Arch Gen
Psychiatry. 2010 Dec;67(12):1211-24.
Inflammation, sanitation, and consternation: loss of contact with coevolved, tolerogenic microorganisms and the pathophysiology and treatment of major depression.
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA. craison@emory.edu
CONTEXT: Inflammation is increasingly recognized as contributing to the pathogenesis of major
depressive disorder (MDD), even in individuals who are
otherwise medically healthy. Most studies in search of sources for this
increased inflammation have focused on factors such as
psychosocial stress and obesity that are known to activate
inflammatory processes and increase the risk for depression. However,
MDD may be so prevalent in the modern world not just because
proinflammatory factors are widespread, but also because we have lost contact with previously available sources of anti-inflammatory, immunoregulatory signaling.
OBJECTIVE: To
examine evidence that disruptions in coevolved relationships with a
variety of
tolerogenic microorganisms that were previously ubiquitous in
soil, food, and the gut, but that are largely missing from
industrialized societies, may contribute to increasing rates of MDD in
the modern world.
DATA SOURCES: Relevant studies were identified using PubMed and Ovid MEDLINE.
STUDY SELECTION: Included were laboratory animal and human studies relevant to immune functioning, the
hygiene hypothesis, and major depressive disorder identified via PubMed and Ovid MEDLINE searches.
DATA EXTRACTION: Studies were reviewed by all authors, and data considered to be potentially relevant to
the contribution of hygiene-related immune variables to major depressive disorder were extracted.
DATA SYNTHESIS: Significant data suggest that a variety of microorganisms (frequently referred to as the
"old friends") were tasked by coevolutionary processes withtraining the human immune system to tolerate a wide array of non-threatening but potentially proinflammatory
stimuli. Lacking such immune training, vulnerable
individuals in the modern world are at significantly increased risk of
mounting inappropriate inflammatory attacks on harmless
environmental antigens (leading to asthma), benign food contents
and commensals in the gut (leading to inflammatory bowel disease), or
self-antigens (leading to any of a host of autoimmune
diseases).
Loss of exposure to the old
friends may promote MDD by increasing background levels of
depressogenic cytokines and may predispose vulnerable individuals
in industrialized societies to mount inappropriately aggressive
inflammatory responses to psychosocial stressors, again leading to
increased rates of depression.
CONCLUSION: Measured exposure to the old friends or their antigens may offer promise for the prevention
and treatment of MDD in modern industrialized societies.
1/ the refrigerator as too much of a good thing is dangerous
2/ the sterilised industrialised food products
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