K KAWAI, K MARUTA, T NAGATSU, R TERADAIRA, H MATSUI, T ITO, M OHTANI, Y SHINOHARA, K FUJITA
BIOGENIC AMINES, 9(2) 83-98, 1992 Peer-reviewed
Serum dopamine-beta-hydroxylase (DBH, dopamine beta-monooxygenase ; EC 1.14.17.1) is derived from peripheral sympathetic nerves together with norepinephrine. Serum DBH shows circadian variations. We have developed a simple method to estimate the circadian variation, and have applied the method for the study of serum DBH in schizophrenic patients. We estimated the times at which the activity of serum DBH showed the maximum and minimum levels from the circadian rhythm in 40 normal controls. We then compared the activities at these two points between schizophrenic patients and normal controls, and evaluated the significance of the circadian variation of serum DBH activity as a biochemical marker in schizophrenia. From the circadian rhythm of the serum DBH activity (IU, mu-mol/min per liter serum) in 40 normal controls, 5:00 a.m. (minimum activity) and 13:00 p.m. (maximum activity) were selected as the two measurement points to estimate circadian variation. The serum DBH activity was then measured at these times in 40 normal controls and 166 volunteer patients with schizophrenia during 5 consecutive days. The mean serum DBH activities at 5:00 and 13:00 were significantly lower in 166 schizophrenic patients than those in 40 normal controls (25.65 +/- 0.91 vs 42.79 +/- 3.59 at 5:00 ; 25.80 +/- 0.92 vs 44.50 +/- 3.67 at 13:00), conforming to our previous report [Fujita, K. et al, (1978) J. Newochem, 30, 1569 - 1572]. The difference between the mean DBH levels at 13:00 and 5:00 was divided by the mean activity of the values at all 10 time points during the 5 days, and this value was defined as the circadian variation in serum DBH activity (%). The circadian variation in serum DBH activity (mean @ SEM) was 4.37 +/- 0.48 (%) in 40 normal controls and 1.05 +/- 0.33 (%) in 166 schizophrenic patients, being significantly smaller in schizophrenic patients than in normal controls (p < 0.001). Furthermore, in 6 from 40 normal controls and 78 from 166 schizophrenic patients whose serum DBH levels were less than 25 IU, the mean circadian variation in serum DBH activity was 6.33 +/- 1.95 (%) in normal controls and 1.02 +/- 0.55 (%) in schizophrenic patients (P < 0.05). Similarly, in schizophrenic patients and normal controls whose serum DBH levels were 25 IU and above, the circadian variation in DBH was 4.03 +/- 0.45 (%) in normal controls and 1.09 +/- 0.39 (%) in schizophrenic patients (p < 0.001). Significantly lower circadian variations were observed in three types of schizophrenia ; hebephrenic, Paranoid and catatonic forms. These results indicate that the circadian variation in serum DBH is significantly decreased in schizophrenic patients regardless of the mean serum DBH activity during 24 hours and of the types of disease. Therefore, the variation in DBH is considered to be useful as a biochemical marker in schizophrenia.