Investigating Sex-Specific Characteristics of Nicotine Addiction Using Metabolic and Structural Magnetic Resonance Imaging

Abstract

Nicotine addiction is known to modulate neurotransmission and alter the brain structure. The detrimental effect of nicotine is more prominent in females as compared to males. This study sought to examine the sex-specific influence of nicotine addiction on gamma amino butyric acid (GABA) and the white matter (WM) microstructure. Sixty healthy subjects (smokers/non-smokers) underwent structural and metabolic magnetic resonance imaging scans. Results showed alterations in WM integrity (measured as changes in fractional anisotropy [FA] and GABA in smokers versus non-smokers and females versus males. No overall significant smoking and sex-specific interactions were observed in this study. However, on comparing female smokers with female non-smokers, significantly higher GABA and FA values were observed in female smokers. However, GABA and FA values did not differ significantly when male smokers were compared against male non-smokers. Our results provide a further rationale to investigate the impact of nicotine on central GABAergic function and WM integrity, in particular due to the potential risk for females to experience depressive/anxiety symptoms during smoking cessation.

Increased spontaneous activity of the superior frontal gyrus with reduced functional connectivity to visual attention areas and cerebellum in male smokers

“…First and foremost, the sample size of the study is relatively small, which may reduce the strength of our results. Secondly, previous studies have shown gender and racial differences in brain function in smokers (Bagga et al, 2018;McCarthy et al, 2019;Lin et al, 2021). The participants included in the current study were all Chinese males, so the results of this study may not account for all smokers.…”

Metabolic Dynamics in the Prefrontal Cortex during a Working Memory Task in Young Adult Smokers

“…The participants received 20 EUR as compensation for their time. Some parts of this section have been adapted from another study by the same authors due to similarities in the recruitment pipeline [33]. Self-Reported Questionnaire Assessment All participants were administered a set of questionnaires at the beginning of the study, namely, the Leiden Index of Depression severity (LEIDS-R: measures vulnerability to depression [34]), the Frankfurter Aufmerksamkeits Inventar (FAIR: performance test for concentration and focused attention; [35]), and the Standard Progressive Matrices (SPM: intelligence test, investigating the participants' ability to find meaning in complex schemata and recall the necessary information for this [36]).…”

Quantifying GABA in Addiction: A Review of Proton Magnetic Resonance Spectroscopy Studies

“…They reported that lower dACC GABA was associated with heightened reactivity to drug cues and more withdrawal symptoms, which suggests that GABA is related to dependence severity [ 74 ]. In the prefrontal cortex, female smokers ( n = 15) had significantly higher levels of GABA compared to female non-smokers ( n = 15), and female smokers had lower GABA than male smokers ( n = 15) [ 73 ]. There was no difference in GABA between male smokers and non-smokers ( n = 15) [ 73 ].…”

“…In the prefrontal cortex, female smokers ( n = 15) had significantly higher levels of GABA compared to female non-smokers ( n = 15), and female smokers had lower GABA than male smokers ( n = 15) [ 73 ]. There was no difference in GABA between male smokers and non-smokers ( n = 15) [ 73 ]. In a male-only nicotine and polysubstance use population, one study found no significant difference in GABA between current smoking males ( n = 48), current smoking and polysubstance use males ( n = 61), and healthy control ( n = 90) [ 81 ].…”