Lois Wingerson

The molecular events that accompany drug abuse and addiction are different for women than for men, according to new studies presented at the annual meeting of the American Psychiatric Association (APA). As yet, little if any of this knowledge has made its way into gender-based differences in pharmacological and behavioral treatments for addiction. But according to some of the speakers, it could and it should.

"It is dangerous at best, and completely wrong at worst, to assume that any neurological disorder has the same underlying causes in men and women, and thus to assume that treatments for the disorder will be essentially the same," said Larry Cahill, PhD, associate professor of neurobiology and behavior at the School of Biological Sciences, University of California, Irvine. "Yet that is precisely the assumption that continues to pervade much of both the clinically applied and basic science worlds."

Even in its epidemiology, addiction shows a gender difference, remarked Jill Becker, PhD, professor of psychology at the University of Michigan, Ann Arbor. Women begin using drugs of abuse at lower doses than men, she said. Their drug use escalates more rapidly to addiction, and they face a greater risk of relapse after abstinence. Laboratory animals show the same kind of gender differences in addiction, which has made it possible to study these phenomena among rats and mice. But there's now plenty of direct evidence from humans.

Women tend to enter treatment sooner after becoming substance dependent than men, but they present with more psychological distress, and particularly with more mood and anxiety disorders, according to research by Christine E. Grella, PhD, research psychologist at the University of California, Los Angeles.

 Most research on gender-based differences in addiction treatment has focused on organizational issues (such as the greater need to provide women with child care and employment training) rather than on pharmacology. But even this focus does not always make its way into changes in the treatment that is actually provided.

As to differences in gender and pharmacology, studies have focused almost exclusively on dosage and on issues involving pregnancy. The new research presented at the APA meeting offers ample evidence to support a search for new medications that are specifically designed for women with addiction problems.

Addiction is widely viewed as a disorder of memory processes. Over the past several years, studies led by Cahill have shown strong hemispheric gender differences in how the brain responds in memory processing after seeing emotionally arousing material. For example, men's responses are stronger from the right amygdala, and women show stronger signals from the left amygdala. More recent work has shown noticeable differences of this kind even in the resting condition.

 Cahill said this research may help to explain previous evidence for effects of the menstrual cycle on craving and also gender differences in the effectiveness of treatments such as the nicotine patch.

There's also direct evidence for effects of the menstrual cycle on phenomena relevant to substance abuse.

 Using positron emission tomography and functional MRI (fMRI) studies, Karen Faith Berman, MD, and colleagues at the NIMH in Bethesda, Md, have found that fluctuations in steroid hormone levels during the menstrual cycle affect neural responses to rewards. They noted striking anatomical differences between the genders in their fMRI studies-when anticipating an uncertain reward, men showed more activity in the ventral putamen than women. When receiving a reward, women showed more activity than men in the anterior medial prefrontal cortex.

On a molecular level, Becker's team has found noteworthy gender differences in the concentration and location of receptors for the neurotransmitter dopamine, which is crucial to modulating phenomena of anticipation and reward.

 For instance, the female hormone estradiol enhances dopamine release among women. "Since the effect of estradiol is seen only in females," she said, "this mechanism may offer unique pharmacological opportunities for the treatment of drug abuse in women."

The presence of cocaine tends to dampen normal gender differences in response to stress, craving, and relaxation, reported Marc N. Potenza MD, PhD, associate professor, and colleagues in the department of psychiatry at Yale University, New Haven, Conn.

 This was largely due to an increase among cocaine-dependent women in activation of the corticolimbic circuitry involved in stress and craving. Potenza’s research team did not notice this increase among men or among women who were not cocaine-dependent.

Grella, who was not present at the APA’s annual meeting, said she is not aware of any direct applications of this kind of research to the pharmacology of addiction. But she added that it has "tremendous potential" to inform relapse-prevention strategies that would be more specific to women.


1. Grella CE. From generic to gender-responsive treatment: changes in social policies, treatment services, and outcomes of women in substance abuse treatment. 

. 2008;(suppl 5):327-343.
2. Cahill LF. Sex differences in amygdale-based emotional memory processes: relevance for addiction. Abstract presented at the American Psychiatric Association Annual Meeting; May 19, 2009; San Francisco.
3. Berman KF. Gonadal steroid hormones and neural mechanisms of cognition and emotion in women. Abstract presented at the American Psychiatric Association Annual Meeting; May 19, 2009; San Francisco.
4. Becker JB. The role of dopamine in sex differences in drug abuse. Abstract presented at the American Psychiatric Association Annual Meeting; May 19, 2009; San Francisco.
5. Potenza MN. Sex differences in fMRI correlates of stress and drug cues in cocaine dependence. Abstract presented at the American Psychiatric Association Annual Meeting; May 19, 2009; San Francisco.

Articles

Gender Differences Should Be Considered in Treatment of Addiction

Schizophrenia Risk May Be Higher in Male Offspring of Young Fathers

Internet Social Media Present New Quandaries for Psychiatrists

As transgender activists protested outside the American Psychiatric Association (APA) meeting, speakers at the meeting were presenting on the same topic: gender identity disorder (GID). Some of their words would add clinical weight to the political slogans.

Some of the speakers are activists themselves, including Rebecca Allison, MD, cardiologist who is transgender, widely published author Sarah Hoffman, whose son is gender variant, and Hewlett-Packard engineer Kelley Winters, PhD, founder of GID Reform Advocates. Winters

 has called on the APA to use the DSM-V revision to affirm that “in the absence of dysphoria, gender identity and expression that vary from assigned birth sex are not, in themselves, grounds for diagnosing a mental disorder.”

Some mental health professionals made the same point in their own presentations. Sidney W. Ecker, MD, a former clinical professor of urology at the Georgetown University School of Medicine, Washington, DC, and chief of urology at the Washington DC VA Medical Center, was scheduled to review studies documenting that factors that influence gender identity are present before birth. While social and hormonal influences act later during childhood, he wrote, “gender identity is determined before and persists despite these effects.”

Diane Ehrensaft, PhD, a professor at the Wright Institute in Berkeley, Calif, had a message more difficult for psychiatrists to hear. “The mental health profession has been consistently doing harm to children who are not ‘gender normal,’ and they need to retrain,” she told Psychiatric Times. Ehrensaft has specialized in therapy for foster children as well as for children with gender issues.

When she trained in the late 1960s, Ehrensaft said, the attitude of psychiatrists who taught her about such matters was that “children with gender identity issues other than normative are confused and are suffering from dysphoria” and need to be reoriented. That is “diametrically opposed” to what has been found since, she added.

To document the harm that has been done, she cited a January 2009 article in Pediatrics that found homosexual and bisexual young adults to have highly significant increases in a history of depression, illegal drug use, unprotected sex, and attempted suicide if their parents had rejected their sexual orientation.

 That study, in turn, cites numerous others over the prior decade with similar results, although none had previously examined parental rejection.

Ehrensaft said she would advise psychiatrists at her presentation that their role today is to help children understand their gender identity-which may not be what the birth certificate says-and to support rather than pathologize or malign their parents. “There’s more evidence of harm now than even 10 years ago,” she added, “and also a developing field of practice that clearly demonstrates means of helping these kids.”

Protestors are also focusing on the fact that the DSM-V Task Force on Sexual and Gender Identity Disorders is being led by Kenneth Zucker, PhD, psychologist-in-chief and head of the gender identity service in the child, youth, and family program at the Centre for Addiction and Mental Health as well as professor in the departments of psychiatry and psychology at the University of Toronto. Zucker has been on the record as saying that parents and clinicians should work to socialize very young children who behave in ways discordant with their physical gender so that they come to identify with it-but that teens who have not done so should be helped to adjust to their discordant gender identity.

A program at Children’s National Medical Center in Washington, DC, takes a different approach, offering in-person and online support groups to help families adjust to and help their children work through their own gender identity issues. Edgardo Menvielle, MD, MSHS, director of the program, was curious whether children seen in Washington have different mental health profiles than kids involved with the Toronto program. Based on Child Behavior Checklist ratings, he reported that the Washington youth showed “less pathological tendencies,” suggesting that peer support may “lessen manifestations of pathology in the child.”

Speaking by telephone before the conference, Menvielle hastened to distance himself from that conclusion. “The implications are not very clear,” he said. “We’re dealing with a population that appears healthier overall, but it could be that we attract different families.”

Menvielle also said there is “a lot of anger about these issues,” and added, “I hope I don’t receive any tomatoes.”

Psychologist Ehrensaft said she’s eager to see studies that compare adults who received treatments intended to “normalize” their gender identities as children with those treated in more accepting environments. Meanwhile, she said, there is a move afoot to change the membership of the Task Force so that it is “more balanced.” She added that she hopes the protests do succeed in reorienting psychiatrists’ thinking about GID.

“We got homosexuality out of the DSM because of protests at the APA,” she pointed out. “Now it’s time to do the same with GID.”


1. Winters K. Beyond conundrum: strategies for diagnostic harm reduction. Abstract presented at the American Psychiatric Association Annual Meeting; May 18, 2009; San Francisco.
2. Ecker SW. Brain gender identity. Abstract presented at the American Psychiatric Association Annual Meeting; May 18, 2009; San Francisco.3. Ryan C, Huebner D, Diaz R, Sanchez J. Family rejection as a predictor of negative health outcomes in white and latino lesbian, gay, and bisexual young adults. 

. 2009;123:346-352..
4. Menvielle EJ. Psychopathology and gender variance in a clinical sample of children. Abstract presented at the American Psychiatric Association Annual Meeting; May 18, 2009; San Francisco.

As transgender activists protested outside the American Psychiatric Association meeting, speakers at the meeting were presenting on the same topic: gender identity disorder. Some of their words would add clinical weight to the political slogans.

Gender Identity Disorder: Has Accepted Practice Caused Harm?

Is it ethical for a psychiatrist to Google a patient? There are no established policies about this, and perhaps there should be, contends Damir Huremovic, MD, co-chair of a session on cyberspace at the American Psychiatric Association meeting.

His fascination with the question arose when he read the printout of an e-mail suicide note, as he stood beside the patient who lay intubated and unconscious in the ICU. There was a link to a blog in the e-mail footer.

“My dilemma was whether or not to open it,” said Huremovic. “I finally did, considering that his blog may yield critical information about his attempt.” The information, and the e-mail, may have saved his life.

“As I skimmed over his personal musings in chronological order,” Huremovic recalled, “I could get an almost instant insight into the course of his drama, his aspirations and hopes, and his big disappointment which culminated with the suicide attempt. I found this way of learning about the patient so easy and almost seductive.” At the same time, he was uneasy about trespassing in a realm of intimacy and privacy-even though the patient had willingly posted the information in the most public of places

Untold amounts of personal information about patients may be freely available on the Internet, but Huremovic urges psychiatrists who might want to go there, to address the issue with patients at the outset. “It’s not a matter of ethics,” he added. “You should tell them in advance to minimize any kind of fallout. In fact, it may be an interesting point of therapy. If they don’t want you to go there, why not?”

On the other hand, he points out, patients may be just as likely to Google a psychiatrist as the other way around. It may be prudent to be aware of what’s out there about yourself, and perhaps also to anticipate this as a point of discussion at the start of a relationship.

The issue arose 3 years ago when Philadelphia psychiatrist Geoffrey Neimark and others

 wrote a letter to the American Journal of Psychiatry describing an earlier example of using Google for background information about a patient who attempted suicide. “What about other potentially useful, although perhaps more controversial, sources of information on the Internet?” they wrote.

“Many states now have websites that list parole absconders and wanted fugitives and offer online registries of sex offenders. In addition, elements of patients’ financial, criminal, and civil histories can be obtained on the Internet. What, if any, role could and should this sort of information have in clinical evaluations, and what are the ethics of this?”

Other issues are whether it is wise to visit Internet forums about mental health issues in search of insights, or even to follow the lightning-speed posts on the new medium of Twitter. People have been known to post successive distressing notes on Twitter in which they threaten suicide, generating immense concern among their followers. (A quick example posted on Twitter 7 seconds before writing these words: “If next Tuesday doesn’t go well . . . I’m going to f---ing commit suicide. No f---ing joke.”)

Humerovic, who practices in East Meadow, NY, writes a blog, but he avoids social media sites such as Twitter and Facebook, because he believes in “certain elements of privacy.” He urges psychiatrists to beware what they click on.

“You may not want to get involved,” Humerovic says. “God forbid something should happen. How would you feel?”

In a separate workshop at the APA meeting, L. Mark Russakoff, MD, of Sleepy Hollow, NY, will be chairing a discussion [Thursday 5/21 at 11 AM] of the use of Internet tools by psychiatric administrators, including the impact of electronic medical records.

He anticipated a wide-ranging conversation directed largely by the interests of the audience, but reflected that some responses are predictable.

“Our experience is that there are generational differences,” he told Psychiatric Times. Younger psychiatrists and administrators are much more receptive to adopting new technologies, he said, but these may alter clinical practice-which older practitioners view as a disruption, not as useful progress.

1. Neimark G, Hurford MO, DiGiacomo J. The internet as collateral informant. 