Teratogenic and Developmental Effects of Lithium
James J. Giles and John G. Bannigan
Affiliation: Conway Institute of Biomolecularand Biomedical Research, University College Belfield, Dublin 4,Ireland.
A review is presented on the effects of lithium in therapeutic doses on the outcome of human pregnancy. The results of various studies including cohort, prospective, retrospective and small number case reports indicate that lithium is a "weak" teratogen in humans. The main effects attributable to lithium are, cardiac malformations and babies with increased birth weight. There is a possibility that, in particular, lithium may be associated with the Ebstein anomaly but present evidence cannot definitely affirm or deny this association. Animal studies with lithium using doses comparable to human therapeutic serum levels have not reported any abnormalities. However, higher doses have produced exencephaly, skeletal and craniofacial defects and abnormalities of blood vessel development. Experiments with other vertebrates have shown that lithium affects dorsoventral specification and inhibition of vasculogenesis. Both these effects can be prevented by pretreatment with myo-inositol indicating that lithium interferes with the phosphatidyl inositol cycle. More recent findings have shown that the effects of lithium on invertebrates may be mediated through inhibition of GSK-3β in the Wnt-GSK-3 pathway.
Keywords: Vasculogenesis, Phosphatidylinositol cycle, Wnt-GSK-3 pathway, Angiogenesis, Ebstein Anomaly, Myo-inositol, Lithium
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