Canada's THC unit: Applications for the legal cannabis market.

The legalization of cannabis in Canada has accelerated the need for a standardized approach to measuring and communicating the amount of delta-9-tetrahydrocannabinol (THC) in cannabis products. This article offers an overview of the considerations associated with establishing and implementing a standard THC unit in the Canadian context. The article begins by discussing the applications of a standard THC unit, emphasizing its potential use in product labelling, consumer education, and product reporting and surveillance. The article then examines key considerations for identifying what a Canadian THC unit should be set at, specifically within the context of a country with a regulated commercial cannabis market. This is followed by a discussion of additional considerations related to the adoption of a Canadian THC unit, including its use across various product formats and modes of administration. A significant focus of this article is on prioritizing public health and safety and informed decision-making among adult consumers as the legal cannabis market evolves. Collaboration among various stakeholders, such as government agencies, industry, and public health professionals, is highlighted as crucial for a successful transition to the use of Canada's THC unit.

Prevalence and factors associated with suicidal ideation, cannabis, and alcohol use during the COVID-19 pandemic in Saskatchewan: findings from a joint-effect modeling.

BACKGROUND: Generally, pandemics such as COVID-19 take an enormous toll on people's lives. As the pandemic now turns to an endemic state, growing attention has been paid to the multiple adverse mental health and behavioral issues, such as suicidal ideation and substance use. However, the interplay of suicidality and substance misuse during the pandemic has been limited. We aimed to investigate the prevalence of co-occurrence of suicide ideation, alcohol and cannabis misuse, and the factors that are associated with these co-occurrences in the province of Saskatchewan during the COVID-19 pandemic. METHODS: We performed a multivariable trivariate probit regression on a sample of 666 Saskatchewan adolescents and adults (16 years or older), drawn from the cycle 10 data collection (March 2022) of the Mental Health Commission of Canada, and Canadian Centre on Substance Use and Addiction (MHCC-CCSA) dataset. RESULTS: The prevalence of suicidal ideation was higher among respondents who reported both problematic cannabis and alcohol use (25.8%) than single users of alcohol (23.2%) and cannabis (18.7%). Younger respondents (16-34 years) and those who reported recent changes in other substance use were independent factors that were associated with the common experience of suicide ideation, problematic cannabis, and alcohol use. Having a diagnosis of mental health disorders either before or during the pandemic, and the perceived inability to bounce back after the pandemic (low resilience) are strong correlates of suicidal ideation. Those who lived alone, between 35 and 55 years of age were more likely to report problematic alcohol use. Those who reported changes in alternative activities, who reported pandemic stress, and declared a LGBTQIA2S + identity had higher probability of problematic cannabis use. CONCLUSIONS: As the pandemic persists, improving access to suicide and substance use interventions for the vulnerable groups identified in this study may be impactful.

Proximity to Legal Cannabis Stores in Canada and Use of Cannabis Sources in the First Three Years of Legalization, 2019-2021.

OBJECTIVE: The accessibility of legal cannabis in Canada may influence how consumers source their cannabis. The aims of this study were to examine (a) the distance between respondents' homes and legal retail stores, (b) the cannabis sources used in the past 12 months, and (c) the association between cannabis sources used and distance to legal retail stores. METHOD: Data were analyzed from Canadian respondents participating in the International Cannabis Policy Study from 2019 to 2021. Respondents were 15,311 past-12-month cannabis consumers of legal age to purchase cannabis. Weighted logistic regression models examined cannabis sources used and their association with the Euclidean distance to the nearest legal store, province of residence, and year (n = 12,928). RESULTS: Respondents lived closer to a legal retail store in 2021 (1.5 km) versus 2019 (6.8 km) as the number of retail stores increased. Respondents in 2020 and 2021 had higher odds of obtaining cannabis from legal sources (e.g., legal stores: 47.9% and 60.0% vs. 38.6%, respectively, adjusted odds ratio [AOR] range: 1.41-2.42) and lower odds of obtaining cannabis from illegal sources versus 2019 (e.g., dealers: 22.6% and 19.9% vs. 29.1%, respectively, AOR range: 0.65-0.54). Respondents who lived closest to legal stores had higher odds of sourcing from legal stores and lower odds of sourcing from legal websites or growing their own cannabis. CONCLUSIONS: Legal cannabis stores are increasingly accessible to people living in Canada 3 years after legalization. Household proximity to a legal cannabis store was associated with sourcing cannabis from legal retail stores, but only among those who live very close (<3 km). Findings suggest that proximity to legal cannabis stores may aid uptake of the legal market, yet there may be diminishing returns after a certain point.

Legal sourcing of ten cannabis products in the Canadian cannabis market, 2019-2021: a repeat cross-sectional study.

BACKGROUND: One of the objectives of cannabis legalization in Canada is to transition consumers from the illegal to the legal market. Little is known about how legal sourcing varies across different cannabis product types, provinces, and frequency of cannabis use. METHODS: Data were analyzed from Canadian respondents in the International Cannabis Policy Study, a repeat cross-sectional survey conducted annually from 2019 to 2021. Respondents were 15,311 past 12-month cannabis consumers of legal age to purchase cannabis. Weighted logistic regression models estimated the association between legal sourcing ("all"/ "some"/ "none") of ten cannabis product types, province, and frequency of cannabis use over time. RESULTS: The percentage of consumers who sourced "all" their cannabis products from legal sources in the past 12 months varied by product type, ranging from 49% of solid concentrate consumers to 82% of cannabis drink consumers in 2021. The percentage of consumers sourcing "all" their respective products legally was greater in 2021 than 2020 across all products. Legal sourcing varied by frequency of use: weekly or more frequent consumers were more likely to source "some" (versus "none") of their products legally versus less frequent consumers. Legal sourcing also varied by province, with a lower likelihood of legal sourcing in Québec of products whose legal sale was restricted (e.g., edibles). CONCLUSION: Legal sourcing increased over time, demonstrating progress in the transition to the legal market for all products in the first three years of legalization in Canada. Legal sourcing was highest for drinks and oils and lowest for solid concentrates and hash.

Increased alcohol use, heavy episodic drinking, and suicide ideation during the COVID-19 pandemic in Canada.

OBJECTIVE: Alcohol use is a known risk factor for suicidality, yet this relationship has not been explored during the pandemic in Canada. As a growing body of evidence demonstrates the negative impact of COVID-19 on alcohol consumption and associated harms in Canada, there is a need to examine this more closely. METHODS: Using the Survey on COVID-19 and Mental Health 2020, we compared the prevalence of suicide ideation among: (1) individuals who reported an increase in alcohol consumption vs those who reported a decrease/no change, and (2) individuals who reported past month heavy episodic drinking vs those who did not. We compared overall unadjusted odds ratios and across a number of sociodemographic and mental health variables. All estimates were weighted to ensure they were nationally representative. RESULTS: The prevalence and likelihood of suicide ideation were significantly higher among people who reported increased alcohol consumption during the pandemic (4.9% vs 2.0%; OR = 2.6, 95% CI: 1.8, 3.7) and people who reported past month heavy episodic drinking (3.4% vs 2.1%; OR = 1.7, 95% CI: 1.2, 2.3). Males and middle-aged and older-aged individuals had the highest odds ratios for increased alcohol consumption and past month heavy episodic drinking with suicide ideation. CONCLUSION: In the Canadian general population during the COVID-19 pandemic, there were significant associations between suicide ideation and increased alcohol use as well as past month heavy episodic drinking across specific sociodemographic subgroups. Future research could explore these associations while adjusting for social determinants of health such as income security, employment, education, social support, stress, and mental health.

RéSUMé: CONTEXTE: La consommation d'alcool est un facteur de risque connu de suicidabilité, mais cette relation n'a pas été explorée pendant la pandémie au Canada. Comme un nombre croissant de preuves démontre les répercussions négatives de la COVID-19 sur la consommation d'alcool et les méfaits associés au Canada, il est nécessaire d'examiner cette question de plus près. MéTHODES: En utilisant l'enquête de 2020 sur la COVID-19 et la santé mentale, nous avons comparé la prévalence des idées suicidaires chez : (1) les individus qui ont déclaré une augmentation de leur consommation d'alcool par rapport à ceux qui ont déclaré une diminution ou aucun changement, et (2) les individus qui ont déclaré une consommation épisodique excessive d'alcool au cours du dernier mois par rapport à ceux qui n'en ont pas déclaré. Nous avons comparé les rapports des cotes globaux non ajustés et selon un certain nombre de variables sociodémographiques et de santé mentale. Toutes les estimations ont été pondérées afin de garantir leur représentativité nationale. RéSULTATS: La prévalence et la probabilité d'idées suicidaires étaient considérablement plus élevées chez les personnes ayant déclaré une consommation d'alcool accrue pendant la pandémie (4,9 % contre 2,0 %; RC=2,6, IC à 95 % : 1,8 à 3,7) et chez les personnes ayant déclaré une consommation épisodique excessive au cours du mois écoulé (3,4 % contre 2,1 %; RC=1,7, IC à 95 % : 1,2 à 2,3). Les hommes, les personnes d'âge moyen et les personnes âgées présentaient les rapports des cotes les plus élevés pour une consommation d'alcool accrue et une consommation épisodique excessive d'alcool au cours du mois précédent avec des idées suicidaires. CONCLUSION: Dans la population générale canadienne, pendant la pandémie de COVID-19, il y avait des associations significatives entre les idées suicidaires et l'augmentation de la consommation d'alcool ainsi que la consommation épisodique excessive d'alcool au cours du dernier mois dans des sous-groupes sociodémographiques précis. Les recherches futures pourraient explorer ces associations tout en ajustant les déterminants sociaux de la santé tels que la sécurité du revenu, l'emploi, l'éducation, le soutien social, le stress et la santé mentale.

Consumer perceptions of legal cannabis products in Canada, 2019-2021: a repeat cross-sectional study.

BACKGROUND: Consumer perceptions of legal cannabis products may drive willingness to purchase from the illegal or legal market; however, little is known on this topic. The current study examined perceptions of legal products among Canadian cannabis consumers over a 3-year period following federal legalization of non-medical cannabis in 2018. METHODS: Data were analyzed from Canadian respondents in the International Cannabis Policy Study, a repeat cross-sectional survey conducted in 2019-2021. Respondents were 15,311 past 12-month cannabis consumers of legal age to purchase cannabis. Weighted logistic regression models examined the association between perceptions of legal cannabis and province of residence, and frequency of cannabis use over time. RESULTS: In 2021, cannabis consumers perceived legal cannabis to be safer to buy (54.0%), more convenient to buy (47.8%), more expensive (47.2%), safer to use (46.8%) and higher quality (29.3%) than illegal cannabis. Except for safety of purchasing, consumers had more favourable perceptions of legal cannabis in 2021 than 2019 across all outcomes. For example, consumers had higher odds of perceiving legal cannabis as more convenient to buy in 2021 than 2019 (AOR = 3.09, 95%CI: 2.65,3.60). More frequent consumers had less favourable perceptions of legal cannabis than less frequent consumers. CONCLUSIONS: Three years since legalization, Canadian cannabis consumers generally had increasingly favourable perceptions of legal vs. illegal products - except for price - with variation across the provinces and frequency of cannabis use. To achieve public health objectives of legalization, federal and provincial governments must ensure that legal cannabis products are preferred to illegal, without appealing to non-consumers.

Examining Risk Factors in the Cannabis-Suicide Link: Considering Trauma and Impulsivity among University Students.

Cannabis is a commonly used substance among university students that may have several negative health repercussions, including suicidal ideation (SI) and suicide attempts (SA). The factors that contribute to or help explain this relation remain uncertain. Earlier negative experiences, especially trauma encountered during early life, have been associated with the development of psychopathology upon later stressor encounters. In the current study, we examined the associations between SI and SA with problematic cannabis use among young adults and the role of earlier trauma experiences and trait impulsiveness in understanding this link. Among university students (N = 539), problematic cannabis use was moderately related to lifetime and past-12-months suicidal ideation and attempts. Impulsiveness mediated the relationship between problematic cannabis use and lifetime SI and SA. Moreover, previous life trauma moderated the relationship between problematic cannabis use and SA, such that the association between problematic cannabis use and SA was stronger among those who experienced high levels of trauma. These findings highlight behavioral and environmental factors that could predict suicide ideation and attempts among young cannabis users. Accordingly, trait impulsiveness and early trauma experiences should be considered, alongside problematic cannabis use, in suicide-risk detection and prevention strategies among young adults.

Guideline No. 425a: Cannabis Use Throughout Women's Lifespans - Part 1: Fertility, Contraception, Menopause, and Pelvic Pain.

OBJECTIVE: To provide health care providers with the best evidence on cannabis use with respect to women's health. Areas of focus include general patterns of cannabis use as well as safety of use; care for women who use cannabis; stigma; screening, brief intervention, and referral to treatment; impact on hormonal regulation; reproductive health, including contraception and fertility; sexual function; effects on perimenopausal and menopausal symptoms; and use in chronic pelvic pain syndromes. TARGET POPULATION: The target population includes all women currently using or contemplating using cannabis. OUTCOMES: Open, evidence-informed dialogue about cannabis use, which will lead to improvement in patient care. BENEFITS, HARMS, AND COSTS: Exploring cannabis use through a trauma-informed approach provides the health care provider and patient with an opportunity to build a strong, collaborative, therapeutic alliance. This alliance empowers women to make informed choices about their own care. It also allows for the diagnosis and possible treatment of cannabis use disorders. Use should not be stigmatized, as stigma leads to poor "partnered care" (i.e., the partnership between the patient and care provider). Multiple side effects of cannabis use may be mistaken for other disorders. Currently, use of cannabis to treat women's health issues is not covered by public funding; as a result, individual users must pay the direct cost. The indirect costs of cannabis use are unknown. Thus, health care providers and patients must understand the role of cannabis in women's health issues, so that women can make knowledgeable decisions. EVIDENCE: PubMed, EMBASE, and grey literature were searched to identify studies of "cannabis use and effect on infertility, contraception, perimenopause and menopausal symptoms, and pelvic pain" published between January 1, 2018 and February 18, 2021. All clinical trials, observational studies, reviews (including systematic reviews and meta-analyses), guidelines, and conference consensus statements were included. Publications were screened for relevance. The search terms were developed using the Medical Subject Headings (MeSH) terms and keywords (and variants), including cannabis, cannabinoids, marijuana, dexanabinol, dronabinol, tetrahydrocannabinol; the specific terms to capture women's health were estrogen, estradiol, medroxyprogesterone acetate, vaginal contraception, oral contraceptives, fertilization, amenorrhea, oligomenorrhea, pelvic pain, dysmenorrhea, endometriosis, interstitial cystitis, vulvodynia, and menopause. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations). INTENDED AUDIENCE: All heath care providers who care for women. SUMMARY STATEMENTS: RECOMMENDATIONS.

Directive clinique no 425a : Le cannabis aux différentes périodes de la vie des femmes - Partie 1 : Fertilité, contraception, ménopause et douleur pelvienne.

OBJECTIF: Fournir aux fournisseurs de soins de santé les meilleures données probantes sur l'utilisation de cannabis et la santé des femmes. Les domaines d'intérêt sont : les profils généraux d'utilisation du cannabis ainsi que la sécurité de la consommation; les soins aux femmes qui utilisent le cannabis; la stigmatisation; le dépistage, l'intervention brève et l'orientation vers le traitement; les effets sur la régulation hormonale; la santé reproductive, y compris la contraception et la fertilité; la fonction sexuelle; les effets sur les symptômes périménopausiques et postménopausiques; et l'utilisation dans le traitement des syndromes de douleur pelvienne chronique. POPULATION CIBLE: La population cible comprend toutes les femmes qui consomment ou utilisent du cannabis ou qui envisagent de le faire. RéSULTATS: Un dialogue ouvert et fondé sur des données probantes relativement à l'utilisation et la consommation de cannabis, dialogue qui mènera à l'amélioration des soins aux patientes. BéNéFICES, RISQUES ET COûTS: L'exploration de l'utilisation et de la consommation de cannabis par une approche basée sur la connaissance des traumatismes donne l'occasion au fournisseur de soins et à la patiente de créer une solide alliance thérapeutique collaborative. Cette alliance permet aux femmes de faire des choix éclairés sur leurs propres soins. Elle facilite également le diagnostic et le traitement possible des troubles de l'usage du cannabis. Il ne faut pas stigmatiser la consommation, car la stigmatisation nuit à l'alliance thérapeutique (c'est-à-dire le partenariat entre la patiente et le fournisseur de soins). Plusieurs effets indésirables de la consommation de cannabis peuvent être confondus avec d'autres problèmes de santé. À l'heure actuelle, l'utilisation du cannabis pour traiter les problèmes de santé féminine n'est pas financée par le secteur public; par conséquent, les utilisatrices doivent assumer les coûts directs. Les coûts indirects de l'utilisation de cannabis sont inconnus. Ainsi, les fournisseurs de soins et les patientes doivent comprendre le rôle du cannabis dans les problèmes de santé féminine de sorte que les femmes puissent prendre des décisions éclairées. DONNéES PROBANTES: Des recherches ont été effectuées dans PubMed, Embase et la littérature grise pour recenser des études publiées entre le 1er janvier 2018 et le 18 février 2021 concernant l'utilisation du cannabis et ses effets sur l'infertilité, la contraception, les symptômes périménopausiques et postménopausiques et la douleur pelvienne. Toutes les publications des types suivants ont été incluses : essais cliniques, études observationnelles, revues (y compris les revues systématiques et les méta-analyses), directives cliniques et déclarations de conférences de consensus. Un survol des publications a été effectué pour en confirmer la pertinence. Les termes de recherche ont été définis à l'aide des termes MeSH (Medical Subject Headings) et mots clés (et variantes) suivants : cannabis, cannabinoids, marijuana, dexanabinol, dronabinol et tetrahydrocannabinol. À ces termes ont été combinés les termes suivants afin de cerner la santé des femmes : estrogen, estradiol, medroxyprogesterone acetate, vaginal contraception, oral contraceptives, fertilization, amenorrhea, oligomenorrhea, pelvic pain, dysmenorrhea, endometriosis, interstitial cystitis, vulvodynia et menopause. MéTHODES DE VALIDATION: Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant l'approche d'évaluation, de développement et d'évaluation (GRADE). Voir l'annexe A en ligne (tableau A1 pour les définitions et tableau A2 pour l'interprétation des recommandations fortes et faibles). PROFESSIONNELS CONCERNéS: Tous les fournisseurs de soins de santé qui prodiguent des soins aux femmes. DÉCLARATIONS SOMMAIRES: RECOMMANDATIONS.

Guideline No. 425b: Cannabis Use Throughout Women's Lifespans - Part 2: Pregnancy, the Postnatal Period, and Breastfeeding.

OBJECTIVE: To provide health care providers with the best evidence on cannabis use and women's health. Areas of focus include screening, dependence, and withdrawal; communication and documentation; pregnancy (including maternal and fetal outcomes); maternal pain control; postpartum care (including second-hand smoking and parenting); and breastfeeding. TARGET POPULATION: The target population includes women who are planning a pregnancy, pregnant, or breastfeeding. BENEFITS, HARMS, AND COSTS: Discussing cannabis use with women who are planning a pregnancy, pregnant, or breastfeeding allows them to make informed choices about their cannabis use. Based on the limited evidence, cannabis use in pregnancy or while breastfeeding should be avoided, or reduced as much as possible if abstaining is not feasible, given the absence of safety and long-term follow up data on cannabis-exposed pregnancies and infants. EVIDENCE: PubMed and Cochrane Library databases were searched for articles relevant to cannabis use during pregnancy and breastfeeding published between January 1, 2018, and February 5, 2021. The search terms were developed using the MeSH terms and keywords and their variants, including cannabis, cannabinoids, cannabidiol, CBD, THC, marijuana, edible, pregnancy, pregnant, prenatal, perinatal, postnatal, breastfeed, breastfed, lactation, nursing, fetus, fetal, neonatal, newborn, and child. In terms of publication type, all clinical trials, observational studies, reviews (including systematic reviews and meta-analyses), guidelines, and conference consensus statements were included. The main inclusion criteria were pregnant and breastfeeding women as the target population, and exposure to cannabis as the intervention of interest. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations). INTENDED AUDIENCE: All health care providers who care for women of reproductive age. SUMMARY STATEMENTS: RECOMMENDATIONS.

Directive clinique no 425b : Le cannabis aux différentes périodes de la vie des femmes - Partie 2 : Grossesse, période postnatale et allaitement.

OBJECTIF: Fournir aux fournisseurs de soins les meilleures données probantes sur l'utilisation de cannabis et la santé des femmes. Les domaines d'intérêt sont le dépistage, la dépendance et le sevrage; la communication et la tenue de dossier; la grossesse (y compris les issues fœtales et maternelles); la gestion de la douleur maternelle; les soins postnataux (y compris la fumée secondaire et la parentalité); et l'allaitement. POPULATION CIBLE: Femmes enceintes, allaitantes ou qui planifient une grossesse. BéNéFICES, RISQUES ET COûTS: Discuter de l'utilisation de cannabis avec les femmes enceintes, allaitantes ou qui planifient une grossesse les aide à faire des choix éclairés. D'après des données probantes limitées, il faut éviter l'utilisation de cannabis pendant la grossesse ou l'allaitement, ou réduire la consommation au maximum si l'abstention n'est pas un objectif atteignable, étant donné l'absence de données sur l'innocuité et le suivi à long terme des grossesses et nourrissons exposés au cannabis. DONNéES PROBANTES: Les auteurs ont interrogé les bases de données PubMed et Cochrane Library pour extraire des articles sur l'utilisation de cannabis pendant la grossesse et l'allaitement publiés entre le 1er janvier 2018 et le 5 février 2021. Les termes de recherche ont été déterminés à partir de termes de recherche MeSH, de mots clés et de leurs variantes : cannabis, cannabinoids, cannabidiol, CBD, THC, marijuana, edible, pregnancy, pregnant, prenatal, perinatal, postnatal, breastfeed, breastfed, lactation, nursing, fetus, fetal, neonatal, newborn et child. Les auteurs ont inclus toutes les publications des types suivants : essais cliniques, études observationnelles, revues (y compris les revues systématiques et les méta-analyses), directives cliniques et déclarations de conférences de consensus. Les principaux critères d'inclusion étaient les femmes enceintes et allaitantes, comme population cible, et l'exposition au cannabis, comme intervention d'intérêt. MéTHODES DE VALIDATION: Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant le cadre méthodologique d'évaluation, de développement et d'évaluation (GRADE). Voir l'annexe A en ligne (tableau A1 pour les définitions et tableau A2 pour l'interprétation des recommandations fortes et faibles). PROFESSIONNELS CONCERNéS: Tous les fournisseurs de soins de santé qui prodiguent des soins aux femmes en âge de procréer. DÉCLARATIONS SOMMAIRES: RECOMMANDATIONS.

Coping With the COVID-19 Pandemic: Examining Gender Differences in Stress and Mental Health Among University Students.

The COVID-19 pandemic has imposed a wide variety of unprecedented challenges, many of which appear to be disproportionately affecting the mental health and well-being of young adults. While there is evidence to suggest university students experience high rates of mental health disorders, less is known about the specific impacts of the COVID-19 pandemic on student mental health and how they are coping with this stress. To address this gap, we conducted an online study among undergraduate students (n = 366) to examine the impact of the COVID-19 pandemic on academics, social isolation, and mental health, as well as the extent to which they have been implementing a variety of coping strategies. The pandemic had a more pronounced negative effect on female students' academics, social isolation, stress and mental health compared to male counterparts. Moreover, for females, frequent use of social media as a coping mechanism was associated with greater perceived negative impacts on their academic performance and stress levels, compared to males. However, frequent social media use related to similar negative mental health effects for both males and females. While male and female students both reported using substances to cope, for males the use of cannabis was associated with greater negative impacts on academic outcomes, stress and mental health compared to females. These findings highlight the need for adequate student support services across the post-secondary sector, and point to the importance of gender informed interventions to address the impacts of the COVID-19 pandemic.

Self-Reported Mild Traumatic Brain Injuries in Relation to Rumination and Depressive Symptoms: Moderating Role of Sex Differences and a Brain-Derived Neurotrophic Factor Gene Polymorphism.

OBJECTIVE: Mild traumatic brain injuries (mTBIs) have frequently been associated with the emergence and persistence of depressive symptoms. However, the factors which contribute to the increased risk for depression after these head injuries remain unclear. Accordingly, we examined the relationship between frequency of self-reported mTBIs and current symptoms of depression and the mediating role of rumination and cognitive flexibility. We also examined whether these relations were moderated by sex differences and the presence of the Val66Met polymorphism in a gene coding for brain-derived neurotrophic factor (BDNF). DESIGN: Retrospective, cross-sectional. SETTING: Carleton University. PARTICIPANTS: Two hundred nineteen Carleton University undergraduate students. MAIN OUTCOME MEASURES: Cognitive flexibility as assessed by the Wisconsin Card Sorting Task (WCST); subtypes of rumination (Ruminative Response Scale; Treynor, Gonzalez, and Nolen-Hoeksema, 2003); depressive symptoms (Beck Depression Inventory; Beck, Ward, and Mendelson, 1961). RESULTS: Greater frequency of self-reported mTBIs was associated with more frequent depressive rumination among women, but not men, which was accompanied by elevated current depressive symptoms. In addition, among Met allele carriers of the BDNF polymorphism, but not those who were Val homozygotes, greater frequency of mTBIs was related to higher levels of brooding, which was accompanied by heightened depressive symptoms. Brain-derived neurotrophic factor genotype also moderated the relationship between self-reported mTBIs and cognitive flexibility in that more frequent mTBIs were associated with more perseverative errors on the WCST among Met carriers, but not Val homozygotes. CONCLUSIONS: The present findings raise the possibility that the evolution of depression after mTBIs may be dependant on a BDNF polymorphism and sex differences.

Understanding the Relation Between Early-Life Adversity and Depression Symptoms: The Moderating Role of Sex and an Interleukin-1ß Gene Variant.

Pro-inflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor-α (TNF-α), are thought to play a fundamental role in the pathogenesis of depression within a subset of individuals. However, the involvement of IL-1ß has not been as consistently linked to depression, possibly owing to difficulties in detecting this cytokine in blood samples or that changes in circulating levels might only be apparent in a subgroup of patients who have experienced early-life adversity. From this perspective, the association between early-life adversity and depressive illness might depend on genetic variants regulating IL-1ß activity. Considering the inflammatory-depression link, and that women are twice as likely to experience depression compared to men, the current study (N = 475 university students) examined the moderating role of three independent cytokine single nucleotide polymorphisms (SNPs; IL-1ß rs16944, IL-6 rs1800795 SNP, TNF-α rs1800629) in the relationship between early-life adversity and depressive symptoms, and whether these relations differed between males and females. The relation between childhood adversity and depressive symptoms was moderated by the IL-1ß SNP, and further varied according to sex. Specifically, among females, higher childhood maltreatment was accompanied by elevated depressive symptoms irrespective of the IL-1ß SNP, but among males, this relationship was particularly pronounced for those carrying the GG genotype of the IL-1ß SNP. These findings suggest that, in the context of early life adversity, genetic variations of IL-1ß functioning are related to depressive symptomatology and this may vary among males and females. The present study also, more broadly, highlights the importance of considering the confluence of experiential factors (e.g., early life adversity) and personal characteristics (e.g., sex and genetics) in understanding depressive disorders, an approach increasingly recognized in developing personalized treatment approaches to this illness.

Acute stressor effects on cognitive flexibility: mediating role of stressor appraisals and cortisol.

Acute stressor experiences may influence cognition, possibly through actions of cognitive flexibility, which comprises the ability to modify cognitive and behavioral strategies in response to changing environmental demands. In the present investigation, we examined the effects of an acute psychosocial stressor (the Trier Social Stress Test) on a specific form of cognitive flexibility, namely that of set-shifting, which was assessed by the Berg's Card Sorting Task (BCST). Among undergraduate students, the stressor promoted better performance on the BSCT relative to that evident among nonstressed individuals, including a reduction of perseverative (an index of enhanced set-shifting) and non-perseverative errors. They also required fewer trials to learn the first sorting category, reflecting augmented acquisition of an attentional set, but did not differ in the ability to maintain a set. Moreover, increased cortisol levels specifically mediated the enhancing effects of the acute stressor on set-shifting, but not the ability to acquire and maintain an attentional set. However, this enhancing effect was minimized among individuals who appraised the stressor as being uncontrollable. These data indicate that an acute, social-evaluative stressor can facilitate certain forms of cognitive flexibility, such as set-shifting. The present investigation also highlights the value of focusing on psychological and physiological mediators in determining the impact of stressful experiences on cognitive functioning. Lay summary A brief social stressor (public speaking) can have an enhancing effect on mental flexibility, and this seems to be related to the stress hormone, cortisol. This cognitive enhancing effect, however, might be minimized if a stressful situation is perceived as beyond a person's control.

Cognitive Control and Flexibility in the Context of Stress and Depressive Symptoms: The Cognitive Control and Flexibility Questionnaire.

Cognitive control and (cognitive) flexibility play an important role in an individual's ability to adapt to continuously changing environments. In addition to facilitating goal-directed behaviors, cognitive control and flexibility have been implicated in emotion regulation, and disturbances of these abilities are present in mood and anxiety disorders. In the context of stressful experiences, the reported studies examined processes related to cognitive control and flexibility, emotional regulation and depressive symptoms. To this end, a brief (18-item) self-report measure - the Cognitive Control and Flexibility Questionnaire (CCFQ) - was developed. This questionnaire measures an individual's perceived ability to exert control over intrusive, unwanted (negative) thoughts and emotions, and their ability to flexibly cope with a stressful situation. In Study 1, the CCFQ was assessed among both university students (N = 300) and a community sample (N = 302). Preliminary analyses suggested a stable and reliable two-factor structure, that of cognitive control over emotion, and appraisal and coping flexibility. Scores on the CCFQ were strongly associated with greater depressive symptoms, even after controlling for other measures that had been taken to reflect cognitive control and (in)flexibility (e.g., the Ruminative Response Scale; Perseverative Thinking Questionnaire). In Study 2 (N = 368), lower scores on the CCFQ were related to more negative stressor appraisals (i.e., greater perceived threat and uncontrollability) of a personally meaningful stressful event. Perceptions of threat and uncontrollability, in turn, partially accounted for the association between CCFQ subscale scores and depressive symptoms. The relation between lower CCFQ scores and heightened depressive symptoms was also partially accounted for by less frequent engagement in problem-focused coping and more use of emotion-focused methods. In Study 3 (N = 47 females), lower scores on the cognitive control over emotion component of the CCFQ predicted elevated negative affect and an exacerbated cortisol response following an acute psychosocial stressor (Trier Social Stress Test). The present research points to the CCFQ as a useful self-report tool to identify ways through which cognitive control and flexibility might be manifested in stressful situations, and how reductions in flexibility might be accompanied by elevated symptoms of depression.

Traumatic Life Events in Relation to Cognitive Flexibility: Moderating Role of the BDNF Val66Met Gene Polymorphism.

Cognitive flexibility plays an important role in an individual's ability to adapt to a continuously changing environment and is considered central to goal-oriented behavior. Accordingly, increasing attention has been devoted to understanding the factors, including genetic and early life experiences, which might contribute to individual differences in this ability. In the present investigation, we examined the contribution of the BDNF Val66Met polymorphism to cognitive flexibility, as assessed by set-shifting ability on the Wisconsin Card Sorting Task (WCST), and whether this polymorphism moderated the relation between trauma experiences (including type and timing of trauma occurrence) and cognitive flexibility. Among undergraduate students (N = 239), greater frequency of total traumas experienced prior to the age 5 was associated with greater difficulties in set-shifting (as indexed by more frequent perseverative errors on the WCST) among individuals carrying the Met allele of the BDNF polymorphism, but not those who were Val homozygotes. By contrast, total traumas experienced between the age of 6 to 12 and 13 to 18 were not related to set-shifting ability, and these relations were not moderated by BDNF genotype. Moreover, greater frequency of general traumas and emotional abuse was associated with set-shifting difficulties for both male and female Met allele carriers, but not Val homozygotes. In contrast, physical punishment was related to difficulties in set-shifting, but only among male Met carriers, an effect that was likely attributed to greater frequency of this form of trauma among males. The present findings suggest that the relationship between early life trauma and later-life cognitive flexibility might depend on the presence of the BDNF Val66Met polymorphism as well as the development stage at which the trauma has occurred. Moreover, the present investigation provides further understanding into the factors (i.e., genetic and early life experiences) that might be associated with individual differences in cognitive functioning and goal-directed behaviors, such as problem-solving and decision-making.