Dr Caroline Leaf and the case of the killer reactions

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Stress! Believe the media and seemingly every disease known to man is in some way linked to it. Heart disease = stress. Cancer = stress. Flatulence = stress.

Dr Caroline Leaf, Communication Pathologist and self-titled cognitive neuroscientist, has been of a similar opinion for the last couple of decades. Dr Leaf must have been kind enough to read my book, because after teaching for the last fifteen years that stress is toxic, a subtle shifting under the weight of evidence has appeared.

In her 2009 book [1], Dr Leaf wrote,
“The result of toxic thinking translates into stress in your body.” (p15)
“Stress is a global term for the extreme strain on your body’s systems as a result of toxic thinking.” (p15)
“Stress is a direct result of toxic thinking.” (p29)
“These stages of stress are scientifically significant because they illustrate how a single toxic thought causes extreme reactions in so many of our systems.” (p39)

In 2013, her position on stress hadn’t really changed that much: “Even a little bit of these negative levels of stress from a little bit of toxic thinking has far-reaching consequences for mental and physical health”, and “The association between stress and disease is a colossal 85 percent.” [2: p36-37]

Again in her 2009 book [1], Dr Leaf devotes an entire chapter to the alleged effects of the toxic stress pathway on our body (chapter 4, p39-43).

Now in her latest social media update, tucked in amongst the gratuitous selfies and holiday snaps, comes something that’s actually about mental health: “Stress does not kill… is good for us! Its our negative reactions to stressful events that pushes into negative stress…and this is what kills! Sistas 2014 NZ”

The problem for Dr Leaf is that any stress, whether it’s caused by our “negative” reactions or not, doesn’t actually kill us.

There is a phrase used in science, “Correlation does not equal causation”. This simply means that just because two things occur together, one doesn’t necessarily cause the other. For example, do my red watery eyes cause my hives? They always appear together, but they don’t cause each other. The common element that causes both of them is actually the cat that I’ve just patted.

Just because stress is correlated with certain illnesses does not mean that stress causes or contributes to those illnesses. In fact, one of Dr Leafs own pivotal references, an article by Cohen and colleagues in the Journal of the American Medical Association in 2007, discussed the weakness of assuming that stress causes most diseases. As they say, “Although stressors are often associated with illness, the majority of individuals confronted with traumatic events and chronic serious problems remain disease-free.” [3]

Even if it were true that it how we react to stress contributes to the outcome of that stress, Dr Leaf’s statement about our killer reactions incorrectly presumes that both how we cope with stress, and the physical outcome of stress are the result of our choices.

Our levels of stress, and the way we cope with our stress, is mostly caused by our genetics. Some people will be naturally less stressed, and some people will be naturally better at coping with stress (see chapter 5 of my book [4] for a full discussion on the science of resilience). Just because you’re more prone to stress doesn’t mean that it’s all down to your bad choices. Assumptions like these only add to your already high levels of stress.

That’s not to say that we don’t have a way to improve our responses. For those of us at the stressed end of the spectrum, successful psychological therapies such as Acceptance and Commitment Therapy will help to improve our coping, and certainly have been shown to improve (not cure) mental illnesses like anxiety and depression, and other chronic conditions like chronic pain (see [5] for a review).

ACT and other modern psychological therapies recognise that trying to change our thoughts doesn’t make any difference to how we cope. So like I said before, it’s partly true that how we react to normal life experience will help us live full and productive lives, but it’s not about fighting or changing our thoughts. It’s about being mentally flexible enough to make room for our thoughts and fears and move forward towards meaningful action. I’m sure that the ladies at ‘Sistas 2014′ wouldn’t be hearing that from Dr Leaf.

Anyways, I’m glad that Dr Leaf is changing her tune on stress, but there’s still more room for change before she meets up with current scientific understanding.

For an in-depth review of the teachings of Dr Leaf, visit http://www.smashwords.com/books/view/466848 where you can download a free copy of “Hold That Thought: Reappraising the work of Dr Caroline Leaf.

References

  1. Leaf, C., Who Switched Off My Brain? Controlling toxic thoughts and emotions. 2nd ed. 2009, Inprov, Ltd, Southlake, TX, USA:
  2. Leaf, C.M., Switch On Your Brain : The Key to Peak Happiness, Thinking, and Health. 2013, Baker Books, Grand Rapids, Michigan:
  3. Cohen, S., et al., Psychological stress and disease. JAMA: the journal of the American Medical Association, 2007. 298(14): 1685-7
  4. Pitt, C.E., Hold That Thought: Reappraising the work of Dr Caroline Leaf, 2014 Pitt Medical Trust, Brisbane, Australia, URL http://www.smashwords.com/books/view/466848
  5. Harris, R., Embracing Your Demons: an Overview of Acceptance and Commitment Therapy. Psychotherapy In Australia, 2006. 12(6): 1-8 http://www.actmindfully.com.au/upimages/Dr_Russ_Harris_-_A_Non-technical_Overview_of_ACT.pdf

Hold That Thought – Reappraising the work of Dr Caroline Leaf

Hold That Thought Cover

It’s been more than a few late nights in the making, but sixteen months and 68,000 words on, the early release of my new book is now available on line through Smashwords: https://www.smashwords.com/books/view/466848.  Apple iBook, Kindle, and a number of other platforms will come online soon.

Dr Caroline Leaf is a South African communication pathologist and self-titled cognitive neuroscientist, now based in the USA.  This book is an in-depth look at the current scientific understanding of thought, stress, free will and choice, as well as a thorough critique of Dr Leaf’s foundational teachings and the evidence she provides as proof of her hypotheses.

In the coming few days, I will make the text of the book available on this blog as well.  If you have any questions, send them in.  I’m happy to put up a FAQ page.  And as always, I’m happy to answer any legitimate criticism of my work, so long as it’s constructive and evidence based, not personal.

And as always, Dr Leaf herself is welcome to comment.  Indeed, I would value her feedback, and I’m sure any comment she wishes to make would be welcome by the Christian community as a whole.

Dr Caroline Leaf and the Myth of the Blameless Brain

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When I came back to Facebook this morning, I found this from Dr Leaf on my feed,

“Don’t blame your physical brain for your decisions and actions. You control your brain!”

Dr Caroline Leaf is a Communication Pathologist and a self-titled Cognitive Neuroscientist. Her post follows her theme of the last couple of weeks, the premise that the mind is the dominant cognitive force, controlling the physical brain, and indeed, all matter. I have written about the Myth of Mind Domination in a previous blog. But Dr Leaf’s latest offering here deserves special attention.

Lets think about her statement in more detail:

“Don’t blame your physical brain for your decisions and actions.”

What Dr Leaf is really saying is that the physical brain has no role in your choices or behaviour whatsoever, because if your physical brain had a role in the decisions and actions you make, it would also carry some blame for your poor decisions and actions.

“You control your brain.”

The question to ask here is, “Which part of ‘you’ controls your brain?” Her answer would be, “Your mind”, although she never says where the mind is. Certainly not in the physical brain or even in our physical body, since “Our mind is designed to control the body, of which the brain is a part, not the other way around.” [1: p33].

So an ethereal, disembodied force is in full control of our physical body, such that our brain has no role in the decisions we make or actions we take. Even at this stage of analysis, Dr Leaf’s statement is ludicrous. But wait, there’s more.

Dr Leaf’s statement puts her at odds with real Cognitive Neuroscientists. Professor Patrick Haggard is the Deputy Director of the Institute of Cognitive Neuroscience at the University College London. He has authored or co-authored over 350 peer-reviewed articles on the neuroscience of making choices. He writes, “Modern neuroscience rejects the traditional dualist view of volition as a causal chain from the conscious mind or ‘soul’ to the brain and body. Rather, volition involves brain networks making a series of complex, open decisions between alternative actions.” [2] Strike one for Dr Leaf.

Dr Leaf’s statement puts her at odds with herself. Two weeks ago when misinterpreting James 1:21, Dr Leaf wrote, “How you react to events and circumstances of your life is based upon your perceptions.” Perception is classically defined in neurobiology as conscious sensory experience [3: p8] although the work of cognitive neuroscientists has shown that perception can also be non-conscious [4, 5]. Either way, perception is based entirely on processing within the brain [3: p6-11]. So one week, Dr Leaf is saying that our brain determines how we behave, and then ten days later, she is telling us that our brain does not determine how we behave. Which is it? Strike two for Dr Leaf.

Finally, Dr Leaf’s statement is borderline insulting to the sufferers of congenital or acquired brain disorders. Would you tell a stroke patient that they shouldn’t blame their physical brain for their immobility, because they’re mind is in control of their brain? What about a child with Cerebral Palsy? Would you tell a mother of a child with Downs Syndrome that their child is having recurrent seizures because they aren’t using their mind properly to control their brain? Dr Leaf is doing exactly that. I find it incredible that she could be so insensitive, given her background as a speech pathologist working with patients with Acquired Brain Injury.

I imagine that her defence would be something along the lines of, “What I meant was, ‘don’t blame your normal physical brain for your decisions and actions. You control your functional brain.’” That sort of explanation would be less insulting to people with strokes or brain injuries, but it then undermines her whole premise. The hierarchy of the brain and the mind doesn’t change just because a part of the brain is damaged.

Besides, changes to brain function at any level can change the way a person thinks and behaves. The classic example was Phineas Gage, who in 1848, accidentally blasted an iron rod through his skull, damaging his left frontal lobe. History records that Gage’s well-mannered, pleasant demeanour changed suddenly into a fitful, irreverent, obstinate and capricious man whose workmates could no longer stand him [6]. Medical science has documented numerous cases of damage to the right ventromedial prefrontal cortex causing acquired sociopathy [7]. How can the mind be in control of the brain when an injury to the brain causes a sudden change in thought pattern and behaviour? Clearly one CAN blame the physical brain for one’s decisions and actions. Strike three. You’re out.

Dr Leaf is welcome to comment here. Perhaps she meant something completely different by her post, although there’s only so many ways that such a statement can be interpreted.

Ultimately, Dr Leaf’s love of posting pithy memes of dubious quality is now getting embarrassing. Being so far behind the knowledge of a subject in which she claims expertise is ignominious. Undermining her own premise and contradicting herself is just plain embarrassing. But to be so insensitive to some of the most vulnerable is poor form. I think she’d be well served by re-examining her facts and adjusting her teaching.

References

  1. Leaf, C.M., Switch On Your Brain : The Key to Peak Happiness, Thinking, and Health. 2013, Baker Books, Grand Rapids, Michigan:
  2. Haggard, P., Human volition: towards a neuroscience of will. Nat Rev Neurosci, 2008. 9(12): 934-46 doi: 10.1038/nrn2497
  3. Goldstein, E.B., Sensation and perception. 8th ed. 2010, Wadsworth, Cengage Learning, Belmont, CA:
  4. Kouider, S. and Dehaene, S., Levels of processing during non-conscious perception: a critical review of visual masking. Philos Trans R Soc Lond B Biol Sci, 2007. 362(1481): 857-75 doi: 10.1098/rstb.2007.2093
  5. Tamietto, M. and de Gelder, B., Neural bases of the non-conscious perception of emotional signals. Nat Rev Neurosci, 2010. 11(10): 697-709 doi: 10.1038/nrn2889
  6. Fumagalli, M. and Priori, A., Functional and clinical neuroanatomy of morality. Brain, 2012. 135(Pt 7): 2006-21 doi: 10.1093/brain/awr334
  7. Mendez, M.F., The neurobiology of moral behavior: review and neuropsychiatric implications. CNS Spectr, 2009. 14(11): 608-20 http://www.ncbi.nlm.nih.gov/pubmed/20173686

 

Dr Caroline Leaf on James 1:21 – Redux

So, we’ve all heard the saying, “If at first you don’t succeed, try and try again.”  Dr Leaf has certainly done that.

Dr Caroline Leaf is a Communication Pathologist and self-titled Cognitive Neuroscientist.  Not content to completely misinterpret James 1:21 only once, she posted on social media today, “James 1:21.  Our thoughts and perceptions have a direct and overwhelmingly significant effect on the cells of our body.”

If for nothing else, Dr Leaf at least gets points for persistence.  A week and a half ago, Dr Leaf again used James 1:21 to attempt to justify a meme on perception.  I’d love to know what version of the Bible that she’s using, because it seems that in her Bible, James 1:21 can be interpreted any way that one wants.

Lets recap: James 1:21 says,

“Wherefore lay apart all filthiness and superfluity of naughtiness, and receive with meekness the engrafted word, which is able to save your souls.” (KJV)

There are too many big words there for my liking, so I went through an on-line, widely used Greek lexicon, to look at the meanings of the words.  Then I translated them into something more understandable, to make sure that I didn’t miss the bit about perception.

Using the Strong’s dictionary and concordance built in to the Blue Letter Bible site (http://www.blueletterbible.org/Bible.cfm?b=Jas&c=1&v=21&t=KJV#s=1147021) I was able to translate the original Greek into something more manageable.

“Therefore shed all the morally defiling wickedness and excess malice, and, with meekness, embrace the teaching that is implanted by your mentors, which has the power to rescue your eternal soul.”

Wait … where did James talk about perception, and how our cells react to our thoughts?  Reviewing the scripture and its translation the second time around didn’t change anything, because there is nothing in James 1:21 that is in any way remotely connected to perception, thinking and our cells biological functioning.

Scripture is the inspired word of God, and “is useful for teaching, rebuking, correcting and training in righteousness, so that the servant of God may be thoroughly equipped for every good work.” (2 Tim 3:16-17, NIV)  What James is writing about is essential, and Christians need to embrace what he was teaching.

Which is why it is so important for Dr Leaf to interpret scripture correctly.  For the second time in two weeks, Dr Leaf has completely misapplied a scripture to one of her memes.  As if that isn’t concerning enough for a woman than regularly interprets scripture to audiences in the thousands every week, there isn’t any scientific evidence to back up her claim either.  As I have written about before, there is no evidence that the mind controls the brain.  Rather, our psychology is dependant on our biology.  More on this in future posts.  But the onus is on Dr Leaf to provide evidence to back up her claim.  I encourage her to publish specific evidence that she believes justifies her claims that our thoughts alter our cellular biology.

Otherwise, I think another popular phrase would better apply: “Quit while you’re ahead”.

UPDATE (17/6/2014)

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I was reviewing Dr Leaf’s posts tonight, and I came across this response that Dr Leaf posted on the 5th of June.  Clearly I wasn’t the only person who wondered exactly how James 1:21 applied to her meme.

Dr Leaf’s explained: “By ‘implanting the word of God your soul will be saved’ (James 1:21) – so by memorizing God’s Word we build healthy thoughts into our brain that improve the health of our cells.”

I’m sure that Dr Leaf thought she was climbing out of a hole, although I think she’s only dug herself deeper.

Firstly, while I’m not a trained theologian, I can read.  Dr Leaf reinterprets this long-suffering scripture again, “By ‘implanting the word of God your soul will be saved’.”  But that’s not what it says at all.  From the KJV which I originally quoted: ” … receive with meekness the engrafted word, which is able to save your souls.” (Emphasis added)  It’s a subtle but important difference.  My understanding is that salvation comes confession and repentance (Romans 10:9-10, 2 Corinthians 7:10).  The word of God is able to save souls, but as the Parable of the Sower (Luke 8:4-15) shows, it doesn’t always bear fruit.  Satan himself knows the Bible inside out, but he certainly isn’t saved.  Perhaps someone who is theologically trained can confirm the points here.  I’d certainly appreciate it.  But for now, I propose that Dr Leaf has misinterpreted this scripture again.

Dr Leaf goes on to claim that by memorizing scripture, “we build healthy thoughts in our brain that improve the health of our cells.”  Dr Leaf is really grasping at straws here.  The “soul” that James is referring to is psyche in the Greek, translated as “the seat of the feelings, desires, affections, aversions (our heart, soul etc.); the (human) soul in so far as it is constituted that by the right use of the aids offered it by God it can attain its highest end and secure eternal blessedness, the soul regarded as a moral being designed for everlasting life; the soul as an essence which differs from the body and is not dissolved by death (distinguished from other parts of the body)”. (http://www.blueletterbible.org/lang/lexicon/lexicon.cfm?Strongs=G5590&t=KJV)  So the word that James used has nothing to do with the body.

Dr Leaf has to apply her own set of assumptions to the scripture, that a saved soul must be healthy thoughts, and that healthy thoughts leads to healthy cells.  Its a myth that healthy thoughts lead to healthy cells (more on this in a future post).  To suggest that salvation and healthy thoughts are one and the same is also an assumption on Dr Leaf’s part, which I don’t think the scripture supports in any way.

So in short, Dr Leaf’s explanation really hasn’t helped her cause.  Her meme is still scripturally and scientifically baseless.

Dr Caroline Leaf and the 98 Percent Myth

Dr Caroline Leaf believes that nearly all our diseases come from our thoughts.

Dr Caroline Leaf believes that nearly all our diseases come from our thoughts.

In the hustle and bustle of daily life, most people wouldn’t stop to consider what makes people sick.  In my profession, I get a front row seat.

In the average week, I get to see a number of different things.  Mostly “coughs, colds and sore holes” as the saying goes, although there are some rarer things too.  And sometimes, people present with problems that aren’t for the faint of heart (or stomach – beware of nail guns is all I can say).

Normally, the statistics of who comes in with what doesn’t make it beyond the desk of the academic or health bureaucrat.  The numbers aren’t as important as the people they represent.

But to Dr Caroline Leaf, Communication Pathologist and self-titled Cognitive Neuroscientist, the numbers are all important.  To support her theory of toxic thoughts, Dr Leaf has stated that “75 to 98% of mental and physical (and behavioural) illness comes from one’s thought life” [1: p37-38].  She has repeated that statement on her website, on Facebook, and at seminars.

As someone with a front row seat to the illnesses people have, I found such a statement perplexing.  In the average week, I don’t see anywhere near that number.  In general practices around Australia, the number of presentations for psychological illnesses is only about eight percent [2].

But Australian general practice is a small portion of medicine compared to the world’s total health burden.  Perhaps the global picture might be different?  The World Health Organization, the global authority on global health, published statistics in November 2013 on the global DALY statistics [3] (a DALY is a Disability Adjusted Life Year).  According to the WHO, all Mental and Behavioural Disorders accounted for only 7.2% of the global disease burden.

You don’t need a statistics degree to know that seven percent is a long way from seventy-five percent (and even further from 98%).

Perhaps a large portion of the other ninety-three percent of disease that was classified as physical disease was really caused by toxic thoughts?  Is that possible?  In short: No.

When considered in the global and historical context, the vast majority of illness is related to preventable diseases that are so rare in the modern western world because of generations of high quality public health and medical care.

In a recent peer-reviewed publication, Mara et al state, “At any given time close to half of the urban populations of Africa, Asia, and Latin America have a disease associated with poor sanitation, hygiene, and water.” [4] Bartram and Cairncross write that “While rarely discussed alongside the ‘big three’ attention-seekers of the international public health community—HIV/AIDS, tuberculosis, and malaria—one disease alone kills more young children each year than all three combined. It is diarrhoea, and the key to its control is hygiene, sanitation, and water.” [5] Hunter et al state that, “diarrhoeal disease is the second most common contributor to the disease burden in developing countries (as measured by disability-adjusted life years (DALYs)), and poor-quality drinking water is an important risk factor for diarrhoea.” [6]

Diarrhoeal disease in the developing world – the second most common contributor to disease in these countries, afflicting half of their population – has nothing to do with thought.  It’s related to the provision of toilets and clean running water.

We live in a society that prevents half of our illnesses because of internal plumbing.  Thoughts seem to significantly contribute to disease because most of our potential illness is prevented by our clean water and sewerage systems.  Remove those factors and thought would no longer appear to be so significant.

In the same manner, modern medicine has become so good at preventing diseases that thought may seem to be a major contributor, when in actual fact, most of the work in keeping us all alive has nothing to do with our own thought processes.  Like sanitation and clean water, the population wide practices of vaccination, and health screening such as pap smears, have also significantly reduced the impact of preventable disease.

Around the world, “Recent estimates of the global incidence of disease suggest that communicable diseases account for approximately 19% of global deaths” and that “2.5 million deaths of children annually (are) from vaccine-preventable diseases.” [7] Again, that’s a lot of deaths that are not related to thought life.

Since 1932, vaccinations in Australia have reduced the death rate from vaccine-preventable diseases by 99% [8].  Epidemiological evidence shows that when vaccine rates increase, sickness from communicable diseases decrease [9: Fig 2, p52 & Fig 8, p67].

Population based screening has also lead to a reduction in disease and death, especially in the case of population screening by pap smears for cervical cancer.  Canadian public health has some of the best historical figures on pap smear screening and cervical cancer. In Canada, as the population rate of pap smear screening increased, the death rate of women from cervical cancer decreased.  Overall, pap smear screening decreased the death rate from cervical cancer by 83%, from a peak of 13.5/100,000 in 1952 to only 2.2/100,000 in 2006, despite an increase in the population and at-risk behaviours for HPV infection (the major risk factor for cervical cancer) [10].

And around the world, the other major cause of preventable death is death in childbirth.  The risk of a woman dying in childbirth is a staggering one in six for countries like Afghanistan [11] which is the same as your odds playing Russian Roulette.  That’s compared to a maternal death rate of one in 30,000 in countries like Sweden.  The marked disparity is not related to the thought life of Afghani women in labour.  Countries that have a low maternal death rate all have professional midwifery care at birth.  Further improvements occur because of better access to hospital care, use of antibiotics, better surgical techniques, and universal access to the health system [11].  Again, unless one’s thought life directly changes the odds of a midwife appearing to help you deliver your baby, toxic thoughts are irrelevant as a cause of illness and death.

Unfortunately for Dr Leaf, her statement that “75 to 98 percent of mental, physical and behavioural illnesses come from toxic thoughts” is a myth, a gross exaggeration of the association of stress and illness.

In the global and historical context of human health, the majority of illness is caused by infectious disease, driven by a lack of infrastructure, public health programs and nursing and medical care.  To us in the wealthy, resource-rich western world, it may seem that our thought life has a significant effect on our health.  That’s only because we have midwives, hospitals, public health programs and internal plumbing, which stop the majority of death and disease before they have a chance to start.

Don’t worry about toxic thoughts.  Just be grateful for midwives and toilets.

References

1.         Leaf, C.M., Switch On Your Brain : The Key to Peak Happiness, Thinking, and Health. 2013, Baker Books, Grand Rapids, Michigan:

2.         FMRC. Public BEACH data. 2010  [cited 16JUL13]; Available from: <http://sydney.edu.au/medicine/fmrc/beach/data-reports/public%3E.

3.         World Health Organization, GLOBAL HEALTH ESTIMATES SUMMARY TABLES: DALYs by cause, age and sex, GHE_DALY_Global_2000_2011.xls, Editor 2013, World Health Organization,: Geneva, Switzerland.

4.         Mara, D., et al., Sanitation and health. PLoS Med, 2010. 7(11): e1000363 doi: 10.1371/journal.pmed.1000363

5.         Bartram, J. and Cairncross, S., Hygiene, sanitation, and water: forgotten foundations of health. PLoS Med, 2010. 7(11): e1000367 doi: 10.1371/journal.pmed.1000367

6.         Hunter, P.R., et al., Water supply and health. PLoS Med, 2010. 7(11): e1000361 doi: 10.1371/journal.pmed.1000361

7.         De Cock, K.M., et al., The new global health. Emerg Infect Dis, 2013. 19(8): 1192-7 doi: 10.3201/eid1908.130121

8.         Burgess, M., Immunisation: A public health success. NSW Public Health Bulletin, 2003. 14(1-2): 1-5

9.         Immunise Australia, Myths and Realities. Responding to arguments against vaccination, A guide for providers. 5th ed. 2013, Commonwealth of Australia, Department of Health and Ageing, Canberra:

10.       Dickinson, J.A., et al., Reduced cervical cancer incidence and mortality in Canada: national data from 1932 to 2006. BMC Public Health, 2012. 12: 992 doi: 10.1186/1471-2458-12-992

11.       Ronsmans, C., et al., Maternal mortality: who, when, where, and why. Lancet, 2006. 368(9542): 1189-200 doi: 10.1016/S0140-6736(06)69380-X

Autism Series 2013 – Part 3: The Autism “Epidemic”

Weintraub, K., Autism counts. Nature, 2011. 479(7371): 22-4.

Weintraub, K., Autism counts. Nature, 2011. 479(7371): 22-4.

It seems that autism is on the rise.  Once hidden away in institutions or just dismissed as odd, society is now faced with a condition that it is yet to come to grips with.  Some out in the community believe that it must be a toxin, or vaccines or mercury.  Others accuse doctors of simply giving in to the unreasonable demands of pushy parents to defraud the system of money – “Things have reached the point these days where any kid that’s not a charming little extrovert will be accused of being, ‘on the spectrum.’”[1]

So is there an epidemic of kids who are “not charming little extroverts”?  It depends on who you ask.

Take, for example, two articles written in the year 2000.  In the first, titled “The autism epidemic, vaccinations, and mercury”, Rimland said,

“While there are a few Flat-Earthers who insist that there is no real epidemic of autism, only an increased awareness, it is obvious to everyone else that the number of young children with autism spectrum disorders (ASD) has risen, and continues to rise, dramatically.”[2]

The other, written by Professor Tony Attwood, a world authority on Aspergers Syndrome, said,

“… is there an epidemic of people being diagnosed as having Asperger’s Syndrome? At present we cannot answer the question, as we are unsure of the diagnostic criteria, the upper and lower levels of expression and the borders with other conditions. Nevertheless, we are experiencing a huge increase in diagnosis but this may be the backlog of cases that have been waiting so long for an explanation.”[3]

I don’t think it’s very often Prof Attwood is lumped with ‘flat-earthers’.  But you can see the change in perspective from one side looking objectively to the other who need for there to be an “epidemic” of autism in order to strengthen their case.

So who’s right?  To see if this autism “epidemic” hypothesis has any real merit, we need to delve into some numbers.

First, some basic epidemiology – because part of the confusion in looking at the autism numbers is defining exactly what those numbers represent.  Here are some important epidemiology terms from the “Physicians Assistant Exam for Dummies”[4]:

Incidence: For any health-related condition or illness, incidence refers to the number of people who’ve newly acquired this condition.

Prevalence: Prevalence concerns the number of people who have this condition over a defined time interval.

Most autism figures are for prevalence, or often more specifically, point prevalence – “the number of people who have this condition at any given point in time.”

The other thing to remember from my last blog is that initially autism was only diagnosed on the strict rules of Kanner, and was considered to be a single disease caused mainly by bad parenting [5].  So through the 1960’s and 1970’s, only the most severe children were diagnosed as having autism because the high-functioning autism would not have met Kanners criteria, and even if they did, most parents didn’t want the label for fear of the social stigma.

So then, what are the numbers?  The early prevalence was estimated to be less than 5/10,000 or 1 in 2000[6], although in surveys done after 1987, the numbers began to rise past 7/10,000[7].  In the 1990’s, Autism prevalence climbed into the teens and the latest prevalence has been documented for autism is 20.6/10,000[7].

But that’s only about 1 in 485.  The CDC estimated a prevalence of 1 in 88 (113/10,000)[8].  Where did the other 400 people go?

This is where the importance of definitions is highlighted.  Autism is considered part of a spectrum, and at the time of the surveys reviewed by Fombonne, DSM III then DSM IV considered conditions like Pervasive Developmental Disorder and then Aspergers Disorder to be part of that spectrum.  Adding in the rate of PDD and you have a figure of 57.7/10,000 and adding in Aspergers gives you a combined rate of 63.7/10,000, or 1 in 157 people surveyed[7].

And yet even then, who you measure and how you measure makes much more of a difference, because a recent, rigorous study targeting all 7 to 12 year old children in a large South Korean populous found a prevalence of 2.64%, which is 264/10,000 or 1 child in every 38.  The authors noted that, “Two-thirds of ASD cases in the overall sample were in the mainstream school population, undiagnosed and untreated. These findings suggest that rigorous screening and comprehensive population coverage are necessary to produce more accurate ASD prevalence estimates and underscore the need for better detection, assessment, and services.”[9]

So if there has been a fifty-fold change in prevalence (from 5 to 264 cases per 10,000 people) in just thirty years, isn’t that an epidemic?

Well, no.  As much as some might ignorantly deny it, there is no real evidence for it.  Remember the definitions from the “Physicians Assistant Exam for Dummies”[4]:

Incidence: For any health-related condition or illness, incidence refers to the number of people who’ve newly acquired this condition.

Prevalence: Prevalence concerns the number of people who have this condition over a defined time interval.

It’s the rapid rise in the number of new cases diagnosed that defines an epidemic, which is the incidence and not the prevalence[10].  While the prevalence has changed a lot, the incidence has been fairly stable.  From Nature, “Christopher Gillberg, who studies child and adolescent psychiatry at the University of Gothenburg in Sweden, has been finding much the same thing since he first started counting cases of autism in the 1970s. He found a prevalence of autism of 0.7% among seven-year-old Swedish children in 1983 and 1% in 1999. ‘I’ve always felt that this hype about it being an epidemic is better explanation’, he said.”[11]

Fombonne agrees. “As it stands now, the recent upward trend in estimates of prevalence cannot be directly attributed to an increase in the incidence of the disorder.”[7]  He said later in the article that a true increase in the incidence could not be ruled out, but that the current epidemiological data which specifically studied the incidence of autism over time was not strong enough to draw conclusions.

While there’s no epidemic, there is the real issue of the genuinely increasing prevalence.  Why the rise in those numbers?  Fombonne went on to explain, “There is good evidence that changes in diagnostic criteria, diagnostic substitution, changes in the policies for special education, and the increasing availability of services are responsible for the higher prevalence figures.”[7]  Nature published a graph from the work of Professor Peter Bearman, showing that 54% of the rise in the prevalence of autism could be explained by the refining of the diagnosis, greater awareness, an increase in the parental age, and clustering of cases in certain geographic areas.

Weintraub, K., Autism counts. Nature, 2011. 479(7371): 22-4. (Adapted from King, M. and Bearman, P., Diagnostic change and the increased prevalence of autism. International Journal of Epidemiology, 2009. 38(5): 1224-34 AND King, M.D. and Bearman, P.S., Socioeconomic Status and the Increased Prevalence of Autism in California. Am Sociol Rev, 2011. 76(2): 320-46.)

Weintraub, K., Autism counts. Nature, 2011. 479(7371): 22-4. (Adapted from King, M. and Bearman, P., Diagnostic change and the increased prevalence of autism. International Journal of Epidemiology, 2009. 38(5): 1224-34 AND King, M.D. and Bearman, P.S., Socioeconomic Status and the Increased Prevalence of Autism in California. Am Sociol Rev, 2011. 76(2): 320-46.)

From Nature: “The fact that he still cannot explain 46% of the increase in autism doesn’t mean that this ‘extra’ must be caused by new environmental pollutants, Bearman says. He just hasn’t come up with a solid explanation yet. ‘There are lots of things that could be driving that in addition to the things we’ve identified,’ he says.”[11]

There is no autism epidemic, just medical science and our population realising just how common autism is as the definition becomes more refined, people become more aware, and some other biosocial factors come into play.

What can we take from the numbers?  That we’re being overtaken by Sheldon clones?  That soon there will be no more “charming little extroverts”?  If the CDC figure is accurate, then one person in every hundred is on the spectrum, so the world is hardly being overtaken by autism.  But the take home message is that Autism Spectrum Disorders are more common that we ever thought, and there are more people on the spectrum “hiding in plain sight”.  If the study from South Korea is accurate then one person in every thirty-eight is on the spectrum, but two thirds of them are undiagnosed.

Should there be more funding, more resources, or more political representation for people on the spectrum?  Perhaps, although the public and research funds are not unlimited, and other health concerns should also be treated fairly.  But since autism is life long and impacts on so many areas of mental health and education, understanding autism and managing it early could save governments billions of dollars into the future.

Rather, I think that the climbing prevalence of ASD is a clarion call for understanding and tolerance.  If we learn to tolerate differences and practice discretionary inclusion, then both the autistic and the neuro-typical can benefit from the other.  That’s a world which we’d all like to live.

REFERENCES

1. Bolt, A. If the autistic don’t get full cover, where’s the money going? 2013  2013 May 11]; Available from: http://blogs.news.com.au/heraldsun/andrewbolt/index.php/heraldsun/comments/if_the_autistic_dont_get_full_cover_wheres_the_money_going/.

2. Rimland, B., The autism epidemic, vaccinations, and mercury. Journal of Nutritional and Environmental Medicine, 2000. 10(4): 261-6.

3. Attwood, T., The Autism Epidemic: Real or Imagined, in Autism Aspergers Digest2000, Future Horizons Inc: Arlington, TX.

4. Schoenborn, B. and Snyder, R., Physician Assistant Exam For Dummies. 2012: John Wiley & Sons.

5. Pitt, C.E. Autism Series 2013 – Part 2: The History Of Autism. 2013  [cited 2013 2013 Aug 15]; Available from: http://cedwardpitt.com/2013/08/15/autism-series-2013-part-2-the-history-of-autism/.

6. Rice, C.E., et al., Evaluating Changes in the Prevalence of the Autism Spectrum Disorders (ASDs). Public Health Reviews. 34(2).

7. Fombonne, E., Epidemiology of pervasive developmental disorders. Pediatric research, 2009. 65(6): 591-8.

8. Baio, J., Prevalence of Autism Spectrum Disorders: Autism and Developmental Disabilities Monitoring Network, 14 Sites, United States, 2008. Morbidity and Mortality Weekly Report. Surveillance Summaries. Volume 61, Number 3. Centers for Disease Control and Prevention, 2012.

9. Kim, Y.S., et al., Prevalence of autism spectrum disorders in a total population sample. American Journal of Psychiatry, 2011. 168(9): 904-12.

10. “Epidemic vs Pandemic”. 2013  [cited 2013 Sept 03]; Available from: http://www.diffen.com/difference/Epidemic_vs_Pandemic.

11. Weintraub, K., Autism counts. Nature, 2011. 479(7371): 22-4.

 

Dr Caroline Leaf – Contradicted by the latest research

UPDATE (14 August 2014):
An in-depth critical analysis of the work of Dr Leaf is now available for free: “HOLD THAT THOUGHT, Reappraising the work of Dr Caroline Leaf” – https://www.smashwords.com/books/view/466848

Mr Mac Leaf, the husband of Dr Caroline Leaf, kindly took the time to respond to my series of posts on the teachings of Dr Leaf at Kings Christian Centre, on the Gold Coast, Australia, earlier this month. As I had intended, and as Mr Leaf requested, I published his  reply, complete and unabridged (here).

This blog is my reply.  It is heavily researched and thoroughly referenced.  I think it’s fair to say that while Dr Leaf draws her conclusions from some scientific documents, there is more than enough research that contradicts her statements and opinions.  I have only listed a small fraction, and only on some of the points she raised.

In fairness, the fields of neurology and neuroscience are vast and rapidly expanding, and it is impossible for one person to cover all of the literature on every subject.  This applies to myself and Dr Leaf.  However, I believe that the information I have read, and referenced from the latest peer-reviewed scholarly works, do not support Dr Leaf’s fundamental premises.  If I am correct, then the strength and validity of Dr Leaf’s published works should be called into question.

As before, I welcome any reply or rebuttal that Dr Leaf wishes to make, which I will publish in full if she requests.  In the interests of healthy public debate, and encouraging people to make their own informed decisions on the teachings of Dr Leaf, any comments regarding the response of Mr Leaf, Dr Leaf or myself, are welcome provided they are constructive.

This is a bit of a lengthy read, but I hope it is worthwhile.

Dear Mr Leaf,

Thank you very much for taking the time out to reply to some of the points raised in my blog.  I am more than happy to publish your response, and to publish any response you wish to make public.

ON INFORMED DECISIONS

I published my blog posts to open up discussion on the statements made by Dr Leaf at the two meetings that I attended at Kings Christian Centre on the Gold Coast.  As you rightly point out, people should be able to make informed decisions.  A robust discussion provides the information required for people to make an informed choice.  Any contributions to this discussion from either yourself or Dr Leaf would be most welcome.

I apologise if you interpreted my blogs as judgemental, or if you believe there are any misunderstandings.  You may or may not have read my final two paragraphs from the third post, in which I acknowledged that I may have misunderstood where she was coming from, but that I would welcome her response.  If there were any misunderstandings, it is likely because Dr Leaf did not make any attempt to reference any of the statements she made on the day.  You may argue that she was speaking to a lay audience, and referencing is therefore not necessary.  However, I have been to many workshops for the lay public by university professors, who have extensively referenced their information during their presentations.  A lay audience does not preclude providing references.  Rather, it augments the speakers authority and demonstrates the depth of their knowledge on the subject at hand.

YOUR DEFENCE

It’s interesting that you feel the need to resort to defence by association, and Ad Hominem dismissal as your primary counter to the points I raised.

Can you clarify how attending the same university as Dr Christaan Barnard, or a Nobel laureate, endorses her arguments or precludes her from criticism?  I attended the University of Queensland where Professor Ian Frazer was based.  He developed the Human Papilloma Virus vaccine and was the 2006 Australian of the Year.  Does that association enhance my argument?

Can you also clarify why a reference from a colleague was preferred to letting Dr Leaf’s statements and conclusions speak for themselves?  Dr Amua-Quarshie’s CV is certainly very impressive, no doubt about that, although he doesn’t list the papers he’s published.  (I’m assuming that to hold the title of Adjunct Professor, he’s published peer-reviewed articles.  Is he willing to list them, for the record?)

Whatever his credentials, his endorsement means very little, since both Dr Leaf and Dr Amua-Quarshie would know from their experience in research that expert opinion is one of the lowest forms of evidence, second worst only to testimonials [1].  Further, both he and Dr Leaf are obviously close friends which introduces possible bias.  His endorsement is noteworthy, but it can not validate every statement made by Dr Leaf.  Her statements should stand up on their own through the rigors of critical analysis.

On the subject of evidence, disparaging your critics is not a substitute for answering their criticism.  Your statement, “By your comments it is obvious that you have not kept up to date with the latest Scientific research” is an assumption that is somewhat arrogant, and ironic since Dr Leaf is content to use superseded references dating back to 1979 to justify her current hypotheses.

DR LEAF’S EVIDENCE

In the blog to which you referred, Dr Leaf makes a number of statements that are intended to support her case.  These include the following.

“A study by the American Medical Association found that stress is a factor in 75% of all illnesses and diseases that people suffer from today.”  She fails to reference this study.

“The association between stress and disease is a colossal 85% (Dr Brian Luke Seaward).”   But again, she fails to reference the quote.

“The International Agency for Research on Cancer and the World Health Organization has concluded that 80% of cancers are due to lifestyles and are not genetic, and they say this is a conservative number (Cancer statistics and views of causes Science News Vol.115, No 2 (Jan.13 1979), p.23).”  It’s good that she provides a reference to her statement.  However, referencing a journal on genetics from 1979 is the equivalent of attempting to use the land-speed record from 1979 to justify your current preference of car.  The technology has advanced significantly, and genetic discoveries are lightyears ahead of where they were more than three decades ago.

“According to Dr Bruce Lipton (The Biology of Belief, 2008), gene disorders like Huntington’s chorea, beta thalassemia, cystic fibrosis, to name just a few, affect less than 2% of the population. This means the vast majority of the worlds population come into this world with genes that should enable the to live a happy and healthy life. He says a staggering 98% of diseases are lifestyle choices and therefore, thinking.”  Even if it’s true that Huntingtons, CF etc account for 2% of all illnesses, they account for only a tiny fraction of genetic disease.  And concluding that the remaining 98% must therefore be lifestyle related is overly simplistic.  It ignores the genetic influence on all other diseases, other congenital, and environmental causes of disease.  I will fully outline this point soon.

Similarly, “According to W.C Willett (balancing lifestyle and genomics research for disease prevention Science (296) p 695-698, 2002) only 5% of cancer and cardiovascular patients can attribute their disease to hereditary factors.”  Science is clear that genes play a significant role in the development of cardiovascular disease and most cancers, certainly greater than 5%.  Again, I will discuss this further soon.

“According to the American Institute of health, it has been estimated that 75 – 90% of all visits to primary care physicians are for stress related problems (http://www.stress.org/americas.htm). Some of the latest stress statistics causing illness as a result of toxic thinking can be found at: http://www.naturalwellnesscare.com/stress-statistics.html”  These websites not peer-reviewed, and both suffer from a blatant pro-stress bias.

You’ll also have to forgive my confusion, but Dr Leaf also wrote, “Dr H.F. Nijhout (Metaphors and the Role of Genes and Development, 1990) genes control biology and not the other way around.”  So is she saying that genes DO control development?

EVIDENCE CONTRADICTING DR LEAF

Influence Of Thought On Health

Dr Leaf has categorically stated that “75 to 98% of all illnesses are the result of our thought life” on a number of occasions.  She repeated the same statement in her most recent book so it is something she is confident in.  However, in order to be true, this fact must be consistent across the whole of humanity.

And yet, in a recent peer-reviewed publication, Mara et al state, “At any given time close to half of the urban populations of Africa, Asia, and Latin America have a disease associated with poor sanitation, hygiene, and water.” [2]  Bartram and Cairncross write that “While rarely discussed alongside the ‘big three’ attention-seekers of the international public health community—HIV/AIDS, tuberculosis, and malaria—one disease alone kills more young children each year than all three combined. It is diarrhoea, and the key to its control is hygiene, sanitation, and water.” [3]  Hunter et al state that, “diarrhoeal disease is the second most common contributor to the disease burden in developing countries (as measured by disability-adjusted life years [DALYs]), and poor-quality drinking water is an important risk factor for diarrhoea.” [4]

Toilets and clean running water have nothing to do with stress or thought.  We live in a society that essentially prevents more than half of our illnesses because of internal plumbing, with additional benefits from vaccination and population screening.  If thoughts have any effect on our health, they are artificially magnified by our clean water and sewerage systems.  Remove those factors and any effects of thought on our health disappear from significance.  Dr Leaf’s assertion that 75 to 98% of human illness is thought-related is a clear exaggeration.

Let me be clear – I understand the significance of stress on health and the economy, but it is not the cause of 75-98% of all illnesses.  I’m not sure if there is a similar study in the US, but the latest Australian data suggests that all psychological illness only counts for 8% of visits to Australian primary care physicians [5].

In terms of cancer, I don’t have time to exhaustively list every cancer but of the top four listed in the review “Cancer Statistics 2013” [6] , here are the articles that list the gene x environment interactions:

  1. PROSTATE – There are only two risk factors for prostate cancer, familial aggregation and ethnic origin. No dietary or environmental cause has yet been identified [7].  It is most likely caused by multiple genes at various loci [8].
  2. BREAST – Genes make up 25% of the risk factors for breast cancer, and significantly interacted with parity (number of children born) [9].
  3. LUNG/BRONCHUS – Lung cancer is almost exclusively linked to smoking, but nicotine addiction has a strong hereditary link (50-75% genetic susceptibility) [10].
  4. COLORECTUM – Approximately one third of colorectal cancer is genetically linked [11].

So the most common cancer is not linked to any environmental factors at all, and the others have genetic influences of 25% to more than 50%.  This is far from being 2% or 5% as Dr Leaf’s sources state.

Also in terms of heart disease, the INTERHEART trial [12] lists the following as significant risk factors, and I have listed the available gene x environment interaction studies that have been done on these too:

  1. HIGH CHOLESTEROL – Genetic susceptibility accounts for 40-60% of the risk for high cholesterol [13].
  2. DIABETES – Genetic factors account for 88% of the risk for type 1 diabetes [14].  There is a strong genetic component of the risk of type 2 diabetes with 62-70% being attributable to genetics [15, 16].
  3. SMOKING – nicotine addiction has a strong hereditary link (50-75% genetic susceptibility) [10].
  4. HYPERTENSION – While part of a much greater mix of variables, genetics are still thought to contribute between 30% and 50% to the risk of developing high blood pressure [17].

So again, while genes are a part of a complex system, it is clear from the most recent evidence that genetics account for about 50% of the risk for cardiovascular disease, which again is a marked difference between the figures that Dr Leaf is using to base her assertions on.

Atrial Natriuretic Peptide

I am aware of research that’s studied the anxiolytic properties of Atrial Natriuretic Peptide.  For example, Wiedemann et al [18] did a trial using ANP to truncate panic attacks.  However, these experiments were done on only nine subjects, and the panic attacks were induced by cholecystokinin.  As such, the numbers are too small to have any real meaning.  And the settling is completely artificial.  Just as CCK excretion does not cause us all to have panic attacks every time we eat, ANP does not provide anxiolysis in normal day to day situations.  Besides, if ANP were really effective at reducing anxiety, then why do people suffering from congestive cardiac failure, who have supraphysiological levels of circulating ANP [19] , also suffer from a higher rate of anxiety and panic disorders than the general population? [20]

The Heart As A Mini-Brain

As for Heartmath, they advance the notion of the heart being a mini-brain to give themselves credibility.  It’s really no different to an article that I read the other day from a group of gut researchers [21] – “‘The gut is really your second brain,’ Greenblatt said. ‘There are more neurons in the GI tract than anywhere else except the brain.’”  The heart as a mini-brain and the gut as a mini-brain are both figurative expressions.  Neither are meant to be taken literally.  I welcome Dr Leaf to tender any further evidence in support of her claim.

Hard-Wired For Optimism

As for being wired for optimism, the brain is likely pre-wired with a template for all actions and emotions, which is the theory of protoconsciousness [22].  Indeed, neonatal reflexes often reflect common motor patterns.  If this is true, then the brain is pre-wired for both optimism and love, but also fear.  This explains the broad role of the amygdala in emotional learning [23] including fear learning.  It also means that a neonate needs to develop both love and fear.

A recent paper showed that the corticosterone response required to learn fear is suppressed in the neonate to facilitate attachment, but with enough stress, the corticosterone levels build to the point where amygdala fear learning can commence [24].  The fear circuits are already present, only their development is suppressed.  Analysis of the cohort of children in the Bucharest Early Intervention Project showed that negative affect was the same for both groups.  However positive affect and emotional reactivity was significantly reduced in the institutionalised children [25].  If the brain is truly wired for optimism and only fear is learned, then positive emotional reactivity should be the same in both groups and the negative affect should be enhanced in the institutionalised cohort.  That the result is reversed confirms that neonates and infants require adequate stimulation of both fear and love pathways to grow into an emotionally robust child, because the brain is pre-wired for both but requires further stimulation for adequate development.

The Mind-Brain Link

If the mind controls the brain and not the other way around as Dr Leaf suggests, why do anti-depressant medications correct depression or anxiety disorders?  There is high-level evidence to show this to be true [26-28].  The same can be said for recent research to show that medications which enhance NDMA receptors have been shown to improve the extinction of fear in anxiety disorders such as panic disorder, OCD, Social Anxiety Disorder, and PTSD [29].

If the mind controls the brain and not the other way around as Dr Leaf suggests, why do some people with acquired brain injuries or brain tumours develop acute personality changes or thought disorders?  Dr Leaf has done PhD research on patients with closed head injuries and treated them in clinical settings according to her CV.  She must be familiar with this effect.

One can only conclude that there is a bi-directional effect between the brain and the stream of thought, which is at odds with Dr Leaf’s statement that the mind controls the brain and not the other way around.

FURTHER CLARIFICATION

One further thing.  Can you clarify which of Dr Leaf’s peer-reviewed articles have definitively shown the academic improvement in the cohort of 100,000 students, as you and your referee have stated?  And can you provide a list of articles which have cited Dr Leaf’s Geodesic Information Processing Model?  Google Scholar did not display any articles that had cited it, which must be an error on Google’s part.  If her theory is widely used as you say, it must have been extensively cited.

I understand that you are both busy, but I believe that I have documented a number of observations, backed by recent peer-reviewed scientific literature, which directly contradict Dr Leaf’s teaching.  I have not had a chance to touch on many, many other points of disagreement.

For the benefit of Dr Leaf’s followers, and for the scientific and Christian community at large, I would appreciate your response.

I would be grateful if you could respond to the points raised and the literature which supports it, rather than an Ad Hominem dismissal or further defense by association.

Dr C. Edward Pitt

REFERENCES

1. Fowler, G., Evidence-based practice: Tools and techniques. Systems, settings, people: Workforce development challenges for the alcohol and other drugs field, 2001: 93-107.

2. Mara, D., et al., Sanitation and health. PLoS Med, 2010. 7(11): e1000363.

3. Bartram, J. and Cairncross, S., Hygiene, sanitation, and water: forgotten foundations of health. PLoS Med, 2010. 7(11): e1000367.

4. Hunter, P.R., et al., Water supply and health. PLoS Med, 2010. 7(11): e1000361.

5. FMRC. Public BEACH data. 2010  16JUL13]; Available from: <http://sydney.edu.au/medicine/fmrc/beach/data-reports/public&gt;.

6. Siegel, R., et al., Cancer statistics, 2013. CA Cancer J Clin, 2013. 63(1): 11-30.

7. Cussenot, O. and Valeri, A., Heterogeneity in genetic susceptibility to prostate cancer. Eur J Intern Med, 2001. 12(1): 11-6.

8. Alberti, C., Hereditary/familial versus sporadic prostate cancer: few indisputable genetic differences and many similar clinicopathological features. Eur Rev Med Pharmacol Sci, 2010. 14(1): 31-41.

9. Nickels, S., et al., Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors. PLoS Genet, 2013. 9(3): e1003284.

10. Berrettini, W.H. and Doyle, G.A., The CHRNA5-A3-B4 gene cluster in nicotine addiction. Mol Psychiatry, 2012. 17(9): 856-66.

11. Hutter, C.M., et al., Characterization of gene-environment interactions for colorectal cancer susceptibility loci. Cancer Res, 2012. 72(8): 2036-44.

12. Yusuf, S., et al., Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet, 2004. 364(9438): 937-52.

13. Asselbergs, F.W., et al., Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci. Am J Hum Genet, 2012. 91(5): 823-38.

14. Wu, Y.L., et al., Risk factors and primary prevention trials for type 1 diabetes. Int J Biol Sci, 2013. 9(7): 666-79.

15. Ali, O., Genetics of type 2 diabetes. World J Diabetes, 2013. 4(4): 114-23.

16. Murea, M., et al., Genetic and environmental factors associated with type 2 diabetes and diabetic vascular complications. Rev Diabet Stud, 2012. 9(1): 6-22.

17. Kunes, J. and Zicha, J., The interaction of genetic and environmental factors in the etiology of hypertension. Physiol Res, 2009. 58 Suppl 2: S33-41.

18. Wiedemann, K., et al., Anxiolyticlike effects of atrial natriuretic peptide on cholecystokinin tetrapeptide-induced panic attacks: preliminary findings. Arch Gen Psychiatry, 2001. 58(4): 371-7.

19. Ronco, C., Fluid overload : diagnosis and management. Contributions to nephrology,. 2010, Basel Switzerland ; New York: Karger. viii, 243 p.

20. Riegel, B., et al., State of the science: promoting self-care in persons with heart failure: a scientific statement from the American Heart Association. Circulation, 2009. 120(12): 1141-63.

21. Arnold, C. Gut feelings: the future of psychiatry may be inside your stomach. 2013  [cited 2013 Aug 22]; Available from: http://www.theverge.com/2013/8/21/4595712/gut-feelings-the-future-of-psychiatry-may-be-inside-your-stomach.

22. Hobson, J.A., REM sleep and dreaming: towards a theory of protoconsciousness. Nat Rev Neurosci, 2009. 10(11): 803-13.

23. Dalgleish, T., The emotional brain. Nat Rev Neurosci, 2004. 5(7): 583-9.

24. Landers, M.S. and Sullivan, R.M., The development and neurobiology of infant attachment and fear. Dev Neurosci, 2012. 34(2-3): 101-14.

25. Bos, K., et al., Psychiatric outcomes in young children with a history of institutionalization. Harv Rev Psychiatry, 2011. 19(1): 15-24.

26. Arroll, B., et al., Antidepressants versus placebo for depression in primary care. Cochrane Database Syst Rev, 2009(3): CD007954.

27. Soomro, G.M., et al., Selective serotonin re-uptake inhibitors (SSRIs) versus placebo for obsessive compulsive disorder (OCD). Cochrane Database Syst Rev, 2008(1): CD001765.

28. Kapczinski, F., et al., Antidepressants for generalized anxiety disorder. Cochrane Database Syst Rev, 2003(2): CD003592.

29. Davis, M., NMDA receptors and fear extinction: implications for cognitive behavioral therapy. Dialogues Clin Neurosci, 2011. 13(4): 463-74.