Blood Levels of Monoamine Precursors and Smoking in Patients with Schizophrenia.
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.
Mood and Anxiety Program, University of Maryland School of Medicine, Baltimore, MD, USA; Saint Elizabeths Hospital Psychiatry Residency Training Program, Washington, DC, USA.
Ashwin Jacob
AJ
Mathai
Mood and Anxiety Program, University of Maryland School of Medicine , Baltimore, MD , USA.
Jyoti
J
Kanwar
Mood and Anxiety Program, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Olaoluwa
O
Okusaga
Division of Biological Chemistry, Biocenter Innsbruck Medical University , Innsbruck , Austria.
Dietmar
D
Fuchs
Department of Integrative Physiology, Center for Neuroscience, University of Colorado Boulder , Boulder, CO , USA.
Christopher A
CA
Lowry
Mood and Anxiety Program, University of Maryland School of Medicine, Baltimore, MD, USA; Saint Elizabeths Hospital Psychiatry Residency Training Program, Washington, DC, USA.
Xiaoqing
X
Peng
Department of Psychiatry, Martin-Luther-University of Halle-Wittenberg , Halle , Germany.
Ina
I
Giegling
Department of Psychiatry, Martin-Luther-University of Halle-Wittenberg , Halle , Germany.
Annette M
AM
Hartmann
Department of Psychiatry, Martin-Luther-University of Halle-Wittenberg , Halle , Germany.
Bettina
B
Konte
Department of Psychiatry, Martin-Luther-University of Halle-Wittenberg , Halle , Germany.
Marion
M
Friedl
Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA; Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA.
Claudia
C
Gragnoli
Division of Child and Adolescent Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA; University of Maryland Child and Adolescent Mental Health Innovations Center, Baltimore, MD, USA.
Gloria M
GM
Reeves
University of South Florida , Tampa, FL , USA.
Maureen W
MW
Groer
Department of Psychiatry, Icahn School of Medicine at Mount Sinai , New York, NY , USA.
Richard N
RN
Rosenthal
Department of Psychiatry, Martin-Luther-University of Halle-Wittenberg , Halle , Germany.
Dan
D
Rujescu
Mood and Anxiety Program, University of Maryland School of Medicine, Baltimore, MD, USA; VISN 5 Capitol Health Care Network Mental Illness Research Education and Clinical Center (MIRECC), Baltimore, MD, USA; Rocky Mountain MIRECC, Denver, CO, USA.
Teodor T
TT
Postolache
kynurenine; phenylalanine; schizophrenia; smoking; tryptophan; tyrosine