Posts tagged mental illness
Articles and news from the latest research reports.
Depression top cause of illness in world’s teens, WHO report
Depression is the top global cause of illness and disability for adolescents, with suicide the third-biggest cause of death, the World Health Organization said on Wednesday.
The finding is in a new report by the UN agency, which has pulled together a wealth of published evidence with direct consultations with 10 to 19-year-olds around the world to assess the health issues that affect them.
“The world has not paid enough attention to the health of adolescents,” says Flavia Bustreo, head of the WHO’s family, women and children’s health division.
Researchers Identify Genetic Marker Linked to OCD
A group of researchers led by Johns Hopkins scientists say they have identified a genetic marker that may be associated with the development of obsessive-compulsive disorder (OCD), whose causes and mechanisms are among the least understood among mental illnesses.
The results of the research are published online May 13 by the journal Molecular Psychiatry.
“If this finding is confirmed, it could be useful,” says study leader Gerald Nestadt, M.D., M.P.H., a professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine and director of Johns Hopkins’ Obsessive-Compulsive Disorder Program. “We might ultimately be able to identify new drugs that could help people with this often disabling disorder, one for which current medications work only 60 to 70 percent of the time.”
Nestadt and his team conducted what is known as a genome-wide association study, scanning the genomes of more than 1,400 people with OCD and more than 1,000 close relatives of people with the mental disorder. A significant association was identified in OCD patients near a gene called protein tyrosine phosphokinase (PTPRD).
OCD is a condition marked by thoughts and images that chronically intrude in the mind and by repetitive behaviors aimed at reducing the associated anxiety. Some of the least disabling forms of the disorder can add an extra hour to the day’s routine, causing distress and interfering with daily life. Some people are so disabled that they can’t leave their homes.
Experts say OCD affects an estimated 1 to 2 percent of the U.S. population, and the World Health Organization has called it one of the more disabling medical conditions worldwide. Antidepressants known as SSRIs work for some people, but not everyone; the same is true of behavioral therapy.
Nestadt says the genome-wide association study findings of a PTRPD-OCD link add to evidence that the genetic region they identified is important. The gene has already been shown in animals to be possibly involved in learning and memory, traits influenced by OCD in humans. Moreover, some cases of attention-deficit hyperactivity disorder (ADHD) have been associated with the gene, and OCD and ADHD have some symptoms in common. He says the gene also works with another gene family, SLITRK, which has also been associated with OCD in animals.
“OCD research has lagged behind other psychiatric disorders in terms of genetics,” Nestadt says. “We hope this interesting finding brings us closer to making better sense of it — and helps us find ways to treat it.”
(Image credit: Jennifer Soo)
Ιn resting brains, Yale researchers see signs of schizophrenia
In an advance that increases hopes of finding biological markers for schizophrenia, Yale researchers have discovered widespread disruption of signals while the brain is at rest in those suffering from the disabling neuropsychiatric disease.
The Yale team used fMRI scans and created a mathematical model that simulates brain activity to discover the disruptions in global signaling — or patterns of neurological activity while the brain is not involved in any particular task. Previously, many researchers had thought that the overall brain activity at rest was mostly “background noise” and not clinically important, said Alan Anticevic, assistant professor in psychiatry at the Yale School of Medicine and senior author of the study, reported online May 5 in the Proceedings of the National Academy of Sciences. “To our knowledge these results provide the first evidence that global whole-brain signals are altered in schizophrenia, calling into question the standard removal of this signal in clinical neuroimaging studies,” Anticevic said.
These novel results have vital and broad implications for neuroimaging, as the search for neuropsychiatric biomarkers that could lead to early intervention and improved patient outcomes remains a prominent focus outlined by the National Institute of Mental Health.
Research in the News: Brain at rest yields clues to origins of mental illness
While at rest, multiple regions of the brain remain engaged in a highly heritable, stable pattern of activity called the default mode network. Researchers have found that this network is often disrupted in people with schizophrenia and bipolar disorder, which appear to share underlying genetic causes. This network is often abnormal in their unaffected close relatives, suggesting common genetic roots.
Now researchers at the Yale University School of Medicine and the Institute of Living in Hartford have devised a method to simultaneously identify many genes that play a role in disrupting this network. “Previous studies have identified small numbers of different genes which each contribute in a small way to schizophrenia and bipolar disorder but tell us little overall about the development of psychosis in an individual,” said Godfrey Pearlson, professor of psychiatry and neurobiology and senior author of the study. “Now we have begun to identify markers for these conditions that consist of hundreds of such genes acting simultaneously in recognized pathways that will eventually help in our designing novel ways to intervene in the disease process.”
The study was published April 28 in the Proceedings of the National Academy of Sciences.
Depression is detectable in the blood
Researchers at the MedUni Vienna have demonstrated the possibility of using a blood test to detect depression. While blood tests for mental illnesses have until recently been regarded as impossible, a recent study clearly indicates that, in principle, depression can in fact be diagnosed in this way and this could become reality in the not too distant future.
Serotonin transporter (SERT) is a protein in the cell membrane that facilitates the transport of the neurotransmitter serotonin (popularly known as the “happiness hormone”) into the cell. In the brain, serotonin transporter regulates neural depression networks. Depressive conditions can frequently be caused by a lack of serotonin. As a result, the serotonin transporter is also the point of action for the major antidepressant drugs.
The serotonin transporter, however, also occurs in large quantities in numerous other organs such as the intestines or blood. Recent studies have shown that the serotonin transporter in the blood works in exactly the same way as in the brain. In the blood, it ensures that blood platelets maintain the appropriate concentration of serotonin in the blood plasma.
Researchers at the MedUni Vienna have now used functional magnetic resonance imaging of the brain and pharmacological investigations to demonstrate that there is a close relationship between the speed of the serotonin uptake in blood platelets and the function of a depression network in the brain.
This network is termed the “default mode network” because it is primarily active at rest and processes content with strong self-reference. Findings from recent years have also demonstrated that it is actively suppressed during complex thought processes, which is essential for adequate levels of concentration. Interestingly, patients with depression find it difficult to suppress this network during thought processes, leading to negative thoughts and ruminations as well as poor concentration.
“This is the first study that has been able to predict the activity of a major depression network in the brain using a blood test. While blood tests for mental illnesses have until recently been regarded as impossible, this study clearly shows that a blood test is possible in principle for diagnosing depression and could become reality in the not too distant future,” explains study leader Lukas Pezawas from the Department of Biological Psychiatry at the University Department of Psychiatry and Psychotherapy within the MedUni Vienna. This result means that the diagnosis of depression through blood tests could become reality in the not too distant future.
Smoking’s toll on mentally ill analyzed
Those in the United States with a mental illness diagnosis are much more likely to smoke cigarettes and smoke more heavily, and are less likely to quit smoking than those without mental illness, regardless of their specific diagnosis, a new study by researchers from the Yale School of Medicine shows.
They also found variations in smoking rates and likelihood of quitting among different diagnoses of mental illness. The results are reported in the April issue of the journal Tobacco Control.
Thirty-nine percent of adults with a psychiatric diagnosis smoked compared to 16% without a diagnosis, according to data from the National Epidemiologic Survey on Alcohol and Related Conditions analyzed by researchers. Two out of every three people with drug use disorder smoke, compared to one out of three with social phobia.
“We know that smokers with mental illness are more susceptible to smoking-related disease, and those with mental illness die 25 years earlier than adults without mental illness,” said Sherry McKee, associate professor of psychiatry, and senior author on the study. “Effective smoking cessation treatments are available and we know that smokers with mental illness can quit smoking. We need to address why smokers with mental illness are not being treated for their smoking.”
Over the three-year study period, 22% of smokers with no psychiatric disorders were able to quit smoking, whereas rates of quitting among those with psychiatric disorders were 25% lower. Rates of quitting were lowest among those with dysthymia (10%), agoraphobia (13%), and social phobia (13%). “We also found that individuals with multiple diagnoses had the lowest quit rates,” added Philip Smith, lead author on the study.
This study adds to evidence that smokers with mental illness consume nearly half of all cigarettes in the United States, despite making up a substantially smaller proportion of the population.
Researchers and policymakers are increasingly calling attention to this important public health issue, and this study helps point to a need for interventions and policy that directly help individuals with mental illness quit smoking.
Experimental Cancer Drug Reverses Schizophrenia in Adolescent Mice
Johns Hopkins researchers say that an experimental anticancer compound appears to have reversed behaviors associated with schizophrenia and restored some lost brain cell function in adolescent mice with a rodent version of the devastating mental illness.
The drug is one of a class of compounds known as PAK inhibitors, which have been shown in animal experiments to confer some protection from brain damage due to Fragile X syndrome, an inherited disease in humans marked by mental retardation. There also is some evidence, experts say, suggesting PAK inhibitors could be used to treat Alzheimer’s disease. And because the PAK protein itself can initiate cancer and cell growth, PAK inhibitors have also been tested for cancer.
In the new Johns Hopkins-led study, reported online March 31 in the Proceedings of the National Academy of Sciences, the researchers found that the compound, called FRAX486, appears to halt an out-of-control biological “pruning” process in the schizophrenic brain during which important neural connections are unnecessarily destroyed.
Working with mice that mimic the pathological progression of schizophrenia and related disorders, the researchers were able to partially restore disabled neurons so they could connect to other nerve cells.
The Johns Hopkins team says the findings in teenage mice are an especially promising step in efforts to develop better therapies for schizophrenia in humans, because schizophrenia symptoms typically appear in late adolescence and early adulthood.
“By using this compound to block excess pruning in adolescent mice, we also normalized the behavior deficit,” says study leader Akira Sawa, M.D., Ph.D., a professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. “That we could intervene in adolescence and still make a difference in restoring brain function in these mice is intriguing.”
For the mouse experiments, Sawa and his colleagues chemically turned down the expression of a gene known as Disrupted-in-Schizophrenia 1 (DISC1), whose protein appears to regulate the fate of neurons in the cerebral cortex responsible for “higher-order” functions, like information processing.
In studies of rodent brain cells, the researchers found that a DISC1 deficit caused deterioration of vital parts of the neuron called spines, which help neurons communicate with one another.
Reduced amounts of DISC1 protein also impact the development of a protein called Kalirin-7 (KAL7), which is needed to regulate another protein called Rac1. Without enough DISC1, KAL7 can’t adequately control Rac1 production and the development of neuronal spines. Excess Rac1 apparently erases spines and leads to excess PAK in the mice.
By using FRAX486 to reduce the activity of PAK, the researchers were able to protect against the deterioration of the spines caused by too little DISC1, halting the process. This normalized the excess pruning and resulted in the restoration of missing spines. They were able to see this by peering into the brains of the mice with DISC1 mutations on the 35th and 60th day of their lives, the equivalent of adolescence and young adulthood.
Sawa, who is also director of the Johns Hopkins Schizophrenia Center, cautions that it has not yet been shown that PAK is elevated in the brains of people with schizophrenia. Thus, he says, it is important to validate these results by determining whether this haywire PAK cascade is also occurring in humans.
In the mice, the researchers also found that their behavior improved when PAK inhibitors were used. The mice were tested for their reaction to noises. There is a neuropsychiatric phenomenon in which any organism will react less to a strong, startling sound when they have first been primed by hearing a weaker one. In schizophrenia, the first noise makes no impact on the reaction to the second one.
The mice in the study showed improvements in their reactions after being treated with the PAK inhibitor. The drug was given in small doses and appeared to be safe for the animals.
“Drugs aimed at treating a disease should be able to reverse an already existing defect as well as block future damage,” Sawa says. “This compound has the potential to do both.”
(Image: iStockphoto)
New evidence that chronic stress predisposes brain to mental illness
University of California, Berkeley, researchers have shown that chronic stress generates long-term changes in the brain that may explain why people suffering chronic stress are prone to mental problems such as anxiety and mood disorders later in life.
Their findings could lead to new therapies to reduce the risk of developing mental illness after stressful events.
Doctors know that people with stress-related illnesses, such as post-traumatic stress disorder (PTSD), have abnormalities in the brain, including differences in the amount of gray matter versus white matter. Gray matter consists mostly of cells – neurons, which store and process information, and support cells called glia – while white matter is comprised of axons, which create a network of fibers that interconnect neurons. White matter gets its name from the white, fatty myelin sheath that surrounds the axons and speeds the flow of electrical signals from cell to cell.
How chronic stress creates these long-lasting changes in brain structure is a mystery that researchers are only now beginning to unravel.
In a series of experiments, Daniela Kaufer, UC Berkeley associate professor of integrative biology, and her colleagues, including graduate students Sundari Chetty and Aaron Freidman, discovered that chronic stress generates more myelin-producing cells and fewer neurons than normal. This results in an excess of myelin – and thus, white matter – in some areas of the brain, which disrupts the delicate balance and timing of communication within the brain.
“We studied only one part of the brain, the hippocampus, but our findings could provide insight into how white matter is changing in conditions such as schizophrenia, autism, depression, suicide, ADHD and PTSD,” she said.
The hippocampus regulates memory and emotions, and plays a role in various emotional disorders.
Kaufer and her colleagues published their findings in the Feb. 11 issue of the journal Molecular Psychiatry.
Does stress affect brain connectivity?
Kaufer’s findings suggest a mechanism that may explain some changes in brain connectivity in people with PTSD, for example. One can imagine, she said, that PTSD patients could develop a stronger connectivity between the hippocampus and the amygdala – the seat of the brain’s fight or flight response – and lower than normal connectivity between the hippocampus and prefrontal cortex, which moderates our responses.
“You can imagine that if your amygdala and hippocampus are better connected, that could mean that your fear responses are much quicker, which is something you see in stress survivors,” she said. “On the other hand, if your connections are not so good to the prefrontal cortex, your ability to shut down responses is impaired. So, when you are in a stressful situation, the inhibitory pathways from the prefrontal cortex telling you not to get stressed don’t work as well as the amygdala shouting to the hippocampus, ‘This is terrible!’ You have a much bigger response than you should.”
She is involved in a study to test this hypothesis in PTSD patients, and continues to study brain changes in rodents subjected to chronic stress or to adverse environments in early life.
Stress tweaks stem cells
Kaufer’s lab, which conducts research on the molecular and cellular effects of acute and chronic stress, focused in this study on neural stem cells in the hippocampus of the brains of adult rats. These stem cells were previously thought to mature only into neurons or a type of glial cell called an astrocyte. The researchers found, however, that chronic stress also made stem cells in the hippocampus mature into another type of glial cell called an oligodendrocyte, which produces the myelin that sheaths nerve cells.
The finding, which they demonstrated in rats and cultured rat brain cells, suggests a key role for oligodendrocytes in long-term and perhaps permanent changes in the brain that could set the stage for later mental problems. Oligodendrocytes also help form synapses – sites where one cell talks to another – and help control the growth pathway of axons, which make those synapse connections.
The fact that chronic stress also decreases the number of stem cells that mature into neurons could provide an explanation for how chronic stress also affects learning and memory, she said.
Kaufer is now conducting experiments to determine how stress in infancy affects the brain’s white matter, and whether chronic early-life stress decreases resilience later in life. She also is looking at the effects of therapies, ranging from exercise to antidepressant drugs, that reduce the impact of stress and stress hormones.
New risk factor found for schizophrenia
Scientists have discovered a link between a largely unstudied gene and schizophrenia.
They also found a link between the same gene and bipolar disorder, depression and autism.
The University of Aberdeen-led research - published in the Journal of Cell Science - set out to look for genes that might be important for schizophrenia.
During analysis of five major patient cohorts, scientists picked out the poorly-understood gene ULK4 which has previously been associated with hypertension but never before with mental health disorders.
They discovered that a mutation of the gene ULK4 was found far more frequently in patients with schizophrenia.
Researchers also found mutation of ULK4 in some people with bipolar disorder, depression and autism.
First author Dr Bing Lang, Research Fellow at the University of Aberdeen, said: “Schizophrenia is a severe psychiatric disorder affecting about 1% of the population. Genetics are estimated to be between 60 and 80% responsible for the condition, but very few specific susceptibility genes for schizophrenia have been firmly confirmed in humans.
“However our results suggest that mutation of the gene UKL4 can be a rare genetic risk factor for schizophrenia as well as other psychiatric disorders.”
The researchers found evidence that ULK4 regulates many important signalling pathways within nerve cells involved in schizophrenia and stress.
They also discovered that mutation of the gene reduced communication between brain cells.
Professor Colin McCaig, one of the researchers and Head of the University’s School of Medical Sciences, added: “This is an important discovery of a gene involved in major mental health disorders which affects basic nerve cell growth and nerve to nerve communication. We expect it will form another important piece of the jigsaw that will produce a fuller understanding of what goes wrong in the brain in conditions such as schizophrenia.”
Dr Lang added: “We are very excited by our findings. We still need to do much more work to understand the mechanisms underlying the role of UKL4 in schizophrenia in the hope that this may lead to the discovery of new drug targets for a condition that deprives some sufferers of the ability to lead normal, independent lives.”
(Source: abdn.ac.uk)
Alcohol, tobacco, drug use far higher in severely mentally ill
In the largest ever assessment of substance use among people with severe psychiatric illness, researchers at Washington University School of Medicine in St. Louis and the University of Southern California have found that rates of smoking, drinking and drug use are significantly higher among those who have psychotic disorders than among those in the general population.
The study is published online in the journal JAMA Psychiatry.
The finding is of particular concern because individuals with severe mental illness are more likely to die younger than people without severe psychiatric disorders.
“These patients tend to pass away much younger, with estimates ranging from 12 to 25 years earlier than individuals in the general population,” said first author Sarah M. Hartz, MD, PhD, assistant professor of psychiatry at Washington University. “They don’t die from drug overdoses or commit suicide — the kinds of things you might suspect in severe psychiatric illness. They die from heart disease and cancer, problems caused by chronic alcohol and tobacco use.”
The study analyzed smoking, drinking and drug use in nearly 20,000 people. That included 9,142 psychiatric patients diagnosed with schizophrenia, bipolar disorder or schizoaffective disorder — an illness characterized by psychotic symptoms such as hallucinations and delusions, and mood disorders such as depression.
The investigators also assessed nicotine use, heavy drinking, heavy marijuana use and recreational drug use in more than 10,000 healthy people without mental illness.
The researchers found that 30 percent of those with severe psychiatric illness engaged in binge drinking, defined as drinking four servings of alcohol at one time. In comparison, the rate of binge drinking in the general population is 8 percent.
Among those with mental illness, more than 75 percent were regular smokers. This compares with 33 percent of those in the control group who smoked regularly. There were similar findings with heavy marijuana use: 50 percent of people with psychotic disorders used marijuana regularly, versus 18 percent in the general population. Half of those with mental illness also used other illicit drugs, while the rate of recreational drug use in the general population is 12 percent.
“I take care of a lot of patients with severe mental illness, many of whom are sick enough that they are on disability,” said Hartz. “And it’s always surprising when I encounter a patient who doesn’t smoke or hasn’t used drugs or had alcohol problems.”
Hartz said another striking finding from the study is that once a person develops a psychotic illness, protective factors such as race and gender don’t have their typical influence.
Previous research indicates that Hispanics and Asians tend to have lower rates of substance abuse than European Americans. The same is true for women, who tend to smoke, drink and use illicit drugs less often than men.
“We see protective effects in these subpopulations,” Hartz explained. “But once a person has a severe mental illness, that seems to trump everything.”
That’s particularly true, she said, with smoking. During the last few decades, smoking rates have declined in the general population. People over age 50 are much more likely than younger people to have been regular smokers at some point in their lives. For example, about 40 percent of those over 50 used to smoke regularly. Among those under 30, fewer than 20 percent have been regular smokers. But among the mentally ill, the smoking rate is more than 75 percent, regardless of the patient’s age.
“With public health efforts, we’ve effectively cut smoking rates in half in healthy people, but in the severely mentally ill, we haven’t made a dent at all,” she said.
Until recently, smoking was permitted in most psychiatric hospitals and mental wards. Hartz believes that many psychiatrists decided that their sickest patients had enough problems without having to worry about quitting smoking, too. There also were concerns about potential dangers from using nicotine-replacement therapy, while continuing to smoke since smoking is so prevalent among the mentally ill. Recent studies, however, have found those concerns were overblown.
The question, she said, is whether being more aggressive in trying to curb nicotine, alcohol and substance use in patients with severe psychiatric illness can lengthen their lives. Hartz believes health professionals who treat the mentally ill need to do a better job of trying to get them to stop smoking, drinking and using drugs.
“Some studies have shown that although we psychiatrists know that smoking, drinking and substance use are major problems among the mentally ill, we often don’t ask our patients about those things,” she said. “We can do better, but we also need to develop new strategies because many interventions to reduce smoking, drinking and drug use that have worked in other patient populations don’t seem to be very effective in these psychiatric patients.”
(Source: news.wustl.edu)