Hayley H. A. Thorpe

Bio: Hayley H. A. Thorpe is an academic researcher from University of Guelph. The author has contributed to research in topics: Medicine & Impulsivity. The author has an hindex of 3, co-authored 8 publications receiving 46 citations.

Adolescent Substance Use and the Brain: Behavioral, Cognitive and Neuroimaging Correlates

Abstract: Adolescence is an important ontogenetic period that is characterized by behaviors such as enhanced novelty-seeking, impulsivity, and reward preference, which can give rise to an increased risk for substance use. While substance use rates in adolescence are generally on a decline, the current rates combined with emerging trends, such as increases in e-cigarette use, remain a significant public health concern. In this review, we focus on the neurobiological divergences associated with adolescent substance use, derived from a cross-sectional, retrospective, and longitudinal studies, and highlight how the use of these substances during adolescence may relate to behavioral and neuroimaging-based outcomes. Identifying and understanding the associations between adolescent substance use and changes in cognition, mental health, and future substance use risk may assist our understanding of the consequences of drug exposure during this critical window.

Intermittent cold exposure improves glucose homeostasis despite exacerbating diet-induced obesity in mice housed at thermoneutrality.

Abstract: Key points Ambient cold exposure is often regarded as a promising anti-obesity treatment in mice. However, most preclinical studies aimed at treating obesity via cold-induced thermogenesis have been confounded by sub-thermoneutral housing temperatures. Therefore, the ability of ambient cold to combat diet-induced obesity in mice housed under humanized thermoneutral conditions is currently unknown. Moreover, mammals such as mice are rarely exposed to chronic ambient cold without reprieve, yet mice are often subjected to experimental conditions of chronic rather than intermittent cold exposure (ICE), despite ICE being more physiologically relevant. Having addressed these issues herein, we provide novel evidence that thermoneutral housing uncouples the effects of ICE on glucose and energy homeostasis suggesting that ICE, despite improving glucose tolerance, is not an effective obesity treatment when mice are housed under humanized thermoneutral conditions. Abstract This study examined whether a physiologically relevant model of ambient cold exposure, intermittent cold exposure (ICE), could ameliorate the metabolic impairments of diet-induced obesity in male and female mice housed under humanized thermoneutral conditions. Male and female C57BL/6J mice housed at thermoneutrality (29 °C) were fed a low-fat diet (LFD) or high-fat diet (HFD) for 6 weeks before being weight matched into groups that remained unperturbed (CTRL) or underwent ICE for four weeks (4 °C for 60 min/day; 5 days/week) while being maintained on their respective diets. ICE induced rapid and persistent hyperphagia exacerbating rather than attenuating HFD-induced obesity over time. These ICE-induced increases in adiposity were found to be energy intake dependent via pair-feeding. Despite exacerbating HFD-induced obesity, ICE improved glucose tolerance, independent of diet, in a sex-specific manner. The effects of ICE on glucose tolerance were not attributed to improvements in whole-body insulin tolerance, tissue specific insulin action, nor to differences in markers of hepatic insulin clearance or pancreatic beta cell proliferation. Instead, ICE increased serum concentrations of insulin and C-peptide in response to glucose, suggesting that ICE may improve glucose tolerance by potentiating pancreatic glucose-stimulated insulin secretion. These data suggest that ICE, despite improving glucose tolerance, is not an effective obesity treatment in mice housed under humanized conditions. Greg L. McKie is a third year PhD Candidate in the Human Health and Nutritional Sciences Department at the University of Guelph, where he works under the supervision of Dr. David C. Wright. Greg's dissertation focuses on the effects of environmental perturbations, such as aerobic exercise and ambient cold exposure, on adipose tissue metabolism, specifically as it relates to promoting non-shivering thermogenesis under translationally relevant thermoneutral conditions. This article is a follow up to Greg's first PhD study, also published in The Journal of Physiology, which demonstrated that housing temperature affects the acute and chronic metabolic adaptations to aerobic exercise in mice. This article is protected by copyright. All rights reserved.

High genes: Genetic underpinnings of cannabis use phenotypes.

Abstract: Cannabis is one of the most widely used substances across the globe and its use has a substantial heritable component. However, the heritability of cannabis use varies according to substance use phenotype, suggesting that a unique profile of gene variants may contribute to the different stages of use, such as age of use onset, lifetime use, cannabis use disorder, and withdrawal and craving during abstinence. Herein, we review a subset of genes identified by candidate gene, family-based linkage, and genome-wide association studies related to these cannabis use phenotypes. We also describe their relationships with other substances, and their functions at the neurobiological, cognitive, and behavioral levels to hypothesize the role of these genes in cannabis use risk. Delineating genetic risk factors in the various stages of cannabis use will provide insight into the biological mechanisms related to cannabis use and highlight points of intervention prior to and following the development of dependence, as well as identify targets to aid drug development for treating problematic cannabis use.

tobacco use before, at and after first episode psychosis: A systematic meta-analysis : c66

Abstract: OBJECTIVE Patients with first-episode psychosis have a high prevalence of tobacco use. We aimed to examine the prevalence and course of tobacco use during early psychosis using meta-analysis. DATA SOURCES Systematic search of MEDLINE (1948-2011), Embase (1947-2011), CINAHL (1984-2011), PsycINFO (1967-2011), and ISI Web of Science (1900-2011) using the search terms [psychosis OR schizophrenia] AND [tobacco OR smoking OR nicotine]. STUDY SELECTION We located 10 studies reporting the age at initiation of daily tobacco use and the age at onset of psychosis, 31 studies reporting prevalence of tobacco use in patients with first-episode psychosis, 10 studies comparing smoking to age-/gender-matched controls, and 7 studies reporting prevalence of tobacco use at intervals after treatment. DATA EXTRACTION The following data were extracted: age at initiation of daily tobacco use and at onset of psychosis, the proportion of patients with first-episode psychosis who used tobacco, the proportion of the general population who used tobacco, and the proportion of patients with psychosis who used tobacco at various intervals after initiation of antipsychotic treatment. RESULTS The pooled estimate for the interval between initiation of tobacco use and the onset of psychosis was 5.3 years (standardized mean difference = 0.85). The estimated prevalence of tobacco users in first episode of psychosis is 58.9% (95% CI, 54.3%-63.4%). There is a strong association between first-episode psychosis and tobacco use (OR = 6.04; 95% CI, 3.03-12.02) compared with healthy controls. The prevalence of tobacco use at intervals between 6 and 120 months after treatment remained unchanged (OR = 0.996; 95% CI, 0.907-1.094). CONCLUSIONS Patients with first-episode psychosis tend to have smoked for some years prior to the onset of psychosis, have high prevalence of tobacco use at the time of presenting for treatment, and are much more likely to smoke than aged-matched controls. Their apparent difficulty in quitting has implications for tobacco cessation programs and efforts to reduce cardiovascular disease among people with mental illness.

Unique, long-term effects of nicotine on adolescent brain.

Abstract: Adolescence is a time of major plasticity of brain systems that regulate motivated behavior and cognition, and is also the age of peak onset of nicotine use. Although there has been a decline in teen use of cigarettes in recent years, there has been a huge increase in nicotine vaping. It is therefore critically important to understand the impact of nicotine on this critical phase of brain development. Animal studies have shown that nicotine has unique effects on adolescent brain. The goal of this review is therefore to systematically evaluate age- and sex-differences in the effects of nicotine on brain and behavior. Both acute and chronic effects of nicotine on brain biochemistry and behavior, particularly drug reward, aversion, cognition and emotion, are evaluated. Gaps in our current knowledge that need to be addressed are also highlighted. This review compares and integrates human and animals findings. Although there can be no experimental studies in humans to confirm similar behavioral effects of teen nicotine exposure, an emerging observational literature suggests similarities across species. Given the substantial evidence for long-term negative impact of adolescent nicotine exposure on brain and behavior, further longitudinal assessment of health outcomes in teen and young adult e-cigarette users is warranted.

Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci

Abstract: Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10−8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10−8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10−3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.

Adolescent Substance Use and the Brain: Behavioral, Cognitive and Neuroimaging Correlates

Abstract: Adolescence is an important ontogenetic period that is characterized by behaviors such as enhanced novelty-seeking, impulsivity, and reward preference, which can give rise to an increased risk for substance use. While substance use rates in adolescence are generally on a decline, the current rates combined with emerging trends, such as increases in e-cigarette use, remain a significant public health concern. In this review, we focus on the neurobiological divergences associated with adolescent substance use, derived from a cross-sectional, retrospective, and longitudinal studies, and highlight how the use of these substances during adolescence may relate to behavioral and neuroimaging-based outcomes. Identifying and understanding the associations between adolescent substance use and changes in cognition, mental health, and future substance use risk may assist our understanding of the consequences of drug exposure during this critical window.

Medical Cannabis in Children.

Abstract: The use of medical cannabis in children is rapidly growing. While robust evidence currently exists only for pure cannabidiol (CBD) to treat specific types of refractory epilepsy, in most cases, artisanal strains of CBD-rich medical cannabis are being used to treat children with various types of refractory epilepsy or irritability associated with autism spectrum disorder (ASD). Other common pediatric disorders that are being considered for cannabis treatment are Tourette syndrome and spasticity. As recreational cannabis use during youth is associated with serious adverse events and medical cannabis use is believed to have a relatively high placebo effect, decisions to use medical cannabis during childhood and adolescence should be made with caution and based on evidence. This review summarizes the current evidence for safety, tolerability, and efficacy of medical cannabis in children with epilepsy and in children with ASD. The main risks associated with use of Δ9-tetrahydrocannabinol (THC) and CBD in the pediatric population are described, as well as the debate regarding the use of whole-plant extract to retain a possible "entourage effect" as opposed to pure cannabinoids that are more standardized and reproducible.