James McPartland, Ph.D., discusses current limitations in autism diagnosis and treatment, noting their reliance on behavioral observations despite the condition’s genetic and neurological underpinnings. He advocates integrating biomarkers as objective, measurable biological indicators that revolutionize clinical practice. The speaker details ongoing research into the N170 biomarker, its connection to social behavior and development, and potential for measuring intervention efficacy. McPartland outlines the collaborative work of the Autism Biomarkers Consortium for Clinical Trials (ABC-CT) and its implications for autism diagnosis and care.

Handouts are online HERE

In this webinar:

5:00 – The need for biomarkers in autism
11:00 – Practical considerations for clinical practice
13:30 – EEGs as a promising biomarker technology
20:00 – The N170 biomarker
28:00 – N170: social and behavioral development
34:00 – Confounds and responses to behavioral interventions
42:00 – Autism Biomarkers Consortium for Clinical Trials (ABC-CT)
47:00 – ABC-CT progress and impact
54:00 – Implications for clinical practice

The need for biomarkers in autism

highlighting that these methods have remained largely unchanged since the initial descriptions in 1943 (5:00). Although today we understand that autism is rooted in genetics and the brain, there are no biological assays—meaning no tests to aid in diagnosis, guide treatment selection, or measure intervention effectiveness. He explains that this lack of biological criteria impedes our ability to provide optimal care (8:17).

The presenter details various categories of biomarkers as defined by the FDA, each serving a distinct “context of use” or purpose:

• Diagnostic biomarkers are used to identify the condition.
• Susceptibility or risk markers can indicate the likelihood of developing autism.
• Pharmacodynamic or response biomarkers show changes in response to treatment.
• Prognostic biomarkers help to predict the course of development.
• Predictive biomarkers estimate response to specific treatments.
• Stratification biomarkers are used to subgroup the highly heterogeneous autistic population meaningfully. This last category, McPartland suggested, represents the “lowest hanging fruit” for immediate impact in autism.

Practical considerations for biomarker adoption in clinical settings include viability across the diverse autism population, cost-effectiveness, and accessibility (11:00).

EEG as a promising biomarker technology

McPartland presents various methods for measuring brain activity in autism, including electroencephalography (EEG), fMRI, PET scans, and eye tracking. He highlights EEG as an ideal technology that detects electrical activity produced by brain cells from the scalp. This technology offers many advantages, especially that it is non-invasive, movement tolerant, widely applicable, cost-effective, and accessible, as they are widely available in hospitals. EEGs have also been used effectively to understand social communicative development, supporting their use in autism research (13:18). The speaker notes the wide variability in clinical presentations of autism and the challenges this presents in using biomarkers for diagnostic purposes (18:00). 

The N170 biomarker and its Implications

The speaker describes the N170, an event-related potential (ERP) component measured by EEG. The N170 is a negative electrical spike that occurs around 170 milliseconds after seeing a human face. This indicates the brain’s rapid recognition of a face as a face, making it highly relevant to social communication (20:00). McPartland outlines a 2004 study that compared the N170 in autistic and allistic (non-autistic) adolescents and adults. Preliminary findings show that autistic participants exhibited a slower N170 response, which was replicated in a younger cohort. These findings, the speaker asserts, suggest a difference at the fundamental stages of face perception (22:30). Further research showed that the N170 latency correlated directly with impaired facial recognition abilities in autistic participants, providing crucial evidence that the N170 is not simply a brain anomaly, but a biomarker associated with a clinically relevant social function.

Event-related brain potentials reveal anomalies in temporal processing of faces in autism spectrum disorder (McPartland et al., 2004)

A biomarker for social behavior and development

To determine if the N170 response is meaningfully tied to social behavior, subsequent research by McPartland and colleagues compared brain responses to faces (social), letters (non-social, an autistic strength), and houses (control). Results indicated the N170 latency is specific to social stimuli, where similar slowness was not observed in response to letters (28:00). The only difference for letters was a tendency for autistic individuals to involve more of the right hemisphere, typically associated with faces (a difference in lateralization). These findings, the presenter asserts, confirm the N170 biomarker’s specificity to the social domain in autism, rather than a general indicator of slower sensory processing. As the findings were replicated in a younger cohort, this study also provides evidence of the N170 biomarker’s relevance to development (32:00). 

Atypical neural specialization for social percepts in autism spectrum disorder (McPartland et al., 2011)

Confounds and responses to behavioral interventions

McPartland briefly touches on research addressing confounds, such as eye gaze patterns. A 2021 study indicated that the N170 differences persisted even when eye gaze was experimentally controlled. This suggests that the brain difference is fundamental and not simply a consequence of where someone is looking, thus strengthening the validity of the N170 as a robust measure of underlying neural processes (34:00). Studies also show that the N170 biomarker may be sensitive to changes in clinical status following behavioral interventions. The speaker explains that this suggests potential for N170 to serve as a response biomarker, capable of measuring the effectiveness of therapeutic interventions (36:00). 

The N170 event-related potential reflects delayed neural response to faces when visual attention is directed to the eyes in youths with ASD (Parker et al., 2021)

Brief Report: Preliminary Evidence of the N170 as a Biomarker of Response to Treatment in Autism Spectrum Disorder (Kala et al., 2021)

Social attention: a possible early indicator of efficacy in autism clinical trials (Dawson et al., 2012)

Brain mechanisms of plasticity in response to treatments for core deficits in autism (Ventola et al., 2013)

Large-scale autism biomarkers consortium for clinical trials 

The presenter outlines the Large-Scale Autism Biomarkers Consortium Study, or the Autism Biomarkers Consortium for Clinical Trials (ABC-CT), a monumental effort to bridge the gap between scientific discovery and clinical application in autism. The overarching goal of the ABC-CT is to accelerate the development of effective treatments for social impairment in autism by identifying, developing, and validating a set of reliable, objective, and quantitative measures that can serve as biomarkers (42:00). McPartland notes the rationale for this multicenter research study, highlighting its potential for bridging the research-to-clinic gap. 

The main study is longitudinal, tracking participants between 6 and 11 years old across multiple time points to evaluate candidate biomarkers’ stability and sensitivity to change. A battery of measures was collected, including clinician and caregiver assessments, biospecimens (DNA samples), and lab-based measures like EEG, eye tracking, and behavior observations (45:00). The ABC-CT specifically investigates well-evidenced candidate biomarkers, such as N170. Candidate biomarkers must meet several criteria, including feasibility and construct validity.

Identifying Age Based Maturation in the ERP Response to Faces in Children With Autism: Implications for Developing Biomarkers for Use in Clinical Trials (Webb et al., 2022)

The Autism Biomarkers Consortium for Clinical Trials: Initial Evaluation of a Battery of Candidate EEG Biomarkers (Webb et al., 2023)

Progress and impact

To date, the ABC-CT reports high levels of successful data acquisition and acceptance of the N170 latency in upright human faces. Therefore, the FDA views the N170 as a promising stratification (subgrouping) biomarker for clinical trials. An eye-tracking biomarker has also been submitted, the Oculomotor Index of Orienting to Human Faces (47:00). In 2020, ABC-CT was renewed for a follow-up study to evaluate long-term stability, sensitivity to change, and longitudinal predictive value in the original cohort. Data collection occurred from May 2021 to August 2022, and a confirmation study was completed in March 2025. A feasibility study was also launched in August of 2024 (49:00). McPartland underscores the importance of increasing inclusivity in neuroscience studies, specifically of autistic people with intellectual disabilities. He presents N170 latency replication studies in this group (50:30). 

Implications for clinical practice

The speaker reiterates the potential impact of ABC-CT as a collaborative effort to develop objective tools that can address the heterogeneity of autism, improve the design and efficiency of clinical trials, and ultimately lead to more personalized and effective treatments for autistic individuals. He reiterates that rigorous study of biomarkers like the N170 holds immense implications for improving clinical understanding and care for autistic individuals via subgrouping, measurements of treatment effectiveness, earlier identification, and enhanced clinical trials (54:00). The presenter asserts that a biomarker’s utility is a “moving target,” evaluated for its purpose in a particular situation. The ongoing research into the N170 and other biomarkers represents a critical step towards a future where objective biological measures significantly enhance clinical understanding and intervention for autism. McPartland provides thanks and acknowledgments before the Q&A (55:02). 

Originally published November 4, 2024

Francesca Solmi, Ph.D., discusses the intricate link between autism and eating disorders. She outlines common eating disorders, noting their overlapping symptoms and similarities to autism traits. The speaker explores potential mechanisms for the connection between eating disorders and autism, including communication difficulties, sensory sensitivities, and emotion regulation. Solmi emphasizes Avoidant/Restrictive Food Intake Disorder (ARFID) and its relevance to autism, underscoring the need for more research and services for this often overlooked condition. The presenter considers future research directions before the Q&A.  

Handouts are online HERE

In this webinar:

1:30 – Common eating disorders
8:00 – Autism and eating disorders
11:00 – Trajectories of autistic traits and eating disorders
20:00 – Potential linking mechanisms
28:00 – Emotion regulation
34:50 – Avoidant/Restrictive Food Intake Disorder (ARFID) and Autism
40:00 – Future research
42:00 – Q&A

Overview of Eating Disorders 

Solmi defines eating disorders as severe psychiatric conditions that typically emerge in early to mid-adolescence. She describes common eating conditions, including Anorexia Nervosa, Bulimia Nervosa, Binge Eating Disorder, and OSFED (Other Specified Feeding or Eating Disorder), highlighting the significant symptom overlaps across conditions (1:35).

• Anorexia Nervosa – frequently the youngest age of onset. Characterized by an intense fear of weight gain, extreme dietary restriction, and often low body weight. Some individuals may also engage in bingeing and purging.
• Bulimia Nervosa – slightly later onset and involves episodes of binging followed by compensatory behaviors like self-induced vomiting or excessive exercise.
• Binge Eating Disorder – the most recently recognized diagnosis. It involves bingeing without compensatory behaviors, often accompanied by feelings of shame or guilt.
• OSFED (Other Specified Feeding and Eating Disorder) is a residual category for individuals whose symptoms don’t fully meet the criteria for other diagnoses. 

The speaker emphasizes the severity of these conditions, noting their association with higher mortality rates (5:00). Despite this, eating disorders are often under-researched compared to other mental health disorders. She also notes their high prevalence in girls and women, suggesting underdiagnosis in men (6:30).  

The Link Between Autism and Eating Disorders 

Solmi discusses the connection between autism and eating disorders. A study by Westwood and colleagues revealed elevated autistic traits in people with anorexia nervosa. Similarly, people with autism and anorexia nervosa mentioned rigidity or rules, intense interests, difficulties recognizing hunger, and social difficulties (8:00). A significant challenge in this research, the presenter explains, is distinguishing between pre-existing autistic traits and those that may be mimicked by severe malnutrition in anorexia nervosa. 

Autism Spectrum Disorder in Anorexia Nervosa: An Updated Literature Review (Westwood et al., 2016)

Research on Autistic Traits and Disordered Eating Trajectories

Solmi presents findings from a study investigating whether autistic traits were present before the onset of disordered eating behaviors (11:00). Researchers found that children who later developed disordered eating behaviors exhibited higher levels of autistic traits at age seven, and these differences persisted throughout adolescence. The speaker asserts that these findings suggest autistic traits may precede the onset of disordered eating (17:00). The study also revealed that more severe eating disorder symptoms correlated with higher autistic trait scores from age seven onwards, indicating a strong association with more severe presentations of eating disorders.

Trajectories of autistic social traits in childhood and adolescence and disordered eating behaviours at age 14 years: A UK general population cohort study (Solmi et al., 2020)

Potential Mechanisms Linking Autism and Eating Disorders 

The presenter explores several mechanisms as potential links between autism and eating disorders. For example, as friendships become more important in adolescence, struggles with social interaction can exacerbate mental health difficulties, with eating disorders potentially serving as a coping mechanism. Children with social communication difficulties may also be more susceptible to bullying, which can lead to internalized weight-stigmatizing thoughts and behaviors like dieting (20:00). Young people with autism often exhibit more sedentary behaviors compared to their peers, which can increase BMI and vulnerability to weight-based stigmas (23:00). 

Emotion regulation difficulties are also common in both autism and eating disorders. Solmi outlines a recent study showing that individuals who later developed anorexia nervosa symptoms exhibited less improvement in emotion regulation skills from early to mid-childhood compared to their peers, where differences emerged around age five (30:00). Further, in girls, social cognition explained around half of the association between emotion regulation difficulties and disordered eating. The association in boys was less clear, likely due to smaller sample sizes (35:00).

The presenter notes that sensory sensitivities, a core aspect of avoidant/restrictive food intake disorder (ARFID), are frequently reported by people with anorexia nervosa. For example, in a qualitative study on autism and anorexia in women, emerging themes included difficulty with sensory sensitivities, social interactions and relationships, and challenges with emotions (33:00). 

A mixed-methods approach to conceptualizing friendships in anorexia nervosa (Datta et al., 2021)

Autism Spectrum Disorder and Obesity in Children: A Systematic Review and Meta-Analysis (Sammels et al., 2022)

Emotional dysregulation in childhood and disordered eating and self-harm in adolescence: prospective associations and mediating pathways (Warne et al., 2022)

“For Me, the Anorexia is Just a Symptom, and the Cause is the Autism”: Investigating Restrictive Eating Disorders in Autistic Women (Brede et al., 2020)

Avoidant/Restrictive Food Intake Disorder (ARFID) and Autism

Solmi discusses ARFID, a disorder now included in the eating and feeding disorder family, noting its relevance to autism. Its three main aspects include limited interest in food, sensory sensitivities (e.g., avoiding specific foods due to texture), and concerns about adverse consequences from eating (34:50). The speaker emphasizes the limited epidemiological research on ARFID, the lack of services (especially for people who are not severely underweight), and the need for more studies to understand its prevalence, risk factors, and effective treatments (37:00).

Future Research Directions 

According to the presenter, future research should aim to understand the complex links between autism and eating disorders more comprehensively. Key areas of investigation include the connections between sensory sensitivities and ARFID, gender differences in the association of autistic traits and eating disorders, links between other autistic traits and different eating disorder presentations, physiological factors like the gut-brain response, and age of autism diagnosis in those with and without eating disorders. These avenues of research, Solmi asserts, will improve diagnostic tools and help to develop better prevention and care strategies (40:00). The speaker summarizes main points before the Q&A (42:20). 

Dr. Daniel Vogt, Ph.D., explores monogenic syndromes and what they can tell us about the underlying causes of autism. He describes signaling pathways critical in early development, highlighting the electrical nature of cell communication and function. The presenter explains how testing the impact of autism risk gene variations on cell signaling pathways can help us understand the roles and outcomes of specific genetic mutations in autism. Vogt presents recent research suggesting disruptions to cell circuitry in autism and highlights the need for research into the connection between cell communication and autistic behaviors. He provides thanks and acknowledgments before the Q&A. 

Handouts are online HERE

In this webinar:

1:00 – Genetic causes of autism
3:00 – Critical signaling pathways
5:15 – Cortical interneurons
9:08 – Parvalbumin theory
13:05 – mTOR signaling pathway mutations
20:50 – MAPK signaling pathway mutations
27:35 – Electrical properties
32:40 – Conclusions
40:15 – Future research
44:00 – Q&A

Genetic causes of autism

Proteins associated with synapses and cellular signaling have been identified as genetic drivers of autism. Vogt and his research lab focus on cell signaling to identify links between events that occur on the cell surface and cytoplasm (inside the cell) (2:00). The speaker introduces two signaling cascades critical to cell growth, division and migration (3:00): 

• mTOR (Mammalian target of rapamycin): leads to translational regulation; inhibited by known autism risk genes Pten in early development and Tsc1 in late development
• MAPK (Mitogen-activated protein kinase): leads to transcriptional regulation; inhibited by known autism risk gene Nf1 at early stages of development

Cortical interneurons (CINs)

To determine what, if any, mutations or effects are common across pathways, Vogt and colleagues study GABAergic cortical interneuron ratios in mice (5:15). Cortical interneurons (CINs) shape neural networks in the brain and originate from embryonic brain structures called the medial and caudal ganglionic eminences (MGE/CGE) (6:20). The speaker explains that the MGE develops around 70% of CINs via four major events: 

• Cell proliferation (birth) and apoptosis (death)
• Cell migration across long distances to final targets in the brain
• Cell fate, or the acquisition of specific properties related to cell function
• Electrical properties used to communicate across the microcircuit synapses

Vogt describes a study that found significantly decreased numbers of Parvalbumin (PV+) CINs (important for brain circuitry and memory) in autistic participants compared to controls (9:08). He touches on the Paravalbumin hypothesis of autism, which asserts that disruption of PV+ CINs may be a root cause of autism symptoms (10:14). Somatostatin (SST+) cells are another subgroup of CINs with a slower electric firing frequency. The presenter outlines mouse model methods for assessing the impact of mutant pathways on CIN subgroup ratios (11:15). 

• The origin and specification of cortical interneurons (Wonders & Anderson, 2006)
• Brief optogenetic inhibition of dopamine neurons mimics endogenous negative reward prediction errors (Chang et al., 2015)
• The Number of Parvalbumin-Expressing Interneurons Is Decreased in the Prefrontal Cortex in Autism (Hashemi et al., 2016)
• The Parvalbumin Hypothesis of Autism Spectrum Disorder (Filice et al., 2020)

For more information on brain development in autism, view Transcranial Magnetic Stimulation and Autism, a free webinar presented by Manuel Casanova, MD.

mTOR signaling pathway

The speaker asserts that converging evidence across multiple phenotypes associated with the loss of Pten suggests the electric cell communication circuit may be impaired in autism (14:11). Vogt outlines the process by which Pten is adjusted in mouse MGE cells to test for different variants and their functions (15:45). Mice with a Pten deletion showed no changes in SST expression, but had significantly reduced PV expression. However, mice with a human variant of Pten were rescued (returned) to control/wild-type levels (17:00). These findings, Vogt claims, show that variations of Pten cannot maintain the pathway, meaning that it is a loss-of-function gene (18:00). Tsc1 mutations also cause increased PV expression, suggesting a hyperactive mTOR pathway (19:30). The speaker reviews that mTOR activity promotes PV+ CINs, that the loss of Pten and Tsc1 lead to hyperactive signaling (e.g., higher expression of PV and lower expression of SST),  and that most genetic variants of Pten and Tsc1 are loss-of-function genes (20:10). 

• The Parvalbumin/Somatostatin Ratio Is Increased in Pten Mutant Mice and by Human PTEN ASD Alleles (Vogt et al., 2015)
• Tsc1 represses parvalbumin expression and fast-spiking properties in somatostatin lineage cortical interneurons (Malik et al., 2019)

MAPK signaling pathway

Deletion of the Nf1 gene or consecutive expression of bRaf leads to hyperactivation of the MAPK pathway. The speaker explains that hyperactive MAPK signaling causes increased levels of SST+ CINs and the repression of the ARX gene, which is critical for MGE and CGE development (20:50). Hyperactive MAPK pathways also have decreased PV expression, further evidencing circuit-based phenotypic variations (23:30). Vogt outlines a study that found decreased SST expression and normal PV levels after deletion of ERK1/2 in a mouse model. He explains that the pathway’s simultaneous hyperactivity and reduced activity suggest a dosage problem that corresponds to SST levels (25:07). 

The speaker reviews MAPK loss-of-function mutations, highlighting that a hyperactive pathway leads to higher SST and lower PV expression. Conversely, loss of ERK1/2 produces fewer SST+ and more PV+ cells (26:20). The speaker continues that some data suggest overproduction of SST in early development may outweigh the ability to make enough Pten later. 

Electrical properties

The presenter explains that by assessing the electrical properties of CINs, we can determine pathways of cell fate and communication (27:35). As noted previously, PV+ CINs have faster electrical spike patterns compared to SST+ CINs. Therefore, Vogt explains, hyperactive mTOR pathways have higher firing properties (more PV), and hyperactive MAPK mutants have slower firing properties (more SST) (30:00). He asserts that these findings show common changes across these pathways that are important for cellular fates, properties, and functionality (31:20). 

What’s next

Researchers have observed that mice with hyperactive MAPK (Nf1 deletion) present behaviors that resemble hyperactivity and a reduced sense of danger, suggesting a link between molecular changes and behaviors (32:40). The presenter discusses changes to transcription factors in the MGE in hyperactive MAPK (Nf1) mice, highlighting that more research is needed to understand the connections between cellular circuitry and behavior (35:25). 

Vogt outlines unpublished research that uses Selumetinib, an FDA-approved MEK inhibitor, to test molecular changes in mice. Preliminary results show that ERK remains active in controls. At the same time, blot test bands were rescued in mice who consumed the drug (36:50). The same study also found that systemic delivery of Selumetinib led to some behavior rescue in Nf1 adult mice. The speaker notes that ARX markers also seem to respond to the drug (38:50). Future directions include switching mTOR mutants with known molecular and cellular changes and using rapamycin to inhibit mTOR and search for other changes that may correlate with behaviors (40:15). Vogt provides thanks and acknowledgments (42:40) before the Q&A (44:00).

• Functional properties of GABA synaptic inputs onto GABA neurons in monkey prefrontal cortex (Rotaru et al., 2015)
• Distinct hyperactive RAS/MAPK alleles converge on common GABAergic interneuron core programs Icon for The Forest of Biologists (Knowles et al., 2023)
• Tsc1 represses parvalbumin expression and fast-spiking properties in somatostatin lineage cortical interneurons (Malik et al., 2019)

Originally published on February 21, 2024