Next-generation precision medicine for mood disorders: reproducible blood biomarkers enable objective diagnostics, subtyping, and targeted therapeutics
Abstract
Mood disorders are highly prevalent in society, often disabling, and can lead to a reduced healthspan and lifespan, including by suicide. Depression and bipolar disorders are currently deemed to be chronic and/or treatment-refractory in up to half the patients treated. Additionally, depression and bipolar disorders need to be better distinguished, especially upon initial depressive presentations, as treatments can be quite different. Lack of widespread use of objective and/or quantitative information has hampered treatment and prevention efforts. We sought to uncover the underlying genomic and biological basis of mood disorders in a way that is reliable, comprehensive, and actionable. Blood biomarkers that track mood state can provide a window into the biology of mood, as well as could help with assessment and treatment of mood disorders. Previous studies by us were encouraging. Here we describe new studies we conducted trans-diagnostically in psychiatric patients, starting with the whole transcriptome, to expand the identification, prioritization, validation and testing of blood gene expression biomarkers for mood disorders, and their practical application. We first studied separately the two diametrical phenotypes, low mood/depression and high mood/mania. For each of the phenotypes, we carried out two separate studies, each of them on two different platforms, microarrays and RNA sequencing, using for each platform and study a multiple independent cohorts design. This was…
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