Posts tagged: addiction

Losing It

Business Logo for Psychological and Neuropsychological IssuesLosing it.  All of us lose “it” at some point.  The “it” appears to be the control exerted by the prefrontal cortex of the brain.  The prefrontal cortex serves many functions, and one of the most important is the inhibition of impulses.  The most common impulses to inhibit are sexual and aggressive urges; though they are not mutually exclusive.  The research of Amy Arnsten at Yale has shown that acute stress releases chemicals that reduces the influence of the prefrontal cortex over these impulses.  Not only is prefrontal control weakened, but more primitive areas of the brain emerge to pick up the slack.

In response to the stress confronting the brain, the less evolved brainstem releases two primary neurotransmitters called dopamine and norepinephrine.  Dr. Arnsten discovered that these neurotransmitters actually diminish the communication between the prefrontal area and other regions of the brain.  Once the regulatory network is down, the base of the brain sends a chemical message to the adrenal glands adjacent to the kidneys, and the adrenal releases a hormone that influences the brain in turn.  Norepinephrine and the adrenal hormone cortisol promotes emotional areas of the brain to be fearful and prepare for possible danger.

Chronic unrelenting stress may actually reduce connections between nerve cells in the inhibitory prefrontal area.  Conversely, nerve connections in the more primitive emotional areas of the brain may expand.  There is some evidence to suggest that shrinkage of neural connections in the prefrontal cortex may play a role in depression, addiction and anxiety disorders.  The neurotransmitter dopamine has been long implicated in addiction, due to its strong influence on habit forming areas of the brain.  It appears that a relatively brief exposure to stress has little lasting affect on brain structure.  The longer stress is experienced, the greater the chance the more primitive emotional brain areas will dominate one’s behavior.

This feedback loop of the brain may play a role in post-traumatic stress disorder.  The habit forming areas of the brain allow us to quickly acquire skills and behaviors that ensure success in novel environments; for example, a war zone.  The prefrontal cortex allows us to formulate plans and inhibit fearful impulses that would reduce effective functioning.  Once the threat is removed, the dangers already experienced may overwhelm the prefrontal cortex’s ability to inhibit the emotional excitement.  Over time, the dopamine, cortisol and norepinephrine may weaken the prefrontal control to the point that the fearful impulses are rarely blocked.  The unfortunate person may re-experience highly emotional scenes in an uncontrolled and repetitive fashion.  This person would experience substantial stress in a peaceful environment, since the brain continues to assault them with feelings and images that inspire fear and avoidance.

It is still a mystery why some people manage chronic stress well, and others-not so much.  It is conjectured that some lucky people have an enhanced ability to digest the dopamine and epinephrine excreted during stress. They would possess an innate biological resistance to stress.  On the other hand, psychological research has revealed that people with a long record of mastering challenging situations are better able to tolerate stress.  People who are often defeated and overwhelmed by events are more liable to suffer with chronic stress and depression.  A person’s perception of control is a key element in the subjective experience of stress.  To what degree the subjective sense of control is a product of training or brain chemistry is anyone’s guess.  As with most psychological phenomenon, it is likely that both elements play an important role.  Effective behavioral training increases a sense of personal control; decreasing the excretion of stress chemicals.  Inheriting favorable brain chemistry may reduce the biological strength of the stress response.  Nature and nurture.  Can’t get away from it.

Genetically Modified Depression

Business Logo for Psychological and Neuropsychological IssuesMost people know that DNA contains the data that programs all living things.  What is less known is how the shape of the DNA affects the ultimate expression of proteins.  The mechanisms that regulate if and when proteins are expressed by the DNA template is a very hot topic of research.  Not only the packing but the chemical markers attached to the DNA appear to be important in gene expression or inhibition.  Vast areas of DNA that had been labelled as “junk” are increasingly found to be important in the regulation of protein production.  Only a few percent of a person’s DNA is actually a blueprint for protein production.  The remainder is an intricate network of feedback and feed forward mechanisms that start and stop protein production.  Tightly packed DNA tends to decrease protein transcription, and relaxed DNA strands increases the chance a gene will be expressed.  Two groups of chemical markers have been discovered that regulate the DNA packaging, and hence the ultimate expression of any particular gene.  So, one may ask, what has this to do with mental health?

The chemical groups that regulate gene expression are critically important to the understanding of addiction and depression.  Within an hour of injecting mice with cocaine, over one hundred genes become activated.  If cocaine is used everyday, particular genes are actually inhibited from expressing proteins.  Prolonged use may render some genes over-activated for weeks and even months, whereas others become chronically inhibited.  The ingestion of this one chemical causes profound genetic alterations in the brain’s reward centers that may persist long after the drug is discontinued.  Many genes remain highly sensitized to the effects of cocaine for several weeks after the mouse was last injected.  The brain is ready and waiting for the next dose of cocaine.  The cocaine causes the epigentic chemicals to loosen the strands of DNA; priming them to be activated.

In depression, the the epigenetic influence on DNA is nearly opposite to that of cocaine abuse.  Depression appears to be the consequence of repressed gene activation in the reward centers of the brain.  Environments that are abusive will tend to make the DNA strands tightly bound; decreasing gene activation.  For example, a mouse that is not able to escape the domination of a more powerful mouse will display decreased activation in twelve hundred genes!  Depression appears to inhibit the activation of DNA in the reward centers that allow an animal to feel good.  Just as many humans are resistant to depression, about one third of the mice in the bully experiment did not manifest symptoms of depression.  The resilient group of mice did not develop the the inhibited gene expression that infected the larger depressed group.  This sizable group of genes in the reward center of higher animals is implicated in the treatment effectiveness of tricyclic antidepressants.  Some antidepressants may actually boost the brain’s natural mechanism to confer resilience.

Addiction and depression are not the only psychological manifestations of epigenetic modulation.  As described by Eric Nestler in Scientific American (2011), epigenetic “modifications can promote behavioral changes that last a lifetime.”  Maternal rat behavior is partially or completely modulated by epigenetics, and this has lasting effects on the offspring.  The memory area of the mother’s brain is inhibited, and this epigenetic reduction increases the stress response of the mother over their lifetime.  Anxious and fearful mothers produce a change in the epigenetic regulation of their pups, and this effect will reverberate down the generations.  The behavior of the mother will alter gene expression in their children, and their children’s children.

As with so many discoveries in neuroscience, what works in a mouse may not generalize to a human.  It is likely that humans have the same epigenetic marks that influence gene expression, but it may deviate from what is observed in mice and rats.  Additionally, the complexity of the human brain often makes it difficult to reduce an observation to a few simple rules of organization.  It is nearly impossible to tease out the influence of genetic inheritance from the effects of the environment.  The relative influence of environment versus heredity has been hotly debated for decades, if not centuries.  If this research proves valid in humans, it renders the nature versus nurture debate practically moot.  Increasingly it appears that the environment has a profound and lasting effect on gene expression.  The role of gene expression can no longer be considered in isolation, as if it is the last word in the life story of the organism.  Perhaps the duality of genes and environment will have the same fate as that of the mind and body.  One can only be understood in relation to the other.

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