Federal regulators have suspended research on human subjects at the Columbia-affiliated New York State Psychiatric Institute, one of the country’s oldest research centers, as they investigate safety protocols across the institute after the suicide of a research participant.

A spokesperson for the U.S. Department of Health and Human Services, Kate Migliaccio-Grabill, confirmed on Wednesday that the agency’s Office of Human Research Protections was investigating the psychiatric institute “and has restricted its ability to conduct H.H.S.-supported human subject research.”

About two weeks before the federal order, on June 12, the institute had “voluntarily paused all studies that included ongoing interactions with human subjects,” according to Carla Cantor, the institute’s director of communications. The decision affected 417 studies, of which 198 have ongoing participation. Of those, 124 receive federal funding.

It is unusual for the U.S. regulatory office to suspend research, and this suggests that investigators are concerned that potential violations of safety protocols occurred more broadly within the institute. Almost 500 studies, with combined budgets totaling $86 million, are underway at the institute, according to its website.

The inquiry followed the death by suicide of a person enrolled in a study led by Dr. Bret R. Rutherford, an associate professor of psychiatry at Columbia University who was testing a drug for Parkinson’s disease, levodopa, as a treatment for depression and reduced mobility in older people.

Dr. Rutherford resigned his position at the institute on June 1 and is no longer a faculty member of Columbia’s psychiatry department, Ms. Cantor said. Dr. Rutherford did not respond to requests for comment left at his home and office.

Asked about the reported suicide, Ms. Cantor would not confirm that a death had occurred during a clinical trial, saying the institute could not provide any information about study participants because of health privacy laws.

The institute’s “top priority is the health and safety of individuals engaged in our award-winning research problems,” Ms. Cantor said in a statement.

She said the institute “worked to assist federal agencies in their audit and has subsequently restructured and strengthened its research compliance and monitoring programs across the institution.”

The institute, which is operated by the state Office of Mental Health, is seeking federal approval for a new research safety plan so that federally funded studies can resume, she said. It is also conducting a safety review of human research studies not funded by the federal government, which is expected to be complete next month.

After the initial audit of the Rutherford laboratory, the National Institutes of Health requested an external audit of all federally funded research, she said.

A spokeswoman for the N.I.H., Amanda Fine, said the agency was working closely with the Office of Human Research Protections, which is investigating the matter. N.I.H. cannot discuss matters under review, she said.

The subject’s suicide and the retractions were reported earlier in Spectrum, a news site focusing on autism research. But the U.S. agency’s decision to order a widespread halt to other studies had not been disclosed before now.

The trial of levodopa for late-life depression, which began in 2018 and received $736,579 in funding from the National Institute of Mental Health, aimed to recruit 90 adults over the age of 60 who suffered from mild to moderate depression and a slowed gait.

The team ended up with just 51, of whom 20 dropped out or were found ineligible, according to records provided to federal oversight agencies. The 31 who remained were assigned to one of two groups, one taking levodopa and one taking a placebo.

On the website clinicaltrials.gov, under the heading “serious adverse events,” researchers reported that the individual who died by suicide had been assigned to the placebo arm of the study.

Dr. Rutherford and his co-authors published several articles based on the trial, reporting that levodopa, which increases dopamine concentrations, led to improvement in mobility, processing and depressive symptoms in the study population.

The promising results were flagged in a commentary in The New England Journal of Medicine, which said that clinicians “might consider levodopa” for patients whose cognition or mobility did not respond to standard depression treatments.

It is not clear when the suicide occurred, but records show that the study was temporarily suspended by the National Institute of Mental Health in January 2022 and terminated in May 2023. This year, three scientific journals ran retractions identifying methodological errors in studies from Dr. Rutherford’s laboratory.

One of them pointed to a specific flaw: Eight subjects had only recently stopped taking an antidepressant, rather than waiting 28 days to “wash out,” as required by the study’s protocol. The average number of days those patients had been off medication was 10; one subject had been off medication only for a day.

A member of Columbia’s faculty since 2010, Dr. Rutherford was a prolific researcher, having received 32 grants totaling more than $15.5 million from N.I.M.H. since 2010.

Subjects in the study were paid $15 in cash for weekly visits and an additional $400 for undergoing M.R.I. and PET scans.

Emily Roberts, a former research assistant in Dr. Rutherford’s laboratory and a co-author on one of his papers, told Spectrum that recruiting for the study had been challenging and that some criteria had been relaxed to increase enrollment.

Ms. Roberts, who managed the clinical trial in its first year, said the experience left her disillusioned and contributed to her decision to leave the field. “I was disappointed at the rigor of the research there,” she said. Ms. Roberts verified her comments to Spectrum, but she would not publicly comment further on the matter.

Some studies of psychiatric drugs require participants to “wash out” — to go off the medications they are taking and allow them to clear their system, so that scientists can test the effectiveness of a new one.

This practice is specific to psychiatric research, and it creates a tension about what is best for patients, said Jeffrey Kahn, a director of the Berman Institute of Bioethics at Johns Hopkins University.

“There isn’t another category of drug trial where you ask someone to go off something they are on,” he said. “It’s a violation of a standard of care. You can’t tell someone, ‘Stop taking your chemotherapy so we can compare it to a new chemotherapy.’”

It is rare for regulators to halt research across an institution.

In 2015, the University of Minnesota suspended enrollment in psychiatric drug trials after a critical report by state auditors on the 2004 suicide of a patient who faced commitment to a state institution when he was enrolled in an industry-sponsored clinical trial of Seroquel, an antipsychotic drug.

In 2001, the Office for Human Research Protections ordered Johns Hopkins University to suspend almost all its federally financed medical research involving human subjects after the death of a volunteer who had inhaled an unapproved asthma drug.

In 2000, the federal agency temporarily suspended all medical research involving human subjects at the University of Oklahoma after an investigation showed that patients had been injected with a vaccine that had been made by unqualified laboratory workers.

If you are having thoughts of suicide, call the National Suicide Prevention Lifeline at 1-800-273-8255 (TALK) or go to SpeakingOfSuicide.com/resources for a list of additional resources.