How do stress cause psychosis? Epidemiology and Psych Sciences. 2014.Sept

16.10.2014

It is generally recognised that psychosocial stress  play a role in causing mental disorders.  Brown & Burley conducted the first major work looking at stress and schizophrenia in 1960s. Nearly half of those with relapse of schizophrenia had a stressful event in the preceding 3 months. These were later replicated in 1990s. Stress was seen as working with the biological vulnerability in precipitating psychosis.

What are the biological systems that are involved in such stress response?

Mondelli reviews the major findings in this area so far  in this editorial.

1. HPA axis: First episode psychosis patients have increased HPA activation . ( cortisol increased, ACTH high, enlarged pitutary volume, blunted cortisol awaking response ). i.e. axis remain in highly activated state along with reduced reactivity to stress.  These are found to be apparent before the start of psychosis. Increased glucocorticoids can increase mesolimbic dopamine ( in animals). It can also impair neuronal plasticity. Higher cortisol levels lead to hippocampal volume loss. Antipsychotics can reduce the cortisol levels in the day time, but do not change the abnormalities in awakening response.

2.Low magnitude, general and  long-term inflammation: Increased inflammatory status is seen prominently in depression. It is also seen at onset of psychosis. Increase in IL6, TNF alpha, IL-1beta are the most consistent findings. These may be interacting with mono amine synthesis pathways, neuro endocrine systems and neural plasticity. It looks like antipsychotics show an initial anti inflammatory effect but this is followed by a gradual rise in cytokines along with an increase in body weight. So may be it have a direct an indirect effect. higher inflammation is also correlated with poorer outcome in psychosis.

The next questions are 1. Can we use the above biomarkers to predict psychosis among those who face stress? 2. Can it predict who is going to be resistant to antipsychotics? 3. Can we develop new therapeutic options along these pathways?

Comments: Reducing stress and providing support is key in maintaining individuals with psychosis well. At least this is what we can practically offer now. At population level, more awareness & options of support  for all who face stress is crucial. Low key interventions might be useful tools in that.

Summary of the article: 

From stress to psychosiswhom, how, when and why?

Mondelli V. Epidemiol Psychiatr Sci. 2014 Sep;23(3):215-8.

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