cigarette smoking is a leading cause of preventable mortality . each day , at least 3800 adolescents in the usa try their first cigarette and 33% of teenagers that are daily smokers will die of a smoking - related condition .
tobacco dependence is also the single most prevalent substance abuse disorder . in 2000 , 18.1% of total deaths in the usa were attributed to tobacco use , making it one of the leading causes of death , followed by poor diet and physical inactivity , which together are responsible for 15.2% of totals deaths , and 3% of total deaths were alcohol - related .
some countries , such as england , have a decreasing tobacco - use trend , but even there , 27% of males and 24% of females reported smoking more than 20 cigarettes ( 1 pack ) a day .
smoking is a risk factor for many health - related diseases , including cardiovascular disease , and it also affects brain function .
it is a well - recognized risk factor for alzheimer disease ( ad ) ; research found that smokers are twice as likely to develop ad compared to those who never smoked .
adverse effects of smoking on cognition are also known , including a decrease in visual search speed .
smoking is related to preclinical changes in the brain , higher risk of cognitive decline , and increased risk of dementia [ 810 ] . even after the cessation of smoking , certain problems remain , such as impaired working memory .
these problems are probably caused by the toxins inhaled in tobacco smoke , including vinyl chloride ( a risk factor for brain cancer ) , hydrogen cyanide , and arsenic .
long - term , daily exposure to these toxins may result in altered vascular and neural processes , which probably result from tissue accumulation and/or assault .
additionally , these changes express themselves by changes in grey matter ( gm ) and white matter ( wm ) volume and brain density .
although gmv decreases linearly with age , global white matter does not decline with age ; however , local areas of relatively accelerated loss and preservation occur . as the world population ages , it is important to determine which brain changes are attributable to normal / healthy aging and which are caused by preventable behaviors such as smoking . a growing number of studies using the voxel - based morphometry technique have compared smokers to non - smokers in terms of the volume of white and grey matter [ 1519 ] .
( 2012 ) reported no differences in wm volume between smokers and non - smokers , whereas yu , zhao , and lu ( 2011 ) reported a regional wm volume increase .
as with gmv , some studies reported smokers have smaller gmv in the dorsolateral prefrontal cortex ( dlpfc ) , while others found a smaller volume in the anterior cingulated cortex ( acc ) and thalamus .
a recent meta - regression analysis showed that a higher number of smoking years was correlated with more gm atrophy in the right superior frontal gyrus , and more cigarettes smoked per day was correlated with more gm atrophy in the right superior frontal gyrus and acc , extending to the paracingulate gyrus .
the following databases were searched in march / april 2015 : medline , embase , and psycinfo . the following string search was used :  grey matter  and  voxel - based  and  smoking  and  cigarette  .
records were obtained when  grey matter  was found in the title of the article and the remaining terms were found in the abstract or in the title .
male and female sample . studies that measured differences in grey matter . studies comparing smokers with non - smokers . studies that used voxel - based morphometry .
articles that did not have full text or that could not be retrieved through our university libraries .
we evaluated the quality of included articles by use of a modified version of the effective public health practice project ( ephpp ) quality assessment tool for quantitative studies .
it is important to note that only 1 study   was conducted in europe and the remaining ones   were in the usa .
all studies used cross - sectional design and only 1 study   was not conducted in 2014 .
there were large differences in the sample sizes : brody ( 2004 ) only included 36 participants , whereas fritz ( 2014 ) had 974 .
none of the studies used power calculation ; therefore , the results need to be interpreted with caution . additionally , all of studies compared smokers to non - smokers , with some   adding further groups for comparison .
for example , franklin ( 2014 ) compared across sexes and hanlon ( 2014 ) compared the differences between young and long - term smokers .
three of the studies   had approximately the same number of smokers as non - smokers , but fritz ( 2014 ) had significantly more non - smokers and significant differences in demographics of the studied population .
all 4 studies used voxel - based morphometry ( vbm ) , which is a neuro - imaging analysis technique that investigates focal differences in brain anatomy [ 1719,24 ] .
brody ( 2004 ) also included hand - drawn regions of interest ( roi ) , which allows extraction of data for a specific structure .
all images were produced by a tesla siemens scanner , and all studies used statistical parametric mapping ( spm ) , which increases the validity of conclusions because the same methodology is applied in each study and the results can not be attributed to the technology or methodology used .
studies by fritz ( 2014 ) , franklin ( 2014 ) , and hanlon ( 2014 ) were scored as strong quality with moderate quality in terms of representativeness of the sample .
brody ( 2004 ) was graded as moderate quality after scoring weak quality in the population component of the questionnaire .
importantly , 3 studies   reported significant ( p<0.001 ) differences between smokers and non - smokers in gmv , and fritz ( 2014 ) also found a significance difference ( p<0.05 ) .
all studies corrected for family - wise error [ 1719,24 ] . decreased gmv in smokers compared to non - smokers was reported , but franklin ( 2014 ) and hanlon ( 2014 ) also noted increased gmv in some brain areas ( table 4 ) .
overall , it is clear that smoking causes decreased gmv , but variations in the specific region affected were found as well .
all 4 studies found decreased gmv in the ventrolateral prefrontal cortex of smokers [ 1719,24 ] , as well as loss of gmv in the dorsal - lateral prefrontal cortex .
two studies found gm loss in the cerebellum of smokers . the only study to find differences in gmv in the olfactory gyrus was by fritz ( 2014 ) .
hanlon ( 2014 ) found a decrease in gmv in the amygdala region in smokers .
a decrease of thalamic gmv in smokers was found by franklin ( 2014 ) and hanlon ( 2014 ) , who also reported differences in the parahippocampal gyrus region .
interestingly , hanlon ( 2014 ) also found decreased gmv in smokers , whereas franklin ( 2014 ) found greater gmv in the parahippocampus in smokers .
although contradictory results in specific areas were found , these may be attributed to the differences in samples studied .
future studies should consider differences between sexes and age groups as well as between smokers and non - smokers .
two studies compared female and male smokers to non - smokers and found certain sex - specific differences .
one found a decrease in smokers in both sexes in the ventromedial prefrontal cortex , while the other found reduced gmv in the thalamus and cerebellum in smokers of both sexes .
fritz ( 2014 ) found gmv loss in the olfactory gyrus in male smokers , and did not find any area of increased gmv , which is a unique finding .
franklin ( 2014 ) , on the other hand , found increased gmv in the bilateral hippocampus and the left putamen in male smokers .
hanlon ( 2014 ) reported decreased gmv in younger smokers compared with a matched control group of non - smokers . compared with a matched control group of non - smokers ,
long - term smokers had changes in the amygdala ( t=6.03 , cluster size=601 , p=0.002 ) and left thalamus ( t=5.75 , cluster size=234 , p<0.000 ) . decreased gmv in the amygdala was not reported by other investigators .
decreased gmv was found in long - term smokers in the insula , parahippocampus , and thalamus .
interestingly , when they compared long - term smokers with their non - smoking matched control group , they found decreased gmv in the same areas : the insula and parahippocampus . in this group comparison , they also found that smokers had decreased gmv in the left occipital cortex .
these results suggest either that nicotine rapidly affects brain regions or that there may be pre - existing abnormalities that lead to nicotine dependence in younger individuals .
lastly , we explored a possible correlation between gmv and age of onset of smoking , cigarettes per day , the length of time smoking , and the pack - years smoked .
hanlon ( 2014 ) reported a negative correlation in long - term smokers between number of pack - years and gmv in the medial prefrontal cortex .
brody ( 2004 ) reported similar correlations between gmv in the prefrontal cortex and pack - years .
fritz ( 2014 ) found that small clusters of reduced gmv in the middle occipital gyrus and anterior and middle cingulate cortex were correlated with number of pack - years ( r=0.192 , t=3 , 45 , p<.001 ) .
lastly , franklin ( 2014 ) reported a positive correlation between gmv in the left putamen and number of pack - years in males ( r=.38 , p=.018 ) .
overall , these studies reported similar results and all found lower gmv in certain brain areas in smokers compared to non - smokers .
two studies   also found brain areas where the gmv was actually higher in smokers than in non - smokers .
lastly , 2 studies   reported a negative correlation between pack - years and gmv .
only 1 study   found a positive correlation between number of pack - years and gmv .
these studies found that smokers have lower gmv in multiple cortical and sub - cortical regions compared with non - smokers .
regard , nicotine and cue - induced prefrontal activation might partially explain the atrophies observed via repeated stimulation during smoking , and this is thought to be associated with lower gmv .
a decrease in gmv in the dlpfc may be associated with cognitive deficits in smokers . in the abstinent state , smokers are not able to compensate higher task loads .
the prefrontal cortex also has a role in emotional processing ( e.g. , regulation ) .
personality - wise , smokers with lower gmv in the pfc are more likely to be impulsive and neurotic than their non - smoking counterparts . the mpfc and vpfc are associated with reward and development , as well as maintenance of addiction .
the insula also plays a role in dysfunction of emotional regulation , as well as a general role in nicotine addiction and craving .
mofc is correlated with inhibition of behavior ; this effect is enhanced in females , explaining why they find it harder to stop smoking .
importantly , 2 studies found lower gmv in the thalamus , which has the highest density of nicotine receptors of any brain region and is the prime target in long - term smoking . cigarette smoking also correlates with increased nicotine binding in the thalamus
. however , controversy exists in that fritz ( 2014 ) and brody ( 2004 ) did not report any areas of decreased gmv in the thalamus , suggesting a role of functional abnormalities in signalling .
the thalamus is associated with memory , attention , and planning , explaining why smokers tend to have worse results on cognitive tasks , including memory .
the severity of compulsivity was also positively correlated with increased gmv in the putamen . in 1 study , this increase was only found in males .
there were also differences found in the hippocampus and amygdala ; these areas also are linked with emotional and drug memories . however , hanlon ( 2014 ) found differences in the amygdala only when comparing young smokers with non - smokers .
interestingly , this difference was lost in long - term smokers . despite these inconsistencies ,
although all 4 studies used the same technique , certain differences may have arisen because the technique was not used at the same place and time . also , all 4 studies were cross - sectional , so we can not know if there were any pre - existing structural differences in the brains of subjects . in younger smokers , nicotine either affects neural tissue volume very quickly or there are pre - existing abnormalities that predispose some individuals to smoking .
lastly , smoking is highly prevalent in people with psychiatric disorders , and smoking can be a strong confounder in brain studies of these patients .
overall , smoking causes differences in gmv in various brain areas , and these differences help explain the cognitive impairment and emotional dysregulation in smokers compared with non - smokers .
there are considerable differences , not only between males and females , but also between younger and older smokers , and any therapeutic treatment must take this into account . to summarize , smoking decreases gmv in most brain areas , and this decrease is believed to be responsible for the cognitive impairment and difficulties with emotional regulation in smokers .
future studies should separate physical changes of the brain from those associated with cognition , which would be useful in determining a therapeutic strategy for treating the associated pathologies of tobacco smoking .
importantly , it can not be ignored that tobacco smoking may be a self - medicating phenomenon , which seeks to relieve a pre - existing pathology ; therefore , an individualized approach to treatment is advised .
 although cigarette smoking is a leading cause of preventable mortality , tobacco is consumed by approximately 22% of the adult population worldwide . 
 smoking is also a risk factor for cardiovascular disease , affects brain processing , and is a recognized risk factor for alzheimer disease ( ad ) . 
 tobacco toxins ( e.g. , nicotine at high levels ) inhaled in smoke may cause disorders resulting in preclinical brain changes . 
 researchers suggest that there are differences in brain volume between smokers and non - smokers . 
 this review examines these differences in brain grey matter volume ( gmv).in march / april 2015 , medline , embase , and psycinfo were searched using the terms :  grey matter  and  voxel - based  and  smoking  and  cigarette.the 4 studies analyzed found brain gmv decreases in smokers compared to non - smokers . 
 furthermore , sex - specific differences were found ; while the thalamus and cerebellum were affected in both sexes , decreased gmv in the olfactory gyrus was found only in male smokers . 
 age - group differences were also found , and these may suggest pre - existing abnormalities that lead to nicotine dependence in younger individuals . 
 only 1 study found a positive correlation between number of pack - years smoked and gmv.smoking decreases gmv in most brain areas . 
 this decrease may be responsible for the cognitive impairment and difficulties with emotional regulation found in smokers compared with non - smokers . 
Background
Data Determination and Sources
Results
Discussion
Conclusions