A gene variant in the CYP2A6 enzyme may help protect some individuals from nicotine addiction, according to a new study funded in part by the National Institute on Drug Abuse of the National Institutes of Health. 

According to the study, which was published in a recent issue of 

, individuals with decreased functionality of CYP2A6 were shown to have greater resistance to nicotine addiction and, if they do smoke, smoke fewer cigarettes than do individuals without the variant gene.

CYP2A6, found in the liver, is primarily responsible for metabolizing nicotine. University of Toronto researchers, led by Rachel F. Tyndale, Ph.D., observed that CYP2A6 variation affects the metabolism of nicotine. Individuals with decreased functional CYP2A6 are less likely to become addicted to nicotine.

Tyndale and her colleagues found three different gene types, or alleles, for CYP2A6: a normal, or wild-type allele, that is fully functional; and two null or inactive alleles. Individuals with the null alleles functionally lack the enzyme and are unable to break down nicotine to cotinine, a major metabolite of nicotine.

When comparing a group of smokers to a group that had tried tobacco but had never become addicted to it, the investigators found that individuals in the nonaddicted group were much more likely to have impaired nicotine metabolism, and to have one null allele for CYP2A6. Thus, those with a null allele had been "protected" against nicotine addiction compared with individuals with the normal or wild-type alleles. 

In addition, among a group of people who do smoke regularly, those with null CYP2A6 alleles smoked fewer cigarettes over the course of a week than those with normal CYP2A6 alleles.

Tyndale said, "These two factors, a reduced propensity to smoke and the need to smoke less, would likely decrease the risk of developing tobacco-related illnesses, such as cancer, among those with CYP2A6-null alleles."

Researchers believe that the protective effect of CYP2A6-null alleles suggests that medications might be developed that can inhibit the enzyme, thus providing innovative approaches to preventing and treating nicotine addiction-LKC

Articles

A gene variant in the CYP2A6 enzyme may help protect some individuals from nicotine addiction, according to a new study funded in part by the National Institute on Drug Abuse of the National Institutes of Health.

CYP2A6 Variation May Protect Against Nicotine Addiction

Before Masters and Johnson came on the scene in the late 1950s, any sexual problem was thought to be the result of a deep-seated neurosis that needed to be unearthed. It is now recognized that an understanding of physiology and couples dynamics-along with a practical approach-are required interventions, said Harvard's Derek Polonsky, M.D.

The psychiatry instructor and lecturer has specialized in couples therapy and sexuality since the turbulent 1970s, when Beth Israel Hospital was a "hotbed of individually oriented psychoanalytic psychotherapy," he recalled. "That's how I got to see couples early on. After a while, they began to bring up issues of sexuality, which I must admit was a shock to me [at the time].

"The field of sexuality over the last 25 years has grown enormously to encompass a full range of disciplines: on the one hand, mental health professionals and on the other, gynecologists, urologists, internists and the lay profession," said Polonsky, author of 

He advises that before beginning couples sex treatment, therapists need to assess three factors. First, do either of the patients have medical conditions that play a role in the problem, such as arteriosclerosis, diabetes, thyroid problems, depression, alcoholism and the side effects from medications? Drugs used for high blood pressure are notorious for dampening sex drive, as are antidepressants, particularly selective serotonin reuptake inhibitors. Despite claims by pharmaceutical companies that only a minority of people experience significant sexual side effects from antidepressants, independent studies report high percentages of subjects who experience effects upon libido, arousal, ability to get or maintain an erection or capacity to have an orgasm.

Second, assess the intrapsychic components-such as issues of self-esteem, intimacy, assertion and conflict around competence or aggression-that each individual brings to a sexual situation. Third, because sexuality often is the stage upon which relationship issues get played out, assess what interpersonal components (the marital couple dynamic, the power play, what gets reenacted from the family of origin) are involved.

"Fifty percent of people deal just fine with the kinds of challenges involved in separating from families of origin, mastering the tasks of forming a close relationship with somebody outside the family and integrating that with sexual feelings in the context of the close relationship," said Polonsky. "But that leaves another 50% of the population who struggle with these [issues]."

Polonsky's treatment approach integrates couples therapy with sex therapy and is analogous to what a coach does. In other words, he identifies the strengths people bring to the relationship, figures out which activities need help and develops drills to help people with those areas.

During the initial meeting with a couple, he inquires about the nature of their sexual difficulty, a history of it over time and the evolution of their relationship. Next, he schedules individual meetings to learn about each person's family of origin "because that supplies the template for behavior and expectations that often get transposed into the marriage." At this time he also gets a more detailed sexual history. Then he brings the pair back and shares his ideas of what he thinks is going on.

He gives the couple an assignment, structuring what they do and reducing their sexual activities to the lowest common denominator by shifting the focus from performance to pleasure and playfulness. The following week's discussion centers around what happened.

Polonsky creates a safe climate for talking about issues of sexuality, providing a model for talking about sex, and using humor and a comfortable vocabulary to diminish anxiety. He educates his patients by providing information about physiology, myths and patterns of behavior.

"Couples therapy differs from traditional psychotherapy in that the therapist is more active," he said. "In addition, the transference occurs between the two partners rather than between patient and therapist."

While on the surface it would appear that as a culture we are more comfortable talking about sexuality, that is deceptive, Polonsky said. "We only have to look back at 1994 when Jocelyn Elders, the Surgeon General, was fired for daring to talk about masturbation, to realize that we still have a long way to go."

Learning to take the sexual history is hard for new therapists because they've had no models for being open and explicit. Most medical schools and training programs have either dropped the programs they had or ignore sexuality altogether.

"When I first started taking histories from my patients, I would choke on some of the words," he said. "At times I would be so hypertechnical using the anatomical jargon that I would be greeted by vacant stares from my patients. They didn't have a clue what I was talking about.

"There also was a cross-generational awkwardness. Many of my patients seemed to be in my parents' age group. To ask them about the details of their sexual relationship just seemed to be crossing a boundary...Now that I'm a parent of an adolescent kid, I'm aware of how parents are similarly uncomfortable about their children's sexuality."

There is no "right" way of getting the history, Polonsky said. Therapists have to experiment until they find a model that is down-to-earth and comfortable for them and their patients. Couples will follow along, in terms of tone and terminology.

He begins with the general ("Tell me about your relationship. Are you satisfied? Would you want anything to be different?") and works toward the specific. He asks couples about patterns of initiation, whether they enjoy fantasies, what kind of experimentation they're comfortable with, whether they read erotic material or watch pornographic movies, whether they are comfortable experimenting with sexual toys. He asks about their communication with each other: Do they talk about their likes and dislikes? Are they comfortable asking for things? Is there reciprocity?

Sometimes you have to be "stupid in listening," he said, and inquire about the fine points rather than make assumptions. Does "losing an erection," for example, refer to an erectile difficulty caused by anxiety? Or does someone really mean premature ejaculation?

These details about the sexual interaction give the therapist a portrait of the couple's relationship. "I don't believe one can do sex therapy in a vacuum," he said. "One has to recognize that [there are] two people involved in this interaction, each with their own histories and backgrounds."

Contrary to finding this intense questioning intrusive-a worry of new therapists-most people are relieved to bring the problem into the open. "Often when a couple has a sexual problem," he said, "they've tried initially to deal with it, failed, and then they enter into a conspiracy of silence where there's a tacit agreement that they're not going to discuss these issues more directly." People go for years, even decades, suffering under an enormous burden of shame, blame and inadequacy. "They're convinced that they are the only ones to flunk Sexuality 101. Just talking with a therapist and being reassured that they are not alone goes far to diminish anxiety," Polonsky added.

Polonsky recognizes that today, practitioners are realizing that sex does not end with youth, but can extend pleasurably into old age. Aging, though, takes a toll; arousal takes longer and requires-particularly for men-more direct tactile stimulation. A couple who is unaware of this might become concerned about what has happened to their formerly good sex life, so education is needed.

Polonsky points out that clinicians have also learned exactly how the penis works: In order to have an erection, a man needs an intact vascular system, an intact nervous system and an intact hormonal system. Erectile difficulties affect 10% of American men, but that's overall; in the age group 40 to 70, organic and medication-related dysfunction become increasingly common, affecting as many as 50% to 60%, said Polonsky. With 38 million baby boomers now falling into this category, the rush is on for new medical treatments.

The National Institutes of Health estimates the number of impotent men in the United States at 30 million. According to Time magazine (May 4), when Viagra hit the market in April of this year, 36,809 prescriptions were issued during the first two weeks alone. 

But Viagra shouldn't be used to circumvent dealing with relationship problems, warned Polonsky. Having "a perfect penis" may not be the whole answer, nor is vaginal intercourse the only means for satisfaction. Genitals are not mechanical devices that should be programmed like VCRs, he said; they are connected to human beings. "In this culture, we are so focused on what I call the mechanical model of sex. We need to broaden the repertoire and broaden the range," Polonsky said. "We also need to combine what is not working right with the physiology and what may not be working right in the balance of the relationship."

According to Polonsky, about 25% of men experience premature ejaculation, and for this a behavioral approach usually is effective. If not, some of the antidepressants that delay ejaculation-an otherwise unwelcome side effect-often help. Polonsky, however, has mixed feelings about using a medication in its full therapeutic dosage to gain access to its side effect.

Only in the past decade has the issue of diminished desire come to the forefront. Affecting 30% to 50% of couples, it is the problem Polonsky most frequently sees. It is more than just a matter of the early passion wearing off, he said. Often there is a mix of issues regarding intimacy, vulnerability, depression, significant physical changes or early sexual abuse.

"The therapy is often slow and complicated, and at times confounding," he said. Contrary to what the media would have people believe, treatment is slow and, in many cases, improvement is negligible. 

The awareness of childhood sexual abuse and its aftermath is a new issue for women. "When I look back on some of the people I saw years ago," Polonsky said, "in retrospect, I think I probably missed the diagnosis where there were issues of sexual aversion or low sexual desire. I think that I just didn't understand, and most of us didn't back then, about the incidence of childhood sexual abuse and its repercussions. We now know that if there is a history of alcoholism, the incidence of childhood sexual abuse is something like 60% in the family."

Prescribing low doses of testosterone for women could become another new trend, according to Polonsky, because some physicians maintain that it can have a beneficial impact upon the diminished sexual desire that some women experience after menopause. He, however, is uncomfortable about "mess[ing] with a variety of hormones."

Polonsky notes that women have been taking increasing control over their own sexuality, a trend that began in the 1960s when sex came out into the open. At first, it became acceptable simply to be receptive to male overtures. Now, he avers, women are feeling sexual in their own right and free to make the advances. Not all men are comfortable with this, however, which can create conflicts in relationships.

With so much new knowledge, so many medical specialties now involved in sexuality, and more products appearing on the market every day, sexual problems are not as hopeless as they once seemed, Polonsky pointed out. Those associated with aging may be the easiest to treat. 

"What the early sexual relationship was like often can predict the outcome of therapy," said Polonsky. "If it was playful and a source of joy, then it absolutely will continue with the use of some of these adjunctive therapies."

Before Masters and Johnson came on the scene in the late 1950s, any sexual problem was thought to be the result of a deep-seated neurosis that needed to be unearthed. It is now recognized that an understanding of physiology and couples dynamics-along with a practical approach-are required interventions

From Mars to Venus-Couples Sex Therapy

Day in and day out, psychiatrists-especially those involved with couples therapy-counsel and treat patients experiencing relationship problems with their spouses or partners. But what about the psychiatrist having a similar problem in his or her own life? Who does a doctor turn to for guidance and insight regarding such intimate matters?

Michael F. Myers, M.D., of Vancouver, British Columbia, asked himself this question about 20 years ago and now, three books and numerous doctor-patients later, he has a thriving couples therapy practice specializing in the healing of physician relationships.

Doctor's Marriages: A Look at the Problems and Their Solutions 

(Plenum Publishing, 1994), talked about the tremendous pressures physicians are faced with today. Foremost, said Myers, is how the decreased income caused by managed care and the changing work scene have altered lifestyles.

"Many men define themselves, not only by what they do, but also by how much money they make," said Myers, "and that outlook definitely holds true in the field of medicine.

"I'm struck by the number of times the male physician is actually quite worried by money, but hasn't identified it as such. He hasn't really explained to his wife that the reason why he's yelling so much or is so out of sorts is because he's really worried about finances. In other [nonphysician] couples I see, it's more overt; they're openly fighting about money."

Myers has also seen many physicians overwork themselves to maintain a standard of living that they had before by either working outside of managed care or working fee-for-service. "What this does, however, is make the physician less available at home, both as a husband or wife and as a parent to the children," he said.

On the opposite end of the spectrum, but still connected to money concerns, is the fact that some physicians are underutilized. "They're not getting as much work, so they don't have the option of working harder even if they could," Myers pointed out.

One unfortunate offshoot of the accumulation of pressure and the demoralization of the physician workforce is what Myers views as an unhealthy competition for jobs.

"I feel that in many areas there is less collegiality among physicians than there was 10 to 15 years ago," Myers explained. "Malpractice litigation continues to increase as well as licensure investigations of doctors. All of which creates a kind of internal angst in physicians, and affects how they communicate at home, how intimate their relationships are with their spouses or partners and, of course, their sexuality."

Another stress side effect Myers has noticed is an increase in mood disorders.

"This is all anecdotal, though," he said. "We don't have empirical research on the incidence or prevalence of mood disorders in doctors. There's some old data, but there's really nothing current.

"Many of my colleagues who work in the area of physician health tell me they are diagnosing more and more doctors with depression, and they're not exactly sure why that is, or what it means. For a while, when the SSRI [selective serotonin reuptake inhibitor] drugs came out, they thought that maybe it was because there are now cleaner drugs, like Prozac, and physicians are more open to embracing antidepressant treatment."

Myers said he also sees a number of doctors who self-medicate. "I get many phone calls that go like this, 'Hi, Dr. Myers, this is Dr. X calling. I've been feeling kind of depressed lately, so I put myself on Prozac about a month ago and I'm feeling a lot better now, but I don't want to self-medicate. Can I come in to see you?'"

Although Myers and his addiction medicine colleagues don't have recent empirical data on chemical dependency in doctors, they still see substance use disorders negatively impacting physician relationships.

"All of my addiction medicine colleagues say the same thing: that even though they don't have recent empirical data, the substance dependency numbers certainly don't seem to be dropping. In other words, we don't think that physicians' drug and alcohol use is lessening.

"I see many doctor-couples each year in which both are living with mood disorders; therefore, I've got them both on antidepressants. One could be bipolar, the other unipolar. Or one has depression, the other has chemical dependency. Let's face it, marriage is tough enough, and when you've got one or both partners living with these illnesses, it really wreaks havoc on your ability to work efficiently and effectively, to communicate well, to make love comfortably, to raise your kids...all kinds of things."

Myers notes that there is also a certain stigma attached to physicians living with depression or chemical dependency, so they delay going for help, or avoid it altogether. "Then," said Myers, "that gets into the whole area of stigma about going for some sort of marital therapy."

Myers said he has a whole group of physicians who come to him because they say it doesn't feel like they are going to a psychiatrist. "They tell me it feels like they're going to counseling, and that makes them feel 'less screwed up.'"

Over the last 20 years, Myers has witnessed changes in the face of the medical workforce. "For one thing, there are more and more women in medicine," he explained. "The percentages of women enrolled in medical school are now pretty close to 45% to 50%. In addition, there are more minorities, international medical graduates, gay and lesbian couples and intercultural and interfaith marriages.

"Because of the cosmopolitan nature of where I live and work in Vancouver, it isn't unusual for me to look after doctor-couples in which one is Asian and the other is from the Indian subcontinent. Still another may be Canadian, the other from Thailand. And that details only interracial differences," he explained.

Myers said these groups bring their own texture to the two-couple therapist. "Most women doctors marry other professionals, many who are physicians themselves, but that's not always the case. I look after some women physicians and their husbands where they have a reverse traditional marriage. She has a much higher level of formal education than he has, and he works in a trade of some sort. Often when they are raising their kids, he is home full-time. It's pretty much like an old-fashioned or traditional male physician marriage."

He has also noticed more doctors coming to him who are in their second or third marriages.

"That could have something to do with physicians just getting older, but it could also represent that they have moved into these new relationships very quickly without resolving the immediate marriage, so their judgment may have been affected."

Myers said these physicians are usually interested in getting some couples work because they want to make sure their current marriage works.

"Many times doctors at first will say, 'I'm so busy, I really don't have time for couples therapy; I just want to live my life.' But then they'll read an article about high divorce in second or third marriages, and panic. Or they'll begin to see patterns in their present marriage that aren't unlike those in the previous ones."

With his younger physician couples, Myers notes that many are adult children of divorce, and openly admit they have some struggles with intimacy.

"It sometimes turns out that they're late in getting married because they develop an almost obsessive sense of 'This has to be perfect.' That's tough because they've put tremendous pressure on themselves. Or it sometimes works the other way around. Because of insecurity that developed through their parents' marriage and divorce, they have coupled very, very young, and are hanging on for dear life. Many times these marriages don't work because they're suffocating each other to death."

On a sad note, Myers said that as of 10 years ago, he had a certain number of physician couples in his caseload where one or both were living with HIV/AIDS.  "With the exception of only one of those couples," Myers noted, "all have now died."

At home in Vancouver, Myers spends half his professional life in private couples' therapy practice, and the other half instructing physicians at a downtown teaching hospital.

When asked what he consistently tells his audiences, comprised mainly of psychiatrists, about counseling the doctor-patient in couples therapy, Myers said, "Make sure you treat your doctor-patient couple as a struggling couple first. See them as a couple who are having problems, both of whom just happen to be physicians. This is very important because if psychiatrists get blindsided by the fact that one or both of their patients are doctors, then sometimes they make assumptions that their problems aren't so bad, or that maybe they can take care of themselves.

"Doctor-patient [couples] need to be approached like any other ailing or struggling couple [that] comes to a psychiatrist. It's a very basic point, but I always like to remind psychiatrists of this, because I hear of so many situations where the physician-couple feels they didn't get the kind of care they thought they were going to get."

Caring for the Physician in Couples Therapy

I stand beneath the bridge and listen
to it flex and sing
as traffic mourns overhead,
the river below
whipped into white scallops
by a fierce south wind.
The forgiven sun
spills road and tower shadows
on churning water.
Across the river, the city grinds
Dominican and Honduran on land
my father walked as a boy
when men piled steel X's,
men who fell
as they strained to connect
the yearning concrete spans.
On ribbon cutting day
he walked across,
the river blue and clean back then,
years before his commute
on the 

bus
over the bridge to his factory
and the smell of leather skins
he swore kept him alive
when rivers of blood
poured from his gut,
and all the years he fell
silent and I did not know
how to risk my life to reach him.
 

The George Washington Bridge - Poetry of the Times

The George Washington Bridge

Using positron emission tomography (PET) to examine the cause of cluster headaches,  researchers found that the hypothalamic region in affected people consistently lit up, indicating activity in that part of the brain. 

The investigators, who presented their findings at the 40th annual scientific meeting of the American Association for the Study of Headache in June, studied cluster headache attacks in 17 patients after administering nitroglycerin to trigger the pain.

By injecting the patients with water labeled with a radioactive tracer, the research team was able to monitor cells undergoing more activity. That activity was recorded by a PET camera, then processed and reconstructed by computer so that the areas of greatest activity "lit up" on a computer-generated image.

The scientists discovered that the hypothalamic region of the brain, the part of the central nervous system that contains the brain's biological clock, lit up more than other regions during an attack. 

"This suggests we need to consider a radical reappraisal of the pathophysiology of cluster headache," said lead researcher, Peter J. Goadsby, M.D., Ph.D., professor of clinical neurology at the Institute of Neurology, Queen Square, London-CLG

Using positron emission tomography (PET) to examine the cause of cluster headaches, researchers found that the hypothalamic region in affected people consistently lit up, indicating activity in that part of the brain.

Brain Imaging Exposes New Information on Cluster Headaches

How much of the beneficial effects of anti-depressant medications can be ascribed to the placebo effect? Irving Kirsch, Ph.D., and Guy Sapirstein, Ph.D., addressed this important question in a recent study that appeared in the first volume of the American Psychological Association's online journal,

 (June 26,1998). Although their methodology and conclusions have met with some controversy, it would be imprudent to invalidate the study and its hypothesis.

Kirsch and Sapirstein calculated the mean effect sizes for 2,318 patients who were randomly assigned to antidepressant medication or placebo groups in 19 double-blind clinical trials. Of the total 2,318 participants, 1,460 received medication and 858 received placebo. The results of the studies were combined through the use of a meta-analysis. To delineate the components of the placebo effect, the authors utilized psychotherapy outcome studies.

The authors divided the 16 medications used in the various studies into four general categories: tricyclics and tetracyclics, selective serotonin reuptake inhibitors, other antidepressants and other medications not considered antidepressants (amylobarbitone, lithium [Lithobid, Eskalith], liothyronine [Cytomel, Triostat], and adinazolam). 

From their data, the authors concluded that "75% of the response to the medications examined in these studies was a placebo response and, at most, 25% might be a true drug effect...[that] means that for a typical patient, 75% of the benefit obtained from the active drug would have also been obtained from an inactive placebo."

Kirsch and Sapirstein attempted to explain the overwhelming efficacy of nonantide-pressant medications. Perhaps, they suggested, these medications are affecting depression indirectly by improving sleep, lowering anxiety and the like. Their effects should have been less than that of true antidepressants, the authors wrote; instead the effect observed was "at least as great as that to conventional antidepressants." 

Another possible answer is that antidepressant medication might function as active placebo, in which the side effects amplify the placebo effect by convincing patients that they are receiving a potent drug. 

Natural history effects also may play a role in the magnitude of placebo effects observed. The authors note that "the promise of future treatment is sufficient to trigger a placebo response." Likewise, the assignment to a control group can cause feelings of hopelessness and, accordingly, increase feelings of depression.

The authors recommend four-arm studies to ascertain definitive effects of active placebos, inactive placebos, active medication and natural history-HAD

How much of the beneficial effects of anti-depressant medications can be ascribed to the placebo effect? Irving Kirsch, Ph.D., and Guy Sapirstein, Ph.D., addressed this important question in a recent study that appeared in the first volume of the American Psychological Association's online journal, Prevention and Treatment (June 26,1998). Although their methodology and conclusions have met with some controversy, it would be imprudent to invalidate the study and its hypothesis.

Controversial Study Investigates Therapeutic Benefit of Placebo

Results of a multicenter, open-label observational trial of DuPont Merck's REVIA (naltrexone) demonstrated that patients were able to decrease their alcohol consumption from 57 to four drinks per week when the medication was part of an overall treatment program.

In this study of 3,000 patients, 71.3% of participants had begun drinking to intoxication before the age of 20, and 70% had been drinking to intoxication for 10 to 29 years. The results of the study found that 79% of the participants remained abstinent over the four weeks of treatment. 

Preliminary results of the trial were presented at the annual meeting of the Research Society on Alcoholism by William J. Lynch Jr., clinical programs manager of medical affairs at DuPont. Lynch reported that the most frequent adverse clinical events were nausea (13.6%), headache (2.2%), dizziness (1.6%), insomnia (1.4%), fatigue (1.2%) and vomiting (1.1%). In addition, the severity of adverse clinical events was mild (43.9%) to moderate (42.4%). To combat nausea, investigators suggested dosing naltrexone with meals or at bedtime, interrupting or reducing the dose for a short period of time, or treating with antacids. Of those who experienced nausea, 77% reported it was a limited acute event. 

The study population included individuals older than 18 who achieved one to six weeks of abstinence immediately prior to screening and who were actively participating in an alcohol rehabilitation treatment program that employed social and/or psychotherapeutic methods. The starting dose of naltrexone was 50 mg orally once daily after patients achieved a minimum of seven days of abstinence from alcohol consumption."Multiple clinical studies have demonstrated the effectiveness of REVIA as a treatment tool for alcohol dependence and also have highlighted nausea as the most significant adverse event," said Lynch. "This trial has provided clinicians with suggestions on treatment modalities that can help to manage nausea and allow patients to more comfortably continue with their alcohol dependency therapy."

Naltrexone was approved by the U.S. Food and Drug Administration for the treatment of alcoholism in January 1995. It was the first medication so approved in over 40 years-MB 

Dramatic Alcohol Treatment Results Seen with Naltrexone

We live in an era of stigma regarding psychiatric illness, psychiatric patients and psychiatric treatments-an era in which a Supreme Court justice suggests in a minority-dissenting opinion that one would be better off talking to one's mother than to a psychotherapist. 

Indeed, psychotherapy is often viewed as a form of hand-holding rather than a "real" treatment. This perspective persists despite the fact that there is overwhelming evidence that it is a highly effective intervention. In psychotherapy studies, the magnitude of the effect size is sufficient to justify interrupting clinical trials on the grounds that it would be unethical to withhold such a highly effective treatment (Ursano & Silberman, 1994).

With advances in the neurosciences, and especially in imaging techniques, we stand at the threshold of demonstrating that psychotherapy is a powerful intervention that affects the brain. While it has been intuitively obvious to most clinicians that psychotherapy must work by affecting the brain (how else could it work?), recent breakthroughs in technology have allowed us to begin demonstrating for the first time what kinds of changes occur with psychotherapy. Documentation of these changes may go a long way toward removing the stigma currently attached to psychotherapy.

While there was a time when psychotherapy was thought to be the appropriate treatment for "psychologically based" disorders, and medication was considered the treatment of choice for "biologically based" disorders, this distinction is now becoming increasingly specious (Gabbard, 1994; Gabbard and Goodwin, 1996). 

In one study of obsessive-compulsive disorder, Baxter et al. (1992) looked at local cerebral metabolic rates for glucose using positron emission tomography scan methodology. They found that both behavior therapy and fluoxetine (Prozac) produced similar decreases in cerebral metabolic rates in the head of the right caudate nucleus, suggesting (but not proving) that this form of psychotherapy and fluoxetine have similar physiological effects at the level of the brain.

There is extensive evidence that cognitive-behavior therapy is an effective treatment for panic disorder. Panic attacks can be triggered by lactate infusion in those with panic disorder. At least one study (Shear et al., 1991) has demonstrated that lactate induction of panic can be effectively reversed through successful cognitive therapy. These findings suggest that psychological interventions can alter the response of the brain to biochemical factors.

Psychiatric researchers in Finland recently published a report showing that psychodynamic therapy may have a significant impact on the neurotransmitter serotonin (Viinamki et al., 1998). At the beginning of a one-year psychotherapy process, single photon emission computed tomography (SPECT) imaging was undertaken with a 25-year-old man suffering from personality disorder and depression. Another young man with similar problems also underwent imaging but did not receive psychotherapy or other treatment.

Initial SPECT imaging showed that both patients had markedly reduced serotonin uptake in the medial prefrontal area and the thalamus compared with 10 healthy control subjects. After one year of dynamic therapy, repeat SPECT imaging showed that the patient who received the psychotherapy had normal serotonin uptake while the control patient who did not receive psychotherapy continued to have markedly reduced serotonin uptake. This study suggests that dynamic psychotherapy may normalize serotonin metabolism.

Cancer research has shown positive effects of group psychotherapy, and by inference, a powerful effect on the brain and the body. Spiegel et al. (1989) conducted a controlled study in which metastatic breast cancer patients were randomly assigned to group psychotherapy or a control condition. Those in group psychotherapy lived an average of 18 months longer than controls. In a study of malignant melanoma patients, Fawzy et al. (1993) placed patients in either a support group or a control condition. They found that patients in the support group have more favorable death rates and more lengthy remissions than the controls. Most remarkable, this effect appeared to occur even though the support group lasted only six weeks.

A group of Pittsburgh investigators (Thase et al. 1998) studied 78 unmedicated patients with mild major depressive episodes. They were examined for sleep architecture changes before and after six weeks of cognitive-behavior therapy. The psychotherapy affected the neurobiological sleep variables in the same way as antidepressant medications.

While all of these studies are preliminary and require replication and further research, there can be little doubt that we are entering a new frontier in the mind-brain specialty known as psychiatry.

We now know that the brain is characterized by considerable plasticity and that genes are not static but responsive to environmental factors which we are only beginning to understand. Kandel (1998) has suggested that by producing changes in gene expression, psychotherapy may alter the strength of synaptic connections. Biological and psychosocial factors appear to have equal weight in development. There is a reciprocal effect of gene expression on environment and environment on gene expression in every family system. We can no longer afford a reductionism in either a biological or psychosocial direction.

All this evidence of the impact of psychotherapy on the brain opens up new lines of investigation to enhance our understanding of psychopathology and treatment: a) the mechanisms of action of psychotherapy, b) the interrelationships of the mechanisms of action of medication and psychotherapy, and c) a clearer understanding of pathogenesis itself and the malleability of some components of the pathogenetic mechanisms of major psychiatric disorders.

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Gabbard GO, Goodwin F (1996), Clinical psychiatry in transition: Integrating biological and psychosocial perspectives. In: Review of Psychiatry, American Psychiatric Press, pp 527-548. 
 

Kandel ER (1998), A new intellectual framework for psychiatry. Am J Psychiatry 155(4):457-469.
 

Shear MK, Fyer AJ, Ball G et al. (1991), Vulnerability to sodium lactate in panic disorder patients given cognitive-behavioral therapy. Am J Psychiatry 148(6):795-797.
 

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(The preceeding is a summary of Dr. Gabbard's presentation as the third annual Gene Usdin, M.D., Distinguished Visiting Lecturer in Psychiatry. Previous lecturers were Jerry M. Lewis, M.D., and Peter V. Rabins, M.D.-Ed.)

With advances in the neurosciences, and especially in imaging techniques, we stand at the threshold of demonstrating that psychotherapy is a powerful intervention that affects the brain. While it has been intuitively obvious to most clinicians that psychotherapy must work by affecting the brain (how else could it work?), recent breakthroughs in technology demonstrate what kinds of changes occur with psychotherapy.

Psychiatric Times Vol 15 No 9