ConLiGen's first and most crucial goal is to define the phenotype of lithium response. Treatment response is a complex construct that requires researchers to make judgments about adequacy of treatment and tolerability as well as assess changes in episode frequency or symptom severity. In many cases this information must be assessed retrospectively, with the inherent limitations associated with recall bias, missing information, or the fact that the treatment has not followed a strict research protocol.
ConLiGen is poised to assess all aspects of the pharmacogenetics of lithium treatment in psychiatric disorders, including the study of genetic susceptibility to potential treatment-emergent adverse events (e.g. weight gain, hypothyroidism, tremor). As its first project, ConLiGen intends to conduct a GWAS of stringently defined response to lithium treatment in bipolar disorder. ConLiGen members and the various research centers which they are affiliated with are joining their samples for a centralized genotyping effort to be performed at the Unit on the Genetic Basis of Mood and Anxiety Disorders of the NIMH and the Department of Genomics of the Life and Brain Center at the University of Bonn, Germany.
Although the combined ConLiGen sample will be the largest sample to date to investigate lithium response on a genome-wide scale, we are aware that any finding, regardless of whether it reaches levels of genome-wide significance, will ultimately have to be confirmed in independent samples. Thus, ConLiGen's mission will not be finished after the completion of its GWAS. On the contrary, ConLiGen will continue to invite researchers to join its efforts in order to increase the available sample size of patients adequately characterized for lithium response. In collaboration with both IGSLI centers and large, long-standing multicenter projects such as the NIMH Bipolar Disorder Genetics Initiative, ConLiGen will be actively engaged in supporting and organizing urgently needed prospective studies of lithium response in bipolar disorder and other conditions.
Since Cade discovered lithium's beneficial effects in the treatment of bipolar disorder 60 years ago, this agent has become almost synonymous with the treatment of bipolar disorder worldwide. Yet, little is known about the genetic underpinnings of lithium response or the development of side effects associated with its use. In a scientific environment characterized by calls for personalized medicine and the growth of large-scale pharmacogenetic studies in many fields of medicine, ConLiGen's goal is to put lithium at the forefront of pharmacogenetic studies in psychiatry.