ABSTRACT
Previous studies have shown hippocampal abnormalities in people with post-traumatic stress disorder (PTSD), but findings of diminished volume in shortages in the hippocampus have been inconsistent. In this study, we investigated changes in hippocampal volume and neuronal metabolites in right-handed PTSD patients to determine their possible relationship(s) with PTSD severity. We performed a case-control study of 11 right-handed PTSD patients and 11 healthy controls using magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy ((1)H MRS). Hippocampal volume and metabolite ratios of N-acetylaspartate (NAA) to creatine (Cr) (NAA/Cr) and choline compounds (Cho) to Cr (Cho/Cr) were calculated. The severity of PTSD was evaluated by the Clinician-Administered PTSD Scale (CAPS). Significantly decreased left and total normalized hippocampal volumes were found in PTSD patients compared with controls (6.6% for the left hippocampus, 5.5% for total hippocampus). Also, the bilateral hippocampal NAA/Cr ratio of PTSD patients was significantly reduced compared with controls. The volume of the left hippocampus was negatively correlated to the CAPS total and CPAS-C scores. The left hippocampal NAA/Cr ratio was negatively correlated to the CAPS-total, CAPS-B, CAPS-C, and CAPS-D scores. The CAPS total and the CAPS-B scores were positively correlated to the Cho/Cr ratio of the right hippocampus. Our results indicate that hippocampal dysfunction is asymmetric in right-handed PTSD patients, with the left side affected more than the right.
Subject(s)
Functional Laterality , Hippocampus/pathology , Stress Disorders, Post-Traumatic/pathology , Adolescent , Adult , Case-Control Studies , Choline/metabolism , Creatine/metabolism , Female , Hippocampus/metabolism , Humans , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Male , Middle Aged , Multimodal Imaging , Organ Size , Stress Disorders, Post-Traumatic/metabolismABSTRACT
Stress-induced hippocampal volume loss and decrease in N-acetylaspartate (NAA) level have been reported to be associated with impaired neural plasticity and neuronal damage in adults. Accordingly, reversing structural and metabolite damage in the hippocampus may be a desirable goal for antidepressant therapy. The present study investigated the effects of tianeptine on chronic stress-induced hippocampal volume loss and metabolite alterations in vivo in 24 Sprague-Dawley rats. Rats were subjected to a consecutive 28-day forced swimming test stress. Tianeptine (50mg/kg) or saline was administered intragastrically 4h after swimming each day. Spontaneous behaviors, serum corticosterone concentration, hippocampal volume and NAA level were evaluated after stress. Chronic tianeptine treatment counteracted the chronic stress-induced suppression of spontaneous behaviors, elevated serum corticosterone concentration, reduced hippocampal volume and decreased NAA level. Moreover, we found asymmetrical right-left hippocampal volume loss in stressed rats, with the left hippocampus more sensitive to chronic stress than the right hippocampus. In addition, stressed rats showed a decreased level of hippocampal metabolites, without significant loss of hippocampal volume. These findings provide experimental evidence for impaired structural plasticity of the brain being an important feature of depressive illness and suggest that prophylactic tianeptine treatments could reverse structural changes in brain. The structural and neurochemical alterations in the hippocampus may be valuable indexes for evaluating the prophylactic and curative effect of antidepressant treatments in depressive and stress-related disorders.
