Elevated incidence of suicide in people living at altitude, smokers and patients with chronic obstructive pulmonary disease and asthma: possible role of hypoxia causing decreased serotonin synthesis

Young, Simon N.

doi:10.1503/jpn.130002

Cited by 67 publications

(58 citation statements)

References 34 publications

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“…Low brain serotonin is also linked to suicidal ideation and attempts ( Joiner et al, 2005). Hypoxia-induced low brain serotonin has also been suggested to contribute to the high suicide rates seen at altitude and in other hypoxic conditions such as COPD, asthma, or cardiac disease, or smokers (Young, 2013).…”

Section: Discussionmentioning

confidence: 99%

Hypobaric Hypoxia Induces Depression-like Behavior in Female Sprague-Dawley Rats, but not in Males

Kanekar

Bogdanova

Olson

et al. 2015

High Altitude Medicine & Biology

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Kanekar, Shami, Olena V. Bogdanova, Paul R. Olson, Young-Hoon Sung, Kristen E. D'Anci, and Perry F. Renshaw. Hypobaric hypoxia induces depression-like behavior in female Sprague-Dawley rats, but not males. High Alt Med Biol 16:52-60, 2015-Rates of depression and suicide are higher in people living at altitude, and in those with chronic hypoxic disorders like asthma, chronic obstructive pulmonary disorder (COPD), and smoking. Living at altitude exposes people to hypobaric hypoxia, which can lower rat brain serotonin levels, and impair brain bioenergetics in both humans and rats. We therefore examined the effect of hypobaric hypoxia on depression-like behavior in rats. After a week of housing at simulated altitudes of 20,000 ft, 10,000 ft, or sea level, or at local conditions of 4500 ft (Salt Lake City, UT), Sprague Dawley rats were tested for depression-like behavior in the forced swim test (FST). Time spent swimming, climbing, or immobile, and latency to immobility were measured. Female rats housed at altitude display more depression-like behavior in the FST, with significantly more immobility, less swimming, and lower latency to immobility than those at sea level. In contrast, males in all four altitude groups were similar in their FST behavior. Locomotor behavior in the open field test did not change with altitude, thus validating immobility in the FST as depression-like behavior. Hypobaric hypoxia exposure therefore induces depression-like behavior in female rats, but not in males.

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Section: Discussionmentioning

confidence: 99%

Hypobaric Hypoxia Induces Depression-like Behavior in Female Sprague-Dawley Rats, but not in Males

Kanekar

Bogdanova

Olson

et al. 2015

High Altitude Medicine & Biology

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“…It has been found that mean serotonin synthesis is 50% higher when the respiratory oxygen concentration reached 60%, compared to 15% oxygen concentration [21]. Young [22] explored the relationship between hypoxia and the risk of suicide. He found that the suicide rate at high altitudes was higher than that at low altitudes, and that other conditions related to hypoxia increased the suicide risk.…”

Section: Hypoxia and Depressionmentioning

confidence: 99%

Histogenous Hypoxia in Depression: A Cross-Sectional Paired Study into Venous Blood Gases in Outpatients with Depression

Hao-ying¹,

Yuan²,

Xu³

et al. 2017

Neuropsychiatry

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Background:It has been suggested that oxidative stress is increased and antioxidant defenses are decreased in depression, and oxidative stress has a complex relationship with hypoxia. Is there a definite hypoxia index in patients with depression? Also, any other correlations between hypoxia indicators and the symptoms of depression remain unreported. Methods:In the present study, a cross-sectional design was undertaken with 1:1 pairs. Patients with depression and healthy participants were recruited from the Guangdong Province Hospital of Traditional Chinese Medicine. Both groups were assessed using the Hamilton Depression Scale (including five factors: anxiety/somatization, weight, cognition impairment, hysteresis and sleep) and had their venous blood gases analyzed. All data were analyzed using the PASW Statistics 18.0 data statistical package. Results were analyzed statistically using the paired t test, Pearson correlation analysis and multiple linear regression analysis. Results:In total 52 cases were recruited to each study group, including 15 (28.8%) males and 37 (71.2%) females. The values of the mean venous pH, PvO 2 , SvO 2 and CvO 2 in the depressed group of patients were higher than those of the control group. PvCO 2 was also lower in the depressed than in the control group, and this difference was statistically significant. The total depressive score and cognitive impairment factor were related to PvO 2 , while the anxiety/somatization and sleep factors were related to the value of the venous pH. Age was positively correlated with venous pH in both study groups. Venous pH had a positive association with P V O 2 in the depressed group (multiple linear regression analysis), but there was no significant correlation between these two factors in the non-depressed control group. Conclusion:Histogenous hypoxia is present in patients with depression and this is related to elevated venous pH; both of these are related to depression. Elevated venous pH and decreased PvCO 2 may explain histogenous hypoxia in depression and venous blood gas concentrations potentially represent a biomarker for depression.

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“…Human and animal studies suggest that adiposity-induced leptin increase and subsequent leptin resistance would affect these transmitters, causing or worsening asthma symptoms. This relates both to orexigenic neuropeptides such as neuropeptide Y (114)(115)(116)(117)(118)(119)(120) , endocannabinoids (121,122) , endogenous opioids (123)(124)(125)(126) ; and anorexigenic neuropeptides such as tachykinins and its most studied members substance P (127)(128)(129)(130)(131)(132) , α-melanocyte-stimulating hormone (133)(134)(135) , corticotropin-releasing factor (136)(137)(138)(139)(140)(141) and serotonin (142)(143)(144)(145)(146)(147)(148)(149)(150) . Altogether, it suggests that these peptides can modulate asthmatic inflammation among obese patients.…”

Section: Possible Linksmentioning

confidence: 99%

Association between obesity and asthma – epidemiology, pathophysiology and clinical profile

2016

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Obesity is a risk factor for asthma, and obese asthmatics have lower disease control and increased symptom severity. Several putative links have been proposed, including genetics, mechanical restriction of the chest and the intake of corticosteroids. The most consistent evidence, however, comes from studies of cytokines produced by the adipose tissue called adipokines. Adipokine imbalance is associated with both proinflammatory status and asthma. Although reverse causation has been proposed, it is now acknowledged that obesity precedes asthma symptoms. Nevertheless, prenatal origins of both conditions complicate the search for causality. There is a confirmed role of neuro-immune cross-talk mediating obesityinduced asthma, with leptin playing a key role in these processes. Obesity-induced asthma is now considered a distinct asthma phenotype. In fact, it is one of the most important determinants of asthma phenotypes. Two main subphenotypes have been distinguished. The first phenotype, which affects adult women, is characterised by later onset and is more likely to be non-atopic. The childhood obesity-induced asthma phenotype is characterised by primary and predominantly atopic asthma. In obesity-induced asthma, the immune responses are shifted towards T helper (Th) 1 polarisation rather than the typical atopic Th2 immunological profile. Moreover, obese asthmatics might respond differently to environmental triggers. The high cost of treatment of obesity-related asthma, and the burden it causes for the patients and their families call for urgent intervention. Phenotype-specific approaches seem to be crucial for the success of prevention and treatment.

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Elevated incidence of suicide in people living at altitude, smokers and patients with chronic obstructive pulmonary disease and asthma: possible role of hypoxia causing decreased serotonin synthesis

Cited by 67 publications

References 34 publications

Hypobaric Hypoxia Induces Depression-like Behavior in Female Sprague-Dawley Rats, but not in Males

Hypobaric Hypoxia Induces Depression-like Behavior in Female Sprague-Dawley Rats, but not in Males

Histogenous Hypoxia in Depression: A Cross-Sectional Paired Study into Venous Blood Gases in Outpatients with Depression

Association between obesity and asthma – epidemiology, pathophysiology and clinical profile

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