Do the sexual side effects of most antidepressants jeopardize romantic love and marriage? Dr. Thompson and I would like to say yes, most likely under some circumstances, but not always. Please don't leave this room thinking that we are opposed to the use of serotonin-enhancing medications. People are different; situations are different. The drugs have been proven to be effective under many circumstances. I'm an anthropologist, not a psychiatrist. What we're trying to do is to bring an interdisciplinary perspective to the table to heighten awareness and add to the dialogue so that we can all learn how to effectively heal our patients better.

Since the release of Prozac (fluoxetine) in 1989, many similar serotonin-enhancing antidepressants have emerged. In fact, the use of these has increased dramatically. In 2002, in the United States alone, 213 million prescriptions for antidepressants were written and indeed most of them were for serotonin-enhancing medications. It's well established that these drugs can cause sexual dysfunction, diminished sexual desire, delayed sexual arousal, and muted or absent orgasm. In fact, some reports say that as many as 73% of patients on some of these medications can suffer from 1 or more of these side effects.

We theorized that these sexual side effects can potentially -- not all the time, but potentially -- have some serious consequences due to the effects that they can have on several evolved, adaptive, unconscious neural mechanisms. These include the ability to attract a mate, to choose a mate, to fall in love, to stay in love, and to sustain a marriage.

In short, it's all connected and when you knock out the sex system, you can jeopardize many other Darwinian mechanisms that evolved millions of years ago to direct courtship, mating, reproduction, and parenting.

In 1998, I proposed that Homo sapiens -- indeed, all of the mammalian and avian species -- evolved 3 distinctly different but related brain systems for courtship, mate selecting, reproduction, and parenting. The 3 brain systems I proposed are lust, attraction, and attachment.

Lust is the libido, the sex drive; it's basically the craving for sexual gratification. W.H. Auden once called it an "intolerable neural itch"; Pablo Neruda called it an "eternal thirst" and an "infinite ache." It's simply the craving for sexual gratification; it often has no object. You can feel it when you're sitting in the subway, reading a book, or driving alone in your car; you can feel it really at any time.

The second brain system is attraction or romantic love, also known as being in love, passionate love, obsessive love, or infatuation. This is the one that I've studied myself. My colleagues and I, and several others have now put 40 people who are madly in love into a functional magnetic resonance imaging (fMRI) brain scanner, and we've begun to see some of the brain circuitry of romantic love. I'm going to talk a little bit about that.

From an anthropological point of view, this is regarded as a universal human phenomenon. In a study of over 150 societies, evidence of it was found in every single one; there was no evidence to the contrary. Everywhere in the world where you look for evidence of romantic love, you find it. Love magic, love poems, love songs, myths, legends, suicide, homicide, and reports from people themselves testify to it. Indeed, the hard data go back almost 4000 years to Sumerian poetry.

There are several main traits of romantic love. I've canvassed the psychological literature of the last 25 years, and have, in fact, done a study of my own in Japan and in the United States. Of course we all know it, but here's what happens when you fall in love. The first thing that happens is that a person takes on what we call "special meaning." Indeed, George Bernard Shaw once said, "Love consists of overestimating the differences between one woman and another." Indeed! Then you focus your attention on this person. Most people who are in love can list what they don't like about their sweetheart, but then they sweep that aside and just focus on what they do like. As Chaucer said, "Love is blind."

Also involved is intensely heightened energy, elation when things are going well, terrible mood swings when things are going poorly, and an intense motivation to win this preferred individual. There also is something that I call the frustration attraction: when there are real barriers to the relationship, like the person dumps you or they don't call or send you an e-mail or something, you just love them harder. In fact, in Roman times, people knew that phenomenon of frustration attraction.

The most powerful characteristic of romantic love, however, is obsessive thinking. When we put these 40 people into the fMRI machine, the very first question that I asked my subjects was: what percentage of the day and night do you actually think about your partner? The response was 95%: I can't stop thinking about her or him, etc. So you have obsessive thinking, along with a deep dependency on this relationship, and more than any one other characteristic, a craving for emotional union with this individual.

The third of these 3 brain systems that evolved from mating and reproduction is male/female attachment, associated with feelings of calm and contentment and a real sense of emotional union with this long-term partner. In people, as well as in other animals, you have nest building, or home building. Mate guarding is a term we use in anthropology -- I think in psychiatry you would call it jealousy. Finally, you have cooperative parenting, the main point of attachment.

Each of these systems is associated with different primary neurochemicals. Lust is well known to be associated with the androgens in human beings and certainly also with the estrogens in other species.

From our study of the brain, we have some nice evidence that elevated activity of dopamine is involved in that intense sense of passion and arousal of romantic love. I also maintain in my book, Why We Love, that we're going to find out sometime that norepinephrine is also involved, largely because heightened activity of norepinephrine is also associated with focused attention, elevated energy, motivation to win a reward, elation, and 2 characteristics of romantic love -- obsessional following and object imprinting.

I also maintain, although we don't have all the evidence for it, that low activity levels of serotonin are going to be involved, largely because the obsessiveness -- the obsessive thinking of romantic love -- is so striking. Indeed, low levels of serotonin are associated with obsessive-compulsive disorder. So that's part of the fingerprint of attraction or romantic love.

Other scientists have done some very elegant work associating basic feelings of attachment with elevated activity of oxytocin and vasopressin.

I believe that each one of these 3 systems is a distinct neural system. In the last 3 years, 4 MRI studies of lust were conducted. Men and women were hooked up to a machine and shown erotic pictures followed by pictures of scenery, etc. In 3 out of those 4 MRI studies, researchers showed that the hypothalamus is involved, which you would expect, and 3 out of 4 have shown that the amygdala is involved. Two of the most convincing ones, I think, indicate that the insula cortex is involved, along with many other regions.

Regarding attraction, or romantic love, what we found in our data is that the right ventral tegmental area is involved, along with the right caudate nucleus (dorsal). In fact, we showed a lot of deactivations, as one does prior to the brain turning off, while others turned on. We also found deactivation in the amygdala.

On the left, the ventral tegmental area is shown becoming active when a person attached to the MRI machine looks at a picture of his or her sweetheart. This happens to be the anteromedial portion of the caudate. Several aspects of the dorsal caudate became active, which -- because the ventral tegmental area is involved, as well as dopamine and the caudate -- led us to believe that romantic love is not an emotion; it's basically a motivation system. I believe it's a basic mating drive that evolved millions of years ago. Indeed, I think that this drive is more powerful than the sex drive. You don't kill yourself when you don't get sex. People kill themselves when they don't get the lover that they are looking for, or they kill somebody else.

Attachment, the third brain system, is not well mapped out yet; certainly the hypothalamic-pituitary axis would be involved because there's so much oxytocin and vasopressin in parts of the hypothalamus. The substantia nigra has a high density of oxytocin and vasopressin receptors, so that's likely to be involved. In a new study of mother/infant attachment -- not male/female attachment, but mother/infant attachment -- researchers found activity in the medial insular, the anterior cingulate, and the lateral orbitofrontal cortex. So as a matter of fact, many parts of the frontal cortex are going to be involved in all 3 of these systems because we think as we feel.

The point is that each system is distinct; they have different feelings, they have different behavior patterns, and I think they each have a different role in human reproduction. I think the sex drive evolved to get us out there looking for really basically anything at all, anything that was remotely appropriate. Romantic love enabled us to focus our mating energy on just 1 mate at a time, thereby conserving mating time and energy. Attachment evolved to enable us to tolerate this individual, really, at least long enough to raise our children as a team.

But I believe they are all primary mating drives; I think they vary from one species to another. A rat seems to show attraction for a very brief period of time; human beings can be in love for months or years. These systems certainly vary from one individual to another. Some people have a much higher sex drive than others. Some people fall in love all the time; others do not. Indeed they vary over the life course.

The point here is that these 3 brain systems interact and there are many ways in which they interact, but I'm going to stick to just the positive relationship between the sex drive and attraction. You know the feeling, if you've fallen in love -- and everybody I would guess has been in love probably more than once. Suddenly the person that you're in love with becomes intensely sexually attractive to you. Three weeks ago, you didn't notice anything. He or she was a nice person; you liked this person very much. Suddenly, the way he or she moves or smiles at you is intensely sexually attractive. I think that this is at least in part because an elevated activity of dopamine and norepinephrine can stimulate testosterone, the hormone of desire. In short, the biology of romantic love can stimulate lust.

Can the reverse be true? Can you be copulating with somebody who's just a friend and then suddenly fall in love with him or her? Not always. Most adults in the Western world have copulated with just a friend and have never fallen in love with him or her. I've got 4 middle-aged friends who either inject testosterone or use testosterone patches; they don't fall in love 36 hours after they've used them. But I do actually have 3 cases of friends who have told me that they have suddenly fallen madly in love with somebody that they were just copulating with as a friend. I don't understand the physiology of this, but I can report that, indeed, an elevated activity of testosterone does stimulate dopamine and norepinephrine. As a matter of fact, it not only stimulates dopamine and norepinephrine, but it suppresses the activity of serotonin, in short creating the ratio of monoamines associated with romantic love. This is one of the reasons that I say to my students: now don't copulate withpeople you don't want to fall in love with because it may just happen to you!

The bottom line is that serotonin-enhancing antidepressants that negatively affect this sex drive can quite logically also negatively affect the brain circuits for romantic love.

Serotonin-enhancing antidepressants cannot only potentially inhibit dopamine and norepinephrine, they can also blunt the emotions. This is why people take them; I'm certainly for that. If you're suffering terribly, it's the time to try to blunt the emotions. Nevertheless, they are going to have an effect on the elation of romantic love. Serotonin-enhancing antidepressants also suppress obsessive thinking, which is a very central component of romantic love. There are many examples of how these things are affected by each other. In 1 case collected by Thompson, a 20-year-old single white woman had an eating disorder. She was suffering from recurrent depression, she had attention deficit disorder, and she was taking high doses of serotonin-enhancing medication. When she was asked about the side effects of this, she said, "No, no, I don't have any." Then she said reluctantly to the doctor, "But I find myself wanting more space; there just isn't that much attraction." Romantic love is acentral aspect of human reproductive planning. It enables the human animal to focus courtship energy on avidly pursuing a particular partner and beginning the breeding process. When you inhibit this brain system, you can potentially -- not always -- inhibit the patient's psychologic well being and I think his or her genetic future.

Serotonin-enhancing antidepressants can inhibit other evolutionarily adaptive mechanisms for mate selection.

One of them is orgasm; it inhibits orgasm and clitoral stimulation, but let's focus on orgasm. With orgasm, one of the main things that happens is that levels of oxytocin and vasopressin go up enormously in the brain. These are feel-good chemicals. They're associated with social bonding, pair formation, and pair maintenance. So when men and women take serotonin-enhancing medications and fail to achieve orgasm, they can fail to stimulate not only themselves, but their partners as well. This neural mechanism, associated with partner attachment, becomes a failed trigger.

From a Darwinian perspective, orgasm also is a primary mechanism by which women unconsciously assess a mating partner. For a long time, anthropologists have thought that this is a bad design; women just don't have an orgasm every time. More recently, we came to realize that. We call it the 'fickle female orgasm' and we regard it now as a very serious adaptive mechanism that enables women to distinguish between those partners who are willing to spend time and energy on them -- those we call Mr. Right -- and those who are impatient or lack empathy and who might not be a good husband and father -- Mr. Wrong. When women take serotonin-enhancing antidepressants that inhibit the orgasmic response, among some of these women you're jeopardizing the ability to assess the commitment level of a partner. Women also use orgasm to assess existing partnerships; women tend to orgasm more regularly with a long-term partner. With the onset of anorgasmia, this can destabilize a match.

A good example of this is once again a case study collected by Thompson, involving a 35-year-old married woman. She had recurrent depression and anxiety disorder. She was taking a serotonin-enhancing medication, which diminished her libido, and she had absent orgasm. She once apparently said, "I think I no longer love my husband." Then she switched to an antidepressant that had no side effects; her normal sex drive and normal orgasmic response returned and indeed she decided not to divorce her husband. She was thinking of divorcing him and now they have a small child. In this way, drugs can affect your biologic future. These systems are very old. Orgasm and clitoral stimulation are very primitive ways in which women measure men. Like drugs that blur your vision, serotonin-enhancing medications can potentially blur a woman's ability to evaluate mating partners, to fall in love, and to sustain an enduring partnership.

These medications also inhibit penile erection in some men. We regard the penis as an internal courtship device; actually we call it an entertainment system, in my business. It is designed to attract and keep women. With no penile erection, a man has less of a chance of doing that. The penis also is regarded as a fitness indicator -- an anthropology term -- because the penis advertises medical health, psychologic health, and physical fitness. When men take serotonin-enhancing medications that produce impotence, the medications can cripple these vital courtship-signaling functions. Penile erection also has antidepressant qualities; this work comes from a friend of mine and his colleagues from 2002.

The researchers looked at the contents of seminal fluid and, as it turns out, it contains dopamine and norepinephrine, associated with romantic love; oxytocin and vasopressin, associated with attachment; testosterone and estrogen, associated with lust; and follicle-stimulating hormone (FSH) and luteinizing hormone (LH), associated with regular cycling. Without orgasm, men are deprived of these courtship mechanisms. In fact, the same researchers also did a study of seminal fluid and found out that it actually does have regular antidepressant qualities. Those women who were directly exposed to it were less depressed than those who used condoms. I'm not recommending it; I'm simply reporting the data. But when men fail to ejaculate due to antidepressant drugs, they jeopardize their ability to adjust a woman's mood as well as to send important courtship signals. All male animals have evolved a host of courtship devices in order to capture females. Indeed, some of those most importantones can be jeopardized by taking antidepressant drugs.

Serotonin-enhancing antidepressants can also inhibit psychologic mechanisms for mate choice.

Motivation, discrimination -- deciding which person walking through a room is just more attractive to talk to -- and one's self-esteem all are important aspects of one's psychologic well being. The most interesting, I think, are the first 2. In the case of motivation, in one study, a 25-year-old man had had some long-term intimate successful relationships with women. He recounted having a panic disorder and taking serotonin-enhancing medications, and reported that he "just stopped dating."

In another very interesting study, Fisher reported that she was interested in knowing whether serotonin-enhancing medications could actually make a change in unconscious psychologic mechanisms that we use to look at a room of people and decide who is or is not attractive to us. She asked 20 women who were on serotonin-enhancing medications and 20 women who were on no medications to sit in front of a computer and rate the faces of men. Those women who were on the selective serotonin reuptake inhibitors (SSRIs) rated the male faces as more unattractive and also looked at and appraised the faces for a shorter period of time. I don't know if it's her term or not, but she called it 'courtship blunting.' There seemed to be any number of examples of this. In one case, a 54-year-old man in the healthcare business reported, after using serotonin-enhancing antidepressants, "It's like the lens I use to look at the world has been changed." A 45-year-old married woman said, "It's like being handicapped; like being blind."

This reads, "Brad, talk to me -- animal to animal." We are animals. As one psychiatrist once wrote: one of the relics of early man is modern man. The brain is built in many ways to aid reproduction and I think we might find many ways in which serotonin-enhancing antidepressants and perhaps many other drugs subtly affect the way men and women discriminate between mates, choose mates, feel romantic love, and feel marital attachment.

I want to conclude with one more very subtle effect. It's the effect that serotonin-enhancing medications can have on depression. If a patient were going to commit suicide, I'd be the first person to say, "For God's sake, take some medication." I want to repeat again: we are not in the business of saying who should use or who should not use these medications. We're only trying to add to the dialogue some interdisciplinary understanding.

Evolutionists have now come to begin to think that depression actually has some adaptive features. When you think about it, it's very expensive metabolically and socially to be extremely depressed. Various scientists have offered explanations of why this brain system could suddenly have evolved. Of all of them, the one I want to mention -- because it impressed me most -- was that of an anthropologist, 2 biologists, and a psychiatrist. These researchers noted that depression is very socially and metabolically costly. They reasoned that the costs of depression are probably its benefits, that depression in itself is a clear, honest signal that something is really wrong. In fact, it's an extortionary mechanism by which one sends out the signals of real need to get social support. It also gives insight, as one of my psychologist friends says: it's a failure of denial when you're totally depressed. Indeed, mildly depressed people often make clearer assessments of themselves and others.To paraphrase Aeschylus, with this pain comes wisdom.

I believe that masking depression can, at times, and under some circumstances, have serious social and genetic consequences. The classic example is that of the woman who says, "I've been on this medication for several years and I feel much better, but I'm still married to the same abusive alcoholic man." The SSRIs may chemically confine patients to bad relationships as well as hinder the ability to attract and fall in love with a better mate.

I'm going to say it again: we are not recommending that patients who are seriously psychologically ill refrain from taking serotonin-enhancing antidepressants. Indeed, we're learning more and more about them. Sometimes people say they can contribute to suicide and clearly they can also save lives.

What we're trying to say is that these medications affect the threshold of other biologic mechanisms and at times can jeopardize unconscious evolutionary mechanisms for mate selection, for romantic love, and for attachment.

This creates the potential for jeopardizing a patient's personal, social, and genetic future.