ABOUT AUTISM SPECTRUM DISORDER (ASD)
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder, present in childhood, involving distinct human deficits or difficulties around social communication and repetitive behaviors. Not every autistic human shares the same difficulties. However, some of the overlapping difficulties involve:
a) Social emotional reciprocity i.e. how you share your social world.
b) Repetitive behaviors of interest and routines, as well as repetitive motor behaviors.
c) An infrequent or inappropriate use of gestures.
d) Challenges in social interactions and relationships.
Other difficulties involve high sensitivity to sounds, light, touch, smell or taste. As well as a lack of sensory reactions to pain, temperature or sounds. Although, all of these features are diagnostic, individuals under the ASD umbrella often represent a wide range of severity and often co-occurring signs and symptoms that can include anxiety, depression, sleep disturbance, epilepsy, or savant skills e.g. obsessive preoccupation with, and memorization of music, maps, historical facts, etc.
Until 2019, according to the statistics, ~ 2.7-3.6% of the American population has been found with an autism diagnosis. Unfortunately, the estimate has been rising over time. Although, ASD ranks at the top of the neuropsychiatric disorders with regard to its relative genetic contribution and variety of clinical manifestations, we still don’t have clear diagnostic biomarkers for it. One of the first successful efforts at isolating true ASD risk genes involved the identification of mutations in Nlg3 and Nlg4 genes. These genes belong to a phylogenetically conserved family of adhesion proteins located in the post-synapsis. Impaired function of Nlg3 and Nlg4 genes is associated with ASD in humans, and impaired social behavior in mice. Nowadays, there is enough evidence to support the association of about a dozen copy number variant (CNV)* loci and more than 100 genes involved in ASD, with this list growing.
The fact that ASD involves very different human features, poses a challenge for the interpretation of results coming from evolutionarily distinct experimental models e.g. mice. For this reason, in addition to the progress in gene discovery, there have been huge efforts to encourage what is known as the “convergence neuroscience research approach”, which involve the intersection among molecular-level, cellular level and circuit level functions across multiple ASD risk genes. This approach has revealed among others that:
1) Developing excitatory neurons in the human cortex differ substantially between ASD and control subjects. In ASD subjects the excitatory neurons in the developing frontal & parietal cortices contain high expression of ASD genes during early mid-gestation.
2) ASD genetic risk may cause disruptions in the neurogenesis of the cortex by disrupting the connectivity of the network within the cortical layers.
3) ASD risk genes are differentially enriched in distinct cell types of the human brain. For example, post-mortem ASD human cortex reveals an increase in the representation of excitatory neurons and microglia in comparison to control brains.
In the last few years, there has been a global phenomenon of increasing autism prevalence. It is not clear what is changing in the developing brains to make autism more common. Early diagnosis contributes to improving the cognitive skills of the ASD population. Thus, there has been tremendous efforts to generate biomarkers that allow for a quick and accurate diagnosis. Some of these efforts involves deep learning algorithms trained to detect particularities at the level of behavior e.g. eye movements & facial gestures, brain imaging & circuits, as well as genetic profiles. Other strategies involve novel gene therapies like gene replacement, editing, and antisense sense oligonucleotide strategies.
Early diagnosis in combination with cognitive and behavioral therapies are fundamental for improving the cognitive skills and life quality of the ASD population. More work needs to be done in order to guarantee access to early diagnosis regardless of race, gender or social status. It turns out to be fundamental to reflect about how the ASD population perceive the world, what their needs are and how we can adapt our environment and social construction for them.
*Copy number variation (CNV) is a phenomenon in which sections of the genome are repeated and the number of repeats in the genome varies between individuals.
1) Willsey H.R. et.al (2022), Genomics convergent neuroscience and progress in understanding autism spectrum disorder, Nature Reviews Neuroscience, 323-341.
2) Autism by the numbers (2021), Spectrum’s Guide to Prevalence Estimates, Spectrum, Simons Foundation.
4) Embracing Autism, A little help for Our Friends Podcast
6) Corthals, et. al., (2017) Neuroligins Nlg2 and Nlg4 affect social behavior in Drosophila Melanogaster, Frontiers in Psychiatry, 1-13.