The Association between Default-mode Network Functional Connectivity and Childhood Trauma on the Symptom Load in Male Adults with Methamphetamine Use Disorder
Shyh-Yuh Wei1, Tsung-Han Tsai1, Tsung-Yu Tsai1, Po See Chen1,2, Huai-Hsuan Tseng1,2, Yen Kuang Yang1,2,3, Tianye Zhai4, Yihong Yang4, Tzu-Yun Wang1
1Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
2Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
3Department of Psychiatry, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan
4Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA
Correspondence to: Tzu-Yun Wang
Department of Psychiatry, National Cheng Kung University Hospital, 138 Sheng Li Road, North Dist., Tainan 70403, Taiwan
E-mail: wangty@mail.ncku.edu.tw
ORCID: https://orcid.org/0000-0002-0561-9967
Received: March 29, 2023; Revised: May 25, 2023; Accepted: August 14, 2023; Published online: September 14, 2023.
© The Korean College of Neuropsychopharmacology. All rights reserved.

This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Objective: The relationship between adverse childhood experiences and methamphetamine use disorder (MUD) has been shown in previous studies; nevertheless, the underlying neural mechanisms remain elusive. Childhood trauma is associated with aberrant functional connectivity (FC) within the default-mode network (DMN). Furthermore, within the DMN, FC may contribute to impaired self-awareness in addiction, while cross-network FC is critical for relapse. We aimed to investigate whether childhood trauma was associated with DMN-related resting-state FC among healthy controls and patients with MUD and to examine whether DMN-related FC affected the effect of childhood trauma on the symptom load of MUD diagnosis.
Methods: Twenty-seven male patients with MUD and 27 male healthy controls were enrolled and completed the Childhood Trauma Questionnaire. DMN-related resting-state FC was examined using functional magnetic resonance imaging.
Results: There were 47.1% healthy controls and 66.7% MUD patients in this study with adverse childhood experiences. Negative correlations between adverse childhood experiences and within-DMN FC were observed in both healthy controls and MUD patients, while within-DMN FC was significantly altered in MUD patients. The detrimental effects of adverse childhood experiences on MUD patients may be attenuated through DMN-executive control networks (ECN) FC.
Conclusion: Adverse childhood experiences were negatively associated with within-DMN FC in MUD patients and healthy controls. However, DMN-ECN FC may attenuate the effects of childhood trauma on symptoms load of MUD.
Keywords: Amphetamines; Adverse childhood experiences; Default mode network; Magnetic resonance imaging; Mediation analysis

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