Since the catecholamine hypothesis of depression was introduced to the psychiatric field as one of the possible major causes of depression, many researchers and clinicians have paid a great deal of attention to exploring the possible link between depression and brain norepinephrine metabolism. Much data about the relationship between 3-methoxy-4-hydroxy phenethylei.e glycol (MHPG: the major metabolite of brain norepinephrine) and depression have been provided by many investigators. However, not all researchers agreed to the results because there are many controversial factors concerning MHPG.
Thus the authors investigated 40 depressed patients and measured their urinary excretion of MHPG and their symptoms and compared the results to a normal control group and to each clinically defined sub-groups of depression. The authors also measured the urinary excretion of MHPG after 4 weeks of treat ment with tricyclic antidepressants and compared the differences of urinary excretion of MHPG between crinically improved and non-improved patients. In addition, the authors explored the possible link between the symptom changes and the metabolism of brain norepinephrine.
The results are as follows:
1. The mean urinary excretion of MHPG of 20 normal Korean male college students was 1.780.15mg/24 hrs. which was not significantly different from previous results reported by western researchers.
2. In the pretreatment state, the urinary excretion of MHPG in patients with bipolar depression (1.390.09mg/24hrs.) is markedly lower than those of the control group and patients with unipolar endogenous depression (p<0.01).
3. While the urinary excretion rates of MH PG in bipolar depressive patients are relatively uniformed, unipolar depressive patients showed wide distribution of urinary excretion rates of MHPG which could be categorized into 3 subgroups according to their pretreatment urinary excretion of MHPG; unipolar depression A (UA) : 8 out of 25 unipolar endogenous depressive patients excreted high urinary MHPG (1.95 0.07mg/24 hrs.), while unipolar depression B (UB, 10 out of 25) had less excretion of urinary MHPG (1.510.05 mg/24hrs.) compared to normal controls. And another 7 out of 25 unipolar endogenous depression had similar excretion rate of urinary MH PG (unipolar depression C, UC ; 1.750.07 mg/24 hrs.) compared to normal control group.
4. After 4 weeks of tricyclic antidepressant treatment, 10 out of 15 bipolar depressive patients showed marked clinical improvement with increased urinary excretion of MHPG (1.60+0.08 mg/24 hrs.), compared to posttreatment urinary excretion of MH PG of 5 patients whose symptoms were not improved (1.360.16 mg/24hrs.) and pretreatment level. The increase of urinary excretion of MHPG in clinically improved bipolar patients was significant (p<0.01).
5. In unipolar endogenous depression, only the patients whose pretreatment urinary MHPG values were lower than those of normal controls (UB group) showed statistically significant increase of urinary MH PG excretion accompanied by clinical improvement (MHPG levels; 1.620.06 mg/ 24hrs.) when compared to patients who showed no proper clinical improvement or pretreatment urinary MHPG levels.
6. After 4 weeks of tricyclic antidepressant treatment, neither patients in UA nor UC showed any significant alteration on their urinary excretion of MHPG regardless to their clinical improvement.
From the above results, the authors could suggest that alteration of brain norepinephrine could be an important cause of bipolar depressive disorders. However, in unipolar depression, there might be a subgroup whose depressive symptoms are caused by brain norepinephrine metabolism. And the other neurotransmitter besides brain norepinephrine might play a major role in the mechanisms of depression in other subgroups of unipolar endogenous depression.
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