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Annotation

Howes OD, Kambeitz J, Kim E, Stahl D, Slifstein M, Abi-Dargham A, Kapur S. The nature of dopamine dysfunction in schizophrenia and what this means for treatment. Arch Gen Psychiatry . 2012 Aug ; 69(8):776-86. PubMed Abstract

Comments on Paper and Primary News
Comment by:  Bryan Roth
Submitted 18 April 2012 Posted 18 April 2012

The dopamine hypothesis of schizophrenia, in various guises, has captivated the attention of, literally, a large army of psychiatric researchers for nearly 50 years (see, e.g., Carlsson and Lindqvist, 1963). Indeed, a PubMed search of the terms "schizophrenia" and "dopamine" elicits nearly 7,000 articles. Further, every approved antipsychotic drug modulates D2-dopamine receptors and—with the exception of aripiprazole, which is a functionally selective D2 agonist—is a D2 antagonist. Finally, despite nearly three decades of research and billions of dollars spent by the pharmaceutical industry, no drug that does not interact with D2 dopamine receptors has proven to be any more effective than haloperidol for non-treatment-resistant schizophrenia.

Despite this focused research on dopamine, dopamine receptors, and schizophrenia, no clear consensus has emerged regarding whether schizophrenia is associated with excessive dopaminergic neurotransmission. As succinctly stated many years ago:

“The dopamine hypothesis of...  Read more


View all comments by Bryan Roth

Comment by:  Christoph Kellendonk
Submitted 18 April 2012 Posted 18 April 2012

The meta-analysis by Howes et al. once more confirms that there are abnormalities in the dopamine system in the striatum of patients with schizophrenia.

What is new is recent evidence about the location of the dopaminergic hyperfunction. Several high-resolution imaging studies performed in the last few years suggest it to be located in the head of the caudate rather than the ventral striatum. The head of the caudate receives projections from the dorsolateral prefrontal cortex, an area important for the cognitive symptoms of schizophrenia. These new findings contradict the widely accepted hypothesis that the dopaminergic hyperfunction in the striatum is mainly in the ventral or “limbic” striatum.

Another interesting new finding is that the abnormalities in the striatal dopamine system are already present in prodromal subjects. They therefore may occur early in the disease process and could be of primary origin. Obviously, to really understand the etiology of the disorder we would have to image the dopamine system at even earlier developmental stages—something...  Read more


View all comments by Christoph Kellendonk
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