McMan's Depression and Bipolar Web
The Brain in Love and Lust
A leading anthropologist explains the birds and the bees.
by John McManamy
In a study published in 2002, anthropologist Helen Fisher PhD of Rutgers University and a multi-disciplinary team of experts recruited 40 young people madly in love - half with love returned, the other half with love rejected - and put them into an MRI with a photo of their sweetheart and one of an acquaintance. Each subject looked at the sweetheart photo for 30 seconds, then - after a diversion task - at the acquaintance photo for another 30 seconds.. They switched back and forth for 12 minutes.
The result was a revealing photo album of the brain in love. Think like a brain scientist and you too would be excited by activity in the right ventral tegmental area. This is the part of the brain where dopamine cells project into other areas of the brain, including the posterior dorsal caudate and its tail, both which are central to the brain’s system for reward and motivation. The sweetheart photos, but not the acquaintance photos, were the cause. In addition, several parts of the prefrontal cortex that are highly wired in the dopamine pathways were mobilized, while the amygdala, associated with fear, was temporarily mothballed.
When Love Blossoms
Romantic love, Dr Fisher explained in a lecture at the 2004 American Psychiatric Association’s annual meeting, is not an emotion. Rather, it’s "a motivation system, it’s a drive, it’s part of the reward system of the brain." It’s a need that compels the lover to seek a specific mating partner. Then the brain links this drive to all kinds of specific emotions depending on how the relationship is going. All the while, she went on to say, the prefrontal cortex is assembling data, putting information into patterns, making strategies, and monitoring the progress toward "life’s greatest prize."
Love also hurts. Dr Fisher cited one recent study where 40 percent of people who had been dumped by their partner in the previous eight weeks experienced clinical depression and 12 percent severe depression. It is estimated that 50 to 70 percent of female homicides are committed by lovers and spouses. Annually one million women and 400,000 men are stalked.
Dr Fisher divides love into three categories involving different brain systems: 1) Lust (the craving for sexual gratification), driven by androgens and estrogens; 2) Attraction (or romantic or passionate love, characterized by euphoria when things are going well, terrible mood swings when they’re not, focused attention, obsessive thinking, and intense craving for the individual), driven by high dopamine and norepinephrine levels and low serotonin; and 3) Attachment (the sense of calm, peace, and stability one feels with a long-term partner) driven by the hormones oxytocin and vasopressin.
"I think the sex drive evolved to get you out there to get looking for anything at all," she told her audience. Romantic love, she thinks, developed to focus one’s mating energy on just one individual while attachment works to tolerate this individual long enough to raise children as a team.
These systems are also connected. "Don’t copulate with people you don’t want to fall in love with," she half-jokingly tells her students, "because indeed you may do just that." Testosterone can kickstart the two love neurotransmitters while an orgasm can elevate the attachment hormones. But the brain systems remained separate units, probably to allow each partner to cheat on the other. This would have enhanced Alley Oop’s chances of transmitting his genes. A philandering Clan of the Cave Bear babe, meanwhile, would have had an insurance policy had her main squeeze ended up as a baby mastodon’s throw toy.
Romantic love, Dr Fisher believes, is a stronger craving than sex. People who don’t get sex don’t kill themselves, she said. On the other hand, it is not adaptive to be romantically in love for 20 years. "First of all," she confided, "we would all die of sexual exhaustion." Not surprisingly, the subjects in her study who had been in love the longest (17 months) displayed markers in the brain indicating the beginnings of "the satiation response."
In a related undertaking, Dr Fisher found evidence that romantic love exists in 150 societies, even though it is discouraged in many of them. But with many women from these countries now entering the workforce and acquiring a sense of independence - together with medical science keeping us relatively younger longer - we can expect to see romantic love on the rise worldwide, she predicted..
Bring it on.
When Love Fades
High levels of oxytocin and vasopressin may interfere with dopamine and norepinephrine pathways, Dr Fisher explained in the same talk, which may explain why attachment grows as mad passionate love fades. The antidote may be doing novel things together to goose the two love neurotransmitters.
Meanwhile, elevated testosterone can suppress oxytocin and vasopressin. There is good evidence, Dr Fisher said, that men with higher testosterone levels tend to marry less often, be more abusive in their marriage, and divorce more regularly. The reverse can also be true. If a man holds a baby, levels of testosterone go down, perhaps in part because of oxytocin and vasopressin going up.
In a 54-item questionnaire Dr Fisher prepared for 430 Americans and 420 Japanese, 95 percent responded yes to the question, "Have you ever been dumped by someone you really love?" An equal number also dumped someone who really loved them. Getting dumped makes you love the person harder, Dr Fisher noted, a term she calls "frustration attraction."
Psychologists also refer to "abandonment rage" and "frustration depression," which may paradoxically work to hasten the relationship’s end. Then comes resignation and despair, where the brain’s reward system begins to realize the you are never going to get what you want. Despair may seem counterproductive, but it is in essence "a failure of denial" that allows us to see the world for what it is and sets us on the road to finding a more suitable partner.
Although the brain images of the men and women in Dr Fisher’s study were basically the same, she and her colleagues did find activity in men in a region of the parietal of the temporal lobe associated with the integration of visual stimuli. Ninety percent of pornography is for men while women spend their lives trying to look good for them, Dr Fisher explained. The Darwinian explanation is that the studs of Leakey Land picked their partners by sizing them up visually.
In women, there was more activity in regions associated with memory recall. From an evolutionary perspective, looks probably weren’t enough to determine if a prospective mate would be a good provider and protector. The belle of the Great Rift Valley needed to remember what that suave suitor with the sexy brow ridge grunted yesterday and promised two months ago.
Love at Risk
At a different APA forum, "Sex, Sexuality, and Serotonin," Dr Fisher warned that antidepressants may jeopardize romantic love. As well as high dopamine and norepinephrine, she said, romantic love is characterized by low serotonin. Low serotonin would explain the obsessive thinking attached to romantic love. In her MRI study, her subjects reported that they thought about their loved one 95 percent of the day and couldn’t stop thinking about them. This kind of obsessive thinking is comparable to OCD, she said, also characterized by low serotonin.
Serotonin-enhancing antidepressants, she said, blunt the emotions, including the elation of romance, and suppress obsessive thinking, a critical component of romance. "When you inhibit this brain system," she warned, "you can inhibit your patient’s well-being and possibly their genetic future."
These antidepressants also inhibit orgasm, clitoral stimulation, penile erection ("the entertainment system, in my business"), and deposit of seminal fluid. From an anthropological perspective, a woman who can’t get an orgasm may fail to distinguish Mr Right from Mr Wrong. As one woman on an SSRI confided to her: "I thought I no longer loved my husband." In a study in press, women on SSRIs rated male faces as more unattractive, a process she calls "courtship blunting."
Seminal fluid contains dopamine and norepinephrine, oxytocin and vasopressin, testosterone and estrogen, and FSH and LH. Without an orgasm, said Dr Fisher, men lose the ability to send courtship signals. Said one man, who lost his motivation and self esteem as a result, "I just stopped dating."
Ironically, because antidepressants inhibit depression, patients may lose their ability to send an honest clear signal for social support and (for those with mild depression) lose the necessary insight to make hard decisions (the failure of denial factor).
Dr Fisher said she didn’t want psychiatrists to stop prescribing serotonin-enhancing antidepressants for their patients, but did stress the need to take the love-relationship picture into account.
When Sex Goes Right
At the same symposium, Anita Clayton MD of the University of Virginia related what goes on molecularly during arousal and orgasm: Testosterone drives sexual activity in men. Testosterone also affects women, plus estrogen and progesterone, associated with permissivity and receptivity, respectively. These three hormones help maintain genital structure and function. Dopamine is tied into sexual desire while norepinephrine is related to subjective excitement. During orgasm, oxytocin levels rise.
When Sex Goes Wrong
At the same symposium, Dr Clayton mentioned that serotonin can dampen sexual desire and excitement. It can also deaden sensation, leading to vasocongestion ("blue balls"). Prolactin can have a negative impact on sexual excitement.
Philip Muskin MD of Columbia University cited these statistics:
* Married couples report having sex 68.5 times a year (1.3 times a week) according to a 2002 University of Chicago National Opinion Research Center Report. According to a 2003 cover story in Newsweek, 15 to 20 percent of couples have sex less than 10 times a year, regarded as a sexless marriage.
* Various studies give the following breakdown for incidence of sexual disorders: Hypoactive sexual desire (27-34 percent women, 13-17 percent men); Sexual arousal disorder (11-27 percent women); Erectile disorders (eight-38 percent men); Orgasmic disorders (15-28 percent women); Premature ejaculation (25-32 percent men); Pain during intercourse (eight-23 percent women).
Dr Clayton cited her 2001 study that found that 37 percent of men taking antidepressants experienced sexual dysfunction. Paxil was the highest at more than 40 percent and Wellbutrin the lowest at about 20 percent. Remeron was surprisingly at the high end of the scale.
Only 14.2 percent of patients spontaneously report antidepressant induced sexual dysfunction to their physicians, according to a 1997 study vs 58.1 percent responding to a questionnaire.
Antipsychotics pose their own set of problems. A 2003 study by Knegtering et al reports that 60 percent of Risperdal patients reported sexual side effects vs about 27 percent for Zyprexa and about 44 percent for old generation antipsychotics.
Risk factors for sexual dysfunction include being at least 50 years old, married, less than college education, not employed full time, tobacco use, higher doses of antidepressants, concomitant meds, co-occurring ills known to cause sexual dysfunction, prior history of antidepressant-induced sexual dysfunction, history of little or no sexual enjoyment, and regarding sexual functioning as not or somewhat important.
According to data from the 1992 National Health and Social Life Survey, 43 percent of women and 30 percent of men have a sexual complaint (a sexual complaint is not of the same magnitude as sexual dysfunction or sexual disorder). In patients with depression, that figure is 70 to 80 percent. Depression itself rarely causes sexual dysfunction, Dr Muskin explained. Untreated depression, however, often causes a lack of interest in sex, and disrupts intimacy.
Dr Muskin says doctors must encourage their patients to accept the reality that getting well is more important than sexual dysfunction. Patients and their partners, he said, may need to reconfigure how they have sex. Arousal may need to be at a higher pitch before intercourse, and orgasm need not be linked to the act.
But patients may want to try these antidotes first, cited by Dr Clayton: Wellbutrin, Viagra (for men), and Buspar (for women), all supported by studies. Other possibilities include hormones (testosterone, estrogen), yohimbine, amantadine, and low dose psychostimulants.
At another APA forum, WebMD reported on a presentation by Richard Brown MD of Columbia University, who noted that although Viagra may improve erection, it doesn't help much with libido and orgasm. The following natural treatments, he said, show promise: Rhodiola (an arctic plant that works for both men and women, may work on dopamine, helps libido and boosts energy); Ginko biloba (for impotence in men and maintains erection); Gingseng (appears to work on dopamine, so woman can benefit too); Maca (a Peruvian root that "can have powerful effects on desire, erections, and orgasms"); Horny goat weed (forgive the term, little data).
Gay and Lesbian Sex
At the same symposium, Serena Volpp MD, MPH of New York University discussed gay and lesbian sex. According to 1994 NHSL Survey figures, nine percent of women and 10 percent of men reported homosexual behavior, desire, or identity. One-third of those who had same sex partners in the past year did not consider themselves homosexual. Fifty percent of gay men and 75 percent of lesbians have had intercourse with the opposite sex. According to figures from a 1983 book by Blumstein and Schwartz, 67 percent of gay male couples have sex at least three times a week in the first two years of marriage compared to 61 percent of sexual couples and 33 percent lesbian couples. Various authorities estimate that gay men have had somewhat less than 50 sexual partners while the figure was less than 10 for lesbians. NHSL Survey data indicates that men have six long-term sexual partners while women have two
Dr Volpp stressed that gay and lesbian sexual practices are essentially the same as for heterosexuals, with the same body parts in play and the goals of achieving a high degree of intimacy and sexual release or orgasm. A 1991 study by Roesser found that gay males had anal intercourse in one-third of their encounters. Oral sex and mutual masturbation made up the other two-thirds. Lesbians engaged in kissing, petting, mutual genital contact, oral-genital contact, body contact, and object-genital insertion.
Unfortunately, owing to the effectiveness of new medications, the younger generation is more complacent about safe sex. New HIV infections among gay men went up 17 percent between 1999 and 2002.
Better Than Cheesecake
"For many of us, sexual orgasm, accomplished within a love relationship, is one of the all-time highs. And sex, like love, can be accompanied by a sense of merger and transcendence." Ethel Peterson MD of Columbia University, at the same APA symposium.
Love Potion Number 32
A Rockefeller University press release dated Feb 15, 2000 began:
"Valentine's Day cards usually depict Cupid's dart as the messenger of love. New scientific research, however, shows that a key messenger molecule, rather than Cupid's dart, is responsible for female sexual receptivity - at least in rats and mice.
"Scientists at New York's Rockefeller University and Houston's Baylor College of Medicine have found that a protein called DARPP-32 is the essential ingredient in the brain pathway that makes female mice and rats sexually receptive. The study is reported in the Feb. 11 issue of Science."
The title for the Science article was a far less suggestive: "Requirement for DARPP-32 in Progesterone-Facilitated Sexual Receptivity in Female Rats and Mice."
When 2000 Nobel Laureate Paul Greengard PhD brought this up at a lecture at the APA’s 2004 annual meeting, the audience burst out into appreciative laughter. Up until this time, Dr Greengard had been giving the equivalent of a master’s class on the fine points of brain science, with a focus on how DARPP-32 acts as a virtual Grand Central Station for routing and rerouting chemical impulses along an interlocking network of molecular signaling pathways inside the neuron.
Dr Greengard’s pioneering work into DARPP-32 has provided new insights into schizophrenia and drug use. Mice with no DARPP-32, for example no longer respond to recreational drugs. This research may have helped Dr Greengard win a Nobel Prize, but it was his findings into female sexual receptivity that got him in the papers. Without DARPP-32, signals that would normally get sent to dopamine and estrogen and progesterone don’t get sent.
Dr Greengard amused his audience with this reading from one media account: "But researchers say the protein will not be available in drug form for five years."
June 26, 2004, reviewed Feb 10, 2008
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