on functional outcomes after psychological treatment in bipolar disorder: A systematic review.

OBJECTIVES: The aim of this study was to advance understanding of stage of illness in bipolar disorder (BD), by interrogating the literature for evidence of an influence of stage of illness on functional (ie non-symptom) outcomes following psychosocial intervention. METHODS: A systematic literature search following PRISMA guidelines was conducted to identify empirical studies of psychosocial interventions for established BD. To investigate stage as a predictor of three functional outcomes (general/social functioning, cognitive functioning and quality of life [QoL]), study samples were dichotomised into earlier and later stage using proxy measures identified in existing staging models. Findings were integrated using data-based convergent synthesis. RESULTS: A total of 88 analyses from 62 studies were identified. Synthesis across studies suggested that psychosocial intervention was more likely to be effective for general functioning outcomes earlier in the course of established BD. No stage-related differences were found for cognitive or QoL outcomes. Exploratory investigations found some evidence of an interaction between specific intervention type and stage of illness in predicting outcomes. CONCLUSIONS: A novel systematic review provided preliminary evidence that benefits general/social functioning may be more pronounced in earlier versus later stages of established BD. The review also generated hypotheses about a potential three-way interaction, whereby specific psychosocial interventions may be best placed to target functional outcomes in earlier versus later stage BD. The strength of conclusions is limited by the overall low-quality and significant heterogeneity of studies. Further research is urgently required to understand the impact of illness stage on the effectiveness of psychosocial interventions.

Online interventions for cannabis use among adolescents and young adults: Systematic review and meta-analysis.

BACKGROUND: Young people present high rates of cannabis use, abuse, and dependence. The United Nations estimates that roughly 3.8% of the global population aged 15-64 years used cannabis at least once in 2017. Cannabis use in young people may impair cognitive skills, interfere with learning, impact relationships, and lead to long term behavioural and psychological consequences. Online cannabis interventions (OCI) are increasingly popular, but their dissemination is not often supported by empirical evidence. AIM: To systematically compile and analyse the effectiveness of OCI for the reduction of cannabis use among adolescents and young adults (AYA). METHODS: Pooled effect sizes of cannabis use between treatment and control groups were estimated. For each comparison, Hedge's g was calculated using a random effects model. RESULTS: The search strategy yielded 4531 articles. Of those, a total of 411 articles were retrieved for detailed evaluation resulting in 17 eligible studies (n = 3525). Analyses revealed that online interventions did not significantly reduce cannabis consumption (Hedge's g = -0.061, 95% CI [-0.363] to [-0.242], p = .695) and high heterogeneity was noted (Q = 191.290). More recent studies using structured interventions, daily feedback, AYA centred designs, and peer support, specifically targeting CU seemed to have positive effects to address CU in this population. CONCLUSIONS: The lack of positive outcomes suggests that more specific and targeted interventions may be necessary to promote cannabis-related behavioural change among young people. These targeted interventions may include structured CU modules, daily feedback, peer support for increased adherence, user-centred design procedures, and input from key stakeholders such as families and service providers.

The impact of persistent social anxiety on social functioning and health-related quality of life in young people with remitted first-episode psychosis.

OBJECTIVE: Comorbid social anxiety is common in psychotic disorders and is associated with multiple negative consequences. However, the long-term effects of persistent social anxiety versus fluctuating or no anxiety on social functioning and health-related quality of life (HR-QoL) have received scant attention. Therefore, we aimed to examine the prevalence of persistent social anxiety to determine its effect on social functioning and HR-QoL in first-episode psychosis (FEP). METHODS: One hundred and eight individuals with remitted FEP were classified into three groups (persistent, fluctuating or no social anxiety) according to the Social Interaction Anxiety Scale over an 18-month follow-up period. The three groups were then compared at 18 months follow-up to assess the influence of social anxiety on social functioning and HR-QoL before and after controlling for confounders. RESULTS: Of the 108 individuals with FEP, 25 (23.1%) had persistent social anxiety. This group presented lower social functioning and HR-QoL levels compared to the groups with fluctuating or no anxiety symptoms. The effect on HR-QoL remained significant after controlling for positive psychotic and depressive symptoms. CONCLUSIONS: In this study, nearly one-quarter of young people with remitted FEP experienced persistent social anxiety symptoms, which had a negative impact on HR-QoL. Thus, individuals with persistent social anxiety constitute a highly vulnerable group and may require targeted interventions to improve their social functioning and HR-QoL.

The Therapeutic Alliance in Digital Mental Health Interventions for Serious Mental Illnesses: Narrative Review.

BACKGROUND: Digital mental health interventions offer unique advantages, and research indicates that these interventions are effective for a range of mental health concerns. Although these interventions are less established for individuals with serious mental illnesses, they demonstrate significant promise. A central consideration in traditional face-to-face therapies is the therapeutic alliance, whereas the nature of a digital therapeutic alliance and its relationship with outcomes requires further attention, particularly for individuals with serious mental illnesses. OBJECTIVE: This narrative review aims to encourage further consideration and critical evaluation of the therapeutic alliance in digital mental health, specifically for individuals with serious mental illnesses. METHODS: A narrative review was conducted by combining 3 main areas of the literature: the first examining the evidence for digital mental health interventions for serious mental illnesses, the second illuminating the nature and role of the therapeutic alliance in digital interventions, and the third surrounding practical considerations to enhance a digital therapeutic alliance. RESULTS: Results indicated that a therapeutic alliance can be cultivated in digital interventions for those with serious mental illnesses, but that it may have unique, yet-to-be-confirmed characteristics in digital contexts. In addition, a therapeutic alliance appears to be less directly associated with outcomes in digital interventions than with those in face-to-face therapies. One possibility is that the digital therapeutic alliance is associated with increased engagement and adherence to digital interventions, through which it appears to influence outcomes. A number of design and implementation considerations may enhance the digital therapeutic alliance, including human support and technological features. CONCLUSIONS: More research is required to further understand the nature and specific role of a therapeutic alliance in digital interventions for serious mental illnesses, particularly in informing their design. This review revealed several key research priorities to advance the therapeutic alliance in digital interventions.

Prevalence rate of social anxiety disorder in individuals with a psychotic disorder: A systematic review and meta-analysis.

Social anxiety disorder (SAD) is characterised as an excessive fear of negative judgment from others and is considered one of the most disabling of the mental ill health conditions. Research findings indicate that it is also a significant issue for individuals diagnosed with a psychotic disorder, with prevalence rates of social anxiety ranging from 8% to 36%. This study was conducted to address the variance of the reported prevalence rates of comorbid SAD amongst individuals with a psychotic disorder diagnosis. Via a systematic review, we collated all available literature on the prevalence of SAD in individuals with a psychotic disorder, and evaluated the prevalence results via meta-analysis. We also synthesised all psychosocial outcomes attributed to SAD comorbidity and conducted a narrative review of the relevant findings. Across 25 studies providing data from 1980 to May 2018 and spanning 13 countries (N = 92,522), we found a pooled prevalence rate of 21% (16%-26%). In outpatient samples, (17 studies), the prevalence was 25% (19%-31%), statistically significantly higher (z = 5.12, p < .001) than that of the inpatient studies six studies, which was 9% (7%-12%). We also found that SAD comorbidity is associated with increased depression, poorer social function, poorer subjective quality of life, greater negative self-evaluation, and greater insight. The results from this systematic review and meta-analysis suggest that SAD is prevalent amongst individuals with a psychotic disorder. More consistent screening for SAD and the development of theoretically driven and empirically supported tailored treatments are recommended.

Does stage of illness influence recovery-focused outcomes after psychological treatment in bipolar disorder? A systematic review protocol.

BACKGROUND: There is great interest in the possibility that 'stage of illness' moderates treatment outcomes in bipolar disorder (BD). Much remains unknown about the construct of stage of illness, but there is evidence that effectiveness of psychosocial interventions may depend on factors that are plausible proxy measures of stage of illness (e.g., number of episodes). To date, reviews of this data have focused solely on clinical outcomes (particularly symptoms and relapse rates), but a range of recovery-focused outcomes (including functioning, cognitive functioning, and quality of life) have been measured in individuals with established BD. The aim of the proposed systematic review is to synthesise existing evidence for plausible proxy measures of stage of illness as moderators of recovery-focused and functional outcomes in psychosocial treatment studies of BD. METHODS: The proposed review will follow PRISMA guidelines; Scopus, PsychINFO, PubMed and Web of Science will be searched for empirical studies of psychosocial interventions used for established (clinical stages 2-4) BD; and findings will be summarised in a narrative synthesis of clinical stage of illness (operationalised in proxy measures identified in existing staging models) as a moderator of recovery-focused and functional outcomes of psychosocial interventions for established bipolar disorder. DISCUSSION: This review will contribute to the literature by expanding upon previous reviews and potentially inform the psychosocial treatment of established BD. Implications include assisting clinicians, consumers and researchers to identify and select interventions most appropriate to recovery-focused goals based on individuals' clinical status. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016037868.

Circadian modulation of human reward function: Is there an evidentiary signal in existing neuroimaging studies?

Reward functioning in animals is modulated by the circadian system, but such effects are poorly understood in the human case. The aim of this study was to address this deficit via a systematic review of human fMRI studies measuring one or more proxies for circadian function and a neural reward outcome. A narrative synthesis of 15 studies meeting inclusion criteria identified 13 studies that show a circadian impact on the human reward system, with four types of proxy (circadian system biology, downstream circadian rhythms, circadian challenge, and time of day) associated with neural reward activation. Specific reward-related regions/networks subserving this effect included the medial prefrontal cortex, ventral striatum, putamen and default mode network. The circadian effect was observed in measures of both reward anticipation and reward receipt, with more consistent evidence for the latter. Findings are limited by marked heterogeneity across study designs. We encourage a systematic program of research investigating circadian-reward interactions as an adapted biobehavioural feature and as an aetiological mechanism in reward-related pathologies.