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A Blood Test May Help Pinpoint the Right Antidepressant for You

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When doctors determine the best medication for a person with depression, they generally rely upon little more than guesswork and patient self-reports, due to insufficient medical evidence. Research out of UT Southwestern Medical Center (UTSMC) previously suggested that such practices were insufficient, and a new study, published in Psychoneuroendocrinology, provides additional diagnostic information that may change the way depression is treated.

The research team drew upon a large body of research that links low levels of inflammation in the body with depression. They say a blood test for an inflammatory biomarker, known as C-reactive protein (CRP), can significantly improve the success rate of two common antidepressants for depressed patients.

Lead author Madhukar Trivedi, a professor of psychiatry at UTSMC and director of the Center for Depression Research and Clinical Care, says doctors typically pick an antidepressant for their patients in one of three ways: personal experience; matching the perceived benefits of one drug with a certain type of patient’s needs; or having the patient pick a drug by ruling out the unwanted side effects of other drugs. “There isn’t a strong evidence base to support one way [of choosing an antidepressant] over another,” he tells mental_floss.

Trivedi says that because many doctors are pressed for time and overloaded with patients, they don't thoroughly address a depressed patient’s needs. “If you have diabetes, the doctor spends a lot of time explaining that it’s a serious illness—there are consequences for ignoring it, and there are treatments you need to do. In depression, that does not happen as much. Patient engagement is not that strong,” he says.

Trivedi led a landmark study more than a decade ago that revealed how serious the medication problem is: Up to one-third of depressed patients don’t see an improvement in their first month of medication, and approximately 40 percent of people who take antidepressants quit within the first three months.

This failure rate is exacerbated by the lingering social stigma accompanying the illness. “It is not fashionable to say, ‘I have depression,’ so people around you may put in their uninformed advice … 'Just go for a walk,' or 'Why are you depressed?'” says Trivedi.

The CRP blood test is traditionally used as a measure of inflammation for such diseases as cardiovascular disease, diabetes, and rheumatoid arthritis, among others, where doctors are looking for high levels of C-reactive protein—approximately 3 to 5 milligrams per blood liter. In the new study, which Trivedi refers to as a “secondary analysis” of a study he led in 2011 (the Co-MED trial), he says, “Our hypothesis was that for depression there may be stress related inflammation in lower levels.”

Trivedi’s lab measured depression remission rates of 106 patients, culled from 440 patients involved in the 2011 study, each of whom had given blood samples. Fifty-one of them had been prescribed only escitalopram (Lexapro), while 55 of them had been prescribed escitalopram plus bupriopion (Wellbutrin), both commonly prescribed SSRI antidepressant drugs.

After analyzing blood samples, the researchers found that for patients whose CRP levels were less than 1 milligram per liter of blood, escitalopram alone was more effective—patients experienced a 57 percent remission rate of their depression versus 30 percent on the other drug. For patients with higher CRP levels, escitalopram plus bupropion was more effective. These patients experienced a 51 percent remission rate, compared to 33 percent on only escitalopram.

Not only do these SSRI antidepressant drugs promote higher levels of retention of the “feel good” neurotransmitters serotonin and dopamine, they trigger an immune response that blocks inflammatory molecules called cytokines.

“The magnitude of the effect was really thrilling,” Trivedi says. “The bottom line in depression is we have not had objective tests that help us with any component of diagnosis or treatment matching—and this is a very solid first step.”

His next step will be to do a clinical trial in which researchers will go to primary care practices and randomize patients, so that half of the participants will get “the best care the provider is willing to do,” he says, and the other half will do the blood test and then get matched with one of the two drug approaches. “We want to show that if you have the treatment matching based on the blood tests, that group of patients will have significantly better outcomes than those who do usual care.”

He hopes that other studies will use the CRP test with other antidepressant drugs, as well. “It’s not a perfect solution for 100 percent of patients, but it helps.”

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Big Questions
What Is Foreign Accent Syndrome?
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One night in 2016, Michelle Myers—an Arizona mom with a history of migraines—went to sleep with a splitting headache. When she awoke, her speech was marked with what sounded like an British accent, despite having never left the U.S. Myers is one of about 100 people worldwide who have been diagnosed with Foreign Accent Syndrome (FAS), a condition in which people spontaneously speak with a non-native accent.

In most cases, FAS occurs following a head injury or stroke that damages parts of the brain associated with speech. A number of recent incidences of FAS have been well documented: A Tasmanian woman named Leanne Rowe began speaking with a French-sounding accent after recovering from a serious car accident, while Kath Lockett, a British woman, underwent treatment for a brain tumor and ended up speaking with an accent that sounds somewhere between French and Italian.

The first case of the then-unnamed syndrome was reported in 1907 when a Paris-born-and-raised man who suffered a brain hemorrhage woke up speaking with an Alsatian accent. During World War II, neurologist Georg Herman Monrad-Krohn compiled the first comprehensive case study of the syndrome in a Norwegian woman named Astrid L., who had been hit on the head with shrapnel and subsequently spoke with a pronounced German-sounding accent. Monrad-Krohn called her speech disorder dysprosody: her choice of words and sentence construction, and even her singing ability, were all normal, but her intonation, pronunciation, and stress on syllables (known as prosody) had changed.

In a 1982 paper, neurolinguist Harry Whitaker coined the term "foreign accent syndrome" for acquired accent deviation after a brain injury. Based on Monrad-Kohn's and other case studies, Whitaker suggested four criteria for diagnosing FAS [PDF]:

"The accent is considered by the patient, by acquaintances, and by the investigator to sound foreign.
It is unlike the patient’s native dialect before the cerebral insult.
It is clearly related to central nervous system damage (as opposed to a hysteric reaction, if such exist).
There is no evidence in the patient’s background of being a speaker of a foreign language (i.e., this is not like cases of polyglot aphasia)."

Not every person with FAS meets all four criteria. In the last decade, researchers have also found patients with psychogenic FAS, which likely stems from psychological conditions such as schizophrenia rather than a physical brain injury. This form comprises fewer than 10 percent of known FAS cases and is usually temporary, whereas neurogenic FAS is typically permanent.

WHAT’S REALLY HAPPENING?

While scientists are not sure why certain brain injuries or psychiatric problems give rise to FAS, they believe that people with FAS are not actually speaking in a foreign accent. Instead, their neurological damage impairs their ability to make subtle muscle movements in the jaw, tongue, lips, and larynx, which results in pronunciation that mimics the sound of a recognizable accent.

"Vowels are particularly susceptible: Which vowel you say depends on where your tongue is in your mouth," Lyndsey Nickels, a professor of cognitive science at Australia's Macquarie University, wrote in The Conversation. "There may be too much or too little muscle tension and therefore they may 'undershoot' or 'overshoot' their target. This leads to the vowels sounding different, and sometimes they may sound like a different accent."

In Foreign Accent Syndromes: The Stories People Have to Tell, authors Nick Miller and Jack Ryalls suggest that FAS could be one stage in a multi-phase recovery from a more severe speech disorder, such as aphasia—an inability to speak or understand speech that results from brain damage.

People with FAS also show wide variability in their ability to pronounce sounds, choose words, or stress the right syllables. The accent can be strong or mild. Different listeners may hear different accents from the speaker with FAS (Lockett has said people have asked her if she's Polish, Russian, or French).

According to Miller and Ryalls, few studies have been published about speech therapy for treating FAS, and there's no real evidence that speech therapy makes a difference for people with the syndrome. More research is needed to determine if advanced techniques like electromagnetic articulography—visual feedback showing tiny movements of the tongue—could help those with FAS regain their original speaking manner.

Today, one of the pressing questions for neurologists is understanding how the brain recovers after injury. For that purpose, Miller and Ryalls write that "FAS offers a fascinating and potentially fruitful forum for gaining greater insights into understanding the human brain and the speech processes that define our species."

Have you got a Big Question you'd like us to answer? If so, let us know by emailing us at bigquestions@mentalfloss.com.

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The Great Yanny vs. Laurel Aural War of 2018, Explained
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It's rare for people to disagree on the internet, but no amount of civility could be spared when a "social media influencer" named Cloe Feldman posted a four-second sound clip on Twitter on May 15, 2018 and asked followers whether they heard a voice say "Yanny" or "Laurel."

Maybe you hear "Yanny." Maybe "Laurel." Proponents of either one recognize a very distinct word, which seems like some kind of aural magic trick. 

Popular Science asked several audiologists to help explain what’s going on. Brad Story, a professor of speech, language, and hearing sciences at the University of Arizona, performed a waveform analysis, which is already more effort directed at this than at the ransom calls for the Lindbergh baby. Story observed that the recording's waveform displays the acoustic features of the "l" and "r" sounds, offering reasonable proof that the voice is saying "Laurel." Whoever engineered the track seems to have layered a second, higher-frequency artifact over it—a frequency that sounds like "Yanny" to some people.

But why do listeners hear one name versus the other? We listen with our brains, and our brains tend to prioritize certain sounds over others. You might be focused on hearing your child talk, for example, over the din of a television. Because "Laurel" and "Yanny" are on different frequencies, some listeners are subconsciously favoring one over the other.

Audiologist Doug Johnson of Doug Johnson Productions provided further proof in his YouTube video analyzing the recording. By isolating each track, it's clear listeners can hear both "Yanny" and "Laurel."

A bigger mystery remains: Who conceived of this recording? It wasn't Feldman, who said she picked it up from a Reddit conversation. According to Wired, the answer is likely Georgia-based high school freshman Katie Hazel, who was looking up the word "laurel" on Vocabulary.com, had the site play it back, and was confused when she heard "Yanny" instead. She shared the discrepancy on Instagram, which was picked up by school senior Fernando Castro. From Castro's Instagram, it landed on Reddit. The original recording was performed for Vocabulary.com in 2007 by an unnamed opera singer and former cast member of the Broadway musical CATS.

Vocabulary.com isn't sure if the singer will come forward to claim their role in this fleeting internet sensation. In the meantime, the "Yanny" and "Laurel" camps continue to feud, mystified by the inability to hear what the other can. Musician Yanni is in the former group.

[h/t Popular Science]

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