These studies make it difficult to ascertain whether alcohol or nicotine use/dependence account for previous findings, as their individual contributions to gray matter structure or brain activity were not examined. Thus, it is critical to investigate the unique contributions of alcohol and nicotine use to brain morphometry in heavy drinking smokers. We hypothesized that there would be gray matter reductions in areas such as the ACC, dorsal striatum, and insula. Multiple regression analyses revealed that ADS scores significantly predicted gray matter density in the hypothalamus and right superior frontal gyrus and thus, the results differed from our initial hypotheses. Contrary to our expectations, there were no significant relationships with respect to quantity of alcohol use or nicotine dependence and quantity of cigarette use variables. The hypothalamus is part of the hypothalamic-pituitary-adrenal axis, which has been consistently shown to be dysregulated in individuals with AUD . HPA-axis dysregulation in alcohol-dependent individuals is marked by elevated blood glucocorticoid levels , which is associated with impairments in various brain regions, such as the prefrontal cortex, hippocampus, and the mesolimbic reward pathway . Impairments in these regions can lead to utilization of habit-based forms of learning or memory over goaldirected forms and profound cognitive memory impairments . The current findings indicating ADS was negatively related to hypothalamic volume in heavy drinking smokers may suggest alterations in hypothalamic gray matter density that could be associated with changes in HPA-axis functioning and related cognitive impairments.
Studies that integrate measures of gray matter density,hydroponic rack cognitive functioning and markers of HPA-axis functioning in heavy drinking smokers are needed to clarify these associations. Moreover, several studies have linked hypothalamic gray matter degradation to the presence of Korsakoff Syndrome . These findings suggest that the development of Korsakoff Syndrome may exist on a spectrum, with hypothalamic gray matter atrophy acting as a relevant biomarker. Thus, our findings support the notion that alcohol dependence severity is related to gray matter degradation observed in the progression of uncomplicated alcoholism to Korsakoff syndrome. However, in a recent study of almost 3,000 Dutch nationals, it was demonstrated that alcohol use was associated with dysregulation in the HPA-axis system while alcohol dependence status was not . Given these contrasting findings from our study, it is necessary to further explore the respective contributions of alcohol use and dependence to the dysregulation of the HPA-axis system. The finding that higher ADS scores were negatively related to gray matter density in the superior frontal gyrus is supported by numerous previous studies indicating lower frontal gray matter density in alcohol users . In a review paper discussing the construct of impulsivity, areas of the PFC, such as the ventromedial and dorsolateral PFC, were posited to be involved in the neural circuitry of delay-related decision making and inhibitory control . Broadly speaking, it is possible that gray matter degradation in the frontal cortex is related to behavioral inhibition and decision making deficits in alcohol dependence , but further research is needed to shed light on how specific features of impulsivity relate to the gray matter atrophy observed in AUD.Various explanations can be offered as to why the results for nicotine dependence severity were non-significant.
The FTND has fewer items than the ADS, so it is possible that lower variance of FTND scores made it difficult to detect relationships with gray matter density. It is also possible that nicotine dependence severity is not related to gray matter structure in the brain to the same extent as alcohol dependence severity. While several regions, such as the ACC, left dorsal striatum/insula, right dorsal striatum/insula, and the posterior cingulate cortex were identified as exhibiting gray matter atrophy in a meta-analysis of alcohol dependent individuals , a meta-analysis of chronic cigarette smokers only found the left ACC to show gray matter atrophy across several studies . The discrepancy may suggest differences between the two substances with respect to biological manifestations in the brain. However, previous studies found that smoking alcohol dependent individuals had significantly decreased cortical thickness in the insula and ACC when compared to nonsmoking alcohol dependent individuals . Additionally, heavy drinking smokers were found to have significantly smaller temporal lobe and total gray matter volumes when compared to non-smoking heavy drinkers . Dissimilar to those studies, quantity of nicotine use or dependence severity were not found to significantly contribute to gray matter density in the current study. Given that Durazzo, Mon, Gazdzinski, and Meyerhoff included a sample with an average FTND score of 5.4 and participants who smoked an average of 20 cigarettes per day, while the present sample had an average FTND score of 3.69 and participants smoked an average of 14.56 cigarettes per day, it is possible that differences in nicotine dependence severity and quantity of use between the current and previous studies explain the discrepant findings. Previous research has found significant gray matter reduction in recovering alcohol users immediately before undergoing detoxification .
This effect is ameliorated in abstaining light drinkers and abstaining recovering alcoholics versus relapsing recovering alcoholics . These findings support the notion that gray matter degradation effects could be attributable to the length of time between the last day an individual consumed alcohol and when he/she was scanned. The significant positive correlation between days to last drinking day and gray matter density in the left postcentral gyrus is consistent with the hypothesis that alcohol may cause dehydration and thus, volumetric reductions in the brain that are, in turn, ameliorated with short-term cessation of alcohol use. However, given that days to last drinking day was not related to gray matter density in the regions related to alcohol dependence severity, it is unlikely that recent alcohol use affected the current results. While our findings demonstrate the unique contribution of alcohol dependence severity to gray matter density in heavy drinking smokers, there are various limitations that should be noted. First, there was no matched control group to the comorbid users in this study. Although the multiple regression approach permits the investigation of specific contributions of alcohol and nicotine dependence and quantity of use to gray matter density, a control group would help ascertain whether the regions identified as significantly relating to alcohol dependence severity also differ in gray matter density from healthy controls. Second, the dependence severity and quantity of use measures did not encompass the exact same time frame, which may have resulted in relationships detected for dependence severity and gray matter density,vertical growing systems but not quantity of use and gray matter density. However, assessing dependence severity over the past 12 months could have reflected severity over the past 30 days prior to study participation, while average DPDD or CPD in the past 30 days could have also been comparable to average DPDD or CPD over the past year. Given that the sample was comprised of non-treatment seeking participants, it is plausible to hypothesize that past month alcohol and nicotine consumption closely reflect past year consumption of these substances in the current sample. Nevertheless, as patterns of alcohol or nicotine use may vary over a longer time frame, variables that capture quantity of use or frequency of use over a longer period of time would be preferred in future studies. Lastly, given that the average FTND scores of the current participants reflected low-to-moderate nicotine dependence severity, alcohol users with more severe nicotine dependence may be required to detect effects of nicotine use on brain structure. In conclusion, we examined the relationship between gray matter density and quantity of use/dependence severity for both alcohol and nicotine in 39 heavy drinking smokers using VBM. The multiple regression analysis revealed a significant negative relationship between ADS scores and gray matter density in two brains regions, such that higher ADS scores correlated with lower gray matter density in the hypothalamus and right superior frontal gyrus, after controlling for nicotine dependence severity, age, gender, and ICV. The current results may help clarify the contribution of alcohol and nicotine use to gray matter density in heavy drinking smokers, which could aid in understanding the neurocognitive consequences of co-morbid substance use in heavy drinking smokers.
HIV infection is a global pandemic and the population is growing due to successful treatment with highly active antiretroviral therapy. Although rates of HIV have been reduced in the United States among most groups as a result of successful public health efforts , sexual risk behavior and subsequent acquisition and/or spread of HIV and other sexually transmitted infections are still of concern among men who have sex with men as well as drug using populations. Thus, it is evident that, despite research and efforts to understand and curb sexual risk behavior within these vulnerable populations, additional work employing novel approaches are needed. Sexual risk behaviors can be viewed as a composite of numerous behaviors that collectively make-up a complex behavioral phenotype. As with most complex phenotypes, sexual risk behavior is heterogeneous and several factors contribute to the variance that can be observed from one individual to another. To date, a majority of work examining risk factors for sexual risk behavior phenotypes have primarily focused on psychosocial factors and/or other complex/heterogeneous behavioral phenotypes such as substance use behaviors as indicators for current or future sexual risk behavior. Ultimately these indicators, upon sufficient replication, become candidates for public health interventions that aim to prevent and reduce sexual risk behaviors. However, the trouble with many of these candidates is that they are too proximal to sexual risk behaviors and often cooccur, making it difficult to disentangle temporal precedence and ultimately limit prevention efforts. One relatively novel approach is to examine intermediate phenotypes or endophenotypes such as neurocognitive factors as well as biological factors. These factors are more distal to the onset of sexual risk behavior and thus are potentially more advantageous candidates for identifying vulnerable individuals and informing prevention efforts for sexual risk behavior. Studies in literature examining neurocognitive and biological factors as indicators for sexual risk behaviors are limited. In fact, only two studies to date have examined neurocognitive factors and none to our knowledge have examined biological factors as potential indicators. Although this paucity of research is surprising given previous work linking both neurocognitive and genetic indicators to other health related behaviors, research has established the dopminergic system as a common link between neurocognitive functioning and sexual behavior. The dopminergic system has been shown to be involved in sexual arousal, motivation and the subsequent rewarding effect of sexual behavior . Furthermore, DA in the human brain, specifically in the prefrontal cortex , has been shown to be necessary for proper cognitive functioning to occur and high or low levels of DA in this brain region are known to contribute to individual cognitive differences in humans. The PFC is of particular importance when examining risk behavior in that executive functions such as decision-making, planning, self-monitoring as well as behavior initiation, organization, and inhibition are largely dependent on PFC integrity. Impairment in executive functioning may result in difficulties in assessing relationships between a person’s current behavior and future outcomes; thereby resulting in choices and/or responses on the premise of immediate rewards versus long term consequences and an ultimate potential increase in the likelihood for participation in sexual risk behaviors. Thus, mechanisms responsible for maintaining a dopamine balance within the brain and in particular the PFC would appear to be good biological candidates for further exploration of an association between executive dysfunction and sexual risk behavior. One such candidate is catechol-O-methyltransferease which is a mammalian enzyme involved in the metabolic degradation of released dopamine, particularly in the PFC. The Val allele of the COMT Val158Met polymorphism is 40% more enzymatically active than the Met allele. Thus, carriers of the Met allele metabolize dopamine at a less efficient rate, resulting in higher levels of dopamine in the synapse and ultimately an escalation in dopamine receptor activation. This differentiation of dopamine receptor activity dependent on COMT genotype has led to several investigations into the relationship between COMT and executive dysfunction in which the Val allele has been putatively linked to poor performance on executive functioning tasks. However, to our knowledge no work has examined the relationship between COMT and sexual risk behavior; albeit studies of similar behaviors such as novelty seeking, reward dependence, as well as affective arousal and regulation have demonstrated significant relationships.