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7 results

  • Association of CNR1 genotypes with changes in neurocognitive performance after eighteen-month treatment in patients with first-episode psychosis

  • Martina Rojnic Kuzman, Dina Bosnjak Kuharic, Lana Ganoci, Porin Makaric, Ivana Kekin, Linda Rossini Gajsak, Nikola Prpic, Tamara Bozina, Zarko Bajic, Nada Bozina
  • Journal:
    European Psychiatry / Volume 61 / September 2019
    Published online by Cambridge University Press:
    01 January 2020, pp. 88-96
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  • Introduction.

    We analyzed the association of cannabinoid receptor CNR1 genotypes with changes in neurocognitive performance in patients with first-episode psychosis (FEP) after 18 months of treatment. Our secondary aim was to analyze the association of CNR1 genotypes with changes of perceived levels of stress.

    Methods.

    We enrolled a sample of 159 patients with FEP from two Croatian psychiatric hospitals between 2014 and 2017. Patients were assessed at baseline and after 18 months. We analyzed the associations of changes in neurocognitive test results and the perceived levels of stress with CNR1 polymorphic loci (rs7766029 and rs12720071) in 121 patients.

    Results.

    In the analysis adjusted only for baseline neurocognitive test scores, carriers of rs7766029 CC genotype had significantly (with false discovery rate, FDR < 15%) higher improvement in verbal memory (Wechsler, Wechsler 30′) and attention (Digit span F) compared with other participants. In such analysis, rs12720071 carriers of AG genotype had significantly (FDR < 15%) higher improvement in executive functions (Block design), but lower improvement in language functions than AA carriers. In the fully adjusted analysis for age, sex, cannabis use and negative symptoms, only the association of rs7766029 genotypes with the change in the Weschler 30′ score was significant (FDR < 15%). In the analysis adjusted only for the baseline neurocognitive tests’ scores, both rs7766029 and rs12720071 genotypes were significantly associated with the change in perceived levels of stress (FDR < 15%). In the fully adjusted analysis, only the association with rs7766029 genotype remained significant.

    Conclusions.

    The rs7766029 CNR1 variants may moderate changes in neurocognitive performance as well as in perceived levels of stress of patients with FEP over time.

  • 4 - Methodological issues in psychopharmacogenetics

  • from Part II - Clinical background and research design
    • By Sheldon H. Preskorn, Psychiatric Research Institute, University of Kansas School of Medicine, Wichita, Kansas, USA
  • Edited by Bernard Lerer, Hadassah-Hebrew Medical Center, Jerusalem
  • Book:
    Pharmacogenetics of Psychotropic Drugs
    Published online:
    20 August 2009
    Print publication:
    29 August 2002, pp 57-71

  • Summary

    This chapter discusses methodological issues relevant to conducting pharmacogenetic studies in clinical psychopharmacology. First, basic pharmacologic principles are reviewed, followed by a discussion of the drug development process. In addition to aiding in the drug discovery process, pharmacogenetic finding would also help with the signal:noise problem, at the human testing phase of drug development (that is, phase I through III). Scientists can select the specific subset of the population (that is, those with the genetic variant) likely to respond to the drug. The chapter reviews the significant potential for advancing psychiatric drug development as a result of improved understanding of the pharmacogenetics and pharmacogenomics relevant to the effects of drugs on the human brain. Last, the research linking cytochrome P-450 CPY2D6 poor metabolizers with increased risk of toxicity on routine doses of tricyclic antidepressants (TCAs) are reviewed as an example of the methodological issues encountered when conducting such studies.

  • 6 - The psychopharmacogenetic–neurodevelopmental interface in serotonergic gene pathways

  • from Part III - Molecular background
    • By K. Peter Lesch, Department of Psychiatry and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany, Jens Benninghoff, Department of Psychiatry and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany, Angelika Schmitt, Department of Psychiatry and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany
  • Edited by Bernard Lerer, Hadassah-Hebrew Medical Center, Jerusalem
  • Book:
    Pharmacogenetics of Psychotropic Drugs
    Published online:
    20 August 2009
    Print publication:
    29 August 2002, pp 95-126

  • Summary

    This chapter appraises prototypical genomic variation with impact on gene expression, and complementary studies of gene and environmental effects on brain development and synaptic plasticity in the mouse model. Special emphasis is given to molecular mechanisms of neurodevelopmental genetics. Relevant conceptual and methodological issues pertinent to the dissection of the psychopharmacogenetic-neurodevelopmental interface are also considered. Many genes that influence complex traits and psychopharmacological drug responses are likely to be distributed continuously. Such genes are referred to as quantitative trait loci. Connecting drug response with relevant functional DNA variants in the brain and with differences in gene expression in brain regions represents the ultimate goal for pharmacogenetic research. The serotonergic gene pathways is a rewarding area of investigation because of numerous and essential functions of the central serotonin (5-HT) system, the wealth of drug targets within this system, and the range of serotonergic compounds available in the clinical setting.

  • 5 - Statistical approaches in psychopharmacogenetics

  • from Part II - Clinical background and research design
    • By Fabio Macciardi, Center for Addiction and Mental Health, University of Toronto. Toronto, Canada
  • Edited by Bernard Lerer, Hadassah-Hebrew Medical Center, Jerusalem
  • Book:
    Pharmacogenetics of Psychotropic Drugs
    Published online:
    20 August 2009
    Print publication:
    29 August 2002, pp 72-92

  • Summary

    The statistical analysis of data in psychopharmacogenetics is a key factor in the evaluation of importance of gene or a set of genes in controlling the response to a given drug or to explain the emergence of side effect as a consequence of the administered drug. The association strategy conceptually entails the candidate gene paradigm based on a 'forward genetics' design. This chapter explains how to analyze the genetic architecture of a pharmacogenetic trait. First, a definition of a pharmacogenetic trait is presented, with the consequential methods of analysis, followed by some considerations for defining a phenotype suitable for investigation. Then, the chapter deals with genetic polymorphisms, with a particular focus on single nucleotide polymorphisms (SNPs). The chapter concludes with a discussion on ethnic and interindividual differences in the distribution of genetic variants, and explains how they can affect any investigation.

  • 1 - Genes and psychopharmacology: exploring the interface

  • from Part I - Introduction
    • By Bernard Lerer, Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah–Hebrew University Medical Center, Jerusalem, Israel
  • Edited by Bernard Lerer, Hadassah-Hebrew Medical Center, Jerusalem
  • Book:
    Pharmacogenetics of Psychotropic Drugs
    Published online:
    20 August 2009
    Print publication:
    29 August 2002, pp 3-18

  • Summary

    This chapter serves as a general introduction to psychopharmacogenetics and to the topics covered in this book, which provides the researcher and clinician with an overview of the pivotal topics in psychopharmacogenetics. For much of its history, the focus of pharmacogenetics has been on drug-metabolizing enzymes. This was because of the availability of techniques to detect phenotypic differences between individuals in the plasma level of drugs and to study their genetic basis. The chapter focuses on the methodological issues in pharmacogenetic research design. The interface between psychopharmacology and molecular genetics is already a focus of considerable research activity and this is likely to intensify as anticipated technological advances provide the tools for even more sophisticated studies. It may take longer than originally thought, but ultimately pharmacogenetics and pharmacogenomics will revolutionize the field of clinical psychopharmacology and the development of psychotropic drugs.

  • Behavioral Responses to Amphetamines in Identical Twins

  • John C. Crabbe, Lissy F. Jarvik, Edward H. Liston, Donald J. Jenden
  • Journal:
    Acta geneticae medicae et gemellologiae: twin research / Volume 32 / Issue 2 / April 1983
    Published online by Cambridge University Press:
    01 August 2014, pp. 139-149
    Print publication:
    April 1983
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  • Male, monozygotic twins (six pairs) were repeatedly tested before and after d-amphetamine, l-amphetamine, or placebo administration. Drug effects on cognitive, psychomotor, personality, mood, and pain variables were assessed. Members of a twin pair tended to respond similarly on several tests under placebo conditions, indicating genetic determination of the behavioral variables. In addition, cotwins tended to show similar responses to amphetamine as measured by one test of cognitive function, by several mood and personality variables (hostility, autonomic arousal, friendliness, feelings of tension and loss of control), and tended to have similar plasma levels of both amphetamine isomers. Although shared environmental effects cannot be ruled out, the results are consistent with genetic mediation of a variety of behavioral effects of amphetamines.