Finding and Fixing Broken Brain Circuits in Depression Conor Liston, MD, PhD Brain and Mind Research Institute and Department of Psychiatry Weill Cornell Medicine
Social and Economic Burdens of Mental Illness Annual Economic $9.7B % of Total Burden of St. Elizabeth’s Hospital, Washington, DC St. Elizabeth’s Hospital, Washington, DC Costs of Depression Disease (Years Lost) $70.7B $ 102B $28B 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, DC Choose 5 or more of 9 symptoms: 1. Depressed or irritable mood 2. Decreased interest in activities 3. Weight loss ( or weight gain ) 4. Insomnia ( or hypersomnia ) 5. Psychomotor agitation ( or retardation ) 6. Fatigue or loss of energy 7. Rumination on guilt / worthlessness 8. Impaired concentration 9. Suicidal thoughts
Defining Subtypes of Depression St. Elizabeth’s Hospital, Washington, DC DEPRESSION Melancholic Atypical Seasonal Catatonic Depression Depression Depression Depression Neurophysiological Neurophysiological Neurophysiological Neurophysiological Correlates Correlates Correlates Correlates
Defining Subtypes of Depression: An Alternative Approach DEPRESSION Neurophysiological Neurophysiological Neurophysiological Subtype 1 Subtype 2 Subtype 3 Clinical Clinical Clinical Correlates Correlates Correlates
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 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 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
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: Anhedonia Anxiety
Fixing Dysfunctional Brain Circuits in Depression Repetitive Transcranial Magnetic Stimulation of the left dorsolateral prefrontal cortex (3000 pulses per session delivered at 10 Hz, 25 sessions) Liston et al., Biol Psych, 2014 With 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: Other Collaborators: Andrew Drysdale Toronto: Rob Fetcho Baila Hall Jonathan Downar Ben Huang Thu Huynh Yale: Yue Meng B.J. Casey Rachel Moda Mitchell Murdock Harvard: Puja Parekh Mike Fox David Rosenthal Alvaro Pasqual-Leone Other Financial Support: Joseph Stujenske Emory: Tim Spellman Jonathan Witztum Helen Mayberg Naomi Xia Stanford: Cornell Collaborators: Amit Etkin Alan Schatzberg Marc Dubin Faith Gunning Karl Deisseroth George Alexopoulos Logan Grosenick Emily Ferenczi Jonathan Power Francis Lee Gary Glover
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