anxiety disorders
Fear Switch in the Brain May Point to Target for Treating Anxiety Disorders Including PTSD
Posted on by Dr. Monica M. Bertagnolli
There’s a good reason you feel fear creep in when you’re walking alone at night in an unfamiliar place or hear a loud and unexpected noise ring out. In those moments, your brain triggers other parts of your nervous system to set a stress response in motion throughout your body. It’s that fear-driven survival response that keeps you alert, ready to fight or flee if the need arises. But when acute anxiety or traumatic events lead to fear that becomes generalized—occurring often and in situations that aren’t threatening—this can lead to debilitating anxiety disorders, including post-traumatic stress disorder (PTSD).
Just what happens in the brain’s circuitry to turn a healthy fear response into one that’s harmful hasn’t been well understood. Now, research findings by a team led by Nicholas Spitzer and Hui-Quan Li at the University of California San Diego and reported in the journal Science have pinpointed changes in the biochemistry of the brain and neural circuitry that lead to generalized fear.1 The intriguing findings, from research supported in part by NIH, raise the possibility that it might be possible to prevent or reverse this process with treatments targeting this fear “switch.”
To investigate generalized fear in the brain, the researchers first studied mice in the lab, looking at parts of the brain known to be linked to panic-like fear responses, including an area of the brainstem known as the dorsal raphe. They found that, in the mouse brain, acute stress led to a switch in the chemical messengers, or neurotransmitters, in some neurons within this portion of the mouse brain. Specifically, the chemical signals in the neurons flipped from producing excitatory glutamate neurotransmitters to inhibitory GABA neurotransmitters, and this led to a generalized fear response. They also found that the neurons that had undergone this switch are connected to brain regions that are known to play a role in fear responses including the amygdala and lateral hypothalamus. Interestingly, the researchers also showed they could avert generalized fear responses by preventing the production of GABA in the mouse brain.
To further support their research, the study team then examined postmortem brains of people who had PTSD and confirmed a similar switch in neurotransmitters to what happened in the mice. Next, they wanted to find out if they could block the switch by treating mice with the commonly used antidepressant fluoxetine. They found that when mice were treated with fluoxetine in their drinking water promptly after a stressful event, the neurotransmitter switch and subsequent generalized fear were prevented.
The researchers made even more findings about the timing of the switch that could lead to better treatments. They found that in mice, the switch to generalized fear persisted for four weeks after an acutely stressful event—a period that for the mice may be the equivalent of three years in people. This suggests that treatments may prevent generalized fear and the development of anxiety disorders when given before the brain undergoes a neurotransmitter switch. The findings may also explain why treatment doesn’t seem to be as effective in people who are initially treated for PTSD after having it for a long time.
Going forward, the researchers want to explore targeted approaches to reversing this fear switch after it has taken place. The hope is to discover new ways to rid the brain of generalized fear responses and help treat anxiety disorders including PTSD, a condition which will affect more than six in every 100 people at some point in their lives.2
References:
[1] Li HQ, et al. Generalized fear after acute stress is caused by change in neuronal cotransmitter identity. Science. DOI: 10.1126/science.adj5996 (2024).
[2] Post-Traumatic Stress Disorder (PTSD). National Institute of Mental Health.
NIH Support: National Institute of Neurological Disorders and Stroke
Distinctive Brain ‘Subnetwork’ Tied to Feeling Blue
Posted on by Dr. Francis Collins
Credit: :iStock/kieferpix
Experiencing a range of emotions is a normal part of human life, but much remains to be discovered about the neuroscience of mood. In a step toward unraveling some of those biological mysteries, researchers recently identified a distinctive pattern of brain activity associated with worsening mood, particularly among people who tend to be anxious.
In the new study, researchers studied 21 people who were hospitalized as part of preparation for epilepsy surgery, and took continuous recordings of the brain’s electrical activity for seven to 10 days. During that same period, the volunteers also kept track of their moods. In 13 of the participants, low mood turned out to be associated with stronger activity in a “subnetwork” that involved crosstalk between the brain’s amygdala, which mediates fear and other emotions, and the hippocampus, which aids in memory.
People Read Facial Expressions Differently
Posted on by Dr. Francis Collins
Credit: Lydia Polimeni, NIH
What do you see in the faces above? We constantly make assumptions about what others are feeling based on their facial expressions, such as smiling or frowning. Many have even suggested that human facial expressions represent a universal language. But an NIH-funded research team recently uncovered evidence that different people may read common facial expressions in surprisingly different ways.
In a study published in Nature Human Behaviour, the researchers found that each individual’s past experience, beliefs, and conceptual knowledge of emotions will color how he or she interprets facial expressions [1]. These findings are not only fascinating, they might lead to new ways to help people who sometimes struggle with reading social cues, including those with anxiety, depression, bipolar disorder, schizophrenia, or autism spectrum disorder.
Measuring Brain Chemistry
Posted on by Dr. Francis Collins
Credit: From the American Chemical Society’s “Personal Stories of Discovery”
Serotonin is one of the chemical messengers that nerve cells in the brain use to communicate. Modifying serotonin levels is one way that antidepressant and anti-anxiety medications are thought to work and help people feel better. But the precise nature of serotonin’s role in the brain is largely unknown.
That’s why Anne Andrews set out in the mid-1990s as a fellow at NIH’s National Institute of Mental Health to explore changes in serotonin levels in the brains of anxious mice. But she quickly realized it wasn’t possible. The tools available for measuring serotonin—and most other neurochemicals in the brain—couldn’t offer the needed precision to conduct her studies.
Instead of giving up, Andrews did something about it. In the late 1990s, she began formulating an idea for a neural probe to make direct and precise measurements of brain chemistry. Her progress was initially slow, partly because the probe she envisioned was technologically ahead of its time. Now at the University of California, Los Angeles (UCLA) more than 15 years later, she’s nearly there. Buoyed by recent scientific breakthroughs, the right team to get the job done, and the support of a 2017 NIH Director’s Transformative Research Award, Andrews expects to have the first fully functional devices ready within the next two years.
Creative Minds: Helping More Kids Beat Anxiety Disorders
Posted on by Dr. Francis Collins
Dylan Gee
While earning her Ph.D. in clinical psychology, Dylan Gee often encountered children and adolescents battling phobias, panic attacks, and other anxiety disorders. Most overcame them with the help of psychotherapy. But not all of the kids did, and Gee spent many an hour brainstorming about how to help her tougher cases, often to find that nothing worked.
What Gee noticed was that so many of the interventions she pondered were based on studies in adults. Little was actually known about the dramatic changes that a child’s developing brain undergoes and their implications for coping under stress. Gee, an assistant professor at Yale University, New Haven, CT, decided to dedicate her research career to bridging the gap between basic neuroscience and clinical interventions to treat children and adolescents with persistent anxiety and stress-related disorders.
