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Prefrontal cortex 5-HT2 receptors in depression: an [18F]setoperone PET imaging study
1Clarke Institute of Psychiatry, Department of Psychiatry, University of Toronto, Ont., Canada. jmeyer@clarke-inst.on.ca
Objective:
Widespread disturbances of serotonin (5-HT) are implicated in the pathophysiology of depression. Of 5-HT receptor abnormalities reported, the most replicated finding is increased 5-HT2 receptor binding in the postmortem prefrontal cortex of depressed suicide victims. The extent to which these findings exist in depressed persons without recent suicide attempts is uncertain. The objective of this study was to evaluate 5-HT2 receptors in depressed patients who were medication-free and who had not made recent suicide attempts.
Method:
With the use of [18F]setoperone and positron emission tomography (PET), 5-HT2 receptor binding potential was assessed in 14 depressed and 19 healthy subjects. Exclusion criteria for depressed patients included use of antidepressant medication within the past 6 months, a history of suicide attempts within the past 5 years, other current axis I disorders including bipolar disorder, and the presence of psychotic symptoms. The 5-HT2 (setoperone) binding potential in the two groups of subjects was compared by analysis of covariance with age as the covariate.
Results:
Age had a significant effect on 5-HT2 binding potential, but depression did not. The interaction of age and depression was not significant.
Conclusions:
The 5-HT2 binding potential is not increased in untreated depressed subjects who have not made recent suicide attempts. This negative finding does not rule out the possibility that there is a role for 5-HT2 receptors in treatment or that 5-HT2 receptors are increased in highly suicidal states.
Insights
This study found no increase in serotonin 5-HT2 receptors in depressed individuals without recent suicide attempts. These findings suggest serotonin 5-HT2 receptor levels may not be elevated in all forms of depression.
Area of Science:
- Neuroscience
- Psychiatry
- Pharmacology
Background:
- Serotonin (5-HT) system disturbances are linked to depression.
- Increased 5-HT2 receptor binding is a replicated finding in postmortem studies of depressed suicide victims.
- It remains unclear if this finding extends to depressed individuals without recent suicide attempts.
Purpose of the Study:
- To investigate 5-HT2 receptor binding potential in medication-free depressed patients without recent suicide attempts.
- To compare 5-HT2 receptor levels between depressed and healthy individuals.
Main Methods:
- Positron emission tomography (PET) with [18F]setoperone was used to assess 5-HT2 receptor binding potential.
- 14 medication-free depressed subjects and 19 healthy controls were studied.
- Exclusion criteria ensured a focus on non-suicidal, unmedicated depressed patients.
Main Results:
- No significant difference in 5-HT2 binding potential was observed between depressed and healthy subjects.
- Age significantly affected 5-HT2 binding potential, but depression did not.
- The interaction between age and depression on 5-HT2 binding was not significant.
Conclusions:
- 5-HT2 receptor binding potential is not elevated in untreated depressed individuals who have not made recent suicide attempts.
- This study does not exclude a role for 5-HT2 receptors in depression treatment or in highly suicidal states.
- Further research is needed to clarify the role of 5-HT2 receptors in the pathophysiology and treatment of depression.