Dysfunctions of cortical excitability in drug-naïve posttraumatic stress disorder patients.
BACKGROUND
The 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 gamma-amino-butiric acid (GABA)/glutamate balance and dysfunction, and to determine whether some of these variables are related to clinical features.


METHODS
In 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 GABA(A) function) and intracortical facilitation (ICF; mainly reflecting glutamatergic function), single-pulse cortical silent period (CSP; mainly reflecting GABA(B)-ergic function), and paired-pulse short-latency afferent inhibition (SAI; reflecting cholinergic mechanisms and their presynaptic GABA(A)-mediated modulation).


RESULTS
The PTSD patients showed widespread impairment of GABA(A)-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.


CONCLUSIONS
Although 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 GABA(A)-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.
Department of Neuroscience, Neurology Section, University of Siena School of Medicine, Siena, Italy. Rossisimo@unisi.it
Simone
S
Rossi
Alberto
A
De Capua
Maricla
M
Tavanti
Sara
S
Calossi
Nicola R
NR
Polizzotto
Antonio
A
Mantovani
Vincenzo
V
Falzarano
Letizia
L
Bossini
Stefano
S
Passero
Sabina
S
Bartalini
Monica
M
Ulivelli
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000503:physiopathology*; D013181:Cortical Spreading Depression / Q000502:physiology*; D004558:Electric Stimulation / Q000379:methods; D004569:Electroencephalography / Q000379:methods; D004576:Electromyography / Q000379:methods; D019054:Evoked Potentials, Motor / Q000502:physiology*; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000502:physiology; D011930:Reaction Time / Q000502:physiology; D012189:Retrospective Studies; D013313:Stress Disorders, Post-Traumatic / Q000473:pathology* / Q000503:physiopathology; D050781:Transcranial Magnetic Stimulation / Q000379:methods; D015599:Trauma Severity Indices; D055815:Young Adult