Transdiagnostic clinical staging for childhood mental health: An adjunctive tool for classifying internalizing and externalizing syndromes that emerge in children aged 5-11 years

Clinical staging is now recognized as a key tool for facilitating innovation in personalized and preventative mental health care. It places a strong emphasis on the salience of indicated prevention, early intervention, and secondary prevention of major mental disorders. By contrast to established models for major mood and psychotic syndromes that emerge after puberty, developments in clinical staging for childhood-onset disorders lags significantly behind. In this article, criteria for a transdiagnostic staging model for those internalizing and externalizing disorders that emerge in childhood is presented. This sits alongside three putative pathophysiological profiles (developmental, circadian, and anxious-arousal) that may underpin these common illness trajectories. Given available evidence, we argue that it is now timely to develop a transdiagnostic staging model for childhood-onset syndromes. It is further argued that a transdiagnostic staging model has the potential to capture more precisely the dimensional, fluctuating developmental patterns of illness progression of childhood psychopathology. Given potential improvements in modelling etiological processes, and delivering more personalized interventions, transdiagnostic clinical staging for childhood holds much promise for assisting to improve outcomes. We finish by presenting an agenda for research in developments of transdiagnostic clinical staging for childhood mental health.

Psychosis in Women: Time for Personalized Treatment

Early detection and prompt treatment of psychosis is of the utmost importance. The great variability in clinical onset, illness course, and response to pharmacological and psychosocial treatment is in great part gender-related. Our aim has been to review narratively the literature focusing on gender related differences in the psychoses, i.e., schizophrenia spectrum disorders. We searched the PubMed/Medline, Scopus, Embase, and ScienceDirect databases on 31 July 2021, focusing on recent research regarding sex differences in early psychosis. Although women, compared to men, tend to have better overall functioning at psychotic symptom onset, they often present with more mood symptoms, may undergo misdiagnosis and delay in treatment and are at a higher risk for antipsychotic drug-induced metabolic and endocrine-induced side effects. Furthermore, women with schizophrenia spectrum disorders have more than double the odds of having physical comorbidities than men. Tailored treatment plans delivered by healthcare services should consider gender differences in patients with a diagnosis of psychosis, with a particular attention to early phases of disease in the context of the staging model of psychosis onset.

In vivo staging of regional amyloid progression in healthy middle-aged to older people at risk of Alzheimer’s disease

Background We investigated regional amyloid staging characteristics in 11C-PiB-PET data from middle-aged to older participants at elevated risk for AD enrolled in the Wisconsin Registry for Alzheimer’s Prevention. Methods We analyzed partial volume effect-corrected 11C-PiB-PET distribution volume ratio maps from 220 participants (mean age = 61.4 years, range 46.9–76.8 years). Regional amyloid positivity was established using region-specific thresholds. We used four stages from the frequency-based staging of amyloid positivity to characterize individual amyloid deposition. Longitudinal PET data was used to assess the temporal progression of stages and to evaluate the emergence of regional amyloid positivity in participants who were amyloid-negative at baseline. We also assessed the effect of amyloid stage on longitudinal cognitive trajectories. Results The staging model suggested progressive accumulation of amyloid from associative to primary neocortex and gradually involving subcortical regions. Longitudinal PET measurements supported the cross-sectionally estimated amyloid progression. In mixed-effects longitudinal analysis of cognitive follow-up data obtained over an average period of 6.5 years following the baseline PET measurement, amyloid stage II showed a faster decline in executive function, and advanced amyloid stages (III and IV) showed a faster decline across multiple cognitive domains compared to stage 0. Conclusions Overall, the 11C-PiB-PET-based staging model was generally consistent with previously derived models from 18F-labeled amyloid PET scans and a longitudinal course of amyloid accumulation. Differences in longitudinal cognitive decline support the potential clinical utility of in vivo amyloid staging for risk stratification of the preclinical phase of AD even in middle-aged to older individuals at risk for AD.

Right Care, First Time: Developing a Theory-Based Automated Protocol to Help Clinically Stage Young People Based on Severity and Persistence of Mental Illness

Most mental disorders emerge before the age of 25 years and, if left untreated, have the potential to lead to considerable lifetime burden of disease. Many services struggle to manage high demand and have difficulty matching individuals to timely interventions due to the heterogeneity of disorders. The technological implementation of clinical staging for youth mental health may assist the early detection and treatment of mental disorders. We describe the development of a theory-based automated protocol to facilitate the initial clinical staging process, its intended use, and strategies for protocol validation and refinement. The automated clinical staging protocol leverages the clinical validation and evidence base of the staging model to improve its standardization, scalability, and utility by deploying it using Health Information Technologies (HIT). Its use has the potential to enhance clinical decision-making and transform existing care pathways, but further validation and evaluation of the tool in real-world settings is needed.

Prodromal Symptoms in Depression: A Systematic Review

<b><i>Introduction</i></b>: Appraisal of prodromal symptoms of unipolar depression may complement the traditional cross-sectional approach and provide a longitudinal perspective, according to a staging model of the illness. <b><i>Objective:</i></b> To provide an updated systematic review of clinical studies concerned with prodromal symptoms of unipolar depression, according to PRISMA guidelines. <b><i>Methods:</i></b> Keyword searches were conducted in PubMed, Scopus, and Web of Science. Longitudinal studies on prodromal symptoms and signs in adult patients primarily diagnosed with unipolar depression were selected. Findings were examined separately according to study design (i.e., retrospective or prospective). <b><i>Results:</i></b> Twenty-five studies met the criteria for inclusion in this systematic review. Findings indicate that a distinct prodromal symptomatology – commonly characterized by anxiety, tension, irritability, and somatic complaints – exists before the onset of unipolar depression. The duration of the prodromal phase was highly variable across studies, ranging from less than a month to several years. Prodromal symptoms profile and duration were consistent within individuals across depressive episodes. There was a close relationship between prodromal and residual symptoms of the same depressive episode. <b><i>Conclusions:</i></b> The present systematic review addresses an important, and yet relatively neglected, clinical issue that deserves further investigation and may be of immediate practical value. The findings provide challenging insights into the pathogenesis and course of unipolar depression, which may result in more timely and effective treatment of recurrences. The definition of a prodromal phase in depression would benefit from the joint use of symptom identification, biomarkers, and neuroimaging.

Clinical Staging in Schizophrenia Spectrum Disorders

The aim of this chapter is to summarize the state-of-the-art knowledge of clinical staging in schizophrenia spectrum disorders. Clinical staging has been introduced to psychiatry in the past two decades. Its primary goal is to divide the course of the disorder into recognizable stages based on seriousness, development and symptom characteristics in order to better predict prognosis and to adopt the most appropriate treatment strategies. The first staging model was developed in 1982. Since then several distinct concepts of clinical staging in psychiatry have emerged. To date, there is no clinical consensus regarding which staging model is the gold standard, nonetheless when merging them together an integrated staging concept arises. The integrated staging model of schizophrenia spectrum disorders is composed of four stages. The chapter will introduce the different staging models in a historical order as well as present the integrated staging model detailing the characteristics, timeline and dominating symptoms of each stage. Appropriate treatment strategies for the distinct stages will also be outlined.

In-Vivo Staging of Regional Amyloid Progression In Healthy Middle Aged To Older People At Risk of Alzheimer’s Disease

Background We investigated regional amyloid staging characteristics in 11C-PiB-PET data from middle-aged to older participants at elevated risk for AD enrolled in the Wisconsin Registry for Alzheimer’s Prevention. Methods We analyzed partial volume effect-corrected 11C-PiB-PET distribution volume ratio maps from 220 participants (mean age = 61.4y, range: 46.9-76.8y). Regional amyloid-positivity was established using region-specific thresholds. We used four stages from frequency-based staging of amyloid-positivity to characterize individual amyloid deposition. Longitudinal PET data was used to assess temporal progression of stages and to evaluate emergence of regional amyloid-positivity in participants who were amyloid-negative at baseline. We also assessed the effect of amyloid stage on longitudinal cognitive trajectories.Results The staging model suggested progressive accumulation of amyloid from associative to primary neocortex and gradually involving subcortical regions. Longitudinal PET measurements supported the cross-sectionally estimated amyloid progression. In mixed-effects longitudinal analysis of cognitive follow-up data obtained over an average period of 6.5 years following the baseline PET measurement, amyloid stage II showed a faster decline in executive function and advanced amyloid stages (III and IV) showed a faster decline across multiple cognitive domains compared to stage 0.Conclusions Overall, the 11C-PiB-PET-based staging model was generally consistent with previously derived models from 18F-labled amyloid PET scans and a longitudinal course of amyloid accumulation. Differences in longitudinal cognitive decline support the potential clinical utility of in-vivo amyloid staging for risk stratification of the preclinical phase of AD even in middle-aged to older individuals at risk for AD.