Threats to social safety and neuro-inflammatory mechanisms underlying sexual orientation disparities in depression symptom severity: A prospective cohort study of young adults.

Sexual minority individuals have a markedly elevated risk of depression compared to heterosexuals. We examined early threats to social safety and chronically elevated inflammation as mechanisms contributing to this disparity in depression symptoms, and compared the relative strength of the co-occurrence between chronic inflammation and depression symptoms for sexual minorities versus heterosexuals. To do so, we analyzed data from a prospective cohort of sexual minority and heterosexual young adults (n = 595), recruited from a nationally representative sample, that included assessments of early threats to social safety in the form of adverse childhood interpersonal events, three biomarkers of inflammation (i.e., CRP, IL-6, TNF-α) measured at two time points, and depression symptoms over four years. In pre-registered analyses, we found that sexual minorities experienced more adverse childhood interpersonal events, were more likely to display chronically elevated inflammation, and reported more severe depression symptoms than heterosexuals. Adverse childhood interpersonal events and chronically elevated inflammation explained approximately 23 % of the total effect of the association between sexual orientation and depression symptom severity. Further, there was an increased coupling of chronically elevated inflammation and depression symptoms among sexual minorities compared to heterosexuals. These results provide novel longitudinal, population-based evidence for the role of chronically elevated inflammation in linking threats to social safety during childhood with depression symptom severity in young adulthood, consistent with the primary tenets of the social signal transduction theory of depression. Our study extends this theory to the population level by finding that members of a stigmatized population (i.e., sexual minorities) experience a greater risk of depression because of their greater exposure to adverse childhood interpersonal events and the subsequent link to chronic inflammation, highlighting potential biopsychosocial intervention targets.

The role of exogenous testosterone and social environment on the expression of sociosexuality and status-seeking behaviors in young Chilean men.

Testosterone plays an important role as a social hormone. Current evidence suggests that testosterone is positively related to sociosexuality increasing the psychological attitudes toward investing in short-term versus long-term mating and promotes status-seeking behaviors both by dominance and prestige. In addition, the social environment may play an important role in the expression of mating effort through changes in sociosexuality and status-seeking behaviors. However, the causal relationships among the mentioned variables are still debated. We employed a double-blind, placebo-controlled within-individual design, in order to test and integrate the proposed causal relationships between testosterone and social environment over short-term and long-term mating orientation and dominant and prestigious status-seeking behaviors in a sample of 95 young Chilean men. We did not find evidence that the administration of exogenous testosterone increased short-term or decreased long-term mating orientation as expected. Moreover, exogenous testosterone did not affect either aggressive or cooperative behavior failing to support the social status hypothesis. We also did not find any relationship between short or long-term mating orientation with status-seeking behaviors. Finally, we found support for the effect of social environment on sociosexual attitudes but not over status-seeking behaviors. Thus, men reported higher levels of short-term mating orientation in the presence of a woman compared to a man and no differences were found for long-term mating orientation. We argue that sociosexuality may be expressed flexibly, but contextual factors such as the presence of women seem more important than changes in testosterone levels.

Ovulatory cycle shifts in human motivational prioritisation of sex and food.

Previous research on the endogenous effects of ovarian hormones on motivational states in women has focused on sexual motivation. The Motivational Priority Shifts Hypothesis has a broader scope. It predicts a shift from somatic to reproductive motivation when fertile. In a highly powered preregistered online diary study across 40 days, we tested whether 390 women report such an ovulatory shift in sexual and eating motivation and behaviour. We compared 209 naturally cycling women to 181 women taking hormonal contraceptives (HC) to rule out non-ovulatory changes across the cycle as confounders. We found robust ovulatory decreases in food intake and increases in general sexual desire, in-pair sexual desire and initiation of dyadic sexual behaviour. Extra-pair sexual desire increased mid-cycle, but the effect did not differ significantly in HC women, questioning an ovulatory effect. Descriptively, solitary sexual desire and behaviour, dyadic sexual behaviour, appetite, and satiety showed expected mid-cycle changes that were diminished in HC women, but these failed to reach our strict preregistered significance level. Our results provide insight into current theoretical debates about ovulatory cycle shifts while calling for future research to determine motivational mechanisms behind ovulatory changes in food intake and considering romantic partners' motivational states to explain the occurrence of dyadic sexual behaviour.

Longitudinal changes in sexual desire and attraction among women who started using the Natural Cycles app.

Many women experience sexual side effects, such as decreased libido, when taking hormonal contraceptives (HCs). However, little is known about the extent to which libido recovers after discontinuing HCs, nor about the timeframe in which recovery is expected to occur. Given that HCs suppress the activities of multiple endogenous hormones that regulate both the ovulatory cycle and women's sexual function, resumption of cycles should predict libido recovery. Here, using a combination of repeated and retrospective measures, we examined changes in sexual desire and partner attraction (among partnered women) across a three-month period in a sample of Natural Cycles users (Survey 1: n = 1596; Survey 2: n = 550) who recently discontinued HCs. We also tested whether changes in these outcomes coincided with resumption of the ovulatory cycle and whether they were associated with additional factors related to HC use (e.g., duration of HC use) or relationship characteristics (e.g., relationship length). Results revealed that both sexual desire and partner attraction, on average, increased across three months after beginning to use Natural Cycles. While the prediction that changes in sexual desire would co-occur with cycle resumption was supported, there was also evidence that libido continued to increase even after cycles resumed. Together, these results offer new insights into relationships between HC discontinuation and women's sexual psychology and lay the groundwork for future research exploring the mechanisms underlying these effects.

Hormonal and cycle phase predictors of within-women shifts in self-perceived attractiveness: Tests of alternative functional models.

Prior research has produced mixed findings regarding whether women feel more attractive during the fertile phase of the menstrual cycle. Here, we analyzed cycle phase and hormonal predictors of women's self-perceived attractiveness (SPA) assessed within a daily diary study. Forty-three women indicated their SPA, sexual desire, and interest in their own partners or other potential mates each day across 1-2 menstrual cycles; saliva samples collected on corresponding days were assayed for estradiol, progesterone, and testosterone; and photos of the women taken at weekly intervals were rated for attractiveness. Contrary to some prior studies, we did not find a significant increase in SPA within the estimated fertile window (i.e., cycle days when conception is possible). However, within-cycle fluctuations in progesterone were significantly negatively associated with shifts in SPA, with a visible nadir in SPA in the mid-luteal phase. Women's sexual desire and SPA were positively associated, and the two variables fluctuated in very similar ways across the cycle. Third-party ratings of women's photos provided no evidence that women's SPA simply tracked actual changes in their visible attractiveness. Finally, for partnered women, changes in SPA correlated with shifts in attraction to own partners at least as strongly as it did with shifts in fantasy about extra-pair partners. Our findings provide preliminary evidence for the idea that SPA is a component of women's sexual motivation that may change in ways similar to other hormonally regulated shifts in motivational priorities. Additional large-scale studies are necessary to test replication of these preliminary findings.

Personal genital satisfaction is associated with differences in perception of male and female sexual anatomy and function.

BACKGROUND: Prior studies primarily of men correlated low personal genital satisfaction (PGS) with decreased sexual activity; however, the association between PGS and genital anatomy perceptions is unknown, and there is a paucity of studies examining women. AIM: We assessed the relationship between genital satisfaction, survey respondent sexual activity, and perceptions of anatomy and function. METHODS: A 54-item REDCap survey was distributed to any-gendered volunteers ≥18 years of age through ResearchMatch from January to March 2023. Responses were split into (1) high PGS and (2) low PGS. Analysis was performed using chi-square tests on survey responses and a Mann Whitney U test on median satisfaction level. OUTCOMES: Outcomes were genital anatomy perceptions, sexual activity, and respondents' PGS. RESULTS: Of the 649 respondents who started the survey, 560 (86.3%) completed it. Median PGS was 7 of 10, forming subgroups of high (≥7 of 10) satisfaction (n = 317 of 560 [56.6%]) and low (<7 of 10) satisfaction (n = 243 of 560 [43.4%]). The mean age was 45.8 ± 16.8 years, and demographics were notable for 72.1% women (n = 404 of 560), 83.2% White (n = 466 of 560), 47.9% married (n = 268 of 560), and 75.5% bachelor's degree holders (n = 423 of 560). Comparing high- and low-PGS groups, more low-PGS respondents felt normal flaccid penis length to be <2 inches (11.1% vs 5.1%; P = .008). High-PGS respondents more often responded that it is normal for women to have orgasms over half the time (20.8% vs 13.2%; P = .0002) or to identify as being sexually active (81.1% vs 71.6%; P = .008). Women were more likely than men to report larger normal testicle sizes as 60.1 to 90 mL (24.5% vs 10.3%; P < .0001), whereas more men felt that normal testicle size was 7 to 15 mL (26.3% vs 11.4%; P < .0001). Orgasm length perceptions also differed: more women felt female orgasm length was 2.6 to 5 seconds (36.6% vs 16.7%; P < .0001), and more men believed female orgasms to be longer, at 7.6 to 10 seconds (29.5% vs 17.3%; P = .002), 10.1 to 12.5 seconds (11.5% vs 5.2%; P = .0008), and >12.5 seconds (12.2% vs 5.7%; P = .009). Respondents' views on their genitalia differed by gender, with women more likely to feel that their genitals are normal compared with men (89.4% vs 75.0%; P < .0001). CLINICAL IMPLICATIONS: PGS may be a useful screening tool given its association with sexual activity. STRENGTHS AND LIMITATIONS: Our large-scale survey assesses public perceptions of genital anatomy and function. Limitations include a lack of gender nonbinary perceptions. CONCLUSION: Gender and PGS interact with perceptions of male anatomy and female sexual activity, and the frequency of sexual activity was higher among high-PGS respondents; however, the direction of these interactions remains unclear and requires future causal analysis.

Genital arousal and responsive desire among women with and without sexual interest/arousal disorder symptoms.

BACKGROUND: Models depicting sexual desire as responsive to sexual arousal may be particularly apt for women experiencing arousal or desire difficulties, and the degree to which arousal triggers desire may depend on the relationship context and desire target and timing-yet, these associations have not been directly tested among women with and without sexual interest/arousal disorder (SIAD). AIM: To assess the role of SIAD status and relationship satisfaction in the associations between genital arousal and 4 types of responsive desire. METHODS: One hundred women (n = 27 meeting diagnostic criteria for SIAD) in romantic relationships with men viewed a sexual film (pleasurable intimate depiction of oral sex and penile-vaginal intercourse) while their genital arousal was recorded via vaginal photoplethysmography (n = 63) or thermal imaging of the labia (n = 37). Partner and solitary desire was assessed immediately before and after the film (immediate desire) and 3 days later (delayed desire). OUTCOMES: Outcomes consisted of genital response (z scored by method) and associations between genital response and responsive sexual desire. RESULTS: The key difference between women with and without SIAD was not in their ability to experience genital arousal but in how their genital responses translated to responsive sexual desire. Women with SIAD actually exhibited greater genital arousal than unaffected women. Associations between genital arousal and desire were significant only for women with SIAD and depended on relationship satisfaction and desire type. For women with SIAD with low relationship satisfaction, higher arousal predicted lower immediate desire for a partner; for those with high relationship satisfaction, arousal was either positively related (vaginal photoplethysmography) or unrelated (thermal imaging of the labia) to immediate desire for a partner. Associations with other desire types were not significant. CLINICAL IMPLICATIONS: Patterns of genital arousal and partner-specific responsive desire among women affected with SIAD were indicative of an avoidance model in response to heightened genital arousal, unless relationship satisfaction was high; attending to genital arousal sensations could be a means of triggering sexual desire for women with SIAD who are satisfied in their relationships. STRENGTHS AND LIMITATIONS: This is one of the first sexual psychophysiologic studies to connect relationship factors to patterns of sexual response. The differing arousal assessment procedures and lack of official diagnosis may have attenuated results. The homogeneous sample and in-person session requirement limit generalizability. CONCLUSION: When compared with unaffected women, women affected by SIAD may exhibit stronger arousal responses with sufficiently incentivized sexual stimuli, and the connection between their genital arousal and responsive desire for their partners may be stronger and more dependent on relationship context.

The impact of male genital self-image on depression, anxiety and sexual functions.

AIM: This study aims to examine the relationship between male genital self-perception and sexual functioning and depression anxieties. METHOD: The study included male patients who were referred to the andrology outpatient clinic between March 2022 and June 2022. Demographic data of the patients were recorded. Cigarette and alcohol consumption was also noted. The Male Genital Self Image Scale (MGSIS) questionnaire was used for the Genital Self Image(GSI) assessment, which consists of 7 questions. The International Index of Erectile Function (IIEF), composed of 15 questions, was used to evaluate sexual function. STAI-I, STAI-II, and BECK scales were used for depression and anxiety. The penis size of the patients was measured in a flask and stretched condition, and the midpenile circumference was recorded. Patients were compared with respect to GSI, depression, anxiety, and sexual functioning. RESULTS: A total of 75 patients were included in the study. The mean age of the patients was 46.69 ± 11.32 (26-72), and the mean BMI was 27.82 ± 3.79 (22.46-40.40) kg/m2. A slightly positive correlation was found between the patients' flask penis size and MGSIS-total scores (r = 0.260, p = .024) and IIEF-SF scores (r = 0.240, p = .038). There was a moderately positive correlation between the stretched penis size and IIEF-OS (r = 0.403, p < .001) and IIEF-SF (r = 0.354, p = .002). While the MGSIS-total score and the STAI-I and STAI-II scores had a moderate negative correlation, there was an advanced negative correlation between the MGSIS-total score and the BECK score. CONCLUSION: Disruption of men's genital self-perception is moderately related to their susceptibility to depression and anxiety. This situation affects the person's sexual performance and causes orgasm problems to increase.

Exploring Women's State-Level Anxiety in Response to Virtual Reality Erotica.

Virtual Reality (VR)-based treatments for anxiety disorders are efficacious but there is a lack of research examining anxious responses to VR erotica, which could innovate treatments for sexual difficulties. We examined erotica features that elicited anxiety and sexual presence in women. Thirty-eight women viewed erotic videos from different modalities (2D, VR) and points of view (1st, 3rd person) and completed anxiety and sexual presence measures before and after each video. Women experienced greater anxiety for VR than 2D films and reported the most anxiety for VR 1st person films. Sexual presence was affected by modality and point of view.

Victim Sexual Arousal During Nonconsensual Sex: A Scoping Review.

Sexual arousal in male and female victims during nonconsensual sex is an understudied phenomenon with many potential psychological, clinical, and legal implications for survivors. The aim of this scoping review was to assess the literature to determine whether we could estimate the frequency and circumstances of physiological sexual arousal (e.g., erection, lubrication, ejaculation, orgasm) among victims during nonconsensual sex. Six reference database and hand searches led to the screening of 13,894 articles and other reports. Eight articles and one book published between 1977 and 2019 included relevant data from 136 male survivors and 250 female survivors. Results confirmed that physiological sexual arousal (only genital responses were mentioned) can occur in both male and female victims during nonconsensual sex. The frequency of these responses could not be determined because of the widely different methodologies used. In addition, it was not possible to determine the circumstances in which victim sexual arousal was more likely to occur although some were inferred. The results of the scoping review highlight that physiological sexual arousal during nonconsensual sex does occur for victims but has not been studied systematically. There is a clear need to properly assess the type, circumstances, consequences, and frequency of sexual arousal during nonconsensual sex in large and diverse populations of male and female survivors.

Primary Headache Associated with Sexual Activity: A Review of the Literature.

PURPOSE OF REVIEW: This review summarizes the evolution in diagnosis, evaluation, and treatment of primary headache associated with sexual activity (PHASA). RECENT FINDINGS: Despite increased access to patient information and advances in imaging, the pathophysiology of PHASA remains not fully understood. There are many secondary headaches that may present with headache during sexual activity, and a thorough workup is indicated to rule out potentially life-threatening etiologies. Many recent case series discuss the efficacy of known treatments of PHASA, as well as suggest other potential therapies for this condition including the newer CGRP-targeted therapies. Headaches during sexual activity can be worrisome events which necessitate urgent evaluation, particularly when presenting with sudden-onset and severe "thunderclap" headaches. A thorough workup including imaging should be conducted to rule out etiologies such as subarachnoid hemorrhage, reversible cerebral vasoconstrictive syndrome (RCVS), vasospasm, and dissection. PHASA is commonly comorbid with migraine, tension-type headache, exertional headache, and hypertension. PHASA can present as a dull headache that progresses with sexual excitement, or an explosive headache at or around orgasm. Pain is primarily occipital, diffuse, and bilateral. The headaches are discrete, recurrent events with bouts that typically self-resolve, but may also relapse and remit or continue chronically in some patients. PHASA can be treated preemptively with indomethacin and triptans administered prior to sexual activity, or treated prophylactically with beta-blockers, topiramate, and calcium channel blockers. CGRP-targeted therapies may provide relief in PHASA based on a few case reports, but there are no randomized controlled trials looking at specific efficacy for these therapies.

The association between female sexual function and metabolic features of the polycystic ovary syndrome in Turkish women of reproductive age.

OBJECTIVE: To investigate the association between female sexual function and metabolic features among women with polycystic ovary syndrome (PCOS) during reproductive age. METHOD: This was a cross-sectional study in which 288 women with PCOS and 180 women without PCOS between the ages of 20 and 40 years were evaluated. All women had serum total testosterone, androstenedione, DHEA-S, fasting glucose, total cholesterol, HDL-C, LDL-C, and triglyceride levels analyzed. The McCoy Female Sexual Questionnaire (MFSQ) was applied to all studied women. Exploratory factor analysis and reliability analysis were done after data collection. The factor loadings of MFSQ domains were compared between women with PCOS and controls. RESULTS: Average factor loadings of the MFSQ sexuality domain and MFSQ sexual partner domain were significantly lower in the PCOS group when compared to controls. There was no correlation between the two sexual function domains of the MFSQ and the PCOS features either in the PCOS group or the controls. CONCLUSION: PCOS is a heterogeneous disease with different metabolic components, such as insulin resistance, obesity, and hyperandrogenism. Although sexual function among women with PCOS was lower than controls, no differences were found in metabolic features of the PCOS and non-PCOS groups with relation to sexual function determined by the MFSQ.

Inclusion of genital, sexual, and gender diversity in human reproductive teaching: impact on student experience and recommendations for tertiary educators.

Western societal norms have long been constrained by binary and exclusionary perspectives on matters such as infertility, contraception, sexual health, sexuality, and gender. These viewpoints have shaped research and knowledge frameworks for decades and led to an inaccurate and incomplete reproductive biology curriculum. To combat these deficiencies in reproductive systems-related education, our teaching team undertook a gradual transformation of unit content from 2018 to 2023, aiming to better reflect real diversity in human reproductive biology. This initiative involved intentional modifications, including clear use of pronoun self-identification by staff. We addressed the historical lack of representation of genital variation and helped students interrogate oversimplified reproductive biology binaries. A novel assignment was also introduced, prompting students to apply reproductive physiology knowledge to propose innovative assisted reproductive technology solutions for diverse demographics. The collective impact of these innovations had a positive effect on student learning. With improved lecture content and inclusive language, the proportion of inclusive group assignment topics chosen by students more than doubled in 2021. By 2022, coinciding with assessment topic changes, the percentage of inclusive assignments topics surpassed 50%. Further development of laboratory activities on intersex genital variation and genital modification raised further understanding of genital, sexual, gender, and cultural diversity. While implementing these changes posed challenges, pushing both staff and students out of their comfort zones at times, collaboration with relevant organizations and individuals with lived experience of queer identity proved integral. Ultimately, these relatively simple adjustments had a substantial impact on student experiences and appreciation for diversity.NEW & NOTEWORTHY We outline the teaching innovations that we have implemented to improve inclusion of diversity in reproductive biology and physiology contexts. This includes improved representation of genital, sexual, and gender diversity considerations in the curriculum. There is a critical need for these innovations as how we teach fundamentally shapes the understanding of our future medical and health professionals and researchers and thus influences the quality of future medical care and research.

Sexual function and fertility in young female adults surgically treated for anorectal malformations.

PURPOSE: The aim was to investigate sexual function and fertility in female adults operated on for anorectal malformations (ARM). METHODS: This was a cross-sectional questionnaire-based study including female adult patients treated for ARM at our institution between 1994 and 2003. Sexual function in females was assessed using the Profile of Sexual Function (PFSF). Additional questions regarding fertility were answered by the participants. Patient characteristics were retrospectively retrieved from the medical records and descriptive statistics were used for analysis. Sexual function outcomes were compared to a control group from a previously published group of females. Composite outcome analysis was performed using previously published data to determine the potential impact of bowel function and health-related quality of life on sexual function. The ethics review authorities approved the study. RESULTS: A total of 14 of 30 (46.7%) females responded to the questionnaires and had a mean age of 21.1 years (range 18-26). No association was found between PFSF and age or bowel function (Bowel Function Score), however, a strong correlation was found between PFSF and health-related quality of life (HRQoL) with a Spearman correlation of ρ 0.82 (p = 0.0011). The general satisfaction question was strongly associated with their total PFSF score (ρ = 0.71, p = 0.0092). Except for the "desire" item, the females in this cohort did not have significantly worse sexual function than the control population(p = 0.015). Ten of fourteen (71.4%) females had had their sexual debut at a mean age of 16.3 years and two of these women (20%) have been pregnant. All females had had menarche at a mean age of 12.7 years. CONCLUSION: Sexual function in adult females was comparable to healthy controls except for the "desire" item where the cohort reported poorer outcomes. The cohort's sexual function had a direct association with their reported HRQoL where individuals with worse HRQoL also reported poorer sexual function. LEVEL OF EVIDENCE: III.

Disgust as a basic, sexual, and moral emotion.

Disgust is a basic emotion that increases the organism's survival success by preventing the transfer of pathogens. In this regard, it directs cognitive processes and motivates avoidance behaviors that prevent pathogens from entering the body. Moreover, disgust has many specific characteristics that distinguish it from other basic emotions. Firstly, unlike other basic emotions, it contaminates neutral objects around it and causes difficult-to-change learning. Another specific characteristic of disgust is that it depends on ideational processes. Objects, situations, and behaviors that do not contain pathogens can also cause disgust. In this regard, disgust appears not only as a basic emotion but also as different adaptations in different fields. In this context, two distinct adaptations of disgust stand out: sexual and moral disgust. These two adaptations of disgust benefit from disgust-related behaviors and motivations in different ways. Sexual disgust works as a gene protection mechanism, while moral disgust helps maintain social rules. The specific characteristics of disgust and its effects on cognitive processes such as attention and memory interact. In conclusion, the multifaceted structure of disgust shows that it needs to be studied more in the subfields of psychology. (Strohminger, Philos Compass 9:478-493, 2014) defines disgust as a psychological nebula that needs to be discovered. However, it is observed that disgust has not been adequately addressed. This review aims to comprehensively explore unique characteristics and diverse aspects of disgust, shedding light on its significance from various perspectives. This study underscores the broader understanding of disgust and its pivotal role in psychological research.

[The role of seminal vesicles in male sexual function].

The seminal vesicle is an important accessory gland of the male reproductive system. In the past, some scholars focused more on its role in the fertilization process and neglected its relationship with male sexual function. Researches show that the seminal vesicle is involved in multiple processes such as sexual desire, penile erection, and ejaculation. Treatment of sexual dysfunction by medication targeting the seminal vesicle has achieved certain therapeutic effects. This article discusses the relationship between the seminal vesicle and sexual function in terms of physiopathology, clinical study and basic research, hoping to provide some new ideas on the clinical diagnosis and treatment of sexual dysfunction.

Pattern recognition reveals sex-dependent neural substrates of sexual perception.

Sex differences in brain activity evoked by sexual stimuli remain elusive despite robust evidence for stronger enjoyment of and interest toward sexual stimuli in men than in women. To test whether visual sexual stimuli evoke different brain activity patterns in men and women, we measured hemodynamic brain activity induced by visual sexual stimuli in two experiments with 91 subjects (46 males). In one experiment, the subjects viewed sexual and nonsexual film clips, and dynamic annotations for nudity in the clips were used to predict hemodynamic activity. In the second experiment, the subjects viewed sexual and nonsexual pictures in an event-related design. Men showed stronger activation than women in the visual and prefrontal cortices and dorsal attention network in both experiments. Furthermore, using multivariate pattern classification we could accurately predict the sex of the subject on the basis of the brain activity elicited by the sexual stimuli. The classification generalized across the experiments indicating that the sex differences were task-independent. Eye tracking data obtained from an independent sample of subjects (N = 110) showed that men looked longer than women at the chest area of the nude female actors in the film clips. These results indicate that visual sexual stimuli evoke discernible brain activity patterns in men and women which may reflect stronger attentional engagement with sexual stimuli in men.

Next-generation GRAB sensors for monitoring dopaminergic activity in vivo.

Dopamine (DA) plays a critical role in the brain, and the ability to directly measure dopaminergic activity is essential for understanding its physiological functions. We therefore developed red fluorescent G-protein-coupled receptor-activation-based DA (GRABDA) sensors and optimized versions of green fluorescent GRABDA sensors. In response to extracellular DA, both the red and green GRABDA sensors exhibit a large increase in fluorescence, with subcellular resolution, subsecond kinetics and nanomolar-to-submicromolar affinity. Moreover, the GRABDA sensors resolve evoked DA release in mouse brain slices, detect evoked compartmental DA release from a single neuron in live flies and report optogenetically elicited nigrostriatal DA release as well as mesoaccumbens dopaminergic activity during sexual behavior in freely behaving mice. Coexpressing red GRABDA with either green GRABDA or the calcium indicator GCaMP6s allows tracking of dopaminergic signaling and neuronal activity in distinct circuits in vivo.

The neural mechanisms and circuitry of the pair bond.

Love is one of our most powerful emotions, inspiring some of the greatest art, literature and conquests of human history. Although aspects of love are surely unique to our species, human romantic relationships are displays of a mating system characterized by pair bonding, likely built on ancient foundational neural mechanisms governing individual recognition, social reward, territorial behaviour and maternal nurturing. Studies in monogamous prairie voles and mice have revealed precise neural mechanisms regulating processes essential for the pair bond. Here, we discuss current viewpoints on the biology underlying pair bond formation, its maintenance and associated behaviours from neural and evolutionary perspectives.

Update on headaches associated with physical exertion.

BACKGROUND: Headaches associated with physical exertion include headache precipitated by coughing or other Valsalva maneuvers, headache brought on by prolonged physical exercise, sexual headaches and cardiac cephalalgia. OBJECTIVE: To review and update the clinical characteristics, etiologies, pathophysiology and management of these headaches related to exertion. METHODS: In depth review of the publications, both in PubMed and in the main textbooks, of the different headaches induced by physical exercise. RESULTS: Cough, exercise and sexual headaches can be primary or secondary; therefore, complementary studies are mandatory to rule out structural lesions. However, clinical characteristics, such as an old age and response to indomethacin for cough headache or being a young male and response to beta-blockers for exercise and sexual headaches, plus a normal examination are suggestive of a primary etiology. Etiology for secondary varieties, as posterior fossa lesions for cough headache or vascular malformations for exercise and sexual headaches, are also different. Finally, headache as a distant manifestation of myocardial ischemia, also known as "cardiac cephalalgia", appears at exertion in around two-thirds of cases and typically lasts less than 30 minutes and is relieved by nitroglycerine. CONCLUSIONS: Primary and secondary cough headache can usually be suspected based on clinical characteristics and separated from exercise and sexual headaches, which share many aspects. Cardiac cephalalgia is not necessarily an exertional headache and should be considered in adult patients with short lasting headaches and patent vascular risk factors.