the sinister plans of southpaws

Sinister is an English word, commonly associated with evil.  Its roots go way back to the Latin word- sinistra- originally meant "left" but by the classical Latin era, took on the meaning of "evil" or "unlucky".  In addition, there are countless myths and superstitions concerning the left side.
Left foot first out of the bed or getting out of the bed's left side= bad day / bad mood
OR ringing in right ear=someone is praising you. Left side? Someone is cursing you
OR an itchy right palm means you'll receive money. Left side? Sorry, you'll dish out moolah

Poor lefties.  Not only are there numerous negative associations, most things are designed for the common righty, often making things uncomfortable and annoying and even dangerous if dealing with power tools and heavy machinery.

In spite of the prejudices and inconveniences, lefties make up 8-15% of the world's population.
Surely, it can't be all that bad if so many are left or mixed handed?!  
Sadly, being left-handed may have even more problems.  Comoridity has been found between lefties, Schizophrenia, Bipolar Disorder, Autoimmune diseases, Autism and Irritable Bowel syndrome. That's quite a few things that  seem to increase the chances that one is left hand dominant:

1.) A team at Oxford University found that a gene called LRRTM1 seems to increase the chance of being left-handed and may also increase the risk of developing schizophrenia.
2.) Gerschwind and Behan found in the early 80's that there was a higher frequency of immune diseases, migranes and developmental disorders among left-handed individuals.
3.) In 2000, research suggested a link between Inflammatory bowel diseases such as Crohn's disease and Ulcerative colitis and left handedness.
4.) Researchers in 2005, found an association between IBS and left-handedness.
5.) Another 80's study found in albeit a small sample, that 62% of the children diagnosed with infantile autism were left-handed, while only 37% of controls (non-ASD kids) were left-handed (which is still higher than the global average).

People search for patterns. For meaning. Is it possible that the negative associations with the "left" weren't quite so unfounded as one might think.  Perhaps people noticed that individuals who displayed strange behaviors (like that of a developmentally delayed, schizophrenic, or autistic person), were often left-handed.  Its fair to say that people with Crohn's disease, ulcerative colitis, IBS, migranes and other auto-immune diseases would have been viewed as unlucky (see earlier definition for "left").  Perhaps a similar association was noticed between chronic illness and left handedness.

Yet in spite of the prejudices and the psychological/behavioral/physical risks that seem to be more prevalent among lefties, their prevalence has stayed around 10%.  Do we see a relatively stable percentage of south paws because they just might have some awesome advantages?

Well, there are some pretty awesome people who are/were lefties: Barack Obama, Bill Gates, Oprah Winfrey, Babe Ruth, Leonardo da Vinci, Marie Curie, Aristotle, Jimi Hendrix and many more.  Some have found people that are left handed are better at divergent thinking and developing new concepts.  Two of 4 studies results found that men who were left handed had higher divergent thinking scores.

Could there be a neurological explanation for the divergent thinking?  Some have speculated that differences in brain lateralization, the specialization of each hemisphere of the brain, might have something to do with it.  Dr. Stephen Williams was not convinced however.  He only found modest differences- that the left side is dominant for language in righties ~95% of the time but only 70% of the time for lefties.  The remaining 30% are either right dominant or used both.

Hmm... brain lateralization doesn't explain it all.    In the Table below, you can see an increase in % when a parent is a lefty too, supporting a hereditary link.  Both parents being left handed more that doubles the percentage of sons or daughters that are left-handed.  If the mother is the only parent who is left-handed, it increases the % or lefties, especially for sons.

Could androgens be a factor? Remember, it was only the left handed men who had higher scores and also, in general more men are left handed.  The common androgen steroid, testosterone is normally inhibited by cortisol but in the fetus, there is a positive link between the two.  Dr. Obel of Aarhus University studied 834 Danish mothers and discovered that a stressful event (triggering cortisol) during the 3rd trimester, increased more than 3X the chance of the having a mixed-handed child.

In addition to life stressors, autoimmune diseases affect cortisol and testosterone levels.  A higher incidence of autoimmune diseases in left hander's families plus the observation that lefties were even more strongly left handed when they had an immune disease points to the influence of testosterone and cortisol.  The connections between schizophrenia and celiac's disease as well as the link between autoimmune diseases and autism show how many different ways, inflammation may manifest.

Could cortisol and testosterone  be involved in Autism as well? Indeed. Research found that Asperger children may dislike changing their routine because of their difference in cortisol levels.  Another study found that testosterone exposure in the womb increases the likelihood of developing autistic traits.
Recently, an opinion article in The New York Times discussed the link between immunity and autism disorders.  One of the most striking things I read was her mention of a Danish study of almost 700,000 births over a decade.  A mother with rheumatoid arthritis increased a child's risk of autism by 80 percent and a mother with celiac disease increased the child's risk 350 percent. Another study found that gene variants seen in those with autoimmune diseases, also increased the risk of autism... again, especially when found in... the mother.

Let's dig even deeper and see what might genetically lay at the heart of inflammation.  The Major histocompatibility complex (MHC) is on the short arm of Chromosome 6 and has been extensively studied because of the many variants at this genetic locus in autoimmune, infectious and inflammatory diseases.  Identifying the disease causing variants within the MHC is difficult given the variability (classical class I- HLA-A, -B, -C and classical II- HLA-DRB1, -DQA1, -DQB1 and classical III).  Research has found some interesting overlaps between the variations in genes involving immunity and Ulcerative colitis (UC), Celiac's Disease (CD), Rheumatoid Arthritis (RA), Lupus (SLE), Type I Diabetes (T1D), and Multiple Sclerosis (MS). 

 (Figure 3) Defining the Role of the MHC in Autoimmunity: A Review and Pooled Analysis. 

Studies on Asian and European populations found that variations in immunity(MHC) were also involved in schizophrenia and bipolar disorder.   MHC associations have been with the null allele C4B of class III and Autism.  I can't help but wonder if associations could be found between handedness and MHC.  Wondering for now is moot.  We need to know more about the implications of the MHC variations.

What a tangled web we weave or rather, what a big fucking mess. We know genes may make us more vulnerable and environmental factors such as pathogens, societal norms, diet, and stressors, play a role in mood disorders, schizophrenia, bipolar disorder, autoimmune diseases, autism and handedness.

But why should we strive to understand not just how things work but why things happen?
Increased awareness, testing or social acceptance doesn't entirely account for the growing numbers of Autoimmunity, Autism and Left handedness .   With medical expenses soaring, certainly more research into the epidemiology and etiology of these immunity related diseases is warranted.

Back to just the southpaws.  Variations in handedness may be more than just an example of evolution promoting diversity and just maybe, southpaws are bigger players in the game called life. We shouldn't be so quick to dismiss the power of the minority's behaviors and attitudes...

What does it take for an idea to spread?  A study found a tipping point.  Only a mere 10% of a population needs to be committed to an idea for it to spread to the entire group.  Recall that roughly 10% of the population is not right handed.  Could those correlates of left handedness to hormones, inflammation, divergent thinking, schizophrenia, autism, autoimmune diseases, mood disorders coalesce into certain beliefs and attitudes that compose more than 10% of the population?

My guess is yes.  And I'd also put my money on that "left" thinkers have influenced social and political changes but to what extent have their perspectives shaped our economy, politics, religion, culture, arts, sciences, fears and hopes?
Here's an interesting lil factoid: Seventy-one percent, 5 of the last 7 presidents have been lefties... including our current president.
Fox News might be right.
Barack Obama probably is pushing his "left" agenda...
left-handed, that is.

So there you have it.  A lot of overlapping research and a lil stretching.  The evidence is clear...


The lefties' evil plot to destroy the world shall commence December 21, 2012.

The incidence of left-handedness: a meta-analysis:

playing god

i remember my first PG-13 movie in theatres.  I was 7 years old and saw Jurassic Park with my dad and cousin.  I was mesmerized (and in parts, quite horrified).  Even then, I was able to take away the lesson that man needs to be careful when screwing around with nature.

“Because the history of evolution is that life escapes all barriers. Life breaks free. Life expands to new territories. Painfully, perhaps even dangerously. But life finds a way.” 
― Michael Crichton, Jurassic Park

Ian Malcolm: From Chaos  by John Larriva & more Jurassic Park inspired art: http://brandonbird.com/jp_show.html

this past spring, i decided to take an online genetics course.  again and again, discussions of ethics came up and  naturally, i resumed thoughts on 'playing god' and of course, jurassic park.

one of the topics that came up was genetic testing for trisomy 21. down syndrome.  if you can prevent it, should you?  many disorders/ diseases aren't so clear cut.  more than likely, you'll hear there is both a genetic and environmental component.  however, more and more research is finding that certain anomalies, SNPs and allele variations may put one at a higher risk for diseases and disorders.  but if you could prevent it... should you?

per usual, Emily Deans, M.D. posted an interesting read on the counter intuitive nature of depression.

Depression- A Deal with the Devil, begins with allele 308A that is associated with an increased risk of depression.  What's curious is that it is also associated with a decreased risk of tuberculosis which would have been quite advantageous before modern medicine.  that allele variant also decreases one's risk for parovirus B19, hepatitis B and for some reason, lowers risk of death when hospitalized when seriously sick.

another area of interest is apolipoproteins.  they are proteins that bind lipids such as fat and cholesterol, forming lipoproteins that then carry the lipids throughout the lymphatic and circulatory systems.  again we find that certain alleles put one both at risk but also at an advantage.  people with the ancestral allele, ApoE4 are more susceptible to Alzheimer's and depression but then instead, are protected against childhood diarrheal illnesses, which were often lethal.  unlike ApoE4, the ApoE2 allele seems to be protective against general inflammation but leaves one more vulnerable to tuberculosis and malaria.

one of the first found genetic correlates with depression and the most studied, are alleles associated with 5HTTLPR.  this gene is what tells cells to make serotonin transporters. any psychology major will tell you, serotonin is kind of a big deal.  we know that serotonin and dopamine are involved in mental health but why people have low/high levels of certain neurotransmitters is the far more interesting question (and more difficult to unravel).

those with one and especially two short alleles are more susceptible to depression after trauma but seem to have a lower risk of dying from SIDs (sudden infant death syndrome).  another interesting tidbit is that those individuals with either 1 or 2 short alleles, respond with more cytokines to stress which would have been adaptive in a pre-modern medicine world when one was wounded/ infected.  it shouldn't be surprising then that in areas where epidemic infections are more common, the short allele is more common among inhabiting populations.

in addition to the sneaky evolutionary benefits of depression Emily Deans, M.D. addressed, creativity has often gone hand in hand with melancholy.  many studies have found an increased rate of bipolar and depressive illnesses in highly creative individuals.  its not really a case of mental illness causing creativity or the creative mind making one prone to mood disorders. its more likely that the genes that influence obsessive tendencies, rumination, abstract thought, etc. that coalesce into creativity, are also what make one more vulnerable to mood and anxiety disorders.

would john nash (a beautiful mind) have had such a beautiful mind without his schizophrenia? perhaps it was the surplus of dopamine that influenced his theories that today are so frequently used in areas such as market economics, computing, evolutionary bio, AI, accounting, politics and military theory.

would actors, artists, comedians and writers be better off without their struggles with mood disorders or is it those struggles that have ultimately make them so damn good at what they do?

what makes us susceptible to one thing, gives us an advantage for another.  in the game of evolution, all that (genetically) matters is being able to survive until reproductive age. what may have been adaptive 100, 1,000, 10,000 or 100,000 years ago may not be quite so beneficial today.  we must be weary when attempting to assign good/bad judgements to traits and genes. genetics has come a long way and has a long way to go yet.

it's not enough to know what genes do.  WHY things happen is the far more important question.  before we even think about playing god and manipulating genes, it's imperative that we understand the evolutionary reasons why we are the way we are.  if we get too hasty, we just might find some unintended consequences.

after all, the road to hell was paved with good intentions.


interesting & FREE read:
The Evolutionary Significance of Depression in Pathogen Host Defense (PATHOS-D)
http://www.nature.com/mp/journal/vaop/ncurrent/pdf/mp20122a.pdf

more info:

http://en.wikipedia.org/wiki/List_of_people_with_bipolar_disorder
http://en.wikipedia.org/wiki/Major_depressive_disorder

http://en.wikipedia.org/wiki/John_Forbes_Nash,_Jr.

http://en.wikipedia.org/wiki/5-HTTLPR

http://en.wikipedia.org/wiki/Apolipoprotein
http://en.wikipedia.org/wiki/List_of_people_with_major_depressive_disorder
http://en.wikipedia.org/wiki/Unintended_consequences
http://www.ncbi.nlm.nih.gov/pubmed/18689294

http://www.psychologytoday.com/blog/evolutionary-psychiatry/201208/depression-deal-the-devil?