Elevated left and reduced right orbitomedial prefrontal fractional anisotropy in adults with bipolar disorder revealed by tract-based spatial statistics

Amelia Versace, Jorge R C Almeida, Stefanie Hassel, Nicholas D Walsh, Massimiliano Novelli, Crystal R Klein, David J Kupfer, Mary L Phillips

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CONTEXT: Diffusion tensor imaging (DTI) studies in adults with bipolar disorder (BD) indicate altered white matter (WM) in the orbitomedial prefrontal cortex (OMPFC), potentially underlying abnormal prefrontal corticolimbic connectivity and mood dysregulation in BD.

OBJECTIVE: To use tract-based spatial statistics (TBSS) to examine WM skeleton (ie, the most compact whole-brain WM) in subjects with BD vs healthy control subjects.

DESIGN: Cross-sectional, case-control, whole-brain DTI using TBSS.

SETTING: University research institute.

PARTICIPANTS: Fifty-six individuals, 31 having a DSM-IV diagnosis of BD type I (mean age, 35.9 years [age range, 24-52 years]) and 25 controls (mean age, 29.5 years [age range, 19-52 years]).

MAIN OUTCOME MEASURES: Fractional anisotropy (FA) longitudinal and radial diffusivities in subjects with BD vs controls (covarying for age) and their relationships with clinical and demographic variables.

RESULTS: Subjects with BD vs controls had significantly greater FA (t > 3.0, P <or= .05 corrected) in the left uncinate fasciculus (reduced radial diffusivity distally and increased longitudinal diffusivity centrally), left optic radiation (increased longitudinal diffusivity), and right anterothalamic radiation (no significant diffusivity change). Subjects with BD vs controls had significantly reduced FA (t > 3.0, P <or= .05 corrected) in the right uncinate fasciculus (greater radial diffusivity). Among subjects with BD, significant negative correlations (P < .01) were found between age and FA in bilateral uncinate fasciculi and in the right anterothalamic radiation, as well as between medication load and FA in the left optic radiation. Decreased FA (P < .01) was observed in the left optic radiation and in the right anterothalamic radiation among subjects with BD taking vs those not taking mood stabilizers, as well as in the left optic radiation among depressed vs remitted subjects with BD. Subjects having BD with vs without lifetime alcohol or other drug abuse had significantly decreased FA in the left uncinate fasciculus.

CONCLUSIONS: To our knowledge, this is the first study to use TBSS to examine WM in subjects with BD. Subjects with BD vs controls showed greater WM FA in the left OMPFC that diminished with age and with alcohol or other drug abuse, as well as reduced WM FA in the right OMPFC. Mood stabilizers and depressed episode reduced WM FA in left-sided sensory visual processing regions among subjects with BD. Abnormal right vs left asymmetry in FA in OMPFC WM among subjects with BD, likely reflecting increased proportions of left-sided longitudinally aligned and right-sided obliquely aligned myelinated fibers, may represent a biologic mechanism for mood dysregulation in BD.

Original languageEnglish
Pages (from-to)1041-1052
Number of pages12
JournalArchives of General Psychiatry
Issue number9
Publication statusPublished - Sep 2008


  • Adult
  • Anisotropy
  • Antipsychotic Agents
  • Bipolar Disorder
  • Case-Control Studies
  • Cross-Sectional Studies
  • Demography
  • Diffusion Magnetic Resonance Imaging
  • Female
  • Functional Laterality
  • Humans
  • Limbic System
  • Male
  • Middle Aged
  • Nerve Net
  • Orbit
  • Prefrontal Cortex

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