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DRD4 Genes Explained – Why Curiosity and Creativity?

DRD4 Genes Explained – Why Curiosity and Creativity?
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Genes for Curiosity, Flexibility, Creativity… and Fun?  

Some of the most steadfast and dedicated researchers are children, who ask “Why?” and “Why?” and “Why?” again. They keep asking questions long after their parents run out of answers. Children are born passionately curious, with natural awe for everything; they have fun and jump for joy. It’s all in our genes. Instincts for wonder, bliss, and exploration motivate us to learn more and more, play while we’re learning, and remember what we’ve learned. If we keep our childlike instincts for curiosity, flexibility, creativity, and fun switched on throughout our lives, we will have discovered the healing spring that restores us, a Lifelong Fountain of Youth.  

One gene most closely associated with curiosity, the DRD4 gene on Chromosome 11, guides the desire to learn and remember through the release of the motivating neurotransmitter dopamine. Increased dopamine levels give us a warm glow, as a reward for being curious. Learning something new might have killed the cat, but it makes us humans feel good as we adapt and develop skills. The reward? Raised levels of brain dopamine that result stick around long enough to keep us asking more questions. No small wonder that children are excited about learning.

A gene variant of DRD4, DRD4-7R, found in only 20% of the population, has been linked with greater degrees of curiosity, change, movement, adventure, novelty-seeking, and risk-taking. “Variant” genes, like the DRD4-7R gene, fine-tune behaviors with specific adaptations that further increase chances of survival. “Promoter” segments of DNA act alongside genes and combinations of genes to activate certain behaviors.  

But epi-genetically, that is, apart from genes and their “promoters,” small and transient molecular “epigenetic tags and markers” – some inherited, some produced, and some discarded – are continually modifying the expression of each gene, and each team of genes. “We all should realize that there isn’t a single gene that makes us adventurous or stick at homes,” explains Richard P. Ebstein, professor of Psychology at the National University in Singapore.

All Who Wander Are Not Lost – We’re Just Doing Research

“Play is the highest form of research,”

– Albert Einstein

Two known genetic derivatives of DRD4, its DRD4-7R and DRD4-2R variants, have been labeled “Wanderlust genes”  because they are found in populations closely associated with migration. Slight variations in the DRD4 gene tend to emphasize particular qualities of lifelong learning, variations in the asking of novel questions and quest for faraway places. Genes for higher levels of curiosity and creativity also carry higher risks of mental problems.

Behavioral qualities and mental problems, however, show no one-to-one correlation. Scientists can be brilliant, curious and creative and never go “mad.” Behaviors and genes give constant feedback to one another, each changing the other in a fluid dynamic. Complex interplays of shifting DNA sequences, thinking, learning, and the swarms of epigenetic modifiers that attach and unattached along the enormous lengths of our chromosomes make gene-behavior interactions extraordinarily complex. And then, exercise, experience, emotional health, environmental toxins, diet, and many generations of family history add their signposts that direct the 20,000 – 25,000 human genes.

Moreover, each time we wander or think new thoughts we absorb a wealth of new information, have important experiences and insights, see people and places differently, and change how those genes are expressed – if only for a time.

“Genes are only one part of the equation, and genes are not deterministic,“ stresses John McGeary, assistant professor of psychiatry and human behavior at Brown University. Like all genes, the DRD4, DRD4-7r and DRD4-2r genes can be nurtured and coaxed to fruition through love, care, “enriched environments,” and early learning experiences during windows of specific imprintings called “critical periods.”  Also, during critical periods genes that promote good health and attitudes can be thwarted, stifled into dormancy, and silenced through disuse or abuse.

Genes for disease enter into the equation if they become activated by stress, bad nutrition, and unhealthy lifestyles. In addition, bad habits can wear away the ends of chromosomes, called telomeres, killing cells prematurely and shortening lifespans.

And yet, healthy habits, positive thinking, and active lifestyles can add new epigenetic tags and markers onto our chromosomes – and erase old ones – all for the better!

The Game-Changing Discovery of Epigenetics

“Some men by the unalterable frame of their constitutions, are stout, others timorous, some confident, others modest, tractable, or obstinate, curious or careless, quick or slow.”  

– John Locke, 1693

“Basically, his whole life has been a series of re-creations of himself in various forms,”

– Robert Soros, about his father, financier/philanthropist George Soros

In the last two decades, game-changing discoveries have shown that small molecular miracle-workers come and go as attachments to our chromosomes. A great many of these attachments that control gene expression get passed on to our offspring, generation after generation. Such “epigenetic” inheritances have been traced back to important events of great-grandparents. While we inherit many different sets of epigenetic tags from our family trees, we also add new ones of our own – generated by the way we think and live, and things that happens to us each moment. Epigenetic tags and markers can be attached both directly to DNA and to the bulging histone proteins wrapped within long coils of DNA. Attachments of epigenetic tags and markers are reversible!

Consequently, neuroscience has had to reframe the concept of “gene” to include this ever-adapting “epigene.” What was considered the functional unit of a sequence of DNA, or gene, does not function independently, but in dynamic concert with millions of modifiers, attendant and complex histone proteins (nucleosomes), many dozens of varieties of RNAs, ever-shifting combinations of other long segments of DNA or genes, and shorter DNA modulator sequences called erasers, promoters, suppressors, switches, and silencers. A functional “gene,” is just one member of this all-inclusive team on our chromosomes.  

Some of the epigenetic attachments that work through histone proteins and directly onto DNA to regulate the expression of segments of DNA are with us at birth, while new ones are continually being added, just as old ones are dissolved. This reversibility happens literally at will, and with each intention. Through healthy habits and positive attitudes we each have the potential to purge the old and supplement with new attachments, collectively called our “epigenome.” With purpose and effort, we can change our epigenome game plan whenever we choose. By substituting the players (tags and markers) one at a time, we can gradually put a whole new team on the field.

Every millisecond, the way we live and how we think decides the attachments, erasures, activations, and suppressions of millions of epigenetic markers on our DNA and the operations of complex histone proteins wrapped inside. Each marker becomes a minuscule fork in our road. Acting as “writer, eraser, and reader” molecules, these minuscule miracle-workers direct the flow of activity along our 46 chromosomes.

Medical research shows that what we believe about our health, our “psychosomatic selves,” decides a minimum 30% of our physical health. Strong beliefs can actually grow large body parts and show physical symptoms that mimic eight months of pregnancy, enough to fool both doctor and patient. Whether we are born with gene variants for certain characteristics, add to them, or subtract as we go, we have the potential to constantly redefine ourselves – both mentally and physically!  

Caution! Creativity at Work!

“Twas brillig, and the slithy toves

 Did gyre and gimble in the wabe:

All mimsy were the borogoves,

 And the mome raths outgrabe.”

– Lewis Carroll, Jabberwocky

You may not recognize the words, nor the “endless associations”  in this poem – they were invented. Yet these words have to mean and come together. Like art, you know it when you see it. People of all ages appreciate creative works, innovative ideas, mental explorations, and “divergent thinking” such as Lewis Carroll’s in Alice’s Adventures in Wonderland.  Scientists at Cornell University have shown that creative artists, musicians and writers who tend toward “divergent thinking,” also tend to have smaller bundles of neural connections between their left and right brain hemispheres. A downscaling of the nerve fibers that pass between hemispheres, the corpus callosum, allows creative people to engage in better “incubation of ideas,” more independent thinking in each half of the brain.

Using different parts of our brains in different ways we each pave our paths to creativity. Neuroscientist Angelia Sutin reports that five distinct personality types show five distinct variations in their neuroanatomy. Individuals with enhanced creative abilities possess more gray matter, especially in the posterior cingulate cortex (PCC) region, a key center for awareness and “internally directed thought.”  More gray matter translates to a greater speed of thinking and greater intelligence.

A 2014 study by researchers at the Medical University of Vienna found that creative individuals maintained naturally enhanced levels of the neurotransmitter serotonin within their posterior cingulate cortex (PCC). Naturally, those with more gray matter in their PCC produce more serotonin there, increasing levels of serotonin and neural connectivity, producing greater divergent thinking.   

Creative Genius, Broad Categories, and Correlations

“My brain is only a receiver; in the Universe there is a core from which we obtain knowledge, strength and inspiration. I have not penetrated into the secrets of this core, but I know that it exists.”

– Nikola Tesla

Sometimes creative genes come with a catch. During the process of meiosis that creates egg and sperm, creative genes can become “linked” with less favorable genes located next door on the same chromosome. As genes mix and match during fertilization, neighboring genes can become “linked,” coupling up and passing on. Genius Nikola Tesla, inventor of AC current, the radio, fluorescent and neon light, X-rays, lasers, and electric motors was also known for his “obsessive-compulsive  eccentricities.

“A certain mental illness – bipolar disorder – is more prevalent in the entire group of people with artistic or scientific professions, such as dancers, researchers, photographers, and authors,” concluded a forty-year study of 1,173,763 patients at the Karolinska Institute in Sweden. “In bipolar mania, you have an excessive fast and divergent thinking, increased self-esteem, and never-ending energy and motivation, often to create,” explains psychiatrist Szabolcs Keri of Semmelweis University in Hungary. “The finding that bipolar is associated with creativity is not surprising.”

Psychiatrist Keri focused his research on neuregulin 1, a gene that strengthens the development of and communication between neurons. People with the highest creative achievements and creative-thinking scores, he discovered, carry a particular variation, a polymorphism, labeled “SNP8NRG243177/rs6994992,” of the promoter region of the neuregulin 1 gene. This promoter, that generates high creativity and achievement by prompting neuregulin 1 to be more active, comes with “an increased risk of psychosis and altered prefrontal activation.”  

If neuregulin 1 genes and variants for creativity are not already active, severe trauma could provide a tipping point. “We found that many individuals with artistic creativity suffered from severe traumas in life, whether it be psychological or physical abuse, neglect, hostility or rejection,” Keri says. Out-of-the-box experiences might be shocking creative genes into out-of-the-box activation.  

Since neuroscience has identified some of the transmitters, epigenetic mechanisms, genes, neurons, and brain regions associated with creative expression, plus some of the risks involved with carrying highly creative genes, we might consider creative intelligence an endowment, a gift that some have and some don’t. True enough, for some. Mozart wrote his first symphony at age 5. But for most of us creative talent is not a given, but must be learned and practiced.

Not only most of us, but natural-born prodigies must practice to stave off the mental rigidity that sets in with inactivity; and instead, stay open to flashes of inspiration and bursts of new ideas. Researchers from the University of Helsinki report that a “flexible mental attitude,” represented by the “breaking and forming of new synapses” between neurons, what they call the “reassembly of information we already know,”  is the key to creative flow. “How brain areas talk to each other is critical when it comes to originality, fluency, and flexibility,” adds Szabolcs Keri of the National Institute of Psychiatry and Addictions in Budapest.               

The Perks of Plasticity, a “Flexible Mental Attitude”

“… reality is purely your perception, and it’s a completely personal experience. The world as you know it only exists to you, as you are right now. Every day you wake up a new person.”  

criminal psychologist Julia Shaw

Lately, convincing evidence has been piling up: keeping an open mind helps the brain age more gracefully. Evidence also shows what courtroom lawyers have known since the first witness: that one of the most flexible brain functions is memory. It’s only human nature to continually select out what we remember, embellish, edit, and revise our recollections in favor of what is good for us in the long term. “What’s good for the person is usually good for the brain,” say psychologists Susan McFadden and Anne Basting.   

In the long run, a selective or flexible memory leads to greater self-preservation. In 1956, Warner Schaie and Sherry Willis at the University of Washington began a study that followed the progression of cognitive function in 5000 adults over a period of 40 years. Their definitive research, The Seattle Longitudinal Study of Adult Intelligence of 1998, concluded that over time a “flexible mental attitude,” as registered at midlife, was one of the most important preventatives of intellectual decline as people reached their 70s and 80s. In addition, a “complex and intellectually stimulating environment” including a spouse with “high intellectual status”  helped determine mental acuity in the last trimester of life. Even more importantly, a flexible mental attitude helps us plan, project into the future, look forward to possibilities, take initiatives, set new goals, and create new opportunities.

Mental flexibility or openness is a personality trait closely linked to curiosity and risk-taking. As we get older and accumulate more experience a part of our personality changes – not always erring on the side of caution. “It’s too often assumed that risk taking changes dramatically with age based largely on generalizations and stereotypes about more cautious older individuals,” says Yale professor of psychology and neuroscience, Dr. Gregory Samanez-Larkin.   

Findings of the German Socio-Economic Panel Longitudinal Study from 2004 to 2014 showed that while the tendency to change work situations (jump off bridges? don the wingsuit to careen the contours of canyon walls?) declines with age (ie. engage in risky recreation) – risk-taking in social interactions remains relatively constant throughout life. Risky recreation, and/or seeking out experiences that are new and different are ways to maintain exuberance and vitality, maybe toss in a few epigenetic activators for adventure? and humor, too?

 

A Funny Gene? You Can’t Be Serious?

“Gene therapy with the HAHA-1 gene could provide laughter for millions of the humor-impaired.”

– Robert Chadwick, Northhaven University

Neuroscience has discovered a few things about genes for creativity, curiosity, and mental flexibility – but what about genes for fun? Is there a gene that makes people laugh at bar jokes? Or satire, or slapstick?  

Horace Epstein, a geneticist at the Lachen Institute in Trenton, New Jersey, wanted to crack the code of what makes some people deadly serious and others the life of the party.  “We didn’t look at undertakers and politicians,” said Epstein. “To study genes for humor our team studied a large, extended family in Gobbler’s Knob, Kentucky. By comparing family members who loved Seinfeld with members who had a fondness for C-SPAN, we were able to narrow down the gene’s location to tracks of DNA sequences on the X chromosome.” Researchers then spliced those tracks of DNA sequences into “good-natured” mice and found that the “retrofitted-for-Seinfeld-humor” mice recorded an increase in their “high-pitched squeaking” when these mice watched a cartoon of an anvil being dropped on a cat.

Behavioral geneticist Epstein claims that “we can safely assume that the humor-spliced mice were laughing at the cat’s misfortune.” The gene responsible for laughter in the  Seinfeld-aficionados of Kentucky and cartoon-watching-mice in New Jersey was named the HAHA-1” gene and hailed as a major breakthrough. Robert Chadwick, a genome researcher at London’s Northhaven University believes that “gene therapy with the HAHA-1 gene could provide laughter for millions of the humor-impaired.”

If you are curious to read more, however, you will find no trace of Horace Epstein, Robert Chadwick, the Lachen Institute, nor any follow-up studies of the “HAHA-1” gene. Science writer David Grimm published this fictional report all in good fun on April 1, 2005, in Science, AAAS   

Live Long and Prosper

“It matters not how strait the gate,

     How charged with punishments the scroll,

     I am the master of my fate,

     I am the captain of my soul.”

Invictus,  William Earnest Henley

Curiosity, creativity, flexibility, and fun can be fountains of youth for inspired living at any age. Age tends to ease the angsts of life and highlight simple pleasures. With less ego on the line, seniors have less to prove. Italian researcher F.M. Antonini studied centenarians in Tuscany and narrowed down these traits of agile aging:    

 

  • To seek new goals
  • To not dwell on past accomplishments

  • To maintain curiosity

  • To keep up with the times

  • To adapt to changing circumstances

Successful seniors have settled in with who they are and what they’ve done. At the same time, they’ve stayed flexible and kept moving forward. Maybe they’ve been through hell or at least high water, but they’ve learned to leave the negatives in the rearview, look forward and high-beam the positives. They stay with us as role models, sources of encouragement and wisdom, love, kindness, and a laugh or two. Plus, they have great stories to tell.

Like Tesla said, the brain is a receiver, drawing knowledge, strength, and inspiration from the core of the universe. The more we open our minds – the more we open our hearts to that core. Genes for curiosity, flexibility, creativity, and maybe fun are important cogs in the gears that keep us vital and vigorous. But mostly, it’s us who drive the machinery and supervise the show of these lifelong fountains of youth.

“The second hundred years are better,”

– Clarice Emley, 105

 

Categories:   Brain Development, Child Development, Genetics

Published by

Burt Glenn

Burt Glenn

Burton Glenn is a former Biology and Chemistry Professor and world traveler. He studies and writes about the effects of aging on the body and mind, as well as his personal experiences transitioning into retirement.