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

Jiali He; Yangyu Wu; Shuming Zhong; Ying Wang; Shunkai Lai; Dong Huang; Jianzhao Zhang; Xiaodan Lu; Xiaodong Song; Qilin Zhong; Pan Chen; Yanbin Jia

doi:10.1016/j.jad.2025.02.081

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

J Affect Disord. 2025 Jun 15:379:10-18. doi: 10.1016/j.jad.2025.02.081. Epub 2025 Feb 27.

Authors

Jiali He¹, Yangyu Wu², Shuming Zhong², Ying Wang³, Shunkai Lai², Dong Huang², Jianzhao Zhang², Xiaodan Lu², Xiaodong Song², Qilin Zhong², Pan Chen³, Yanbin Jia⁴

Affiliations

¹ Department of Psychiatry, First Affiliated Hospital, Jinan University, Guangzhou, China; Department of Psychology, Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
² Department of Psychiatry, First Affiliated Hospital, Jinan University, Guangzhou, China.
³ Medical Imaging Center, First Affiliated Hospital, Jinan University, Guangzhou, China.
⁴ Department of Psychiatry, First Affiliated Hospital, Jinan University, Guangzhou, China. Electronic address: yanbinjia2006@163.com.

PMID: 40023261
DOI: 10.1016/j.jad.2025.02.081

Abstract

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 (¹H-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.

Keywords: Age of onset; Cognition; Early-onset depression; Late-onset depression; Metabolism.

Publication types

Comparative Study

MeSH terms

Adult
Age of Onset
Aspartic Acid / analogs & derivatives
Aspartic Acid / metabolism
Ceruloplasmin / metabolism
Choline / blood
Choline / metabolism
Cognition* / physiology
Creatine / blood
Creatine / metabolism
Depressive Disorder, Major* / blood
Depressive Disorder, Major* / diagnosis
Depressive Disorder, Major* / metabolism
Depressive Disorder, Major* / psychology
Female
Humans
Male
Middle Aged
Neuropsychological Tests
Proton Magnetic Resonance Spectroscopy

Substances

Creatine
Choline
Aspartic Acid
N-acetylaspartate
Ceruloplasmin