Commonalities in frailty and psychopathology predict chronotype across severe mental disorders from a comorbidity...

Individuals with severe mental illness (SMI) have increased risk of physical comorbidities, linked to worse outcomes such as greater psychopathology, frailty, and neurocognitive impairment. Mechanisms underlying this burden remain unclear. This study examined whether frailty and psychopathology predict evening chronotype, especially in SMI with comorbidities.

A longitudinal study assessed 165 participants at two time points over one year: schizophrenia (n = 30), bipolar disorder (n = 42), major depressive disorder (n = 35), and healthy controls (n = 58). The SMI group (n = 107) was divided into SMI with comorbidities (SMI-C; n = 47) and without (SMI; n = 60). Measures included psychopathology, frailty, chronotype, neurocognitive and functional performance, and hematological biomarkers.

Neurocognitive and functional impairments were greater in SMI groups than controls (F = 10.3-31.4; p < 0.0001; η²p = 0.12-0.34). The SMI-C group showed worse frailty than controls at T1 (F = 4.3; p < 0.01; η²p = 0.05) and than SMI at T2 (F = 8.5; p < 0.0001; η²p = 0.12), and elevated MCV/MCH (F = 3.8-9.4; p < 0.05-0.0001; η²p = 0.04-0.11). Chronotype distribution did not differ. Frailty and psychopathology predicted chronotype in SMI (p < 0.05-0.01); in controls, frailty and performance did so (p < 0.05).

Psychopathological and hematological profiles are associated with chronotype and may help identify subgroups for chronobiology-informed interventions. These findings support more personalized treatment approaches.