Lithium response across generations

Abstract

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.

The Early Natural History of Bipolar Disorder: What We Have Learned from Longitudinal High-Risk Research

“…[45][46][47] Further, the nature of the clinical course is one of the characteristics differentiating BD subtypes and is related to differential pathophysiological correlates, family history, treatment response, and prognosis. [48][49][50][51][52] In our experience, customizing treatment by incorporating the clinical profile of the individual patient (for example, nature of the clinical course, the family history of psychiatric disorders, and the familial response to treatment) into the selection of the mood stabilizer for that patient improves their outcome dramatically, compared with outcomes from randomly chosen treatments listed in generic treatment guidelines. 35,36,53 The other key finding from the high-risk research is the evidence that the early natural history of BD unfolds in a series of predictable clinical stages.…”

Smaller hippocampal volumes in patients with bipolar disorder are masked by exposure to lithium: a meta-analysis

“…It is clear that only a proportion of patients with diag nosed bipolar disorder will respond to Li. 46,57 Thus, response to Li likely varied within the available studies. Furthermore, recent reports have shown an association between Li levels in the brain and N-acetylaspartate, a marker of neuronal density, 58 as well as increases in the brain-derived neurotrophic factor levels in Li-treated patients.…”

Interventions for Youth at Risk of Bipolar Disorder

“…Selected prophylactic treatment based on individual patient profile, however, is associated with very high success and tolerability rates [77]. Evidence suggests, for example, that BD patients who respond to long-term lithium prophylaxis are characterized by an episodic remitting illness course, a family history of recurrent mood disorders (not schizophrenia) or poorly remitting psychotic disorders, and a family history of lithium response and classical acute episodes with or without psychosis (lithium has antipsychotic effects) [78,79]. Lithium is also very effective in treating suicidal thoughts and behaviour, even as an adjunct in patients who would otherwise not be good long-term responders to lithium monotherapy [10, 14•].…”