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Review
. 2009;11(4):363-76.
doi: 10.31887/DCNS.2009.11.4/pgerretsen.

The intersection of pharmacology, imaging, and genetics in the development of personalized medicine

Philip Gerretsen  1 , Daniel J Müller, Arun Tiwari, David Mamo, Bruce G Pollock
Affiliations
Review

The intersection of pharmacology, imaging, and genetics in the development of personalized medicine

Philip Gerretsen et al. Dialogues Clin Neurosci. 2009.

Abstract
in English, Spanish, French

We currently rely on large randomized controlled trials and meta-analyses to make clinical decisions; this places us at a risk of discarding subgroup or individually specific treatment options owing to their failure to prove efficacious across entire populations. There is a new era emerging in personalized medicine that will focus on individual differences that are not evident phenomenologically. Much research is directed towards identifying genes, endophenotypes, and biomarkers of disease that will facilitate diagnosis and predict treatment outcome. We are at the threshold of being able to predict treatment response, primarily through genetics and neuroimaging. In this review we discuss the most promising markers of treatment response and adverse effects emerging from the areas of pharmacogenetics and neuroimaging in depression and schizophrenia.

Actualmente se cuenta con numerosos ensayos controlados, randomizados y meia-análisis para tomar decisiones clínicas; lo que nos coloca en riesgo de descartar opciones terapéuticas específicas para un subgrupo de pacientes o en forma individual debido a su fracaso en la demostración de eficacia en grandes poblaciones. En la medicina personalizada está emergiendo una nueva era que se focalizará en las diferencias individuales, las que no son evidentes fenomenológicamente. Hay mucha investigatión orientada a identificar genes, endofenotipos y biomarcadores de enfermedad lo que facilitará el diagnóstico y la prediccíon de la evolucíon terapéutica. Estamos en el umbral de la capacidad de predecir la respuesta al tratamiento, fundamentalmente a través de la genética y de las neuroimágenes. En esta revisión se analizan los marcadores más prometedores de la respuesta terapéutica y de los efectos adversos, que están surgiendo desde la farmacogenética y de las neuroimágenes en la depresión y la esquizofrenia.

Nous nous appuyons actuellement sur de grandes études contrôlées randomisées et sur des metaanalyses pour prendre des décisions cliniques, ce qui risque d'écarter des options thérapeutiques spécifiques individuelles ou de sous-groupes à cause de leur incapacité à prouver leur efficacité dans la population toute entière, La médecine personnalisée, stratégie d'apparition récente, a pour objectif de se pencher sur des différences individuelles qui ne sont pas évidentes sur le plan phénoménologique. Afin de faciliter le diagnostic et de prévoir l'évolution des traitements, la recherche se dirige vers l'identification des gènes, des endophénotypes et des biomarqueurs de la maladie. Nous sommes sur le point de pouvoir prédire la réponse au traitement, en particulier grâce à la génétique et à la neuro-imagerie. Cet article se propose d'examiner les marqueurs les plus prometteurs de la réponse au traitement et des effets indésirables issus de la pharmacogénétique et de la neuro-imagerie dans la dépression et la schizophrénie.

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Figures

Figure 1.
Figure 1.. The influence of pharmacokinetic, pharmacodynamic and environmental factors on pharmacotherapy response and side effects (source: www.silvermedia.ca).
Figure 2.
Figure 2.. The interaction between peripheral molecules and central pathways modulating food/energy intake. AgRP, Agouti related protein, GABA, gamma aminobutyricacid, MC4, melanocortin receptor 4, NPY, neuropeptide, POMC, proopiomelanocortin, α-MSH, alpha melanocyte stimulating hormone, (source: www.silvermedia.ca) Adapted from ref 30: Muller DJ, Kennedy JL. Genetics of antipsychotic treatment emergent weight gain in schizophrenia. Pharmacogenomics. 2006;7:863-887. Copyright © Future Medicine Ltd, 2006.
Figure 3.
Figure 3.. Serotonin transporter gene (SLC6A4) and function. 5-HTTLPR x PFOAmygdala endophenotype interaction. Allelic variation of the serotonin transporter (5-HTT), including the serotonin-transporter-gene-linked polymorphic region (5-HTTLPR), the variable number of tandem repeats (Intron 2 VNTR), rs25531 single nucleotide polymorphism (SNP), and the missense variant He425Val (I425V). The long (L) allele (orange) of 5-HTTLPR produces significantly less 5-HTT mRNA and protein expression, than the short (S) allele (blue), leading to higher concentrations of serotonin in the synaptic cleft. 5-HTTLPR s allele carriers show significantly less functional coupling between the amygdala and perigenual anterior cingulate cortex than LA individuals. MAOA, monoamine oxidase A. (source: www.silvermedia.ca)
See this image and copyright information in PMC

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