Associations Between Cognitive Functions and Subsequent Mood Disorder Prognosis in Low-Risk, High-Risk and Affected Monozygotic Twins: A Seven-Year Follow-Up Study

Introduction: Aberrant cognition is common among individuals at familial risk for mood disorders (MD) and those already affected. However, long-term prospective studies are needed to determine whether specific cognitive features predict illness onset and relapse; and whether cognitive impairments reflect neurodevelopmental traits or neuroprogressive decline. Methods: This seven-year prospective study examined the relationship between cognition and illness progression in monozygotic twins with mood disorders, their healthy high-risk monozygotic co-twins, and low-risk twins without a family history. Emotional and non-emotional cognition was assessed at baseline (n = 204) and follow-up (n = 124). Cox regression models tested whether baseline cognition predicted future illness onset in unaffected individuals (n = 89) or relapse in affected ones (n = 112). Longitudinal cognitive changes were analyzed using mixed models. Results: Greater attentional vigilance toward consciously processed happy faces at baseline was associated with a reduced risk of both illness onset (Exp(B) = 0.995, CI [0.990; 1.000], p = 0.03) and relapse (Exp(B) = 0.997, CI [0.995; 0.999], p = 0.003). Paradoxically, better verbal fluency at baseline was linked to an increased risk of illness onset (Exp(B) = 1.589, CI [1.204; 2.097], p < 0.001). Over time, onset was associated with increasing avoidance of subliminal fearful faces (group-by-time interaction, p < 0.001), whereas avoidance decreased in those who remained well. Verbal fluency declined in twins who developed a mood disorder (p = 0.02) but remained stable in those who stayed unaffected. No significant longitudinal cognitive differences emerged between affected twins with and without relapse. Conclusions: Positive attentional biases may protect against illness onset and relapse, while greater baseline verbal fluency may unexpectedly signal vulnerability. Verbal fluency decline after illness onset likely reflects scar effects. The findings underscore the importance of early identification of cognitive-emotional vulnerabilities and suggest targets for preventive interventions.