Association between schizophrenia and T102C polymorphism of the 5-hydroxytryptamine type 2a-receptor gene

Williams, Julie; Spurlock, Gillian; McGuffin, Peter; Owen, Michael John; Mallet, Jacques; Nöthen, M. M.; Gill, Michael; Aschauer, Harald; Nylander, Per-Olof; Macciardi, Fabìo

doi:10.1016/s0140-6736(96)90939-3

Cited by 228 publications

(118 citation statements)

References 12 publications

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“…In addition, there was no clear trend of differential distribution between patients and controls. These results could not confirm previous findings of association with schizophrenia [Inayama et al, 1996;Williams et al, 1996;Joober et al, 1999;Araga and Narasu, 2002]. However, it is likely that serotonergic associations are stronger when specific phenotypes such as suicidal behaviour and clinical dimensions are considered [Bonnier et al, 2002;Golimbet et al, 2002] and therefore could not be detected in our sample.…”

Section: Discussioncontrasting

confidence: 92%

“…However, association and linkage genetic studies have failed to produce consistent results supporting the involvement of serotonergic mutations in mental illnesses such as schizophrenia and bipolar disorder. Polymorphisms in the gene coding for 5-HT2A receptors have been related to schizophrenia, bipolar disorder and psychotic symptomatology [Inayama et al, 1996;Williams et al, 1996;Du et al, 1999;Joober et al, 1999;Nacmias et al, 2001;Araga and Narasu, 2002;Bonnier et al, 2002;Golimbet et al, 2002]. Genetic variants of the serotonin transporter (5-HTT) have also been associated with psychotic disorders Malhotra et al, 1998;Hranilovic et al, 2000;Kaiser et al, 2001;Tsai et al, 2002].…”

Section: Introductionmentioning

confidence: 99%

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Serotonergic polymorphisms and psychotic disorders in populations from North Spain

Mata¹,

Arranz²,

Patiño

et al. 2003

American J of Med Genetics Pt B

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There is strong biological evidence relating alterations in the serotonergic system with mental disorders. These alterations may be originated at the DNA level by sequence mutations that alter the functioning of serotonin receptors and transporter. To test this hypothesis we investigated three genetic variants of the 5-HT2A receptor (-1438G/A, 102T/C and His452Tyr) and two variants of the serotonin transporter (a VNTR in the second intron and a 44 bp insertion/delition in the promoter region of the gene) in a clinical sample recruited in a human isolate and in surrounding areas in Northern Spain (N = 257) and in ethnically matched controls (N = 334). No clear association was found between 5-HT2A variants and psychosis. However, marginal associations were observed between the 5-HTT LPR and VNTR variants and psychosis (P≤0.05) indicating a minor contribution to psychosis of genetic alterations in this gene.

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Section: Discussioncontrasting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Serotonergic polymorphisms and psychotic disorders in populations from North Spain

Mata¹,

Arranz²,

Patiño

et al. 2003

American J of Med Genetics Pt B

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“…A significant association between T102C and schizophrenia is reported (Williams et al, 1996;Williams et al, 1997). The C allele was associated with diagnosis of schizophrenia with an odds ratio of 1.3 (p ¼ 0.008).…”

Section: Introductionmentioning

confidence: 97%

Association of Serotonin 5-HT2A Receptor Binding and the T102C Polymorphism in Depressed and Healthy Caucasian Subjects

Khait

Huang

Zalsman

et al. 2004

Neuropsychopharmacol

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Serotonin 5-HT 2A receptor (5-HT 2A ) binding is reported to be altered in individuals with suicidal behavior, mood disorders, and aggressive-impulsive traits. Genetic association with major depression, suicidal behavior, and aggressive-impulsive traits has not been established. This study examines the possible association of the 5-HT 2A gene C102T polymorphism with the receptor binding kinetics, and clinical overt phenotypes. The study population included 63 healthy volunteers and 152 subjects with mood disorders, 56 of whom had a history of suicide attempts. All were Caucasian. Platelet 5-HT 2A binding kinetics (B max and K D ) were assayed and adjusted for seasonal variation. All subjects were genotyped for the T102C polymorphism. Clinical phenotype was determined by structured clinical interview. The TT genotype was associated with higher B max in all subjects (F ¼ 3.53, df ¼ 2,211; p ¼ 0.03), controlling for diagnosis. Bonferroni-adjusted post hoc testing showed higher binding in the TT compared with TC genotype in the control group (F ¼ 7.56, df ¼ 2,60, p ¼ 0.001), but not in the mood-disordered subjects. No difference was found in genotype and allele distribution between the mood-disordered subjects, with and without suicide attempt history, and controls. B max was not related to a diagnosis of mood disorders.The TT genotype appears associated with higher platelet 5-HT 2A B max in the healthy population, but this genotypic effect appears absent in mood disorders and unrelated to psychopathology.

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“…The 5-HT 2A receptor has been associated with a number of the more common psychiatric conditions, including major depression, obsessive-compulsive disorder, excessive impulsivity, anorexia nervosa, and schizophrenia (de Angelis, 2002). Converging lines of evidence, including linkage (Williams et al, 1996; although see Serretti et al, 2000), postmortem neurochemical (Burnet et al, 1996;Gurevich and Joyce, 1997), and neuroimaging studies (Ngan et al, 2000) suggest that the 5-HT 2A receptor may play an especially important role in the etiology of schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

The Selective Serotonin-2A Receptor Antagonist M100907 Reverses Behavioral Deficits in Dopamine Transporter Knockout Mice

Barr

Lehmann-Masten

Paulus

et al. 2003

Neuropsychopharmacol

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A hyperdopaminergic state in humans has been hypothesized to contribute to the pathology of a number of psychiatric illnesses, including schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder. Mice that display elevated synaptic levels of dopamine due to a genetically engineered deletion of the dopamine transporter (DAT) model behavioral deficits that simulate the above conditions. As novel treatment strategies for these disorders have focused on the serotonin (5-HT) 2A receptor, we determined the capacity of the highly selective 5-HT 2A receptor antagonist M100907 to reverse behavioral deficits in DAT knockout (KO) mice. Prior to drug treatment, DAT KO mice exhibited increased levels of locomotor activity and highly linearized movement in a novel environment, as well as reduced prepulse inhibition (PPI) of acoustic startle, compared to wild-type littermates. Treatment with M100907 (0.3-1.0 mg/ kg, but not 0.1 mg/kg) reversed locomotor deficits in DAT KO mice. Similarly, treatment with 1.0 mg/kg M100907 reversed the PPI deficits in DAT KO mice. These data indicate that selective 5-HT 2A receptor antagonists, such as M100907, may represent a class of drugs that can be used to treat conditions in which a chronic, elevated dopaminergic tone is present and contributes to abnormal behavior and sensorimotor gating deficits.

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Association between schizophrenia and T102C polymorphism of the 5-hydroxytryptamine type 2a-receptor gene

Cited by 228 publications

References 12 publications

Serotonergic polymorphisms and psychotic disorders in populations from North Spain

Serotonergic polymorphisms and psychotic disorders in populations from North Spain

Association of Serotonin 5-HT2A Receptor Binding and the T102C Polymorphism in Depressed and Healthy Caucasian Subjects

The Selective Serotonin-2A Receptor Antagonist M100907 Reverses Behavioral Deficits in Dopamine Transporter Knockout Mice

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