Basics: Job Description Grows for Our Utility Hormone

Researchers lately have learned that serotonin plays an impressive number of critical roles throughout the body, both below the neck and above it, and from the earliest days of prenatal pre-sentience. One team has found that serotonin starts seeping into the embryonic forebrain during the first trimester of pregnancy, helping to shape the basic neural circuitry that later in life will be applied to learning, emoting and consulting a psychiatrist.

More surprising still, Pat Levitt of the Zilkha Neurogenetic Institute at the University of Southern California and his colleagues reported in the April 21 issue of the journal Nature, the creator of all that architectonic prenatal serotonin turns out to be an organ long dismissed as a passive sieve: the placenta. Other researchers have determined that serotonin in the gut helps orchestrate the remodeling of bone, the lifelong buildup and breakdown of osteoclasts and osteoblasts that make the human skeleton such an exciting organ system to own.

The latest findings may never lead to a satisfying pharmacologic fix for what the psychologist Kay Redfield Jamison has called “ordinary existential angst” and others “terminal you-ness,” but they may someday help stiffen the spine, and they remind us that it’s worth listening to serotonin no matter what it has to say.

“If I didn’t admit to being surprised by the scope of serotonin function, and how important it is to tissues like bone,” said Patricia Ducy, who studies the effect of serotonin on bone biology at Columbia University Medical Center, “I would be lying.”

Serotonin is a tiny molecule, a bibelot built of just 10 carbon atoms, a dozen hydrogens, two nitrogens and a single oxygen. The molecule was first detected in 1948, in blood serum, and it was shown be a vascular toning agent that causes blood vessels to constrict — hence its name, a conjoinment of “serum” and “tone.” Five years later, scientists found serotonin in brain extracts as well, and they soon learned that the recently invented hallucinogenic drug lysergic acid diethylamide worked by tapping into the brain’s serotonin system and that if you took too much LSD you might end up wearing hair garlands and overusing the word “wow.”

Serotonin and serotoninlike molecules have also been found throughout the animal, plant and fungal communities. As a vasoconstrictor, serotonin helps give a wasp sting its zing, and as a powerful hormone serotonin specifies the body plan of a sea urchin developing in its egg.

To synthesize their serotonin, humans and other species must start with tryptophan, an essential amino acid found in many dietary items, including turkey, cheese, tofu, nuts, seeds and bananas, a fruit that, despite its notorious comedic associations, always ends up on lists of “very wholesome foods with possible medicinal value.”

Much effort has been devoted to the study of how serotonin operates in the brain, where it serves as a neurotransmitter, a chemical that activates brain cells to fire messages at each other through their impulsive Morse code. In the adult brain, all serotonin is supplied by a handful of cells located in the hindbrain, atop the spinal cord, but those neurons share their bounty widely through filamentous projections.

Not surprisingly, the serotonin signaling system is wondrously complex. Scientists have identified at least 15 distinct serotonin receptors, proteins that clasp onto serotonin and react accordingly. In addition, there is the serotonin transporter, a janitorial protein that removes the serotonin from the little cleft between nerve cells once the molecule’s transmission task is through.

For all the intricacy, serotonin in the brain has a basic personality. “It’s a molecule involved in helping people cope with adversity, to not lose it, to keep going and try to sort everything out,” said Philip J. Cowen, a serotonin expert at Oxford University and the Medical Research Council. In the fine phrase of his Manchester University colleague Bill Deakin, “it’s the ‘Don’t panic yet’ neurotransmitter,” said Dr. Cowen. Given serotonin’s job description, disturbances in the system can contribute to depression, anxiety, panic attacks and mental calcification, an inability to see the world anew — at least in otherwise vulnerable people.

Dr. Cowen emphasizes that serotonin disruption alone does not directly cause depression. Experiments have shown that if you shut down serotonin production in normal people by subjecting them to an extreme tryptophan-free diet, they may not notice the difference; those with a history of depression, however, may well fall back into their gloom.

Prozac, Zoloft and other so-called serotonin-specific reuptake inhibitors seek to enhance serotonin trafficking by blocking the serotonin transporter, thus allowing the neurotransmitter to linger longer in neuronal vestibules and keep supplying its stimulus package to any shovel-ready receptor that will have it.

This article has been revised to reflect the following correction:

Correction: May 5, 2011

The Basics column on Tuesday, about the many functions of the hormone serotonin, misstated the academic credentials of Kay Redfield Jamison. Though she is a professor of psychiatry at the Johns Hopkins School of Medicine, Dr. Jamison is a psychologist, not a psychiatrist.

 

Basics: Job Description Grows for Our Utility Hormone

Researchers lately have learned that serotonin plays an impressive number of critical roles throughout the body, both below the neck and above it, and from the earliest days of prenatal pre-sentience. One team has found that serotonin starts seeping into the embryonic forebrain during the first trimester of pregnancy, helping to shape the basic neural circuitry that later in life will be applied to learning, emoting and consulting a psychiatrist.

More surprising still, Pat Levitt of the Zilkha Neurogenetic Institute at the University of Southern California and his colleagues reported in the April 21 issue of the journal Nature, the creator of all that architectonic prenatal serotonin turns out to be an organ long dismissed as a passive sieve: the placenta. Other researchers have determined that serotonin in the gut helps orchestrate the remodeling of bone, the lifelong buildup and breakdown of osteoclasts and osteoblasts that make the human skeleton such an exciting organ system to own.

The latest findings may never lead to a satisfying pharmacologic fix for what the psychologist Kay Redfield Jamison has called “ordinary existential angst” and others “terminal you-ness,” but they may someday help stiffen the spine, and they remind us that it’s worth listening to serotonin no matter what it has to say.

“If I didn’t admit to being surprised by the scope of serotonin function, and how important it is to tissues like bone,” said Patricia Ducy, who studies the effect of serotonin on bone biology at Columbia University Medical Center, “I would be lying.”

Serotonin is a tiny molecule, a bibelot built of just 10 carbon atoms, a dozen hydrogens, two nitrogens and a single oxygen. The molecule was first detected in 1948, in blood serum, and it was shown be a vascular toning agent that causes blood vessels to constrict — hence its name, a conjoinment of “serum” and “tone.” Five years later, scientists found serotonin in brain extracts as well, and they soon learned that the recently invented hallucinogenic drug lysergic acid diethylamide worked by tapping into the brain’s serotonin system and that if you took too much LSD you might end up wearing hair garlands and overusing the word “wow.”

Serotonin and serotoninlike molecules have also been found throughout the animal, plant and fungal communities. As a vasoconstrictor, serotonin helps give a wasp sting its zing, and as a powerful hormone serotonin specifies the body plan of a sea urchin developing in its egg.

To synthesize their serotonin, humans and other species must start with tryptophan, an essential amino acid found in many dietary items, including turkey, cheese, tofu, nuts, seeds and bananas, a fruit that, despite its notorious comedic associations, always ends up on lists of “very wholesome foods with possible medicinal value.”

Much effort has been devoted to the study of how serotonin operates in the brain, where it serves as a neurotransmitter, a chemical that activates brain cells to fire messages at each other through their impulsive Morse code. In the adult brain, all serotonin is supplied by a handful of cells located in the hindbrain, atop the spinal cord, but those neurons share their bounty widely through filamentous projections.

Not surprisingly, the serotonin signaling system is wondrously complex. Scientists have identified at least 15 distinct serotonin receptors, proteins that clasp onto serotonin and react accordingly. In addition, there is the serotonin transporter, a janitorial protein that removes the serotonin from the little cleft between nerve cells once the molecule’s transmission task is through.

For all the intricacy, serotonin in the brain has a basic personality. “It’s a molecule involved in helping people cope with adversity, to not lose it, to keep going and try to sort everything out,” said Philip J. Cowen, a serotonin expert at Oxford University and the Medical Research Council. In the fine phrase of his Manchester University colleague Bill Deakin, “it’s the ‘Don’t panic yet’ neurotransmitter,” said Dr. Cowen. Given serotonin’s job description, disturbances in the system can contribute to depression, anxiety, panic attacks and mental calcification, an inability to see the world anew — at least in otherwise vulnerable people.

Dr. Cowen emphasizes that serotonin disruption alone does not directly cause depression. Experiments have shown that if you shut down serotonin production in normal people by subjecting them to an extreme tryptophan-free diet, they may not notice the difference; those with a history of depression, however, may well fall back into their gloom.

Prozac, Zoloft and other so-called serotonin-specific reuptake inhibitors seek to enhance serotonin trafficking by blocking the serotonin transporter, thus allowing the neurotransmitter to linger longer in neuronal vestibules and keep supplying its stimulus package to any shovel-ready receptor that will have it.

This article has been revised to reflect the following correction:

Correction: May 5, 2011

The Basics column on Tuesday, about the many functions of the hormone serotonin, misstated the academic credentials of Kay Redfield Jamison. Though she is a professor of psychiatry at the Johns Hopkins School of Medicine, Dr. Jamison is a psychologist, not a psychiatrist.

 

Concern Grows Over Window Blind Safety

But before they left, she decided to put her 2-year-old foster son, Angel, down for a nap. A short time later, her daughter came out of the bedroom and announced that Angel was “sleeping in the window with something around his neck.”

Ms. Leeson, who lives in Montgomery Village, Md., found him lifeless and hanging an inch off the floor, with a window-blind cord wrapped around his neck. “I was screaming his name and shaking him, and the realization hit me, ‘Oh my God. This can’t be happening.’?”

For the last 25 years or so, manufacturers of window blinds have installed safety features and offered tips to parents to try to minimize the dangers from their products. Even so, children like Angel continue to strangle on the cords with grim regularity, an average of one a month.

Now, prodded by a Missouri mother whose daughter was strangled in a window blind, the Consumer Product Safety Commission has asked manufacturers to devise a way to eliminate the risks from window cords or perhaps face mandatory regulations. Critics of the industry complain that manufacturers have dragged their feet on addressing safety hazards for decades, making minor tweaks or putting the onus on parents to shorten cords or buy tie-down devices. Until recently, regulators have done little to crack down, they say.

In response to the commission’s latest push, the industry, working with a task force of regulators and consumer advocates, says it will come up with a fix by the fall.

But the negotiations have gotten off to a rocky start. Like some other regulatory battles that involve consumer safety, this one comes down to a sobering question: how much should manufacturers, and ultimately consumers, be required to pay to prevent the maiming or death of a child?

Manufacturers of window blinds have offered several fixes that they say would reduce the hazards, but consumer advocates on the task force say they are inadequate and have threatened to quit.

“It was my understanding that we were eliminating the hazard,” said Carol Pollack-Nelson, a safety consultant and member of the task force. “Now they are talking about reducing the hazard. We don’t want reduced strangulation. We want no chance of it.”

Regulators at the Consumer Product Safety Commission also rejected the industry’s proposals, and they urged manufacturers to try again. Inez Tenenbaum, the commission’s chairwoman, emphasized that the commission staff plans to continue negotiating with manufacturers to find a solution.

“We are going to stay at the table,” Ms. Tenenbaum said, adding, “I hope everyone will stay at the table.”

What makes the debate over window blinds so vexing is that a solution has been available for several decades: cordless blinds. But cordless blinds are more difficult to manufacture than corded blinds, and can cost considerably more in stores, by some estimates, twice as much.

In an interview, Ms. Tenenbaum said cordless blinds were part of the solution. But the additional cost, she said, had prompted her to push manufacturers to find cheaper alternatives, too, like retractable cords or cords that are covered and therefore inaccessible to children.

Ralph J. Vasami, executive director of the Window Covering Manufacturers Association, said it was unrealistic to expect the industry to eliminate every possible hazard. Window blinds are not children’s products, he said, nor are they defective. His trade group urges parents of young children to install cordless shades.

“The objective is to minimize the hazard as much as possible,” said Mr. Vasami. “I don’t know if you have it in your power to eliminate every hazard for every product.”

Mr. Vasami argued that the industry’s efforts have had a positive effect, citing the fairly stable rate of strangulation deaths even as the industry has grown. He predicted that the number of deaths would inevitably decline as older products were replaced by those with more safety features. “Just looking at it from a statistical standpoint, there will be a lessening over time,” he said.

There are more than one billion blinds in the United States. Americans buy new shades, on average, every seven years, Mr. Vasami said.