Autism spectrum disorders (ASD) are defined by disruption of normal socialization, communication and behavior. There seems to be predisposing genetics, but this area is poorly understood. Numerous studies indicate that development of the brain before and after birth is sensitive to immunological stress and in some combination of disruption can result in ASD. The affected areas of the brain appear to remain intact, as revealed by return of some normal function during fevers. Recent research identifies the locus coeruleus (LC) portion of the brain as pivotal in ASD behavior disruption and fever response.
Fever Reduces ASD Symptoms
There are numerous anecdotal observations by parents that symptoms of ASD abate during infection-related fevers. A detailed study published in Pediatrics, comparing behavior changes associated with fevers in children with and without ASD, provided evidence that fever normalizes behavior in children with ASD. This effect was notable for irritability, hyperactivity, and inappropriate speech. In each case, the onset of fever initiated a window of more normal behavior that continued temporarily after the fever abated.
Locus Coeruleus is Associated with Fever
The region of the brain called the locus coeruleus (ceruleus, blue spot) has been identified as being involved in control of fever in response to infections. Researchers have shown that if the nerves leading from LC are cut, then the fever response to bacteria does not occur. Similarly, functional connections between the LC and the rest of the brain are required for fever to be initiated after interleukin-1, an inflammatory cytokine, is experimentally elevated in the blood stream.
Locus Coeruleus and ASD
The LC is one of the most complex regions of the brain with numerous input from and output connections to other parts of the brain. It is also the brain’s major source of norepenephrine, involved in the fight-or-flight, activation response. LC has been implicated in numerous psychiatric conditions including post-traumatic stress disorders, neurodegenerative diseases and depression. It is the complexity and vulnerability of the LC that has drawn researchers’ attention in ASD. The unusual complexity of the LC makes it particularly vulnerable to immunological stress of inflammation that has been identified prenatally (particularly mid gestation) and postnatally as contributing to ASD. This is also consistent with the reported prevention of ASD by omega-3 oils taken prenatally.
Prevention and Treatment of ASD May Target the LC
Protection of the developing brain has been an ongoing aspect of ASD prevention. Healthy diets rich in omega-3 fish oils (supplements as high as 3 grams/day of DHA/EPA have been shown to be safe) are recommended to minimize immunological/inflammatory stress during pregnancy. Breastfeeding women are also encouraged to supplement their diets to supply needed anti-inflammatory fatty acids to their babies. The impact of fever on ASD behavior is encouraging evidence that many functional neural networks are present in an underutilized state. Fever is probably altering the signaling in the LC. Drugs that have a similar impact and normalize ASD behavior are now being sought. Long chain, omega-3 fish oil treatmen for ASD also shows promise.
references:
Curran LK, Newschaffer CJ, Lee LC, Crawford SO, Johnston MV, Zimmerman AW. 2007. Behaviors associated with fever in children with autism spectrum disorders. Pediatrics. 120(6):e1386-92.
Mehler MF, Purpura DP. 2008. Autism, fever, epigenetics and the locus coeruleus. doi:10.1016/J. Brain Res Rev. 2008.11.001.
Amminger GP, Berger GE, Schäfer MR, Klier C, Friedrich MH, Feucht M. 2007. Omega-3 fatty acids supplementation in children with autism: a double-blind randomized, placebo-controlled pilot study. Biol Psychiatry. 61(4):551-3.
 |
