Hostname: page-component-848d4c4894-4hhp2 Total loading time: 0 Render date: 2024-05-20T00:09:15.145Z Has data issue: false hasContentIssue false
  • English
  • Français

White matter endophenotype candidates for ADHD: a diffusion imaging tractography study with sibling design

Published online by Cambridge University Press:  22 May 2019

Huey-Ling Chiang ,
Yung-Chin Hsu ,
Chi-Yuan Shang ,
Wen-Yih Isaac Tseng  and
Susan Shur-Fen Gau Open the ORCID record for Susan Shur-Fen Gau [Opens in a new window]
Huey-Ling Chiang
Affiliation:
Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan Department of Psychiatry, Far Eastern Memorial Hospital, New Taipei City, Taiwan
Yung-Chin Hsu
Affiliation:
Institute of Medical Device and Imaging, National Taiwan University College of Medicine, Taipei, Taiwan AcroViz Technology Inc., Taipei, Taiwan
Chi-Yuan Shang
Affiliation:
Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
Wen-Yih Isaac Tseng*
Affiliation:
Institute of Medical Device and Imaging, National Taiwan University College of Medicine, Taipei, Taiwan Molecular Imaging Center, National Taiwan University, Taipei, Taiwan
Susan Shur-Fen Gau*
Affiliation:
Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan Graduate Institute of Clinical Medicine, and Graduate Institute of Brain and Mind Sciences, National Taiwan University College of Medicine, Taipei, Taiwan
*
Author for correspondence: Susan Shur-Fen Gau, E-mail: gaushufe@ntu.edu.tw; and Wen-Yih Isaac Tseng, E-mail: wytseng@ntu.edu.tw
Author for correspondence: Susan Shur-Fen Gau, E-mail: gaushufe@ntu.edu.tw; and Wen-Yih Isaac Tseng, E-mail: wytseng@ntu.edu.tw
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Brain structural alterations are frequently observed in probands with attention-deficit/hyperactivity disorder (ADHD). Here we examined the microstructural integrity of 76 white matter tracts among unaffected siblings of patients with ADHD to evaluate the potential familial risk and its association with clinical and neuropsychological manifestations.

Methods

The comparison groups included medication-naïve ADHD probands (n = 50), their unaffected siblings (n = 50) and typically developing controls (n = 50, age-and-sex matched with ADHD probands). Whole brain tractography was reconstructed automatically by tract-based analysis of diffusion spectrum imaging (DSI). Microstructural properties of white matter tracts were represented by the values of generalized fractional anisotropy (GFA), fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD).

Results

Compared to the control group, ADHD probands showed higher AD values in the perpendicular fasciculus, superior longitudinal fasciculus I, corticospinal tract, and corpus callosum. The AD values of unaffected siblings were in the intermediate position between those of the ADHD and control groups. These AD values were significantly associated with ADHD symptoms, sustained attention and working memory, for all white matter tracks evaluated except for the perpendicular fasciculus. Higher FA and lower RD values in the right frontostriatal tract connecting ventrolateral prefrontal cortex (FS-VLPFC) were associated with better performance in spatial span only in the unaffected sibling group.

Conclusions

Abnormal AD values of specific white matter tracts among unaffected siblings of ADHD probands suggest the presence of familial risk in this population. The right FS-VLPFC may have a role in preventing the expression of the ADHD-related behavioral phenotype.

ClinicalTrials.gov number

NCT01682915

Keywords

Attention deficit/Hyperactivity disorderaxial diffusivitydiffusion imagingendophenotypeneuropsychological function
Type
Original Articles
Information
Psychological Medicine , Volume 50 , Issue 7 , May 2020 , pp. 1203 - 1213
Copyright
Copyright © Cambridge University Press 2019

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Alexander, AL, Lee, JE, Lazar, M and Field, AS (2007) Diffusion tensor imaging of the brain. Neurotherapeutics 4, 316–329.10.1016/j.nurt.2007.05.011CrossRefGoogle ScholarPubMed
Aoki, Y, Yoncheva, YN, Chen, B, Nath, T, Sharp, D, Lazar, M, Velasco, P, Milham, MP and Di Martino, A (2017) Association of white matter structure with autism spectrum disorder and attention-deficit/hyperactivity disorder. JAMA Psychiatry 74, 1120–1128.10.1001/jamapsychiatry.2017.2573CrossRefGoogle ScholarPubMed
Aoki, Y, Cortese, S and Castellanos, FX (2018) Research review: diffusion tensor imaging studies of attention-deficit/hyperactivity disorder: meta-analyses and reflections on head motion. Journal of Child Psychology and Psychiatry 59, 193–202.CrossRefGoogle ScholarPubMed
Ashburner, J and Friston, KJ (2011) Diffeomorphic registration using geodesic shooting and Gauss-Newton optimisation. Neuroimage 55, 954–967.CrossRefGoogle ScholarPubMed
Barber, AD, Jacobson, LA, Wexler, JL, Nebel, MB, Caffo, BS, Pekar, JJ and Mostofsky, SH (2015) Connectivity supporting attention in children with attention deficit hyperactivity disorder. NeuroImage: Clinical 7, 68–81.CrossRefGoogle ScholarPubMed
Basser, PJ, Mattiello, J and LeBihan, D (1994) Estimation of the effective self-diffusion tensor from the NMR spin echo. Journal of Magnetic Resonance, Series B 103, 247–254.CrossRefGoogle ScholarPubMed
Bralten, J, Greven, CU, Franke, B, Mennes, M, Zwiers, MP, Rommelse, NN, Hartman, C, van der Meer, D, O'Dwyer, L, Oosterlaan, J, Hoekstra, PJ, Heslenfeld, D, Arias-Vasquez, A and Buitelaar, JK (2016) Voxel-based morphometry analysis reveals frontal brain differences in participants with ADHD and their unaffected siblings. Journal of Psychiatry & Neuroscience 41, 272–279.CrossRefGoogle ScholarPubMed
Casals, M, Girabent-Farres, M and Carrasco, JL (2014) Methodological quality and reporting of generalized linear mixed models in clinical medicine (2000–2012): a systematic review. PLoS One 9, e112653.CrossRefGoogle ScholarPubMed
Chamberlain, SR, Robbins, TW, Winder-Rhodes, S, Muller, U, Sahakian, BJ, Blackwell, AD and Barnett, JH (2011) Translational approaches to frontostriatal dysfunction in attention-deficit/hyperactivity disorder using a computerized neuropsychological battery. Biological Psychiatry 69, 1192–1203.CrossRefGoogle ScholarPubMed
Chen, YJ, Lo, YC, Hsu, YC, Fan, CC, Hwang, TJ, Liu, CM, Chien, YL, Hsieh, MH, Liu, CC, Hwu, HG and Tseng, WY (2015) Automatic whole brain tract-based analysis using predefined tracts in a diffusion spectrum imaging template and an accurate registration strategy. Human Brain Mapping 36, 3441–3458.CrossRefGoogle Scholar
Chen, YL, Shen, LJ and Gau, SS (2017) The mandarin version of the kiddie-schedule for affective disorders and Schizophrenia-epidemiological version for DSM-5 - a psychometric study. Journal of the Formosan Medical Association 116, 671–678.CrossRefGoogle ScholarPubMed
Chiang, HL, Chen, YJ, Lo, YC, Tseng, WY and Gau, SS (2015) Altered white matter tract property related to impaired focused attention, sustained attention, cognitive impulsivity and vigilance in attention-deficit/ hyperactivity disorder. Journal of Psychiatry & Neuroscience 40, 325–335.CrossRefGoogle ScholarPubMed
Chiang, HL, Chen, YJ, Shang, CY, Tseng, WY and Gau, SS (2016) Different neural substrates for executive functions in youths with ADHD: a diffusion spectrum imaging tractography study. Psychological Medicine 46, 1225–1238.CrossRefGoogle ScholarPubMed
Chiang, HL, Chen, YJ, Lin, HY, Tseng, WI and Gau, SS (2017) Disorder-specific alteration in white matter structural property in adults with autism spectrum disorder relative to adults with adhd and adult controls. Human Brain Mapping 38, 384–395.CrossRefGoogle ScholarPubMed
Chmielewski, WX, Muckschel, M, Dippel, G and Beste, C (2016) Concurrent information affects response inhibition processes via the modulation of theta oscillations in cognitive control networks. Brain Structure & Function 221, 3949–3961.CrossRefGoogle ScholarPubMed
Cohen-Adad, J, El Mendili, MM, Lehericy, S, Pradat, PF, Blancho, S, Rossignol, S and Benali, H (2011) Demyelination and degeneration in the injured human spinal cord detected with diffusion and magnetization transfer MRI. Neuroimage 55, 1024–1033.CrossRefGoogle ScholarPubMed
Davey, J, Thompson, HE, Hallam, G, Karapanagiotidis, T, Murphy, C, De Caso, I, Krieger-Redwood, K, Bernhardt, BC, Smallwood, J and Jefferies, E (2016) Exploring the role of the posterior middle temporal gyrus in semantic cognition: integration of anterior temporal lobe with executive processes. Neuroimage 137, 165–177.CrossRefGoogle ScholarPubMed
Duan, K, Chen, J, Calhoun, VD, Lin, D, Jiang, W, Franke, B, Buitelaar, JK, Hoogman, M, Arias-Vasquez, A, Turner, JA and Liu, J (2018) Neural correlates of cognitive function and symptoms in attention-deficit/hyperactivity disorder in adults. NeuroImage: Clinical 19, 374–383.CrossRefGoogle ScholarPubMed
Fassbender, C and Schweitzer, JB (2006) Is there evidence for neural compensation in attention deficit hyperactivity disorder? A review of the functional neuroimaging literature. Clinical Psychology Review 26, 445–465.CrossRefGoogle ScholarPubMed
Francx, W, Zwiers, MP, Mennes, M, Oosterlaan, J, Heslenfeld, D, Hoekstra, PJ, Hartman, CA, Franke, B, Faraone, SV, O'Dwyer, L and Buitelaar, JK (2015) White matter microstructure and developmental improvement of hyperactive/impulsive symptoms in attention-deficit/hyperactivity disorder. Journal of Child Psychology and Psychiatry 56, 1289–1297.CrossRefGoogle ScholarPubMed
Gau, SS and Huang, WL (2014) Rapid visual information processing as a cognitive endophenotype of attention deficit hyperactivity disorder. Psychological Medicine 44, 435–446.CrossRefGoogle ScholarPubMed
Gau, SS and Shang, CY (2010) Executive functions as endophenotypes in ADHD: evidence from the Cambridge Neuropsychological Test Battery (CANTAB). Journal of Child Psychology and Psychiatry 51, 838–849.CrossRefGoogle Scholar
Gau, SF and Soong, WT (1999) Psychiatric comorbidity of adolescents with sleep terrors or sleepwalking: a case-control study. Australian & New Zealand Journal of Psychiatry 33, 734–739.CrossRefGoogle ScholarPubMed
Gau, SS, Chong, MY, Chen, TH and Cheng, AT (2005) A 3-year panel study of mental disorders among adolescents in Taiwan. American Journal of Psychiatry 162, 1344–1350.CrossRefGoogle ScholarPubMed
Gau, SS, Shang, CY, Liu, SK, Lin, CH, Swanson, JM, Liu, YC and Tu, CL (2008) Psychometric properties of the Chinese version of the Swanson, Nolan, and Pelham, version IV scale - parent form. International Journal of Methods in Psychiatric Research 17, 35–44.CrossRefGoogle ScholarPubMed
Glahn, DC, Knowles, EE, McKay, DR, Sprooten, E, Raventos, H, Blangero, J, Gottesman, II and Almasy, L (2014) Arguments for the sake of endophenotypes: examining common misconceptions about the use of endophenotypes in psychiatric genetics. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 165B, 122–130.CrossRefGoogle ScholarPubMed
Gottesman, II and Gould, TD (2003) The endophenotype concept in psychiatry: etymology and strategic intentions. American Journal of Psychiatry 160, 636–645.CrossRefGoogle ScholarPubMed
Greven, CU, Bralten, J, Mennes, M, O'Dwyer, L, van Hulzen, KJ, Rommelse, N, Schweren, LJ, Hoekstra, PJ, Hartman, CA, Heslenfeld, D, Oosterlaan, J, Faraone, SV, Franke, B, Zwiers, MP, Arias-Vasquez, A and Buitelaar, JK (2015) Developmentally stable whole-brain volume reductions and developmentally sensitive caudate and putamen volume alterations in those with attention-deficit/hyperactivity disorder and their unaffected siblings. JAMA Psychiatry 72, 490–499.CrossRefGoogle ScholarPubMed
Han, GT, Chen, YL, Tsai, FJ and Gau, SS (2018) Temporal and reciprocal relations between ADHD symptoms and emotional problems in school-age children. Journal of Attention Disorders, doi: 10.1177/1087054718787891.Google ScholarPubMed
Hsu, YC and Tseng, WY (2018) An efficient regularization method for diffusion MAP-MRI estimation. 2018 ISMRM-ESMRMB Joint Annual Meeting.Google Scholar
Hsu, YC, Hsu, CH and Tseng, WY (2012) A large deformation diffeomorphic metric mapping solution for diffusion spectrum imaging datasets. NeuroImage 63, 818–834.CrossRefGoogle ScholarPubMed
Hsu, YC, Lo, YC, Chen, YJ, Wedeen, VJ and Tseng, WY (2015) NTU-DSI-122: a diffusion spectrum imaging template with high anatomical matching to the ICBM-152 space. Human Brain Mapping 36, 3528–3541.CrossRefGoogle ScholarPubMed
Jones, DK, Knosche, TR and Turner, R (2013) White matter integrity, fiber count, and other fallacies: the do's and don'ts of diffusion MRI. Neuroimage 73, 239–254.CrossRefGoogle ScholarPubMed
Kuo, LW, Chen, JH, Wedeen, VJ and Tseng, WY (2008) Optimization of diffusion spectrum imaging and q-ball imaging on clinical MRI system. Neuroimage 41, 7–18.CrossRefGoogle ScholarPubMed
Larsson, H, Chang, Z, D'Onofrio, BM and Lichtenstein, P (2014) The heritability of clinically diagnosed attention deficit hyperactivity disorder across the lifespan. Psychological Medicine 44, 2223–2229.CrossRefGoogle ScholarPubMed
Lawrence, KE, Levitt, JG, Loo, SK, Ly, R, Yee, V, O'Neill, J, Alger, J and Narr, KL (2013) White matter microstructure in subjects with attention-deficit/hyperactivity disorder and their siblings. Journal of the American Academy of Child and Adolescent Psychiatry 52, 431–440.e434.CrossRefGoogle ScholarPubMed
Lin, CP, Wedeen, VJ, Chen, JH, Yao, C and Tseng, WY (2003) Validation of diffusion spectrum magnetic resonance imaging with manganese-enhanced rat optic tracts and ex vivo phantoms. Neuroimage 19, 482–495.CrossRefGoogle ScholarPubMed
Luciana, M and Nelson, CA (1998) The functional emergence of prefrontally-guided working memory systems in four- to eight-year-old children. Neuropsychologia 36, 273–293.CrossRefGoogle ScholarPubMed
Mous, SE, Muetzel, RL, El Marroun, H, Polderman, TJ, van der Lugt, A, Jaddoe, VW, Hofman, A, Verhulst, FC, Tiemeier, H, Posthuma, D and White, T (2014) Cortical thickness and inattention/hyperactivity symptoms in young children: a population-based study. Psychological Medicine 44, 3203–3213.CrossRefGoogle ScholarPubMed
Mulder, MJ, Baeyens, D, Davidson, MC, Casey, BJ, van den Ban, E, van Engeland, H and Durston, S (2008) Familial vulnerability to ADHD affects activity in the cerebellum in addition to the prefrontal systems. Journal of the American Academy of Child and Adolescent Psychiatry 47, 68–75.CrossRefGoogle ScholarPubMed
Muster, R, Choudhury, S, Sharp, W, Kasparek, S, Sudre, G and Shaw, P (2019) Mapping the neuroanatomic substrates of cognition in familial attention deficit hyperactivity disorder. Psychological Medicine 49, 1–8.CrossRefGoogle ScholarPubMed
Orinstein, AJ and Stevens, MC (2014) Brain activity in predominantly-inattentive subtype attention-deficit/hyperactivity disorder during an auditory oddball attention task. Psychiatry Research 223, 121–128.CrossRefGoogle ScholarPubMed
Ozarslan, E, Koay, CG, Shepherd, TM, Komlosh, ME, Irfanoglu, MO, Pierpaoli, C and Basser, PJ (2013) Mean apparent propagator (MAP) MRI: a novel diffusion imaging method for mapping tissue microstructure. Neuroimage 78, 16–32.CrossRefGoogle ScholarPubMed
Parlatini, V, Radua, J, Dell'Acqua, F, Leslie, A, Simmons, A, Murphy, DG, Catani, M and Thiebaut de Schotten, M (2017) Functional segregation and integration within fronto-parietal networks. Neuroimage 146, 367–375.CrossRefGoogle ScholarPubMed
Pironti, VA, Lai, MC, Muller, U, Dodds, CM, Suckling, J, Bullmore, ET and Sahakian, BJ (2014) Neuroanatomical abnormalities and cognitive impairments are shared by adults with attention-deficit/hyperactivity disorder and their unaffected first-degree relatives. Biological Psychiatry 76, 639–647.CrossRefGoogle ScholarPubMed
Reese, TG, Heid, O, Weisskoff, RM and Wedeen, VJ (2003) Reduction of eddy-current-induced distortion in diffusion MRI using a twice-refocused spin echo. Magnetic Resonance in Medicine 49, 177–182.CrossRefGoogle ScholarPubMed
Shang, CY, Lin, HY, Tseng, WY and Gau, SS (2018) A haplotype of the dopamine transporter gene modulates regional homogeneity, gray matter volume, and visual memory in children with attention-deficit/hyperactivity disorder. Psychological Medicine 48, 2530–2540.CrossRefGoogle ScholarPubMed
Shaw, P, Eckstrand, K, Sharp, W, Blumenthal, J, Lerch, JP, Greenstein, D, Clasen, L, Evans, A, Giedd, J and Rapoport, JL (2007) Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation. Proceedings of the National Academy of Sciences of the United States of America 104, 19649–19654.CrossRefGoogle ScholarPubMed
Simmonds, DJ, Hallquist, MN, Asato, M and Luna, B (2014) Developmental stages and sex differences of white matter and behavioral development through adolescence: a longitudinal diffusion tensor imaging (DTI) study. Neuroimage 92, 356–368.CrossRefGoogle ScholarPubMed
Song, SK, Sun, SW, Ramsbottom, MJ, Chang, C, Russell, J and Cross, AH (2002) Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water. Neuroimage 17, 1429–1436.CrossRefGoogle ScholarPubMed
Streiner, DL and Norman, GR (2011) Correction for multiple testing: is there a resolution? Chest 140, 16–18.CrossRefGoogle ScholarPubMed
Sudre, G, Choudhuri, S, Szekely, E, Bonner, T, Goduni, E, Sharp, W and Shaw, P (2017) Estimating the heritability of structural and functional brain connectivity in families affected by attention-deficit/hyperactivity disorder. JAMA Psychiatry 74, 76–84.CrossRefGoogle ScholarPubMed
Tamm, L, Barnea-Goraly, N and Reiss, AL (2012) Diffusion tensor imaging reveals white matter abnormalities in attention-deficit/hyperactivity disorder. Psychiatry Research 202, 150–154.CrossRefGoogle ScholarPubMed
Tomasino, B and Gremese, M (2016) The cognitive side of M1. Frontiers in Human Neuroscience 10, 298.CrossRefGoogle ScholarPubMed
Tzourio-Mazoyer, N, Landeau, B, Papathanassiou, D, Crivello, F, Etard, O, Delcroix, N, Mazoyer, B and Joliot, M (2002) Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage 15, 273–289.CrossRefGoogle ScholarPubMed
van Ewijk, H, Heslenfeld, DJ, Zwiers, MP, Faraone, SV, Luman, M, Hartman, CA, Hoekstra, PJ, Franke, B, Buitelaar, JK and Oosterlaan, J (2014) Different mechanisms of white matter abnormalities in attention-deficit/hyperactivity disorder: a diffusion tensor imaging study. Journal of the American Academy of Child and Adolescent Psychiatry 53, 790–799.e3.CrossRefGoogle ScholarPubMed
Vangberg, TR, Skranes, J, Dale, AM, Martinussen, M, Brubakk, AM and Haraldseth, O (2006) Changes in white matter diffusion anisotropy in adolescents born prematurely. Neuroimage 32, 1538–1548.CrossRefGoogle ScholarPubMed
van Rooij, D, Hartman, CA, Mennes, M, Oosterlaan, J, Franke, B, Rommelse, N, Heslenfeld, D, Faraone, SV, Buitelaar, JK and Hoekstra, PJ (2015 a) Altered neural connectivity during response inhibition in adolescents with attention-deficit/hyperactivity disorder and their unaffected siblings. NeuroImage: Clinical 7, 325–335.CrossRefGoogle ScholarPubMed
van Rooij, D, Hoekstra, PJ, Mennes, M, von Rhein, D, Thissen, AJ, Heslenfeld, D, Zwiers, MP, Faraone, SV, Oosterlaan, J, Franke, B, Rommelse, N, Buitelaar, JK and Hartman, CA (2015 b) Distinguishing adolescents with ADHD from their unaffected siblings and healthy comparison subjects by neural activation patterns during response inhibition. American Journal of Psychiatry 172, 674–683.CrossRefGoogle ScholarPubMed
Veazie, PJ (2006) When to combine hypotheses and adjust for multiple tests. Health Services Research 41, 804–818.CrossRefGoogle ScholarPubMed
Waddell, J and McCarthy, MM (2012) Sexual differentiation of the brain and ADHD: what is a sex difference in prevalence telling us? Current Topics in Behavioral Neurosciences 9, 341–360.CrossRefGoogle ScholarPubMed
Wedeen, VJ, Wang, RP, Schmahmann, JD, Benner, T, Tseng, WY, Dai, G, Pandya, DN, Hagmann, P, D'Arceuil, H and de Crespigny, AJ (2008) Diffusion spectrum magnetic resonance imaging (DSI) tractography of crossing fibers. Neuroimage 41, 1267–1277.CrossRefGoogle ScholarPubMed
Supplementary material: File

Chiang et al. supplementary material

Table S1

Download Chiang et al. supplementary material(File)
File 29.1 KB