Lithium response across generations


  • Invited paper

Paul Grof MD, PhD, FRCP, Mood Disorders Center of Ottawa, Smyth Medical Centre, 202-1929 Russell Rd., Ottawa, ON, K1G 4G3, Canada.


Objective:  To describe and integrate observations from bipolar patients responsive to lithium stabilization and their children.

Method:  Selected findings are described from the clinical and biological investigations of adults meeting research criteria for bipolar disorder and for responsiveness to lithium stabilization; and from prospective studies of the children of lithium responders and non-responders.

Results:  Response to prophylactic lithium identifies a valid subtype of bipolar disorder, however the search for biological markers of lithium response, while promising, has so far remained inconclusive. Adult responders to lithium stabilization exhibit definable clinical features which are also observable in their affected children. In prospective studies the children of bipolar parents develop symptoms earlier than reported previously, with marked differences between the offspring of lithium responders and non-responders. The illness evolves in predictable clinical stages, first from non-specific sleep and anxiety disorders to mood symptoms and then, often starting in adolescence, major depressive and later activated episodes.

Conclusion:  Investigating and comparing unequivocal responders and non-responders to long-term lithium treatment and their offspring is a fertile research strategy for addressing a multitude of clinical and research questions.