Posts tagged bipolar disorder
Articles and news from the latest research reports.
Bipolar Disorder Discovery at the Nano Level
A nano-sized discovery by Northwestern Medicine® scientists helps explain how bipolar disorder affects the brain and could one day lead to new drug therapies to treat the mental illness.
Scientists used a new super-resolution imaging method — the same method recognized with the 2014 Nobel Prize in chemistry — to peer deep into brain tissue from mice with bipolar-like behaviors. In the synapses (where communication between brain cells occurs), they discovered tiny “nanodomain” structures with concentrated levels of ANK3 — the gene most strongly associated with bipolar disorder risk. ANK3 is coding for the protein ankyrin-G.
“We knew that ankyrin-G played an important role in bipolar disease, but we didn’t know how,” said Northwestern Medicine scientist Peter Penzes, corresponding author of the paper. “Through this imaging method we found the gene formed in nanodomain structures in the synapses, and we determined that these structures control or regulate the behavior of synapses.”
Penzes is a professor in physiology and psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine. The results were published Oct. 22 in the journal Neuron.
High-profile cases, including actress Catherine Zeta-Jones and politician Jesse Jackson, Jr., have brought attention to bipolar disorder. The illness causes unusual shifts in mood, energy, activity levels and the ability to carry out day-to-day tasks. About 3 percent of Americans experience bipolar disorder symptoms, and there is no cure.
Recent large-scale human genetic studies have shown that genes can contribute to disease risk along with stress and other environmental factors. However, how these risk genes affect the brain is not known.
This is the first time any psychiatric risk gene has been analyzed at such a detailed level of resolution. As explained in the paper, Penzes used the Nikon Structured Illumination Super-resolution Microscope to study a mouse model of bipolar disorder. The microscope realizes resolution of up to 115 nanometers. To put that size in perspective, a nanometer is one-tenth of a micron, and there are 25,400 microns in one inch. Very few of these microscopes exist worldwide.
“There is important information about genes and diseases that can only been seen at this level of resolution,” Penzes said. “We provide a neurobiological explanation of the function of the leading risk gene, and this might provide insight into the abnormalities in bipolar disorder.”
The biological framework presented in this paper could be used in human studies of bipolar disorder in the future, with the goal of developing therapeutic approaches to target these genes.
(Source: northwestern.edu)
Depression Deconstructed
A drug being studied as a fast-acting mood-lifter restored pleasure-seeking behavior independent of – and ahead of – its other antidepressant effects, in a National Institutes of Health trial. Within 40 minutes after a single infusion of ketamine, treatment-resistant depressed bipolar disorder patients experienced a reversal of a key symptom – loss of interest in pleasurable activities – which lasted up to 14 days. Brain scans traced the agent’s action to boosted activity in areas at the front and deep in the right hemisphere of the brain.
“Our findings help to deconstruct what has traditionally been lumped together as depression,” explained Carlos Zarate, M.D., of the NIH’s National Institute of Mental Health. “We break out a component that responds uniquely to a treatment that works through different brain systems than conventional antidepressants – and link that response to different circuitry than other depression symptoms.”
This approach is consistent with the NIMH’s Research Domain Criteria project, which calls for the study of functions – such as the ability to seek out and experience rewards – and their related brain systems that may identify subgroups of patients in one or multiple disorder categories.
Zarate and colleagues reported on their findings Oct. 14, 2014 in the journal Translational Psychiatry.
Although it’s considered one of two cardinal symptoms of both depression and bipolar disorder, effective treatments have been lacking for loss of the ability to look forward to pleasurable activities, or anhedonia. Long used as an anesthetic and sometimes club drug , ketamine and its mechanism-of-action have lately been the focus of research into a potential new class of rapid-acting antidepressants that can lift mood within hours instead of weeks.
Based on their previous studies, NIMH researchers expected ketamine’s therapeutic action against anhedonia would be traceable – like that for other depression symptoms – to effects on a mid-brain area linked to reward-seeking and that it would follow a similar pattern and time course.
To find out, the researchers infused the drug or a placebo into 36 patients in the depressive phase of bipolar disorder. They then detected any resultant mood changes using rating scales for anhedonia and depression. By isolating scores on anhedonia items from scores on other depression symptom items, the researchers discovered that ketamine was triggering a strong anti-anhedonia effect sooner – and independent of – the other effects.
Levels of anhedonia plummeted within 40 minutes in patients who received ketamine, compared with those who received placebo – and the effect was still detectable in some patients two weeks later. Other depressive symptoms improved within 2 hours. The anti-anhedonic effect remained significant even in the absence of other antidepressant effects, suggesting a unique role for the drug.
Next, the researchers scanned a subset of the ketamine-infused patients, using positron emission tomography (PET), which shows what parts of the brain are active by tracing the destinations of radioactively-tagged glucose – the brain’s fuel. The scans showed that ketamine jump-started activity not in the middle brain area they had expected, but rather in the dorsal (upper) anterior cingulate cortex, near the front middle of the brain and putamen, deep in the right hemisphere.
Boosted activity in these areas may reflect increased motivation towards or ability to anticipate pleasurable experiences, according to the researchers. Depressed patients typically experience problems imagining positive, rewarding experiences – which would be consistent with impaired functioning of this dorsal anterior cingulate cortex circuitry, they said. However, confirmation of these imaging findings must await results of a similar NIMH ketamine trial nearing completion in patients with unipolar major depression.
Other evidence suggests that ketamine’s action in this circuitry is mediated by its effects on the brain’s major excitatory neurotransmitter, glutamate, and downstream effects on a key reward-related chemical messenger, dopamine. The findings add to mounting evidence in support of the antidepressant efficacy of targeting this neurochemical pathway. Ongoing research is exploring, for example, potentially more practical delivery methods for ketamine and related experimental antidepressants, such as a nasal spray .
However, ketamine is not approved by the U.S. Food and Drug Administration as a treatment for depression. It is mostly used in veterinary practice, and abuse can lead to hallucinations, delirium and amnesia.
Attention deficits are central to psychiatric disorders such as schizophrenia or bipolar disorder, and are thought to precede the presentation of the illnesses. A new study led by Wayne State University School of Medicine researcher Vaibhav Diwadkar, Ph.D. suggests that the brain network interactions between regions that support attention are dysfunctional in children and adolescents at genetic risk for developing schizophrenia and bipolar disorder.
The brain network mechanisms that mediate these deficits are poorly understood, and have rarely been tackled using complex image analytic methods that focus on how brain regions communicate, said Dr. Diwadkar, associate professor of psychiatry and behavioral neurosciences and co-director of the departments Brain Imaging Research Division
The desire to understand dysfunctional brain mechanisms motivated Dr. Diwadkar and his team of colleagues and WSU medical students in the study titled, “Dysfunction and dysconnection in cortical-striatal networks during sustained attention: genetic risk for schizophrenia or bipolar disorder and its impact on brain network function, featured in the May issue of Frontiers in Psychiatry.
The study is clinically significant because the estimated lifetime incidence of schizophrenia or bipolar disorder in the groups studied is approximately 10-20 times what is generally observed. We believe that genetic risk may confer vulnerability for dysfunctional brain network communication. This abnormal network communication in turn might amplify risk for psychiatric illnesses. By identifying markers of network dysfunction we believe we can elucidate these mechanisms of risk. This knowledge may in turn increase focus on possible premeditative intervention strategies, Dr. Diwadkar said.
The researchers identified dysfunctional brain mechanisms of sustained attention using functional Magnetic Resonance Imaging data and complex modeling of fMRI signals. Data were collected in 46 children and adolescents ages 8 to 20, half at genetic risk for schizophrenia or bipolar disorder by virtue of having one or both parents with either illness. During the 20-minute fMRI, participants completed a sustained attention task, adapted to engage specific brain regions.
The researchers induced variations in the degree of demand on these brain regions a method of assessing how genetic risk might impair the brains ability to respond to attention challenges by varying task difficulty. Increased attention demand led to increased engagement in the typical control group. The genetically at-risk group did not respond the same. Instead, interactions between the dorsal anterior cingulate, a principal control region in the brain, and the basal ganglia were highly dysfunctional in that group, suggesting impaired communication between specific brain networks.
The study indicates that brain networks supporting basic psychological functions such as attention do not communicate appropriately in young individuals at genetic risk for illnesses such as schizophrenia or bipolar disorder.
Genetics and neurodevelopment are inextricably linked. How psychiatric illnesses emerge from their combination is a central question in medicine. Analytic tools developed in the last few years offer the promise of answers at the level of how these processes impact brain network communication, Dr. Diwadkar said.
Listening to bipolar disorder: Smartphone app detects mood swings via voice analysis
A smartphone app that monitors subtle qualities of a person’s voice during everyday phone conversations shows promise for detecting early signs of mood changes in people with bipolar disorder, a University of Michigan team reports.
While the app still needs much testing before widespread use, early results from a small group of patients show its potential to monitor moods while protecting privacy.
The researchers hope the app will eventually give people with bipolar disorder and their health care teams an early warning of the changing moods that give the condition its name. The technology could also help people with other conditions.
"We only ask that an individual use his or her smart phone as he or she normally would," said Emily Mower Provost, assistant professor of computer science and engineering who co-led the project. "We collect speech data from the smart phone and process the data in a privacy preserving manner to learn the acoustic patterns associated with harmful mood variations."
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.
Precise brain mapping can improve response to deep brain stimulation in depression
Experimental studies have shown that deep brain stimulation (DBS) within the subcallosal cingulate (SCC) white matter of the brain is an effective treatment for many patients with treatment-resistant depression. Response rates are between 41 percent and 64 percent across published studies to date. One of the proposed mechanisms of action is through modulation of a network of brain regions connected to the SCC. Identifying the critical connections within this network for successful antidepressant response is an important next step.
A new study using MRI analysis of the white matter connections examined the architecture of this network in patients who demonstrated significant response to SCC DBS. Researchers found that all responders showed a common pattern defined by three distinct white matter bundles passing through the SCC. Non-responders did not show this pattern.
The study is published online in the journal Biological Psychiatry, with the title “Defining Critical White Matter Pathways Mediating Successful Subcallosal Cingulate Deep Brain Stimulation for Treatment-Resistant Depression.”
"This study shows that successful DBS therapy is not due solely to local changes at the site of stimulation but also in those regions in direct communication with the SCC," says Helen Mayberg, MD, senior author of the article, professor of psychiatry, neurology and radiology and the Dorothy C. Fuqua Chair in Psychiatric Imaging and Therapeutics at Emory University School of Medicine.
"Precisely delineating these white matter connections appears to be very important to a successful outcome with this procedure. From a practical point of view, these results may help us to choose the optimal contact for stimulation and eventually to better plan the surgical placement of the DBS electrodes."
Led by researchers at Emory University, Case Western Reserve University and Dartmouth University, the study included 16 patients with treatment-resistant depression who previously received SCC DBS at Emory. Computerized tomography was used post-operatively to localize the DBS contacts on each electrode. The activation volumes around the active contacts were modeled for each patient. Sophisticated neuroimaging combined with computerized analysis was used to derive and visualize the specific white matter fibers affected by ongoing DBS.
Therapeutic outcome was evaluated at six months and at two years. Six of the patients had responded positively to DBS at six months, and by two years these six plus six more patients responded positively. All shared common involvement of three distinct white matter bundles: the cingulum, the forceps minor and the uncinate fasciculus.
The conversion of six of the patients who were not responding at six months to being responders at two years was explained by the inclusion of all three bundles due to changes in stimulation settings. Non-responders at both six months and two years showed incomplete involvement of these three tracts.
"In the past, placement of the electrode relied solely on anatomical landmarks with contact selection and stimulation parameter changes based on a trial-and-error method," says Patricio Riva-Posse, MD, Emory assistant professor of psychiatry and behavioral sciences and first author of the paper. "These results suggest that clinical outcome can be significantly influenced by optimally modulating the response network defined by tractography. This obviously will need to be tested prospectively in additional subjects here and by other teams exploring the use of this experimental treatment."
This new information will allow us to develop a refined algorithm for guiding surgical implantation of electrodes and optimizing the response through fine tuning of stimulation parameters,” notes Mayberg. “That said, improving anatomical precision alone doesn’t account for all non-responders, so that is an important next focus of our research.”
The researchers now plan to study DBS therapy in a prospective protocol of similar treatment-resistant depressed patients, using presurgical mapping of an individual patient’s network structure, precisely targeting the three SCC fiber bundles, and systematically testing the stimulation contacts.
(Source: news.emory.edu)
First stem cell study of bipolar disorder yields promising results
Stem cell model shows nerve cells develop, behave and respond to lithium differently – opening doors to potential new treatments
What makes a person bipolar, prone to manic highs and deep, depressed lows? Why does bipolar disorder run so strongly in families, even though no single gene is to blame? And why is it so hard to find new treatments for a condition that affects 200 million people worldwide?
New stem cell research published by scientists from the University of Michigan Medical School, and fueled by the Heinz C. Prechter Bipolar Research Fund, may help scientists find answers to these questions.
The team used skin from people with bipolar disorder to derive the first-ever stem cell lines specific to the condition. In a new paper in Translational Psychiatry, they report how they transformed the stem cells into neurons, similar to those found in the brain – and compared them to cells derived from people without bipolar disorder.
The comparison revealed very specific differences in how these neurons behave and communicate with each other, and identified striking differences in how the neurons respond to lithium, the most common treatment for bipolar disorder.
It’s the first time scientists have directly measured differences in brain cell formation and function between people with bipolar disorder and those without.
The researchers are from the Medical School’s Department of Cell & Developmental Biology and Department of Psychiatry, and U-M’s Depression Center.
Stem cells as a window on bipolar disorder
The team used a type of stem cell called induced pluripotent stem cells, or iPSCs. By taking small samples of skin cells and exposing them to carefully controlled conditions, the team coaxed them to turn into stem cells that held the potential to become any type of cell. With further coaxing, the cells became neurons.
“This gives us a model that we can use to examine how cells behave as they develop into neurons. Already, we see that cells from people with bipolar disorder are different in how often they express certain genes, how they differentiate into neurons, how they communicate, and how they respond to lithium,” says Sue O’Shea, Ph.D., the experienced U-M stem cell specialist who co-led the work.
“We’re very excited about these findings. But we’re only just beginning to understand what we can do with these cells to help answer the many unanswered questions in bipolar disorder’s origins and treatment,” says Melvin McInnis, M.D., principal investigator of the Prechter Bipolar Research Fund and its programs.
“For instance, we can now envision being able to test new drug candidates in these cells, to screen possible medications proactively instead of having to discover them fortuitously.”
The research was supported by donations from the Heinz C. Prechter Bipolar Research Fund, the Steven M. Schwartzberg Memorial Fund, and the Joshua Judson Stern Foundation. The A. Alfred Taubman Medical Research Institute at the U-M Medical School also supported the work, which was reviewed and approved by the U-M Human Pluripotent Stem Cell Research Oversight committee and Institutional Review Board.
O’Shea, a professor in the Department of Cell & Developmental Biology and director of the U-M Pluripotent Stem Cell Research Lab, and McInnis, the Upjohn Woodworth Professor of Bipolar Disorder and Depression in the Department of Psychiatry, are co-senior authors of the new paper.
McInnis, who sees firsthand the impact that bipolar disorder has on patients and the frustration they and their families feel about the lack of treatment options, says the new research could take treatment of bipolar disorder into the era of personalized medicine.
Not only could stem cell research help find new treatments, it may also lead to a way to target treatment to each patient based on their specific profile – and avoid the trial-and-error approach to treatment that leaves many patients with uncontrolled symptoms.
More about the findings:
The skin samples were used to derive the 42 iPSC lines. When the team measured gene expression first in the stem cells, and then re-evaluated the cells once they had become neurons, very specific differences emerged between the cells derived from bipolar disorder patients and those without the condition.
Specifically, the bipolar neurons expressed more genes for membrane receptors and ion channels than non-bipolar cells, particularly those receptors and channels involved in the sending and receiving of calcium signals between cells.
Calcium signals are already known to be crucial to neuron development and function. So, the new findings support the idea that genetic differences expressed early during brain development may have a lot to do with the development of bipolar disorder symptoms – and other mental health conditions that arise later in life, especially in the teen and young adult years.
Meanwhile, the cells’ signaling patterns changed in different ways when the researchers introduced lithium, which many bipolar patients take to regulate their moods, but which causes side effects. In general, lithium alters the way calcium signals are sent and received – and the new cell lines will make it possible to study this effect specifically in bipolar disorder-specific cells.
Like misdirected letters and packages at the post office, the neurons made from bipolar disorder patients also differed in how they were ‘addressed’ during development for delivery to certain areas of the brain. This may have an impact on brain development, too.
The researchers also found differences in microRNA expression in bipolar cells – tiny fragments of RNA that play key roles in the “reading” of genes. This supports the emerging concept that bipolar disorder arises from a combination of genetic vulnerabilities.
The researchers are already developing stem cell lines from other trial participants with bipolar disorder, though it takes months to derive each line and obtain mature neurons that can be studied. They will share their cell lines with other researchers via the Prechter Repository at U-M. They also hope to develop a way to use the cells to screen drugs rapidly, called an assay.
New gene for bipolar disorder discovered
Team of researchers searched for the foundations of manic-depressive disorder in about 24,000 people
First on top of the world and then in the depths of despair – this is what the extreme mood changes for people with bipolar disorder are like. Under the direction of scientists from the University of Bonn Hospital, the Central Institute of Mental Health of Mannheim and the University of Basel Hospital, an international collaboration of researchers discovered two new gene regions which are connected with the prevalent disease. In addition, they were able to confirm three additional suspect genes. In this unparalleled worldwide study, the scientists are utilizing unprecedented numbers of patients. The results are now being published in the renowned journal “Nature Communications”.
Throughout the course of their lives, about one percent of the population suffers from bipolar disorder, also known as manic-depressive disorder. The patients undergo a veritable rollercoaster of emotions: During extreme shifts, they experience manic phases with delusions of grandeur, increased drive and a decreased need for sleep as well as depressive episodes with a severely depressed mood to the point of suicidal thoughts. The causes of the disease are not yet fully understood, however in addition to psychosocial triggers, genetic factors play a large role. “There is no one gene that has a significant effect on the development of bipolar disorder,” says Prof. Dr. Markus M. Nöthen, Director of the Institute of Human Genetics of the University of Bonn Hospital. “Many different genes are evidently involved and these genes work together with environmental factors in a complex way.”
Scale of the investigation is unparalleled worldwide
In recent years, scientists at the Institute of Human Genetics were already involved in decoding several genes associated with bipolar disorder. The researchers working with Prof. Dr. Marcella Rietschel from the Central Institute of Mental Health of Mannheim, Prof. Dr. Markus M. Nöthen from the University of Bonn Hospital and Prof. Dr. Sven Cichon from the University of Basel Hospital are now using unprecedented numbers of patients in an international research collaboration: New genetic data from 2266 patients with manic-depressive disorder and 5028 control persons were obtained, merged with existing data sets and analyzed together. In total, data on the genetic material of 9747 patients were compared with data from 14,278 healthy persons. “The investigation of the genetic foundations of bipolar disorder on this scale is unique worldwide to date,” says Prof. Rietschel from the Central Institute of Mental Health of Mannheim.
The search for genes involved in manic-depressive disorder is like looking for a needle in a haystack. “The contributions of individual genes are so minor that they normally cannot be identified in the ‘background noise’ of genetic differences,” explains Prof. Cichon from the University of Basel Hospital. Only when the DNA from very large numbers of patients with bipolar disorder are compared to the genetic material from an equally large number of healthy persons can differences be confirmed statistically. Such suspect regions which indicate a disease are known by scientists as candidate genes.
Two new gene regions discovered and three known gene regions confirmed
Using automated analysis methods, the researchers recorded about 2.3 million different regions in the genetic material of patients and comparators, respectively. The subsequent evaluation using biostatistical methods revealed a total of five risk regions on the DNA associated with bipolar disorder. Two of these regions were newly discovered: The gene “ADCY2” on chromosome five and the so-called “MIR2113-POU3F2” region on chromosome six. The risk regions “ANK3”, “ODZ4” and “TRANK1” have already been described in prior studies. “These gene regions were, however, statistically better confirmed in our current investigation - the connection with bipolar disorder has now become even clearer,” says Prof. Nöthen.
The researchers are particularly interested in the newly discovered gene region “ADCY2”. It codes an enzyme which is involved in the conduction of signals into nerve cells. “This fits very well with observations that the signal transfer in certain regions of the brain is impaired in patients with bipolar disorder,” explains the human geneticist of the University of Bonn Hospital. With their search for genetic regions, the scientists are gradually clarifying the causes of manic-depressive disorder. “Only when we know the biological foundations of this disease can be also identify starting points for new therapies,” says Prof. Nöthen.
Understanding the basic biology of bipolar disorder
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 the 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."
The researchers assessed 738 adults, 181 of whom have severe bipolar disorder. They used high-resolution 3-D images of the brain, questionnaires evaluating temperament and personality traits of individuals diagnosed with bipolar disorder and their non-bipolar relatives, and an extensive battery of cognitive tests assessing long-term memory, attention, inhibitory control and other neurocognitive abilities.
Approximately 50 of these measures showed strong evidence of being influenced by genetics. Particularly interesting was the discovery that the thickness of the gray matter in the brain’s temporal and prefrontal regions — the structures that are critical for language and for higher-order cognitive functions like self-control and problem-solving — were the most promising candidate traits for genetic mapping, based on both their strong genetic basis and association with the disease.
"These findings are really just the first step in getting us a little closer to the roots of bipolar disorder," Bearden said. "What was really exciting about this project was that we were able to collect the most extensive set of traits associated with bipolar disorder ever assessed within any study sample. These data will be a really valuable resource for the field."
The individuals assessed in this study are members of large families living in Costa Rica’s central valley and Antioquia, Colombia. The families were founded by European and native Amerindian populations about 400 years ago and have a very high incidence of bipolar disorder. The groups were chosen because they have remained fairly isolated since their founding and their genetics are therefore simpler for scientists to study than those of general populations.
The fact that the findings aligned so closely with those of previous, smaller studies in other populations was surprising even to the scientists, given the subjects’ unique genetic background and living environments.
"This suggests that even if the specific genetic variants we identify may be unique to this population, the biological pathways they disrupt are likely to also influence disease risk in other populations," Bearden said.
The researchers’ next step is to use the genomic data they collected from the families — including full genome sequences and gene expression data— to begin identifying the specific genes that contribute to risk for bipolar disorder. The researchers also plan to extend their investigation into the children and teens in these families. They hypothesize that many of the bipolar-related brain and behavioral differences found in adults with bipolar disorder had their origins in adolescent neurodevelopment.
Smoking during pregnancy may increase risk of bipolar disorder in offspring
A study published today in the American Journal of Psychiatry suggests an association between smoking during pregnancy and increased risk for developing bipolar disorder (BD) in adult children. Researchers at the New York State Psychiatric Institute and the Department of Epidemiology at the Mailman School of Public Health at Columbia University, in collaboration with scientists at the Kaiser Permanente Division of Research in Oakland, California, evaluated offspring from a large cohort of pregnant women who participated in the Child Health and Development Study (CHDS) from 1959-1966. The study was based on 79 cases and 654 comparison subjects. Maternal smoking during pregnancy was associated with a twofold increased risk of BD in their offspring.
Smoking during pregnancy is known to contribute to significant problems in utero and following birth, including low birth weight and attentional difficulties. This is the first study to suggest an association between prenatal tobacco exposure and BD, a serious psychiatric illness marked by significant shifts in mood that alternate between periods of depression and mania. Symptoms typically become noticeable in the late teens or early adulthood.
"These findings underscore the value of ongoing public health education on the potentially debilitating, and largely preventable, consequences that smoking may have on children over time," said Alan Brown, MD, MPH, senior author and Professor of Clinical Psychiatry and Epidemiology at the New York State Psychiatric Institute, Columbia University and Mailman School of Public Health.
The authors wrote: “Much of the psychopathology associated with prenatal tobacco exposure clusters around the ‘externalizing’ spectrum, which includes attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), conduct disorder (CD), and substance abuse disorders. Although not diagnostically classified along the externalizing spectrum, BD shares a number of clinical characteristics with these disorders, including inattention, irritability, loss of self-control, and proclivity to drug/alcohol use.” In effect, children who were exposed to tobacco smoke in utero may exhibit some symptoms and behaviors that are found in BD.
A previous study by Dr. Brown and colleagues found that flu virus in pregnant mothers was associated with a fourfold increased risk that their child would develop BD.
(Image: istockphoto)