Potentially confounding medical conditions (e.g., hypertension, diabetes, insulin-resistance, chronic obstructive pulmonary disease, atherosclerosis, neurodegenerative diseases) and comorbid alcohol use/misuse, substance use/misuse, and psychiatric conditions (particularly mood disorders) were not consistently screened or statistically accounted for in many studies. Several psychiatric disorders known to have adverse effects on brain neurobiology and neurocognition are highly prevalent in chronic smokers, including anxiety disorders [156], attention deficit/hyperactivity disorder [157,158], alcohol and substance use disorders [13,157,159], mood disorders [160,161], and schizophrenia-spectrum disorders [162,163]. Additionally, the potential influence of sex, exercise, diet, body mass index, exposure to secondary/environmental smoke, nicotine withdrawal and genetic predispositions [e.g., ApoE4 genotype, single nucleotide polymorphisms in nicotinic acetlycholinergic receptors (nAChr), brain derived neurotrophic factor (BDNF), dopamine receptor D2 (DRD2), catechol-O-methyl transferace (COMT)] were not considered. The aforementioned factors are likely mediators or moderators of brain neurobiology and neurocognition in controls and addictive disorders [146,147,149,164–181]. Finally, the potential effects of nicotine withdrawal on the primary measures of interest were not addressed in many studies.
