ASD and GP

“You see, but you do not observe. The distinction is clear.” ~ Sherlock Holmes (A Scandal in Bohemia)

Autism. It’s a condition that we see weekly as general practitioners. The question is, do we observe it? And if we do, what do we see it as, a series of deficits, or as a set of different strengths that can be celebrated?

For the last few days, I’ve enjoyed being a delegate at the Asia-Pacific Autism Conference in Sydney, a series of some cognitively stimulating discussions covering the full spectrum of being on the spectrum.

There’s always so much that can be gleaned from conferences like these, but for me, the take-home messages as a GP came at the book-ends of the first session and the last.

One of the first keynote presentations came from researchers at the Olga Tennison Autism Research Centre (http://www.latrobe.edu.au/otarc). Prof Cherl Dissanayake and Dr Josephine Barbaro presented their research on a tool they developed called SACS-R, an early detection tool to screen for infants at higher risk for developmental disorders.

Early detection of children on the autism spectrum is very important, something recognised by the AMA in their position statement late last year (https://ama.com.au/position-statement/autism-spectrum-disorder-2016). Despite being important, early detection can also be tricky, and many children on the autism spectrum who are relatively high functioning are often missed in general practice.

Barbaro and Dissanayake have previously tested this tool, training community child health nurses to use it as part of the standard infant health checks. The results of their work showed that the tool was robust (Estimated sensitivity ranged from 69% to 83.8%, and estimated specificity ranged from 99.8% to 99.9% for babies between 12 and 24 months – Barbaro and Dissanayake, 2010).

Barbaro and Dissanayake have continued to develop the tool, but more importantly, they have refined the tool to utilise only the factors that had the highest sensitivity, and then turned the tool into a free app, untethering the initial assessment process from the domain of professionals and potentially putting it in the hands of every parent anywhere in the world via a smart phone. The results of their study are still being finalised, but they claim that the SACS-R tool on the app has a positive predictive value of 82%, a negative predictive value of 97%, a specificity of 99.58% and a sensitivity of 72%.

The power shift that an app like this brings is important for us as GP’s. In time, parents will be doing their own assessments at home and coming in to their GP with a recommendation to have a further assessment, and we need to be prepared for this and take the recommendation seriously. But there’s also a prime opportunity here, to use the app to enhance early screening for developmental disorders in general practice, by sending a link to the parents booking in for their baby’s 12 and 18-month immunisations and discussing the results of the assessment with them when they come in. This could also be in addition to the professional version of the program that Barbaro and Dissanayake are in the process of developing.

Given the preliminary results of their longitudinal study (not yet published but in its final stages) showing a prevalence of up to 1 in 43 children, it’s likely that we will be picking up several new cases a year.

If you want to review the app yourself or consider recommending it to your patients, it’s called ASDetect and it’s available from the App Store or Google Play.

At the other end of the conference, Dr Barry Prizant presented a keynote address on “Uniquely Human: a different way of seeing autism”, based on his book of the same name and his decades of work with people on the autism spectrum.

His theme was that most people see autism as a negative. In times gone by, children on the autism spectrum were seen as profoundly deficient, to the point that they weren’t considered a person. Even today, some pundits have said that “autism is a lost, hellish world” while others have likened having autism to being a victim of the holocaust.

On the other hand, self-advocacy is growing amongst those with autism, who are working to try and change the social view that autism is a series of weaknesses to overcome, but differences to be celebrated. Not only that, but more people on the spectrum are designing research projects to understand the condition better and to translate those advances into tangible benefits, taking self-advocacy to a whole new level.

Prizant not only promoted autism self-advocacy, but also discussed the concept of neuroharmony – that there is no such thing as autistic behaviour, but only human behaviour; that so many people with autism have succeeded in their chosen fields and have made lasting contributions to the benefit of our society. He championed the notion that rather than expecting autistic people to be ‘normal’, ‘normal’ society should be embracing the differences that those on the spectrum have. As one father of a child on the spectrum told him, “You don’t grow out of autism, you grow into autism.” As John Elder Robison wrote, “Asperger’s is not a disease. It’s a way of being. There is no cure, nor is there a need for one. There is, however, a need for knowledge.”

As GP’s, when we see those children on the spectrum picked up by the enhanced early screening tools, we need to ensure we give their parents the balanced view. It’s easy to look at the negatives and the weaknesses inherent in a diagnosis of ASD. I’m not suggesting that we sugar-coat things and tell only the positive side of the story, but we need to balance out any concerns the parents have with a generous serving of hope. As one father put it, “The people who have been the most helpful to us have are those who do not take away our hope. We have learned to keep away from the ‘doom and gloom’ crowd”, while one mother wrote, “Some call it autism, others call it despair and sorrow. I happen to call it hope, beauty and fascination.”

For ASD and the average GP, change is coming – good change that will empower parents to get an earlier diagnosis, and for those with ASD to get the early intervention that will benefit their weaknesses, complement their strengths and accept who they are as people. As GP’s, we need to be flexible and accepting, observing the strengths that autism can bring to our patients, not just seeing the weaknesses.

References

Barbaro J. and Dissanayake C., “Prospective identification of autism spectrum disorders in infancy and toddlerhood using developmental surveillance: the social attention and communication study.” J Dev Behav Pediatr. 2010 Jun;31(5):376-85

Post-script, 21 September 2017

I received an e-mail from Erin from La Trobe today:

  “My name is Erin and I am a Research Assistant at La Trobe University. Currently, I am working with Dr. Josephine Barbaro on the ASDetect project.
   We would also like you and your readers to know that we’re currently seeking parents/caregivers of young children aged 11-30 months for our research study looking at how ASDetect identifies early signs of Autism (Australia only). You can register at asdetect.org/app or SMS 0409 758 602. You must register via this website to be eligible for study, so just downloading the app won’t enrol you.”

If you can, please get involved.  This is important research that has the potential to have profound benefits for some of our most vulnerable patients ~ CEP

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Can you really Think and Eat Yourself Smart?

Sydney_skyline_at_dusk_-_Dec_2008

Today I’m in Sydney, a vibrant, bustling city which centres on one of the most beautiful harbours in the world.  When I booked my flights in April, I was originally going to spend the day attending Dr Caroline Leaf’s Australian Think and Eat Yourself Smart workshop.  Dr Leaf and her minions revoked my ticket a few weeks later.  She also changed the workshop twitter hashtag from #thinkandeatsmart to just #eatsmart, so perhaps Dr Leaf doesn’t want free thinking at the workshop.

It’s such a shame really, because I was looking forward to being part of the history of Dr Leaf’s first workshop on Australian soil.  But no matter … why waste a perfectly good plane ticket when I can have a day to sightsee, take photos, and catch a few Pokemon here and there as well.

And as a special something for all the people who’re attending the workshop today with Dr Leaf, I thought I’d pen a blog in their honour … something for them to ponder as they listen to Dr Leaf’s presentation, and maybe even provide them with a nidus of a question to pose to her during the day.  So here goes …

As the name would suggest, the Think and Eat Yourself Smart workshop is based on Dr Leaf’s book, Think and Eat Yourself Smart.  Does the book (and the subsequent workshop) deliver what it promises?  That is, can you really think and eat yourself smart?  It’s all well and good for Dr Leaf to espouse her fringe opinions on the food industry and modern farming, and to recycle nutritional information that doctors and dieticians have been promoting for years, but if her book can’t deliver on its titular promise, then it’s just an unoriginal rehash.

To support her thesis that we can think and eat ourselves smart, Dr Leaf declares that what you think affects what you eat, and what you eat affects what you think.  It’s on these intertwined ideas that Dr Leaf’s book stands or falls.  Let’s look at those statements in more detail.

Statement number 1 – “What you think affects what you eat”

Dr Leaf has a broad approach with this premise.  She suggests that the mindset that you have will not only determine what you consume, but also how your body will process it.

For example, she said on page 84 of Think and Eat Yourself Smart, “Research shows that 75 – 98 percent of current mental, physical, emotional and behavioural illnesses and issues come from our thought life; only 2 – 25 percent come from a combination of genetics and what enters our bodies through food, medications, pollution, chemicals, and so on.  These statistics show that the mindset behind the meal – the thinking behind the meal – plays a dominant role in the process of human food related health issues, approximately 80 percent.  Hence the title of this book: you have to think and eat yourself smart, happy and healthy.”

She goes on to say, “If we do not have a healthy mind, then nothing else in our life will be healthy, including our eating habits.”

We can break down these statements to assess their validity.

First of all, this statement is predicated on her 98 percent myth, something which I’ve previously proven to be implausible, but which Dr Leaf continues to use despite the overwhelming evidence against it.  To arrive at this conclusion, Dr Leaf has over-extrapolated, paraphrased, and exaggerated a handful of sources that were either out-of-date, clearly biased, or irrelevant.  She even had the gall to ascribe a made-up figure to an article which, ironically, twice contradicted her.  If you want to know more, see Chapter 10 in my book (http://www.debunkingdrleaf.com/chapter-10/)

This means that Dr Leaf’s statement, and indeed, her entire book, is built on gross misrepresentations of illegitimate resources.  Genetics and our external environment actually play a much greater role than she is willing to give credit for.  The mindset behind the meal is largely irrelevant – nowhere near 80 percent as Dr Leaf suggests.

But for the sake of argument, let’s take a couple of well-known medical conditions that are often associated with lifestyle and compare the research examining the difference that thinking and food make to them.  After all, if your mindset really is responsible for more than 80 percent of our health, then these two very common conditions should improve by more than 80 percent when thought patterns are changed.

Example 1: Hypertension.

Hypertension is also known as high blood pressure.  First, a brief explanation of what the numbers mean when talking about blood pressure so we’re on the same page: Blood pressure is measured in units of millimetres of mercury (or mmHg).  The old sphygmomanometers were hand pumps attached to a rubber bladder and a column of liquid metal mercury.  The blood pressure reading was however high the column of mercury rose at the two ends of the cardiac cycle.  There are always two numbers, expressed as ‘number 1 over number 2’ and written as N1/N2, like 120/80 or ‘one hundred and twenty over eighty’.  The top number is the maximum pressure in the arterial system when the heart pumps the blood into the arteries.  The bottom number is the pressure left over in the arterial system just before the heart beats again.  A blood pressure of 120/80 is the gold-standard physiological reference of normal blood pressure.  A blood pressure consistently above 140/90 is considered high.

Primary hypertension, which accounts for about 95 percent of all cases, has a strong genetic component.  According to eMedicine, “Epidemiological studies using twin data and data from Framingham Heart Study families reveal that BP has a substantial heritable component, ranging from 33-57%.” (http://emedicine.medscape.com/article/241381-overview#a4)  Environmental causes account for nearly all of the rest.  Secondary hypertension is related to a number of different diseases of the arteries, kidneys, hormone system and many others.  Diet is clearly part of those environmental causes.  Psychological stress is in there too, but the question is, how important is it?  If Dr Leaf is right, it should be 80 percent.

According to medical research, reducing alcohol intake to one standard drink per day or less reduces the systolic blood pressure (the top number) by between 2 and 4 mmHg.  Reducing salt to less than 6g a day decreases the systolic blood pressure by between 2 and 8 mmHg.   At best, that’s a 12mmHg reduction.  The DASH diet is as close to Dr Leaf’s macrobiotic tree-hugging anti-MAD diet as one could reasonably get, relying not just on cutting out salt, but also consuming low fat milk and lots of fruit and vegetables.  At best, the DASH diet could shave another 6mmHg from the standard low salt diet.  So that’s a grand total of 18mmHg with even the most optimistic of expectations.

Compared to diet, the best improvement in blood pressure from mind control is 5mmHg at best (and given the size and quality of the studies, that’s being generous) (Anderson et al, 2008; Barnes et al, 2008).

So for hypertension, changing your thinking has, at best, only about a quarter as powerful as changing your diet, not four times more powerful as Dr Leaf would have us believe.  One more nail in in the coffin for Dr Leaf’s theories.

Example 2: Dyslipidaemia.

Dyslipidaemia is medical jargon for cholesterol behaving badly.  Cholesterol is a waxy substance that’s found as a component of the fats in our diet.  To simplify a complex process, we need cholesterol to make our cell membranes, and cholesterol is also an essential building block for most of our hormones.  Cholesterol is usually carried around the body on protein transports called lipoproteins.  If there’s over-production of these lipoprotein particles or they’re not cleared by the liver properly, then the cholesterol they carry can get up to mischief.  The pathways and means of lipid metabolism in the human body reflect complex processes, and genetics, certain medical conditions, medications, and environmental factors can change how the lipoproteins behave.

So how much does thinking affect our cholesterol?  Well, there isn’t a lot of research looking at the subject, but a few studies have looked at cholesterol (specifically triglycerides, one of the lipids in the cholesterol ‘team’) and ‘mind-body practices’ (such as self-prayer, meditation, yoga, breathing exercises, or any other form of mind-body related relaxation technique or practice).  In a cross-sectional analysis of a cohort from the Rotterdam Study, Younge and colleagues examined the association between mind-body practices and the blood levels of triglyceride.  They found that mind-body practices were associated with a triglyceride level 0.00034 mmol/L less than those who did not perform mind-body practices (Younge et al, 2015).  That’s nearly imperceptible, possibly an artefact.  In fact, the average effect of placebos (the fake pills given as a control in therapeutic drug trials) are far greater – 0.1 mmol/L on average (Edwards and Moore, 2003).  Dietary interventions such as low carbohydrate diets decreased triglycerides by 0.26 mmol/L compared to low fat diets (Mansoor et al, 2016), and low fat diets up to 0.27 mmol/L lower than standard diets (Hooper, 2012).  Statins, the lipid-lowering medications, reduce triglycerides by between 0.2-0.4 mmol/L depending on the specific drug studied (Edwards and Moore, 2003).

The point of all this isn’t so much the specific numbers but the obvious difference between the (lack of) power of thought over an important lifestyle condition compared to the effectiveness of diet and medications.  If thinking was four times more important to the process of human food related health issues as Dr Leafs proposes, then thought-related ‘mind-body’ interventions should be at least four times more effective than any other intervention.  But the numbers don’t reflect that – ’Mind-body’ interventions are 1000 times weaker than dietary or drug interventions.

So Dr Leaf’s pronouncement that “the mindset behind the meal – the thinking behind the meal – plays a dominant role in the process of human food related health issues, approximately 80 percent” is complete bunkum.  There is no evidence to support the 98 percent myth which forms her statements underlying premise, and the examples of hypertension and dyslipidaemia, two common lifestyle conditions with proven genetic and dietary links, prove that thought based interventions are much, much weaker than dietary or drug interventions.

Therefore Dr Leaf’s claim that what you think affects what you eat is entirely baseless.

Statement number 2 – “What you eat affects what you think”

Dr Leaf writes, “Although your brain is only 2 percent of the weight of your body, it consumes 20 percent of the total energy (oxygen) and 65 percent of the glucose – what you eat will directly affect the brain’s ability to function on a significant scale.  Your brain has ‘first dibs’ on everything you eat.  I call this the ’20 percent factor’ or the eating behind the thinking, and it underscores the fact that how and what we eat affects our mind, brain and body.” (p84-5)

On face value, the statement seems to hold some weight.  Food does have an impact on how our brain works.  It certainly isn’t the only factor though – demands in the environment, our oxygen levels, our hormones, the function of our major organs, infections or injury, and our levels of sleep, all play a significant role on how our brain functions too.  But strictly speaking, what we eat does have an impact on how we think – if we haven’t eaten, or if we don’t consume enough calories, especially carbohydrates, our body slows some of our bodily functions down to preserve energy, including some of our cerebral functions.  So when you hear people complain that they can’t think because they have low blood sugar, that may in fact be true.  On the other hand, a pure glucose load can shift the balance of the amino acid tryptophan in our body, which enables the brain to produce more of the neurotransmitter serotonin, which can lift our mood.  Or ingesting food or drinks with stimulants like caffeine, such as my morning espresso, also improves how we think by making us more alert.

Unfortunately, Dr Leaf’s application of this premise goes several steps too far.  Later on page 85, Dr Leaf says, “if you eat while emotional, your body does not digest your food correctly.”

Well, that statement may contain an element of truth but only because it’s so hazy and indefinite that it’s applicable in the broadest sense.  Technically, we’re always emotional to one degree or another.  Even if I assume that Dr Leaf’s is meaning ‘angry’ when she says ‘emotional’ then it’s not so much that our body digests food incorrectly, but just differently.   When you’re highly aroused (physiologically, not sexually, just to clarify), your body goes into fight or flight mode.  The body diverts blood away from your intestines and towards your muscles, heart and lungs, so that you have the energy to handle the crisis.  The food in your stomach and guts isn’t going anywhere, and your body leaves it where it is to come back to it later when the crisis has been averted.  This is a normal physiological response.  The body still digests the food and absorbs it correctly, things are just delayed a little (Kiecolt-Glaser, 2010).

The biggest problem with Dr Leaf’s ‘eating behind the thinking’ argument is that it directly undermines her previous teaching.

Dr Leaf has made multiple social media posts claiming that the mind is separate from the brain and controls the brain.  She’s written much the same sentiment in her books.  Take a meme she posted to social media in May 2016.  It said, “As triune beings made in God’s image, we are spirit, mind (soul) and body – and our brain being part of the body does the bidding of the mind …”, and “God has designed the mind as separate from the brain. The brain simply stores the information from the mind and your mind controls your brain.”

Screen Shot 2016-05-29 at 10.25.58 PM

So the obvious question is, “If God designed our mind (our thinking) to be separate from the brain and to control the brain, then how can the food we eat make any difference to what we think? My diet affects my brain through the amount and timing of glucose I ingest, but can my diet can’t affect my thinking if the mind is separate to the brain and controls the brain?

Either the mind is separate to the brain, or it’s not.  It can’t be both.  If the mind is separate to the brain, then what you eat can’t affect what you think and the book becomes an emaciated shadow of rhetoric.  If the mind is dependent on the brain then the book and seminar maintain some semblance of validity, but the rest of Dr Leaf’s ministry crumbles like a well-made cheesecake crust, since the entirety of Dr Leaf’s ministry rests on her idea that the mind is separate from the brain and controls the brain, not the other way around (https://cedwardpitt.com/2016/05/30/dr-caroline-leaf-and-the-mind-brain-revisited/).

At the very least, this must be embarrassing for Dr Leaf, and if she keeps shooting herself in the foot, people will eventually notice that she’s limping.

So other than the free-range, fair-trade, grass fed, organic agro-ecologically produced kale and spinach root muffins and the chia and dandelion broth, it appears that the attendees at Dr Leaf’s workshop today may not be getting what they signed up for.  What you think does not radically change your health, or influence what your food does to your body, and the food you eat does not significantly change how you think.  Our diet is important to our health, but we can’t think and eat ourselves smart.

To all the attendees at the workshop, I hope you got something valuable out of the workshop.  While you were all sitting in a small room, listening to Dr Leaf and snacking on lemon and quinoa stuffed free-range quail giblets, Sydney was outdoing itself.  Not that I’m rubbing it in or anything, but see for yourself …

Kirribilli View

Dr Mary Booth lookout

Milsons Point

Milsons Point

IMG_4312

Milsons Park, Neutral Bay

Cremorne20160820 Web

Cremorne

Point Piper

Point Piper

Macquarie Lighthouse

Macquarie Lighthouse

Blues Point Reserve

Blues Point Reserve

Blues Point Reserve

Blues Point Reserve

References

Anderson JW, Liu C, Kryscio RJ. Blood pressure response to transcendental meditation: a meta-analysis. Am J Hypertens 2008 Mar;21(3):310-6

Barnes VA, Pendergrast RA, Harshfield GA, Treiber FA. Impact of breathing awareness meditation on ambulatory blood pressure and sodium handling in prehypertensive African American adolescents. Ethn Dis 2008 Winter;18(1):1-5

Edwards JE, Moore RA. Statins in hypercholesterolaemia: a dose-specific meta-analysis of lipid changes in randomised, double blind trials. BMC Family practice. 2003 Dec 1;4(1):1.

Hooper L, Abdelhamid A, Moore HJ, Douthwaite W, Skeaff CM, Summerbell CD. Effect of reducing total fat intake on body weight: systematic review and meta-analysis of randomised controlled trials and cohort studies. Bmj. 2012 Dec 6;345:e7666.

Kiecolt-Glaser JK. Stress, food, and inflammation: psychoneuroimmunology and nutrition at the cutting edge. Psychosomatic Medicine. 2010 May;72(4):365.

Mansoor N, Vinknes KJ, Veierød MB, Retterstøl K. Effects of low-carbohydrate diets v. low-fat diets on body weight and cardiovascular risk factors: a meta-analysis of randomised controlled trials. British Journal of Nutrition. 2016 Feb 14;115(03):466-79.

Younge JO, Leening MJ, Tiemeier H, Franco OH, Kiefte-de Jong J, Hofman A, Roos-Hesselink JW, Hunink MM. Association between mind-body practice and cardiometabolic risk factors: The Rotterdam Study. Psychosomatic medicine. 2015 Sep 1;77(7):775-83.

The pain and gain of grief

Floral tribute to the Sydney siege victims, at Martin Place, Sydney

Floral tribute to the Sydney siege victims, at Martin Place, Sydney

In many ways, 2014 hasn’t been the best of years, unless you’re a florist.

A dear friend of mine recently went through an unimaginable personal loss, but politely requested that no one send her flowers, because the unintentional metaphor of receiving something beautiful that soon withered and died simply reminded her of what she had lost. Not that I could have given her flowers anyway – it seems like all of Australia’s bouquets have been laid in Martin Place.

The siege in the Lindt Cafe was an assault on Australia’s national psyche as much as it was an attack on a small café in the CBD of Sydney, and marks a highpoint of suffering in the midst of several tragedies back to back. Soon after the tragic events in Martin Place, news came of the murder of eight children from the one family in Cairns. Two weeks before, we were rocked by the sudden death of cricketer, Phil Hughes.

Like many, many others in the last few weeks, I’ve felt that discombobulating mix of sadness, compassion, anxiety, and numbness (and many other feelings) that accompanies loss. I was grieving.

Grief is not fun. There are a wide variety of ways in which people grieve, of course, though grief is rarely described as joyous. Rather than being the five stages of grief that used to be dutifully learned by every medical and psychology student, grief is now considered a mish-mash of nearly every different emotion that a human can experience, for different lengths of time, at different intensities, in different patterns. Like your fingerprint, your emotional pattern of adapting to loss is as individual as you are. I felt helpless at the news from my close friend, shock at the death of Phil Hughes, and anxious when thinking about the Lindt Café. Each tragedy was also accompanied by a deep sadness.

As well as being emotionally draining, the process of grieving can have physical effects as well, associated with high levels of pro-inflammatory cytokine release and the changes that are associated with that (O’Connor, Irwin & Wellisch, 2009). Pro-inflammatory cytokines are also released because of physical stress or infection, so grief would physically feel like you have the flu, which is probably why grieving makes you feel physically awful as well as mentally distraught.

As awful as these feelings are, they are important to our healing and restoration. Grief functions as a way of helping us adjust to life on the other side of our loss. Like our body has to heal and adapt to physical wounds, grief helps us heal and adapt emotionally. Grief is not a disease, but a normal process that everyone experiences at one point or another.

Some authors teach that negative feelings and emotions are toxic, or that the outcome of different stresses in our life is dependent on our personal choices. If there was ever a case-in-point of the benefit of “negative” emotions, and why the outcome of stressful events is not entirely under our control, it’s grief. Grieving is a process which, by definition, is distressing. The storms of painful emotion roll through us, triggered and controlled by our subconscious brain, with our conscious mind along for the ride. As distressing as those emotions can be, they are not ‘negative’ emotions, but the process of healing,

At times of intense sorrow, we can try and ‘help’ those who are grieving by telling them how they should feel, or what they should do, but during times of grief, being too directional is usually not helpful. The blog today is more general in nature because I don’t want to try and push one particular way of grieving over another. There is no right or wrong way to grieve.

My Physical Education teacher often used to say, “No pain, no gain.” Actually, it was more barking through his megaphone, trying to make me run faster in my cross-country race. It may seem an odd match, but the principle applies here too. If you are feeling the sadness and loss over the Lindt Café, Phil Hughes, Robin Williams, or any other personal loss you may have experienced, it’s ok to feel the distress. The pain is hard. The feelings are raw, and they are real. But you will get through them, and they will help you to experience the joy in life again.

I am coming to terms with each of these different tragedies in my own way. Lets pray that 2015 is a much better year.

If you are struggling and don’t know where to go to talk or find assistance, see your GP or psychologist, visit BeyondBlue (http://www.beyondblue.org.au), or the Australian Centre for Grief and Bereavement (http://www.grief.org.au).

If you want to donate to the funds or foundations set up in honour of the Sydney siege victims, please go to http://www.beyondblue.org.au/get-involved/make-a-donation or http://thekatrinadawsonfoundation.org.

References

O’Connor, M.-F., Irwin, M. R., & Wellisch, D. K. (2009). When grief heats up: Proinflammatory cytokines predict regional brain activation. NeuroImage, 47(3), 891–896. doi:10.1016/j.neuroimage.2009.05.049