finding and fixing broken brain circuits in depression...256 unique manifestations of depression...
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Finding and Fixing Broken Brain Circuits
in Depression
Conor Liston, MD, PhD
Brain and Mind Research Instituteand Department of Psychiatry
Weill Cornell Medicine
Social and Economic Burdens of Mental Illness
St. Elizabeth’s Hospital, Washington, DCSt. Elizabeth’s Hospital, Washington, DC% of Total Burden of
Disease (Years Lost)
Annual Economic
Costs of Depression
$70.7B
$28B
$ 102B
$9.7B
Total Annual Costs
in US:
$210 billion
Sources: World Health Organization; CDC;
Jiang & Hessler, 2012; Greenberg et al., 2010
256 unique manifestations of depression
St. Elizabeth’s Hospital, Washington, DCChoose 5 or more of 9 symptoms:
1. Depressed or irritable mood2. Decreased interest in activities3. Weight loss (or weight gain)4. Insomnia (or hypersomnia)5. Psychomotor agitation (or retardation)6. Fatigue or loss of energy7. Rumination on guilt / worthlessness8. Impaired concentration9. Suicidal thoughts
Defining Subtypes of Depression
St. Elizabeth’s Hospital, Washington, DC
MelancholicDepression
AtypicalDepression
SeasonalDepression
CatatonicDepression
DEPRESSION
NeurophysiologicalCorrelates
NeurophysiologicalCorrelates
NeurophysiologicalCorrelates
NeurophysiologicalCorrelates
Defining Subtypes of Depression: An Alternative Approach
Neurophysiological Subtype 1
DEPRESSION
ClinicalCorrelates
Neurophysiological Subtype 2
Neurophysiological Subtype 3
ClinicalCorrelates
ClinicalCorrelates
Defining Subtypes of Depression: An Alternative Approach
Finding Broken Brain Circuits in Depression
Whole-brain “connectivity” map
Correlated fluctuations in “connected”brain regions
Finding Broken Brain Circuits in Depression
Cornell: Andrew Drysdale, Marc
Dubin, B.J. Casey, Faith Gunning,
George Alexopoulos, Henning Voss
Stanford: Amit Etkin, Alan Schatzberg
Emory: Helen Mayberg
Toronto: Jonathan Downar
Harvard: Mike Fox, Alvaro Pasqual-
Leone
Consultation and Advice: Jonathan
Power (NIMH), Damien Fair (OHSU),
Logan Grosenick (Stanford)
1000 Functional Connectomes Project
Dataset 1: 711 subjects (333 unipolar depressed patients from 5 sites) => training/optimization
Dataset 2: 477 subjects (215 unipolar depressed patients from 4 sites) => replication
Finding Broken Brain Circuits in Depression
Drysdale et al., Nature Medicine, 2017
Finding Broken Brain Circuits in Depression
Drysdale et al., Nature Medicine, 2017
Broken Circuits Underlying Four Depression Subtypes
Drysdale et al., Nature Medicine, 2017
Broken Circuits Underlying Four Depression Subtypes
Drysdale et al., Nature Medicine, 2017
Broken Circuits Underlying Four Depression Subtypes
Subtype 1 Subtype 2 Subtype 3 Subtype 4
Depression Subtypes Predict Differing Symptoms
Developing Biomarkers for Diagnosing Depression Subtypes
Developing Biomarkers for Diagnosing Depression Subtypes
“Depression Subtypes” Cross Diagnostic Boundaries
“Depression Subtypes” Cross Diagnostic Boundaries
MDD:
AnxietyAnhedonia
Fixing Dysfunctional Brain Circuits in Depression
Repetitive Transcranial Magnetic Stimulationof the left dorsolateral prefrontal cortex
(3000 pulses per session delivered at 10 Hz, 25 sessions)
Liston et al., Biol Psych, 2014With Marc Dubin, Ashley Chen, Amit Etkin
Fixing Dysfunctional Brain Circuits in Depression
Toward Precision Medicine For Depression
With Jonathan Downar, Marc Dubin, Faith Gunning
Thank you!Cornell Lab Members:
Andrew Drysdale
Rob Fetcho
Baila Hall
Ben Huang
Thu Huynh
Yue Meng
Rachel Moda
Mitchell Murdock
Puja Parekh
David Rosenthal
Joseph Stujenske
Tim Spellman
Jonathan Witztum
Naomi Xia
Cornell Collaborators:
Marc Dubin
Faith Gunning
George Alexopoulos
Jonathan Power
Francis Lee
Other Financial Support:
Other Collaborators:
Toronto:
Jonathan Downar
Yale:
B.J. Casey
Harvard:
Mike Fox
Alvaro Pasqual-Leone
Emory:
Helen Mayberg
Stanford:
Amit Etkin
Alan Schatzberg
Karl Deisseroth
Logan Grosenick
Emily Ferenczi
Gary Glover