Sex Differences in Substance Use Disorders: A Neurobiological Perspective

Abstract

Clinical studies provide fundamental knowledge of substance use behaviors (substance of abuse, patterns of use, relapse rates). The combination of neuroimaging approaches reveal correlation between substance use disorder (SUD) and changes in neural structure, function, and neurotransmission. Here, we review these advances, placing special emphasis on sex specific findings from structural neuroimaging studies of those dependent on alcohol, nicotine, cannabis, psychostimulants, or opioids. Recent clinical studies in SUD analyzing sex differences reveal neurobiological changes that are differentially impacted in common reward processing regions such as the striatum, hippocampus, amygdala, insula, and corpus collosum. We reflect on the contribution of sex hormones, period of drug use and abstinence, and the potential impact of these factors on the interpretation of the reported findings. With the overall recognition that SUD impacts the brains of females and males differentially, it is of fundamental importance that future research is designed with sex as a variable of study in this field. Improved understanding of neurobiological changes in males and females in SUD will advance knowledge underlying sex-specific susceptibility and the neurobiological impact in these disorders. Together these findings will inform future treatments that are tailor designed for improved efficacy in females and males with SUD.

Influence of Age and Genetic Background on Ethanol Intake and Behavioral Response Following Ethanol Consumption and During Abstinence in a Model of Alcohol Abuse

“…Moreover, it should be emphasized the lack of testing in female rats in the present study. Indeed, it is well recognized that sex/gender may affect substance abuse in general ( Becker and Chartoff, 2019 ; Cornish and Prasad, 2021 ) and alcohol-induced outcomes, such as drinking pattern, sensitivity to ethanol, anxiety, and neuroinflammation ( Robinson et al, 2021 ). Therefore, further investigation will need to extend the results of the present study to female rats.…”

DeepBiomarker2: Prediction of alcohol and substance use disorder risk in post-traumatic stress disorder patients using electronic medical records and multiple social determinants of health

“…Other SDoH parameters such as low neighborhood social-economic index (nSES index), females, younger patients, black majority zip codes, low normalized difference vegetation, low aridity, zip codes with higher number of USA citizens, USA born patients, number of households with limited English speaking capacity, number of widowed partners who are males and patients belonging to zipcodes with higher income segregation all were found to have an association with PTSD and ASUD both in our study and in mental health literature [104][105][106][107][108][109][110][111][112][113][114][115][116][117][118] and thus should be taken into account when reforming the health care system to respond to the challenge of health disparities.…”

Zhx2 Is a Candidate Gene Underlying Oxymorphone Metabolite Brain Concentration Associated with State-Dependent Oxycodone Reward

“…This study highlights the importance of assessing pharmacokinetic measures in genetic analysis of drug-induced behaviors. It also highlights how Sex can dramatically alter brain metabolite concentration in a genotype-dependent manner, which is important given sex differences in substance use disorders (Cornish & Prasad, 2021) including opioid use disorder (Chartoff & McHugh, 2016). This study also highlights the limitations of relying solely on short read DNA sequencing to annotate genetic variants and the utility of including proteomics in genetic regulation of gene expression associated with complex traits.…”