Hannah Belcher, Ph.D., Autistic researcher, speaker, and author, discusses the often late and missed diagnosis of autistic females. She dives into the gender gap inherent in autism research, assessments, and clinical understanding, demonstrating how this has led to late and misdiagnosis of autism in women. The speaker presents contemporary research working to uncover a female autism phenotype and discusses masking as implicated in mental health and diagnosis. Belcher continually asserts the societal need for greater understanding and accommodation of autistic womens’ lived experiences and outlines what needs to change before the question and answer session.

Learn more about our speaker Hannah Belcher, Ph.D. HERE

Take the knowledge quiz for this presentation HERE

In this webinar: 

1:27 – About Hannah Belcher
3:09 – Taking off the Mask book highlight
3:36 – Language, terminology, and content warning
5:38 – Key content
6:00 – What do we know about autistic women?
7:30 – Missed diagnosis and current diagnostic basis
8:54 – Autism Quotient background
9:48 – Study: Autism quotient gender bias
11:11 – Study: Assessment measures gender bias
12:45 – Changing prevalence rates
13:30 – Autism gender gap
14:25 – Female phenotype theory
17:30 – Study: Diagnosed vs potentially undiagnosed autistic women
19:30 – Masking and hiding traits
22:45 – Why do autistic people mask?
24:40 – Study: First impressions of autistic women and men
27:29 – Effects of masking on mental health (personal flowchart)
30:05 – Why masking has this effect
34:23 – Clinician bias
37:28 – A hidden population
38:50 – Borderline Personality Disorder
41:38 – What needs to change?
45:10 – Closing, thanks, and Q & A

Belcher provides terminology and underscores identity-first language (autistic person(s)) (3:36). She uses the terms ‘male’ and ‘female’ because the majority of available research uses this binary lens. However, she notes that many autistic people do not identify with these labels. The speaker outlines key content (5:38) and notes that these topics have been discussed anecdotally for decades. However, she states that today, we don’t deal with anecdotes; it’s time for real numbers and research.

What we know about autistic females:

Autism has historically been considered a male disease, and consequently, the voices of women are largely absent from the research literature (7:38). Due to this imbalance in literature and, subsequently, in our foundational understanding of autism, an accurate description of autistic females does not exist (6:00). 

“From the beginning, we have not included women in the research or built our systems and conceptions of autism around their experiences.” 

The foundations of current diagnostic systems:

The speaker describes gender imbalances in the original description of autism and the validation of the Autism Quotient (AQ), the primary diagnostic screening tool in the UK (8:54). She outlines recent studies that revealed the AQ does not measure identical traits in males and females (9:48) and that the ADOS-2, a golden standard assessment, shows signs of significant gender bias (11:11). Therefore, Belcher states the very foundations of current diagnostic systems innately lack the female perspective.

The female phenotype theory:

The Female Phenotype Theory asserts that autistic males and females express autistic traits differently (13:20). Belcher briefs findings that support this theory and concludes that autistic females present as much more social than their male counterparts, which contrasts the idea of autism as a “social disorder” (15:25) and supports the gender biases revealed in the AQ and ADOS-2. 

To determine if there is a female phenotype, researchers investigated 243 diagnosed autistic women and 767 potentially undiagnosed women (PUW), hypothesizing that PUW would present as more exaggerated in these social areas (missed by assessments) (17:30). PUW scored significantly higher on empathy and general functioning measures than diagnosed women. This suggests, Belcher states, that social abilities may be an aspect of the different autism phenotypes. This challenges the idea that autistic people lack empathy and always have a talent for systemizing things (18:20). 

Masking and mental health

Masking is when autistic individuals hide or compensate for their autistic traits to appear more “normal” and fit in with others (19:30). The speaker describes a study assessing differences in first impressions of autistic men and women in a group of people who didn’t know their diagnoses (24:40). Results showed that autistic females rated better than males, that self-reported masking was not related to impressions, and that better first impressions are related to age at diagnosis. Belcher posits that these findings suggest some unconscious physical presentation of autism that affects the age of diagnosis and that non-autistic people pick up on these behaviors (25:40). 

Masking significantly predicts suicidal behaviors in autistic individuals and positively correlates with depression and anxiety. Belcher describes how relentless self-monitoring (conscious or not) and adapting to social situations with different people all day is exhausting and leaves little time for self-expression or care (30:05). Therefore, Belcher insists, 

“We need to minimize and move the onus of fitting in from autistic people masking toward non-autistic people learning to accept autistic people as they are. Consequences are severe if this is not the case… masking natural behaviors and traits denies expression of our true selves and identity.”

Misdiagnosis

Atypical autism presentations (not reported in the research or clinical knowledge) often lead to increased mental health issues and, subsequently, a diagnosis of other psychiatric conditions instead of autism (32:48). In fact, the speaker explains, autistic women often receive their diagnosis as the last in a series of mental health conditions, which is not the case for men (37:28). Borderline Personality Disorder (BPD) (aka emotion regulation disorder) is of particular concern for autistic women as the symptomology significantly overlaps with autism. Belcher describes a study that found 15% of patients attending a clinic for BPD fulfilled the criteria for autism (38:50). Such symptom overlap, coupled with the fact that BPD more often occurs in females, has created a clinical bias toward diagnosing BPD, leaving these individuals without the help and support they need (39:40). 

What needs to change:

To successfully support autistic women moving forward, Belcher says that clinicians need to have more awareness of different autism presentations and how the current tools may miss some cases or look like other conditions (41:38). Similarly, research must address the intersectionality among autistic adults. And finally, as a society, we need to help autistic people reduce the need to mask (42:55). Belcher gives thanks and acknowledgments before opening the question and answer session (45:10).  

Kaustubh Supekar, Ph.D., examines recent findings about gender/sex differences in autism phenotypes and brain organization. He highlights the underrepresentation of females in autism and underscores the need for a large-scale science approach. The speaker details contemporary research methods and outcomes which revealed gender differences in autism symptom presentation and structural and functional brain organization. Supekar provides study implications, discusses limitations, and outlines future research, diagnosis, and treatment priorities.

Learn more about our speaker Kaustubh Supekar, Ph.D. HERE
Take the knowledge quiz for this webinar HERE

In this webinar:

1:00 – Autism and gender heterogeneity
3:45 – Why are there fewer females with autism?
5:23 – Questions of interest and implications
7:15 – Why we know so little
9:40 – Large-scale science approach
12:40 – Question 1
14:00 – Findings and replication studies
17:25 – Study: Co-occurring conditions
19:10 – Age and gendered socio-ecological effects
19:53 – Interim summary
20:27 – Question 2
23:33 – Findings
25:10 – Study: Correlation of symptom presentation and brain structure
27:04 – Interim summary
29:30 – Question 3
32:00 – Clinical vs functional MRI
36:52 – Findings
37:25 – Major finding: Visual-spatial attention systems
38:15 – Robustness and specificity to autism
40:30 – Study: Functional organization patterns associated with RRB
42:02 – Interim summary
44:40 – Overall summary
46:53 – Limitations and priorities for future research
49:35 – Acknowledgments and Q & A

Autism is a highly heterogeneous neurodevelopmental disorder (1:00). Supekar discusses the skewed gender ratio of women to men (ratio of 1 to 4) in autism diagnoses and asserts that this lack of female representation is a key source of heterogeneity in autism symptom presentation, treatments, and research (2:20). He stresses the historical consistency of the sex/gender bias (7:15) and discusses why we know so little about behavioral symptoms and brain signatures of females with autism (4:00). Supekar presents the unanswered question of why there are fewer females with autism as a fundamental building block for the future of autism research and treatments (3:45). 

The speaker describes the large-scale science approach, which collects publicly available data from multiple studies, sites, languages, populations, and investigators (9:40). Such datasets provide large sample sizes, robust and replicable findings, and population variance (10:15). Supekar uses the large-scale science approach to address three research questions (12:04): 

1. What are the behavioral/symptom presentations of autism in females, and how do they differ from those in males (12:40)?

Supekar and his colleagues compared female and male clinical data (13:00) and found that girls with autism exhibit less severe restricted/repetitive behavior (RRB) than autistic boys (14:00). These findings have been replicated in multiple large-scale studies (15:20). The presenter outlines subsequent research on co-occurring conditions (17:25), which revealed a lower prevalence of ADHD and a higher prevalence of epilepsy in autistic females compared to males (18:03). He also describes evidence suggesting an influence of age and gendered socio-ecological contexts on symptom presentation in autistic females (19:10). Supekar states that these findings show significantly different phenotypes between autistic males and females where the female presentation is more nuanced (19:53). 

2. What is the structural organization of autistic brains in females, and how do they differ from those in males (20:27)? 

Researchers applied multivariate pattern analysis (MVPA) (22:18) to clinical and structural MRI data to assess gray matter volume maps. Their findings revealed that structural brain organization in females with autism is significantly different from that of autistic males, especially in brain regions belonging to the motor, language, and visual-motor systems (23:33). Supekar’s team subsequently correlated those brain regions with clinical scores and found a relationship between RRB domains and gray matter volume in girls with autism (25:10). The speaker suggests these results reveal gender discrepancies in autistic structural brain organization that are associated with significantly different sex/gender phenotypes (27:04). 

3. What is the functional organization of autistic brains in females, and how do they differ from those in males (29:30)?

Supekar and his colleagues used deep learning neural networks (33:16) to assess differences in clinical and functional MRIs in multiple brain regions (32:00). Despite the heterogeneity of the dataset, the model was consistently (86%) accurate in differentiating males and females with autism (36:28). Further, this study revealed sex/gender differences in brain systems associated with visual-spatial attention in autistic individuals (37:25). Such findings had never been recorded in autism literature before and have since been replicated in a fully-independent cohort (38:15). 

Brain regions showing differences were subsequently correlated with clinical scores, which revealed that regions belonging to motor systems predicted the severity of RRB in autistic females (40:30) but not in autistic males. Supekar asserts that these findings suggest the presence of domain-specific effects associated with RRB in females and some level of female protective effect (5:54) in those brain regions (41:35).

Supekar summarizes the research findings (44:40), noting that gender differences in autistic structural and functional brain organization significantly differed from normative sex differences (24:16; 39:20). He lists the implications of their results, including the need for sex-specific diagnostic instruments and treatments. The presenter outlines priorities for future research (46:53) before the question and answer session (50:12). 

Gregory Wallace, Ph.D., discusses eating-related behaviors in autism. He examines potential drivers of food neophobia and presents novel studies on the cognitive/behavioral correlates of eating in the absence of hunger (EAH). Wallace defines selective overeating as a new subtype of autism and details recent studies on taste perception and cortical taste pathways in ASD compared to typically developing groups. The presenter highlights limitations to current research and the need for longitudinal studies. Wallace closes with a Q&A discussing picky eating, GI difficulties, ASD and anorexia, and more.

The presenter’s slides are online HERE (English)
Learn more about our speaker Gregory Wallace, Ph.D. HERE
Take the knowledge quiz for this webinar HERE

A Spanish translation of this webinar will be available at a later date.

In this webinar: 

2:50 – Why study eating in ASD?
4:00 – Nutritional intake and focus on exercise
5:00 – Appetitive traits
5:40 – Food neophobia and “picky” eating is autism
8:15 – Studies: Food neophobia in ASD during childhood & FN in adolescents and adults with autism
9:18 – Study: Possible underpinnings of food selectivity
11:40 – Clinical significance and ARFID
12:38 – Summary of findings
14:10 – Eating in the absence of hunger in autism
15:00 – Study: Cognitive/behavioral correlates of EAH in ASD
17:55 – Study: Relationship between EAH and BMI in children with ASD
21:18 – Summary of findings
25:56 – Selective overeating in autism – a new subtype & study
28:50 – Study – Infrequency of food type consumption by eating subtype in children with ASD
29:53 – Neural correlates of eating-related behaviors in ASD
31:13 – Study: Taste perception in autism
33:37 – Cortical taste pathway explanation
37:02 – Study: fMRI self-report and gustatory mapping
41:24 – Summary of findings
42:50 – Presentation summary, study limitations, and links to more information
45:16 – Q & A

Suboptimal health outcomes are common in individuals with autism. Studies have found an increased risk for obesity, high cholesterol, hypertension, and diabetes in individuals with ASD compared to the general population (2:50). Wallace discusses diminished nutritional intake (4:00), hyperfocus on exercise (4:10), and appetitive traits as contributors to poor health outcomes. Food neophobia (FN), or a fear of trying new foods, is a common and seemingly adaptive appetitive trait of early eating that generally diminishes across child development (5:40). However, FN and other selective eating symptoms often persist into adulthood in autistic individuals and interfere with everyday function (7:20). 

Wallace examines sensory processing differences and behavioral/cognitive inflexibility as potential drivers of persistent selective eating in autism (9:18). He presents studies on the possible causes of food selectivity (9:50) and the clinical significance of Avoidant Restrictive Food Intake Disorder (ARFID) in autism (11:40). Other selective eating symptoms like eating in the absence of hunger (EAH) are scarcely studied in ASD (14:10). The speaker outlines two new studies that assess the relationship between EAH and 1) cognitive/behavioral correlates in ASD (15:00) and 2) body mass index (BMI) (17:55). Findings reveal that EAH is positively associated with behavioral inflexibility and BMI and that EAH is more prevalent in individuals with ASD than the general population (21:18).  

The speaker defines selective overeating (a new autism subtype) as the co-occurrence of picky eating and overeating (25:56). A novel study using parent ratings of autistic versus typically developing children found a greater number of children with ASD linked to selective eating and selective overeating. Further, Wallace explains, autistic children with EAH had significantly higher rates of selective eating than children without EAH (26:00). Combining these findings with those of the first two studies, Wallace asserts that increased behavioral inflexibility is most elevated for individuals who engage in selective overeating (28:50). 

Individuals with autism have divergent sensory processing experiences across all sensory systems. Therefore, Wallace states, taste perception/processing is a prime candidate for assessing neural correlates related to eating behaviors (30:20). Multiple studies suggest that while individuals with ASD can perceive taste, they struggle with taste identification or sensory integration (31:13). The speaker defines sensory integration difficulties as a cortical issue and briefly describes the cortical taste pathway (33:37) and using functional magnetic resonance imaging (fMRI) to assess brain blood flow in response to stimuli (34:33). Wallace outlines a 2018 study using gustatory mapping (fMRI) (37:45) and self-reports (37:02) to assess (35:50) response to tastants (taste samples) in the gustatory cortex and their relation to self-reported taste reactivity in autism. 

Researchers found no differences in neural response to tastants between ASD and typically developing age-matched groups (39:15). They also found no association between self-rated taste reactivity and brain response to sweet tastants in the neurotypical group. However, autistic individuals who self-rated as highly taste-reactive showed a strong positive relationship with gustatory response to the sweet tastants relative to the neutral flavor (40:13). Wallace explains that although there is no evidence of overall atypical gustatory cortical function in ASD, findings suggest that individual differences in self-rated taste reactivity modulate activity in the gustatory cortex. The speaker posits that these findings also suggest atypical brain functions for individuals with autism and food selectivity that could impact BMI through diet variation (41:24). 

Wallace summarizes his presentation, noting that more work is needed to establish longitudinal relationships between eating-related behaviors, their causes, and their outcomes. He touches on the need for more interventions for food-related behaviors to improve physical health and overall quality of life for individuals with autism (42:50). Wallace discusses the limitations of the presented studies (43:50) and provides links to more information (44:50) before the question and answer session (45:16). 

Jennifer Frankovich MD MS, clinical professor at Stanford University/Lucile Packard Children’s Hospital, discusses the co-occurrence of systemic inflammatory and autoimmune diseases – including the overlap between pediatric acute-onset neuropsychiatric syndrome (PANS) and autism. She outlines the presentation of classic rheumatologic diseases noting the prevalence of mental health symptoms and provides clinical criteria for PANS. Frankovich discusses PANS as a relapsing/remitting condition and explores the clinical management options, citing recent studies on steroid use. She concludes by reemphasizing the association of psychiatric symptoms with autoimmune and rheumatologic diseases and states the importance of post-flare rehabilitation before opening the floor to questions.

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In this presentation

3:20 – Inflammatory diseases with comorbid psychiatric symptoms
20:20 – PANS clinical criteria
34:54 – PANS model
22:15 – Prevalence of PANS comorbid traits
23:48 – Non-specific inflammatory signs
29:00 – Clinical Management of PANS
33:30 – Study: Impact of steroid treatments on PANS episode duration
37:15 – Study: Monocyte subsets associated with PANS clinical states
44:16 – Q & A session

Summary

Classic rheumatologic conditions such as Lupus (4:30), Behçet’s syndrome (5:43), Sjögren’s syndrome (9:30), Scleroderma (9:53), Spondyloarthritis (10:31), Inflammatory bowel disease (11:30), Psoriasis/Psoriatic Arthritis (12:03), CNS Vasculitis (13:05), and Sydenham Chorea (SC) (13:20) are associated with psychiatric symptoms such as OCD, anxiety, depression and/or other behavior changes. PANS (20:20) also presents with acute onset of OCD or eating disorders. These psychological comorbidities – specifically OCD – overlap with common symptoms of autism spectrum disorder making inflammatory diseases difficult to diagnose in children on the spectrum. Psychiatric symptoms in individuals with autism can distract from rheumatologic symptoms due to subtle/masked physical manifestations and/or communication difficulties. The onset of certain diseases – especially PANS – can also exacerbate psychological symptoms of ASD and often lead to autoimmune disease diagnosis (2:35).

There is a historic association of pediatric streptococcal throat infections with mental disorders – particularly OCD and tic disorders (18:00). This is especially true in cases of SC and PANS/PANDAS where patients generally present with symptoms 1 – 8 months after exposure to a Group A Streptococcal infection (13:20). Studies have also shown increased volume of basal ganglia during the first episode(s) of CS and PANS (18:42) demonstrating onset of encephalitis. PANS cases present with an acute onset of OCD or eating restrictions and at least 2 of seven comorbid symptoms (20:20). Patients display a very abrupt deterioration in performance, behavior, and mental stability – parents have described it as a personality shift overnight.

Clinical management of PANS (29:00) varies based on each patient. Treatments are generally approached in three stages:

1.   Find and treat active infections (i.e. strep, sinusitis, etc.)
2.   Treat post-infectious inflammation and autoimmunity (if present)
3.   Note that inflammation can cause tissue injury making post-flare rehabilitation highly important (40:00)
4.   Treat psychiatric symptoms

Post-infectious inflammation is often treated with steroids (NSAIDS, IVIG, etc.). 5 day oral steroid bursts have proven helpful if administered at the beginning of an episode and IVIG trials are taking shape currently (32:00). PANS is understood as a relapsing/remitting disease (21:35) and most patients will return to baseline within a few months after the initial episode. Later, likely following some sort of infection, they will have a relapse episode lasting around 3 months. If flares are caught quickly and treated properly, over time episode length can shrink. However, without treatment, after 4 or 5 flares the symptoms become more chronic (33:30). Episodes generally decrease with age but it is suspected that patients maintain the predisposition to episodes throughout their lifetime and a number of patients develop autoimmune diseases over time (27:30).

Frankovich concludes (38:42) by emphasizing the strong association of post-infectious inflammatory disorders and autoimmune diseases with psychiatric symptoms. She notes that psychiatric symptoms can precede full presentation of inflammatory conditions and urges clinicians and parents to use PANS evaluation guidelines when a child with ASD suddenly develops new psychiatric traits. During the Q&A Frankovich comments on differences between regressive autism and PANS, treatment options, limitations to diagnosis and clinician assistance, international programs and more.

For treatment recommendations and steroid regimens see appendix B of the treatment guidelines found at med.stanford.edu/PANS (publications tab).