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Cerebrospinal Fluid Leptin in Anorexia Nervosa: Correlation with Nutritional Status and Potential Role in Resistance to Weight Gain¹

Division of Endocrinology, Department of Medicine (C.M., J.S.F.), and the Department of Psychiatry (D.C.J.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215; the Department of Psychiatry, University of Texas Medical School (M.D.L.), Houston, Texas 77025; and the Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina (T.D.B.), Charleston, South Carolina 29425

Address all correspondence and requests for reprints to: Dr. David C. Jimerson, Department of Psychiatry, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, Massachusetts 02215. ; or to Dr. Jeffrey S. Flier, Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, Massachusetts 02215. Email: jflier{at}bidmc.harvard.edu

Studies in rodents have shown that leptin acts in the central nervous system to modulate food intake and energy metabolism. To evaluate the possible role of leptin in the weight loss of anorexia nervosa, this study compared cerebrospinal fluid (CSF) and plasma leptin concentrations in anorexic patients and controls. Subjects included 11 female patients with anorexia nervosa studied at low weight and after treatment, and 15 healthy female controls. Concentrations of leptin in blood and CSF were measured by RIA. Patients with anorexia nervosa, compared to controls, had decreased concentrations of leptin in CSF (98 ± 26 vs. 160 ± 58 pg/mL; P < 0.0005) and plasma (1.75 ± 0.46 vs. 7.01 ± 3.92 ng/mL; P < 0.005). The CSF to plasma leptin ratio, however, was higher for patients (0.060 ± 0.023) than for controls (0.025 ± 0.007; P < 0.0001). At posttreatment testing, although patients had not yet reached normal body weight, CSF and plasma leptin concentrations had increased to normal levels. These results demonstrate the dynamic changes in plasma and CSF leptin during positive energy balance in anorexia nervosa. The results further suggest that normalization of CSF leptin levels before full weight restoration during treatment of anorexic patients could contribute to resistance to weight gain and/or incomplete weight recovery.

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