The relationship between wearable-derived sleep features and relapse in Major Depressive Disorder.

BACKGROUND: Changes in sleep and circadian function are leading candidate markers for the detection of relapse in Major Depressive Disorder (MDD). Consumer-grade wearable devices may enable remote and real-time examination of dynamic changes in sleep. Fitbit data from individuals with recurrent MDD were used to describe the longitudinal effects of sleep duration, quality, and regularity on subsequent depression relapse and severity. METHODS: Data were collected as part of a longitudinal observational mobile Health (mHealth) cohort study in people with recurrent MDD. Participants wore a Fitbit device and completed regular outcome assessments via email for a median follow-up of 541 days. We used multivariable regression models to test the effects of sleep features on depression outcomes. We considered respondents with at least one assessment of relapse (n = 218) or at least one assessment of depression severity (n = 393). RESULTS: Increased intra-individual variability in total sleep time, greater sleep fragmentation, lower sleep efficiency, and more variable sleep midpoints were associated with worse depression outcomes. Adjusted Population Attributable Fractions suggested that an intervention to increase sleep consistency in adults with MDD could reduce the population risk for depression relapse by up to 22 %. LIMITATIONS: Limitations include a potentially underpowered primary outcome due to the smaller number of relapses identified than expected. CONCLUSION: Our study demonstrates a role for consumer-grade activity trackers in estimating relapse risk and depression severity in people with recurrent MDD. Variability in sleep duration and midpoint may be useful targets for stratified interventions.

Sickness absence and associations with sociodemographic factors, health risk behaviours, occupational stressors and adverse mental health in 40,343 UK police employees.

AIMS: Police employees may experience high levels of stress due to the challenging nature of their work which can then lead to sickness absence. To date, there has been limited research on sickness absence in the police. This exploratory analysis investigated sickness absence in UK police employees. METHODS: Secondary data analyses were conducted using data from the Airwave Health Monitoring Study (2006-2015). Past year sickness absence was self-reported and categorised as none, low (1-5 days), moderate (6-19 days) and long-term sickness absence (LTSA, 20 or more days). Descriptive statistics and multinomial logistic regressions were used to examine sickness absence and exploratory associations with sociodemographic factors, occupational stressors, health risk behaviours, and mental health outcomes, controlling for rank, gender and age. RESULTS: From a sample of 40,343 police staff and police officers, forty-six per cent had no sickness absence within the previous year, 33% had a low amount, 13% a moderate amount and 8% were on LTSA. The groups that were more likely to take sick leave were women, non-uniformed police staff, divorced or separated, smokers and those with three or more general practitioner consultations in the past year, poorer mental health, low job satisfaction and high job strain. CONCLUSIONS: The study highlights the groups of police employees who may be more likely to take sick leave and is unique in its use of a large cohort of police employees. The findings emphasise the importance of considering possible modifiable factors that may contribute to sickness absence in UK police forces.

The association between persistent cognitive difficulties and depression and functional outcomes in people with major depressive disorder.

BACKGROUND: Cognitive symptoms are common during and following episodes of depression. Little is known about the persistence of self-reported and performance-based cognition with depression and functional outcomes. METHODS: This is a secondary analysis of a prospective naturalistic observational clinical cohort study of individuals with recurrent major depressive disorder (MDD; N = 623). Participants completed app-based self-reported and performance-based cognitive function assessments alongside validated measures of depression, functional disability, and self-esteem every 3 months. Participants were followed-up for a maximum of 2-years. Multilevel hierarchically nested modelling was employed to explore between- and within-participant variation over time to identify whether persistent cognitive difficulties are related to levels of depression and functional impairment during follow-up. RESULTS: 508 individuals (81.5%) provided data (mean age: 46.6, s.d.: 15.6; 76.2% female). Increasing persistence of self-reported cognitive difficulty was associated with higher levels of depression and functional impairment throughout the follow-up. In comparison to low persistence of objective cognitive difficulty (<25% of timepoints), those with high persistence (>75% of timepoints) reported significantly higher levels of depression (B = 5.17, s.e. = 2.21, p = 0.019) and functional impairment (B = 4.82, s.e. = 1.79, p = 0.002) over time. Examination of the individual cognitive modules shows that persistently impaired executive function is associated with worse functioning, and poor processing speed is particularly important for worsened depressive symptoms. CONCLUSIONS: We replicated previous findings of greater persistence of cognitive difficulty with increasing severity of depression and further demonstrate that these cognitive difficulties are associated with pervasive functional disability. Difficulties with cognition may be an indicator and target for further treatment input.

The usability of daytime and night-time heart rate dynamics as digital biomarkers of depression severity.

BACKGROUND: Alterations in heart rate (HR) may provide new information about physiological signatures of depression severity. This 2-year study in individuals with a history of recurrent major depressive disorder (MDD) explored the intra-individual variations in HR parameters and their relationship with depression severity. METHODS: Data from 510 participants (Number of observations of the HR parameters = 6666) were collected from three centres in the Netherlands, Spain, and the UK, as a part of the remote assessment of disease and relapse-MDD study. We analysed the relationship between depression severity, assessed every 2 weeks with the Patient Health Questionnaire-8, with HR parameters in the week before the assessment, such as HR features during all day, resting periods during the day and at night, and activity periods during the day evaluated with a wrist-worn Fitbit device. Linear mixed models were used with random intercepts for participants and countries. Covariates included in the models were age, sex, BMI, smoking and alcohol consumption, antidepressant use and co-morbidities with other medical health conditions. RESULTS: Decreases in HR variation during resting periods during the day were related with an increased severity of depression both in univariate and multivariate analyses. Mean HR during resting at night was higher in participants with more severe depressive symptoms. CONCLUSIONS: Our findings demonstrate that alterations in resting HR during all day and night are associated with depression severity. These findings may provide an early warning of worsening depression symptoms which could allow clinicians to take responsive treatment measures promptly.

Patient preferences for key drivers and facilitators of adoption of mHealth technology to manage depression: A discrete choice experiment.

BACKGROUND: In time, we may be able to detect the early onset of symptoms of depression and even predict relapse using behavioural data gathered through mobile technologies. However, barriers to adoption exist and understanding the importance of these factors to users is vital to ensure maximum adoption. METHOD: In a discrete choice experiment, people with a history of depression (N = 171) were asked to select their preferred technology from a series of vignettes containing four characteristics: privacy, clinical support, established benefit and device accuracy (i.e., ability to detect symptoms), with different levels. Mixed logit models were used to establish what was most likely to affect adoption. Sub-group analyses explored effects of age, gender, education, technology acceptance and familiarity, and nationality. RESULTS: Higher level of privacy, greater clinical support, increased perceived benefit and better device accuracy were important. Accuracy was the most important, with only modest compromises willing to be made to increase other factors such as privacy. Established benefit was the least valued of the attributes with participants happy with technology that had possible but unknown benefits. Preferences were moderated by technology acceptance, age, nationality, and educational background. CONCLUSION: For people with a history of depression, adoption of technology may be driven by the desire for accurate detection of symptoms. However, people with lower technology acceptance and educational attainment, those who were younger, and specific nationalities may be willing to compromise on some accuracy for more privacy and clinical support. These preferences should help shape design of mHealth tools.

Depression, anxiety and PTSD symptoms before and during the COVID-19 pandemic in the UK.

BACKGROUND: The impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health is still being unravelled. It is important to identify which individuals are at greatest risk of worsening symptoms. This study aimed to examine changes in depression, anxiety and post-traumatic stress disorder (PTSD) symptoms using prospective and retrospective symptom change assessments, and to find and examine the effect of key risk factors. METHOD: Online questionnaires were administered to 34 465 individuals (aged 16 years or above) in April/May 2020 in the UK, recruited from existing cohorts or via social media. Around one-third (n = 12 718) of included participants had prior diagnoses of depression or anxiety and had completed pre-pandemic mental health assessments (between September 2018 and February 2020), allowing prospective investigation of symptom change. RESULTS: Prospective symptom analyses showed small decreases in depression (PHQ-9: -0.43 points) and anxiety [generalised anxiety disorder scale - 7 items (GAD)-7: -0.33 points] and increases in PTSD (PCL-6: 0.22 points). Conversely, retrospective symptom analyses demonstrated significant large increases (PHQ-9: 2.40; GAD-7 = 1.97), with 55% reported worsening mental health since the beginning of the pandemic on a global change rating. Across both prospective and retrospective measures of symptom change, worsening depression, anxiety and PTSD symptoms were associated with prior mental health diagnoses, female gender, young age and unemployed/student status. CONCLUSIONS: We highlight the effect of prior mental health diagnoses on worsening mental health during the pandemic and confirm previously reported sociodemographic risk factors. Discrepancies between prospective and retrospective measures of changes in mental health may be related to recall bias-related underestimation of prior symptom severity.

COVID-19 ethnic inequalities in mental health and multimorbidities: protocol for the COVEIMM study.

PURPOSE: The COVID-19 pandemic may have exacerbated ethnic health inequalities, particularly in people with multiple long-term health conditions, the interplay with mental health is unclear. This study investigates the impact of the pandemic on the association of ethnicity and multimorbidity with mortality/service use among adults, in people living with severe mental illnesses (SMI). METHODS: This study will utilise secondary mental healthcare records via the Clinical Record Interactive Search (CRIS) and nationally representative primary care records through the Clinical Practice Interactive Research Database (CPRD). Quasi-experimental designs will be employed to quantify the impact of COVID-19 on mental health service use and excess mortality by ethnicity, in people living with severe mental health conditions. Up to 50 qualitative interviews will also be conducted, co-produced with peer researchers; findings will be synthesised with quantitative insights to provide in-depth understanding of observed associations. RESULTS: 81,483 people in CRIS with schizophrenia spectrum, bipolar or affective disorder diagnoses, were alive from 1st January 2019. Psychiatric multimorbidities in the CRIS sample were comorbid somatoform disorders (30%), substance use disorders (14%) and personality disorders (12%). In CPRD, of 678,842 individuals with a prior probable diagnosis of COVID-19, 1.1% (N = 7493) had an SMI diagnosis. People in the SMI group were more likely to die (9% versus 2% in the non-SMI sample) and were more likely to have mental and physical multimorbidities. CONCLUSION: The effect of COVID-19 on people from minority ethnic backgrounds with SMI and multimorbidities remains under-studied. The present mixed methods study aims to address this gap.

Predictors of engagement with remote sensing technologies for symptom measurement in Major Depressive Disorder.

BACKGROUND: Remote sensing for the measurement and management of long-term conditions such as Major Depressive Disorder (MDD) is becoming more prevalent. User-engagement is essential to yield any benefits. We tested three hypotheses examining associations between clinical characteristics, perceptions of remote sensing, and objective user engagement metrics. METHODS: The Remote Assessment of Disease and Relapse - Major Depressive Disorder (RADAR-MDD) study is a multicentre longitudinal observational cohort study in people with recurrent MDD. Participants wore a FitBit and completed app-based assessments every two weeks for a median of 18 months. Multivariable random effects regression models pooling data across timepoints were used to examine associations between variables. RESULTS: A total of 547 participants (87.8% of the total sample) were included in the current analysis. Higher levels of anxiety were associated with lower levels of perceived technology ease of use; increased functional disability was associated with small differences in perceptions of technology usefulness and usability. Participants who reported higher system ease of use, usefulness, and acceptability subsequently completed more app-based questionnaires and tended to wear their FitBit activity tracker for longer. All effect sizes were small and unlikely to be of practical significance. LIMITATIONS: Symptoms of depression, anxiety, functional disability, and perceptions of system usability are measured at the same time. These therefore represent cross-sectional associations rather than predictions of future perceptions. CONCLUSIONS: These findings suggest that perceived usability and actual use of remote measurement technologies in people with MDD are robust across differences in severity of depression, anxiety, and functional impairment.

Chronic fatigue syndrome and occupational status: a retrospective longitudinal study.

BACKGROUND: Few studies into chronic fatigue syndrome (CFS) have emphasized work-related consequences, including return to work after illness. AIMS: This paper explores socio-demographic, work and clinical characteristics that are associated with occupational status among patients who were assessed at baseline and a follow-up point. METHODS: Longitudinal data were assessed from patients affected by CFS who attended an outpatient CFS treatment service between 2007 and 2014. Employment status at baseline and follow-up was available for 316 patients. Data were also included on gender, age, duration of CFS, fatigue severity, type and number of treatment sessions, coping strategies, functional impairment, common mental disorders and physical functioning. RESULTS: Most patients were female (73%) and had been affected by CFS for longer than 2 years (66%). Patients were followed up for an average of 285 days and over this period 53% of patients who were working remained in employment. Of the patients who were not working at baseline, 9% had returned to work at follow-up. However, of those working at baseline, 6% were unable to continue to work at follow-up. Age, fatigue severity, functional impairment, cognitive and behavioural responses, and depressive symptoms impacted on a patients' work status at follow-up. CONCLUSIONS: The findings indicated that it is possible for people with CFS to remain in work or return to work, despite having had a disabling illness. Work-related outcomes should be targeted in all people of working age.

Variation in rates of self-harm hospital admission and re-admission by ethnicity in London: a population cohort study.

PURPOSE: To compare sex-specific rates of hospital admission and repeat admission following self-harm between ethnic groups in London and test whether differences persist after adjustment for socio-economic deprivation. METHODS: A population-based cohort of all individuals aged over 11 admitted to a general hospital for physical health treatment following self-harm between 2008 and 2018, using administrative Hospital Episode Statistics for all people living in Greater London. RESULTS: There were 59,510 individuals admitted to the hospital following self-harm in the 10 year study period, ethnicity data were available for 94% of individuals. The highest rates of self-harm admission and readmission were found in the White Irish group. Rates of admission and readmission were lower in Black and Asian people compared to White people for both sexes at all ages and in all more specific Black and Asian ethnic groups compared to White British. These differences increased with adjustment for socio-economic deprivation. People of Mixed ethnicity had higher rates of readmission. Rates were highest in the 25-49 age group for Black and Mixed ethnicity men, but in under-25 s for all other groups. There were substantial differences in rates within the broader ethnic categories, especially for the Black and White groups. CONCLUSION: In contrast to earlier UK studies, self-harm rates were not higher in Black or South Asian women, with lower self-harm admission rates seen in almost all ethnic minority groups. Differences in rates by ethnicity were not explained by socio-economic deprivation. Aggregating ethnicity into broad categories masks important differences in self-harm rates between groups.

Time-dependent cognitive and somatic symptoms of depression as predictors of new cardiac-related events in at-risk patients: the UPBEAT-UK cohort.

BACKGROUND: Evidence suggests that somatic rather than cognitive depressive symptoms are risk factors for recurrent cardiac events in at-risk patients. However, this has never been explored using a time-dependent approach in a narrow time-frame, allowing a cardiac event-free time-window. METHODS: The analysis was performed on 595 participants [70.6% male, median age 72 (27-98)] drawn from the UPBEAT-UK heart disease patient cohort with 6-monthly follow-ups over 3 years. Depressive symptomatology was measured using the Patient Health Questionnaire-9 (PHQ-9) (four somatic, five cognitive items). New cardiac events (NCEs) including cardiac-related mortality were identified by expert examination of patient records. Analyses were performed using Cox proportional hazard models with delayed entry, with time-dependent depressive dimensions and covariates measured 12-18 months (median: 14.1, IQR: 3.5) prior to the event, with a 12-month cardiac event-free gap. RESULTS: There were 95 NCEs during the follow-up [median time-to-event from baseline: 22.3 months (IQR: 13.4)]. Both the somatic (HR 1.12, 95% CI 1.05-1.20, p = 0.001) and cognitive dimensions (HR 1.11, 95% CI 1.03-1.18, p = 0.004) were time-dependent risk factors for an NCE in the multi-adjusted models. Specific symptoms (poor appetite/overeating for the somatic dimension, hopelessness and feeling like a failure for the cognitive dimension) were also significantly associated. CONCLUSION: This is the first study of the association between depressive symptom dimensions and NCEs in at-risk patients using a time-to-event standardised approach. Both dimensions considered apart were independent predictors of an NCE, along with specific items, suggesting regular assessments and tailored interventions targeting specific depressive symptoms may help to prevent NCEs in at-risk populations.

Invited Review: The spectrum of neuropathology in COVID-19.

There is increasing evidence that patients with Coronavirus disease 19 (COVID-19) present with neurological and psychiatric symptoms. Anosmia, hypogeusia, headache, nausea and altered consciousness are commonly described, although there are emerging clinical reports of more serious and specific conditions such as acute cerebrovascular accident, encephalitis and demyelinating disease. Whether these presentations are directly due to viral invasion of the central nervous system (CNS) or caused by indirect mechanisms has yet to be established. Neuropathological examination of brain tissue at autopsy will be essential to establish the neuro-invasive potential of the SARS-CoV-2 virus but, to date, there have been few detailed studies. The pathological changes in the brain probably represent a combination of direct cytopathic effects mediated by SARS-CoV-2 replication or indirect effects due to respiratory failure, injurious cytokine reaction, reduced immune response and cerebrovascular accidents induced by viral infection. Further large-scale molecular and cellular investigations are warranted to clarify the neuropathological correlates of the neurological and psychiatric features seen clinically in COVID-19. In this review, we summarize the current reports of neuropathological examination in COVID-19 patients, in addition to our own experience, and discuss their contribution to the understanding of CNS involvement in this disease.

Depressive and anxiety symptomatology among people with asthma or atopic dermatitis: A population-based investigation using the UK Biobank data.

The present study investigated the association of depression and anxiety symptomatology (DAS) with asthma and atopic dermatitis (AD) diagnosis during mid-adult years. The study employed data from 502,641 participants in the UK Biobank. Neutrophils to Lymphocytes Ratios (NLRs) of patients with asthma and AD were calculated and evaluated in relation to DAS, measured via the Patient Health Questionnaire-4 (PHQ-4). Age of asthma or AD onset association with DAS were also estimated. Multivariable regression analyses were implemented among participants with asthma or AD, compared to those without these disorders. Out of 58,833 participants with asthma and 13,462 with AD, the prevalence of DAS was 11.7% and 2.7%, respectively. DAS increased among participants with either asthma or AD, being highest within patients having both (ß = 0.41, 95% confidence interval (95%CI), 0.34,0.49). NLR showed a linear increase with PHQ scores in asthma patients, (tertile 1, ß = 0.30, 95% CI, 0.27,0.34; tertile 2, ß = 0.36, 95%CI, 0.32,0.39, and tertile 3, ß = 0.43, 95%CI, 0.39,0.46). An inverted U-shaped association was seen between age of asthma onset and PHQ, with the 40-59 age group (ß = 0.54, 95%CI, 0.48,0.59) showing the highest risk followed by the 60+ (ß = 0.43, 95%CI, 0.34,0.51 and 20-39 groups (ß = 0.32, 95%CI, 0.27,0.38). Similar patterns emerged within AD. Asthma and AD were associated with increased DAS during mid-adult years, being strongest among participants reporting both disorders. A dose-response relationship between NLR and DAS was observed. Asthma or AD onset during mid-adult years (40-59) were associated with the highest increment in DAS.

Processes of consent in research for adults with impaired mental capacity nearing the end of life: systematic review and transparent expert consultation (MORECare_Capacity statement).

BACKGROUND: Involving adults lacking capacity (ALC) in research on end of life care (EoLC) or serious illness is important, but often omitted. We aimed to develop evidence-based guidance on how best to include individuals with impaired capacity nearing the end of life in research, by identifying the challenges and solutions for processes of consent across the capacity spectrum. METHODS: Methods Of Researching End of Life Care_Capacity (MORECare_C) furthers the MORECare statement on research evaluating EoLC. We used simultaneous methods of systematic review and transparent expert consultation (TEC). The systematic review involved four electronic databases searches. The eligibility criteria identified studies involving adults with serious illness and impaired capacity, and methods for recruitment in research, implementing the research methods, and exploring public attitudes. The TEC involved stakeholder consultation to discuss and generate recommendations, and a Delphi survey and an expert 'think-tank' to explore consensus. We narratively synthesised the literature mapping processes of consent with recruitment outcomes, solutions, and challenges. We explored recommendation consensus using descriptive statistics. Synthesis of all the findings informed the guidance statement. RESULTS: Of the 5539 articles identified, 91 met eligibility. The studies encompassed people with dementia (27%) and in palliative care (18%). Seventy-five percent used observational designs. Studies on research methods (37 studies) focused on processes of proxy decision-making, advance consent, and deferred consent. Studies implementing research methods (30 studies) demonstrated the role of family members as both proxy decision-makers and supporting decision-making for the person with impaired capacity. The TEC involved 43 participants who generated 29 recommendations, with consensus that indicated. Key areas were the timeliness of the consent process and maximising an individual's decisional capacity. The think-tank (n = 19) refined equivocal recommendations including supporting proxy decision-makers, training practitioners, and incorporating legislative frameworks. CONCLUSIONS: The MORECare_C statement details 20 solutions to recruit ALC nearing the EoL in research. The statement provides much needed guidance to enrol individuals with serious illness in research. Key is involving family members early and designing study procedures to accommodate variable and changeable levels of capacity. The statement demonstrates the ethical imperative and processes of recruiting adults across the capacity spectrum in varying populations and settings.

Prevalence and duration of gastrointestinal symptoms before diagnosis of Inflammatory Bowel Disease and predictors of timely specialist review: a population-based study.

BACKGROUND AND AIMS: Lack of timely referral and significant waits for specialist review amongst individuals with unresolved gastrointestinal (GI) symptoms can result in delayed diagnosis of Inflammatory Bowel Disease (IBD). AIMS: To determine the frequency and duration of GI symptoms and predictors of timely specialist review before the diagnosis of both Crohn's Disease (CD) and ulcerative colitis (UC). METHODS: Case-control study of IBD matched 1:4 for age and sex to controls without IBD using the Clinical Practice Research Datalink from 1998-2016. RESULTS: We identified 19,555 cases of IBD, and 78,114 controls. 1 in 4 cases of IBD reported gastrointestinal symptoms to their primary care physician more than 6 months before receiving a diagnosis. There is a significant excess prevalence of GI symptoms in each of the 10 years before IBD diagnosis. GI symptoms were reported by 9.6% and 10.4% at 5 years before CD and UC diagnosis respectively compared to 5.8% of controls. Amongst patients later diagnosed with IBD, <50% received specialist review within 18 months from presenting with chronic GI symptoms. Patients with a previous diagnosis of irritable bowel syndrome or depression were less likely to receive timely specialist review (IBS: HR=0.77, 95%CI 0.60-0.99, depression: HR=0.77, 95%CI 0.60-0.98). CONCLUSIONS: There is an excess of GI symptoms 5 years before diagnosis of IBD compared to the background population which are likely attributable to undiagnosed disease. Previous diagnoses of IBS and depression are associated with delays in specialist review. Enhanced pathways are needed to accelerate specialist referral and timely IBD diagnosis.

Factors associated with work status in chronic fatigue syndrome.

BACKGROUND: Work status in people with chronic fatigue syndrome (CFS) has not been extensively researched. AIMS: To explore occupational outcomes in patients with CFS by socio-demographic, well-being and disease characteristics. METHODS: We assessed cross-sectional data from patients attending a UK specialist CFS treatment service between 1 January 2007 and 31 December 2014. The main outcome was self-reported current employment status: currently in employment, temporarily interrupted employment or permanently interrupted employment. Other variables included sex, age, ethnicity, education, marital status, CFS duration, fatigue severity, anxiety, depression, activity limitations and functional impairment. We used multinominal logistic regression models to identify factors associated with current work status. RESULTS: Two hundred and seventy-nine (55%) patients were currently working, with 83 (16%) reporting temporarily interrupted employment and 146 (29%) stopping work altogether. Factors strongly associated with permanently interrupted employment were older age (adjusted odds ratio (AOR) 5.24; 95% CI 2.67-10.28), poorer functioning (AOR 6.41; 95% CI 3.65-11.24) and depressive symptoms (AOR 2.89; 95% CI 1.82-4.58) compared to patients currently working. Higher educated patients (AOR 0.60; 95% CI 0.37-0.97) and being in a relationship (AOR 0.34; 95% CI 0.21-0.54) were associated with being currently employed. Anxiety symptoms were common; 230 patients (45%) met caseness criteria. CONCLUSIONS: Many patients with CFS were not working. This was exacerbated by high levels of depressive symptoms. Health professionals should assess co-morbid mental health conditions and consider treatment options when patients with CFS present themselves. The early involvement of occupational health practitioners is recommended to maximize the chances of maintaining employment.

Emotional outcomes in clinically isolated syndrome and early phase multiple sclerosis: a systematic review and meta-analysis.

OBJECTIVE: To study depression, anxiety, suicide risk, and emotional health-related quality of life (HRQoL) in people with clinically isolated syndrome (CIS) and in early phase multiple sclerosis (MS). METHODS: A systematic literature review was conducted with inclusion criteria of observational studies on outcomes of depression, anxiety, suicide risk, and emotional HRQoL in CIS and within five years since diagnosis of MS. Studies were screened using the Preferred Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, and study quality was determined for included studies. Meta-analysis and meta-regression were performed if applicable. RESULTS: Fifty-one studies were included in the systematic review. In early phase MS, meta-analyses of the Hospital Anxiety Depression Scale (HADS) indicated prevalence levels of 17% (95% confidence interval (CI): 9 to 25%; p < .001) for depressive and 35% (95% CI: 28 to 41%; p < .001) for anxiety symptoms. Meta-regression analyses revealed an increase in mean HADS-D and HADS-A associated with larger sample size, and higher HADS-D mean with increased study quality. Similar depressive and anxiety symptoms were observed in CIS, and increased suicide risk and low emotional HRQoL was associated with depressive symptoms in early phase MS. The methodological quality of the studies was considered fair. CONCLUSIONS: Findings suggest that mild-to-moderate symptoms of depression and anxiety might be prevalent in CIS and in early phase MS. Future research on both clinical populations are needed, especially longitudinal monitoring of emotional outcomes.

Remote assessment of disease and relapse in major depressive disorder (RADAR-MDD): a multi-centre prospective cohort study protocol.

BACKGROUND: There is a growing body of literature highlighting the role that wearable and mobile remote measurement technology (RMT) can play in measuring symptoms of major depressive disorder (MDD). Outcomes assessment typically relies on self-report, which can be biased by dysfunctional perceptions and current symptom severity. Predictors of depressive relapse include disrupted sleep, reduced sociability, physical activity, changes in mood, prosody and cognitive function, which are all amenable to measurement via RMT. This study aims to: 1) determine the usability, feasibility and acceptability of RMT; 2) improve and refine clinical outcome measurement using RMT to identify current clinical state; 3) determine whether RMT can provide information predictive of depressive relapse and other critical outcomes. METHODS: RADAR-MDD is a multi-site prospective cohort study, aiming to recruit 600 participants with a history of depressive disorder across three sites: London, Amsterdam and Barcelona. Participants will be asked to wear a wrist-worn activity tracker and download several apps onto their smartphones. These apps will be used to either collect data passively from existing smartphone sensors, or to deliver questionnaires, cognitive tasks, and speech assessments. The wearable device, smartphone sensors and questionnaires will collect data for up to 2-years about participants' sleep, physical activity, stress, mood, sociability, speech patterns, and cognitive function. The primary outcome of interest is MDD relapse, defined via the Inventory of Depressive Symptomatology- Self-Report questionnaire (IDS-SR) and the World Health Organisation's self-reported Composite International Diagnostic Interview (CIDI-SF). DISCUSSION: This study aims to provide insight into the early predictors of major depressive relapse, measured unobtrusively via RMT. If found to be acceptable to patients and other key stakeholders and able to provide clinically useful information predictive of future deterioration, RMT has potential to change the way in which depression and other long-term conditions are measured and managed.

Longitudinal patterns of mental health service utilisation by those with mental-physical comorbidity in the community.

OBJECTIVE: Successful healthcare integration demands an understanding of current service utilisation by people with comorbidity. Physical illness may impact on mental health service use (MHSU), but longitudinal studies of comorbidity and MHSU are rare. This study 1) estimated associations between mental-physical comorbidity and longitudinal MHSU patterns; 2) tested whether associations between comorbidity and continuous MHSU are driven by "need". METHODS: Survey data from a South East London community cohort were used (N = 1052). Common mental disorder symptoms (CMDS) were measured using the Clinical Interview Schedule Revised and self-report of long-standing disorders. A checklist of common conditions measured chronic physical conditions. MHSU captured self-reported use of mental health services in the past year at two time points. "Need" indicators included CMDS at follow-up, suicidal ideation, somatic symptom severity, self-rated health, daily functioning problems and perceived functioning limitations due to emotional health. Analyses used logistic and multinomial regression. RESULTS: Continuous MHSU (at both time-points) was twice as commonly reported by those with comorbidity than those without physical comorbidity (30.9% vs 12.3%). CMDS at follow-up, suicidal ideation, and perceived functioning limitations due to emotional health only partially explained the association between CMDS-physical comorbidity and continuous MHSU. In the adjusted model, comorbidity remained associated with continuous MHSU (RRR = 3.23, 95% CI: 1.39-7.51; p = .002), while the association for non-comorbid CMDS was fully attenuated (RRR = 1.08, 95% CI: 0.40-2.93; p = .85). CONCLUSION: CMDS-physical comorbidity was strongly associated with continuous MHSU, and "need" did not account for this association, suggesting that comorbidity itself represents a "need" indicator.

Childhood abuse and psychotic experiences - evidence for mediation by adulthood adverse life events.

AIMS: We have previously reported an association between childhood abuse and psychotic experiences (PEs) in survey data from South East London. Childhood abuse is related to subsequent adulthood adversity, which could form one pathway to PEs. We aimed to investigate evidence of mediation of the association between childhood abuse and PEs by adverse life events. METHODS: Data were analysed from the South East London Community Health Study (SELCoH, n = 1698). Estimates of the total effects on PEs of any physical or sexual abuse while growing up were partitioned into direct (i.e. unmediated) and indirect (total and specific) effects, mediated via violent and non-violent life events. RESULTS: There was strong statistical evidence for direct (OR 1.58, 95% CI: 1.19-2.1) and indirect (OR 1.51, 95% CI: 1.32-1.72) effects of childhood abuse on PEs after adjustment for potential confounders, indicating partial mediation of this effect via violent and non-violent life events. An estimated 47% of the total effect of abuse on PEs was mediated via adulthood adverse life events, of which violent life events made up 33% and non-violent life events the remaining 14%. CONCLUSIONS: The association between childhood abuse and PEs is partly mediated through the experience of adverse life events in adulthood. There is some evidence that a larger proportion of this effect was mediated through violent life events than non-violent life events.