Stanford Scientists Classify 5 Subtypes of Anxiety and Depression

Stanford researchers identify five different types of anxiety, each correlating with the activation of different brain networks.

One of the more informative revelations in our quest to understand autism is the wide ranges that exist in behavior and effect. Journalist Steve Silberman opens his tour de force, Neurotribes, by detailing just how varied what is now known as “the spectrum” can be. One hundred people could feasibly have one hundred different genetic causes, resulting in a popular sentiment in the autism community: “If you meet one person with autism, you’ve met one person with autism.” 

Could the same be true of anxiety and depression? We know degrees exist, but types? There’s a giant disparity between feeling jitters and a full-blown panic attack, between being awkward at a party and refusing to ever step foot inside any social gathering. To help us understand such distinctions, a new study from Stanford researchers states at least five different types of anxiety exist, each correlating with the activation of different brain networks. 

Led by Katherine Grisanzio, research lab manager in the Neuroscience Research Lab at Stanford Medicine’s Williams PanLab, the study, published in JAMA Psychiatry, could lead to more specific therapies for sufferers of the general terms anxiety and depression—two distinct psychological disorders that share numerous qualities. According to the study, at least 50 percent of individuals suffering from one form display concurrent diagnoses applicable to other categories. 

Heterogeneity within each disorder manifests not only at the symptom level but also in underlying behavior and physiology, and this limits the opportunity for health care professionals to understand disease mechanisms and to identify valid biomarkers for disease progression and intervention targets.

Only one-third of sufferers in this spectrum of disorders fully recover, a percentage the Stanford team hopes increases through its work. Data from 420 participants (with a second, independent sample of 381 participants) were collected. The mean ages was 39.8; 61 percent of volunteers were female. Tests included self-reporting, brain maps, and psychiatric diagnostic testing. The researchers were also interested in how social anxiety affects everyday living. 

Participants were first classified based on self-reporting their negative mood, anxiety, and stress symptoms. Once placed into subtypes, an independent sample was conducted. Symptom subtypes were then expressed at each participant’s level of behavioral and psychological functioning. Finally, the team investigated clinically meaningful differences in functional capacity of each subtype. 

In the study, the team describes the five subtypes as:

Tension: This type is defined by irritability. People are overly sensitive, touchy, and overwhelmed. The anxiety makes the nervous system hypersensitive.

Anxious arousal: Cognitive functioning, such as the ability to concentrate and control thoughts, is impaired. Physical symptoms include a racing heart, sweating, and feeling stressed. “People say things like ‘I feel like I’m losing my mind,” Williams says. “They can’t remember from one moment to the next.”

Melancholia: People experience problems with social functioning. Restricted social interactions further cause distress.

Anhedonia: The primary symptom is an inability to feel pleasure. This type of depression often goes unrecognized. People are often able to function reasonably well while in a high state of distress. “We see it in how the brain functions in overdrive,” Williams says. “People are able to power through but at some time become quite numb. These are some of the most distressed people.”

General anxiety: A generalized type of anxiety with the primary features involving worry and anxious arousal — a more physical type of stress.

If psychiatry and the broader medical world are to make progress on treatment, this field guide is an important step forward. According to Leanne Williams, who runs the lab:

"Currently, the treatments would be the same for anyone in these broad categories. By refining the diagnosis, better treatment options could be prescribed, specifically for that type of anxiety or depression."

In My Age of Anxiety, Scott Stossel notices that the increased rate of SSRI consumption that has occurred in America has only resulted in “substantially higher rates of anxiety and depression.” This one-size-fits all approach to treatment is making people more anxious, and subsequently more depressed, due in part to acclimation to the drug and the inability to properly measure if the drug is even effective in the first place. 


Not all is lost. As Joseph Ledoux writes in Anxious, “just as the brain can learn to be anxious, it can also learn to not be that way.” That one-third of sufferers do fully recover is a sign that certain therapies are effective. It might just be a matter of sourcing which one is most beneficial.

Hopefully this research from Stanford will help doctors prescribe better treatments individualized for their patients. There is rarely a silver bullet in science. Until we treat each patient on their own terms we’re not going to see effective therapy on a widespread level. And this has to begin with a reduction in scripts written anytime someone feels a little anxious. More time with each patient and a more comprehensive assessment of their neurological functioning are required.


Derek is the author of Whole Motion: Training Your Brain and Body For Optimal Health. Based in Los Angeles, he is working on a new book about spiritual consumerism. Stay in touch on Facebook and Twitter.

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Yale scientists restore brain function to 32 clinically dead pigs

Researchers hope the technology will further our understanding of the brain, but lawmakers may not be ready for the ethical challenges.

Still from John Stephenson's 1999 rendition of Animal Farm.
Surprising Science
  • Researchers at the Yale School of Medicine successfully restored some functions to pig brains that had been dead for hours.
  • They hope the technology will advance our understanding of the brain, potentially developing new treatments for debilitating diseases and disorders.
  • The research raises many ethical questions and puts to the test our current understanding of death.

The image of an undead brain coming back to live again is the stuff of science fiction. Not just any science fiction, specifically B-grade sci fi. What instantly springs to mind is the black-and-white horrors of films like Fiend Without a Face. Bad acting. Plastic monstrosities. Visible strings. And a spinal cord that, for some reason, is also a tentacle?

But like any good science fiction, it's only a matter of time before some manner of it seeps into our reality. This week's Nature published the findings of researchers who managed to restore function to pigs' brains that were clinically dead. At least, what we once thought of as dead.

What's dead may never die, it seems

The researchers did not hail from House Greyjoy — "What is dead may never die" — but came largely from the Yale School of Medicine. They connected 32 pig brains to a system called BrainEx. BrainEx is an artificial perfusion system — that is, a system that takes over the functions normally regulated by the organ. The pigs had been killed four hours earlier at a U.S. Department of Agriculture slaughterhouse; their brains completely removed from the skulls.

BrainEx pumped an experiment solution into the brain that essentially mimic blood flow. It brought oxygen and nutrients to the tissues, giving brain cells the resources to begin many normal functions. The cells began consuming and metabolizing sugars. The brains' immune systems kicked in. Neuron samples could carry an electrical signal. Some brain cells even responded to drugs.

The researchers have managed to keep some brains alive for up to 36 hours, and currently do not know if BrainEx can have sustained the brains longer. "It is conceivable we are just preventing the inevitable, and the brain won't be able to recover," said Nenad Sestan, Yale neuroscientist and the lead researcher.

As a control, other brains received either a fake solution or no solution at all. None revived brain activity and deteriorated as normal.

The researchers hope the technology can enhance our ability to study the brain and its cellular functions. One of the main avenues of such studies would be brain disorders and diseases. This could point the way to developing new of treatments for the likes of brain injuries, Alzheimer's, Huntington's, and neurodegenerative conditions.

"This is an extraordinary and very promising breakthrough for neuroscience. It immediately offers a much better model for studying the human brain, which is extraordinarily important, given the vast amount of human suffering from diseases of the mind [and] brain," Nita Farahany, the bioethicists at the Duke University School of Law who wrote the study's commentary, told National Geographic.

An ethical gray matter

Before anyone gets an Island of Dr. Moreau vibe, it's worth noting that the brains did not approach neural activity anywhere near consciousness.

The BrainEx solution contained chemicals that prevented neurons from firing. To be extra cautious, the researchers also monitored the brains for any such activity and were prepared to administer an anesthetic should they have seen signs of consciousness.

Even so, the research signals a massive debate to come regarding medical ethics and our definition of death.

Most countries define death, clinically speaking, as the irreversible loss of brain or circulatory function. This definition was already at odds with some folk- and value-centric understandings, but where do we go if it becomes possible to reverse clinical death with artificial perfusion?

"This is wild," Jonathan Moreno, a bioethicist at the University of Pennsylvania, told the New York Times. "If ever there was an issue that merited big public deliberation on the ethics of science and medicine, this is one."

One possible consequence involves organ donations. Some European countries require emergency responders to use a process that preserves organs when they cannot resuscitate a person. They continue to pump blood throughout the body, but use a "thoracic aortic occlusion balloon" to prevent that blood from reaching the brain.

The system is already controversial because it raises concerns about what caused the patient's death. But what happens when brain death becomes readily reversible? Stuart Younger, a bioethicist at Case Western Reserve University, told Nature that if BrainEx were to become widely available, it could shrink the pool of eligible donors.

"There's a potential conflict here between the interests of potential donors — who might not even be donors — and people who are waiting for organs," he said.

It will be a while before such experiments go anywhere near human subjects. A more immediate ethical question relates to how such experiments harm animal subjects.

Ethical review boards evaluate research protocols and can reject any that causes undue pain, suffering, or distress. Since dead animals feel no pain, suffer no trauma, they are typically approved as subjects. But how do such boards make a judgement regarding the suffering of a "cellularly active" brain? The distress of a partially alive brain?

The dilemma is unprecedented.

Setting new boundaries

Another science fiction story that comes to mind when discussing this story is, of course, Frankenstein. As Farahany told National Geographic: "It is definitely has [sic] a good science-fiction element to it, and it is restoring cellular function where we previously thought impossible. But to have Frankenstein, you need some degree of consciousness, some 'there' there. [The researchers] did not recover any form of consciousness in this study, and it is still unclear if we ever could. But we are one step closer to that possibility."

She's right. The researchers undertook their research for the betterment of humanity, and we may one day reap some unimaginable medical benefits from it. The ethical questions, however, remain as unsettling as the stories they remind us of.

Scientists see 'rarest event ever recorded' in search for dark matter

The team caught a glimpse of a process that takes 18,000,000,000,000,000,000,000 years.

Image source: Pixabay
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