From: rpattree2@gmail.com   
      
        
   Psychoneuroimmunology—How Inflammation Affects Your Mental Health    
   April 17, 2014 | 222,069 views    
      
      
      
      
      
   Visit the Mercola Video Library    
      
   Depression    
   Story at-a-glance +    
   By Dr. Kelly Brogan    
      
   Psychoneuroimmunology. This is what I aim to practice. Medical terms of this   
   length command our respect for the interconnectedness of different   
   subspecialties, for the futile segmentation and compartmentalization of the   
   body into different organ systems.    
      
   As discussed in this previous article I wrote for Dr. Mercola, deconstructing   
   the serotonin model of depression, psychiatry is in a crisis. It can no longer   
   stand on its own, throwing more and more medications at its perceived target.    
      
   It seems, therefore, fitting that psychiatry would follow the investigative   
   path of other lifestyle-triggered chronic diseases such as cancer,   
   autoimmunity, and heart disease. There already exists a bidirectional   
   relationship between all of the major    
   chronic diseases and psychiatric diagnoses (patients who struggle with chronic   
   diseases are more likely to be depressed and vice versa).    
      
   The role of inflammation, across these disease states, is better elucidated   
   each day. Let's deconstruct what is known as it applies to mental health.    
      
   Inflammation and Depression    
      
   In this model, depression is a non-specific fever that tells us little about   
   what is actually causing the body to react and protect itself in this way. The   
   body is "hot" and we need to understand why. Depressive symptoms are the   
   manifestation of many    
   downstream effects on hormones and neurotransmitters, but if we swim up to the   
   source, we will find a river of inflammatory markers coursing by.    
      
   The source itself may be singularly or multiply-focused as stress, dietary,   
   and toxic exposures, and infection, as we will discuss here. As explored in   
   the medical literature,1 inflammation appears to be a highly relevant   
   determinant of depressive    
   symptoms such as flat mood, slowed thinking, avoidance, alterations in   
   perception, and metabolic changes. We understand this relationship based on:    
      
   Biomarkers      
      
   Psychiatrists have longed to be legitimized in their role as science-based   
   physicians. Despite this, there are no diagnostic tests that are validated for   
   the assessment of psychiatric pathology. In the practice of functional   
   medicine, however, the    
   diagnosis becomes secondary to the individual's personalized interplay of   
   factors and the "biomarkers" that can light the way toward healing.    
      
   Cytokines in the blood, or inflammatory messengers, such as CRP, IL-1, IL-6,   
   and TNF-alpha have taken the stage as predictive2 and linearly3 correlative   
   with depression.    
      
   Researchers have validated4 that, in melancholic depression, bipolar disorder,   
   and postpartum depression, white blood cells called monocytes express   
   pro-inflammatory genes leading to secretion of cytokines, while simultaneously   
   leading to decreased    
   cortisol sensitivity, the body's stress hormone and inflammatory buffer – a   
   feedforward cycle.    
      
   Once triggered in the body, these inflammatory agents transfer information to   
   the nervous system, typically through stimulation of major nerves such as the   
   vagus, which connects5 the gut and brain. Specialized cells called microglia   
   in the brain    
   represent the brain's immune hubs and are activated in inflammatory states.    
      
   In activated microglia, an enzyme called IDO (indoleamine 2 3-dioxygenase) has   
   been shown6 to direct tryptophan away from the production of serotonin and   
   melatonin and towards the production of an NMDA agonist called quinolinic acid   
   that may be    
   responsible for symptoms of anxiety and agitation.    
      
   These are just some of the changes that may conspire to let your brain in on   
   what your body may know is wrong.    
      
   Animal Models    
      
   While an animal model of depression may seem like an absurd idea, currently,   
   lipopolysaccharide (LPS), an endotoxin produced by gram-negative bacteria, is   
   used to induce these clinical models in rodents.    
      
   Mice that lack IL1-B7 (a cytokine that mediates inflammatory response),   
   however, are protected against these LPS-mediated "depressive symptoms" (i.e.,   
   as demonstrated by loss of interest in sugar water), supporting the critical   
   role of inflammatory    
   messengers in the depressogenic cascade.    
      
   Pharmacology    
      
   One of the most predictable side effects of interferon therapy for Hepatitis C   
   is depression. In fact, 45 percent of patients develop depression8 with   
   interferon treatment, which appears to be related to elevated levels of   
   inflammatory cytokines IL-6 and    
   TNF.    
      
   A number of trials have examined the role of anti-inflammatory agents in the   
   treatment of depression. In one recent trial,9 a subset of patients resistant   
   to antidepressant treatment and identified by serum markers of inflammation,   
   most notably C-   
   reactive protein >3mg/L, were responsive to treatment with the TNF-alpha   
   antagonist (anti-inflammatory) infliximab (Remicade).    
      
   The pain-killer celecoxib (Celebrex) has been found in randomized,   
   placebo-controlled trials10 to be superior to placebo in antidepressant   
   augmentation. In the setting of psoriasis treatment with etanercept (Enbrel),   
   mood was improved11 independent of    
   psoriatic relief.    
      
   There has even been suggestion that the mechanism of action of antidepressants   
   is through an anti-inflammatory effect, particularly on IL6. However, these   
   observational studies have been largely inconclusive.12    
      
   The Gut-Brain Dance    
      
   What is driving this inflammation? How does it get kicked off? And how does it   
   induce depression? With the limited clinical applications and revelations that   
   came with the completion of the Human Genome Project in 2002, we have begun to   
   focus on where we    
   have outsourced our physiologic functions.    
      
   The microbiome has become an important consideration, and particularly, the   
   gut, which houses at least 10 times as many human cells as there are in our   
   bodies, and 150 times as many genes as are in our genome. These microbes   
   control many vital operations    
   and are responsible for synthesis of neuroactive and nutritional compounds,   
   for immune modulation, and for inflammatory signaling.    
      
      
   [continued in next message]   
      
   --- SoupGate-Win32 v1.05   
    * Origin: you cannot sedate... all the things you hate (1:229/2)