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Compared with other areas of mental health research that are focused on the active and early management of youth presenting in the early stages of major mental disorders, there has been a relative lack of focus on young people with emerging or established bipolar disorders. Recently, this has stimulated both international professional societies (e.g., International Society for Bipolar Disorders [ISBD] Early Intervention Task Force) and funding agencies from Canada, UK, Australia, and the USA – including the Daymark Foundation (Jain et al. 2023), Wellcome Trust (2022), National Health and Medical Research Council, and BD2 – to promote a focus on identifying the major challenges in this field and gathering support for novel research and clinical service programmes.
Functional impairment is a major concern among those presenting to youth mental health services and can have a profound impact on long-term outcomes. Early recognition and prevention for those at risk of functional impairment is essential to guide effective youth mental health care. Yet, identifying those at risk is challenging and impacts the appropriate allocation of indicated prevention and early intervention strategies.
Methods
We developed a prognostic model to predict a young person’s social and occupational functional impairment trajectory over 3 months. The sample included 718 young people (12–25 years) engaged in youth mental health care. A Bayesian random effects model was designed using demographic and clinical factors and model performance was evaluated on held-out test data via 5-fold cross-validation.
Results
Eight factors were identified as the optimal set for prediction: employment, education, or training status; self-harm; psychotic-like experiences; physical health comorbidity; childhood-onset syndrome; illness type; clinical stage; and circadian disturbances. The model had an acceptable area under the curve (AUC) of 0.70 (95% CI, 0.56–0.81) overall, indicating its utility for predicting functional impairment over 3 months. For those with good baseline functioning, it showed excellent performance (AUC = 0.80, 0.67–0.79) for identifying individuals at risk of deterioration.
Conclusions
We developed and validated a prognostic model for youth mental health services to predict functional impairment trajectories over a 3-month period. This model serves as a foundation for further tool development and demonstrates its potential to guide indicated prevention and early intervention for enhancing functional outcomes or preventing functional decline.
Since lack of culture-specific foods in dietary assessment methods may bias reported dietary intake, we identified foods and dishes consumed by residents not born in Sweden and describe consequences for reported foods and nutrient intake using a culturally adapted dietary assessment method. Design consisted of cross-sectional data collection using (semi-)qualitative methods of dietary assessment (and national diet survey instrument RiksmatenFlex) with subsequent longitudinal data collection using quantitative methods for method comparison (December 2020–January 2023). Three community-based research groups were recruited that consisted of mothers born in Sweden, Syria/Iraq, and Somalia, with a median age of 34, 37, and 36 years, respectively. Women born in Syria/Iraq and Somalia who had lived in Sweden for approximately 10 years, reported 78 foods to be added to RiksmatenFlex. In a subsequent study phase, 69% of these foods were reported by around 90% of the ethnic minority groups and contributed to 17% of their reported energy intake. However, differences between the three study groups in median self-reported energy intake remained (Sweden 7.19 MJ, Syria/Iraq 5.54 MJ, and Somalia 5.69 MJ). The groups also showed differences in relative energy contribution from fats and carbohydrates, as well as differences in energy intake from food groups such as bread and sweet snacks. We conclude that a dietary assessment instrument containing culture-specific foods could not resolve group differences in reported energy intake, although these foods provided content validity and contributed 17% of energy intake. The dietary habits collected in this study serve to develop new dietary assessment instruments.
Edited by
Allan Young, Institute of Psychiatry, King's College London,Marsal Sanches, Baylor College of Medicine, Texas,Jair C. Soares, McGovern Medical School, The University of Texas,Mario Juruena, King's College London
Bipolar disorders (BD) are recurrent conditions and many clinical and social impairments persist even with optimal pharmacotherapy. This chapter explores the development of psychological treatments, from initial uncertainties about offering therapies for BD, and then following the tentative steps to offer support to individuals with BD and to their families. Much of the focus is on the rationale, evolution and testing of specific psychological treatments. As well as examining any added value attained from providing psychological treatments alongside medications, we also consider how therapies might be further developed in the future. For example, we discuss how network meta-analysis might shed light on active ingredients that are common to all successful therapies and consider if these components might herald the introduction of multi-modal interventions. The chapter ends by noting the progress being made regarding the mediators and moderators of therapeutic effects and highlighting the importance of continuing to undertake efficacy trials but also comparative effectiveness trials that will enable researchers, clinicians and patients to determine how best to deploy psychological treatments in the real world.
At first glance, the formulation of the principle of inertia—not. yet complete with Galileo, more precise with Gassendi, finally systematic with Newton—seems to constitute but one of the aspects of a process of deep transformations at the end of which traditional cosmology was replaced by various world systems. These transformations—or, to use a more classic term, this “ scientific revolution” —have been the object of numerous works, a list, of which would alone fill the pages of a thick volume. But the principle of inertia itself, a principle about which can be said without exaggeration that it expressed the essence of this revolution at the same time as it stimulated it, has perhaps not received all the attention it deserves. And especially the impact of this principle on Western culture has not been fully measured. True, Alexandre Koyré has always insisted on the fact that, by reducing movement to a state like that of the state of rest, the principle of inertia expressed a new vision of the world more than a scientific result. But his admirable analyses deal more with the slow advent of the priciple of inertia among the natural philosophers who preceded, accompanied and then followed Galileo than with the theological, philosophical and literary impact of this principle. Moreover, by examining this impact, we discover that it is necessary to make a distinction between Euclidian space and absolute space, a distinction which is frequently implicit with certain scientific historians, but, and this must be emphasized, is more often ignored.
The recognised heterogeneity of clinical cohorts of people with depression and other mood disorders has been held to be one of the central reasons why so many studies of causation, neurobiological or psychological correlates, or the effectiveness of treatments have failed to yield significant findings or be easily replicated by independent groups.
A clinical concept that has been taken up with some enthusiasm in mental health services for young people experiencing major mental disorders is that of clinical staging, with the emphasis on identifying and intervening in youth with various ‘at-risk’, ‘sub-threshold’ or ‘attenuated’ syndromes, before the onset of first major episodes (Shah et al 2020). While these concepts were initially developed within the rather focused context of major psychotic disorders, they are now being deployed much more widely and applied to young people presenting with a variety of mental disorders (Hickie et al 2019; Shah 2019).
The most basic distinction between depressive (and other mood) disorders and other major mental disorders is the notion that they are primarily mood or affective disorders and not fundamentally perturbations of other cognitive, perceptual, motor, communication, impulse, sleep−wake, fear-response, arousal, developmental or personality functions. The primacy of mood or affective state is captured in the ‘core’ criteria for major depression (depressed mood or loss of pleasure) and the other major mood disorders (e.g., for dysthymia – prolonged depressed mood) (American Psychiatric Association, 2013). For bipolar disorder, while the presence of manic features (with increased motor activity) (Scott et al., 2017) is the core element, the depressive phase is described in similar terms, with the emphasis on the same shared features of major depression (i.e., depressed mood or loss of pleasure).
The needs of young people attending mental healthcare can be complex and often span multiple domains (e.g., social, emotional and physical health factors). These factors often complicate treatment approaches and contribute to poorer outcomes in youth mental health. We aimed to identify how these factors interact over time by modelling the temporal dependencies between these transdiagnostic social, emotional and physical health factors among young people presenting for youth mental healthcare.
Methods
Dynamic Bayesian networks were used to examine the relationship between mental health factors across multiple domains (social and occupational function, self-harm and suicidality, alcohol and substance use, physical health and psychiatric syndromes) in a longitudinal cohort of 2663 young people accessing youth mental health services. Two networks were developed: (1) ‘initial network’, that shows the conditional dependencies between factors at first presentation, and a (2) ‘transition network’, how factors are dependent longitudinally.
Results
The ‘initial network’ identified that childhood disorders tend to precede adolescent depression which itself was associated with three distinct pathways or illness trajectories; (1) anxiety disorder; (2) bipolar disorder, manic-like experiences, circadian disturbances and psychosis-like experiences; (3) self-harm and suicidality to alcohol and substance use or functioning. The ‘transition network’ identified that over time social and occupational function had the largest effect on self-harm and suicidality, with direct effects on ideation (relative risk [RR], 1.79; CI, 1.59–1.99) and self-harm (RR, 1.32; CI, 1.22–1.41), and an indirect effect on attempts (RR, 2.10; CI, 1.69–2.50). Suicide ideation had a direct effect on future suicide attempts (RR, 4.37; CI, 3.28–5.43) and self-harm (RR, 2.78; CI, 2.55–3.01). Alcohol and substance use, physical health and psychiatric syndromes (e.g., depression and anxiety, at-risk mental states) were independent domains whereby all direct effects remained within each domain over time.
Conclusions
This study identified probable temporal dependencies between domains, which has causal interpretations, and therefore can provide insight into their differential role over the course of illness. This work identified social, emotional and physical health factors that may be important early intervention and prevention targets. Improving social and occupational function may be a critical target due to its impacts longitudinally on self-harm and suicidality. The conditional independence of alcohol and substance use supports the need for specific interventions to target these comorbidities.
Subthreshold/attenuated syndromes are established precursors of full-threshold mood and psychotic disorders. Less is known about the individual symptoms that may precede the development of subthreshold syndromes and associated social/functional outcomes among emerging adults.
Methods
We modeled two dynamic Bayesian networks (DBN) to investigate associations among self-rated phenomenology and personal/lifestyle factors (role impairment, low social support, and alcohol and substance use) across the 19Up and 25Up waves of the Brisbane Longitudinal Twin Study. We examined whether symptoms and personal/lifestyle factors at 19Up were associated with (a) themselves or different items at 25Up, and (b) onset of a depression-like, hypo-manic-like, or psychotic-like subthreshold syndrome (STS) at 25Up.
Results
The first DBN identified 11 items that when endorsed at 19Up were more likely to be reendorsed at 25Up (e.g., hypersomnia, impaired concentration, impaired sleep quality) and seven items that when endorsed at 19Up were associated with different items being endorsed at 25Up (e.g., earlier fatigue and later role impairment; earlier anergia and later somatic pain). In the second DBN, no arcs met our a priori threshold for inclusion. In an exploratory model with no threshold, >20 items at 19Up were associated with progression to an STS at 25Up (with lower statistical confidence); the top five arcs were: feeling threatened by others and a later psychotic-like STS; increased activity and a later hypo-manic-like STS; and anergia, impaired sleep quality, and/or hypersomnia and a later depression-like STS.
Conclusions
These probabilistic models identify symptoms and personal/lifestyle factors that might prove useful targets for indicated preventative strategies.
The challenge of identifying efficacious out-patient treatments for depression is amplified by the increasing desire to find interventions that reduce the time to sustained improvement. One potential but underexplored option is triple chronotherapy (TCT). To date, use of TCT has been largely restricted to specialist units or in-patients. Recent research demonstrates that it may be possible to undertake sleep deprivation in out-patient settings, raising the possibility of delivering TCT to broader populations of individuals with depression. Emerging evidence suggests that out-patient TCT is a high-benefit, low-risk intervention but questions remain about how to target TCT and its mechanisms of action. Like traditional antidepressants, TCT probably acts through several pathways, especially the synchronisation of the ‘master clock’. Availability of reliable and valid methods of out-patient measurement of intra-individual circadian rhythmicity and light exposure are rate-limiting steps in the wider dissemination of TCT.
Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of chronic liver disease that accompanies obesity and the metabolic syndrome. Excess fructose consumption can initiate or exacerbate NAFLD in part due to a consequence of impaired hepatic fructose metabolism. Preclinical data emphasized that fructose-induced altered gut microbiome, increased gut permeability, and endotoxemia play an important role in NAFLD, but human studies are sparse. The present study aimed to determine if two weeks of excess fructose consumption significantly alters gut microbiota or permeability in humans.
Methods:
We performed a pilot double-blind, cross-over, metabolic unit study in 10 subjects with obesity (body mass index [BMI] 30–40 mg/kg/m2). Each arm provided 75 grams of either fructose or glucose added to subjects’ individual diets for 14 days, substituted isocalorically for complex carbohydrates, with a 19-day wash-out period between arms. Total fructose intake provided in the fructose arm of the study totaled a mean of 20.1% of calories. Outcome measures included fecal microbiota distribution, fecal metabolites, intestinal permeability, markers of endotoxemia, and plasma metabolites.
Results:
Routine blood, uric acid, liver function, and lipid measurements were unaffected by the fructose intervention. The fecal microbiome (including Akkermansia muciniphilia), fecal metabolites, gut permeability, indices of endotoxemia, gut damage or inflammation, and plasma metabolites were essentially unchanged by either intervention.
Conclusions:
In contrast to rodent preclinical findings, excess fructose did not cause changes in the gut microbiome, metabolome, and permeability as well as endotoxemia in humans with obesity fed fructose for 14 days in amounts known to enhance NAFLD.
Black, Asian and minority ethnicity groups may experience better health outcomes when living in areas of high own-group ethnic density – the so-called ‘ethnic density’ hypothesis. We tested this hypothesis for the treatment outcome of compulsory admission.
Methods
Data from the 2010–2011 Mental Health Minimum Dataset (N = 1 053 617) was linked to the 2011 Census and 2010 Index of Multiple Deprivation. Own-group ethnic density was calculated by dividing the number of residents per ethnic group for each lower layer super output area (LSOA) in the Census by the LSOA total population. Multilevel modelling estimated the effect of own-group ethnic density on the risk of compulsory admission by ethnic group (White British, White other, Black, Asian and mixed), accounting for patient characteristics (age and gender), area-level deprivation and population density.
Results
Asian and White British patients experienced a reduced risk of compulsory admission when living in the areas of high own-group ethnic density [odds ratios (OR) 0.97, 95% credible interval (CI) 0.95–0.99 and 0.94, 95% CI 0.93–0.95, respectively], whereas White minority patients were at increased risk when living in neighbourhoods of higher own-group ethnic concentration (OR 1.18, 95% CI 1.11–1.26). Higher levels of own-group ethnic density were associated with an increased risk of compulsory admission for mixed-ethnicity patients, but only when deprivation and population density were excluded from the model. Neighbourhood-level concentration of own-group ethnicity for Black patients did not influence the risk of compulsory admission.
Conclusions
We found only minimal support for the ethnic density hypothesis for the treatment outcome of compulsory admission to under the Mental Health Act.
During the first wave of the severe acute respiratory syndrome-coronavirus-2 epidemic in the Netherlands, notifications consisted mostly of patients with relatively severe disease. To enable real-time monitoring of the incidence of mild coronavirus disease 2019 (COVID-19) – for which medical consultation might not be required – the Infectieradar web-based syndromic surveillance system was launched in mid-March 2020. Our aim was to quantify associations between Infectieradar participant characteristics and the incidence of self-reported COVID-19-like illness. Recruitment for this cohort study was via a web announcement. After registering, participants completed weekly questionnaires, reporting the occurrence of a set of symptoms. The incidence rate of COVID-19-like illness was estimated and multivariable Poisson regression used to estimate the relative risks associated with sociodemographic variables, lifestyle factors and pre-existing medical conditions. Between 17 March and 24 May 2020, 25 663 active participants were identified, who reported 7060 episodes of COVID-19-like illness over 131 404 person-weeks of follow-up. The incidence rate declined over the analysis period, consistent with the decline in notified cases. Male sex, age 65+ years and higher education were associated with a significantly lower COVID-19-like illness incidence rate (adjusted rate ratios (RRs) of 0.80 (95% CI 0.76–0.84), 0.77 (0.70–0.85), 0.84 (0.80–0.88), respectively) and the baseline characteristics ever-smoker, asthma, allergies, diabetes, chronic lung disease, cardiovascular disease and children in the household were associated with a higher incidence (RRs of 1.11 (1.04–1.19) to 1.69 (1.50–1.90)). Web-based syndromic surveillance has proven useful for monitoring the temporal trends in, and risk factors associated with, the incidence of mild disease. Increased relative risks observed for several patient factors could reflect a combination of exposure risk, susceptibility to infection and propensity to report symptoms.
Despite its pivotal role in prophylaxis for bipolar-I-disorders (BD-I), variability in lithium (Li) response is poorly understood and only a third of patients show a good outcome. Converging research strands indicate that rest–activity rhythms can help characterize BD-I and might differentiate good responders (GR) and non-responders (NR).
Methods
Seventy outpatients with BD-I receiving Li prophylaxis were categorized as GR or NR according to the ratings on the retrospective assessment of response to lithium scale (Alda scale). Participants undertook 21 consecutive days of actigraphy monitoring of sleep quantity (SQ), sleep variability (SV) and circadian rhythmicity (CR).
Results
Twenty-five individuals were categorized as GR (36%). After correcting statistical analysis to minimize false discoveries, four variables (intra-daily variability; median activity level; amplitude; and relative amplitude of activity) significantly differentiated GR from NR. The odds of being classified as a GR case were greatest for individuals showing more regular/stable CR (1.41; 95% confidence interval (CI) 1.08, 2.05; p < 0.04). Also, there was a trend for lower SV to be associated with GR (odds ratio: 0.56; 95% CI 0.31, 1.01; p < 0.06).
Conclusions
To our knowledge, this is the largest actigraphy study of rest–activity rhythms and Li response. Circadian markers associated with fragmentation, variability, amount and/or amplitude of day and night-time activity best-identified GR. However, associations were modest and future research must determine whether these objectively measured parameters, singly or together, represent robust treatment response biomarkers. Actigraphy may offer an adjunct to multi-platform approaches aimed at developing personalized treatments or stratification of individuals with BD-I into treatment-relevant subgroups.
Predictors of new-onset bipolar disorder (BD) or psychotic disorder (PD) have been proposed on the basis of retrospective or prospective studies of ‘at-risk’ cohorts. Few studies have compared concurrently or longitudinally factors associated with the onset of BD or PDs in youth presenting to early intervention services. We aimed to identify clinical predictors of the onset of full-threshold (FT) BD or PD in this population.
Method
Multi-state Markov modelling was used to assess the relationships between baseline characteristics and the likelihood of the onset of FT BD or PD in youth (aged 12–30) presenting to mental health services.
Results
Of 2330 individuals assessed longitudinally, 4.3% (n = 100) met criteria for new-onset FT BD and 2.2% (n = 51) met criteria for a new-onset FT PD. The emergence of FT BD was associated with older age, lower social and occupational functioning, mania-like experiences (MLE), suicide attempts, reduced incidence of physical illness, childhood-onset depression, and childhood-onset anxiety. The emergence of a PD was associated with older age, male sex, psychosis-like experiences (PLE), suicide attempts, stimulant use, and childhood-onset depression.
Conclusions
Identifying risk factors for the onset of either BD or PDs in young people presenting to early intervention services is assisted not only by the increased focus on MLE and PLE, but also by recognising the predictive significance of poorer social function, childhood-onset anxiety and mood disorders, and suicide attempts prior to the time of entry to services. Secondary prevention may be enhanced by greater attention to those risk factors that are modifiable or shared by both illness trajectories.
Opioid use disorder is a major public health crisis, and evidence suggests ways of better serving patients who live with opioid use disorder in the emergency department (ED). A multi-disciplinary team developed a quality improvement project to implement this evidence.
Methods
The intervention was developed by an expert working group consisting of specialists and stakeholders. The group set goals of increasing prescribing of buprenorphine/naloxone and providing next day walk-in referrals to opioid use disorder treatment clinics. From May to September 2018, three Alberta ED sites and three opioid use disorder treatment clinics worked together to trial the intervention. We used administrative data to track the number of ED visits where patients were given buprenorphine/naloxone. Monthly ED prescribing rates before and after the intervention were considered and compared with eight nonintervention sites. We considered whether patients continued to fill opioid agonist treatment prescriptions at 30, 60, and 90 days after their index ED visit to measure continuity in treatment.
Results
The intervention sites increased their prescribing of buprenorphine/naloxone during the intervention period and prescribed more buprenorphine/naloxone than the controls. Thirty-five of 47 patients (74.4%) discharged from the ED with buprenorphine/naloxone continued to fill opioid agonist treatment prescriptions 30 days and 60 days after their index ED visit. Thirty-four patients (72.3%) filled prescriptions at 90 days.
Conclusions
Emergency clinicians can effectively initiate patients on buprenorphine/naloxone when supports for this standardized evidence-based care are in place within their practice setting and timely follow-up in community is available.
Light is the most important environmental influence (zeitgeber) on the synchronization of the circadian system in humans. Excess light exposure during the evening and night-time affects secretion of the hormone melatonin, which in turn modifies the temporal organization of circadian rhythms, including the sleep–wake cycle. As sleep disturbances are prominent in critically ill medical and psychiatric patients, researchers began to examine the impact of light exposure on clinical outcomes and length of hospitalization. In psychiatric inpatients, exposure to bright morning light or use of blue blocking glasses have proved useful interventions for mood disorders. Recently, knowledge about light and the circadian system has been applied to the design of inpatient facilities with dynamic lighting systems that change according to time of day. The installation of ‘circadian lighting’ alongside technologies for monitoring sleep–wake patterns could prove to be one of the most practical and beneficial innovations in inpatient psychiatric care for more than half a century.