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Chronic Disease, Clinical Trials, Mental Health, Research, Stanford News

Treating insulin resistance may speed recovery from major depression

Treating insulin resistance may speed recovery from major depression

depressionIn a randomized, placebo-controlled clinical trial detailed in this study in Psychiatry Research, pioglitazone – a generically available drug that’s approved for type 2 diabetes – helped to relieve symptoms of major depression in patients whose blues had withstood an assault by standard therapeutic regimens for six months or longer.

But this beneficial effect was seen only in depressed patients who were also insulin-resistant.

Depression is remarkably common. Stanford psychiatric researcher Natalie Rasgon, MD, PhD, the study’s senior author, told me that close to one in five Americans are diagnosed with depressive illness at some point in their lives.

Insulin resistance, a stepping stone on the path to type 2 diabetes (not to mention cardiovascular disease and probably Alzheimer’s), is even more common: About one in three otherwise healthy Americans – and an even greater share of people with depression – are insulin-resistant. Especially prevalent among overweight people, insulin resistance also occurs more often than one might expect even among thinner folks, a lot of whom don’t have the faintest idea that’s the case.

Insulin, released by the pancreas in response to food intake, alerts cells throughout the body to the presence of glucose, the body’s primary energy source, in the blood. Insulin-resistant people’s cells fail to take up glucose adequately, leaving high residual blood levels of the sugar to wreak havoc on the body’s tissues. Because the brain is a glucose glutton – it soaks up about 20 percent of all glucose consumption in a healthy, active person – it’s easy to imagine that lousy glucose uptake in the brain would have all kinds of deleterious effects, including effects on mood. Food for thought, anyway.

Here’s how my news release described the study:

[R]esearchers were blinded as to which patients were receiving pioglitazone versus a placebo. The patients didn’t know which they were getting, either. … All the patients had been experiencing episodes of depression lasting, on average, more than one year. Their symptoms had failed to remit under standard treatment regimens. They remained on these regimens for the duration of the Stanford study and, in addition, were given either pioglitazone or a placebo. … The patients were tested for depression severity and insulin resistance at the study’s outset and then roughly every two weeks from the beginning of the trial to the end.

A total of 37 patients – 29 women and eight men – completed the 12-week study. The insulin-sensitive subjects did about as well on the drug as they did on placebo. But among the insulin-resistant group, those given pioglitazone showed a much greater improvement than those who got a placebo. They also showed more improvement than insulin-sensitive patients did.

The more insulin-resistant a participant was at the beginning of the study, the better the drug’s antidepressant effect. Possible, but not proven, explanation: It could be that for some patients standard antidepressant therapies can kick into gear only once these patients’ insulin resistance is reduced. Hungry brains gotta eat.

Previously: Survey shows nearly a quarter of U.S. workers have been diagnosed with depression in their lifetime, Revealed: the brain’s molecular mechanism behind why we get the blues, and International led by Stanford researchers identifies gene linked to insulin resistance
Photo by S.Hart Photography

Behavioral Science, Mental Health, Patient Care

Take it from me: To improve compliance with psychiatric meds, we must educate patients

Take it from me: To improve compliance with psychiatric meds, we must educate patients

We’ve partnered with Inspire, a company that builds and manages online support communities for patients and caregivers, to launch a patient-focused series here on Scope. Once a month, patients affected by serious and often rare diseases share their unique stories; this month’s column comes from mental health advocate Gabe Howard.

3926259585_5f265f6683_zWhenever I give a speech to psychiatric practitioners, I start by giving the group index cards and pens and asking them to write down their most important goal for their patients.

Answers like “be med-compliant,” “miss fewer appointments,” and “follow my instructions” are always the most popular. Patients’ answers are much different. They write “live well,” “go to Hawaii,” or “get back to work.” This exercise serves as a reminder to physicians that taking medication is not a final goal, but a step toward the ultimate goal of living well.

It’s important to realize that patients aren’t failing to take their medication as prescribed because they are incompetent, lazy, or intentionally self-sabotaging. Patients often skip doses or skew directions because they are scared of something, often due to a misunderstanding.

They may misunderstand the prescription instructions or the way the drugs work and this misinformation quickly becomes fact in a patient’s mind. They may already be confused by their diagnosis and lack knowledge about their condition.

Once I understood how difficult it was to find the correct combination of medications, I felt much more hopeful.

More often than not, patients suffer from side effects or even a perceived moral failure by taking psychiatric medications. I’m surprised that many clinicians aren’t aware of the stigma patients feel about taking medication. They believe it means they are “less of a man,” “not capable of being a good mother,” or other such nonsense. Psychiatric medications are often first prescribed to people in their early 20s who are not used to taking medication. Most 20-somethings are still in the “I’m invincible” phase.

I believe this can be remedied with education.

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Bioengineering, Events, Mental Health, Research, Stanford News, Videos

Stanford’s Karl Deisseroth talks about the work he was “destined to do”

Stanford's Karl Deisseroth talks about the work he was "destined to do"

Earlier this week we announced the exciting news that Stanford bioengineer Karl Deisseroth, MD, PhD, had won a $3 million 2016 Breakthrough Prize in Life Sciences. Before he took the stage to accept his award during a star-studded Academy Awards-like ceremony Sunday evening, the video above was shown to highlight the significance of his work. One of Deissoroth’s quotes:

There are deep questions about the brain that may never be answered, but we’re making headway with optogenetics… We’re headed down a path that gets us to understanding [questions like] why does one person feel the way they do and why does it create a disease when they do a particular way, and what can be done to correct it?

Noting that the suffering of people with psychiatric disease “is a very, very serious and pervasive matter,” he also says “the nature of the illnesses – their complexity, the amount of suffering and the mystery – has made this what I was destined to do.”

Previously: Stanford bioengineer Karl Deisseroth wins 2016 Breakthrough Prize in Life SciencesInside the brain of optogenetics pioneer Karl DeisserothLightning strikes twice: Optogenetics pioneer Karl Deisseroth’s newest technique renders tissues transparent, yet structurally intact and An in-depth look at the career of Stanford’s Karl Deisseroth, “a major name in science”
Video courtesy of National Geographic Channel

Medical Education, Mental Health, Research, Surgery, Women's Health

Stereotype perception linked to psychological health in female surgeons

Stereotype perception linked to psychological health in female surgeons

8116089104_be12619731_oFemale surgeons who believe there’s a stereotype that men are better doctors are more likely to suffer from psychological distress, according to a recent study led by a former Stanford resident.

First author Arghavan Salles, MD, PhD, looked at the correlation between the perception of a stereotype — whether individuals think others believe certain groups are superior physicians — and the overall mental well-being of residents.

The team surveyed 382 residents from 14 medical specialties. To examine views on stereotypes, participants were asked: “Do you think residents in your program expect men or women to generally be better [doctors]?” They were also given standard psychological assessments.

Female surgeons were the only group where stereotype perception was correlated with psychological health. Surgery has traditionally been dominated by men and remains a specialty chosen by about twice as many men as women, leading to the persistence of gender stereotypes.

“As a surgical resident, I was aware of the stereotype that men are better surgeons than women. Although I found the stereotype upsetting, I didn’t think about it too much,” Salles told me. Then, after studying stereotype perception while pursuing a doctorate in education, Salles decided to combine her two specialties to determine whether residents experience stereotype threat; a question that no one had asked before.

The link she found has implications for physician productivity and patient care, Salles said.

“I think it’s important to realize that in the world of medicine, although the ratio of males to females is changing, some of these old stereotypes still have an impact on the practitioners,” said co-senior author Claudia Mueller, MD, PhD.

The belief that others think women aren’t good enough adds an unnecessary stressor to the female residents’ already harried lives, Mueller said. It could also contribute to the high attrition rate of females in surgical disciplines, the study states.

Mueller said the study, which appears in the Journal of the American College of Surgeonsis noteworthy for its rare integration of two quite disparate fields, surgery and psychology.

The authors suggest that simply increasing the number of female surgeons may help dissipate the stereotype. Sharing information about the stereotype may also help, as could investigating any practices that may have a differential effect on men and women, the researchers write.

Salles is now querying residents, faculty members and members of the public to see how prevalent stereotypes about gender-based differences in ability actually are.

Previously: How two women from different worlds are changing the face of surgery, Keeping an even keel: Stanford surgery residents learn to balance work and life and Stanford Medicine magazine opens up the world of surgery
Photo by Phalinn Ooi

In the News, Medicine and Society, Mental Health, Public Health

Turning loss into hope for others: New website teaches about mental health

Turning loss into hope for others: New website teaches about mental health


Suicide slices close to the heart for me, and I remember well the story of Shelby Drazan, a Woodside, Calif. 17-year-old who died by suicide last year.

Now, the Drazan family is going public with their efforts to help others suffering from mental illness. A recent article in the Almanac explains their efforts:

The Drazans say they hope talking publicly about what happened to Shelby will ease some of the stigma attached to mental illness.

“A lot of people are struggling,” Stacy Drazan says, “a lot of people especially in this area. We’ve got to help get rid of the stigma so that people can seek help, and earlier.”

Her daughter Mackenzie has created an online trove of resources, Teaching Everyone About Mental Health or TEAM. “Hopefully we can lower the learning curve for everybody else,” Mackenzie said.

At the same time, Stacy Drazan is working to expand the number of adolescent beds for psychiatric patients in the San Francisco Bay area. Stanford’s Steven Adelsheim, MD, a child psychiatrist, is among those working with the family to expand local mental-health resources.

Previously: Advice and guidance on teen suicide, “Every life is touched by suicide:” Stanford psychiatrist on the importance of prevention and Stanford’s Keith Humphreys on Golden Gate Bridge suicide prevention: Get the nets
Photo courtesy of TEAM

Behavioral Science, Mental Health, Pediatrics, Stanford News

Beyond behavior: Stanford expert on recognizing and helping traumatized kids

Beyond behavior: Stanford expert on recognizing and helping traumatized kids

beyond_behavior_fullWhen Victor Carrion, MD, was a pediatric psychiatry fellow in the mid-1990s, he had an “a-ha” moment about some of his poorly behaved patients that set the trajectory of his career. These kids had been traumatized, and the adults around them didn’t recognize it.

He described what happened for my feature story in Stanford Medicine magazine:

“Kids were coming to see me with little notes from their teachers that said, ‘This child has ADHD. Please place on Ritalin,’” Carrion says. Chuckling slightly, he recalls his half-facetious reaction to these missives: “Wow: A diagnosis has been made; there’s a treatment plan; there’s not much for me to do here.”

But after carefully obtaining life histories for several patients, he realized that although some had ADHD, many others had been traumatized by such experiences as abuse, neglect or witnessing violence in their homes or communities. Their reactions — a triad of self-protective behaviors that experts summarize as “freeze, fight or flee” — were being misinterpreted as ADHD’s signature inattentiveness, hyperactivity, aggression and poor cooperation.

Childhood trauma, Carrion realized, was very poorly understood. People assumed kids were more resilient in the face of trauma than adults (they’re not), that you could deal with trauma by ignoring it (no) or that children traumatized before they had the vocabulary to describe what was going on would simply forget what had happened (no again). He wanted to understand what was really going on.

Now, 20 years later, his work and that of many other trauma experts across the country clearly shows we can’t afford to ignore the long shadow cast by early-life abuse, neglect, violence and other instability. “We need to address trauma because it impacts health, period,” Carrion told me. “Not just mental health; it impacts physical health as well.”

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Mental Health, Patient Care, Research

A detailed look at delirium, from the inside

A detailed look at delirium, from the inside

16070214393_8b9ce40d42_zFrom the outside it looks scary enough: A patient so ill their connection to reality has frayed.

Now, a paper in the American Journal of Critical Care provides an inside look at the experiences of patients in intensive care who have suffered delirium, which is characterized by altered consciousness and disorganized thoughts. The work confirms that delirium is frightening, disorienting and can lead to long-lasting anxiety and post-traumatic stress disorder.

Delirium is a common symptom of the severe brain dysfunction caused by many serious disorders that send patients to the ICU. A team of Canadian researchers interviewed 10 patients who had suffered from the condition, distilling four main themes that characterize the experience:

  • Memory loss — Some patients reported feeling anxiety and shame because they couldn’t recall what had occurred during some portions of their illness, the authors wrote.
  • Disconnection – Patients said they were frustrated and fearful when they were unable to communicate with family members and caregivers. One patient said, “It felt like I was living in a bubble; I couldn’t move my arms or legs. And, ah, people all around me but no one answering me… I would be calling out to people but no one would even look up.”
  • Processing – Both during and after the delirium, patients struggled to distinguish events that were real from hallucinations or other thoughts. Some of their hallucinations included, “frozen turkeys in a kitchen, car lights on the wall, large black birds, savage monkeys in the lights, fairies and a lady picking flowers.” Patients also often did not know if they were asleep or awake.
  • Fear — Nearly all patients experienced the sense that they or their family members were in danger. These feelings were so strong several patients developed habits to try to prevent a reoccurrence, such as avoiding surgery or sleeping pills.

“Delirium puts additional emotional and physical stress on a patient whose health is already compromised and our findings demonstrate how potentially psychologically harmful ICU delirium can be,” said lead author Karen Whitehorne, RN, a nurse therapist at Eastern Health in Newfoundland, Canada in a release. These findings add to existing knowledge about the condition and “can facilitate development of treatment plans,” she and her colleagues conclude in the paper.

Photo by Dean Hochman

Behavioral Science, Mental Health, Neuroscience, Stanford News

Decisions, Decisions: How mental-health issues alter decision-making

Decisions, Decisions: How mental-health issues alter decision-making

Research in neuroscience, psychology, business and economics tells us that a plethora of influences can alter the decisions we make. The author explored some of these factors in a Worldview Stanford course and wrote about them in a Stanford story package, Decisions, Decisions. This post is part of a series on what she learned. 

Here’s something truly unfair. People with mental-health issues have changes in their brains that make it harder for them to make decisions that will benefit their health.

Just when you need good decision-making the most, it fails you.

Child psychiatrist Kathleen Fitzpatrick, MD, works with kids who have anorexia. She said that in those people, their risk/reward pathways are aligned so that not eating is rewarding and eating is cause for anxiety. And, like anyone, they decide in favor of the rewarding experience.

Fitzpatrick put it like this, “I will work for the reward of a cupcake. They will work for the reward of removing all cupcakes.”

In my story I also talk with psychiatrist Manpreet Singh, MD, who says people with depression face similar issues. That’s in part why mental-health conditions are so hard to treat. They change a person’s brain in ways that make it even harder to recover.

Previously: Decisions, Decisions: How emotions alter our decisionsDecisions, Decisions: The way we express a decision alters the outcome and Decisions, Decisions: How decisions change with age
Video courtesy of Worldview Stanford

Mental Health, Public Health, Public Safety, Sleep, Stanford News

From A to ZZZZs: The trouble with teen sleep

From A to ZZZZs: The trouble with teen sleep

go_to_bed_fullWhen I recently began working on a story on teen sleep for Stanford Medicine magazine, I was afraid I might not find teens who were troubled by sleep issues and willing to talk about them. I need not have worried: Virtually every teen I encountered had a story to tell about consistently having late nights stressing out over tests or papers or texting friends and cruising the web. It also wasn’t unusual for teens to say that they kept their cell phones on at night in case they got a message from a friend who needed to talk.

Some were tortured by the lack of sleep, often nodding off in class, but said they felt compelled to stay up in order to compete academically in these high-pressure local communities that worship at the altar of academic achievement.

“I’ve heard horror stories of being sleep-deprived,” one 17-year-old told me. “You’re not able to focus on homework, you feel moody and are not able to pay attention in class.”

Another teen reinforced what the National Sleep Foundation found in a recent poll – that 87 percent of American teens are chronically sleep-deprived. “You could probably talk to any teen when they reach their breaking point,” she told me. “You’ve pushed yourself so much and not slept enough and you just lose it.”

In my research, I learned that these students pay a heavy price, potentially compromising their physical and mental health. Study after study in the medical literature sounded the alarm over what can go wrong when teens suffer chronic sleep deprivation: drowsy driving incidents, poor academic performance, anxiety, depression, suicidal thoughts and even suicide attempts.

“I think high school is the real danger spot in terms of sleep deprivation,” Stanford’s William Dement, MD, PhD, the famed sleep researcher, told me. “It’s a huge problem.”

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Genetics, In the News, Mental Health, Neuroscience, Research, Stanford News

Bright Young Mind: Stanford postdoc featured as a top young scientist

Bright Young Mind: Stanford postdoc featured as a top young scientist
100315_nobels_rajasethupathy_resizedYoung researchers don’t always get the accolades they deserve, so I was delighted to see a recent story that’s bucking this trend. This week Science News released its list of “10 scientists who are making their mark,” and Stanford neuroscientist Priya Rajasethupathy, MD, PhD, a postdoctoral research fellow in the lab of Karl Deisseroth, MD, PhD, was featured among them.

Rajasethupathy was nominated for this honor by another group of outstanding scientists: Science News polled 30 Nobel Prize winners to learn which young researchers are doing work that’s worth watching.

Rajasethupathy’s research on how memories are made and stored caught their eye because she’s found that long-term memories may leave lasting marks on DNA. (Her work “has been called groundbreaking, compelling and beautifully executed,” according to the piece.) By studying sea slugs, she and her colleagues have also identified a tiny molecule that may be involved in memory.

Now Rajasethypathy is expanding on this early work and investigating the neural circuits involved in memory recall. To do this, she’s exploring specific genetic mutations to see if they result in abnormal memory behavior. This work may offer insights into neurological disorders, she explains.

Previously: Exploring the role of prion-like proteins in memory disordersNo long-term cognitive effects seen in younger post-menopausal women on hormone therapy and Individuals’ extraordinary talent to never forget could offer insights into memory
Photo by Connie Lee; courtesy of Pryia Rajasethupathy

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