Reduced fractional anisotropy in bipolar disorder v. major depressive disorder independent of current symptoms

Psychol Med. 2023 Jul;53(10):4592-4602. doi: 10.1017/S0033291722001490. Epub 2022 Jul 14.


Background: Patients with bipolar disorder (BD) show reduced fractional anisotropy (FA) compared to patients with major depressive disorder (MDD). Little is known about whether these differences are mood state-independent or influenced by acute symptom severity. Therefore, the aim of this study was (1) to replicate abnormalities in white matter microstructure in BD v. MDD and (2) to investigate whether these vary across depressed, euthymic, and manic mood.

Methods: In this cross-sectional diffusion tensor imaging study, n = 136 patients with BD were compared to age- and sex-matched MDD patients and healthy controls (HC) (n = 136 each). Differences in FA were investigated using tract-based spatial statistics. Using interaction models, the influence of acute symptom severity and mood state on the differences between patient groups were tested.

Results: Analyses revealed a main effect of diagnosis on FA across all three groups (ptfce-FWE = 0.003). BD patients showed reduced FA compared to both MDD (ptfce-FWE = 0.005) and HC (ptfce-FWE < 0.001) in large bilateral clusters. These consisted of several white matter tracts previously described in the literature, including commissural, association, and projection tracts. There were no significant interaction effects between diagnosis and symptom severity or mood state (all ptfce-FWE > 0.704).

Conclusions: Results indicated that the difference between BD and MDD was independent of depressive and manic symptom severity and mood state. Disruptions in white matter microstructure in BD might be a trait effect of the disorder. The potential of FA values to be used as a biomarker to differentiate BD from MDD should be further addressed in future studies using longitudinal designs.

Keywords: Bipolar disorder; diffusion tensor imaging; major depressive disorder; mood state; trait; white matter microstructure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anisotropy
  • Bipolar Disorder* / diagnostic imaging
  • Cross-Sectional Studies
  • Depressive Disorder, Major* / diagnostic imaging
  • Diffusion Tensor Imaging / methods
  • Humans
  • Mania
  • White Matter* / diagnostic imaging