The impact of ACTH levels on neurotransmitters and antioxidants in patients with major depressive disorder: A novel investigation

• Published in: Journal of affective disorders Vol. 365; pp. 587 - 596
• Main Authors: Tian, Shiyun, Liu, Meichen, Yang, Chun, Du, Wei, Gao, Bingbing, Li, Mengying, Pan, Tao, Liu, Tieli, Song, Qingwei, Lin, Liangjie, Zhang, Huimin, Miao, Yanwei
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.11.2024
• Subjects: ACTH; Adrenocorticotropic Hormone - blood; Adult; Antioxidants - metabolism; Case-Control Studies; Depressive Disorder, Major - blood; Depressive Disorder, Major - metabolism; Depressive Disorder, Major - physiopathology; Female; GABA; gamma-Aminobutyric Acid - blood; gamma-Aminobutyric Acid - metabolism; Glutathione - blood; Glutathione - metabolism; Glx; GSH; Gyrus Cinguli - metabolism; HPA axis; Humans; Hypothalamo-Hypophyseal System - metabolism; Hypothalamo-Hypophyseal System - physiopathology; Major depressive disorder; Male; Middle Aged; Neurotransmitter Agents - blood; Neurotransmitter Agents - metabolism; Oxidative Stress - physiology; Pituitary-Adrenal System - metabolism; Pituitary-Adrenal System - physiopathology; ACTH; GABA; Glx; HPA axis; GSH; Major depressive disorder
• ISSN: 0165-0327; 1573-2517; 1573-2517
• DOI: 10.1016/j.jad.2024.08.142

The relationship between neurotransmitters and oxidative stress in Major Depressive Disorder (MDD) patients, considering HPA axis activity and psychological and cognitive states, is unclear. This study examines changes in neurotransmitters (GABA, Glx) and antioxidants (GSH) in the dorsal anterior cingulate cortex (dACC) of MDD patients under varying levels of ACTH, and their relationship with psychological and cognitive conditions. Forty-five MDD patients were divided into high-ACTH (>65 pg/mL; n = 16) and normal-ACTH (7–65 pg/mL; n = 29) groups based on blood ACTH levels, along with 12 healthy controls (HC). All participants underwent HAM-D, HAM-A assessments, and most completed MMSE and MoCA tests. GABA+, Glx, and GSH levels in the dACC were measured using the MEGA-PRESS sequence. Intergroup differences and correlations between clinical factors, HPA axis activity, and metabolites were analyzed. Compared to HC, the normal ACTH group showed higher Glx and lower GSH levels. Glx and GSH were negatively correlated with MDD severity. In the high-ACTH MDD group, Glx positively correlated with delayed memory, and GSH positively correlated with abstraction. Factors influencing GABA included ACTH levels, depression duration, and negative events. Predictive factors for HAM-D scores were GSH and GABA. The sample size is small. MDD patients exhibit neurochemical differences in the brain related to HPA axis levels, MDD severity, and cognitive function. Clinical factors, neurotransmitters, and neuroendocrine levels significantly influence depression severity. [Display omitted] •Compared to healthy controls, the normal ACTH MDD patients had higher Glx and lower GSH levels•Glx and GSH levels were inversely related to MDD severity•In the high ACTH MDD group, Glx positively correlated with delayed memory, and GSH with abstraction•Neurochemical differences in MDD patients' brains at varying HPA axis levels are linked to MDD severity and cognitive function