Newborn horses with a troubling disorder display some of the same symptoms as children with autism, including detachment, a failure to recognize their mothers, and a lack of interest in nursing.
Abnormal levels of naturally occurring neurosteroids may be the connection, researchers say.
“The behavioral abnormalities in these foals seem to resemble some of the symptoms in children with autism,” says John Madigan, a veterinary professor at the University of California, Davis.
Detachment in kids and foals
Neonatal maladjustment syndrome in foals also caught the attention of Isaac Pessah, professor of molecular biosciences at the UC Davis School of Veterinary Medicine and a faculty member of the UC Davis MIND Institute, who investigates environmental factors that may play a role in the development of autism in children.
“There are thousands of potential causes for autism, but the one thing that all autistic children have in common is that they are detached,” Pessah says.
In newborn foals, neonatal maladjustment syndrome, or dummy foal syndrome, occurs in 3 to 5 percent of live births. With around-the-clock bottle or tube feeding plus intensive care in a veterinary clinic for up to a week or 10 days, 80 percent of the foals recover.
For years, the syndrome has been attributed to hypoxia—insufficient oxygen during the birthing process. Madigan and veterinary neurologist Monica Aleman began sleuthing around for other potential causes, noting that hypoxia usually causes serious, permanent damage and most foals with the maladjustment syndrome survive with no lingering health problems.
Biochemical ‘on switch’
One of their prime suspects was a group of naturally occurring neurosteroids, which are key to sustaining pregnancies in horses, especially in keeping the foal “quiet” before birth.
“Foals don’t gallop in utero,” Madigan says, pointing out the dangers to the mare if a four-legged, hoofed fetus were to suddenly become active in the womb. The prenatal calm is made possible by neurosteroids that act as sedatives for the unborn foal.
However, immediately after birth, the infant horse must make an equally important transition to consciousness. In nature, a baby horse would be easy prey for many natural enemies, so the foal must be ready to run just a few hours after it is born.
In short, somewhere between the time a foal enters the birth canal and the moment it emerges from the womb, a biochemical “on switch” must be flicked that enables the foal to recognize the mare, nurse, and become mobile. Madigan and Aleman suspect that the physical pressure of the birthing process may be that important signal.
Blood-brain barrier
“We believe that the pressure of the birth canal during the second stage of labor, which is supposed to last 20 to 40 minutes, is an important signal that tells the foal to quit producing the sedative neurosteroids and ‘wake up,'” Madigan says.
The theory is supported by the fact that the maladjusted foal syndrome appears more frequently in horses that were delivered via cesarean section or experienced unusually rapid births, Madigan says. Perhaps those foals don’t experience significant physical pressure to trigger the change in neurosteroids.
Furthermore, researchers have found for the first time that sedative neurosteroids persist, and their levels often rise, in the bloodstream of foals born with symptoms of the maladjustment syndrome. These neurosteroids are known to be able to cross the blood-brain barrier and impact the central nervous system, acting on the same receptor as do sedatives and anesthetics.
They also have demonstrated that maladjustment symptoms can be brought on temporarily in normal, healthy foals by administering short infusions of a neurosteroid called allopregnanolone. When the neurosteroid levels drop, the foals return to their normal state.
Gentle ‘hug’ wakes foals up
Amazingly, the veterinary researchers have found that they can reduce maladjustment symptoms in foals by using several loops of a soft rope to gently squeeze the foal’s upper torso and mimic the pressure normally experienced in the birth canal. When pressure is applied with the rope, the foal lies down and appears to be asleep.
After 20 minutes—about the same time a foal would spend in the birth canal—the rope is loosened and the squeeze pressure released. In initial cases, the foals have responded well to the procedure and recovered, some rising to their feet within minutes and then bounding over to join the mare and nurse.
The researchers suspect that the pressure triggers biochemical changes in the central nervous system that are critical for transitioning the foal from a sleeplike state in the womb to wakefulness at birth.
In spite of the strong observational effects, a larger, controlled clinical trial of national and international scope is now needed to reproduce those observed results and provide a better understanding of the mechanisms at work in the foals.
Links to autism?
The early findings have compelling implications for the health of newborn foals, and have caused the researchers to also explore possible links to autism, which includes a group of complex brain-development disorders. While the symptoms vary, these disorders are generally marked by difficulties with social interactions, verbal and nonverbal communication, and repetitive behaviors.
“The concept that a disruption in the transition of fetal consciousness may be related to children with autism is intriguing,” said Pessah, noting that the behaviors seen in the maladjusted foal syndrome truly are reminiscent of those in some autistic children.
Some children with autism do outgrow autistic behaviors by the time they reach their teen years, Pessah says. Could this be a parallel to the recovery of the foals with the maladjustment syndrome?
[related]
A new group called the Comparative Neurology Research Group, consisting of veterinarians, physicians, epidemiologists, and basic-science researchers, has formed to pursue further studies in this area. Madigan is working with researchers at the Stanford University School of Medicine, exploring the mechanisms of post-birth transitions of consciousness related to neonatal care of infants.
Using data from the foal research, Pessah and Madigan are also working with environmental epidemiologist Irva Hertz-Picciotto at the MIND Institute to investigate neurosteroids in children with varying degrees of autism, ranging from some developmental delay to full-spectrum autism.
The researchers are exploring whether abnormal regulation of neurosteroids during the time around childbirth could be one of many factors that might contribute to autism and related neurodevelopmental disorders. A recent study has reported elevated levels of neurosteroids in children with autism spectrum disorder.
Researchers will next look to see whether there are alterations in blood levels of certain neurosteroids that may serve as a marker for the disorder. They caution, however, that the relationship right now is just a theory that remains to be validated or disproven.
Source: UC Davis
