Brain Plasticity: The Effects of Antidepressants on Major Depression · Biol Psychiatry 2009....

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• Brain Plasticity: The Effects of Antidepressants on Major Depression J. John Mann MD Paul Janssen Professor of Translational Neuroscience Columbia University Director, Division of Molecular Imaging and Neuropathology New York State Psychiatric Institute

Transcript of Brain Plasticity: The Effects of Antidepressants on Major Depression · Biol Psychiatry 2009....

  • • Brain Plasticity: The Effects of Antidepressants on Major Depression

    J. John Mann MDPaul Janssen Professor of Translational Neuroscience

    Columbia UniversityDirector, Division of Molecular Imaging and Neuropathology

    New York State Psychiatric Institute

  • Disclosures:

    • 1. This talk is based on research funded by NIMH & BBRF.

    • 2. Recipient of royalties from Research Foundation for Mental Hygiene for commercial use of the C-SSRS.

  • Scope of Lecture

    • Can the neurobiology of major depression explain why certain medications are antidepressants?

    • Targets of antidepressants may help identify new faster acting and more effective treatments.

    J Mann.2019

  • Pharmacotherapy for Major Depressive Episode

    • MDD: SSRIs, NERIs, SNRIs, NGAs, MAOIs, lithium or ketamine.

    • Bipolar disorders: lithium, anticonvulsants, NGAs.• These subtypes of medication are based on their first

    identified disease target. • How do their pharmacological targets fit with the

    known neurobiology of major depressive episodes?

    J Mann.2019

  • Neurobiology of Major Depressive Episodes: six pathways

    • 1. High 5-HT1A autoreceptors > low firing>serotonin release>low activity>loss of trophic effect

    • 2. Low CSF MHPG = low noradrenergic activity• 3. Low GABA = low GABAergic activity• 4. High glutamate>neurotoxicity• 5. High HPA axis activity>neurotoxicity• 6. Low omega 3/6 PUFA ratio, stress>neuroinflammation

    and altered brain activity/neurotoxicity

    J Mann.2019

  • SEROTONIN

    J Mann.2019

  • CSF 5-HIAA: an index of brain serotonin system trait activity

    • Low CSF 5-HIAA in mood disorders.• Low CSF 5-HIAA reflects less serotonin release. • Low serotonin release can be result of fewer

    serotonin neurons or less serotonin in each neuron or less serotonin neuron firing and release.

    J Mann.2019

  • Serotonin Neurons and Serotonin Content

    • Postmortem studies of MDD suicides:

    • More serotonin neurons• More tryptophan

    hydroxylase per neuron• More serotonin in

    neurons.

    J Mann.2019

  • Serotonin5-HT1A Receptor

    Transporter

    Imaging the Serotonin SynapseLess Transporter = less

    serotonin activity

    5-HT2AReceptor

    5-HT1A Autoreceptor

    J Mann.2019

  • Mouse Phenotype of High and Low 5-HT1AAutorecptors

    Richardson-Jones et al Neuron, 2009J Mann.2019

  • High (gray) and Low 5-HT1A Autoreceptorsand “Depression” Behavioral Phenotype in

    Mice

    Forced Swim Test Tail Suspension Repeat TestJ Mann.2019

  • Depressed Suicides have more 5-HT1A Autoreceptor Binding in

    Rostral DRN

    Boldrini et al. , J Psychiatric Res. 2007J Mann.2019

  • 5-HT1A Receptor Binding Imaged by PET

    Autoreceptors

    J Mann.2019

  • Elevated 5-HT1A Binding in Not-Recently Medicated Depressed MDD

    Parsey et al Biol Psychiatry(2006)

    J Mann.2019

  • Higher 5-HT1A Binding in Unmedicated Depressed Bipolar Disorder

    Sullivan et al Biol Psychiatry 2009J Mann.2019

  • Summary

    • Depressive episodes as part of MDD or Bipolar Disorder are characterized by higher 5-HT1Aautoreceptors binding.

    J Mann.2019

  • 5-HT1A receptor binding is elevated in remitted unmedicated Major Depressive

    Disorder

    Stats: remitted vs. controls, p=0.028. remitted vs. NRM currently depressed, NS. Miller et al NPP 2005

    3 groups including new cohorts

    RNRNRN7.492265735413.54788493289.3344576459

    VPFCVPFCVPFC8.681014124114.967865075411.2671458939

    MPFCMPFCMPFC8.873805317115.585586906511.4195939733

    DLPFCDLPFCDLPFC8.710198223114.06991677110.5576792711

    ACNACNACN10.354690152616.035868268714.3895170624

    CINCINCIN8.566583697515.040415058611.0786647265

    AMYAMYAMY12.471468954317.278820525715.3929794667

    HIPHIPHIP16.686830163823.195580392123.1921038842

    PHGPHGPHG15.298369237821.878820299120.1936701111

    INSINSINS13.261824694922.920658356217.8084711352

    TEMTEMTEM12.101941747419.946775279515.8221701544

    PARPARPAR8.440411711914.171730280510.1046441222

    OCCOCCOCC7.216706825711.03847068268.6962901659

    Controls (n=51)

    Remitted Depressed (n=15)

    NRM Currently Depressed (n=30)

    Region of Interest

    5-HT1A Receptor Binding Potential

    21.7889265519

    25.2464326004

    30.4718713231

    28.8755687121

    29.7639608173

    37.1899551243

    29.7140609778

    34.8570568736

    38.2397841536

    27.6040819752

    32.3624460488

    35.4495696169

    33.984176322

    40.5377181827

    41.4723789282

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    35.0177218558

    36.2823119519

    46.4806337717

    48.8908069598

    52.9639533939

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    63.5181596374

    45.61675593

    60.6387273028

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    46.6270061947

    49.4350536622

    57.9965195566

    39.2489356457

    47.8394399426

    49.9585335897

    25.8777223421

    29.4443546541

    33.4441930562

    21.6021594137

    25.6196982704

    26.7811357719

    CtrlsVsDepVsRem weightcalc

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Chronobiological theories of mood disorder · Background: Major depressive disorder (MDD) remains the most prevalent mental disorder and a leading cause of disability, affecting approximately

Chronobiological theories of mood disorder · Background: Major depressive disorder (MDD) remains the most prevalent mental disorder and a leading cause of disability, affecting approximately

Acupuncture for Major Depressive Disorder - rand.org treatment as usual, waitlists, no treatment, or other active treatments in reducing depressive symptoms in adults with MDD?

Acupuncture for Major Depressive Disorder - rand.org treatment as usual, waitlists, no treatment, or other active treatments in reducing depressive symptoms in adults with MDD?

HIGHLIGHTS OF PRESCRIBING INFORMATION WARNINGS …Major Depressive Disorder (MDD) WELLBUTRIN XL ® (bupropion hydrochloride extended-release tablets) is indicated for the treatment

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Q11: Are antidepressants (Tricyclic antidepressants (TCA

Q11: Are antidepressants (Tricyclic antidepressants (TCA

MAJOR DEPRESSIVE DISORDER – EPIDEMIOLOGY FORECAST TO … · Major depressive disorder (MDD), also known as clinical depression or major depression, is widely recognized as one of

MAJOR DEPRESSIVE DISORDER – EPIDEMIOLOGY FORECAST TO … · Major depressive disorder (MDD), also known as clinical depression or major depression, is widely recognized as one of

Bipolar Depression Update 2016media-ns.mghcpd.org.s3.amazonaws.com... · 3. Maintenance treatment with adjunctive antidepressants may be considered if a patient relapses into a depressive

Bipolar Depression Update 2016media-ns.mghcpd.org.s3.amazonaws.com... · 3. Maintenance treatment with adjunctive antidepressants may be considered if a patient relapses into a depressive

Value of Collaborative Care in Major Depressive Disorder · depressive disorders.3 MDD Overview ... self-management of chronic disease. 11 ... and recovery from depression.2 Collaborative

Value of Collaborative Care in Major Depressive Disorder · depressive disorders.3 MDD Overview ... self-management of chronic disease. 11 ... and recovery from depression.2 Collaborative

UvA-DARE (Digital Academic Repository) Major depressive ... · systems, year prevalence rates of MDD in primary care (PC) vary across the world from 12 to 25%4 and so MDD is among

UvA-DARE (Digital Academic Repository) Major depressive ... · systems, year prevalence rates of MDD in primary care (PC) vary across the world from 12 to 25%4 and so MDD is among

Major depressive disorder (MDD) is a debilitating condition that has been increasingly recognized among youth Prevalence of current or recent depression.

Major depressive disorder (MDD) is a debilitating condition that has been increasingly recognized among youth Prevalence of current or recent depression.

The Economic Burden of Adults With Major Depressive ... · The Economic Burden of Adults With Major Depressive Disorder in the United ... least 2 ICD-9-CM claims for MDD—296.2 (single

The Economic Burden of Adults With Major Depressive ... · The Economic Burden of Adults With Major Depressive Disorder in the United ... least 2 ICD-9-CM claims for MDD—296.2 (single

RADAR-base: Major Depressive Disorder and Epilepsy Case Studies · 2018-10-25 · the case for Fitbits worn in the MDD study. The two studies, MDD and epilepsy, generate data with

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Seung Hyo (Daniella) Ki Major Depressive Disorder (MDD)

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Mitochondrial DNA Copy Number Raises the Potential of Left ... · depressive disorder (MDD) rely on clinical assessment of symptoms. However, the depressive mood states of BD and

Mitochondrial DNA Copy Number Raises the Potential of Left ... · depressive disorder (MDD) rely on clinical assessment of symptoms. However, the depressive mood states of BD and

kclpure.kcl.ac.uk · Web viewEvidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2008 British Association for Psychopharmacology guidelines.

kclpure.kcl.ac.uk · Web viewEvidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2008 British Association for Psychopharmacology guidelines.

Identification and Treatment of Major Depressive Disorder ... A… · Identification and Treatment of Major Depressive Disorder (MDD) for Adults . Guidelines are intended to be flexible.

Identification and Treatment of Major Depressive Disorder ... A… · Identification and Treatment of Major Depressive Disorder (MDD) for Adults . Guidelines are intended to be flexible.

University of Groningen The two sides of the coin of ... · Major depressive disorder, neuroinflammation, microglia, pro-inflammatory cytokines, antidepressants Introduction Major

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Association of BDNF Val66Met Polymorphism and Brain BDNF ...€¦ · Brain-derived neurotrophic factor (BDNF) is implicated in the pathophysiology of major depressive disorder (MDD)

Association of BDNF Val66Met Polymorphism and Brain BDNF ...€¦ · Brain-derived neurotrophic factor (BDNF) is implicated in the pathophysiology of major depressive disorder (MDD)

Postmortem Studies in Mood Disorders Indicate Altered ......in the neuropathology of major depressive disorder (MDD) and bipolar disorder (BPD, manic–depressive). In both MDD and

Postmortem Studies in Mood Disorders Indicate Altered ......in the neuropathology of major depressive disorder (MDD) and bipolar disorder (BPD, manic–depressive). In both MDD and

Duloxetine Hydrochloridesearch.cosmobio.co.jp/cosmo_search_p/search_gate2/docs/...Duloxetine is indicated in major depressive disorder (MDD), generalised anxiety disorder (GAD), pain

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Double-blind, randomized pilot clinical trial targeting ... · (tACS) for the treatment of major depressive disorder (MDD) Morgan L. Alexander1,2, Sankaraleengam Alagapan 1,2, Courtney

Double-blind, randomized pilot clinical trial targeting ... · (tACS) for the treatment of major depressive disorder (MDD) Morgan L. Alexander1,2, Sankaraleengam Alagapan 1,2, Courtney