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Cerebrospinal Fluid and Plasma Leptin Measurements: Covariability with Dopamine and Cortisol in Fasting Humans¹

Department of Psychiatry, University of Cincinnati College of Medicine (M.M.H., R.J.S., S.C.W., N.N.E., D.G.B., K.K.H., M.D.W., T.D.G.), Cincinnati, Ohio 45267-0559; Psychiatry Service, Cincinnati Veterans Affairs Medical Center (D.G.B., K.K.H., M.D.W., T.D.G.), Cincinnati, Ohio 45220; the Department of Nutrition, University of California (P.J.H.), Davis, California 95616; the Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine (A.H.M.), Atlanta, Georgia 30322; and Linco Research, Inc. (R.L.G.), St. Charles, Missouri 63304

Address all correspondence and requests for reprints to: M. M. Hagan, Ph.D., Department of Psychiatry, University of Cincinnati College of Medicine, P.O. Box 670559, Cincinnati, Ohio 45267-0559.

Leptin (OB protein) is an important signal in the regulation of energy balance. Leptin levels correlate with adiposity, but also decrease acutely with caloric restriction and increase with refeeding. The brain is an established critical site of leptin function, yet little is known about leptin concentrations in the central nervous system relative to plasma levels, psychiatric diagnoses, and other endocrine parameters. Therefore, using a novel ultrasensitive leptin assay, we explored relationships of human plasma and cerebrospinal fluid (CSF) leptin levels to body mass index, smoking, posttraumatic stress disorder diagnosis, and levels of dopamine, monoamine metabolites, ß-lipotropin, glucocorticoid, and thyroid and cytokine hormones. A strong linear relation between CSF and plasma leptin levels in the am (r = 0.63; P < 0.002) and afternoon (r = 0.90; P < 0.0001) was revealed. CSF and plasma leptin concentrations decreased during a 12- to 20-h period of fasting. A strong association was found between plasma leptin and CSF dopamine levels (r = 0.74; P < 0.01) as well as between CSF leptin levels and urinary free cortisol (r = 0.73; P < 0.01). Both of these parameters covaried with leptin independently of adiposity, as estimated by body mass index. Implications for leptin transport, regulation, and its potential role in therapeutic strategies for obesity and diabetes are discussed.

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