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Nat Med. 2017 Jan;23(1):28-38. doi: 10.1038/nm.4246. Epub 2016 Dec 5.

Resting-state connectivity biomarkers define neurophysiological subtypes of depression.

Author information

1
Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, New York, USA.
2
Department of Psychiatry, Weill Cornell Medical College, New York, New York, USA.
3
Sackler Institute for Developmental Psychobiology, Weill Cornell Medical College, New York, New York, USA.
4
Department of Bioengineering and Center for Mind, Brain and Computation, Stanford University, Stanford, California, USA.
5
Department of Statistics, Columbia University Medical Center, New York, New York, USA.
6
Department of Psychiatry, Toronto Western Hospital, Toronto, Canada.
7
Department of Psychiatry, Columbia University Medical Center, New York, New York, USA.
8
Center for Neuromodulation in Depression and Stress and Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
9
Department of Psychiatry and Behavioral Science, Stanford University, Stanford, California, USA.
10
Veteran Affairs Palo Alto Health Care System, Stanford University, Stanford, California, USA.
11
Department of Psychiatry, Emory University School of Medicine, Atlanta, Georgia, USA.
12
Institute of Geriatric Psychiatry, Weill Cornell Medical College, New York, New York, USA.
13
Berenson-Allen Center for Noninvasive Brain Stimulation and Harvard Medical School, Boston, Massachusetts, USA.
14
Department of Radiology, Weill Cornell Medical College, New York, New York, USA.
15
Department of Psychology, Yale University, New Haven, Connecticut, USA.

Abstract

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.

PMID:
27918562
DOI:
10.1038/nm.4246
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