The Transdiagnostic Association between Cognitive Functioning and Psychopathology Exploratory Modeling of Cognitive Structure in a Naturalistic Patient Sample

Abstract Background Impairments in cognitive functioning (CF) contribute to the onset, severity, and persistence of psychiatric symptoms. While specific CF domains may relate differentially to psychopathology, evidence also supports a general factor of cognitive impairment (the C-factor). We aimed to examine how general and domain-specific CF impairments relate to psychopathology using both diagnosis-specific and transdiagnostic symptom frameworks. Methods Data were drawn from five cognitive tasks administered in the deep-phenotyped, naturalistic MIND-Set cohort. A bifactor model of CF was estimated in a discovery sample (n = 206) and internally validated in a separate subsample (n = 312). Factor scores were then explored in relation to broad diagnostic clusters (stress-related disorders, neurodevelopmental disorders, comorbid disorders, and healthy controls), presence of specific diagnoses, number of diagnoses, and transdiagnostic symptom domains. Results The bifactor model comprised a general CF factor (C-factor) and five specific subfactors—Reaction Time, Incompatibility, Working Memory, Inhibition, and Flexibility—and successfully replicated, although the general factor was relatively weak. Diagnosis-specific analyses showed that only individuals with stress-related disorders differed significantly from healthy controls on the C-factor and the Incompatibility factor. Higher impairment on the Incompatibility factor was associated with mood disorder diagnoses, while both the C-factor and Incompatibility factor were correlated with greater diagnostic burden. At the symptom level, the Incompatibility factor was associated with Negative Valence and Arousal domains, the C-factor with Negative Valence, and the Flexibility factor with Arousal. Conclusion These findings indicate that broader cognitive impairment and deficits on tasks requiring inhibition under cognitive load are primarily related to mood disorders, ADHD, and transdiagnostic symptoms of negative valence and arousal. More generally, cognitive impairment appears to reflect symptom burden and transdiagnostic expression rather than diagnostic category alone, suggesting that dimensional symptom measures may provide a more informative framework for understanding cognitive impairment in clinical populations.