Dysfunctional Attitudes and Serotonin-2 Receptors in Patients with Depression and Self-Harm
Dr. Jeffrey Meyer
Toronto, Canada, Presenter

Dr. Meyer studied possible involvement of serotonin-2 receptors in the formation of dysfunctional attitudes in healthy controls, subjects with major depression, and depressed persons with histories of repeated self-harming behaviors.

Dysfunctional attitudes are negative assumptions that reflect biases toward negative information and avoidance of positive information. They are common in patients with major depression and in people who commit self-injurious actions.

Dr. Meyer talked about postmortem studies of serotonin-2 receptors in persons who completed suicide and of in vivo studies of serotonin-2 receptors in people with depression. He discussed the effects of serotonin releasing factors on dysfunctional attitudes. He also discussed an imaging experiment on dysfunctional attitudes that evaluated serotonin binding, depressive episodes, and chronic self-harming behaviors.

In one study, people who completed suicide were found to have increased density of serotonin-2 receptors in the prefrontal cortex. Imaging studies of depressed patients showed abnormalities in serotonin-2 receptors in prefrontal cortex.

In the first study that Dr. Meyer discussed in detail, researchers tested the hypothesis that negative biases or assumptions can be induced in normal subjects with use of the serotonin releasing agent d-fenfluramine. The study included 29 subjects with no personal or family histories of psychiatric disorders or substance abuse. Evaluated with Dr. Meyer's dysfunctional attitude scale before and after treatment with d-fenfluramine, the subjects showed a large reduction in ratings of dysfunctional attitudes one hour after d-fenfluramine administration. Dr. Meyer believes that the findings are consistent with involvement of serotonin as a modulator of dysfunctional attitudes in healthy people.

In another study, Dr. Meyer's group used functional neuro-imaging with the [18F]-betoperone (a radio-ligand selective for the serotonin-2a receptor) to evaluate 27 healthy, 22 depressed, and 18 chronically self-injurious and depressed subjects. In subjects who had major depressive disorder, there was a strong correlation between betoperone binding bilaterally in prefrontal cortex and dysfunctional attitudes. There was no such correlation in the subjects who were depressed and engaged in self-harm. However, there was a 20-30% increase in serotonin-2 binding potential in prefrontal cortex in self-harming subjects compared with controls.

Dr. Meyer concludes that serotonin-2 receptors may modulate dysfunctional attitudes. He speculates that serotonin binding and dysfunctional attitudes may contribute to risk of self-harm and mortality in major depression.


Reporter: Elizabeth A Osuch, M.D.

 

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