Can Early Symptoms Predict Bipolar Disorder? Evidence Shows Differing Patterns of Risk Factors

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Two patterns of antecedent or “prodromal” psychiatric symptoms may help to identify young persons at increased risk of developing bipolar disorder (BD), according to a new analysis in the Harvard Review of Psychiatry.

Early signs of BD can fall into a relatively characteristic “homotypic” pattern, consisting mainly of symptoms or other features associated with mood disorders; or a “heterotypic” pattern of other symptoms including anxiety and disruptive behavior. Environmental risk factors and exposures can also contribute to BD risk, according to the analysis by Ciro Marangoni, MD, at the Department of Mental Health, Mater Salutis Hospital, Legnato, Italy; Gianni L. Faedda, MD, Director of the Mood Disorder Center of New York, NY, and Co-Chairman of a Task Force of the International Society for Bipolar Disorders on this topic; and Professor Ross J. Baldessarini, MD, Director of the International Consortium for Bipolar & Psychotic Disorders Research of the Mailman Research Center at McLean Hospital in Belmont, Mass.

The authors reviewed and analyzed data from 39 studies of prodromal symptoms and risk factors for later development of BD. Their analysis focused on high-quality evidence from prospective studies in which data on early symptoms and risk factors were gathered before BD was diagnosed.

BD is commonly preceded by early depression or other symptoms of mental illness, sometimes years before BD develops, as indicated by onset of mania or hypomania. Nevertheless, the authors note that “the prodromal phase of BD remains incompletely characterized, limiting early detection of BD and delaying interventions that might limit future morbidity.”

The evidence reviewed suggested two patterns of early symptoms that “precede and predict” later BD. A homotypic pattern consisted of affective or mood-associated symptoms that are related to, but fall short of, standard diagnostic criteria for BD: for example, mood swings, relatively mild symptoms of excitement, or major depression, sometimes severe and with psychotic symptoms.
The authors note that homotypic symptoms have “low sensitivity” — that is, most young people with these mood symptoms do not later develop BD. However, this symptom pattern also had “moderate to high specificity” — homotypic symptoms do occur in many patients who go on to develop BD.

The heterotypic pattern consisted of other types of prodromal symptoms, such as early anxiety and disorders of attention or behavior. This pattern had low sensitivity and specificity: relatively few patients with such symptoms develop BD, while many young people without heterotopic symptoms do develop BD.

The study findings also associate several other factors with an increased risk of developing BD, including preterm birth, head injury, drug exposures (especially cocaine), physical or sexual abuse, and other forms of stress. However, for most of these risk factors, both sensitivity and specificity are low.

Although many elements of the reported patterns of prodromal symptoms and risk factors have been identified previously, the study increases confidence that they are related to the later occurrence of BD. The researchers note that the findings of high-quality data from prospective studies are “encouragingly similar” to those of previous retrospective and family-risk studies.

“There was evidence of a wide range of [psychiatric] symptoms, behavioral changes, and exposures with statistically significant associations with later diagnoses of BD,” the authors conclude. With further study, the patterns of prodromal symptoms and risk factors may lead to new approaches to identifying young persons who are likely to develop BD, and might benefit from early treatment. The investigators add that predictive value might be even higher with combinations of multiple risk factors, rather than single predictors.

Materials provided by Wolters Kluwer Health

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Gene Breakthrough on Lithium Treatment for Bipolar Disorder

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Genes linked to schizophrenia in psychiatric patients suffering from bipolar disorder are the reason why such patients don’t respond to the “gold standard” treatment for bipolar – the drug lithium – according to international research led by the University of Adelaide.

Lithium has been widely used as a treatment for bipolar disorder since the 1950s because of its mood stabilising effect. It has unique protective properties against both manic and depressive episodes, and an ability to decrease the risk of suicide.

However, about 30% of patients are only partially responsive, more than a quarter show no clinical response at all, and others have significant side-effects to lithium.

Until now, researchers have not understood why these patients have not responded to the common treatment, while others have responded well to the drug.

Published in the journal JAMA Psychiatry>, an international consortium of researchers led by the University of Adelaide’s Professor Bernhard Baune reports a major discovery that could affect the future quality of treatment for people with this significant mental health condition.

Known as the international Consortium on Lithium Genetics, the group has studied the underlying genetics of more than 2500 patients treated with lithium for bipolar disorder.

“We found that patients clinically diagnosed with bipolar disorder who showed a poor response to lithium treatment all shared something in common: a high number of genes previously identified for schizophrenia,” says Professor Baune, Head of the Discipline of Psychiatry at the University of Adelaide and lead author on the paper.

“This doesn’t mean that the patient also had schizophrenia – but if a bipolar patient has a high ‘gene load’ of schizophrenia risk genes, our research shows they are less likely to respond to mood stabilisers such as lithium.

“In addition, we identified new genes within the immune system that may play an important biological role in the underlying pathways of lithium and its effect on treatment response,” Professor Baune says.

Understanding the underlying biology of people’s response to lithium treatment is a key area of research and urgent clinical need in mental health.

“These findings represent a significant step forward for the field of translational psychiatry,” Professor Baune says.

“In conjunction with other biomarkers and clinical variables, our findings will help to advance the highly needed ability to predict the response to treatment prior to an intervention. This research also provides new clues as to how patients with bipolar disorder and other psychiatric disorders should be treated in the future.”

Text provided by the University of Adelaide.

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Bipolar Genes Linked to Autism

Many psychiatric diseases share genetic roots. A new study, run by researchers at three different laboratories, suggests that rare genetic variations linked to bipolar disorder are also linked to schizophrenia and especially autism.

The study, by researchers at Johns Hopkins School of Medicine, Cold Spring Harbor Laboratory, and the University of Iowa Carver College of Medicine, is among the first to demonstrate the overlap between bipolar disorder and autism.

Despite bipolar disorder’s demonstrated inheritability, pinpointing genes relating to the disease has been exorbitantly difficult. But advances made in medical science recently have allowed scientists to start to figure out which genetic variations affect patients with bipolar disorder.

The researchers behind the study linking autism with bipolar disorder combined a case-control approach with “family-based exome sequencing” to try to discover which genetic variations contribute to bipolar. Case-control approaches look at genetic variants in people who have the disorder compared to people who don’t to figure out which genes increased susceptibility to the disease. The key to this approach is large pools of data.

Family-based exome sequencing is more difficult to perform. Scientists compare all the expressed genes in a genome (known as the exome). The researchers first examine the DNA that encodes proteins (known as exons), and then put that DNA into sequence using computers. This allows technicians to see variants that “travel with” the disease, especially in cases where the disorder is passed from parent to child.

This two-pronged approach identified 84 rare variants in 82 genes that traveled with bipolar disorder. The research team then examined these

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84 variants in three case-control datasets of 3,541 individuals with bipolar disorder and 4,774 control patients to figure out which variants predicted the disorder.

 

Nineteen genes were over-represented in bipolar disorder patients compared to the controls. However, while the data on these genes wasn’t enough to specifically pinpoint the genetic culprits of bipolar disorder, several of the genes were linked to autism and schizophrenia, with autism being especially prominent.

The findings suggest that schizophrenia, bipolar disorder, and autism have similar roots, and are simply different manifestations of similar diseases. The researchers from the study hope that by linking these diseases and finding which genes are responsible, new treatments will be discovered for all of them.

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