Schizophrenia Research Today is a free monthly online journal that collates and summarizes the latest research about Schizophrenia, including details on paranoia, symptoms, treatment, depression, medication.

The effect of antipsychotics on the high-affinity state of D2 and D3 receptors: a positron emission tomography study With [11C]-(+)-PHNO.

Graff-Guerrero A, Mamo D, Shammi CM, Mizrahi R, Marcon H, Barsoum P, Rusjan P, Houle S, Wilson AA, Kapur S

PO Box 053, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, England.

CONTEXT: Most antipsychotics are thought to have an effect on D(2) and D(3) receptors. The development of carbon 11-labeled (+)-4-propyl-9-hydroxynaphthoxazine ([(11)C]-(+)-PHNO), the first agonist radioligand with higher affinity for D(3) than D(2) receptors, allows one to differentiate the effects of antipsychotics on high-affinity vs low-affinity sites of the D(2) receptor and on D(3) vs D(2) receptor subtypes. OBJECTIVES: To examine the effects of antipsychotics (clozapine, risperidone, or olanzapine) on the high- vs high- + low-affinity sites of the D(2) and D(3) receptors by comparing the [(11)C]-(+)-PHNO and [(11)C]raclopride binding in the D(3) receptor-rich (globus pallidus and ventral striatum) and D(2) receptor-rich (caudate and putamen) regions. DESIGN: Two sequential studies with different participants and appropriate controls were performed. The first compared the occupancy produced by 3 antipsychotics as measured with [(11)C]-(+)-PHNO and [(11)C]raclopride. The second was a double-blind, placebo-controlled experiment to compare the effect of pramipexole (a D(3) receptor-preferring agonist) vs placebo on the increased [(11)C]-(+)-PHNO signal observed in the globus pallidus of patients. SETTING: Positron Emission Tomography Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. PARTICIPANTS: Twenty-three patients with schizophrenia and 23 healthy controls. MAIN OUTCOME MEASURES: Antipsychotic occupancies as measured with [(11)C]-(+)-PHNO and [(11)C]raclopride. RESULTS: The antipsychotic-treated patients showed high occupancies with both [(11)C]-(+)-PHNO and [(11)C]raclopride in the dorsal striatum, with [(11)C]raclopride occupancies about 20% higher. Most strikingly, patients did not show any occupancy with [(11)C]-(+)-PHNO in the globus pallidus as compared with normal controls or with their own scans using [(11)C]raclopride. This unblocked [(11)C]-(+)-PHNO signal was displaced by a single dose of pramipexole. CONCLUSIONS: Antipsychotics block both the high- and low-affinity states of the D(2) receptors across the brain, but antipsychotic treatment does not block the [(11)C]-(+)-PHNO signal in the D(3) receptor-rich regions, despite the ongoing D(2) receptor blockade. This [(11)C]-(+)-PHNO signal in regions such as the globus pallidus seems increased despite antipsychotic treatment and is displaceable by a D(3) receptor-preferring agonist. The radiotracer [(11)C]-(+)-PHNO and the data open up new avenues for exploring the potential therapeutic significance of the D(3) receptor in schizophrenia.

Published 2 June 2009 in Arch Gen Psychiatry, 66(6): 606-15.
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Articles on Schizophrenia published 2 June 2009:

Familiality of novel factorial dimensions of schizophrenia.   Arch Gen Psychiatry, 66(6): 591-600.

CONTEXT: Factor analysis of the signs and symptoms of schizophrenia yields dimensional phenotypes that may relate to underlying genetic variation. Examination of familiality of factor scores can demonstrate whether they are likely to be of use in genetic research. OBJECTIVE: To produce a broader set of factorial phenotypes that are tested for familiality including core symptoms of schizophrenia and additional indicators of social, work, and educational dysfunction. DESIGN: The study used ... [Abstract] [Full-text]

Articles on Schizophrenia published 1 June 2009:

Classification of schizophrenia with spectro-temporo-spatial MEG patterns in working memory.   Clin Neurophysiol, 120(6): 1123-34.

OBJECTIVE: To investigate whether temporo-spatial patterns of brain oscillations extracted from multichannel magnetoencephalogram (MEG) recordings in a working memory task can be used successfully as a biometric marker to discriminate between healthy control subjects and patients with schizophrenia. METHODS: Five letters appearing sequentially on a screen had to be memorized. The letters constituted a word in one condition and a pronounceable non-word in the other. Power changes of 248 channel ... [Abstract] [Full-text]

Articles on Schizophrenia published 20 May 2009:

Schizophrenia, substance abuse, and violent crime.   JAMA, 301(19): 2016-23.

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Articles on Schizophrenia published 11 May 2009:

A disturbed sense of self in the psychosis prodrome: linking phenomenology and neurobiology.   Neurosci Biobehav Rev, 33(6): 807-17.

Interest in the early phase of psychotic disorders has risen dramatically in recent years. Neurobiological investigations have focused specifically on identifying brain changes associated with the onset of psychosis. The link between these neurobiological findings and the complex phenomenology of the early psychosis period is not well understood. In this article, we re-cast some of these observations, primarily from neuroimaging studies, in the context of phenomenological models of "the ... [Abstract] [Full-text]

Articles on Schizophrenia published 5 May 2009:

Widespread reductions of cortical thickness in schizophrenia and spectrum disorders and evidence of heritability.   Arch Gen Psychiatry, 66(5): 467-77.

CONTEXT: Schizophrenia is a brain disorder with predominantly genetic risk factors, and previous research has identified heritable cortical and subcortical reductions in local brain volume. To our knowledge, cortical thickness, a measure of particular interest in schizophrenia, has not previously been evaluated in terms of its heritability in relationship to risk for schizophrenia. OBJECTIVE: To quantify the distribution and heritability of cortical thickness changes in schizophrenia. DESIGN: ... [Abstract] [Full-text]

Articles on Schizophrenia published 4 May 2009:

Conception season and cerebral asymmetries among American baseball players: implications for the seasonal birth effect in schizophrenia.   Psychiatry Res, 167(3): 287-93.

People with schizophrenia and children born with neural tube defects both tend to be conceived most often in May-June, about a month before the summer solstice, and least often in November-December, a month before the winter solstice. Such timings, coupled with evidence of cerebral asymmetry deficits in schizophrenia, and evidence that asymmetry development and neural tube closure represent concurrent fourth-embryonic-week processes both sensitive to oxidant stress, led us to the hypothesis ... [Abstract] [Full-text]

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Past research suggests that unawareness of illness in schizophrenia is associated with deficits in executive functions; however, the relationships between executive processes and the various dimensions of insight are still unclear. Recent models of executive functioning have proposed that four executive processes - inhibition, updating, shifting and dual task coordination - are moderately related yet separable. In this study, we proposed to investigate and clarify the relationships between ... [Abstract] [Full-text]

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Suicide is the single major cause of death among patients with schizophrenia. Despite great efforts in the prevention of such deaths, suicide rates have remained alarming, pointing to the need for a better understanding of the phenomenon. The present sample comprised 20 male patients with schizophrenia who committed suicide and who were investigated retrospectively for a large number of characteristics. Controls were 20 living patients with schizophrenia. The results suggest that suicide ... [Abstract] [Full-text]

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