An Investigation of Psychosis Subgroups With Prognostic Validation and Exploration of Genetic Underpinnings

Abstract

Identifying psychosis subgroups could improve clinical and research precision. Research has focused on symptom subgroups, but there is a need to consider a broader clinical spectrum, disentangle illness trajectories, and investigate genetic associations. OBJECTIVE To detect psychosis subgroups using data-driven methods and examine their illness courses over 1.5 years and polygenic scores for schizophrenia, bipolar disorder, major depression disorder, and educational achievement. DESIGN, SETTING, AND PARTICIPANTS This ongoing multisite, naturalistic, longitudinal (6-month intervals) cohort study began in January 2012 across 18 sites. Data from a referred sample of 1223 individuals (765 in the discovery sample and 458 in the validation sample) with DSM-IV diagnoses of schizophrenia, bipolar affective disorder (I/II), schizoaffective disorder, schizophreniform disorder, and brief psychotic disorder were collected from secondary and tertiary care sites.

Identification of transdiagnostic psychiatric disorder subtypes using unsupervised learning

“…A transdiagnostic study identified a cluster containing mainly healthy controls and exhibiting the lowest symptom scores in the observed dimensions [34], likely corresponding to our cluster 0. Our highly impaired cluster 4, with its high percentage of schizophrenic patients, low functioning, and significantly lower EA PGS, may correspond to the severe psychosis subtype from a previous study [32]. Moreover, a single-disorder subtyping study [5] detected five clusters of MDD exhibiting different symptom severities, with one subtype showing an absence of many symptoms, similar to our cluster 0.…”

“…Transdiagnostic clustering supports the existence of diagnostically mixed subtypes across two [4, 29–31] or more disorders [32–35]. However, previous transdiagnostic clustering studies were limited by small samples and analyzed few disorders or variables [36, 37].…”

Glucocorticoid Receptor Antagonist Mifepristone Does Not Alter Innate Anxiety-Like Behavior in Genetically-Selected Marchigian Sardinian (msP) Rats

“…In addition, acute versus chronic mifepristone treatment would impact non-genomic versus genomic GR signaling (respectively), likely representing differential mechanisms of action [ 38 ]. It should also be noted that mifepristone has demonstrated clinical efficacy in patients suffering from psychotic depression (reviewed in [ 39 ]). As such, to detect beneficial effects of mifepristone, future studies may involve chronic treatment regimens prior to behavioral assessments, as well as additional measures of negative affect.…”

Transdiagnostic neurocognitive subgroups and functional course in young people with emerging mental disorders: a cohort study

“…These studies will be important to determine whether observed subgroups represent biologically meaningful, ‘natural kinds’ of groupings, 57 or instead represent segments of a neurocognitive continuum distributed throughout the population. Moreover, future studies should utilise machine-learning approaches to better select variables to be used in clustering algorithms (for example Dwyer et al 58 ), and to broaden outcome variables to model relationships between data-driven subgroups and other clinical and functional outcomes (for example clinical stage transition, admission to hospital), which may assist in planning of personalised interventions. 59…”