A functional MRI study of working memory in adolescents and young adults at genetic risk for bipolar disorder: preliminary findings

Authors

  • Heidi W Thermenos,

    1. Division of Public Psychiatry, Department of Psychiatry, Massachusetts Mental Health Center, Beth Israel Deaconess Medical Center, Boston
    2. Massachusetts General Hospital/Martinos Center for Biomedical Imaging, Charlestown
    3. Department of Psychiatry, Harvard Medical School, Massachusetts General Hospital, Boston
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  • Nikos Makris,

    1. Massachusetts General Hospital/Martinos Center for Biomedical Imaging, Charlestown
    2. Department of Psychiatry, Harvard Medical School, Massachusetts General Hospital, Boston
    3. Departments of Neurology and Radiology, Center for Morphometric Analysis, Massachusetts General Hospital, Boston
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  • Susan Whitfield-Gabrieli,

    1. McGovern Institute for Brain Research and Poitras Center for Affective Disorders Research, Massachusetts Institute of Technology, Cambridge, MA
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  • Ariel B Brown,

    1. Massachusetts General Hospital/Martinos Center for Biomedical Imaging, Charlestown
    2. Department of Psychiatry, Harvard Medical School, Massachusetts General Hospital, Boston
    3. McGovern Institute for Brain Research and Poitras Center for Affective Disorders Research, Massachusetts Institute of Technology, Cambridge, MA
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  • Anthony J Giuliano,

    1. Division of Public Psychiatry, Department of Psychiatry, Massachusetts Mental Health Center, Beth Israel Deaconess Medical Center, Boston
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  • Erica H Lee,

    1. Division of Public Psychiatry, Department of Psychiatry, Massachusetts Mental Health Center, Beth Israel Deaconess Medical Center, Boston
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  • Stephen V Faraone,

    1. Departments of Psychiatry, Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY
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  • Ming T Tsuang,

    1. Department of Psychiatry, Center for Behavioral Genomics, University of California at San Diego, La Jolla, CA, USA
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  • Larry J Seidman

    1. Division of Public Psychiatry, Department of Psychiatry, Massachusetts Mental Health Center, Beth Israel Deaconess Medical Center, Boston
    2. Massachusetts General Hospital/Martinos Center for Biomedical Imaging, Charlestown
    3. Department of Psychiatry, Harvard Medical School, Massachusetts General Hospital, Boston
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  • LJS reports no financial disclosures or conflicts of interest for the past two years; he has been a speaker for Shire Pharmaceuticals and has received an unrestricted educational grant from Janssen Pharmaceuticals within the past five years. HWT, NM, SW-G, ABB, AJG, EHL, SVF, and MTT have no conflicts of interest to report.

Corresponding author:
Heidi W. Thermenos, Ph.D.
Athinoula A. Martinos Center for Biomedical Imaging
Building 149, 2nd Floor, Room 2602E
13th Street
Charlestown, MA 02129, USA
E-mail: hthermen@bidmc.harvard.edu

Abstract

Thermenos HW, Makris N, Whitfield-Gabrieli S, Brown AB, Giuliano AJ, Lee EH, Faraone SV, Tsuang MT, Seidman LJ. A functional MRI study of working memory in adolescents and young adults at genetic risk for bipolar disorder: preliminary findings.
Bipolar Disord 2011: 13: 272–286. © 2011 The Authors.
Journal compilation © 2011 John Wiley & Sons A/S.

Objectives:  In this report, we seek to (i) identify a potential neuroimaging endophenotype for bipolar disorder (BD) in emotion regulatory and autonomic circuitry in young first-degree relatives of persons with BD; and (ii) replicate our previous work identifying the functional neuroanatomy of working memory (WM) in an older sample of relatives of persons with BD.

Methods:  Ten adolescent and young adult (age 13–24) unmedicated, non-ill, first-degree relatives of persons with BD (RELS) and 10 demographically comparable healthy controls performed a 2-back WM task and a 0-back control task during functional magnetic resonance imaging (fMRI). fMRI data were collected on a 1.5 Tesla scanner and analyzed using SPM-2. Mood was assessed on the day of scanning.

Results:  The groups did not differ on any demographic, neuropsychological, or in-scanner task performance variables. In contrast to controls, RELS showed (i) weak task-dependent modulation activity in the cerebellar vermis (CV), insula, and amygdala/parahippocampal region, and (ii) exaggerated modulation of activity in the frontopolar cortex and brainstem, even after controlling for potential confounders. Many of the group differences were driven by differences in activity in the low-level (0-back) baseline task.

Conclusions:  Young, unmedicated RELS exhibited altered task-dependent modulation of frontopolar, CV, and insula activity during WM, especially during the low-level (0-back) baseline task. Results are largely consistent with our initial study of older adult RELS, suggesting these alterations may represent biomarkers of genetic risk for BD.

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