A new study from the Centre for Addiction and Mental Health indicates that stressful situations affect the brain and body differently in people with schizophrenia, compared to people without the mental illness, or to individuals at high risk for developing psychosis.

The findings may provide clues into how to act early to prevent schizophrenia.

“We found a disrupted stress response in people with schizophrenia, which did not occur in either healthy individuals or people at clinical high risk for developing psychosis,"

said Dr. Christin Schifani, Postdoctoral Research Fellow in the Research Imaging Centre in CAMH’s Campbell Family Mental Health Research Institute, and lead author of the study.

Building Stress Resilience

As most people with schizophrenia experience psychosis, identifying differences between people at high risk for psychosis and those with schizophrenia may shed light on how schizophrenia develops and ways to prevent its onset.

“The fact we see this disrupted stress response in people with schizophrenia, but not in people at high risk for psychosis, suggests an opportunity to intervene to prevent schizophrenia. Developing strategies to cope with stress and build resilience may be the opportunity,"

said senior author Dr. Romina Mizrahi, Clinician Scientist in the Campbell Institute at CAMH.

These results come from examining two important chemical messengers - dopamine and cortisol - in people under stress. Dopamine is a neurotransmitter, a chemical that carries signals from one brain cell, or neuron, to another.

In this study, the researchers focused on dopamine released in the prefrontal cortex, the region at the front of the brain involved in complex functions, including regulating emotions. Cortisol is a hormone, released from the adrenal glands to help the body handle stressful situations.

Dopamine And Cortisol

In healthy individuals, both dopamine and cortisol levels typically increase when people experience stress. This link between dopamine release and cortisol release did not appear in people with schizophrenia.

“Cortisol is the main stress hormone, so this suggests a disrupted stress regulatory system in people with schizophrenia,"

said Dr. Mizrahi.

To investigate responses to stress, the researchers used a math test. In the first stage of the study, participants answered math questions on a computer screen without any time limit while a positron emission tomography (PET) scanner produced an image of dopamine in their brain as they completed the task.

In the second stage - the stress test - participants answered math questions under time constraints and while receiving negative verbal feedback, also in the PET scanner. Saliva samples were collected during both stages to measure cortisol levels.

The study included 14 people with schizophrenia, 14 people at clinical high risk for psychosis and 12 people without mental illness.

Complex Brain Regulatory Systems

The findings build on Dr. Mizrahi’s earlier research in another region of the brain, the striatum.

“Our previous research had shown that people at high risk for psychosis and those experiencing a first episode of psychosis have abnormal, or increased dopamine release in response to stress in the striatum,” says Dr. Mizrahi. “Since the prefrontal cortex is involved in regulating striatal dopamine release, we wanted to understand what was happening in the step before the striatum."

But, contrary to what they had expected, the researchers did not find significant differences in dopamine release in the prefrontal cortex among the three groups of participants.

“Our findings of an increase in dopamine release in the striatum, but not in the cortex, show the complex brain regulatory systems in both people at high risk for psychosis and people with schizophrenia,"

said Dr. Mizrahi.

Christin Schifani, Huai-Hsuan Tseng, Miran Kenk, Abanti Tagore, Michael Kiang, Alan A Wilson, Sylvain Houle, Pablo M Rusjan, Romina Mizrahi Cortical stress regulation is disrupted in schizophrenia but not in clinical high risk for psychosis Brain, Volume 141, Issue 7, 1 July 2018, Pages 2213–2224, https://doi.org/10.1093/brain/awy133

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