NIH CFS Workshop Report: Juan Lopez, M.D., on the Effects of Stress & Antidepressants on the Brain in Chronic Fatigue Syndrome

By Rich Van Konynenburg, Ph.D.

Juan Lopez, M.D., is an Associate Professor in the Department of Psychiatry, and an Assistant Research Scientist in the Mental Health Research Institute of the University of Michigan. Dr. Lopez has clinical expertise in the diagnosis and treatment of mood disorders, and his research area involves the effects of stress hormones and antidepressants on the brain. His talk was entitled "Stress and Antidepressant Modulation of the Limbic-Hypothalamic-Pituitary- Adrenal Axis."

Juan discussed experiments in rats in which the effects of stress and antidepressant drugs on the regulation of corticosteroid and serotonin receptors in the brain were studied. He found that antidepressants prevented the downregulation of corticosteroid receptors and the changes in serotonin receptors that were caused by stress. He also found that tricyclic antidepressants (TCAs) were more effective than selective serotonin reuptake inhibitors (SSRIs) for this purpose.

I think that the main value of this type of work for CFS is that it sheds some light on the interaction between the HPA axis and the neurotransmitters in the brain. We know that there are abnormalities in both the HPA axis and the serotonin system in CFS.

I suspect that the HPA axis is upregulated for a long time prior to onset in many of the cases of sudden onset of CFS, as a result of a long-term load of various stressors. Later in the illness, the HPA axis appears to be downregulated or blunted.

On the other hand, there is evidence in the literature for upregulation of the serotonergic system in many PWCs. These characteristics appear to be opposite to what is observed in major depression, where the glucocorticoid levels are found to be high, and benefit is found from drugs that raise the serotonin levels.

In "pure" CFS, I don't think antidepressant drugs have been found to be very helpful, and these opposite characteristics from major depression may be the reason. By contrast, in "pure" fibromyalgia there is evidence for low serotonergic activity, and SSRI antidepressants have often been found to be helpful for alleviating pain in this disorder.

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