Cognitive and metabolic signatures of early and late-onset depression: A comparative study.

BACKGROUND

Early-onset depression (EOD) and late-onset depression (LOD) are prevalent subtypes of major depressive disorder (MDD), but the clinical distinction between EOD and LOD remains blurred due to nonspecific symptoms and lack of biomarkers. This study aims to elucidate the characteristics in cognitive function and biochemical metabolism of EOD and LOD, and to identify biological factors influencing age of onset (AOO).

METHODS

Seventy patients with MDD (40 with EOD and 30 with LOD) and sixty-eight age-matched healthy controls (HC) were included in this study. Participants were evaluated for clinical features, cognitive function, and serum trace elements levels. Proton magnetic resonance spectroscopy (H-MRS) was employed to quantify neurometabolites levels, including N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr).

RESULTS

Patients with LOD experienced more episodes and severe depressive symptoms than those with EOD (p = 0.025, p < 0.001). EOD patients performed significantly worse than LOD patients on social cognition (p = 0.005), while LOD patients performed worse than EOD patients on reasoning and problem solving (p = 0.005). Additionally, LOD patients displayed higher ceruloplasmin (Cp) levels compared to EOD patients (p = 0.004), but no difference was found in neurometabolic levels between EOD and LOD. Multiple linear regression indicated a positive correlation between serum Cp levels and AOO of depression (p < 0.001), while bilateral thalamic NAA/Cr showed a negative correlation with AOO (p = 0.012, p = 0.016).

CONCLUSIONS

Patients with EOD were characterized by social cognition impairments, while patients with LOD were marked by reasoning and problem-solving deficits. Serum Cp levels demonstrated an AOO-related effect and served as a positive predictor for the AOO of depression. Furthermore, a negative correlation has been established between bilateral thalamic NAA/Cr and the AOO of MDD.

LIMITATIONS

The limited sample size and the challenge in distinguishing whether observed results are attributed to age or AOO effects.