Through 'bridge symptoms' social anxiety can develop into depression, and vice versa

Researchers have changed their tune on how the disorders develop.

  • The study examined the relationships between symptoms of major depressive disorder and social anxiety disorder.
  • Traditionally, shared symptoms haven't been viewed as interacting elements that can cause someone suffering from one disorder to develop the other.
  • The researchers argue that symptoms of one disorder can act as "bridges" that lead to the other. The findings suggest that treatments for depression and social anxiety can be improved by focusing on specific bridge symptoms instead of general underlying factors.

Major depressive disorder and social anxiety disorder affect millions of people worldwide, and they rank among the top three most prevalent psychiatric conditions in the U.S. The two disorders have a high rate of comorbidity, and they share some of the same symptoms: irritability, unstable mood and feelings of worthlessness. When someone develops both conditions, these effects become more debilitating.

Traditionally, researchers have seen these symptoms as manifestations of the underlying forces that led to either disorder, and not as interacting elements that can cause someone suffering from one disorder to develop the other.

A recent study published in the Journal of Affective Disorders, from researchers at Washington University in St. Louis, provides a new theory for the relationship between depression and social anxiety — it's one that conceptualizes their symptoms in a causal network. The authors wrote that the shared symptoms of the disorders can be seen as interacting elements, or "nodes," and that some nodes can act as "bridge symptoms" that cause people already suffering from, say, depression, to develop social anxiety.

"A bridge symptom can be conceptualized as a stepping-stone in a pathway from one disorder to another; the presence of this symptom increases the likelihood that an individual will develop the secondary disorder," the researchers wrote, adding later: "For example, one such pathway might begin with a person who becomes socially fearful, then starts avoiding social situations, and then develops a depressed mood as a result of the social isolation."

The seven nodes

The researchers selected seven symptoms they believed might play a bridge role between depression and social anxiety:

  • Anxiety when in an embarrassing situation with a specific person (an authority figure, a stranger, or a possible romantic figure).
  • Anxiety when having to speak in front of a specific other person (same categories as above).
  • Intensity of feelings of depression.
  • Inability to feel happy, as shown by not being able to laugh easily or to feel cheerful.
  • Feelings of worthlessness.
  • Irritability.
  • Unstable mood, such as feeling that you're "going to pieces" when you're under a great deal of stress.

Then, they asked a sample 130 women between the ages of 18 and 59, many of whom suffered from one or both disorders, to complete inventories on social anxiety and depression, including one inventory based on the Big Five model of personality.

The results showed that feelings of worthlessness seemed to be the strongest bridge symptom between depression and social anxiety. In other words, someone suffering from anxiety might develop a sense of inferiority over their inability to navigate social situations, and those feelings could lead to depression. Meanwhile, they found that the so-called "hallmark symptoms" of each disorder — social fear and depression — did not appear to be connected.

Improved treatments

The analysis didn't reveal whether one disorder plays a stronger role than the other in leading people to develop a secondary disorder. But the results do suggest that viewing social anxiety and depression in a network model, and focusing on specific shared symptoms, can lead to better treatments for people suffering from both conditions.

The authors wrote that "targeting a symptom that appears at the center of the network may facilitate reductions in symptoms of both disorders."

Study: Julia K. Langer , Natasha A. Tonge , Marilyn Piccirillo , Thomas L. Rodebaugh , Renee J. Thompson , Symptoms of Social Anxiety Disorder and Major Depressive Disorder: A Network Perspective, Journal of Affective Disorders (2018).

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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.

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