The Doctor Weighs In

By Dov Michaeli MD, Ph.D

An article in the Sept. 17 2007 issue of Time magazine tweaked my interest. In it the author, John Cloud, argues that the recent crop of Republican homosexual legislators deserves our understanding of their weakness, rather the opprobrium of hypocrisy. To quote Cloud, he is offering “a moistly liberal request: Can we have a moment of pity for moralizers who fall?”

His argument runs as follows:

“Hypocrisy is among the most universal and well-studied of psychological phenomena, and the research suggests that Craig, Haggard and the others may be guilty not so much of moral hypocrisy as moral weakness. The distinction may sound trivial at first, but as a society, we tend to forgive the weak and shun the hypocritical.

Assume for a moment that Craig and Haggard actually believed what they said--that homosexuality is sin. They spent most of their lives fighting for the conservative cause. But in Craig's case, the Idaho Statesman has published allegations that there were at least three other slipups involving men, beginning in 1967. What if, like the radio host who gets fat but commits to losing weight, the moralizers were trying through their "pro-family" endeavors to expiate their lustful sins? You may think they are wrong about homosexuality (I do), but that doesn't make them hypocrites.”

With all due respect, this argument is not “moistily lliberal”, it is down right wrong on scientific and moral grounds.

What did  Larry (wide stance) Craig actually say? Here is one quote: “It is important for us to stand up now and protect traditional marriage, which is under attack by a few unelected judges and litigious activists”. Here is a man who married a woman and for decades fought against equality for gays.

So that we are not accused of picking on one unfortunate soul, remember Mark Foley?

Here is what he said: “For those pedophiles and predators across this country that have harmed or are considering harming a child, let me tell you that you are on notice… Your days in the shadows are over.” How prophetic, and how poetically just. This is the stuff Greek tragedies are made of.

Is it classical hubris, or is it hypocrisy?

The classical Greeks did not have Freud to kick around. They attributed human failings to hubris, a cardinal sin in the eyes of the Olympian gods. And the retribution that followed was swift and merciless. No moistily liberal excuses for them.

Two thousand years later, Shakespeare took a more nuanced approach to human failing. The hubris of the proud and vain King Lear had to be paid for, and dearly. But the process of suffering cleansed him of his hubris and opened his heart to love. His tragic death broke the hearts of millions.

Enter Freud, about 300 years later. His original psychoanalytic theories have been largely discredited, but the psychobabble residue they have left behind is still with us. Hence the “psychological” and moral sleight of hand a la Cloud: these people are not hypocritical at all, they are just weak.

Neurobiology refutes this argument

A recent review in Science (“Social Decision-Making: Insights from Game Theory and Neuroscience”) makes the point that social decision-making is controlled by a complex network of centers in the brain. The middle area of the prefrontal cortex (MPFC) and the area just below it (the orbitofrontal cortex, or OFC) constitute the “executive center”, making final judgments that balance inputs from the anterior and posterior cingulate cortex (ACC and PCC) which are the reward areas, and from the amygdala and the insula (AMY and INS), which process the more primitive urges, such as fright, aggression, hatred, rage, etc (Dr. Freud, is this the anatomical locus of your concept of the “subconscious”?).

What is important about this new research is showing the part of emotions in the overall mix of inputs into our decision-making. And this brings us to a potential explanation for what is called “cognitive dissonance”. What is meant by that is the nagging, and sometimes profound discomfort we feel when our behaviors don’t align with our beliefs. Our prefrontal cortex will keep nagging us, disturbing our peace of mind, interfere with our sleep, afflict us with unpleasant dreams—until we bring our behavior into alignment with our beliefs, which in reality are the products of the judgments made in the prefrontal cortex.

I accept that if you say one thing and then do another, the cognitive dissonance you will suffer is a result of your weakness. But when you do one thing and then say another—this is no weakness, this is willful hypocrisy. Larry Craig did not become a homosexual last month or last year. He was probably gay before he was a senator. Science tells us that he probably was born a homosexual. Mark Foley didn’t discover children when he first saw a congressional intern. They were most likely the objects of his desire decades ago.

Which leads me to the most “unmoistily liberal” conclusion: these people are hypocritical. The excuse of weakness or “the devil made me do it” doesn’t wash: Your prefrontal cortex warned you time and again that your behavior is reprehensible; you chose to ignore it. You did one thing and then chose to say or do something antithetical, in order to advance your political career. If the consequences began and ended with you alone—nobody cares. But your decision-making had social consequences. Your words, votes, actions— they inflicted grave harm on innocent people who have done you no wrong.

Dov Michaeli MD, Ph.D is in biotech and brooks no B.S.

A few weeks ago (May 9, 2007) we posted a comment on Gina Kolata’s article in the New York Times (May 8, 2007) The article basically laid the blame for the obesity epidemic afflicting us at our genes. Kolata reviewed work suggesting that genes are involved in obesity, with the implication that a fight to lose and maintain a lower weight is not only excruciating, it is practically futile.

That simply didn’t sound right. At least 10 genes have been discovered thus far that are involved in obesity and diabetes; more are bound to be discovered. We also know that the US population is fast approaching the 50% mark of overweight (BMI 25-29.99) or obese (BMI > 30). These genes presumably are not recent mutations. Why is it then, that only relatively recently did these genes express themselves to cause the outbreak of obesity? I think the answer is quite obvious: we have here a classic case of genetic/ environmental interaction. The genes have been there all along; they haven’t changed. The new elements that caused such a massive upward shift in BMI are the invention of the car, television, computers, all leading to a sedentary life style. Couple this with profound changes in our dietary and eating habits, resulting in a significant increase in caloric intake, and you’ve got an inescapable outcome: weight gain.

Don’t go shopping for food when you are hungry

I don’t know who first pronounced this maxim, but I am sure many of us rediscovered it many times, independently. What we actually discovered is that hunger is such a powerful physiological drive that no rational, moderating influence can keep it in check.

The hunger drive

Our gut reaction, so to speak, to hunger is primarily hormonal. Fat cells secrete a hormone, leptin (leptos means thin, in Greek), that travels to the brain, and signals a message of satiety; the more leptin, the less hunger. Another hormone, called ghrelin is secreted from the stomach when it is empty, and its signal to the brain is hunger; the more ghrelin, the more hunger. This description is obviously a vast oversimplification, but the basic mechanism is clear: our sense of hunger or satiety is a balance between hormones with opposing influences on the center in the brain that controls feeding. This area, called the hypothalamus has neuronal connections to two other important areas: the amygdala, and the nucleus accumbens. Activation of the amygdala, when the hypothalamus senses hunger, causes a sense of alarm, sometimes accompanied by aggressiveness, easy irritability and other hard-edged feelings. On the other hand, a sense of satiety and fullness activates the nucleus accumbens, which is the seat of all the warm and fuzzy feelings, like reward and pleasure. The neurotransmitter that mediates this sense of pleasure is dopamine.

The cocaine connection

It turns out that dopamine is also secreted in the nucleus accumbens in response to cocaine, amphetamines and other recreational drugs. In fact, the response of the cells that carry the dopamine receptors to the sudden rise in dopamine concentration is to reduce the number of receptors, so as to keep the stimulus within manageable bounds, so to speak. This phenomenon is called receptor downregulation. To keep the pleasurable sensation at its previous level one needs to take even more cocaine, which in turn causes even more downregulation. You can readily see the neurobiological downward spiral that we call addiction.

Lo and behold, the same pattern is seen in brain scans during binge eating: Surfeit of dopamine, activation of the nucleus accumbens, and downregulation of dopamine receptors.

The brain’s “adult supervision”

Of course, being civilized creatures we could not let ourselves be governed by such “primitive” drives as pleasure and reward on the one hand, or anxiety, aggression and rage on the other. Indeed, evolution endowed us with a highly developed area in the brain called the prefrontal cortex. This is the seat of judgment and rational decision-making. It weighs the messages arriving from the reward and anxiety centers and renders judgments that find their expression in what we call behavior.

However, this Solomonic wisdom does not always prevail. When exceptionally strong messages arrive from one center, they overwhelm the messages from the other, and the judgment of the prefrontal cortex becomes skewed, or completely overwhelmed by the flood of the incoming powerful signals. Each one of us, after along period of fasting, must have felt an overwhelming desire to binge-eat. Only when we are finally disgustingly stuffed, do we ask ourselves: what am I doing? In neurobiological terms, the storm of signals from the amygdala (hunger to the point of anxiety) and the nucleus accumbens (“how sweet it is”, and the hell with the diet!) subsided, and the ever stern, judgmental prefrontal cortex reasserts itself (“have you no shame?”).

So, is it genes or addiction?

I believe that the addiction model is a more plausible explanation of the overeating epidemic that is afflicting us now. It also explains the extreme difficulty in “kicking the habit”, losing weight and maintaining it over a long period of time. As any recovered drug addict will tell you: one never really kicks the habit; it is a constant battle, and one is always on the brink.

The encouraging aspect of this grim picture is that addiction is susceptible to therapeutic intervention. There are drugs that can blunt the addictive urge. For instance, the drug naloxone reverses the effects of morphine. Interestingly, naloxone also blunts the hunger drive and reverses binge-eating.

Dov Michaeli, MD, Ph.D

If you enjoyed reading this, you may also want to read:

• Obesity:  The devil made me do it
• Genes and food -- good and genes

Genes

In 1993 scientists reported on a Dutch family, 14 members of whom were sociopaths, involved in aggressive crimes such as bullying, physical violence, rape, and arson. They all had in common a mutation in a gene that makes an enzyme called MAOA. The function of this enzyme is break down neurotransmitters such as serotonin and noradrenaline (or norepinephrine, a chemical first cousin of adrenaline). The ready conclusion was: defective enzyme caused elevated level of serotonin and noradrenaline, resulting in overactive brain circuits that serve aggressive behavior.

Case closed? Not so fast…

In a wonderful summary of the topic in Newsweek magazine ( April 30, 2007 ) one of my favorite writers on the subject, Sharon Begley) describes a 2002 study in New Zealand of 442 men who were followed since their birth. Indeed, men with low MAOA were more likely to engage in persistent fighting, bullying, cruelty and violent crime. But not all of them; only men who had been neglected or abused as children fit the bill. Men who grew up in a normal environment exhibited none of the violent traits.

Neuroanatomy

In previous postings we waxed scientific about the amygdala, two almond-shaped structures deep inside the brain, that are the seat of primitive emotions such as rage and fear; these constitute the emotional basis of the fight or flight reaction, which is mediated by noradrenaline. These waves of seemingly overwhelming emotions are checked and inhibited by another, more modern structure in the brain: the prefrontal cortex. This structure is the seat of judgment, planning, abstract thinking. It inhibits inappropriate or impulsive behavior, and is engaged in constant self-monitoring (could it be the anatomical seat of the Freudian super ego?). So in typical Ying/Yang fashion, the outcome of our behavior must then be the product of the amygdala and prefrontal interaction. Remember the then famous case of Kip Kinkel, a 15 year old who in 1998 killed his parents and two dozen schoolmates in Springfield , Oregon ? His brain scan showed a completely silent prefrontal lobe; he had nothing to check and balance his raging anger emanating from his amygdala.

Is this it? Not quite…

Hormones

Women love to point out, without much evidence I might add, that men’s aggressive behavior can be traced to their testosterone-addled brain. Only partly true. The level of testosterone is within normal limits between 20% and 200% of the mean; that’s a huge range of normal. However, if the level of testosterone exceeds 400% of the mean, then indeed women are right—men with these levels are more prone to violence. In fact, testosterone is an equal opportunity hormone; in a species of hyenas (I forget which) the first newborn in a litter, be it male or female, will eat the rest of the brood within days of birth. It turns out that this vicious sibling has inordinately high levels of testosterone in its brain, much higher then the other hapless siblings.

But to assume that we are simple automatons, following helplessly the script written by our genes, brain circuits and hormones, would deny a self evident fact—we don’t behave automatically, we do have a certain degree of free will.

Psychology

The interaction of biology and the life one leads turns out to be of paramount importance in shaping the criminal mind. The most important characteristic of the behavior of mass killers is paranoia. They have the sense that the whole world is against them, that everybody but themselves is responsible for their troubles, that the world is unfair. They are usually depressed and socially isolated.

This kind of personality, you might say, could be the product of brain circuitry gone awry. But here is a fascinating finding from animal and human studies: behavior can change brain circuitry and function-- an outstanding example of nature/nurture interaction. So what are the non-biological roots of violent behavior? We finally arrive at the inevitable:

Society and culture

It is the social environment that allows, indeed encourages, psychopathic criminal behavior. Many societies have members with genes gone awry, with malfunctioning brain circuits, with males suffering from raging hormones, with children raised in violent homes. But, sad to say, we have the dubious distinction of being the champions of gun violence in the civilized world. In 2004 there were 29,645 deaths due to gun violence in the US , or 10.08 per 100,000. For comparison, France had 4.93, Belgium 3.67,and Spain 0.75 per 100,000.

In 5 years of war in Iraq about 3200 of our soldiers got killed. Yet, we tend to see the situation in Iraq as intolerable but we dismiss  the carnage in our own streets with a helpless shrug: "It’s the culture… "

We mentioned the case of Kip Kinkel. Yes, his prefrontal lobe did not do its job. But here is rest of the story: a psychotherapist actually suggested that his dad buy him a gun so they could have something to do together.

As Pogo said: we have met the enemy, and it is us.

Dov Michaeli MD, Ph.D

A recent paper in the Journal Nature, Damage to the Prefrontal Cortex Increases Utilitarian Moral Judgments  (Nature, advance online publication 21 March 2007),  has provided strong evidence that we are indeed moral animals, and that certain aspects of our moral behavior are hardwired in our brain. The institutions involved in this research (U. Iowa Dept. of Neurology, Harvard U. Dept. of Psychology, and the Brain and Creativity Institute at the U. Southern California) reflect the multi-disciplinary approach required for such a study.

Where in the brain is Morality?

Our brain is organized in layers, somewhat like an onion. The deepest layer, like the brain stem and the structures around it, is the most ancient, or primitive, from an evolutionary point of view. These structures control vegetative functions, like heart rate, breathing, gastrointestinal motility, etc. These functions are essential for life, and are shared by organisms from the most primitive to the most complex.

Next in evolution came another layer of behavioral complexity: diverse functions such as thirst, hunger, sexual attraction, fight-or-flight responses to danger, responses to day-light cycles, short and long term memories. These functions are mediated by structures deep inside the brain called the midbrain.  The midbrain contains structures, such as the amygdala (fight of flight, rage, aggression), the hypothalamus (hunger), the nucleus accumbens (reward, pleasure) and the hippocampus (memory). These functions are not voluntary; they are found in mice and humans alike.

A more recent layer of the brain tissue, called prefrontal cortex, was added when monkeys started to evolve. In this layer resides the ability to function as a social animal, for instance traits like empathy and moral judgment. The last and outermost layer, added relatively recently, is called the frontal cortex.  It is most developed in humans. Messages from the brainstem, midbrain and prefrontal cortex feed into this area (situated right behind the eyes), where they are all integrated, weighed, judged, contemplated—and then translated into action.

What did the Nature paper find?

It has been suspected for about 10 years that an area within the prefrontal cortex, called the ventromedial prefrontal cortex or VMFC, is required for emotions and moral judgments. When subjects in a brain imaging study were presented with a scenario requiring moral judgments, the area that lit up was the VMFC. What kind of situations were they? Highly aversive ones; for instance, sacrificing one person in order to save several other. The anguish of such decisions is captured in Sophie’s Choice, or in King Solomon’s famous trial of the two women.

The vast majority of people will recoil from making a “utilitarian” calculation of killing one person so as to save others. Indeed, in this experiment over 80% refused this option. But in a group of 6 patients who had some kind of pathology in their VMFC, such as an aneurysm or a tumor, the judgment was completely utilitarian—kill the few to save the many. No hesitation, no compunction. In fact, Antonio Damasio, one of the authors of present study, published a study in 1999 of two patients who have had a defect in their VMFC since infancy ( Nature Neuroscience vol. 2, pp. 1032 - 1037 (1999). As adults, the two early-onset patients had severely impaired social behavior despite normal basic cognitive abilities.  They showed insensitivity to future consequences of decisions, defective autonomic responses to punishment contingencies and failure to respond to behavioral interventions. The authors concluded: “Thus early-onset prefrontal damage resulted in a syndrome resembling psychopathy.”

What does it all mean?

The implications of these studies are enormous. For instance:

• We may finally get a handle on extreme psychopathic behavior, such as serial killing, serial raping, extreme levels of domestic violence.
• Our legal system will have to, sooner or later, come to grips with criminal behavior engendered by structural defects in the brain. Evidence of brain imaging (fMRI), is already being introduced in court, and juries are becoming receptive to the evidence.
• On a more hopeful note, but probably less imminent, we may learn one day how to intervene and enhance individuals' moral judgments. Wouldn’t that be a welcome development of this "1984 science?"

 Moral philosophers have dismissed evolutionary biologists and neuroscientists forays into the realm of ethical and moral judgment. They are now having second thoughts, and the more intellectually open and curious among them (a more developed frontal cortex?) are listening attentively. Can the days when vexing issues such as religion and faith in a higher being find a biological explanation be far off? Is conflict resolution between individuals and nations amenable to biological treatment? Science is what we make it to be. If we put it to good use it can promise humanity.

Dov Michaeli MD, Ph.D