. 2023 Aug 29;48(4):E315-E324.

doi: 10.1503/jpn.220209. Print 2023 Jul-Aug.

Brain network structural connectome abnormalities among youth with attention-deficit/hyperactivity disorder at varying risk for bipolar I disorder: a cross-sectional graph-based magnetic resonance imaging study

Affiliations

¹ From the Huaxi MR Research Center (HMRRC), Department of Radiology, The Center for Medical Imaging, West China Hospital of Sichuan University, Chengdu, China (Zhu, Qin, X. Li, Gong); the Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH (Zhu, Qin, Tallman, Patino, Fleck, Aghera, Sweeney, McNamara, DelBello); the College of Medical Informatics, Chongqing Medical University, Chongqing, China (Lei); the Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, Sichuan, China (X. Li); the Department of Magnetic Resonance Imaging, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China (W. Li); the Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, Sichuan, China (Gong); the Department of Radiology, West China Xiamen Hospital of Sichuan University, Xiamen, Fujian, China (Gong).
² From the Huaxi MR Research Center (HMRRC), Department of Radiology, The Center for Medical Imaging, West China Hospital of Sichuan University, Chengdu, China (Zhu, Qin, X. Li, Gong); the Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH (Zhu, Qin, Tallman, Patino, Fleck, Aghera, Sweeney, McNamara, DelBello); the College of Medical Informatics, Chongqing Medical University, Chongqing, China (Lei); the Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, Sichuan, China (X. Li); the Department of Magnetic Resonance Imaging, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China (W. Li); the Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, Sichuan, China (Gong); the Department of Radiology, West China Xiamen Hospital of Sichuan University, Xiamen, Fujian, China (Gong) alien18@163.com qiyonggong@hmrrc.org.cn.

^# Contributed equally.

PMID: 37643802
PMCID: PMC10473038
DOI: 10.1503/jpn.220209

Brain network structural connectome abnormalities among youth with attention-deficit/hyperactivity disorder at varying risk for bipolar I disorder: a cross-sectional graph-based magnetic resonance imaging study

Ziyu Zhu et al. J Psychiatry Neurosci. 2023.

. 2023 Aug 29;48(4):E315-E324.

doi: 10.1503/jpn.220209. Print 2023 Jul-Aug.

Authors

Affiliations

¹ From the Huaxi MR Research Center (HMRRC), Department of Radiology, The Center for Medical Imaging, West China Hospital of Sichuan University, Chengdu, China (Zhu, Qin, X. Li, Gong); the Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH (Zhu, Qin, Tallman, Patino, Fleck, Aghera, Sweeney, McNamara, DelBello); the College of Medical Informatics, Chongqing Medical University, Chongqing, China (Lei); the Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, Sichuan, China (X. Li); the Department of Magnetic Resonance Imaging, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China (W. Li); the Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, Sichuan, China (Gong); the Department of Radiology, West China Xiamen Hospital of Sichuan University, Xiamen, Fujian, China (Gong).
² From the Huaxi MR Research Center (HMRRC), Department of Radiology, The Center for Medical Imaging, West China Hospital of Sichuan University, Chengdu, China (Zhu, Qin, X. Li, Gong); the Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH (Zhu, Qin, Tallman, Patino, Fleck, Aghera, Sweeney, McNamara, DelBello); the College of Medical Informatics, Chongqing Medical University, Chongqing, China (Lei); the Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, Sichuan, China (X. Li); the Department of Magnetic Resonance Imaging, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China (W. Li); the Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, Sichuan, China (Gong); the Department of Radiology, West China Xiamen Hospital of Sichuan University, Xiamen, Fujian, China (Gong) alien18@163.com qiyonggong@hmrrc.org.cn.

^# Contributed equally.

PMID: 37643802
PMCID: PMC10473038
DOI: 10.1503/jpn.220209

Abstract

Background: Attention-deficit/hyperactivity disorder (ADHD) is highly prevalent among youth with or at familial risk for bipolar-I disorder (BD-I), and ADHD symptoms commonly precede and may increase the risk for BD-I; however, associated neuropathophysiological mechanisms are not known. In this cross-sectional study, we sought to investigate brain structural network topology among youth with ADHD, with and without familial risk of BD-I.

Methods: We recruited 3 groups of psychostimulant-free youth (aged 10-18 yr), namely youth with ADHD and at least 1 biological parent or sibling with BD-I (high-risk group), youth with ADHD who did not have a first- or second-degree relative with a mood or psychotic disorder (low-risk group) and healthy controls. We used graph-based network analysis of structural magnetic resonance imaging data to investigate topological properties of brain networks. We also evaluated relationships between topological metrics and mood and ADHD symptom ratings.

Results: A total of 149 youth were included in the analysis (49 healthy controls, 50 low-risk youth, 50 high-risk youth). Low-risk and high-risk ADHD groups exhibited similar differences from healthy controls, mainly in the default mode network and central executive network. We found topological alterations in the salience network of the high-risk group, relative to both low-risk and control groups. We found significant abnormalities in global network properties in the high-risk group only, compared with healthy controls. Among both low-risk and high-risk ADHD groups, nodal metrics in the right triangular inferior frontal gyrus correlated positively with ADHD total and hyperactivity/impulsivity subscale scores.

Limitations: The cross-sectional design of this study could not determine the relevance of these findings to BD-I risk progression.

Conclusion: Youth with ADHD, with and without familial risk for BD-I, exhibit common regional abnormalities in the brain connectome compared with healthy youth, whereas alterations in the salience network distinguish these groups and may represent a prodromal feature relevant to BD-I risk.

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Conflict of interest statement

Competing interests: Rodrigo Patino receives research funding from the National Institutes of Health (NIH), the Patient-Centered Outcomes Research Institute (PCORI), Abbvie, Allergan, Janssen, Johnson & Johnson, Lundbeck, Lilly, Otsuka, Pfizer and Sunovion. Melissa DelBello receives research support from the NIH, PCORI, Acadia, Alkermes, Allergan, Janssen, Johnson & Johnson, Lundbeck, Otsuka, Pfizer, Sage, Sunovion and Vanda. She is also a consultant, on the advisory board or has received honoraria for speaking for Alkermes, Allergan, Assurex, CMEology, Janssen, Johnson & Johnson, Lundbeck, Myriad, Neuronetics, Otsuka, Pfizer, Sage, Sunovion and Supernus. She has received travel support from the American Academy of Child and Adolescent Psychiatry. No other competing interests were declared.

Figures

**Figure 1**
Global topological metrics among high-risk youth with attention-deficit/hyperactivity disorder (ADHD), low-risk youth with ADHD and healthy controls (HC), including (A) global efficiency (E_glob), (B) local efficiency (E_loc), (C) clustering coefficient (Cp), (D) small-worldness (σ), (E) characteristic path length (Lp), (F) normalized characteristic path length (λ) and (G) normalized clustering coefficient (γ). Presented p values are from the analysis of variance; post hoc 2-sample comparisons are corrected by false discovery rate.*HC v. high-risk group.

**Figure 2**
Brain regions exhibiting nodal centrality differences among high-risk youth with attention-deficit/hyperactivity disorder (ADHD), low-risk youth with ADHD and healthy controls (HC). The nodes were mapped onto the cortical surfaces by using the BrainNet Viewer package (www.nitrc.org/projects/bnv). IFGoperc = opercular part of inferior frontal gyrus; IFGtriang = triangular part of inferior frontal gyrus; IOG = inferior occipital gyrus; L = left; PHG = parahippocampalgyrus; R = right; REC = gyrus rectus; ROL = rolandic operculum; SPG = superior parietal gyrus.

**Figure 3**
(A) Localization of the right triangular inferior frontal gyrus (IFG). Correlations between nodal metrics in the right triangular IFG and ratings of attention-deficit/hyperactivitiy disorder (ADHD) scores on the ADHD Rating Scale (ADHD-R), including (A) nodal degree and ADHD total score (B) nodal efficiency and ADHD hyperactivity/impulsivity subscale score and (C) nodal degree and ADHD hyperactivity/impulsivity subscale score among both low-risk and high-risk ADHD groups.

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Brain network structural connectome abnormalities among youth with attention-deficit/hyperactivity disorder at varying risk for bipolar I disorder: a cross-sectional graph-based magnetic resonance imaging study

Affiliations

Brain network structural connectome abnormalities among youth with attention-deficit/hyperactivity disorder at varying risk for bipolar I disorder: a cross-sectional graph-based magnetic resonance imaging study

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Abstract

Conflict of interest statement

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