Studies On Norepinephrine Signal Transduction Pathway And Auditory Evoked Potentials In Depression

Background: Depression is a chronic and easily relapsed psychiatric disease. The etiology of depression is still not clear. Because of lack of sensitive biochemical indicators, the identification ratio of depression is low. Among researches on neurobiological changes of depression, norepinephrine (NE) system plays an important role. NE mediated signal transduction pathway consists of β2-adrenergic receptor( β2-AR) , adenylyl cyclase (AC) and second messenger cyclic adenosine monophosphate (cAMP). Auditory evoked potentials is a valuable electroneurophysiological instrument in assessing the depressive state.Objective:1.To explore sensitive biochemical indicators of depression, β2-AR sensitivity in lymphocytes, basal and forskolin-stimulated AC activities in membranes of platelets, are measured. cAMP level in plasma is also measured.2.To investigate the relationship between long latency auditory evoked potentials and depression, long latency auditory evoked potentials is performed in depressive patients. Latencies of N1, P2 waves in Cz position are compared between patients group and normal controls. Amplitudes of N1, P2, N1/P2 waves in Cz position are compared between patients group and normal controls.Method:1. Isoproterenol, a specific β2-AR agonist ,was used to activate β2-AR in lymphocytes. β2-AR sensitivity was expressed as ratio of isoproterenol -stimulated cAMP to basal cAMP in lymphocytes. cAMP was determined by 125I cAMP radioimmunoassay kit. 2. Forskolin, which could directly activate AC, was used to stimulate AC . Basal- and forskolin-activated AC activities in membranes of platelets were expressed as pmol cAMP produced per mg membranal protein per minute. 3.cAMP level in plasma was determined by 125I cAMP radioimmunoassay kit. 4. Long latency auditory evoked potentials were recorded from every subject, using a Keypoint instrument. 5. We used Hamilton Depression Scale (HAMD) to assess the severity of depressive state. Results:1. The sensitivity of β2-AR of depressed patients was significantly lower than that of the normal controls.2. Basal and forskolin-activated AC activities of patients were both significantly lower than those of the normal controls.3. cAMP level in plasma was similar in normal controls and depressed subjects.4. Compared with normal controls, N, latency of patient group was significantly longer in 70dB, 80dB, 90dB stimulus intensities. β2 latency was similar in two groups. N, amplitudes in four stimulus intensities were significantly lower than those of the controls. β2 amplitudes were significantly lower than those of the controls in 90 dB, 100 dB stimulus intensities. N1/β2 amplitudes in four stimulus intensities were significantly lower than those of the controls.5. There was no correlation between each index mentioned above and the severity of depressive symptoms.Conclusions:1. Decreased β2-AR sensitivity may play a role in depression, and may be a sensitive biological marker in depression diagnosis.2. Decreased AC activity is closely related with etiology of depression, and may be a promising indicator in identifying depression in early stage.3. Inhibition of NE signal transducion system may play an important role in neurobiological changes of depression.4. Changes of long latency auditory evoked potentials in depressive patients are prolonged N, latency and decreased amplitudes of N1, P2, N,/P2.