Which factors drive autism? This is a question to which researchers still have no answer. Now, a new study conducted in mice and assessing data from humans suggests that a unique genetic mutation may play a key role in early brain development, contributing to autism.
Autism — which scientists and healthcare professionals often refer to as autism spectrum disorder (ASD) — is different for different individuals, and its traits usually become visible in childhood.
Specialists consider autism to be a "developmental disorder," and autistic individuals may have different experiences in terms of relating to other people; they may learn differently and engage in repetitive movement.
For some people, these traits are not an obstacle in their day-to-day life. Others may find these or aspects of these traits unhelpful, or that they cause difficulties in terms of engaging with people around them.
In these situations, healthcare professionals may advise on different ways of coping or strategies for self-development. These may include participating in cognitive behavioral therapy (CBT), behavioral management therapy, or social skills training. Others may suggest taking some medication, such as antidepressants or anti-anxiety drugs, where appropriate.
According to the World Health Organization (WHO), about 1 in every 160 children around the world is autistic. Despite this, scientists are still unsure exactly what factors drive the development of autistic traits.
A new study from the University of North Carolina (UNC) School of Medicine in Chapel Hill, suggests that a genetic mutation that drives features of the early development of the cerebral cortex may play a key role in autism.
The scientists conducted their research in mouse models and also assessed genetic information collected from humans. The authors present their findings in a study paper that appears in the journal Neuron.
"[The new] finding suggests that ASD can be caused by disruptions occurring very early on when the cerebral cortex is just beginning to construct itself."
Senior author Prof. Eva Anton
A gene key to early brain development
The research team focused on the cerebral cortex because, in humans, this part of the brain regulates higher-order functions, such as speech, consciousness, and memory.
Scientists are yet to learn exactly how the cerebral cortex develops, but they do know that a type of precursor cells — which later differentiate, becoming specialized cells — called radial glial cells are key to early cortical development.
These cells form at the base of the cortex in a particular "design" that researchers refer to as a "tiled pattern." Each radial glial cell in part then generates a "basal process" — a stem-like emanation that acts as a "scaffold" and helps new neurons (brain cells) to organize and slot into their assigned positions.
In their new animal study, the UNC researchers found that a gene called Memo1 disrupts the pattern of the radial glial cells, their basal processes, and the whole initial organization of new brain cells.
The team explains that previous studies have found that mutations in MEMO1 in humans sometimes have associations with autism. However, it remained unclear whether or how that mutation might contribute to the development of autism.
For their current research, Prof. Anton and colleagues decided to work with mice, in which they deleted the Memo1 gene in an early phase of cortical development. The team wanted to find out what effect if any, this would have on the brain.
After doing this, the researchers noted disruptions of the radial glial cells, whose pattern, they say, would typically remain stabilized by the action of the Memo1 protein, encoded by the gene of the same name.
Without it, the scaffolding that emanated from the radial glial cells branched out excessively and altered the tiling of the radial glial cells themselves. This resulted in the disorganization of new brain cells, some of which slotted into the wrong positions entirely.
Genetic mutations in humans
Prof. Anton and team note that a similar type of neural cell disorganization is present in the brains of some autistic children, according to existing studies.
Based on the clues offered by their findings in rodents and by previous human studies, the researchers then went on to analyze mutations of the MEMO1 gene in autistic people who presented characteristic behaviors and also experienced intellectual disabilities.
In doing so, the team found out that a mutation of this gene in humans encoded a shortened form of the MEMO1 protein, which, as the authors put it in their paper, "results in functional loss of MEMO1" and impacts the development of radial glial cells.
Moreover, when the investigators looked at the engineered mice once more, they noted that the knockdown rodents displayed certain behaviors — lack of interest in exploring, for instance — consistent with some behaviors typical of autism.
"For disorders of brain development, such as ASD, it is important to understand the origins of the problem, even if we are still far away from being able to correct developmental disruptions occurring in utero," says Prof. Anton.
"We need this foundational knowledge if we are to truly get to the root causes of these conditions and eventually develop better diagnostic or therapeutic strategies," she continues.
Such findings may, in the future, lead to better treatment options for individuals in whom certain features of autism lead to disability or behavioral issues. However, autistic advocates continue to urge scientists not to regard autism, on the whole, as a medical condition or a problem that needs solving.
"Healthcare disparities need to be remedied and beneficial therapies made more widely available; however, the use of scientifically unproven treatments and those that focus on normalization rather than teaching useful skills should be discouraged," warn the Autistic Self Advocacy Network.