An analysis of neuroscience and psychiatry papers published from 2009 and 2019 outlines opportunities for increasing discovery of sex differences

Rechlin, Rebecca K.; Splinter, Tallinn F L; Hodges, Travis E.; Albert, Arianne; Galea, Liisa A.M.

doi:10.1038/s41467-022-29903-3

Cited by 122 publications

(92 citation statements)

References 69 publications

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“…This left 12 articles that met our eligibility criteria: eight studies in animal models and four studies in humans. Initially, our plan was to present only results from analyses that included sex as a “discovery” variable (i.e., as a main effect or part of an interaction term), in line with a recent review of inclusion of sex as a biological variable in neuroscience and psychiatric papers [ 47 ]. However, since there were already so few studies identified for this review, and since unfortunately most preclinical studies did not consistently include sex as a discovery variable or did not clearly present between-sex comparisons when there were significant sex-by-drug treatment condition interactions, we present here a mix of between-sex and within-sex comparisons.…”

Section: Resultsmentioning

confidence: 99%

“…A study was considered to have a sex-based analysis when one of two conditions was met: (1) sex was analyzed as a main effect when the outcome of interest was CBD concentrations or pharmacokinetics (e.g., a t -test to determine if males and females differed in physiological concentrations of CBD); or (2) the study had a factorial design with sex as a factor that entered into an interaction term with a drug exposure or treatment factor (e.g., a two-way ANOVA to determine if there was an interaction between sex and CBD dose group on a relevant endpoint). This definition was based on previous literature describing appropriate reporting of sex differences [ 47 , 48 ]. The article was a primary, peer-reviewed research article available in English.…”

Section: Methodsmentioning

confidence: 99%

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Sex Differences in the Neuropsychiatric Effects and Pharmacokinetics of Cannabidiol: A Scoping Review

2022

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Cannabidiol (CBD) is a non-intoxicating cannabinoid compound with diverse molecular targets and potential therapeutic effects, including effects relevant to the treatment of psychiatric disorders. In this scoping review, we sought to determine the extent to which sex and gender have been considered as potential moderators of the neuropsychiatric effects and pharmacokinetics of CBD. In this case, 300 articles were screened, retrieved from searches in PubMed/Medline, Scopus, Google Scholar, PsycInfo and CINAHL, though only 12 met our eligibility criteria: eight studies in preclinical models and four studies in humans. Among the preclinical studies, three suggested that sex may influence long-term effects of gestational or adolescent exposure to CBD; two found no impact of sex on CBD modulation of addiction-relevant effects of Δ⁹-tetrahydrocannabinol (THC); two found antidepressant-like effects of CBD in males only; and one found greater plasma and liver CBD concentrations in females compared to males. Among the human studies, two found no sex difference in CBD pharmacokinetics in patient samples, one found greater plasma CBD concentrations in healthy females compared to males, and one found no evidence of sex differences in the effects of CBD on responses to trauma recall in patients with post-traumatic stress disorder (PTSD). No studies were identified that considered the role of gender in CBD treatment effects. We discuss potential implications and current limitations of the existing literature.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Sex Differences in the Neuropsychiatric Effects and Pharmacokinetics of Cannabidiol: A Scoping Review

2022

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“…To investigate the association between predictor variables and suicide risk specifically in males and females, the logistic regression models described above were stratified by sex. The examination of sex-stratified analyses may improve sensitivity to uncover effects that would not otherwise be found when the sexes are combined ( 32 ). Finally, multivariate analyses of variance (ANOVAs) were performed to compare mental state indicators for individuals deemed as non-suicidal vs. those at elevated suicide risk (with suicide plan or attempt).…”

Section: Methodsmentioning

confidence: 99%

Sex Differences in Determinants of Suicide Risk Preceding Psychiatric Admission: An Electronic Medical Record Study

et al. 2022

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BackgroundIndividuals requiring inpatient psychiatric care represent a group at higher risk of progressing toward suicide attempt. Using electronic medical record (EMR) data collected from psychiatric inpatient admissions, the objective of this study was to identify sex differences in risk factors for suicide plans and/or attempts within the 30 days preceding hospital admission.MethodsResident Assessment Instrument for Mental Health (RAI-MH) intake data were obtained for patients admitted to a Canadian tertiary-care hospital deemed a “threat or danger to self” during a 10-year period (2008–2018). Data was extracted for individuals categorized into three groups: non-suicidal (N = 568), presence of suicide plan (N = 178), and presence of suspected suicide attempt (N = 124) in the 30 days prior to hospital admission. Multivariate logistic regression models were used to examine determinants of suicide risk.ResultsAcross all models, diagnosis of depression was the strongest predictor of suicide plan and/or attempt (OR = 5.54, 95% CI = 3.71–8.27, p < 0.001). Comparing clinical symptoms between suicidal and non-suicidal groups at the time of admission, the largest effect sizes were found for hopelessness (p < 0.001, η2 = 0.11), and guilt or shame (p < 0.001, η2 = 0.09). Female sex was identified as a significant factor for elevated suicidal risk (OR = 1.56, 95% CI = 1.01–2.21, p = 0.01), thus we stratified the regression model by sex to identify specific risk factors for suicide plan and/or attempt for males and females. Among males, having no confidant (OR = 2.13, 95% CI = 1.19–3.80, p = 0.01), presence of recent stressors (OR = 1.95, 95% CI = 1.16–3.29, p = 0.01), and participation in social activities (OR = 1.67, 95% CI = 1.02–2.71, p = 0.04) were important predictors, while among females, younger age (OR = 0.96, 95% CI = 0.94–0.97, p < 0.001) increased odds of suicide plan and/or attempt.ConclusionEMR-derived findings highlight different psychosocial and clinical determinants for males and females associated with suicide plan or attempt prior to psychiatric admission. Identifying precipitating factors that elevate imminent suicide risk may inform suicide prevention efforts for psychiatric inpatients.

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“…The objective of this work was to expand our understanding of what USVs can tell us about affective states, and whether these patterns differ between male and female rodents. As we continue to normalize the use of female rodents in behavioral neuroscience, it is critical to know if the same experimental measures collected for decades using only males reflect the same emotional states in females, or whether behavioral repertoires are sex-biased (Bangasser & Cuarenta, 2021; Rechlin et al, 2022; Shansky & Murphy, 2021).…”

Section: Introductionmentioning

confidence: 99%

Sounding the alarm: sex differences in rat ultrasonic vocalizations during Pavlovian fear conditioning and extinction

Laine

Mitchell

Rhyner

et al. 2022

Preprint

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Pavlovian fear conditioning is a prevalent tool in the study of aversive learning, which is a key component of stress-related psychiatric disorders. Adult rats can exhibit various threat-related behaviors, including freezing, motor responses and ultrasonic vocalizations (USVs). While these responses can all signal aversion, we know little about how they relate to one another. Here we characterize USVs emitted by male and female rats during cued fear acquisition and extinction and assess the relationship between different threat-related behaviors. To probe the effects of aversive stimulus intensity, we exposed the rats to mild (0.3 mA), moderate (0.5 mA) or strong (1 mA) foot shocks. We found that males consistently emitted more alarm calls than females, and male alarm calls were more closely contingent on shock intensity than were female alarm calls. Furthermore, 25 % of males and 45 % of females did not emit alarm calls. Males that made alarm calls had significantly higher levels of freezing than males who did not, while no differences in freezing were observed between female alarm callers and non-callers. Alarm call emission was also affected by the predictability of the shock; when unpaired from a tone cue, both males and females started emitting alarm calls significantly later. Some rats continued to alarm-call during extinction learning (90% of males, 30% of females) and retrieval (65% of males, 20% of females). Collectively these data suggest sex-dependence in how behavioral readouts relate to innate and conditioned threat responses. Importantly, we suggest that the same behaviors can signal sex-dependent features of aversion.

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An analysis of neuroscience and psychiatry papers published from 2009 and 2019 outlines opportunities for increasing discovery of sex differences

Cited by 122 publications

References 69 publications

Sex Differences in the Neuropsychiatric Effects and Pharmacokinetics of Cannabidiol: A Scoping Review

Sex Differences in the Neuropsychiatric Effects and Pharmacokinetics of Cannabidiol: A Scoping Review

Sex Differences in Determinants of Suicide Risk Preceding Psychiatric Admission: An Electronic Medical Record Study

Sounding the alarm: sex differences in rat ultrasonic vocalizations during Pavlovian fear conditioning and extinction

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