3.3.1: Preparation S.3

The next unit explores the statistical analysis process through the perspective of clinical studies and sociological studies. The three studies introduced in this preparation will be used again during the collaboration, and you will be expected to be familiar with them during Collaboration S.3.

Begin by reading the press release below about a brain imaging study:

STUDY 1:

Brain Imaging Study Suggests Long-Term Steroid Use Can Lead to Significant Brain Structural and Functional Abnormalities

Belmont, MA - Results of the first systematic brain imaging study conducted on long-term users of anabolic-androgenic steroids reveal significant brain structural and functional abnormalities, according to doctors at McLean Hospital.

An article detailing their findings, “Brain and Cognition Abnormalities in Long-Term

Anabolic-Androgenic Steroid Users,” was published last month in the journal Drug and Alcohol Dependence.

“Anabolic steroids are the newest of the world’s major forms of drug abuse,” said Harrison G. Pope Jr. MD¹¹, co-director of the Biological Psychiatry Laboratory¹² at McLean, professor of psychiatry at Harvard Medical School, and co-author of the article. “This is a public health problem that is just coming over the horizon now and we’re only beginning to understand its consequences. Widespread use of steroids did not appear until the 1980s in the United States, so this is a very young form of substance abuse in contrast to other drugs like marijuana and opiates that have been around for thousands of years.”

And while professional athletes make the headlines for steroid use, he said, that is not where the abuse is rampant.

“Professional athletes account for a tiny fraction of steroid users,” said Pope. “The great majority of steroid users are not competitive athletes at all, but are rank-and-file guys at the gym who just want to get big. This is one of the reasons that the problem has not been widely recognized, because the public has been focused on the occasional high-profile athletes who have been found to take steroids.”

There are approximately three million American men who have used steroids at some time in their lives, he said. From that number, it is estimated that one million have developed steroid dependence where they continue to take steroids for long periods of time, often in spite of the adverse effects, and this number is likely growing.

While studies have been published by Pope and others on the cardiovascular, endocrine, and cognitive effects of long-term steroid use, this is the first time that doctors have been able to systematically examine changes in the brain from long-term steroid use, said Marc J. Kaufman, PhD, director of the Translational Imaging Laboratory19 at McLean, associate professor of psychiatry at Harvard, and also one of the article’s co-authors.

“We used three types of imaging methods to examine different parts of the brain, including magnetic resonance imaging (MRI), which tells you about brain structure; functional magnetic resonance imaging (fMRI), which measures brain activity by detecting changes in blood oxygenation; and magnetic resonance spectroscopy (MRS), which looks at levels of different chemicals in the brain.”

The study ran from the fall of 2013 to the summer of 2014, using subjects drawn from a pool of 150 male weightlifters ages 35 to 55, with the average age being 42. Brain images of those reporting long-term use of steroids were compared with images from non-users.

One of the key findings with the structural imaging data, said Kaufman, centered on the amygdala, the part of the brain related to emotion regulation, aggression, anxiety, and possibly even depression, which was enlarged in those who were chronic steroid users as compared to the non-users.

“The amygdala in the steroid users wasn’t just a little bit larger than the control group, it was more than 20 percent larger,” said Kaufman. “That is a really marked difference, and it is particularly interesting because previous studies have shown that amygdala enlargement has been associated with aggression among other types of substance abuse populations.”

The study uncovered another abnormality among steroid users: a decrease in the brain levels of a sugar known as scyllo-inositol, which plays a key role in preventing neurotoxic proteins from clumping, particularly beta-amyloid protein which is known to play a role in the development of Alzheimer’s disease and other dementias.

“Clumping of beta-amyloid protein basically gums up the pipes in cells and leads to early cell death. The levels of this protective scyllo-inositol were significantly lower in steroid users,” said Kaufman. “If scyllo-inositol depletion is a widespread phenomenon among steroid users,” he said, “we could be seeing more cases of dementia or Alzheimer’s in these men as they age.”

Said Pope, “Another reason for concern is that unlike alcohol and most illicit drugs, which leave your body fairly quickly after use, steroids can be present in the system at levels 20 to 40 times greater than natural testosterone levels, 24 hours a day, seven days a week, for the entire duration of a course, or so-called ‘cycle,’ of steroid use.”

“The body can never be rid of them because users are typically injecting long-acting steroids regularly throughout their cycle,” he said. “As a result, there’s never a break. The body has no moment to rest from the effects. That is quite different from most drugs that are abused. And that’s why we worry that steroids might have unique forms of toxicity that we don’t typically see with other drugs of abuse.”

Pope also pointed out that steroids are not addictive in the sense that alcohol or drugs are addictive, but users develop a different type of dependence syndrome. He gave three reasons for steroid dependency:

• Body image: Weightlifters get big and they become fixated on wanting to stay that way. This fixation develops in much the same way that women with anorexia nervosa can weigh 87 pounds and look in the mirror and still think that they look fat. In steroid users, the pattern is simply the reverse; they may weigh 230 pounds with a 32-inch waist and still think that they are not muscular enough.
• Endocrine effects: When a male takes steroids, which are all synthetic derivatives of testosterone, the body subsequently shuts down its own production of testosterone. If that person then stops using steroids, his own testosterone production may take weeks, months, or occasionally years to return to normal. He may develop impaired erectile function, loss of sex drive, and sometimes depression when coming off steroids, which often motivates him to go back to using the drugs.
• Hedonic effects: There’s a pleasure experience that is associated with taking steroids. It’s not the same as getting high as with drugs or alcohol, but there is a reinforcing quality of some type. Some steroid users describe this as feeling self-confident or invincible. Scientists are convinced of this phenomenon because male hamsters in laboratory studies will self-inject steroids to the point of death if they are given the opportunity.

When trying to get off of steroids, the user has to be given medications to try and stimulate his own testosterone function while slowly tapering the external steroids, Pope said. “It’s an elaborate program that requires an expert endocrinologist and sometimes also a psychiatrist, so it’s a difficult process.”

Kaufman pointed out that while the findings of the study are alarming, they are preliminary. “The results merit an extended, more comprehensive sample in order to build a strong scientific foundation,” he said. “We are applying for funding to conduct a larger study. These results need to be followed up because they have many implications. For example, clinical trials are already underway to establish whether replacement of scyllo-inositol can be useful for preventing cognitive decline in people with early Alzheimer’s, an approach that may prove useful in steroid users.” In any case, said Pope, “It is urgent to pursue this area of research, given the potential implications for the millions of men who have used or who are contemplating using steroids.”¹³

Now answer the questions below.

1. Which of the options below is presented in the article as one of the most serious health concerns for male steroid users?

1. Increased likelihood of dementia
2. Breathing difficulties
3. Extreme weight loss
4. Heart failure

2. The following hypothetical data sets contain amygdala volumes for two samples of male weightlifters. (Note: Samples were used since it is not practical to obtain the amygdala volume of all male weightlifters who are steroid users or non-users.)

1. Find the mean of each sample. Round each answer to two decimal places.

Sample A (in cubic centimeters)	Sample B (in cubic centimeters)
1.22, 1.17, 1.08, 1.26, 1.45, 1.42	1.16, 1.64, 1.41, 1.52, 1.29, 1.61

2. Assuming that one of the samples is from the population of male weightlifters who are steroid users and the other is from the population of male weightlifters who are non-users, which sample is most likely to be from the steroid users? Explain.

Now read the press release below about a treatment for depression:

STUDY 2:

Researchers See Promise in Potential Depression Treatment

Belmont, MA - Individuals with major depressive disorder or bipolar disorder who receive low-field magnetic stimulation (LFMS) show immediate and substantial mood improvement, report McLean Hospital researchers in the August 1 issue of Biological Psychiatry.

“LFMS is unlike any current treatment. It uses magnetic fields that are a fraction of the strength but at a higher frequency than the electromagnetic fields used in TMS and ECT,” explained first author Michael Rohan, PhD, a physicist at McLean Hospital’s Brain Imaging Center¹⁴ and a lecturer at Harvard Medical School.

According to Rohan, although other brain stimulation treatments like electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS) are often effective for the treatment of depression, they typically take longer to have an impact on mood. In addition, in the case of ECT, it is associated with side effects, such as memory loss.

Likewise, antidepressant medications can be highly effective in treating depression but can take between four to six weeks before mood changes can be detected.

“Importantly, LFMS appears to have an immediate effect on mood and thus has the potential to provide relief in emergency situations,” explained Rohan, who first reported on the potential use of LFMS to treat depression in a ground-breaking study in 2004. “In addition to providing quick relief from symptoms, the other exciting piece about LFMS is that no side effects have been observed.”

Using a portable tabletop LFMS device that Rohan designed, the researchers conducted the study with 63 volunteers between the ages of 18 and 65. All participants were diagnosed with either major depressive disorder or bipolar disorder and were on a stable regimen of antidepressants or mood-stabilizing medications for at least six weeks. Of the study participants, 34 actively received LFMS, while the other 29 went through the process of receiving LFMS, but did not actually receive any brain stimulation. Since neither the patients nor the researchers knew which treatment each person actually received, the true effect of the LFMS could be measured.

Each participant rated their mood before and after the single 20-minute treatment of LFMS using two common self-assessment tools—a visual analog scale and the positive and negative affect schedule. The participants who actively received the LFMS treatment indicated a marked improvement in their mood, while those who did not receive LFMS reported no change in mood.

“We observed immediate improvement in mood following relatively brief exposure to LFMS,” noted Rohan. “Although larger research studies are needed, we think LFMS could be a powerful tool as a rapidly acting treatment for depression either alone or in combination with medication.”

Biological Psychiatry also published commentary from experts on brain stimulation who said Rohan’s work on LFMS is exciting and showed great promise.

“If the results described in this study are replicated in larger studies and the effects are shown to be durable, LFMS would be a welcome addition to the clinical armamentarium in the treatment of depression, may find application in other psychiatric and neurologic diseases, and may help to inform and guide us toward future directions in neuromodulation,” wrote Mouhsin Shafi, MD, Philip Stern, MD, and Alvaro Pascual-Leone, MD, PhD.

According to Rohan, additional research is already underway to find the best parameters for LFMS use in the clinical treatment of depression. He has also stated a research study to evaluate the effects of multiple compared to single treatments, and how long the antidepressant effects last following treatment.¹⁵

Answer the questions below.

3. Recall that important factors for a decision or situation, or the factors analyzed in a study, are called variables. What variables did the researchers examine in this study?

4. Doctors who are familiar with the details and results of this study commented that if the study is “replicated” and the results are shown to be “durable,” this treatment approach would be a welcome addition to existing treatment options for major depressive disorder and bipolar disorder. Explain what these comments mean in your own words.

STUDY 3:

The final reading in this preparation discusses a relationship between abuse as a child and homelessness. Read the article, “Abuse as a Child Linked to Longer Term Homeless,” from the Sydney Morning Herald, available at the link below:

http://www.smh.com.au/federal-politics/political-news/abuse-as-a-child-linked-to-longer-term-homeles s-20120418-1x7hx.html

5. The study described in the article was conducted on two groups of people. Define these two groups.

6. The researchers examined several variables that contribute to long-term homelessness. What variables did they examine?

7. (a) Which of the following statements accurately describe the New York Times article on Universal Basic Income linked below? Check all that apply.

Finland’s Basic Income Trial Boosts Happiness, but Not Employment

https://carnegiemathpathways.org/go/nyt_finland_basic_income

1. According to the study, proponents of the Universal Basic Income (UBI) believe that UBI will significantly reduce homelessness and substance abuse.
2. After the initial success of this trial, Finland is planning to implement the UBI program on a national scale in 2021. This idea is supported by all major political parties in Finland.
3. The study doesn’t provide any detailed information about the control group. However, it’s safe to assume that it consists of people who did not receive UBI.
4. Proponents of the Universal Basic Income (UBI) hoped to show that UBI recipients would be more likely to work.

(b) Which of the following statements accurately describe the New York Times article on the benefits of the Mediterranean Diet linked below? Check all that apply.

That Huge Mediterranean Diet Study Was Flawed. But Was It Wrong?

https://carnegiemathpathways.org/go/nyt_diet_study

1. In the original study, the trial enrolled 7,447 participants aged 55 to 80 who were assigned one of three diets: a Mediterranean diet with at least four tablespoons a day of extra virgin olive oil; the same diet with an ounce of mixed nuts; or a traditional low-fat diet.
2. The researchers claim that the Mediterranean diet can cut the risk of type 2 diabetes and sleep apnea by about 20 percent in those at high risk.
3. The study has come under a lot of scrutiny because of its flawed design.
4. After re-analysing the results of the initial study, there is now consensus in the scientific community about the conclusion of the study. The Mediterranean diet does indeed cut the risk of heart attacks and strokes by about 30 percent in those at high risk.

(c) Which of the following statements accurately describe the Science Daily article on the effect of social media and well-being linked below? Check all that apply.

Social media use increases depression and loneliness:

https://www.sciencedaily.com/releases/2018/11/181108164316.htm

1. The link between the use of social media and substance abuse has been talked about for years, but a causal connection had never been proven. For the first time, University of Pennsylvania research based on experimental data connects Facebook, Snapchat, and Instagram use to increased substance abuse.
2. The link between the use of social media and depression has been talked about for years, but a causal connection had never been proven. For the first time, University of Pennsylvania research based on experimental data connects Facebook, Snapchat, and Instagram use to decreased well-being.
3. Each of 143 participants completed a survey to determine mood and well-being at the study's start, plus shared shots of their iPhone battery screens to offer a week's worth of baseline social-media data. Participants were then randomly assigned to a control group, which had users maintain their typical social-media behavior, or an experimental group that limited time on Facebook, Snapchat, and Instagram to 10 minutes per platform per day.
4. Each of 143 participants completed a survey to determine mood and well-being at the study's start, plus shared shots of their iPhone battery screens to offer a week's worth of baseline social-media data. Participants were then randomly assigned to a control group, which had users not use any social media, or an experimental group that limited time on Facebook and Twitter to 30 minutes per platform per day.

After Preparation S.3 (survey)

You should be able to do the following things for the next collaboration. Rate how confident you are on a scale of 1–5 (1 = not confident and 5 = very confident).

Before beginning Collaboration S.3, you should understand the concepts and demonstrate the skills listed below:

Skill or Concept: I can …	Rating from 1 to 5
identify the purpose of a scientific study or statistical study.
identify variables of interest in a scientific study or statistical study.
identify the conclusion of a scientific study or statistical study.
identify potential limitations in a scientific study or statistical study.

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¹¹ http://www.mcleanhospital.org/biography/harrison-pope

¹² http://www.mcleanhospital.org/research-programs/biological-psychiatry-laboratory

¹³ http://www.mcleanhospital.org/news/2015/06/15/brain-imaging-study-suggests-long-term-steroid-use-can-lead-significant-brain

¹⁴ http://www.mcleanhospital.org/research-programs/brain-imaging-center

¹⁵ http://www.mcleanhospital.org/news/2014/07/28/researchers-see-promise-potential-depression-treatment