130 research outputs found

    Dopamine D_1 Receptors and Nonlinear Probability Weighting in Risky Choice

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    Misestimating risk could lead to disadvantaged choices such as initiation of drug use (or gambling) and transition to regular drug use (or gambling). Although the normative theory in decision-making under risks assumes that people typically take the probability-weighted expectation over possible utilities, experimental studies of choices among risks suggest that outcome probabilities are transformed nonlinearly into subjective decision weights by a nonlinear weighting function that overweights low probabilities and underweights high probabilities. Recent studies have revealed the neurocognitive mechanism of decision-making under risk. However, the role of modulatory neurotransmission in this process remains unclear. Using positron emission tomography, we directly investigated whether dopamine D_1 and D_2 receptors in the brain are associated with transformation of probabilities into decision weights in healthy volunteers. The binding of striatal D_1 receptors is negatively correlated with the degree of nonlinearity of weighting function. Individuals with lower striatal D_1 receptor density showed more pronounced overestimation of low probabilities and underestimation of high probabilities. This finding should contribute to a better understanding of the molecular mechanism of risky choice, and extreme or impaired decision-making observed in drug and gambling addiction

    Clozapine and Antipsychotic Monotherapy

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    Background: Although clozapine is effective for treatment-resistant schizophrenia (TRS), the rate of clozapine prescription is still low. Whereas antipsychotic monotherapy is recommended in clinical practice guidelines, the rate of antipsychotic polypharmacy is still high. There is little evidence on whether a clozapine prescription influences changes in the rate of monotherapy and polypharmacy, including antipsychotics and other psychotropics. We therefore hypothesized that the rate of antipsychotic monotherapy in patients with TRS who were prescribed clozapine would be higher than that in patients with schizophrenia who were not prescribed clozapine. Methods: We assessed 8306 patients with schizophrenia nationwide from 178 institutions in Japan from 2016 to 2019. We analyzed the psychotropic prescription data at discharge in patients diagnosed with TRS and with no description of TRS (ND-TRS) based on the diagnosis listed in the discharge summary. Results: The rate of antipsychotic monotherapy in the TRS with clozapine group (91.3%) was significantly higher than that in the TRS without clozapine group (45.9%; P < 2.0 × 10−16) and the ND-TRS without clozapine group (54.7%; P < 2.0 × 10−16). The rate of antipsychotic monotherapy without any other concomitant psychotropics in the TRS with clozapine group (26.5%) was significantly higher than that in the TRS without clozapine group (12.6%; P = 1.1 × 10−6) and the ND-TRS without clozapine group (17.0%; P = 5.9 × 10−6). Conclusions: Clozapine prescription could be associated with a high rate of antipsychotic monotherapy. Patients will benefit from the correct diagnosis of TRS and thus from proper clozapine prescription

    Effective Biomarkers for Proof-of-Concept

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    Effective biomarkers have been needed for diagnostic purpose and evaluation of the effects of drugs.Positron emission tomography(PET)enables us to viualize several components of brain activites including glucise metabolism of brain activity and neurotransmitter receptors and transporters.In vivo neuroimaging including neuroreceptor imaging and enzyme activity imaging have contributed to drug evaluation by1)ratinal drug dosing,2)biodistribution of drug,3)therapeutic rationale for drug utilization,and4)mechanism of drug action[1].In this article,we focused on rational drug dosing using receptor occupancy and proof-of-concept of drugs,as well as new therapeutic methods using PET

    Differences in Neuroticism Between Patients with Glaucoma Who Have Discontinued Visits to Ophthalmologists and Those Who Make Regular Visits: Implications for Adherence to Topical Glaucoma Medications

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    <p><b>Article full text</b></p> <p><br></p> <p>The full text of this article can be found here<b>.</b> <a href="https://link.springer.com/article/10.1007/s40123-016-0059-1">https://link.springer.com/article/10.1007/s40123-016-0059-1</a></p><p></p> <p><br></p> <p><b>Provide enhanced content for this article</b></p> <p><br></p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p><br></p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p><br></p> <p>Other enhanced features include, but are not limited to:</p> <p><br></p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p

    Association between Striatal Subregions and Extrastriatal Regions in Dopamine D1 Receptor Expression: A Positron Emission Tomography Study

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    The mesencephalic dopamine (DA) system is the main DA system related to affective and cognitive functions. The system consists of two different cell groups, A9 and A10, which originate from different regions of the midbrain. The striatum is the main input from the midbrain, and is functionally organized into associative, sensorimotor and limbic subdivisions. At present, there have been few studies to investigate the associations of DA functions between striatal subdivisions and extrastriatal regions. The aim of this study was to investigate the relationship of DA D1 receptor (D1R) expression between striatal subdivisions and extrastriatal regions in humans using positron emission tomography (PET) with voxel-by-voxel whole brain analysis. The PET study was performed on 30 healthy subjects using [11C]SCH23390 to measure D1R expression. Parametric images of binding potentials (BPND) were created using the simplified reference tissue model. Regions of interest were defined for striatal subdivisions. Multiple regression analysis was undertaken to determine extrastriatal regions that were associated with each striatal subdivision in BPND using statistical parametric mapping 5. The BPND values of associative, sensorimotor and limbic subdivisions were similarly correlated with those of multiple brain regions. Regarding the interrelationships among striatal subdivisions, mutual correlations were found among associative, sensorimotor and limbic subdivisions in BPND as well. The relationships in BPND between striatal subdivisions and extra-striatal regions suggest that differential striatal subdivisions and extrastriatal regions have a similar biological basis of D1R expression. Different DA projections from the midbrain did not explain the associations between striatal subdivisions and extrastriatal regions in D1R expression, and the DA-related neural networks among the midbrain, striatum and the other regions would contribute to a similar D1R expression pattern throughout the whole brain

    Association between striatal subregions and extrastriatal regions in dopamine D(1) receptor expression: a positron emission tomography study.

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    The mesencephalic dopamine (DA) system is the main DA system related to affective and cognitive functions. The system consists of two different cell groups, A9 and A10, which originate from different regions of the midbrain. The striatum is the main input from the midbrain, and is functionally organized into associative, sensorimotor and limbic subdivisions. At present, there have been few studies investigating the associations of DA functions between striatal subdivisions and extrastriatal regions. The aim of this study was to investigate the relationship of DA D(1) receptor (D(1)R) expression between striatal subdivisions and extrastriatal regions in humans using positron emission tomography (PET) with voxel-by-voxel whole brain analysis. The PET study was performed on 30 healthy subjects using [(11)C]SCH23390 to measure D(1)R expression. Parametric images of binding potentials (BP(ND)) were created using the simplified reference tissue model. Regions of interest were defined for striatal subdivisions. Multiple regression analysis was undertaken to determine extrastriatal regions that were associated with each striatal subdivision in BP(ND) using statistical parametric mapping 5. The BP(ND) values of associative, sensorimotor and limbic subdivisions were similarly correlated with those of multiple brain regions. Regarding the interrelationships among striatal subdivisions, mutual correlations were found among associative, sensorimotor and limbic subdivisions in BP(ND) as well. The relationships in BP(ND) between striatal subdivisions and extra-striatal regions suggest that differential striatal subdivisions and extrastriatal regions have a similar biological basis of D(1)R expression. Different DA projections from the midbrain did not explain the associations between striatal subdivisions and extrastriatal regions in D(1)R expression, and the DA-related neural networks among the midbrain, striatum and the other regions would contribute to a similar D(1)R expression pattern throughout the whole brain
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