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Suicide and Altitude….Relevance for Life in the Mountains. Perry F. Renshaw M.D., Ph.D. VISN19 Rocky Mountain MIRECC Investigator. With more than a little help from my friends…. Namkug Kim Ph.D. Kristen Delmastro B.S. Tracy Hellem R.N. Doug Kondo M.D. YH Sung M.D.

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suicide and altitude relevance for life in the mountains

Suicide and Altitude….Relevance for Life in the Mountains

Perry F. Renshaw M.D., Ph.D.

VISN19 Rocky Mountain MIRECC Investigator

with more than a little help from my friends

With more than a little help from my friends…..

Namkug Kim Ph.D.

Kristen Delmastro B.S.

Tracy Hellem R.N.

Doug Kondo M.D.

YH Sung M.D.

Deborah Yurgelun-Todd Ph.D.

slide4

Established Theory #1

Source: Pat Bagley. The Salt Lake Tribune. Sunday, July 14, 2010.

slide5

Established Theory #2

Source: Dyer Realty, Inc.

slide6

Off the Deep End

Source: www.images.com

age adjusted suicide rate and mean elevation of each us county
Age Adjusted Suicide Rate and Mean Elevation of Each US County

r=0.51

Source: Kim et al. (2010) American Journal of Psychiatry. In press.

slide8

Table 1 Correlations between elevation and age adjusted suicide rates

Per-County Per-State***

r-value p-value r-value p-value

Age Adjusted Suicide Rate 0.51* 1.45E-175* 0.79 3.81E-11

Age Adjusted Firearm Suicide Rate 0.41** 3.33E-99** 0.64 1.08E-6

Age Adjusted non-Firearm Suicide Rate 0.32** 1.24E-58** 0.53 1.15E-4

* 2618 Counties (excluding Alaska, Hawaii)

**2368 Counties (excluding Alaska, Hawaii)

***48 states + DC (excluding Alaska, Hawaii)

Source: Kim et al. (2010) American Journal of Psychiatry. In press.

slide9

Correlation Between Suicide Risk Factor and Age-Adjusted Suicide Rate

Risk Factor/Suicide Rate Correlation

Source: Kim et al. (2010) American Journal of Psychiatry. In press.

slide10

Circumstances Associated With Suicide Deaths

% of suicide deaths

Source: Psychiatry News. June 4, 2010; 45 (11): 1.

having at least one major depressive episode in past year vs altitude
Having at Least One Major DepressiveEpisode in Past Year vs. Altitude

Correlation r-value 0.1865(p-value; 0.0004)

Source: DelMastro et al. (2010) Submitted.

slide13

Top 5 Classes of Drugs by # of Prescriptions in Utah *

# of prescriptions in UT by class of drug

* This data is for patients with commercial insurance only.

Source: May, H. (2010, June 24). Depression and diabetes drive up health care costs. The Salt Lake Tribune, pp. A1, A8.

cocaine altitude and suicide
Cocaine, Altitude, and Suicide
  • Longstanding history of coca leaf use by high mountain dwellers. Coca leaf use proportional to altitude in Peru.
  • Coca said to reduce symptoms of altitude sickness (nausea, dizziness, headache, fatigue).
  • Cocaine use highly associated with suicide, more than alcohol or other drugs of abuse.
slide16

Cocaine Use in Past Year vs. Altitude of Substate Region of Residence

t = 6.5725, df = 323, p = 1.985e-10

R = 0.343574

Analysis by Namkug Kim, Ph.D.

References: 1) Substance Abuse and Mental Health Services Administration, Office of Applied Statistics, 2008b. Substate substance abuse estimates from the 1991-2001 National Surveys on Drug Use and Health. Rockville, MD. http://oas.samhsa.gov/substate2k5/SecD.htm. 2) National Geospatial-Intelligence Agency and National Aeronautics and Space Administration, 2000. Shutte Radar Topography Mission (STRM) Dataset. United States Geological Survey, Souix Falls, SD.

creatine kinase reaction

Creatine Kinase Reaction

PCr2- + ADP3- + H+ Cr + ATP4-

Spatial and temporal buffer of ATP concentration

(i.e. energy supply) in muscle & brain

slide19

Ratios of PCr/γ-ATP in left ventricle wall in Sherpas in acclimated and deacclimating states compared to lowlanders

*Acclimated Sherpas: as soon as possible after arrival from altitude

**Deacclimating Sherpas: after 27 days at low altitude

***Lowlanders: subjects acclimatized to altitude of about 300m

(Table generated with data from Hochachka et al., PNAS, 1996)

slide20

Baseline PCr Levels in:

MDD Treatment RespondersMDD Non-RespondersControls

“Baseline PCr” as a Predictorof Treatment Response

- Sensitivity = 83%- Specificity = 75%Area under the ROC curve = 0.88

(Iosifescu et al., Biological Psychiatry2008;63:12)

slide21

Δ PCr

Δ β-NTP

Lyoo et al. Psychiatry Research: Neuroimaging 123 (2003) 87-100.

typical in vivo spectra
Typical in-vivo spectra

(a) In-vivo brain 31PMR spectra vs. MT saturation time tsat, while saturating γ-ATP to measure the apparent relation rate R1’, and (b) spectra for thermal equilibrium magnetizations with and without RF bleedover effect. The signal intensity of PCr line is plotted with respect to the saturation time to measure the apparent relaxation rate R1’.

slide24

Adults with MDD treated with escitalopram + creatine or placebo

Renshaw and Lyoo. Unpublished data.

slide25

Changes in CDRS Scores with Creatine

* Treatment begins at Week 0

** Treatment ends at Week 8

slc va open label creatine trial ind and irb submitted
SLC VA Open Label Creatine Trial (IND and IRB submitted)

Creatine Begin

Creatine End

MDD subjects

Weeks 1, 2, 4, 6

Week 10

Screen

Week 0

Week 8

  • Male, 18-55yrs
  • Comorbidities OK (no substance abuse)
  • MADRS ≥18
  • Minimal response to adequate trial of antidepressant med
  • SCID, CSSRS, MADRS, CGI
  • Labs, vitals
  • CSSRS, MADRS, CGI
  • MRI/MRS
  • Vitals
  • CSSRS, MADRS, CGI
  • AE’s, Vitals
  • CSSRS, MADRS, CGI
  • MRI/MRS
  • Labs, vitals
  • CSSRS, MADRS, CGI
  • AE’s, Vitals
other ways forward

Other ways forward….

Changes in brain pH

Changes in sunlight intensity

slide28

Brain pH before, at end, and after 1 wk at simulated altitude of 4,267m

(Goldberg et al., 1992)

slide29

Pyrimidines in Humans

Cytidine

Cytidine

Uridine

UTP

CTP

Cytidine

slide31

MRS and Energy:The Effects of TAU in Raising Brain pH in subjects with Bipolar Disorder

Line plot of Brain pH pre and post TAU treatment in

Bipolar subjects who responded to TAU treatment

slide32

CDRS-R Scores During 6 weeks of Treatment with Uridine

*Treatment begins Week 0

**Treatment ends Week 6

slide33

Locations of latitude/suicide studies

Several study findings suggest there is an increase in suicide rates in April – June in the northern hemisphere and November – December in the southern hemisphere (red dots). One study suggested seasonality did not influence a change in suicide rates (green dot).

slide34

Increased Intensity of Sunlight with Altitude

The proportion of atmosphere that the light must pass through before striking the Earth relative to its overhead path length, and is equal to Y/X. Therefore, an increase in altitude results in an increase in sunlight intensity.

http://pvcdrom.pveducation.org/SUNLIGHT/AIRMASS.HTM