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Chronic Stress (Thousand Oaks). 2018 Jan-Dec;2. doi: 10.1177/2470547018786390. Epub 2018 Jul 6.

Cerebellar and prefrontal cortical alterations in PTSD: structural and functional evidence.

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Department of Psychiatry, Yale School of Medicine, New Haven, CT.
Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT.
Child Study Center, Yale School of Medicine, New Haven, CT.
U.S. Department of Veteran Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT.



Neuroimaging studies have revealed that disturbances in network organization of key brain regions may underlie cognitive and emotional dysfunction in posttraumatic stress disorder (PTSD). Examining both brain structure and function in the same population may further our understanding of network alterations in PTSD.


We used tensor-based morphometry (TBM) and intrinsic connectivity distribution (ICD) to identify regions of altered volume and functional connectivity in unmedicated individuals with PTSD (n=21) and healthy comparison (HC) participants (n=18). These regions were then used as seeds for follow-up anatomical covariance and functional connectivity analyses.


Smaller volume in the cerebellum and weaker structural covariance between the cerebellum seed and middle temporal gyrus were observed in the PTSD group. Individuals with PTSD also exhibited lower whole-brain connectivity in the cerebellum, dorsolateral prefrontal cortex (dlPFC) and medial prefrontal cortex (mPFC). Functional connectivity in the cerebellum and grey matter volume in the dlPFC were negatively correlated with PTSD severity as measured by the DSM-5 PTSD checklist (PCL-5; r= -.0.77, r=-0.79). Finally, seed connectivity revealed weaker connectivity within nodes of the central executive network (right and left dlPFC), and between nodes of the default mode network (mPFC and cerebellum) and the supramarginal gyrus, in the PTSD group.


We demonstrate structural and functional alterations in PTSD converging on the PFC and cerebellum. Whilst PFC alterations are relatively well established in PTSD, the cerebellum has not generally been considered a key region in PTSD. Our findings add to a growing evidence base implicating cerebellar involvement in the pathophysiology of PTSD.


PTSD; cerebellum; connectivity; multimodal; structural

Conflict of interest statement

Declaration of Conflicting Interests Dr. Krystal acknowledges the following relevant financial interests. He is a co-sponsor of a patent for the intranasal administration of ketamine for the treatment of depression that was licensed by Janssen Pharmaceuticals, the maker of s-ketamine. He has a patent related to the use of riluzole to treat anxiety disorders that was licensed by Biohaven Medical Sciences. He has stock or stock options in Biohaven Medical Sciences, ARett Pharmaceuticals, Blackthorn Therapeutics, and Luc Therapeutics. He consults broadly to the pharmaceutical industry, but his annual income over the past year did not exceed $5,000 for any organization. He receives over $5,000 in income from the Society of Biological Psychiatry for editing the journal Biological Psychiatry. He has fiduciary responsibility for the International College of Neuropsychopharmacology as president of this organization. The other authors declare no conflict of interest.

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