Abstract
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.
Highlights
Cigarette smoking is more prevalent in patients with schizophrenia in comparison to the general population as well as patients with other severe mental illnesses [1]
In the first study of its kind, we provide evidence that, among patients with a diagnosis of schizophrenia, smoking is associated with a decrease in Tyr levels
We had previously reported that plasma Phe levels and Phe:Tyr ratio were elevated in schizophrenia patients when compared with normal controls with no difference in continuous Tyr levels
Summary
Cigarette smoking is more prevalent in patients with schizophrenia in comparison to the general population as well as patients with other severe mental illnesses [1]. Smoking is an important modifiable risk factor for increased cardiovascular morbidity and mortality reported in patients with schizophrenia [4, 5]. Smoking leads to increased dopaminergic neurotransmission [9] and is purported [10] to improve “hypofrontality,” which is manifested as negative and cognitive symptoms of schizophrenia [11]. Smoking briefly normalizes P50 amplitude in schizophrenia probands and their relatives, and nicotine improves PPI and cognition in patients with schizophrenia [14].These findings lend evidence to the self-medication hypothesis which suggests that increased smoking in schizophrenia may be an attempt to compensate for attentional deficits and other symptoms of the illness [15]
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