Genetic manipulation boosts growth of brain cells linked to learning, enhances antidepressants

DALLAS -- UT Southwestern Medical Center investigators have identified a genetic manipulation that increases the development of neurons in the brain during aging and enhances the effect of antidepressant drugs.

The research finds that deleting the Nf1 gene in mice results in long-lasting improvements in neurogenesis, which in turn makes those in the test group more sensitive to the effects of antidepressants.

"The significant implication of this work is that enhancing neurogenesis sensitizes mice to antidepressants – meaning they needed lower doses of the drugs to affect 'mood' – and also appears to have anti-depressive and anti-anxiety effects of its own that continue over time," said Dr. Luis Parada, director of the Kent Waldrep Center for Basic Research on Nerve Growth and Regeneration and senior author of the study published in the Journal of Neuroscience.

Just as in people, mice produce new neurons throughout adulthood, although the rate declines with age and stress, said Dr. Parada, chairman of developmental biology at UT Southwestern. Studies have shown that learning, exercise, electroconvulsive therapy and some antidepressants can increase neurogenesis. The steps in the process are well known but the cellular mechanisms behind those steps are not.

"In neurogenesis, stem cells in the brain's hippocampus give rise to neuronal precursor cells that eventually become young neurons, which continue on to become full-fledged neurons that integrate into the brain's synapses," said Dr. Parada, an elected member of the prestigious National Academy of Sciences, its Institute of Medicine, and the American Academy of Arts and Sciences.

The researchers used a sophisticated process to delete the gene that codes for the Nf1 protein only in the brains of mice, while production in other tissues continued normally. After showing that mice lacking Nf1 protein in the brain had greater neurogenesis than controls, the researchers administered behavioral tests designed to mimic situations that would spark a subdued mood or anxiety, such as observing grooming behavior in response to a small splash of sugar water.

The researchers found that the test group mice formed more neurons over time compared to controls, and that young mice lacking the Nf1 protein required much lower amounts of anti-depressants to counteract the effects of stress. Behavioral differences between the groups persisted at three months, six months and nine months. "Older mice lacking the protein responded as if they had been taking antidepressants all their lives," said Dr. Parada.

"In summary, this work suggests that activating neural precursor cells could directly improve depression- and anxiety-like behaviors, and it provides a proof-of-principle regarding the feasibility of regulating behavior via direct manipulation of adult neurogenesis," Dr. Parada said.

Dr. Parada's laboratory has published a series of studies that link the Nf1 gene – best known for mutations that cause tumors to grow around nerves – to wide-ranging effects in several major tissues. For instance, in one study researchers identified ways that the body's immune system promotes the growth of tumors, and in another study, they described how loss of the Nf1 protein in the circulatory system leads to hypertension and congenital heart disease social worker ceus

The current study's lead author is former graduate student Dr. Yun Li, now a postdoctoral researcher at the Massachusetts Institute of Technology. Other co-authors include Yanjiao Li, a research associate of developmental biology, Dr. Renée McKay, assistant professor of developmental biology, both of UT Southwestern, and Dr. Dieter Riethmacher of the University of Southampton in the United Kingdom.

The study was supported by the National Institutes of Health's National Institute of Neurological Disorders and Stroke, and National Institute of Mental Health. Dr. Parada is an American Cancer Society Research Professor.

This news release is available on our World Wide Web home page at www.utsouthwestern.edu/home/news/index.html

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Excessive worrying may have co-evolved with intelligence

What is usually seen as pathology may aid survival of the species

Worrying may have evolved along with intelligence as a beneficial trait, according to a recent study by scientists at SUNY Downstate Medical Center and other institutions. Jeremy Coplan, MD, professor of psychiatry at SUNY Downstate, and colleagues found that high intelligence and worry both correlate with brain activity measured by the depletion of the nutrient choline in the subcortical white matter of the brain. According to the researchers, this suggests that intelligence may have co-evolved with worry in humans.

"While excessive worry is generally seen as a negative trait and high intelligence as a positive one, worry may cause our species to avoid dangerous situations, regardless of how remote a possibility they may be," said Dr. Coplan. "In essence, worry may make people 'take no chances,' and such people may have higher survival rates. Thus, like intelligence, worry may confer a benefit upon the species."

In this study of anxiety and intelligence, patients with generalized anxiety disorder (GAD) were compared with healthy volunteers to assess the relationship among intelligence quotient (IQ), worry, and subcortical white matter metabolism of choline. In a control group of normal volunteers, high IQ was associated with a lower degree of worry, but in those diagnosed with GAD, high IQ was associated with a greater degree of worry. The correlation between IQ and worry was significant in both the GAD group and the healthy control group. However, in the former, the correlation was positive and in the latter, the correlation was negative. Eighteen healthy volunteers (eight males and 10 females) and 26 patients with GAD (12 males and 14 females) served as subjects.

Previous studies have indicated that excessive worry tends to exist both in people with higher intelligence and lower intelligence, and less so in people of moderate intelligence. It has been hypothesized that people with lower intelligence suffer more anxiety because they achieve less success in life.

The results of their study, "The Relationship between Intelligence and Anxiety: An Association with Subcortical White Matter Metabolism," was published in a recent edition of Frontiers in Evolutionary Neuroscience, and can be read at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269637/pdf/fnevo-03-00008.pdf.

The study was selected and evaluated by a member of the Faculty of 1000 (F1000), placing it in their library of the top 2% of published articles in biology and medicine.

SUNY Downstate Medical Center, founded in 1860, was the first medical school in the United States to bring teaching out of the lecture hall and to the patient's bedside. A center of innovation and excellence in research and clinical service delivery, SUNY Downstate Medical Center comprises a College of Medicine, Colleges of Nursing and Health Related Professions, a School of Graduate Studies, a School of Public Health, University Hospital of Brooklyn, and an Advanced Biotechnology Park and Biotechnology Incubator.

SUNY Downstate ranks eighth nationally in the number of alumni who are on the faculty of American medical schools. More physicians practicing in New York City have graduated from SUNY Downstate than from any other medical school social worker continuing education

Mothers and OCD children trapped in rituals have impaired relationships

News Release: Tuesday, April 10, 2012

A new study from Case Western Reserve University finds mothers tend to be more critical of children with obsessive-compulsive disorder than they are of other children in the family. And, that parental criticism is linked to poorer outcomes for the child after treatment.

Parent criticism has been associated with child anxiety in the past, however, researchers wanted to find out if this is a characteristic of the parent or something specific to the relationship between the anxious child and the parent.

“This suggests that mothers of anxious children are not overly critical parents in general. Instead they seem to be more critical of a child with OCD than they are of other children in the home,” said Amy Przeworski, assistant professor of psychology. She is the lead author of the study, “Maternal and Child Expressed Emotion as Predictors of Treatment Response in Pediatric Obsessive-Compulsive Disorder,” in the recent journal, Child Psychiatry & Human Development.

OCD is found in one in 200 children, according to the American Academy of Child and Adolescent Psychiatry. The psychological disorder overcomes individuals with repetitive thoughts that lead to anxiety, which is then acted out in exacting routines or behaviors that can range from foot tapping to eating rituals to school or bedtime preparations.

This research evolved from other studies that found parental criticism is associated with less success in therapy and a relapse of behavior.

“Parents’ criticism may be a reaction to the child’s anxiety. This research is not blaming the parent for the child’s OCD. But it does suggest that the relationship between parents and children with OCD is important and should be a focus of treatment. This means that parents can help children with OCD to get better.” Przeworski says.

“OCD sneaks up on the kids and parents,” Przeworski says.

The psychology professor, who specializes in anxiety disorders, says some parents become concerned when their children show some early warning signs for OCD:

• Rigidity in a child, with things routinely done or said in exactly the same way or order.
• Asking for reassurance many times in the day.
• Repetition of a task from tapping the foot, checking on the stove, washing hands that the child cannot stop when asked.
• Routines that have prescribed patterns or are excessive lengthy: An example is a two-hour shower or raw and chapped hands that look like the child is wearing red gloves.
• Bedtime or dinner rituals, where there is a prescribed order for eating food, placement of food on the plate, etc.
• Temper tantrums where the child goes beyond being stubborn but has anxiety associated with them.
• Children want symmetry in appearance or things around them.

Parents initially may think it is a phase, a habit or stubbornness. Over time, the behaviors become so exacting that the child and family members have to act in prescribed ways. Parents may end up criticizing the child in an effort to get them to drop obsessive-compulsive behaviors.

The researchers videotaped interviews with 62 mother-child pairs just before the child’s OCD treatment began. Children either had medication, therapy, a combination of the two, or a placebo. The children were between the ages of 7 and 17.

Because most mothers bring their children for treatment appointments, the researchers focused on the mother’s view of their children. Mothers were asked to give a five-minute description of their relationship with the child with OCD and the mother’s relationship with the sibling closest in age to the child with OCD. The researchers asked the children to describe their relationships with their mothers and fathers.

The researchers examined the presence of criticism and emotional over-involvement (over-protection or excessive self-sacrificing) in these descriptions. The tone of the OCD child and parent tended toward criticism, they said. The other sibling received more loving expressions. Parent criticism was associated with poorer child functioning after treatment.

Przeworski said treatment of OCD has good results, but many times parents misjudge these rigid routines as stubbornness or “just going through a phase” until the behavior takes over family life. Then parents realize the behavior requires therapy professional counselor continuing education

Collaborating with Przeworski were: Lori Zoellner from University of Washington; Martin E. Franklin and Edna B. Foa, University of Pennsylvania School of Medicine; and Abbe Garcia and Jennifer Freeman, Brown University. The study was supported with funds from the National Institute of Mental Health.


Posted by: Susan Griffith, April 10, 2012 01:19 PM | News Topics: Official Release

Spontaneous Gene Glitches Linked to Autism Risk with Older Dads

Non-Inherited Mutations Spotlight Role of Environment – NIH-Supported Study, Consortium ceus for nurses

Researchers have turned up a new clue to the workings of a possible environmental factor in autism spectrum disorders (ASDs): fathers were four times more likely than mothers to transmit tiny, spontaneous mutations to their children with the disorders. Moreover, the number of such transmitted genetic glitches increased with paternal age. The discovery may help to explain earlier evidence linking autism risk to older fathers.

The results are among several from a trio of new studies, supported in part by the National Institutes of Health, finding that such sequence changes in parts of genes that code for proteins play a significant role in ASDs. One of the studies determined that having such glitches boosts a child’s risk of developing autism five to 20 fold.

Taken together, the three studies represent the largest effort of its kind, drawing upon samples from 549 families to maximize statistical power. They reveal sporadic mutations widely distributed across the genome, sometimes conferring risk and sometimes not. While the changes identified don’t account for most cases of illness, they are providing clues to the biology of what are likely multiple syndromes along the autism spectrum.

“These results confirm that it’s not necessarily the size of a genetic anomaly that confers risk, but its location – specifically in biochemical pathways involved in brain development and neural connections. Ultimately, it’s this kind of knowledge that will yield potential targets for new treatments,” explained Thomas, R. Insel, M.D., director of the NIH’s National Institute of Mental Health (NIMH), which funded one of the studies and fostered development of the Autism Sequencing Consortium, of which all three groups are members.

Multi-site research teams led by Mark Daly, Ph.D., of the Harvard/MIT Broad Institute, Cambridge, Mass., Matthew State, M.D., Ph.D., of Yale University, New Haven, Conn., and Evan Eichler, Ph.D., of the University of Washington, Seattle, report on their findings online April 4, 2012 in the journal Nature.

The study by Daly and colleagues was supported by NIMH – including funding under the American Recovery and Reinvestment Act. The State and Eichler studies were primarily supported by the Simons Foundation Autism Research Initiative. The studies also acknowledge the NIH’s National Human Genome Research Institute, National Heart Lung and Blood Institute, and National Institute on Child Health and Human Development and other NIH components.

All three teams sequenced the protein coding parts of genes in parents and an affected child – mostly in families with only one member touched by autism. One study also included comparisons with healthy siblings. Although these protein-coding areas represent only about 1.5 percent of the genome, they harbor 85 percent of disease-causing mutations. This strategy optimized the odds for detecting the few spontaneous errors in genetic transmission that confer autism risk from the “background noise” generated by the many more benign mutations.

Like larger deletions and duplications of genetic material previously implicated in autism and schizophrenia, the tiny point mutations identified in the current studies are typically not inherited in the conventional sense – they are not part of parents’ DNA, but become part of the child’s DNA. Most people have many such glitches and suffer no ill effects from them. But evidence is building that such mutations can increase risk for autism if they occur in pathways that disrupt brain development.

State’s team found that 14 percent of people with autism studied had suspect mutations – five times the normal rate. Eichler and colleagues traced 39 percent of such mutations likely to confer risk to a biological pathway known to be important for communications in the brain.

Although Daly and colleagues found evidence for only a modest role of the chance mutations in autism, those pinpointed were biologically related to each other and to genes previously implicated in autism.

The Eichler team turned up clues to how environmental factors might influence genetics. The high turnover in a male’s sperm cells across the lifespan increases the chance for errors to occur in the genetic translation process. These can be passed-on to the offspring’s DNA, even though they are not present in the father’s DNA. This risk may worsen with aging. The researchers discovered a four-fold marked paternal bias in the origins of 51 spontaneous mutations in coding areas of genes that was positively correlated with increasing age of the father. So such spontaneous mutations could account for findings of an earlier study that found fathers of boys with autism were six times – and of girls 17 times – more likely to be in their 40’s than their 20’s.

“We now have a path forward to capture a great part of the genetic variability in autism – even to the point of being able to predict how many mutations in coding regions of a gene would be needed to account for illness,” said Thomas Lehner, Ph.D., chief of the NIMH Genomics Research Branch, which funded the Daly study and helped to create the Autism Sequencing Consortium. “These studies begin to tell a more comprehensive story about the molecular underpinnings of autism that integrates previously disparate pieces of evidence.”

References

Sanders SJ, Murtha MT, Gupta AR, Murdoch JD, Raubeson MJ, Willsey AJ, Ercan-Sencicek AG, DiLullo NM, Parikshak NN, Stein JL, Walker MF, Ober GT, Teran NA, Song Y, El-Fishawy P, Murtha RC, Choi M, Overton JD, Bjornson RD, Carriero NJ, Meyer KA, Bilguvar K, Mane SM, Sestan N, Lifton RP, Günel M, Roeder K, Geschwind DH, Devlin B, State MW. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. April 5, 2012. Nature.

O’Roak BJ, Vives L, Girirajan S, Karakoc E, Krumm N, Coe BP, Levy R, Ko A, Lee C, Smith JD, Turner EH, Stanaway IB, Vernot B, Malig M, Baker C, Reilly B, Akey JM, Borenstein E, Rieder MJ, Nickerson DA, Bernier R, Shendure J, Eichler EE. Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature. April 5, 2012.

Neale BM, Kou Y, Liu L, Ma’ayan A, Samocha KE, Sabo A, Lin CF, Stevens C, Wang LS, Makarov V, Polak P, Yoon S, Maguire J, Crawford EL, Campbell NG, Geller ET, Valladares O, Schafer C, Liu H, Zhao T, Cai G, Lihm J, Dannenfelser R, Jabado O, Peralta Z, Nagaswamy U, Muzny D, Reid JG, Newsham I, Wu Y, Lewis L, Han Y, Voight BF, Lim E, Rossin E, Kirby A, Flannick J, Fromer M, Shair K, Fennell T, Garimella K, Banks E, Poplin R, Gabriel S, DePristo M, Wimbish JR, Boone BE, Levy SE, Betancur C, Sunyaev S, Boerwinkle E, Buxbaum JD, Cook EH, Devlin B, Gibbs RA, Roeder K, Schellenberg GD, Sutcliffe JS, Daly MJ. Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature. April 5, 2012.

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The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit the NIH website.

Antipsychotic drug may be helpful treatment for anorexia nervosa

Mouse model of anorexia offers opportunity to study drugs effective for disorder

Low doses of a commonly used atypical antipsychotic drug improved survival in a mouse model of anorexia nervosa, University of Chicago researchers report this month. The result offers promise for a common and occasionally fatal eating disorder that currently lacks approved drugs for treatment.

Mice treated with small doses of the drug olanzapine were more likely to maintain their weight when given an exercise wheel and restricted food access, conditions that produce activity-based anorexia (ABA) in animals. The antidepressant fluoxetine, commonly prescribed off-label for anorexic patients, did not improve survival in the experiment.

"We found over and over again that olanzapine was effective in harsher conditions, less harsh conditions, adolescents, adults — it consistently worked," said the paper's first author Stephanie Klenotich, graduate student in the Committee on Neurobiology at the University of Chicago Biological Sciences.

The study, published in Neuropsychopharmacology, was the product of a rare collaboration between laboratory scientists and clinicians seeking new treatment options for anorexia nervosa. As many as one percent of American women will suffer from anorexia nervosa during their lifetime, but only one-third of those people will receive treatment.

Patients with anorexia are often prescribed off-label use of drugs designed for other psychiatric conditions, but few studies have tested the drugs' effectiveness in animal models.

"Anorexia nervosa is the most deadly psychiatric disorder, and yet no approved pharmacological treatments exist," said Stephanie Dulawa, PhD, assistant professor of Psychiatry & Behavioral Neuroscience at the University of Chicago Medicine and senior author of the study. "One wonders why there isn't more basic science work being done to better understand the mechanisms and to identify novel pharmacological treatments."

One challenge is finding a medication that patients with anorexia nervosa will agree to take regularly, said co-author Daniel Le Grange, PhD, professor of Psychiatry & Behavioral Neuroscience and director of the Eating Disorders Clinic at the University of Chicago Medicine. Drugs that directly cause weight gain or carry strong sedative side effects are often rejected by patients.

"Patients are almost uniformly very skeptical and very reluctant to take any medication that could lower their resolve to refrain from eating," Le Grange said. "There are long-standing resistances, and I think researchers and clinicians have been very reluctant to embark on that course, since it's just littered with obstacles."

Both fluoxetine and olanzapine have been tried clinically to supplement interventions such as family-based treatment and cognitive-behavioral therapy. But their direct effect on anorexia nervosa behavior — in humans or animals — is lacking in sufficient data.

To test the effectiveness of these drugs in laboratory mice, Klenotich adapted the ABA protocol from previously published rat studies: Mice given 24-hour access to a running wheel but only six hours a day of food access become hyperactive, eat less and rapidly lose weight, with a 25 percent reduction from baseline considered to be the "drop-out" survival point.

In Klenotich's study, mice were pretreated with fluoxetine, olanzapine or saline before starting the ABA protocol, and treatment continued throughout the ABA period. Researchers then measured how many mice in each group reached the drop-out point for weight loss over 14 days of food restriction and exercise wheel access. Treatment with the antipsychotic olanzapine significantly increased survival over the control group, while fluoxetine treatment produced no significant effects on survival.

Importantly, a low dose of olanzapine did not decrease overall running activity in the mice, indicating that sedative effects of the drug were minimal. In future experiments, the researchers hope to use different drugs and genetic methods to determine exactly how olanzapine is effective against symptoms of anorexia nervosa, perhaps pointing toward a better drug without the negative image or side effects of an antipsychotic.

"We can dissect the effect of olanzapine and hopefully identify the mechanisms of action, and identify what receptor systems we want to target," Klenotich said. "Hopefully, we can develop a newer drug that we can aim towards the eating disorders clinic as an anorexic-specific drug that might be a little more acceptable to patients."

The study offers support for the clinical use of olanzapine, for which clinical trials are already under way to test in patients. Le Grange said the development of a pharmacological variant that more selectively treats anorexia nervosa could be a helpful way to avoid the "stigma" of taking an antipsychotic while giving clinicians an additional tool for helping patients.

"I think the clinical field is certainly very ready for something that is going to make a difference," Le Grange said. "I'm not saying there's a 'magic pill' for anorexia nervosa, but we have been lacking any pharmacological agent that clearly contributes to the recovery of our patients. Many parents and many clinicians are looking for that, because it would make our job so much easier if there was something that could turn symptoms around and speed up recovery."

Additionally, the study demonstrated the innovative experimental design and translational results that can come from a collaboration of laboratory and clinical experts.

"We don't talk to one another often enough in basic science and clinical science," Le Grange said. "More of that would be helpful for clinicians to understand the neurobiology of this disease. I'm very excited about the way this project is going, and I think it's going to be clinically very informative."


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The paper, "Olanzapine, but not fluoxetine, treatment increases survival in activity-based anorexia in mice," was published online March 7 by Neuropsychopharmacology (doi: 10.1038/npp.2012.7). In addition to Klenotich, Dulawa and Le Grange, authors include Mariel Seiglie and Priya Dugad of the University of Chicago and Matthew S. McMurray and Jamie Roitman of the University of Illinois at Chicago. Funding for the research was provided by the National Institute of Mental Health.

For more news from the University of Chicago Medical Center, follow us on Twitter at @UChicagoMed, or visit our Facebook page at facebook.com/UChicagoMed, our research blog at sciencelife.uchospitals.edu, or our newsroom at uchospitals.edu/news. counselor ceus

How stress influences disease: Carnegie Mellon study reveals inflammation as the culprit

PITTSBURGH—Stress wreaks havoc on the mind and body. For example, psychological stress is associated with greater risk for depression, heart disease and infectious diseases. But, until now, it has not been clear exactly how stress influences disease and health.

A research team led by Carnegie Mellon University's Sheldon Cohen has found that chronic psychological stress is associated with the body losing its ability to regulate the inflammatory response. Published in the Proceedings of the National Academy of Sciences, the research shows for the first time that the effects of psychological stress on the body's ability to regulate inflammation can promote the development and progression of disease continuing education for social workers

"Inflammation is partly regulated by the hormone cortisol and when cortisol is not allowed to serve this function, inflammation can get out of control," said Cohen, the Robert E. Doherty Professor of Psychology within CMU's Dietrich College of Humanities and Social Sciences.

Cohen argued that prolonged stress alters the effectiveness of cortisol to regulate the inflammatory response because it decreases tissue sensitivity to the hormone. Specifically, immune cells become insensitive to cortisol's regulatory effect. In turn, runaway inflammation is thought to promote the development and progression of many diseases.

Cohen, whose groundbreaking early work showed that people suffering from psychological stress are more susceptible to developing common colds, used the common cold as the model for testing his theory. With the common cold, symptoms are not caused by the virus — they are instead a "side effect" of the inflammatory response that is triggered as part of the body's effort to fight infection. The greater the body's inflammatory response to the virus, the greater is the likelihood of experiencing the symptoms of a cold.

In Cohen's first study, after completing an intensive stress interview, 276 healthy adults were exposed to a virus that causes the common cold and monitored in quarantine for five days for signs of infection and illness. Here, Cohen found that experiencing a prolonged stressful event was associated with the inability of immune cells to respond to hormonal signals that normally regulate inflammation. In turn, those with the inability to regulate the inflammatory response were more likely to develop colds when exposed to the virus.

In the second study, 79 healthy participants were assessed for their ability to regulate the inflammatory response and then exposed to a cold virus and monitored for the production of pro-inflammatory cytokines, the chemical messengers that trigger inflammation. He found that those who were less able to regulate the inflammatory response as assessed before being exposed to the virus produced more of these inflammation-inducing chemical messengers when they were infected.

"The immune system's ability to regulate inflammation predicts who will develop a cold, but more importantly it provides an explanation of how stress can promote disease," Cohen said. "When under stress, cells of the immune system are unable to respond to hormonal control, and consequently, produce levels of inflammation that promote disease. Because inflammation plays a role in many diseases such as cardiovascular, asthma and autoimmune disorders, this model suggests why stress impacts them as well."

He added, "Knowing this is important for identifying which diseases may be influenced by stress and for preventing disease in chronically stressed people."

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In addition to Cohen, the research team included CMU's Denise Janicki-Deverts, research psychologist; Children's Hospital of Pittsburgh's William J. Doyle; University of British Columbia's Gregory E. Miller; University of Pittsburgh School of Medicine's Bruce S. Rabin and Ellen Frank; and the University of Virginia Health Sciences Center's Ronald B. Turner.

The National Center for Complementary and Alternative Medicine, National Institute of Mental Health, National Heart, Lung and Blood Institute and the MacArthur Foundation Research Network on Socioeconomic Status and Health funded this research.

Pattern Recognition Technology May Help Predict Future Mental Illness in Teens

Pattern Recognition Technology May Help Predict Future Mental Illness in Teens


Source: NIMH

A technique combining computer-based pattern recognition and brain imaging data accurately distinguished teens at risk for mental disorders from those with low risk and may someday be useful in predicting risk in individuals, according to an NIMH-funded study published February 15, 2012, in the journal PLoS One.

Background

Research on risk for mental disorders generally describes risk factors that apply to groups. To date, no biological measures can accurately predict an individual’s risk of future mental disorders.

Mary Phillips, M.D., of the University of Pittsburgh School of Medicine, and colleagues evaluated the use of computer-based techniques that automatically find patterns in data—these techniques are collectively called machine learning—with functional magnetic resonance imaging (fMRI) data. The researchers obtained fMRI data from 32 teens, half of whom had at least one biological parent diagnosed with bipolar disorder and were therefore at genetic risk for future psychiatric disorders. The other half of teens had no history of mental disorders either personally or in their immediate families.

The teens’ brain activity was assessed as they identified the gender of actors depicting various emotional facial expressions (happy, fearful, or neutral) in a series of photographs. Previous research has linked various mental disorders, especially depression and bipolar disorder, with abnormal patterns of brain activity during this task. Based on this fMRI data, the researchers used machine learning to calculate each participant’s odds for future mental illness social worker ceus

The participants were also assessed clinically and with fMRI at the start of the study, and clinically assessed again about two years later, on average. Long-term follow up is ongoing, with successive face-to-face assessments occurring every other year.

Results

Machine learning combined with fMRI accurately identified most of the healthy teens at genetic risk of future mental disorders vs. healthy teens with low genetic risk. Four of the 16 at-risk teens were misidentified as having low risk.

At the two-year follow up, none of the at-risk teens had developed bipolar disorder, but six were diagnosed with major depression or an anxiety disorder. Among all the at-risk teens identified through machine learning, these six had received the highest odds for belonging to the at-risk group.

Three of the four at-risk teens misidentified as belonging to the low risk group at the start of the study remained healthy at the second assessment. Clinical information for the fourth teen was not available at the time of follow-up.

Significance

Though still a very preliminary study, according to the researchers, machine learning combined with fMRI shows promise for predicting individual risk of developing future mental disorders, especially in at-risk populations.

The ongoing follow-up may also yield further insights into the relationship between depression, anxiety disorders, and bipolar disorder. Many studies have shown that bipolar disorder is often preceded by depression or anxiety disorders, and that these disorders may affect the course of subsequent bipolar disorder.

What’s Next

Larger studies using machine learning and fMRI will help to better define the extent to which pattern recognition techniques can accurately identify people at risk for future mental disorders. Research in this area may also inform early treatment or prevention efforts.

Reference

Mourão-Miranda J, Oliveira L, Ladouceur CD, Marquand A, Brammer M, Birmaher B, Axelson D, Phillips ML. Pattern recognition and functional neuroimaging help to discriminate healthy adolescents at risk for mood disorders from low risk adolescents. PLoS One. 2012;7(2):e29482. Epub 2012 Feb 15. PubMed PMID: 22355302; PubMed Central PMCID: PMC3280237.

Related Funding: K01 MH083001-04; R01 MH060952-11