Uncovering rheumatoid arthritis mechanisms through genome wide association studies (GWAS)

The completion of the Human Genome Project, sequencing of DNA and gene mapping, in 2003 laid the foundation for in-depth gene specific disease research. Most recently, genome wide association studies (GWAS) are being completed to uncover variations within individual genes that may contribute to numerous diseases. GWAS scan markers through genomes of many individuals to discover genetic variations that may be associated with a particular disease (NIH 2013). One disease that has been widely studied through GWAS analysis is rheumatoid arthritis (RA), an autoimmune disease that causes severe joint inflammation, deformity, and chronic pain.

My mother and sister both suffer from rheumatoid arthritis. It is likely that I will also one day suffer from this autoimmune disease, as there are genetic origins. This made me very curious to discover what these underlying genetic mechanisms are. One recent genome wide association study meta-analysis, or compilation of current research, was completed to examine functional mechanisms that may underlie associations for RA. In this study, researchers were able to examine publicly available data to discover 8 single nucleotide variations on 5 genes that are related to immune response through function (Deng 2013). The ability to survey publicly available data to uncover the functional mechanisms and locations of such disease associations can be a powerful tool to allow many more people to access and analyze this GWAS data. Additionally, being able to narrow down the specific locus, or location on a chromosome, where a mutation is occurring will allow for better screening and potentially future treatment/prevention of some diseases.

Another GWAS analysis used data regarding a specific locus, CCR6, related to rheumatoid arthritis in Japan. The researchers were able to use this data to create a study specifically regarding this gene locus and screen study subjects for a specific antibody and DNA sequence variation in CCR6 locus to determine risk for development of rheumatoid arthritis. The study found that a variation in the CCR6 gene locus was a risk factor for developing RA in females but conversely was a protective factor against disease development in males (Teng 2012). The gender differences observed are not necessarily triggered by one particular factor, but it was suggested that it could possibly be related to individual environment. As environmental influence, nature vs. nurture, is discussed in numerous fields from psychology to biochemistry, these associations have broad impacts.

Genome wide association studies are the next step in identifying specific individual genetic variations and disease implications. With all the information that is available through the Internet, it can become concerning to think about all of the implications of a single change within your entire genome causing a disease. One thing to remember is that although we cannot consciously control if our DNA is replicating correctly or not, we can control many aspects of our health. Decreasing stress, eating healthily, and exercising regularly are all things each person can control and will not only make you feel better, but can also potentially prevent negative modifications within your genome.

Deng F, Lei S, Zhu H, Zhang Y, Zhang Z. 2013. Integrative analyses for functional mechanisms underlying associations for rheumatoid arthritis. J Rheumatol. 40;1063-1068.

National Institutes of Health (NIH). 2013. Genome Wide Association Studies. Available From: http://www.genome.gov/20019523

Teng E, Leong K, Li H, Thong B, Koh E, Loi P, Zhao Y, Tan E. 2012. Analysis of a genome-wide association study-linked locus (CCR6) in Asian rheumatoid arthritis. DNA and Cell Biology. 32(4):607-610. 

Anesthesia Awareness

We've all heard the terrifying stories about people who claim to be awake during surgery, paralyzed, feeling the pain and not being able to move or indicate their distress. This has been the plot to a Hollywood film a few years ago, but I wonder, is anesthesia awareness real?

A few searches online led me to the short answer: yes, anesthesia awareness is real.


A study from the University of Iowa's department of anesthesia found that some patients reported anesthesia awareness. Patients would mostly recall hearing sounds, and few patients actually reported this awareness during the stay in the operating room. Surprisingly though, most of the patients would report awareness much later, maybe as memory came back to them. Further, a study out of the University of Washington reported that some patients recalled pain! Terrifying. Both studies make note of the psychological trauma inflicted upon these patients. Among the more severe were post traumatic stress disorder and fears of future anesthesia.



These findings beg the question: how can we avoid this phenomenon? Surely anesthesiologists are highly trained individuals who know what they're doing. They artfully poison us, highlighting the delicate line between drug and poison – too much, we die, too little, we feel. They can't just crank up the knobs on their machine and deliver more Substance X to us, and there's no way for someone experiencing anesthesia awareness to ask for more Substance X. Thankfully, this experience happens in much less than %1 of all surgeries, which still doesn't seem to be a low enough number given the nature of the phenomenon. But either way, maybe it would be a better practice to be more heavy handed with the anesthesia? This is a hard thought experiment in my mind. There is so much variation among humans – height, weight, tolerance, medication use- that I find it miraculous we even have standards to calculate proper dosages for anesthesia. All I know is that if I had the choice between risking feeling awake during a major operation or having a groggy, rough awakening and subsequent “hangover” from being well put-under, it would be an easy choice for me to make.



References:

Bruchas R, Kent C, Wilson H, Domino K. Anesthesia Awareness: Narrative Review of Psychological Sequelae, Treatment, and Incidence. Journal of Clinical Psychology in Medical Settings. 18(3): 257-267. 2011

Ghoneim M, Block R, Haffarnan M, Mathews M. Awareness during anesthesia: risk factors, causes and sequelae: a review of reported cases in the literature. Anesth Analg. 108(2):527-35. 2009. 

"I Think I Can, I Think I Can"... Why we can all learn a little something from Thomas the Train.

      You are 25.2 miles into a 26.2 mile run, only after completing a 112 mile bike ride and a 2.4 mile swim. It is pitch black, you are exhausted and reach in your pocket to find that you ate your last GU over a mile ago, but you are only a mile away from finishing your first ever Ironman Triathlon. The stress that your body is going through is monumental: you begin thinking things such as "I could have sworn I felt my feet just an hour ago" or "Holy Crap is that Brad Pitt riding on a glow in the dark unicorn?!?!". Yes you are in very bad condition and the stress you are under is reaping havoc on your body, but just as you begin to ask Pitt to catch a ride back your mind begins to kick in a training tool that you may not even know you had developed - you begin talking to yourself in a good way. Maybe it appears to you that the unicorn is doing all of the talking, but nonetheless you are telling yourself "It is only one more mile, you got this, you are so strong and fit and brave and couragous, and you don't even like riding unicorns anyways: they are uncomfortable and smelly". This form of talk continues, and suddenly you have crossed the finish line felling much better than you might have thought!
       It is very common in the endurance athlete world that self affirmations are a very effective tool however, you do not need to be enduring through a triathlon to experience the positive effects of self affirmations during chronic stress. Recent research shows that positive affirmations physiologically buffer the responses of chronic stress and every day stress. In one study participants at a college age level had their urine samples measured for epinephrine and norepinephrine throughout the course of studying for their most stressful final examination. There were two groups the affirmation and no affirmation group. Each participants urine was measured 14 days prior to the exam as a baseline. Throughout the course of the two weeks the affirmation group had to write two essays about their values and use encouraging thoughts. Finally a urine same was taken 15 hours before the exam (the peak of stress prior to exam). Results of this study found that students in the affirmation condition did not have significantly different levels of norepinephrine and epinephrine from their baseline, while the other students all had levels significantly higher. Students in the self affirmation group also indicated that they felt much better going into the test and had felt they would be able to mentally cope better even if they thought the exam didn't go as well as planned. Other studies such as this have found that self affirmations can improve academic performance during chronic stress, decrease negative effects of chronic stress as well as even assist in weight loss/ exercise programs.
    So whether you are about to complete a triathlon, trying to lose weight, or simply just needing to get through this next examination...it wouldn't be such a bad idea to find the Thomas the Train within you and give yourself some positive thought!

references
Sherman DK, Bunyan DP, Creswell JD, Jaremka LM (2009) Psychological vulnerability and stress: The effects of self-affirmation on sympathetic nervous system responses to naturalistic stressors. Health Psychology 28: 554–562. [PubMed]
 Sherman DK, Cohen GL (2006) The psychology of self-defense: Self-affirmation theory. In: Zanna MP, editor. Advances in Experimental Social Psychology. San Diego, CA: Academic Press, Vol. 38: 183–242.
Creswell JD, Dutcher JM, Klein WM, Harris PR, Levine JM. Self Affirmation improves problem solving under stress. Journal of psychology. 2013. doi: 10.1371/journal.pone.0062593. Print 2013.

My Life: With Grave’s Disease

Before I begin talking to you about my experience with Grave’s Disease, I would like to give you some general background information. Grave’s Disease is an autoimmune disorder that most commonly results in the overproduction of thyroid hormones thyroxine (T4) and triiodothyronine (T3). The clinical term that is associated with overproduction of thyroid hormones is Hyperthyroidism. The thyroid gland is an important organ in secreting hormones responsible for the body’s metabolism. Regulating metabolism is critical for maintaining constant conditions within our bodies that include: controlling mood, weight, mental and physical energy. The maintenance of the bodies constant conditions is known as Homeostasis. When you have over stimulation of these metabolic processes (leads to homeostasis not being maintained), symptoms like: anxiety, fatigue, insomnia, eye problems, heat intolerance, irregular menstrual cycles, shortness of breath, tremors, irregular heartbeat, and weight loss often occur. I happened to have experienced all of these symptoms.

The event that started my investigation into finding out what was going on happened in 2007 (16 years old) when I had my first panic attack. I remember feeling like I could not breathe that whole day. It was not until that night when my oldest sister checked my temperature and I had a fever of 104°, minutes after I was hyperventilating and quickly on my way to passing out. Finally, when the fire department arrived after my sisters horrified call, they gave me oxygen and I was able to break my fever and return to my normal breathing. However, this was just one of the many times this would occur.

Two years later in 2009 I was officially diagnosed with Grave’s Disease. It was winter break and I had just finished my first semester of college. I thought I was getting sick, because I had just went through my first finals week, which we all know exams can be stressful (stress over long periods of time can cause illness among other things). Therefore I thought these symptoms were relatively normal, I mean it was my freshman year of college after all! Unfortunately I got so sick (only weighed 90-92 lbs) that my parents had to take me to the hospital, which ended up being on Christmas Eve. The best part was that I was able to see an Endocrinologist who took radioactive imaging of my thyroid with iodine131 along with what seemed like a million blood tests. By the end of the day he confirmed that my thyroid was not malignant and that I indeed had Grave’s disease which caused me to have a hyperactive thyroid. (MERRY CHRISTMAS to me!!)

Part of my reaction was a sigh of relief to know after all this time what was going on. After finding out what Grave's Disease was, it all made sense why I felt the way I did. The doctor gave me three choices on how to treat my thyroid problem, first with radio active iodine therapy, second with a thyroidectomy and lastly with anti-thyroid medications. I choose to start taking anti-thyroid medications (Methimazole generic for Tapazole) as my form of treatment, because it was the least permanent. I have taken this medication everyday for the last four years, up until two months ago when I visited the lovely endocrinologist and luckily for me I am now in "remission". Although til this day I still have to get my blood (TSH levels) tested and monitored, it is better to be on the safe side.

Just like with anything in life, I have good days and I have bad days. I am thankful to be in remission, but I do not plan on my thyroid behaving as it should for long. For that I worry about the time when I decide to make a family. I have seen first hand, where a close family friend struggled to get pregnant with Grave's Disease. I just hope when I am ready, my pregnancy will be a smooth and healthy process.

If you take anything away from this entry, know that I would not change this experience. Not only has it pushed me to be a stronger person, it has boosted my interest in the medical field that much more!

References:

http://thyroid.org/wp-content/uploads/patients/brochures/Graves_brochure.pdf

http://www.nlm.nih.gov/medlineplus/ency/article/000358.htm

Proof that even too much ACUTE stress can be chronically harmful

We all know that it is important to get a good dose of exercise in on a frequent basis in order to live a long, happy life. But how much is too much? Regis’ very own Eric Robertson, from the PT department, has provided some crucial, and now widely circulated, information about a recent, popular form of exercise, CrossFit. Just hearing “CrossFit” before ever reading this article made me shudder, because, having tried a few of the workouts myself in the past, I know how hard CrossFit junkies work in the gym. Now, though, Robertson has opened my eyes to a whole new reason to be weary of these exercises.

Physical exercise activates the sympathetic (“fight or flight”) nervous system. When the sympathetic nervous system is activated, heart rate and respiratory rate increase, blood flow is directed primarily to skeletal muscle, energy is mobilized, pupils dilate, and the list goes on. Basically, a hoard of changes occurs throughout the various systems in the body. All this is in an effort to maintain homeostasis, which is a dynamic state of balance in which our body functions optimally. This sympathetic response to stress evolved so that animals could respond to acute (a.k.a. intense, sudden, and short-lived) stressors. Unfortunately, humans, apart from other species, have a tendency to experience chronic psychological stress; we can remain in a stressed state for days, months, even years at a time. Remaining in a chronic stressed state can be deleterious, causing heart problems, depression, sleep disturbance, and more. However, Robertson’s story is one that maintains that even too much ACUTE stress can be harmful.

Robertson’s colleague pushed her body too far during one workout; she was not working for days or weeks on end. CrossFit workouts being designed the way they are, her bout of exercise probably hadn’t lasted much longer than half an hour, and yet, she is still feeling the detrimental effects of it to this day. Rhabdomyolysis, according to Robertson, may or may not get better with treatment. So, just like a person undergoing copious amounts of psychological stress may see themselves chronically affected by something like a stroke, so may a CrossFit athlete experience lasting effects just from one workout where they pushed their muscles too far. Overall, it is well understood that, in the right amount, stress can help us, but this is further proof that too much stress, whether ongoing and psychological or brief and physical, is not a good thing.

Source: http://www.huffingtonpost.com/eric-robertson/crossfit-rhabdomyolysis_b_3977598.html

Vodka Redbull: Not as great as it may seem

Many have had those days, following a stressful week of exams, where they are exhausted yet still want to go out and have an alcoholic beverage. Some may think mixing alcohol with caffeine or energy drinks will promote alertness and stamina when drinking, but research suggests otherwise. It seems to be a common misconception that alcohol and caffeine will prevent or lessen the negative effects of alcohol consumption.

In general, drugs and their rewarding symptoms work through activation of the median forebrain bundle, which includes the nucleus accumbens (NA) and the ventral tegmental area (VTA). This is called the reward pathway. Alcohol works through the activation of GABA (an inhibitory neurotransmitter) to further decrease neuron activity, thus resulting in decreased reaction times.  Alcohol also weakens glutamate’s stimulatory effects in the NA and VTA (2). Because of its effects, alcohol is called a depressant (depresses the nervous system). Caffeine is a stimulant that works in the reward pathway by blocking an inhibitory neurotransmitter called adenosine. By blocking this inhibitory neurotransmitter, caffeine allows for more neuron stimulation (1). Knowing this, it seems that mixing a depressant with a stimulant will balance out, right? Wrong, research suggests that consuming alcohol with caffeine or energy drinks is not any better than alcohol without caffeine, when it comes to driving or attention/reaction time performance.

            In comparing the effects of alcohol without caffeine and caffeinated alcoholic beverages between participants on simulated driving and attention/reaction times, one study found there was no difference in reaction times, attention and driving between the groups (Howland et al. 2010).  Furthermore, people’s expectations that caffeine has reversal effects have been shown to result in further impairment than in people who did not expect caffeine to counteract alcohol (Fillmore, Roach, and Rice 2002). With this said, it is evident that the “beneficial” effects of drinking alcohol with caffeine can actually lead to further impairment if one expects the caffeine to counteract the alcohol.  Though caffeine may make one “feel” more alert and less impaired it has not been proven to reverse the depressant effects of alcohol.  

[1]  http://ibgwww.colorado.edu/cadd/a_drug/essays/essay4.htm

[2] http://thebrain.mcgill.ca/flash/i/i_03/i_03_m/i_03_m_par/i_03_m_par_alcool.html

Fillmore MT, Roach EL, Rice JT. 2002. Does Caffeine Counteract Alcohol-Induced Impairment? The Ironic Effects of Expectancy. Journal of Studies on Alcohol. 63(6):745-754

Howland J, Rohsenow DJ, Arnedt TJ, Bliss CA, Hunt SK, Vehige Calise T, Heeren T, Winter M, Littlefield C, Gottlieb DJ. 2010. The acute effects of caffeinated versus non-caffeinated alcoholic beverage on driving performance and attention/reaction time. Addiction. 106: 335–3.

Facing the Facts of Facebook Fame and Addiction.

     Chances are that at least 95% of the people about to read this blog have a Facebook. Most of us say that we have a Facebook and use it for different reasons: the pictures, staying connected, reading "silly" comments posted by people, or posting about your life. Regardless of your reason or excuse, you still have a Facebook and you still probably use it at least once a day. But why? What is it about Facebook or "social networking" that will drive us to mind numbingly sift through pictures or posts for what seems to be hours on end? New studies show that you are not to blame per say but the biology of your nucleus accumbens sure is!
      The Nucleus accumbens is an area of the brain that is responsible for many things including reward, pleasure, reinforcement learning, addiction, and reputation perception. That definition in and of itself should make it clear why the accumbens is deserving of blame. But a recent study in August of 2013 completed by Meshi, D., Morawetz, C. , Heekeren, R., tested nucleus accumbens activation and Facebook usage. In this study experimenters monitored the level of activation in the nucleus accumbens when a person received positive feedback about themselves and other individuals in the form of a video. They found that the amount of activation in the Nucleus accumbens was highest when the person received positive feedback about themselves. Furthermore, the group of individuals who used Facebook most had the highest degree of activation. This essentially indicates that reputation upkeep or positive feedback is a prime driver in the use of Facebook. So in the end the 95% of users can say that pictures, and "staying connected" are the only reason why you spend hours on Facebook instead of studying for Pysiology, but for some of us I think our nucleus accumbens would beg to differ!

References

 Meshi, D., Morawetz, C. , Heekeren, R. Nucleus accumbens response to gains in reputation for the self relative to gains for others predicts social media use. Journals of Frontiers in Neuroscience. 2013 Aug 29;7:439. doi: 10.3389/fnhum.2013.00439.

http://www.nbcnews.com/science/addicted-facebook-fame-blame-your-brains-nucleus-accumbens-8C11036930 

Is there an out for prisoners?: Examining the stress of parolees

You’re kicked out of a place that provided free shelter, food, library, and prescription medication if needed. No transportation, no job, no money, two-week temporary housing vouchers, paying for mandatory drug tests and some food stamps. Is this a stressful situation? Yes. As we have learned about in class, chronic stress can only cause elevated risks of stress-related diseases such as heart disease. According to the Denver Post article, this is a situation that many people face after being released from jail. This type of situation is not solved within two hours so it would be chronic stress that parolees experience. Not only would their glucocorticoid levels be extremely high from these stressful situations but they are also receiving many more stimulants than they are used to receiving from within the prison walls. As the case for inmates that have served several years, their synapses have changed or learned responses for a different set of stimulants as they habituated themselves within the prison. Along with stressors mentioned above, they are receiving many stimulants from the outside world that they have been shielded from for many years. Being able to interpret these stimulants as stressful or non-stressful can be another burden to these former inmates.

11% of parolees end up back in prison because of, as the article alludes to, the difficulties these parolees face in meeting all of their requirements. A former inmate and parolee mentioned that he would have thought he would be better off in prison. One of these factors is the level of stress they receive and the inability to handle stressful situations. This leads to the tax payers money being spent for their rent and food which they could not provide for themselves outside because it may have been too stressful. The article later describes the fact that providing Cognitive Behavior Therapy for newly released offenders and parolees in how to deal with stress and the outside environment could help parolees deal with their situation. There is therapy for those who are mentally ill, but what about those who are not mentally ill but simply need to learn how to deal with stressors in their lives outside of prison. Giving people the tools to deal with stressful situations such as parolees may give them the ability to make their lives better and not feel that their only option is to return to the four walls they are used to, prison.

Reference: 

http://www.denverpost.com/parole/ci_24157488/colorado-parolees-many-life-outside-harder-than-prison

Awesome Animals: Human-Animal Interaction and Homeostatic Balance

            Many of us have heard about Animal-Assisted Therapy (AAT). In fact, Regis’s Active Minds brings in therapy dogs during finals weeks specifically to provide students with AAT. This is because animals have been shown to relieve stress in a variety of settings—they relieve stress in patients just prior to receiving ECT (Barker, 2003), and they relieve stress in survivors of sexual assault suffering from PTSD (Lefkowitz, Paharia, Prout, Debiak, & Bleiberg, 2005). In less extreme circumstances, and directly related to the Active Minds activity, Human-Animal Interaction (HAI) relieves stress in college freshman who are leaving home for the first time (Adamle and Riley, 2010), stress brought on by the mental stressor of mental math (Allen, Shykoff, & Izzo, 2001), and even state anxiety associated with the presence of a tarantula (Shiloh, Sorek, & Terkel, 2003). All of these studies were experimental, introducing animals to participants upon arrival to a lab study or monitoring participants after providing them with a pet dog or cat. And together, these studies found decreases in stress using both anxiety inventories and blood pressure.

            As implied above, animals decrease blood pressure. Not only do they decrease blood pressure, but they also significantly and positively impact human health. Along the same lines as decreasing blood pressure, studies show that the risk factor for cardiovascular disease is lower for pet owners than for non-pet owners. Similarly, elderly participants who had frequent HAI had lower levels of serum triglycerides (Wells, 2009). Additionally, in dog and cat owners HAI results in reductions in the frequency of minor physical ailments such as headaches, colds, and dizziness (Wells, 2009).

            The physical effects of animals are easy to explain. HAI decreases stress—disturbances in homeostatic balance—due to psychological factors (such as mental math). These decreases in stress can be directly linked to reductions in the sympathetic nervous system response, with corresponding decreases heart rate and blood pressure. In pet owners, these reductions can aid long-term health. In these pet owners, chronically high heart rate and blood pressure no longer strains the hearts, and this removed strain lowers risk for cardiovascular disease. Similarly, decreasing the sympathetic nervous system response allows the parasympathetic nervous system to function properly. This then aids the immune system, thereby reducing frequency of minor physical ailments associated with minor illnesses, such as headaches and colds. Thus, essentially, animals positively impact human health by decreasing stress to allow your body to return to that homeostatic balance that was knocked out of balance by the stressors.

            The psychological effects of animals are not quite as easy to explain. We know that petting a real animal leads to increased levels of several neurochemicals, including oxytocin, beta-endorphin, prolactin, and dopamine, as well as decreased cortisol levels (Odendaal, 2000). These data support the idea that HAI decreases the stress response. We just don’t really know how that happens. We do know that tactile stimulation is important in the stress-relieving effects, as the simple act of petting animals can lead to decreased heart rate and blood pressure (Vormbrock & Grossberg, 1988). However, we also know that the petting action is not enough to relieve stress, as petting a stuffed animal does not decrease stress (Shiloh, Sorek, & Terkel, 2003). Thus, while we know that HAI decreases the stress response to improve human health, we don’t know the mechanisms by which animals elicit this response.

            There are some limits to these beneficial effects of HAI. For example, if someone with an animal phobia interacts with an animal, the effects on stress will be counter-productive. However, for people who do like animals, spending an extra few minutes petting your dog—or even walking a dog at a shelter—can decrease your stress levels to improve your health.

           

References

Adamle, K. N., & Riley, T. A. (2010). Evaluating college student interest in pet therapy. Journal of American College Health, 57, 545-548. doi: 10.3200/JACH.57.5.545-548

Allen, K., Shykoff, B. E., & Izzo Jr., J. L. (2001). Pet ownership, but Not ACE inhibitor therapy, blunts home blood pressure responses to mental stress. Hypertension: Journal of the American Heart Association, 38, 815-820. Retrieved from http://hyper.ahajournals.org/content/38/4/815.full.pdf+html

Barker, S. B., Pandurangi, A. K., & Best, A. M. (2003). Effects of animal-assisted therapy on patients’ anxiety, fear, and depression before ECT. The Journal of ECT, 19, 38-44. Retrieved from http://ovidsp.tx.ovid.com.dml.regis.edu/sp-3.6.0b/ovidweb.cgi?WebLinkFrameset=1&S=HGPDFPGEEMDDALMHNCPKBFDCODGKAA00&returnUrl=ovidweb.cgi%3f%26Full%2bText%3dL%257cS.sh.18.19%257c0%257c00124509-200303000-00008%26S%3dHGPDFPGEEMDDALMHNCPKBFDCODGKAA00&directlink=http%3a%2f%2fgraphics.tx.ovid.com%2fovftpdfs%2fFPDDNCDCBFMHEM00%2ffs041%2fovft%2flive%2fgv012%2f00124509%2f00124509-200303000-00008.pdf&filename=Effects+of+Animal-Assisted+Therapy+on+Patients%27+Anxiety%2c+Fear%2c+and+Depression+Before+ECT.&pdf_key=FPDDNCDCBFMHEM00&pdf_index=/fs041/ovft/live/gv012/00124509/00124509-200303000-00008

Lefkowitz, C., Paharia, I., Prout, M., Debiak, D., & Bleiberg, J. (2005). Animal-assisted prolonged exposure: A treatment for survivors of sexual assault suffering posttraumatic stress disorder. Society & Animals, 13, 275. doi: 10.1163/156853005774653654

Odendaal, J. S. (2000). Animal-assisted therapy — magic or medicine?. Journal of

Psychosomatic Research, 49, 275-280. doi: 10.1016/S0022-3999(00)00183-5

Shiloh, S., Sorek, G., & Terkel, J. (2003). Reduction of state anxiety by petting animals in a controlled laboratory experiment. Anxiety, Stress & Coping: An International Journal, 16, 387-395. doi: 10.1080/1061580031000091582

Vormbock,  J. K., & Grossberg, J. M. Cardiovascular effects of human-pet dog interactions. Journal of Behavioral Medicine, 11, 509-517. doi: 10.1007/BF00844843

Wells, D. L. (2009). The effects of animals on human health and well-being. Journal of Social Issues, 65, 523-543. doi: 10.1111/j.1540-4560.2009.01612.x