Gray and white matter trajectories in patients with bipolar disorder

Gabriele Sani, Chiara Chiapponi, Fabrizio Piras, Elisa Ambrosi, Alessio Simonetti, Emanuela Danese, Delfina Janiri, Roberto Brugnoli, Sergio De Filippis, Paolo Girardi, Gianfranco Spalletta

Research output: Contribution to journalArticle

21 Citations (Scopus)


Objectives: Findings on brain structural abnormalities in patients with bipolar disorder (BP) are inconsistent and little is known about age-related evolution of these changes. We employed a cross-sectional, case-control study to compare structural age-related brain trajectories in patients with BP and healthy control subjects (HC) over a period of approximately 50 years. The primary aim was to understand whether white (WM) and gray matter (GM) abnormalities are present from the beginning of the illness and how they change over time. Methods: Seventy-eight patients with BP and 78 HC matched for age, gender, and educational level underwent a high-resolution structural magnetic resonance imaging protocol. A voxel-based morphometry (VBM) analysis was used to capture GM and WM differences between subjects with BP and HC. Factorial analysis of covariance was used to compare brain volume alterations at different ages between the groups. Results: We found an age-related atrophy in GM and WM volumes both in patients with BP and HC. A main effect of diagnosis emerged in the posterior cingulate cortex bilaterally, in the right thalamus, in the cerebellum bilaterally, and in the left posterior limb of the internal capsule. No interaction between diagnosis and age emerged, indicating that the volumes of these areas were permanently reduced in subjects with BP throughout the entire age range under investigation. Conclusions: Brain alterations in patients with BP are present from the beginning of the illness and remain stable over time. All the affected areas are involved in mood and psychomotor control process. This suggests a possible neurodevelopmental involvement in the mechanism of BP.
Original languageEnglish
Pages (from-to)52-62
Number of pages11
JournalBipolar Disorders
Publication statusPublished - 2016


  • Adult
  • Age Factors
  • Atrophy
  • Bipolar Disorder
  • Bipolar disorder
  • Brain
  • Brain alterations
  • Case-Control Studies
  • Cerebellum
  • Cross-Sectional Studies
  • Female
  • Gray Matter
  • Gyrus Cinguli
  • Humans
  • Internal Capsule
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Organ Size
  • Posterior cingulate cortex
  • Posterior limb of the internal capsule
  • Thalamus
  • Voxel-based morphometry
  • White Matter

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