Obsessive-Compulsive Disorder, 5-HTTLPR polymorphism and treatment response

Bella, Daniela Di; Erzegovesi, Stefano; Cavallini, Maria Cristina; Bellodi, Laura

doi:10.1038/sj.tpj.6500090

Cited by 69 publications

(42 citation statements)

References 41 publications

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“…113,114 In addition, based on the efficacy of SRIs in OCD, polymorphisms in the promoter region of the serotonin transporter have been studied in OCD pedigrees. 18,177,178 However, no differences in SRI responses were found among the different genotypes studied. 178 In sum, the data on phenotypic features and knowledge of candidate genes that could predict treatment response in OCD are still very preliminary and represent additional evidence that a better definition of the OCD phenotype is needed.…”

Section: Treatment Implicationsmentioning

confidence: 79%

“…18,177,178 However, no differences in SRI responses were found among the different genotypes studied. 178 In sum, the data on phenotypic features and knowledge of candidate genes that could predict treatment response in OCD are still very preliminary and represent additional evidence that a better definition of the OCD phenotype is needed. Future studies attempting to identify the pharmacogenetic targets that mediate antiobsessive effects on key neuronal functions may provide a theoretical foundation for important changes in the antiobsessive paradigm (today modeled based on specific actions of antidepressants).…”

Section: Treatment Implicationsmentioning

confidence: 79%

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Obsessive-compulsive disorder phenotypes: implications for genetic studies

et al. 2004

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Obsessive-compulsive disorder (OCD) clinical presentation is remarkably diverse, and can vary both within and across patients over time. This variability in the phenotypic expression has led to the hypothesis that OCD is a heterogeneous disorder and that this heterogeneity obscures the findings of clinical, natural history and treatment response studies and complicates the search for vulnerability genes. A complete understanding of what comprises OCD and the underlying etiological mechanisms will require a dramatic change in how the disorder is conceptualized. In this review, several different approaches that may represent the first steps in this reconceptualization are discussed. These approaches include (1) narrowing the phenotype to identify categorically defined more homogeneous and mutually exclusive subtypes of OCD, (2) considering OC symptom dimensions as quantitative components of the more complex OCD phenotype and (3) broadening the phenotype to include other etiologically related conditions. A combined dimensional approach within distinctive subgroups is proposed as probably the most effective in helping to identify the heritable components of OCD. By identifying heritable components of OCD, it should be possible to find genes for these separate components. The review continues with the illustration of the possible role of some epigenetic risk and protective factors in the OCD presentation and the relevance of examining associated traits and/or endophenotypes to enhance our ability to understand the genetic basis of OCD. To conclude, we discuss the variability in treatment outcome and the significance of the development of specific pharmacological and/or behavioral based therapies tailored to each of these phenotypes. Molecular Psychiatry (2005) 10, 258-275.

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Section: Treatment Implicationsmentioning

confidence: 79%

Section: Treatment Implicationsmentioning

confidence: 79%

Obsessive-compulsive disorder phenotypes: implications for genetic studies

et al. 2004

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“…In both studies, antidepressant response was stronger and faster among l/l homozygotes compared to heterozygotes and s/s homozygotes. On the contrary, Billett et al (1997) failed to find a relationship between the antiobsessive efficacy and 5-HTTLPR variants while Di Bella et al (2002) found a relationship only in some OCD subtypes. This discordance could be the expression of different biochemical pathways probably subtending or conditioning the efficacy of SSRIs.…”

Section: Introductionmentioning

confidence: 74%

Antipanic Efficacy of Paroxetine and Polymorphism within the Promoter of the Serotonin Transporter Gene

Perna

Favaron

Bella

et al. 2005

Neuropsychopharmacol

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Serotonin selective reuptake inhibitors (SSRIs) are the drugs of choice in the treatment of panic disorder (PD). The serotonin transporter (5-HTT) is a prime target for SSRIs. A functional polymorphism within the promoter region of the 5-HTT gene, leading to different transcriptional efficiency, was repeatedly reported to influence the response to SSRIs in mood disorders while the response of patients with OCD seems unrelated. We tested the hypothesis that allelic variation of the 5-HTT promoter could be related to the antipanic response to paroxetine. In total, 92 patients with PD completed a treatment with a variable dose of paroxetine for 12 weeks. The severity of panic-phobic symptomatology was measured before the beginning of the treatment and after 12 weeks. Allelic variation in each subject was determined using a PCR-based method. Both homozygotes for the long variant (l/l) of the 5-HTT promoter and heterozygotes (l/s) showed a better response to paroxetine than homozygotes for the short variant (s/s) (w 2 ¼ 6.9, po0.03). This result emerged in the whole sample, but was related only to female patients (w 2 ¼ 7.6, po0.02). The presence of the long allelic variant was associated with a better response of panic attacks while was not significantly associated with the response of anticipatory anxiety or phobic avoidance. In conclusion, paroxetine efficacy in PD seems to be related to allelic variation within the promoter of the 5-HTT gene in female subjects. This gender effect might be related to the genomic effects of sex hormones. Understanding the interaction between gender and genes coding for structures target of psychotropic drugs could help to individualize the pharmacological treatment of PD.

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“…An example of an interesting gene is SLC6A4, an integral membrane protein that transports the neurotransmitter serotonin 30 and is a target of many psychomotor stimulants such as amphetamines and cocaine. Variation in this gene is responsible for a wide range of neurological pathogenic conditions such as aggressive behaviour 31 , obsessive-compulsive disorder 32 , depression and autism 33,34 . The most striking aspect is compulsive disorders, of which the two species share many similar phenotypes.…”

Section: Resultsmentioning

confidence: 99%

The genomics of selection in dogs and the parallel evolution between dogs and humans

et al. 2013

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The genetic bases of demographic changes and artificial selection underlying domestication are of great interest in evolutionary biology. Here we perform whole-genome sequencing of multiple grey wolves, Chinese indigenous dogs and dogs of diverse breeds. Demographic analysis show that the split between wolves and Chinese indigenous dogs occurred 32,000 years ago and that the subsequent bottlenecks were mild. Therefore, dogs may have been under human selection over a much longer time than previously concluded, based on molecular data, perhaps by initially scavenging with humans. Population genetic analysis identifies a list of genes under positive selection during domestication, which overlaps extensively with the corresponding list of positively selected genes in humans. Parallel evolution is most apparent in genes for digestion and metabolism, neurological process and cancer. Our study, for the first time, draws together humans and dogs in their recent genomic evolution.

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Obsessive-Compulsive Disorder, 5-HTTLPR polymorphism and treatment response

Cited by 69 publications

References 41 publications

Obsessive-compulsive disorder phenotypes: implications for genetic studies

Obsessive-compulsive disorder phenotypes: implications for genetic studies

Antipanic Efficacy of Paroxetine and Polymorphism within the Promoter of the Serotonin Transporter Gene

The genomics of selection in dogs and the parallel evolution between dogs and humans

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