The molecular pathophysiology of mood disorders: from the analysis of single molecular layers to multi-omic integration.

Abstract

Next-generation sequencing now enables the rapid and affordable production of reliable biological data at multiple molecular levels, collectively referred to as “omics”. To maximize the potential for discovery, computational biologists have created and adapted integrative multiomic analytical methods. When applied to diseases with traceable pathophysiology such as cancer, these new algorithms and statistical approaches have enabled the discovery of clinically relevant molecular mechanisms and biomarkers. In contrast, these methods have been much less applied to the field of molecular psychiatry, although diagnostic and prognosticbiomarkers are similarly needed. In the present review, we first briefly summarize main findings from two decades of studies that investigated single molecular processes in relation to mood disorders. Then, we conduct a systematic review of multi-omic strategies that have been proposed and used more recently. We also list databases and types of data available to researchers for future work. Finally, we present the newest methodologies that have been employed for multi-omics integration in other medical fields, and discuss their potential for molecular psychiatry studies.

Functional genomic mechanisms of opioid action and opioid use disorder: a systematic review of animal models and human studies

“…Therefore, combined investigation of multiple epigenetic marks, possibly at the single-cell scale, have the potential to suggest molecular interactions that can then be dissected and manipulated in vivo . Importantly, such multi-omic assessment requires implementing dedicated bioinformatic frameworks, which are only emerging in psychiatry [150]. These integrative approaches, by describing how multiple molecular layers of regulation interact, are expected to better capture the chain of events linking disease causes (whether genetic, developmental, environmental, or a combination thereof) to their behavioral manifestation [151].…”