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Pulsatile Rhythms of Adrenocorticotropin (ACTH) and Cortisol in Women with Endogenous Depression: Evidence for Increased ACTH Pulse Frequency^*

JOSEPH F. MORTOLA, JAMES H. LIU, J. CHRISTIAN GILLIN, DENNIS D. RASMUSSEN^|| and SAMUEL S. C. YEN^**

Department of Reproductive Medicine, School of Medicine (T-002), and the General Clinical Research Center, University of California-San Diego La Jolla, California 92093

Address all correspondence and requests for reprints to: Dr. Samuel S. C. Yen, Department of Reproductive Medicine, University of California, La Jolla, California 92093.

Plasma ACTH and serum cortisol levels were measured at 20-min intervals for 24 h in six young women with unipolar endogenous depression and in eight normal women during the early follicular phase of the menstrual cycle. The women with depression had a marked increase (P < 0.005) in mean ACTH pulse frequency [14.5 ± 0.6 (±SE) pulses/24 h] compared with normal women (9.9 ± 0.7 pulses/24 h), while mean ACTH pulse amplitude and 24-h transverse mean ACTH levels were similar in the two groups. In contrast, 24-h transverse mean cortisol levels were higher (P < 0.02) in the depressed women (242 ± 28 nmol/L) than in the normal women (163 ± 10 nmol/L). This hypercortisolemia in the depressed women was accompanied by markedly increased (P < 0.001) episodic cortisol secretion (286 ± 24 x 10² nmol/L·min) compared with that in normal women (155 ± 17 x 10² nmol/L·min), and the secretory episodes were both longer in duration (P < 0.05) and of higher amplitude (P < 0.05) in the depressed women.

The circadian variations in ACTH and cortisol were maintained in these depressed women, and the times of the circadian nadir, as determined by cosinor analysis, were similar to those in the normal women. However, the mean length of the evening quiescent period of cortisol secretion was far shorter (P < 0.005) in the depressed women (27 ± 8 vs. 202 ± 40 min). Moreover, the postlunch rise in serum cortisol was significantly higher (P < 0.02) in the depressed women (204 ± 29 vs. 111 ± 15 nmol/L).

These results provide evidence that the hypercortisolism in depressed women is associated with an increase in ACTH pulse frequency, expanded cortisol secretory episodes, including a greater postlunch rise in cortisol, and a shortened evening quiescent period of cortisol secretion. Our findings provide evidence for centrally mediated activation of the ACTH-cortisol system in women with depression without a phase shift in circadian rhythm.

^* This work was supported by the NIH NICHHD Grant HD-12303 and in part by the Mellon Foundation and the UCSD General Clinical Research Center, NIH/Division of Research Resources (Grant RR-00827). This research was conducted in part by the Clayton Foundation for Research.

Fellow in Reproductive Medicine.

Associate Physician, General Clinical Research Center.

Department of Psychiatry, University of California, San Diego.

^|| Mellon Foundation Faculty Scholar.

^** Clayton Foundation Investigator.

Received April 16, 1987.

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