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Immune targets for therapeutic development in depression: towards precision medicine.

Published version
Peer-reviewed

Type

Article

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Authors

Drevets, Wayne C 
Wittenberg, Gayle M 
Manji, Husseini K 

Abstract

Over the past two decades, compelling evidence has emerged indicating that immune mechanisms can contribute to the pathogenesis of major depressive disorder (MDD) and that drugs with primary immune targets can improve depressive symptoms. Patients with MDD are heterogeneous with respect to symptoms, treatment responses and biological correlates. Defining a narrower patient group based on biology could increase the treatment response rates in certain subgroups: a major advance in clinical psychiatry. For example, patients with MDD and elevated pro-inflammatory biomarkers are less likely to respond to conventional antidepressant drugs, but novel immune-based therapeutics could potentially address their unmet clinical needs. This article outlines a framework for developing drugs targeting a novel patient subtype within MDD and reviews the current state of neuroimmune drug development for mood disorders. We discuss evidence for a causal role of immune mechanisms in the pathogenesis of depression, together with targets under investigation in randomized controlled trials, biomarker evidence elucidating the link to neural mechanisms, biological and phenotypic patient selection strategies, and the unmet clinical need among patients with MDD.

Description

Keywords

Antidepressive Agents, Biomarkers, Depression, Depressive Disorder, Major, Humans, Precision Medicine

Journal Title

Nat Rev Drug Discov

Conference Name

Journal ISSN

1474-1776
1474-1784

Volume Title

Publisher

Springer Science and Business Media LLC
Sponsorship
Wellcome Trust (104025/Z/14/Z)
Medical Research Council (MC_G0802534)
Medical Research Council (MR/L014815/1)
Johnson and Johnson