Circulating PACAP levels are associated with altered imaging measures of entorhinal cortex neurite density in posttraumatic stress disorder

  • 0Division of Depression and Anxiety Disorders, McLean Hospital, Belmont, MA, USA.

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Summary

This summary is machine-generated.

Higher levels of Pituitary adenylate cyclase-activating polypeptide (PACAP) correlate with altered neuronal density in the entorhinal cortex (EC) in individuals with trauma exposure. This suggests PACAP may influence memory circuits relevant to posttraumatic stress disorder (PTSD).

Area Of Science

  • Neuroscience
  • Psychiatry
  • Neuroimaging

Background

  • Pituitary adenylate cyclase-activating polypeptide (PACAP) is implicated in arousal, memory, and posttraumatic stress disorder (PTSD).
  • Animal models suggest PACAP influences entorhinal cortex (EC) and hippocampus interactions, affecting fear conditioning.
  • PACAP is linked to altered amygdala activity and amygdala-hippocampal connectivity in PTSD, but structural changes remain unexplored.

Purpose Of The Study

  • To investigate the association between peripheral PACAP levels and neuronal morphology in the amygdala, hippocampus, and EC in adults with trauma exposure.
  • To explore potential structural underpinnings of PACAP's role in PTSD-related neural circuits.

Main Methods

  • Sixty-four adults with trauma exposure underwent clinical assessment (CAPS-5), blood draw for PACAP38, and MRI.
  • Neurite Orientation Dispersion and Density Imaging (NODDI) quantified Neurite Density Index (NDI) and Orientation Dispersion Index (ODI) in the amygdala, hippocampus, and EC.
  • Associations between PACAP levels and NDI/ODI, and with clinical measures, were analyzed.

Main Results

  • Higher circulating PACAP levels were significantly associated with greater EC Neurite Density Index (NDI).
  • Higher PACAP levels were also associated with lower EC Orientation Dispersion Index (ODI).
  • No significant associations were found between PACAP levels and NDI/ODI in the hippocampus or amygdala, nor between EC NDI/ODI and clinical PTSD measures.

Conclusions

  • Peripheral PACAP levels are linked to altered neuronal density and organization in the entorhinal cortex, but not the amygdala or hippocampus.
  • These findings suggest PACAP may specifically impact the structural integrity of the EC, a key region in arousal-associated memory circuits.
  • The study provides novel evidence for PACAP-related structural alterations in a brain region critical for memory processing in the context of trauma exposure and PTSD.