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Abnormal frontal white matter tracts in bipolar disorder: a diffusion tensor imaging study
Caleb M Adler1, Scott K Holland, Vince Schmithorst
1Bipolar and Psychotic Disorders Research Program, Department of Psychiatry, University of Cincinnati College of Medicine, OH 45267-0559, USA. cal.adler@psychiatry.uc.edu
Objectives:
Prefrontal white matter has been hypothesized to be integral to the pathophysiology of bipolar disorder. Recent morphometric studies however, have not observed changes in white matter in bipolar patients. We hypothesized that changes in prefrontal function in bipolar disorder, widely reported in the literature, may be related to a loss of white matter tract integrity with a resultant dysconnectivity syndrome. In this study we utilized diffusion tensor imaging (DTI) to examine prefrontal white matter in patients with bipolar disorder.
Methods:
Nine patients with bipolar disorder and nine healthy controls were recruited. DTI and localizing anatomic data were acquired, and regions of interest (ROIs) identified in the prefrontal white matter at 15, 20, 25, and 30 mm superior to the anterior commissure (AC). Fractional anisotropy (FA) and trace apparent diffusion coefficient (TADC) were compared by ROI between study groups.
Results:
The FA of ROIs 25 and 30 mm above the AC was significantly reduced in patients with bipolar disorder; FA of all ROIs showed high-medium to large effect sizes. No significant group differences were identified in TADC.
Conclusions:
Our findings suggest that a loss of bundle coherence is present in prefrontal white matter. This loss of coherence may contribute to prefrontal cortical pathology in patients with bipolar disorder.
Insights
Bipolar disorder patients show reduced white matter tract integrity in the prefrontal cortex. This loss of coherence in white matter may explain prefrontal dysfunction in bipolar disorder.
Area of Science:
- Neuroimaging
- Neuropsychiatry
- White Matter Integrity
Background:
- Prefrontal white matter integrity is hypothesized to be crucial in bipolar disorder pathophysiology.
- Previous morphometric studies have not consistently identified white matter changes in bipolar patients.
- Functional changes in bipolar disorder may stem from white matter tract dysconnectivity.
Purpose of the Study:
- To investigate prefrontal white matter integrity in bipolar disorder using diffusion tensor imaging (DTI).
- To test the hypothesis that reduced white matter tract integrity underlies prefrontal functional deficits in bipolar disorder.
Main Methods:
- Diffusion tensor imaging (DTI) was used to examine prefrontal white matter in nine bipolar disorder patients and nine healthy controls.
- Regions of interest (ROIs) were defined in prefrontal white matter at varying distances superior to the anterior commissure (AC).
- Fractional anisotropy (FA) and trace apparent diffusion coefficient (TADC) were compared between groups.
Main Results:
- Significantly reduced FA was observed in prefrontal white matter ROIs located 25 and 30 mm superior to the AC in bipolar disorder patients.
- Effect sizes for FA differences were medium to large across all ROIs.
- No significant differences in TADC were found between patient and control groups.
Conclusions:
- Findings suggest a loss of white matter bundle coherence in the prefrontal region of individuals with bipolar disorder.
- This compromised white matter integrity may contribute to the observed prefrontal cortical pathology in bipolar disorder.
- The results support a dysconnectivity model of bipolar disorder pathophysiology.
