What, When and Where of Autism – Critical Periods and Sensitive Periods

When time is of the essence

All kinds of dysfunctions may appear in autistic brains, which in itself make it a highly complex condition. There is also the when and where aspects of these dysfunctions, which often gets overlooked, or lost in oversimplification.

This then has to fit into the concept of critical periods, that I introduced in an earlier post. 

Critical Periods in the Biology of Autism – Not to miss the Boat

Critical periods are times during the brain’s development when it is particularly vulnerable to any disturbance, for example an excitatory/inhibitory imbalance.

This then leads to another related concept which is that of sensitive periods; these are periods when the person should be responsive to particular therapy.

Sensitive periods are very important to be understood by those planning clinical trials, because a therapy may indeed be effective only when given within a specific time window. During this time the person is sensitive to the therapy, but they will not be a responder after the time window has passed.

I am pleased to say that more research is beginning to consider the when aspect and not just the what aspect of biological dysfunction in autism.

The where aspect reflects the fact that in one part of the brain there might be, say, NMDA hypofunction, while in another part the opposite is present, NMDA hyperfunction.  Since most therapies come as pills you swallow, you cannot treat one part of the brain for one problem and another part of the brain for the opposite problem. There is currently no way around this issue, you just have to do what is best for the brain overall. In practical terms it means you may make one problem better, but create a new one. 

Earlier treatment could help reverse autistic-like behavior in tuberous sclerosis.  Scientists find a sensitive period for reversing social deficits  

New research in a mouse model suggests that the drug rapamycin can reverse autism-like social deficits -- but only if given early. The study is the first to shed light on the crucial timing of therapy to improve social impairments in a condition associated with autism spectrum disorder. Its findings could help inform future clinical trials in children with tuberous sclerosis complex. 

Full Paper:

Sensitive Periods for Cerebellar-Mediated Autistic-like Behaviors

  

Mefenamic Acid

I have mentioned mefenamic acid (Ponstan) in several posts. It is the only human autism therapy currently in development that has a treatment window.  It is suggested that the sensitive period to take this drug is the second year of life, to avoid severe non-verbal autism. 

Conclusion

The good news is that we have seen time and again that it is never too late to treat autism. Clearly the earlier you do start, the more extensive the long term benefit should be. So once you realize that intervention is possible, best not to delay.

When autism  is of a single gene origin, there really should eventually be scope to make some kind of permanent fix, if you can intervene very early and so still during that intervention’s sensitive period.  This might involve something very clever like gene editing, which you cannot do at home, or it might be just some drug therapy, like Rapamycin in TSC1 as in the above study.