Steroid Use Causes Long-term Agression, Northeastern University Report Indicates

 BOSTON, Mass. (11-20-03) -– With the recent revelations about steroid use in Major League Baseball and the bust last week of several Oakland Raiders players for drug abuse, Northeastern University psychology professor Richard Melloni, who studies the link between steroid use and aggression, has recently found evidence that use of anabolic steroids may have long-term effects on behavior and aggression levels well after they stop abusing these performance enhancing drugs.

With funding from the NIH (recently extended through 2008), Melloni and doctoral student Jill Grimes have been studying how steroids used during adolescence may permanently alter the brain's ability to produce serotonin. In their experiments, adolescent Syrian hamsters – given their similar brain circuitry to human adolescents – were administered doses of anabolic steroids and then measured for aggressiveness over certain periods of time.

The researchers initially hypothesized that steroid use during adolescence might permanently alter the brain's chemistry and a person's tendency toward aggression long after use has stopped. Their most recent findings, published this week in Hormones and Behavior, enabled them to confirm this hypothesis and conclude that there is indeed a lengthy price – namely long-term aggression – to pay for drug abuse even after the ingestion of steroids ceases.

"We know testosterone or steroids affect the development of serotonin nerve cells, which, in turn, decreases serotonin availability in the brain," Melloni says. "The serotonin neural system is still developing during adolescence and the use of anabolic steroids during this critical period appears to have immediate and longer-term neural and behavioral consequences. What we know at this point is that aggressiveness doesn't simply cease after the ingestion of steroids does."

Based on this research, Melloni also believes that athletes who abuse steroids may also be inclined toward aggressive behavior long after their drug abuse – and musculature – have waned.

Promising Drug Proves Ineffective As Treatment For Hearing Loss

NewsPsychology (Oct. 8, 2003) — Researchers have demonstrated that Methotrexate, a promising drug to treat hearing loss in patients with autoimmune inner ear disease (AIED), proved no more effective than placebo in a recently concluded four-year study.

In findings published in the October 8, 2003 issue of the Journal of the American Medical Association (JAMA), a team headed by University of California, San Diego (UCSD) Professor and Chief of Otolaryngology Head and Neck Surgery, Jeffrey Harris, M.D., also noted that the steroid Prednisione proved very effective in both stabilizing and helping over 57% of the AIED patients regain hearing.

“AIED is a rapidly progressive form of sensorineural hearing loss. If left untreated or treated inadequately, AIED can result in profound deafness,” says Harris. “We’ve known for some time that steroids are effective in improving hearing loss in AIED.”

However, he noted, the many side effects associated with maintaining prolonged steroid therapy has led to the search for more effective drugs to treat this condition over the long term. And, once the steroids are withdrawn, the hearing loss may reoccur. Methotrexate has been considered a promising drug to treat AIED, due to its long track record as an effective anti-inflammatory, says Harris, improving patients with rheumatoid arthritis, an autoimmune disease that affects the body’s joints. Since AIED is also an autoimmune condition, Harris says researchers hoped the drug would have the same therapeutic effect.

AIED starts with the rapid appearance of bilateral, fluctuating and progressive, asymmetrical sensorineural hearing loss. Patients show hearing loss and usually tinnitus. Several blood tests are now being tested to identify patients with AIED. Approximately two-thirds of patients exhibit this autoimmune disease in their ears. In the other third, patients may have some of the well-known rheumatic diseases occurring concurrently with the hearing loss.

“In earlier studies where Methotrexate was used to treat AIED, the initial results appeared positive. The current study was designed to determine in a controlled, double-blind fashion if Methotrexate could maintain the hearing improvement achieved initially with Prednisone,” Harris says.

The study enrolled 116 patients with AIED, treating each of them with one month of high dose Prednisone. At the end of the first phase, 67 who showed significant hearing improvement were randomized to receive either Methotrexate or placebo. Prednisone was slowly tapered in both groups over a 3-month period while the Methotrexate and placebo doses were increased.

The results showed that Methotrexate was no more effective than the placebo in maintaining the hearing gain achieved with Prednisone. Of the 67 patients who went on to receive Methotrexate or placebo, 61 were disqualified from continuing the study due to further hearing losses.

Of the 116 patients who received the initial high dose steroids, 63% responded to Prednisone in one ear while 37% responded in both ears, and the researchers observed that long-term Prednisone was well tolerated under the close management of the treating physicians involved in this study.

Harris says the results underscore the importance of well-controlled studies to test the efficacy of drugs in the treatment of AIED, adding it also demonstrates the urgent need to discover more effective and lasting treatments for this condition that usually leads to acute deafness.


The study published in JAMA was sponsored by the National Institute on Deafness and Communication Disorders. Co-authors were Michael H. Weisman, M.D., Cedars-Sinai Medical Center, Los Angeles; Jennifer M. Derebery, M.D., and Ralph A. Nelson, M.D., House Ear Institute, Los Angeles; Mark A. Espeland, PhD, Wake Forest University, Winston-Salem, NC; Bruce J. Gantz, M.D., University of Iowa, Iowa City; A. Julianna Gulya, M.D., National Institute on Deafness and Other Communication Disorders, Bethesda, MD; Paul E. Hammerschlag, M.D., New York University, NYC; Maureen Hannley, PhD, American Academy of Ototlaryngology-Head & Neck Surgery, Alexandria, VA; Gordon B. Hughes, M.D., The Cleveland Clinic, Cleveland, OH, Richard Moscicki, M.D., Massachusetts General Hospital, Boston, MA; John K. Niparko, M.D., Johns Hopkins University, Baltimore, MD; Steven D. Rauch, M.D., Massachusetts Eye and Ear Infirmary, Boston, MA; Steven A. Telian, M.D., University of Michigan, Ann Arbor, MI; and Patrick E. Brookhouser, M.D., Boystown National Research Hospital, Omaha, NE.

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The above story is reprinted (with editorial adaptations by newsPsychology staff) from materials provided by University Of California – San Diego.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of NewsPsychology or its staff.

Research Links Adolescent Steroid Use To Reduction In Serotonin, Altered Signaling

BOSTON, Mass. — With more than one in ten boys admitting to using steroids, muscle- and strength-enhancing drug use among teenagers has caused considerable concern among parents and researchers over the past decade, but until now, the longer-term physiological and neurological effects of its use on the developing brain have not been fully examined. Now, new research from Northeastern University, published in the latest issue of the journal Pharmacology, Biochemistry and Behavior, documents the link between adolescent anabolic steroid use and aggression and partly associates the increases in aggression with deficits in the brain"s serotonin system. The study will examine longer-term deficiencies of serotonin levels in the brain as a result of damage from steroid use, suggesting that a tendency toward aggression and impulsiveness may actually linger long after both the steroid use and the muscles and strength developed have waned.

With funding from the National Institute of Health, Northeastern University psychology professor Richard Melloni and graduate student Jill Grimes examined the phenomenon of long-term steroid use through a series of experiments on groups of adolescent male Syrian hamsters. During adolescence, this particular breed of hamster displays a natural form of territorial aggression, has similar neurological circuitry to human beings and similar aggression and dominance patterns during its adolescent years, making it a natural model for neurological and behavioral experiments.

During the first experiment, the researchers administered a "high dose" of anabolic steroids to adolescent hamsters over the course of a month, a period corresponding to five years repeated dosage in human adolescents. Those hamsters given steroids were, as other studies have shown, more aggressive than those not treated with steroids.

In the second stage of the experiment, the researchers administered fluoxtine (Prozac), commonly used in treating depression in humans by encouraging the presence of serotonin (the "feel good" receptor), to the hamsters treated with chronic levels of steroids, and found that the previously aggressive tendencies were notably decreased. As in humans, aggressions were mellowed in the presence of Prozac, or serotonin.

Finally, the brains of the anabolic steroid-treated hamsters were examined under a microscope to determine the effect the drugs have on the developing nervous system. In those animals exposed to steroids, significantly lower levels of serotonin were present in the neural connections in their brains, particularly in areas related to aggression and violence.

Melloni and his students plan to conduct a series of follow-up experiments to examine whether the observed serotonin deficits in light of steroid use cause permanent and irreversible damage to the brain and how the neural abnormalities of adolescent anabolic steroid use may affect humans into adulthood. The researchers hypothesize that steroid exposure during adolescence decreases naturally occurring levels of the feel good receptor serotonin particularly in the hypothalamus, the area of the brain pinpointed for aggression and violence, and they plan to conduct a series of follow-up experiments to examine whether the serotonin deficiencies linger and what the longer-term abnormalities of adolescent steroid use actually are into adulthood.

"We know testosterone or steroids affect the development of serotonin nerve cells, which, in turn, decreases serotonin availability in the brain," Melloni said. "The serotonin neural system is still developing during adolescence and the use of anabolic steroids during this critical period appears to have immediate neural and behavioral consequences. Further research will allow us to determine whether or not these deficits are present into adulthood."

Continued steroid use during adolescence is linked not only to aggression and violence, but to a host of physiological problems, including liver diseases, problems with physical growth and development, and sexual dysfunction. Melloni notes that there is currently no long-term understanding of the effects of certain drug use on young people, and that drugs like Ritalin, among others, have no research indicating what aftereffects remain well into adulthood.

Steroid use, he says, is considerably on the rise, with more than ten percent of boys and three percent of girls admitting to regular use.

"Given the fact that we know so little about steroid"s long-term effects, the prospect of results from our research will be doubtlessly interesting and perhaps even frightening," Melloni said. "Perhaps through this sort of research we"ll be able to decrease the popularity of steroid use among teenagers."

Northeastern University, a private research institution located in Boston, Massachusetts, is a world leader in practice-oriented education. Building on its flagship cooperative education program, Northeastern links classroom learning with workplace experience and integrates professional preparation with study in the liberal arts and sciences. For more information, please visit

Stress Delays Puberty, Dutch Researchers Find

NWO research at Utrecht University has shown that when carp are subjected to stress, the development of their genital organs is delayed, so that they reach puberty later. It is likely that the stress hormone cortisol plays a major role in delaying puberty.

Changes in water temperature produce stress in fish. Dimitri Consten of Utrecht University subjected carp to a rapid reduction in water temperature three times a week from 25°C down to 14°C. This led to delayed development of their reproductive cells and the fish reached puberty later than normal. The researchers assumed that the hormone cortisol, which is released when an animal is under stress, plays a major role in this. This assumption was confirmed by means of two tests. In one of them, the biologists ‘switched off’ the cortisol in the stressed fish. These animals then developed to puberty in the normal manner. In a second test, cortisol was administered to fish which were not subjected to stress. In these fish, puberty was delayed.

Cortisol would seem to affect the testes. It directly delays the development of reproductive cells into sperm cells. This slows the growth of the sexual organs and also the supply of steroids to the blood. During puberty, steroids from the testes ensure that the brain, the pituitary gland and testes develop properly. Because the cortisol produced under stress reduces the supply of steroids, communication to the brain and the pituitary (a gland under the brain) is reduced. This means that, like the testes, these organs develop more slowly, thus slowing down overall development.

The whole complex of hormones involved in puberty is self-regulatory. The brain produces the gonadotropin-releasing hormone, which stimulates cells in the pituitary. On order, the pituitary then excretes the gonadotropins, the luteinising hormone and the hormone which stimulates the follicles. In the testes, the gonadotropins promote the production of reproductive cells and steroid hormones. The steroid hormones contribute to the production of the reproductive cells and ensure communication between the brain and the pituitary gland, thus completing the cycle.

Scientists Identify New Pathway Of Antidepressant Action

Scientists at UC San Francisco have discovered a new chemical pathway in the brain by which the most common antidepressants may alter mood. The research demonstrates that many popular mood modulators trigger chemical activity along more than one track at a time. It shows too how a brain chemical, known as a neurosteroid, might make a prime target for drugs to improve severe mood swings.

The researchers are publishing their study in the November 9 issue of the Proceedings of the National Academy of Sciences (PNAS).

Antidepressants such as Prozac, Paxil and Zoloft are thought to relieve depression by increasing the availability of one of the body's natural mood-enhancing chemicals, the neurotransmitter serotonin. But the UCSF experimenters examined the effect of these same antidepressants on an entirely different chemical pathway — one increasingly thought to play a role in mood regulation as well. It involves a natural brain compound called a neurosteroid, only recognized in the last 10 or 15 years.

The scientists discovered that all three of these antidepressants, known as SSRI's, not only affect serotonin availability, but also greatly increase the synthesis of a key neurosteroid — 10 to 30-fold. The profound effect, they found, comes from the SSRI's ability to greatly boost the action of the final enzyme involved in the synthesis of the neurosteroid in the brain.

"Each of these three serotonin reuptake inhibitors, or SSRI's, shows a dramatic positive effect on the levels of allopregnanolone, a steroid made in the brain, which most likely modulates mood and plays a role in heightened anxiety and depression found in severe premenstrual disorders and other conditions," said Synthia Mellon, PhD, senior author on the PNAS study and a professor of reproductive endocrinology at UCSF.

"The study points to the likelihood that SSRI's control mood by more than the one pathway that has received most of our attention, and it suggests that the steroids synthesized in the human brain may play a strong physiological role in regulating anxiety and depression."

Lead author on the PNAS paper is Lisa D. Griffin, MD, PhD, assistant professor of neurology at UCSF.

Studies by other researchers have shown below-normal brain neurosteroid levels among people with some depressive disorders, and SSRI's such as Prozac have been shown to elevate these brain steroid levels and alleviate symptoms of anxiety and depression among women suffering from a severe premenstrual disorder, Mellon and Griffin said.

Since the disorder occurs during a specific phase of the menstrual cycle, researchers have deduced that it is affected by levels of ovarian hormones such as progesterone. Subsequent studies, in rats, showed that Prozac does increase levels of the neurosteroid allopregnanolone, a derivative of progesterone, they said.

As a result of these and related studies, the brain's allopregnanolone has become a focus of interest in the continuing search for the body's natural mood modulators and what regulates them. The study reported by Mellon and Griffin clarifies the specific way SSRI's lead to increased neurosteroid levels.

Interest in allopregnanolone has also been spurred by the fact that it is synthesized in the brain, unlike most of the body's potent steroids which are made in the sex glands. The term "neurosteroids" was coined to reflect the rather unexpected fact that the brain is the site of the steroid's synthesis.

While it is widely assumed that SSRI's relieve depression through their effect on the neurotransmitter serotonin, their effect on the neurosteroid allopregnanolone follows a different route: the so-called GABA pathway. In this pathway, the steroid boosts mood-enhancing neurotransmitter receptors by increasing how many and how long certain openings in the neuron's membranes –called GABA ion channels — remain open. (The anti-anxiety medication valium works by stimulating this GABA pathway.)

To study the effects of the antidepressants on allopregnanolone, Griffin, Mellon and their laboratory colleagues cloned from both rat and human tissues the DNA (cDNA) of the intermediate enzymes known to be the key players in synthesizing the neurosteroid. They subjected both the rat and human enzymes to the antidepressants in solution. They tested the three SSRI's and a tricyclic antidepressant known as imipramine.

The scientists found that each of the three SSRI's greatly increased the affinity of both the rat and human enzyme 3-alpha HSD for the steroid precursor, resulting in surges of allopregnanolone synthesis. The tricyclic antidepressant showed no such effect.

Mellon says the research strengthens the likelihood that the enzymes that synthesize neurosteroids can make prime targets for mood-regulating drugs.

"We're interested in finding compounds that may directly affect these enzymes in the brain, and thus regulate mood disorders with minimal side effects," she said.

The research was supported by the National Institutes of Health and the National Alliance for Research on Schizophrenia and Depression.

Steroids May Reverse Loss Of Substance Tied To Nervous-System Diseases

 CHAMPAIGN, Ill. — Steroids help to reduce inflammation, but University of Illinois scientists suggest they also could be used to reverse a loss of myelin — a major problem in multiple sclerosis and other demyelinating diseases and injuries associated with the central and peripheral nervous systems.

Treatment of MS already includes the use of steroids, because they relieve inflammation and speed remission. The new findings — published in September's biochemistry section of the Proceedings of the National Academy of Sciences — indicate that the steroids dexamethasone and progesterone actually signal the initiation and dramatically increase the rate of myelin synthesis.

"I think this work is very important in that it helps clarify the signals that are responsible for the synthesis of myelin," said Jonah R. Chan, a doctoral student in the department of biochemistry and neuroscience program at the U. of I.

Myelin is a white substance made of fat and proteins that forms in a protective spiral sheath around the axon of nerve fibers. The sheath is a vital component of the body's efficient and rapid

nerve-communication system. When myelin fails to form, nerve signaling breaks down, jeopardizing nerve communications and leading to altered sensations and a multitude of other problems.

What causes a loss of myelin — demyelination — in MS cases is not known, but is believed to be the result of an abnormal immune response to bacteria and viruses. While MS affects everyone differently, demyelination is a focal point of research around the world.

"Steroids seem to be very important in regulating the initiation and synthesis," said Michael Glaser, professor of biochemistry and lead investigator of the project. "They had been implicated as having a role in the overall process, but not for enhancing the actual synthesis. It is our hope that this line of work will lead to a line of treatment for nerve injuries and demyelinating diseases."

Last year in the Journal of Neuroscience Research, Glaser's team reported the first technique for observing the continual synthesis of myelin by Schwann cells around axons of neurons. In their new work, researchers added various forms of steroids and antagonists, observing their effects on the cells under a fluorescence digital-imaging microscope. When dexamethasone and progesterone were added, individually, to the tissue culture cells, the initiation of myelin production began 24 hours earlier than it did under control conditions, and the peak rate of myelin formation increased by more than 2-fold.

Their findings provided the first live look at the signals initiating myelin formation in live cells, Glaser said. Before his new assay was developed, researchers were restricted to simply observing myelin at a single stage of production.

The PNAS paper was written by Chan, Glaser and Lornie J. Phillips II, a Howard Hughes Medical Institute predoctoral fellow. The research is supported by the Multiple Sclerosis Society.

Allergy-Linked Fatigue May Stem From Nasal Congestion, Interrupted Sleep

HERSHEY, Penn. — New research from Penn State's College of Medicine finds that people with perennial allergies may attribute their daytime fatigue to causes such as the side effects of medications, when, in fact, the fatigue may be a result of nasal congestion and associated sleep fragmentation.

"We treated the subjects with topical nasal corticosteriod. A few sprays on each side improved night time sleep and reduced daytime fatigue," explains the study's lead author, Timothy Craig, D.O., associate professor of medicine at Penn State's College of Medicine.

"Unlike steroids you get by injection or orally, this has very few adverse side effects," adds Craig, also an allergist/immunologist with the Penn State Geisinger Health System.

Approximately 15 to 20 percent of the population in the United States suffer from allergic rhinitis (AR), more commonly known as hay fever. The two-month study involved 20 patients. All the patients were perennial allergy suffers. Subjects with only seasonal allergies, known sleep apnea or other respiratory diseases were not involved in the study. Over the study period, patients completed a daily diary with questions pertaining to the severity of the nasal symptoms, sleep and their response to medication. There were nine questions about the severity of symptoms.

"We found a significant reduction in nasal stuffiness and sleep problems. Simply, if these people can breath easier at night, they have a less interrupted sleep pattern," states Craig. "The subjects' sleep is often interrupted with what we call microarousals. They don't wake up during the night, however, they may complain of being tired as soon as they wake up."

In at least 75 percent of patients, nasal steroids are an effective method of reducing symptoms and are recommended as the first line of medical therapy in adults having AR with nasal congestion, says the Penn State medical researcher.

Craig's research also suggests that the use of nasal steroids during the pollen season for seasonal allergy suffers is an effective treatment.

"We believe that the seasonal allergy patient will get the same benefits as the perennial suffer including improved sleep, nasal symptoms and overall improvement to their quality of life," he says.

Craig and his colleagues' paper titled, "Nasal Congestion Secondary to Allergic Rhinitis as a Cause of Sleep Disturbance and Daytime Fatigue and the Response to Topical Nasal Corticosteroids," was published in the May issue of the Journal Allergy and Clinical Immunology.