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Low Central Nervous System Serotonergic Responsivity Is Associated with the Metabolic Syndrome and Physical Inactivity

Divisions of Clinical Pharmacology (M.F.M.) and Endocrinology and Metabolism (K.V.W., M.T.K.), Department of Medicine, University of Pittsburgh School of Medicine; Department of Epidemiology, Graduate School of Public Health (R.H.M.); and Behavioral Physiology Laboratory, Department of Psychology (J.D.F., S.B.M.), University of Pittsburgh, Pittsburgh, Pennsylvania 15260

Address all correspondence and requests for reprints to: Dr. Matthew F. Muldoon, Old Engineering Hall, Room 506, University of Pittsburgh, Pittsburgh, Pennsylvania 15260. E-mail: mfm10{at}pitt.edu.

The metabolic syndrome, recognized by the co-occurrence of general or abdominal obesity, hypertension, dyslipidemia, insulin resistance, and dysglycemia, appears to involve disturbances in metabolism, autonomic function, and health-related behaviors. However, physiological processes linking the components of the metabolic syndrome remain obscure. The current study examined associations of central nervous system serotonergic function with each metabolic syndrome risk variable, the metabolic syndrome, and physical activity. The subjects were 270 adult volunteers who participated in a study of cardiovascular disease risk factors and neurobehavioral functioning. Central serotonergic responsivity was indexed as the prolactin (PRL) response evoked by the serotonin-releasing agent, fenfluramine. Across the sample, low PRL response was associated with greater body mass index, higher concentrations of triglycerides, glucose, and insulin, higher systolic and diastolic blood pressure, greater insulin resistance, and less physical activity (P < 0.03–0.001). There also existed an inverse linear relationship between PRL response and the number of metabolic syndrome risk factors individuals possessed (P for trend = 0.002). Finally, a 1 SD decline in PRL response was associated with an odds ratio for the metabolic syndrome of 2.05 (95% confidence interval, 1.10–3.83; P = 0.002) and 5.70 (95% confidence interval, 1.69–19.25; P = 0.005), according to the definitions of the National Cholesterol Education Program and the World Health Organization, respectively. These findings reveal a heretofore unrecognized association between reduced central serotonergic responsivity and the metabolic syndrome.

This work was supported by National Institutes of Health Public Health Service Grants HL-40962 and HL-46328.

Abbreviations: BMI, Body mass index; BP, blood pressure; CNS, central nervous system; CVD, cardiovascular disease; HDL, high-density lipoprotein; LDL, low-density lipoprotein; NCEP, National Cholesterol Education Program; PRL, prolactin; PRL_AUC, PRL area under the curve; WHO, World Health Organization.

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