by Mahbod Ebrahimi

Graphic design by Jo Choi

Autism and attention-deficit hyperactivity disorder (ADHD) are common neurodevelopmental conditions with a worldwide prevalence of around 1% and 6%, respectively.¹ The typical symptoms of ADHD include hyperactivity, impulsivity, and/or inattention and have a continual impact on one’s daily life.¹ Autism is typically characterized by difficulty with social interactions and restricted and repetitive patterns of behavior and activities.¹ Although ADHD and autism are distinct from each other, there is an intriguing crossover between these two conditions: ADHD is present in 30-80% of individuals with autism, and autism is present in 20-50% of individuals with ADHD.² Both conditions are neurodevelopmental, that is, the conditions develop during early childhood and have overlapping symptoms, such as self-dysregulation. Self-dysregulation manifests itself in three key aspects: emotions, behavior, and cognition.² In the context of these key aspects, self-dysregulation may involve internalizing issues like anxiety, depression, and suicidality, or externalizing issues such as aggression and impulsivity. Understanding these patterns becomes crucial as they are observed at higher rates in individuals with autism and ADHD. Further, autism and ADHD also have intricate relationships with  another neurodevelopmental condition, intellectual disabilities (ID). 

Dr. Hsiang-Yuan Lin, a psychiatrist and clinician-scientist with the Azrieli Adult Neurodevelopment Centre at the Centre for Addiction and Mental Health (CAMH) and assistant professor of Psychiatry and IMS, concentrates on treatment innovation for self-dysregulation in neurodevelopmental conditions by integrating clinical trials and multimodal neuroimaging and computational methods to understand atypical neurodevelopment throughout one’s life, with a particular focus on autism, ID, and ADHD. Dr. Lin obtained his medical degree in 2007 and completed his residency in Child and Adult Psychiatry from National Taiwan University Hospital in Taiwan in 2013. He then received further training in advanced neuroimaging methods at the QIMR Berghofer Medical Research Institute in Australia. 

Dr. Lin’s current research at CAMH focuses on clinical trials and neuroimaging studies with the aim of discovering novel treatment methods to improve the quality of life for people with autism, ID, or ADHD. This can be broken down into four main areas described below.

1. Nabilone trial: In Dr. Lin’s efforts for treatment innovation, his lab has conducted the world’s first Phase I pilot open-label clinical trial with nabilone for adults with intellectual and developmental disabilities (including autism) and severe behavioural problems. Nabilone is a synthetic cannabinoid and a THC analog that has previously been used for treating behavioural issues in dementia and Parkinson’s disease. Since the mechanism of nabilone, which involves influencing our cannabinoid receptors, is relatively well understood, Dr. Lin aimed to test the feasibility of using nabilone as a treatment to help reduce aggression in adults with ID. In this open-label pilot clinical trial, 12 participants with ID and aggressive behaviours were enrolled in and completed a 4-week medication course. Following this period, aggression was evaluated through clinical assessments and standardized questionnaires filled out by caregivers. The results indicate a promising 60-70% decrease in aggressive behaviours. The observed improvement encompassed all forms of aggression, including self-injury as well as aggression towards others. Dr. Lin hopes to take this investigation further by collaborating with colleagues at the University of Montreal to conduct a multisite, double-blind, randomized control trial (RCT) with the objective of assessing and confirming the scalability, tolerability, and effectiveness of nabilone for treating aggression in people with intellectual and developmental disabilities.
2. Psilocybin-assisted therapy in autism: Dr. Lin’s laboratory has another intriguing project in the pipeline involving the exploration of psilocybin, a psychedelic compound present in magic mushrooms, for addressing treatment-resistant depression in autistic adults, with an additional focus on brain mechanism based on dense sampling (i.e., scanning an individual’s brain at multiple time points and under varying conditions) functional MRI. Despite the burgeoning interest in psilocybin therapy, its application remains unexplored in the realm of autism treatment. Notably, this initiative marks the inaugural attempt to investigate the viability of psilocybin-assisted therapy as a potential intervention for depression in individuals on the autism spectrum. The recruitment phase for this clinical trial is slated to commence in Spring 2024. 
3. Repetitive Transcranial Magnetic Stimulation (rTMS) in Youth with Autism: In collaboration with colleagues in Taiwan, Dr. Lin and the team have conducted three double-blind RCTs utilizing rTMS targeting specific brain regions in autistic youth. rTMS is a process where a machine directs a magnetic field to bring about a neurophysiological change in the brain. The primary goal of these trials was to assess whether rTMS could effectively address emotional dysregulation and repetitive behaviours frequently observed in this population. More than 200 participants were enrolled in these trials, with ~100 receiving active rTMS and ~100 receiving sham stimulation. The findings from these RCTs did not reveal significant changes in the core symptoms or overall quality of life in the autistic individuals undergoing TMS treatment, prompting the exploration of alternative brain regions and rTMS methodological considerations. Based on these results, the team and Dr. Lin are currently working on a pilot study focusing on stimulating the cerebellum using rTMS. The effect of TMS on the cerebellum would be especially interesting since this brain region is responsible for an array of biological functions and is very sensitive to external stimulation. A previous neurotypical adult study suggests cerebellar TMS may increase functional connectivity within the social network, making this feasibility effort an innovative and intricate approach within the scope of TMS applications.
4. Imaging Neuroscience: Delving into the realm of neuroimaging, Dr. Lin’s research unfolds an intriguing perspective on autism and ADHD. A pivotal question driving Dr. Lin’s team revolves around discovering potential disparities in the brains of individuals with varying intellectual abilities within the autism spectrum. Intellectual ability is defined by a person’s IQ measurements and adaptability. Dr. Lin’s team has discovered that the brains of individuals with autism, both intellectually capable and disabled, differ from those of the general population. Furthermore, the brains of intellectually capable individuals with autism differ from those of intellectually disabled individuals with autism. This investigation has critical significance, as most of the existing literature in autism research predominantly features individuals on the higher end of the intellectual spectrum. Furthermore, another captivating neuroimaging study that is ongoing in Dr. Lin’s lab involves unravelling the intricate relationship between the menstrual cycle, brain dynamics, and cognitive patterns in females with ADHD. This project entails the dense sampling approach, thereby observing the intricate fluctuations within the brain. 

Dr. Lin and his team are continuously engaged in captivating and transformative research endeavours aimed at enhancing the lives of individuals with autism, ID, ADHD, and other neurodevelopmental conditions. A pivotal point Dr. Lin emphasizes in both his medical practice and research is to embrace individuals’ neurodiversity. As Dr. Lin puts it, “Respect neurodiversity. We don’t want to eradicate the conditions, [rather] aim to only improve the core symptoms [for people with autism or ADHD] when these endeavours could facilitate a better quality of life. People should focus more on how we can improve and help [people with autism or ADHD] to keep their identity but also adapt to the neurotypical society in a happier and less anxious manner.” Looking ahead, Dr. Lin’s future aspirations revolve around discovering innovative and effective interventions to improve self-dysregulation and elevate the well-being of individuals with neurodevelopmental conditions.

References

1. Fast K, Wentz E, Roswall J, et al. Prevalence of Attention‐deficit/Hyperactivity Disorder and Autism in 12‐year‐old Children: A Population‐based Cohort. Developmental Medicine & Child Neurology. 2023 Sept 22. 
2. Lau-Zhu A, Fritz A, McLoughlin G. Overlaps and Distinctions between Attention Deficit/Hyperactivity Disorder and Autism Spectrum Disorder in Young Adulthood: Systematic Review and Guiding Framework for EEG-Imaging Research. Neuroscience & Biobehavioral Reviews. 2019 Jan; 96:93-115.