Brain dopamine d1 receptors in twins discordant for schizophrenia.
ABSTRACT It has been suggested that deficits in higher-order cognitive functions serve as intermediate phenotypic indicators of genetic vulnerability to schizophrenia. The dopamine hypothesis of schizophrenia postulates that insufficiency of dopamine transmission in the prefrontal cortex contributes to the cognitive deficits observed in patients with the disease, and there is robust empirical evidence for a central role of prefrontal cortex dopamine D(1) receptors in working memory functions.
The authors examined the genetic and nongenetic effects on D(1) receptor binding in schizophrenia by studying monozygotic and dizygotic twin pairs discordant for schizophrenia as well as healthy comparison twins using positron emission tomography (PET) and the D(1) receptor antagonist ligand [(11)C]SCH 23390. Performance on neuropsychological tests sensitive to frontal lobe functioning was evaluated.
High D(1) receptor density in the medial prefrontal cortex, superior temporal gyrus, and heteromodal association cortex (angular gyrus) was associated with increasing genetic risk for schizophrenia (comparison twins < unaffected dizygotic co-twins < unaffected monozygotic co-twins). Medicated schizophrenia patients demonstrated a widespread reduction in D(1) receptor binding when compared with the unaffected co-twin, and higher doses of antipsychotics were associated with lower D(1) receptor binding in the frontotemporal regions.
This study demonstrated an association between genetic risk for schizophrenia and alterations in cortical D(1) receptor binding, an observation that has implications for future studies of the molecular genetics of schizophrenia. In addition, the data indicate a widespread reduction of D(1) receptor binding in medicated schizophrenia patients, supporting a link between antipsychotic drug action and dopamine D(1) receptor down-regulation.
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ABSTRACT: Introduction: Antipsychotic drugs date back to the 1950s and chlorpromazine. Soon after, it was established that blockade of dopamine and, in particular, the D2 receptor was central to this effect. Dopamine continues to represent a critical line of investigation, although much of the work now focuses on its potential in other symptom domains. Areas covered: A search was carried out for investigational drugs using the key words 'dopamine', 'schizophrenia' and 'Phase III' in an American clinical trial registry (clinicaltrials.gov), published articles using the National Library of Medicine's PubMed database, and supplemented results with a manual search of cross-references and conference abstracts. Drugs were excluded that were already FDA approved. Expert opinion: There remains interest, albeit diminished, in developing better antipsychotic compounds. The greatest enthusiasm currently centres on dopamine's role in negative and cognitive symptom domains. With theories conceptualising hypodopaminergic activity as underlying these deficits, considerable effort is focused on drug strategies that will enhance dopamine activity. Finally, a small body of research is investigating dopaminergic compounds vis-à-vis side-effect treatments. In domains beyond psychosis, however, dopamine arguably is not seen as so central, reflected in considerable research following other lines of investigation.Expert Opinion on Pharmacotherapy 12/2013; · 2.86 Impact Factor
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ABSTRACT: Individuals with serious mental illness (SMI) experience impairment in personal, social, and occupational domains of functioning. They interact with several systems to fulfill their day-to-day functioning. This paper reviews literature to identify systems with which the SMI population interacts with and highlights the ways those systems help or deter their functioning in society. The new Council on Social Work Education (CSWE) Educational Policy and Accreditation Standards (EPAS) requires competency-based curriculum to educate social workers on how best to serve hard-to-reach populations. This article includes four competencies essential in educating social workers to work with the SMI population. Finally, there is a discussion of the ways that the CSWE's new accreditation standards for social work can be incorporated in a curriculum that focuses on understanding the experiences and needs of individuals with SMI.Journal of Human Behavior in the Social Environment 02/2012; 22(2):213-233.