Less Stress, Less Cortisol, Less Psychosis?by Carla Clark, PhD | March 4, 2015
In an increasingly fast-paced modern world, many race against the clock by unnaturally and continuously hijacking the body’s innate stress response. So is it any wonder that the increasing incidence of psychosis diagnoses (reportedly tripled since the 1970s) is being linked to how our bodies deal with stress?
Studies are linking the mismanagement of stress in the body with psychotic disorders left, right and center. Supporting a rapidly emerging sociodevelopmental cognitive model, it could account for the perplexingly vast nonuniformity in psychosis symptom presentation, progression, response to antipsychotic drugs and genetics.
Indeed, causes of increased rates of psychosis may result from improvements to diagnostic systems and increased awareness of early psychosis. However, chronic contemporary psychological stress is so prevalent that it has even been dubbed the “21st century equivalent of the Black Death”, and the mismanagement of stress in the body is undoubtedly an etiological factor for psychosis disorders.
Stress-Related Risk Factors
There are a myriad of stress-related risk factors for development of psychosis, including:
- Past exposure to adverse social environments, which increases physiological and psychological stress levels, thus increases one’s chances of experiencing first episode psychosis.
- Belonging to a social minority group, recently immigrating, living in poverty, bullying, being subjected to domestic violence or having had an abusive childhood places people at higher risk of developing psychosis and are all linked with measurably increased stress levels at the molecular and neurological level.
- Simply living in a more stressful urban environment, as opposed to the quieter environs of the countryside, places urbanites at higher risk of psychosis in multiple studies.
- Women tend to increasingly present symptoms of psychosis during times in their life where stress hormone levels, like cortisol, are naturally higher, such as when premenstrual, during the puerperium and the menopause. Similarly, adolescence is a high-risk age for onset of psychosis, a time in life where we experience a naturally enhanced response to stress.
- Considering that even acute intake of legal drugs and toxins such as nicotine and alcohol overactivate the body’s stress response and associated stress hormone levels, it is unsurprising that first episode psychosis patients are twice as likely to be substance abusers in comparison with the general population.
- Even certain disease states result in a higher risk of developing psychosis. In particular, a large body of epidemiologic evidence links autoimmune and inflammatory diseases, the mothers of all stress-related diseases, with an increased risk of developing psychotic disorders. Moreover, anti-inflammatory and antioxidant medication has proven potential for the treatment of psychotic disorders.
Epigenetics and Risk
Looking at the above list of at risk groups, one would think that we should all develop psychosis. However, using schizophrenia as an example, even though it has high heritability (~80%), even genetically identical twins show a high discordance rate, with only a ~50% chance of both twins developing psychosis.
A recent review article published in Frontiers in Psychiatry, focusing particularly on schizophrenia, mirrors a multitude of recently published papers that aptly explain this disparity by outlining the:
‘…(potentially crucial) role of epigenetics in setting gene-expression levels that mediate the stress response, and ultimate causal (though presently unproven) effect on developing brain networks that sub-serve many of the cognitive functions impaired in schizophrenia.’
Epigenetic mechanisms include the physical tagging of genes with chemical groups that can turn them on or off. Such mechanisms may alter their expression in response to the environment, where different life experiences result in differences in both the marking of and subsequent expression of genes. These may explain differences in behavior and personality in genetically identical twins.
In the stress-based psychosis model, stress, or more specifically, our reaction to stressful experiences (e.g. social-experience, bad diet and nutrition, and exposure to toxins), even when we are in the womb, can cause a stress hormone cascade (e.g. cortisol) that can induce epigenetic marking of stress-related genes in the blood, with these changes being more pronounced for those that are already genetically and/or epigenetically at risk.
Various combinations of epigenetic changes and disease-linked forms of stress sensitivity genes are then hypothesized to alter brain activation and connectivity patterns in stress-sensitive brain regions that promote psychosis onset and development.
In fact, levels of cell signalling molecules which are overproduced in response to chronic stress, called proinflammatory cytokines, were able to predict the rate of grey matter loss in the brains of those at clinical high risk of developing psychosis and more importantly, those with the greatest losses developed psychosis 12 months later.
As Dr. John Krystal, Editor of Biological Psychiatry sums up the research:
‘This report suggests that neuroinflammation may be a process that in some cases ‘tips people over’ from the at-risk state into psychosis.’
So for example, if both twins have inherited psychosis-related genes from a psychosis prone family, one twin may have inadvertently learned an effective way to deal with stress, the other not; or one may have had a more toxic and stressful lifestyle or more traumatic experiences, the other not. Put simply, one twin’s life experiences may result in the marking of genes that makes them, the other, a set of epigenetic marks that breaks them.
It’s like a complex epigenetic relay race, where the batons represent the psychosis promoting epigenetic marks and the stress sensitivity genes are the runners. Our physiological response to stressful experiences can give the runners the batons and fire the gun, where the baton is passed on to gene copies in subsequent cell divisions, unless something causes the psychosis-promoting baton to be dropped (e.g. lifestyle changes, therapy and medication). With genes that promote a pathological sensitivity to stress you would rather they stay quiet, take it easy and drop out of the race.
Interestingly, even the variability in both adverse and beneficial effects of antipsychotic medications fits an epigenetic stress-based model.
Antipsychotic drug use has been recently linked to altered DNA methylation (epigenetic tagging) of stress sensitive genes in both monozygotic human twins and in an animal model of psychosis. However, the pre-existing genetic and epigenetic landscape before taking any medication controls the expression of drug processing genes and nuclear receptors, many of which are also well-known to be influenced by stress, and will ultimately result in individual differences in the physiological response to these antipsychotic drugs.
Although we do not know which antipsychotic drug-induced epigenetic changes are a part of the cause – an effect of, or a solution to the psychosis disease process – a paradigm shift in the understanding of psychosis is finally off the starting blocks.
Until the complex, multifaceted, interconnected genetic and epigenetic gene-environment interactions are mapped out, learning to effectively deal with potentially stressful situations, and minimizing stressful and toxic living, is the best free preventative antipsychotic “medication” that can currently be prescribed.
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