Single photon emission computed tomography in posttraumatic stress disorder before and after treatment with a selective serotonin reuptake inhibitor

Background: Posttraumatic stress disorder (PTSD) is recognized as a disorder mediated by specific neurobiological circuits. Functional imaging studies using script-driven trauma imagery and pharmacological challenges have documented altered cerebral function (activation and deactivation) in several brain regions, including the amygdala, hippocampus, prefrontal cortex and anterior cingulate. However, the neural substrates of PTSD remain poorly understood and the effect of selective serotonin reuptake inhibition on regional cerebral activity is deserving of further investigation. Methods: Eleven adult patients (seven men, four women) (mean age+S.D.=33.6±9.2 years) with a DSM-IV diagnosis of PTSD, as determined by the Structured Clinical Interview for DSM-IV (SCID-I) and the Clinician-Administered PTSD Scale (CAPS), underwent single photon emission computed tomography (SPECT) with Tc-99m HMPAO pre- and post-8 weeks of treatment with the selective serotonin reuptake inhibitor, citalopram. Symptoms were assessed at baseline and at 2-week intervals with the Clinician-Administered PTSD Scale (CAPS), Montgomery-Asberg Depression Rating Scale (MADRS), and the Clinical Global Impression Scale (CGI). Image analysis of baseline and post-treatment scans was performed using Statistical Parametric Mapping (SPM). Results: Treatment with citalopram resulted in significant deactivation in the left medial temporal cortex irrespective of clinical response. On covariate analysis, a significant correlation between CAPS score reduction and activation in the left paracingulate region (medial prefrontal cortex) was observed post-treatment. No significant pre-treatment differences were observed between responders and non-responders in anterior cingulate perfusion. Conclusions: These preliminary findings are consistent with clinical data indicating temporal and prefrontal cortical dysfunction in PTSD and preclinical data demonstrating serotonergic innervation of these regions. However, further studies, in particular in vivo receptor imaging studies, are needed to confirm whether these regional abnormalities correlate with clinical features and treatment response.