White matter microstructure in untreated first episode bipolar disorder with psychosis: Comparison with schizophrenia

Lisa H. Lu, Xiaohong Joe Zhou, Sarah K. Keedy, James L. Reilly, John A. Sweeney

Research output: Contribution to journalArticlepeer-review

86 Scopus citations


Objectives: White matter abnormalities have been reported in bipolar disorder. The present study aimed to investigate white matter integrity in untreated first episode patients with psychotic bipolar disorder using diffusion tensor imaging, and to compare observations with those from untreated first episode schizophrenia patients. Methods: Fractional anisotropy and mean diffusivity were measured in first episode psychotic patients with bipolar disorder (n=13) or schizophrenia (n=21) and healthy individuals (n=18). Group differences were evaluated using voxel-based morphometry. Axial and radial diffusivity were examined in regions with altered fractional anisotropy in post-hoc analyses. Results: Patients with bipolar disorder showed lower fractional anisotropy than healthy controls in several white matter tracts. Compared with schizophrenia patients, bipolar disorder patients showed lower fractional anisotropy in the cingulum, internal capsule, posterior corpus callosum, tapetum, and occipital white matter including posterior thalamic radiation and inferior longitudinal fasciculus/inferior fronto-occipital fasciculus. Lower fractional anisotropy in bipolar disorder was characterized by increased radial diffusion rather than axial diffusion along the orientation of fiber tracts. Across several white matter tracts, both patient groups showed greater mean diffusivity than healthy individuals. Conclusions: Selectively increased radial diffusivity in bipolar disorder patients suggests structural disorganization in fiber tract coherence of neurodevelopmental origin or alterations in myelin sheaths along fiber tracts. In contrast, increased isotropic diffusion along white matter tracts in schizophrenia patients with alterations in both radial and axial diffusivity suggests increased water content outside the axonal space. Thus, the present results suggest that different pathophysiological mechanisms may underlie white matter microstructural abnormalities in bipolar disorder and schizophrenia.

Original languageEnglish (US)
Pages (from-to)604-613
Number of pages10
JournalBipolar Disorders
Issue number7-8
StatePublished - Nov 2011


  • Diffusion tensor imaging
  • First episode psychosis
  • Fractional anisotropy
  • Mean diffusivity
  • Radial diffusivity

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry


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