DEPRESSION
and its possible causes
a S’eclairer teaching topic
June 2013
7/22/2013 1
DEPRESSION and its
possible causes
◦ A Personal experience
◦ DSM V criteria
◦ Sherwin Nuland video
◦ World Health Organiza...
PERSONAL EXPERIENCE
7/22/2013 3
DSM V DEFINITIONS
 Major Depression (MDD) Five or more of
the following for 2 weeks or more:
-depressed mood
-anhedonia (...
Sherwin Nuland presentation
 Prominent surgeon at Yale-New
Haven hospital
 Major breakdown at age 42
 Presentation on t...
NULAND PRESENTATION
http://embed.ted.com/talks/sherwin_nul
and_on_electroshock_therapy.html
7/22/2013 6
WHAT IS THE IMPACT OF
DEPRESSION?
WORLD HEALTH ORGANIZATION
Global Burden of Disease
Leading Causes of Disability
2004 Sur...
2004 2030
 Lower respiratory
infections
 Diarrheal diseases
 Unipolar depression
 Unipolar depression
 Ischemic heart...
What causes depression?
 Monoamine hypothesis
 Glutamate hypothesis
 Systemic hypothesis
 Trauma
7/22/2013 9
Monoamine hypothesis-
not enough:
 Serotonin
 Norepinephrine
 Dopamine
7/22/2013 10
Glutamatergic hypothesis:
 Too much glutamate at the NMDA
receptor
 Resulting in too much excitation in
the prefrontal c...
LIKELY SEQUENCE OF
TREATMENTS:
 SSRIs (Prozac, Zoloft)
 SNRIs (Cymbalta)
 Atypical antidepressants
(bupropion/Wellbutri...
ECT TREATMENT
1973 CASE:
 “tangle of twisted wires in my head”
 NIH: ECT seizures cause discharge of
neurotransmitters
H...
GLUTAMATE RECEPTORS
 IONOTROPIC: (ion channels)
-NMDA (N-methyl-D-aspartate)
-AMPA
-Kainate
 METABOTROPIC:
(G-protein-co...
GLUTAMATERGIC SYSTEMSource: Machado-Vieira R & Zarate CA
Proof of Concept Trials in Bipolar Disorder and Major Depressive ...
SYSTEMIC HYPOTHESIS
Bodily disorders destabilize the brain
 Systemic inflammation
 Vitamin/mineral deficiencies
 Heavy ...
SYSTEMIC INFLAMMATION
 Infections
 Stress
 Excess sugar
 Toxins
 Autoimmune disease
 Insulin resistance
7/22/2013 17
VITAMIN/MINERAL
deficiencies, e.g.
 Folate
 B6
 B12
 Vitamin D
 Zinc
 Magnesium
 Selenium
7/22/2013 18
HEAVY METAL TOXICITY
 Mercury
-amalgam fillings
-fish
 Lead
-paint
-smoke
7/22/2013 19
TRAUMA
 Combat
 Non-combat
7/22/2013 20
RICARDO
A 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...
CURRENT SYMPTOMS
 photo sensitivity
 nausea
 headaches 2 x / day
 poor sleep 4-5 hours
 left ear tinnitus
……………………………...
DIAGNOSES
 Current:
 Adjustment disorder with
anxiety and depression
 Memory loss; post combat stress
symptoms
……………………...
REFERENCES
 2001 TED presentation- Sherwin Nuland on ECT
 World Health Organization- Global Burden of Disease-
2004
 Mu...
REFERENCES cont’d
 Stahl, Stephan. Essential
Psychopharmacology: The Prescriber’s
Guide. Cambridge University Press, New
...
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Depression

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As part of an early Educational Grand Round, Peter Brengel, MPAS, PA-C, MBA gives his talk about Depression.

Want an audio version? Subscribe to our Podcast on iTunes!

Want to join us for the live discussion? Check out our Social Media in the noon hour every Monday as we sit down on Google Hangout OnAir! Follow us on Twitter, Facebook, or Google+ to get updated with the link when we start!

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Depression

  1. 1. DEPRESSION and its possible causes a S’eclairer teaching topic June 2013 7/22/2013 1
  2. 2. 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 7/22/2013 2
  3. 3. PERSONAL EXPERIENCE 7/22/2013 3
  4. 4. DSM V DEFINITIONS  Major 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 7/22/2013 4
  5. 5. Sherwin Nuland presentation  Prominent surgeon at Yale-New Haven hospital  Major breakdown at age 42  Presentation on the west coast in 2001 7/22/2013 5
  6. 6. NULAND PRESENTATION http://embed.ted.com/talks/sherwin_nul and_on_electroshock_therapy.html 7/22/2013 6
  7. 7. WHAT IS THE IMPACT OF DEPRESSION? WORLD HEALTH ORGANIZATION Global Burden of Disease Leading Causes of Disability 2004 Survey Unit of measurement= DALY (Disability Associated Life Year) 7/22/2013 7
  8. 8. 2004 2030  Lower respiratory infections  Diarrheal diseases  Unipolar depression  Unipolar depression  Ischemic heart disease  Traffic accidents WORLD HEALTH ORGANIZATION Global Burden of Disease Leading Causes of Disability 7/22/2013 8
  9. 9. What causes depression?  Monoamine hypothesis  Glutamate hypothesis  Systemic hypothesis  Trauma 7/22/2013 9
  10. 10. Monoamine hypothesis- not enough:  Serotonin  Norepinephrine  Dopamine 7/22/2013 10
  11. 11. Glutamatergic hypothesis:  Too much glutamate at the NMDA receptor  Resulting in too much excitation in the prefrontal cortex of the brain 7/22/2013 11
  12. 12. LIKELY SEQUENCE OF TREATMENTS:  SSRIs (Prozac, Zoloft)  SNRIs (Cymbalta)  Atypical antidepressants (bupropion/Wellbutrin)  Antiepileptics for mood control (valproic acid, carbamazepine)  “cocktail” of foregoing  Psychotherapy concurrently  ECT  Ketamine 7/22/2013 12
  13. 13. 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 7/22/2013 13
  14. 14. GLUTAMATE RECEPTORS  IONOTROPIC: (ion channels) -NMDA (N-methyl-D-aspartate) -AMPA -Kainate  METABOTROPIC: (G-protein-coupled) 7/22/2013 14
  15. 15. 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 Treatments Published online 24 February 2011 in Wiley Online Library 7/22/2013 15
  16. 16. SYSTEMIC HYPOTHESIS Bodily disorders destabilize the brain  Systemic inflammation  Vitamin/mineral deficiencies  Heavy metals toxicity 7/22/2013 16
  17. 17. SYSTEMIC INFLAMMATION  Infections  Stress  Excess sugar  Toxins  Autoimmune disease  Insulin resistance 7/22/2013 17
  18. 18. VITAMIN/MINERAL deficiencies, e.g.  Folate  B6  B12  Vitamin D  Zinc  Magnesium  Selenium 7/22/2013 18
  19. 19. HEAVY METAL TOXICITY  Mercury -amalgam fillings -fish  Lead -paint -smoke 7/22/2013 19
  20. 20. TRAUMA  Combat  Non-combat 7/22/2013 20
  21. 21. RICARDO A 12-B combat engineer who suffered Traumatic Brain Injury in 2012 in Afghanistan
  22. 22. 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.
  23. 23. 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
  24. 24. DIAGNOSES  Current:  Adjustment disorder with anxiety and depression  Memory loss; post combat stress symptoms ………………………………………………..  Per prior post:  PTSD not warranted  Depression not warranted
  25. 25. 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 7/22/2013 25
  26. 26. REFERENCES cont’d  Stahl, 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. 7/22/2013 26

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