TY - JOUR
T1 - Blood Levels of Monoamine Precursors and Smoking in Patients with Schizophrenia
AU - Mathai, Ashwin Jacob
AU - Kanwar, Jyoti
AU - Okusaga, Olaoluwa
AU - Fuchs, Dietmar
AU - Lowry, Christopher A.
AU - Peng, Xiaoqing
AU - Giegling, Ina
AU - Hartmann, Annette M.
AU - Konte, Bettina
AU - Friedl, Marion
AU - Gragnoli, Claudia
AU - Reeves, Gloria M.
AU - Groer, Maureen W.
AU - Rosenthal, Richard N.
AU - Rujescu, Dan
AU - Postolache, Teodor T.
N1 - Funding Information:
This work was supported by Distinguished Investigator Award from the American Foundation for Suicide Prevention (TTP, PI, DR, co-I, DIG 1-162-12), with additional funding from the P30 DK072488 NIDDK (NORC pilot/ developmental grant) from the National Institutes of Health, Bethesda, MD, USA, and Joint Institute for Food Safety and Applied Nutrition/ UMD, through the cooperative agreement FDU.001418 (TTP, PI). Additional support from Rocky Mountain MIRECC for Suicide Prevention, Denver, CO, USA (TTP), VISN5 MIRECC,
Funding Information:
Supported by a Distinguished Investigator Award from the American Foundation for Suicide Prevention (TTP, PI, DR, Co-I). Additional support for the writing of the manuscript was provided by the Rocky Mountain MIRECC, Denver, CO, USA (TTP and CAL), VISN5 MIRECC, Baltimore, MD, USA (TTP), the DC Department of Behavioral Health, Washington, DC, USA (AJM and JK), the Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, TX, USA (OO), and Joint Institute for Food Safety and Applied Nutrition/UMD, through the cooperative agreement FDU.001418 (TTP, PI). We thank Dipika Vaswani, MD and Aamar Sleemi, MD for data management and logistics, and Nupur Hegde for final proof-reading. The findings and conclusions in this study belong to the authors and do not necessarily represent the official positions of the American Foundation for Suicide Prevention, Food and Drug Administration, Veterans? Administration, or other sponsors. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© Copyright © 2016 Mathai, Kanwar, Okusaga, Fuchs, Lowry, Peng, Giegling, Hartmann, Konte, Friedl, Gragnoli, Reeves, Groer, Rosenthal, Rujescu and Postolache.
PY - 2016/8/30
Y1 - 2016/8/30
N2 - Smoking is highly prevalent in patients with schizophrenia and exerts a negative impact on cardiovascular mortality in these patients. Smoking has complex interactions with monoamine metabolism through the ability of cigarette smoke to suppress Type 1 T helper cell (Th1) type immunity, the immunophenotype that is implicated in phenylalanine hydroxylase (PAH) dysfunction and tryptophan (Trp) breakdown to kynurenine (Kyn) via indoleamine 2,3-dioxygenase. Nicotine also induces tyrosine hydroxylase (TH) gene expression, leading to increased synthesis of catecholamines. Furthermore, there is evidence for PAH dysfunction in schizophrenia. This study aimed to compare the plasma levels of selected monoamine precursors and their metabolites in smokers vs. non-smokers in a large sample of patients with schizophrenia. We measured plasma phenylalanine (Phe), tyrosine (Tyr), Trp, and Kyn levels using high-performance liquid chromatography and calculated Phe:Tyr and Kyn:Trp ratios in 920 patients with schizophrenia. Analysis of variance and linear regression analyses were used to compare these endpoints between three groups of patients with schizophrenia: (1) current smokers, (2) past smokers, and (3) non-smokers. There were significant differences among the three groups with regards to Tyr levels [F(2,789) = 3.77, p = 0.02], with current smokers having lower Tyr levels when compared with non-smokers (p = 0.02). Kyn levels and Kyn:Trp ratio were different among the three groups [F(2,738) = 3.17, p = 0.04, F(2,738) = 3.61, p = 0.03] with current smokers having lower Kyn levels (p = 0.04) and higher Kyn:Trp ratio (p = 0.02) when compared with past smokers. These findings need to be replicated with protocols that include healthy controls to further elucidate the neurobiological underpinnings of altered Tyr and Kyn levels in smokers. Results do suggest potential molecular links between schizophrenia and smoking that may represent biomarkers and treatment targets for reducing an important modifiable cause of general morbidity and mortality in patients with schizophrenia.
AB - Smoking is highly prevalent in patients with schizophrenia and exerts a negative impact on cardiovascular mortality in these patients. Smoking has complex interactions with monoamine metabolism through the ability of cigarette smoke to suppress Type 1 T helper cell (Th1) type immunity, the immunophenotype that is implicated in phenylalanine hydroxylase (PAH) dysfunction and tryptophan (Trp) breakdown to kynurenine (Kyn) via indoleamine 2,3-dioxygenase. Nicotine also induces tyrosine hydroxylase (TH) gene expression, leading to increased synthesis of catecholamines. Furthermore, there is evidence for PAH dysfunction in schizophrenia. This study aimed to compare the plasma levels of selected monoamine precursors and their metabolites in smokers vs. non-smokers in a large sample of patients with schizophrenia. We measured plasma phenylalanine (Phe), tyrosine (Tyr), Trp, and Kyn levels using high-performance liquid chromatography and calculated Phe:Tyr and Kyn:Trp ratios in 920 patients with schizophrenia. Analysis of variance and linear regression analyses were used to compare these endpoints between three groups of patients with schizophrenia: (1) current smokers, (2) past smokers, and (3) non-smokers. There were significant differences among the three groups with regards to Tyr levels [F(2,789) = 3.77, p = 0.02], with current smokers having lower Tyr levels when compared with non-smokers (p = 0.02). Kyn levels and Kyn:Trp ratio were different among the three groups [F(2,738) = 3.17, p = 0.04, F(2,738) = 3.61, p = 0.03] with current smokers having lower Kyn levels (p = 0.04) and higher Kyn:Trp ratio (p = 0.02) when compared with past smokers. These findings need to be replicated with protocols that include healthy controls to further elucidate the neurobiological underpinnings of altered Tyr and Kyn levels in smokers. Results do suggest potential molecular links between schizophrenia and smoking that may represent biomarkers and treatment targets for reducing an important modifiable cause of general morbidity and mortality in patients with schizophrenia.
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UR - http://www.scopus.com/inward/citedby.url?scp=85048621039&partnerID=8YFLogxK
U2 - 10.3389/fpubh.2016.00182
DO - 10.3389/fpubh.2016.00182
M3 - Article
AN - SCOPUS:85048621039
SN - 2296-2565
VL - 4
JO - Frontiers in Public Health
JF - Frontiers in Public Health
M1 - 182
ER -