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Study Finds Disrupted Stress Response in Schizophrenia Patients

A new Canadian study published in the journal Brain shows that stress tends to impact the brain and body differently in schizophrenia patients than in healthy people or even in those at high risk for developing psychosis.

Specifically, the researchers found that the association between two chemicals released when people experienced stress — one released in the brain and the other in saliva — differs in people with 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 lead author Dr. Christin Schifani from the Campbell Family Mental Health Research Institute at the Centre for Addiction and Mental Health (CAMH).

Since most schizophrenia patients experience psychosis, identifying differences between those at high risk for psychosis and those with schizophrenia may shed light on how the mental illness 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,” said senior author Dr. Romina Mizrahi, clinician scientist in the Campbell Institute at CAMH.

“Developing strategies to cope with stress and build resilience may be the opportunity.”

Mizrahi heads the Focus on Youth Psychosis Prevention (FYPP) Clinic and research program at CAMH, which is dedicated to the early identification and treatment of people aged 16 to 35 who are at high risk of developing psychosis.

Helping patients identify sources of stress and learn coping strategies is a key focus of the clinic’s work. The researchers plan to study the impact of these stress management techniques to reduce psychosis and schizophrenia risks.

The study involved 14 people with schizophrenia, 14 people at clinical high risk for psychosis and 12 people without mental illness. The researchers specifically examined two important stress chemicals: dopamine and cortisol.

Dopamine is a neurotransmitter that carries signals from one brain cell, or neuron, to another. The research team focused on dopamine released in the prefrontal cortex, an area of the brain involved in complex functions, including emotion regulation. Cortisol is a hormone released from the adrenal glands to help the body handle stressful situations.

In healthy people, both dopamine and cortisol levels typically increase during stress. However, this connection 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 Mizrahi.

To investigate each participant’s stress response, the researchers used a math test. In the first part of the experiment, 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 part of the test, participants in the PET scanner had to answer math questions under time constraints while also receiving negative verbal feedback. Saliva samples were collected during both experiments to measure cortisol levels.

The new findings build on previous research by Mizrahi which focused on 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,” said 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 their expectations, the team did not find any major 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,” Mizrahi said.

Source: Centre for Addiction and Mental Health



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