Effects of persisting emotional impact from child abuse and norepinephrine transporter genetic variation on antidepressant efficacy in major depression: a pilot study

OBJECTIVE: Previous studies suggest child abuse and serotonergic polymorphism influence depression susceptibility and antidepressant efficacy. Polymorphisms of the norepinephrine transporter (NET) may also be involved. Research in the area is possibly clouded by under reporting of abuse in researcher trials. METHODS: Adults (n=51) with major depressive disorder has 8 weeks treatment with escitalopram or venlafaxine. Abuse history was obtained, the ongoing emotional impact of which was measured with the 15-item impact of event scale (IES-15). The 17-item Hamilton Depression Rating Scale (HDRS) was applied serially. Two NET polymorphisms (rs2242446 and rs5569) were assayed, blinded to HDRS ratings and abuse history. RESULTS: No subjects reporting abuse with high impact in adulthood (IES-15 ≥26, n=12) remitted; whereas 77% reporting low impact (IES-15 <26; n=26) remitted (p<0.001). Subjects reporting high impact abuse (n=12) had a 50-fold (95% confidence interval=4.85-514.6) greater odds of carrying rs2242446-TT genotype, but the small sample size leaves this finding vulnerable to type I error. CONCLUSIONS: The level of persisting impact of child abuse appears relevant to antidepressant efficacy, with susceptibility to such possibly being influence by NET rs2242446 polymorphism. Larger studies may be merited to expand on this pilot level finding given potential for biomarker utility

Assessing Neuropsychological Performance in a Migrant Farm Working Colonia in Baja California, Mexico: A Feasibility Study

Neuropsychological impairments (NPI) can lead to difficulties in daily functioning and ultimately contribute to poor health outcomes. However, evidence for the feasibility of NPI assessment in resource-limited settings using tests developed in high literacy/high education cultures is sparse. The main objectives were to: (1) determine the feasibility and appropriateness of conducting neuropsychological assessments among a migrant farm worker population in Baja California, Mexico and (2) preliminary describe neuropsychological test performance in this unique population. A neuropsychological test battery was administered to 21 presumably healthy adults (8 men, 13 women) during a two-day international health services and research collaboration. All but one neuropsychological test (i.e. figure learning) was feasible and appropriate to administer to the study population. Contrary to expectations, participants performed better on verbal rather than nonverbal neuropsychological tests. Results support inclusion of neuropsychological tests into future studies among migrant farm worker populations in Baja California, Mexico

Formative Assessment of ARM-U: A Modular Intervention for Decreasing Risk Behaviors Among HIV-Positive and HIV-Negative Methamphetamine-Using MSM

BACKGROUND: Methamphetamine is a major contributor to HIV transmission among men who have sex with men (MSM). Recent studies show that up to one-third of methamphetamine-using MSM (MUMSM) inject the drug. We developed a behavioral intervention for MUMSM to decrease unprotected anal intercourse and increase awareness of parenteral HIV transmission risk. This 6-session (3 in-person, 3 by telephone) modular intervention was designed to be tailored to participants' HIV (+/-) and injection drug user ([IDU] yes/no) status. We present results of formative research used to evaluate the content and to assess feasibility and acceptability of this individual-level HIV risk-reduction intervention. SETTING: HIV research clinic in a high MSM and methamphetamine prevalence neighborhood. PROJECT: Avoiding Risks from Methamphetamine-Use (ARM-U) is a brief toolbox intervention that allows counselors to select modules that suit a client's individual risk profile and intervention needs employing motivational interviewing and cognitive behavioral theory. We evaluated the format and content of the intervention through focus groups and pre-testing of the entire intervention using volunteers from the target population stratified into four groups (HIV+/IDU, HIV-/IDU, HIV+/non-IDU, HIV-/non-IDU). Four individuals in each stratum were recruited to undergo the intervention and complete a satisfaction survey at the end of each in-person session. RESULTS: In total, 25 MUMSM attended one of five focus groups. Participants thought all proposed intervention topics were important and could aid in reducing sexual risk behaviors among MUMSM. However, the neurocognitive effects of methamphetamine were reported to be a barrier to practicing safer sex, condom use negotiation or HIV status disclosure. Fifteen (94%) of 16 participants completed all 6 sessions and the satisfaction survey. On average, participants felt the intervention was useful for MUMSM, made them contemplate and move toward behavior change, and would recommend the program to their peers. LESSONS LEARNED: Based on our formative research, we revised the ARM-U intervention to emphasize pre-planning to avoid combining methamphetamine use and sex or develop strategies to avoid sex risk following methamphetamine use. We also increased emphasis on referrals for care and other requested services. Future efficacy trials are needed to evaluate the intervention's ability to reduce HIV-associated risk behaviors

Commercial pharmacogenetic-based decision-support tools in psychiatry

Despite a compendium of pharmacotherapies available for treating psychiatric illnesses, suboptimal response to these therapies is typical and thought to be in part a result of genetic variation. This notion has sparked a personalised psychiatry movement, which has in turn led to the development of several commercial pharmacogenetic-based decision support tools marketed to psychiatrists as an alternative to typical, trial-and-error, prescribing. However, there is considerable uncertainty about the validity and usefulness of these tools and whether there is sufficient evidence to support their adoption. In this Personal View, we provide an introduction to these tools and assess their potential usefulness in psychiatry practice. We conclude with clinical considerations and development strategies for improving future pharmacogenetic-based decision support tools for clinical use

Experience, Knowledge, and Perceptions of Pharmacogenomics among Pharmacists and Nurse Practitioners in Alberta Hospitals

Background: Despite evidence of clinical utility and the availability of prescription guidelines, pharmacogenomics (PGx) is not broadly used in institutional settings in Canada. To inform future implementation, this study aimed to identify healthcare provider knowledge, experience, and perceptions of PGx in Alberta, Canada. Methods: An online 44-item survey was distributed to pharmacists, nurse practitioners, and physicians employed or contracted with Alberta Health Services from January to May 2022. Questions included: demographics, professional history, PGx education and exposure, knowledge, and ability to use PGx, and attitudes towards, feasibility, clinical utility, education, and implementation. Results: Ninety-one pharmacists, 37 nurse practitioners, and 6 physicians completed the survey. Fifty-nine percent had 10 or more years of experience, and 71% practiced in urban settings. Only one-third had training in PGx, and one-quarter had used PGx. Most respondents (63%) had no knowledge of PGx resources, including the Pharmacogenomics Knowledge Base (75%), or the Clinical Pharmacogenetics Implementation Consortium guidelines (85%). While participants agreed that they understood genetic (75%) and PGx (63%) concepts, most disagreed with their ability regarding practical applications of PGx such as translating genotype to phenotype (74%) or counselling patients on results (66%). Participants agreed on the clinical utility of PGx in preventing adverse drug reactions (80%) and enhancing medication efficacy (77%), and identified oncology (62%), cardiovascular/stroke (60%), and psychiatry (56%) as therapeutic areas to consider implementation. At present, healthcare provider knowledge (87%), cost (81%), and limited guidelines/evidence (70%) are seen as the greatest barriers to implementation. Conclusion: Alberta healthcare providers have limited training, experience, or knowledge in PGx. However, most appear to have a positive outlook regarding clinical utility, especially within oncology, cardiology, and psychiatry. More effort is required to socialize the availability and quality of evidence and guidelines for the interpretation of PGx test results, address other knowledge gaps, and improve financial limitations