Dysfunctions of Cortical Excitability in Drug-Naïve Posttraumatic Stress Disorder Patients

BackgroundThe investigation of a wide set of transcranial magnetic stimulation (TMS)-related variables in both hemispheres might help to identify a pattern of cortical excitability changes in posttraumatic stress disorder (PTSD) patients, reflecting γ-amino-butiric acid (GABA)/glutamate balance and dysfunction, and to determine whether some of these variables are related to clinical features.MethodsIn 20 drug-naive PTSD patients without comorbidity and 16 matched healthy control subjects we tested bilaterally with standard TMS procedures: resting motor threshold (RMT) to single-pulse TMS (reflecting ion channel function), paired-pulse short-latency intracortical inhibition (SICI; mainly reflecting GABAA function) and intracortical facilitation (ICF; mainly reflecting glutamatergic function), single-pulse cortical silent period (CSP; mainly reflecting GABAB-ergic function), and paired-pulse short-latency afferent inhibition (SAI; reflecting cholinergic mechanisms and their presynaptic GABAA-mediated modulation).ResultsThe PTSD patients showed widespread impairment of GABAA-ergic SICI, which was reversed toward facilitation in both hemispheres in one-half of the patients, marked increase of glutamatergic ICF in the right hemisphere, and right-sided impairment of SAI. Illness duration and avoidance symptoms but not anxiety correlated with right-lateralized dysfunctions of cortical excitability.ConclusionsAlthough the neurobiological complexity of each TMS variable makes current results theoretical, the pattern of cortical excitability accompanying PTSD symptoms suggests a bilateral decrease of the GABAA-ergic function. This prevails in the right hemisphere, in association with a relative prevalence of the glutamatergic tone, a new finding that current neuroimaging investigations cannot provide due to the lack of reliable glutamate tracers. Results might help to disclose new pathophysiological aspects of PTSD symptoms, providing a rationale for future neuromodulatory strategies of treatment.