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Research paper
A smaller amygdala is associated with anxiety in Parkinson’s disease: a combined FreeSurfer—VBM study
  1. Chris Vriend1,2,3,4,
  2. Premika SW Boedhoe1,2,3,
  3. Sonja Rutten1,2,
  4. Henk W Berendse3,4,
  5. Ysbrand D van der Werf2,3,5,
  6. Odile A van den Heuvel1,2,3
  1. 1Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands
  2. 2Department of Anatomy & Neurosciences, VU University Medical Center, Amsterdam, The Netherlands
  3. 3Neuroscience Campus Amsterdam, VU/VUMC, Amsterdam, The Netherlands
  4. 4Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands
  5. 5Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands
  1. Correspondence to Chris Vriend, Department of Psychiatry, VU University Medical Center, Medical Faculty Building, Department of Anatomy and Neuroscience, room G102-b, van der Boechorststraat 7, Amsterdam 1081 BT, The Netherlands; c.vriend{at}


Background Up to 50% of all patients with Parkinson's disease (PD) suffer from anxiety symptoms, a much higher percentage than in the general population. This suggests that PD associated pathological alterations partly underlie these symptoms, although empirical evidence is limited.

Methods Here we investigated the association between anxiety symptoms measured with the Beck Anxiety Inventory (BAI) and hippocampal and amygdalar volume in 110 early-stage patients with PD. Measures of anxiety in PD are often obscured by overlap with the somatic symptoms. We therefore also used a subscale of the BAI, established by our recent factor analysis, that reflects ‘psychological’ anxiety symptoms and is independent of the severity of PD-related motor and autonomic symptoms. We used FreeSurfer and voxel-based morphometry for the volumetric analyses.

Results Both software packages showed a negative correlation between the ‘psychological’ subscale of the BAI, but not total BAI and volume of the left amygdala, independent of the severity of motor symptoms, autonomic dysfunction and dopaminergic or anxiolytic medication status.

Conclusions These results confirm studies in non-PD samples showing lower left amygdalar volume in anxious patients. The results also indicate that the ‘psychological’ BAI subscale is a better reflection of neural correlates of anxiety in PD. Whether the left amygdalar volume decrease constitutes a premorbid trait, a PD-associated neurobiological susceptibility to anxiety or arises as a consequence of chronic anxiety symptoms remains to be determined by future prospective longitudinal studies. Nonetheless, we speculate that the Parkinson pathology is responsible for the reduction in amygdalar volume and the concomitant development of anxiety symptoms.

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