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Clinical Chemistry 0: clinchem.2007.099986v1, 2008; 10.1373/clinchem.2007.099986
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Received on January 28, 2008
Accepted on January 29, 2008

Reviews

Clinical Utility of Monoamine Neurotransmitter Metabolite Analysis in Cerebrospinal Fluid

Keith Hyland 1*

1 Horizon Molecular Medicine, Atlanta, GA

* To whom correspondence should be addressed. E-mail: khyland{at}horizonmedicine.com.

BACKGROUND: Measurements of monoamine neurotransmitters and their metabolites in plasma and urine are commonly used to aid in the detection and monitoring of neuroblastoma and pheochromocytoma and the evaluation of hypotension or hypertension. Measurements of these neurotransmitters and metabolites can also be helpful in the investigation of disorders that primarily affect the central nervous system, but only when the measurements are made in cerebrospinal fluid (CSF).

CONTENT: I describe CSF profiles of monoamine metabolites in the primary and secondary defects affecting serotonin and catecholamine metabolism. I outline the methods required to analyze these metabolites together with details of specific sample handling requirements, sample stability, and interfering compounds, and I emphasize a need for age-related reference intervals.

SUMMARY: Measured values of monoamine metabolites in CSF provide only a single-time snapshot of the overall turnover of the monoamine neurotransmitters within the brain. Because these measurements reflect the average concentrations accumulated from all brain regions plus the regional changes that occur within the spinal cord, they may miss subtle abnormalities, in particular brain regions or changes that occur on a minute-to-minute or diurnal basis. Clearly defined diagnosed disorders are currently limited to those affecting synthetic and catabolic pathways. In many cases, abnormal monoamine metabolite concentrations are found in CSF and an underlying etiology cannot be found. Molecular screening of candidate genes related to steps in the neurotransmission process, including storage in presynaptic nerve vesicles, release, interaction with receptors, and reuptake, might be a fruitful endeavor in these cases.







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