Bipolar disorders research

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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 [1]. 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 [2] and Cardno, 1999 [3]).

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.[4] Inhibitors of the enzyme GSK-3β may mimic the therapeutic action of mood stabilizers like lithium.[5]

Current and ongoing research

Research Seeking User Participation

The following research is seeking user participation, which is essential for the furthering of our understanding of bipolar disorder.

Research is being conducted in London investigating 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. (This study is non-profit, it is funded entirely by research councils and non-profit foundations. It is not a commercial clinical trial).

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 seeking research funding to open up its recruitment to volunteers from all over the world (see Remote eMonitoring) (This study is non-profit as well. It is funded entirely by research councils and non-profit foundations. It is not a commercial clinical trial).

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.

Phenomenological Reseach

Johns Hopkins and NIMH researchers [6] 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.

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[7] 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.[8] Better understanding of the neural circuits involved in regulating mood states, and genetic factors such as the cadherin gene FAT linked to bipolar disorder,[7] 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 patients[citation needed]. 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.[9],[10]

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[3].

Transcranial magnetic stimulation is another fairly new technique being studied.

Pharmaceutical research is extensive and ongoing, as seen at

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

See also


  1. Baum, A E; McMahon, F J (8 May 2007), "A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder.", Molecular Psychiatry
  2. [1] Kieseppa T, Partonen T, Haukka J, Kaprio J, Lonnqvist J. (2004) High concordance of bipolar I disorder in a nationwide sample of twins.
  3. [2] 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.
  4. Barrett TB, Hauger RL, Kennedy JL, Sadovnick AD, Remick RA, Keck PE, McElroy SL, Alexander M, Shaw SH, Kelsoe JR. (2003). "Evidence that a single nucleotide polymorphism in the promoter of the G protein receptor kinase 3 gene is associated with bipolar disorder". Molecular Psychiatry. 8 (5): 546–57. doi:10.1038/ Unknown parameter |month= ignored (help)
  5. Kozikowski AP et al. (2007): JACS 8332. Full text
  6. Potash, JB; Toolan, J; Steele, J; Miller, EB; Pearl, J; Zandi, PP; Schulze, TG; Kassem, L; Simpson, SG; Lopez, V; NIMH Genetics Initiative Bipolar Disorder Consortium; Mackinnon, DF; McMahon, FJ (2007), "The bipolar disorder phenome database: a resource for genetic studies", Am J Psychiatry, 164 (August): 1229–37, doi:10.1176/appi.ajp.2007.06122045
  7. 7.0 7.1 Prefrontal Cortex in Bipolar Disorder
  8. Kempton, M.J., Geddes, J.R, Ettinger, U. et. al. (2008). "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
  9. LFMS: Low Field Magnetic Stimulation: Original EP-MRSI Study in Volunteers with Bipolar Disorder McLean Hospital Neuroimaging Center.
  10. Rohan, Michael (2004). "Low-Field Magnetic Stimulation in Bipolar Depression Using an MRI-Based Stimulator". American Journal of Psychiatry. 161 (1): 93–98. doi:10.1176/appi.ajp.161.1.93. PMID 14702256. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)