Mental illness: Probing the causes of schizophrenia, depression and anxiety

New research identifies the brain chemicals and circuits involved in mental illnesses like schizophrenia, depression, and anxiety, giving potential new directions to their treatment. In addition, research with children shows that early-life depression and anxiety changes the structure of the developing brain. The findings were presented at Neuroscience 2011, the Society for Neuroscience’s annual meeting and the world’s largest source of emerging news about brain science and health.

One in 17 Americans suffer from a serious mental illness, such as schizophrenia, major depression, or bipolar disorder, making it one of the leading causes of disability. Yet science is only beginning to understand the underlying physical causes of these diseases.

It is difficult to identify the causes of schizophrenia, but research suggests that several physical, genetic, psychological and environmental factors interact and make people more likely to develop the condition. Current thinking is that some people may be prone to schizophrenia, but sometimes a stressful or emotional life event might trigger a psychotic episode. However, it is not known why some people develop symptoms while others do not.

There are some risk factors for schizophrenia that you cannot change.

Genetics
Brain development
Neurotransmitters
Infection
Pregnancy and birth complications
Head injury
Triggers

Today’s new findings show:

  -  Childhood anxiety and depression alter the way the amygdala connects to other regions of the brain. This finding may help explain how early life stress can lead to future emotional and behavioral issues (Shaozheng Qin, PhD, abstract 927.06).

  -  In animal studies, a link between two factors associated with schizophrenia, prenatal infection and impaired function of a molecule important in memory (Melissa Burt, abstract 763.11).

  -  Researchers have identified a brain chemical important to antidepressant response in mice. The findings may help in the design of therapies for major depression (Maha Elsayed, abstract 904.10).

  -  The connections between two specific areas of the brain - the prefrontal cortex and the dorsal raphe nucleus - may contribute to depression. Stimulating these circuits in rats had an antidepressant effect (Melissa Warden, PhD, abstract 306.15).

  -  An enzyme called STEP is elevated in the brains of people with schizophrenia. Mice lacking this chemical did not develop schizophrenia-like behaviors (Nikisha Carty, PhD, abstract 238.03).

“If we can fully understand the roots of mental illness in brain circuitry and systems, we may be able to develop better treatment targets for the millions suffering from these diseases,” said press conference moderator Carol Tamminga, MD, of the University of Texas Southwestern, who is an expert on schizophrenia.

What causes schizophrenia?
Experts think schizophrenia is caused by several factors.

Genes and environment. Scientists have long known that schizophrenia runs in families. The illness occurs in 1 percent of the general population, but it occurs in 10 percent of people who have a first-degree relative with the disorder, such as a parent, brother, or sister. People who have second-degree relatives (aunts, uncles, grandparents, or cousins) with the disease also develop schizophrenia more often than the general population. The risk is highest for an identical twin of a person with schizophrenia. He or she has a 40 to 65 percent chance of developing the disorder.

We inherit our genes from both parents. Scientists believe several genes are associated with an increased risk of schizophrenia, but that no gene causes the disease by itself. In fact, recent research has found that people with schizophrenia tend to have higher rates of rare genetic mutations. These genetic differences involve hundreds of different genes and probably disrupt brain development.

Other recent studies suggest that schizophrenia may result in part when a certain gene that is key to making important brain chemicals malfunctions. This problem may affect the part of the brain involved in developing higher functioning skills. Research into this gene is ongoing, so it is not yet possible to use the genetic information to predict who will develop the disease.

Despite this, tests that scan a person’s genes can be bought without a prescription or a health professional’s advice. Ads for the tests suggest that with a saliva sample, a company can determine if a client is at risk for developing specific diseases, including schizophrenia. However, scientists don’t yet know all of the gene variations that contribute to schizophrenia. Those that are known raise the risk only by very small amounts. Therefore, these “genome scans” are unlikely to provide a complete picture of a person’s risk for developing a mental disorder like schizophrenia.

In addition, it probably takes more than genes to cause the disorder. Scientists think interactions between genes and the environment are necessary for schizophrenia to develop. Many environmental factors may be involved, such as exposure to viruses or malnutrition before birth, problems during birth, and other not yet known psychosocial factors.
Scientists are learning more about brain chemistry and its link to schizophrenia.

Different brain chemistry and structure. Scientists think that an imbalance in the complex, interrelated chemical reactions of the brain involving the neurotransmitters dopamine and glutamate, and possibly others, plays a role in schizophrenia.
Neurotransmitters are substances that allow brain cells to communicate with each other. Scientists are learning more about brain chemistry and its link to schizophrenia.

Also, in small ways the brains of people with schizophrenia look different than those of healthy people. For example, fluid-filled cavities at the center of the brain, called ventricles, are larger in some people with schizophrenia. The brains of people with the illness also tend to have less gray matter, and some areas of the brain may have less or more activity.

Studies of brain tissue after death also have revealed differences in the brains of people with schizophrenia. Scientists found small changes in the distribution or characteristics of brain cells that likely occurred before birth. Some experts think problems during brain development before birth may lead to faulty connections. The problem may not show up in a person until puberty. The brain undergoes major changes during puberty, and these changes could trigger psychotic symptoms. Scientists have learned a lot about schizophrenia, but more research is needed to help explain how it develops.

Scientists have learned a lot about schizophrenia, but more research is needed to help explain how it develops.


This research was supported by national funding agencies, such as the National Institutes of Health, as well as private and philanthropic organizations.

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Kat Snodgrass,
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Press Room, Nov. 12–16: (202) 249-4080          

Melissa Malski,
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