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 disorder (BP), managing mood symptoms and reducing suicide risk.
• Individual responses to Li vary significantly across BP subtypes (BP-I, BP-II) and are linked to side effects and comorbidities.
• Genetic factors are increasingly recognized as contributors to Li treatment variability in BP.

Approach:

• Leveraged the Consortium on Lithium Genetics (ConLiGen) cohort (N=2,064) to investigate the genetic basis of Li effects in BP.
• Analyzed the association between Li response, linked genes, psychiatric symptoms, and polygenic load for medical comorbidities.
• Specifically examined differential genetic effects between BP-I and BP-II subtypes.

Key Points:

• Clinical response to Li (Alda scale) correlated with reduced mania, depression, substance abuse, psychosis, and suicidal ideation in BP-I, and depression in BP-II.
• Stronger Li response was associated with lower polygenic load for diabetes and hypertension in BP-I, but not BP-II.
• Identified specific genes influencing Li response variability, psychiatric symptomatology (manic/depressive episodes), 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.
• These genetic modulations exhibit differential impacts between BP-I and BP-II subtypes.