Sex/gender differences in the brain and cognition in schizophrenia

The early conceptualizations of schizophrenia have noted some sex/gender differences in epidemiology and clinical expression of the disorder. Over the past few decades, the interest in differences between male and female patients has expanded to encompass brain morphology and neurocognitive function. Despite some variability and methodological shortcomings, a few patterns emerge from the available literature. Most studies of gross neuroanatomy show more enlarged ventricles and smaller frontal lobes in men than in women with schizophrenia; finding reflecting normal sexual dimorphism. In comparison, studies of brain asymmetry and specific corticolimbic structures, suggest a disturbance in normal sexual dimorphism. The neurocognitive findings are somewhat consistent with this picture. Studies of cognitive functions mediated by the lateral frontal network tend to show sex differences in patients which are in the same direction as those observed in the general population, whereas studies of processes mediated by the corticolimbic system more frequently reveal reversal of normal sexual dimorphisms. These trends are faint and future research would need to delineate neurocognitive differences between men and women with various subtypes of schizophrenia (e.g., early versus late onset), while taking into consideration hormonal status and gender of tested participants.     

Sex differences during humor appreciation in child-sibling pairs

The developmental origin of sex differences in adult brain function is poorly understood. Elucidating neural mechanisms underlying comparable cognitive functionality in both children and adults is required to address this gap. Humor appreciation represents a particularly relevant target for such developmental research because explanatory theories apply across the life span, and underlying neurocircuitry shows sex differences in adults. As a positive mood state, humor is also of interest due to sex differences in rates of depression, a disorder afflicting twice as many women as men. In this study, we employed functional magnetic resonance imaging (fMRI) to investigate brain responses to funny versus positive (and neutral) video clips in 22 children, ages 6–13 years, including eight sibling-pairs. Our data revealed increased activity to funny clips in bilateral temporo-occipital cortex, midbrain, and amygdala in girls. Conversely, we found heightened activation to positive clips in bilateral inferior parietal lobule, fusiform gyrus, inferior frontal gyrus, amygdala, and ventromedial prefrontal cortex in boys. Many of these effects persisted when looking at sibling-pairs only. We interpret such findings as reflecting the presence of early sex divergence in reward saliency or expectation and stimulus relevance attribution. These findings are discussed in the context of evolutionary and developmental theories of humor function.     

Sex differences in animal models of schizophrenia shed light on the underlying pathophysiology

Sex differences in schizophrenia are apparent in almost all features of the illness, from incidence and mean age of onset to symptomatology, course of illness and response to pharmacological treatments. Understanding how men and women with schizophrenia differ provides significant clues into the pathophysiology of the disorder. Animal models are powerful tools when dissecting the molecular biology which underlies behavioural disturbances, and allow structured comparisons of biological sex differences without the social environmental gender influence that so often confounds human sex comparison studies. This review will provide a summary of sex differences described in developmental, genetic and drug-induced animal models of schizophrenia and will link sex-specific molecular and behavioural phenotypes of these models in an attempt to unravel the role that sex plays in the pathophysiology of schizophrenia. Both sex and stress hormones interact to shape the developing brain and behaviour and animal models of schizophrenia that include both sexes provide significant insight into the complexities of these interactions and can direct toward novel therapeutic strategies.     

Sex differences in cognitive impairment in Alzheimer’s disease

Sex differences in neurocognitive abilities have been extensively explored both in the healthy population and in many disorders. Until recently, however, little work has examined such differences in people with Alzheimer’s disease (AD). This is despite clear evidence that AD is more prevalent in women, and converging lines of evidence from brain imaging, post-mortem analyses, hormone therapy and genetics suggesting that AD affects men and women differently. We provide an overview of evidence attesting to the poorer cognitive profiles in women than in men at the same stage of AD. Indeed, men significantly outperform women in several cognitive domains, including: Language and semantic abilities, visuospatial abilities and episodic memory. These differences do not appear to be attributable to any differences in age, education, or dementia severity. Reasons posited for this female disadvantage include a reduction of estrogen in postmenopausal women, greater cognitive reserve in men, and the influence of the apolipoprotein E ε4 allele. Assessment of cognitive abilities contributes to the diagnosis of the condition and thus, it is crucial to identify the role of sex differences if potentially more accurate diagnoses and treatments are to emerge.     

Sex differences in cocaine- and nicotine-induced antinociception in the rat

Several recent reports describe sex differences in opioid antinociception. The present study examined sex differences in stimulant-induced antinociception. On the 50°C hotplate test, cocaine (0.1–1.0 μg i.c.v.) produced dose- and time-dependent increases in response latency in male but not female Sprague–Dawley rats. In contrast, nicotine (3–30 μg i.c.v.) produced increases in hotplate latency in both sexes, but produced greater effects in females; nicotine also decreased spontaneous locomotor activity significantly more in females than in males. These sex differences probably are not due to differential pharmacokinetics, and underscore the importance of including female subjects in experimental drug research.     

Sex differences in drug addiction and response to exercise intervention: From human to animal studies

Accumulated research supports the idea that exercise could be an option of potential prevention and treatment for drug addiction. During the past few years, there has been increased interest in investigating of sex differences in exercise and drug addiction. This demonstrates that sex-specific exercise intervention strategies may be important for preventing and treating drug addiction in men and women. However, little is known about how and why sex differences are found when doing exercise-induced interventions for drug addiction. In this review, we included both animal and human that pulled subjects from a varied age demographic, as well as neurobiological mechanisms that may highlight the sex-related differences in these potential to assess the impact of sex-specific roles in drug addiction and exercise therapies.     

Usage de Jeux de hasard et d’argent et d’Internet dans une population de patients en demande de soins en addictologie–Étude multicentrique

BackgroundTransversal grouping of addictions under the heading “Substance related and addictive disorders” in the DSM-5 has led to a common policy on addictions and the promotion of addiction services covering all types of addictions, including behavioral addictions.Material and methodsThe main objective of this study was to describe the prevalence of problem gambling in a population of patients seeking treatment in addictive disorders center. Secondary objectives were: to describe the use of Internet and the prevalence of gaming disorder, sexual addiction and compulsive buying online ; to describe a population of patients consulting in addictive disorders center; to explore associated factors related to problem gambling. A self-questionnaire was built, evaluating the socio-demographic elements, the addiction pathway, problem gambling and Internet use with a focus on video game disorder, sexual addiction and compulsive buying. It was offered to consultants from five addictology centers in Brittany.Results252 patients seeking treatment for addictive disorders were included. Problem gambling was present in 9.9 % of patients. Problem gamblers were more likely to have been asked about their gambling by the addictology team than other patients. The rate of identification of gambling habits, whether in addiction or outside, was generally low. Internet use was 83 %. The prevalence of other online behavioral addictions was low.Discussion and conclusionThe prevalence of problem gambling is almost 4 times higher among addictology consultants, compared to the general population, probably related to addictive comorbidities. The identification of gambling habits concerned a small proportion of the patients included, whether in specialized care or outside. There is significant room for improvement in the identification of problem gambling, in addictology and beyond. It is important to question gambling habits for any reason for addiction consultation and to repeat this identification over time. As the Internet is widely used by addictology consultants, it can represent a key element in care, both in the identification of behavioral addictions and in follow-up.     

Sex differences in Parkinson’s disease

Parkinson’s disease (PD) displays a greater prevalence and earlier age at onset in men. This review addresses the concept that sex differences in PD are determined, largely, by biological sex differences in the NSDA system which, in turn, arise from hormonal, genetic and environmental influences. Current therapies for PD rely on dopamine replacement strategies to treat symptoms, and there is an urgent, unmet need for disease modifying agents. As a significant degree of neuroprotection against the early stages of clinical or experimental PD is seen, respectively, in human and rodent females compared with males, a better understanding of brain sex dimorphisms in the intact and injured NSDA system will shed light on mechanisms which have the potential to delay, or even halt, the progression of PD. Available evidence suggests that sex-specific, hormone-based therapeutic agents hold particular promise for developing treatments with optimal efficacy in men and women.     

Sex differences in EEG in adult gonadectomized rats before and after hormonal treatment

EEG activity was recorded from the left and right parietal cortex in adult male and female Wistar rats that were gonadectomized (GNX) after puberty during 2 days without and 3 days with hormonal treatment (either testosterone propionate, 5-DHT or vehicle in males and progesterone, estradiol benzoate or vehicle in females). In contrast to EEG characteristics reported for intact rats, GNX abolished right over left parietal activation in both sexes and, sex differences in EEG interhemispheric correlation and in theta and delta relative power in the right parietal; additionally GNX males showed higher absolute power than females. Hormonal treatment reestablished interparietal asymmetry in both sexes and a lack of sex differences in absolute power, however, it was not enough to reestablish sex differences in delta and theta proportion in the right parietal nor in interhemispheric correlation. Differential effects were obtained with testosterone propionate and 5-DHT in males suggesting that activational effects of testosterone on EEG are probably exerted through testosterone or its aromatized metabolites. The results of our study indicate that the activational effects of gonadal steroids after puberty are necessary for maintaining sex differences in the EEG of the adult rat.     

Sex differences in the performance of cognitive tasks in a murine model of metabolic syndrome

The metabolic syndrome includes changes in blood glucose levels, arterial hypertension, triglycerides, dyslipidemia and central obesity. Countless reports have described the correlation between the metabolic syndrome and cognitive impairment. However, only a few reports have assessed cognitive impairment associated with the metabolic syndrome in animals of both sexes. For this purpose, Sprague‐Dawley male and female rats were fed either with a hypercaloric diet as model of the metabolic syndrome or with a standard chow diet as controls. Subsequently, spatial learning and memory (Morris water maze) as well as short‐ and long‐term memory (passive avoidance task) were evaluated. Body weight, blood pressure, triglycerides, and total cholesterol significantly increased (F(1, 36) = 94.89, p < .001) in rats fed with hypercaloric diet compared to control rats. Furthermore, cognitive impairment was observed in spatial learning and spatial memory on male rats but not on female rats fed with hypercaloric diet. In addition, a long‐term memory impairment was observed in both groups fed with hypercaloric diet in comparison to their respective control group (F(1, 32) = 10.61, p = .0027). Immunohistochemistry results showed no changes in the number of positive cells for NeuN, GFAP and Ox‐42. In males fed with a hypercaloric diet, a decrease in testosterone levels was observed, whereas estradiol levels decreased in females when compared with their respective control group (p < .0001). In this MetS animal model, metabolic and cognitive differences were observed in males and females, which demonstrates that sex hormones play a significant role in metabolic regulation and neuroprotection related to the CA1 region of the hippocampus.     

Sex differences in the human olfactory system

The olfactory system (accessory) implicated in reproductive physiology and behavior in mammals is sexually dimorphic. These brain sex differences present two main characteristics: they are seen in neural circuits related to sexual behavior and sexual physiology and they take one of two opposite morphological patterns (male>female or female>male). The present work reports sex differences in the olfactory system in a large homogeneous sample of men (40) and women (51) using of voxel-based morphology. Gray matter concentration showed sexual dimorphism in several olfactory regions. Women have a higher concentration in the orbitofrontal cortex involving Brodmann's areas 10, 11 and 25 and temporomedial cortex (bilateral hippocampus and right amygdala), as well as their left basal insular cortex. In contrast, men show a higher gray matter concentration in the left entorhinal cortex (Brodmann's area 28), right ventral pallidum, dorsal left insular cortex and a region of the orbitofrontal cortex (Brodmann's area 25). This study supports the hypothesis that the mammalian olfactory system is a sexually dimorphic network and provides a theoretical framework for the morphofunctional approach to sex differences in the human brain.     

Sex differences in cognitive impairment and Alzheimer’s disease

Studies have shown differences in specific cognitive ability domains and risk of Alzheimer’s disease between the men and women at later age. However it is important to know that sex differences in cognitive function during adulthood may have their basis in both organizational effects, i.e., occurring as early as during the neuronal development period, as well as in activational effects, where the influence of the sex steroids influence brain function in adulthood. Further, the rate of cognitive decline with aging is also different between the sexes. Understanding the biology of sex differences in cognitive function will not only provide insight into Alzheimer’s disease prevention, but also is integral to the development of personalized, gender-specific medicine. This review draws on epidemiological, translational, clinical, and basic science studies to assess the impact of sex differences in cognitive function from young to old, and examines the effects of sex hormone treatments on Alzheimer’s disease in men and women.     

Sex matters in stroke: A review of recent evidence on the differences between women and men

For the most part, stroke is a disease of old age. With the predicted increase in the aged population and longer life expectancies, the number and proportion of people living with stroke is expected to increase, especially among women and the elderly. For those who suffer stroke, there is a high likelihood of experiencing death and severe disability. Therefore, the issue of stroke amongst women (and men) is a key priority in global public health. In this review, we consider sex and gender differences in ischemic and hemorrhagic stroke, and we summarize data that outlines the epidemiology, risk factor, treatment recovery and prevention of stroke. We discuss possible mechanisms for the sex differences, specifically in areas of biology, medical management and social and behavioral context. With evidence showing that women and men experience stroke differently, sex must be taken into account when treating patients and when designing clinical trials.     

Gender differences in autoimmune disease

Autoimmune diseases are a range of diseases in which the immune response to self-antigens results in damage or dysfunction of tissues. Autoimmune diseases can be systemic or can affect specific organs or body systems. For most autoimmune diseases there is a clear sex difference in prevalence, whereby females are generally more frequently affected than males. In this review, we consider gender differences in systemic and organ-specific autoimmune diseases, and we summarize human data that outlines the prevalence of common autoimmune diseases specific to adult males and females in countries commonly surveyed. We discuss possible mechanisms for sex specific differences including gender differences in immune response and organ vulnerability, reproductive capacity including pregnancy, sex hormones, genetic predisposition, parental inheritance, and epigenetics. Evidence demonstrates that gender has a significant influence on the development of autoimmune disease. Thus, considerations of gender should be at the forefront of all studies that attempt to define mechanisms that underpin autoimmune disease.     

Sex differences in the psychopathology of inpatients

Summary In a sample of more than 2000 patients from the Department of Psychiatry of the Free University of Berlin (58.8% men, and 41.2% women), the sex differences in the diagnostic distribution and in the severity of the depressive symptomatology were investigated on the basis of data documented by the AMP system. Due to patient selection by the hospital, men with depressive neuroses were found to be over-represented contrary to expectation; depressive psychoses, however, were prevalent in women as expected. In the total group of patients, depressive symptomatology at the symptom and syndrome levels prevailed in women. Within homogeneous diagnostic groups, depressiveness in minor depressive disorders like depressive neuroses was more severe in women, but in psychotic depression men were more seriously depressed than women. Attempts are made to interprete these findings on the basis of constitution-biological and role-theoretical concepts, but especially on the basis of sex-specific help-seeking behaviour.Dedicated to Prof. Dr. H. Hippius for this 60th birthday     

Sex differences in biopsychosocial correlates of binge eating disorder: a study of treatment-seeking obese adults in primary care setting

Objective

Although community-based studies suggest equivalent levels of physical and psychological impairment by binge eating disorder (BED) in men and women, men with BED are still underrepresented in clinical studies. This study aimed to provide a comprehensive analysis of sex differences in biopsychosocial correlates of treatment-seeking obese patients with BED in primary care.

Method

One hundred-ninety obese adults (26% men) were recruited in primary care settings for a treatment study for obesity and BED.

Results

Very few significant sex differences were found in the developmental history and in current levels of eating disorder features, as well as psychosocial factors. Women reported significantly earlier age at onset of overweight and dieting and greater frequency of dieting. Men reported more frequent strenuous exercise. Men were more likely than women to meet criteria for metabolic syndrome; men were more likely to show clinically elevated levels of triglycerides, blood pressure, and fasting glucose levels.

Conclusion

Despite few sex differences in behavioral and psychosocial factors, metabolic problems associated with obesity were more common among treatment-seeking obese men with BED than women. The findings highlight the importance of including men in clinical studies of BED and active screening of BED in obese men at primary care settings.     

Neuropsychological test performance and MEG-based brain lateralization: Sex differences

Magnetoencephalographic (MEG) auditory evoked fields (EF) were recorded from left and right hemispheres of 9 normal males and 12 normal females. Source location of the 100 ms latency component (M100) was localized to superior temporal lobes bilaterally using an inverse solution algorithm. All subjects also were administered the Wechsler block design and visual reproduction subtests, and the California Verbal Learning Test (CVLT). M100 source locations demonstrated significant sex differences in interhemispheric asymmetry. Males had source locations further anterior than females, with the differences most pronounced in the right hemisphere. Expected sex differences were found in neuropsychological test performance, with males performing better on block design ad visual reproduction, and females performing better on the CVLT. Across both sexes, block design scores correlated significantly with right hemisphere M100 location, with more anterior source locations associated with better performance. CVLT scores were negatively correlated with right hemisphere M100 source locations. These findings suggest MEG-based measures of interhemispheric asymmetry may be related to specific neuropsychological test performance measures.     

Sex differences in stress-induced hyperalgesia and its mechanisms

Chronic stress induces a variety of physiological and/or psychological abnormalities, including hyperalgesia. Researchers have discovered sex differences in the prevalence of stress-induced hyperalgesia (SIH) in recent years. Sex differences may be one of the reasons for the heterogeneity of susceptibility to stress-related diseases. In this review, the potential mechanisms of sex differences in SIH are discussed, such as hypothalamus–pituitary–adrenal axis responses, regulation of sex hormones, and immune system responses.