Increased dietary α-linolenic acid has sex-specific effects upon eicosapentaenoic acid status in humans: re-examination of data from a randomised, placebo-controlled, parallel study

Background: There is a metabolic pathway by which mammals can convert the omega-3 (n-3) essential fatty acid α-linolenic acid (ALA) into longer-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). As far as we know there are currently no studies that have specifically examined sex differences in the LC n-3 PUFA response to increased dietary ALA intake in humans, although acute studies with isotope-labelled ALA identified that women have a significantly greater capacity to synthesise EPA and DHA from ALA compared to men. Findings: Available data from a placebo-controlled, randomised study were re-examined to identify whether there are sex differences in the LC n-3 PUFA response to increased dietary ALA intake in humans. There was a significant difference between sexes in the response to increased dietary ALA, with women having a significantly greater increase in the EPA content of plasma phospholipids (mean +2.0% of total fatty acids) after six months of an ALA-rich diet compared to men (mean +0.7%, P = 0.039). Age and BMI were identified as predictors of response to dietary ALA among women. Conclusions: Women show a greater increase in circulating EPA than men during increased dietary ALA consumption. Further understanding of individual variation in the response to dietary ALA could inform nutrition advice, with recommendations being specifically tailored according to habitual diet, sex, age and BMI.

Sex differences in the programming effects of prenatal stress on psychopathology and stress responses: an evolutionary perspective

There is strong evidence from animal studies that prenatal stress has different effects on male and female offspring. In general, although not always, prenatal stress increases anxiety, depression and stress responses, both hypothalamic–pituitary–adrenal and cardiovascular, in female offspring rather than in male. Males are more likely to show learning and memory deficits. There have been few studies so far in humans which differentiate effects of prenatal stress on male and female psychopathology. Some studies support the animal models, but the evidence is inconsistent. The mediating mechanisms for any sex specific effects are little understood, but there is evidence that placental function can differ depending on the sex of the fetus. We suggest that there may be an evolutionary reason for any sex differences in the long term effects of prenatal stress. In a stressful environment it may be adaptive for females, who are more likely to stay in one place and look after children, to be more vigilant, alert to danger and thus show more stress responsiveness. This can give rise to a more anxious or depressed phenotype. With males it may be more adaptive to go out and explore new environments, compete with other males, and be more aggressive. For this it may help to be less responsive to external stressors. More research is needed into sex differences in the effects of prenatal stress in humans, to test these ideas.

Maternal antenatal anxiety, postnatal stroking and emotional problems in children: outcomes predicted from pre and postnatal programming hypotheses

Background Mothers' self-reported stroking of their infants over the first weeks of life modifies the association between prenatal depression and physiological and emotional reactivity at 7 months, consistent with animal studies of the effects of tactile stimulation. We now investigate whether the effects of maternal stroking persist to 2.5 years. Given animal and human evidence for sex differences in the effects of prenatal stress we compare associations in boys and girls. Method From a general population sample of 1233 first-time mothers recruited at 20 weeks gestation we drew a random sample of 316 for assessment at 32 weeks, stratified by reported inter-partner psychological abuse, a risk indicator for child development. Of these mothers, 243 reported at 5 and 9 weeks how often they stroked their infants, and completed the Child Behavior Checklist (CBCL) at 2.5 years post-delivery. Results There was a significant interaction between prenatal anxiety and maternal stroking in the prediction of CBCL internalizing (p = 0.001) and anxious/depressed scores (p < 0.001). The effects were stronger in females than males, and the three-way interaction prenatal anxiety × maternal stroking × sex of infant was significant for internalizing symptoms (p = 0.003). The interactions arose from an association between prenatal anxiety and internalizing symptoms only in the presence of low maternal stroking. Conclusions The findings are consistent with stable epigenetic effects, many sex specific, reported in animal studies. While epigenetic mechanisms may be underlying the associations, it remains to be established whether stroking affects gene expression in humans.

Sex-dependent age modulation of frontostriatal and temporo-parietal activation during cognitive control

Developmental functional imaging studies of cognitive control show progressive age-related increase in task-relevant fronto-striatal activation in male development from childhood to adulthood. Little is known, however, about how gender affects this functional development. In this study, we used event related functional magnetic resonance imaging to examine effects of sex, age, and their interaction on brain activation during attentional switching and interference inhibition, in 63 male and female adolescents and adults, aged 13 to 38. Linear age correlations were observed across all subjects in task-specific frontal, striatal and temporo-parietal activation. Gender analysis revealed increased activation in females relative to males in fronto-striatal areas during the Switch task, and laterality effects in the Simon task, with females showing increased left inferior prefrontal and temporal activation, and males showing increased right inferior prefrontal and parietal activation. Increased prefrontal activation clusters in females and increased parietal activation clusters in males furthermore overlapped with clusters that were age-correlated across the whole group, potentially reflecting more mature prefrontal brain activation patterns for females, and more mature parietal activation patterns for males. Gender by age interactions further supported this dissociation, revealing exclusive female-specific age correlations in inferior and medial prefrontal brain regions during both tasks, and exclusive male-specific age correlations in superior parietal (Switch task) and temporal regions (Simon task). These findings show increased recruitment of age-correlated prefrontal activation in females, and of age-correlated parietal activation in males, during tasks of cognitive control. Gender differences in frontal and parietal recruitment may thus be related to gender differences in the neurofunctional maturation of these brain regions.

Mind-reading difficulties in the siblings of people with Asperger's syndrome: evidence for a genetic influence in the abnormal development of a specific cognitive domain

Background: Previous research suggests that the phenotype associated with Asperger's syndrome (AS) includes difficulties in understanding the mental states of others, leading to difficulties in social communication and social relationships. It has also been suggested that the first-degree relatives of those with AS can demonstrate similar difficulties, albeit to a lesser extent. This study examined 'theory of mind' (ToM) abilities in the siblings of children with AS relative to a matched control group. Method: 2 7 children who had a sibling with AS were administered the children's version of the 'Eyes Test'(Baron-Cohen, Wheelwright, Stone, & Rutherford, 1999). The control group consisted of 27 children matched for age, sex, and a measure of verbal comprehension, and who did not have a family history of AS/autism. Results: A significant difference was found between the groups on the Eyes Test, the 'siblings' group showing a poorer performance on this measure of social cognition. The difference was more pronounced among female siblings. Discussion: These results are discussed in terms of the familial distribution of a neuro-cognitive profile associated with AS, which confers varying degrees of social handicap amongst first-degree relatives. The implication of this finding with regard to the autism/AS phenotype is explored, with some discussion of why this neuro-cognitive profile (in combination with corresponding strengths) may have an evolutionary imperative.

Sex differences in reward-related decision processing under stress

Recent research indicates gender differences in the impact of stress on decision behavior, but little is known about the brain mechanisms involved in these gender-specific stress effects. The current study used functional magnetic resonance imaging (fMRI) to determine whether induced stress resulted in gender-specific patterns of brain activation during a decision task involving monetary reward. Specifically, we manipulated physiological stress levels using a cold pressor task, prior to a risky decision making task. Healthy men (n = 24, 12 stressed) and women (n = 23, 11 stressed) completed the decision task after either cold pressor stress or a control task during the period of cortisol response to the cold pressor. Gender differences in behavior were present in stressed participants but not controls, such that stress led to greater reward collection and faster decision speed in males but less reward collection and slower decision speed in females. A gender-by-stress interaction was observed for the dorsal striatum and anterior insula. With cold stress, activation in these regions was increased in males but decreased in females. The findings of this study indicate that the impact of stress on reward-related decision processing differs depending on gender.

Sex/gender differences and autism: setting the scene for future research

Objective The relationship between sex/gender differences and autism has attracted a variety of research ranging from clinical, neurobiological to etiological, stimulated by the male bias in autism prevalence. Findings are complex and do not always relate to each other in a straightforward manner. Distinct but interlinked questions on the relationship between sex/gender differences and autism remain under addressed. To better understand the implications from existing research and to help design future studies, we propose a four-level conceptual framework to clarify the embedded themes. Method We searched PubMed for publications before September 2014 using search terms “‘sex OR gender OR females’ AND autism.” 1,906 citations were screened for relevance, along with publications identified via additional literature reviews, resulting in 329 reports that were reviewed. Results Level 1 “Nosological and diagnostic challenges” concerns the question “How should autism be defined and diagnosed in males and females?” Level 2 “Sex/gender-independent and sex/gender-dependent characteristics” addresses the question “What are the similarities and differences between males and females with autism?” Level 3 “General models of etiology: liability and threshold” asks the question “How is the liability for developing autism linked to sex/gender?” Level 4 “Specific etiological-developmental mechanisms” focuses on the question “What etiological-developmental mechanisms of autism are implicated by sex/gender and/or sexual/gender differentiation?” Conclusions Using this conceptual framework, findings can be more clearly summarized, and the implications of the links between findings from different levels can become clearer. Based on this four-level framework, we suggest future research directions, methodology, and specific topics in sex/gender differences and autism.