Smoking, race, ancestry and prospective abstinence

Background: Factors influencing cessation include biopsychosocial characteristics, treatments and responses to treatment. The first cessation trial designed to assess cessation disparities between African American and White cigarette smokers demonstrated that socioeconomic, treatment, psychosocial and smoking characteristics explained cessation disparities. Ongoing translational efforts in precision cessation treatment grounded in genetically informed biomarkers have identified cessation differences by genotype, metabolism, ancestry and treatment. Methods: In planned analyses, we evaluated six smoking-related measures, demographic and socioeconomic covariates, and prospective abstinence (7-day point prevalence at 12 weeks with bupropion, nicotine replacement and counseling treatments). We assessed concurrent and predictive validity in two covariate models differing by inclusion of Office of Management and Budget (OMB) race/ethnicity or genomic ancestry. Results: We studied Pharmacogenetic Study participants (N=456, mean age 49.5 years, 41.5% female, 7.4% African American, 9.4% Multiracial, 6.5% Other, and 6.7% Hispanic). Cigarettes per day (OR=0.95, P<.001), Fagerström score (OR=0.89, P≤.014), Time-To-First-Cigarette (OR=0.75, P≤.005) and predicted urinary nicotine metabolite ratio (OR=0.57, P≤.039) were associated with abstinence. OMB African American race (ORs from 0.31 and 0.35, p-values≤.007) and African genomic ancestry (ORs from 0.21 and 0.26, p-values≤.004) were associated in all abstinence models. Conclusions: Four smoking-related measures exhibited association with abstinence, including predicted nicotine metabolism based on a novel genomic model. African genomic ancestry was independently associated with reduced abstinence. Treatment research that includes social, psychological, treatment and biological factors is needed to reduce cessation disparities.

Pharmacogenetics and Forensic Toxicology: A New Step towards a Multidisciplinary Approach

Pharmacogenetics analyzes the individual behavior of DNA genes after the administration of a drug. Pharmacogenetic research has been implemented in recent years thanks to the improvement in genome sequencing techniques and molecular genetics. In addition to medical purposes, pharmacogenetics can constitute an important tool for clarifying the interpretation of toxicological data in post-mortem examinations, sometimes crucial for determining the cause and modality of death. The purpose of this systematic literature review is not only to raise awareness among the forensic community concerning pharmacogenetics, but also to provide a workflow for forensic toxicologists to follow in cases of unknown causes of death related to drug use/abuse. The scientific community is called on to work hard in order to supply evidence in forensic practice, demonstrating that this investigation could become an essential tool both in civil and forensic contexts. The following keywords were used for the search engine: (pharmacogenetics) AND (forensic toxicology); (pharmacogenetics) AND (post-mortem); (pharmacogenetics) AND (forensic science); and (pharmacogenetics) AND (autopsy). A total of 125 articles were collected. Of these, 29 articles were included in this systematic review. A total of 75% of the included studies were original articles (n = 21) and 25% were case reports (n = 7). A total of 78% (n = 22) of the studies involved deceased people for whom a complete autopsy was performed, while 22% (n = 6) involved people in good health who were given a drug with a subsequent pharmacogenetic study. The most studied drugs were opioids (codeine, morphine, and methadone), followed by antidepressants (tricyclic antidepressants and venlafaxine). Furthermore, all studies highlighted the importance of a pharmacogenetics study in drug-related deaths, especially in cases of non-overdose of drugs of abuse. This study highlights the importance of forensic pharmacogenetics, a field of toxicology still not fully understood, which is of great help in cases of sudden death, deaths from overdose, deaths after the administration of a drug, and also in cases of complaint of medical malpractice.

Preliminary Pharmacogenetic Study to Explore Putative Dopaminergic Mechanisms of Antidepressant Action

Background: There is sufficient evidence that interference of dopaminergic neurotransmission contributes to the therapeutic effects of antidepressants in unipolar and bipolar depression. Methods: Hamilton depression rating scale (HAMD 17) scores of 163 at least moderately ill patients with major depressive disorders were used to establish treatment response. HAMD 17 score status was measured before initiation, after two weeks, and after four weeks of treatment with various antidepressants. The possible association between response and genotype in a total of 14 variants of dopamine neurotransmission-related proteins was investigated. Results: DRD4 rs11246226 CA heterozygous patients were found with a greater improvement of HAMD 17 score when compared to homozygous C patients during 0–2 weeks and 0–4 weeks. Patients with MAOB rs1799836 heterozygous GA and homozygous A also demonstrated improved scores during 2–4 weeks and 0–4 weeks. Conclusions: The results are preliminary due to the limited population size and the small number of variants. Further research into the involvement of habenular dopamine D4 receptors in the antidepressant response is desirable.