Bipolar disorder future or investigational therapies

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]


Future or Investigational Therapies

Genetic research

There is increasing evidence for a genetic component in the causation of bipolar disorder, provided by a number of twin studies and gene linkage studies.

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

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. [3]

A 2007 gene-linkage study by an international team coordinated by the NIMH has identified a number of genes as likely to be involved in the etiology of bipolar disorder, suggesting that bipolar disorder may be a polygenic disease. The 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 [4].

The following studies are ongoing, and are recruiting volunteers:

The Maudsley Bipolar Twin Study, based at the Institute of Psychiatry in London is conducting research 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 II.

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 eMonitoring)

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 [5] and hippocampus.

Better understanding of the neural circuits involved in regulating mood states, and genetic factors such as the cadherin gene FAT linked to bipolar disorder, [5] may influence the development of new and better treatments, and may ultimately aid in early diagnosis and even a cure.

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. [6][7]

NIMH has initiated a large-scale study at 20 sites across the United States 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 5-8 years. For more information, visit the Clinical Trials page of the NIMH Web site. [8]

Transcranial magnetic stimulation is another fairly new technique being studied.

Pharmaceutical research is extensive and ongoing, as seen at


  1. [1] Kieseppa T, Partonen T, Haukka J, Kaprio J, Lonnqvist J. (2004) High concordance of bipolar I disorder in a nationwide sample of twins.
  2. [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.
  3. 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)
  4. 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 Check date values in: |date= (help)
  5. 5.0 5.1 Cortex in Bipolar Disorder
  6. LFMS: Low Field Magnetic Stimulation: Original EP-MRSI Study in Volunteers with Bipolar Disorder McLean Hospital Neuroimaging Center.
  7. Rohan, Michael (2004). "Low-Field Magnetic Stimulation in Bipolar Depression Using an MRI-Based Stimulator". American Journal of Psychiatry. 161 (1): 93–98. PMID 14702256. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  8. "". External link in |title= (help)

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