Peripheral immune factors are elevated in women with current or recent alcohol dependence and associated with altered mood and memory

Abstract

Background The adverse effects of alcohol on brain function result, in part, from inflammatory processes. The sex-specific neuropsychiatric consequences and inflammatory status of active alcohol dependence and early remission from dependence have not been investigated. Methods Neuropsychiatric symptoms, inflammatory factors, and liver enzymes were compared in a prospective cohort study of adults with (n = 51) or without (n = 31) a current or recent history of alcohol dependence. Results Neuropsychiatric profiles were similar in adults with current or recent alcohol dependence regardless of sex. In male and female participants measures of depression (female p < 0.05, male p < 0.001), anxiety (female p < 0.001, male p < 0.001), and memory complaints (female p < 0.001, male p < 0.05) were elevated, relative to non-dependent controls. Significant sex × alcohol dependence history interactions were observed for plasma levels of tissue inhibitor of metalloproteinase 1 (TIMP-1) and brain derived neurotrophic factor (BDNF), with women in the alcohol dependent group exhibiting increased levels of both analytes (p < 0.05) relative to controls. Positive correlations between TIMP-1 levels and measures of depression (r2 = 0.35, p < 0.01), anxiety (r2 = 0.24, p < 0.05) and memory complaints (r2 = 0.44, p < 0.01) were found in female, but not male, participants. Conclusions Though neuropsychiatric profiles were similar for men and women with current or recent alcohol dependence, plasma factors associated with increases in depression, anxiety, and memory impairment differed and support the need to tailor treatments based on sex.

The relationship between interleukin-6 and functional connectivity in methamphetamine users

“…Lastly, there were only four women with a history of MA dependence in this study, thereby limiting our power to examine the interactive effects of sex. A growing literature, however, highlights sex differences in drug use behavior (52), and we recently reported that in alcohol use disorder, there are sex differences in the effects of alcohol use history on peripheral immune-related factors [i.e., tissue inhibitor of metalloproteinase 1 (TIMP-1) and brain derived neurotrophic factor (BDNF)] (53). Future studies with more women with MA use disorder are warranted to determine the mechanisms by which inflammation may interact with sex.…”

Neuroinflammation in addiction: A review of neuroimaging studies and potential immunotherapies

“…Repeated alcohol-mediated neurotoxic insults may compromise the innate immune response or result in complex compensatory and neuroadaptive processes that limit neuroinflammation. Individual differences such as age and sex, however, are important factors in the neuroimmune response (Pascual et al, 2017;Wilhelm et al, 2017), and more studies are needed to better identify the mechanisms by which alcohol use affects immune signaling.…”

The Interplay of Inflammatory Processes and Cognition in Alcohol Use Disorders—A Systematic Review

“…Wilhelm et al (31) investigated plasma levels of the pro-inflammatory compound tissue inhibitor of metalloproteinases (TIMP-1) and found them to be associated to self-reported memory complaints in a small sample of female (but not male) alcohol-dependent patients.…”