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DEPRESSION and its possible causes

a S’eclairer teaching topic

June 2013

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DEPRESSION and its possible causes

◦A Personal experience◦DSM V criteria◦Sherwin Nuland video◦World Health Organization Study◦What Causes Depression?

-Monoamine hypothesis-Glutamate hypothesis-Systemic hypothesis

-Trauma

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PERSONAL EXPERIENCE

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DSM V DEFINITIONSMajor Depression (MDD) Five or more of

the following for 2 weeks or more: -depressed mood -anhedonia (loss of interest or pleasure) -weight gain/loss -insomnia/hypersomnia -loss of energy -feelings of worthlessness/guilt -loss of concentration/decisiveness -thoughts of death/suicide -psychomotor agitation

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Sherwin Nuland presentation

Prominent surgeon at Yale-New Haven hospital

Major breakdown at age 42Presentation on the west

coast in 2001

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NULAND PRESENTATION

http://embed.ted.com/talks/sherwin_nuland_on_electroshock_therapy.html

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WHAT IS THE IMPACT OFDEPRESSION?

WORLD HEALTH ORGANIZATIONGlobal Burden of Disease

Leading Causes of Disability2004 Survey

Unit of measurement= DALY (Disability

Associated Life Year)

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2004 2030Lower respiratory

infections Diarrheal diseases Unipolar depression

Unipolar depression Ischemic heart

diseaseTraffic accidents

WORLD HEALTH ORGANIZATIONGlobal Burden of Disease

Leading Causes of Disability

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What causes depression?

Monoamine hypothesis

Glutamate hypothesis

Systemic hypothesis

Trauma

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Monoamine hypothesis- not enough:

SerotoninNorepinephrineDopamine

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Glutamatergic hypothesis:

Too much glutamate at the NMDA receptor

Resulting in too much excitation in the prefrontal cortex of the brain

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LIKELY SEQUENCE OF TREATMENTS:

SSRIs (Prozac, Zoloft)SNRIs (Cymbalta)Atypical antidepressants

(bupropion/Wellbutrin)Antiepileptics for mood control

(valproic acid, carbamazepine)“cocktail” of foregoingPsychotherapy concurrently ECTKetamine

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ECT TREATMENT 1973 CASE: “tangle of twisted wires in my head” NIH: ECT seizures cause discharge of

neurotransmitters HISTORY: Discovered in 1938 in Rome Precise mechanism unknown Efficacy studies vary widely CURRENT PRACTICE: Sedation plus muscle relaxant Pulsed was continuous 6 to 10 treatments over 2 to 3 weeks Bitemporal, unilateral, bifrontal Reported memory loss

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GLUTAMATE RECEPTORSIONOTROPIC: (ion channels) -NMDA (N-methyl-D-aspartate) -AMPA -KainateMETABOTROPIC: (G-protein-coupled)

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GLUTAMATERGIC SYSTEMSource: Machado-Vieira R & Zarate CA Proof of Concept Trials in Bipolar Disorder and Major Depressive Disorder: A Translational Perspective in the Search for Improved TreatmentsPublished online 24 February 2011 in Wiley Online Library

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SYSTEMIC HYPOTHESISBodily disorders destabilize the brain

Systemic inflammation

Vitamin/mineral deficiencies

Heavy metals toxicity

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SYSTEMIC INFLAMMATION

InfectionsStressExcess sugarToxinsAutoimmune diseaseInsulin resistance

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VITAMIN/MINERALdeficiencies, e.g.

FolateB6B12Vitamin DZincMagnesiumSelenium

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HEAVY METAL TOXICITY

Mercury -amalgam fillings -fishLead -paint -smoke

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TRAUMA

CombatNon-combat

RICARDOA 12-B combat engineer who suffered Traumatic Brain Injury in 2012 in Afghanistan

RICARDO U.S. citizen born in South America H.S. grad, enlisted at 26 now 28 Wife and sons 6 and 7 No prior medical history Afghanistan 2011-2012: 12B infantry Combat engineer “search for explosives if

found detonate them” Learned Pashto, conversed with villagers Multiple IED exposures and unit casualties Feb 2012: gunner on RG 31, near rollover- Concussion 850.9, loss of consciousness Currently in treatment for TBI in U.S.

CURRENT SYMPTOMS photo sensitivity nausea headaches 2 x / day poor sleep 4-5 hours left ear tinnitus

…………………………………………….. dizziness vertigo, anxiety photophobia (wears sunglasses) malaise/fatigue Irritability emotional lability apathy memory loss that began 3 months post concussion

DIAGNOSESCurrent:Adjustment disorder with anxiety

and depressionMemory loss; post combat stress

symptoms ………………………………………………..Per prior post:PTSD not warrantedDepression not warranted

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REFERENCES 2001 TED presentation- Sherwin Nuland on ECT World Health Organization- Global Burden of Disease- 2004 Murrough JW and Charney DS Cracking the Moody Brain:

Lifting the mood with ketamine Nature Medicine 16.1384-1385 (2010)

Messer MM and Haller IV Maintenance Ketamine Treatment Produces Long-Term Recovery from Depression Primary Psychiatry 2010;17(4): 48-50

Murrough JW et al Safety and efficacy of repeated-dose intravenous ketamine for treatment-resistant depression http://www.ncbi.nlm.nih.gov/pubmed/19897179

Zarate CA et al A Randomized Add-on Trial of an N-methyl-D aspartate Antagonist in Treatment-Resistant Bipolar Depression Arch Gen Psychiatry 2010;67 (8):793-802

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REFERENCES cont’dStahl, Stephan. Essential

Psychopharmacology: The Prescriber’s Guide. Cambridge University Press, New York, NY 2008.

Herman, Judith. Trauma and Recovery. Basic Books, NYC, NY 1997.

Doidge, Norman. The Brain That Changes Itself. Penguin Books, London, England 2007.

Hyman, Mark. The Ultra Mind Solution. Scribner, New York, NY 2009.

Restak, Richard. Optimizing Brain Fitness. The Great Courses, Chantilly, VA. 2011.