Innovative neuroscience research is vital, but individuals with mental illness pose some unique ethical concerns in terms of their participation.

The results of a recent study provided some reassurance on the decision-making processes of individuals.1 Researchers surveyed 25 individuals with a mood disorder and 55 individuals without a mood disorder about four psychiatric research projects: an experimental medication (pill form), noninvasive magnetic brain stimulation, experimental medication, (IV infusion), and implantation of a device in the brain.

Respondents rated the research projects as somewhat to highly risky, regardless of their health status. The more risk they perceived, the less willing they were to participate, regardless of whether they had a mood disorder.

Neuroscience researchers have to consider several issues, according to James J. Giordano, PhD, MPhil, chief of the neuroethics studies program at the Georgetown University Edmund D. Pellegrino Center for Clinical Bioethics.

Whether the pathology itself in some way interferes with the individual’s capability to be fully informed. “The absence of neuropsychiatric capacity renders these patients incompetent. By definition, the incompetent patient does not understand what information is being provided and, therefore, they can’t consent,” Giordano says. A person with medical power of attorney to make decisions for that patient may be able to provide consent for the individual under those circumstances.

Whether patients are entering the trial with “therapeutic misconception.” Many research participants have an underlying assumption that they are going to receive treatment. This may be particularly prevalent in neuropsychiatry patients.

“What tends to happen is that patients participate in a clinical trial with implicit hope that the trial will give them some benefit,” Giordano explains.

This is a difficult problem to address fully. “Even where it’s actively and explicitly addressed, misconceptions about incurred benefit of treatment rendered in a clinical trial seem to loom on as a potential emotional bias,” Giordano observes.

There are two points that are especially important to convey: What assignment to treatment and control groups entails, and that participants will not know which group they are in. “Even so, many still believe that participation in the trial will gain them some therapeutically beneficial outcome,” Giordano adds.

That any patient with any form of cognitive compromise, where they cannot fully comprehend what is involved in the protocol, is part of a vulnerable population. “There are particular concerns and caveats that researchers must attend to when dealing with vulnerable populations, particularly as it relates to possibilities for implicit coercion and relative burden and harms that may be inflicted,” Giordano says.

Inclusion of such vulnerable patients often is important, as they might be the population targeted for potential therapeutic effect. “Necessary precautions need to be taken so that these individuals are fully informed, to the extent of their capacity, about all phases and methods of the study and their ability to withdraw without penalization,” Giordano says.

Most individuals working in this area are keenly aware of necessary safeguards that are incumbent to the research. Still, things can go wrong. “There may be some misapprehension on whether subjects are fully comprehending,” Giordano notes. “Therefore, it is best to be overly cautious and diligent in ensuring active informed consent.”

Big data also pose ethical issues unique to neuropsychiatric research. On the positive side, it “increases the scope, types, and extent of information capable of being gathered and synthesized in psychiatric research,” Giordano offers.

For researchers, the ability to use massive amounts of diverse data certainly is appealing. “However, it’s important to realize the information that we are gaining in current studies may be useful, and utilized, for studies in the future,” Giordano says.

The way the data are used could change depending on how they are correlated with other future findings. “In some cases, such data may be de-anonymized, both at present and in the future,” Giordano suggests. “This has implications medically, socially, and perhaps legally for research subjects.”

For example, information collected today may be correlated to emerging data to infer pre-existing neuropsychiatric disorders. “That could incur problematic issues for individuals’ insurability, access to care, employability, and social regard and treatment,” Giordano explains.

For researchers, this means patients and subjects need to be fully informed on how their data could be used. “A comprehensive informed consent process needs to address each area that may be a potential issue or problematic,” Giordano says.


  1. Tsungmey T, Kim JP, Dunn LB, et al. Negative association of perceived risk and willingness to participate in innovative psychiatric research protocols. J Psychiatr Res 2020;122:9-16.