Evidence of diffuse damage in frontal and occipital cortex in the brain of patients with post-traumatic stress disorder.

A number of MRI studies have shown focal or diffuse cortical gray matter (GM) abnormalities in patients with post-traumatic stress disorder (PTSD). However, the results of these studies are unclear regarding the cortical regions involved in this condition, perhaps due to the heterogeneity of the PTSD population included or to the differences in the methodology used for the quantification of the brain structures. In this study, we assessed differences in cortical GM volumes between a selected group of 25 drug-naive PTSD patients with history of adulthood trauma and 25 matched non-traumatized controls. Analyses were performed by using two different automated methods: the structural image evaluation using normalization of atrophy (SIENAX) and the voxel-based morphometry (VBM), as we trusted that if these complementary techniques provided similar results, it would increase the confidence in the validity of the assessment. Results of SIENAX and VBM analyses similarly showed that cortical GM volume decreases in PTSD patients when compared to healthy controls, particularly in the frontal and occipital lobes. These decreases seem to correlate with clinical measures. Our findings suggest that in drug-naïve PTSD patients with a history of adulthood trauma, brain structural damage is diffuse, with a particular prevalence for the frontal and occipital lobes, and is clinically relevant.

Magnetic resonance imaging volumes of the hippocampus in drug-naïve patients with post-traumatic stress disorder without comorbidity conditions.

Most brain imaging studies have showed smaller hippocampal volume in adults with chronic PTSD; however, some other studies have not replicated this finding. Most of these investigations included subjects with other psychiatric comorbidities, such as major depression or alcohol abuse. The prevalence of psychiatric comorbidities in PTSD is generally high and this makes it difficult, if not impossible, to disentangle the contribution of other disorders to hippocampal volume. Therefore, the main goal of the current study is to compare hippocampal volumes of healthy subjects and drug-naïve patients with PTSD caused by different types of mixed civilian traumas (i.e. car accident, physical abuse, sudden death of a family member, assault or robbery, natural disaster and traumatic abortion) and without comorbidity conditions. Magnetic resonance imaging (MRI) was used to measure the hippocampi, total cerebrum, gray matter, white matter and cerebrospinal fluid volumes in 34 patients with single diagnosis of PTSD, and 34 case-matched non-PTSD comparison subjects. The patients with single diagnosis of PTSD had an 11.8% smaller left hippocampus (p<0.001) and an 8.7% smaller right hippocampus (p=0.003) than the healthy controls. The results were controlled for the total brain volume and for gray matter volumes. Subjects with PTSD also displayed lower overall gray matter volume (p=0.006). There were no significant correlations between hippocampal volumes and illness duration or severity of PTSD. The findings indicate the presence of smaller hippocampal volumes in drug-naïve patients with single diagnosis of PTSD, compared with healthy subjects.

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.