Bipolar disorders research

Bipolar disorder research

Heritability or inheritance of the illness

More than two-thirds of people with bipolar disorder have at least one close relative with the disorder or with unipolar major depression, indicating that the disease has a genetic component. Studies seeking to identify the genetic basis of bipolar disorder indicate that susceptibility stems from multiple genes. Scientists are continuing their search for these genes using advanced genetic analytic methods and large samples of families affected by the illness. The researchers are hopeful that identification of susceptibility genes for bipolar disorder, and the brain proteins they code for, will make it possible to develop better treatments and preventive interventions targeted at the underlying illness process.

Recent genetic research

Researchers at NIMH have found a correlation between DGKH (diacylglycerol kinase eta) and bipolar disorder.The portion of the genome that encodes DGKH, a key protein in the lithium-sensitive phosphatidyl inositol pathway [ Citation
last1 = Baum | first1 = A E
last2 = McMahon | first2 = F J
title= A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder.
journal = Molecular Psychiatry
date = 8 May 2007
year = 2007
url = http://www.nature.com/mp/journal/vaop/ncurrent/abs/4002012a.html] . A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder. The DGKH enzyme is related to the reactions of medications used in lithium therapy. The actual mechanism(s) and chemical effects of lithium in the brain with respect to mental illnesses it still not completely known. Researchers are developing better medications by looking at molecular compounds acting on the DGKH enzyme to control the rate at which it is produced. These therapies and medicines could potentially control how much of the enzyme, and at what rate it is produced. This could beneficial for people with bipolar disorder or other related mental illnesses. This first genome-wide association study of bipolar disorder shows that several genes, each of modest effect, reproducibly influence disease risk.

Bipolar disorder may be a polygenic disease.

Bipolar disorder is considered to be a result of complex interactions between genes and environment. The monozygotic concordance rate for the disorder is 70%. This means that if a person has the disorder, an identical twin has a 70% likelihood of having the disorder as well. Dizygotic twins have a 23% concordance rate. These concordance rates are not universally replicated in the literature, recent studies have shown rates of around 40% for monozygotic and <10% for dizygotic twins (see Kieseppa, 2004 [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15465978&query_hl=8&itool=pubmed_docsum] Kieseppa T, Partonen T, Haukka J, Kaprio J, Lonnqvist J. (2004) High concordance of bipolar I disorder in a nationwide sample of twins.] and Cardno, 1999 [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10025441&query_hl=8&itool=pubmed_docsum] Cardno AG, Marshall EJ, Coid B, Macdonald AM, Ribchester TR, Davies NJ, Venturi P, Jones LA, Lewis SW, Sham PC, Gottesman II, Farmer AE, McGuffin P, Reveley AM, Murray RM. (1999) Heritability estimates for psychotic disorders: the Maudsley twin psychosis series.] ).

In 2003, a group of American and Canadian researchers published a paper that used gene linkage techniques to identify a mutation in the GRK3 gene as a possible cause of up to 10% of cases of bipolar disorder. This gene is associated with a kinase enzyme called G protein receptor kinase 3, which appears to be involved in dopamine metabolism, and may provide a possible target for new drugs for bipolar disorder.cite journal | author = Barrett TB, Hauger RL, Kennedy JL, Sadovnick AD, Remick RA, Keck PE, McElroy SL, Alexander M, Shaw SH, Kelsoe JR. | month = May | year = 2003 | title = Evidence that a single nucleotide polymorphism in the promoter of the G protein receptor kinase 3 gene is associated with bipolar disorder | journal = Molecular Psychiatry | volume = 8 | issue = 5 | pages = 546–57| doi = 10.1038/sj.mp.4001268 | url = http://www.nature.com/mp/journal/v8/n5/abs/4001268a.html ] Inhibitors of the enzyme GSK-3"β" may mimic the therapeutic action of mood stabilizers like lithium. [Kozikowski AP et al. (2007): JACS 8332. [http://pubs.acs.org/cgi-bin/sample.cgi/jacsat/2007/129/i26/pdf/ja068969w.pdf Full text] ]

Current and ongoing research

* [http://nimhgenetics.org/| NIMH Genetics Initiative Bipolar Disorder Consortium] The goal of this Initiative is to establish a national resource of clinical data and biomaterials that are collected from individuals with Alzheimer disease, schizophrenia, or bipolar I disorder (BP), in order to aid researchers in understanding the genetic bases of these disorders.

* [http://www.nimh.nih.gov/dnbbs/7g-grr.cfm| Human Genetics Initiative and Genomic Resources Program (7G-GRR)] Topics of interest to this program include the development and distribution of genomic resources (such as DNA and cDNA arrays, gene chips, and gene expression neuroinformatics tools).

Areas of Emphasis:Generation and distribution of mutant mouse strains and phenotypic data for animals with defects in neural function and complex behavior. Co-support of other NIH-funded research that generates structural genetic data for humans and other species. Using the NIMH Human Genetics Initiative to share data and biomaterials collected in various genetic studies.

* [http://www.nimh.nih.gov/studies/studies_ct.cfm?id=4 NIMH: Clinical Trials of Bipolar Disorder (Manic-Depressive Illness)] at NIMH - (The National Institute of Mental Health).

* [http://bioinformoodics.jhmi.edu/gm/phenome/ The Bipolar Disorder Phenome Database] at Johns Hopkins Medicine (Johns Hopkins University School of Medicine)

Johns Hopkins and NIMH researchers [Citation
last = Potash
first = JB
last2 = Toolan
first2 = J
last3 = Steele
first3 = J
last4 = Miller
first4 = EB
last5 = Pearl
first5 = J
last6 = Zandi
first6 = PP
last7 = Schulze
first7 = TG
last8 = Kassem
first8 = L
last9 = Simpson
first9 = SG
last10 = Lopez
first10 = V
last11 = NIMH Genetics Initiative Bipolar Disorder Consortium
first11 =
last12 = Mackinnon
first12 = DF
last13 = McMahon
first13 = FJ
title = The bipolar disorder phenome database: a resource for genetic studies
journal = Am J Psychiatry
volume = 164
issue = August
pages = 1229-37
date =
year = 2007
url =
doi = 10.1176/appi.ajp.2007.06122045
id = ] created a database for bipolar disorder and the database is comparable to large-scale genetics efforts, e.g. HapMap, Human Genome Project and Genetic Analysis Information Network. The database offers power to define novel clinical subtypes of bipolar disorder, test for familial aggregation, and carry out genetic linkage and association studies that use specific clinical features as covariates or as primary phenotypes. Blood samples were collected in five sub-projects with various instruments over a 20-year period and that information is combined to database. The information from series of interviews was validated. After data cleansing and analysis the result is combined Bipolar Disorder Phenome Database which consists of 5,721 subjects (3,186 affected) in 1,177 families, 197 variables, and 1,127,037 datapoints. There is different possibilities to new research with this database but it should be remembered that this (only) a phenomenological database. Users of the Bipolar Disorder Phenome Database has to have a legitimate scientific aim and researchers has to apply for user rights.

The following studies are ongoing and are recruiting volunteers:

* [http://www.iop.kcl.ac.uk/twinstudy The Maudsley Bipolar Twin Study] , based at the Institute of PsychiatryResearch is being conducted in London about the genetic basis of bipolar disorder using twin methodology. Currently recruiting volunteers: identical and non-identical twins pairs where either one or both twins has a diagnosis of Bipolar I or Bipolar II.

* [http://www.bipolarlab.com/emonitoring The Maudsley Bipolar eMonitoring Project] , another research study based at the Institute of Psychiatry in London, is conducting novel research on electronic monitoring methodologies (electronic mood diaries and actigraphy) for tracking bipolar symptom fluctuations in Bipolar individuals who are interested in self-managing their condition. The study is currently recruiting volunteers from all over the world (see [http://www.bipolarlab.com/emonitoring/remote Remote eMonitoring] )

* The Bipolar Disorders Clinic at the Department of Psychiatry and Behavioral Sciences at Stanford University School of Medicine manages clinical trials and neuroimaging studies. SMRI is the largest nonprofit provider of research funding for schizophrenia and bipolar disorder in the United States.

Medical imaging

Researchers are using advanced brain imaging techniques to examine brain function and structure in people with bipolar disorder, particularly using the functional MRI and positron emission tomography. An important area of neuroimaging research focuses on identifying and characterizing networks of interconnected nerve cells in the brain, interactions among which form the basis for normal and abnormal behaviors. Researchers hypothesize that abnormalities in the structure and/or function of certain brain circuits could underlie bipolar and other mood disorders and studies have found anatomical differences in areas such as the prefrontal cortex [http://www.neurotransmitter.net/bipolarpfc.html Prefrontal Cortex in Bipolar Disorder] Neurotransmitter.net.] and hippocampus. A meta-analysis of 98 MRI or CT neuroimaging studies reported that patients with bipolar disorder had lateral ventricles which were 17% larger than controls and patients were 2.5 times more likely to have deep white matter hyperintensities. [Kempton, M.J., Geddes, J.R, Ettinger, U. et. al. (2008). " [http://archpsyc.ama-assn.org/cgi/content/short/65/9/1017 Meta-analysis, Database, and Meta-regression of 98 Structural Imaging Studies in Bipolar Disorder] ," "Archives of General Psychiatry", 65:1017–1032 see also MRI database at [http://www.bipolardatabase.org www.bipolardatabase.org] .] Better understanding of the neural circuits involved in regulating mood states, and genetic factors such as the cadherin gene "FAT" linked to bipolar disorder,cite web | author = Emma Young | year = 2006 | url = http://www.newscientist.com/article.ns?id=dn8572&feedId=online-news_rss20 | title = New gene linked to bipolar disorder | work = New Scientist | accessyear = 2006] may influence the development of new and better treatments and may ultimately aid in early diagnosis and even a cure.

Personality types or traits

An evolving literature exists concerning the nature of personality and temperament in bipolar disorder patients, compared to major depressive disorder (unipolar) patients and non-sufferers. Such differences may be diagnostically relevant. Using MBTI continuum scores, bipolar patients were significantly more extroverted, intuitive and perceiving, and less introverted, sensing, and judging than were unipolar patientsFact|date=February 2007. This suggests that there might be a correlation between the Jungian extraverted intuiting process and bipolar disorder. There are limitations to this study in that many bipolar individuals, particularly poets, writers, scientists and artists tend to be introverted.

Research into new treatments

In late 2003, researchers at McLean Hospital found tentative evidence of improvements in mood during echo-planar magnetic resonance spectroscopic imaging (EP-MRSI), and attempts are being made to develop this into a form which can be evaluated as a possible treatment. [http://www.mclean.harvard.edu/research/neuroimaging/bic/mri-bipolar-summaryepmrsi.php LFMS: Low Field Magnetic Stimulation: Original EP-MRSI Study in Volunteers with Bipolar Disorder] McLean Hospital Neuroimaging Center.] ^,cite journal | first = Michael | last = Rohan | coauthors = Aimee Parow, Andrew L. Stoll, Christina Demopulos, Seth Friedman, Stephen Dager, John Hennen, Bruce M. Cohen, and Perry F. Renshaw | month = January | year = 2004 | title = Low-Field Magnetic Stimulation in Bipolar Depression Using an MRI-Based Stimulator | journal = American Journal of Psychiatry | volume = 161 | issue = 1 | pages = 93–98 | pmid = 14702256 | url = http://ajp.psychiatryonline.org/cgi/content/full/161/1/93 | doi = 10.1176/appi.ajp.161.1.93]

NIMH has initiated a large-scale study at twenty sites across the U.S. to determine the most effective treatment strategies for people with bipolar disorder. This study, the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), will follow patients and document their treatment outcome for 5 to 8 years. For more information, visit the Clinical Trials page of the NIMH Web site [http://www.nimh.nih.gov/studies/studies_ct.cfm?id=4] .

Transcranial magnetic stimulation is another fairly new technique being studied.

Pharmaceutical research is extensive and ongoing, as seen at [http://clinicaltrials.gov clinicaltrials.gov] .

Gene therapy and nanotechnology are two more areas of future development.

ee also

* Mood (psychology)
* Emotion
* List of people believed to have been affected by bipolar disorder
* List of songs about bipolar disorder
* Bipolar spectrum
* Seasonal affective disorder
* Oppositional Defiance Disorder
* Emotional dysregulation
* Creativity and bipolar disorder
* Bipolar disorder
* Bipolar I
* Bipolar II

References