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Objectives: To assess the impact of reducing the dose of antipsychotics on cognition and dopaminergic D2 receptor availability in the whole striatum, and identify their relationship in patients with schizophrenia aged 50 years or older.Design: Open-label prospective PET [11C]-raclopride study.Setting: A tertiary care center outpatient setting.Participants: Thirty-seven clinically stable participants with schizophrenia or schizoaffective disorder, aged 50 years or greater, and having been treated with olanzapine or risperidone monotherapy at the same dose for at least 6 months.Intervention: Gradual reduction in their olanzapine or risperidone daily dose of up to 40%.Measurements: Clinical and cognitive assessments, and [11C]-raclopride PET to determine D2 receptor availability at baseline and after the dose reduction. Main outcome measures were overall cognition and D2 receptor availability in whole striatum.Results: Reducing the antipsychotic dose resulted in an increase in D2 receptor availability in the whole striatum and an association between D2 receptor availability and overall cognition despite lack of change in the latter. There was also an association between change in D2 receptor availability and change in overall cognition.Conclusions: Our findings suggest that optimizing D2 receptor availability by reducing antipsychotic dose allows this system to contribute more significantly to cognitive function in patients with schizophrenia. This uncovered association could be harnessed by cognitive-enhancing interventions. [ABSTRACT FROM AUTHOR]

Endogenous dopamine (DA) levels at dopamine D2/3 receptors (D2/3R) have been quantified in the living human brain using the agonist radiotracer [11C]-(+)-PHNO. As an agonist radiotracer, [11C]-(+)-PHNO is more sensitive to endogenous DA levels than antagonist radiotracers. We sought to determine the proportion of the variance in baseline [11C]-(+)-PHNO binding to D2/3Rs which can be accounted for by variation in endogenous DA levels. This was done by computing the Pearson's coefficient for the correlation between baseline binding potential (BPND) and the change in BPND after acute DA depletion, using previously published data. All correlations were inverse, and the proportion of the variance in baseline [11C]-(+)-PHNO BPND that can be accounted for by variation in endogenous DA levels across the striatal subregions ranged from 42-59%. These results indicate that lower baseline values of [11C]-(+)-PHNO BPND reflect greater stimulation by endogenous DA. To further validate this interpretation, we sought to examine whether these data could be used to estimate the dissociation constant (Kd) of DA at D2/3R. In line with previous in vitro work, we estimated the in vivo Kd of DA to be around 20 nM. In summary, the agonist radiotracer [11C]-(+)-PHNO can detect the impact of endogenous DA levels at D2/3R in the living human brain from a single baseline scan, and may be more sensitive to this impact than other commonly employed radiotracers. [ABSTRACT FROM AUTHOR]

Positron emission tomography with antagonist radiotracers has showed that striatal dopamine D2/3 receptor (D2/3R) availability decreases with age. However, no study has specifically assessed whether D2/3R availability decreases with age in healthy persons as measured with agonist radiotracers. Moreover, it is unknown whether D3R availability changes with age in healthy humans. Thus, we explored the relationship between age and D2/3R availability in healthy humans using the D3 receptor (D3R)-preferential agonist radiotracer [11C]-(+)-PHNO (n=72, mean±s.d. age=40±15, range=18 to 73) and the antagonist [11C]-Raclopride (n=70, mean±s.d. age =40±14, range=18 to 73) (both, n=33). The contribution of D3R to the [11C]-(+)-PHNO signal varies across regions of interest; the substantia nigra and hypothalamus represent D3R-specific regions, the ventral pallidum, globus pallidus, and ventral striatum represent D2/3R-mixed regions, and the caudate and putamen represent D2 receptor (D2R)-specific regions. With [11C]-(+)-PHNO, a negative correlation was observed between age and nondisplaceable binding potential (BPND) in the caudate (r(70)=−0.32, P=0.005). No correlations were observed in the other regions. With [11C]-Raclopride, negative correlations were observed between age and BPND in the caudate (r(68)=−0.50, P<0.001), putamen (r(68)=−0.41, P<0.001), and ventral striatum (r(68)=−0.43, P<0.001). In conclusion, in contrast with the age-dependent decrease in D2R availability, these findings suggest that D3R availability does not change with age. [ABSTRACT FROM AUTHOR]

The article discusses research which was conducted to investigate the therapeutic window for striatal dopamine D2/3 receptor occupancy in older patients with schizophrenia. Researchers evaluated nine subjects that had been treated previously with risperidone.They found that there was a lower therapeutic window for older patients with schizophrenia than in younger patients.

Objective: We explored whether prior findings of reduction in serotonin 2A receptor (5-HT(2A) R) binding with age could be replicated and whether high resolution research tomography (HRRT) for positron emission tomography could compensate for partial volume effects in the presence of age-related brain atrophy, which has been a traditional concern for radioligand PET studies in the elderly. Methods: We derived 5-HT(2A) R nondisplaceable binding potentials (BP(ND) ) in frontal, temporal, anterior-cingulate, insula, caudate and putamen volumes of interest (VOIs) for 28 healthy subjects (mean ± SD age = 43.9 ± 17.0 years, range: 19-78 years) using HRRT. Partial volume correction (PVC) was performed in the VOI analysis. Results: The 5-HT(2A) R BP(ND) s decreased with age, a relationship best described by an exponential-decay regression. The BP(ND) s were found to be consistent before and after PVC, with an intra-class correlation coefficient of 0.84 and 95% confidence interval = 0.78-0.88. Conclusions: These new findings update current knowledge, in that the aging process is not always uniform across the life span and suggest that PVC may not be necessary with HRRT in healthy subjects. [ABSTRACT FROM AUTHOR]

Objective We explored whether prior findings of reduction in serotonin 2A receptor (5-HT2AR) binding with age could be replicated and whether high resolution research tomography (HRRT) for positron emission tomography could compensate for partial volume effects in the presence of age-related brain atrophy, which has been a traditional concern for radioligand PET studies in the elderly. Methods We derived 5-HT2AR nondisplaceable binding potentials (BPND) in frontal, temporal, anterior-cingulate, insula, caudate and putamen volumes of interest (VOIs) for 28 healthy subjects (mean ± SD age = 43.9 ± 17.0 years, range: 19-78 years) using HRRT. Partial volume correction (PVC) was performed in the VOI analysis. Results The 5-HT2AR BPNDs decreased with age, a relationship best described by an exponential-decay regression. The BPNDs were found to be consistent before and after PVC, with an intra-class correlation coefficient of 0.84 and 95% confidence interval = 0.78-0.88. Conclusions These new findings update current knowledge, in that the aging process is not always uniform across the life span and suggest that PVC may not be necessary with HRRT in healthy subjects. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]