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Aims and Objectives: Substance use‐targeted harm reduction (HR) has successfully expanded from public health into clinical settings. Hospital‐based providers are in positions to encounter, precipitate and/or mediate ethically fraught situations that can arise around clinical HR‐informed interventions. We examine why these situations occur and how they might be better addressed. Method: Literature focused on principles, ethics, and clinical implementation of HR are reviewed to identify core elements of this approach. Next, ethical vulnerabilities within those elements are identified and critiqued. A more productive discourse for acknowledging, voicing and addressing ethical dilemmas in HR is sought. Results: Public health orientation and humane concern for substance users, along with a strong anti‐stigmatization mission and occasional aversion to a rigid medical model and 'establishment' contributed to HR's successes but can also frame any dissent over its methods as being stigma‐fuelled. Practically distilled concepts from moral philosophy and the medical humanities can inform good faith discussions based on common‐ground concern for patients. Conclusion: HR's use in the general hospital and other clinical settings is a positive development, but one that brings with it new ethical demands. Broader knowledge of the principles of HR, of the application of those principles to the hospital setting, and of common‐ground concepts from outside of HR could help facilitate productive ethical engagement around substance‐using patients. [ABSTRACT FROM AUTHOR]

Dopamine neurons in the ventral tegmental area calculate reward prediction error by subtracting input from neighbouring GABA neurons. Dopamine and GABA neurons assess rewards Associative learning requires comparison between an actual reward against the expected reward, a process that is thought to depend on dopamine neurons in the ventral tegmental area. How this 'prediction error' is calculated has been the subject of much debate. Naoshige Uchida and colleagues used optogenetics and extracellular recordings in behaving mice to show that the calculation involves subtraction rather than division, and that GABA neurons in the ventral tegmental area (which encode reward expectation) provide dopamine neurons with a signal that prompts prediction-error calculation. Dopamine neurons are thought to facilitate learning by comparing actual and expected reward.sup.1,2. Despite two decades of investigation, little is known about how this comparison is made. To determine how dopamine neurons calculate prediction error, we combined optogenetic manipulations with extracellular recordings in the ventral tegmental area while mice engaged in classical conditioning. Here we demonstrate, by manipulating the temporal expectation of reward, that dopamine neurons perform subtraction, a computation that is ideal for reinforcement learning but rarely observed in the brain. Furthermore, selectively exciting and inhibiting neighbouring GABA ([gamma]-aminobutyric acid) neurons in the ventral tegmental area reveals that these neurons are a source of subtraction: they inhibit dopamine neurons when reward is expected, causally contributing to prediction-error calculations. Finally, bilaterally stimulating ventral tegmental area GABA neurons dramatically reduces anticipatory licking to conditioned odours, consistent with an important role for these neurons in reinforcement learning. Together, our results uncover the arithmetic and local circuitry underlying dopamine prediction errors., Author(s): Neir Eshel [sup.1] , Michael Bukwich [sup.1] , Vinod Rao [sup.1] , Vivian Hemmelder [sup.1] , Ju Tian [sup.1] , Naoshige Uchida [sup.1] Author Affiliations: (1) Department of Molecular [...]

Background and Objectives: Recent work highlights an increase in the overlap of autism spectrum disorder (ASD) and substance use disorder (SUD). Little is known about the presence of ASD symptoms in SUD‐treatment‐seeking populations. Methods: The informant‐rated Social Responsiveness Scale‐2 (SRS‐2) was completed at intake to an outpatient SUD clinic for youth aged 16–26 (N = 69). Comparisons were made between those with elevated SRS‐2 scores on demographic, psychiatric, and substance use variables. Results: Parents of sixty‐nine patients with SUD completed the SRS‐2. Fourteen (20%) (average age 18.7 ± 2.5) had elevated SRS‐2 Total T‐scores (≥66) and 55 (average age 18.1 ± 2.8) had non‐clinical SRS‐2 Total T‐scores. There were few differences between groups; however, those with elevated SRS‐2 Total T‐scores were more likely to have a stimulant use disorder (odds ratio [OR] = 7.59, 95% confidence interval [CI] = 0.77, 101.88; p = 0.05) or an opioid use disorder (OR = 5.02, 95% CI = 0.59, 43.27; p = 0.08) than patients with normal SRS‐2 Total T‐scores as well as alcohol use in the week prior to intake. Discussion and Conclusions: A significant proportion of treatment‐seeking SUD outpatients suffer from clinically elevated autistic traits. These findings highlight the importance of assessing for autistic traits in SUD treatment settings yet additional research is needed to determine if these findings are specific to the presence of ASD or secondary to sequelae of specific SUD presentations. Scientific Significance: This study is, to our knowledge, the first to have examined the prevalence, morbidity, or clinical characteristics, associated with ASD symptoms in a SUD‐specific population. [ABSTRACT FROM AUTHOR]

Author(s): Neir Eshel; Michael Bukwich; Vinod Rao; Vivian Hemmelder; Ju Tian; Naoshige Uchida Nature 525, 243-246 (2015); doi:10.1038/nature14855 In this Letter, the x -axis labels of Fig. 3b and d [...]

Subdural hemorrhage in association with D2-hydroxyglutaric aciduria (D2-HGA) Type II has only been described once in the medical literature in a 15-month-old child (1). Our case report describes a much younger 3-month-old infant previously diagnosed with D2-HGA Type II, who presented clinically with seizures and identified to have bilateral subdural hematomas concerning for possible physical abuse. This case report discusses the genetic diagnosis of D2-HGA and interpretation of subdural hemorrhage in context of evaluating possible physical abuse concerns. When an underlying medical condition is known to be present and a child presents with findings that may be concerning for physical abuse, it is critical to consider the possibility that the underlying medical condition may contribute to or may be the cause of the findings. [ABSTRACT FROM AUTHOR]