Right orbitofrontal corticolimbic and left corticocortical white matter connectivity differentiate bipolar and unipolar depression

Amelia Versace, Jorge R.C. Almeida, Karina Quevedo, Wesley K. Thompson, Robert A. Terwilliger, Stefanie Hassel, David J. Kupfer, Mary L. Phillips

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143 Scopus citations


Objectives: The absence of pathophysiologically relevant diagnostic markers of bipolar disorder (BD) leads to its frequent misdiagnosis as unipolar depression (UD). We aimed to determine whether whole brain white matter connectivity differentiated BD from UD depression. Methods: We employed a three-way analysis of covariance, covarying for age, to examine whole brain fractional anisotropy (FA), and corresponding longitudinal and radial diffusivity, in currently depressed adults: 15 with BD-type I (mean age 36.3 years, SD 12.0 years), 16 with recurrent UD (mean age 32.3 years, SD 10.0 years), and 24 healthy control adults (HC) (mean age 29.5 years, SD 9.43 years). Depressed groups did not differ in depression severity, age of illness onset, and illness duration. Results: There was a main effect of group in left superior and inferior longitudinal fasciculi (SLF and ILF) (all F < 9.8; p ≤ .05, corrected). Whole brain post hoc analyses (all t < 4.2; p ≤ .05, corrected) revealed decreased FA in left SLF in BD, versus UD adults in inferior temporal cortex and, versus HC, in primary sensory cortex (associated with increased radial and decreased longitudinal diffusivity, respectively); and decreased FA in left ILF in UD adults versus HC. A main effect of group in right uncinate fasciculus (in orbitofrontal cortex) just failed to meet significance in all participants but was present in women. Post hoc analyses revealed decreased right uncinate fasciculus FA in all and in women, BD versus HC. Conclusions: White matter FA in left occipitotemporal and primary sensory regions supporting visuospatial and sensory processing differentiates BD from UD depression. Abnormally reduced FA in right fronto-temporal regions supporting mood regulation, might underlie predisposition to depression in BD. These measures might help differentiate pathophysiologic processes of BD versus UD depression.

Original languageEnglish (US)
Pages (from-to)560-567
Number of pages8
JournalBiological psychiatry
Issue number6
StatePublished - Sep 15 2010

Bibliographical note

Funding Information:
This study was supported in part by Grant 1 R01 MH076971-01 (MLP) from the National Institutes of Health (NIH) , K25 MH076981-01 (WKT) from the NIH , a National Alliance for Research on Schizophrenia and Depression (NARSAD) Independent Investigator Award (Nellie Blumenthal Investigator) (MLP), DMS-0806106 from the National Science Foundation (WKT), and an NIH NARSAD Young Investigator Award (AV).


  • Depression
  • diffusion tensor imaging
  • inferior longitudinal fasciculus
  • mood disorders
  • superior longitudinal fasciculus
  • uncinate fasciculus


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