Tag: depression

Measuring depression with wearables

Depression and emotional disorders can occur at any time of year — and do for millions of Americans. But feeling sad, lonely, anxious and depressed may seem particularly isolating during this holiday season, which is supposed to be a time of joy and celebration.

A team of Stanford researchers believes that one way to work towards ameliorating this suffering is to develop a better way to quantitatively measure stress, anxiety and depression.

“One of the biggest barriers for psychiatry in the field that I work in is that we don’t have objective tests. So the way that we assess mental health conditions and risks for them is by interview and asking you how do you feel,” said Leanne Williams, MD, a professor in psychiatry and behavioral sciences at Stanford, when she spoke at a Stanford Reunion Homecoming alumni celebration.

She added, “Imagine if you were diagnosing and treating diabetes without tests, without sensors. It’s really impossible to imagine, yet that is what we’re doing for mental health, right now.”

Instead, Stanford researchers want to collect and analyze data from wearable devices to quantitatively characterize mental states. The multidisciplinary team includes scientists from the departments of psychiatry, chemical engineering, bioengineering, computer science and global health.

Their first step was to use functional magnetic resonance imaging to map the brain activity of healthy controls compared to people with major depressive disorder who were imaged before and after they were treated with antidepressants.

The researchers identified six “biotypes” of depression, representing different ways brain circuitry can be disrupted to cause specific symptoms. They classified the biotypes as rumination, anxious avoidance, threat dysregulation, anhedonia, cognitive dyscontrol and inattention.

“For example, threat dysregulation is when the brain stays in alarm mode after acute stress and you feel heart racing, palpitations, sometimes panic attacks,” presented Williams, “and that’s the brain not switching off from that mode,” Williams said.

The team, which includes chemical engineer Zhenan Bao, PhD, then identified links between these different brain biotypes and various physiological differences, including changes in heart rate, skin conductance, electrolyte levels and hormone production. In particular, they found correlations between the biotypes and production of cortisol, a hormone strongly related to stress level.

Now, they are developing a wearable device — called MENTAID — that measures the physiological parameters continuously. Their current prototype can already measure cortisol levels in sweat in agreement with standard laboratory measurements. This was an incredibly challenging task due to the extremely low concentration and tiny molecular size of cortisol.

Going forward, they plan to validate their wearable device with clinical trials, including studies to assess its design and user interface. Ultimately, the researchers hope MENTAID will help prevent and treat mental illness — for example, by better predicting and evaluating patient response to specific anti-depressants.

Photo by Sora Sagano

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Tackling caregiver depression in rural China: A Q&A

After studying early childhood development in China for several years, Alexis Medina, assistant director of Stanford’s Rural Education Action Program (REAP), and her colleagues got a question from a colleague that opened up a whole new line of inquiry. I spoke with Medina recently to learn more:

How did your project on caregiver depression get started?

We have been studying early childhood development in rural China since 2012. We’ve learned that rural babies and toddlers in China lag behind global averages on a number of outcomes, including nutrition, cognition and both language and social-emotional development. Parenting behaviors are also lacking — less than half of rural parents read to, play with or tell stories to their young children. And fewer than 10% of families engage in all three behaviors.

During a seminar in London, an Oxford psychology professor asked us if part of the reason for these low cognition levels and low rates of engagement might be maternal or grandmother depression. We hadn’t considered this before, and felt it was worthy of deeper study.

What did your study find?

We added in a measure of adult depression to our survey forms, and then conducted a large-scale survey of 1,787 caregivers across 118 villages in one northwestern province. When the results (which appear in Frontiers in Psychology) came back, we were shocked. Nearly one-quarter of women caregivers showed signs of depression. As our Oxford friend predicted, depressed caregivers were also significantly more likely to have children with social-emotional delays.

We also found a large generational disparity: under 20% of mothers showed signs of depression, compared with 35% of grandmothers. This was actually the opposite of what we expected going into the study.

In our study, we also conducted a series of in-depth household interviews with 55 of the caregivers to delve deeper into the potential contributing factors associated with depression. We uncovered some interesting trends that we think of as side effects of a rapidly changing society.

For example, we found that depressed grandmothers consistently felt out of place both within their own household and in society at large. These women were brought up in a struggling rural economy to be farmers and farmers’ wives. Many cannot read. They feel like they’re unemployable in the modern economy, and therefore unable to meaningfully contribute to their family. Meanwhile, they’re often saddled with full-time childcare for energetic toddlers whose parents are off in the big cities working skilled jobs. They are tired, they are lonely and they repeatedly told us that they feel ‘worthless.’

How does mental health differ in China?

We know from our research that there is little understanding of mental health among rural families. We found indications of depression among many rural women caring for toddlers, yet less than half of these had even heard of depression. Mental health is highly stigmatized. And there are a lot of misconceptions, such as assuming everyone with a mental health issue will behave in extreme ways: ‘standing naked in freezing water,’ ‘doing stupid things’ or engaging in violence. And treatment is nearly non-existent.

There is relatively more research done on mental health in urban areas of China. This research shows that levels of stress, anxiety and depression are also quite high. Although there are still large misperceptions about the sources of mental health problems and ways of treating these conditions among urban Chinese, their understanding is much better than that of rural Chinese residents.

What are the next steps?

Our next steps will be to explore ways of addressing these high rates of caregiver depression. We’ve built over 100 village-based parenting centers, where caregivers and their children can visit and play together six days a week. By building a sense of community and empowering caregivers, we hope to help alleviate some of the depressive symptoms we’ve observed. One of our graduate students is currently measuring the impact of these centers on caregiver depression.

We’re also working on an intervention that will provide caregivers with monthly, in-home mental health support. We would like to also learn more about any existing resources offered through rural health centers, and see if we can work with local governments to build on existing programs.

On the most fundamental level, there needs to be more awareness of the issues — from both families and health care workers — so that talking about mental health can become less stigmatized.

Photo by Laura Jonsson courtesy of REAP

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Will antidepressants work? Brain activity can help predict

You, or someone you care about, probably take an antidepressant — given that one in eight Americans do. Despite this widespread use, many experts question whether these drugs even work. Studies have shown that antidepressants are only slightly more effective than a placebo for treating depression.

“The interpretation of these studies is that antidepressants don’t work well as medications,” said Stanford psychiatrist and neurobiologist Amit Etkin, MD, PhD. “An alternative explanation is that the drugs work well for a small portion of people, but we’re giving them to too broad of a population and diminishing overall efficacy. Right now, we prescribe antidepressants based on patients’ clinical symptoms rather than an understanding of their biology.”

In a new study, Etkin and his collaborators sought a biologically-based method for predicting whether antidepressants will work for an individual patient.

The researchers analyzed data from the EMBARC study, the first randomized clinical trial for depression with both neuroimaging and a placebo control group. EMBARC included over 300 medication-free depressed outpatients who were randomized to receive either the antidepressant sertraline (brand name Zoloft) or a placebo for eight weeks.

Etkin’s team analyzed functional magnetic resonance imaging (fMRI) data — taken before treatment started — to view the patients’ brain activity while they performed an established emotional-conflict task. The researchers were interested in the brain circuitry that responds to emotion because depression is known to cause various changes in how emotions are processed and regulated.

During the task, the patients were shown pictures of faces and asked to categorize whether each facial expression depicted fear or happiness, while trying to ignore a word written across the face. The distracting word either matched or mismatched the facial expression. For example, the fearful face either had “happy” or “fear” written across it, as shown below.

Participants were asked to decide if this expression was happy or fearful.
(Image courtesy of Amit Etkins)

As expected, having a word that was incongruent with the facial expression slowed down the participants’ response time, but their brains were able to automatically adapt when a mismatch trial was followed by another mismatch trial.

“You experience the mismatched word as less interfering, causing less of a slowdown in your behavior, because your brain has gotten ready for it,” explained Etkin.

However, the participants varied in their ability to adapt. The study found that the people who could adapt well to the mismatched emotional stimuli had increased activity in certain brain regions, but they also had massively decreased activity in other brain regions — particularly in places important for emotional response and attention. In essence, these patients were better able to dampen the distracting effects of the stimuli.

Using machine learning, the researchers determined that they could use this fMRI brain activation signature to successfully predict which individual patients responded well to the antidepressant compared to the placebo.

“The better you’re able to dampen the effects of emotional stimuli on emotional and cognitive centers, the better you respond to an antidepressant medication compared to a placebo,” Etkin said. “This means that we’ve established a neurobiological signature reflective of the kind of person who is responsive to antidepressant treatment.”

This brain activation signature could be used to separate the people for whom a regular antidepressant works well from those who might need something new and more tailored. But it could also be used to assess potential interventions — such as medications, brain stimulation, cognitive training or mindfulness training — to help individuals become treatment responsive to antidepressants, he said.

“I think the most important result is that it turns out that antidepressants are not ineffective. In fact, they are quite effective compared to placebo if you give them to the right people. And we’ve identified who those people are using objective biological measures of brain activity.”

The team is currently investigating in clinics around the country whether they can replace the costly fMRI neuroimaging with electroencephalography, a less expensive and more widely available way to measure brain activity.  

Etkin concluded with a hopeful message for all patients suffering from depression: “Our data echoes the experience that antidepressants really help some people. It’s just a question of who those people are. And our new understanding will hopefully accelerate the development of new medications for the people who don’t respond to an antidepressant compared to placebo because we also understand their biology.”

Feature image by inspiredImages

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Head injuries alter genes linked to serious brain disorders, new study shows

Photo by geralt

Traumatic brain injuries, like those caused by concussions, are common. But suffering even a mild brain injury boosts the likelihood of developing neurological and psychiatric disorders, such as Alzheimer’s disease and posttraumatic stress disorder, years later. Exactly how and why that happens remains a mystery.

“Very little is known about how people with brain trauma — like football players and soldiers — develop neurological disorders later in life,” said Fernando Gomez-Pinilla, PhD, a University of California, Los Angeles professor of neurosurgery and of integrative biology and physiology, in a recent news release.

Now, Gomez-Pinilla and his colleagues have discovered that a brain injury harms “master” genes that control other genes throughout the body. This triggers the alteration of hundreds of genes, which are linked to disorders like Alzheimer’s disease, Parkinson’s disease, PTSD, attention deficit hyperactivity disorder and depression. Their study was recently published in EBioMedicine.

In the study, the researchers trained 20 rats to navigate through a maze. They then injected a fluid into the brain of half the rats to simulate a concussion-like brain injury. When all the rats were retested in the maze, the rats with a brain injury took about 25 percent longer than the controls to solve the maze — indicating a change in basic cognitive function.

Next, the team investigated how the brain injuries altered the rats’ genes. They analyzed RNA samples from the rats’ white blood cells and hippocampi, the part of the brain that plays a central role in memory processes. In the injured rats, they found almost 300 genes had been altered in the hippocampus and over 1200 genes in the white blood cells.

More than 100 of these altered genes have counterparts in humans that are linked to neurological and psychiatric disorders. The researchers concluded that concussive brain injury reprograms key genes and this reprogramming could make neurological and psychiatric disorders more likely.

In addition, almost two dozen of the altered genes occurred in both the hippocampus and white blood cells. The researchers hope this genetic signature can be used to develop a gene-based blood test that determines whether a brain injury has occurred and whether future neurological disorders are likely.

They also hope their identification of master genes can give scientists new targets to develop better pharmaceuticals for brain disorders. However, more research is needed to fully understand the role of these master genes. Gomez-Pinilla said he now plans to study the phenomenon in people who have suffered a traumatic brain injury.

This is a reposing of my Scope blog story, courtesy of Stanford School of Medicine.

Chronic pain is correlated with major depression — for sufferer and spouse, study finds

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Image by Stefano Vitale via Stanford Medicine magazine

Chronic pain — pain that lasts longer than three months — debilitates over 100 million Americans and costs the United States over half a trillion dollars annually, but we still don’t really understand its underlying risk factors.

According to a new study recently published in PLOS Medicine, genetics and your home environment substantially contribute to your risk of chronic pain. The study also found that chronic pain is correlated with major depressive disorder (MDD), and both conditions are in part caused by a variety of genes.

The study was conducted by Andrew McIntosh, MD, chair of biological psychiatry at the University of Edinburgh, and his colleagues using data from two large United Kingdom population studies — including 23,960 individuals from the Generation Scotland: Scottish Family Health Study and 112,151 individuals with genotyping and phenotypic data from the United Kingdom Biobank.

It makes sense that someone with chronic pain has a higher risk of being severely depressed. But the study found that you also have increased risk for major depression if you’re living with a spouse or partner with chronic pain.

The authors discuss possible reasons for this spousal effect, which were summarized in a recent news story:

  • “You may choose a spouse similar to yourself, with similar existing predispositions to the conditions (assortative mating).
  • It’s possible that caring for a spouse with chronic illness makes you more likely to develop depression.
  • The environment you share with your spouse may contribute to both your risks of chronic pain and MDD; shared environmental factors could include diet, infectious disease, and hobbies.”

Determining the extent of these environmental factors was beyond the scope of the current study, but the authors recommend future research to identify the causal mechanisms that link chronic pain and major depressive disorder. They concluded in the paper:

“The answers to these questions are likely to signpost new directions for therapeutic interventions and highlight the symptoms that are most amenable to treatment, as well as prevention.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

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