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Multivariate Resting-State Functional Connectivity Features Linked to Transdiagnostic Psychopathology in Early Psychosis

2025· article· en· W4415681463 on OpenAlexaff
Haley R Wang, Zhen-Qi Liu, Jason S. Nomi, Charles Schleifer, Carrie E. Bearden, Bratislav Mišić, Lucina Q. Uddin, Katherine H. Karlsgodt

Bibliographic record

VenueBiological Psychiatry · 2025
Typearticle
Languageen
FieldNeuroscience
TopicFunctional Brain Connectivity Studies
Canadian institutionsMcGill UniversityMontreal Neurological Institute and Hospital
FundersNational Institutes of HealthNational Institute of Mental HealthAmerican Psychological Foundation
KeywordsPsychopathologyPsychosisArousalEarly psychosisCognitionMultivariate statisticsFunctional connectivity

Abstract

fetched live from OpenAlex

BACKGROUND: Early psychosis (EP) is characterized by neurobiological changes, including alterations in resting-state functional connectivity (RSFC). We now understand that symptoms and neural changes may overlap across EP diagnostic categories. However, the relationship between RSFC patterns and transdiagnostic symptom dimensions remains poorly understood. METHODS: We used partial least squares correlation to examine multivariate relationships between whole-brain RSFC and clinical symptoms in 124 patients with EP (ages 16-35 years) diagnosed with schizophrenia, schizoaffective disorder, or a psychotic mood disorder. RSFC was computed among 216 cortical and subcortical regions. Clinical assessment included 41 symptom measures spanning positive, negative, general psychopathology, and manic dimensions. RESULTS: Analysis revealed one significant latent component (p < .001) capturing 41.6% of the RSFC symptom covariance. This component was characterized by increased between-network connectivity, particularly involving sensory-motor, default mode, and subcortical regions including the amygdala and thalamus. The associated symptom profile included cognitive rigidity and arousal dysregulation (stereotyped thinking, anxiety, and somatic concerns) rather than traditional positive or negative symptoms. This brain-behavior relationship was consistent across diagnoses and independent of medication and substance use. The clinical relevance of this relationship was validated through significant correlations with standardized measures of hostility (r = 0.23), negative affect (r = 0.25), and perceived stress (r = 0.22). CONCLUSIONS: Our findings reveal a distinct transdiagnostic phenotype in EP characterized by cognitive inflexibility and arousal dysregulation that is associated with altered integration between sensory, default mode, and subcortical networks. This work suggests that specific patterns of network-level FC may relate to symptom dimensions that cut across conventional diagnostic boundaries, potentially informing more targeted therapeutic approaches.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.048
GPT teacher head0.308
Teacher spread0.261 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2025
Admission routes1
Has abstractyes

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