As a child growing up with a neurologist for a dad, I always heard the phrase “don’t forget to wear your helmet!” whenever I wanted to ride my bike or rollerblade or whenever I took horseback riding lessons. I always thought that it was lame. None of my friends wore helmets so why should I? I always thought they would pick on me or say I wasn’t cool because I had a helmet on. I was embarrassed by it.
Fast forward to now. As a soon to be graduate with a degree in neuroscience, I now completely understand the importance of wearing a helmet whether its simply riding a bike or flying down the slopes on my snowboard.
What happens when you don’t wear a helmet?
Not wearing a helmet increases your risk of brain injury. The most common type of traumatic injuries are concussions. Concussions can occur even with wearing a helmet if the impact is hard enough. Concussions most commonly result from falls, motor vehicle accidents, and sporting accidents.
What happens during a concussion?
Concussions occur when the brain moves inside the skull. After the skull hits a stationary object, that force causes the brain to swirl around inside the skull. The brain bumps into the sides of the skull and damages tissue.
Concussions are not fun. They can cause both temporary and long-lasting problems in cognitive abilities and proper brain function.
Some short-term effects of a concussion include:
Temporary loss of consciousness
Headache
Dizziness
Feeling foggy
Ringing in ears
Nausea or vomiting
Blurred vision
Sensitivity to light and sound
Fatigue
Some long-term effects of a concussion include:
Difficulties concentrating
Memory issues
Irritability or other changes in personality
Sleep issues
Depression or other psychological problems
Though there is no concussion proof helmet, it is still an important thing to wear. Yes, you can still get a concussion even by wearing a helmet. This happened to me while snowboarding. But wearing a helmet can help minimize the effects. If the helmet can take most of the force, the brain won’t move around as much and not bump into the sides of the skull as hard.
Concussions are caused by head trauma, often a blow to the head in which the brain hits the opposite side of the interior of the skull. Common causes of concussion include motor vehicle accidents, falls, and sports injuries. Concussions are classified as mild traumatic brain injury and often characterized by mild cognitive impairments without physical signs identifiable by an MRI or CT scan.
After a concussion occurs, a series of events known as a neurometabolic cascade occurs. The steps occur as follows:
Non-specific depolarization
Cells contain small molecules called ions that normally exist at specific concentrations inside and outside the cell. When these concentrations are disrupted, the charge of the cell changes and causes other events to occur
Release of excitatory neurotransmitters
Potassium efflux
Increased activity of ion pumps to restore the resting state
Hyper glycolysis to generate more ATP
Lactate accumulation
Calcium influx and sequester into mitochondria leading to oxidative metabolism
Decreased ATP production
Overactivity leads to cell death
These changes occur in a cascade one after another and the whole process can have impacts for approximately 7-10 days. These changes make the person especially susceptible to another brain injury. This is where second impact syndrome comes in and why injured people are not supposed to return to their prior activities too quickly. After a concussion, the brain uses all of its resources to repair the damage, so there is nothing else for it to give. When a second concussion occurs, there is nothing left to heal the damage. This is especially important because 50% of all athletes who have experienced second impact syndrome died.
Long term impacts of concussion
A lesser understood risk of concussion is development of a neurodegenerative disorder called CTE. CTE is a form of dementia with similar symptoms to Alzheimer’s disease, but important differences occur. Both disorders can only be diagnosed through autopsy and neither disorder has a cure. Repeated brain injury increases risk for all kinds of degenerative disorders, but each one has its own unique risk factors and these changes are not well understood.
Symptoms of CTE include
Confusion and agitation
Personality changes
Erratic behavior
Troubles with organization and planning
Balance and motor skill problems
Symptoms of Alzheimer’s include:
Difficulty remembering new information is usually the first sign
Gradual increase in level of severity
Disorientation
Mood and behavior changes (often directed toward family members)
Eventually difficulty in life maintaining activities like eating, moving, and breathing
Clearly, concussions are dangerous and can have severe impacts. The question then becomes: What do we do about it?
Lately, helmets have been a large topic of discussion surrounding concussions. . From 2016 to 2017, concussions in the NFL increased by 16%. 2017 and 2018 showed a slight decrease in concussions, though the league still recorded well over 200 concussions each year. As of 2019, the NFL passed new regulations that required all players to wear an approved helmet to engage in any kind of practice or games on the field. The regulation was the first of its kind as players could “grandfather in” helmet types that had been used in the past. Before this, helmets had not changed significantly since the 70s.
Current relevance
On November 15th, 2019 Myles Garrett hit Mason Rudolph with his own helmet during the final seconds of the third quarter in a game between the Steelers and the Brown. The whole story as well as video is available here. After hearing some of the science behind head injury, you may see this story a little differently. Are there viable changes that can be made to the sport or is head injury simply and inevitable consequence of playing professional football?
The increasingly competitive nature of sports is constantly pushing athletes to the limit of human capabilities. This provides a more enjoyable sporting event for the fans, but has the potential to have several adverse effects on the athletes. Major league sports has seen a dramatic rise in many types of injures such as torn ACL’s and Tommy John replacement because of the physical demand now being placed on individuals. In recent years however there has been a rise of another kind of injury, one which often goes undiagnosed until after the athlete has completed his or her career. This disease is CTE and is caused by repeated trauma to the head. These repeated concussions lead to changes of behavior, cognitive function, physiologic function. In order to better understand concussions, many researchers are now examining the neurochemistry of the disorder in order to find potential cures and remedies for CTE.
Much of the neurochemistry of concussions is still unknown and research is constantly being done to better understand what is happening within the brain. Some things are known however. Upon the initial the membranes of neurons can become damaged. This leads to calcium ions to enter the cells in concentrations much higher than normal leading to a depolarization as potassium leaves the cell. It is hypothesized that these ion fluxes could be one of the main causes of migraine in regards to concussions. Also, the mitochondria of these synaptic nerves then absorbs this calcium which leads to an energy crisis within the cell as these organelles attempt to restore homeostasis. This lack of energy within the cell can lead to vulnerability of the individual to receive concussions more easily. Energy depletion and abundant calcium within the cell then leads to the alteration of normal neurotransmitters, changing the wiring within the brain. Repeated concussions lead to permanent rewiring of the brain thus leading to the changes already discussed with CTE.
This more complete understanding of concussions has allowed for the advancement of safety equipment in many major league sports. The NFL is a prime example of such innovation when it comes to safety equipment and concussion protocol. Every year the NFL makes alterations in helmet design and regulation, in an attempt to protect their players. However, there are some individuals who do not support all of the advances in safety regulation. Many of these people make the argument that these safety regulations are changing the nature of the sport. For example boxing is a sport, MMA, and UFC are all sports which thrive off of combat. However, is it right to make individuals use more protective gear when the nature of the sport is obviously human-human combat? Also, the individuals partaking in the sport have a voice? If an individual knows the risk of a sport and deems the risks worth the reward who has the right to stop them from potentially being harmed.
The world of sports is rapidly changing. These changes may be more interesting for the audience but can take a demanding toll on an athletes body. With this rise in completion there is also a rise in injury. Knowledge of concussions has been essential for the advancement of safety equipment utilized to keep athletes safe, but how much is too much? Providing to much safety equipment can change the nature of a sport which has a variety of implications. If athletes are aware of the issues shouldn’t they be allowed to take the risks? Finding the balance between safety to prevent concussions while still being true to the sport will be no easy task.
Autism spectrum disorder is a developmental disorder. Children with ASD often have difficulties
Communicating and interacting with others
Restricted interests in specific things or activities
Repetitive behaviors.
These call all impact how well a child functions at home, school, or other areas in life. Autism is often associate with low intelligence.
However, some wonder if autism is really a disorder of high intelligence. Recent studies have shown that the genetic components that are associated with autism, overlap significantly and substantially with the same components associated with high intelligence.
Before digging in, we must first define what is intelligence. Intelligence is defined as general cognitive problem-solving skills. It is a mental ability involved in reasoning, perception, calculation, learning quickly, etc. Intelligence is often studied from psychometric, genetic, neurological, and psychological points of view.
How does a researcher test this?
This is a challenging topic to study. How does someone on the autism spectrum who may have difficulties communicating or interacting with others take an IQ test? Are we able to give someone with ASD the same test we would someone without ASD? Tests today are becoming more accurate at testing intelligence without being thrown off by symptoms of autism. One such test is the Test of Nonverbal Intelligence (TONI). This test allows researchers or psychologists to test and assess individuals who may have difficulties with speaking or motor tasks.
So, what is the correlation between ASD and intelligence?
One correlation is brain size. Large brain size and large head circumference are a typical phenotypic correlate of ASD. Studies have shown that increases in brain size in ASD involve a higher number of neurons, thicker cortex, and an increased volume of the hippocampus. This increase in cortical thickness has been shown to be accelerated during development followed by accelerated thinning later in adolescence.
In 2015, Cambridge University conducted a study with over half a million participants. They discovered that people with autistic traits are more likely to be involved in the sciences, technology, engineering, or math fields. Though this does not prove that autism is correlated with intelligence, it is still an interesting discovery.
It’s simple logic. As with anything else in the body, if your brain is hurt (in an injury such as a concussion), give it a rest. The concept itself seems easy enough to grasp. Given how important the brain is, why would anyone even bother second guessing the time it takes for the brain to rest and recover? Nonetheless, you’ve probably known (or maybe you are) someone who’s brushed off a head injury as a “minor incident” or who’s been reluctant to let a concussion keep them from participating in athletics. The Return-to-Play rules governing concussed athletes are relentlessly stringent, and it’s certainly frustrating to be kept off the court by what many young athletes consider a “pounding headache.” But they are there for a reason. We often are familiar with the immediate affects of suffering a concussion, but what actually goes on up there when the brain is hit with a sudden force? And with ugly truths emerging in recent NFL brain injury studies, what devastating long-term impacts can result from a single blow to the head?
What’s the Fuss Behind the Concussed?
More than just a splitting headache!
Before we discuss the concussed, some of you might be wondering: what exactly is a concussion? The CDC defines a concussion as “a type of traumatic brain injury—or TBI—caused by a bump, blow, or jolt to the head or by a hit to the body that causes the head and brain to move rapidly back and forth.” It is this sudden motion that can damage the brain and its cells, causing the symptoms we are all too familiar with. We are well aware of what happens during an immediate concussion. Vision gets blurry, memory gets fuzzy, and speech gets slurred. If you are not yet aware, some of the common post-concussion symptoms are:
Dizziness
Fatigue
Anxiety
Headache
Sensitivity to light and sound
Loss of concentration and memory
Confusion
Low energy levels, irritability, sleep problems
For a full list of symptoms and more about concussions, visit the Mayo Clinic page here.
But what about a child’s long term health? Many parents of young athletes are familiar with the importance of proper brain development throughout childhood and in the teen years. Recent studies indicate that although long term amnesia or cognitive declines are rare in those who have suffered a concussion, if enough brain damage is sustained (for example, obtaining a second concussion while still recovering from a first) the outcomes can be dire. Long term deficits, such as
CTE (chronic traumatic encephalopathy, caused by repeated head injury, which can display as the below symptoms)
Alzheimer’s-like memory loss
Cognitive decline
might occur in patients when they grow older. A shocking statistic? In a study done on 111 brains of post-mortem NFL players, 110 had CTE – which really sheds the light on just how serious a “simple concussion” can turn out to be. Next, let’s look at the science that actually causes these symptoms and underlies a concussion.
Stark contrast between normal brain and one with advanced CTE
[A concussion is] a type of traumatic brain injury—or TBI—caused by a bump, blow, or jolt to the head or by a hit to the body that causes the head and brain to move rapidly back and forth.
Heads up – What’s Going on Up There?
So, a ball slams into the head, and the brain jolts. What next? The steps that occur in the brain following blunt impact can be summarized as follows:
Impact stretches cell membranes of brain cells (neurons and supporting cells), damaging them and making the membranes porous
Chemical gradient disrupted due to pores (K+ out and Na+ in), causing unintentional depolarizations and irregular action potentials.
Irregular action potentials lead to release of neurotransmitters in a neuron, especially glutamate (a major excitatory neurotransmitter in the brain), and neurotransmitter imbalance results
Glutamate binds to a molecule, called an NMDA receptor, on the downstream neuron.
Together, the depolarization and the glutamate binding opens NMDAr, which allows calcium to enter the neuron.
This overabundance of Ca2+ can set off a variety of chemical cascades. In concussions, it mainly affects the mitochondrion (yes, the “powerhouse of the cell”)
In an attempt to reset the chemical imbalance between K+ and Na+, a molecule “pump” called an ATPase pumps out 3 Na+ for 2 K+ in. This requires a form of “energy currency,” called ATP, the “power” generated by the mitochondrion.
The mitochondria work harder to produce more ATP to power this process
In doing so, the mitochondria deplete energy stores and use too much glycogen
This causes a state known as “hyperglycolysis,” where too much glycogen is broken down (why concussed patients are often “tired”
This is also a supply demand problem – during a concussion, there’s decreased blood flow to the brain
Less blood means less oxygen to the brain, so the mitochondria must rely on anaerobic respiration, generating harmful lactic acid
The mitochondria also try to contain some of the excess Ca2+ in the meantime
Bottom line: Mitochondria are overstressed, overworked, and underpaid.
Why is this so detrimental? The ability of a neuron to fire depends on the maintenance of a chemical gradient and ability to send action potentials, which is the means by which neurons communicate. If the chemical gradient of Na+ and K+ is disrupted, as described previously, neurons might struggle to fire, leading to problems in brain function and some of the immediate symptoms listed previously.
In the long term, these overworked, stressed mitochondria produce less ATP than they’d normally be able to. This chronic low-level energy lasts for a while and throughout most of the concussion recovery process, leading to low metabolism and low energy levels as the brain tries to recover. The lactic acid produced (the same stuff that makes your muscles sore after a workout) also might make brain conditions overly acidic (acidosis), which can further prevent chemical gradients from re-establishing, denature/damage proteins, and altogether cause more brain damage. Ultimately, this imbalance can cause structural damage to filaments and other elements of brain cells, and ultimately cell death or “apoptosis” (programmed cell death).
In the case of repeated head injuries and conditions such as CTE, imagine this entire process happening again while the brain is still trying to recover. It is this combination of events that leads the brain to a point where it literally cannot recover – causing long term brain damage.
The problem of concussions persists in many of today’s sports
So what can we do to keep young athletes from suffering brain injuries? We can’t just tell everyone to stop playing football (or any other sport, for that matter). Because concussions have become so relevant in modern day athletics, recent research has gone into developing better gear (such as football helmets) that can reduce, mitigate, or detect the amount of impact a player is receiving. Some prototypic helmets even have impact sensors that can indicate how much force the brain has received, so players can be pulled out when the limit is reached! Moving beyond athletics, technology is constantly being developed to reduce impact during car crashes, accidents, and other potential TBI-inducing situations.
So what do we gain from all this? Hopefully less minor brain injury for our future youth athletes. At the end of the day, the brain is incredibly complex, and this pink, wrinkly organ holds the key to one’s limitless thought and action. But the brain does have its own limits – the brain is just as delicate as it is complex and crucial for one’s survival. At the end of the day, it’s important to recognize when to pull your head out of the game and let the brain work its own magic.
Concussions are one of the brain diseases that are often overlooked. Too often approached as something that athletes can tough out, they have not been taken as a serious medical condition amongst laypeople until recent years. Investigations into chronic traumatic encephalopathy (CTE) based off of injuries from NFL players have caused concussions to come to the forefront of many conversations. Questions about how athletes conduct themselves and how they are treated when incidents occur have become increasingly important. Check out this quick 30-second video for a definition of a concussion.
As mentioned in the video, concussions are actually mild traumatic brain injuries, or mTBIs, which means they must be taken seriously in order to allow the brain and person to heal fully.
Concussions are a type of traumatic brain injury. In 2014 there were approximately 2.87 million concussions in the United States, but many people fail to receive treatment for concussions. Symptoms include headache, loss of consciousness, ringing in the ears, nausea, slurred speech, and fatigue. These symptoms can last for a few days after the incident to weeks or months later. https://www.mayoclinic.org/diseases-conditions/concussion/symptoms-causes/syc-20355594
Concussions happen when impact to the head causes the brain to forcefully make contact with the skull. This causes a myriad of effects within the brain. The neurons in the brain depolarize and there is a release of excitatory neurotransmitters, causing further depolarization. Ions rush out of the cell and the activity of the enzyme that break ATP into ADP. This causes the mitochondria to go into overdrive in an attempt to restore normal levels of ATP in the cell. Calcium also rushes into the cell and is stored in the mitochondria which makes it more difficult for them to produce ATP, causing a decrease in production. This can lead to apoptosis and a loss of neurons. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479139/ The loss of neurons is believed to lead to chronic traumatic encephalopathy which is seen in people who have sustained multiple traumatic brain injuries.
Chronic Traumatic Encephalopathy (CTE)
A diagnosis of CTE can only be made during an autopsy. However, there are some behavioral characteristics associated with CTE. These include difficulty thinking, impulsive behavior, short-term memory loss, emotional instability, substance abuse, and suicidal ideation. Many cases of CTE that have been studied occurred in football players, boxers, or military personnel who were exposed to IEDs. CTE occurs in a relatively slow progression and signs can begin to appear years after the trauma. Scientists do not currently know why some people with similar histories of head trauma develop CTE and others do not. The photo above shows the contrast between a healthy brain and the degeneration that found in the brain of someone with CTE. https://www.mayoclinic.org/diseases-conditions/chronic-traumatic-encephalopathy/symptoms-causes/syc-20370921
Diagnosis of Concussion
Concussion diagnoses typically rely on neurological and cognitive testing. A neurological test involves tests of vision, hearing, and balance for any deficits that may have been caused by brain trauma. Cognitive tests typically involve tests of memory and concentration that are typically impaired by a concussion. https://www.mayoclinic.org/diseases-conditions/concussion/diagnosis-treatment/drc-20355600 Brain imaging can be used for cases where severe trauma has occurred to assess the level of damage. Two methods that can be used are functional Magnetic Resonance Imaging (fMRI) and Diffusion Tensor Imaging (DTI). fMRI can help detect areas in the brain that have been damaged by concussion and the extent of that damage. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3995073/ One effect of concussions is damage to axons. DTI can determine where the axonal damage has occurred through abnormal levels of diffusion of water throughout the brain. https://www.mdedge.com/neurology/article/76185/traumatic-brain-injury/dti-may-detect-axonal-injury-after-sports-related The image is a simplified version of a DTI scan. The areas in red indicate where there has been damage to the axons and the areas in blue indicate where diffusion levels are higher than normal which suggests those areas are compensating for the damage. https://medicalxpress.com/news/2016-06-concussion-outcome-advanced-imaging.html
Prevention of Concussion
The detrimental effects of concussion have led to efforts to prevent concussions. One arena where many prevention efforts have been focused is on athletics. Improvements have been made to helmets to help them cushion the head from blows. Another important area has been a focus on delaying when children are allowed to start using increasingly violent maneuvers in athletics. The age when kids can start tackle football or when soccer players can head a ball has been pushed later in an effort to delay concussion injuries. Another focus has been on proper training for these maneuvers. Serious injuries often happen when a maneuver is done incorrectly and teaching kids when and how to use them correctly can help lessen injuries without changing the sport.
There is no definite cause of schizophrenia. Most studies point to issues during pregnancy including genetics, abnormal brain development, infection during pregnancy, and complications during birth. Some studies suggest head injuries, stressful life events, and social isolation. https://www.steadyhealth.com/articles/schizophrenia-development Patients with schizophrenia show delays in milestones as children which suggests that development of schizophrenia develops much earlier than the timing of the onset of schizophrenic symptoms. https://onlinelibrary.wiley.com/doi/abs/10.1111/cge.12111
Current Drug Treatments
The most commonly used treatment is antipsychotic drugs that block dopamine receptors. There are issues with these medications however, they tend to present serious adverse side effects such as lightheadedness and blurred vision. They can also cause tardive dyskinesia, which is characterized by involuntary, repetitive movements. https://www.mayoclinic.org/diseases-conditions/schizophrenia/diagnosis-treatment/drc-20354449 Lithium is also used as a treatment for schizophrenia in conjunction with other drugs but is more commonly used for the treatment of bipolar disorder. It seems to work through the inhibition of GSK. https://onlinelibrary.wiley.com/doi/abs/10.1111/cge.12111
The Wnt Pathway
https://youtu.be/NGVP4J9jpgs This video gives a great overview of how the Wnt pathway works. The Wnt pathway has been implicated in schizophrenia. The antipsychotics mentioned earlier act on dopamine. The dopamine pathway ties into Wnt signaling through GSK3 which is decreased by the decrease of activation of dopamine receptors. https://onlinelibrary.wiley.com/doi/abs/10.1111/cge.12111
Lithium seems to work in a similar fashion. Lithium competes with magnesium and inhibits GSK3. There is also some evidence that lithium destabilizes the destruction complex mentioned in the video that exists when the Wnt pathway is off. This activates the Wnt pathway and helps to regulate some of the symptoms seen in both bipolar disorder and schizophrenia. https://onlinelibrary.wiley.com/doi/abs/10.1111/cge.12111
The Role of Genetics
Schizophrenia is fairly rare in the general population, occurring in about 1% of people. However, it occurs in 10% of people who have a close family member with schizophrenia. This leads to the assumption that there are genetic factors at play. https://www.nih.gov/news-events/nih-research-matters/mutated-genes-schizophrenia-map-brain-networks Researchers have found that spontaneous mutations, that are not inherited from either parent play a role in schizophrenia development. Some of these mutations cause an increase in activity of GSK3 and a decrease in Wnt signaling. Mutations that are linked to schizophrenia all appear in the prefrontal cortex which is related to executive functioning in the brain.
Other studies have found that there are mutations in deleted genes that are passed down from parents. Genetic mutations can cause unnecessary pruning of communications in the brains of teenagers who will later experience schizophrenic symptoms. Normally pruning in the brain is a good thing and gets rid of unnecessary connections within the brain as shown in the picture above. However, this goes wrong in schizophrenia. A gene known as C4 seems to be the culprit. C4 is responsible for tagging synapses for pruning, in schizophrenia it is overactive and causes too much pruning. https://www.nih.gov/news-events/news-releases/schizophrenias-strongest-known-genetic-risk-deconstructed
Schizophrenia and Bipolar
Earlier I mentioned that GSK3 seems to be have an effect on both schizophrenia and bipolar disorder. In schizophrenia elevated GSK3 affects brain development through deficits in the corpus callosum (connections between brain hemispheres) and connections to the thalamus which acts as the relay station for brain signals. There is evidence that in adults, elevated GSK3 interferes with microtubules which allow signals to be transmitted through the brain. https://www.cell.com/trends/neurosciences/fulltext/S0166-2236(07)00035-5
Bipolar disorder also has an increase in GSK3 activity. The difference is what it does in the brain. The evidence suggests that the main action of GSK3 in bipolar disorder is apoptosis activity (cell death). This leads to smaller brain volume and the loss of neurons in areas of the brain that are related to the regulation of emotions. This relates to the extreme manic and depressive symptoms and quick switches between the two seen in bipolar disorder. https://www.sciencedirect.com/science/article/pii/S0149763407000243
Conclusion
An increase in GSK3 and decrease in Wnt signaling presents a new target for the treatment of both schizophrenia and bipolar disorder. The regulation of the Wnt pathway could allow for a treatment without the adverse effects of antipsychotic treatments. Genetic factors play a role in the development of schizophrenia that have not been fully discovered but some seem to directly affect Wnt signaling.
The current Diagnostic and Statistical Manual categorizes Autism as a spectrum. The benefit of using a spectrum model is it allows for differences in how it manifests including what symptoms exist and how severe they are. Some possible symptoms of Autism Spectrum Disorder (ASD) are social impairments, communication difficulties, repetitive movements, and obsessive interests. ASD is more common in boys and can be found in 1 out of 68 children. ASD is a disorder that is highly heritable and there are many genetic disorders that are linked to the development of ASD. There is still a lot that we do not know about ASD and no cure currently exists. https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Autism-Spectrum-Disorder-Fact-Sheet
Related Disorders
There are a number of genetic disorders that are related to ASD. One of these disorders is Fragile X Syndrome. Fragile X Syndrome occurs when there is a mutation on a gene (FMR1) that makes a protein (FMRP). This mutation means that FMRP is not formed. FMRP has a crucial role in regulating the translation of mRNA and can inhibit long term depression at the synapse. Long term depression occurs at the synapse when connections weaken and are pruned when they are no longer needed. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3722574/ The lack of FMRP can lead to an increase in immature dendritic spines which is characteristic of both Fragile X and ASD. There is significant symptom overlap between Fragile X and ASD and many people with Fragile X also have ASD. This makes Fragile X and the issues caused by a lack of FMRP a useful target to try to understand ASD. https://www.cdc.gov/ncbddd/fxs/facts.htmhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4024105
What is Happening in the ASD Brain?
Many of the genes that are involved with the development of ASD involve the glutamate pathway. The glutamate pathway is involved with the strength of synapses and when a lot of glutamate is present synapses are strengthened. https://flowpsychology.com/long-term-potentiation-definition-psychology/ The other important part of this process is that synapses that are not needed are pruned. However, in ASD this pruning does not happen. This may be due to overactive mTOR signaling. Autophagy is used to break down components of unneeded synapses. This process is inhibited by an overactivation of mTOR. The photo above shows the underdevelopment of a brain of a child with ASD and the lack of synaptic connection strength. The pruning that happens normally in childhood and adolescence is believed to allow for the rise of executive cognitive functioning, reasoning, and abstract thought. Many of these abilities are not present in people with ASD. Treatment with mTOR blockers may seem like an easy solution to rescue some of the cognitive deficits that are seen in ASD. Unfortunately, it is not that easy, mTOR signaling occurs throughout most of the body and cannot be target to only the areas that are affected by ASD. https://www.cell.com/action/showPdf?pii=S0896-6273%2814%2900651-5
Treatment Options
Further research is taking place to determine how mTOR can be targeted without causing damaging effects to other parts of the body. There are some treatments that currently exist for ASD. Early intervention treatments are helpful when a person is diagnosed with ASD as a young child. These treatments are focused on helping the child reach developmental milestones. Behavioral interventions can be used to reduce repetitive behaviors and to increase social skills. Sensory integration therapy can also be useful for people with ASD who are easily overwhelmed by sensory stimuli. Dietary interventions and supplements may also be necessary because many people with ASD experience gastrointestinal issues and others may refuse to eat certain types of food and miss out on necessary nutrients. Current treatments are focused on reducing the more severe symptoms of ASD and increasing social and life skills. https://www.cdc.gov/ncbddd/autism/treatment.html
Addiction is a psychology and physical inability to stop consuming a drug, activity or substance, despite it causing physical and psychological harm. People can be addicted to a number of different things, but I would like to focus on drug addiction. Addiction manifests itself in physical and psychological symptoms. Tolerance is related to physical addictions. Tolerance occurs when the body begins to get used to the drug of abuse and effects of the drug are not as strong as they once were. This is why drug users will say that they never reach the level of their first high again.
Psychological addiction manifests in withdrawals and cravings. Withdrawal has physical symptoms including agitation, insomnia, muscle tension, and vomiting. The underlying cause of withdrawal is psychological. Tolerance makes the body dependent on drug use to achieve normal levels of neurotransmitters. When that drug is not used, levels are much lower than they would normally be, leading to physical symptoms. Cravings are the body’s desire for the drug. This leads to desire to use the drug again and is the major culprit in relapse. https://emeraldcoastjourneypure.com/physical-vs-psychological-addiction/
Hijacking the Reward System
Drugs of addiction directly or indirectly affect levels of dopamine in the brain. The reward pathway in the brain relies on dopaminergic projections between two brain areas, known as the nucleus accumbens and the ventral tegmental area. Shown in the photo on the left. In normal circumstances this is good. The reward pathway allows us to feel good when we eat, drink, or have sex. Drugs of abuse also trigger this pathway by increasing the amount of available dopamine through inhibiting reuptake or enhancing release into the synapse. That is why drug use feels good. This is also why people who are trying to quit using drugs feel so awful during this experience because their body has started to produce less dopamine to compensate for the boost from the drug use. This means that when that boost isn’t happening things that should be naturally reinforcing aren’t. https://www.sciencedirect.com/science/article/pii/S0092867415009629
Synaptic plasticity is of crucial importance to normal brain function. Synaptic plasticity is the brain’s way of strengthening connections that are used frequently and getting rid of ones that are no longer needed, like the plot of the book you were forced to read in fifth grade. The following video does a good job of explaining what is going on in the brain during synaptic plasticity.
As mentioned earlier, drugs of abuse cause an increase of dopamine at the synapse. This excess dopamine. One of the receptors that dopamine binds to causes AMPA receptors to allow more glutamate in or can stimulate the release of more glutamate into the synapse. This means that more LTP takes place.
The graphic above gives a good representation of what happens in the brain when drug addiction occurs. Two things happen when in regards to synaptic plasticity when drug use occurs. One is that initial drug use causes a strengthening of the connection between the drug use and the reward pathway. After continued drug use, AMPA receptors are removed from the synapse. This means more drug use is needed to achieve the same amount of stimulation that exists in someone who has never used drugs. The brain knows there is a connection between the use of the drug and an increase in dopamine and glutamate levels and this can lead to drug-seeking behaviors.
A Glimmer of Hope: Addiction Treatment
Addiction changes connections in the brain. This shows why it can be so hard for people to quit. The bright side is that there are a lot of treatment options out there for people who want to quit.
Medications can be used but are typically used in conjunction with another treatment option. The medications are meant to make the transition off drugs easier. They can curb some of the cravings which make people less likely to relapse. They can also curb some of the nasty symptoms that come with withdrawal. Medications are also helpful when people have a co-occurring mental illness that the drugs were being used to manage the symptoms of.
Therapy can also be used to treat addiction and can happen in either an inpatient or outpatient setting. Therapies are meant to change thoughts about drug use and increase life skills, such as coping. Therapy can also be used to treat co-occurring mental health conditions. Therapy can be used successfully in maintaining sobriety.
Traumatic Encephalopathy (CTE)
ly rely on neurological and cognitive testing. A neurological test involves tests of vision, hearing, and balance for any deficits that may have been caused by brain trauma. Cognitive tests typically involve tests of memory and concentration that are typically impaired by a concussion. 
bly.com/
current Diagnostic and Statistical Manual categorizes Autism as a spectrum. The benefit of using a spectrum model is it allows for differences in how it manifests including what symptoms exist and how severe they are. Some possible symptoms of Autism Spectrum Disorder (ASD) are social impairments, communication difficulties, repetitive movements, and obsessive interests. ASD is more common in boys and can be found in 1 out of 68 children. ASD is a disorder that is highly heritable and there are many genetic disorders that are linked to the development of ASD. There is still a lot that we do not know about ASD and no cure currently exists. 
pathway. The glutamate pathway is involved with the strength of synapses and when a lot of glutamate is present synapses are strengthened. 
