Role of Inflammation in Short Sleep Duration Across Childhood and Psychosis in Young Adulthood.

Importance: Short sleep duration over a prolonged period in childhood could have a detrimental impact on long-term mental health, including the development of psychosis. Further, potential underlying mechanisms of these associations remain unknown. Objective: To examine the association between persistent shorter nighttime sleep duration throughout childhood with psychotic experiences (PEs) and/or psychotic disorder (PD) at age 24 years and whether inflammatory markers (C-reactive protein [CRP] and interleukin 6 [IL-6]) potentially mediate any association. Design, Setting, and Participants: This cohort study used data from the Avon Longitudinal Study of Parents and Children. Data analysis was conducted from January 30 to August 1, 2023. Exposures: Nighttime sleep duration was collected at 6, 18, and 30 months and at 3.5, 4 to 5, 5 to 6, and 6 to 7 years. Main Outcomes and Measures: PEs and PD were assessed at age 24 years from the Psychosislike Symptoms Interview. CRP level at ages 9 and 15 years and IL-6 level at 9 years were used as mediators. Latent class growth analyses (LCGAs) were applied to detect trajectories of nighttime sleep duration, and logistic regressions were applied for the longitudinal associations between trajectories of nighttime sleep duration and psychotic outcomes at 24 years. Path analyses were applied to test CRP and IL-6 as potential mediators. Results: Data were available on 12 394 children (6254 female [50.5%]) for the LCGA and on 3962 young adults (2429 female [61.3%]) for the logistic regression and path analyses. The LCGA identified a group of individuals with persistent shorter nighttime sleep duration across childhood. These individuals were more likely to develop PD (odds ratio [OR], 2.50; 95% CI, 1.51-4.15; P < .001) and PEs (OR, 3.64; 95% CI, 2.23-5.95; P < .001) at age 24 years. Increased levels of IL-6 at 9 years, but not CRP at 9 or 15 years, partially mediated the associations between persistent shorter sleep duration and PD (bias-corrected estimate = 0.003; 95% CI, 0.002-0.005; P = .007) and PEs (bias-corrected estimate = 0.002; 95% CI, 0-0.003; P = .03) in young adulthood. Conclusions and Relevance: Findings of this cohort study highlight the necessity of addressing short sleep duration in children, as persistence of this sleep problem was associated with subsequent psychosis. This study also provides preliminary evidence for future targeted interventions in children addressing both sleep and inflammatory responses.

Shorter night-time sleep duration and later sleep timing from infancy to adolescence.

BACKGROUND: Here, we (a) examined the trajectories of night-time sleep duration, bedtime and midpoint of night-time sleep (MPS) from infancy to adolescence, and (b) explored perinatal risk factors for persistent poor sleep health. METHODS: This study used data from 12,962 participants in the Avon Longitudinal Study of Parents and Children (ALSPAC). Parent or self-reported night-time sleep duration, bedtime and wake-up time were collected from questionnaires at 6, 18 and 30 months, and at 3.5, 4-5, 5-6, 6-7, 9, 11 and 15-16 years. Child's sex, birth weight, gestational age, health and temperament, together with mother's family adversity index (FAI), age at birth, prenatal socioeconomic status and postnatal anxiety and depression, were included as risk factors for persistent poor sleep health. Latent class growth analyses were applied first to detect trajectories of night-time sleep duration, bedtime and MPS, and we then applied logistic regressions for the longitudinal associations between risk factors and persistent poor sleep health domains. RESULTS: We obtained four trajectories for each of the three sleep domains. In particular, we identified a trajectory characterized by persistent shorter sleep, a trajectory of persistent later bedtime and a trajectory of persistent later MPS. Two risk factors were associated with the three poor sleep health domains: higher FAI with increased risk of persistent shorter sleep (OR = 1.20, 95% CI = 1.11-1.30, p < .001), persistent later bedtime (OR = 1.28, 95% CI = 1.19-1.39, p < .001) and persistent later MPS (OR = 1.30, 95% CI = 1.22-1.38, p < .001); and higher maternal socioeconomic status with reduced risk of persistent shorter sleep (OR = 0.99, 95% CI = 0.98-1.00, p = .048), persistent later bedtime (OR = 0.98, 95% CI = 0.97-0.99, p < .001) and persistent later MPS (OR = 0.99, 95% CI = 0.98-0.99, p < .001). CONCLUSIONS: We detected trajectories of persistent poor sleep health (i.e. shorter sleep duration, later bedtime and later MPS) from infancy to adolescence, and specific perinatal risk factors linked to persistent poor sleep health domains.

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.

Randomised controlled trial of the Community Navigator programme to reduce loneliness and depression for adults with treatment-resistant depression in secondary community mental health services: trial protocol.

BACKGROUND: New treatments are needed for people with treatment-resistant depression (TRD), who do not benefit from anti-depressants and many of whom do not recover fully with psychological treatments. The Community Navigator programme was co-produced with service users and practitioners. It is a novel social intervention which aims to reduce loneliness and thus improve health outcomes for people with TRD. Participants receive up to 10 individual meetings with a Community Navigator, who helps them to map their social world and set and enact goals to enhance their social connections and reduce loneliness. Participants may also access group meet-ups with others in the programme every 2 months, and may be offered modest financial support to enable activities to support social connections. METHODS: A researcher-blind, multi-site, 1:1 randomised controlled trial with N = 306 participants will test the effectiveness of the Community Navigator programme for people with TRD in secondary community mental health teams (CMHTs). Our primary hypothesis is that people who are offered the Community Navigator programme as an addition to usual CMHT care will be less depressed, assessed using the PHQ-9 self-report measure, at 8-month, end-of-treatment follow-up, compared to a control group receiving usual CMHT care and a booklet with information about local social groups and activities. We will follow participants up at end-of-treatment and at 14 months, 6 months after end-of-treatment follow-up. Secondary outcomes include the following: loneliness, anxiety, personal recovery, self-efficacy, social network, social identities. We will collect data about health-related quality of life and service use to investigate the cost-effectiveness of the Community Navigator programme. DISCUSSION: This trial will provide definitive evidence about the effectiveness and cost-effectiveness of the Community Navigator programme and whether it can be recommended for use in practice. The trial is due to finish in August 2025. TRIAL REGISTRATION: Prospectively registered on 8th July 2022 at: ISRCTN13205972.

Digital Training Program for Line Managers (Managing Minds at Work): Protocol for a Feasibility Pilot Cluster Randomized Controlled Trial.

BACKGROUND: Mental health problems affect 1 in 6 workers annually and are one of the leading causes of sickness absence, with stress, anxiety, and depression being responsible for half of all working days lost in the United Kingdom. Primary interventions with a preventative focus are widely acknowledged as the priority for workplace mental health interventions. Line managers hold a primary role in preventing poor mental health within the workplace and, therefore, need to be equipped with the skills and knowledge to effectively carry out this role. However, most previous intervention studies have directly focused on increasing line managers' understanding and awareness of mental health rather than giving them the skills and competencies to take a proactive preventative approach in how they manage and design work. The Managing Minds at Work (MMW) digital training intervention was collaboratively designed to address this gap. The intervention aims to increase line managers' knowledge and confidence in preventing work-related stress and promoting mental health at work. It consists of 5 modules providing evidence-based interactive content on looking after your mental health, designing and managing work to promote mental well-being, management competencies that prevent work-related stress, developing a psychologically safe workplace, and having conversations about mental health at work. OBJECTIVE: The primary aim of this study is to pilot and feasibility test MMW, a digital training intervention for line managers. METHODS: We use a cluster randomized controlled trial design consisting of 2 arms, the intervention arm and a 3-month waitlist control, in this multicenter feasibility pilot study. Line managers in the intervention arm will complete a baseline questionnaire at screening, immediately post intervention (approximately 6 weeks after baseline), and at 3- and 6-month follow-ups. Line managers in the control arm will complete an initial baseline questionnaire, repeated after 3 months on the waitlist. They will then be granted access to the MMW intervention, following which they will complete the questionnaire post intervention. The direct reports of the line managers in both arms of the trial will also be invited to take part by completing questionnaires at baseline and follow-up. As a feasibility pilot study, a formal sample size is not required. A minimum of 8 clusters (randomized into 2 groups of 4) will be sought to inform a future trial from work organizations of different types and sectors. RESULTS: Recruitment for the study closed in January 2022. Overall, 24 organizations and 224 line managers have been recruited. Data analysis was finished in August 2023. CONCLUSIONS: The results from this feasibility study will provide insight into the usability and acceptability of the MMW intervention and its potential for improving line manager outcomes and those of their direct reports. These results will inform the development of subsequent trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT05154019; https://clinicaltrials.gov/study/NCT05154019. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48758.

Using intervention mapping to develop evidence-based toolkits that support workers on long-term sick leave and their managers.

BACKGROUND: Managing long-term sickness absence is challenging in countries where employers and managers have the main responsibility to provide return to work support, particularly for workers with poor mental health. Whilst long-term sick leave and return to work frameworks and guidance exist for employers, there are currently no structured return to work protocols for employers or for their workers encompassing best practice strategies to support a positive and timely return to work outcome. PURPOSE: To utilise the intervention mapping (IM) protocol as a framework to develop return to work toolkits that are underpinned by relevant behaviour change theory targeting mental health to promote a positive return to work experiensce for workers on long-term sick leave. METHODS: This paper provides a worked example of intervention mapping (IM) to develop an intervention through a six-step process to combine theory and evidence in the development of two toolkits - one designed for managers and one to be used by workers on long-term sick leave. As part of this process, collaborative planning techniques were used to develop the intervention. A planning group was set up, through which researchers would work alongside employer, worker, and mental health professional representatives to develop the toolkits. Additionally, feedback on the toolkits were sought from the target populations of workers and managers and from wider employer stakeholders (e.g., human resource specialists). The implementation and evaluation of the toolkits as a workplace intervention were also planned. RESULTS: Two toolkits were designed following the six steps of intervention mapping. Feedback from the planning group (n = 5; psychologist, psychiatrist, person with previous experience of poor mental health, employer and charity worker) and participants (n = 14; employers = 3, wellbeing director = 1; human resources = 2, managers = 2, employees with previous experience of poor mental health = 5) target populations indicated that the toolkits were acceptable and much needed. CONCLUSIONS: Using IM allowed the development of an evidence-based practical intervention, whilst incorporating the views of all the impacted stakeholder groups. The feasibility and acceptability of the toolkits and their supporting intervention components, implementation process and methods of assessment will be evaluated in a feasibility pilot randomised controlled trial.

Rates and associations of relapse over 5 years of 2649 people with bipolar disorder: a retrospective UK cohort study.

BACKGROUND: Evidence regarding the rate of relapse in people with bipolar disorder (BD), particularly from the UK, is lacking. This study aimed to evaluate the rate and associations of clinician-defined relapse over 5 years in a large sample of BD patients receiving routine care from a UK mental health service. METHOD: We utilised de-identified electronic health records to sample people with BD at baseline. Relapse was defined as either hospitalisation, or a referral to acute mental health crisis services, between June 2014 and June 2019. We calculated the 5-year rate of relapse and examined the sociodemographic and clinical factors that were independently associated with relapse status and the number of relapses, over the 5-year period. RESULTS: Of 2649 patients diagnosed with BD and receiving care from secondary mental health services, 25.5% (n = 676) experienced at least one relapse over 5 years. Of the 676 people who relapsed, 60.9% experienced one relapse, with the remainder experiencing multiple relapses. 7.2% of the baseline sample had died during the 5-year follow-up. Significant factors associated with experiencing any relapse, after adjustment for relevant covariates, were history of self-harm/suicidality (OR 2.17, CI 1.15-4.10, p = 0.02), comorbidity (OR 2.59, CI 1.35-4.97, p = 0.004) and psychotic symptoms (OR 3.66, CI 1.89-7.08, p < 0.001). Factors associated with the number of relapses over 5 years, after adjustment for covariates, were self-harm/suicidality (ß = 0.69, CI 0.21-1.17, p = 0.005), history of trauma (ß = 0.51, CI = 0.07-0.95, p = 0.03), psychotic symptoms (ß = 1.05, CI 0.55-1.56, p < 0.001), comorbidity (ß = 0.52, CI 0.07-1.03, p = 0.047) and ethnicity (ß = - 0.44, CI - 0.87 to - 0.003, p = 0.048). CONCLUSIONS: Around 1 in 4 people with BD in a large sample of people with BD receiving secondary mental health services in the UK relapsed over a 5-year period. Interventions targeting the impacts of trauma, suicidality, presence of psychotic symptoms and comorbidity could help to prevent relapse in people with BD and should be considered in relapse prevention plans.

Personality traits as risk factors for relapse or recurrence in major depression: a systematic review.

Background: Major depressive disorder (MDD) is highly recurrent. Identifying risk factors for relapse in depression is essential to improve prevention plans and therapeutic outcomes. Personality traits and personality disorders are widely considered to impact outcomes in MDD. We aimed to evaluate the role of personality aspects in the risk of relapse and recurrence in MDD. Method: A PROSPERO-registered systematic review was conducted using Medline, Embase, PsycINFO, Web of Science and CINAHL as data sources, together with hand searching of four journals over the five years till 2022. There was independent abstract selection, quality assessment and data extraction from each study. Results: Twenty two studies me t eligibility criteria involving 12,393 participants. Neurotic personality features are significantly associated with the risk of relapse and recurrence of depression, though the data is not uniform. There is some, though limited, evidence that borderline, obsessive-compulsive and dependent personality traits or disorders increase the risk for relapse in depression. Limitations: The small number, in addition to the methodological heterogeneity of the included studies, did not allow further analysis, such as meta-analysis. Conclusion: People with high neuroticism and dependent personality traits, borderline personality disorder or obsessive-compulsive personality disorder, compared to those without, may be at a higher risk of experiencing relapse or recurrence of MDD. Specific and targeted interventions may potentially reduce relapse and recurrence rates in these groups and could improve outcomes. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=235919, identifier: CRD42021235919.

The effectiveness of a primary care-based collaborative care model to improve quality of life in people with severe mental illness: PARTNERS2 cluster randomised controlled trial.

BACKGROUND: Individuals living with severe mental illness can have significant emotional, physical and social challenges. Collaborative care combines clinical and organisational components. AIMS: We tested whether a primary care-based collaborative care model (PARTNERS) would improve quality of life for people with diagnoses of schizophrenia, bipolar disorder or other psychoses, compared with usual care. METHOD: We conducted a general practice-based, cluster randomised controlled superiority trial. Practices were recruited from four English regions and allocated (1:1) to intervention or control. Individuals receiving limited input in secondary care or who were under primary care only were eligible. The 12-month PARTNERS intervention incorporated person-centred coaching support and liaison work. The primary outcome was quality of life as measured by the Manchester Short Assessment of Quality of Life (MANSA). RESULTS: We allocated 39 general practices, with 198 participants, to the PARTNERS intervention (20 practices, 116 participants) or control (19 practices, 82 participants). Primary outcome data were available for 99 (85.3%) intervention and 71 (86.6%) control participants. Mean change in overall MANSA score did not differ between the groups (intervention: 0.25, s.d. 0.73; control: 0.21, s.d. 0.86; estimated fully adjusted between-group difference 0.03, 95% CI -0.25 to 0.31; P = 0.819). Acute mental health episodes (safety outcome) included three crises in the intervention group and four in the control group. CONCLUSIONS: There was no evidence of a difference in quality of life, as measured with the MANSA, between those receiving the PARTNERS intervention and usual care. Shifting care to primary care was not associated with increased adverse outcomes.

Supporting employers and their employees with Mental hEalth problems to remain eNgaged and producTive at wORk (MENTOR): A feasibility randomised controlled trial protocol.

Employees with mental health problems often struggle to remain in employment. During the COVID-19 pandemic, these employees face multiple additional stressors, which are likely to worsen their mental health and work productivity. Currently, it is unclear how to best support employees with mental health problems (and their managers) to improve wellbeing and productivity. We aim to develop a new intervention (MENTOR) that will jointly involve employees, managers, and a new professional (mental health employment liaison worker, MHELW), to help employees who are still at work with a mental health condition and currently receiving professional support for their mental health. A feasibility pilot study will then be undertaken to examine the feasibility and acceptability of the intervention from the perspective of employees and line managers. The study involves a feasibility randomised controlled study comparing outcomes of participants randomised to receive the intervention (MENTOR) with wait-list controls. Participants allocated to the waitlist control group will receive the intervention after three months. We aim to randomise 56 employee-manager pairs recruited from multiple organisations in the Midlands region of England. An intervention including 10 sessions for employees and managers (3 individual sessions and 4 joint sessions) will be delivered over 12 weeks by trained MHELWs. Primary outcomes include measures of feasibility and acceptability of the intervention and work productivity. Secondary outcomes include mental health outcomes. Qualitative interviews will be undertaken with a purposively selected sub-sample of employees and line managers at three-month post-intervention assessment. To our knowledge, this will be the first trial with a joint employee-manager intervention delivered by MHELWs. Anticipated challenges are dual-level consent (employees and managers), participants' attrition, and recruitment strategies. If the intervention and trial processes are shown to be feasible and acceptable, the outcomes from this study will inform future randomised controlled trials. Trial registration: This trial is pre-registered with the ISRCTN registry, registration number: ISRCTN79256498. Protocol version: 3.0_March_2023. https://www.isrctn.com/ISRCTN79256498.

Empirically driven transdiagnostic stages in the development of mood, anxiety and psychotic symptoms in a cohort of youth followed from birth.

Staging models with transdiagnostic validity across mood, psychotic, and anxiety disorders could advance early intervention efforts as well as our understanding of the common underpinnings of such psychopathology. However, there are few well-supported operationalisations for such transdiagnostic models, particularly in community-based samples. We aimed to explore the inter-relationships among mood, psychotic, and anxiety symptom stages, and their common risk factors to develop data-informed transdiagnostic stages. We included participants from the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective ongoing birth cohort study. We developed operational thresholds for stages of depressive, hypomanic, anxiety, and psychotic symptoms based on the existing literature, refined further by expert consensus. We selected 1b level as the primary stage or outcome of interest. This represents moderate symptoms that are likely to be associated with the onset of the need for clinical mental health care. We used questionnaire and clinic data completed by young people ages 18 and 21 years. We used descriptive methods and network analyses to examine the overlap among Stage 1b psychopathology. We then examined the patterns of relationships between several risk factors and 1b stages using logistic regressions. Among 3269 young people with data available to determine all symptom stages, 64.3% were female and 96% Caucasian. Descriptive and network analyses indicated that 1b level depressive, anxiety, and psychotic symptom stages were inter-related while hypomania was not. Similarly, anxiety, depressive, and psychotic 1b stages were associated with the female sex, more emotional and behavioral difficulties in early adolescence, and life events in late adolescence. Hypomania was not related to any of these risk factors. Given their inter-relationships and similar risk factors, anxiety, psychotic and depressive, symptoms could be combined to form a transdiagnostic stage in this cohort. Such empirical transdiagnostic stages could help with prognostication and indicated prevention in youth mental health.

Impact of anxiety and depression across childhood and adolescence on adverse outcomes in young adulthood: a UK birth cohort study.

BACKGROUND: Little is still known about the long-term impact of childhood and adolescent persistent depression and anxiety in adulthood. AIMS: To investigate the impact of persistent anxiety, depression, and comorbid anxiety and depression across childhood and adolescence on the development of multiple adverse outcomes in young adulthood. METHOD: This study used data from 8122 participants in the Avon Longitudinal Study of Parents and Children cohort. The Development and Well-Being Assessment (DAWBA) examined child anxiety and depression symptomatology. The DAWBA generalised anxiety and mood subscales at 8, 10 and 13 years were selected, and a measure of comorbid anxiety and depression symptoms was created at each time point. Further, several mental and physical health, substance misuse and education/employment problems were assessed at 24 years. Latent class growth analyses were used to detect trajectories of anxiety, depression and comorbid anxiety and depression; and logistic regression to examine how persistent anxiety, depression or both were associated with adverse outcomes at 24 years. RESULTS: All three classes with persistent anxiety, depression or both were significantly associated with presenting with any mental health problems and any education/employment problem. Persistent high levels of depression and high levels of comorbid anxiety and depression, but not persistent high anxiety, were significantly associated with any physical health problem. High levels of comorbid anxiety and depression was the only DAWBA domain significantly associated with substance misuse; and overall, this was the domain that exerted the greatest negative impact, as it presented the highest odd ratio values. CONCLUSIONS: Children and adolescents with comorbid anxiety and depression are at the highest risk for having more adverse outcomes at 24 years.

Non-Pharmacological Therapies for Post-Viral Syndromes, Including Long COVID: A Systematic Review.

BACKGROUND: Post-viral syndromes (PVS), including Long COVID, are symptoms sustained from weeks to years following an acute viral infection. Non-pharmacological treatments for these symptoms are poorly understood. This review summarises the evidence for the effectiveness of non-pharmacological treatments for PVS. METHODS: We conducted a systematic review to evaluate the effectiveness of non-pharmacological interventions for PVS, as compared to either standard care, alternative non-pharmacological therapy, or placebo. The outcomes of interest were changes in symptoms, exercise capacity, quality of life (including mental health and wellbeing), and work capability. We searched five databases (Embase, MEDLINE, PsycINFO, CINAHL, MedRxiv) for randomised controlled trials (RCTs) published between 1 January 2001 to 29 October 2021. The relevant outcome data were extracted, the study quality was appraised using the Cochrane risk-of-bias tool, and the findings were synthesised narratively. FINDINGS: Overall, five studies of five different interventions (Pilates, music therapy, telerehabilitation, resistance exercise, neuromodulation) met the inclusion criteria. Aside from music-based intervention, all other selected interventions demonstrated some support in the management of PVS in some patients. INTERPRETATION: In this study, we observed a lack of robust evidence evaluating the non-pharmacological treatments for PVS, including Long COVID. Considering the prevalence of prolonged symptoms following acute viral infections, there is an urgent need for clinical trials evaluating the effectiveness and cost-effectiveness of non-pharmacological treatments for patients with PVS. REGISTRATION: The study protocol was registered with PROSPERO [CRD42021282074] in October 2021 and published in BMJ Open in 2022.

The role of inflammation in the prospective associations between early childhood sleep problems and ADHD at 10 years: findings from a UK birth cohort study.

BACKGROUND: Several underlying mechanisms potentially account for the link between sleep and attention deficit and hyperactivity disorder (ADHD), including inflammation. However, studies so far have been cross sectional. We investigate (a) the association between early childhood sleep and probable ADHD diagnosis in childhood and (b) whether childhood circulating inflammatory markers mediate these prospective associations. METHODS: Data from the Avon Longitudinal Study of Parents and Children were available for 7,658 10-year-old children. Parent-reported sleep duration, night awakening frequency and regular sleep routines were collected at 3.5 years. The Development and Wellbeing Assessment was administered to capture children with clinically relevant ADHD symptoms, or probable ADHD diagnosis. Blood samples were collected at 9 years, from which two inflammatory markers were obtained [interleukin-6 (IL-6) and C-reactive protein (CRP)]. Logistic regression analyses were applied to investigate the associations between sleep variables at 3.5 years and probable ADHD diagnosis at 10 years. Further, path analysis was applied to examine the potential mediating role of inflammation at 9 years (as measured by CRP and IL-6) in the associations between early sleep and ADHD at 10 years. RESULTS: Less regular sleep routines (OR = 0.51, 95% CI = 0.28-0.93, p = .029), shorter nighttime sleep (OR = 0.70, 95% CI = 0.56-0.89, p = .004) and higher night awakening frequency (OR = 1.27, 95% CI = 1.06-1.52, p = .009) at 3.5 years were associated with higher odds of ADHD at 10 years. Further, IL-6 at 9 years, but not CRP, mediated the association between irregular sleep routines and ADHD (bias-corrected estimate, -0.002; p = .005) and between night awakening and ADHD (bias-corrected estimate, 0.002; p = .003). CONCLUSIONS: Several sleep problems in early childhood constitute a risk factor for probable ADHD diagnosis at 10 years. Further, these associations are partially mediated by IL-6 at 9 years. These results open a new research vista to the pathophysiology of ADHD and highlight sleep and inflammation as potential preventative targets for ADHD.

Novel and emerging treatments for major depression.

Depression is common, costly, debilitating, and associated with increased risk of suicide. It is one of the leading global public health problems. Although existing available pharmacological treatments can be effective, their onset of action can take up to 6 weeks, side-effects are common, and recovery can require treatment with multiple different agents. Although psychosocial interventions might also be recommended, more effective treatments than those currently available are needed for people with moderate or severe depression. In the past 10 years, treatment trials have developed and tested many new targeted interventions. In this Review, we assess novel and emerging biological treatments for major depressive disorder, evaluate their putative brain and body mechanisms, and highlight how close each might be to clinical use.

Maternal postnatal depression and anxiety and the risk for mental health disorders in adolescent offspring: Findings from the Avon Longitudinal Study of Parents and Children cohort.

OBJECTIVE: The impacts of postnatal psychiatric disorders on different types of mental health problems in offspring are unclear. We investigated the prospective associations of maternal postnatal depression, and anxiety, with offspring depression, anxiety, psychotic-like experiences and Borderline Personality Disorder symptoms, in adolescence, and examined whether these were independent of each other. METHODS: Data were obtained from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Maternal postnatal depression and anxiety at 8 weeks were measured using the Edinburgh Postnatal Depression Scale and Crown-Crisp Index, respectively. Offspring mental health outcomes were measured at 10-13 years old, using a variety of questionnaire-based and interview assessments. Logistic regression analyses were used to assess the associations between maternal postnatal risk factors and offspring mental health, and path analysis was used to investigate the pathways of maternal postnatal factors to adolescent offspring outcomes. RESULTS: Data were available for 14,054 mothers with information reported on postnatal depression and 13,892 on postnatal anxiety. Logistic regression analyses found significant associations between maternal postnatal depression and offspring anxiety at 10 years old (odds ratio = 1.039, 95% confidence interval = [1.005, 1.073], p = 0.022) and between maternal postnatal anxiety and offspring psychotic experiences at 12/13 years old (odds ratio = 1.042, 95% confidence interval = [1.008, 1.077], p = 0.016). These significant associations remained after applying path analyses, when we controlled for potential offspring psychopathological overlay. CONCLUSION: These findings suggest that mothers with postnatal depression are more likely to have offspring with anxiety at 10 years old, and that mothers with postnatal anxiety are more likely to have offspring with psychotic experiences at 12/13 years old. Our findings suggest specific pathways in the association between postnatal anxiety/depression and offspring mental health and contribute to the importance of identifying mothers and their offspring with increased vulnerability to adverse outcomes resulting from postnatal mental health disorders.

Associations between primary care recorded cannabis use and mental ill health in the UK: a population-based retrospective cohort study using UK primary care data.

BACKGROUND: Cannabis use is a global public health issue associated with increased risks of developing mental health disorders, especially in young people. We aimed to investigate the relationships between cannabis exposure and risks of receiving mental illness diagnoses or treatment as outcomes. METHODS: A population based, retrospective, open cohort study using patients recorded in 'IQVIA medical research data', a UK primary care database. Read codes were used to confirm patients with recorded exposure to cannabis use who were matched up to two unexposed patients. We examined the risk of developing three categories of mental ill health: depression, anxiety or serious mental illness (SMI). RESULTS: At study entry, the exposed cohort had an increased likelihood of having experienced mental ill health [odds ratio (OR) 4.13; 95% confidence interval (CI) 3.99-4.27] and mental ill health-related prescription (OR 2.95; 95% CI 2.86-3.05) compared to the unexposed group. During the study period we found that exposure to cannabis was associated with an increased risk of developing any mental disorder [adjusted hazard ratio (aHR) 2.73; 95% CI 2.59-2.88], also noted when examining by subtype of disorder: anxiety (aHR 2.46; 95% CI 2.29-2.64), depression (aHR 2.34; 95% CI 2.20-2.49) and SMI (aHR 6.41; 95% CI 5.42-7.57). These results remained robust in sensitivity analyses. CONCLUSION: These findings point to the potential need for a public health approach to the management of people misusing cannabis. However, there is a gross under-recording of cannabis use in GP records, as seen by the prevalence of recorded cannabis exposure substantially lower than self-reported survey records.