This document discusses depression, including its DSM-V criteria, possible causes, treatments, and impact. It notes that major depression involves 5 out of 9 symptoms for at least 2 weeks. Possible causes discussed include monoamine, glutamate, and systemic hypotheses as well as trauma. Treatments mentioned range from SSRIs and SNRIs to ECT. The World Health Organization study found depression to be a leading cause of disability worldwide in 2004 and projected to remain so in 2030. The case of Ricardo, a veteran with traumatic brain injury, is also summarized.

1. DEPRESSION
and its possible causes
a S’eclairer teaching topic
June 2013
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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
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3. PERSONAL EXPERIENCE
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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
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5. Sherwin Nuland presentation
 Prominent surgeon at Yale-New
Haven hospital
 Major breakdown at age 42
 Presentation on the west coast in
2001
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6. NULAND PRESENTATION
http://embed.ted.com/talks/sherwin_nul
and_on_electroshock_therapy.html
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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)
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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
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9. What causes depression?
 Monoamine hypothesis
 Glutamate hypothesis
 Systemic hypothesis
 Trauma
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10. Monoamine hypothesis-
not enough:
 Serotonin
 Norepinephrine
 Dopamine
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11. 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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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
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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
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14. GLUTAMATE RECEPTORS
 IONOTROPIC: (ion channels)
-NMDA (N-methyl-D-aspartate)
-AMPA
-Kainate
 METABOTROPIC:
(G-protein-coupled)
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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
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16. SYSTEMIC HYPOTHESIS
Bodily disorders destabilize the brain
 Systemic inflammation
 Vitamin/mineral deficiencies
 Heavy metals toxicity
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17. SYSTEMIC INFLAMMATION
 Infections
 Stress
 Excess sugar
 Toxins
 Autoimmune disease
 Insulin resistance
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18. VITAMIN/MINERAL
deficiencies, e.g.
 Folate
 B6
 B12
 Vitamin D
 Zinc
 Magnesium
 Selenium
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19. HEAVY METAL TOXICITY
 Mercury
-amalgam fillings
-fish
 Lead
-paint
-smoke
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20. TRAUMA
 Combat
 Non-combat
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21. RICARDO
A 12-B combat engineer who suffered
Traumatic Brain Injury in 2012 in
Afghanistan

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. 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. DIAGNOSES
 Current:
 Adjustment disorder with
anxiety and depression
 Memory loss; post combat stress
symptoms
………………………………………………..
 Per prior post:
 PTSD not warranted
 Depression not warranted

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
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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.
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