An epigenetic synopsis of parental substance use.

The rate of substance use is rising, especially among reproductive-age individuals. Emerging evidence suggests that paternal pre-conception and maternal prenatal substance use may alter offspring epigenetic regulation (changes to gene expression without modifying DNA) and outcomes later in life, including neurodevelopment and mental health. However, relatively little is known due to the complexities and limitations of existing studies, making causal interpretations challenging. This review examines the contributions and influence of parental substance use on the gametes and potential transmissibility to the offspring's epigenome as possible areas to target public health warnings and healthcare provider counseling of individuals or couples in the pre-conception and prenatal periods to ultimately mitigate short- and long-term offspring morbidity and mortality.

More people, especially those of reproductive age, are using substances, and there is growing evidence to suggest that parental substance use before and during pregnancy may adversely affect offspring and result in issues later in life, including mental health challenges. Such relationships have been demonstrated with nicotine, alcohol, cannabis, opioids and illegal drugs (e.g., heroin, cocaine, methamphetamines). Some of these adverse impacts on offspring can potentially be passed down in families even after parents have quit using the substance. Because more individuals are using drugs, especially during the COVID-19 pandemic, it is important that families learn more about the potential impact of substance use on their future offspring before they try to get pregnant.

Substance use and common contributors to morbidity: A genetics perspective.

Excessive substance use and substance use disorders (SUDs) are common, serious and relapsing medical conditions. They frequently co-occur with other diseases that are leading contributors to disability worldwide. While heavy substance use may potentiate the course of some of these illnesses, there is accumulating evidence suggesting common genetic architectures. In this narrative review, we focus on four heritable medical conditions - cardiometabolic disease, chronic pain, depression and COVID-19, which are commonly overlapping with, but not necessarily a direct consequence of, SUDs. We find persuasive evidence of underlying genetic liability that predisposes to both SUDs and chronic pain, depression, and COVID-19. For cardiometabolic disease, there is greater support for a potential causal influence of problematic substance use. Our review encourages de-stigmatization of SUDs and the assessment of substance use in clinical settings. We assert that identifying shared pathways of risk has high translational potential, allowing tailoring of treatments for multiple medical conditions. FUNDING: SSR acknowledges T29KT0526, T32IR5226 and DP1DA054394; RLK acknowledges AA028292; AA acknowledges DA054869 & K02DA032573. The funders had no role in the conceptualization or writing of the paper.

Putative COVID- 19 Induction of Reward Deficiency Syndrome (RDS) and Associated Behavioral Addictions with Potential Concomitant Dopamine Depletion: Is COVID-19 Social Distancing a Double Edged Sword?

BACKGROUND: The overwhelming fatalities of the global COVID-19 Pandemic will have daunting epigenetic sequala that can translate into an array of mental health issues, including panic, phobia, health anxiety, sleep disturbances to dissociative like symptoms including suicide. Method: We searched PUBMED for articles listed using the search terms "COVID 19 Pandemic", COVID19 and genes," "stress and COVID 19", Stress and Social distancing: Results: Long-term social distancing may be neurologically harmful, the consequence of epigenetic insults to the gene encoding the primary receptor for SARS-CoV2, and COVID 19. The gene is Angiotensin I Converting-Enzyme 2 (ACE2). According to the multi-experiment matrix (MEM), the gene exhibiting the most statistically significant co-expression link to ACE2 is Dopa Decarboxylase (DDC). DDC is a crucial enzyme that participates in the synthesis of both dopamine and serotonin. SARS-CoV2-induced downregulation of ACE2 expression might reduce dopamine and serotonin synthesis, causing hypodopaminergia. Discussion: Indeed, added to the known reduced dopamine function during periods of stress, including social distancing the consequence being both genetic and epigenetic vulnerability to all Reward Deficiency Syndrome (RDS) addictive behaviors. Stress seen in PTSD can generate downstream alterations in immune functions by reducing methylation levels of immune-related genes. Conclusion: Mitigation of these effects by identifying subjects at risk and promoting dopaminergic homeostasis to help regulate stress-relative hypodopaminergia, attenuate fears, and prevent subsequent unwanted drug and non-drug RDS type addictive behaviors seems prudent.