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Research Paper
Open Access

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, Du Lei, Kun Qin, Xiuli Li, Wenbin Li, Maxwell J. Tallman, L. Rodrigo Patino, David E. Fleck, Veronica Aghera, Qiyong Gong, John A. Sweeney, Robert K. McNamara and Melissa P. DelBello
J Psychiatry Neurosci August 29, 2023 48 (4) E315-E324; DOI: https://doi.org/10.1503/jpn.220209
Ziyu Zhu
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)
PhD
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Du Lei
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)
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Kun Qin
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)
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Xiuli Li
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)
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Wenbin Li
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)
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Maxwell J. Tallman
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)
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L. Rodrigo Patino
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)
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David E. Fleck
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)
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Veronica Aghera
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)
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Qiyong Gong
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)
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John A. Sweeney
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)
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Robert K. McNamara
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)
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Melissa P. DelBello
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)
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Article Figures & Tables

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  • Figure 1
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    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 (Eglob), (B) local efficiency (Eloc), (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.

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    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.

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    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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    Table 1

    Demographic and clinical characteristics

    VariableNo. (%) of participants*p value†Low-risk youth v. high-risk youth
    Healthy controls
    n = 49
    Low-risk youth
    n = 50
    High-risk youth
    n = 50
    p value‡
    Age, yr, mean ± SD14.60 ± 2.4314.06 ± 2.5313.77 ± 2.580.2510.569
    Sex, male30 (61.2)33 (66.0)33 (66.0)0.8491.000
    Handedness, right47 (96.0)40 (80.0)43 (86.0)0.0571.000
    BMI, mean ± SD22.53 ± 4.6123.80 ± 6.7624.21 ± 7.380.4020.776
     Z score0.56 ± 1.060.76 ± 1.190.83 ± 1.310.5320.801
     Percentile65.49 ± 29.0468.34 ± 29.4270.60 ± 32.570.7020.716
    ADHD type
     ADHD-I–28 (56.0)13 (26.0)–< 0.001
     ADHD-H–0 (0.0)1 (2.0)––
     ADHD-C–22 (44.0)36 (72.0)–< 0.001
    Previous psychostimulant exposure–17 (34.0)23 (46.0)–0.221
    ADHD-R, mean ± SD
     Total score3.20 ± 3.9333.46 ± 10.0036.00 ± 10.60< 0.0010.221
     Inattention subscale1.86 ± 2.2720.96 ± 4.8319.98 ± 5.66< 0.0010.354
     Hyperactivity/impulsivity subscale1.35 ± 2.1012.50 ± 8.0616.02 ± 7.21< 0.0010.023
    CDRS-R total score, mean ± SD18.00 ± 2.3124.04 ± 5.9127.30 ± 8.18< 0.0010.024
    YMRS total score, mean ± SD0.73 ± 1.932.98 ± 3.295.76 ± 5.67< 0.0010.004
    CGAS total score, mean ± SD88.27 ± 5.8852.60 ± 6.8650.56 ± 7.26< 0.0010.152
    CGI-S, mean ± SD–4.02 ± 0.554.30 ± 0.68-0.026
    CBCL, mean ± SD
     Total score6.81 ± 6.5537.38 ± 18.1854.17 ± 28.64< 0.001< 0.001
     Internalizing subscore2.30 ± 2.408.19 ± 6.3712.74 ± 9.12< 0.0010.001
     Externalizing subscore1.49 ± 1.788.29 ± 6.8314.85 ± 12.39< 0.001< 0.001
     Dysregulation score2.87 ± 2.8521.10 ± 9.6526.34 ± 13.34< 0.0010.009
    • ADHD = attention-deficit/hyperactivity disorder; ADHD-R = Attention-Deficit Hyperactivity Disorder Rating Scale; BMI = body mass index; CBCL = Child Behaviour Checklist; CDRS-R = Children’s Depression Rating Scale-Revised; CGAS = Children’s Global Assessment Scale; CGI-S = Clinical Global Impression-Severity Scale; SD = standard deviation; YMRS = Young Mania Rating Scale.

    • ↵* Unless indicated otherwise.

    • ↵† One-way analysis of variance or χ2.

    • ↵‡ t test or χ2.

    • View popup
    Table 2

    Regions with altered nodal centralities

    Brain region*p value
    Nodal degreeNodal efficiencyNodal betweenness
    Low-risk v. high-risk v. healthy controls
     Left parahippocampal gyrus (DMN)0.0015*0.00370.0166
     Right gyrus rectus (DMN)0.0035*0.0012*0.2399
     Right inferior frontal gyrus, triangular part (CEN)0.0016*0.0003*0.0210
     Right superior parietal gyrus (CEN)0.0033*0.0014*0.0209
     Right inferior frontal gyrus, opercular part (SN)0.00740.00380.0011*
     Right rolandic operculum0.01010.0020*0.2190
     Right inferior occipital gyrus0.01180.0035*0.4445
    Low-risk v. healthy controls
     Left parahippocampal gyrus (DMN)0.0003*↓0.0010*↓0.0013*↓
     Right gyrus rectus (DMN)0.0194*↑0.0175*↑0.0439
     Right inferior frontal gyrus, triangular part (CEN)0.0148*↑0.0174*↑0.0523↑
     Right superior parietal gyrus (CEN)0.0061*↑0.0089*↑0.0118*↑
     Right rolandic operculum0.0019*↑0.0013*↑0.0430
    High-risk v. healthy controls
     Left parahippocampal gyrus (DMN)0.0076*↓0.0418*↓0.0260*↓
     Right gyrus rectus (DMN)0.0001*↑0.0001*↑0.1711
     Right inferior frontal gyrus, triangular part (CEN)0.0004*↑0.0002*↑0.0018*↑
     Right superior parietal gyrus (CEN)0.0014*↑0.0008*↑0.0120*↑
     Right inferior frontal gyrus, opercular part (SN)0.0015*↑0.0006*↑0.0002*↑
     Right rolandic operculum0.0055*↑0.0009*↑0.1115
     Right inferior occipital gyrus0.0045*↓0.0008*↓0.4641
    High-risk v. low-risk
     Right inferior frontal gyrus, opercular part (SN)0.0016*↑0.0008*↑0.0003*↑
     Right inferior occipital gyrus0.0075*↓0.0028*↓0.1444↓
    • DMN = default mode network; CEN = central executive network; FDR = false discovery rate; SN = salience network.

    • ↵* Brain regions were considered abnormal if they exhibited significant differences across groups or between 2 groups (p < 0.05, FDR corrected) in at least 1 node centrality parameter (marked by asterisk). All p values were obtained using a permutation test. The upward arrow signifies an increase in the measured value of the first group compared to the latter, whereas the downward arrow signifies a decrease in the measured value of the first group compared to the latter.

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Journal of Psychiatry and Neuroscience: 48 (4)
J Psychiatry Neurosci
Vol. 48, Issue 4
29 Aug 2023
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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
Ziyu Zhu, Du Lei, Kun Qin, Xiuli Li, Wenbin Li, Maxwell J. Tallman, L. Rodrigo Patino, David E. Fleck, Veronica Aghera, Qiyong Gong, John A. Sweeney, Robert K. McNamara, Melissa P. DelBello
J Psychiatry Neurosci Aug 2023, 48 (4) E315-E324; DOI: 10.1503/jpn.220209

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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
Ziyu Zhu, Du Lei, Kun Qin, Xiuli Li, Wenbin Li, Maxwell J. Tallman, L. Rodrigo Patino, David E. Fleck, Veronica Aghera, Qiyong Gong, John A. Sweeney, Robert K. McNamara, Melissa P. DelBello
J Psychiatry Neurosci Aug 2023, 48 (4) E315-E324; DOI: 10.1503/jpn.220209
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