A report by Bloomfield et al. in the January 2016 issue of American Journal of Psychiatry showed further evidence that psychosis is associated with increased inflammatory activity in the brain. What the researchers did was to use a marker, [11C]PBR28, which binds to activated white blood cells (microglia) in the brain. None of the subjects had been treated with antipsychotic medications. The researchers showed that in persons who are at high risk for the development of psychosis and in those in whom psychosis had emerged, there was a greater degree of binding of the marker indicating more activated microglia in the brain. Moreover, they noted that degree of binding (degree of microglia activation) was correlated with the level of symptoms.
The Bloomfield et al. report fits in well with a larger literature pointing the finger at dysfunction in fast spiking GABA interneurons as the culprit in causing hallucinations and cognitive impairment. (This story is reviewed in chapter 6 in Neuroscience for Psychologists and Other Mental Health Professionals.) Inflammation negatively impacts fast spiking GABA interneurons. Oxidative stress, a component of inflammation, also impairs the function of NMDA receptors which are the drive on the fast spiking GABA interneurons (Sorce, Schiavone, Tucci et al., 2010; Sullivan & O’Donnell, 2012). Stressful life experiences can also increase oxidative stress and thus provides a mechanism for how trauma can increase the emergence of psychosis (Cabungcal, Steullet et al., 2013; Jing et al., 2013). Many persons with psychosis relapse when they incur infections in other parts of the body which than can raise inflammatory factors in brain (see Brian Miller, 2016).
The Impact of Antipsychotic Drugs on Brain Inflammation: Bloomfield et al. (2016) cited two studies using microglia cells in a petri dish which showed that antipsychotics tamed activation of these cells (Bian et al., 2008; Kato et al., 2008). They also cited a study by Zhu et al. (2014) in live rats which showed that when a molecule of the wall of a bacterium (lipopolysaccharide) is injected into the brain of a rat and subsequently the rat is given a 14 day administration of an antipsychotic the brain’s inflammatory response to the provocation is attenuated. Bloomfield et al. did not cite the study by Cotel et al. The Cotel et al. study showed that antipsychotic treatment activates inflammation in the brain, the opposite of what the studies cited by Bloomfield et al. showed. Arguably, the Cotel et al. study is more relevant to the question of how antipsychotic drugs influence inflammation in the brain. Cotel et al. administered antipsychotics for 8 weeks, much longer than in the other studies. Moreover, Cotel et al. did not use another activator of an inflammatory response (as was done in the other studies). Cotel et al. only examined the impact of the antipsychotics in brains which were not exposed to another inflammatory provocation. The Cotel et al. study, which found that antipsychotics create brain inflammation, is important because it might offer an explanation/mechanism for how antipsychotics shrink cortex which was shown in the humans (see Ho et al., 2011) and in the primate studies (Dorph-Petersen et al., 2005). A study by Shao et al. (2013) further confirmed that blocking dopamine receptors, as antipsychotics do, will increase brain inflammation.
The Search for Alternatives to Antipsychotics: There is a literature on using anti-inflammatories to treat psychosis. In fact, in a study of children at high risk of converting to psychosis, omega-3s (which are anti-inflammatory) was the only treatment that prevented the emergence of frank psychosis with 27.5% becoming psychotic in the control group versus 4.9% in the omega-3 group at the 12 month follow-up (Amminger et al., 2010). There is also a literature attesting to the beneficial effects of anti-inflammatories on psychosis. The anti-inflammatories have included aspirin, minocycline, statins, N-acetylcysteine, and the COX-2 inhibitor, celecoxib (Keller et al., 2013; Sommer et al., 2014). Sommer et al. concluded that aspirin, estrogen, and N-acetyl-cysteine showed the best effects. Additionally, social support can also reduce systemic inflammation. Hopefully, in the future, we’ll have drug trials of anti-inflammatories as the sole pharmacological treatment along with attention to an anti-inflammatory diet and Soteria Project support. (There is little reason to believe that any chemical anti-inflammatory can eclipse the impact of an inflammatory diet.) Perhaps the future will offer a better way.
Readers on this website may object to any notion that biology influences human behavior. At risk of offending this audience, I present the findings in these studies because they demonstrate the folly of antipsychotics even for those who believe in physiological explanations for hearing voices. Since doctors probably won’t ever give up their prescription pads, perhaps they can be coaxed into gentler drugs to prescribe. I think that for those who are involuntarily committed to the psychiatric hospital, telling the doctor to prescribe “this” instead of “that” and backing up the demand with a study published in a legitimate journal might hold some weight. If asking for a legitimate alternative does not influence the doctor, it might influence a judge. In fact, most states have informed consent laws which mandate that physicians discuss all the options available for treating a given condition so that the patient can choose which option they prefer.
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