Genome-wide Association Study of Depression and Suicidal Ideation Emerging during Interferon Treatment Investigators:

Investigators:

Gonzalo Laje, MD, MHSc, Marc Ghany, MD

Hypotheses/Aims

Hypothesis: Genetic markers associate with interferon/ribavirin emergent depressive symptoms and suicidal ideation or behavior.

Specific Aim 1: Test if genetic markers associate with interferon/ribavirin treatment emergent or worsening symptoms of depression. We will search the entire genome for genetic markers with predictive power to detect emerging or worsening symptoms of depression.

Specific Aim 2: Confirm and characterize the association between genetic variation in GRIK2, GRIA3, PAPLN and IL28RA and treatment-emergent suicidal ideation in patients treated with interferon/ribavirin. Our Preliminary Studies have shown that genetic variation in GRIK2, GRIA3, PAPLN and IL28RA is associated with treatment-emergent suicidal ideation. We aim to test this association in an independent cohort treated with interferon/ribavirin.

Specific Aim 3: Test if new markers associate with interferon/ribavirin treatment emergent suicidal ideation or behavior.  Based on published work, interferon/ribavirin treatment increases the risk for suicide and suicidal ideation. Our preliminary studies have also shown that genetic variation may have predictive value in detecting those at risk of developing suicidal ideation, however the described markers have a combined sensitivity of only 88% and a specificity of 99% for citalopram treated patients. This raises the question of whether there are additional markers that have more predictive power and whether depression, suicidal ideation or behavior emergent from IFN/ribavirin treatment is mediated through different pathways and therefore could associate with different markers.