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White matter architecture in major depression with anxious distress symptoms

Heij, G. J., Penninx, B. W. H. J., van Velzen, L. S., van Tol, M-J., van der Wee, N. J. A., Veltman, D. J. & Aghajani, M., 30-Aug-2019, In : Progress in Neuro-Psychopharmacology & Biological Psychiatry. 94, 13 p., 109664.

Research output: Contribution to journalArticleAcademicpeer-review

  • Gijs J Heij
  • Brenda W H J Penninx
  • Laura S van Velzen
  • Marie-José van Tol
  • Nic J A van der Wee
  • Dick J Veltman
  • Moji Aghajani

Background: Comorbid anxious distress is common in Major Depressive Disorder (MDD), and associated with significantly worse clinical course and treatment response. While DSM-5 recently introduced the Anxious Distress (AD) specifier as a potentially useful symptom-based subtyping scheme for MDD, its neurobiological underpinnings remain unclear. The current study hence uniquely probed whether MDD with co-occurring AD (MDD/AD+) relates to distinct perturbations in frontolimbic white matter (WM) pathways tentatively theorized in MDD/AD+ pathophysiology.

Methods: Tract-based spatial statistics (TBSS) was therefore used to analyze diffusion tensor imaging data on WM microstructure, in MDD/AD+ patients (N = 20) relative to MDD patients without AD (MDD/AD-; N = 29) and healthy controls (HC; N = 39). Using TBSS, we probed fractional anisotropy and axial/radial/mean diffusivity as proxies for WM integrity. Categorical (between-groups) and dimensional (within-patients) analyses subsequently assessed how Anxious Distress in MDD impacts frontolimbic WM connectivity. Receiver-Operating Characteristics additionally assessed classification capabilities of between-groups WM effects.

Results: Compared to MDD/AD- and HC participants, MDD/AD+ patients exhibited diminished integrity within the anterior thalamic radiation (ATR). Higher AD specifier scores within MDD patients additionally related to diminished integrity of the uncinate fasciculus and cingulum pathways. These effects were not confounded by key clinical (e.g., comorbid anxiety disorder) and sociodemographic (e.g., age/sex) factors, with altered ATR integrity moreover successfully classifying MDD/AD+ patients from MDD/AD- and HC participants (90% sensitivity vertical bar 73% specificity vertical bar 77% accuracy).

Conclusions: These findings collectively link MDD/AD+ to distinct WM anomalies in frontolimbic tracts important to adaptive emotional functioning, and may as such provide relevant, yet preliminary, clues on MDD/AD+ pathophysiology.

Original languageEnglish
Article number109664
Number of pages13
JournalProgress in Neuro-Psychopharmacology & Biological Psychiatry
Volume94
Publication statusPublished - 30-Aug-2019

    Keywords

  • ANTERIOR THALAMIC RADIATION, MEDIAL FOREBRAIN-BUNDLE, FUNCTIONAL CONNECTIVITY, UNCINATE FASCICULUS, MICROSTRUCTURE ALTERATIONS, FRACTIONAL ANISOTROPY, SPATIAL STATISTICS, DIFFUSION, DISORDER, ANXIETY

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