Sex and seasonal differences in hippocampal volume and neurogenesis in brood‐parasitic brown‐headed cowbirds (Molothrus ater)

Brown‐headed cowbirds (Molothrus ater) are one of few species in which females show more complex space use than males. Female cowbirds search for, revisit, and parasitize host nests and, in a previous study, outperformed males on an open field spatial search task. Previous research reported a female‐biased sex difference in the volume of the hippocampus, a region of the brain involved in spatial memory. Neurons produced by adult neurogenesis may be involved in the formation of new memories and replace older neurons that could cause interference in memory. We tested for sex and seasonal differences in hippocampal volume and neurogenesis of brood‐parasitic brown‐headed cowbirds and the closely related non‐brood‐parasitic red‐winged blackbird (Agelaius phoeniceus) to determine whether there were differences in the hippocampus that reflected space use in the wild. Females had a larger hippocampus than males in both species, but hippocampal neurogenesis, measured by doublecortin immunoreactivity (DCX+), was greater in female than in male cowbirds in the absence of any sex difference in blackbirds, supporting the hypothesis of hippocampal specialization in female cowbirds. Cowbirds of both sexes had a larger hippocampus with greater hippocampal DCX+ than blackbirds. Hippocampus volume remained stable between breeding conditions, but DCX+ was greater post‐breeding, indicating that old memories may be lost through hippocampal reorganization following breeding. Our results support, in part, the hypothesis that the hippocampus of cowbirds is specialized for brood parasitism. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1275–1290, 2016     

The impact of sex on brain responses to smoking cues: a perfusion fMRI study

Background

Anecdotal and clinical theories purport that females are more responsive to smoking cues, yet few objective, neurophysiological examinations of these theories have been conducted. The current study examines the impact of sex on brain responses to smoking cues.

Methods

Fifty-one (31 males) cigarette-dependent sated smokers underwent pseudo- continuous arterial spin-labeled perfusion functional magnetic resonance imaging during exposure to visual smoking cues and non-smoking cues. Brain responses to smoking cues relative to non-smoking cues were examined within males and females separately and then compared between males and females. Cigarettes smoked per day was included in analyses as a covariate.

Results

Both males and females showed increased responses to smoking cues compared to non-smoking cues with males exhibiting increased medial orbitofrontal cortex and ventral striatum/ventral pallidum responses, and females showing increased medial orbitofrontal cortex responses. Direct comparisons between male and female brain responses revealed that males showed greater bilateral hippocampal/amygdala activation to smoking cues relative to non-smoking cues.

Conclusions

Males and females exhibit similar responses to smoking cues relative to non-smoking cues in a priori reward-related regions; however, direct comparisons between sexes indicate that smoking cues evoke greater bilateral hippocampal/amygdalar activation among males. Given the current literature on sex differences in smoking cue neural activity is sparse and incomplete, these results contribute to our knowledge of the neurobiological underpinnings of drug cue reactivity.

     

Review: magnetic resonance imaging of male/female differences in human adolescent brain anatomy

ABSTRACT: Improvements in neuroimaging technologies, and greater access to their use, have generated a plethora of data regarding male/female differences in the developing brain. Examination of these differences may shed light on the pathophysiology of the many illnesses that differ between the sexes and ultimately lead to more effective interventions. In this review, we attempt to synthesize the anatomic magnetic resonance imaging (MRI) literature of male/female brain differences with emphasis on studies encompassing adolescence -- a time of divergence in physical and behavioral characteristics. Across all ages total brain size is consistently reported to be about 10 % larger in males. Structures commonly reported to be different between sexes include the caudate nucleus, amygdala, hippocampus, and cerebellum -- all noted to have a relatively high density of sex steroid receptors. The direction and magnitude of reported brain differences depends on the methodology of data acquisition and analysis, whether and how the subcomponents are adjusted for the total brain volume difference, and the age of the participants in the studies. Longitudinal studies indicate regional cortical gray matter volumes follow inverted U shaped developmental trajectories with peak size occurring one to three years earlier in females. Cortical gray matter differences are modulated by androgen receptor genotyope and by circulating levels of hormones. White matter volumes increase throughout childhood and adolescence in both sexes but more rapidly in adolescent males resulting in an expanding magnitude of sex differences from childhood to adulthood.     

Developmental Changes in the Corpus Callosum from Infancy to Early Adulthood: A Structural Magnetic Resonance Imaging Study

Previous research has reported on the development trajectory of the corpus callosum morphology. However, there have been only a few studies that have included data on infants. The goal of the present study was to examine the morphology of the corpus callosum in healthy participants of both sexes, from infancy to early adulthood. We sought to characterize normal development of the corpus callosum and possible sex differences in development. We performed a morphometric magnetic resonance imaging (MRI) study of 114 healthy individuals, aged 1 month to 25 years old, measuring the size of the corpus callosum. The corpus callosum was segmented into seven subareas of the rostrum, genu, rostral body, anterior midbody, posterior midbody, isthmus and splenium. Locally weighted regression analysis (LOESS) indicated significant non-linear age-related changes regardless of sex, particularly during the first few years of life. After this increase, curve slopes gradually became flat during adolescence and adulthood in both sexes. Age of local maximum for each subarea of the corpus callosum differed across the sexes. Ratios of total corpus callosum and genu, posterior midbody, as well as splenium to the whole brain were significantly higher in females compared with males. The present results demonstrate that the developmental trajectory of the corpus callosum during early life in healthy individuals is non-linear and dynamic. This pattern resembles that found for the cerebral cortex, further suggesting that this period plays a very important role in neural and functional development. In addition, developmental trajectories and changes in growth do show some sex differences.     

No effect of social group composition or size on hippocampal formation morphology and neurogenesis in mountain chickadees (Poecile gambeli)

Brain plasticity and adult neurogenesis may play a role in many ecologically important processes including mate recognition, song learning and production, and spatial memory processing. In a number of species, both physical and social environments appear to influence attributes (e.g., volume, neuron number, and neurogenesis) of particular brain regions. The hippocampus in particular is well known to be especially sensitive to such changes. Although social grouping in many taxa includes the formation of male and female pairs, most studies of the relationship between social environment and the hippocampus have typically considered only solitary animals and those living in same‐sex groups. Thus, the aim of this study was to compare the volume of the hippocampal formation, the total number of hippocampal neurons, and the number of immature neurons in the hippocampus (as determined by doublecortin expression) in mountain chickadees (Poecile gambeli) housed in groups of males and females, male–female pairs, same sex pairs of either males or females, and as solitary individuals. The different groups were visually and physically, but not acoustically, isolated from each other. We found no significant differences between any of our groups in hippocampal volume, the total number of hippocampal neurons, or the number of immature neurons. Our results thus provided no support to the hypothesis that social group composition and/or size have an effect on hippocampal morphology and neurogenesis. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70:538–547, 2010     

Dysregulation of neonatal hippocampal cell genesis in the androgen insensitive Tfm rat

The first two weeks of life are a critical period for hippocampal development. At this time gonadal steroid exposure organizes sex differences in hippocampal sensitivity to activational effects of steroids, hippocampal cell morphology and hippocampus dependent behaviors. Our laboratory has characterized a robust sex difference in neonatal neurogenesis in the hippocampus that is mediated by estradiol. Here, we extend our knowledge of this sex difference by comparing the male and female hippocampus to the androgen insensitive testicular feminized mutant (Tfm) rat. In the neonatal Tfm rat hippocampus, fewer newly generated cells survive compared to males or females. This deficit in cell genesis is partially recovered with the potent androgen DHT, but is more completely recovered following estradiol administration. Tfm rats do not differ from males or females in the level of endogenous estradiol in the neonatal hippocampus, suggesting other mechanisms mediate a differential sensitivity to estradiol in male, female and Tfm hippocampus. We also demonstrate disrupted performance on a hippocampal-dependent contextual fear discrimination task. Tfm rats generalize fear across contexts, and do not exhibit significant loss of fear during extinction exposure. These results extend prior reports of exaggerated response to stress in Tfm rats, and following gonadectomy in normal male rats.     

Stress experienced in utero reduces sexual dichotomies in neurogenesis, microenvironment, and cell death in the adult rat hippocampus

Hippocampal function and plasticity differ with gender, but the regulatory mechanisms underlying sex differences remain elusive and may be established early in life. The present study sought to elucidate sex differences in hippocampal plasticity under normal developmental conditions and in response to repetitive, predictable versus varied, unpredictable prenatal stress (PS). Adult male and diestrous female offspring of pregnant rats exposed to no stress (control), repetitive stress (PS-restraint), or a randomized sequence of varied stressors (PS-random) during the last week of pregnancy were examined for hippocampal proliferation, neurogenesis, cell death, and local microenvironment using endogenous markers. Regional volume was also estimated by stereology. Control animals had comparable proliferation and regional volume regardless of sex, but females had lower neurogenesis compared to males. Increased cell death and differential hippocampal precursor kinetics both appear to contribute to reduced neurogenesis in females. Reduced local interleukin-1beta (IL-1beta) immunoreactivity (IR) in females argues for a mechanistic role for the anti-apoptotic cytokine in driving sex differences in cell death. Prenatal stress significantly impacted the hippocampus, with both stress paradigms causing robust decreases in actively proliferating cells in males and females. Several other hippocampal measures were feminized in males such as precursor kinetics, IL-1beta-IR density, and cell death, reducing or abolishing some sex differences. The findings expand our understanding of the mechanisms underlying sex differences and highlight the critical role early stress can play on the balance between proliferation, neurogenesis, cell death, and hippocampal microenvironment in adulthood.     

Neonatal MeCP2 is important for the organization of sex differences in vasopressin expression

Several neurodevelopmental disorders are marked by atypical Methyl-CpG-binding protein 2 (MeCP2) expression or function; however, the role of MeCP2 is complex and not entirely clear. Interestingly, there are sex differences in some of these disorders, and it appears that MeCP2 has sex-specific roles during development. Specifically, recent data indicate that a transient reduction in MeCP2 within developing amygdala reduces juvenile social play behavior in males to female-typical levels. These data suggest that MeCP2 within the amygdala is involved in programming lasting sex differences in social behavior. In the present study, we infused MeCP2 or control siRNA into the amygdala of male and female rats during the first three days of postnatal life in order to assess the impact of a transient reduction in MeCP2 on arginine vasopressin (AVP), a neural marker that is expressed differentially between males and females and is linked to a number of social behaviors. The expression of AVP, as well as several other genes, was measured in two-week old and adult animals. Two-week old males expressed more AVP and galanin mRNA in the amygdala than females, and a transient reduction in MeCP2 eliminated this sex difference by reducing the expression of both gene products in males. A transient reduction in MeCP2 also decreased androgen receptor (AR) mRNA in two-week old males. In adulthood, control males had more AVP-immunoreactive (AVP-ir) cells than females in the centromedial amygdala (CMA), bed nucleus of the stria terminalis (BST) and in the fibers that project from these cells to the lateral septum (LS). A transient reduction in MeCP2 eliminated this sex difference. Interestingly, there were no lasting differences in galanin or AR levels in adulthood. Reducing MeCP2 levels during development did not alter estrogen receptorα, neurofilament or Foxg1. We conclude that a transient reduction in MeCP2 expression in the developing male amygdala has a transient impact on galanin and AR expression but a lasting impact on AVP expression, highlighting the importance of MeCP2 in organizing sex differences in the amygdala.     

Neonatal MeCP2 is important for the organization of sex differences in vasopressin expression

Several neurodevelopmental disorders are marked by atypical Methyl-CpG-binding protein 2 (MeCP2) expression or function; however, the role of MeCP2 is complex and not entirely clear. Interestingly, there are sex differences in some of these disorders, and it appears that MeCP2 has sex-specific roles during development. Specifically, recent data indicate that a transient reduction in MeCP2 within developing amygdala reduces juvenile social play behavior in males to female-typical levels. These data suggest that MeCP2 within the amygdala is involved in programming lasting sex differences in social behavior. In the present study, we infused MeCP2 or control siRNA into the amygdala of male and female rats during the first three days of postnatal life in order to assess the impact of a transient reduction in MeCP2 on arginine vasopressin (AVP), a neural marker that is expressed differentially between males and females and is linked to a number of social behaviors. The expression of AVP, as well as several other genes, was measured in two-week old and adult animals. Two-week old males expressed more AVP and galanin mRNA in the amygdala than females, and a transient reduction in MeCP2 eliminated this sex difference by reducing the expression of both gene products in males. A transient reduction in MeCP2 also decreased androgen receptor (AR) mRNA in two-week old males. In adulthood, control males had more AVP-immunoreactive (AVP-ir) cells than females in the centromedial amygdala (CMA), bed nucleus of the striaterminalis (BST) and in the fibers that project from these cells to the lateral septum (LS). A transient reduction in MeCP2 eliminated this sex difference. Interestingly, there were no lasting differences in galanin or AR levels in adulthood. Reducing MeCP2 levels during development did not alter estrogen receptorα, neurofilament or Foxg1. We conclude that a transient reduction in MeCP2 expression in the developing male amygdala has a transient impact on galanin and AR expression but a lasting impact on AVP expression, highlighting the importance of MeCP2 in organizing sex differences in the amygdala.Key words: epigenetics, MeCP2, amygdala, sexual differentiation, development, arginine vasopressin, galanin     

Sex differences,laterality, and hormonal regulation of androgen receptor immunoreactivity in rat hippocampus

Sex differences, laterality, and hormonal regulation of androgen receptor (AR) immunoreactivity in rat hippocampal CA1 pyramidal cells were examined using the PG21 antibody. Adult male rats were either castrated or sham-operated at least 2 weeks prior to sacrifice. Gonadally intact females were sacrificed on the day of proestrus. Animals received an injection of either testosterone propionate (TP) or vehicle 2 h prior to sacrifice. Within CA1, both the intensity of staining and the number of AR+ cells were assessed. AR immunostaining was detected in all the groups with marked variation among them. The overall ranking of staining intensity was: gonadally intact males > females given TP > castrated males given TP > females > castrated males given vehicle. The number of AR+cells within subregions of CA1 showed the same basic pattern: among control-treated animals, gonadally intact males have more than females, but castrated males have the least, and acute TP treatment increases the number in both sexes. The increased level of AR immunoreactivity in CA1 of castrated males following acute TP treatment suggests that testicular androgens in adulthood normally increase AR immunoreactivity there, producing a sex difference favoring males in gonadally intact animals. We also found a higher number of AR+ CA1 cells on the left than on the right, but only in gonadally intact males and in females given TP. These results suggest that a laterality of AR distribution in the rat hippocampus may lead to lateralities in hippocampal structure and function.     

Impairment of GABAergic neurotransmitter system in the amygdala of young rats after 4-week zinc deprivation

On the basis of the evidence that the excitability of hippocampal glutamatergic neurotransmitter system is enhanced by dietary zinc deficiency, the response of amygdalar neurotransmitter system was checked in young rats fed a zinc-deficient diet for 4 weeks. Extracellular zinc concentration in the amygdala, which was measured by the in vivo microdialysis, was almost the same as that in the hippocampus and decreased by zinc deficiency. Extracellular zinc concentration in the amygdala was increased both in the control and zinc-deficient rats by stimulation with 100 mM KCl, suggesting that the increase in extracellular zinc in the amygdala, as well as that in the hippocampus, is linked with neuronal depolarization. In amygdalar extracellular fluid, the basal glutamate concentration was not significantly different between the control and zinc-deficient rats and was increased to almost the same extent between them by stimulation with 100 mM KCl, unlike more increase in extracellular glutamate concentration in the hippocampus in zinc deficiency. On the other hand, the basal GABA concentration in the amygdalar extracellular fluid was significantly lower in zinc-deficient rats and was not increased both in the control and zinc-deficient rats by stimulation with 100 mM KCl. These results suggest that GABAergic neurotransmitter system is critically impaired in the amygdala of young rats after 4-week zinc deprivation.     

Bilateral MR volumetry of the amygdala in chronic PTSD patients

Posttraumatic stress disorder (PTSD) patients experience symptoms which implicate dysfunction of emotional memory circuits, and possible damage of the amygdala. Laterality differences in activity of the amygdala have been reported in PTSD patients, with presumed adaptive plasticity in the hippocampus and the amygdala. The aim of this study was to investigate possible interhemispheric differences of amygdalar volume in chronic PTSD patients, with calculation of right-to-left volume ratios. Bilateral magnetic resonance (MR) volumetry was applied in 11 chronic PTSD patients. The mean right amygdalar volume of our patients was significantly smaller than the left one (p = 0.031), with the right-to-left volume ratio of 0.96 +/- 0.06. This tendency towards smaller right amygdala may be an acquired effect as a result of stress-induced plasticity, however we can not exclude the possibility of a predisposing condition.     

A developmental sex difference in hippocampal neurogenesis is mediated by endogenous oestradiol

Background

Oestradiol is a steroid hormone that exerts extensive influence on brain development and is a powerful modulator of hippocampal structure and function. The hippocampus is a critical brain region regulating complex cognitive and emotional responses and is implicated in the aetiology of several mental health disorders, many of which exhibit some degree of sex difference. Many sex differences in the adult rat brain are determined by oestradiol action during a sensitive period of development. We had previously reported a sex difference in rates of cell genesis in the developing hippocampus of the laboratory rat. Males generate more new cells on average than females. The current study explored the effects of both exogenous and endogenous oestradiol on this sex difference.

Methods

New born male and female rat pups were injected with the mitotic marker 5-bromo-2-deoxyuridine (BrdU) and oestradiol or agents that antagonize oestradiol action. The effects on cell number, proliferation, differentiation and survival were assessed at several time points. Significant differences between groups were determined by two- or thee-Way ANOVA.

Results

Newborn males had higher rates of cell proliferation than females. Oestradiol treatment increased cell proliferation in neonatal females, but not males, and in the CA1 region many of these cells differentiated into neurons. The increased rate of proliferation induced by neonatal oestradiol persisted until at least 3 weeks of age, suggesting an organizational effect. Administering the aromatase inhibitor, formestane, or the oestrogen receptor antagonist, tamoxifen, significantly decreased the number of new cells in males but not females.

Conclusion

Endogenous oestradiol increased the rate of cell proliferation observed in newborn males compared to females. This sex difference in neonatal neurogenesis may have implications for adult differences in learning strategy, stress responsivity or vulnerability to damage or disease.     

Evidence for an extended duration of GABA-mediated excitation in the developing male versus female hippocampus

Gamma-aminobutyric acid (GABA) is as an excitatory neurotransmitter during brain development. Activation of GABA(A) receptors in neonatal rat hippocampus results in chloride efflux and membrane depolarization sufficient to open voltage sensitive calcium channels. As development progresses, there is a decline in the magnitude of calcium influx subsequent to GABA(A) receptor activation and the number of cells that respond to GABA with excitation. By the second postnatal week in the rat, GABA action in the hippocampus is predominantly inhibitory. The functional consequences and endogenous regulation of developmental GABA-mediated excitation remains under-explored. Hippocampal neurons in the newborn male and female rat respond to GABA(A) receptor activation with increased intracellular calcium and are susceptible to GABA-mediated damage -- both being indicative of the excitatory nature of GABA. In the present study we observed that by postnatal day 7, only males are susceptible to GABA(A) agonist-induced damage and respond to GABA(A) agonist administration with elevated levels of intracellular calcium in cultured hippocampal neurons. By postnatal day 14, GABA(A) agonist administration was without effect on intracellular calcium in both males and females. The age-related sex difference in the impact of GABA(A) receptor activation correlates with a sex difference in chloride co-transporter expression. Males have elevated protein levels of pNKCC1 on PN0 and PN7, with no sex difference by PN14. In contrast, females displayed elevated levels of KCC2 on PN7. This converging evidence infers that sex affects the duration of GABA(A) receptor-mediated excitation during normal hippocampal development, and provides a mechanism by which the effect is mediated.     

Development of epiphyseal union in Japanese macaques of known chronological age

Forty epiphyseal unions were studied in the two subspecies of the Japanese macaque at known chronological ages. The age standards of the beginning and completion of epiphyseal union were estimated. The total score of the ratings of the unions revealed significant correlations with chronological age before 9 years of age. The linear regressions were calculated in each group of different sex and different subspecies in order to enable predictions to be made of the chronological age from the total score. Although males and females generally showed the same pattern of sequences, the unions of the females united earlier than those of the males in both subspecies before 9 years of age. The Yaku subspecies demonstrated an earlier union than the common Japanese macaque in both sexes before the age of 9 years old. The epiphyseal union of the Japanese macaque usually developed earlier than the reported union in the rhesus macaque. A large number of epiphyseal unions united at least partially and the total score deviated widely during the range from around 4 to 6 years of age. This period was in accordance with the adolescent growth period, especially in males, with rapid growth of body size as observed based on by somatometrical measurements. The skeletal growth of the trunk was generally late compared with that of the limbs. During the range after 8 years of age, some unions of the trunk united earlier in males than in females. The epiphyseal union could allow a more precise age estimation than the body mass or dental eruption during a certain range of ages. However, developmental estimations obtained from animals fed artificially, as the present samples were, must be applied with caution to wild animals.     

Sex and estrous cycle-dependent differences in glial fibrillary acidic protein immunoreactivity in the adult rat hippocampus

Sex differences in the morphology and function of the hippocampus have been reported in several species, but it is unknown whether a sexual dimorphism exists in glial fibrillary acidic protein (GFAP) expression in the rat hippocampus. We analyzed GFAP immunoreactivity in the hippocampus of intact adult male rats as well as in females during diestrus and proestrus phases of the estrous cycle. We found that in CA1, CA3, and dentate gyrus, GFAP immunoreactivity was higher in proestrus females as compared with males and diestrus females. In CA1, a similar GFAP immunoreactivity was found in males and in diestrus females, but in dentate gyrus, males presented the lowest GFAP content. Interestingly, differences in astrocyte morphology were also found. Rounded cells with numerous and short processes were mainly observed in the hippocampus during proestrus whereas cells with stellate shape with few and long processes were present in the hippocampus of males and diestrus females. The marked sex and estrous cycle-dependent differences in GFAP immunoreactivity density and in astrocyte number and morphology found in the rat hippocampus, suggest the involvement of sex steroid hormones in the sexually dimorphic functions of the hippocampus, and in the change in its activity during the estrous cycle.     

Individual Subject Classification of Mixed Dementia from Pure Subcortical Vascular Dementia Based on Subcortical Shape Analysis

Subcortical vascular dementia (SVaD), one of common causes of dementia, has concomitant Alzheimer''s disease (AD) pathology in over 30%, termed “mixed dementia”. Identifying mixed dementia from SVaD is important because potential amyloid-targeted therapies may be effective for treatment in mixed dementia. The purpose of this study was to discriminate mixed dementia from pure SVaD using magnetic resonance imaging (MRI). We measured brain amyloid deposition using the 11C-Pittsburgh compound B positron emission tomography (PiB-PET) in 68 patients with SVaD. A PiB retention ratio greater than 1.5 was considered PiB(+). Hippocampal and amygdalar shape were used in the incremental learning method to discriminate mixed dementia from pure SVaD because these structures are known to be prominently involved by AD pathologies. Among 68 patients, 23 (33.8%) patients were positive for PiB binding. With use of hippocampal shape analysis alone, PiB(+) SVaD could be discriminated from PiB(-) SVaD with 77.9% accuracy (95.7% sensitivity and 68.9% specificity). With use of amygdalar shape, the discrimination accuracy was 75.0% (87.0% sensitivity and 68.9% specificity). When hippocampal and amygdalar shape were analyzed together, accuracy increased to 82.4% (95.7% sensitivity and 75.6% specificity). An incremental learning method using hippocampal and amygdalar shape distinguishes mixed dementia from pure SVaD. Furthermore, our results suggest that amyloid pathology and vascular pathology have different effects on the shape of the hippocampus and amygdala.     

Development and sexual dimorphism of the pituitary gland

The pituitary gland plays a central role in sexual development and brain function. Therefore, we examined the effect of age and gender on pituitary volume in a large sample of healthy children and adults. Volumetric magnetic resonance imaging (MRI) was conducted in one hundred and fifty four (77 males and 77 females) healthy participants. Males were between the ages of 7 to 35 years (16.91+/-5.89 years) and females were 7 to 35 years of age (16.75+/-5.75 years). Subjects were divided into subgroups of age (7 to 9, 10 to 13, 14 to 17, 18 to 21, 22 and older) and sex (male/female). Pituitary gland volume differed between sexes when comparing the age groups (F=3.55, df=2, 143, p=0.03). Females demonstrated larger pituitary glands than males in the age 14 to 17 year old groups (p=0.04). Young (19 years and under) and old (20 years and older) females demonstrated a correlation between pituitary volume and age. Males did not show this relationship. These findings provide additional evidence for gender differences in the normative anatomy of the pituitary and may have relevance for the study of various childhood onset neuropsychiatric disorders in which pituitary dysfunction has been implicated.     

Sex-Related Neuroanatomical Basis of Emotion Regulation Ability

Behavioral research has demonstrated that males have a higher capability of regulating their own and others'' emotions than females; however, little is known about the sex-specific brain mechanisms involved in emotion regulation ability. In the present study, we used voxel-based morphometry to investigate the neural basis underlying emotion regulation ability in a large sample of young adults. Assessment of emotion regulation ability was performed using the Wong and Law Emotional Intelligence Scale. As expected, males significantly scored higher in emotion regulation ability than females did. More importantly, we found the sex differences in the neuroanatomical basis of emotion regulation ability. Males showed a stronger positive relation between emotion regulation ability and regional gray matter volume (rGMV) in the right dorsolateral prefrontal cortex. In contrast, females demonstrated a stronger positive relation between emotion regulation ability and rGMV in an anatomical cluster that extends from the left brainstem to the left hippocampus, the left amygdala and the insular cortex. The present study provides the first empirical evidence regarding the sex-linked neuroanatomical correlates of emotion regulation ability. These findings may help understand why there is a higher prevalence of affective disorders in females and maladaptive behaviors in males.