Psychopharmacogenetics : psychopharmacology

Humans are strategically more prosocial when their actions are being watched by others than when they act alone. Using a psychopharmacogenetic approach, we investigated the endocrinological and computational mechanisms of such audience-driven prosociality. One hundred and ninety-two male participants received either a single dose of testosterone (150 mg) or a placebo and performed a prosocial and self-benefitting reinforcement learning task. Crucially, the task was performed either in private or when being watched...

Psychopharmacogenetics was born with the development of psychotropic drugs in psychiatry, that is, slightly after the discovery of the role of lithium in bipolar disorders and of antipsychotic agents in schizophrenia. Psychopharmacogenetics relies on the analyses of the genes involved in treatment response adverse effects, efficacy, and their mechanisms. The utility of psychopharmacogenetics may be substantial. Being able to give each patient the appropriate dosage of the right treatment should enhance not only its immediate efficacy, but also compliance and therefore long-term efficacy...

Response to psychopharmacologic drugs is genetically complex, results from an interplay of multiple genomic variations with environmental influences, and depends on the structure or functional expression of gene products, which are direct drug targets or indirectly modify the development and synaptic plasticity of neural networks critically involved in their effects. During brain development, the serotonin (5HT) system, which is commonly targeted by antidepressant, anxiolytic, and antipsychotic drugs, controls neuronal specification, differentiation, and phenotype maintenance...

Genetic factors play a major role in the differential responses to treatment or the incidence of adverse drug effects in psychopharmacotherapy. The aim of pharmacogenetics is to elucidate this variability caused by hereditary differences. From hypotheses on the mechanisms of drug action, several mutations in genes coding for neurotransmitter receptors, neurotransmitter-degrading enzymes, transport proteins or enzymes of the drug metabolizing system have been identified and investigated. Although there exists some controversy among the results, many studies are supportive of the hypothesis that psychopharmacogenetics will be helpful in predicting an individual's drug response while minimizing the rate of side effects...

Individual differences in drug effects and treatment response are relatively enduring, continuously distributed, as well as substantially heritable, and are therefore likely to result from an interplay of multiple genomic variations with environmental influences. As the etiology and pathogenesis of behavioral and psychiatric disorders is genetically complex, so is the response to drug treatment. Psychopharmacologic drug response depends on the structure and functional expression of gene products, which may be direct drug targets or may indirectly modify the development and synaptic plasticity of neural networks critically involved in drug response...

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No abstract text is available yet for this article.

In light of the emerging evidence for genetic vulnerability to adverse drug reactions, this article attempts to elucidate the natural history of medication-induced movement disorders from a psychopharmacogenetic perspective. Studies of the risk factors, neurobiology, and pharmacogenetics are reviewed concurrently. The relevant variables associated with 10 genetically mediated movement disorders are tabulated and compared with those of medication-induced movement disorders without a clear-cut genetic basis. As a result of this integrated analysis, it is evident that there is an intimate genetic and pathophysiological link between neuropsychiatric movement disorders of diverse origins...

Comparative studies of behavioral responses to centrally acting drugs in inbred strains of mice which show differences in brain neurotransmitter activity represent a major strategy in the investigation of the neurochemical bases underlying behavioural expression. Moreover, these studies represent a preliminary stage in behavioral genetic research since they allow quantitative scales to be established and suggest correlations to be tested in recombinant inbred strains. The present review evaluates results obtained in mice of the C57BL/6 (C57) and DBA/2 (DBA) inbred strains which have been used for studies of the behavioral pharmacology of dopamine (DA) and investigated for the functional and anatomical characteristics of their brain DA systems...

Interethnic child and adolescent psychopharmacology research is essentially unstudied. Recently there have been reports of interethnic differences in psychopharmacology research on adults. This article addresses the need to focus research on psychopharmacogenetics, pharmacokinetics, pharmacodynamics, and issues of efficacy and effectiveness in child and adolescent populations of different ethnic groups.

Experimental results are reviewed which indicate that memory storage can be altered by a number of post-training treatments that affect different hormones and neurotransmitters. Moreover, evidence was reported which suggests that the action of treatments effective on memory processes involves interactions among different systems, consistently with the complexity of brain systems. In the last decade, inbred strains have been exploited to investigate the role of neurotransmitter and hormone systems in learning and memory, leading to behavioural and neurochemical correlations based on strain differences that provide unique information on the biological systems underlying behaviour...

This article attempts to elucidate the theory and practice of psychopharmacogenetics. Eight working models were identified and characterized with a distinct view of risk factors in the host, the pathophysiology of disease, and the strategies for optimum therapy. The biochemical culprits related to adverse drug reaction in each case can be used to identify a risk and thus contribute to prevention research. Since the phenomenology of these uncommon conditions covers a broad spectrum of neuropsychiatric manifestations, the insights they generated might presage a better understanding of the natural history of a wider range of mental disorders associated with genetic vulnerability...

Unlike simple Mendelian characteristics, individual differences in complex quantitative phenotypes studied in psychopharmacology are generally distributed continuously and are likely to be influenced by many genes. Recombinant inbred (RI) strains are valuable not only for their traditional use of detecting major gene segregation and linkage but also for identifying associations between quantitative traits and quantitative trait loci (QTL) that account for relatively small amounts of variation in phenotypes as well as loci that account for greater amounts of variation...

1. Individual response to drugs is to a great extent influenced by hereditary factors. 2. The interaction between genetic and environmental factors affecting drug metabolism in man is of crucial importance to the understanding of therapeutic response in psychopharmacology. This proposition is illustrated for various psychotropic drugs such as the monoamineoxydase inhibitors (MAOI), tricyclic drugs and lithium salts as well as for enzymes involved in the synthesis and degradation of biogenic amines. 3. New perspectives in pharmacogenetics and their relevance to psychopharmacology are discussed...