Psychiatric morbidity is associated with cognitive impairment, whereas diagnostic category may shape its profile: a transdiagnostic study of inflammation, salivary biomarkers, and health-related quality of life

Abstract

Background Cognitive impairment is highly prevalent across psychiatric disorders, but it remains unclear how psychiatric morbidity and diagnostic category contribute to its presence and profile and whether inflammation and salivary synaptic proteins are associated with cognitive impairment across diagnoses. This transdiagnostic study integrated clinical, cognitive, inflammatory, and salivary biomarker data to examine these questions. Methods Cross-sectional assessment of 131 participants (controls, n = 63; major depressive disorder, n = 20; schizophrenia, n = 20; substance use disorder, n = 28). Systemic inflammation was indexed by neutrophil-to-lymphocyte ratio (NLR). Salivary synaptophysin (SYP), synaptotagmin-1 (SYT1), and synapsin-II (SYN2) were quantified as exploratory biomarkers. Logistic, multinomial, and linear regression models were used to identify variables independently associated with cognitive impairment, subjective distress, and inflammation. Results The presence of any psychiatric disorder was the strongest independent correlate of cognitive impairment (OR = 5.23, 95% CI 2.05–13.35). Exploratory diagnosis-specific analyses suggested heterogeneity in cognitive, inflammatory, and psychosocial profiles. NLR was associated with psychiatric morbidity but was not independently associated with cognitive impairment. SYP showed an exploratory association with cognitive impairment (OR = 0.993 per ng/mL increase; corresponding OR = 0.681 across the observed interquartile range), although this finding was attenuated in sensitivity analyses and should be interpreted cautiously. Subjective distress was not independently associated with diagnosis or biomarkers but was strongly associated with health-related quality of life (HRQoL) (SF-12 physical and mental components; Nagelkerke R 2 = 0.734), indicating a distinct psychosocial dimension; however, this finding should be interpreted cautiously because of conceptual overlap between self-reported constructs. Limitations Cross-sectional design precludes causal inference. Sample size limits statistical power for diagnostic subgroup comparisons. The neuropsychological assessor was not blinded to participants’ diagnostic status. Universal psychopharmacological treatment precludes disentangling illness from medication effects. Conclusion Psychiatric morbidity was associated with the presence of cognitive impairment in this baseline cross-sectional analysis, whereas the diagnostic category may contribute to heterogeneity in the impairment profile. Systemic inflammation was associated with psychiatric morbidity but was not independently associated with cognitive impairment. Subjective distress was strongly associated with HRQoL and appeared largely independent of the biological markers examined. These findings support an integrative multilevel framework in which cognitive impairment and HRQoL represent complementary transdiagnostic dimensions. Routine cognitive screening across psychiatric settings may be warranted. The observed SYP and HRQoL associations should be considered hypothesis-generating and require longitudinal validation.

The authors' abstract, as published at the source. Frontiers in Psychology, 2026 · DOI ↗