Peer review
2
CAFFEINE
Effects of Caffeine on Autism Spectrum Disorder
15
PSY625: Biological Bases of Behavior
Instructor: Dr. Irene Nielsen
May 22, 2018
Title of Grant Proposal
Specific Aims
Autism Spectrum disorder (ASD) is a neurological disorder that effects people of all ages. Generally, this disorder will show different symptoms based on the age range of the person (Gottfried, Bambini-Junior, Francis, Riesgo, & Savino, 2015). Therefore, a close attention is paid to the age range of the groups being tested when doing a study. ASD has many different symptoms. The most common are related to language developmental impairments, social interaction inabilities, learning disabilities, anxieties, and unawareness of others’ emotions.
Caffeine plays a large role in the central nervous system. Caffeine is a drug that acts as an antagonist for the adenosine receptors (Diukova, Ware, Smith, Evans, Murphy, Rogers, & Wise, 2012). This causes interference within the vascular and neural regions. A direct impact on the frontal cortex via the use of caffeine can create an increase if focus. The frontal cortex is responsible for the higher-thinking processes, and the executive thinking processes. The use of caffeine has a sole purpose of creating an increased amount of concentration and motivation (Cappeletti, Daria, Sani, & Aromatario, 2015).
The specific aim of this study is to research the effects caffeine may have on children suffering with ASD. Caffeine in the amount of 50mg given to children is low enough to hopefully be non-addictive. Anything more than 200mg can create an addiction, seizures, dehydration, and create fatigue while affecting the heart.
Past research has determined the effects caffeine plays within the brain. It’s ability to enhance concentration and act as a stimulant can have a huge impact on a child with ASD. This impact can be strong enough to allow a better ability to treat this disorder. By comparing the role caffeine plays on children with ASD to children of normalcy the same age with the use of fMRI screenings and various surveys, the theory caffeine will help children with ASD may be determined. Thus, can offer a better option to treat.
Background
There really are no concrete research-based affiliations between caffeine and Autism Spectrum Disorder (ASD). Caffeine may help with concentration, but caffeine also has many other side effects. Just as any drug, there are side effects. Caffeine is a stimulant that will attach to the receptors of adenosine. Adenosine is a neuromodulator that can be found throughout the body. This is specifically found within the central nervous system.
Adenosine plays an important role in the alteration of many symptoms related to ASD. These may include epilepsy and sleep disorders, which are commonly found in patients with ASD. The adenosine modulator must be increased to achieve the reverse effect of seizures and sleep disorders (Masino, Svedova, Kawamura, Dimario, & Eigsti, 2011). Coupling adenosine with caffeine to alter the effects of ASD is the basis of this study.
Adenosine will build up within the central nervous system throughout the day which makes a person feel tired at the end of the day. A person with ASD may have a low level of adenosine making them sleep deprived. Patients with a high level of adenosine may feel exhausted all the time and sleep more frequently. When adenosine is paired with a methylxanthine, the metabolism and cell signaling are affected. When adenosine was paired with the G-proteins (A1, A2A, A2B, and A3 receptors), the cell signaling became more enhanced (Masino, Svedova, Kawamura, Dimario, & Eigsti, 2011). To help increase focus, the trimethylxanthine (pure alkaloid) caffeine is used to target the sub-types of adenosine. These subtypes targeted are A1R and A2R (Masino, Svedova, Kawamura, Dimario, & Eigsti, 2011). There is a limit to the amount of this pure alkaloid to prevent harmful side effects.
Caffeine is found in many of the beverages and foods that are taken in daily. Regulating the amount of caffeine can have a reverse effect of harmful side effects for a person with ASD. Although a person with ASD may be unable to focus, they are also susceptible to seizures. An increased amount of caffeine can trigger epileptic seizures (Chroœciñska-Krawczyk, Jargieo-Baszak, Waek, Tylus, & Czuczwar, 2011). Research found the normal amount of methylxanthine (caffeine) per person to be on average 200mg per day (Chroœciñska-Krawczyk, Jargieo-Baszak, Waek, Tylus, & Czuczwar, 2011). When rodents were given double that amount (400mg) the rodents became subjected to epileptic seizures (Chroœciñska-Krawczyk, Jargieo-Baszak, Waek, Tylus, & Czuczwar, 2011).
To put in theory, ASD patients suffer from a multitude of symptoms, and some of the prescriptions provided for the treatment are drugs with some harmful side effects. The levels of adenosine in a patient with ASD should be increased to allow for reverse effects of behavior defects, epileptic seizures, and sleep disorders. Caffeine paired with adenosine helps to improve cell signaling which can help improve focus and may alter sleep disorders. If caffeine is given within a safe range of ≤ 200mg daily, then there will be a decline in seizure risks, and a reverse for the better affect in behavior defects while increasing metabolism and sensory concerns.
Significance
Autism Spectrum Disorder is becoming more common. This is still a new disorder because it is many disorders combined into one disorder. The method of treatment is based on therapy combined with antipsychotic medications. These medications can have some detrimental side effects and can alter the moods of these patients. Some have been found to be like zombies or in their own world and not themselves. This proposed study will elicit the use of caffeine to patients with ASD in a safe dose range. The comparisons between the patients taking the medications with treatment, and the patients being give caffeine and treatment should give basic insight to the issue regarding the use of antipsychotic medications.
This project will enhance the knowledge of the disorder further to help scientist develop a better strategy to helping a person with ASD to cope with their world in a healthy manner. Teachers will gain from this study because they will be better equipped with handling their students that suffer with ASD. Doctors will not have to keep changing the medications for the patients that are having unwanted side effects.
Teachers and parents will be able to work easier with their children who suffer with this disorder because they will not be dealing with the side effects of the antipsychotic medications and will be more able to provide a healthy therapy for their patients. If the proposed aims of this study are achieved, the entire outlook of autism spectrum disorder can be looked at from a different angle. The basic treatment can be based on the use of caffeine with a combination of a specific diet and therapy.
What does caffeine do to a child’s brain between the ages of 8 and 13? What does caffeine do to a child’s brain that has autism spectrum disorder? These are the questions that need to be answered from this study. To hypothesize, if caffeine is given to a child with ASD, the prefrontal cortex will be affected to enhance the higher executive thinking processes. To conduct this study the variable needed are based on children between the ages of 8 and 13 with ASD taking and not taking medicine. The control group are the children that do not have any diagnosis or symptoms of ASD and are not on any medication.
Patients with ASD have trouble being social. Their language is interrupted, their level of anxiety is increased. Based on a neurological stand point, the entire brain is affected by ASD. The specific area that is affected by this disorder and interferes with the social ability is known as the superior temporal sulcus, also known as the social river (Deweerdt, 2016). This river is what is responsible for the social phenomena. The ability to carry on a conversation or even decode body language are within this region. Based on fMRI research, there is still much more to be studied regarding the responsibilities of the superior temporal sulcus, and the effects it has in patients with ASD (Deweerdt, 2016).
Proposed Study
Participants:
Being that Autism Spectrum Disorder is found common in children at young ages, the study will consist of children between the age ranges of 8 to 13 years. There will consist an equal amount of each sex. There will be 15 girls and 15 boys in this study to equal a total of 30 participants. The participants will be divided up into three groups. The first group will consist of 5 girls and five boys with diagnosed ASD that are taking medication. In the second group, there will also be 5 girls and 5 boys with diagnosed ASD without taking medication. Lastly, the control group will contain 5 girls and 5 boys as well, but these participants will have no history of ASD symptoms, no diagnosis, and no history of epilepsy or seizures.
As a precaution, this study includes children that are taking medication. These children will need approval from their doctors as well as their parents to participate. Each participant will undergo an fMRI test. This test is radioactive; therefore, this too needs approval. Any one getting or giving this exam will need safety gear to protect them from radiation exposure. Any pregnancies shall be reported, any metal within the body shall also be reported prior to examination. Any allergies shall be reported in case of medical attention. Allergies to any dyes (such as iodine), latex, and caffeine if such exists.
Procedures:
After all required consents have been provided, the participants will be divided up into their groups. These participants will take a short survey to show the extent of their symptoms before any caffeine is given. The participants will be evaluated by a professional in ASD (psychologist) that will provide a thorough description of each participants mental state prior to administration of caffeine.
The amount of caffeine given to a child is important. A child that starts taking caffeine at an early age can become addicted to caffeine very quickly. The addiction comes from caffeine being a drug. As like any drug, a person has a high risk of having side effects. This drug affects the central nervous system in many ways. The main use of caffeine is the stimulant effect it has on the central nervous system.
If caffeine is given in an excess of over 200mg per day, there is a high risk of a child not only becoming addicted to the drug, but sudden seizures can occur. ASD patients have a variety of symptoms, and one of those symptoms is seizures. Caffeine given in a small dose can help decrease the episodes of seizures. The amount of caffeine in an 8oz cup of coffee is averaged at 100mg. This study will administer half that amount. Using half a cup of black coffee, the amount of caffeine given per participant will be 50mg. This will be done consecutively for 14 days. After the 14 days, the participants will be monitored for 7 days of any withdrawal symptoms that may have been caused from the caffeine. This will show how addicting the given dosage may be for a child between the ages of 8 and 13.
While the participants are using the drug caffeine, they will be evaluated by the same professional in ASD to distinguish any differences no matter how slight. The participants will also be examined through an fMRI test. Caffeine has been noted to show a bold signal in the prefrontal cortex region of the brain (Diukova, Ware, Smith, Evans, Murphy, Rogers & Wise, 2012). The prefrontal cortex region of the brain is responsible for any higher-level thinking skills. The problem with patients with ASD, their thinking skills and attention can be affected, or disrupted, because of the symptoms caused by the disorder.
Hypotheses & Analysis:
If a small dose of caffeine is given to a child between the ages of 8 and 13 with ASD, the child will have enhanced higher thinking skills and a decreased chance of seizures. To prove this hypothesis, the data needs to be collected and administered correctly. Based on the survey, the evaluation, and the fMRI, the data will be collected and examined thoroughly. The data will be compared based on the before and the after effects of caffeine. The data will also be compared based on gender, and the different groups that either take medication or not and the control group that does not have ASD getting caffeine.
The effects of caffeine and the effects of the diagnosed antipsychotic drug utilized for the treatment of ASD will be compared. This will show which drug is a healthier choice to use if a drug is absolutely needed for the treatment of ASD. If the dosage of caffeine used in this study is low enough to have no effect on addiction, but can improve higher thinking abilities, then the drug can be used temporarily to get a child started on their therapeutic treatment without drugs in the future.
Budget Justification
This research study requires some expenses. The total expense needed is $60,000.00. This study requires fees for needed personnel such as: Instructor T.J. Bailey which shall receive $8,000.00 which is 10% of the effort of the annual amount earned of $80,000.00. A research assistant is needed for the help with the research who shall receive 50% for six months totaling $12,500.00. A psychologist is needed for evaluation of all participants and will receive 10% of salary ($80,000) which totals to $8,000.
The participants shall receive $100.00 for participation fee for each participant. There are 30 participants in all. This totals out to $3,000 total for all participants stipend money. The stipends for the participants are to act as an incentive as well as a contract binder. Being the participants are below age, the money will go to the parents of the participants because the allowance to do the study is coming from the parents.
An fMRI test is required for this study to measure the difference in brain activity before and after caffeine is administered. This machine costs a total of $20,000.00. This machine is known as the Toshiba Visart 1.5T MRI System. This is a state of the art system that can show all parts of the brain that can be affected by any substance.
There is a request for a small travel fee for the PI to facilitate the PI to arrive at meetings when needed. There is also a request for help with some much-needed supplies. These supplies are needed for the research and data collection for this study. The supplies include a new Apple computer system with three 1TB hard drives to help keep track of participants data. Printers with fax and copy capable are also needed. The supplies total to $5,000.00 with all office supplies and data collecting supplies included. Lastly, there is a total of $2,000.00 needed for indirect costs that may arise. Below are the figures needed for this study.
See Appendix A: Budget for detailed budget figures.
References
Cappelletti, S., Daria, P., Sani, G., & Aromatario, M. (2015). Caffeine: Cognitive and Physical Performance Enhancer or Psychoactive Drug? Current Neuropharmacology, 13(1), 71–88. http://doi.org/10.2174/1570159X13666141210215655
Cornacchio, D., Crum, K. I., Coxe, S., Pincus, D. B., & Comer, J. S. (2016). Irritability and Anxiety Severity Among Youth with Anxiety. Journal of the American Academy of Child and Adolescent Psychiatry, 55(1), 54–61. http://doi.org/10.1016/j.jaac.2015.10.007
Diukova, A., Ware, J., Smith, J. E., Evans, C. J., Murphy, K., Rogers, P. J., & Wise, R. G. (2012). Separating neural and vascular effects of caffeine using simultaneous EEG–FMRI: Differential effects of caffeine on cognitive and sensorimotor brain responses. Neuroimage, 62(1), 239–249. http://doi.org/10.1016/j.neuroimage.2012.04.041
Dombrowski, S. C. (2013). Autism spectrum disorder. Salem Press Encyclopedia of Health,
Gottfried, C., Bambini-Junior, V., Francis, F., Riesgo, R., & Savino, W. (2015). The Impact of Neuroimmune Alterations in Autism Spectrum Disorder. Frontiers in Psychiatry, 6, 121. http://doi.org/10.3389/fpsyt.2015.00121
Magdalena Chroœciñska-Krawczyk, Magorzata Jargieo-Baszak, Magdalena Waek, Boydar Tylus, & Stanisaw J. Czuczwar. (2011). Caffeine and the Anticonvulsant Potency of Antiepileptic Drugs: Experimental and Clinical Data. Institute of Pharmacology Polish Academy of Sciences. Retrieved from: http://www.ifpan.krakow.pl/pjp/pdf/2011/1_12.pdf
Sarah Deweerdt. (2016). Brain’s Social ‘River’ Carries Clues about Autism. Retrieved from: https://www.spectrumnews.org/news/brains-social-river-carries-clues-about-autism/
Sherkow, S. P., & Harrison, A. M. M. (2013). Autism spectrum disorder: perspectives from psychoanalysis and neuroscience. Retrieved from https://ebookcentral-proquest-com.proxy-library.ashford.edu
Susan A. Masino, Julia Svedova, Masahito Kawamura, Jr., Francis D. DiMario, Jr., & Inge-Marie Eigsti. (2011). Adenosine and Autism - Recent Research and a New Perspective. Trinity College Trinity College Digital Repository. Retrieved from: https://pdfs.semanticscholar.org/2e63/2987b857c590b834346ec59f07d3615d73f2.pdf
Van der Heijden, K. B., Stoffelsen, R. J., Popma, A., & Swaab, H. (2018). Sleep, chronotype, and sleep hygiene in children with attention-deficit/hyperactivity disorder, autism spectrum disorder, and controls. European Child & Adolescent Psychiatry, 27(1), 99–111. http://doi.org/10.1007/s00787-017-1025-8
Verly, M., Verhoeven, J., Zink, I., Mantini, D., Peeters, R., Deprez, S., … Sunaert, S. (2014). Altered functional connectivity of the language network in ASD: Role of classical language areas and cerebellum. Neuroimage: Clinical, 4, 374–382. http://doi.org/10.1016/j.nicl.2014.01.008
Appendix A: Budget
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SUMMARY PROPOSAL BUDGET
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FOR INSTITUTION USE ONLY |
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ORGANIZATION Spectrum Awareness |
PROPOSAL NO. |
DURATION (MONTHS) |
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PRINCIPAL INVESTIGATOR (PI)/PROJECT DIRECTOR Instructor, PhD |
AWARD NO. |
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A. PERSONNEL: PI/PD, Co-PIs, Faculty, Graduate Assistants, etc. |
Funds |
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List each separately with name and title. |
Requested By |
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Proposer |
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1. Instructor T.J. Bailey, PhD ($80,000/year) - 10% effort for 12 months |
$8,000 |
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2. Research Assistant (RA) - 50% effort for 6 months |
$12,500 |
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3. Psychologist |
$ 8,000 |
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TOTAL SALARIES |
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$20,500 |
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B. EQUIPMENT (LIST ITEM AND DOLLAR AMOUNT FOR EACH ITEM EXCEEDING $5,000.) |
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Toshiba Visart 1.5T MRI System |
$20,000 |
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TOTAL EQUIPMENT |
$20,000 |
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C. TRAVEL |
1. DOMESTIC - PI attendance at national meeting |
$1,500 |
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TOTALTRAVEL |
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$1,500 |
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D. PARTICIPANT SUPPORT |
$3,000 |
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1. STIPENDS |
$ |
100 |
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2. TRAVEL |
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3. SUBSISTENCE |
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4. OTHER |
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TOTAL NUMBER OF PARTICIPANTS (30) TOTAL PARTICIPANT COSTS |
$3,000 |
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E. OTHER DIRECT COSTS |
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1. MATERIALS AND SUPPLIES- Computer for patient training, data collection and analysis |
$4,000 |
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2. OTHER Office supplies |
$1,000 |
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3. OTHER |
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TOTAL OTHER DIRECT COSTS |
$5,000 |
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F. TOTAL DIRECT COSTS (A THROUGH E) |
$58,000 |
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G. TOTAL INDIRECT COSTS (F&A) (Rate = 37.5%) |
$2,000 |
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H. TOTAL DIRECT AND INDIRECT COSTS (F + G) |
$60,000 |
PSY 625: Biological Bases of Behavior Ashford University