Study Investigated Sex Differences Research Articles

SEX DIFFERENCES IN THE ASSOCIATION BETWEEN BODY COMPOSITION AND 2-YEAR CHANGE IN COGNITIVE FUNCTION

Abstract In the process of aging, the loss of lean mass and increase in fat mass are associated with cognitive decline. This study investigated sex differences in the association between body composition and changes in cognitive function in community-dwelling older adults in Korea. A total of 1,420 participants (aged 70–84 years, 54.2% men) of the Korean Frailty and Aging Cohort Study with data from baseline and 2-year follow-up surveys were included. Body composition was measured using dual-energy X-ray absorptiometry and cognitive function was assessed using the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease Assessment Packet. The total fat mass was lower in men than in women (p< 0.001), whereas total lean mass was higher in men than in women (p< 0.001). Total body fat mass was positively associated with the time taken to finish the Trail Making Test-A only in women (standardized beta coefficient [ß]= -1.371, p=0.018), and a negative association was observed between trunk fat mass and digit span total only in men (ß= -0.092, p=0.039). Appendicular lean mass was significantly positively associated with word list recognition only in women (ß=0.087, p=0.010) and was significantly positively associated with digit span total (ß=0.108, p=0.027) and digit span forward (ß=0.081, p=0.025) only in men. The results of this study indicated that higher fat mass was associated with the protection of decline in cognitive function only in women, while lean mass was positively associated with a change in cognitive function in both sexes.

Sex differences in the sustained attention of elementary school children

BackgroundThe study investigates sex differences in sustained attention among children.MethodsForty-five children (23 girls) from Grades 2–5 (mean age of 7.47 ± 0.73 years) wore an actigraph for a continuous five to seven days including school and non-school days. Sustained attention using the psychomotor vigilance test (PVT) was measured twice a day on two school days and on one non-school day.ResultsNo sex differences were found for sleep patterns. However, sex differences in PVT performance were documented. While boys were faster (shorter reaction time) and showed fewer lapses than girls, they showed higher number of false starts than girls, on both weekdays and weekends.ConclusionsThe findings suggest that sex differences should been taken into account in studies investigating neurobehavioral functioning, particularly, sustained attention across various age groups.

Sex differences in cardiovascular risk factor responses to resistance and endurance training in younger subjects.

This study compared differences in cardiovascular (CV) risk factor responses between males and females following endurance (END) and resistance (RES) training. We present the frequency of responders to each training modality and the magnitude of response. Using a randomized crossover design, 68 healthy adults [age: female (F): 24.5 ± 4.6; male (M): 27.3 ± 6.6] completed 3 mo of RES and END, with 3 mo washout. Peak oxygen consumption (V̇o2peak), strength, body composition, blood pressure, glucose, insulin, and lipids were measured. V̇o2peak (L/min) significantly increased in both sexes following END, but not RES. The magnitude of change was larger in males (F: +0.20 L/min; M: +0.32 L/min), although this did not achieve statistical significance (P = 0.051). Strength significantly increased in both sexes following RES (P < 0.01), with a larger increase in males (Leg press: F: +39 kg; M: +63 kg; P < 0.05). Lean mass significantly increased in both sexes (P < 0.01) following RES and fat mass decreased in females following END (P = 0.019). The change in C-reactive protein following END was significantly different between sexes (F: -0.4 mg/L; M: +0.5 mg/L; P = 0.035). There were no differences between sexes in the proportion of individuals who responded positively to any variable following RES or END; differences between sexes were due to the magnitude of change. Males had a larger increase in V̇o2peak following END and strength following RES. There were no sex differences in other CV risk factors. This suggests differences in physiological responses to strength and V̇o2peak may not translate to changes in CV risk in healthy subjects.NEW & NOTEWORTHY This study investigated sex differences in cardiovascular risk factors in response to different exercise training modalities. Males had a larger improvement in peak oxygen consumption following endurance training and strength following resistance training compared with females. These changes in peak oxygen consumption and strength did not translate to changes in other cardiovascular risk factors. Despite the greater magnitude of change in males, there were no sex differences in the proportion of individuals who responded to training.

Does Sex Matter in Liver Surgery? Comparison of Severity Assessments between Female and Male Rats after Partial Hepatectomy: A Pilot Study

Introduction: Current animal-based biomedical research, including studies on liver function and disease, is conducted almost exclusively on male animals to mitigate confounding effects of the estrous cycle. However, liver diseases afflict both men and women, so translational research findings should also be applicable to female patients. This pilot study investigated sex differences in objective and subjective severity assessment parameters in rats following 50% partial hepatectomy. Materials and Methods: This study was performed using Wistar Han rats, in which measurements of body weight, spontaneous motor activity in the open field (OF) (movement distance, movement velocity, rearing frequency), and fecal corticosterone metabolites were conducted at baseline and at multiple times after partial hepatectomy. Subjective postsurgical severity assessments were conducted using modified score sheets. Blood parameters such as leukocyte count and serum aspartate aminotransferase, as well as estrogens and testosterone were measured from samples obtained during partial hepatectomy and at sacrifice. In addition, the amount of resected liver tissue was measured at partial hepatectomy, and the proliferated liver was weighed at sacrifice. Results: Fecal corticosterone metabolite concentrations differed significantly between males and females at baseline and following hepatectomy. Also, leukocyte counts and estrogen concentrations were significantly different between sexes before partial hepatectomy. Alternatively, there were no sex differences in severity assessments, body weight changes, and behavior in the OF at any measurement time point. Liver weight was significantly different in males and females at the time point of partial hepatectomy and sacrifice. Conclusion: The results of this pilot study suggest that males and females respond similarly following partial hepatectomy. Examination of both sexes is very important for translation to humans, where both men and women suffer from liver disease. Furthermore, the use of both sexes in animal-based research would improve the utilization of the animal breeding in terms of the 3 Rs. However, due to some limitations, larger scale investigations including a broader spectrum of pathophysiolological, behavioral, and pharmacokinetic measures are planned.

Sex differences in personality disorders in a Chinese clinical population.

IntroductionSex differences in the frequency and severity of personality disorders (PDs) have been widely reported in Western countries. However, limited literature suggests a similar sex distribution in the Chinese clinical population. This study investigated sex differences in self-reported and interviewed patients with PDs in a clinical population in China.Materials and methodsThe participants were 1,389 consecutive outpatients with a mean age of 30.5 years, including 634 (45.6%) males and 755 (54.4%) females. Self-reported PD traits were assessed using the Personality Diagnostic Questionnaire Fourth Edition Plus (PDQ-4+). PDs were diagnosed according to the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Axis II (SCID-II).ResultsMale outpatients reported more paranoid, schizotypal, antisocial, and passive-aggressive PD traits, whereas females reported more borderline PD traits on the PDQ-4+. Self-reported PD traits in male outpatients were more likely to reach the positive threshold of antisocial PD than in females (χ2 = 5.293, p = 0.021). Males were more likely to meet the criteria for schizoid (χ2 = 5.050, p = 0.025), narcissistic (χ2 = 27.244, p < 0.001), antisocial (χ2 = 11.430, p = 0.001), avoidant (χ2 = 5.098, p = 0.024), and obsessive-compulsive PD (χ2 = 5.496, p = 0.019) diagnoses in the SCID-II. In contrast, females were more likely to meet the criteria of histrionic (χ2 = 12.327, p = 0.001), borderline (χ2 = 28.538, p < 0.001), and dependent (χ2 = 4.919, p = 0.027) diagnoses.DiscussionThese findings indicate gender differences in the traits, frequency, and pattern of PDs when assessed in a Chinese clinical population.

Stress and sex-dependent effects on conditioned inhibition of fear.

Anxiety and stress-related disorders are highly prevalent and are characterized by excessive fear to threatening and nonthreatening stimuli. Moreover, there is a large sex bias in vulnerability to anxiety and stress-related disorders-women make up a disproportionately larger number of affected individuals compared with men. Growing evidence suggests that an impaired ability to suppress fear in the presence of safety signals may in part contribute to the development and maintenance of many anxiety and stress-related disorders. However, the sex-dependent impact of stress on conditioned inhibition of fear remains unclear. The present study investigated sex differences in the acquisition and recall of conditioned inhibition in male and female mice with a focus on understanding how stress impacts fear suppression. In these experiments, the training context served as the "fear" cue and an explicit tone served as the "safety" cue. Here, we found a possible sex difference in the training requirements for safety learning, although this effect was not consistent across experiments. Reductions in freezing to the safety cue in female mice were also not due to alternative fear behavior expression such as darting. Next, using footshock as a stressor, we found that males were impaired in conditioned inhibition of freezing when the stress was experienced before, but not after, conditioned inhibition training. Females were unaffected by footshock stress when it was administered at either time. Extended conditioned inhibition training in males eliminated the deficit produced by footshock stress. Finally, exposing male and female mice to swim stress impaired safety learning in male mice only. Thus, we found sex × stress interactions in the learning of conditioned inhibition and sex-dependent effects of stress modality. The present study adds to the growing literature on sex differences in safety learning, which will be critical for developing sex-specific therapies for a variety of fear-related disorders that involve excessive fear and/or impaired fear inhibition.

Sex-related differences in violence exposure, neural reactivity to threat, and mental health.

The prefrontal cortex (PFC), hippocampus, and amygdala play an important role in emotional health. However, adverse life events (e.g., violence exposure) affect the function of these brain regions, which may lead to disorders such as depression and anxiety. Depression and anxiety disproportionately affect women compared to men, and this disparity may reflect sex differences in the neural processes that underlie emotion expression and regulation. The present study investigated sex differences in the relationship between violence exposure and the neural processes that underlie emotion regulation. In the present study, 200 participants completed a Pavlovian fear conditioning procedure in which cued and non-cued threats (i.e., unconditioned stimuli) were presented during functional magnetic resonance imaging. Violence exposure was previously assessed at four separate time points when participants were 11-19 years of age. Significant threat type (cued versus non-cued) × sex and sex × violence exposure interactions were observed. Specifically, women and men differed in amygdala and parahippocampal gyrus reactivity to cued versus non-cued threat. Further, dorsolateral PFC (dlPFC) and inferior parietal lobule (IPL) reactivity to threat varied positively with violence exposure among women, but not men. Similarly, threat-elicited skin conductance responses varied positively with violence exposure among women. Finally, women reported greater depression and anxiety symptoms than men. These findings suggest that sex differences in threat-related brain and psychophysiological activity may have implications for mental health.

Sex-related differences in somatic plasticity and possible role of ERK1/2: An in-vivo study of young-adult rats

The present study investigates sex differences in hippocampal functions in the context of synaptic plasticity, which is the cellular basis of learning and memory, and differences in the mitogen-activated protein kinase (MAPK) pathway that accompanies plasticity in young-adult rats. The long-term potentiation (LTP) and long-term depression (LTD) were induced by stimulating the perforant pathway (PP) and field potentials composed of the field excitatory post-synaptic potential (fEPSP) and population spike (PS) were recorded from the dentate gyrus (DG). Following the completion of the electrophysiological recordings, the hippocampi were removed bilaterally, and the protein and gene expression levels of the extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK) and P38-MAPK were determined by Western blot analysis and real-time PCR, respectively. No significant difference was found in synaptic and neuronal function before (basal) and after high-frequency stimulation between male and female rats. Nevertheless, female, but not male, rats were able to express long term depression at the PP – DG synapses, suggesting that sex differences in plasticity are stimulation paradigm specific. MAPK1 expression was higher in males and MAPK3 expression was higher in females, but these differences disappeared after induction of plasticity in both sexes. While the expression of MAPK8 is influenced by sex, independent of the induction of plasticity, MAPK14 expression was down regulated by plasticity induction in females, but not males. No effect of sex, HFS and LFS on total and phosphorylated levels of MAPKs was found except phosphorylated ERK1/2. Phosphorylation of ERK1/2 was up regulated after LFS in male rats but did not change in female rats. These findings indicate that LFS-induced plasticity is differentially modulated between sexes, probably as a result of increased activation of ERK1/2 in male rats.

Sex differences in motor unit behaviour: A review

The lack of systematic investigations on sex-related differences in motor unit behaviour poses a challenge in understanding and optimizing health and performance in males and females. Limited investigations revealed that sex differences in motor unit behaviour might be present in human muscles. This review summarizes the current knowledge on sex differences in motor unit behaviour and potential factors that may contribute to these differences. We show significant under-representation of female participants in motor unit studies and a limited number of studies investigating sex differences in motor unit behaviour. We place the current insights within the context of methodological limitations and outline several recommendations and future directions to improve female representation in this research area. We conclude that there is an urgent need to gather more data in females and investigate sex differences in motor unit behaviour. The knowledge gained could be used to develop sex-specific approaches to improve neuromuscular performance and rehabilitation.

Sex Differences in Demographic and Pharmacological Factors in Alzheimer Patients With Dementia and Cognitive Impairments.

ObjectiveThe current study investigates sex differences associated with pharmacological and demographic characteristics in Alzheimer patients (AD) with dementia (ADD) or mild cognitive impairment (MCI).MethodA retrospective analytical approach was used to analyze data from 45,696 AD patients with MCI or ADD. The univariate analysis was used to determine differences in demographic, and pharmacological characteristics for male and female ADD and MCI-AD patients. Multivariate analysis was used to predict specific pharmacological and demographic factors that are associated with male and female MCI and ADD patients.ResultIn the adjusted analysis for male patients, Hispanics [0.166,0.020 – 1.355, P = 0.094] or African Americans [OR = 2.380, 95% CI,2.120 – 2.674, P < 0.001], were more likely to have MCI-AD and be treated with galantamine [OR = 0.559, 95% CI, 0.382 – 0.818, P = 0.003], donepezil [OR = 1.639, 95% CI,1.503 – 1.787, P < 0.001], rivastigmine [OR = 1.394, 95% CI,1.184 – 1.642, P < 0.001], olanzapine [OR = 2.727, 95% CI,2.315 – 3.212, P < 0.001], risperidone [OR = 2.973, 95% CI,2.506 – 3.526, P < 0.001], present with increasing age [1.075,1.071 – 1.079, P < 0.001], and are on tobacco use [OR = 1.150, 95% CI,1.054 – 1.254, P = 0.002]. For female patients, buspirone [OR = 0.767, 95% CI, 0.683 – 0.861, P < 0.001] and a history of alcohol (ETOH) use [OR = 0.484, 95% CI, 0.442 – 0.529, P < 0.001] were associated with MCI-AD. Increasing age [OR = 1.096, 95% CI, 1.093 – 1.100, P < 0.001], donepezil [OR = 2.185, 95% CI, 2.035 – 2.346, P < 0.001], memantine [OR = 2.283, 95% CI, 2.104 – 2.477, P < 0.001] aripiprazole [OR = 1.807, 95% CI, 1.544 – 2.113, P < 0.001] olanzapine [OR = 2.289, 95% CI, 1.986 – 2.640, P < 0.001] risperidone [OR = 2.548, 95% CI, 2.246 – 2.889, P < 0.001] buspirone [OR = 0.767, 95% CI, 0.683 – 0.861, P < 0.001] escitalopram [OR = 1.213, 95% CI,1.119 – 1.315, P < 0.001] African Americans [OR = 1.395, 95% CI, 1.268 – 1.535, P < 0.001] and tobacco use [OR = 1.150, 95% CI, 1.073 – 1.233, P < 0.001] were associated with ADD.ConclusionOur findings reveal that MCI-AD patients were more likely to be Hispanics or African American males treated with rivastigmine, olanzapine and citalopram. African American females were associated with ADD and more likely to be treated with buspirone and presented with a history of ETOH. This finding suggests the need for a pharmacological treatment approach encompassing sex-sensitive strategies for MCI-AD and ADD patients.

Differences between Elite Male and Female Badminton Athletes Regarding Heart Rate Variability, Arterial Stiffness, and Aerobic Capacity.

Cardiovascular health and aerobic capacity play crucial roles in determining the performance of athletes in the highly competitive sport of badminton. Few studies have directly compared heart rate variability (HRV), arterial stiffness, and aerobic capacity between male and female athletes, especially among badminton athletes. This study investigated sex differences in HRV, arterial stiffness, and aerobic capacity in badminton athletes. Elite badminton athletes were recruited and divided into male (n = 20, 21.0 ± 1.8 years old) and female (n = 16, 21.2 ± 2.3 years old) groups. Both groups performed an incremental treadmill running test for the evaluation of maximal oxygen consumption (O2max), anaerobic threshold, and time to exhaustion. They started exercising at a treadmill speed of 2.7 km/h and an inclination of 10% gradient for 3 min, and the speed and inclination were gradually increased every 3 min until they were exhausted or fatigued volitionally. HRV was examined using the Polar heart rate monitor over a period of 5 min at rest in the supine position. Subsequently, the index of arterial stiffness was examined under the same condition. Our results revealed significant differences between the male and female athletes in O2max (men: 60.38 ± 8.98 mL/kg/min, women: 48.13 ± 7.72 mL/kg/min, p < 0.05), anaerobic threshold (men: 41.50 ± 7.26 mL/kg/min, women: 32.51 ± 6.19 mL/kg/min, p < 0.05), time to exhaustion (men: 902.15 ± 120.15 s, women: 780.56 ± 67.63 s, p < 0.05), systolic blood pressure (men: 125.27 ± 7.76 mmHg, women: 107.16 ± 11.09 mmHg, p < 0.05), and arterial stiffness index (men: 63.56 ± 12.55, women: 53.83 ± 8.03, p < 0.05). However, no significant differences in HRV measures were observed between the two groups. These findings suggested that the male badminton athletes demonstrated significantly higher aerobic capacity than did the female athletes, but there were no significant differences in HRV measures. The female athletes exhibited superior arterial function, compared with their male counterparts.

Sex-specific differences in the metabolic enzyme activity and transporter levels in mouse skeletal muscle during postnatal development.

Although sex-associated differences in energy metabolism in adults are well-characterized, developmental sex-specific changes in skeletal muscle metabolism are largely unknown. This study investigated sex differences in high-energy phosphate, glycolytic, and mitochondrial enzyme activities and metabolite transporter protein levels in mouse skeletal muscles during the early postnatal period (day 10), post-weaning (day 28), sexual maturity (day 56), and adult life (day 140). No significant sex-specific differences were observed on days 10 and 28, except for glucose transporter (GLUT) 4 level. The hexokinase, phosphofructokinase, and lactate dehydrogenase activities of skeletal muscle were higher and the citrate synthase, cytochrome c oxidase, and β-hydroxyacyl-CoA dehydrogenase activities were lower in female mice than those in male mice on days 56 and 140. The GLUT4 and FAT/CD36 protein levels were higher and the monocarboxylate transporter 4 level was lower in the skeletal muscles of female mice than those of male mice, particularly on days 56 and 140. At 140 days of age, the respiratory exchange ratio during treadmill running (15m/min, 60min) was lower in females than that in males, despite no sex differences at rest. In summary, sex differences were not evident in the early postnatal and post-weaning periods but became apparent after the mice reached sexual maturity. These findings indicate that sexually mature animals are a better model for investigating sex differences, particularly in the context of studying energy metabolism in mice.

Androgens and Parkinson's Disease: A Review of Human Studies and Animal Models.

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. A greater prevalence and incidence of PD are reported in men than in women, suggesting a potential contribution of sex, genetic difference and/or sex hormones. This review presents an overview of epidemiological and clinical studies investigating sex differences in the incidence and symptoms of PD. This sex difference is replicated in animal models of PD showing an important neuroprotective role of sex steroids. Therefore, although gender and genetic factors likely contribute to the sex difference in PD, focus here will be on sex hormones because of their neuroprotective role. Androgens receive less attention than estrogen. It is well known that endogenous androgens are more abundant in healthy men than in women and decrease with aging; lower levels are reported in PD men than in healthy male subjects. Drug treatments with androgens, androgen precursors, antiandrogens, and drugs modifying androgen metabolism are available to treat various endocrine conditions, thus having translational value for PD but none have yet given sufficient positive effects for PD. Variability in the androgen receptor is reported in humans and is an additional factor in the response to androgens. In animal models of PD used to study neuroprotective activity, the androgens testosterone and dihydrotestosterone have given inconsistent results. 5α-Reductase inhibitors have shown neuroprotective activity in animal models of PD and antidyskinetic activity. Hence, androgens have not consistently shown beneficial or deleterious effects in PD but numerous androgen-related drugs are available that could be repurposed for PD.

Sex differences in behavior, response to LPS, and glucose homeostasis in middle-aged mice

Sex and age have distinct influences and roles in behavior and immune reactivity; yet, most studies use adult male rodents with little attention to middle age, a time associated with key physiological transitions in both sexes. Thus, this study investigated sex differences during middle age in behavior, immune response to lipopolysaccharide (LPS), and glucose regulation in C57BL/6 mice with GFP-tagged monocytes/microglia. Behaviorally, males performed better in tests of motor function (Open Field [OF], Grip Strength, Sticker Removal, Gait, and Pole tests) and displayed less depressive- and anxiety-like behaviors across multiple mood tests (OF, Elevated Zero Maze, Sucrose Preference, and Swim test). However, females performed better in tests of cognition (Barnes Maze and Novel Object Recognition). Following behavioral assessment, mice were given LPS to characterize sex-dependent inflammagen responses. Females displayed greater sickness behavior in the OF, higher levels of peripheral cytokines, and subtle neuroinflammation in the cortex, striatum, and hippocampus. A separate middle-aged cohort was used for glucose tolerance and insulin sensitivity testing. Both sexes had excessive blood glucose rebound after insulin challenge, but displayed differences following glucose administration, where males had higher baseline glucose and females remained hyperglycemic. This study suggests that during middle-age male mice have better emotional regulation and motor function, but not cognitive ability than females. Further, males are less sensitive than females to the acute effects of LPS peripherally and centrally, but both sexes showed sex-specific impairments in blood glucose regulation. Overall, it appears that middle age is an important transition point with multiple sex differences, some of which are unique to this stage of life.

Changing sex differences in undernutrition of African children: findings from Demographic and Health Surveys.

The study investigates sex differences in the prevalence of undernutrition in sub-Saharan Africa. Undernutrition was defined by Z-scores using the CDC-2000 growth charts. Some 128 Demographic and Health Surveys (DHS) were analysed, totalling 700,114 children under-five. The results revealed a higher susceptibility of boys to undernutrition. Male-to-female ratios of prevalence averaged 1.18 for stunting (height-for-age Z-score <-2.0); 1.01 for wasting (weight-for-height Z-score <-2.0); 1.05 for underweight (weight-for-age Z-score <-2.0); and 1.29 for concurrent wasting and stunting (weight-for-height and height-for-age Z-scores <-2.0). Sex ratios of prevalence varied with age for stunting and concurrent wasting and stunting, with higher values for children age 0-23 months and lower values for children age 24-59 months. Sex ratios of prevalence tended to increase with declining level of mortality for stunting, underweight and concurrent wasting and stunting, but remained stable for wasting. Comparisons were made with other anthropometric reference sets (NCHS-1977 and WHO-), and the results were found to differ somewhat from those obtained with CDC-2000. Possible rationales for these patterns are discussed.

Revealing Sex Differences During Upper and Lower Extremity Neuromuscular Fatigue in Older Adults Through a Neuroergonomics Approach.

Background: Sex differences in neuromuscular fatigue is well-documented, however the underlying mechanisms remain understudied, particularly for the aging population. Objective: This study investigated sex differences in fatigability of the upper and lower extremity of older adults using a neuroergonomics approach. Methods: Thirty community-dwelling older adults (65 years or older; 15 M, 15 F) performed intermittent submaximal fatiguing handgrip and knee extension exercises until voluntary exhaustion on separate days. Muscle activity from prime muscles of the hand/arm and knee extensors were monitored using electromyography, neural activity from the frontal, motor, and sensory areas were monitored using functional near infrared spectroscopy, and force output were obtained. Results: While older males were stronger than females across both muscle groups, they exhibited longer endurance times and greater strength loss during knee extension exercises. These lower extremity findings were associated with greater force complexity over time and concomitant increase in left motor and right sensory motor regions. While fatigability during handgrip exercises was comparable across sexes, older females exhibited concurrent increases in the activation of the ipsilateral motor regions over time. Discussion: We identified differences in the underlying central neural strategies adopted by males and females in maintaining downstream motor outputs during handgrip fatigue that were not evident with traditional ergonomics measures. Additionally, enhanced neural activation in males during knee exercises that accompanied longer time to exhaustion point to potential rehabilitation/exercise strategies to improve neuromotor outcomes in more fatigable older adults.

How do lipids influence risk of violence, self-harm and suicidality in people with psychosis? A systematic review.

Objectives:Low cholesterol has been linked with violent and suicidal behaviour in people with schizophrenia. This association, if consistently present, may be a promising biological marker that could assist clinicians in decision making regarding risk and treatment. We conducted a systematic review to assess whether there is a reliable association between lipid profile (total cholesterol, high- and low-density lipoprotein cholesterol, and triglycerides) and aggression, self-harm or suicide in people with schizophrenia, and whether effects are similar in males and females.Method:Relevant databases were searched to identify primary research studies (up to November 2020) that (1) involved adults (some samples also included 16- to 18-year olds) with a confirmed diagnosis of schizophrenia, schizoaffective disorder or psychosis; and (2) included a standardised assessment of verbal aggression, physical aggression against objects, physical aggression against self (including suicide) or others. The search yielded 23 studies eligible for inclusion following a quality appraisal.Results:Suicidality was the most commonly assessed subtype of aggression (20 studies). For suicidality, about half the studies, including the study with the largest sample size, found a link with total cholesterol. An association between low total cholesterol and violence towards others was found in six of nine studies that investigated this. The evidence for a link with violence was the strongest for total cholesterol, followed by low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, and the weakest for triglycerides. Only a few studies investigated sex differences and yielded mixed evidence. Studies focussed on self-harm as well as involving females in forensic settings were lacking.Conclusion:There is encouraging evidence of an association between low total cholesterol and aggression towards others as well as suicidality in schizophrenia. Future studies should systematically explore this association in people with schizophrenia who have a significant history of violence, suicidality and self-harm, both inpatients and community, and also investigate underlying mechanisms.

Sex Differences in the Relationships between Forms of Peer Victimization and Reactive and Proactive Aggression in Schoolchildren.

The original study investigated sex differences in the relationships between multiple forms of peer victimization (physical victimization, verbal victimization, and social exclusion) and subtypes of aggression (reactive aggression and proactive aggression) in schoolchildren. A self-report questionnaire assessing levels of peer victimization and aggression was administered to 3790 schoolchildren (1916 males and 1874 females) aged 11 to 17 (M = 13.19; SD = 1.17) from 10 middle schools in Hong Kong. The pure effect of each subtype of aggression were evaluated by statistically controlling for another subtype of aggression in analyses. Furthermore, participants were classified as non-aggressors, reactive aggressors, proactive aggressors, and reactive–proactive aggressors to investigate their differences in specific forms of peer victimization. Data were analyzed by hierarchical linear regression and ANOVA. The results showed: (1) Sex significantly moderated the relationship between specific forms of peer victimization and subtypes of aggression; (2) In males, reactive aggression was positively predicted by verbal victimization; proactive aggression was positively predicted by physical victimization and social exclusion, and negatively predicted by verbal victimization; (3) In females, reactive aggression was positively predicted by physical victimization and social exclusion; proactive aggression was negatively predicted by social exclusion; and (4) Reactive–proactive aggressors reported more physical victimization than other types of aggressors. The findings have significant implications for distinctive functions of reactive and proactive aggression and the need to develop differentiated interventions for male and female schoolchildren.

The development and maintenance of sex differences in dietary breadth and complexity in Bornean orangutans

Orangutans show a pronounced sexual dimorphism, with flanged males (i.e., males with fully grown secondary sexual characteristics) reaching twice the size of adult females. Furthermore, adult orangutans show sex-specific dispersal and activity patterns. This study investigates sex differences in adult foraging behavior and sheds light on how these differences develop in immatures. We analyzed 11 years of feeding data on ten adult female, seven flanged male, and 14 immature Bornean orangutans (Pongo pygmaeus wurmbii) at Tuanan in Central Kalimantan, Indonesia. We found that the diets of the adult females were significantly broader and required more processing steps before ingestion than the diets of flanged males. We also found evidence for a similar difference in overall diet repertoire sizes. For the immatures, we found that whereas females reached 100% of their mothers’ diet spectrum size by the age of weaning, males reached only around 80%. From the age of 4 years on (i.e., years before being weaned) females had significantly broader daily diets than males. We found no difference in daily or overall diet processing intensity of immature males and females but found preliminary evidence that immature males included fewer items of their mother’s diet in their own diets that were processing-intensive. Overall, our results suggest that by eating a broader variety and more complex to process food items, female orangutans go to greater lengths to achieve a balanced diet than males do. These behavioral differences are not just apparent in adult foraging behavior but also reflected in immature development from an early age on.Significance StatementIn many species, males and females have different nutritional needs and are thus expected to show sex-specific foraging behavior. Sex differences in several aspects of foraging behavior have been found in various species, but it remains largely unclear when and how those develop during ontogeny, which is especially relevant for long-lived altricial species that learn foraging skills over many years. In our study, we analyzed a cross-sectional and longitudinal data set containing more than 750,000 feeding events of adult and immature Bornean orangutans (Pongo pygmaeus wurmbii). We found that adult females had significantly broader and more complex diets than males. We also found that these differences started to develop during infancy, suggesting that immature orangutans prepare for their sex-specific foraging niches long before those become physiologically relevant while they are still in constant association with their mothers and before being frequently exposed to other role models.

Sex differences in effort-related decision-making: role of dopamine D2 receptor antagonism.

Depressed individuals demonstrate debilitating symptoms, including depressed mood, anhedonia, and effort-related deficits. Effort-related decision-making can be measured through providing subjects with a choice between high effort/reward and low effort/reward options, which is a dopamine (DA)-dependent behavior. While previous research has shown sex differences in depression rates, this has not been examined within operant-based effort-related decision-making tasks nor has DA been shown to underlie this behavior in female rats. The current study investigated sex differences in an effort-related decision-making task prior to and following administration of the DA D2 receptor antagonist haloperidol (HAL). Adult rats were food restricted or fed freely and trained in an effort-related progressive ratio choice task. After stable responding, HAL was administered acutely (0.05-0.2 mg/kg) prior to testing. Results indicate a significant effect of sex on training variables, with males having a greater number of lever presses, higher ratios, and longer active lever times. Pretreatment with HAL significantly reduced the same measures in both sexes for the high-valued reward, while increasing chow consumption in the food restricted males. Food restricted rats showed a greater number of total lever presses and achieved higher ratios; however, the effect in male food restricted rats was greatest. These data suggest that, although there are sex differences in training, HAL decreases behavior across sexes, demonstrating that the D2 mechanism is similar in both sexes. These findings provide a better understanding of motivational dysfunction in both sexes and potential treatment targets for depression.