Abnormalities in thalamo-cortical connections in patients with first-episode schizophrenia: a two-tensor tractography study

  • Hesham M. Hamoda
  • A. T. Makhlouf
  • J. Fitzsimmons
  • Y. Rathi
  • N. Makris
  • R. I. Mesholam-Gately
  • J. D. Wojcik
  • J. Goldstein
  • R. W. McCarley
  • L. J. Seidman
  • M. Kubicki
  • M. E. Shenton
ORIGINAL RESEARCH
  • 36 Downloads

Abstract

The “cognitive dysmetria” hypothesis suggests that impairments in cognition and behavior in patients with schizophrenia can be explained by disruptions in the cortico-cerebellar-thalamic-cortical circuit. In this study we examine thalamo-cortical connections in patients with first-episode schizophrenia (FESZ). White matter pathways are investigated that connect the thalamus with three frontal cortex regions including the anterior cingulate cortex (ACC), ventrolateral prefrontal cortex (VLPFC), and lateral oribitofrontal cortex (LOFC). We use a novel method of two-tensor tractography in 26 patients with FESZ compared to 31 healthy controls (HC), who did not differ on age, sex, or education. Dependent measures were fractional anisotropy (FA), Axial Diffusivity (AD), and Radial Diffusivity (RD). Subjects were also assessed using clinical functioning measures including the Global Assessment of Functioning (GAF) Scale, the Global Social Functioning Scale (GF: Social), and the Global Role Functioning Scale (GF: Role). FESZ patients showed decreased FA in the right thalamus-right ACC and right-thalamus-right LOFC pathways compared to healthy controls (HCs). In the right thalamus-right VLPFC tract, we found decreased FA and increased RD in the FESZ group compared to HCs. After correcting for multiple comparisons, reductions in FA in the right thalamus- right ACC and the right thalamus- right VLPC tracts remained significant. Moreover, reductions in FA were significantly associated with lower global functioning scores as well as lower social and role functioning scores. We report the first diffusion tensor imaging study of white matter pathways connecting the thalamus to three frontal regions. Findings of white matter alterations and clinical associations in the thalamic-cortical component of the cortico-cerebellar-thalamic-cortical circuit in patients with FESZ support the cognitive dysmetria hypothesis and further suggest the possible involvement of myelin sheath pathology and axonal membrane disruption in the pathogenesis of the disorder.

Keywords

Schizophrenia Thalamus Tractography MRI 

Notes

Acknowledgements

The authors would like to thank Laura Levin-Gleba, BS, Xue Gong, BA, Dominick Newell, BA, and Anni Zhu, BA for their support as research assistants. We also thank the clinical, research assistant, and data management staff from the Boston CIDAR study, including: Caitlin Bryant, BS, Ann Cousins, PhD, APRN, Grace Francis, PhD, Molly Franz, BA, Michelle Friedman-Yakoobian, PhD, Lauren Gibson, EdM, Anthony J. Giuliano, PhD, Andréa Gnong-Granato, MSW, Maria Hiraldo, PhD, Sarah Hornbach, BA, Matcheri Keshavan, MD, Kristy Klein, PhD, Grace Min, EdM, Corin Pilo, LMHC, Janine Rodenhiser-Hill, PhD, Julia Schutt, BA, Rachael Serur, BS, Shannon Sorenson, BA, Reka Szent-Imry, BA, Alison Thomas, BA, Chelsea Wakeham, BA, and Kristen A. Woodberry, MSW, PhD, Finally, we are grateful for the hard work of many research volunteers, including, Devin Donohoe, Zach Feder, Sylvia Khromina, Alexandra Oldershaw, Elizabeth Piazza, Julia Reading, and Olivia Schanz.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Hesham M. Hamoda
    • 1
    • 2
  • A. T. Makhlouf
    • 2
    • 3
  • J. Fitzsimmons
    • 2
  • Y. Rathi
    • 2
    • 4
  • N. Makris
    • 2
    • 5
  • R. I. Mesholam-Gately
    • 6
  • J. D. Wojcik
    • 6
  • J. Goldstein
    • 5
    • 7
  • R. W. McCarley
    • 8
  • L. J. Seidman
    • 5
    • 6
  • M. Kubicki
    • 2
    • 4
  • M. E. Shenton
    • 2
    • 4
    • 8
  1. 1.Department of PsychiatryBoston Children’s Hospital and Harvard Medical SchoolBostonUSA
  2. 2.Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA
  3. 3.Department of Psychiatry and Psychology, Mayo ClinicRochesterUSA
  4. 4.Department of Radiology, Brigham and Women’s HospitalHarvard Medical SchoolBostonUSA
  5. 5.Department of Psychiatry, Massachusetts General HospitalHarvard Medical SchoolBostonUSA
  6. 6.Massachusetts Mental Health Center, Public Psychiatry Division, Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonUSA
  7. 7.Division of Women′s Health, Connors Center for Women′s Health & Gender Biology; Departments of Psychiatry and Medicine, Brigham and Women′s HospitalHarvard Medical SchoolBostonUSA
  8. 8.Veterans Affairs Boston Healthcare SystemBrocktonUSA

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