Cerebrospinal Fluid Neopterin is Brain-derived and Not Associated with Blood-CSF Barrier Dysfunction in Non-inflammatory Affective and Schizophrenic Spectrum Disorders

Many psychiatric patients have a minor blood-CSF barrier dysfunction and increased Cerebrospinal fluid (CSF) neopterin concentrations. The source of normal CSF neopterin, a biomarker in inflammatory and non-inflammatory neurological diseases, has never been shown explicitly, a precondition for sensitive detection of pathologically increased CSF neopterin. Neopterin concentrations (ELISA) in CSF and serum of normal controls (n = 26) are evaluated by inter-individual variation propagation. Normal CSF neopterin is brain-derived: The inter-individual variation of CSF neopterin in the control group does not depend on serum neopterin concentration variation (coefficient of variation, CV-CSF = 9.7% < CV-serum = 24.5%). Additionally individual normal CSF neopterin concentrations are invariant to the variation of the albumin quotient, QAlb, i.e. CSF neopterin does not derive from leptomeninges. Subsequently CSF neopterin was interpreted with reference to its absolute concentration in CSF (cut off = 5.5 nmol/l). Patients (N = 44), retrospectively selected from a larger group with schizophrenic and affective spectrum disorder, are characterized by the absence of any clinical and neurochemical signs of inflammation. In this group 30% had an increased CSF neopterin concentration and 30% had an increased QAlb with only 7% combined pathologies. Increased CSF neopterin did not correlate with the blood-CSF barrier dysfunction. In the discussion we point to possible sources of both independent pathologies, connected either with reduced CSF flow rate (QAlb) or microglial activation (neopterin). With CSF neopterin analysis earlier in vitro studies about microglia activation in schizophrenic spectrum disorders or corresponding therapeutic efforts could get a more direct, in-vivo analytical tool.