Researchers at the school’s Feinberg School of Medicine are working on a variety of web-based, mobile and virtual technologies to treat depression and other mood disorders.

Other projects include a virtual human therapist who will work with teens to prevent depression; a medicine bottle that reminds you to take antidepressant medication and tells your doctor if the dosage needs adjusting; and a web-based social network to help cancer survivors relieve sadness and stress.

“We’re inventing new ways technology can help people with mental health problems,” said psychologist Dr. David Mohr, director of the new Center for Behavioral Intervention Technologies and a professor of preventive medicine at Northwestern’s Feinberg School.

“The potential to reduce or even prevent depression is enormous.”

The new approaches could offer new treatment options to people who are unable to access traditional services or are uncomfortable with standard therapy, he added. “They also can be offered at significantly lower costs, which makes them more viable in an era of limited resources.”

Topping the list of projects is a smartphone that spots symptoms of depression by harnessing all the sensor data within the phone to interpret a person’s location, activity level (via an accelerometer), social context and mood. If the phone — which learns your usual patterns — senses you are isolated, it will send a suggestion to call or see friends. The technology, which still is being tweaked, is called Mobilyze! and has been tested in a small pilot study, researchers said, noting it helped reduce symptoms of depression.

“By prompting people to increase behaviors that are pleasurable or rewarding, we believe that Mobilyze! will improve mood,” Mohr said.

“It creates a positive feedback loop. Someone is encouraged to see friends, then enjoys himself and wants to do it again. Ruminating alone at home has the opposite effect and causes a downward spiral.”

The new medicine bottle now in development will track if you forgot your daily dose of antidepressant medication and remind you to take it.

“People whose depression is being treated by primary care doctors often don’t do very well, partly because patients don’t take their medications and partly because the doctors don’t follow up as frequently as they should to optimize the medication and dosage when necessary,” Mohr said. “This pill dispenser addresses both issues.”

The bottle is part of a MedLink system, which will include a mobile app that monitors the patient’s depressive symptoms and any medication side effects and will provide tailored advice to manage problems, he explained. The information is then sent to the physician or health care provider with a recommendation, such as a change in the dose or drug, if necessary. The MedLink system also will be used to improve medication adherence in patients with schizophrenia and HIV.

Also in the works is a virtual programmable human who will role-play with adolescents and adults to teach social and assertiveness skills to prevent and treat depression. A prototype is being developed with researchers from the University of Southern California.

“We think this will be especially helpful for kids, who often are reluctant to see a therapist,” Mohr said.

The program will allow them to practice these behaviors in the safety of virtual space, he said, noting that existing online interventions for teens “look like homework,” while the virtual human feels like a game.

The Northwestern lab will be evaluating a number of social interactions that are hard for teens and adults.

“Having trouble with those situations makes people more vulnerable to depression,” Mohr said. “When people have the confidence and skills to better manage difficult interpersonal interactions, they are less likely to become depressed.”

Previous research also has shown that intervening early in adolescents who have difficulty with social skills can help prevent the first onset of depression, researchers said.

Lastly, the researchers are working on web-based content to help cancer survivors manage stress and depression. They note this is more effective when a human coach checks in on their progress via a phone call or e-mail.

“People are more likely to stick with an online program if they know that someone they like or respect can see what they’re doing,” Mohr said.

His group is creating a social network and collaborative learning environment where peers can serve that function for each other.

“People can get feedback from the group, share goals and check in with members if someone has stayed offline for too long,” he said.

Source: Northwestern University

Teenager on phone photo by shutterstock.

The research on brain activity during competitive social interactions is described in a paper in the Proceedings of the National Academy of Sciences.

Experts say this is the first investigation to use a computational approach to analyze differing patterns of brain activity during these interactions.

“When players compete against each other in a game, they try to make a mental model of the other person’s intentions, what they’re going to do and how they’re going to play, so they can play strategically against them,” said University of Illinois postdoctoral researcher Kyle Mathewson, Ph.D. “We were interested in how this process happens in the brain.”

Previous studies have tended to consider only how one learns from the consequences of one’s own actions, called reinforcement learning, Mathewson said.

These studies have found heightened activity in the basal ganglia, a set of brain structures known to be involved in the control of muscle movements, goals and learning. Many of these structures signal via the neurotransmitter dopamine.

“That’s been pretty well studied and it’s been figured out that dopamine seems to carry the signal for learning about the outcome of our own actions,” Mathewson said.

“But how we learn from the actions of other people wasn’t very well characterized.”

Researchers call this type of learning “belief learning.”

Investigators used functional magnetic resonance imaging (fMRI) to track activity in the brains of participants while they played a competitive game, called a Patent Race, against other players.

The goal of the game was to invest more than one’s opponent in each round to win a prize (a patent worth considerably more than the amount wagered), while minimizing one’s own losses (the amount wagered in each trial was lost). The fMRI tracked activity at the moment the player learned the outcome of the trial and how much his or her opponent had wagered.

A computational model evaluated the players’ strategies and the outcomes of the trials to map the brain regions involved in each type of learning.

“Both types of learning were tracked by activity in the ventral striatum, which is part of the basal ganglia,” Mathewson said. “That’s traditionally known to be involved in reinforcement learning, so we were a little bit surprised to see that belief learning also was represented in that area.”

Belief learning also spurred activity in the rostral anterior cingulate, a structure deep in the front of the brain. This region is known to be involved in error processing, regret and “learning with a more social and emotional flavor,” Mathewson said.

The findings offer new insight into the workings of the brain as it is engaged in strategic thinking, says co-author Ming Hsu. This in turn may aid the understanding of neuropsychiatric illnesses that undermine those processes.

“There are a number of mental disorders that affect the brain circuits implicated in our study,” Hsu said.

“These include schizophrenia, depression and Parkinson’s disease. They all affect these dopaminergic regions in the frontal and striatal brain areas. So to the degree that we can better understand these ubiquitous social functions in strategic settings, it may help us understand how to characterize and, eventually, treat the social deficits that are symptoms of these diseases.”

Source: University of Illinois

Woman playing cards photo by shutterstock.

Unfortunately, despite their widespread use, most of the medications are known to cause the metabolic side effects of obesity and diabetes.

Naturally this presents a significant dilemma to individuals as they weigh a choice between improving their mental health and damaging their physical health.

A new paper in the journal Molecular Psychiatry, discusses the biochemical changes triggered by the antipsychotic drugs.

The medications interfere with normal metabolism by activating a protein called SMAD3. The SMAD3 protein, in turn, is an important component of a cellular conduit termed the transforming growth factor beta (TGFbeta) pathway.

The TGFbeta pathway regulates many biological processes, including cell growth, inflammation, and insulin signaling.

In the current study, all antipsychotics that cause metabolic side effects activated SMAD3, while antipsychotics free from these side effects did not.

What’s more, SMAD3 activation by antipsychotics was completely independent from their neurological effects, raising the possibility that antipsychotics could be designed that retain beneficial therapeutic effects in the brain, but lack the negative metabolic side effects.

“We now believe that many antipsychotics cause obesity and diabetes because they trigger the TGFbeta pathway. Of all the drugs we tested, the only two that didn’t activate the pathway were the ones that are known not to cause metabolic side effects,” said Fred Levine, M.D., Ph.D., senior author of the study.

The TGFbeta pathway also plays an important role in metabolic disease in people who don’t take antipsychotic medications.

“It’s known that people who have elevated TGFbeta levels are more prone to diabetes. So having a dysregulated TGFbeta pathway — whether caused by antipsychotics or through some other mechanism — is clearly a very bad thing,” said Dr. Levine.

“The fact that antipsychotics activate this pathway should be a big concern to pharmaceutical companies. We hope this new information will lead to the development of improved drugs.”

Source: Sanford-Burnham Medical Research Institute

Prior studies have linked the virus to mental illnesses such as bipolar disorder, schizophrenia, anxiety disorder and dementia. Investigators were open-minded to the possibility as genetic fragments and antibodies to this RNA virus causes behavior disorders in a range of mammals and birds.

Moreover, although the results have been inconclusive, traces of the virus have been found to be prevalent in psychiatric patients.

But Mady Hornig, M.D., director of translational research at the Center for Infection and Immunity (CII) at Columbia University, said, “Our study provides compelling evidence that bornaviruses do not play a role in schizophrenia or mood disorders.”

Hornig and collaborators at seven other institutions in the U.S, Germany and Australia, published their findings online in the journal Molecular Psychiatry.

As part of the study, scientists evaluated 198 patients in California with schizophrenia, bipolar disorder and major depressive disorder. They then carefully matched each one of them with a healthy control of the same sex, age, region and socio-economic status, and tested blood of patients and controls for the presence of BDV genetic material and antibodies to BDV.

The investigators hypothesized that if the virus was, in fact, associated with a psychiatric disorder, genetic evidence of infection would be apparent in blood samples taken at the onset and/or at the peak of a psychiatric episode, and antibody evidence would be detectable several weeks afterward.

To test the hypothesis, blood samples were collected within six weeks of the onset of an acute mental episode or upon clinically significant worsening of symptoms. Blood samples were then taken again after six weeks to allow for changes in viral load or antibody levels.

Researchers found no evidence of active or historical infection with BDV in any of the subjects, nor did they discover a relationship between mental illness and bornavirus.

In a commentary in the same issue of the journal, Michael B.A. Oldstone, M.D., an expert in molecular virology and central nervous system infections at the Scripps Research Institute, observes that the design and experimental procedures carried out in the Hornig study provide a gold standard for investigating links between persistent viral infection and human disease.

CII director, W. Ian Lipkin, M.D., senior author of the paper, notes that “it was concern over the potential role of BDV in mental illness and the inability to identify it using classical techniques led us to develop molecular methods for pathogen discovery.

“Ultimately these new techniques enabled us to refute a role for BDV in human disease. But the fact remains that we gained strategies for the discovery of hundreds of other pathogens that have important implications for medicine, agriculture and environmental health.”

Source: Columbia University

Recent technological advances suggest that, for some purposes, cultured neural stem cells may be studied in order to research psychiatric disease mechanisms. But the problem of obtaining the live neural stem cells still persists.

To solve the dilemma, schizophrenia researchers are turning to the nose.

Although it may seem odd, the idea makes sense because the olfactory mucosa, the sense organ of smell in the nose, is continually regenerating new sensory neurons from “adult” stem cells.

These neurons are among the very few nerve cells outside of the skull that connect directly to nerve cells in the brain.

Researchers have learned that by taking small pieces of olfactory tissue from the nose, they are able to gain access to the stem cells from patients with schizophrenia and compare them to cells from healthy individuals.

“We have discovered that patient cells proliferate faster – they are running with a faster speed to their clock controlling the cell cycle – and we have identified some of the molecules that are responsible,” explained Dr. Alan Mackay-Sim, an author of the study.

The findings clearly indicate that the natural cell cycle is dysregulated in individuals diagnosed with schizophrenia.

“This is a first insight into real differences in patient cells that could lead to slightly altered brain development,” Mackay-Sim added. This is an important finding, as scientists are already aware of many developmental abnormalities in the schizophrenic brain.

Dr. John Krystal, editor of Biological Psychiatry, commented: “The current findings are particularly interesting because when we look closely at the clues to the neurobiology of psychiatric disorders, we find new and often unexpected mechanisms implicated.”

Source: Elsevier

Nose photo by shutterstock.

Investigators discovered the genetic variation can cause a six-fold greater risk for children to develop metabolic syndrome. Metabolic syndrome is a combination of symptoms that increase the risk for cardiovascular disease.

The study showed susceptible children displayed an increased risk to develop high blood pressure and elevated fasting blood sugar levels (a precursor to diabetes).

The research is published in the medical research journal Translational Psychiatry.

“This is the first report of an underlying biological factor predisposing children to complications associated with second-generation antipsychotic medication use,” said Dr. Dina Panagiotopoulos, study co-author.

“It’s concerning because these children take medications to treat a chronic disease – mental illness – and then develop risk factors for a second chronic disease,” said co-author Dr. Angela Devlin.

Second-generation antipsychotics such as quetiapine (Seroquel) and risperidone (Risperdal) are prescribed to approximately 5,500 children and youth in British Columbia for psychotic disorders like schizophrenia, mood and anxiety disorders, attention deficit hyperactivity disorder, autism spectrum disorders, adjustment disorders and substance abuse.

Researchers assessed 209 children who were inpatients between April 2008 and June 2011 at the Child & Adolescent Psychiatry Department at BC Children’s Hospital.
Their average age was 13 years, and 105 of the children were treated with second-generation anti-psychotics while 112 did not use these drugs.

DNA analysis showed that eight per cent of children from both groups had a genetic variation called C677T on the MTHFR gene. Children with the MTHFR C677T variant who used these medications were six times more likely to have metabolic syndrome.

The researchers targeted the MTHFR C677T variant because it is known to be associated with metabolic syndrome in adults who have schizophrenia, and with cardiovascular disease in adults who don’t have psychiatric illness.

Devlin and Panagiotopoulos said their discovery is an important step in preventing and managing metabolic complications associated with second-generation antipsychotic medications.

Researchers believe the knowledge is critically important to reduce these risks in childhood because adults with mental illness have a 19 per cent increased mortality rate that is largely due to cardiovascular disease risk.

Future investigations will incorporate a study of vitamin B status among affected children as the MTHFR gene is involved in metabolizing the B-vitamin folate.

“We now plan to assess B vitamin status and dietary intake in children who take these medications to gain a better understanding of this association,” said Panagiotopoulos.

Source: Child & Family Research Institute

PCE is widely used in industry and to dry clean clothes. Prior studies suggests PCE is a neurotoxin that can cause mood changes, anxiety, and depression in people who work with it.

Although the long-term effect of this chemical on children exposed to PCE has been less clear, there is some evidence that children of people who work in the dry cleaning industry have an increased risk of schizophrenia.

In a new study, published in BioMed Central’s open access journal Environmental Health, researchers discovered exposure to PCE as a child was associated with an increased risk of bipolar disorder and post-traumatic stress disorder (PTSD).

In the study, researchers from Boston University followed the incidence of mental illness among adults from Cape Cod, born between 1969 and 1983, who were consequently exposed to PCE both before birth and during early childhood.

Researchers studied this geographic cohort because from 1968, until the early 1980s, water companies in Massachusetts installed vinyl-lined (VL/AC) water pipes that were subsequently found to be leaching PCE into the drinking water supply.

While there was no increase seen in the incidence of depression, regardless of PCE exposure, people with prenatal and early childhood exposure to PCE had almost twice the risk of bipolar disorder, compared to an unexposed group, and their risk of PTSD was raised by 50 percent.

Epidemiologist Dr. Ann Aschengrau from Boston University School of Public Health warned, “It is impossible to calculate the exact amount of PCE these people were exposed to – levels of PCE were recorded as high as 1,550 times the currently recommended safe limit.

“While the water companies flushed the pipes to address this problem, people are still being exposed to PCE in the dry cleaning and textile industries, and from consumer products, and so the potential for an increased risk of illness remains real.”

Source: BioMed Central

Glass of water photo by shutterstock.

The University of Pittsburgh study compared the brain activity of adolescent and adult rats involved in a task in which they anticipated a reward.

The researchers found increased brain cell activity in an area of the brain called the dorsal striatum (DS) — a site commonly associated with habit formation, decision-making, and motivated learning.

However, when adult rats were exposed to the situation, this area of the adult rat brain did not become activated by an anticipated reward.

“The brain region traditionally associated with reward and motivation, called the nucleus accumbens, was activated similarly in adults and adolescents,” said Bita Moghaddam, Ph.D., a coauthor of the paper. “But the unique sensitivity of adolescent DS to reward anticipation indicates that, in this age group, reward can tap directly into a brain region that is critical for learning and habit formation.”

Rather than studying the difference or similarities between the behaviors of adolescents and adults, researchers studied brain actions to see if similar activities were present among the two groups.

The researchers’ predictions proved accurate. Even though the behavior was the same for both adult and adolescent rats, the researchers observed age-related neural response differences that were especially dramatic in the DS during reward anticipation.

This shows that not only is reward expectancy processed differently in an adolescent brain, but also it can affect brain regions directly responsible for decision-making and action selection.

“Adolescence is a time when the symptoms of most mental illnesses—such as schizophrenia and bipolar and eating disorders—are first manifested, so we believe that this is a critical period for preventing these illnesses,” Moghaddam said.

“A better understanding of how the adolescent brain processes reward and decision-making is critical for understanding the basis of these vulnerabilities and designing prevention strategies.”

Researchers state that future research will continue to compare adolescent and adult behavior, especially as it relates to stimulants—such as amphetamines—and their influence on brain activity.

Researchers published a paper on their findings in the Proceedings of the National Academy of Sciences.

Source: University of Pittsburgh

New research finds that brain activity increases during delusional thinking, a finding that may allow new interventions and retraining for people with the disorder.

The study, found in the journal Biological Psychiatry, compared brain activity as statements were read to a group of individuals with schizophrenia and to a group without schizophrenia.

“We studied a type of delusion called a delusion of reference, which occurs when people feel that external stimuli such as newspaper articles or strangers’ overheard conversations are about them,” said researcher and neuropsychologist Dr. Mahesh Menon.

Delusions of reference occur in up to two-thirds of people with schizophrenia. “Then they come up with an explanation for this feeling to make sense of it or give it meaning,” Menon said.

Investigators called the study an initial attempt to prove that the overactive firing of dopamine neurons in specific brain regions is involved in converting neutral, external information into personally relevant information among people with schizophrenia.

The neuronal hyperactivity, they surmised, may lead to symptoms of delusions. “We wanted to see if we could find a way to ‘see’ these delusions during magnetic resonance imaging scanning,” said Menon.

A better understanding of the brain activity and thinking patterns leading to delusions could point the way to more focused treatment options, the researchers say.

Researchers studied 14 people with a schizophrenia diagnosis and 15 people in a control group. Sixty statements were read to the participants while they were in an MRI scanner. For each statement, participants were asked whether they felt it was about them.

Twenty statements were specific to each participant, and included details taken from initial screening interviews. The remaining 40 statements were generic, and evenly divided between statements that were neutral (“he collects CDs”) or that had an emotional connotation (“everybody hates her”).

People with schizophrenia and in the comparison group were just as likely to agree that personalized statements were about themselves. However, those with schizophrenia were significantly more likely to say that the generic statements also referred to them.

“The participants with schizophrenia had a harder time telling the difference between personally relevant and non-relevant statements,” said Menon.

Researchers studied brain activity when participants were read a statement. They found that when a statement was personal, specific brain areas “lit up” in the scanner, indicating activity in these areas.

Among those with schizophrenia, this brain activity occurred even when they said “no” to a statement that was not about them, suggesting that they had greater difficulty in distinguishing what was self-relevant to what was not.

The control group, which was more likely to respond “no” to irrelevant statements, showed little brain activity in response to generic statements.

Even when people with schizophrenia agreed a generic statement was not about them, they took longer to respond and the difference in certain brain activity levels was not as great as in the control group.

Additional research is indicated to explore these initial findings. For instance, patients in this study were all taking anti-psychotic medication. Other studies could look at people early in illness who are not on medication, and could also follow people over time, before and after they take medication.

Source: Centre for Addiction and Mental Health

The study supports recent findings that linked psychotic disorders such as schizophrenia and certain types of international immigration. Investigators believe the research suggests the mental health of young children can be adversely affected by traumatic social upheaval.

Sadly, children who immigrated when under the age of five had a twofold higher risk of such disorders than those who immigrated at age 10-14 years, and a threefold higher risk than those who immigrated as adults.

The study, conducted by investigators at Columbia University’s Mailman School of Public Health and the Parnassia Psychiatric Institute, The Hague, is found in the American Journal of Psychiatry.

“Our findings are consistent with the hypothesis that early life is an important risk period for psychotic disorders. They join the growing body of literature suggesting that adverse social experiences in early life, such as childhood trauma or parental separation raise the risks,” said Ezra Susser, M.D., DrPH.

Researchers studied the four largest immigrant groups in the Dutch city of The Hague –immigrants from Surinam, the Netherlands Antilles, Turkey, and Morocco.

Investigators compared the reports of psychotic disorders among immigrants who migrated at various ages to the incidence among second-generation citizens and among Dutch citizens.

Second-generation citizens (Dutch-born citizens with at least one foreign-born parent) were included to determine if migration itself contributed to the risk or if the long-term experience of being an ethnic minority was the more relevant factor.

Study methodology included identification of every citizen of The Hague, ages 15-54, who contacted a physician over a 7-year period from 1997 to 2005 for a possible psychotic disorder.

The diagnoses were identified and then confirmed by two psychiatrists. Patients diagnosed with any form of psychotic disorder were included in the analysis and were classified according to country of birth and country of parents’ birth.

In total, 273 immigrants, 119 second-generation citizens, and 226 Dutch citizens were diagnosed as having a psychotic disorder.

“Compared with the risk of psychotic disorders among Dutch citizens, the risk among immigrants was most significantly elevated among non-Western immigrants who migrated between the ages of 0 and 4 years,” observed Susser.

“We also found that the risk gradually decreased among those who migrated at older ages and this was the case among male and female immigrants and among all the immigrant groups in this large study.”

A study limitation includes the acknowledgment that many factors may contribute to an increased risk of a psychiatric disorder.

For example, the stress of minority ethnic status appears to contribute. Researchers discovered second-generation immigrants have higher rates of psychotic disorders than native Dutch.

Previous studies also suggest that the social changes associated with cultural and geographic dislocation may be an important factor. Other factors might include vitamin D deficiencies that are common among immigrants.

“This study also goes a long way toward ruling out ‘selective migration’ as an explanation for the increased rates of psychosis among immigrants to The Hague. Young children are unlikely to influence their parents’ decision to migrate,” noted lead author Wim Veling, M.D., Ph.D.

Investigators believe a better understanding of the factors that increase the risk of psychosis will aid the development of proactive strategies to mitigate psychological trauma.

“It might be useful,” they write, “to develop interventions aimed at social empowerment and identity development.”

Source: Columbia University

The new study also found that adolescents with schizophrenia showed an increase in cerebrospinal fluid in the frontal lobe of their brain.

“Progressive loss of brain gray matter has been reported in childhood-onset schizophrenia,” the authors note in the new study. “However, it is uncertain whether these changes are shared by pediatric patients with different psychoses.”

The study was conducted by Celso Arango, M.D., Ph.D., of the Hospital General Universitario Gregorio Marañón, Madrid, Spain, and colleagues, and was designed to examine the progression of brain changes in first-episode early-onset psychosis in teens. The research also wanted to look at the relationship to diagnosis and prognosis after two years.

The patients in the study were drawn from six child and adolescent psychiatric units in Spain.

The authors performed magnetic resonance imaging (MRI) of the brain for 61 patients (25 diagnosed with schizophrenia, 16 with bipolar disorder and 20 with other psychoses) and 70 healthy control participants. MRI scans were conducted at the onset of the study, and then again after two years.

Compared with control patients, those diagnosed with schizophrenia showed greater gray matter volume loss in the frontal lobe during the two-year follow-up. Patients with schizophrenia also showed cerebrospinal fluid increase in the left frontal lobe.

Additionally, changes for total brain gray matter and left parietal gray matter were significantly different in patients with schizophrenia compared with patients in the control group.

Among patients with schizophrenia, progressive brain volume changes in certain areas were related to markers of poorer prognosis, such as more weeks of hospitalization during follow-up and less improvement in negative symptoms.

Greater left frontal gray matter volume loss was related to more weeks of hospitalization whereas severity of negative symptoms correlated with cerebrospinal fluid increase in patients with schizophrenia.

The study could not determine whether the brain changes were a result of the schizophrenia, or whether schizophrenia was the result of the brain changes.

The authors did not find any significant changes in patients with bipolar disorder compared to control patients, and longitudinal brain changes in the control group were consistent with the expected pattern described for healthy adolescents.

“In conclusion, we found progression of gray matter volume loss after a two-year follow-up in patients who ended up with a diagnosis of schizophrenia but not bipolar disease compared with healthy controls,” the authors write.

“Some of these pathophysiologic processes seem to be markers of poorer prognosis. To develop therapeutic strategies to counteract these pathologic progressive brain changes, future studies should focus on their neurobiological underpinnings.”

The new study appears in the January 2012 issue of the journal Archives of General Psychiatry.

Source: JAMA

The variants, also known as CNVs, are alterations in which there are too few or too many copies of sections of DNA. Researchers have known that spontaneously occurring or de novo CNVs, which are genetic mutations not inherited from parents, increase the risk for some neuropsychiatric conditions, such as schizophrenia or autism.

But their role was unclear in bipolar disorder, according to principal investigator Jonathan Sebat, Ph.D., assistant professor of psychiatry and cellular and molecular medicine at the University of California San Diego’s Institute of Genomic Medicine.

Sebat and his colleagues found that de novo CNVs contribute “significant” genetic risk in about 5 percent of early-onset bipolar disorder, which appears in childhood or early adulthood.

The cause — or causes — of bipolar disorder remain unclear, noted the study’s first author Dheeraj Malhotra, Ph.D., assistant project scientist in Sebat’s lab.

Researchers know there is a clear genetic component as the disease runs in families, but previous studies that focused on commonly inherited variants have met with limited success in identifying key susceptibility genes, he said.

Malhotra noted that while the findings do not conclusively pinpoint a specific gene or genomic region, they show “convincing” evidence that rare copy number mutations contribute to the development of early onset bipolar disorder.

He added that sequencing of complete genomes or exomes of a large number of bipolar families is needed to determine the genetic contribution of all forms of de novo mutations to the risk for bipolar disorder.

The findings were published in the Dec. 22 issue of the journal Neuron.

Source: University of California, San Diego

DNA photo by shutterstock.

The new findings suggest that drugs already in development for other diseases might eventually offer hope as a treatment for schizophrenia and related conditions in the elderly.

The research shows the deficit is especially pronounced in younger people. This suggests that treatment might be most effective early on at minimizing or even reversing symptoms of schizophrenia

Schizophrenia is a usually-serious mental disorder characterized by hallucinations, delusions, and emotional difficulties, among other problems.

“We’re excited by the findings,” said Scripps Research Associate Professor Elizabeth Thomas, a neuroscientist who led the study, “and there’s a tie to other drug development work, which could mean a faster track to clinical trials to exploit what we’ve found.”

Working with lead author Bin Tang, a postdoctoral fellow in her lab, and Brian Dean, an Australian colleague at the University of Melbourne, Thomas obtained post-mortem brain samples from schizophrenic and healthy brains held at medical ”Brain Banks” in the United States and Australia. The brains come from either patients who themselves agreed to donate some or all of their bodies for scientific research after death, or from patients whose families agreed to such donations.

Compared to healthy brains, the brain samples from subjects with schizophrenia showed lower levels of a vital chemical in certain DNA portions that would block normal gene expression.

Another critical finding was that in younger subjects with schizophrenia, the problem was much more pronounced.

Thomas sees great potential in her new findings.

Based on the more pronounced results in younger brains, she believes that treatment with certain types of medications called histone deacetylase inhibitors might well prove helpful in reversing or preventing the progression of the condition, especially in younger patients.

The Details of the Research

Over the past few years, researchers have increasingly recognized that cellular-level changes not tied to genetic defects play important roles in causing disease. There is a range of such so-called epigenetic effects that change the way DNA functions without changing a person’s DNA code.

One critical area of epigenetic research is tied to histones. These are the structural proteins that DNA has to wrap around. “There’s so much DNA in each cell of your body that it could never fit in your cells unless it was tightly and efficiently packed,” said Thomas. Histone “tails” regularly undergo chemical modifications to either relax the DNA or repack it. When histones are acetylated, portions of DNA are exposed so that the genes can be used.

The histone-DNA complexes, known as chromatin, are constantly relaxing and condensing to expose different genes, so there is no single right or wrong configuration. But the balance can shift in ways that can cause or exacerbate disease.

DNA is the guide that cellular machinery uses to construct the countless proteins essential to life. If portions of that guide remain closed when they shouldn’t because histones are not acetylated properly, then genes can be effectively turned off when they shouldn’t be with any number of detrimental effects. Numerous research groups have found that altered acetylation may be a key factor in other conditions, from neurodegenerative disorders such as Huntington’s disease and Parkinson’s disease to drug addiction.

Thomas had been studying the roles of histone acetylation in Huntington’s disease and began to wonder whether similar mechanisms of gene regulation might also be important in schizophrenia. In both diseases, past research in the Thomas lab had shown that certain genes in sufferers were much less active than in healthy people. “It occurred to me that we see the same gene alterations, so I thought, ‘Hey, let’s just try it,’” she said.

It turns out she was right, according to this initial research study.

Interestingly, some of the cognitive deficits that plague elderly people look quite similar biologically to schizophrenia, and the two conditions share at least some brain abnormalities. So deacetylase inhibitors might also work as a treatment for age-related problems, and might even prove an effective preventive measure for people at high risk of cognitive decline based on family history or other indicators.

The study is available online in the journal Translational Psychiatry.

Source: The Scripps Research Institute

Half also have irregular body clocks out of sync with the pattern of night and day.

Twenty patients with schizophrenia were involved in the research. Severe disruption in the sleep patterns were found in all 20 patients, despite their mood being stable and each being on a steady drug regime. 

All patients took longer to fall asleep, spent longer in bed, slept longer and had much more variable sleep patterns, compared with a control group of 21 healthy unemployed people.

The research team insists that the severe impact of these long-term sleep disturbances need to be considered during treatment along with the other symptoms of schizophrenia, because they have such a strong effect on mood, social function, mental abilities and quality of life.

“The people in our study were stable in mood, taking medication and yet they still experienced enormous sleep problems,” says first author Dr. Katharina Wulff of the Nuffield Department of Clinical Neurosciences at the University of Oxford. 

“Clinicians may need to start thinking about treating their patients’ sleep problems as well, or refer them to sleep specialists,” she says.

The variable sleep patterns are unlikely to be simply caused by having unstructured days without any routine, since those in the control group may also not have a pattern to their daily lives.  The sleep disturbances also appeared unrelated to the different drugs taken by those with schizophrenia.

Ten of the patients also had irregular body clocks: Their internal 24-hour rhythm was delayed compared with all the others, or longer than 24 hours. They were often sleeping at times other than at night. 

For example, an individual may only fall asleep after 4 a.m. and get up in the afternoon or have ‘free-running’ sleep patterns unrelated to the 24-hour day.

Although the study provides strong evidence of an association between schizophrenia and severely disrupted sleep patterns, there is not yet a demonstrated causal link between the two. 

Sleep disturbances are considered common in many mental health disorders, including schizophrenia. However, this is one of the first studies to provide solid evidence as well as look for body clock abnormalities.

“Patients often complain of being so tired they can’t concentrate, can’t work, that dealing with their sleep problems would make life so much better. There are also lots of anecdotal stories from psychiatrists of patients being unable to settle to sleep and running around all night, or not turning up to consultations organized for mornings,” says Professor Russell Foster of Oxford University, who headed the research group.

“We now know many of the patients are also essentially suffering persistent jetlag with their body clocks out of synch with day and night. This immediately opens up a lot of new avenues for research in understanding the links between sleep problems and mental ill health.

“But regardless of whether or not there is a mechanistic link between the body clock and psychiatric conditions, it is clear that treating sleep problems could improve the lives of many patients.’

The Oxford University-led study, with colleagues from UCL and the University of Surrey, is published online by the British Journal of Psychiatry.

Source:  University of Oxford

If replicated in humans, acupuncture could offer a therapy for stress, which is often difficult to treat.

“It has long been thought that acupuncture can reduce stress, but this is the first study to show molecular proof of this benefit,” said the study’s lead author, Ladan Eshevari, Ph.D., an assistant professor.

Eshkevari, a certified acupuncturist, conducted the study because many of the patients she treats with acupuncture reported a “better overall sense of well-being — and they often remarked that they felt less stress.”

While the World Health Organization states that acupuncture is useful as adjunct therapy in more than 50 disorders, including chronic stress, Eshevari said that no one has biological proof that it does so.

She designed a study to test the effect of acupuncture on blood levels of neuropeptide Y (NPY), a peptide that is secreted by the sympathetic nervous system in humans. This system is involved in the “flight or fight” response to stress.

Rats are often used to research the biological determinants of stress because they mount a stress response when exposed to winter-like cold temperatures for an hour a day.

Eshevari allowed the rats to become familiar with her, and encouraged them to rest by crawling into a small sock that exposed their legs. She conditioned them to become comfortable with the kind of stimulation used in electroacupuncture — an acupuncture needle that delivers a painless, small electrical charge.

This form of acupuncture is a little more intense than manual acupuncture and is often used for pain management, she said, adding “I used electroacupuncture because I could make sure that every rat was getting the same treatment dose.”

She then selected a single acupuncture spot to test: Zuslanli (ST 35 on the stomach meridian), which is said to help relieve a variety of conditions, including stress. That acupuncture point for rats — and humans — is on the leg below the knee.

The study, published online in December in Experimental Biology and Medicine, utilized four groups of rats for a 14-day experiment: A control group that was not stressed and received no acupuncture; a group that was stressed for an hour a day and did not receive acupuncture; a group that was stressed and received “sham” acupuncture near the tail; and the experimental group that were stressed and received acupuncture to the Zuslanli spot on the leg.

She found NPY levels in the experimental group came down almost to the level of the control group, while the rats that were stressed and not treated with Zuslanli acupuncture had high levels of the protein.

In a second experiment, she stopped acupuncture in the experimental group but continued to stress the rats for an additional four days, and found NPY levels remained low. “We were surprised to find what looks to be a protective effect against stress,” she said.

Source: Georgetown University Medical Center

Rat photo by shutterstock.