New scientific findings raise questions about research development: What do NKU scientists have to say?

September 17, 2022

The field of scientific research has been met with skepticism with the surfacing of two new developments that call into question commonly accepted theories: an umbrella review suggesting low serotonin levels are not necessarily linked to depression and the exposure of research misconduct in an influential Alzheimer’s study. 

An article published by Science brings to attention an incident of research fraud, in which the scientist manipulated images to elicit a certain result: a result that would become the foremost explored cause for Alzheimer’s. The 2006 study suggested beta-amyloid–a protein that clumps in the brain–causes cognitive impairment, rendering the theory a basis for further research. The study has been cited over 2,200 times to date.

The umbrella review published in Molecular Psychiatry in 2022 examines research done on the link between serotonin levels and depression, suggesting the common belief that depression is caused by lower serotonin levels may be false. This finding is impactful, as over 37 million people in the US are prescribed antidepressants, of which selective serotonin reuptake inhibitors (SSRIs) are the most common, according to Winston-Salem Journal. SSRIs are said to work by increasing serotonin levels in the brain, but can also induce a spate of negative side effects, according to a Science Daily article featuring insights from the researchers that wrote the initial paper.

Both of these recent cases represent the tendency for scientific research to rely on previous findings to advance the area of study.

Dr. Valerie Hardcastle, executive director of the Institute for Health Innovation and vice president for Health Innovation at NKU, explained that when research yields a hopeful result that seems to inch closer to ascertaining the root of an issue or finding a solution, scientists tend to home in on that angle. These findings shape the research agenda posited by various federal institutions, such as the National Science Foundation and National Institutes of Health, whose funding is highly competitive and necessary to make noticeable strides in research fields, according to Dr. Hardcastle.

“When you apply to the federal government for funding, about 10 percent of applications are funded,” Hardcastle said. “Generally, the people who win that prize are people that are building off of what’s come before, but they are trying to take it in a completely new direction. Taking everything we know, if we tweak it, we could learn something really new.”

The pattern of scientific research development and funding is designed to arrive at new answers to improve the lives of humans, but the system can, in some instances, encourage pursuits that are based on faulty grounds.

To prevent such incidents where previous research leads researchers to ask the wrong questions and steer down unproductive avenues, policies and procedures are in place to help ensure sound and ethical research is conducted.

NKU psychology professor and Director of the Interdisciplinary Minor in Neuroscience Dr. Mark Bardgett explained that researchers who receive federal grants and the staff hired to aid in research are required to complete a thorough training program that teaches proper research conduct and ethics.

Another key criterion in the funding application review process that ensures new research is founded on accurate ground, according to Bardgett, is evaluating the credibility and rigor of that prior research. Research that builds on studies that have been replicated by other scientists and that contain representative, comprehensive data–a standard measured by a process called a power analysis–is more likely to earn funding, Bardgett explained. 

However, scholarly scientific journals don’t commonly publish papers that find what are called negative results–results that contradict a commonly believed theory–according to Bardgett.

Both Bardgett and Dr. Ty Brumback, assistant professor and clinical psychologist, mentioned a burgeoning measure in psychological research publications that works to normalize publishing negative results called study preregistration, a process where scientists comprehensively delineate their intended research process before carrying it out. In return, approved studies will receive the journal’s word to publish the findings no matter the outcome, Bardgett and Brumback explained. 

Dr. Jordan Wagge, NKU alumni and professor of psychology and cognitive science at Avila University, received a $267,741 National Science Foundation grant to fund the Collaborative Replications and Education Project, a project she directs that aims to advance the field of psychology by replicating published studies and providing valuable research experience for undergrad students. 

“It’s really difficult to prove a negative. It’s easy to prove a positive,” Bardgett said. “We have to be able to publish things that say this didn’t work.”

The scientific research field’s monetarily dependent and discovery-driven nature perpetuates what Brumback called the file drawer phenomenon: the tendency for studies that do not arrive at new discoveries to not be shared.

These initiatives that aim to ensure sound scientific research indicate a push towards open science, which is “the idea that we should share everything. So share our data. Share our methods, share our analyses, and put it all out in the open,” according to Brumback. 

The open science research model allows scientists to access other researchers’ datasets and develop well-informed research inquiries; it also helps scientists and healthcare workers confer the current state of progress in various lines of research more accurately to the public, encouraging individuals to make well-informed health decisions, according to Brumback. 

With caution in evaluating the legitimacy of previous research and programs that encourage replicating studies on the rise in scientific research, misconduct can still slip though the cracks, like in the uncovering of image fabrication that marred the original Alzheimer’s study positing the beta-amyloid theory. 

Scientific research is a self-policed field, and although experts in the field evaluate and approve federal grants and peer review papers before publication, how individuals act within a lab is relatively under wraps, according to Brumback. 

“What I hope the public realizes is that it’s a single person doing that,” Bardgett said. “In science, you’re going to have good people doing it; you’re going to have people that are maybe a little shady doing it.”

But according to Hardcastle, discussion in the field of biomedical research has been open to the idea of tackling Alzheimer’s research with different approaches even before this scandal came to light; these studies slide underpublic radar because they are scarcely published. This is because if nothing enlightening is discovered, it’s usually not published. 

“My perspective on this is it’s actually out there, but it just hasn’t worked its way down to the average person,” Hardcastle said.

Although both of the studies mentioned here raise questions about commonly believed theories, these are highly complex issues that can’t be narrowly understood. 

“The serotonin study and the Alzheimer’s study, they paint the problem with a broad brushstroke,” Bardgett said. “It’s not black and white. It would be really important for science to look outside and say, ‘What are some other things leading to depression or Alzheimer’s disease?’” 

Hardcastle compared these trends to the ambiguities of the science regarding vaccinations, masking and variant strains that have been developed through the COVID-19 pandemic. Science gradually peels the layers of important issues, with promising information disseminating to the public. Changing developments can irritate the public and rouse skepticism, but trial, error and fluidity is the nature of science.

“When you look at the way science progresses, I think what you see is this little chewing away at these problems,” Hardcastle said.

When revelations like these pop up, it can shift how issues are explored, sending research development and funding allocation into a state of disarray.

“We thought this was it, and all at once, we’re realizing, maybe that’s not the case,” Hardcastle said. “And so, when that happens, you get this whole flood of new perspectives and new ways of doing things. Really what’s happening is people are kind of just throwing money at everything to see who’s going to come up with the next thing we can really focus our attention and drill down on.”

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