Transdiagnostic risk identification: A validation study of the Clinical High At Risk Mental State (CHARMS) criteria.

A set of clinical criteria, the Clinical High At-Risk Mental State (CHARMS) criteria, have been developed to identify symptomatic young people who are at-risk of disorder progression. The current study aimed to validate the CHARMS criteria by testing whether they prospectively identify individuals at-risk of progressing from attenuated symptomatology to a first episode of serious mental disorder, namely first episode psychosis, first episode mania, severe major depression, and borderline personality disorder. 121 young people completed clinical evaluations at baseline, 6- and 12-month follow-up. The Kaplan-Meier method was used to assess transition rates. Cox regression and LASSO were used to examine baseline clinical predictors of transition. Linear mixed effects modelling was used to examine symptom severity. 28 % of CHARMS+ individuals transitioned to a Stage 2 disorder by 12-month follow-up. The CHARMS+ group had more severe symptoms at follow-up than the CHARMS- group. 96 % of Stage 2 transitions were initially to severe depression. Meeting criteria for multiple CHARMS subgroups was associated with higher transition risk: meeting one at-risk group = 24 %; meeting two at-risk groups = 17 %, meeting three at-risk groups = 55 %, meeting four at-risk groups = 50 %. The strongest baseline predictor of transition was severity of depressive symptoms. The CHARMS criteria identified a group of individuals at-risk of imminent onset of severe mental disorder, particularly severe depression. Larger scale studies and longer follow-up periods are required to validate and extend these findings.

The association between stressful experiences and OCD symptoms in young adults at transdiagnostic risk.

BACKGROUND: It is unclear whether there is a specific association between stressful experiences and obsessive-compulsive symptoms or whether this relationship is due to stressful experiences increasing risk for psychopathology generally. AIMS: The current study examined the association between stressful experiences and obsessive-compulsive symptom dimensions, while adjusting for coexisting psychiatric symptoms and psychological distress in a young adult transdiagnostic at-risk sample. METHODS: Forty-three participants completed self-report measures assessing obsessive-compulsive symptoms, stressful experiences, and a range of other psychiatric symptoms. Regression models examined the relationship between stressful experiences and different obsessive-compulsive symptoms dimensions (i.e., symmetry, fear of harm, contamination, and unacceptable thoughts), adjusting for the influence of coexisting psychiatric symptoms and psychological distress. RESULTS: The results showed that there was an association between stressful experiences and obsessive-compulsive symptoms dimension of symmetry. Symptoms of borderline personality disorder were positively associated with the obsessive-compulsive symptom dimensions of symmetry and fear of harm symptoms. Symptoms of psychosis were found to be negatively associated with the obsessive-compulsive symptoms dimension of fear of harm. CONCLUSIONS: These findings have implications for understanding the psychological mechanisms that underlie symmetry symptoms and highlight the need to study OCS dimensions separately to inform more precise, mechanism-targeted interventions.

Changing the Care Paradigm for Patients: Advanced Illness Beds Care Model.

BACKGROUND: Over 90 million Americans suffer from advanced illness (AI) and spend their last days of life in critical care units receiving costly, unwanted, aggressive medical care. OBJECTIVE: Evaluate the impact of a specialized care model in medical/surgical units for hospitalized geriatric patients and patients with complex care requirements where designated AI beds align care with patient's wishes/goals, minimize aggressive interventions, and influence efficient resource utilization. DESIGN: US based multi-facility retrospective, longitudinal descriptive study of screened positive AI patients in AI Beds (N = 1,237) from 3 facilities from 2015 to 2017. RESULTS: Patient outcomes included 60% referrals to AI beds from ICU, a decrease of 39-49% in average ICU LOS, a 23% reduction of AI bed patient expirations, 9.0% referrals to hospice, and projected cost savings of $4,361.66/patient, US dollars. CONCLUSION: Allocating AI beds to deliver care to AI patients resulted in a decreased cost of care by reducing overall hospital LOS, mortality, and efficient use of both critical care and hospital resources.

Broad clinical high-risk mental state (CHARMS): Methodology of a cohort study validating criteria for pluripotent risk.

AIM: The development of the ultra-high risk (UHR) criteria for psychosis created a new paradigm for the prevention research in psychiatry. Since (1) prevention research faces the challenge of achieving adequate statistical power when focusing on single low-incidence syndromes and (2) early clinical phenotypes are overlapping and non-specific, this study broadens the UHR state beyond psychosis as an outcome. The CHARMS (clinical high at-risk mental state) study aims to prospectively validate a set of trans-diagnostic criteria to identify help-seeking young people at risk of developing a range of serious mental illnesses. METHODS: This paper describes the methodology of the CHARMS study, which involves applying the CHARMS criteria to a cohort of help-seeking young people aged 12 to 25 attending youth mental health services in Melbourne. New referrals meeting the CHARMS criteria are allocated to the CHARMS+ group; referrals not meeting CHARMS threshold are allocated to CHARMS- group (control group); referrals meeting criteria for a full-threshold disorder are excluded. Transition status and clinical and functional outcomes are re-assessed at 6 and 12 months. CONCLUSIONS: This study will be the first to introduce and validate clinical criteria to identify a broader at-risk patient population, which may facilitate young people's access to clinical services and early treatment by reducing the reliance on "caseness" defined according to current diagnostic categories being required for service entry. These criteria may introduce a new, trans-diagnostic approach for understanding risk factors and pathogenic mechanisms that drive the onset of severe mental illness and the next generation of preventive intervention trials.

Beyond the "at risk mental state" concept: transitioning to transdiagnostic psychiatry.

The "at risk mental state" for psychosis approach has been a catalytic, highly productive research paradigm over the last 25 years. In this paper we review that paradigm and summarize its key lessons, which include the valence of this phenotype for future psychosis outcomes, but also for comorbid, persistent or incident non-psychotic disorders; and the evidence that onset of psychotic disorder can at least be delayed in ultra high risk (UHR) patients, and that some full-threshold psychotic disorder may emerge from risk states not captured by UHR criteria. The paradigm has also illuminated risk factors and mechanisms involved in psychosis onset. However, findings from this and related paradigms indicate the need to develop new identification and diagnostic strategies. These findings include the high prevalence and impact of mental disorders in young people, the limitations of current diagnostic systems and risk identification approaches, the diffuse and unstable symptom patterns in early stages, and their pluripotent, transdiagnostic trajectories. The approach we have recently adopted has been guided by the clinical staging model and adapts the original "at risk mental state" approach to encompass a broader range of inputs and output target syndromes. This approach is supported by a number of novel modelling and prediction strategies that acknowledge and reflect the dynamic nature of psychopathology, such as dynamical systems theory, network theory, and joint modelling. Importantly, a broader transdiagnostic approach and enhancing specific prediction (profiling or increasing precision) can be achieved concurrently. A holistic strategy can be developed that applies these new prediction approaches, as well as machine learning and iterative probabilistic multimodal models, to a blend of subjective psychological data, physical disturbances (e.g., EEG measures) and biomarkers (e.g., neuroinflammation, neural network abnormalities) acquired through fine-grained sequential or longitudinal assessments. This strategy could ultimately enhance our understanding and ability to predict the onset, early course and evolution of mental ill health, further opening pathways for preventive interventions.

What Box: A task for assessing language lateralization in young children.

The assessment of active language lateralization in infants and toddlers is challenging. It requires an imaging tool that is unintimidating, quick to setup, and robust to movement, in addition to an engaging and cognitively simple language processing task. Functional Transcranial Doppler Ultrasound (fTCD) offers a suitable technique and here we report on a suitable method to elicit active language production in young children. The 34-second "What Box" trial presents an animated face "searching" for an object. The face "finds" a box that opens to reveal a to-be-labelled object. In a sample of 95 children (1 to 5 years of age), 81% completed the task-32% with ≥10 trials. The task was validated (ρ = 0.4) against the gold standard Word Generation task in a group of older adults (n = 65, 60-85 years of age), though was less likely to categorize lateralization as left or right, indicative of greater measurement variability. Existing methods for active language production have been used with 2-year-old children while passive listening has been conducted with sleeping 6-month-olds. This is the first active method to be successfully employed with infants through to pre-schoolers, forming a useful tool for populations in which complex instructions are problematic.

Cognition, temperament, and cerebral blood flow velocity in toddlers and preschool children with sleep-disordered breathing or behavioral insomnia of childhood.

BACKGROUND: Cognitive decrements, problematic behaviors, and increased cerebral blood flow velocities (CBFVs) have been reported in children aged 3-7 years with sleep-disordered breathing (SDB). Whether similar impairments exist in younger children or those with behavioral insomnia of childhood (BIC) remains unclear. This study aimed to compare cognition and temperament in children aged 1-5 years with SDB or BIC to healthy control children, and to investigate whether cognitive or behavioral deficits associated with sleep problems are related to changes in CBFV. METHOD: Toddlers and preschool-aged children (12-67 months) who had been referred for the clinical evaluation of SDB (n = 20) or BIC (n = 13) and a comparative sample of non-snoring healthy sleepers (controls; n = 77) were recruited from the community. Children underwent cognitive assessment (Mullen's Scale of Early Learning) and measurement of resting bilateral CBFV in the middle cerebral artery (MCA) using Transcranial Doppler. Parents completed temperament scales (Early Childhood or Childhood Behavior Questionnaire), a sleep problem questionnaire (Pediatric Sleep Problem Survey Instrument) and performed home-based pediatric sleep monitoring (Actigraphy and Sleep Diary). RESULTS: SDB children demonstrated impaired receptive skills, more hyperactive and energetic temperaments, and higher bilateral CBFV than controls and children with BIC. Logistic regression analyses indicated that impaired cognition, temperamental difficulties, and increased CBFV are independently associated with SDB. CONCLUSIONS: During early childhood, problematic temperaments, cognitive deficits, and altered cerebrovascular functioning are associated with SDB but not BIC. CBFV does not appear to mediate these daytime deficits and instead may be an independent outcome of SDB. The findings support the need for an early intervention in pediatric SDB.