Talking to experts at the School, who have varied backgrounds— psychology, neurobiology, sociology, economics, and health policy—it becomes clear that, not only is mental health as broad a field as physical health, the two worlds are also inextricably linked.
Not many people would take a three-month-old to see a psychologist, but there’s still plenty happening in the area of mental health for babies, even before birth. The human brain begins forming during week three of a pregnancy, and early life abounds with opportunity to steer the mind in a healthy direction. From a public health perspective, early interventions are the most effective and have the biggest payoff down the line. It’s all about evaluating the conditions during pregnancy and infancy that prevent negative outcomes such as mental illness and lead to a healthy, happy adult population.
Stress, gestation, and forces of nature
When Professor Ray Catalano looks at population-level reactions to stress and anxiety, he thinks, “How did we get here?” And he puzzles over not just the current population, but all the populations that might have been.
“Only 30 percent of human conceptions get born—probably fewer,” he says. “So that any given time the human population will have in gestation a much larger number of possible humans than actually become live humans. And my job is to try to figure out what the filters are, what the criteria are by which you pass from being a potential human into a live human.”
If you’re reading this, Catalano believes you have passed some “tests” in utero that were developed by evolutionary mechanisms over hundreds of thousands of years. Clearly, the efficacy of these tests has been proven—from an evolutionary standpoint—by the fact that humans as a species are still around. Unfortunately, passing these tests was likely to have had more benefit many thousands of years ago, and does not necessarily guarantee success as a human living in modern society. In fact, the opposite may be true.
“So what we find today is that there probably are these atavistic mechanisms that made perfectly good sense in our evolutionary history, which may not be so obviously beneficial any longer, but they are still at work,” says Catalano. “The classic example of how this impacts mental health being that a stressed mother both epigenetically and behaviorally can influence characteristics of her offspring such that they become more reactive to stressful circumstances. And that that kind of heightened stress response will affect their later life health.”
The possible negative consequences of this mechanism include increases in physical health problems exacerbated by stress, such as increased cardiovascular disease, and also elevated mental health problems for some populations— specifically, clinical levels of anxiety. People who are clinically anxious respond biologically and behaviorally to events that most people don’t feel are provocative or require any particular response, to the point where it gets in the way of daily life. They may need psychological or psychiatric treatment in order to manage their reactions to small stressors. Catalano believes this high level of anxiety did not get bestowed on some members of a given population due to chance, but in fact because responsiveness to stress is a beneficial quality to have in a challenging environment.
“It’s possible that a population that includes pregnant women who are being subjected to high levels of challenge may produce a generation of people who respond at lower levels of challenge in the hopes that you will get more survivors given that environmental circumstance,” says Catalano. “If the environment then becomes less challenging, what you’ve got are people who are hyper-responsive, which puts them at higher risk for behavioral and physiological problems.”
All this is not to say that everything is fixed prenatally, with no room for change later on. “Some people make claims that early life exposures change dramatically what people do later. It’s not so clear to me that that’s right,” says Catalano, “because there’s a lot of plasticity and malleability. After you’ve been selected and made epigenetically who you are, then after that there’s probably considerable leeway in what you’re going to do within the parameters that are available to you.”
Catalano also looks at other ways stressors affect gestation on a population level. Along with Tim Bruckner at UC Irvine and other researchers, he evaluated the phenomenon that catastrophic events and economic stressors—such as the 9/11 terrorist attacks, recessions, or mass layoffs—result in fewer male babies being born. They concluded this response is due to selection in utero, i.e., a higher number of male fetuses being spontaneously aborted in times of stress. The scientific evidence suggests that male fetuses, especially smaller males, are more susceptible than female fetuses to stress-induced hormones during pregnancy, because the mechanisms that test males and females for fitness are different. The ratio shift is small, but statistically significant, and shows that the gestation process can be affected by external stressors at a population level.
Should these population-level findings affect health and economic policy on a broad scale, or influence expectant mothers’ choices at an individual level? Catalano believes such decisions, made by public health professionals and the populations they serve, should be informed by rigorous research and exploration of basic science.
“Public health as a science is trying to understand how we come to be as we are,” he says. “It’s our job to study, at the frontier, what are the things that affect populations and population health. The fodder for the decision-making mill has to come from somewhere, and that has to come from science. That’s probably what Berkeley does better than most schools of public health, because we are embedded in a campus that has always been committed to basic science.”
Neurobiology, environmental enrichment, and better stress management
The stress reaction—or “freaking out”—is an unavoidable part of life, and not always a bad one. The ability to react to stress, to deal with imminent threat, is critical to survival. The bad part comes when the stress response is activated chronically and inappropriately—”freaking out over nothing.” That can lead to increased vulnerability to stress related diseases and mental pathologies. The ability to distinguish between controllable and uncontrollable stressors can be the key to becoming a healthy, happy, functional adult. And, in part, this ability—or lack of ability—is formed very early on in life.
“I’m interested in what contributes to an efficient and healthy stress response,” says Darlene Francis, assistant professor of public health, who is an expert in neurobiology and has a joint appointment with the UC Berkeley Department of Psychology. “And we know from our work that the quality of parenting, or maternal care, absolutely trumps just about any other factor for determining the trajectories in which your stress response develops over time.”
Francis learns about the development of the stress response by working with rats and mice, but her ultimate goal is to improve the lives of humans. She can see from her extensive experience with rat families that their social interactions resemble those of humans in many ways. Moreover, animal models allow her to look closely at the biological mechanisms that underpin stress reactions and behaviors, to determine causal relationships, and test possible interventions at specific stages of life.
Katherine Saxton MPH ’06, a doctoral student in epidemiology who works in Francis’s lab, also sees the value of animal research to human public health. “From my point of view, there’s a lot we can’t do with people,” says Saxton. “But we can look at the rat brains; we can run experiments and control, or at least measure, maternal care and stress. So we can actually look at what matters, when it matters, and how it works.” And, she adds, “To answer a simple question about development, you don’t want to wait 50 years. Maybe some people do, but I’m impatient.”
A good example of the power of animal research models is Francis’s research into the efficacy of mental health interventions in early childhood. In human and rat brains alike, the hippocampus is a critical component in the coordination of the stress response, because glucocorticoid receptors located in the hippocampus bind stress hormones in order to turn off the stress response. Basically, having more glucocorticoid receptors gives a greater ability to “fine tune” reactions to stress. Francis has learned from her research and others’ that rats with highly maternal environments (more licking and grooming) will develop double or triple the amount of glucocorticoid receptors than rats with weak maternal environments.
Francis then looked at how a large-scale intervention might positively affect the rats that had grown up in low maternal care environments. She threw “all the good stuff [she]could imagine” into their environment, including larger cages to roam, other rats for social time, and toys for play time. “This massive intervention for the animals was able to successfully reverse the phenotype,” she says. “So my prediction was that we must have reversed the levels of glucocorticoid receptors.”
However, she found that her prediction was “absolutely false” and that, although the intervention was a success in terms of the rats’ behaviors, their glucocorticoid receptor levels had remained fixed. She then theorized that the intervention was, in effect, creating a work-around in a part of the brain that develops later in life, probably the frontal cortex. “Rather than thinking about undoing, it’s more about looking for opportunities where you can effect change,” concludes Francis.
Results like these in animal models have many implications for the direction of public health interventions for humans.
Changes to the environment during pregnancy and the first few years of life, when critical brain structures such as the hippocampus are forming, will undoubtedly have the greatest impact on functioning as an adult. But it’s also true that the brain is malleable, and can create many different routes to the same desired destination.
“An appealing piece of this for public health people is the environmental enrichment,” says Saxton. “You might not be able to go back and change someone’s parenting experience, but you can change the environment they are in later and work around it that way. So when you’re thinking about racial disparities, poverty, trauma, or abuse, outside interventions later on in life can still make a difference.”
Francis believes many—perhaps all!—public health and mental health problems throughout the lifespan can be viewed in terms of stress management. “It’s really hard to escape,” she says. “When you’re thinking about any intervention for just about any mental or physical health outcome, managing stress will give you a huge bang for your buck.”
Adolescence encompasses a broad age range that’s getting broader. Recent studies at the School show that puberty is beginning earlier in girls, as early as age 8 or 9. Additionally, some teens are delaying adulthood and postponing the time they strike out on their own in the world into their mid- to late-20s. But whatever the time frame, adolescence—the transition from childhood to adulthood—is a time of change in the brain. It is filled with potential but fraught with pitfalls. For public health experts, the goal is to understand how to steer adolescent minds in a healthy direction; avoid preventable disease; and prevent deaths from car accidents, homicide, suicide, and substance abuse.
Sleep, trajectories, and the adolescent mind
The word “teen” brings to mind adjectives like “sullen,” “lazy,” and “rebellious.” But for Professor Ronald Dahl, adolescence is more synonymous with phrases like “window of opportunity” or “endless possibility.” He sees it as a time where the stakes are high and the risks are great, but—importantly—the potential rewards are enormous.
“Adolescence is a really a key window of time for the emergence of a lot of difficulties with emotions and behavior,” he says, pointing out that most problems with depression and anxiety as well as alcohol and drug problems and risk-taking behaviors often begin to emerge during adolescence. “But even more broadly, it’s a key time in the trajectory toward a healthy adult lifestyle.”
Like Francis, Dahl approaches social problems with an emphasis on neurobiological processes. He looks at the development of neural systems that underpin self-regulation, emotion regulation, and how experience and learning can sculpt these systems during development—including some unique maturational changes. He joined the School’s faculty this semester, and is excited to leverage the latest advances in developmental neuroscience to inform the strategies, timing, and targets for behavioral interventions, as well as social policies to promote healthy outcomes.
“By understanding windows in time in brain development when things are at a tipping point or rapidly changing, these advances can help us zoom in on a specific behavior intervention or social policies that take advantage of that knowledge and create positive changes with a more enduring impact,” he explains.
One key neural system undergoing a shift during adolescence is sleep regulation. There are two changes in the sleep system that happen at puberty: Kids want and need more sleep than they did pre-puberty, and there is also a subtle shift in the circadian system that causes a tendency to prefer staying up late and sleeping in late. This preference does not mean teens are incapable of getting out of bed before 10 a.m. or falling asleep before 11 p.m. but, when the natural tendency is combined with early school start times, access to artificial light, and the simulating distractions of modern life—television, cell phones, video games, Facebook, instant messaging—the end result is a surprising number of sleep-deprived teens.
“Thirty to forty percent of kids are sleep deprived in American schools,” says Dahl. “Japan is probably worse. These problems are increasing around the world in adolescents, this pressure to do more and more, staying up later, and using stimulants like caffeine.” Sleep deprivation may be great for the health of the coffee industry (“the second-most-traded commodity in the world after oil,” Dahl points out). But it’s bad for the health of adolescents, their parents’ sanity, and the safety of those sharing the road with “chronically jet-lagged” teens learning how to drive. Sleep deprivation also increases irritability and the tendency towards alcohol and drug use.
It negatively impacts emotion regulation, concentration, and attention, and can cause teens to fall asleep during quiet activities like school or driving. There’s also evidence that it interferes with metabolic regulation in a way that predisposes to energy storage, thereby contributing to weight gain and obesity. And its effects are amplified in populations that are already at risk in other ways.
“It’s hard enough for motivated, well-supported kids,” says Dahl, “but think about those kids who don’t have parental support and who are already struggling with depression, anxiety, violence, or drug use; the sleep deprivation can really add to a downward spiral of health problems for them.”
Dahl also believes there’s more to making sure kids get enough sleep than just avoiding the negative impact of sleep deprivation. “The neuroscience tells us that having an impact in positive ways on the trajectory of people doing well in their lives can be much larger than preventing people from going into some category of pathology,” he says. “I think of adolescence as a tipping point, and if you can tip it more positively during this inflection point, that can pay dividends for 30, 40, 50 years of life.”
High school, peer pressure, and youth-led empowerment for at-risk teens
Some people may throw up their hands in despair when dealing with difficult teenagers, and it’s hard to blame them. But Emily Ozer doesn’t give up. As an associate professor of community health and human development, Ozer has observed a dearth of interventions and prevention programs available for adolescents. She’s looking to fill the gap by evaluating evidence based programs and youth-led participatory research in high schools.
“Adolescence is when we have the onset of a lot of psychological disorders, but there’s still a lot of chance for interventions,” Ozer says. “However, there’s not much out there for teenagers. Most of the work is being done at the grade school level. Teens are a harder group to work with.”
Part of the reason for this is that adolescents may already have begun experimenting with risky behaviors. Says Ozer, “If you’re trying to work with young people who are already using drugs, your approach has to be more subtle and differentiated than a broad curriculum that is implemented across the country.”
While it may be easier to develop and test programs for younger kids, it’s still very important not to neglect the health of adolescents and teenagers, especially at-risk individuals and populations. The top three causes of death in teens—automobile accidents, homicides, and suicides—are all preventable and related to mental health and behavioral issues. Beyond mortality, about one in five adolescents is suffering from mental health disorders nationwide, one in ten with a “serious emotional disturbance.” The most common mental health problems during adolescence are anxiety and depressive disorders—which can lead to performance problems in school and increased risk for alcohol and substance abuse, violence, and suicide.
Ozer has been struck by two movements in the field of youth violence and substance abuse prevention: evidence based programs, which have been proven effective based on rigorous examination, and participatory programs, which engage the community in a collaborative way. The goal of much of her research is to combine the two concepts. “I think both movements have a lot of validity,” she says, “but there’s no real exchange between the two. How do we use evidence-based practices and programs, but also try to make them locally relevant?”
For the past five years, Ozer has been working to evaluate the efficacy of youth-led participatory programs in five San Francisco high schools. She collaborates with San Francisco Peer Resources, a program that staffs elective classes on peer mentoring and conflict resolution in San Francisco high schools. In each school, Ozer randomly selects one class to get a specialized “youth research in action” curriculum, during which young people are trained to identify a problem, research it, and develop ways to effect change in their communities. Ozer believes this type of intervention holds great promise for at-risk teens.
“It’s an incredibly promising and powerful intervention that’s very developmentally appropriate for teenagers,” she says. “If you look at an elementary school classroom, usually even kindergarteners will be asked to come up with rules to put on the wall. But when teenagers get to junior high and high school, they’re no longer able to have autonomy or participate in important decisions in their lives. This creates ‘developmental mismatch,’ that at the time kids are becoming more developmentally capable of having more control over their lives, they are put in a kind of lockdown environment, especially in public schools.”
An inspiring example of this method: One issue students identified at John O’Connell High School was teaching practices—they felt teachers often taught in a way that wasn’t engaging to students and students were tuning out. So the class developed an observational tool, where students would go into a teacher’s classroom, observe what the teacher was doing that seemed to engage students, and then give the teachers individualized feedback sessions about what seemed to be working.
“You have a situation where these students, who I think have been seen as the problem in a lot of ways, are ending up doing professional development for their teachers and becoming experts through the research process,” says Ozer. “They’re interacting in school in roles they never would have had before. I think it’s really powerful in that way.”
The teachers were responsive as well, perhaps in part because the students (with guidance from O’Connell teacher Gary Cruz) smartly decided to only give positive feedback through their “Best Practices Club,” and also started with the teachers with whom they thought they would be most successful. “It was amazing,” says Ozer. “The students did a really thoughtful job of engaging the teachers as allies.”
This type of intervention shows promise in improving the mental health of teens, not only in reducing youth violence and substance abuse, but also creating conditions within the schools that provide positive influences on mental health and well-being: connection to the school community, meaningful opportunities to effect change, and improved communication skills.
Not neglecting the evidence-based side of the equation, Ozer and a graduate student, Marieka Schotland, spent a lot of time developing quantitative measures of tricky concepts like psychological empowerment. “Because it’s an area that hasn’t had a lot of systematic study, a lot of my time has been about defining a good implementation, process-wise, and developing measures to assess outcomes,” says Ozer.
Ozer will spend the next year doing in-depth quantitative analysis and use her results to determine next steps. “I’m in a great place to build a bigger study,” she says. “The question is what will be the most fruitful next step?”
Mental illness is an all-too-common disabler of people who might otherwise be in their most productive years. Because they have trouble functioning in society, adults with the most severe mental disorders are oftentimes of low socioeconomic status. As a result, Medicaid is the biggest payer for mental health care in the United States. One strength of the School—which boasts a wealth of health policy and management experts—is its ability to evaluate public sector mental health systems in terms of access, utilization, cost-effectiveness, and outcomes. What works, what doesn’t work, and what could work even better? Also, what can we afford?
Emergency rooms, socioeconomic forces, and disparities in the system
A “fifty-one-fifty” (5150) is an involuntary psychiatric hold, i.e., being committed to an institution against your will. Section 5150 of the California Welfare and Institutions Code allows a qualified officer or clinician to involuntarily confine a person deemed to have a mental disorder that makes the person a danger to him or herself, a danger to others, and/or gravely disabled.
Professor Lonnie Snowden describes the process in more detail: “A person is in psychiatric crisis, having an acute episode of psychosis, they’re disruptive, maybe they’re seeing things. So someone intervenes, calls the police or takes them to the emergency room themselves. At the emergency room, they’re judged to determine whether they should be involuntarily committed.”
Clearly a 5150 is not ideal for anyone—not for the suffering person, the police officer, the hospital staff, or the taxpayers. Like most emergency room visits, it’s a traumatic and expensive event. And it happens to African Americans, both adults and children, at much higher rates than white Americans and also other minorities. As well, African Americans appear in emergency rooms, in general, for mental health problems in numbers much greater than their representation in the U.S. population at large, and are more likely to receive inpatient treatment or institutionalization than outpatient care, such as psychiatric visits or talk therapy.
This phenomenon has been robustly documented, but there has been little investigation to date of possible reasons or remedies. Snowden, a mental health policy expert who has a vision to improve California’s public mental health system, wants to understand the reasons behind this pattern of care in order to design systems and programs to eliminate it. He is pursuing, with the support of the National Institute of Mental Health and the California Program on Access to Care, several lines of research toward this end.
“There are a lot of factors, a lot of possible explanations,” says Snowden. “I want to try to point people in the direction of things they can study to try to sort out the explanations, find out which are valid.”
Snowden, Professor Ray Catalano, and UCSF professor Martha Shumway published a paper in a recent issue of Psychiatric Services, which identified variables that might explain how being African American translates into being exposed more often than white Americans to conditions that promote greater use of psychiatric emergency services. These variables include differences in the mental health system—for example, the fact that African Americans are less likely to have a trusting, ongoing relationship with a primary care provider who could give care directly or a timely referral to outpatient mental health care.
There are also broader sociocultural and economic factors at work—and shifts in these conditions over time have particularly detrimental effects on African Americans. In previous work, Catalano has shown that in times of economic stress, people are less tolerant of mental illness and the rates of involuntary commitments rise.
“When the economy gets worse, people simply become less tolerant of the kinds of petty differences we have among each other,” says Catalano. “There are some kinds of deviance we’re willing to put up with when everything is okay; when things aren’t okay we aren’t so willing to put up with that. The argument is, when things get bad, people get nasty.”
Says Snowden, “People who bring you to the emergency room themselves are under stress. And African Americans are more exposed to those things because of lower levels of income and more precariousness in the labor market.”
There is also greater scrutiny on mental health expenditures during economic downturns; budgets are likely to be cut and the safety net shrinks. This can lead to reduced access to primary care and outpatient care for people who depend on the public sector for treatment, which can result in more visits to the emergency room. Another complication is the high prevalence of comorbidities in mental health, meaning cuts to service in one area could have negative consequences in others.
“Especially for people who use public sector services, the problems that are most prevalent are schizophrenia, major depressive disorders, and bipolar disorders,” says Snowden. “Also, a lot of times those problems co-occur with substance abuse problems—drugs and alcohol. This can complicate treatment and complicate financing to some extent, because they may need dual programs.”
Integrating substance abuse and mental illness programs is a challenging proposition, but one Snowden believes could lead to much more successful treatment of both conditions. In general, Snowden sees more integration of mental health care and “regular” health care system as a positive direction, one that can lead to decreased recidivism to the emergency room.
“From a public health perspective, the overlaps are hard to escape,” he says. “We now know to do more in response to the areas of overlap. One thing we see is that people with mental health problems, especially depression, show up in primary care. And there has been a lot of effort in the last decade to have primary care to respond more productively, in terms of recognition, referral, and/or treatment.”
Colorado’s example, capitation, and the challenge of cost-effective care
The State of Colorado presented health organization and management expert Joan Bloom with a challenge: Is it possible to spend less money and still provide quality mental health services? Bloom, who chairs the School’s Health Policy and Management Division, took up the challenge and then some—gathering Berkeley experts and others to explore the question in great detail over the course of two NIMH grants and a decade, and publishing more than 15 papers on their findings. The short answer: Yes, it’s very possible. This is good news, not just for Colorado, but nationwide in terms of creating more efficient mental health systems.
In 1992, the Colorado State Legislature passed a bill to establish and evaluate a pilot program of a prepaid capitation system to provide comprehensive mental health services to Medicaid recipients. In a capitation model, each of the participating community health centers is provided with a fixed amount of money based on the number of people they serve, as opposed to the more traditional fee-for-service payment model. The system was implemented in 1995, with seven of Colorado’s 17 community health centers switching to the managed care model.
Colorado provided a natural fit for evaluation, because some counties remained in the traditional fee-for-service model, including the large mental health center in Denver. Additionally, some of the mental health centers were run by a for-profit behavioral health organization, while others were run by not-for-profit agencies. This unique set up provided many opportunities to compare and contrast the cost, utilization, and access offered by the different models of service.
The state hoped that the financial incentives introduced by capitation would lead to reduced reliance on inpatient care in favor of community-based outpatient care and an increased emphasis on preventative care. But there were also community concerns that people with severe and persistent mental illness—whose treatment is often the most complex, long-term, and expensive—would not be able to get the care they needed.
“There was a lot of concern that you were dealing with the most vulnerable population and that capitation was a dangerous thing to use, and they would cut back services and save money, but people would do worse,” says Bloom. “But we didn’t find that. We didn’t find any large difference in outcomes.”
It wasn’t for lack of searching—Bloom’s team had a stratified random sample of 522 severely mentally ill subjects from across Colorado, and conducted a three-year analysis of how people fared, using measures including symptoms, functioning, quality of life, alcohol/drug use, public safety, and welfare. They also checked to see if anyone had filed grievances complaining that they weren’t getting enough services.
“There weren’t any grievances from the population; everybody pretty much liked the program, although they had lots of concerns to start with,” Bloom says.
Bloom’s team looked at costs pre- and post-capitation, developing a shadow billing system to evaluate costs post-capitation. They determined that a cost savings was achieved during the first year and maintained over the next two years. “When we looked at both cost and use, the capitated areas were cost effective,” says Bloom. “They provided a good service and had good outcomes.”
Professor Emeritus Teh-wei Hu, an expert on the costs and outcomes of mental health care methods, was very involved with the Colorado study and concurs with Bloom on the findings. “Managed care is an effective delivery approach to contain costs,” Hu concludes. “Capitation may be an effective financing approach to contain cost, but it depends on the incentives and design of capitation.”
“There have been some other experiments in the country, and generally what they’ve found is you save money in capitation programs because you keep people out of the hospitals; the hospitalization is the most expensive part of the services,” says Bloom. “But nobody had really looked beyond one or two years or had the comparisons that we were able to do. So that’s where we brought in some new information.”
After the initial three-year study, Bloom began a five-year follow-up that looked at the differences between the for-profit and not-for-profit capitation models. She found that in both the for-profit and not-for-profit areas the cost for inpatient, outpatient, and total services were reduced, although the strategies to achieve the savings were different between the two models.
“The southern part of the state—the for-profit area— hospitalized people and got them stable, but they put a discharge planner in the hospital to get them out early,” says Bloom. “One of the big things when you’re dealing with the mentally ill is housing, and they made sure that when they got out they had a place to go when they were released and were getting services to maintain their medications.”
The not-for-profit center in Northern Colorado had a different strategy: They created a “red team” that did an assessment to see if people needed to be hospitalized or if they could be treated within the community, with an emphasis on avoiding hospitalization. Also, the for-profit centers focused on schizophrenia, while the not-for-profits took on major depression.
“Both strategies worked,” reports Bloom. “It was an interesting finding; it shows there’s more than one way to reach your goals.”
Also within this follow up, Catalano analyzed emergency room visits as an indicator of the system’s effectiveness, and found that emergency room use went down after capitation was implemented. Snowden looked at differences between the African American, Latino, and white communities, and did not find that health disparities increased under managed care.
“It’s not always easy to get publicity on good news; most people want to hear about the terrible things that happened,” Bloom speculates. “But most of our news was good news.”
In the United States over the past 100 years, the percentage of the population aged 65 and older has grown from 4 percent to more than 13 percent. By the time the entire baby boom generation reaches age 65, about one in five Americans will be over the age of 65. This demographic shift has major public health implications. The need for effective and appropriate mental health care for older adults will continue to grow, as will the field of healthy aging. As well, maintaining long-term cognitive functioning becomes more and more important, including the battle against dementia and Alzheimer’s disease.
Alzheimer’s, amyloids, and the Neuroimaging Initiative
Much of Professor William Jagust’s research is devoted to the early detection of a disease for which there is currently no cure—Alzheimer’s disease. Jagust anticipates a question: “You might say, why do we want to do that, because we can’t treat Alzheimer’s?” But he has good reasons: to be ready when an effective treatment is found, and also to help facilitate the search for a cure.
“There is hope that an effective drug will be found to treat Alzheimer’s in the not-so-distant future, and it will be important to treat people as early as possible,” he says. “Also, finding early indicators of Alzheimer’s will help identify subjects on whom new drugs should be tested, helping speed the development of such drugs.”
A leading theory in the cause of Alzheimer’s disease is that the build-up of a protein called beta-amyloid in the brain triggers the progression of the disease, loss of memory, and cognitive failure. This hypothesis has led to the development of drugs that block either the deposit of amyloid or the effects of amyloid.
“A handful of these drugs have been tested on patients with Alzheimer’s disease,” says Jagust. “And so far, they’ve all failed. They haven’t made people better.”
These disappointing results have led to two theories (“and I actually believe both of these,” Jagust says): That something besides amyloid needs to be targeted in the brain in order to treat Alzheimer’s, and that treatment needs to be started earlier before there has been too much degeneration in the brain for the removal of amyloid to have an effect.
The Jagust Lab—which includes researchers from the UC Berkeley School of Public Health, the UC Berkeley Helen Wills Neuroscience Institute, and the Lawrence Berkeley National Laboratory—develops and uses brain imaging techniques to try to find biomarkers that will help detect Alzheimer’s in people with very mild symptoms or no symptoms at all. The lab is also part of a nationwide effort, the Alzheimer’s Disease Neuroimaging Initiative (ADNI), involving 60 centers, which has been at work for five years and will continue for another five years. The Jagust Lab uses a type of positron emission tomography (PET) scan that actually detects the levels of beta-amyloid in the brain. One of these types of PET scans is being utilized in ADNI as well as in the Jagust Lab research.
“We’re using these scans to detect this amyloid in people with very mild symptoms and people who are completely normal,” says Jagust, “and then we’re going to see what happens to them over time and if we can use these kinds of amyloid measures to find who might be at risk.”
To date, Jagust is pretty confident that the build-up of amyloid is the first thing to “go wrong” in the progression of Alzheimer’s, the first change in the brain that can be seen. In fact, the PET scans can detect the presence of amyloid in people who are functioning completely normally. Other changes, like brain shrinkage, occur later and can be detected by MRIs.
The project has revealed a lot about how biochemistry and brain structure and function change over time. In addition, the lab has developed a lot of standardized methods for the biomarkers and collection of imaging data—methods which have been adopted in other countries and by drug companies. The Michael J. Fox Foundation for Parkinson’s disease has also picked up on it, with modifications.
“ADBNI been a very big success from the perspective of developing standards,” says Jagust. But he worries that it may not lead to a cure. “The proof will be whether we can use these things to develop drugs and whether there are any drugs that work,” he says. “It’s going to be fairly difficult to test these drugs in early stages, because people may have to be followed for a while before we can see a change.”
While waiting on progress in drug therapies, Jagust is working to learn more about how the presence of amyloid affects brain functioning and the impact of lifestyle factors on the incidence of Alzheimer’s disease. His lab has selected a smaller group of people, aged 65 and older, who have healthy cognitive functioning, and performed amyloid PET and a variety of types of other imaging techniques including MRI on them to determine whether or not amyloid is present in their brains. The researchers also interview them and test their cognition over time. One of the key scientific problems they are trying to understand is why some people remain cognitively healthy despite high levels of amyloid in the brain, while others get Alzheimer’s disease.
“There’s this whole chain of evidence that says if you’re cognitively engaged in life, your risk of getting Alzheimer’s is lower,” says Jagust. “It’s certainly not as simple as ‘use it or lose it,’ but we are finding out that it’s not simply a matter of being born with this and having a gene and you’re getting it—it’s also related to your lifestyle.”
Epidemiologic studies have shown a correlation between a good diet, exercise, cognitive stimulation and decreased incidence of Alzheimer’s disease. “Some of the studies we’re doing that are focused on causes and etiology over the lifespan will likely have a public health impact,” says Jagust. “What kinds of things people are exposed to really does affect what happens to their brain as they get older. There’s no doubt in my mind that that’s true.”
But Jagust cautions that there has not yet been a lifestyle intervention that’s been shown to have been effective in reducing the incidence of Alzheimer’s disease. This may be because these kinds of interventions are difficult to implement and test, partly because a good intervention would need to start much earlier in life.
“If you start doing crossword puzzles when you’re 60, and you think that’s going to prevent you from getting Alzheimer’s disease, I don’t think it’s too likely,” says Jagust. “If you have a lifelong pattern of good health behaviors, then that will have an impact. That’s a tough intervention, and I think it’s hard to test. But it’s the right thing to do anyway. I think we can add cognition to the reasons to do it. We already have a million reasons to do it, so now there’s a million and one.”
Depression, the built environment, and successful aging
Thanks in no small part to the field of public health, life expectancy keeps getting longer. But, as anyone with chronic pain can attest, healthy aging is not just about longevity; quality of life is equally important. As we age, we want to remain high functioning, physically and cognitively, and we want to be happy and enjoy life.
Bill Satariano, professor of epidemiology and community health, is an expert on “successful aging,” a goal that encompasses physical, psychological, and social health. His book, Epidemiology of Aging: An Ecological Approach, examines many practicalities about growing older, including survival, disease, social capital, sense of control, and living situation. Satariano says that a major threat to quality of life for older populations is depression, and notes that elderly people who are depressed are at increased risk for cognitive impairment, falls and injuries, and even death.
“Depression is a key condition, a key comorbid condition,” says Satariano. “Regardless of what else you have, if you’re also depressed, it just makes everything worse.”
Satariano has done several studies on depression in older adults, including determining what factors in the environment contribute to increased incidence of depression, and what lifestyle steps people can take to help maintain good mental health. With Adjunct Professor David Ragland, who directs UC Berkeley’s Safe Transportation Research and Education Center, he looked at whether driving cessation leads to increased depressive symptoms in older people.
They found that, two years after people stopped driving, their depressive symptoms increased, independent of other factors. Satariano believes there are three factors at work: the loss of connectivity to society, the cessation of the cognitive process of driving itself, and the symbolic nature of not being capable of driving.
“With older people, it represents a significant public policy issue,” says Satariano. “Because on the one hand we know how important it is that older people have access to goods and services, that they have access to friends and relatives. But on the other hand, there’s the issue of public safety. I think with the aging of the population it’s going to become more and more significant.”
Connectivity is a big factor in helping prevent depression in general. The ability to get around—whether it’s driving, taking public transportation, or walking—can have an impact on state of mind. At a policy level, Satariano looks at what we can change about the built environment in order to allow people to be healthier, especially when it comes to getting out and walking.
“One of the important things that someone might do if they’re feeling depressed is just start walking,” he says. “There’s evidence to suggest that older people who live in environments that are perceived as unsafe or where it’s more difficult to walk or there’s a concern about crime are more likely to be depressed,” says Satariano. “Conversely the people who live in an environment that encourages physical activity and social interaction seem to be less likely to be depressed.”
The ideal walking path for an older person would be safe, away from traffic and other hazards, with shade and places to rest, stop for a drink, or use the restroom. Reconfiguring the built environment with these considerations in mind, especially near senior centers, is a great goal, albeit expensive and time intensive. A more immediate intervention, perhaps to be done concurrently, is the creation and distribution of walking maps showing the best routes for walking.
“So you live here, and these are routes that you may want to take that are reasonably safe and the sidewalks don’t have many cracks or breaks,” says Satariano. “This is not necessarily changing the environment, but trying to link older people to the best that their current environment has to offer.”
Satariano also recommends walking programs and mall walking as a viable option for older people— especially those who live in areas with bad weather—because of amenities offered there. “It’s a safe environment, it’s an opportunity to see what’s in the stores, but also to meet friends at a coffee spot in the mall,” he says.
While walking and spending time with friends will not prevent all mood disorders in older people, Satariano believes broad-based programs to increase these activities will go a long way towards improving the mental health of an aging population. He sees public health as working in concert with clinical medicine in this area.
“I think we can improve the mood and the well-being of a lot of people with these types of programs,” says Satariano. “This is a way in which public health can focus on large populations of people, and deal with factors that can serve to prevent or lessen the impact of certain conditions.”