SummaryThe goal of the present study was to investigate inter-individual and age-dependent variation of global DNA methylation in human tissues. In this work, we examined 5-methyldeoxycytidine ( met C) content by HPLC in human peripheral blood leukocytes obtained from 76 healthy individuals of ages varying from 4 to 94 years (yr), and 39 human placentas from various gestational stages. The HPLC analysis revealed a significant variation of met C across individuals and is consistent with the previous findings of age-dependent decrease of global methylation levels in human tissues. The age-dependent decrease of met C was relatively small, but statistically highly significant (p = 0.0002) in the aged group (65.9 ± 8.9 [mean age ± SD] yr; n = 22) in comparison to the young adult group (19.3 ± 1.4 yr; n = 21). Males showed a subtle but statistically significant higher mean met C content than females. In contrast to the peripheral blood samples, DNA extracted from placentas exhibited gestational stage-dependent increase of methylation levels that appeared to inversely correlate with the expression levels of human endogenous retroviruses. These data may be helpful in further studies of DNA methylation, such as inheritance of epigenetic patterns, environment-induced changes, and involvement of epigenetic changes in disease.

SUMMARY The anti‐manic, anti‐depressive and prophylactic effects of carbamazepine (CAZP, Tegretol‐Ciba Geigy) on the endogenous mani‐depressive psychosis (MDP) were investigated on 50 MDP cases. The dosage of the drug ranged from 200 to 1,200 mg daily (usually 400 to 600 mg). The effect of CAZP on 33 manic states was: “markedly effective” seven (23%), “effective” six (19%), “slightly effective” five (16%), “ineffective” 13 (42%), whereas the effect on six depressive states was: “markedly effective” one and “ineffective” five. No definite relationship was found between the kinds of drugs in combination use and the effect of CAZP. No significant difference of the CAZP effect was found in the four patient groups with different age of onset of the illness, nor among the “continuous,”“frequent” and “periodic” type cases. The prophylactic effect of CAZP on 27 cases in which the assessment of the effect on the manic episode was possible was: “markedly effective” 13 (48%), “effective” seven (26%) and “ineffective” seven (26%), whereas that for depressive episode was: 12 (45%), two (7%) and 13 (48%), and the result of the general assessment on each patient was 14 (43%), 10 (30%) and nine (27%), respectively. The kinds of drugs in combination use, age of onset and type of course of the illness did not have any influence on the prophylactic effect of CAZP. The prophylactic effect on MDP of CAZP did not parallel that of lithium salt, but CAZP may be effective on cases which did not respond to lithium and vice versa. Side‐effects such as ataxia, dizziness, exanthema, drowsiness and headache were observed in five of the cases, and the CAZP was discontinued in four of them. The mechanism of effectiveness of the CAZP on MDP was discussed.

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