Brain networks differ among those with severe schizophrenia, CAMH study shows

People with a severe form of schizophrenia have major differences in their brain networks compared to others with schizophrenia, bipolar disorder and healthy individuals, a new study from the Centre for Addiction and Mental Health (CAMH) shows.

The study, which used a novel approach to map brain networks, was led by researchers at the Campbell Family Mental Health Research Institute at CAMH and published in this week’s JAMA Psychiatry.

“Finding ways to help this particular group of people with schizophrenia is a priority as recovery is unlikely, even up to 20 years after the initial diagnosis. Social isolation, lack of work and relationships, and chronic disability are very common,” says Dr. Aristotle Voineskos, senior author on the paper and Director of the Slaight Family Centre for Youth in Transition at CAMH.

Schizophrenia, which affects one in 100 people, is generally known for symptoms of delusions and hallucinations, which can be treated with antipsychotic medications. However, lack of motivation and social withdrawal are also characteristic symptoms of the illness. These are known as negative symptoms.

Approximately one in five people with schizophrenia experience these negative symptoms in a pronounced way, says lead author Dr. Anne Wheeler, CAMH post-doctoral fellow. At this point, there is no treatment for negative symptoms, yet they have the greatest impact on a person’s daily functioning once the psychosis is managed.

The value of having a biological, brain-based indicator is that it may help identify this group of patients when they initially present for treatment of psychosis. Otherwise it can take years to determine social disability through clinical observation, says Dr. Voineskos.

What is schizophrenia?
Schizophrenia is a severe and debilitating brain and behavior disorder affecting how one thinks, feels and acts. People with schizophrenia can have trouble distinguishing reality from fantasy, expressing and managing normal emotions and making decisions. Thought processes may also be disorganized and the motivation to engage in life’s activities may be blunted. Those with the condition may hear imaginary voices and believe others are reading their minds, controlling their thoughts or plotting to harm them.

Most people with schizophrenia suffer from symptoms either continuously or intermittently throughout life and are often severely stigmatized by people who do not understand the disease. Contrary to popular perception, people with schizophrenia do not have “split” or multiple personalities and most pose no danger to others. However, the symptoms are terrifying to those afflicted and can make them unresponsive, agitated or withdrawn. People with schizophrenia attempt suicide more often than people in the general population, and estimates are that up to 10 percent of people with schizophrenia will complete a suicide in the first 10 years of the illness - particularly young men with schizophrenia.

While schizophrenia is a chronic disorder, it can be treated with medication, psychological and social treatments, substantially improving the lives of people with the condition.

Brain networks differ among those with severe<a class= schizophrenia" align="right" /> The study involved magnetic resonance brain imaging (MRI) with 128 people with schizophrenia and 130 healthy individuals at two sites, and with 39 patients with bipolar disorder and 43 healthy individuals at a third site. Patients with bipolar disorder also experience psychotic symptoms but not negative symptoms, so these patients served as an additional comparison group. The three sites were at CAMH, the Zucker Hillside Hospital in Glen Oaks, New York, and the Central Institute of Mental Health in Mannheim, Germany.

Researchers used a unique approach called network analysis to study the overall network density, or level of connectivity, in the brain.

“We found alterations in a number of relationships between brain regions among those with more severe schizophrenia compared with the other groups, including those with less severe schizophrenia,” says Dr. Voineskos. “This provides strong evidence that schizophrenia is not just one brain disorder.”

The study also confirms previous research from his team showing changes in the white matter tissues connecting those same regions in the brain, among those with more severe schizophrenia.

What are the subtypes of schizophrenia?

  Paranoid schizophrenia
- feelings of extreme suspicion, persecution or grandiosity, or a combination of these.
  Disorganized schizophrenia - incoherent thoughts, but not necessarily delusional.
  Catatonic schizophrenia - withdrawal, negative affect and isolation, and marked psychomotor disturbances.
  Residual schizophrenia - delusions or hallucinations may go away, but motivation or interest in life is gone.
  Schizoaffective disorder - symptoms of both schizophrenia and a major mood disorder, such as depression.

At what age do the symptoms of schizophrenia appear?
Schizophrenia affects men and women equally. It occurs at similar rates in all ethnic groups around the world. Symptoms such as hallucinations and delusions usually start between ages 16 and 30.
Men tend to experience symptoms earlier than women. Most of the time, people do not get schizophrenia after age 45. Schizophrenia rarely occurs in children, but awareness of childhood onset schizophrenia is increasing.

It can be difficult to diagnose schizophrenia in teens. This is because the first signs can include a change of friends, a drop in grades, sleep problems and irritability - behaviors that are common among teens.

These impaired networks are important to the brain processes related to negative symptoms and social function that patients experience, the authors write. Based on these findings, the investigators are also funded by the U.S. National Institute of Mental Health to conduct a multi-centre study of a large number of people with schizophrenia to establish the full range of impairment in brain circuitry that predicts social impairment.

Through this research, specific brain circuits can be targeted to develop new therapeutic approaches for negative symptoms and social impairment. Such studies are now underway at CAMH using virtual reality technology and brain stimulation.


The current study was funded through the Ontario Mental Health Foundation, Canadian Institutes of Health Research, Brain and Behavior Research Foundation, and the CAMH Foundation.

The Centre for Addiction and Mental Health (CAMH) is Canada’s largest mental health and addiction teaching hospital, and one of the world’s leading research centres in its field. CAMH combines clinical care, research, education, policy development and health promotion to help transform the lives of people affected by mental health and addiction issues. CAMH is fully affiliated with the University of Toronto, and is a Pan American Health Organization/World Health Organization Collaborating Centre.


Kate Richards

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Centre for Addiction and Mental Health

  JAMA Psychiatry

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