The Molecule of More

Figure 5
The dopamine transporter is like a vacuum cleaner. Its job is to limit 
the amount of time dopamine spends stimulating the cells around it. 
When a dopamine-producing cell fires, it releases its store of dopamine, 
which then binds to receptors on other brain cells. Then, to bring the 
interaction to an end, the dopamine transporter sucks the dopamine 
back into the cell where it came from so the process can start all over 
again. The transporter is sometimes called a reuptake pump because it 
pumps the dopamine back into the cell.
What happens when the transporter doesn’t function normally? We 
can answer this question by looking at the behavior of people who abuse 
cocaine. Cocaine blocks the dopamine transporter like a sock shoved 
into a vacuum cleaner nozzle. The blockage allows the dopamine to 
interact with its receptor over and over again. When that happens, 
people experience increased energy, goal-directed activity, and sexual 
drive. They have elevated self-esteem, euphoria, and racing thoughts 
that jump from one topic to another. Cocaine intoxication is so similar 
to mania that doctors have trouble telling them apart.

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THE MOLECULE OF MORE
DO BIPOLAR GENES DRIVE IMMIGRATION?
I learned very quickly that when you emigrate, you lose the crutches that have 
been your support; you must begin from zero, because the past is erased with 
a single stroke and no one cares where you’re from or what you did before. 
—Isabel Allende, writer
Bipolar disorder isn’t all or nothing. Some people have severe forms of
the illness and others have more mild forms. Some people have only 
a bipolar tendency. We can see things in the personalities of this lat-
ter group that suggest unusually elevated moods, but not so bad that 
we would diagnose them with a medical illness. It all depends on how 
many risk genes a person inherits from her parents, and how much 
vulnerability these genes confer. The genetic risk then interacts with a 
person’s environment (a stressful childhood, for example), and the final 
product is some manifestation of bipolar disorder, or bipolar character-
istics not severe enough to cause the actual illness.
Is it possible that minor dysfunction in the dopamine transporter— 
just a few risk genes or genes that have only a mild effect—could give 
people “itchy feet,” so to speak? Might that play a role in the decision to 
leave one’s home and seek new opportunities in a foreign country? It’s 
not easy to pull up one’s roots, to say goodbye to friends and family, and 
leave a community that’s familiar, comfortable, and supportive. Andrew 
Carnegie, a nineteenth-century Scottish immigrant who started work-
ing in a factory for pennies a day and later became the richest man in 
the world, wrote, “[the] contented do not brave the waves of the stormy 
Atlantic, but sit helplessly at home.”
If bipolar genes promote emigration, these ambitious people would 
carry their risk genes with them, and we would expect to find high 
concentrations of bipolar genes in countries that have lots of immi-
grants. The United States is populated almost entirely by immigrants 
and their descendants. It also has the highest rate of bipolar disorder: 
4.4 percent, which is about twice the rate of the rest of the world. Are 
the two related?

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PROGRESS
Japan, which has almost no immigration, has a bipolar rate of 0.7 
percent, one of the lowest in the world. People in the United States with 
bipolar disorder also start to have symptoms at a younger age, a marker 
of a more severe form of the illness. About two-thirds develop symp-
toms before the age of 20, compared to only a quarter in Europe. That 
supports the idea that the gene pool in the United States has a greater 
concentration of high-risk genes.
The gene that tells the body how to make the dopamine transporter 
is one of these genes, but there are many others. No one knows pre-
cisely how many, but it’s clear that some form of genetic inheritance is 
playing a role. Children of bipolar parents are at least twice as likely 
to develop bipolar disorder compared to the general population. Some 
studies have found the risk to be ten times as high. But sometimes the 
children get lucky. They get the advantages bipolar people enjoy with-
out getting the illness itself.
As noted, bipolar disorder isn’t all or nothing. Mood-disorder spe-
cialists talk about a bipolar spectrum. At one end of the spectrum is bipo-
lar I. People with this form of the illness experience severe mania and 
severe depression. Next comes bipolar II. People with bipolar II experi-
ence severe depression, but more mild episodes of elevated mood called 
hypomania (hypo means below, like a hypodermic injection that delivers 
a drug underneath the skin). Farther down the spectrum is cyclothymia, 
which is characterized by cycles of hypomania and mild depressive 
episodes. Then there is something called hyperthymic temperament, 
derived from the Greek word thymia, which means state of mind.
Hyperthymic temperament is not considered an illness. It doesn’t 
occur in episodes like bipolar disorder. People with hyperthymic tem-
perament just have a “hyper” personality, and they have it all the time. 
According to Hagop Akiskal, who did much of the pioneering work in 
this area, people with hyperthymic temperaments are upbeat, exuber-
ant, jocular, overoptimistic, overconfident, boastful, and full of energy 
and plans. They are versatile with broad interests, overinvolved and 
meddlesome, uninhibited and risk-taking, and they generally don’t 
sleep very much. They become overly enthusiastic about new directions 
in their lives, such as diets, romantic partners, business opportunities, 

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THE MOLECULE OF MORE
even religions, and then quickly lose interest. They often accomplish a 
great deal, but they can be difficult to live with.
The last stage of the bipolar spectrum belongs to people who inherit 
a very limited amount of genetic risk. These people don’t experience any 
abnormal symptoms, but they do enjoy such things as enhanced motiva-
tion, creativity, a tendency toward bold action and risk-taking, and other 
characteristics that reflect higher than average levels of dopamine activity.
DOPAMINE NATION
We find bipolar genes and bipolar disorder in a relatively high con-
centration in the United States. What about those non-pathological 
expressions of the condition? Is there any evidence that these condi-
tions are also widespread? In fact, the evidence is abundant, going all 
the way back to the early years of the republic.
One of the earliest observers of American culture was Alexis de 
Tocqueville, a French diplomat, political scientist, and historian. Toc-
queville described his observations of the character of Americans 
during the nineteenth century in his book Democracy in America. He stud-
ied the new country because he believed that democracy was likely to 
supplant aristocracy back in Europe. He thought that a study of the 
effects of democracy in the United States would be useful to Europeans 
as they navigated new forms of government.
Much of what Tocqueville observed could be attributed to the demo-
cratic principle of egalitarianism. But he also described characteristics of
Americans that did not seem to be related to political philosophy. Some 
of these characteristics are strikingly similar to the symptoms of bipolar 
disorder, or at least a dopaminergic personality. For example, he devotes 
a chapter to “Fanatical Enthusiasm in Some Americans.” He wrote,
Although the desire of acquiring the good things of this world 
is the prevailing passion of the American people, certain 
momentary outbreaks occur, when their souls seem suddenly 
to burst the bonds of matter by which they are restrained, and 

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to soar impetuously towards heaven.
In this single sentence we see the passionate pursuit of more as well as 
an attraction to things beyond the realm of the physical senses—even 
a reference to the extrapersonal space of up, the realm of heaven. Toc-
queville found that behaviors of this nature were particularly common 
“in the half-peopled country of the Far West,” a notion consistent with 
the likelihood that the adventurous pioneers who settled the western 
states were more likely to have risk-taking, sensation-seeking personali-
ties, and possibly genetic loading for hyperdopaminergic states.
A subsequent chapter titled “Causes of the Restless Spirit of Amer-
icans in the Midst of Their Prosperity” expanded on the dopaminergic 
theme of never enough. Tocqueville noted that despite living in “the 
happiest circumstances which the world affords,” Americans pursued a 
better life with “feverish ardor.” He wrote: