Focus on HTR2C: A possible suggestion for genetic studies of complex disorders

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Focus on HTR2C : A possible suggestion for genetic studies of complex disorders. / Drago, Antonio; Serretti, Alessandro.

I: American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, Bind 150B, Nr. 5, 05.07.2009, s. 601-37.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Drago, A & Serretti, A 2009, 'Focus on HTR2C: A possible suggestion for genetic studies of complex disorders', American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, bind 150B, nr. 5, s. 601-37. https://doi.org/10.1002/ajmg.b.30864

APA

Drago, A., & Serretti, A. (2009). Focus on HTR2C: A possible suggestion for genetic studies of complex disorders. American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, 150B(5), 601-37. https://doi.org/10.1002/ajmg.b.30864

CBE

Drago A, Serretti A. 2009. Focus on HTR2C: A possible suggestion for genetic studies of complex disorders. American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics. 150B(5):601-37. https://doi.org/10.1002/ajmg.b.30864

MLA

Drago, Antonio og Alessandro Serretti. "Focus on HTR2C: A possible suggestion for genetic studies of complex disorders". American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics. 2009, 150B(5). 601-37. https://doi.org/10.1002/ajmg.b.30864

Vancouver

Drago A, Serretti A. Focus on HTR2C: A possible suggestion for genetic studies of complex disorders. American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics. 2009 jul. 5;150B(5):601-37. https://doi.org/10.1002/ajmg.b.30864

Author

Drago, Antonio ; Serretti, Alessandro. / Focus on HTR2C : A possible suggestion for genetic studies of complex disorders. I: American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics. 2009 ; Bind 150B, Nr. 5. s. 601-37.

Bibtex

@article{88fed5ff139e4a00be9b379d4155819c,
title = "Focus on HTR2C: A possible suggestion for genetic studies of complex disorders",
abstract = "HTR2C is one of the most relevant and investigated serotonin receptors. Its role in important brain structures such as the midbrain, the lateral septal complex, the hypothalamus, the olfactory bulb, the pons, the choroid plexus, the nucleus pallidus, the striatum and the amygdala, the nucleus accumbens and the anterior cingulated gyrus candidate it as a promising target for genetic association studies. The biological relevance of these brain structures is reviewed by way of the focus on HTR2C activity, with a special attention paid to psychiatric disorders. Evidence from the genetic association studies that dealt with HTR2C is reviewed and discussed alongside the findings derived from the neuronatmic investigations. The reasons for the discrepancies between these two sets of reports are discussed. As a result, HTR2C is shown to play a pivotal role in many different psychiatric behaviors or psychiatric related disrupted molecular balances, nevertheless, genetic association studies brought inconsistent results so far. The most replicated association involve the feeding behavior and antipsychotic induced side effects, both weight gain and motor related: Cys23Ser (rs6318) and -759C/T (rs3813929) report the most consistent results. The lack of association found in other independent studies dampens the clinical impact of these reports. Here, we report a possible explanation for discrepant findings that is poorly or not at all usually considered, that is that HTR2C may exert different or even opposite activities in the brain depending on the structure analyzed and that mRNA editing activity may compensate possible genetically controlled functional effects. The incomplete coverage of the HTR2C variants is proposed as the best cost-benefit ratio bias to fix. The evidence of brain area specific HTR2C mRNA editing opens a debate about how the brain can differently modulate stress events, and process antidepressant treatments, in different brain areas. The mRNA editing activity on HTR2C may play a major role for the negative association results.",
keywords = "Animals, Base Sequence, Brain, Genetics, Population, Humans, Mental Disorders, Molecular Sequence Data, Protein Processing, Post-Translational, Receptor, Serotonin, 5-HT2C",
author = "Antonio Drago and Alessandro Serretti",
note = "2008 Wiley-Liss, Inc.",
year = "2009",
month = jul,
day = "5",
doi = "10.1002/ajmg.b.30864",
language = "English",
volume = "150B",
pages = "601--37",
journal = "American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics",
issn = "1552-4841",
publisher = "JohnWiley & Sons, Inc.",
number = "5",

}

RIS

TY - JOUR

T1 - Focus on HTR2C

T2 - A possible suggestion for genetic studies of complex disorders

AU - Drago, Antonio

AU - Serretti, Alessandro

N1 - 2008 Wiley-Liss, Inc.

PY - 2009/7/5

Y1 - 2009/7/5

N2 - HTR2C is one of the most relevant and investigated serotonin receptors. Its role in important brain structures such as the midbrain, the lateral septal complex, the hypothalamus, the olfactory bulb, the pons, the choroid plexus, the nucleus pallidus, the striatum and the amygdala, the nucleus accumbens and the anterior cingulated gyrus candidate it as a promising target for genetic association studies. The biological relevance of these brain structures is reviewed by way of the focus on HTR2C activity, with a special attention paid to psychiatric disorders. Evidence from the genetic association studies that dealt with HTR2C is reviewed and discussed alongside the findings derived from the neuronatmic investigations. The reasons for the discrepancies between these two sets of reports are discussed. As a result, HTR2C is shown to play a pivotal role in many different psychiatric behaviors or psychiatric related disrupted molecular balances, nevertheless, genetic association studies brought inconsistent results so far. The most replicated association involve the feeding behavior and antipsychotic induced side effects, both weight gain and motor related: Cys23Ser (rs6318) and -759C/T (rs3813929) report the most consistent results. The lack of association found in other independent studies dampens the clinical impact of these reports. Here, we report a possible explanation for discrepant findings that is poorly or not at all usually considered, that is that HTR2C may exert different or even opposite activities in the brain depending on the structure analyzed and that mRNA editing activity may compensate possible genetically controlled functional effects. The incomplete coverage of the HTR2C variants is proposed as the best cost-benefit ratio bias to fix. The evidence of brain area specific HTR2C mRNA editing opens a debate about how the brain can differently modulate stress events, and process antidepressant treatments, in different brain areas. The mRNA editing activity on HTR2C may play a major role for the negative association results.

AB - HTR2C is one of the most relevant and investigated serotonin receptors. Its role in important brain structures such as the midbrain, the lateral septal complex, the hypothalamus, the olfactory bulb, the pons, the choroid plexus, the nucleus pallidus, the striatum and the amygdala, the nucleus accumbens and the anterior cingulated gyrus candidate it as a promising target for genetic association studies. The biological relevance of these brain structures is reviewed by way of the focus on HTR2C activity, with a special attention paid to psychiatric disorders. Evidence from the genetic association studies that dealt with HTR2C is reviewed and discussed alongside the findings derived from the neuronatmic investigations. The reasons for the discrepancies between these two sets of reports are discussed. As a result, HTR2C is shown to play a pivotal role in many different psychiatric behaviors or psychiatric related disrupted molecular balances, nevertheless, genetic association studies brought inconsistent results so far. The most replicated association involve the feeding behavior and antipsychotic induced side effects, both weight gain and motor related: Cys23Ser (rs6318) and -759C/T (rs3813929) report the most consistent results. The lack of association found in other independent studies dampens the clinical impact of these reports. Here, we report a possible explanation for discrepant findings that is poorly or not at all usually considered, that is that HTR2C may exert different or even opposite activities in the brain depending on the structure analyzed and that mRNA editing activity may compensate possible genetically controlled functional effects. The incomplete coverage of the HTR2C variants is proposed as the best cost-benefit ratio bias to fix. The evidence of brain area specific HTR2C mRNA editing opens a debate about how the brain can differently modulate stress events, and process antidepressant treatments, in different brain areas. The mRNA editing activity on HTR2C may play a major role for the negative association results.

KW - Animals

KW - Base Sequence

KW - Brain

KW - Genetics, Population

KW - Humans

KW - Mental Disorders

KW - Molecular Sequence Data

KW - Protein Processing, Post-Translational

KW - Receptor, Serotonin, 5-HT2C

U2 - 10.1002/ajmg.b.30864

DO - 10.1002/ajmg.b.30864

M3 - Journal article

C2 - 18802918

VL - 150B

SP - 601

EP - 637

JO - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics

SN - 1552-4841

IS - 5

ER -