TAG: "Psychiatry"

UCI researchers find epigenetic tie to neuropsychiatric disorders


“Our work presents new leads to understanding neuropsychiatric disorders,” UC Irvine's Emiliana Borrelli said.

Dysfunction in dopamine signaling profoundly changes the activity level of about 2,000 genes in the brain’s prefrontal cortex and may be an underlying cause of certain complex neuropsychiatric disorders, such as schizophrenia, according to UC Irvine scientists.

This epigenetic alteration of gene activity in brain cells that receive this neurotransmitter showed for the first time that dopamine deficiencies can affect a variety of behavioral and physiological functions regulated in the prefrontal cortex.

The study, led by Emiliana Borrelli, a UCI professor of microbiology & molecular genetics, appears online in the journal Molecular Psychiatry.

“Our work presents new leads to understanding neuropsychiatric disorders,” Borrelli said. “Genes previously linked to schizophrenia seem to be dependent on the controlled release of dopamine at specific locations in the brain. Interestingly, this study shows that altered dopamine levels can modify gene activity through epigenetic mechanisms despite the absence of genetic mutations of the DNA.”

Dopamine is a neurotransmitter that acts within certain brain circuitries to help manage functions ranging from movement to emotion. Changes in the dopaminergic system are correlated with cognitive, motor, hormonal and emotional impairment. Excesses in dopamine signaling, for example, have been identified as a trigger for neuropsychiatric disorder symptoms.

Borrelli and her team wanted to understand what would happen if dopamine signaling was hindered. To do this, they used mice that lacked dopamine receptors in midbrain neurons, which radically affected regulated dopamine synthesis and release.

The researchers discovered that this receptor mutation profoundly altered gene expression in neurons receiving dopamine at distal sites in the brain, specifically in the prefrontal cortex. Borrelli said they observed a remarkable decrease in expression levels of some 2,000 genes in this area, coupled with a widespread increase in modifications of basic DNA proteins called histones – particularly those associated with reduced gene activity.

Borrelli further noted that the dopamine receptor-induced reprogramming led to psychotic-like behaviors in the mutant mice and that prolonged treatment with a dopamine activator restored regular signaling, pointing to one possible therapeutic approach.

The researchers are continuing their work to gain more insights into the genes altered by this dysfunctional dopamine signaling.

Borrelli is affiliated with UCI’s Center for Epigenetics & Metabolism and manages the INSERM/UCI U904 laboratory there. Karen Brami-Cherrier, Andrea Anzalone, Maria Ramos and Fabio Macciardi of UCI, as well as Ignasi Forne and Axel Imhof of Ludwig Maximilian University of Munich, contributed to the study, which received support from the National Institutes of Health (grant DA024689) and INSERM (grant 44790).

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Understanding the basic biology of bipolar disorder


Scientists from UCLA, UCSF take steps to ID genetic component to mental illness.

Brain regions

Scientists know there is a strong genetic component to bipolar disorder, but they have had an extremely difficult time identifying the genes that cause it. So, in an effort to better understand the illness’s genetic causes, researchers at UCLA tried a new approach.

Instead of only using a standard clinical interview to determine whether individuals met the criteria for a clinical diagnosis of bipolar disorder, the researchers combined the results from brain imaging, cognitive testing, and an array of temperament and behavior measures. Using the new method, UCLA investigators — working with collaborators from UC San Francisco, Colombia’s University of Antioquia and the University of Costa Rica — identified about 50 brain and behavioral measures that are both under strong genetic control and associated with bipolar disorder. Their discoveries could be a major step toward identifying the specific genes that contribute to the illness.

The results are published in today’s (Feb. 12) edition of the Journal JAMA Psychiatry.

A severe mental illness that affects about 1 to 2 percent of the population, bipolar disorder causes unusual shifts in mood and energy, and it interferes with the ability to carry out everyday tasks. Those with the disorder can experience tremendous highs and extreme lows — to the point of not wanting to get out of bed when they’re feeling down. The genetic causes of bipolar disorder are highly complex and likely involve many different genes, said Carrie Bearden, a senior author of the study and an associate professor of psychiatry and psychology at the UCLA Semel Institute for Neuroscience and Human Behavior.

“The field of psychiatric genetics has long struggled to find an effective approach to begin dissecting the genetic basis of bipolar disorder,” Bearden said. “This is an innovative approach to identifying genetically influenced brain and behavioral measures that are more closely tied to the underlying biology of bipolar disorder than the clinical symptoms alone are.”

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Brain trauma raises risk of later PTSD in active-duty Marines


Deployment-related injuries are biggest predictor, but not the only factor.

Dewleen Baker

Dewleen Baker

In a novel study of U.S. Marines investigating the association between traumatic brain injury (TBI) and the risk of post-traumatic stress disorder (PTSD) over time, a team of scientists led by researchers from the Veterans Affairs San Diego Healthcare System and UC San Diego School of Medicine report that TBIs suffered during active-duty deployment to Iraq and Afghanistan were the greatest predictor for subsequent PTSD, but found pre-deployment PTSD symptoms and high combat intensity were also significant factors.

The findings are published in the Dec. 11 online issue of JAMA Psychiatry.

The team, headed by principal investigator Dewleen G. Baker, M.D., research director at the VA Center of Excellence for Stress and Mental Health, professor in the Department of Psychiatry at UC San Diego and a practicing psychiatrist in the VA San Diego Healthcare System, analyzed 1,648 active-duty Marines and Navy servicemen from four infantry battalions of the First Marine Division based at Camp Pendleton in north San Diego County. The servicemen were evaluated approximately one month before a scheduled 7-month deployment to Iraq or Afghanistan, one week after deployment had concluded, and again three and six months later.

PTSD is a psychiatric condition in which stress reactions become abnormal, chronic and may worsen over time. The condition is linked to depression, suicidal tendencies, substance abuse, memory and cognition dysfunction and other health problems.

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Kids whose bond with mother was disrupted early in life show changes in brain


UCLA researchers examine impact on amygdala.

Nim Tottenham, UCLA

Nim Tottenham, UCLA

Children who experience profound neglect have been found to be more prone to a behavior known as “indiscriminate friendliness,” characterized by an inappropriate willingness to approach adults, including strangers.

UCLA researchers are now reporting some of the first evidence from human studies suggesting that this behavior is rooted in brain adaptations associated with early-life experiences. The findings appear in the Dec. 1 issue of the peer-reviewed journal Biological Psychiatry.

The UCLA group used functional magnetic resonance imaging (fMRI) to demonstrate that youths who experienced early maternal deprivation — specifically, time in an institution such as an orphanage prior to being adopted — show similar responses to their adoptive mother and to strangers in a brain structure called the amygdala; for children never raised in an institutional setting, the amygdala is far more active in response to the adoptive mother.

This reduced amygdala discrimination in the brain correlated with parental reports of indiscriminate friendliness. The longer the child spent in an institution before being adopted, the greater the effects.

“The early relationship between children and their parents or primary caregivers has implications for their social interaction later in life, and we believe the amygdala is involved in this process,” said Aviva Olsavsky, a resident physician in psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA and the study’s first author. “Our findings suggest that even for children who have formed attachments to their adoptive parents, this early period of deprivation has led to changes in the brain that were likely adaptations and that may persist over time.”

Indiscriminate friendliness is in some sense a misnomer. The behavior is not characterized by a deep friendliness but simply by a lack of reticence that most young children show toward strangers.

“This can be a very frightening behavior for parents,” said Nim Tottenham, an associate professor of psychology at UCLA and the study’s senior author. “The stranger anxiety or wariness that young children typically show is a sign that they understand their parents are very special people who are their source of security. That early emotional attachment serves as a bedrock for many of the developmental processes that follow.”

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For anxious children and teens, context counts


Specific area of the brain linked to anxiety disorders in youth.

Tara Peris, UCLA

Tara Peris, UCLA

Anxiety disorders are common in children and adolescents, affecting up to 25 percent of the youth population. Anxiety causes distress and functional impairment and, if left untreated, can result in bad grades, problems at home and increased rates of psychiatric disorders in adulthood.

These risks constitute a significant public health burden, and they underscore the importance of continued efforts to understand the cause and course of the disorder.

While earlier research found that anxious youths are apt to interpret neutral or ambiguous information as threatening, fueling the feelings of distress that characterize anxiety disorders, what happens in the brain and how the brain may be impacted has been unclear. In particular, where in the brain neutral information is transformed into “threatening” information in anxious youth has remained unknown.

Now researchers at UCLA have shown that teenagers with anxiety disorders show increased activity in a specific part of the brain, the medial prefrontal cortex, when they are interpreting a situation negatively. The results appear in the current online edition of the journal Biology of Mood and Anxiety Disorders.

For the study, 16 teenagers with anxiety disorders and 15 non-anxious teens underwent functional MRI while being shown pictures of people with a neutral look on their face. The faces were paired with either of two sentences: one that was viewed as neutral (“She is watching a presentation”) and one that might be viewed as more intimidating (“She is about to give a presentation”).

Teenagers without anxiety disorders were unaffected by the context when they interpreted the faces. But those with anxiety disorders often found neutral faces more threatening when they were presented in an “anxiety-provoking” situation — one in which they might feel judged by peers. This was not a great surprise. But when researchers measured brain activity in these situations, they found increased activity in the medial prefrontal cortex.

“We know that the medial prefrontal cortex plays a role in social and emotional processes, and it is an area of the brain that is still developing through childhood and adolescence, so it was a natural candidate for examination,” said co-author Tara Peris, an assistant professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA. “The role this area of the brain plays is of particular interest, then, given prior research that implicates it in inferring what another person is feeling.”

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Let’s be friends: Book, app help socially challenged youth make, keep friends


Strategies are based on research done at UCLA.

Elizabeth Laugeson, UCLA

Elizabeth Laugeson, UCLA

Socially challenged teens and young adults, such as those with autism, often have trouble making and keeping friends and can become easy targets for bullying, a situation that challenges their coping skills.

Now, a new book written by a UCLA researcher can guide parents in helping their children become more adept at establishing meaningful connections with their peers. An accompanying DVD and mobile application called FriendMaker is designed to provide real-time advice and video demonstrations of appropriate behavior for the teens and young adults when they find themselves in a challenging social situation.

The book, “The Science of Making Friends,” and the app are based on research done in the UCLA Program for the Education and Enrichment of Relational Skills (PEERS) Clinic, the only evidence-based social skills intervention available for teens and young adults with autism, attention deficit hyperactivity disorder, anxiety, depression and other social impairments.

The strategies in the book, while geared toward the socially challenged, could also apply to any teen who is trying to fit in or is being bullied, said author Dr. Elizabeth Laugeson, director of the PEERS Clinic and an assistant clinical professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA.

“Kids with special needs are already at a disadvantage. They have trouble reading social cues and interpreting the thoughts and feelings of others,” Laugeson said. “Because of this, they are more likely to be teased and bullied, and they don’t always know how to respond appropriately. Kids with autism in particular often exhibit odd behavior, which sets them up to be teased and bullied. They also tend to be isolated and alone, making them even easier targets.”

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Psychiatric patients who quit smoking less likely to be rehospitalized


UCSF study debunks myth that smoking can be helpful in mental health treatment.

Patients who participated in a smoking-cessation program during hospitalization for mental illness were able to quit smoking and were less likely to be hospitalized again for their psychiatric conditions, according to a new study by researchers at Stanford and UC San Francisco.

The findings counter a longstanding assumption held by many mental-health experts that smoking serves as a useful tool in treating some psychiatric patients.

Smoking among such patients has been embedded in the culture for decades, with cigarettes used as part of a reward system. Indeed, clinicians sometimes smoke alongside patients as a way of creating a rapport with them, said Judith Prochaska, Ph.D., M.P.H., associate professor of medicine at the Stanford Prevention Research Center who led the study while an associate professor at UCSF. The result is that psychiatric patients are among the country’s most prolific smokers and among those most likely to die of smoking-related ailments, Prochaska said.

Nearly half of the cigarettes sold in the United States are to people with psychiatric or addictive disorders, according to data from the U.S. Centers for Disease Control and Prevention. And the average life expectancy for people with severe mental illness is 25 years less than that of the general population, and their leading cause of death is chronic illness, mostly tobacco-related.

The study is the first to examine the impact of a stop-smoking intervention in adult psychiatric patients. It was published online Aug. 15 in the American Journal of Public Health.

Co-authors of the study are Stephen Hall, M.D., director of acute services at Langley Porter Psychiatric Institute; Kevin Delucchi, Ph.D., professor of biostatistics in psychiatry; and Sharon Hall, Ph.D., professor of psychiatry, all of UCSF.

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UC Davis researchers receive $2.5M grant to study telepsychiatry


Five-year study will compare store-and-forward to real-time telepsychiatry.

Peter Yellowlees,UC Davis

Peter Yellowlees,UC Davis

Researchers at UC Davis have received a five-year, $2.5 million grant to study whether viewing videotaped interviews with patients to assess them and guide their mental health treatment is more cost-effective and better for patient outcomes and satisfaction than real-time telepsychiatric evaluation.

The study will involve videotaping interviews of patients and their providers in their primary care clinic that later are viewed and evaluated by psychiatrists, who will make diagnostic evaluations and treatment plans that can be carried out by primary care doctors and community therapists. This approach is called “store-and-forward,” or asynchronous telepsychiatry, because the patient is not being evaluated in real time.

The research will compare the effectiveness of this style of telepsychiatry to real-time, or synchronous telepsychiatry, in which a psychiatrist evaluates patients via live, interactive videoconferencing. In both approaches, the psychiatrist provides primary care providers with assessments and treatment plans and is available for follow-up consultation by phone or email.

Asynchronous technology is used extensively for such specialties as dermatology, pathology and radiology, where photos of skin conditions, slides or X-rays are sent electronically for expert evaluation. UC Davis researchers have spearheaded its use for psychiatry evaluations over several years. The approach is generally used to assess patients with mood disorders, substance abuse disorders or anxiety disorders and is not intended to replace traditional psychotherapy.

The study principal investigator is Peter Yellowlees, professor in the Department of Psychiatry and Behavioral Sciences and director of the Graduate Program in Health Informatics. Yellowlees is an international leader in the use of telepsychiatry to expand the availability of psychiatric consultation.

“Using store-and-forward technology allows us to provide opinions to primary-care doctors much more quickly than would usually be the case,” Yellowlees said. “We’ve demonstrated that this approach is feasible and very efficient in earlier research, and patients report that it is highly convenient for them as they are able to have their full evaluation done in their primary care office.”

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Note to teens: Just breathe


Youth Empower Seminar helps adolescents control impulses, UCLA study finds.

Teen reading a bookIn May, the Los Angeles school board voted to ban suspensions of students for “willful defiance” and directed school officials to use alternative disciplinary practices. The decision was controversial, and the question remains: How do you discipline rowdy students and keep them in the classroom while still being fair to other kids who want to learn?

A team led by Dara Ghahremani, an assistant researcher in the department of psychiatry at UCLA’s Semel Institute for Neuroscience and Human Behavior conducted a study on the Youth Empower Seminar, or YES!, a workshop for adolescents that teaches them to manage stress, regulate their emotions, resolve conflicts and control impulsive behavior. Impulsive behavior, in particular — including acting out in class, engaging in drug or alcohol abuse, and risky sexual behaviors — is something that gets adolescents in trouble.

The YES! program, run by the nonprofit International Association for Human Values, includes yoga-based breathing practices, among other techniques, and the research findings show that a little bit of breathing can go a long way. The scientists report that students who went through the four-week YES! for Schools program felt less impulsive, while students in a control group that didn’t participate in the program showed no change.

“The program helps teens to gain greater control over their actions by giving them tools to respond to challenging situations in constructive and mindful ways, rather than impulsively,” said Ghahremani, who conducted the study at the UCLA Center for Addictive Behaviors and UCLA’s Laboratory for Molecular Neuroimaging. “The program uses a variety of techniques, ranging from a powerful yoga-based breathing program called Sudarshan Kriya to decision-making and leadership skills that are taught via interactive group games. We found it to be a simple yet powerful approach that could potentially reduce impulsive behavior.”

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Lewis Judd to step down after 36 years as psychiatry department chair


UC San Diego mental health leader helped shape evolution of psychiatry.

Lewis Judd, UC San Diego

In a career that has spanned almost half a century, most of it at the UC San Diego School of Medicine, Dr. Lewis Judd has watched – and to a remarkable degree, helped shape – the evolution of psychiatry from its decidedly charismatic but often controversial past to its empirical present as a data-driven, hard-charging neuroscience.

For the last 36 years, Judd has served as chair of the department of psychiatry, during which time he has built an organization consistently ranked among the top 10 in the nation, with a research and clinical faculty second to none.

This summer, he plans to step down as department chairman after serving as a department chair longer than anyone at UC San Diego. Indeed, Judd has been psychiatry chair for an astounding 70 percent of the university’s existence.

That kind of durability provides extraordinary perspective and a keen sense of history, particularly for someone who has played an active part. Judd was among the first and leading proponents for treating mental disorders like depression as the result of neurological and biological dysfunction, and arguing that they could be effectively treated with appropriate, rigorously developed psychopharmaceuticals.

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Altered neural circuitry may lead to anorexia and bulimia


UC San Diego research may offer pathway to better treatments for these eating disorders.

Walter Kaye, UC San Diego

Anorexia nervosa and bulimia nervosa – disorders characterized by extreme eating behavior and distorted body image – are among the deadliest of psychiatric disorders, with few proven effective treatments.

A landmark study, with first author Tyson Oberndorfer, M.D., and led by Walter H. Kaye, M.D., professor of psychiatry at the UC San Diego School of Medicine, suggests that the altered function of neural circuitry contributes to restricted eating in anorexia and overeating in bulimia.  The research, published today (June 4) in the early online edition of the American Journal of Psychiatry, may offer a pathway to new and more effective treatments for these serious eating disorders.

“It has been unknown whether individuals with anorexia or bulimia have a disturbance in the system that regulates appetite in the brain, or whether eating behavior is driven by other phenomena, such as an obsessional preoccupation with body image,” said Kaye, director of the UCSD Eating Disorders Treatment and Research Program.  “However, this study confirms earlier studies by our group and others that establish a clear link between these disorders and neural processes in the insula, an area of the brain where taste is sensed and integrated with reward to help determine whether an individual hungry or full.”

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Depression linked to telomere enzyme, aging, chronic disease


Activity of telomerase is greater, on average, in untreated individuals with major depression.

Owen Wolkowitz, UC San Francisco

The first symptoms of major depression may be behavioral, but the common mental illness is based in biology — and not limited to the brain.

In recent years, some studies have linked major, long-term depression with life-threatening chronic disease and with earlier death, even after lifestyle risk factors have been taken into account.

Now a research team led by Owen Wolkowitz, M.D., professor of psychiatry at UC San Francisco, has found that within cells of the immune system, activity of an enzyme called telomerase is greater, on average, in untreated individuals with major depression. The preliminary findings from his latest, ongoing study was reported today (May 22) at the annual meeting of the American Psychiatric Association in San Francisco.

Telomerase is an enzyme that lengthens protective end caps on the chromosomes’ DNA, called telomeres. Shortened telomeres have been associated with earlier death and with chronic diseases in population studies.

The heightened telomerase activity in untreated major depression might represent the body’s attempt to fight back against the progression of disease, in order to prevent biological damage in long-depressed individuals, Wolkowitz said.

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