Clinical and genetic factors in response to treatment of bipolar disorder

Most people with bipolar disorder require ongoing treatment to prevent further recurrences of mania or depression. Several medications have been found effective in this indication, but each works only in a proportion of patients. The treatment in individual patients is commonly chosen by trial-and-error; each such trial takes a number of months and, as a result, most people achieve stability after considerable amount of time. We propose to test three groups of factors that could differentiate people who do and do not respond to one of the most effective treatments, lithium. First, we will study detailed clinical characteristics of lithium responders and non-responders from four cohorts totaling more than 1800 individuals and followed prospectively for several decades. Second, we will analyze genetic data from a cohort of over 3000 patients studied in collaboration with international consortium, ConLiGen. To understand better whether people respond better specifically to lithium or whether they would improve with other treatments as well, we will compare results in the lithium group with patients treated with other commonly used medications, valproate and lamotrigine. Finally, the lack of adequate response could be related to factors that modify activity of certain genes; we will study this by examining so called epigenetic marks on these patients' DNA. Together, these studies will help in selecting optimal long-term treatment in a timely fashion.