In Addition to Stigma: Cognitive and Autism-Related Predictors of Mental Health in Transgender Adolescents.

OBJECTIVE: Autism spectrum disorder (ASD) is significantly over-represented among transgender adolescents. Independently, ASD and gender diversity are associated with increased mental health risks. Yet, mental health in autistic-transgender adolescents is poorly understood. This study investigates mental health in the largest matched sample to date of autistic-transgender, non-autistic (allistic) transgender, and autistic-cisgender adolescents diagnosed using gold-standard ASD diagnostic procedures. In accordance with advancing understanding of sex/gender-related autism phenotypes, slightly subthreshold autistic diagnostic presentations (common in autistic girls/women) are modeled. METHOD: This study includes 93 adolescents aged 13-21, evenly divided between autistic-transgender, autistic-cisgender, and allistic-transgender groups; 13 transgender adolescents were at the margin of ASD diagnosis and included within a larger "broad-ASD" grouping. Psychological and neuropsychological evaluation included assessment of mental health, IQ, LGBT stigma, ASD-related social symptoms, executive functioning (EF), and EF-related barriers to achieving gender-related needs. RESULTS: Autistic-transgender adolescents experienced significantly greater internalizing symptoms compared to allistic-transgender and autistic-cisgender groups. In addition to stigma-related associations with mental health, ASD-related cognitive/neurodevelopmental factors (i.e., poorer EF and greater social symptoms) were associated with worse mental health: specifically, social symptoms and EF gender barriers with greater internalizing and EF problems and EF gender barriers with greater suicidality. Comparing across all ASD and gender-related groups, female gender identity was associated with greater suicidality. CONCLUSIONS: Parsing the heterogeneity of mental health risks among transgender youth is critical for developing targeted assessments and interventions. This study identifies ASD diagnosis, ASD phenotypic characteristics, and EF-related gender barriers as potential risks for poorer mental health in transgender adolescents.

Matrix Protein 2 Extracellular Domain-Specific Monoclonal Antibodies Are an Effective and Potentially Universal Treatment for Influenza A.

Influenza virus infection causes significant morbidity and mortality worldwide. Humans fail to make a universally protective memory immune response to influenza A. Hemagglutinin and Neuraminidase undergo antigenic drift and shift, resulting in new influenza A strains to which humans are naive. Seasonal vaccines are often ineffective and escape mutants have been reported to all treatments for influenza A. In the absence of a universal influenza A vaccine or treatment, influenza A will remain a significant threat to human health. The extracellular domain of the M2-ion channel (M2e) is an ideal antigenic target for a universal therapeutic agent, as it is highly conserved across influenza A serotypes, has a low mutation rate, and is essential for viral entry and replication. Previous M2e-specific monoclonal antibodies (M2e-MAbs) show protective potential against influenza A, however, they are either strain specific or have limited efficacy. We generated seven murine M2e-MAbs and utilized in vitro and in vivo assays to validate the specificity of our novel M2e-MAbs and to explore the universality of their protective potential. Our data shows our M2e-MAbs bind to M2e peptide, HEK cells expressing the M2 channel, as well as, influenza virions and MDCK-ATL cells infected with influenza viruses of multiple serotypes. Our antibodies significantly protect highly influenza A virus susceptible BALB/c mice from lethal challenge with H1N1 A/PR/8/34, pH1N1 A/CA/07/2009, H5N1 A/Vietnam/1203/2004, and H7N9 A/Anhui/1/2013 by improving survival rates and weight loss. Based on these results, at least four of our seven M2e-MAbs show strong potential as universal influenza A treatments.IMPORTANCE Despite a seasonal vaccine and multiple therapeutic treatments, Influenza A remains a significant threat to human health. The biggest obstacle is producing a vaccine or treatment for influenza A is their universality or efficacy against not only seasonal variances in the influenza virus, but also against all human, avian, and swine serotypes and, therefore, potential pandemic strains. M2e has huge potential as a target for a vaccine or treatment against influenza A. It is the most conserved external protein on the virus. Antibodies against M2e have made it to clinical trials, but not succeeded. Here, we describe novel M2e antibodies produced in mice that are not only protective at low doses, but that we extensively test to determine their universality and found to be cross protective against all strains tested. Additionally, our work begins to elucidate the critical role of isotype for an influenza A monoclonal antibody therapeutic.

Transgender Youth Executive Functioning: Relationships with Anxiety Symptoms, Autism Spectrum Disorder, and Gender-Affirming Medical Treatment Status.

Executive function (EF) underlies broad health and adaptive outcomes. For transgender youth, navigating gender discernment and gender affirmation demand EF. Yet, factors associated with transgender youth EF are unknown. We investigate hypothesized predictors of EF: over-represented conditions among transgender youth (anxiety and depression symptoms, autism spectrum disorder [ASD]) and gender-affirming care. One-hundred twenty-four transgender 11-21-year-olds participated. Parents/caregivers completed EF and mental health report measures. ASD diagnostics and gender-affirming medication histories were collected. 21 % of non-autistic and 69 % of autistic transgender youth had clinically elevated EF problems. Membership in the gender-affirming hormone treatment group was associated with better EF. ASD, anxiety symptoms, and membership in the long-duration pubertal suppression group were associated with poorer EF. Given the importance of EF skills for multiple outcomes, and the unique and additional EF demands specific to transgender youths' experiences, EF skill monitoring-and when appropriate, supports-should be considered for transgender youth.

Natural language markers of social phenotype in girls with autism.

BACKGROUND: Girls with autism spectrum condition (ASC) are chronically underdiagnosed compared to boys, which may be due to poorly understood sex differences in a variety of domains, including social interest and motivation. In this study, we use natural language processing to identify objective markers of social phenotype that are easily obtained from a brief conversation with a nonexpert. METHODS: 87 school-aged children and adolescents with ASC (17 girls, 33 boys) or typical development (TD; 15 girls, 22 boys) were matched on age (mean = 11.35 years), IQ estimates (mean = 107), and - for ASC participants - level of social impairment. Participants engaged in an informal 5-min 'get to know you' conversation with a nonexpert conversation partner. To measure attention to social groups, we analyzed first-person plural pronoun variants (e.g., 'we' and 'us') and third-person plural pronoun variants (e.g., 'they' and 'them'). RESULTS: Consistent with prior research suggesting greater social motivation in autistic girls, autistic girls talked more about social groups than did ASC boys. Compared to TD girls, autistic girls demonstrated atypically heightened discussion of groups they were not a part of ('they', 'them'), indicating potential awareness of social exclusion. Pronoun use predicted individual differences in the social phenotypes of autistic girls. CONCLUSIONS: Relatively heightened but atypical social group focus is evident in autistic girls during spontaneous conversation, which contrasts with patterns observed in autistic boys and TD girls. Quantifying subtle linguistic differences in verbally fluent autistic girls is an important step toward improved identification and support for this understudied sector of the autism spectrum.

AuNP-M2e + sCpG vaccination of juvenile mice generates lifelong protective immunity to influenza A virus infection.

BACKGROUND: Influenza virus infection causes significant morbidity and mortality worldwide. Humans fail to make a universally protective memory response to influenza A because of high mutation rates in the immune-dominant influenza epitopes. We seek the development of a universal influenza A vaccine. The extracellular domain of the M2-ion channel (M2e) is an ideal antigenic target, as it is highly conserved, has a low mutation rate, and is essential for viral entry and replication. Considering the potential of a universal influenza vaccine for lifelong protection, we aimed to examine this potential using a recently published gold nanoparticle M2e vaccine with CpG as an adjuvant (AuNP-M2e + sCpG). Intranasal vaccination induces an M2e-specific memory response, which is protective against lethal infection with H1N1, H3N2, and H5N1 serotypes, in young BALB/c mice. Protection with AuNP-M2e + sCpG has been published up to 8 months after vaccination. However, the highest risk population during most influenza seasons is adults over 65 years old. Additionally, the efficacy of many vaccines decrease after aging and requiring booster vaccinations to remain effective. RESULTS: To determine if the AuNP-M2e + sCpG vaccine is a viable option as a universal vaccination capable of protection through geriatric age, we tested if the AuNP-M2e + sCpG vaccination loses efficacy after aging mice to geriatric age (over 18 months). Our data shows that mice aged 15 months after vaccination (~ 18-21 months old) retain significant M2e-specific antibody titers in total IgG, IgG1, IgG2a, and IgG2b. These mice are significantly protected from lethal influenza challenge (H1N1, 8.3 PFU). Further, these antibody titers increase upon infection with influenza A and remain elevated for 3 months, suggesting the elderly mice retain effective M2e-specific memory B cells. CONCLUSIONS: Our results demonstrate that protective M2e-specific memory in mice developed at a young age can persist until geriatric age. Additionally, this memory is protective and M2e-specific B cells produced by vaccination with AuNP-M2e + sCpG are maintained and functional. If the results of this study persist in humans, they suggest that a universal influenza A vaccine could be administered early in life and maintain lifelong protection into geriatric age.

Shifts in Gender-Related Medical Requests by Transgender and Gender-Diverse Adolescents.

PURPOSE: Gender-affirming hormones and/or surgeries seeking to change the body can have potentially lasting effects. Changes in requests for these therapies among gender-diverse youth are not well-understood. The study aim is to characterize factors associated with shifts in gender-related medical requests. METHODS: This mixed-methods study used retrospective chart review and qualitative interviews with clinicians. Of 130 youth receiving clinical gender care at Children's National Hospital, 68 met inclusion criteria. Qualitative interview analysis was performed to identify patterns and themes around shifts in gender-related medical requests over time. Statistical analysis employed chi-square and t-tests to compare characteristics in the shift versus no-shift groups and kappa statistics to calculate qualitative coding agreement. RESULTS: Of the 68 youth followed over time (mean age 15.11 years, 47% autistic, 22% nonbinary), 20 (29%) reported a shift in request. No significant differences were found by age, autism status, or designated sex at birth. More youth with shifts were nonbinary (p = .012). Six shift profiles were identified from qualitative interviews with excellent reliability (κ = 0.865). Four of the profiles reflect shifts in request prior to starting treatment (85% sample); two involved shifts after commencing treatment (15%). The most common profile reflected a medical request that was made, withdrawn, and re-requested (45%). DISCUSSION: Shifts in gender-affirming medical requests by gender-diverse youth may not be uncommon during the adolescent's gender discernment process, and may more likely occur among nonbinary youth. Many individuals who experience shifts away from medical treatment may later resume the request.

The Gender Self-Report: A multidimensional gender characterization tool for gender-diverse and cisgender youth and adults.

Gender identity is a core component of human experience, critical to account for in broad health, development, psychosocial research, and clinical practice. Yet, the psychometric characterization of gender has been impeded due to challenges in modeling the myriad gender self-descriptors, statistical power limitations related to multigroup analyses, and equity-related concerns regarding the accessibility of complex gender terminology. Therefore, this initiative employed an iterative multi-community-driven process to develop the Gender Self-Report (GSR), a multidimensional gender characterization tool, accessible to youth and adults, nonautistic and autistic people, and gender-diverse and cisgender individuals. In Study 1, the GSR was administered to 1,654 individuals, sampled through seven diversified recruitments to be representative across age (10-77 years), gender and sexuality diversity (∼33% each gender diverse, cisgender sexual minority, cisgender heterosexual), and autism status (> 33% autistic). A random half-split subsample was subjected to exploratory factor analytics, followed by confirmatory analytics in the full sample. Two stable factors emerged: Nonbinary Gender Diversity and Female-Male Continuum (FMC). FMC was transformed to Binary Gender Diversity based on designated sex at birth to reduce collinearity with designated sex at birth. Differential item functioning by age and autism status was employed to reduce item-response bias. Factors were internally reliable. Study 2 demonstrated the construct, convergent, and ecological validity of GSR factors. Of the 30 hypothesized validation comparisons, 26 were confirmed. The GSR provides a community-developed gender advocacy tool with 30 self-report items that avoid complex gender-related "insider" language and characterize diverse populations across continuous multidimensional binary and nonbinary gender traits. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The Gender-Diversity and Autism Questionnaire: A Community-Developed Clinical, Research, and Self-Advocacy Tool for Autistic Transgender and Gender-Diverse Young Adults.

Background: Autistic transgender people face unique risks in society, including inequities in accessing needed care and related mental health disparities. Given the need for specific and culturally responsive accommodations/supports, the characterization of key experiences, challenges, needs, and resilience factors within this population is imperative. This study developed a structured self-report tool for autistic transgender young adults to communicate their experiences and needs in a report format attuned to common autistic thinking and communication styles. Methods: This cross-nation project developed and refined the Gender-Diversity and Autism Questionnaire through an iterative community-based approach using Delphi panel methodology. This proof-of-principle project defined "expertise" broadly, employing a multi-input expert search approach to balance academic-, community-, and lived experience-based expertise. Results: The expert collaborators (N = 24 respondents) completed a two-round Delphi study, which developed 85 mostly closed-ended items based on 90% consensus. Final item content falls within six topic areas: the experience of identities; the impact of experienced or anticipated discrimination, bias, and violence toward autistic people and transgender people; tasks and experiences of everyday life; gender diversity- or autism-related care needs and history; the experience of others doubting an individual's gender identity and/or autism; and the experience of community and connectedness. The majority of retained items relate to tasks and experiences of everyday life or the impact of experienced or anticipated discrimination, bias, and violence. Conclusions: This study employed a multipronged multimodal search approach to maximize equity in representation of the expert measure development team. The resulting instrument, designed for clinical, research, and self-advocacy applications, has parallel Dutch and English versions and is available for immediate use. Future cross-cultural research with this instrument could help identify contextual risk and resilience factors to better understand and address inequities faced by this large intersectional population.

Why is this an important issue?: Transgender and gender-diverse are words used to describe people whose gender varies from their assigned sex at birth. Many autistic people identify as being transgender/gender-diverse. Autistic gender-diverse/transgender young adults often describe difficulties getting the care they need, which can increase their chances of experiencing stress and mental health challenges. This study created a self-report questionnaire for autistic transgender/gender-diverse young adults to share about their health care, support needs, and broader experiences. What were the results of the study?: A diverse group of experts in the autism and gender diversity co-occurrence, including autistic transgender people, worked together to develop the questionnaire. The researchers found experts by searching the internet and talking to people in the community and research field. The questionnaire is called the Gender-Diversity and Autism Questionnaire and has 85 questions that are grouped into 6 different areas: the experience of identities; the impact of experienced or anticipated discrimination, bias, and violence toward autistic people and transgender people; tasks and experiences of everyday life; gender diversity- or autism-related care needs and history; the experience of others doubting an individual's gender identity and/or autism; and the experience of community and connectedness. The questionnaire has English and Dutch versions so it can be used for research in different countries. What do the authors recommend for future research on this topic?: Researchers are currently using the new questionnaire to compare the experiences and needs of autistic transgender young adults in the Netherlands and the United States. The results may help explain why some outcomes are different between autistic transgender young people in the two countries and how culture and society play a role. How will these findings help autistic adults now or in the future?: We created the questionnaire to be used in different settings, including clinics and in research. The questionnaire gives autistic transgender young adults a structured way to communicate their experiences, needs, challenges, and areas of strength. The answers that an autistic transgender young adult gives on the questionnaire could help other people understand the clinical and community supports that the young adult wants and needs. Future studies may use the questionnaire to understand obstacles that autistic transgender young adults may face.

Psychological Distress Among the U.S. General Population During the COVID-19 Pandemic.

The COVID-19 pandemic is taking a significant global toll on emotional well-being, but evidence of mental health impacts in the United States remains limited. In April 2020, we conducted an exploratory survey of U.S. residents to understand prevalence of and factors associated with psychological distress during the pandemic. Data collection was conducted using Qualtrics, an online survey platform, and U.S. adult respondents were recruited via Amazon's Mechanical Turk platform. Among 1,366 respondents, 42% (n = 571) reported clinically significant anxiety and 38% (n = 519) reported clinically significant depression. Factors associated with anxiety and depressive symptoms included Hispanic/Latino ethnicity; younger age; lower income; employment as or living with a health care worker-first responder; caregiver status; SARS-CoV-2 infection status; decreased frequency of engagement in healthy behaviors; and changed frequency of engagement in unhealthy behaviors. That some of these factors are associated with elevated distress during the pandemic is not yet widely appreciated and might be useful in informing management of mental health care resources.

Do Student Characteristics Affect Teachers' Decisions to Use 1:1 Instruction?

One-to-one instruction is a critical component of evidence-based instruction for students with autism spectrum disorder, but is not used as often as recommended. Student characteristics may affect teachers' decisions to select a treatment and/or implement it. This study examined the associations between students' clinical and demographic characteristics and teachers' reported use of discrete trial training (DTT) and pivotal response training (PRT). Children's higher sensory symptoms, lower social approach, lower verbal skills and higher self-regulation difficulties were associated with more frequent 1:1 DTT and PRT. Results suggest that teachers give more frequent 1:1 instruction to children with more observable impairments, do not match children to type of 1:1 intervention, and may inadvertently neglect other students for whom individualized intervention may still be beneficial.