Neurological markers may identify risk for psychotic disorders

Researchers have found neurological markers in the human brain that can be used to detect the presence of psychotic disorder.

People, who may hear and see things that are not there, could have symptoms of psychosis, better known as psychotic disorders.

 

Researchers  have found neurological markers in the human brain that can be used to detect people at risk for developing psychotic disorders and to understand when this risk has been successfully treated.

 

“Psychotic disorders like schizophrenia are often lifelong and disabling for individuals,” said a professor of psychology.

Researchers said psychotic disorders are associated with increased levels of dopamine a chemical released by nerve cells in a subregion of the brain called the striatum. This area is wired to process positive versus negative feedback for learning, often resulting in a person’s thoughts and actions based on what they’ve experienced in the past.

Therefore, researchers suggest that psychotic disorders involve faulty feedback in learning that then drives a person’s faulty beliefs and perceptions.

However, measuring levels of dopamine in people is costly, invasive and not feasible in everyday clinical practice. In this new study, researchers used an MRI at MU’s Brain Imaging Center and found that people at risk for psychotic disorders exhibit evidence of dysfunction in the striatum.

“This dysfunction is most evident when performing tasks where people need to learn from positive and negative feedback,” said the Dr.

“For instance, we have found that the risk for psychotic disorders involves increased activation in the striatum for positive feedback, and negative feedback involves decreased activation in the same subregion of the brain,” he added.

Researchers believe this pattern of activation could explain symptoms of psychotic disorders.

For example, activation resulting from increased positive feedback could make a person’s assumption seem truer than it really is, meanwhile activation from decreased negative feedback could make someone less likely to discard negative ideas.

The team will conduct future research to examine how well an MRI can predict the risk of psychotic disorders and whether prevention treatments can ‘normalise’ MRI scans. They hope that their research will help prevent psychotic disorders, improve the lives of millions of people and greatly reduce public health costs.

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In vitro cell culture findings could lead to novel interventions for schizophrenia

A study recently  has shown how using cultured cells from patients with psychotic disorders, such as schizophrenia, to investigate abnormalities in nerve connections in the brain could lead to new treatments. Strong correlations were observed between the findings in the cells in culture—grown outside the body in a controlled environment—and findings from brain imaging performed on the very same human participants. 

"The findings are important, because if the health of cells in culture reflects the health of the same cells in a human brain, we may be able to create a better model for studying psychotic disorders," said the study's senior author. He said such a model could give researchers a greater capacity to find genetic and biochemical targets in the brain. Using these targets, he said, "could enable us to develop novel and more effective interventions for psychotic disorders."

For their work, the team  drew on studies showing that altered pathways of brain development can be found across most cases of schizophrenia and that inaccurate connections and "leaks" in signaling between nerve cells are a feature of many psychotic disorders. A substance called myelin, produced by cells called oligodendrocytes, serves as a kind of insulation to prevent these leaks. In studies , myelin was measured and found to be reduced in the brain in patients with schizophrenias.

Based on this prior research, the researchers drew on a repository of cell lines they had obtained from patients with psychiatric disorders. These samples were reprogrammed from skin cells into brain-like cells in the laboratory. The reprogrammed cell lines, taken from both ill and healthy patients, produced nerve cells and support cells called glia, including oligodendrocytes, in laboratory cultures. Investigations into these cells revealed significant abnormalities in the development of oligodendrocytes grown from subjects with psychotic disorders.

The research also revealed a strong correlation between the number of oligodendrocytes in culture and the amount of myelin made by these cells in the brains of the same subjects who provided the cells. This finding, Cohen explained, "means that we can now study the causes of the abnormality of myelin that we have observed in living brain tissue in a laboratory setting."

For the researchers, the prospect of using lab cultures to examine differences in the brains of individuals with psychotic illnesses is "an exciting development." For example, the Prof. said, researchers have observed that not all genes and proteins necessary to make oligodendrocytes are affected in these cells, and they can now begin to identify exactly what genes and proteins are different in these cells. It would be impossible, he said, to do these detailed studies in living brain tissue.

Such studies, the researchers believe, could lead to better treatment approaches for individuals with psychotic conditions. "Using in vitro cell cultures to study these abnormalities could help us identify specific genetic and biochemical targets that might be addressed by novel drug treatments, cell transplantation, or other interventions," the Prof. said.

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Tourette's Syndrome

Understanding What Is Tourette’s Syndrome
Tourette’s syndrome is attributed to involuntary and repetitive movements and sounds produced in a body. These are uncontrollable actions and at present approximately 1 million people in India suffer from this syndrome. It is neurological problem, first diagnosed by Dr. Georges Gilles De La Tourette in 1885 in a 86-year old French woman.

It is a chronic condition where symptoms can occur as early as in a 3-years old. While the most severe symptoms are presented in the teen years, most of these symptoms improve during the late teens and into adulthood.

Symptoms:
Generally, the involuntary movements also known as tics are classified as simple and complex.

1. Simple: As far as the basic version of this condition is concerned, you will find that it is limited to sudden and jerky movements associated with certain muscle groups. For instance, the simple tics include eye blinking, shrugging, facial grimacing, and vocalizations. The vocalization can be in form of grunting, sniffling or throat clearing where the condition is mild.
   
2. Complex: The motor tics in the complex version of this condition may include head twists, violent shoulder shrugs, hops, bending, twisting or even touching objects. As far as the vocalizations go, it may include words and phrases while the dramatic symptoms may present the person using cuss words as well.
   

Implications and Treatment:
One positive thing associated with this syndrome is that it doesn’t cause an impairment and therefore there is no medication prescribed for it. Tourette’s syndrome does not affect one’s intelligence and hence it need not stop people from seeking a career of their choice.

However, the biggest concern of people affected by it is the social acceptance of their condition.
Also, those who are suffering from it must be provided with an ideal, tolerant and compassionate set-up where they are encouraged to work and learn to their full potential.

Further, as tic symptoms often do not cause an impairment, a majority of people suffering from it do not require any medication for tic suppression. However, effective medications are available for those whose symptoms interfere with their day-to-day functioning. Neuroleptics (drugs that may be used to treat psychotic and non-psychotic disorders) are the most consistently useful medications for tic suppression.

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Do antipsychotics do more good than harm?

According to an international group of experts, the benefits of anti-psychotic medications outweigh the risks.

The experts concluded that, for the patients with schizophrenia and related psychotic disorders, anti-psychotic medications do not have negative long-term effects on patients` outcomes or the brain.

In addition, the benefits of these medications are much greater than their potential side effects.Jeffrey Lieberman, Lawrence C. Kolb from the Columbia University College of Physicians and Surgeon and colleagues from institutions in the United States, Germany, The Netherlands, Austria, Japan, and China undertook a comprehensive examination of clinical and basic research studies that examined the effects of anti-psychotic drug treatment on the clinical outcomes of patients and changes in brain structure.

Lieberman noted that the evidence from randomized clinical trials and neuroimaging studies overwhelmingly suggested that the majority of patients with schizophrenia benefit from anti-psychotic treatment, both in the initial presentation of the disease and for longer-term maintenance to prevent relapse.

Moreover, whatever side effects that these medications might cause are greatly outweighed by their therapeutic benefits."Anyone who doubts this conclusion should talk with people whose symptoms have been relieved by treatment and literally given back their lives," Lieberman added.

The studies also revealed that delaying or withholding treatment has been associated with poorer long-term outcomes. "While a minority of patients who recover from an initial psychotic episode may maintain their remission without anti-psychotic treatment, there is currently no clinical biomarker to identify them, and it is a very small number of patients who may fall into this subgroup," said Lieberman.

"Consequently, withholding treatment could be detrimental for most patients with schizophrenia."And while pre-clinical studies in rodents suggested that anti-psychotic medications can sensitize dopamine receptors, there is no evidence that anti-psychotic treatment increases the risk of relapse.

While anti-psychotic medications can increase the risk for metabolic syndrome, which is linked to heart disease, diabetes, and stroke, the study did not include a risk-benefit analysis.

"While more research is needed to address these questions, the strong evidence supporting the benefits of anti-psychotic medications should be made clear to patients and their families, while at the same time they should be used judiciously," continued Lieberman.

These findings are published in the American Journal of Psychiatry.

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