Friday, April 29, 2016

Trolleys and Genes

Last week was school vacation week.  The family day-care was closed.  I was assigned to entertain my 2 1/2 year-old grandson; a job I welcomed. I decided to make the kid happy.  A day of bliss.
It was a cool spring day and there could be no better time for a boy of his age to ride on the MBTA, the Boston trolley and subways system.  Soon we were at the station and the Green Line Trolley came around the curve. The boy pointed and screamed with joy.  As we boarded we got a big hello from the driver.  We sat in the front seat so we could see down the track.  The doors closed, the bell rang three times and we were rolling.
A huge smile.  His eyes were open wide. And then, what’s that?  Another trolley coming in the other direction!! Trolley!  Trolley! he pointed and yelled.  The whole car shared in his delight.
He is the third of my grandchildren.  Each of my two children have an older girl and a younger boy.  The girls never cared about balls or trains.  This one is entranced by anything with a motor: trains, trucks, planes, fire engines.  The other boy, who is even younger, is all about balls.  He has about fifty of them scattered throughout his house so that wherever h is he can pick one up and throw it. Especially down the stairs.  Ball!  Ball!

On the morning that I was to go on my trolley ride I was reading an article about a molecular biologist at UCLA, T.C. Ngun, who had studied the genetic material of 47 pairs of identical twins.  Using a computerized search algorithm that scanned the genome of male twins, one of whom declared himself to be gay while the other was straight, Ngun and his team were able to find nine areas of difference between the two groups.  However, the differences were not in the gene itself, but in the epigene, the material that the body uses to get a gene to turn on and to create the chain of proteins that it is programmed to create.
What makes this even more interesting, is that the epigene often changes over time.  It responds to the environment it is in.  It could be stress, or diet, or even a close relationship. It could even be something that happens in utero.  But under different conditions will it turn a gene on, or off.  That can partially explain how two sets of genes that are identical, as they are in identical twins, turn out two very different people.

I’ve been a therapist for a long time.  I’ve had many patients who were gay, and many more who weren’t.  I began seeing people at the time when it was still dangerous to be gay.  People were often beaten, beaten by the police, just for being in gay bars.  So, not everyone was comfortable with admitting how they felt at that time, even to themselves. 
I also came to understand that the paths people walked on before they decided they were gay were very varied.  Some people realized by the time they were six that they were different, even if they couldn’t say why.  Others felt the urges much more powerfully some time during adolescence.  Many other men and women either didn’t realize their sexual preference, or covered it over in order to appear more normal, or perhaps, learned that they could feel very differently at different times in their lives. 
That is why I find it fascinating to watch the gyrations this country is going though about how to deal with transgendered people, or people who feel more comfortable thinking of themselves as of a different gender than of how they were born.  During all my time as a therapist, and with the many people I worked with who struggled to be more comfortable with their sexual feelings, I never had anyone tell me that they thought they were members of the opposite sex. But perhaps that was because they didn’t know they could.

I thought about this as I watched my grandson riding the train.  He was enrolled with the experience.  He was wearing a shirt that had airplanes on it.  When we got downtown he wanted to watch the construction machines.  These seemed like very typical boy behaviors.  The girls, who are a few years older, never cared about any of that stuff.  They are just moving out of the princess stage, but are still very aware of colors and clothes.  The girls are also very aware that they can be anything they want, and both often play games of being like their mothers, who go to meetings, run businesses, and work at their laptops.

It seems as if many of our new technologies are leading to new discoveries about who we area as people, and how we get that way.  I have been following a lot of that progress, and most of what we are learning is that things are much more complex that we thought.  As a psychologist I am not at all surpassed that our development is a complex interaction of nature and nurture.  I am a bit surprised that this interaction can take place down at the cellular level, and in our genes.
Of course it makes sense.  But it warns us that dealing with all of these tendencies and behaviors is also much more complex than many people had hoped.  It means that the results of a major life event, such as a trauma, or starvation, or a being infected by a toxin or virus, can create changes in a person’s genes, and that reversing those changes can be very difficult.  It can also mean that just giving a person a drug to change their brain, without changing their environment and social interactions, may not be very helpful.
It opens up so many questions about who is what sexually, who is what socially, what is a family, what is a race or a tribe?
Of course, I think a lot about what the world will be like when this kid grows up.  Will there still be trolleys with bells that go “ding-ding,” or just self-driving robot cars that take people exactly where they want to go.  

I am confident there will be a lot of interesting and beneficial things he will be able todo, especially if he goes into behavioral-genetics. But before I could discuss that prospect with him, he fell asleep, two stops from home.

Friday, April 15, 2016

Do You Know Where You Are?

I have patients who are very nervous about diving.  Some of them get very anxious on highways because the traffic moves so fast. Too much stimulation!!
Others are afraid that some monster truck will jump out of a hidden driveway and eat them up.  For a lot of them the underlying worry is that they will get lost.  For many, it is not a rational fear, and that can be treated. But for others it is true; they don’t know where they are, and they can’t relate where they are to other places they’ve been. There can be reasons for this; sometimes it’s trauma.  Some people just don’t want to go back there again.

There are older studies that show that men and women navigate differently.  It has been shown several times that men rely more of knowing directions, like north and south, and also distances, like three blocks or five miles. Women seem to navigate by landmarks   They go to the school and take a left and then over the hill to the church and take a right. But all that was before there were electronic GPS systems.  Now a GPS is part of almost all of our lives.  It’’s in our phones and usually connected right to the speakers in the car.  I have many friends who won’t go anywhere without asking Siri how to get to the same restaurant that they went to last week. 
My wife and I have taken several long road trips and I am still amazed that the GPS is so accurate, not flawless, but accurate.  And since it is in the phone it is linked to other things in the phone.   I can find a gas station, a hotel or a restaurant near by.  My kids know where we are and I know where they are.  CNN can track me too.  The weather app tells me the local weather.  I get local traffic and local hiking trails.  All amazing stuff.
Of course, there is a price to pay, and it may be the the price is more than we think.  A recent, 2014, Nobel Prize in Physiology or Medicine 2014 was divided, one half awarded to John O'Keefe, the other half jointly to May-Britt Moser and Edvard I. Moser "for their discoveries of cells that constitute a positioning system in the brain”.  They found that our brains seem to draw girds, just like maps, and we use those cells to establish a consistent idea of where we are located. 
Building on that work other researchers have learned that these cells also link their ability to locate in space with an ability to locate in time.  That plays a large role in the way the brain creates and stores memories. It relates to our ability to create, maintain and tell stories.  Stories usually involve telling where people are, and what they do there. It is those links that seem to deteriorate from  Alzheimer’s Disease.  Without those links, people get lost in space, time and memory.

So, when you jump in your car and ask your GPS how to get there, you are letting that part of your brain slip away.  You probably remember the study done on the brains of London cab drivers.  They have to learn all of the convoluted streets of London without a GPS (I don’t know if that is still true).  MRI tests of their brains showed that the hippocampus of their brains had a much thicker cluster of nerve cells and that these brain changes occurred as they were learning the map. Further studies showed that these drivers, who could recall all of the details of the London streets, performed less well than non-drivers on other memory tasks. Later, when they stopped driving a cab, they regained their ability to remember other things.
Knowing all of this a group consisting of a psychologist, a neurologist, a physicist and an oceanographer went off the the Marshall Islands in the South Pacific Ocean to study the wave pilots.  They found one man who had the knowledge of the ancient skill of navigating between the islands by reading and riding the winds and currents.  He was the last of the non-tech navigators and they wanted to be able to learn his unique skills before they were lost forever.  One of researchers had once gotten lost in a fog while kayaking.  He was able to find his way back using his sense of direction and finding some landmarks that he recognized.  He later learned that two others did not have those skills and drowned.  He, and many others, wonder what would happen to any of us if the power goes off?
In just the past fifteen years more and more of us have learned to use machines and electronics to help us get where we want to go, and to do what we need to do.   We do this because it is easy and effective.  I’m not old-school on this.  As I said, these things are amazing and often save hours of aggravation.
But we have to be aware of the effects it could have on us.  If we use the time and effort these tools save us to think about other things, such as focusing on the reasons we are gong, then these electronic aids can be very helpful.  But if we just drift away and let the electronics do it all, we may just forget why we were going there in the first place.  Eventually, we might even forget how to remember. 
Or else, some people may develop an entirely new ways of remembering and of creating stories about what happened. I wonder how different those stories will be?

If all this confuses you, try this:

Saturday, April 09, 2016

My Father Didn't Go to War

(I realize this is kind of rambling, but I wanted to get it posted. I've really been getting swept up with this kind of research into who we all are and what we are becoming)

        The Scientific American has a very brief report this month (April 2016) about how orphaned bugs, earwigs in this case, who were deserted by their parents, grow up to be less attentive parents themselves.  Apparently most earwigs are watchful and devoted to their eggs and nymphs, but those who did not receive such attention did not administer such caring behavior to their offspring.
The report did not say if this was then carried on through future generations, or if these unattended children had a lower rate of survival, and thus were slowly eliminated from the gene pool. In fact it did say that the first generation of unattended children grew bigger and stronger than their peers.  It was not until they became parents that they showed the effects of their lack of maternal care.
Joel Meurnier,  a evolutionary biologist who is at the University of Tours, France, said that these studies could reflect goes on in humans. He noted that these insects represent one of the most primitive forms of family life, which evolved from there. That prompted me to begin to search for studies of humans, and to see if any research has found if some of the effects of the trauma of losing a parent early in life can be genetically transmitted to the next generation.
Searching around the web, which is much easier than going to the library and searching through six hundred journals, which is what I had to do in grad school, revealed that there are  studies that show that there are several ways in which the effects of trauma can be transmitted to the next generation.  One of the ways seems to be directly through the genes of both the mother and the father.
Anyone who has dealt with families has seen that traumatized parents, such as concentration camp survivors, often raised their children in an atmosphere of fear and distrust. Many of their children learned to be constantly vigilant.  Much of this was understandable, given the life experiences of both the parents and children.  So it is possible that  environmental factors could explain much of the behavior of these children. It is difficult to determine if their are biological causes as well.
Then I found an article by Virginia Hughes that was published in Nature in April of 2014.  She cites a study done by Isabelle Mansuy  of the University of Zurich, Switzerland, who found changes in the RNA in the sperm of mice who had been traumatized.  This seemed to be one vehicle by which a tendency towards anxiety and depression was passed down to the next generation.
There are other studies that show that this happens to the genetics of the mother also. There is a growing recognition that the causes of anxiety, depression and other behavior patterns are not just environmental, and not just inherited traits that have been passed through many generations, but are also epigenetic.  That means that environmental events that happen in one generation can be passed on to the next.  For over a century, this kind of thinking was rejected.  Evolution was not supposed to be so directly affected by the life experiences of an individual.  But there is increasing evidence that things are more complex and more interactive.

From these studies I made a huge speculative jump and began to wonder: 

As you may have realized by now I am not good at details, but big picture stuff always floats through my mind.  I was reading and thinking about the 20th Century. It was a time of many awful traumas, most of which were worse than what is going on today.  The wars and the severe economic depressions affected nearly everyone, all over the world.  Entire cities, countries and even continents were devastated.  Many millions of people were killed, many more had their homes destroyed, were turned into refugees.  Millions more, who may not have been directly, physically harmed, were still subjected to constant fear, anger and horror that lasted for years.
The first world war made no sense, especially to those who were fighting it.  There were national rivalries between the leaders of countries, but the people who fought the battles really felt no natural animosity toward each other.  Yet, at the Battle of Verdun, in WWI, men lived in trenches for months, just yards away from each other, killing each other one at a time until 800,000 people had died. The men who survived were never the same, psychologically. They were traumatized , yet that was rarely recognized as such. Although there were descriptions of “battle fatigue” and “shell shock,”  no one knew how to treat it.
WWII was worse in terms of devastation and death.  The weapons were more powerful and came from greater distances, culminating in two nuclear bombs falling on Japan.  There were invasions of The Soviet Union that killed millions.  Japan invaded China with traumatic effects. There were large revolutions and coups in Africa in which hundred of thousands if not millions of people were killed and displaced.
Many of these soldiers were referred to as “The Greatest Generation” and hailed as heroes.  The standard behavior seemed to be that most of them did not talk about the war.  They tried to be stoic and move on, rejoin society and have a life. Was this possible?  I doubt it.

That’s what brings me back to the kind of research that I cited above.  It now seems likely that the effects of trauma can be carried through the sperm of the father, and by cell changes in the blood of the pregnant mother. To state it in the more exact language of one study: “the role of glucocorticoid hormones in signaling and epigenetic mechanisms participating in the effects of stress on gene transcription in hippocampal neurons” can be passed on to the next generation. (Johannes M. H. M. Reul*, Psychiatry, 22 January 2014).
What that means is that trauma affects the RNA of the person who experiences it, and that these genetic changes can be passed on to his or her offspring, and that those offspring are more likely to experience anxiety and depression than children whose parents were not traumatized.  Anxiety runs rampant through my generation, the baby boomers. 
I don’t mean to diminish he suffering of previous generations.  I don’t know if Russian serfs felt traumatized or just accepted life as it was. There have always been wars, plagues, invasions, slaughter and trauma.  I can only imagine that most American slaves, especially those who actually made the crossing, were greatly affected.  Certainly, by today’s standards, most human lives were short and miserable for thousands of years.  But they didn’t have today’s standards; the kind of life we live today was unimaginable.

What was the effect of going to war on the men who returned from battle, in any generation?   Were they more distant emotionally?  How did that affect their marriages?  Their parenting skills?  Their politics?  
There were no studies done about this afterWorld War II, and certainly none done after the Battle of Waterloo or at Hastings.  War was too common then to think that such a study would be necessary.  Now, during America’s prolonged wars in the Middle East there have been many studies.  They show that there are many difficulties of sending a parent off to war,problems with the soldier, the spouse and the children. Psychologists are trying to find ways to minimized the damage.
My generation was the first to really have psychologists and psychotherapy offered to everyone.  Through many technical and social advances we have much higher expectations for the quality of our lives.  We do not expect to suffer, to live in fear, to feel constantly victimized, or to watch our children die.  We were also the first generation, possibly in the history of the world, in which many of its members stood up to the government and refused to go to war. We were more sensitive to social justice, more skeptical of power, and a bit more selfish and spoiled.   
Due to his age and other physical restraints, my father did not go to war.  He was not traumatized, and was a pretty open and accessible father, at least for his generation.  That probably helped shape who I became. Some of the folks who also marched against the war in Vietnam had fathers who had been soldiers  in WWII,with whom many had difficult relationships.
These are things that make me wonder. Is it possible that being in battle not only changed the soldiers emotionally, it changed them genetically?  If that is the case, that would help explain why so many veterans are still suffering, even after years of treatment. The only studies I found of genetics of Vietnam veterans and their children focused on Agent Orange and on major birth defects.  What I would look for would be much more subtle, and probably is too difficult to find after so many years.  

For me the question remains: how much of a tendency toward anxiety, depression and anger has been passed on through both genetics and epigenetics?  If some of the results of a personal trauma can be passed on from one generation to the next, how much does it have ripple effects through our society, or any society that has suffered major disruptions.  Why do some regions, such as the Balkans or the Middle East seem to have such insolvable problems, that go on for generation after generation. Also, how much do epigenetic effects explain some of the families I have seen that have been full of physical and sexual abuse for a few generations?

The follow-up question is even more intriguing: can some of these epigenetic changes be undone in a generation?  Can people learn to trust and be more open and caring.  If so, would these  positive experiences create changes in a father’s sperm, or a mothers cortisol level that would be passed on to the next generation?
It turns out that such research has already begun.  There are studies which show that mindfulness training does produce some of these effects.  Many people who learn to meditate in a meaningful way report feeling calmer and have a more positive outlook.  They also show physiological changes in their genes that affect inflammation and other aspects of body chemistry that affect mood.  It is not yet knows if they changes can be transmitted to the next generation. 
But it would be helpful if we could get the whole world to chill-out for an hour a day, and pass the effects on to the next generation.  I know a woman who is advocating this, an evangelical Buddhist.  Now I understand it more, on a cellular level.  But she’s not getting much traction so far, especially in today’s political climate.  Still, we’ve got to start somewhere, and it certainly can’t hurt.