No evidence for interaction between 5-HT2A receptor and serotonin transporter genes in schizophrenia

Pae, Chi‐Un; Artioli, Paola; Serretti, Alessandro; Kim, Tae-Suk; Kim, Jung-Jin; Lee, Chang-Uk; Lee, Soo-Jung; Lee, Chul; Paik, In‐Ho

doi:10.1016/j.neures.2005.03.006

Cited by 13 publications

(5 citation statements)

References 32 publications

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“…Table 1 describes the baseline characteristics of 46 studies that were included in this meta-analysis. The studies included 35 articles about 5-HTTLPR,16,36–68 17 studies about Stin2,16,37,39–41,44,47,53,59,65,69–75 four articles about rs1042173,40,47,76,77 and four articles about rs140700 71,76,78,79…”

Section: Resultsmentioning

confidence: 99%

Association between the <em>SLC6A4</em> gene and schizophrenia: an updated meta-analysis

Xu¹,

Wang²,

Yao³

2018

NDT

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Background: In order to explore the association between the SLC6A4 gene and the risk of schizophrenia, an updated meta-analysis was conducted using a total of 46 scientific articles. Methods: Through a literature search, papers studied included 35 articles on serotonin-transporter-linked polymorphic region (5-HTTLPR) with 8,752 cases and 10,610 controls, 17 articles on second intron variable number of tandem repeats with 7,284 cases and 8,544 controls, four studies on rs1042173 with 1,351 cases and 2,101 controls, and four studies on rs140700 with 1,770 cases and 2,386 controls. Pooled, subgroup, and sensitivity analyses were performed, and the results were visualized by forest and funnel plots. Results: An association between 5-HTTLPR and the risk of schizophrenia was not found, except for an Indian subgroup analysis (P z =0.014, OR =1.749, 95% CI =1.120-2.731). A 10 repeats/12 repeats (10R/12R) genotype was a protective factor against schizophrenia (P z =0.020, OR =0.789, 95% CI =0.646-0.963), but a 12R/12R genotype was a risk factor for schizophrenia (P z =0.004, OR =1.936, 95% CI =1.238-3.029) in the pooled analyses. In Caucasians, a GG genotype of rs1042173 may be a risk factor for schizophrenia (P z =0.006, OR =1.299, 95% CI =1.079-1.565). No association was found between rs140700 and the risk for schizophrenia. Conclusion: Through meta-analysis, we were able to gain insight into previously reported associations between SLC6A4 polymorphism and schizophrenia.

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Section: Resultsmentioning

confidence: 99%

Association between the <em>SLC6A4</em> gene and schizophrenia: an updated meta-analysis

Xu¹,

Wang²,

Yao³

2018

NDT

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“…The association studies between the serotonin receptor gene polymorphisms and schizophrenia gave mixed results. (Abdolmaleky et al 2004;Williams et al 1997;Sáiz et al 2007); however, a number of studies failed to replicate these previous positive associations (Chen et al 2001;Pae et al 2005;Lin et al 1999;Ohara et al 1999). Taken together, these predominantly negative results indicate that 5HT2A receptor genes may not be good candidate genes for schizophrenia.…”

Section: Discussionmentioning

confidence: 97%

Effect of Serotonin-Related Gene Polymorphisms on Pathogenesis and Treatment Response in Korean Schizophrenic Patients

Kim

Yoon

2011

Behav Genet

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Serotonin has been implicated in the pathophysiology of several psychiatric disorders including schizophrenia. Serotonergic system-related genes may be good candidates in investigating the genetic basis of schizophrenia. We aimed to investigate the associations of HTR1A C-1019G, HTR2A-1438A/G, TPH1 218A/C, and TPH2-703G/T variants with schizophrenia. A total of 202 patients with schizophrenia and 165 normal controls were genotyped for HTR1A C-1019G, HTR2A-1438A/G, TPH1 218A/C, and TPH2-703G/T single nucleotide polymorphisms (SNPs). In order to assess the severity of a patient's psychiatric symptoms, the brief psychiatric rating scale (BPRS), the positive and negative symptom scale (PANSS), and the Calgary depression scale for Schizophrenia (CDSS) were administered. Genotype and allele frequencies were compared between groups via χ(2) statistics. Associations between the genotypes of candidate SNPs with the severity of symptoms were examined with ANOVA by comparing the mean scores of BPRS, PANSS, and CDSS according to genotype. No significant differences in the genotype distributions and allele frequencies of four SNPs were found between patients with schizophrenia and normal controls. There was a trend towards association of HTR1A C-1019G polymorphism with negative symptom. Negative symptom score of PANSS was lower in the patients with CC genotype than in the G allele carriers. These results suggested that C allele might be associated with lesser negative symptom. More studies are needed to confirm these findings. In the future, we plan to study the associations between schizophrenia and other genetic polymorphisms.

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“…23 Functional polymorphisms of 5-HT transporter (SERT) genes, eg, rs479554 (a 44-bp insertion/deletion of the promoter regions; L and S) have also been extensively studied in relation to schizophrenia. [24][25][26] Thus, L-allele carriers with schizophrenia show more severe psychotic symptoms, 27,28 while S-allele carriers may be predisposed to suicidal behavior. 29 We sought to determine the effect of variations in functional candidate genes involved in 5-HT activity on endophenotypic measures in subjects with schizophrenia.…”

Section: Influence Of 5-ht Receptor Polymorphisms On Endo-phenotypic mentioning

confidence: 99%

Serotonin1A receptors in the pathophysiology of schizophrenia: development of novel cognition-enhancing therapeutics

Sumiyoshi

Bubeníková-Valešová²,

Horáček³

et al. 2008

Adv Therapy

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Serotonin (5-HT) receptors have been suggested to play key roles in psychosis, cognition, and mood via influence on neurotransmitters, synaptic integrity, and neural plasticity. Specifically, genetic evidence indicates that 5-HT(1A), 5-HT(2A), and 5-HT(2C) receptor single-nucleotide polymorphisms (SNPs) are related to psychotic symptoms, cognitive disturbances, and treatment response in schizophrenia. Data from animal research suggest the role of 5-HT in cognition via its influence on dopaminergic, cholinergic, glutamatergic, and GABAergic function. This article provides up-to-date findings on the role of 5-HT receptors in endophenotypic variations in schizophrenia and the development of newer cognition-enhancing medications, based on basic science and clinical evidence. Imaging genetics studies on associations of polymorphisms of several 5-HT receptor subtypes with brain structure, function, and metabolism suggest a role for the prefrontal cortex and the parahippocampal gyrus in cognitive impairments of schizophrenia. Data from animal experiments to determine the effect of agonists/antagonists at 5-HT(1A), 5-HT(2A), and 5-HT(2C) receptors on behavioral performance in animal models of schizophrenia based on the glutamatergic hypothesis provide useful information. For this purpose, standard as well as novel cognitive tasks provide a measure of memory/information processing and social interaction. In order to scrutinize mixed evidence for the ability of 5-HT(1A) agonists/antagonists to improve cognition, behavioral data in various paradigms from transgenic mice overexpressing 5-HT(1A) receptors provide valuable insights. Clinical trials reporting the advantage of 5-HT(1A) partial agonists add to efforts to shape pharmacologic perspectives concerning cognitive enhancement in schizophrenia by developing novel compounds acting on 5-HT receptors. Overall, these lines of evidence from translational research will facilitate the development of newer pharmacologic strategies for the treatment of cognitive disturbances of schizophrenia.

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No evidence for interaction between 5-HT2A receptor and serotonin transporter genes in schizophrenia

Cited by 13 publications

References 32 publications

Association between the <em>SLC6A4</em> gene and schizophrenia: an updated meta-analysis

Association between the <em>SLC6A4</em> gene and schizophrenia: an updated meta-analysis

Effect of Serotonin-Related Gene Polymorphisms on Pathogenesis and Treatment Response in Korean Schizophrenic Patients

Serotonin1A receptors in the pathophysiology of schizophrenia: development of novel cognition-enhancing therapeutics

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