Methodological flaws and inconsistencies confound interpretation of today's literature. Based on this synthesis of available evidence and our clinical experience, we propose recommendations for further discussion.

In replicating and extending previous results, this study provides strong evidence that geographic regions with higher natural lithium concentrations in drinking water are associated with lower suicide mortality rates.

Several studies have indicated that patients with bipolar disorder (BD) who respond well to lithium prophylaxis constitute a biologically distinct subgroup. Lithium is thought to stablize mood by acting at the phosphoinositide cycle. We have investigated a polymorphism located in the gene (PLCG1) that codes for a ␥-1 isozyme of phospholipase (PLC), an enzyme that plays an important role in the phosphoinositide second messenger system. A population-based association study and a family-based linkage study were carried out on patients who were considered excellent responders to lithium prophylaxis. Response to lithium was evaluated prospectively with an average follow-up of 14.4 ± 6.8 years. The PLCG1 polymorphism was investigated in 136 excellent lithium responders and 163 controls. In addition, the segregation of this marker was studied in 32 families ascertained through lithium-responsive bipolar probands. The allele distributions between lithium-responsive bipolar patients and controls were different, with a higher frequency of one of the PLCG1 polymorphisms in patients ( 2 = 8.09; empirical P = 0.033). This polymorphism, however, confers only a small risk (OR = 1.88, CI 1.19-3.00). Linkage studies with the same marker yielded modest support for the involvement of this gene in the pathogenesis of BD when unilineal families were considered (Max LOD = 1.45; empirical P = 0.004), but not in the whole sample. Our results provide preliminary evidence that a PLC isozyme may confer susceptibility to bipolar disorder, probably accounting for a fraction of the total genetic variance. Whether this polymorphism is implicated in the pathogenesis of BD or in the mechanism of lithium response remains to be determined.

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Clinical research centers in Aarhus, Berlin, Hamilton and Vienna collected mortality data for 827 manic-depressive and schizoaffective patients given lithium treatment for more than 6 months. The average duration of the treatment was 81 months and the total time on lithium 5600 patient-years. For each patient, the mortality risk was calculated by entering the appropriate national life tables for the general population. The number of observed deaths was 44; the number of expected deaths was 49.7. The standardized mortality ratio, 0.89, did not differ significantly from 1.0. The mortality of manic-depressive patients is 2-3 times that of the general population. Our data show that the mortality of manic-depressive and schizoaffective patients given long-term lithium treatment does not differ significantly from that of the general population.

Background: Prenatal nicotine exposure is associated with increased neonatal mortality, low birth weight, and smaller head circumference. Opioid-dependent pregnant women show a particularly high prevalence of tobacco smoking and are at greater risk for additional adverse events. However, little is known about the impact of tobacco smoking on opioid-maintained pregnant women and neonatal outcomes. Patients and Methods: This study examined the effect of cigarette smoking on 139 opioid-maintained pregnant women and their neonates. Forty-five percent of the participants were maintained on slow-release oral morphine (SROM), 39% received methadone maintenance, and 16% received buprenorphine. Participants were divided into two groups: (1) women who reported a low cigarette consumption of ≤10 cigarettes/day (56.8%) and (2) those reporting heavy consumption of ≥20 cigarettes/day (43.2%). Neonatal outcome measures were assessed, and a standardized Finnegan score was applied to determine the neonatal abstinence syndrome (NAS). Results: Fifty-two percent of the newborns did not require treatment for NAS (54% of neonates born to methadone-maintained mothers, 30% born to SROM-maintained mothers, and 95% born to buprenorphine-maintained mothers; p < 0.001). Heavy cigarette consumption was associated with significantly lower neonatal birth weight (p < 0.001), smaller birth length (p = 0.017) as well as with the severity of NAS (p = 0.03). With regard to concomitant consumption of opioids (p = 0.54), cocaine (p = 0.25), amphetamines (p = 0.90) or benzodiazepines (p = 0.09), no significant differences between heavy or low nicotine consumption were noted. Conclusion: Heavy tobacco smoking in opioid-maintained pregnant women is associated with adverse medical and developmental consequences for the newborn. Future treatment programs for this target group should focus on an individualized approach to opioid maintenance therapy in addition to offering specially tailored counseling for smoking cessation.

It appears that individuals with remitted bipolar affective disorder do not show cognitive vulnerability as proposed in Beck's theory of depression if they only report subthreshold levels of depressive symptoms. Perhaps, the cognitive vulnerability might only be observable if mood induction procedures are used.