Archive for category Harvard Medical School

Low Estrogen Linked to PTSD


Low Estrogen Linked to PTSDHigh levels of estrogen may help protect a woman from mood disorders, while low levels of the hormone can make a woman more susceptible to trauma at certain times in her menstrual cycle, according to new research by Harvard and Emory University neuroscientists.

Depression and anxiety disorders are twice as common in women as in men, but the reason for this gender difference has remained unclear.  The new research, however, suggests that women are most at risk for symptoms of post-traumatic stress disorder (PTSD) when their estrogen is low during the menstrual cycle.

“PTSD is a disorder of recovery,” said author Mohammed Milad, associate professor of psychiatry at Harvard Medical School (HMS) and director of the Behavioral Neuroscience Laboratory at Massachusetts General Hospital (MGH).

Men may be less susceptible to mood disorders since testosterone is regularly converted into estrogen in the male brain, resulting in a more steady flow of estrogen.

In healthy women and female rats, estrogen calms the fear response, according to the Harvard researchers, who were led by Kelimer Lebron-Milad, an HMS instructor of psychiatry.

The Emory researchers, led by postdoctoral researcher Ebony Glover, proved that the same is true for women suffering from PTSD. The higher their blood levels of estrogen were when they completed a fear-extinction task, the less likely women were to act startled.

Both studies used “fear-conditioning” experiments, in which the participant is trained to fear a safe “conditioned stimulus” such as a colored shape, paired with a frightening or painful “unconditioned stimulus” like a shock to the finger or a puff of air to the neck or eye.

Overall, women or female rats showed less fear to the neutral stimulus when their estrogen levels were high rather than low.

PTSD is common in women after a trauma such as rape or sexual assault, which studies say are experienced by 25 to 30 percent of women in their lifetimes, and the symptoms last on average four times as long in women as in men after trauma.

This new research suggests the reason for this vulnerability may be the monthly menstrual change in estrogen.

“People are afraid to look into the influence of sex hormones on ‘fear learning’ and extinction,” said Mohammed Milad, “because it’s such a complex system.”

When Milad studied fear as a Ph.D. student, his lab used only male rats. But when he began to study fear in humans as a postdoctoral researcher, he saw that female data were much more variable.

“The data led me there,” to sex differences, Milad said. “Since females add variance, scientists have tended to avoid studying them” in rodent research, he said. Studies of the human brain would tend to combine men and women, assuming that neurological gender differences were minimal. But this attitude is changing.

In addition, since birth control pills affect estrogen levels, they may be used as a future treatment against post-traumatic stress.

The research is published in Biological Psychiatry.

Source:  Biological Psychiatry

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First Marijuana Use Linked to Psychosis in Vulnerable People


Among individuals with psychosis who are also heavy marijuana users, the age they first used marijuana is strongly linked to the age of their first bout of psychosis, according to a study of 57 patients.

Although marijuana use by itself is neither sufficient nor needed to trigger schizophrenia, “if cannabis use precipitates the onset of psychosis, efforts should be focused on designing interventions to discourage cannabis use in vulnerable individuals,” Dr. Juan A. Galvez-Buccollini and his associates said.

This caution pertains to someone with a first-degree relative with psychosis, which is “the highest risk factor for schizophrenia,” said Dr. Lynn E. Delisi, senior investigator for the study, a psychiatrist at the Boston VA Medical Center in Brockton, Mass., and professor of psychiatry at Harvard Medical School, Boston.

If someone had a first-degree relative, “I would caution them about the consequences of cannabis use and the association with schizophrenia,” she said.

Findings from previous research has shown that marijuana use is associated with an earlier age of psychosis onset in people abusing multiple substances, but studies have not looked at a possible link between the onset of cannabis use itself and resulting psychosis.

Because of this, Dr. Galvez-Buccollini, a psychiatry researcher at VA Boston Healthcare System and Harvard, and his colleagues interviewed 57 patients with a current diagnosis of schizophrenia, schizoaffective disorder, schizophreniform disorder, or psychosis not otherwise specified, who also had a history of heavy cannabis use before the onset of psychosis. They defined heavy cannabis use as 50 or more uses during a one year period.

Average age of the subjects was 25 years with a range of 18-39 years. Of the total, 83 percent were men, and 88 percent were not married. The average age of psychosis onset was 22 years, and the average age for first psychosis-related hospitalization was 23.

Schizophrenia was the most common psychosis (42 percent), followed by schizoaffective disorder (32 percent). The average age of first marijuana use was 15, preceding psychosis onset by an average of 7 years.

During the study period, the prevalence of daily cannabis was 59 percent with another 30 percent reporting use 2-5 days per week, and the remaining 11 percent reporting weekly use. Alcohol abuse was 16 percent and alcohol dependence was 8 percent.

The researchers found a statistically significant link between the age when cannabis use first started and the age when psychosis was first diagnosed. This association was consistent after researchers excluded patients with any diagnosis of alcohol abuse or dependency during their lifetime.

The analysis also showed a strong link between the time a patient first smoked marijuana and their age of first psychosis hospitalization.

Marijuana affects dopamine receptors and can have other neurochemical effects.

“There are two components of cannabis, one that potentiates and another that antagonizes psychotic symptoms,” said Delisi. The balance between these two effects can differ among various strains of cannabis, she added.

Source: Schizophrenia Research

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