Tetrahydrobiopterin Pathway may Provide Novel Molecular Targets for Acute and Long Term Efficacy of Mood-Regulating Drugs

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Existing treatments for depression usually take several weeks to achieve their antidepressant effects, and a significant number of patients do not have adequate improvement or are treatment refractory even after long-term drug administration. Moreover, the increased risk of suicide is a serious public health concern that can occur particularly during the initial stages of antidepressant pharmacotherapy. Thus, there is an urgent need for therapeutics with improved efficacy that can exert their effects within hours or days of their administration. The pteridine tetrahydrobiopterin (BH4) is an essential co-factor for production of many neurotransmitters including serotonin. Given the pivotal role of BH4 in several processes fundamental to the pathobiology of mood disorders and the mechanisms of action of mood-regulating drugs, it is surprising that only a few studies have examined the potential role of BH4 pathway genes in individual variability in susceptibility to mood disorders and their treatment outcomes. Although previous studies have examined BH4 in these contexts, there were methodological shortcomings, as well as conflicting findings. However, more recent studies have provided new evidence for the importance of the BH4 pathway in mood disorders and their treatment. For example, the recent finding that the SSRI antidepressant paroxetine substantially affects the level of the protein sepiapterin reductase, which catalyzes the final step in the biosynthesis of BH4, in neural cells, has suggested a need to re-examine the BH4 pathway in the context of the pathobiology of mood disorders and, more importantly, as a potential target for mood-regulating drugs.

LanguageEnglish
Pages174-181
Number of pages8
JournalCurrent Pharmacogenomics and Personalized Medicine
Volume8
Issue number3
DOIs
Publication statusPublished - 2010
Externally publishedYes

Fingerprint

Mood Disorders
Antidepressive Agents
sepiapterin reductase
Pharmaceutical Preparations
Pteridines
Paroxetine
Therapeutics
Suicide
Neurotransmitter Agents
Serotonin
Public Health
Depression
Drug Therapy
sapropterin
Genes
Proteins

Cite this

@article{de4e9d74368f45f7ad6fdb3394e49ece,
title = "Tetrahydrobiopterin Pathway may Provide Novel Molecular Targets for Acute and Long Term Efficacy of Mood-Regulating Drugs",
abstract = "Existing treatments for depression usually take several weeks to achieve their antidepressant effects, and a significant number of patients do not have adequate improvement or are treatment refractory even after long-term drug administration. Moreover, the increased risk of suicide is a serious public health concern that can occur particularly during the initial stages of antidepressant pharmacotherapy. Thus, there is an urgent need for therapeutics with improved efficacy that can exert their effects within hours or days of their administration. The pteridine tetrahydrobiopterin (BH4) is an essential co-factor for production of many neurotransmitters including serotonin. Given the pivotal role of BH4 in several processes fundamental to the pathobiology of mood disorders and the mechanisms of action of mood-regulating drugs, it is surprising that only a few studies have examined the potential role of BH4 pathway genes in individual variability in susceptibility to mood disorders and their treatment outcomes. Although previous studies have examined BH4 in these contexts, there were methodological shortcomings, as well as conflicting findings. However, more recent studies have provided new evidence for the importance of the BH4 pathway in mood disorders and their treatment. For example, the recent finding that the SSRI antidepressant paroxetine substantially affects the level of the protein sepiapterin reductase, which catalyzes the final step in the biosynthesis of BH4, in neural cells, has suggested a need to re-examine the BH4 pathway in the context of the pathobiology of mood disorders and, more importantly, as a potential target for mood-regulating drugs.",
keywords = "Antidepressants, GTP cyclohydrolase I feedback regulator, Mood disorders, Neurotransmitters, Pharmacogenomics, Sepiapterin reductase, SSRIs, Tetrahydrobiopterin",
author = "McHugh, {Patrick C.}",
year = "2010",
doi = "10.2174/187569210792246272",
language = "English",
volume = "8",
pages = "174--181",
journal = "Current Pharmacogenomics and Personalized Medicine",
issn = "1875-6921",
publisher = "Bentham Science Publishers B.V.",
number = "3",

}

TY - JOUR

T1 - Tetrahydrobiopterin Pathway may Provide Novel Molecular Targets for Acute and Long Term Efficacy of Mood-Regulating Drugs

AU - McHugh, Patrick C.

PY - 2010

Y1 - 2010

N2 - Existing treatments for depression usually take several weeks to achieve their antidepressant effects, and a significant number of patients do not have adequate improvement or are treatment refractory even after long-term drug administration. Moreover, the increased risk of suicide is a serious public health concern that can occur particularly during the initial stages of antidepressant pharmacotherapy. Thus, there is an urgent need for therapeutics with improved efficacy that can exert their effects within hours or days of their administration. The pteridine tetrahydrobiopterin (BH4) is an essential co-factor for production of many neurotransmitters including serotonin. Given the pivotal role of BH4 in several processes fundamental to the pathobiology of mood disorders and the mechanisms of action of mood-regulating drugs, it is surprising that only a few studies have examined the potential role of BH4 pathway genes in individual variability in susceptibility to mood disorders and their treatment outcomes. Although previous studies have examined BH4 in these contexts, there were methodological shortcomings, as well as conflicting findings. However, more recent studies have provided new evidence for the importance of the BH4 pathway in mood disorders and their treatment. For example, the recent finding that the SSRI antidepressant paroxetine substantially affects the level of the protein sepiapterin reductase, which catalyzes the final step in the biosynthesis of BH4, in neural cells, has suggested a need to re-examine the BH4 pathway in the context of the pathobiology of mood disorders and, more importantly, as a potential target for mood-regulating drugs.

AB - Existing treatments for depression usually take several weeks to achieve their antidepressant effects, and a significant number of patients do not have adequate improvement or are treatment refractory even after long-term drug administration. Moreover, the increased risk of suicide is a serious public health concern that can occur particularly during the initial stages of antidepressant pharmacotherapy. Thus, there is an urgent need for therapeutics with improved efficacy that can exert their effects within hours or days of their administration. The pteridine tetrahydrobiopterin (BH4) is an essential co-factor for production of many neurotransmitters including serotonin. Given the pivotal role of BH4 in several processes fundamental to the pathobiology of mood disorders and the mechanisms of action of mood-regulating drugs, it is surprising that only a few studies have examined the potential role of BH4 pathway genes in individual variability in susceptibility to mood disorders and their treatment outcomes. Although previous studies have examined BH4 in these contexts, there were methodological shortcomings, as well as conflicting findings. However, more recent studies have provided new evidence for the importance of the BH4 pathway in mood disorders and their treatment. For example, the recent finding that the SSRI antidepressant paroxetine substantially affects the level of the protein sepiapterin reductase, which catalyzes the final step in the biosynthesis of BH4, in neural cells, has suggested a need to re-examine the BH4 pathway in the context of the pathobiology of mood disorders and, more importantly, as a potential target for mood-regulating drugs.

KW - Antidepressants

KW - GTP cyclohydrolase I feedback regulator

KW - Mood disorders

KW - Neurotransmitters

KW - Pharmacogenomics

KW - Sepiapterin reductase

KW - SSRIs

KW - Tetrahydrobiopterin

UR - http://www.scopus.com/inward/record.url?scp=78649254956&partnerID=8YFLogxK

U2 - 10.2174/187569210792246272

DO - 10.2174/187569210792246272

M3 - Article

VL - 8

SP - 174

EP - 181

JO - Current Pharmacogenomics and Personalized Medicine

T2 - Current Pharmacogenomics and Personalized Medicine

JF - Current Pharmacogenomics and Personalized Medicine

SN - 1875-6921

IS - 3

ER -