Suicidality in clinic-referred transgender adolescents.

Gender and sexually diverse adolescents have been reported to be at an elevated risk for suicidal thoughts and behaviors. For transgender adolescents, there has been variation in source of ascertainment and how suicidality was measured, including the time-frame (e.g., past 6 months, lifetime). In studies of clinic-referred samples of transgender adolescents, none utilized any type of comparison or control group. The present study examined suicidality in transgender adolescents (M age, 15.99 years) seen at specialty clinics in Toronto, Canada, Amsterdam, the Netherlands, and London, UK (total N = 2771). Suicidality was measured using two items from the Child Behavior Checklist (CBCL) and the Youth Self-Report (YSR). The CBCL/YSR referred and non-referred standardization samples from both the U.S. and the Netherlands were used for comparative purposes. Multiple linear regression analyses showed that there was significant between-clinic variation in suicidality on both the CBCL and the YSR; in addition, suicidality was consistently higher among birth-assigned females and strongly associated with degree of general behavioral and emotional problems. Compared to the U.S. and Dutch CBCL/YSR standardization samples, the relative risk of suicidality was somewhat higher than referred adolescents but substantially higher than non-referred adolescents. The results were discussed in relation to both gender identity specific and more general risk factors for suicidality.

Validation of the Chinese Version of the Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults.

BACKGROUND: The number of individuals with potential gender dysphoria (GD) being referred to specialized gender identity clinics or programs is increasing internationally; these cases are initially screened using the Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults (GIDYQ-AA). AIM: The current study aimed to assess the psychometric properties of the GIDYQ-AA in a sample of adolescents and young adults from China. METHODS: A cross-sectional study was conducted in October 2020. Sociodemographic information of the participants was first collected. Participants then completed the GIDYQ-AA, the Generalized Anxiety Disorder-7 scale, the Patient Health Questionnaire-9, and a suicidal ideation assessment. A total of 2,533 participants with a mean age of 19.30 (SD = 1.19) years were recruited. Of the participants, 841 (33.2%) were cis men, 1,589 (62.7%) were cis women, 66 (2.6%) self-identified as transgender, 17 (0.7%) self-identified as non-binary, and 20 (0.8%) self-identified as gender queer. RESULTS: The GIDYQ-AA had high internal consistency with a Cronbach's alpha = 0.89. Exploratory factor analysis showed that the GIDYQ-AA had a four-factor structure in China. The GIDYQ-AA was significantly correlated with anxiety symptoms (r = -0.32, P < .01), depressive symptoms (r = -0.33, P < .01), and suicidal ideation (r = -0.20, P < .01). CLINICAL TRANSLATION: The Chinese version of GIDYQ-AA is a useful measurement with high practical value, which could promote the assessment and research of GD across China or among Chinese migrants in other countries. STRENGTHS AND LIMITATIONS: This is the first study assessing the psychometric properties of the GIDYQ-AA in Chinese adolescents and young adults. The convergent and divergent validity of the GIDYQ-AA were not examined due to the unavailability of data. Also, the sample did not have an equal distribution of male to males and female to females. CONCLUSION: The Chinese version of GIDYQ-AA is a useful measure, which could promote both the assessment and research of GD in the Chinese population. Wang Y, Feng Y, Su D, et al. Validation of the Chinese Version of the Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults. J Sex Med 2021;18:1632-1640.

Male homosexuality and maternal immune responsivity to the Y-linked protein NLGN4Y.

We conducted a direct test of an immunological explanation of the finding that gay men have a greater number of older brothers than do heterosexual men. This explanation posits that some mothers develop antibodies against a Y-linked protein important in male brain development, and that this effect becomes increasingly likely with each male gestation, altering brain structures underlying sexual orientation in their later-born sons. Immune assays targeting two Y-linked proteins important in brain development-protocadherin 11 Y-linked (PCDH11Y) and neuroligin 4 Y-linked (NLGN4Y; isoforms 1 and 2)-were developed. Plasma from mothers of sons, about half of whom had a gay son, along with additional controls (women with no sons, men) was analyzed for male protein-specific antibodies. Results indicated women had significantly higher anti-NLGN4Y levels than men. In addition, after statistically controlling for number of pregnancies, mothers of gay sons, particularly those with older brothers, had significantly higher anti-NLGN4Y levels than did the control samples of women, including mothers of heterosexual sons. The results suggest an association between a maternal immune response to NLGN4Y and subsequent sexual orientation in male offspring.

A method yielding comparable estimates of the fraternal birth order and female fecundity effects in male homosexuality.

The fraternal birth order effect (FBOE) is the finding that older brothers increase the probability of homosexuality in later-born males, and the female fecundity effect (FFE) is the finding that the mothers of homosexual males produce more offspring than the mothers of heterosexual males. In a recent paper, Khovanova proposed a novel method for computing independent estimates of these effects on the same samples and expressing the magnitude and direction of the effects in the same metric. In her procedure, only families with one or two sons are examined, and daughters are ignored. The present study investigated the performance of Khovanova's method using archived data from 10 studies, comprising 14 samples totalling 5390 homosexual and heterosexual subjects. The effect estimate for the FBOE showed that an increase from zero older brothers to one older brother is associated with a 38% increase in the odds of homosexuality. By contrast, the effect estimate for the FFE showed that the increase from zero younger brothers to one younger brother is not associated with any increase in the odds of homosexuality. The former result supports the maternal immune hypothesis of male homosexuality; the latter result does not support the balancing selection hypothesis.

Birth Order and Sibling Sex Ratio in Androphilic Males and Gynephilic Females Diagnosed With Gender Dysphoria From Iran.

BACKGROUND: This study investigated the effect of older brothers on sexual orientation in male adults diagnosed with gender dysphoria and the effect of older sisters on sexual orientation in female adults diagnosed with gender dysphoria from Iran. AIM: To assess for the presence of a fraternal birth order effect in transgender androphilic males and a sororal birth order effect in transgender gynephilic females. METHODS: The subjects were 92 transgender males and 107 transgender females (all of whom met the DSM-5 criteria for gender dysphoria), together with 72 male and 78 female clinical controls. All the transgender males were androphilic, all the transgender females were gynephilic (preferentially attracted to members of their own biological sex), and all of the clinical controls were heterosexual (none were transgender or had a diagnosis of gender dysphoria). OUTCOMES: In relation to the probands, we analyzed the sibship composition of our groups with regard to birth order and sibling sex ratio (brothers to sisters). RESULTS: The results for the transgender males confirmed the findings of 2 recent meta-analyses that older brothers increase the odds of androphilia in later-born males. The results for the transgender females did not clearly confirm one previous finding that older sisters increase the odds of gynephilia in later-born females-a finding obtained in a relatively large study that included gynephilic cisgender girls as well as girls diagnosed with gender dysphoria who will probably be predominantly gynephilic. CLINICAL IMPLICATIONS: The fraternal (later-born) birth order effect that we found for the transgender androphilic males, similar to that found in gay men, suggests a common underlying causal mechanism. STRENGTHS AND LIMITATIONS: Our study on Iranian patients diagnosed with gender dysphoria provides further generalizability for the study of birth order and sibling sex ratio that has, more often than not, been restricted to Western samples of adults diagnosed with gender dysphoria. It would be important to study these variables in Iranian gay men and lesbian women (without gender dysphoria) to further examine evidence for cross-cultural similarities when compared to Western samples. CONCLUSIONS: In contrast to the well-established fraternal birth order effect for males, the possible sororal birth order effect for females needs to be examined with additional samples. Khorashad BS, Zucker KJ, Talaei A. Birth Order and Sibling Sex Ratio in Androphilic Males and Gynephilic Females Diagnosed With Gender Dysphoria from Iran. J Sex Med 2020;17:1195-1202.

Debate: Different strokes for different folks.

A gender social transition in prepubertal children is a form of psychosocial treatment that aims to reduce gender dysphoria, but with the likely consequence of subsequent (lifelong) biomedical treatments as well (gender-affirming hormonal treatment and surgery). Gender social transition of prepubertal children will increase dramatically the rate of gender dysphoria persistence when compared to follow-up studies of children with gender dysphoria who did not receive this type of psychosocial intervention and, oddly enough, might be characterized as iatrogenic. Parents who bring their children for clinical care hold different philosophical views on what is the best way to help reduce the gender dysphoria, which require both respect and understanding.

Adolescents with Gender Dysphoria: Reflections on Some Contemporary Clinical and Research Issues.

This article provides an overview of five contemporary clinical and research issues pertaining to adolescents with a diagnosis of gender dysphoria: (1) increased referrals to specialized gender identity clinics; (2) alteration in the sex ratio; (3) suicidality; (4) "rapid-onset gender dysphoria" (ROGD) as a new developmental pathway; (5) and best practice clinical care for adolescents who may have ROGD.

Evidence for a Change in the Sex Ratio of Children Referred for Gender Dysphoria: Data From the Gender Identity Development Service in London (2000-2017).

INTRODUCTION: The prevalence of gender dysphoria in children is not known; however, there are some data on the sex ratio of children referred to specialized gender identity clinics. AIM: We sought to examine the sex ratio of children, and some associated factors (age at referral and year of referral), referred to the Gender Identity Development Service in the United Kingdom, the largest such clinic in the world. METHODS: The sex ratio of children (N = 1,215) referred to the Gender Identity Development Service between 2000-2017 was examined, along with year of referral, age-related patterns, and age at referral. MAIN OUTCOME MEASURE: Sex ratio of birth-assigned boys vs birth-assigned girls. RESULTS: The sex ratio significantly favored birth-assigned boys over birth-assigned girls (1.27:1), but there were also age and year of referral effects. The sex ratio favored birth-assigned boys at younger ages (3-9 years), but favored birth-assigned girls at older ages (10-12 years). The percentage of referred birth-assigned boys significantly decreased when 2 cohorts were compared (2000-2006 vs 2007-2017). On average, birth-assigned boys were referred at a younger age than birth-assigned girls. CLINICAL IMPLICATIONS: The evidence for a change in the sex ratio of children referred for gender dysphoria, particularly in recent years, matches a similar change in the sex ratio of adolescents referred for gender dysphoria. The reasons for this remain understudied. STRENGTH & LIMITATIONS: The United Kingdom data showed both similarities and differences when compared to data from 2 other gender identity clinics for children (Toronto, Ontario, Canada, and Amsterdam, The Netherlands). Such data need to be studied in more gender identity clinics for children, perhaps with the establishment of an international registry. CONCLUSION: Further study of the correlates of the sex ratio for children referred for gender dysphoria will be useful in clinical care and management. de Graaf NM, Carmichael P, Steensma TD, et al. Evidence for a Change in the Sex Ratio of Children Referred for Gender Dysphoria: Data From the Gender Identity Development Service in London (2000-2017). J Sex Med 2018;15:1381-1383.

Behavior Problems and Psychiatric Diagnoses in Girls with Gender Identity Disorder: A Follow-Up Study.

This study evaluated the presence of clinical range behavior problems and psychiatric diagnoses in 25 girls referred for gender identity disorder (GID) in childhood (mean age: 8.88 years) at the time of follow-up in adolescence or adulthood (mean age: 23.2 years). At follow-up, three (12%) of the girls were judged to have persistent GID based on DSM-IV criteria. With regard to behavior problems at follow-up, 39.1% of the girls had a clinical range score on either the Child Behavior Checklist or Adult Behavior Checklist as rated by their mothers, and 33.3% had a clinical range score on either the Youth Self-Report or the Adult Self-Report. On either the Diagnostic Interview for Children and Adolescents or the Diagnostic Interview Schedule, the girls had, on average, 2.67 diagnoses (range: 0-10); 46% met criteria for three or more diagnoses. From the childhood assessment, five variables were significantly associated with a composite Psychopathology Index (PI) at follow-up: a lower IQ, living in a non-two-parent or reconstituted family, a composite behavior problem index, and poor peer relations. At follow-up, degree of concurrent homoeroticism and a composite index of gender dysphoria were both associated with the composite PI. Girls with GID show a psychiatric vulnerability at the time of follow-up in late adolescence or adulthood, although there was considerable variation in their general well-being.

Separation anxiety among birth-assigned male children in a specialty gender identity service.

Previous research suggested that separation anxiety disorder (SAD) is overrepresented among birth-assigned male children clinic-referred for gender dysphoria (GD). The present study examined maternally reported separation anxiety of birth-assigned male children assessed in a specialty gender identity service (N = 360). SAD was determined in relation to DSM-III and DSM-IV criteria, respectively. A dimensional metric of separation anxiety was examined in relation to several additional factors: age, ethnicity, parental marital status and social class, IQ, gender nonconformity, behavioral and emotional problems, and poor peer relations. When defined in a liberal fashion, 55.8% were classified as having SAD. When using a more conservative criterion, 5.3% were classified as having SAD, which was significantly greater than the estimated general population prevalence for boys, but not for girls. Dimensionally, separation anxiety was associated with having parents who were not married or cohabitating as well as with elevations in gender nonconformity; however, the association with gender nonconformity was no longer significant when statistically controlling for internalizing problems. Thus, SAD appears to be common among birth-assigned males clinic-referred for GD when defined in a liberal fashion, and more common than in boys, but not girls, from the general population even when more stringent criteria were applied. Also, the degree of separation anxiety appears to be linked to generic risk factors (i.e., parental marital status, internalizing problems). As such, although separation anxiety is common among birth-assigned male children clinic-referred for GD, it seems unlikely to hold unique significance for this population based on the current data.

Psychosocial and Psychological Vulnerability in Adolescents with Gender Dysphoria: A "Proof of Principle" Study.

For adolescents with gender dysphoria, it has become common to be offered hormonal treatment to either delay or suppress pubertal development and/or to masculinize or feminize the body. At the same time, it has been our clinical impression that the psychological vulnerability of at least some of these youth has been overlooked. Fifty consecutive referrals of adolescents with a DSM-IV-TR diagnosis of gender identity disorder (GID) constituted the sample. Information obtained at intake was coded for the presence or absence of 15 psychosocial and psychological vulnerability factors. The mean number of psychosocial/psychological vulnerability factors coded as present was 5.56 (range, 0-13). Over half of the sample had six or more of the vulnerability factors. The number of factors coded as present was significantly correlated with behavioral and emotional problems on the Youth Self-Report Form and the Child Behavior Checklist, but not with demographic variables or IQ. The findings supported the clinical impression that a large percentage of adolescents referred for gender dysphoria have a substantial co-occurring history of psychosocial and psychological vulnerability, thus supporting a "proof of principle" for the importance of a comprehensive psychologic/psychiatric assessment that goes beyond an evaluation of gender dysphoria per se.

The Prevalence of Only-Child Status Among Children and Adolescents Referred to a Gender Identity Service Versus a Clinical Comparison Group.

Several studies indicate that homosexual males have a high proportion of older brothers compared to heterosexual males. Natal males with gender dysphoria who are likely to be homosexual also display this sibship pattern. Until recently, there was little evidence linking homosexuality and/or gender dysphoria in females to unique sibship characteristics. Two studies have indicated that natal female youth clinically referred for gender dysphoria are more likely to be only children (Schagen, Delemarre-van de Waal, Blanchard, & Cohen-Kettenis, 2012; VanderLaan, Blanchard, Wood, & Zucker, 2014). However, these studies did not include control groups of youth clinically referred for other reasons. Thus, it is unclear whether the increased likelihood of only-child status is specific to gender-referred natal females. This study compared only-child status among youth referred to a mental health service for gender dysphoria (778 males, 245 females) versus other reasons (783 males, 281 females). Prehomosexual gender-referred males were less likely to be only children than clinical controls. Contrary to previous findings, gender-referred females were not more likely to be only children, indicating that increased likelihood of only-child status is not specific to gender-referred females, but is characteristic of clinic-referred females more generally.

Gay Male Only-Children: Evidence for Low Birth Weight and High Maternal Miscarriage Rates.

Recent findings suggest that there may be a maternal immune response underpinning the etiology of sexual orientation of gay male only-children. This maternal immune response appears to be distinct from that which is purported to explain the classic fraternal birth order effect found in studies of male sexual orientation. We tested two predictions related to the hypothesized maternal immune response in mothers of gay male only-children: (1) elevated fetal loss among mothers who have had gay male only-children and (2) lower birth weight in gay male only-children. Mothers of at least one gay son (n = 54) and mothers of heterosexual son(s) (n = 72) self-reported their pregnancy histories, including the birth weights of newborns and number of fetal losses (e.g., miscarriages). Mothers of gay male only-children (n = 8) reported significantly greater fetal loss compared with mothers of males with four other sibship compositions (gay with no older brothers, gay with older brothers, heterosexual only-children, heterosexual with siblings) (n = 118). Also, firstborn gay male only-children (n = 4) had a significantly lower birth weight than firstborn children in the four other sibship compositions (n = 59). Duration of pregnancy was not significantly different among the groups of firstborn children in the birth weight analyses. Thus, this study found further support for a distinct pattern of maternal immune response implicated in the etiology of male sexual orientation. Mechanisms that may underlie this potential second type of maternal immune response are discussed.

BIRTH ORDER AND ANDROPHILIC MALE-TO-FEMALE TRANSSEXUALISM IN BRAZIL.

Previous research has indicated that biological older brothers increase the odds of androphilia in males. This finding has been termed the fraternal birth order effect. The maternal immune hypothesis suggests that this effect reflects the progressive immunization of some mothers to male-specific antigens involved in fetal male brain masculinization. Exposure to these antigens, as a result of carrying earlier-born sons, is hypothesized to produce maternal immune responses towards later-born sons, thus leading to female-typical neural development of brain regions underlying sexual orientation. Because this hypothesis posits mechanisms that have the potential to be active in any situation where a mother gestates repeated male fetuses, a key prediction is that the fraternal birth order effect should be observable in diverse populations. The present study assessed the association between sexual orientation and birth order in androphilic male-to-female transsexuals in Brazil, a previously unexamined population. Male-to-female transsexuals who reported attraction to males were recruited from a specialty gender identity service in southern Brazil (n=118) and a comparison group of gynephilic non-transsexual men (n=143) was recruited at the same hospital. Logistic regression showed that the transsexual group had significantly more older brothers and other siblings. These effects were independent of one another and consistent with previous studies of birth order and male sexual orientation. The presence of the fraternal birth order effect in the present sample provides further evidence of the ubiquity of this effect and, therefore, lends support to the maternal immune hypothesis as an explanation of androphilic sexual orientation in some male-to-female transsexuals.

Neural Correlates of Psychosis and Gender Dysphoria in an Adult Male.

Gender dysphoria (GD) (DSM-5) or transsexualism (ICD-10) refers to the marked incongruity between the experience of one's gender and the sex at birth. In this case report, we describe the use of LSD as a triggering factor of confusion in the gender identity of a 39-year-old male patient, with symptoms of psychosis and 25 years of substance abuse, who sought psychiatric care with the desire to undergo sex reassignment surgery. The symptoms of GD/psychosis were resolved by two therapeutic measures: withdrawal of psychoactive substances and use of a low-dose antipsychotic. We discuss the hypothesis that the superior parietal cortical area may be an important locus for body image and that symptoms of GD may be related to variations underlying this brain region. Finally, this case report shows that some presentations of GD can be created by life experience in individuals who have underlying mental or, synonymously, neurophysiological abnormalities.

Gender Dysphoria in Adults.

Gender dysphoria (GD), a term that denotes persistent discomfort with one's biologic sex or assigned gender, replaced the diagnosis of gender identity disorder in the Diagnostic and Statistical Manual of Mental Disorders in 2013. Subtypes of GD in adults, defined by sexual orientation and age of onset, have been described; these display different developmental trajectories and prognoses. Prevalence studies conclude that fewer than 1 in 10,000 adult natal males and 1 in 30,000 adult natal females experience GD, but such estimates vary widely. GD in adults is associated with an elevated prevalence of comorbid psychopathology, especially mood disorders, anxiety disorders, and suicidality. Causal mechanisms in GD are incompletely understood, but genetic, neurodevelopmental, and psychosocial factors probably all contribute. Treatment of GD in adults, although largely standardized, is likely to evolve in response to the increasing diversity of persons seeking treatment, demands for greater client autonomy, and improved understanding of the benefits and limitations of current treatment modalities.