Mitochondrial function is related to alterations at brain SPECT in depressed patients.

INTRODUCTION: 99mTc-d,l-hexamethylpropylene amine oxime (99mTc-HMPAO) retention in brain is proportional to cerebral blood flow and related to both the local hemodynamic state and to the cellular content of reduced glutathione. Alterations of the regional distribution of 99mTc-HMPAO retention, with discrepant results, have been reported at functional brain imaging of unipolar depression. Since mitochondrial involvement has been reported in depressed patients, the aim of the study was to explore whether the 99mTc-HMPAO retention at single-photon emission computed tomography in depressed patients may relate to different levels of mitochondrial function. METHODS: All patients had audiological and muscular symptoms, somatic symptoms that are common in depression. Citrate synthase (CS) activity assessed in muscle mitochondria correlated strongly with the activities of three mitochondrial respiratory chain enzymes and was used as a marker of mitochondrial function. K-means clustering performed on CS grouped eight patients with low and 11 patients with normal CS. Voxel-based analysis was performed on the two groups by statistical parametric mapping. RESULTS: Voxel-based analysis showed significantly higher 99mTc-HMPAO retention in the patients with low CS compared with the patients with normal CS in the posterior and inferior frontal cortex, the superior and posterior temporal cortex, the somato-sensory cortex, and the associative parietal cortex. CONCLUSION: Low muscle CS in depressed patients is related to higher regional 99mTc-HMPAO retention that may reflect cerebrovascular adaptation to impaired intracellular metabolism and/or intracellular enzymatic changes, as previously reported in mitochondrial disorder. Mitochondrial dysfunction in varying proportions of the subjects may explain some of the discrepant results for 99mTc-HMPAO retention in depression.

Effects of EMDR psychotherapy on 99mTc-HMPAO distribution in occupation-related post-traumatic stress disorder.

BACKGROUND: Post-traumatic stress disorder (PTSD) is a derangement of mood control with involuntary, emotionally fraught recollections that may follow deep psychological trauma in susceptible individuals. This condition is treated with pharmacological and/or cognitive therapies as well as psychotherapy with eye movement desensitization and reprocessing (EMDR). However, only a very limited number of studies have been published dealing with work-related PTSD, and investigations on the effect of treatment on cerebral blood flow represent an even smaller number. AIM: To investigate the short-term outcome of occupation-related PTSD after EMDR therapy by 99mTc-HMPAO SPECT. METHOD: Fifteen patients, either train drivers suffering from PTSD after having been unintentionally responsible for a person-under-train accident or employees assaulted in the course of duty, were recruited for the study. 99mTc-HMPAO SPECT was performed on these patients both before and after EMDR therapy while they listened to a script portraying the traumatic event. Tracer distribution analysis was then carried out at volume of interest (VOI) level using a three-dimensional standardized brain atlas, and at voxel level by SPM. The CBF data of the 15 patients were compared before and after treatment as well as with those of a group of 27 controls who had been exposed to the same psychological traumas without developing PTSD. RESULTS: At VOI analysis significant CBF distribution differences were found between controls and patients before and after treatment (P=0.023 and P=0.0039, respectively). Eleven of the 15 patients responded to treatment, i.e., following EMDR they no longer fulfilled the DSM-IV criteria for PTSD. When comparing only the eleven responders with the controls, the significant group difference found before EMDR (P=0.019) disappeared after treatment. Responders and non-responders showed after therapy significant regional differences in frontal, parieto-occipital and visual cortex and in hippocampus. SPM analysis showed significant uptake differences between patients and controls in the orbitofrontal cortex (Brodmann 11) and the temporal pole (Brodmann 38) both before and after treatment. A significant tracer distribution difference present before treatment in the uncus (Brodmann 36) disappeared after treatment, while a significant difference appeared in the lateral temporal lobe (Brodmann 21). CONCLUSION: Significant 99mTc-HMPAO uptake regional differences were found, mainly in the peri-limbic cortex, between PTSD patients and controls exposed to trauma but not developing PTSD. Tracer uptake differences between responders and patients not responding to EMDR were found after treatment suggesting a trend towards normalization of tracer distribution after successful therapy. These findings in occupational related PTSD are consistent with previously described effects of psychotherapy on anxiety disorders.

Regional cerebral blood flow during auditory recall in 47 subjects exposed to assaultive and non-assaultive trauma and developing or not posttraumatic stress disorder.

OBJECTIVE: Psychological trauma leads to posttraumatic stress disorder (PTSD) in susceptible subjects. The aim of this study was to investigate the differences in regional cerebral blood flow (rCBF) between two groups of subjects exposed to different types of traumatic stressor either developing or not developing PTSD. METHODS: Twenty subjects developing (S) and 27 not developing (NS) PTSD after being exposed to either earlier person-under-the-train accident (NA) or being assaulted in the underground environment (A) were included in the study. 99mTc-HMPAO SPECT was performed and the uptake in 29 regions of the brain (VOIs), bilaterally, was assessed. rCBF distribution was compared, using analysis of variance (ANOVA), between groups (S/NS) and type (A/NA) during a situation involving an auditory evoked re-experiencing of the traumatic event. Discriminant analysis was applied to test the concordance between clinical diagnosis and SPECT findings. RESULTS: In the general analyses significant differences were found between groups and types and there was a significant hemisphere x type interaction. S showed higher CBF than NS and so did A as compared to NA, particularly in the right hemisphere. Discriminant analysis correctly classified 66% of cases (p < 0001) in testing S/NS and 72% (p < 0001) in testing NA/A. CONCLUSIONS: Under recall of their traumatic experience we found higher relative CBF distribution values in S as compared to NS. CBF was higher in the right hemisphere and particularly in assaulted subjects. These findings underscore the role upon trauma recall of both the right hemisphere and the nature of the stressing event.