The Psychopath Inside (8 page)

The neurotransmitter dopamine is implicated in several psychiatric disorders. Drugs that increase dopamine transmission can alleviate symptoms of depression, and drugs that reduce it can alleviate schizophrenia. The impetus to initiate a behavior “considered” by the prefrontal cortex is largely under the energetic control of dopamine, which is mostly produced in the midbrain.
When dopamine is released, things happen. Dopamine doesn't decide exactly
what
will happen, but how quickly and strongly something happens, and for how long, much like an accelerator pedal on a car.

How much the monoamines such as serotonin and dopamine affect each person depends on the person's genetic makeup and the maturity of the underlying circuitry—especially for the genes that control the synthesis of these neurotransmitters—but much more importantly on the enzymes, such as MAO-A, that break them down and terminate their synaptic action. Also of significance are the levels of synthesis and activity of the receptors for these monoamines, which number in the dozens, as well as the genes controlling the efficacy of synaptic membrane protein transporters, which pull neurotransmitters out of the synapses, or spaces between cells, and stop their signaling. These transporters are implicated in some pretty exotic brain functions, for example creative dance performance and a sense of spirituality. It is apparent that with all the possible allelic combinations of monoamine-relevant genes, as well as glutamate, the amino acid gamma amino butyric acid (GABA), and cholinergic systems in these cortices, there are thousands of kinds of “normal” prefrontal cortices. These thousands of types of prefrontal cortices can possess different amounts of highly variable traits such as memory, emotionality, aggressiveness, and sexuality. Likewise, because of all the genetic variables, there are really a limitless number of ways to be schizophrenic or depressed. Some prefrontal disorders are more complex than others, and certainly schizophrenia is one of the
most complex. But there are also probably many ways to be a psychopath, too, considering all of the combined neural systems and genetic factors involved. Unfortunately, very little is known of the biological basis, especially genetics, of the brains of psychopaths.

Despite the impressive numbers associated with the human genome, the information carried on those twenty thousand genes, forty-six chromosomes, and six billion base pairs tells only 5 percent of the story. The remaining 95 percent resides in a still-mysterious garnish of noncoding nucleic acids, bits of DNA and RNA that are now believed to profoundly affect what ultimately is produced by the genetic code in the nucleus. They help direct the functions of the cell, the social interactions between cells in tissues and organs, interactions between organ systems—and what a psychopath dreams and schemes and does to others in his everyday predatory wanderings. One way to look at the way the genetic information is actually laid out in the nucleus of cells is quite different from how we all learned it, with all the forty-six chromosomes tightly coiled into their classic X shapes during a brief phase of cell division. Most of the time, that DNA is uncoiled into long strands, like so much pasta in a bowl of Italian wedding soup. The long strands of pasta (the DNA strands) float in a large sea of broth and spices and herbs (transposable elements and other small noncoding bits of DNA and RNA) and the occasional meatball (histones—proteins that act as DNA spools).

These nongene structures are now thought to be at the causal root of some disorders, including schizophrenia, depression, and
addiction, as well as many forms of cancer and immune disorders. These elements appear to have been taken up from other organisms such as viruses and bacteria during our evolution, but also from the foods we eat. What was once considered junk DNA prior to 2000 is now known to be far from junk, although many of their functions remain a mystery. The person responsible for this discovery was Barbara McClintock, who did Nobel Prize–winning research at the University of Missouri and Cold Spring Harbor Laboratory on Long Island from the 1920s to the 1950s, although her discovery of the nature of “junk DNA” would not be understood for many decades.

One implication of the existence of these noncoding genetic regulators is that even if we do determine the coding gene combinations that underlie psychopathy, there will still be a million or more combinations of these with the noncoding nuclear elements that we will then need to consider in order to understand the real genetic basis of psychopathy. But we do know some things.

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In 2006, I was aware of the warrior gene having a proven effect on aggression and violence, and this allele was certainly on the long list of potential candidate genes associated with psychopathic traits. But this had not been proven, and it was correctly assumed that more genes would impact psychopathic traits. There were several candidates that were known to affect aggression, and these were mostly associated with the monoamine neurotransmitter systems.

The monoamine neurotransmitters, or modulators, as they
are often called, are like volume buttons in the brain. Neurons “talk” to each other by releasing tiny molecules called neurotransmitters into clefts between them called synapses. The signaling neuron releases a packet of transmitters, which can then lock into receptors on the receiving neuron, altering that neuron's behavior. Then the transmitters are broken down or transported back inside the signaling neuron. The two most important neurotransmitters are glutamate and GABA. Glutamate is excitatory, meaning that when it's released and encounters a receptor, it encourages that second neuron to “fire” and send its own neurotransmitters to still more neurons. GABA is the chief inhibitory neurotransmitter, meaning that it tells neurons not to fire. Without it, the brain would go haywire.

Glutamate and GABA form the basis of hardwired behaviors, but if they worked alone you'd have kind of a clunky machine. The monoamines, in particular serotonin, dopamine, and norepinephrine, modulate synaptic signaling and help the machine work more smoothly. These are the transmitters most implicated in psychiatric disorders from schizophrenia to depression and bipolar disorder. For instance, the most popular antidepressants, including Prozac and Zoloft, are SSRIs, or selective serotonin reuptake inhibitors. They prevent the reuptake of serotonin back into the signaling neuron, allowing it to continue doing its job. Less popular types of antidepressant are MAOIs, or monoamine oxidase inhibitors, which block the enzymes MAO-A and MAO-B. These enzymes break down monoamines, so blocking them increases serotonin transmission.

There is a misconception in the popular literature that if one has a “low-serotonin system,” one can just ingest more serotonin or take nutraceuticals or foods that will directly increase the amount of serotonin in the brain. However, the brain system is much more subtly tuned with feedback regulation than that. And all the genes that regulate this vast cast of characters interact with each other within a cell's system, and between each other at multiple levels of organization of the cell, the neuronal circuit, and beyond. But in spite of the complexities of the genetics and epigenetics, more and more findings keep reminding us of the power of the genetics, and not the environment, to be the prime mover in behavior.

As mentioned, the warrior gene is a form of the gene that produces MAO-A, and it leads to an underproduction of this enzyme. With less of the enzyme breaking down monoamines, you end up with too much of the monoamines, including serotonin. That sounds like a good thing, but the brain is a complex system and you don't want too much of anything.

It turns out that during fetal brain development, serotonin is released early on, since it is one of the earliest neurotransmitter systems to develop. So if the fetus has inherited the low-activity, high-risk form of the MAOA promoter, less MAO-A will be produced, there will be less of it to break down monoamines such as serotonin, and the fetal brain will be bathed in a higher-than-normal amount of that neurotransmitter. The response of the body, including the brain, to too much of a neurotransmitter or hormone is to try to dampen that chemical's effect. It will produce
fewer of the receptors for that neurotransmitter or hormone, and even change the size and cell structure and connections of the brain areas impacted by the flood. Those areas that turn off in fetal development stay pretty much turned off after birth and into adulthood. So this kind of altered brain area will not respond like the average brain when serotonin is released.

There may, in fact, be plenty of serotonin released—let's say after an anger-producing event—but no one is listening. That is, the brain areas that should turn off the anger and rage after a minute or so are permanently altered so that there are fewer neurons to respond, and fewer serotonin receptors to turn on or off. This type of genetic effect that impacts fetal and early postnatal brain development is rather common. No one has definitively shown that the warrior gene causes all this to happen, but it's clear that messing with a neurotransmitter system that regulates emotion should lead to some problems.

Behavioral evidence supports this prediction. It was shown in the 1990s that mice bred to completely lack the gene that produces MAO-A become more aggressive. The Dutch researcher Han Brunner and his colleagues found that several generations of men in one Dutch family had a rare mutation in this gene such that they produced little MAO-A, and these men showed particularly inappropriate behavior and crimes such as arson, exhibitionism, and attempted rape. A wide statistical analysis of boys with the low-producing form of the MAOA gene, conducted by Avshalom Caspi and Terrie Moffitt of King's College London, found that they had greater mental health problems, including ADHD and
antisocial behavior, than other boys. Kevin Beaver of Florida State University and collaborators found that males with the warrior gene were more likely than others to join gangs. Compared with their fellow ruffian gang members, they were more violent and twice as likely to use a weapon in a fight. And in a laboratory study by Rose McDermott of Brown University, Dustin Tingley of Princeton, and colleagues, subjects with the warrior gene reacted more aggressively to provocation—while playing an economics game, they were more likely to force an opponent who took their earnings to eat hot sauce.

The warrior gene has also been linked to changes in brain structure. One study by Andreas Meyer-Lindenberg and colleagues at the National Institutes of Health found that in males the gene reduced the volume of the amygdala, anterior cingulate, and orbital cortex—all areas implicated in antisocial behavior and psychopathy—by 8 percent.

The warrior gene's effect is felt mostly by males. That's because it's located on the X chromosome, one of the two so-called sex chromosomes, the other being the Y chromosome. It occurs on about 30 percent of X chromosomes. As anyone who mastered sixth-grade biology knows, females carry the XX sex chromosome combination, while males carry the XY combination. Since a male child inherits only one X chromosome, from his mother, he will definitely suffer if he receives the low-functioning variant, because there is no other gene to counteract it. Females receive one X from their father and one from their mother. After fertilization and early egg cell divisions, one of the X chromosomes in
the pairing in a female is inactivated randomly, but for some genes, including MAOA, both remain active. So they need the low-expressing version of the MAOA gene on both X's for them to have not enough MAO-A and thus too much serotonin. Therefore women are not as susceptible to the effects of the warrior gene. Since there is a 30 percent incidence of the warrior gene on each X chromosome, the chances of a female having it on both are 30 percent times 30 percent, or 9 percent. This explains, at least in part, why there are more aggressive males in the population than females. And this difference is increased by the presence of testosterone, which affects aggressive behavior in males more than in females.

In understanding the genetics of psychopathy one might also take a look at the gene responsible for the serotonin transporter, which is a protein that vacuums serotonin out of synapses and back into serotonin neurons for recycling. Near the gene for this transporter is its promoter, the bit of DNA that initiates the transporter's production. A long variant of the promoter that leads to the overproduction of the transporter and thus a decrease of serotonin hanging around in synapses is of considerable importance to the effects of drugs like amphetamine, cocaine, and ecstasy, as well as posttraumatic stress disorder and aggressive behavior in Alzheimer's patients. The high-risk variant of this promoter is also associated with alcoholism, depression, social phobia, hypertension, obsessive-compulsive disorder, and even difficulty experiencing and expressing romantic love. This is not the kind of genetic variant one wants to inherit or pass on.

In addition to serotonin, dopamine appears to play a role in psychopathy. In 2010, Joshua Buckholtz of Vanderbilt University showed that psychopathic traits are associated with greater dopamine release in the brain, and more dopamine means a greater drive to seek rewards. Genes that increase dopamine transmission could explain the addictive behaviors often seen in psychopaths, as they look for more and more stimulation, whether from drugs, sex, or gruesome violence.

Another gene possibly related to psychopathy is the one producing corticotropin-releasing hormone (CRH). This substance activates the body's stress response and often rises just before an addict relapses. CRH in the amygdala is thought to create a profound sense of yearning, loss, and anxiety. This might happen when a loved one dies, when one is under constant anxiety, and when an addict goes into withdrawal, creating another type of “loss of a loved one.” For those people who have the low-functioning alleles of genes controlling CRH and other stress hormones, or their receptors, there may be very little effect of stress and anxiety, as is found in some psychopaths.