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Bjorklund and Kipp (1996) provide an evolutionary framework predicting that there is a female advantage in inhibition and self-regulation due to differing selection pressures placed on males and females. The majority of the present review will summarize sex differences in self-regulation at the behavioral level. The neural and hormonal underpinnings of this potential sexual dimorphism will also be investigated and the results of the experiments summarized will be related to the hypothesis advanced by Bjorklund and Kipp (1996). Paradoxically, sex differences in self-regulation are more consistently reported in children prior to the onset of puberty. In adult cohorts, the results of studies examining sex differences in self-regulation are mixed. A few recent experiments suggesting that females are less impulsive than males only during fertile stages of the menstrual cycle will be reviewed. A brief discussion of an evolutionary framework proposing that it is adaptive for females to employ a self-regulatory behavioral strategy when fertile will follow.

Previous research shows that women outperform men in the classic Stroop task, but it is not known why this difference occurs. There are currently two main hypotheses: (1) women have enhanced verbal abilities, and (2) women show greater inhibition. In two Stroop experiments, we examined the Inhibition hypothesis by adopting a procedure, often used in visual cognition paradigms, that induces a particular inhibitory component. So-called Negative Priming occurs when a distracting non-target stimulus on one trial becomes the target on the following trial. Results from our experiments showed that the degree to which this type of inhibition occurs within the Stroop effect is no different for men and women. This was the case irrespective of whether participants made a vocal response (Experiment 1; n  = 64, 32 men and 32 women) or a manual response (Experiment 2; n  = 64, 32 men and 32 women). These results do not therefore support the Inhibition hypothesis. We additionally review findings from a range of paradigms that can be seen as indexing the different components required for the Stroop task (e.g., distractor suppression). This review suggests that the sex effect is due to superior color naming ability in women.

The sex difference in the prevalence of autism spectrum disorder (ASD) may be magnified by sex differences on diagnostic measures. The current study compared autistic males and females on items on the gold-standard diagnostic measure, the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2). In a sample of 8-to-17-year old autistic individuals from research (n = 229) and clinical settings (n = 238), females were less likely to show atypicalities on most items related to social-communication behaviors and on total and subscale scores. When controlling for overall intensity of symptomatology, no sex differences survived statistical corrections. Diagnostic criteria and/or gold-standard assessments may be less sensitive to female presentations of ASD and/or autistic females may exhibit fewer or less intense behaviors characteristic of ASD.

ABSTRACT Unique populations of basolateral amygdala (BLA) neurons regulate anxiety and reward through projections targeting downstream regions like the bed nucleus of the stria terminalis (BNST) and nucleus accumbens (NAC). We showed previously that withdrawal from chronic ethanol exposure (CIE/WD) produced population‐ and sex‐specific alterations to distinct glutamatergic inputs. The current study examined GABAergic function in these distinct populations (BLANAC and BLABNST neurons). We found that CIE/WD diminished feed‐forward GABA release from lateral paracapsular cells (LPCs) specifically onto male BLANAC neurons. Pharmacological manipulations showed this dysregulation was caused by the enhanced activity of μ‐opioid receptors. CIE/WD did not alter evoked GABA release from local interneurons onto either population. However, females expressed greater GABA release from these local interneurons compared to males. Immunostaining and confocal microscopy revealed lower colocalization between the GABA vesicular transporter, vGAT and parvalbumin in females, indicating that greater GABA releases from local interneurons in this sex may be a compensatory response to lower levels of perisomatic innervation by PV+ interneurons. Consistent with this, there were no sex differences related to spontaneous GABAergic synaptic events although CIE/WD decreased their frequency specifically in BLABNST neurons from both sexes. Altogether, these findings demonstrate that CIE/WD dynamically alters GABAergic function in an input‐, sex‐ and population‐specific fashion. Moreover, there are basal sex differences in both the anatomy of BLA GABAergic synapses and their function. Rat basolateral amygdala principal neurons projecting to the nucleus accumbens (BLANAc) and bed nucleus of the stria terminalis (BLABNST) represent independent cell populations. In male BLANAc neurons only (left), CIE/WD decreases feedforward GABA release from lateral paracapsular interneurons. In BLABNST neurons (right), GABA release from ‘local’ feedback interneurons is greater in females; but CIE/WD diminishes spontaneous GABA release attributable to these ‘local’ interneurons in both sexes. Thus, CIE/WD dysregulation of BLA GABAergic neurotransmission is sex‐, synapse‐ and population‐specific.

•Antibody responses and protection to a cHA-based universal influenza virus vaccine declines with advanced age.•Age-associated decline in antibody responses and protection is more prominent in females than males.•Serum from vaccinated adult mice is not sufficient to protect naïve aged, sex-matched mice.•Age and sex should be considered in preclinical and clinical studies with universal influenza virus vaccines. To determine if biological sex and age intersect to affect universal influenza vaccine-induced immunity, adult and aged male and female C57BL/6 mice were sequentially immunized with a chimeric-hemagglutinin (cHA) stalk-based H1 vaccine. Adult mice developed greater quantity and quality of H1-stalk antibodies, that were more cross-reactive with other group 1, but not group 2, influenza viruses, than aged mice. The vaccine did not induce neutralizing or hemagglutination inhibition antibodies, but rather antibody-dependent cellular cytotoxicity, which was greater in adult than aged mice. Vaccinated adult mice were better protected than aged mice after challenge with 2009 H1N1 virus, experiencing less morbidity and having lower pulmonary virus titers. The age-associated decline in immunity and protection was consistently greater among females than males, with the reduction in immunity and protection for aged as compared with adult females often being the sole comparison driving the overall age-associated significant differences. The age-associated reduction in stalk-based immunity in females was not, however, associated with changes in estradiol. To determine if the better antibodies in adults could be utilized to protect aged mice, serum was passively transferred from vaccinated adult mice into naïve sex-matched aged mice. Even with transferred serum from young adult mice, aged females still suffered greater morbidity than aged males. These data suggest there are sex-dependent effects of aging on cHA-based universal influenza virus vaccine-induced immunity that cannot be reversed through transfer of serum from young animals. The lack of consideration of sex-specific effects of aging on immunity could hinder efforts toward universal vaccines.

Introduction: In the German population women are affected by depression twice as often as men (prevalence 20.1% vs. 10.8%) [1]. Various drugs are available to treat depressive disorders, among them the non-selective monoamine reuptake inhibitors (NSMRI) which are also used (sometimes off-label) for other indications [2]. In Germany, the most frequently prescribed NSMRI are amitriptyline, opipramol, doxepin and trimipramine [2]. The German product information does not recommend different dosages for male and female patients. However, adverse drug reactions (ADR) of NSMRI may affect female patients more often than male ones [3]. Aim: To analyze whether spontaneous ADR reports on amitriptyline, opipramol, doxepin and trimipramine are more frequent in female compared to male patients. Methods: Spontaneous reports on amitriptyline, opipramol, doxepin and trimipramine (suspect/interacting), reported to the Drug Commission of the German Medical Association (DCGMA) from May 1, 2007 to December 31, 2021, are included. Reports on SOC (MedDRA system organ class) \"injury, poisoning and procedural complications\" (which contains medication errors and intentional overdoses) were excluded, as were reports about subjects <18 years or with missing age information. We then performed a sex-disaggregated analysis of patient characteristics, medication-specific information and reported reactions. Results: Of the overall 49.287 case reports collected by the DCGMA between May 2007 and December 2021, 95 ADR reports (females 66 [69.5 %], males 29 [30.5 %]) were included; 32 on amitriptyline, 31 on opipramol, 13 on doxepin and 20 on trimipramine (one patients was simultaneously treated with trimipramine and doxepin). Fifty-two of the reports (54.2 %) were classified as serious, 37 in females (55.2% of a total of 66), 15 in males (51.7 % of 29). In both sexes, liver-related reactions were among the most frequently reported ADRs. Conclusions: About two-thirds of the case reports on amitriptyline, opipramol, doxepin and trimipramine were in female patients in accordance with the prevalence of depressive disorders in the general population. The proportion of serious reports was similar in male and female patients in our sample. Given that our data are based on spontaneous reporting, no conclusion can be drawn about the incidence of these ADRs in the overall user population. However, given the discrepancy between the known sex-specific side effects in female and male patients using NSMRI and our data, further studies should investigate potential sources of sex- and gender-based bias in spontaneous reporting and recording patterns of ADRs.

Girls and boys might differ in autistic symptoms and associated cognitive difficulties such as executive function (EF). We investigated sex differences in the relationship between parent rated EF and autistic symptoms in 116 children and adolescents (25 girls) aged 5–19 years with an intelligence quotient above 70 and an autism spectrum disorder (ASD) diagnosis. They were rated with the behavior rating inventory of executive function (BRIEF) and the autism diagnostic interview revised (ADI-R). We found a positive association between EF and the ADI-R domains of reciprocal social interaction (p < 0.001) and communication (p = 0.001) in girls, while these relationships were small and non-significant in boys. Our results provide a greater understanding of the sex-specific characteristics of children and adolescents with ASD.

Numerous studies have shown a decrease in executive functions (EF) associated with aging. However, few investigations examined whether this decrease is similar between sexes throughout adulthood. The present study investigated if age-related decline in EF differs between men and women from early to late adulthood. A total of 302 participants (181 women) aged between 18 and 78 years old completed four computer-based cognitive tasks at home: an arrow-based Flanker task, a letter-based Visual search task, the Trail Making Test, and the Corsi task. These tasks measured inhibition, attention, cognitive flexibility, and working memory, respectively. To investigate the potential effects of age, sex, and their interaction on specific EF and a global EF score, we divided the sample population into five age groups (i.e., 18-30, 31-44, 45-54, 55-64, 65-78) and conducted analyses of covariance (MANCOVA and ANCOVA) with education and pointing device as control variables. Sex did not significantly affect EF performance across age groups. However, in every task, participants from the three youngest groups (< 55 y/o) outperformed the ones from the two oldest. Results from the global score also suggest that an EF decrease is distinctly noticeable from 55 years old onward. Our results suggest that age-related decline in EF, including inhibition, attention, cognitive flexibility, and working memory, becomes apparent around the age of 55 and does not differ between sexes at any age. This study provides additional data regarding the effects of age and sex on EF across adulthood, filling a significant gap in the existing literature.

Gender differences in psychiatric disorders such as addiction may be modulated by the steroid hormone estrogen. For instance, 17β-estradiol (E2), the predominant form of circulating estrogen in pre-menopausal females, increases ethanol consumption, suggesting that E2 may affect the rewarding properties of ethanol and thus the development of alcohol use disorder in females. The ventral tegmental area (VTA) is critically involved in the rewarding and reinforcing effects of ethanol. In order to determine the role of E2 in VTA physiology, gonadally intact female mice were sacrificed during diestrus II (high E2) or estrus (low E2) for electrophysiology recordings. We measured the excitation by ethanol and inhibition by dopamine (DA) of VTA DA neurons and found that both excitation by ethanol and inhibition by dopamine were greater in diestrus II compared with estrus. Treatment of VTA slices from mice in diestrus II with an estrogen receptor antagonist (ICI 182,780) reduced ethanol-stimulated neuronal firing, but had no effect on ethanol-stimulated firing of neurons in slices from mice in estrus. Surprisingly, ICI 182,780 did not affect the inhibition by DA, indicating different mechanisms of action of estrogen receptors in altering ethanol and DA responses. We also examined the responses of VTA DA neurons to ethanol and DA in ovariectomized mice treated with E2 and found that E2 treatment enhanced the responses to ethanol and DA in a manner similar to what we observed in mice in diestrus II. Our data indicate that E2 modulates VTA neuron physiology, which may contribute to both the enhanced reinforcing and rewarding effects of alcohol and the development of other psychiatric disorders in females that involve alterations in DA neurotransmission.