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Studying the networks of connections in the brains of people affected by schizophrenia, bipolar disease or depression has allowed Dr. Peter Williamson, from Western University, to gain a better understanding of the biological basis of these important diseases. Dr. Williamson and colleagues have shown that different networks, found specifically in humans, are disrupted in different psychiatric diseases. These results were presented at the 2013 Canadian Neuroscience Meeting, the annual meeting of the Canadian Association for Neuroscience – Association Canadienne des Neurosciences (CAN-ACN).

Previously, researchers had attempted to use genetic approaches to help explain the biological basis of neuropsychiatric diseases, but genetics can only explain a small percentage of cases. Today researchers have begun using new imaging techniques to study connections in the brains of living patients, and this approach is revealing important differences between patients suffering from schizophrenia, bipolar disorder, and depression, and persons not affected by these disorders.

Schizophrenia and bipolar disorder are uniquely human diseases. Though some animal models exist for these diseases, animals cannot experience these diseases as we do, since they lack our language capacities, and the ability to represent feelings and ideas, their own and those of others, across time. These specifically human capabilities are encoded in specifically human neural networks, such as an emotional encoding network, found to be disrupted in mood disorders, such as depression and bipolar disorder, and the directed effort network which fails in schizophrenia.

Concluding quote from Dr. Williamson: “We are not likely to understand the extremely complex interactions between the hundreds of genes and environmental events that underlie neuropsychiatric disorders in our lifetimes. The challenge of our time is to find the final common pathways of these disorders”

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MRI may be an effective way to diagnose mental illnesses such as bipolar disorder, according to experts from the Icahn School of Medicine at Mount Sinai. In a landmark study using advanced techniques, the researchers were able to correctly distinguish bipolar patients from healthy individuals based on their brain scans alone. The data are published in the journal Psychological Medicine.

Currently, most mental illnesses are diagnosed based on symptoms only, creating an urgent need for new approaches to diagnosis. In bipolar disorder, there may be a significant delay in diagnosis due to the complex clinical presentation of the illness. In this study, Sophia Frangou, MD, Professor of Psychiatry and Chief of the Psychosis Research Program at the Ichan School of Medicine at Mount Sinai teamed up with Andy Simmons, MD, of the Kings College London and Janaina Mourao-Miranda, MD, of University College London, to explore whether brain imaging could help correctly identify patients with bipolar disorder.

“Bipolar disorder affects patients’ ability to regulate their emotions successfully, which puts them at great disadvantage in their lives,” said Dr. Frangou. “The situation is made worse by unacceptably long delays, sometimes of up to 10 years, in making the correct diagnosis. Bipolar disorder may be easily misdiagnosed for other disorders, such as depression or schizophrenia. This is why bipolar disorder ranks among the top ten disorders causing significant disability worldwide.”

Dr. Frangou and her team used MRI to scan the brains of people with bipolar disorder and of healthy individuals. Using advanced computational models, they were successful in correctly separating people with bipolar disorder from healthy individuals with 73 percent accuracy using their brain imaging scans alone. They replicated their finding in a separate group of patients and healthy individuals and found a 72 percent accuracy rate.

Dr. Simmons added, “The level of accuracy we achieved is comparable to that of many other tests used in medicine. Additionally, brain scanning is very acceptable to patients as most people consider it a routine diagnostic test.”

“This approach does not undermine the importance of rigorous clinical assessment and the importance of building relationships with patients but provides biological justification for the type of diagnosis made,” said Dr. Frangou. “However, diagnostic imaging for psychiatry is still under investigation and not ready for widespread use. Nonetheless, our results together with those from other labs are a harbinger of a major shift in the way we approach diagnosis in psychiatry.”

Dr. Frangou recently joined Mount Sinai as Chief of the Psychosis Research Program in the Division of Psychiatric Genomics in the Department of Psychiatry at Mount Sinai. A leading authority on neuroimaging in schizophrenia and bipolar disorder, Dr. Frangou was recruited to Mount Sinai to establish a clinical and translational psychosis program. By building on Mount Sinai’s strengths in clinical investigation, the program aims to translate research in genetics, neuroimaging, and neurobiology into clinical trials and clinical care.

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Research from North Carolina State University, the Research Triangle Institute (RTI) and the University of South Florida shows that outpatient treatment of mental illness significantly reduces arrest rates for people with mental health problems and saves taxpayers money.

“This study shows that providing mental health care is not only in the best interest of people with mental illness, but in the best interests of society,” says Dr. Sarah Desmarais, an assistant professor of psychology at NC State and co-author of a paper describing the research.

The researchers wanted to determine the extent to which treating mental illness can keep people with mental health problems out of trouble with the law. It is well established that people with mental health problems, such as schizophrenia or bipolar disorder, make up a disproportionate percentage of defendants, inmates and others who come into contact with the criminal justice system.

The researchers identified 4,056 people who had been hospitalized for mental illness in 2004 or 2005 and then tracked them from 2005 to 2012. The researchers were able to determine which individuals were receiving government-subsidized medication and which were receiving government-subsidized outpatient services, such as therapy. The researchers were also able to determine who was arrested during the seven-year study period.

“Our research shows that people receiving medication were significantly less likely to be arrested,” Desmarais says. “Outpatient services also resulted in a decreased likelihood of arrest.”

The researchers also compared criminal justice costs with mental health treatment costs. Individuals who were arrested received less treatment and each cost the government approximately $95,000 during the study period. Individuals who were not arrested received more treatment and each cost the government approximately $68,000 during the study period.

“It costs about $10 less per day to provide treatment and prevent crime. That’s a good investment,” Desmarais says.

“Effects of Outpatient Treatment on Risk of Arrest of Adults With Serious Mental Illness and Associated Costs”

Abstract: Objective: This study examined whether possession of psychotropic medication and receipt of outpatient services reduce the likelihood of posthospitalization arrest among adults with serious mental illness. A secondary aim was to compare service system costs for individuals who were involved with the justice system and those who were not. Methods: Claims data for prescriptions and treatments were used to describe patterns and costs of outpatient services between 2005 and 2012 for 4,056 adult Florida Medicaid enrollees with schizophrenia or bipolar disorder after discharge from an index hospitalization. Multivariable time-series analysis tested the effects of medication and outpatient services on arrest (any, felony, or misdemeanor) in subsequent 30-day periods. Results: A total of 1,263 participants (31%) were arrested at least once during follow-up. Monthly medication possession and receipt of outpatient services reduced the likelihood of any arrests (misdemeanor or felony) and of misdemeanor arrests. Possession of medications for 90 days after hospital discharge also reduced the likelihood of arrest. Prior justice involvement, minority racial-ethnic status, and male sex increased the risk of arrest, whereas older age decreased it. Criminal justice and behavioral health system costs were significantly higher for the justice-involved group than for the group with no justice involvement. Conclusions: Routine outpatient treatment, including medication and outpatient services, may reduce the likelihood of arrest among adults with serious mental illness. Medication possession over a 90-day period after hospitalization appears to confer additional protection. Overall, costs were lower for those who were not arrested, even when they used more outpatient services.

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Researchers have discovered a pathway by which the brain controls a molecule critical to forming long-term memories and connected with bipolar disorder and schizophrenia.

The discovery was made by a team of scientists led by Alexei Morozov, an assistant professor at the Virginia Tech Carilion Research Institute.

The mechanism – a protein called Rap1 – controls L-type calcium channels, which participate in the formation of long-term memories. Previous studies have also linked alterations in these ion channels to certain psychiatric disorders. The discovery of the channels’ regulation by Rap1 could help scientists understand the physiological genesis of bipolar disorder and schizophrenia.

“People with genetic mutations affecting L-type calcium channels have higher rates of bipolar disorder and schizophrenia,” said Morozov. “This suggests that there might be a relationship between the activation of L-type calcium channels and these psychiatric disorders. Understanding how these ion channels are controlled is the first step to determining how their functioning or malfunctioning affects mental health.”

A single neuron in the brain can have thousands of synapses, each of which can grow, strengthen, weaken, and change structurally in response to learning new information. Electric signals traveling from neuron to neuron jump across these synapses through chemical neurotransmitters. The release of these chemicals is caused by the flow of electrically charged atoms through a particular subset of ion channels known as voltage-gated calcium channels.

Previous studies have shown that blocking these ion channels inhibits the formation of long-term memories. Although it was known that L-type calcium channels are activated in response to learning, how they are controlled was a mystery.

In the experiment, Morozov and colleagues knocked out the gene responsible for coding the enzyme Rap1, which he suspected played a role in activating L-type calcium channels. The researchers then used live imaging techniques to monitor the release of neurotransmitters and electron microscopy to visualize L-type channels at synapses. They discovered that, without Rap1, the L-type calcium channels were more active and more abundant at synapses all the time, increasing the release of neurotransmitters. The results showed that Rap1 is responsible for suppressing L-type calcium channels, allowing them to activate only at the proper moments, possibly during long-term memory formation.

“Our next step is to determine whether this new signaling pathway is altered in cases of mental disease,” said Morozov. “If so, it could help us gain a better understanding of the molecular underpinnings of channel-related psychiatric disorders, such as bipolar disorder and schizophrenia. Such knowledge would go a long way toward developing new therapeutic methods.”

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Lithium can reduce suicide risk and help prevent deliberate self harm in people with mood disorders, according a new study in British Medical Journal (BMJ).

The research showed that the drug appeared to lower the likelihood of death and suicide by over 60% compared with placebo.

The finding “reinforces lithium as an effective agent to reduce the risk of suicide in people with mood disorders,” the scientists said.

Mood disorders are a major cause of global disability – the two main types are unipolar, which is commonly known as clinical depression, and bipolar disorder, which can also be called manic depression.

Both conditions are severe and long-term and involve extreme mood swings. Patients with bipolar disorder, however, also experience episodes of mania or hypomania.

People affected by a mood disorder have a 30 times higher likelihood of suicide than the general population. Mood stabilizing drugs, such as lithium, anticonvulsants or antipsychotics, used for the treatment of these conditions can help keep mood within normal limits.

However, experts have not known their role in suicide prevention, and therefore, researchers from the universities of Oxford, UK and Verona, Italy set out to examine whether lithium has a particular preventive effect for suicide and self harm in patients with unipolar and bipolar mood disorders.

Forty-eight randomized controlled trials consisting of 6,674 volunteers were examined. The studies compared lithium with either placebo or active drugs in long-term treatment for mood disorders.

Results showed that lithium was more successful than placebo in lowering the number of suicides and deaths from any cause.

However, no clear benefits were found for lithium in preventing deliberate self harm compared with placebo.

The experts said:

“When lithium was compared with each active individual treatment, a statistically significant difference was found only with carbamazepine for deliberate self harm. Overall, lithium tended to be generally better than the other active treatments, with small statistical variation between the results.”

“This updated systematic review reinforces lithium as an effective agent to reduce the risk of suicide in people with mood disorders,” explained the investigators.

The drug’s anti-suicidal effects may be exerted by “reducing relapse of mood disorder,” the authors said.

However, they pointed out “there is some evidence that lithium decreases aggression and possibly impulsivity, which might be another mechanism mediating the anti-suicidal effect.”

Lithium has many side effects, the scientists pointed out. However, doctors “need to take a balanced view of the likely benefits and harm of lithium in the individual patient.”

The authors concluded:

“Understanding the mechanism by which lithium acts to decrease suicidal behavior could lead to a better understanding of the neurobiology of suicide.”

A 2009 study suggested that very low levels of lithium in drinking water may help prevent suicide in the general population.

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