Investigating TSPO levels in occupation-related posttraumatic stress disorder.

Microglia are immune brain cells implicated in stress-related mental illnesses including posttraumatic stress disorder (PTSD). Their role in the pathophysiology of PTSD, and on neurobiological systems that regulate stress, is not completely understood. We tested the hypothesis that microglia activation, in fronto-limbic brain regions involved in PTSD, would be elevated in participants with occupation-related PTSD. We also explored the relationship between cortisol and microglia activation. Twenty participants with PTSD and 23 healthy controls (HC) completed positron emission tomography (PET) scanning of the 18-kDa translocator protein (TSPO), a putative biomarker of microglia activation using the probe [18F]FEPPA, and blood samples for measurement of cortisol. [18F]FEPPA VT was non-significantly elevated (6.5-30%) in fronto-limbic regions in PTSD participants. [18F]FEPPA VT was significantly higher in PTSD participants reporting frequent cannabis use compared to PTSD non-users (44%, p = 0.047). Male participants with PTSD (21%, p = 0.094) and a history of early childhood trauma (33%, p = 0.116) had non-significantly higher [18F]FEPPA VT. Average fronto-limbic [18F]FEPPA VT was positively related to cortisol (r = 0.530, p = 0.028) in the PTSD group only. Although we did not find a significant abnormality in TSPO binding in PTSD, findings suggest microglial activation might have occurred in a subgroup who reported frequent cannabis use. The relationship between cortisol and TSPO binding suggests a potential link between hypothalamic-pituitary-adrenal-axis dysregulation and central immune response to trauma which warrants further study.

Effects of short-term, high-frequency repetitive transcranial magnetic stimulation to bilateral dorsolateral prefrontal cortex on smoking behavior and cognition in patients with schizophrenia and non-psychiatric controls.

BACKGROUND: High rates of tobacco smoking and smoking cessation failure in schizophrenia may be related to prefrontal cortical dysfunction. Novel treatment options for tobacco use disorder are needed given the limited efficacy of current pharmacotherapies. Preliminary evidence suggests high-frequency repetitive transcranial magnetic stimulation (rTMS) to bilateral dorsolateral prefrontal cortex (DLPFC) may suppress tobacco craving in smokers with schizophrenia. The goal of this study was to determine effects of rTMS for tobacco craving and cognition using a short-term (3-day) human laboratory paradigm. METHODS: Bilateral active (20Hz) versus sham rTMS stimulation was administered in a counterbalanced, double-blind, cross-over design to thirteen smokers with schizophrenia and n=14 non-psychiatric smoking controls. Participants were studied at baseline (smoking satiated), after 16h of smoking abstinence, and after smoking reinstatement. Primary outcome measures included tobacco craving, withdrawal and cognition. RESULTS: Overnight abstinence produced a significant increase in tobacco craving and withdrawal, and impaired verbal memory and visuospatial working memory in both diagnostic groups; these effects were reversed with smoking reinstatement. However, active rTMS did not modify this pattern of results. Moreover, active versus sham rTMS had no significant effects on cognitive outcomes, and was not associated with significant adverse events. CONCLUSIONS: Our preliminary findings suggest that short-term rTMS administration may not be sufficient enough to modify cognition, craving, and withdrawal outcomes in smokers with schizophrenia (NCT00736710). Longer-term, controlled treatment studies examining effects of rTMS on smoking behaviors and cognition in schizophrenia are warranted.