in Depression Conor Liston, MD, PhD Brain and Mind Research - - PowerPoint PPT Presentation

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in Depression Conor Liston, MD, PhD Brain and Mind Research - - PowerPoint PPT Presentation

Nov 04, 2023 262 likes •503 views

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

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Finding and Fixing Broken Brain Circuits in Depression

Conor Liston, MD, PhD

Brain and Mind Research Institute and Department of Psychiatry Weill Cornell Medicine

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Social and Economic Burdens of Mental Illness

  • St. Elizabeth’s Hospital, Washington, DC
  • St. 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

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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
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Defining Subtypes of Depression

  • St. Elizabeth’s Hospital, Washington, DC

Melancholic Depression Atypical Depression Seasonal Depression Catatonic Depression

DEPRESSION

Neurophysiological Correlates Neurophysiological Correlates Neurophysiological Correlates Neurophysiological Correlates

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Defining Subtypes of Depression: An Alternative Approach

Neurophysiological Subtype 1

DEPRESSION

Clinical Correlates

Neurophysiological Subtype 2 Neurophysiological Subtype 3

Clinical Correlates Clinical Correlates

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Defining Subtypes of Depression: An Alternative Approach

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Finding Broken Brain Circuits in Depression

Whole-brain “connectivity” map

Correlated fluctuations in “connected” brain regions

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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

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Finding Broken Brain Circuits in Depression

Drysdale et al., Nature Medicine, 2017

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Finding Broken Brain Circuits in Depression

Drysdale et al., Nature Medicine, 2017

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Broken Circuits Underlying Four Depression Subtypes

Drysdale et al., Nature Medicine, 2017

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Broken Circuits Underlying Four Depression Subtypes

Drysdale et al., Nature Medicine, 2017

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Broken Circuits Underlying Four Depression Subtypes

Subtype 1 Subtype 2 Subtype 3 Subtype 4

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Depression Subtypes Predict Differing Symptoms

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Developing Biomarkers for Diagnosing Depression Subtypes

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Developing Biomarkers for Diagnosing Depression Subtypes

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“Depression Subtypes” Cross Diagnostic Boundaries

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“Depression Subtypes” Cross Diagnostic Boundaries

MDD:

Anxiety Anhedonia

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Fixing Dysfunctional Brain Circuits in Depression

Repetitive Transcranial Magnetic Stimulation

  • f 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

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Fixing Dysfunctional Brain Circuits in Depression

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Toward Precision Medicine For Depression

With Jonathan Downar, Marc Dubin, Faith Gunning

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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