Overlapping expression of serotonin transporters and neurokinin-1 receptors in posttraumatic stress disorder: a multi-tracer PET study.

The brain serotonergic system is colocalized and interacts with the neuropeptidergic substance P/neurokinin-1 (SP/NK1) system. Both these neurochemical systems have independently been implicated in stress and anxiety, but interactions between them might be crucial for human anxiety conditions. Here, we examined the serotonin and substance P/neurokinin-1 (SP/NK1) systems individually as well as their overlapping expression in 16 patients with posttraumatic stress disorder (PTSD) and 16 healthy controls. Participants were imaged with the highly selective radiotracers [(11)C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile (DASB) and [(11)C]GR205171 assessing serotonin transporter (SERT) and NK1 receptor availability, respectively. Voxel-wise analyses in the amygdala, our a priori-defined region of interest, revealed increased number of NK1 receptors, but not SERT in the PTSD group. Symptom severity, as indexed by the Clinician-administered PTSD Scale, was negatively related to SERT availability in the amygdala, and NK1 receptor levels moderated this relationship. Exploratory, voxel-wise whole-brain analyses revealed increased SERT availability in the precentral gyrus and posterior cingulate cortex of PTSD patients. Patients, relative to controls, displayed lower degree of overlapping expression between SERT and NK1 receptors in the putamen, thalamus, insula and lateral orbitofrontal gyrus, lower overlap being associated with higher PTSD symptom severity. Expression overlap also explained more of the symptomatology than did either system individually, underscoring the importance of taking interactions between the neurochemical systems into account. Thus, our results suggest that aberrant serotonergic-SP/NK1 couplings contribute to the pathophysiology of PTSD and, consequently, that normalization of these couplings may be therapeutically important.

Cerebral blood flow in subjects with social phobia during stressful speaking tasks: a PET study.

OBJECTIVE: The central nervous system representation of social phobia (social anxiety disorder) is largely unknown. The aim of this study was to examine brain activity during symptom provocation in social phobics. METHOD: Positron emission tomography with the use of (15)O water was used to measure regional cerebral blood flow (rCBF) in 18 subjects with DSM-IV-defined social phobia and a nonphobic comparison group while they were speaking in front of an audience and in private. Heart rate and subjective anxiety were also recorded. RESULTS: During public versus private speaking, subjective anxiety increased more in the social phobics than in the comparison group. Increased anxiety was accompanied by enhanced rCBF in the amygdaloid complex in the social phobics relative to the comparison subjects. Cortically, brain blood flow decreased in the social phobics and increased in the comparison subjects more during public than private speaking in the orbitofrontal and insular cortices as well as in the temporal pole and increased less in the social phobics than in the comparison group in the parietal and secondary visual cortices. Furthermore, rCBF increased in the comparison group, but not in the social phobics, in the perirhinal and retrosplenial cortices. CONCLUSIONS: An rCBF pattern of relatively increased cortical rather than subcortical perfusion was observed in the nonphobic subjects, indicating that cortical evaluative processes were taxed by public performance. In contrast, the social phobia symptom profile was associated with increased subcortical activity. Thus, the functional neuroanatomy of social phobia involves the activation of a phylogenetically older danger-recognition system.

Brain function in a patient with torture related post-traumatic stress disorder before and after fluoxetine treatment: a positron emission tomography provocation study.

We report positron emission tomographic measurements of regional cerebral blood flow (rCBF) in a male patient with war and torture related post-traumatic stress disorder (PTSD) during symptom provocation. The subject was exposed to war related sounds before and after treatment with a selective serotonin reuptake inhibitor (SSRI; Fluoxetine; Fontex((R))). Therapy reduced PTSD symptoms, provoked anxiety and heart rate. Before treatment trauma reminders resulted in decreased rCBF in the insula, prefrontal, and inferior frontal cortices. Increased activity was evident in the cerebellum, precuneus and supplementary motor cortex. This was normalized after SSRI administration. Prefrontal and cingulate rCBF correlated with heart rate. Hence, the anxiolytic effect of SSRI for PTSD could be mediated by prefrontal and paralimbic cortices. Data suggest that SSRI treatment normalize provocation induced rCBF alterations in areas involved in memory, emotion, attention and motor-control.