Pharmacogenetics of antidepressant response. J Psychiatry Neurosci

Institute of Psychiatry, University of Bologna, Bologna, Italy.
Journal of psychiatry & neuroscience: JPN (Impact Factor: 5.86). 03/2011; 36(2):87-113. DOI: 10.1503/jpn.100059
Source: PubMed

ABSTRACT Personalized medicine - the adaptation of therapies based on an individual's genetic and molecular profile - is one of the most promising aspects of modern medicine. The identification of the relation between genotype and drug response, including both the therapeutic effect and side effect profile, is expected to deeply affect medical practice. In this paper, we review the current knowledge about the genes related to antidepressant treatment response and provide methodologic proposals for future studies. We have mainly focused on genes associated with pharmacodynamics, for which a list of promising genes has been identified despite some inconsistency across studies. We have also synthesized the main results for pharmacokinetic genes, although so far they seem less relevant than those for pharmaco dynamic genes. We discuss possible reasons for these inconsistent findings and propose new study designs.

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    • "ollock , 2008 ) , suggesting a rs4795541 allele dose - dependent 5 - HT reuptake from the syn - aptic cleft ( Lesch et al . , 1996 ) . Many studies investigated the SLC6A4 gene locus role in the SSRI treatment response of MDD and their findings are still a theme of debate ( Huezo - Diaz et al . , 2009 ; Keers , 2011 ; Kraft et al . , 2005 , 2007 ; Porcelli et al . , 2011 , 2012 ; Taylor et al . , 2010 ) . On the other hand , the few studies conducted on LLD patients did not consider the whole SLC6A4 locus , focusing only on rs4795541 alleles ( Alexopoulos et al . , 2009 ; Durham et al . , 2004 ; Kim et al . , 2006 ; Lotrich et al . , 2008 ; Murphy et al . , 2004 ; Pollock et al . , 2000 ) . Given the ab"
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    ABSTRACT: It has been suggested that the serotonin or 5-hydroxytriptamine (5-HT) transporter (5-HTT) and its gene-linked polymorphic region (5-HTTLPR) are selective serotonin reuptake inhibitor (SSRI) response modulators in late-life depression (LLD), and particularly in late-life major depressive disorder (MDD). Previous studies differed in design and results. Our study aimed to investigate the solute carrier family 6 (neurotransmitter transporter and serotonin) member 4 (SLC6A4) gene locus, encoding 5-HTT and SSRI treatment response in late-life MDD. For a prospective cohort study, we enrolled 234 patients with late-life MDD to be treated with escitalopram, sertraline, paroxetine or citalopram for 6 months. The SLC6A4 polymorphisms rs4795541 (5-HTTLPR), rs140701 and rs3813034 genotypes spanning the SLC6A4 locus were investigated in blinded fashion. No placebo group was included. We assessed responder or non-responder phenotypes according to a reduction in the 21-item version of the Hamilton Depression Rating Scale (HDRS-21) score of ⩾ 50%. At follow-up, 30% of the late-life MDD patients were non-responders to SSRI treatment. No time-course of symptoms and responses was made. A poor response was associated with a higher baseline HDRS-21 score. We observed a significant over-representation of the rs4795541-S allele in the responder patients (0.436 versus 0.321; p = 0.023). The single S-allele dose-additive effect had OR = 1.74 (95% CI 1.12-2.69) in the additive regression model. Our findings suggested a possible influence of 5-HTTLPR on the SSRI response in patients with late-life MDD, which is potentially useful in identifying the subgroups of LLD patients whom need a different pharmacological approach. © The Author(s) 2015.
    Journal of Psychopharmacology 03/2015; 29(5). DOI:10.1177/0269881115578159 · 3.59 Impact Factor
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    • "El blanco primario de la mayoría de antidepresivos ISRS es el transportador de serotonina. Los genes de la triptófano hidrolasa (la enzima que limita la síntesis de serotonina a partir del triptófano ), TPH1 [45] [52] [55] [56] [57] [58] [59] [60] [61] [62] [63] y TPH2 [55] [59] [60] [61] [62] [64] [65] pueden modificar la respuesta a los antidepresivos ISRS. Los genes del transportador de serotonina SLC6A4 [66] [67] [68] [69] [70] [71] [72] [73] y 5HTTLPR [63] [74] [75] se hallan bajo intensa investigación porque los resultados obtenidos hasta ahora son contradictorios en lo referente a la respuesta a los antidepresivos. "
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    • "In psychiatry, biomarker identification remains at its infancy despite advances in pharmacogenomics [1,2], proteomics, as well as translational sciences [3,4]. In recent years, several investigators have reported variations in mRNA levels between patients and control subjects based on peripheral and accessible tissues and also between pre- and post-treatment conditions in major depressive disorder (MDD) and bipolar disorder (BD) [5-11]. "
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    ABSTRACT: Although psychiatric disorders are frequently characterized by clinical heterogeneity, high recurrence, and unpredictable prognosis, studies of mRNA expression variations in blood cells from psychiatric patients constitute a promising avenue to establish clinical biomarkers. We report here, to our knowledge, the first genetic monitoring of a major depressive episode (MDE). The subject is a 51-year-old male, who was healthy at baseline and whose blood mRNA was monitored over 67 weeks for expression variations of 9 candidate genes. At week 20 the subject experienced a mild to moderate unexpected MDE, and oral antidepressant treatment was initiated at week 29. At week 36, the patient recovered from his MDE. After 6 months, antidepressant treatment was discontinued and the subject remained free of depressive symptoms. Genetic monitoring revealed that mRNA expression of SLC6A4/5HTT increased with the emergence of a depressive state, which later returned to basal levels after antidepressant treatment and during MDE recovery. PDLIM5, S100A10 and TNF mRNA showed also an interesting pattern of expression with regards to MDE evolution. This case demonstrated the applicability of peripheral mRNA expression as a way to monitor the natural history of MDE.
    BMC Psychiatry 03/2014; 14(1):73. DOI:10.1186/1471-244X-14-73 · 2.21 Impact Factor
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