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PubMed2000

An fMRI study of sex differences in regional activation to a verbal and a spatial task.

Sex differences in cognitive performance have been documented, women performing better on some phonological tasks and men on spatial tasks. An earlier fMRI study suggested sex differences in distributed brain activation during phonological processing, with bilateral activation seen in women while men showed primarily left-lateralized activation. This blood oxygen level-dependent fMRI study examined sex differences (14 men, 13 women) in activation for a spatial task (judgment of line orientation) compared to a verbal-reasoning task (analogies) that does not typically show sex differences. Task difficulty was manipulated. Hypothesized ROI-based analysis documented the expected left-lateralized changes for the verbal task in the inferior parietal and planum temporal regions in both men and women, but only men showed right-lateralized increase for the spatial task in these regions. Image-based analysis revealed a distributed network of cortical regions activated by the tasks, which consisted of the lateral frontal, medial frontal, mid-temporal, occipitoparietal, and occipital regions. The activation was more left lateralized for the verbal and more right for the spatial tasks, but men also showed some left activation for the spatial task, which was not seen in women. Increased task difficulty produced more distributed activation for the verbal and more circumscribed activation for the spatial task. The results suggest that failure to activate the appropriate hemisphere in regions directly involved in task performance may explain certain sex differences in performance. They also extend, for a spatial task, the principle that bilateral activation in a distributed cognitive system underlies sex differences in performance.

Brain↗
PubMed2006

Low efficacy opioids: implications for sex differences in opioid antinociception.

It is becoming increasingly evident that the sex of an organism is a critical determinant of responsiveness to opioid analgesics. However, the factors that determine the magnitude and direction of sex differences in opioid antinociception have not been fully elucidated. One factor that has received attention is the relative efficacy of the opioid. This review summarizes recent findings in which opioid efficacy was systematically manipulated as an independent variable to probe underlying sex differences in opioid system function. Overall, in rodents and nonhuman primates, mu and kappa opioids are generally more potent and effective in males than in females. The data indicate that although sex differences in the potency of high efficacy opioids such as morphine are generally less than 3.0-fold, sex differences with lower efficacy opioids can be greater than 90-fold. Moreover, that these drugs can function as full agonists in males while functioning as antagonists in females under identical conditions suggests some fundamental sex difference in opioid system function. In addition to efficacy, a number of other variables can affect the outcomes of these studies, including the drug history, genotype, and nociceptive stimulus modality, duration, and intensity. These factors may interact with opioid efficacy to determine the specific conditions under which sex differences are observed. The testing of low efficacy opioids by other laboratories and under other experimental conditions will determine the extent to which this variable affords a strategic research tool. The potential utility of low efficacy opioids in other domains of behavioral pharmacology is also discussed.

Analgesics, Opioid↗
PubMed1981

A sex difference of the concentrations of gonadotropins, its subunits and sex steroids in cord veins.

In order to elucidate the sex difference of cord blood hormones, concentration of hCG, hCG-alpha, hCG-beta, hLH, hFSH, estradiol (E2), progesterone (P) and testosterone (T) in cord veins were assayed by radioimmunoassays. Mean concentrations of cord vein hCG, hCG-alpha and hLH were significantly higher in female than in male, but those of hFSH and T were significantly higher in male than in female. Male and female cord vein levels of hCG-beta, E2 and P were not significantly different and hCG-beta and hFSh levels in cord veins at term are low in both sexes. These lower concentrations of hLH in male may be a result of the feedback inhibitory action by the higher concentrations of T in male at term. These data suggest a sex difference in the synthesis and secretion of gonadotropins by the pituitary gland in the human foetus at term.

Female↗
PubMed1993

Sex differences in striatal dopamine: in vivo microdialysis and behavioral studies.

Experiments were conducted to examine sex differences in striatal dopamine function using in vivo microdialysis in freely moving rats. We report here a sex difference in basal extracellular striatal dopamine determined by quantitative microdialysis (the no net flux method) when castrated and ovariectomized rats were compared. There was no sex difference in dopamine uptake into synaptosomes. This indicates that the sex difference in extracellular dopamine is most likely due to sex differences in dopamine release, synthesis, and/or metabolism. Within 30 min after a single injection (s.c.) of either estradiol benzoate (2.0 micrograms/100 g) or 17 beta-estradiol (1.5 micrograms/100 g) the amphetamine-stimulated release of dopamine was enhanced in the striatum of ovariectomized rats, but there was no effect in castrated male rats. The enhanced amphetamine-induced striatal dopamine release in ovariectomized rats was associated with an enhanced frequency of stereotyped head and limb movements and an increased peak in extra 1/4 turns. There were also sex differences in stereotyped behavior and extra 1/4 turns whether or not animals received estrogen treatment. Thus, there are sex differences in striatal extracellular dopamine and in the effect of estrogen on the striatal dopamine neurochemical and behavioral responses to amphetamine.

Amphetamine↗
PubMed1998

The higher the dose, the greater the sex differences in escape-avoidance response in mice after acute administration of haloperidol.

Sex differences in the effects of haloperidol in the escape-avoidance response have previously been found in various studies carried out in our laboratory in which mice were used as experimental subjects. Males were more affected than females by the disruptive effects of this neuroleptic of frequent clinical use. In the present work these sex differences were evaluated in a unique training session using several doses of the drug (0.075, 0.25, and 0.75 mg/kg i.p.). The number of avoidances, escapes, nonresponses, crossings during the adaptation period, crossings during intertrial intervals, and response latencies were analyzed. Statistically significant sex differences were found in the number of escapes and nonresponses: males showed fewer escape responses and more nonresponses than females. These sex differences were dose dependent: a positive correlation was obtained between doses of haloperidol and sex differences observed in the number of escapes and nonresponses. The higher the dose, the greater the sex differences. These are related not only to the impairment of motor activity, because no sex differences were found in the number of crossings during the adaptation period and intertrial intervals.

Animals↗
PubMed2003

Neural, not gonadal, origin of brain sex differences in a gynandromorphic finch.

In mammals and birds, sex differences in brain function and disease are thought to derive exclusively from sex differences in gonadal hormone secretions. For example, testosterone in male mammals acts during fetal and neonatal life to cause masculine neural development. However, male and female brain cells also differ in genetic sex; thus, sex chromosome genes acting within cells could contribute to sex differences in cell function. We analyzed the sexual phenotype of the brain of a rare gynandromorphic finch in which the right half of the brain was genetically male and the left half genetically female. The neural song circuit on the right had a more masculine phenotype than that on the left. Because both halves of the brain were exposed to a common gonadal hormone environment, the lateral differences indicate that the genetic sex of brain cells contributes to the process of sexual differentiation. Because both sides of the song circuit were more masculine than that of females, diffusible factors such as hormones of gonadal or neural origin also likely played a role in sexual differentiation.

Animals↗
PubMed2000

Beyond intimacy: conceptualizing sex differences in same-sex friendships.

This study was designed to replicate and extend prior findings that same-sex friendships of women and men are equally important but that women's friendships are more intimate. A group of adolescents and a group of adults were asked to complete an anonymous questionnaire regarding the quality of their close friendships, the degree to which they would support a close friend in times of difficulty, and the degree to which they would celebrate with a friend in times of success. Results demonstrated that both females and males saw and spoke with their close friends and were equally willing to confront and trust their close friends. Females, however, reported more desire to spend time with a close friend in times of difficulty and to celebrate with a close friend who had just experienced a positive event. Results are discussed in terms of the differing functions of women's and men's same-sex friendships and women's greater general interest in and attention to transitions in the lives of other individuals.

Adolescent↗
PubMed1996

No sex difference occurs in hippocampus, food-storing, or memory for food caches in black-capped chickadees.

A number of recent studies have described sex differences in the relative size of the hippocampus that are associated with sex differences in the use of space. Voles, kangaroo rats, and cowbirds all exhibit a sex difference in relative size of the hippocampal formation that is correlated with a sex difference in spatial behaviour. We wished to determine whether sex differences in the size of the hippocampus occur in the absence of a difference in the use of space, and whether the previously described correlations could be adventitious. Relative hippocampal size was determined in wild-caught black-capped chickadees (Parus atricapillus) following behavioural observations of food caching and spatial memory for cache sites. There was no indication of a sex difference in either relative size of the hippocampus or in food-caching behaviour and memory for cache sites. These results show that sex differences in relative size of the hippocampus do not occur as a matter of course, and are consistent with the hypothesis that sex differences in spatial behaviour and spatial ability are predictive of sex differences in the relative size of the hippocampus.

Animals↗
PubMed1999

The development of brain sex differences: a multisignaling process.

In order to account for the development of sex differences in the brain, we took, as an integrative model, the vomeronasal pathway, which is involved in the control of reproductive physiology and behavior. The fact that brain sex differences take place in complex neural networks will help to develop a motivational theory of sex differences in reproductive behaviors. We also address the classic genomic actions in which three agents (the hormone, the intracellular receptor, and the transcription function) play an important role in brain differentiation, but we also point out refinements that such a theory requires if we want to account of the existence of two morphological patterns of sex differences in the brain, one in which males show greater morphological measures (neuron numbers and/or volume) than females and the opposite. Moreover, we also consider very important processes closely related to neuronal afferent input and membrane excitability for the developing of sex differences. Neurotransmission associated to metabotropic and ionotropic receptors, neurotrophic factors, neuroactive steroids that alter membrane excitability, cross-talk (and/or by-pass) phenomena, and second messenger pathways appear to be involved in the development of brain sex differences. The sexual differentiation of the brain and reproductive behavior is regarded as a cellular multisignaling process.

Animals↗
PubMed1997

First-episode major depression. Few sex differences in course.

BACKGROUND: There is a sex difference in the prevalence of unipolar major depression. This study sought to determine whether there is a sex difference in its course. METHODS: The National Institute of Mental Health Collaborative Program on the Psychobiology of Depression-Clinical Studies provided data on 96 male and 101 female subjects who were diagnosed as having a first episode of unipolar major depressive disorder at intake and on whom prospective data were available. We looked for differences at intake in factors other than sex that might affect the course of illness: demographic factors, characteristic features of the first depressive episode, psychiatric history, and family history of depression. We then examined the course of depression of these subjects during the following 15 years. RESULTS: The subjects were similar at intake, enabling us to focus on sex when we looked for differences in the course. Most subjects recovered from their first episode of major depression, but the majority had at least 1 recurrence in the following 5 years. During the following 15 years, male and female subjects did not differ significantly in the time to recovery, the overall time to first recurrence, of the number or severity of recurrences of major depressive episodes. There was no evidence for a more chronic course of depression in women. CONCLUSION: There were few significant sex differences in the course of major depressive disorder in this study population.

Adult↗
PubMed1980

Quantitative analysis of sex differences in hormone accumulation in the zebra finch brain: methodological and theoretical issues.

The autoradiographic method was used to compare the numbers of hormone accumulating cells in several brain regions in male and female zebra finches (Poephila guttata) after injection of tritiated testosterone. The brain regions examined were the caudal nucleus of the hyperstriatum ventrale (HVc), magnocellular nucleus of the anterior neostriatum (MAN), robust nucleus of the archistriatum (RA), nucleus intercollicularis of the midbrain (ICo), the tracheosyringeal hypoglossal motor nucleus (nXIIts), and periventricular magnocellular nucleus of the anterior hypothalamus (PVM). All but the last of these regions are thought to be involved in the control of vocalizations in passerine song birds. Males have significantly more labelled cells in HVc and MAN. In RA, there is no difference in total percentage of labelled cells, but there is a sex difference in size distribution of labelled cells. No sex difference was detected in other brain regions. These differences are found when using a criterion for cell labelling which is based on the Poisson distribution, and the relative merits are evaluated of various quantitative criteria used in the analysis of steroid autoradiograms. The magnitude of the observed sex difference may be influenced by several biasing factors, yet the sex difference persists when corrections are applied to eliminate the biases, indicating that the sex difference is not an artifact of autoradiographic procedure. The magnitude of the sex difference in hormone accumulation has certain implications for the process of sexual differentiation of the brain.

Animals↗
PubMed1998

Sex differences in response to cutaneous anesthesia: a double blind randomized study.

The existing literature on experimentally induced pain indicates that there are sex differences, with females displaying greater sensitivity. In epidemiological studies, sex differences are also noted in the prevalence of a number of pain syndromes, with females reporting more severe pain, more frequent pain, and pain of longer duration. Complicating the interpretation of pain differences between men and women in clinical samples are reports of sex differences in response to pain-reducing medications. Studies in human subjects suggest that women respond better to certain opioid analgesics than men following third molar extraction, but few studies have assessed sex effects in effectiveness of topical anesthetics. The purpose of this study was to test for sex differences in response to a topical anesthetic, Lidocaine, using double blind, placebo controlled experimental methodology, in combination with a magnitude matching psychophysical protocol using a pressure algometer. The subjects were 21 female and 23 male adult volunteers. Twenty-four subjects (12 males and 12 females) were randomly assigned to the Lidocaine condition and 20 subjects were randomly assigned to the placebo control condition (9 males and 11 females). The effect size across sex for subjects in the Lidocaine treatment condition on the response bias variable was large indicating the males rated the stimuli as less painful than the females. Sex differences were not observed for discriminability in the Lidocaine treatment condition. This study did not show sex differences in the placebo condition. These results are particularly interesting in light of previous work that has shown similar pain stimuli (pressure pain) to be the stimulation most sensitive to sex differences. Results of this study suggest that the protocol employed (pressure pain stimulus with magnitude matching task) is sensitive to both anesthetic treatment and sex differences and represents an improvement in pain assessment methodology for use in experimental studies and in the clinic.

Adolescent↗
PubMed1983

Sex differences in human mortality: the role of genetic factors.

This paper reviews evidence concerning genetic factors that influence sex differences in human mortality, with attention to the interactions between genetic and environmental factors. Some widely quoted earlier conclusions, for example, that males have consistently higher fetal mortality than females, are not supported by current evidence. For example, for late fetal mortality, males had higher rates than females in earlier historical data, but not in recent data for several advanced industrial countries. This reflects a changing balance between an inherently greater female vulnerability for one major type of late fetal mortality and inherently greater male vulnerability for several other types of late fetal mortality that have declined in importance as health care has improved. Males appear to be inherently more vulnerable than females to infant mortality, although the causes of this vulnerability are poorly understood. X-linked immunoregulatory genes appear to contribute to greater female resistance to infectious diseases. Despite these apparent inherent advantages for females, in some situations females have had higher infant mortality and higher infectious disease mortality than males, apparently due to environmental disadvantages for females, such as less adequate diet and health care. Inherent sex differences in reproductive physiology and anatomy contribute to higher female mortality for breast cancer and maternal mortality. For these causes of death, as for the other categories discussed, the death rates and thus the contributions to sex differences in total mortality vary considerably depending on environmental conditions. Several hypothesized contributions of sex hormones to sex differences in mortality are at present controversial due to contradictions and limitations in the available data. There may be effects of male sex hormones on sex differences in behavior which contribute to males' higher death rates for accidents and other violent causes. Women's endogenous sex hormones may reduce women's risk of ischemic heart disease. For both violent deaths and ischemic heart disease it appears that any genetic contributions to sex differences in mortality are strongly reinforced by the cultural influences that foster more risky behavior in males, including more use of weapons, employment in hazardous occupations, heavy alcohol consumption and cigarette smoking. It appears that these cultural influences on sex differences in behavior are widespread cross-culturally in part because of the effects of inherent sex differences in reproductive functions on the cultural evolution of sex roles. These examples illustrate the complexity and importance of interactions between genetic and environmental factors in determining sex differences in human mortality.

Accidents↗
PubMed2007

Sex differences in projections from preoptic area aromatase cells to the periaqueductal gray in Japanese quail.

In many vertebrate species the medial preoptic area projects to a premotor nucleus, the periaqueductal central gray (PAG). This connection plays an important role in the control of reproductive behavior. In male Japanese quail (Coturnix japonica) specifically, the medial preoptic nucleus (POM), where various types of sensory inputs converge, is a critical site for the activational action of testosterone on male sexual behavior. To activate male copulatory behavior, testosterone must be aromatized to estradiol within the POM and aromatase-immunoreactive cells in the POM are the main source of projections to the PAG. The POM-PAG connection is thus an important functional circuit integrating the sensory with premotor components of sexual behavior. Contrary to what is observed in males, testosterone does not activate male-typical copulatory behavior in females and we investigated here via retrograde tracing methods whether this behavioral sexual difference is associated with a sex difference in connectivity between POM and PAG. Fluorescent microspheres were injected in the PAG of male and female quail and retrogradely labeled fluorescent cells counted in four fields of the POM in sections that had been immunolabeled for aromatase. Males had more aromatase-immunoreactive neurons projecting to the PAG than females and this difference was most prominent in the caudolateral part of the nucleus that has been specifically implicated in the control of male copulatory behavior. These data therefore support the hypothesis that sex differences in POM-PAG connectivity are causally linked to the sex difference in the behavioral response to testosterone.

Analysis of Variance↗
PubMed1997

Sex differences in phonetic processing: speed of identification of alphabetical sequences.

Research on the sex difference in speed of matching strings of letters or digits has suggested that the difference is associated with the speed of the comparison and decision processes rather than with symbol recognition. In addition, the size of the difference is affected by whether the code used for the comparisons is figural or verbal. Given recent evidence on both the critical role of phonological processing in reading and sex differences in the lateralization of phonological processes in the brain, it was hypothesized that on a speeded task with high demands for phonological efficiency sex differences might be found even though no perceptual comparisons were required. In a study with 57 male and 60 female college students, the women were significantly faster in identifying alphabetical sequences and were more accurate than men. There were no significant sex differences on a perceptual matching condition. The results suggest that the verbal processes implicated in earlier work on sex differences in speed of symbol matching may be primarily due to sex differences in the efficiency of phonological processing.

Adult↗
PubMed2004

Sex differences in behavioral taste responses to and ingestion of sucrose and NaCl solutions by rats.

Sex differences in the ingestion of food and concentrated NaCl solutions by rats have been investigated for more than a quarter of a century, though the underlying mechanism(s) and the role of reproductive hormones remain the subject of debate. We hypothesized that sex differences in the ingestion of sucrose and NaCl solutions are attributable, in part, to sex differences in taste responses/taste perception. We employed short-access, 10-s tests along with 18-h, two-bottle preference tests to examine sex differences in sensitivity to and ingestion of sucrose and NaCl solutions. To evaluate the role of estrogen, we ovariectomized (OVX) female rats and then used an estrogen-replacement schedule that mimics the pattern of fluctuation of estrogen levels in intact female rats. We observed striking sex differences in the rate of licking NaCl mixed in a dilute sucrose solution. Compared to males, OVX rats with or without estrogen licked at higher rates to more concentrated NaCl solutions, suggesting that female rats are less sensitive to concentrated NaCl solutions. Although less pronounced, we also observed sex differences in the rate of licking to sucrose, particularly at lower concentrations. Compared to males, OVX rats with or without estrogen licked less, suggesting that female rats are less sensitive to lower concentrations of sucrose. Estrogen appeared to play, at most, a small role in mediating taste responses to specific concentrations of sucrose in these testing procedures. Nonetheless, sex differences in taste responses were clear, and it seems likely that such differences underlie, in part, observed differences in ingestion.

Animals↗
PubMedDate not supplied

Sex differences in opioid analgesia: "from mouse to man".

BACKGROUND: Numerous experimental studies, conducted primarily over the past 10 years, show that there are sex differences in opioid analgesia. This review summarizes the published literature on sex differences in analgesia produced by acute administration of drugs acting at mu-, kappa-, and delta-opioid receptors, in animals and humans. Additionally, methodological issues in research into opioid sex differences are discussed. CONCLUSIONS: Procedural variables that may influence the outcome of studies examining sex differences in opioid analgesia include modality and intensity of the noxious stimulus used in the pain test, opioid type (efficacy and selectivity), and experimental design and data analytic techniques. Subject variables that may be important to consider include subject genotype and gonadal steroid hormone state of the subject at the time of analgesia testing. Evidence is provided for multiple mechanisms underlying sex differences in opioid analgesia, including both pharmacokinetic and pharmacodynamic factors. Future research directions are suggested, such as examining sex differences in opioid tolerance development, sex differences in opioid analgesia using models of acute inflammatory pain and chronic pain, and sex differences in effects of opioids other than analgesia, which may limit their therapeutic use.

Analgesics, Opioid↗
PubMed1999

Vulnerability to assaultive violence: further specification of the sex difference in post-traumatic stress disorder.

BACKGROUND: We examine potential sources of the sex differences in post-traumatic stress disorder (PTSD) in the community. METHODS: Data were obtained from a representative sample of 2181 persons aged 18-45 years in the Detroit primary metropolitan statistical area, which is a six-county area containing more than four million residents. A random digit dialling method was used to select the sample and a computer-assisted telephone interview was used to obtain the data. DSM-IV PTSD was assessed with respect to a randomly selected trauma from the list of qualifying traumas reported by each respondent. RESULTS: The lifetime prevalence of exposure and the mean number of traumas were lower in females than males. The overall conditional risk of PTSD (i.e. the probability of PTSD among those exposed to a trauma) was approximately twofold higher in females than males, adjusting for the sex difference in the distribution of trauma types. The sex difference was due primarily to females' greater risk following assaultive violence. The sex difference in the avoidance and numbing symptom group following assaultive violence exceeded the sex differences in other symptom groups. CONCLUSIONS: Future research should focus on sex differences in the response to assaultive violence, including potential explanations for females' greater probability to experience avoidance and numbing.

Adolescent↗