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Translation of Science to Service: Melissa P. DelBello, MD, MS, University of Cincinnati

July 19th, 2010

Translation of Science to Service: Series on Pediatric Bipolar Disorder Scientific Evolution
Melissa P. DelBello, MD, MS

Associate Professor of Psychiatry and Pediatrics
Vice-Chair of Clinical Research
University of Cincinnati College of Medicine, Ohio

Programmatic Approach

            The mission of the Division of Bipolar Disorders Research at the University of Cincinnati is to use novel methods to clarify the brain changes that are associated with bipolar disorder in order to develop new treatments for bipolar disorder.  Our ultimate goal is to improve the day-to-day life of children, adolescents, and adults with bipolar disorder.

            Dr. DelBello’s previous research has focused on neuroimaging (brain scanning) studies of children with bipolar disorder.  A further area of focus has centered on how having early-onset bipolar disorder affects brain development over time. Focusing on how risk and protective factors impact the clinical and neurodevelopmental course of bipolar disorder. Furthermore, Dr. DelBello’s work has focused on establishing the safety and effectiveness of medications for use in children and adolescents with and with a familial risk for developing bipolar disorder. The future direction of Dr. DelBello’s research will include integrating neuroimaging and treatment studies to identify how bipolar disorder develops, early-intervention and prevention strategies, and neurobiological chemical markers of illness and treatment response and outcome.

Questions Being Asked

  • How are children and adolescents with bipolar disorder different from adults with bipolar disorder?  Children are not just little adults.  They have a brain that is rapidly developing and therefore, may require different treatments than adults with bipolar disorder. In order to answer this question, we need to gain knowledge of how pediatric bipolar disorder develops, progresses over time, and is successfully treated. Additionally, the brain changes that are associated with bipolar disorder in adolescents may be different than those associated with adult bipolar disorder. Studies examining theses changes in children, adolescents and adults with bipolar disorder are needed.  
  • What ways are there to predict, and subsequently diagnose, the development of child and adolescent bipolar disorder?  Unlike many medical illnesses, there is no physical test that is reliably used in clinical practice to diagnose or predict the development of bipolar disorder.  However, there are several areas of investigation that may eventually help us to diagnose bipolar disorder early in its illness course, as well as predict the onset of bipolar disorder in those with a familial risk for developing the illness. Studies that include individuals with a familial risk (having a parent or sibling with a mood or bipolar disorder), genetic analyses, and brain function and chemistry measurements (obtained through brain scans) are all being used to answer these questions.  This will assist in establishing that bipolar disorder is a brain-based biological illness and, ultimately, to identify early-intervention and prevention strategies.  
  • What are the most effective and safe treatments available for child and adolescent bipolar disorder?  Having medicines that work and are also safe and well-tolerated is of paramount importance for children and adolescents with bipolar disorder. What may be appropriate for the treatment of adults with bipolar disorder may not work to treat children with bipolar disorder.  Additionally, there may be medications or psychotherapies that are not effective for adults with bipolar disorder but are effective for children and adolescents with bipolar disorder. There may also be more alternative approaches in treating bipolar disorder that have yet to be explored.  Answering this question involves clinical trials so that physicians and patients are better equipped with evidence-based medicine. 
  • What are the most effective and safe treatments available for children and adolescents with bipolar disorder who have other co-occurring diagnoses? Children and adolescents with bipolar disorder often present with other diagnoses, whether mental illness related (such as Attention Deficit/Hyperactivity Disorder [ADHD], Marijuana Abuse, Alcohol Abuse, and Generalized Anxiety Disorder), or medical illness related (such as diabetes and obesity).  While it is important to treat the underlying illness of bipolar disorder, left untreated, the other illnesses may adversely impact the course of bipolar disorder. Research is now being done to see how safe and effective certain combinations of medicines may be in treating bipolar disorder and co-occurring illness.

Studies

Experiment 1 (Melissa P. DelBello, MD, Stephen M. Strakowski, MD, Caleb M. Adler, MD, Drew H. Barzman, MD, Paula K. Shear, PhD):

  1. Description:  Investigators of this study are seeking to identify predictors of developing bipolar disorder in children of parents who have bipolar disorder. 
  2. Findings:   Although this is a current, ongoing research study, previous research has found that children of bipolar parents are significantly at risk to developing mood disorders (like bipolar disorder) as well as attention deficit/hyperactivity disorder.    Previous research of this population has also shown that changes in brain function and chemistry may serve as potential markers for bipolar disorder in children of parents with bipolar disorder, thereby allowing early diagnosis and intervention in order to minimize the morbidity and mortality that is often associated with delayed diagnosis and treatment.  
  3. Clinical Impact
    • How and where it improved our understanding:  The current research study will be one of the largest samples of brain scanned, at-risk children data to date.  It will also provide insight into how these children’s brains are different structurally, functionally, and chemically.   
    • How can you apply this in your clinical practice:  Knowing the early signs and symptoms of bipolar disorder will help identify those with a high risk for developing bipolar disorder. Early education and perhaps even treatment may lessen the severity of this illness. 
  4. Reference:  Review of studies of child and adolescent offspring of bipolar parents.  DelBello MP, Geller B. Bipolar Disorder. 2001 Dec;3(6):325-34. Review. 

 Experiment 2 (Melissa P. DelBello, MD, Robert McNamara, PhD, Jayasree Nandagopal, MD, Richard A Komoroski, PhD, Jeffrey Welge, PhD, Stephen Strakowski, MD):

  1. Description:  This research study is investigating how a substance in the human body, called omega-3 fatty acids, may help protect the brain and therefore, be useful for treating and preventing mood problems.  Specifically, children of parents who have bipolar disorder and depressive symptoms will be taking an omega-3 fatty acids supplement or placebo (a sugar pill). 
  2. Findings:  Although this is a current, ongoing research study, previous research has suggested higher omega-3 fatty acid levels act to protect the brain, which in turn may reduce mood disorders like bipolar disorder. 
  3. Clinical Impact
    • How and where it improved our understanding:  The current research will provide preliminary data as to whether omega-3 supplementation is a viable option for treatment of mood disorders and their development.
    • How can you apply this in your clinical practice:  One of the most difficult clinical dilemmas is how best to treat depression in a child with a parent who has bipolar disorder. Antidepressants may worsen the course of illness by precipitating mania and it may be premature and unnecessary to use medications that are used to treat bipolar disorder, which often are associated with significant side effects.  Therefore, omega-3 fatty acids supplementation could be used as a safe, relatively inexpensive, alternative strategy for treating  children with depression who are at risk for developing a mania.  Further research into the effects of omega-3 fatty acids may also show that it has neuroprotective properties in this population. 
  4. Reference:  National Institutes of Mental Health Research Grant, entitled, “Neurochemical Effects of Omega-3 Fatty Acids in Adolescents at Risk for Mania” 

 Experiment 3 (Melissa P. DelBello, MD, MS, Kim M. Cecil, PhD, Strakowski, SM):

  1. Description:  Twenty adolescents, hospitalized for bipolar disorder and treated with a medicine called olanzapine, received brain chemical scans at three time points, 1) before receiving olanzapine, 2) seven days after taking olanzapine, and 3) twenty-eight days after taking olanzapine.  The brain chemicals were then analyzed to see if certain amounts of chemicals corresponded to an increase or decrease in manic symptoms. 
  2. Findings: Although a specific brain chemical, called N-acetyl-aspartate (NAA), did not increase over the course of the study for all subjects, it did however increase in a certain brain area in subjects who had a significant reduction in bipolar symptoms. Research study subjects who experienced a reduction in bipolar symptoms while taking olanzapine also showed a higher level of a brain chemical called choline in their first scan, before any medicine was administered.  
  3. Clinical Impact
    • How and where it improved our understanding: This is the first research study looking at olanzapine’s brain chemical effects in adolescents with bipolar disorder.  Furthermore, this research study suggests the brain chemicals NAA and choline could be used as indicators of treatment response.  In other words, these chemicals may show physicians what child and adolescent patients are likely to respond to olanzapine. 
    • How can you apply this in your clinical practice:  Although there is no current method to determine how well patients will respond to psychiatric medicines, studies such as this may one day provide physicians a better way to prescribe medicines in their practice.  This research study also provides chemical and clinical evidence that olanzapine may reduce manic symptoms in some children and adolescents with bipolar disorder.   
  4. Reference: Neurochemical effects of olanzapine in first-hospitalization manic adolescents: a proton magnetic resonance spectroscopy study. DelBello MP, Cecil KM, Adler CM, Daniels JP, Strakowski SM. Neurpsychopharmacology. 2006 Jun;31(6):1264-73.

 Experiment 4 (Jonathan Pfeifer, MD, MS, Jeffrey Welge, PhD, Stephen M. Strakowski, MD, Caleb M. Adler, MD, Melissa P. DelBello, MD):

  1. Description:  Since a brain structure called the amygdala (which is thought to help one regulate their emotion) possibly varies in size in people with bipolar disorder, an analysis of all studies looking at amygdala size in this population was conducted.  Eleven studies that examined amygdala size through brain scanning were included in the analysis. 
  2. Findings: Smaller amygdala volumes were found in children and adolescents with bipolar disorder compared with healthy children and adolescents used as a comparison. Amygdala volumes in adults with bipolar disorder were not significantly different from the comparison group of healthy adults.  
  3. Clinical Impact
    • How and where it improved our understanding: The results of this multi-study analysis suggest structural amygdala abnormalities are likely present in youths with bipolar disorder, whereas the same structural abnormalities do not seem present in adults with the same condition. Such findings further indicate that adolescent bipolar disorder presents differently than that of adult bipolar disorder.   
    • How can you apply this in your clinical practice: Smaller brain structures do not necessarily mean problems or that bipolar disorder is present.  Moreover, MRI scans can be expensive and cannot diagnose mental illnesses such as bipolar disorder. For those and other reasons, amygdala size is too specific to measure in clinic patients. However, seeing trends in adolescent brains, through studies such as these, may provide a future direction for medicines to target those problem areas. 
  4. Reference:  Meta-analysis of amygdala volume in children and adolescents with bipolar disorder. Pfeifer MC, Welge J, Strakowski SM, Adler CM, DelBello MP. J Am Acad Child Adolesc Psychiatry. 2008 Nov;47(11):1289-98. 

 Experiment 5 (Melissa P. DelBello, MD, MS, Dennis Hanseman, PhD, Caleb M. Adler, MD, David E. Fleck, PhD, Stephen M. Strakowski, MD): 

  1. Description:  Seventy-one adolescents, having been hospitalized for the first time due to bipolar disorder, were seen by a research study psychiatrist initially and every four months thereafter for a year.  During their initial and subsequent visits, study patients were asked questions about their mood, how often they took their psychiatric medicines, and about any substance use (such as alcohol and illegal drugs). 
  2. Findings: Over time, many of the study patients got better, as a significant number recovered from their first episode of mania (meaning they no longer met clinical criteria for mania).  However, symptoms of mania persisted in a large number of study patients, even well after being hospitalized and after no longer meeting technical criteria for mania.  Specifically, patients who were diagnosed with ADHD, and/or who didn’t take their medicines regularly had more symptoms of mania over the course of the study.  Those patients who used alcohol, were treated with antidepressants, and who did not see a therapist were more likely to have a poor outcome. 
  3. Clinical Impact
    • How and where it improved our understanding:  This data set, one of the largest to characterize children and adolescents with bipolar disorder after their first psychiatric hospitalization, identifies how bipolar disorder develops over time in adolescents.  Furthermore, this study illustrates what factors lead to having more manic symptoms and recurring mania in this population. 
    • How can you apply this in your clinical practice:  Knowing what factors improve and worsen the course of adolescent bipolar disorder is of vital importance to clinicians.  Moreover, this study found high rates of non-adherence to medications, suggesting the importance of having open discussions with patients regarding adherence.   
  4. Reference:  Course of illness in first-hospitalization mania. DelBello MP, Hanseman D, Adler CM, Fleck DE, Strakowski SM. Am J Psychiatry. 2007 Apr;164(4):582-90. 

 In summary, what impact did your research have in the history of child psychiatry research in PBD?

Dr. Melissa P. DelBello’s research studies have influenced child and adolescent psychiatry, specifically with regards to bipolar disorder, in many ways by:   

  • Helping to establish once unproven treatments to be a part of the current standard-of-care. 
  • Confirming that differences exist between bipolar disorder in childhood and adolescence as compared to adult bipolar disorder.
  • Describing a large child and adolescent sample with bipolar disorder over time to see how this population recovers from their onset of illness.
  • Identifying risk factors and predictors for developing bipolar disorder in order to establish targeted early-intervention studies.

Connection to where there is Action:

  1. Clinical Contact: Liz Rusche
    ruscheem@ucmail.uc.edu
    (513) 558-4489
  1. Research Contact:
    Holly Bryan or Michelle Durling
    holly.bryan@uc.edu    michelle.durling@uc.edu
    (513) 558-3191      (513) 558-5393
    University of Cincinnati’s Division of Bipolar Disorders Research
    260 Stetson St., ML 0516
    Cincinnati, OH  45219-0516
  1. Community Support in the Local Region:
    NAMI of Hamilton County (Ohio)
    www.nami-hc.org

    Sandra Thompson or Pat Brown  (513) 351-3500
    Email:            info@nami-hc.org

            NAMI of Hamilton County (Ohio) Urban Cincinnati
            Gloria Walker (513) 251-9699 Gerry Frazier (513) 931-0836
            Email:  gwconsultingandeducation@earthlink.net  or gfraziege@gmail.com 

            DBSA of Cincinnati Metro Area
            www.dbsacincinnati.org
            Eileen Andrews, Director
            (513) 541-7114
            Email:  info@dbsacincinnati.org

            Cincinnati Children’s Hospital Medical Center Psychiatric Intake Response Center (PIRC)
           
(513) 636-4124  or  1-800-344-2462  Ext. 4124
            http://www.cincinnatichildrens.org/svc/alpha/p/psychiatry/psychiatric-intake/
            Email:  psychiatryresponse@cchmc.org

            Mental Health Access Point (MHAP)
            (513) 558-9999
            http://www.centralclinic.org/?page_id=140

            Mental Health Association of the Cincinnati Area
            (513) 721-2910
            2400 Reading Rd. #412
            Cincinnati, OH  45202-1462
            http://www.mentalhealthassn.org/
            Email:  mha@mhaswoh.org




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