Reduced temporal mismatch negativity in late-life depression: An event-related potential index of cognitive deficit and functional disability?

Abstract

Depression in older people has been consistently linked with a variety of neurobiological brain changes. One measure of preattentive auditory processing, the mismatch negativity (MMN), has not been previously examined in late-life depression. This study examined MMN elicited by duration deviant stimuli in older people with lifetime depression, and explored its relationship with neuropsychological functioning and disability. Twenty-two older health-seeking patients (mean age=65.2 years) with lifetime major depressive disorder and twelve age and sex-matched control participants (mean age=64.6 years) completed detailed clinical and neuropsychological assessments and the WHO-DAS as a measure of disability. MMN amplitudes were elicited using a two-tone passive auditory oddball paradigm and measured at frontal (Fz), central (Cz) and temporal (left and right mastoid: M1 and M2, respectively) sites. Patients with depression demonstrated reduced mean MMN amplitude at temporal (M1, t=3.1, p<0.01; M2, t=3.8, p<0.01), but not fronto-central sites. Reduced temporal MMN amplitudes did not relate to depressive symptom severity, but were associated with reduced semantic fluency and greater self-rated functional disability. The contribution of depressive symptom 'state' and medications on MMN need to be considered. Reduced mean amplitudes of mastoid MMN in older patients with lifetime depression may reflect underlying brain changes. This preattentive marker relates to neuropsychological probes of frontotemporal circuits, and importantly, is associated with disability. Longitudinal analysis of MMN in this group will determine its predictive utility as a biomarker for ongoing cognitive decline and illness chronicity.