Hyperexcitability: From Normal Fear to Pathological Anxiety and Trauma

Jeffrey B Rosen; Jay Schulkin

doi:10.3389/fnsys.2022.727054

Hyperexcitability: From Normal Fear to Pathological Anxiety and Trauma

Front Syst Neurosci. 2022 Aug 4:16:727054. doi: 10.3389/fnsys.2022.727054. eCollection 2022.

Authors

Jeffrey B Rosen¹, Jay Schulkin²

Affiliations

¹ Department of Psychological and Brain Sciences, University of Delaware, Newark, DE, United States.
² School of Medicine, University of Washington, Seattle, WA, United States.

Abstract

Hyperexcitability in fear circuits is suggested to be important for development of pathological anxiety and trauma from adaptive mechanisms of fear. Hyperexcitability is proposed to be due to acquired sensitization in fear circuits that progressively becomes more severe over time causing changing symptoms in early and late pathology. We use the metaphor and mechanisms of kindling to examine gains and losses in function of one excitatory and one inhibitory neuropeptide, corticotrophin releasing factor and somatostatin, respectively, to explore this sensitization hypothesis. We suggest amygdala kindling induced hyperexcitability, hyper-inhibition and loss of inhibition provide clues to mechanisms for hyperexcitability and progressive changes in function initiated by stress and trauma.

Keywords: CRF; PTSD; anxiety; fear; hyperexcitability; neural circuitry; somatostatin; threat.

Publication types

Review