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Background: Several epidemiological studies have shown the inverse association of lithium levels in drinking water and suicide rates; however, it is necessary to perform a clinical study dealing with individual patients., Methods: We analyzed 199 patients including 31 patients with suicide attempts, 21 patients with self-harm, and 147 control patients. All were transferred to a university emergency department suffering from intoxication or injury, were aged 20 or more years, and were alive at the start of the study. The exclusion criteria consisted of suffering from schizophrenia and a past or present history of lithium therapy. These exclusions were applied because it is difficult to determine whether their suicide attempt was induced by the intent to end their life or by psychotic symptoms such as auditory hallucinations, and if the patient had received lithium therapy, the association between the small amount of lithium taken from drinking water and food and serum lithium levels cannot be detected., Results: There was a significant difference (p = 0.043) between the three groups whereby patients with suicide attempts had significantly lower lithium levels than control patients (p = 0.012) in males but not females. Multivariate logistic regression analysis with adjustment for age and gender revealed that patients with suicide attempts had significantly lower lithium levels than control patients (p = 0.032, odds ratio 0.228, 95% CI 0.059-0.883)., Limitations: The limitations of the present study are the nature of observational research which cannot reveal a causal relationship and the relatively small number of subjects., Conclusions: The present findings suggest that higher serum lithium levels may be protective against suicide attempts in lithium therapy-naive individuals.

Rationale: Hyperthymic temperament is one of several premorbid temperaments putatively associated with bipolar disorder. Several reports suggest that depressive patients with hyperthymic temperament may belong to the proposed soft bipolar spectrum., Objectives: To investigate biological aspects of hyperthymic temperament, the present study examined daily activity, sleep time, central serotonergic function, and other relevant variables in relation to hyperthymic temperament in healthy subjects., Methods: Fifty six healthy subjects were monitored via the actigraphy system to measure daily total activity, sleep time, and illuminance. A neuroendocrine challenge test was performed to estimate central serotonergic function., Results: Multiple regression analysis revealed that higher illuminance of daytime, greater fluctuation in sleep time, and lower central serotonergic function significantly and independently predicted hyperthymic temperament scores., Conclusions: The present findings suggest that light, sleep, and serotonin are crucial factors in understanding hyperthymic temperament, which may be common to bipolar disorder.

We have recently reported inhibitory effects of carbamazepine (CBZ) on ion channel-mediated secretion of catecholamines in bovine adrenal medullary cells. Here, we report the effects of carbamazepine-10,11-epoxide (CBZ-E), an active metabolite of CBZ, and carbamazepine-10,11-diol (CBZ-D), a non-active metabolite, on 22Na+ influx, 45Ca2+ influx and catecholamine secretion in cultured adrenal medullary cells. CBZ-E, but not CBZ-D inhibited 22Na+ influx, 45Ca2+ influx and catecholamine secretion induced by carbachol or veratridine with a half-maximal inhibitory concentration (IC50) of 0.26 or 0.68 microg/ml, respectively. CBZ-E also inhibited high K+-evoked 45Ca2+ influx and catecholamine secretion (IC50 = 0.3 microg/ml), but CBZ-D did not. These findings suggest that CBZ-E, but not CBZ-D, attenuates catecholamine secretion by inhibiting nicotinic acetylcholine receptor-associated ion channels, voltage-dependent Na+ channels and voltage-dependent Ca2+ channels in the cells. This inhibition of CBZ-E as well as CBZ may be related to the clinical effects in neuropsychiatric disorders.