Leo Sher, M.D.

Our research report, “Prolactin response to fenfluramine administration in patients with unipolar and bipolar depression and healthy controls” was published 20 years ago, in the May 2003 issue of Psychoneuroendocrinology (1).

The serotonergic system plays an important role in the etiology and pathogenesis of mood disorders. Studies suggest that a deficit in central serotonergic neurotransmission permits the expression of bipolar disorder, and that both the manic and depressive phases of bipolar disorder are characterized by low central serotonergic neurotransmission. The hormonal response to the serotonin releasing agent/uptake inhibitor fenfluramine has been used in studies as an indicator of central serotonin system function.

We compared the prolactin response to fenfluramine administration in unipolar depressed patients (major depressive disorder), depressed patients with bipolar disorder, and healthy controls. Healthy volunteers were free from any Axis I disorders and did not have first-degree relatives with major depression, schizophrenia, or suicidal behavior. All study participants had been free of antidepressants, antipsychotics and other medication known to affect serotonergic function for at least 2 weeks (4 weeks for oral antipsychotics, 6 weeks for fluoxetine).

We found a trend towards a blunted prolactin response in depressed patients compared to healthy controls, after controlling for sex, family history, family history-by-gender interaction, and baseline levels. There was no significant difference between unipolar and bipolar patients in the baseline prolactin levels or the response to fenfluramine administration. We also found a negative correlation between aggression and impulsivity scores and prolactin responses in the subgroup with unipolar but not bipolar depression. Female patients with unipolar depression who had first-degree relatives with unipolar depression and normal controls had significantly higher prolactin responses than female patients with unipolar depression who did not have first-degree relatives with unipolar depression.

The lack of difference in the response to fenfluramine administration between unipolar and bipolar depressed patients may indicate that overall serotonergic function in unipolar and bipolar depressed patients is similarly impaired. Although we found that overall serotonergic function in unipolar and bipolar depressed patients is similar, we could not exclude the possibility that the impairment of serotonergic function in unipolar and bipolar depressed patients may involve different components of the serotonin system in different brain regions.

Reference

1. Sher L, Oquendo MA, Li S, Ellis S, Brodsky BS, Malone KM, Cooper TB, Mann JJ. Prolactin response to fenfluramine administration in patients with unipolar and bipolar depression and healthy controls. Psychoneuroendocrinology. 2003 May;28(4):559-73. doi: 10.1016/s0306-4530(02)00040-9.