September 14, 2020

From grief comes new hope

Prechter family creates largest bipolar study in the nation 

This article appeared in the Grosse Ile Grand newspaper. 

By Paula Neuman

Self-made millionaire, business mogul and high-level Republican fundraiser Heinz Prechter, 59, took his own life in the pool house of his Grosse Ile home in July 2001.

His suicide shocked the many employees at his Downriver businesses as well as top politicians across the country. His funeral at the Grosse Ile Presbyterian Church drew hundreds of people, including Michigan Gov. John Engler, White House adviser Karl Rove and two members of President George W. Bush’s cabinet.

Only after his death did the world learn that the larger-than-life man sometimes called “the Duke of Downriver” suffered from bipolar disorder — a type of mental illness that causes dramatic shifts in a person’s mood, energy and ability to think clearly.

People with bipolar disorder, sometimes called manic depression, experience severe high and low moods — known as mania and depression — that differ from the typical ups and downs most people experience, according to the National Alliance on Mental Illness.

Four months after her husband’s death, Prechter’s wife Waltraud “Wally” Prechter and the couple’s two children founded the Heinz C. Prechter Bipolar Research Fund. It was a way to channel their grief into something positive and to honor his memory.

“As I look back to when I first created the fund in November 2001, I wanted answers to why this terrible illness took Heinz from us,” Prechter said last week. “I had no idea then about the complexities of bipolar in the context of science and research.”

And neither did the medical research community at the time.

In 2004, she moved the fund to the University of Michigan Health System, and it’s now the Heinz C. Prechter Bipolar Research Program at the school’s Frances and Kenneth Eisenberg and Family Depression Center under the leadership of Dr. Melvin McInnis, Fellow of the Royal College of Psychiatrists.

“Under the leadership of Dr. McInnis, the program today with its flagship longitudinal study has become the largest bipolar study of its kind in the nation,” Prechter said. “We are looking at the biology of the brain, investigating genes, collaborating with numerous disciplines across the university as well as with researchers from around the globe, and looking at strategies on how to detect mood stages via cellphone apps, just to name a few of the projects.”

Some years ago, researchers thought they might be able to identify one or two genes that created bipolar disorder, which tends to run in families. But that has not proved to be the case, McInnis said.

“What we’re finding is that there are many elements to bipolar disorder,” he said. “We and others have found genes that contribute a very small amount of susceptibility to bipolar disorder. There’s a lot of variability. There are likely to be hundreds of genes that contribute very small amounts.”

The disorder has a biological foundation, and also is influenced by personal, social and environmental surroundings, according to the Prechter research program. A research approach exploring all those factors is needed to understand an individual with the disease.

One frequent contributing factor to bipolar disorder is childhood abuse, the data shows, McInnis said.

“Childhood abuse can compromise mood swings and the ability to function in a normal way,” he said. “The history of abuse will lower functionality later in life.”

And quite possibly brain nerve cells and how they communicate with each other play a role, as well.

Researchers in the U of M Center for Pluripotent Stem Cell Research, working with the Prechter program, are looking at neuronal cells — cells within the nervous system that transmit information to other cells — as a potential contributing factor to the disorder.

“We have shown that neuronal cells derived from people with bipolar disorder signal to each other more frequently and more strongly,” said Dr. K. Sue O’Shea, director of the stem cell research center, in a 2019 Prechter Program publication.

One way cells signal to each other is via packets of chemical signals called exosomes.

“We are very excited about exploring exosomes and their contents —what chemicals they carry and how the numbers, size and uptake is different between control and bipolar brain cells,” O’Shea said.

McInnis said: “This is an important stride forward. An individual with bipolar probably has a nervous system with a little more excitability than someone without the disorder. Why is still a mystery. We are focusing on cellular mechanisms for maintaining the equilibrium in the cells — making sure the plumbing is working right, if you will.”

Finding ways to help the neuronal cells work better through medication or other therapy techniques could help a person with the disorder.

“Even when they are well, a person with bipolar has a propensity toward impulsive behavior,” McInnis said. “I’m very encouraged by the lab finding of this excitability.”

Another area of the program’s study is showing that adding omega-3 fatty acids and antioxidants — the stuff one gets from eating fruits, vegetables, nuts, seeds and fish — improves the work of those neuronal cells.

That study, still in “the infancy stage” needs to be looked at in more detail, McInnis said.

“We have found that by and large people with bipolar don’t have a very good diet,” he said. “They are prone to easy, fast foods whether at home or in the environment. The quality of meals is not very high.”

What goes “in the gut” can create “a very mild inflammatory condition,” he said. “It is very likely that there are inflammatory disruptions contributing to the illness.”

Another area of the program’s research is called The PRIORI Study. PRIORI stands for Predicting Individual Outcomes for Rapid Intervention, and it involves the study of repeated voice patterns in people with bipolar disorder.

McInnis described patients’ family members telling of how they can tell if a loved one with bipolar disorder is heading for an episode of severe depression sometimes weeks ahead of time by somehow hearing it in their voices.

“So what we did was we went to the computer science people looking at speech detection,” he said.

PRIORI principal investigator Dr. Emily Mower Provost began the study with 51 individuals with bipolar disorder and nine healthy controls. The study had the participants use a cellphone app to capture audio from their conversations and transmit that data to the researchers. From the tones and acoustics of speech, the scientists developed accurate emotion recognition algorithms.

“We used the algorithms’ predictions to differentiate between individuals at risk for suicide and health controls and to determine when interventions may be necessary to help the patient,” Provost said in the 2019 program publication. “We have shown that speech collected in clinical environments and in natural personal interactions can be measured to detect changes in mood symptom severity.”

“The challenge there is how we utilize this information to predict when somebody’s heading for a problem,” McInnis said. “It’s very expensive and very intensive work. We’re moving incrementally forward on that. There are a whole series of challenges around it, including privacy issues.”

The program’s lab now includes 13 years of data from more than 1,330 research participants. But meaningful research takes time — lots of time — and that can be frustrating for patients and supporters and also for the scientists themselves.

McInnis said he is grateful to work with researchers who are “finicky and fussy and rigorous,” who do thorough work with careful scientific method in spite of the pressure to make faster progress.

The program is collaborating with other researchers worldwide to gather “more detailed data over the course of time” the better to “understand what causes and what are the mechanisms that help to treat the illness,” he said.

Bipolar disorder is treated with a variety of medications and treatments that include electroconvulsive therapy and transcranial magnetic stimulation, and also with talk therapy.

“No one intervention can solve every problem,” McInnis said. “There are many options. The goal I emphasize to all patients is that you can be 80 percent well 80 percent of the time. People have a tendency to think a bad day means everything’s going to hell in a handbasket, and that’s not the case. It may take a couple of years for them to achieve that goal.”

The disorder affects approximately 5.7 million adult Americans, or about 2.6% of the U.S. population age 18 and older every year, according to the National Institute of Mental Health. 

The median age of diagnosed onset for bipolar disorder is 25, although the illness can start in childhood or as late as the 40s and 50s. An equal number of men and women develop bipolar illness and it is found in all ages, races, ethnic groups and social classes.

As many as one in five people with bipolar disorder commit suicide, victims like Heinz Prechter, whose death ultimately led to the program making strides to help.

“What started out of pain and desperation has taken on a life of its own and become more than I could have imagined, and I am very proud of the Heinz C. Prechter Bipolar Research Program,” said program founder Wally Prechter.

“I have tremendous respect for the researchers and their work, and I know we are on our way to finding the answers to a very complex illness.”