Glutamate is a ubiquitous principal
Glutamate is a ubiquitous principal excitatory neurotransmitter in the Clindamycin HCl that plays a central role in a variety of brain functions (Delgado, 2013, Hawkins, 2009). Several studies reported that CSF glutamate was associated with mental illness, including major depressive disorder, anxious and intellectual impairment (Bruno et al., 2017, Hashimoto et al., 2016, Ogawa et al., 2018). In refractory patients with affective disorders, CSF glutamate levels decreased notably (Frye et al., 2007). CSF glutamate levels also decreased in patients with major depressive disorder and negatively correlated with the recency ratio, a novel cognitive marker of intellectual impairment (Bruno et al., 2017).
Nicotine impacts areas of the brain involved in addiction and reward, and causes alterations in levels of neurotransmitters such as dopamine, serotonin, norepinephrine and glutamate (Lenoir and Kiyatkin, 2013, Singer et al., 2004). A study found that repeated and intermittent exposure to nicotine clouds increase the release of glutamate in the brain (Lenoir and Kiyatkin, 2013). Nevertheless, the immediate metabolism of CSF glutamate related to tobacco smoking remains unclear. In the present study, we measured levels of CSF glutamate in a group of Chinese subjects to investigate the relationship between CSF glutamate levels and mental status induced by heavy smoking.
Results In the present study, the mean age was 32.61 ± 10.62 years, BMI value was 25.48 ± 4.29 kg/m2 and glutamate level was 64.45 ± 53.16 µmol/L. Baseline characteristics and CSF glutamate levels of all subjects are presented in Table 1. The age of the HS-group was higher than that of the NS-group (p = 0.001), but the education years in HS-group was significantly lower than that of the NS-group (p = 0.008). Between the groups, BMI was not significantly different (p = 0.246). To control the influence of age and education years, an analysis of covariance was performed to evaluate the difference of other variables between two groups. The levels of CSF glutamate were also different, and it was significantly higher in the HS-group (p = 0.003). The impulsivity between the groups was different: the BIS total scores in the HS-group were higher than those of the NS-group (p = 0.034), the BIS action scores were also higher (p = 0.017). SAS scores between the groups showed no difference (p = 0.5); however, BDI scores in the HS-group were significantly higher than those of the NS-group (p = 0.04) (Table. 1). Multivariable linear regression using BDI scores as the dependent variable showed that years of smoking contributed to the BDI scores (p = 0.001) after adjusting for education year, BMI, pain level and CSF glutamate levels (Table 2). Partial correlation analyses found that CSF glutamate levels negatively correlated with BDI scores (r = −0.289, P = 0.012) (Fig. 1B) in the HS-group with age and education years as covariates; however, Haplotype correlation did not show in the NS-group (r = 0.092, P = 0.576) (Fig. 1A). Furthermore, SAS scores did not correlate with CSF glutamate after adjusting for the above mentioned covariates (p > 0.025).
Discussion The main finding of the present study was that subjects with heavy smoking history had lower CSF glutamate levels and higher BDI scores, and were more prone to be impulsive (Table 1). We found a negative correlation between CSF glutamate levels and BDI scores in heavy smokers. Furthermore, we failed to observe a correlation between CSF glutamate levels and SAS scores. To the best of our knowledge, this is the first study to evaluate alterations in CSF glutamate levels in subjects who were heavy smokers. Several studies suggested that impulsivity was strongly associated with tobacco smoking (Hosking et al., 2014, Perry and Carroll, 2008, Tsutsui-Kimura et al., 2010). This relationship appeared to be bidirectional. In animal models, nicotine administration significantly enhanced impulsivity (Dallery and Locey, 2005, Kayir et al., 2014). A recent meta-analysis of human studies covered 57 articles and a total of 3329 subjects confirmed that smokers had higher impulsivity than did non-smokers (MacKillop et al., 2011). Nicotine addiction was characterized by impulses, urges and lack of self-control towards tobacco smoking, meaning that impulsivity was always accompanied with nicotine addiction. Through the Barratt impulsiveness scale, we found that heavy smokers had higher action scores and total scores of impulsivity, consisting of the abovementioned studies.