Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Aug 1:334:238-245.
doi: 10.1016/j.jad.2023.04.125. Epub 2023 May 5.

Regional microstructural differences in ADHD youth with and without a family history of bipolar I disorder

Du Lei  1 , Kun Qin  2 , Wenbin Li  2 , Ziyu Zhu  2 , Maxwell J Tallman  3 , L Rodrigo Patino  3 , David E Fleck  3 , Veronica Aghera  3 , Qiyong Gong  4 , John A Sweeney  2 , Melissa P DelBello  3 , Robert K McNamara  3
Affiliations

Regional microstructural differences in ADHD youth with and without a family history of bipolar I disorder

Du Lei et al. J Affect Disord. .

Abstract

Background: Having a first-degree relative with bipolar I disorder (BD) in conjunction with prodromal attention deficit/hyperactivity disorder (ADHD) may represent a unique phenotype that confers greater risk for developing BD than ADHD alone. However, underlying neuropathoetiological mechanisms remain poorly understood. This cross-sectional study compared regional microstructure in psychostimulant-free ADHD youth with ('high-risk', HR) and without ('low-risk', LR) a first-degree relative with BD, and healthy controls (HC).

Methods: A total of 140 (high-risk, n = 44; low-risk, n = 49; and HC, n = 47) youth (mean age: 14.1 ± 2.5 years, 65 % male) were included in the analysis. Diffusion tensor images were collected and fractional anisotropy (FA) and mean diffusivity (MD) maps were calculated. Both tract-based and voxel-based analyses were performed. Correlations between clinical ratings and microstructural metrics that differed among groups were examined.

Results: No significant group differences in major long-distance fiber tracts were observed. The high-risk ADHD group exhibited predominantly higher FA and lower MD in frontal, limbic, and striatal subregions compared with the low-risk ADHD group. Both low-risk and high-risk ADHD groups exhibited higher FA in unique and overlapping regions compared with HC subjects. Significant correlations between regional microstructural metrics and clinical ratings were observed in ADHD groups.

Limitations: Prospective longitudinal studies will be required to determine the relevance of these findings to BD risk progression.

Conclusions: Psychostimulant-free ADHD youth with a BD family history exhibit different microstructure alterations in frontal, limbic, and striatal regions compared with ADHD youth without a BD family history, and may therefore represent a unique phenotype relevant to BD risk progression.

Keywords: ADHD; Bipolar disorder; DTI; Fractional anisotropy; Limbic system; Mean diffusivity.

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interest Dr. Sweeney consults to VeriSci. Dr. McNamara has received research support from Martek Biosciences Inc., Royal DSM Nutritional Products, LLC, Inflammation Research Foundation, Ortho-McNeil Janssen, AstraZeneca, Eli Lilly, NARSAD, and national institutes of health (NIH), and previously served on the scientific advisory board of the Inflammation Research Foundation. Dr. Patino and Dr. DelBello have received research support from NIMH, PCORI, Acadia, Alkermes, Allergan, Janssen, Johnson and Johnson, Lundbeck, Myriad, Otsuka, Pfizer, Sunovion and Shire and Dr. DelBello has provided consultation or advisory board services for Alkermes, Allergan, CMEology, Janssen, Johnson and Johnson, Lundbeck, Medscape, Myriad, Pfizer, Sage, Sunovion. All other authors declare that they have no competing interests.

Figures

Figure 1.
Figure 1.
Significant group differences in regional fractional anisotropy (FA) and mean diffusivity (MD) in low-risk and high-risk ADHD groups and healthy controls. Abbreviations: CUN, Cuneus; HIP, Hippocampus; CC, Corpus Callosum; CAU, Caudate; PUT, Putamen; ANG, angular gyrus; PreCG, Precentral gyrus; PCUN, Precuneus; AMYG, Amygdala; IFG_orb, orbital part of inferior frontal gyrus, IFGtriang, triangular part of inferior frontal gyrus; SFG, superior frontal gyrus;Ins, insula; ; L, left; R, right. Blue = negative T value (LR> HR, HC>LR/HR; Tan/red=positive T value (LR<HR, HC<LR/HR).
Figure 2.
Figure 2.
Significant correlations between microstructural metrics and clinical scores among low-risk ADHD youth (A) and among both low-risk and high-risk ADHD youth (B). Abbreviations: FA, fractional anisotropy; MD, mean diffusivity; SFG, superior frontal gyrus; CBCL, Child Behavior Checklist; YMRS, Young’s Mania Rating Scale.
See this image and copyright information in PMC

References

    1. Achenbach T, Rescorla L J.R.C.f.C., Youth,, Families, 2001. Manual for the ASEBA school-age forms & profiles: an integrated system of multi-informant assessment Burlington, VT: University of Vermont. 1617.
    1. Alexander AL, Lee JE, Lazar M, Field AS, 2007. Diffusion tensor imaging of the brain. Neurotherapeutics 4, 316–329. - PMC - PubMed
    1. Althoff RR, Ayer LA, Rettew DC, Hudziak JJ, 2010. Assessment of Dysregulated Children Using the Child Behavior Checklist: A Receiver Operating Characteristic Curve Analysis. Psychological Assessment 22, 609–617. - PMC - PubMed
    1. Anderson AW, 2001. Theoretical analysis of the effects of noise on diffusion tensor imaging. Magn Reson Med 46, 1174–1188. - PubMed
    1. Aron AR, 2011. From reactive to proactive and selective control: developing a richer model for stopping inappropriate responses. Biol Psychiatry 69, e55–68. - PMC - PubMed

Publication types