Exploring the genetics of lithium response in bipolar disorders

Area of Science:

• Psychiatry and Genetics
• Pharmacogenomics
• Bipolar Disorder Research

Background:

• Lithium (Li) is a primary treatment for bipolar disorders (BP), managing mood, sleep, and cardiovascular symptoms.
• Individual responses to Li vary significantly across BP subtypes (BP-I, BP-II), with concerns about long-term side effects like thyroid and renal disease.
• Genetic studies, including the Consortium on Lithium Genetics (ConLiGen), are identifying factors influencing Li treatment variability in BP.

Purpose of the Study:

• To investigate the genetic underpinnings of Li treatment response in a large BP cohort (N=2064).
• To examine the association between Li response, psychiatric symptoms, and polygenic load for medical comorbidities.
• To identify differential genetic effects between BP-I and BP-II subtypes.

Main Methods:

• Utilized the ConLiGen cohort (N=2064) for genetic analyses.
• Assessed clinical response to Li using the Alda scale.
• Analyzed the association between Li response, psychiatric symptoms, and polygenic risk scores for comorbidities.

Main Results:

• Stronger Li response correlated with reduced mania, depression, substance abuse, psychosis, and suicidal ideation in BP-I; depression only in BP-II.
• Enhanced Li response was linked to lower polygenic load for diabetes and hypertension in BP-I, but not BP-II.
• Identified genes previously associated with Li response showed differential relationships with psychiatric symptoms and polygenic load for comorbidities like diabetes, hypertension, and hypothyroidism.

Conclusions:

• Common genetic factors partially modulate Li's effects on symptomatology and comorbidity in bipolar disorder.
• Differential genetic influences exist between BP-I and BP-II subtypes regarding Li treatment response.