Cobbers on the Brain

Autism symptoms

Autism spectrum disorder is a developmental disability that can cause significant social, communication and behavioral challenges. The learning, thinking, and problem-solving abilities of people with ASD can range from gifted to severely challenged. Some people with ASD need a lot of help in their daily lives while others need less or no help at all. People with ASD might repeat certain behaviors and might not want change in their daily activities. Many people with ASD also have different ways of learning, paying attention, or reacting to things. (CDC et al., 2021). This all comes from the spectrum aspect of ASD; there is such a wide variety of different types of autism. ASD is caused by genetic and environmental influences, but I will be focusing more on the genetic mutations causing ASD, specifically, in the PI3K-AKT/mTOR pathway.

PTEN’s role in the mTOR pathway

PTEN is a lipid and protein phosphatase that regulates cell growth and survival. In PTENS role as a lipid phosphatase, PTEN catalyzes the removal of the 3-phosphate from PIP3, generating PIP2 and directly antagonizing the activity of the class I PI3K. This process leads to multiple cell functions including, growth, survival, gene transcription, protein translation, cytoskeletal organization, and membrane trafficking (Skelton et al., 2019).

PTEN gene mutation

The PTEN protein is part of a signaling network that contains multiple ASD-associated gene products and represents a potentially common etiological mechanism for ASD and related neurodevelopmental disorders. PTEN acts as a lipid phosphatase which inhibits AKT activation by immediately inhibiting PI3K activity (Skelton et al., 2019). Mutation in PTEN causes mTORC1 hyperactivation (Sharma et al., 2021). This upregulation is associated with axonal dysregulation, megalocephaly, alteration of neuron size, protein synthesis, cerebral cell proliferation, and neuronal circuit connectivity between different brain regions.

TSC1/2 gene mutation

TSC is an autosomal dominant hamartomatosis with multisystem involvement in the body. TSC proteins play an important role in transmitting signals from a wide range of cell pathways that inhibit the mTORC1. mTORC1 was identified as long-term neurotransmission that regulates memory and incorporates signals from multiple neural surface receptor sites. This leads to increased mTORC1 activity due to loss of TSC1 and TSC2. This increased activity appears to be what leads to autism (Sharma et al., 2021). TSC is caused by a mutation in the TSC1 or TSC2 gene (Guo et al., 2012). TSC is a high-risk co-morbid disorder of autism spectrum disorder where the mutation of TSC1 or TSC2 dimerizes the signaling of mTOR with a negative effect (Sharma et al., 2021).

Works Cited

Centers for Disease Control and Prevention. (2020, March 25). What is autism spectrum disorder? Centers for Disease Control and Prevention. Retrieved from https://www.cdc.gov/ncbddd/autism/facts.html.

Guo, X., Tu, W.-J., & Shi, X.-D. (2012, September). Tuberous sclerosis complex in autism. Iranian journal of pediatrics. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564100/.

Sharma, A., & Mehan, S. (2021). Targeting PI3K-AKT/mtor signaling in the prevention of autism. Neurochemistry International, 147, 105067. https://doi.org/10.1016/j.neuint.2021.105067

Skelton, P. D., Stan, R. V., & Luikart, B. W. (2019). The role of PTEN in Neurodevelopment. Molecular Neuropsychiatry, 5(1), 60–71. https://doi.org/10.1159/000504782

What is Autism?

Autism is a developmental disability typically affecting communication and social interaction. Symptoms are usually apparent in the first three years of life. Autism is considered a “spectrum disorder.” This means its symptoms vary from person to person and ranges from mild to severe. There is no given set of characteristics that applies to all individuals with autism. It affects a person’s brain function in differing ways and at varying degrees. Thus, each individual affected with autism is unique in his or her own way. There is no single cause associated with autism; however, research indicates biological or neurological differences in the brain. It is five times more prevalent in males than in females but is not limited to any race, ethnicity, or socio-economic background.

Diagnostic and Statistical Manual of Mental Disorders V Classification of Autism

According to the DSM 5, the term Autism Spectrum Disorders (ASD) is a single umbrella term that encompasses the following subtypes:
-Autism,
-Asperger’s Syndrome (ASP),
-Childhood Disintegrative Disorder(CDD)
-Pervasive Developmental Disorder-Not otherwise specified (PDD-NOS)

It also emphasizes that individuals with ASD must possess symptoms from early childhood even though they may not become apparent until later in life. These diagnostic labels are based on the commonalities and the distinctiveness of the symptoms in each type of ASD. The defining symptom of ASD is substantial deficit in the area of social relations and communication. Asperger’s Syndrome is mostly considered to be a mild form of ASD, and it’s considered to be at the high functioning end of the spectrum. PDD-NOS is commonly used for those individuals that do not fully meet the criteria for ASD or Asperger’s Syndrome. CDD differs from autism in its occurrence as it develops in children with normal development that later start regressing. The ease with which an autistic child learns to socialize depends greatly on his or her communication skills. Parents, teachers, siblings as well as peers play a very important role in fostering life skills required for developing social skills.

Learning with Autism

Teaching social skills one-on-one may not be very effective unless interactions are linked with normal peers. Thus, a natural learning environment plays a pivotal role in nurturing social development in children with autism. At school, they should be encouraged to interact with other students mostly during recess, lunch time, or during special activities such as sports, arts, or drama/music. At home, parents and siblings can work together to provide an autistic child with opportunities for positive social interactions.

What Causes Autism

Though there are many different factors that could contribute to autism such as environment, problems during development, and illnesses females may experience during gestation, genetics is going to be mostly focused on here.

Mothers who contain gene variants of ASD are more likely to pass this onto their children. Females are less likely to present signs of ASD and to be a carrier of it. They can carry the same genetic risk factors without the signs of it but if they were to have a male child then that individual is more likely to be diagnosed with ASD after birth. The gene that is most commonly known to cause autism or autism spectrum disorder is fragile X syndrome. All males carry an X and a Y chromosome, and receive the X from their mothers. Females carry two X chromosomes, receiving one from each parent. Hence girls can inherit fragile X from either parent, while boys inherit it only from their mothers. Females are protected from fragile X syndrome to a degree because they have two X chromosomes. Because one of their X chromosomes is most likely to be normal, the effect of the abnormal one is less pronounced, and they usually have milder problems than males, with only 30 percent having intellectual disability and the rest having emotional or learning problems.

Figure 1: The generally accepted symptoms of Autism Spectrum Disorder.

What’s the deal with Autism Spectrum Disorder (ASD)?

To begin the discussion about what ASD is, it is first important to discuss what the disorder all entails. Unlike many of the neurological disorders or conditions we have discussed this semester, ASD is outlined more by the symptoms and the characteristics of the disorder rather than by the specific brain region or pathway that has been misregulated. These symptoms include but aren’t limited to: problems with social communication and interaction, motor skills, perceptive thinking, and restricted or repetitive behaviors or interests. It is important to note that some people without ASD may also display these symptoms, but for people with ASD, these symptoms can add new challenges to life. Because ASD is inherently a spectrum disorder, there is a wide range in the severity of symptoms and thus there is a wide range of individual challenges faced by those diagnosed with ASD.

Figure 2: A side by side comparison of the classical ASD spectrum and the newly used ASD spectrum.

ASD Spectrum Misconceptions

The use of the word “spectrum” is inherently misleading when used to describe any kind of disorder. Classically “spectrum” is used to describe a range that includes everyone, from no present symptoms to all possible symptoms. However, in the case of ASD, the spectrum only applies to those that have been diagnosed with ASD, where then the spectrum is used to characterize the severity of an individual’s symptoms. In Figure 2 above, there is a comparison to show the different kind of spectrums used to classify ASD. The left diagram is the classic linear spectrum that many people think of when they hear “spectrum,” however, this spectrum is used to classify the severity of an individual’s symptoms and the associated level of care. Whereas, the diagram on the right is a diagram used to classify the severity of an individual’s specify autistic symptoms.

Figure 3: A brief cartoon showing an overview of the available treatments for ASD.

What treatments are there for ASD?

Discussing the treatments for ASD, brings up an interesting question: Is there something wrong with those that have ASD? Speaking generally, this is more of an ethical question rather than a medical one, however, it is interesting to note that is a study of over half a million people, people working in a science or engineering job were more likely to display autistic traits than their nontechnical jobbed counterparts. So perhaps it is a good thing? There again, this is tricky to say  because in more sever cases there is something wrong neurologically. As discussed in class, there are multiple ways in which disruptions in the PI3K-Akt/mTOR signaling pathway that can develop into autistic-like behaviors. These disruptions lead to: serotonergic degeneration, translation dysregulation, decreased neuronal autophagy, neuroinflammation, apoptosis, and increased oxidative stress. So there are some autistic behaviors that can be caused my misregulated pathways, which is more serious.

However, despite the potential severity of a misregulated pathway, there are no real medial treatments for ASD. The treatments largely rely on Applied Behavioral Analysis (ABA) treatments. These ABA treatments look at how behavior works, how it is effected by the environment, and how learning works. This approach then uses this information to help a patient realize what behavior is appropriate using the ABC’s of ABA. “A” standing for antecedent is a stimulus that occurs right before a target behavior, which then results in the “B” for behavior. The important part comes from the “C” meaning consequence. To help patients, positive reinforcement is used when the behavior displayed is appropriate for the antecedent, whereas there is no reaction for inappropriate behavior.

Figure 4: A diagram showing drug treatments for neurologic misregulations associated with the development of autistic behaviors.

What does this mean for the future of ASD?

To conclude, ASD is a disorder that is commonly diagnosed by its symptoms rather than by a specific neuronal irregularity. Because of this, there is no specific treatment for possible misregulations in the PI3K-Akt/mTOR pathway, but rather the treatments include things like ABA treatment that is targeted at correcting the symptoms in a patient with ASD. Despite this, there may be a future in drug treatments as shown by Figure 4 above. However, by dispelling some of the misconceptions about ASD, there opens new avenues for children diagnosed with ASD to be better integrated into schools and social settings, despite their impaired social interactions.

Anxiety is something we have all experienced on multiple occasions in our lifetime. The first time I remember feeling anxious was when I was three years old. I was onstage in a pink tutu, my hair was in a slicked-back bun, and I had leather ballet shoes on my feet. It was my first dance recital. I included an image to the left so you can picture three-year-old me.

At that time, I was just starting my dance career, and I had never been on the stage before. I remember the lights were shining on me so brightly, and I knew my family (along with dozens of other people) were watching me. I was so nervous to perform in front of all of those people, and I decided that the best way to get out of that situation was to run offstage, tears falling down my face as I did so. My dance teacher at the time (bless his heart) talked to me and calmed me down from my panic before convincing me to go back onto the stage. I followed his advice, and I proceeded to take the stage that night and for fifteen years following that event. The anxiety I felt before going onstage never really went away, but it became a normal part of my life and became more manageable. This is a specific instance, but I have had many experiences with the feelings of anxiety—worry or unease about a specific event or condition.[1] In addition, I have been surrounded by anxiety disorders my entire life (even if I wasn’t aware of what it was at the time).

Anxiety disorders run in my family. I can think of multiple family members that have some sort of anxiety disorder, whether they admit it or not. Generalized anxiety, post-traumatic stress disorder, separation anxiety, and obsessive-compulsive tendencies are all anxiety disorders I have witnessed in my family. Anxiety disorders, however, are different from anxiety. Yes, they tend to share similar physical symptoms, but there are nuances that separate anxiety from anxiety disorders. As I previously stated, anxiety is the feeling of fear or unease concerning a specific event or condition. Physical symptoms of anxiety include elevated heart rate, sweating, having difficulty breathing, and nausea. Though anxiety disorders have these physical symptoms, as well, it is the effect the anxiety has on one’s life that makes it different from anxiety. Anxiety, because it is triggered by an event, has an anticipated end. If you are anxious about an exam you have, the anxiety will likely go away after you finish that exam. Anxiety disorders, on the other hand, are unpredictable—both in duration and triggers. The feeling of uneasiness can last twenty minutes, or it can last for three hours. The triggers can also be unpredictable. A family member I have that has PTSD is triggered anytime she sees rapids in a river, but my anxiety (GAD) is not necessarily triggered by anything. Anxiety disorders are unpredictable, but they are primarily characterized by feelings of anxiety and panic that are out of control, not appropriate for the situation, and interfere with daily activities.[2] More differences are outlined in the picture below.

Many people in today’s society think the term “anxiety” is synonymous with anxiety disorders. The incorrect terminology has been perpetuated through media and has had a generalization effect on anxiety disorders. Many people are guilty of generalizing anxiety disorders (I’m on the proverbial soapbox, but I have also been guilty of doing this), but this generalization makes it hard for anyone with diagnosed with an anxiety disorder to be taken seriously and feel understood. A common response to being startled is “you gave me a panic attack.” This statement invalidates people with panic disorder because now a panic attack is nothing more than a simple fright. Some individuals clean and straighten things up because “my OCD is bothering me.” This statement is invalidating to people with obsessive-compulsive disorder because OCD is now associated only with cleanliness and order—it disregards the two main characteristics of this disorder: obsessive thoughts and overwhelming compulsions.

The main point of this post is not to shame anyone or call anyone out (though I realize now that it seems like it). I just think it is important to spread awareness about the differences between anxiety and anxiety disorders. There are significant differences between anxiety disorders and the feeling of anxiety, and I think not a lot of people are aware of these differences. I think it is important to shed light on the generalization of anxiety disorders and how these generalizations can be hurtful.

[1] https://www.healthline.com/health/anxiety

[2] https://www.mayoclinic.org/diseases-conditions/anxiety/symptoms-causes/syc-20350961

[3] http://invermeresummityouthcentre.org/anxiety/ 

Hippocampus is crucial for memory consolidation, from working memory to long-term memory. The subregions loop through dentate gyrus and CA3 and CA1 areas,.

Cortisol is released by the adrenal glands and is involved in glucose metabolism, blood pressure regulation, inflammatory responses among many others.

Cortisol is necessary when it comes to the fight-or-flight mechanisms, by causing faster breathing, heart rate in case of a stressful event. This is important in small quantity, due to anxiety behaviors caused by elevated cortisol levels in the body. It can potentially be caused by eating disorders, lack of exercise hence making it necessary to practice meditation, exercising, eating nutrient-rich foods.

Along with Cortisol, adrenal glands also secrete glucocorticoid in the hypothalamus, which similarly produces stress response and coping.

The exposure is largely caused by negative events affecting the brain. This could go even beyond into  . There are three major ways that may lead to the occurrence of a trauma/ anxiety behavior. The event,the experience of the event, and the effctts of the event.