More threads by David Baxter PhD

David Baxter PhD

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Dopamine hypothesis for bipolar disorder supported by review
By Liam Davenport
29 August 2007
Acta Psychiatr Scand 2007; 116: 41-49

There appears to be increased dopaminergic drive during the manic phase of bipolar disorder, with the opposite seen in depressive phases, concludes an international team of scientists.

If confirmed, the findings could have implications for drug treatment of this condition, say Michael Berk, from the University of Melbourne in Geelong, Australia, and colleagues.

The lack of a pathophysiological model to explain bipolar disorder has held back the rational development of specific treatments. However, there is evidence to suggest excessive dopamine neurotransmission is involved in the development of manic symptoms in bipolar disorder, and that dopamine deficits play an important role in depression.

To investigate further, Berk and team conducted a literature search of the Embase, PsychLIT, PubMed, and MEDLINE databases using keywords relevant to bipolar disorder and dopamine metabolism.

In all, over 100 articles were reviewed, with approximately 75% found to be relevant to the study. The findings indicated that, in bipolar disorder, there is cyclical dysregulation of quantitative dopaminergic transmission, with an increase during the manic phase.

Endogenous homeostatic adaptive mechanisms then result in secondary down-regulation, which dampens the cycle, leading to the decreased dopaminergic transmission that is characteristic of the depressive phase. The team suggests that secondary upregulation, again by endogenous homeostatic mechanisms, may then terminate the depressive episode and lead to the next phase.

The researchers note that some Parkinson's disease patients given levodopa as primary therapy, augmented by dopamine agonists, have symptoms similar to those in patients with bipolar disorder, with self-administered escalating doses, in spite of the persisting dyskinesias, leading to psychiatric syndromes. When the intake of dopamine precursors was reduced, profound depression followed.

Among other evidence revealed by the review, the team found clinical data to suggest that dopamine administration produces hypomanic episodes in patients with bipolar disorder, and that dopaminergic antagonists appear to have a class effect in treating mania. Furthermore, lithium has been shown to decrease the amount of dopamine and its metabolites in unipolar and bipolar women.

The researchers say: "The results of this review support the hypothesis of a dopamine dysregulation syndrome in bipolar disorder... The findings summarized in this paper confirm that initial hypothesis, demonstrating that most of the current knowledge as regards bipolar disorder is still consistent with the dopaminergic model.

"As new functions of dopaminergic neurotransmission become clearer, continued exploration of the transcriptional neuroanatomy of these unique neurones will be vital for producing targeted, selective, and effective therapeutic agents."

The research is published in the journal Acta Psychiatrica Scandinavica.

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