Journal Article

Resting-state connectivity biomarkers define neurophysiological subtypes of depression

Keller, Jennifer, Alexopoulos, George S, Sudheimer, Keith, Gunning, Faith M, Mayberg, Helen S, Fox, Michael D, Dubin, Marc J, Schatzberg, Alan F, Downar, Jonathan, Etkin, Amit, Grosenick, Logan, Fetcho, Robert N, Pascual-Leone, Alvaro, Drysdale, Andrew T, Liston, Conor, Zebley, Benjamin, Voss, Henning U, Mansouri, Farrokh, Casey, BJ, Meng, Yue, Dunlop, Katharine, Oathes, Desmond J

2017

Overview

Using functional MRI in a large multisite sample of more that 1,000 patients, four distinct neurophysiological biotypes of depression are defined. These biotypes are used to develop diagnostic classifiers that distinguish patients with depression from controls in separate multisite validation and replication cohorts, and can predict patient responsiveness to therapy. Biomarkers have transformed modern medicine but remain largely elusive in psychiatry, partly because there is a weak correspondence between diagnostic labels and their neurobiological substrates. Like other neuropsychiatric disorders, depression is not a unitary disease, but rather a heterogeneous syndrome that encompasses varied, co-occurring symptoms and divergent responses to treatment. By using functional magnetic resonance imaging (fMRI) in a large multisite sample ( n = 1,188), we show here that patients with depression can be subdivided into four neurophysiological subtypes ('biotypes') defined by distinct patterns of dysfunctional connectivity in limbic and frontostriatal networks. Clustering patients on this basis enabled the development of diagnostic classifiers (biomarkers) with high (82–93%) sensitivity and specificity for depression subtypes in multisite validation ( n = 711) and out-of-sample replication ( n = 477) data sets. These biotypes cannot be differentiated solely on the basis of clinical features, but they are associated with differing clinical-symptom profiles. They also predict responsiveness to transcranial magnetic stimulation therapy ( n = 154). Our results define novel subtypes of depression that transcend current diagnostic boundaries and may be useful for identifying the individuals who are most likely to benefit from targeted neurostimulation therapies.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 59/36 / 631/378/1689/1414 / 692/53/2421 / 692/53/2423 / 692/699/476/1414 / Adult / Biological markers / Biomarkers / Biomedicine / Biotypes / Brain - physiopathology / Cancer Research / Care and treatment / Cluster Analysis / Clustering / Depression (Mood disorder) / Depressive Disorder, Major - classification / Depressive Disorder, Major - physiopathology / Development and progression / Diagnostic systems / Female / Frontal Lobe - physiopathology / Functional magnetic resonance imaging / Functional Neuroimaging / Health aspects / Humans / Infectious Diseases / Limbic System - physiopathology / Magnetic fields / Magnetic Resonance Imaging / Male / Mental depression / Mental disorders / Metabolic Diseases / Methods / Molecular Medicine / Neural networks / Neural Pathways - physiopathology / Neural stimulation / Neurosciences / Patient outcomes / Patients / Psychiatry / Substrates / Transcranial magnetic stimulation / Ventral Striatum - physiopathology