DIURNAL-VARIATION OF CEREBROSPINAL-FLUID IMMUNOREACTIVE CORTICOTROPIN-RELEASING HORMONE LEVELS IN HEALTHY-VOLUNTEERS

CRH is not only secreted into hypophyseal portal blood where it is bel ieved to regulate the circadian rhythm of pituitary-adrenal activity, but is also measurable in cerebrospinal fluid (CSF). Altered CSF immun oreactive CRH (IR-CRH) levels have been found in patients with a numbe r of neuropsychiatric disorders and have been implicated in some of th e symptoms of these disorders. To further study the potential function al relevance of CRH in human CSF, we examined whether a nonuniform tem poral pattern of IR-CRH levels existed in CSF using hourly sampling ov er a 30-h period in six healthy volunteers. CSF was withdrawn continuo usly at 6 mL/h through a catheter placed in the lumbar subarachnoid sp ace and connected to a miniroller pump and fraction collector. A signi ficant diurnal variation in CSF IR-CRH levels was observed (P < 0.001) , with highest levels between 1830-2330 h and lowest levels around 073 0 h. This pattern was nearly opposite that of plasma cortisol levels, which showed the expected peak around 0800 h and nadir around 2000-220 0 h. In addition, CSF IR-CRH levels in three of the six volunteers sho wed significant negative correlations with simultaneous plasma cortiso l levels. These data suggest that CSF IR-CRH concentrations are negati vely modulated by peripheral cortisol secretion, which may be one fact or involved in the entrainment of this rhythm. Although the functional significance of this diurnal variation in CSF IR-CRH levels is unknow n, the presence of a distinct temporal organization of CRH release int o the CSF in humans is compatible with the idea that CSF may play a fu nctional role in or otherwise reflect nonsynaptic information processi ng in the central nervous system. Diurnal factors should be taken into account in future studies of CRH concentrations in human CSF.