Recently Published Findings from PET Studies Increase Understanding of Psychiatric Disorders

Several articles from the brain imaging laboratory directed by Ramin Parsey, MD, PhD that explore the biological mechanisms underlying psychiatric disorders through the use of PET imaging have been published recently.

A study published in Depression and Anxiety in October 2012 was the first report of elevated binding of one type of serotonin (5-HT) receptor, 5-HT1A, in the brainstem and forebrain of patients with PTSD. The group compared levels of 5-HT1A binding in 13 regions of the brain known to be associated with psychiatric disorders in 20 patients with posttraumatic stress disorder (PTSD) and in 49 healthy volunteers. They found higher levels of 5-HT1A binding in the PTSD group in all brain regions, ranging from a 43% increase in the raphe nuclei to 19% in the hippocampus. By comparing binding levels in PTSD patients with and without comorbid major depressive disorder, they were able to establish that the higher binding levels in PTSD were independent of major depressive disorder.

In November 2012 the journal Biological Psychiatry published the results of a PET study comparing data from medication-free patients with major depressive disorder before and after a course of treatment with selective serotonin reuptake inhibitors (SSRIs). The study revealed that 5-HT1A binding was reduced 18% in the raphe after treatment, but the degree of reduction was unrelated to improvement in depression. This finding suggests that the effect of SSRI treatment on the binding potential may be a necessary but not sufficient condition for clinical improvement. The authors suggested a follow up study using a newer radioligand, [11C]CUMI-101 (developed in Dr. Parsey’s research group!), which has the potential to yield additional information about how SSRIs interact with 5-HT1A receptors to relieve depression.

In a paper published in Philosophical Transactions of the Royal Society on 25 February 2013, Natalie Hesselgrave and Dr. Parsey described the results of studies analyzing PET data from four groups: patients with major depressive disorder who were recently exposed to antidepressant treatment, patients with major depressive disorder who were not recently medicated, patients whose depressive disorder was in remission, and a comparison group of healthy volunteers. They found that depressed patients who had not taken antidepressants recently had higher 5-HT1A binding potential than healthy controls or patients who were recently medicated.  They also observed that 5-HT1A binding potential was higher in patients in remission and in subjects with the C(-1019)G promoter polymorphism than in controls. Their findings suggest a model of depression in which alterations in 5-HT1A binding potential is a trait abnormality of major depressive disorder. 

On January 18, 2013 Biological Psychiatry published the results of a PET study that compared serotonin transporter binding in the midbrains of depressed patients who had previously attempted suicide, depressed patients who had not attempted suicide and a control group of healthy volunteers. They found that patients who had attempted suicide had lower serotonin transporter binding in their midbrains than the healthy controls or depressed patients who had not attempted suicide. There was no significant difference when all depressed patients were compared with healthy controls, suggesting that low midbrain serotonin transporter binding is related to suicidal behavior rather than major depressive disorder.