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Tuesday, 14 January 2020

The Role of Nurture over Genetics in Autism



Children with deprived childhoods become adults with smaller brains

Autism is not just about genetics and environmental factors; the potential of nurture should not be overlooked.

Today’s post was prompted by another follow-on study quantifying the benefit of nurture in early childhood.

In the past I did look in depth at the long running US study called the Bucharest Early Intervention Project (BEIP). A similar study is the English and Romanian Adoptees (ERA) study.  They are relevant to this autism blog because they quantify the benefit of nurture in very early childhood and more importantly the lack of nurture.

Quantifying the Benefits of Stimulation over Neglect in Early Childhood


You may wonder why all these studies relate to Romania. Under the Communist dictator Nicolae Ceauşescu, contraception and abortion were forbidden, because he wanted population growth. Then in 1982 he decided that foreign debt is bad and must be paid off urgently; much of the country's economic output was redirected in order to repay foreign debt.  This caused a great increase in poverty, meaning families could not feed their children and so many handed babies over to orphanages which did not have capacity to take them.  As a result conditions in Romanian orphanages became very bad and dire stories later emerged in Western media.

After the fall of communism in 1989 there were many foreign adoptions, but many of those children did not develop normally in their new homelands. This prompted several scientific investigations.

Severe autism – a case of self-exclusion from nurture

Babies and very young children with severe autism often “self-exclude” from nurture; they appear lost in their own world.  The end result is a bad situation made worse.

Whereas typical babies and tiny children are constantly seeking attention, stimulation and interaction from all around them, even complete strangers just passing by, severely autistic babies completely miss out.

We saw in a mouse study how “forced-inclusion” is beneficial. The autistic mouse pup was reared among typical mice fared much better than the autistic mouse pup reared among autistic mice.  Social interaction increased myelination.

Improving Myelination through Social Interaction and more on Clemastine



Lost time before diagnosis

In many countries there can be long delays obtaining an autism diagnosis and some pediatricians suggest a wait and see approach (“some boys are late talkers … just wait”, etc). It looks like immediate action should be recommended in the case of any developmental delay, regardless of diagnosis.


Genetic non-verbal

As more and more people seek a genetic diagnosis, there is a risk that genetic observations become self-fulfilling.  Some single gene dysfunctions are in indeed associated with the person being unable to speak, but I do recall one physician highlighting the case of her patient who struggled over years to learn to talk, and was later tested by WES to reveal the presence of a “non-verbal” genetic dysfunction.  Had the parents known about this genetic disorder; would they have struggled so relentlessly to encourage their child to speak? Probably not.

Genetic dysfunctions are best viewed as probabilities not certainties.

Very many conditions are in fact polygenic, a combination of multiple genes determines the outcome.  This is why some parents of children with autism may share the same single gene dysfunction, but not be affected by it.  They wonder "why not me?"


The English and Romanian Adoptees (ERA) study

In the study below we see that deprivation early in life has consequences measurable in adulthood and that the longer the deprivation (lack of nurture) the greater the effect.  In this study they measure the volume of the brain and the assumption is a bigger brain is a better brain.

In autism, a bigger brain is not a better brain, because it is an overgrown brain that developed too quickly and not quite as it should.

The overall point though remains valid; increased nurture in early life produces life-long benefits.




In the English and Romanian Adoptees (ERA) study, adoptees entered the institutions in the first few weeks of life and then, spent between 2 wk and 43 mo living there before being adopted into families in the United Kingdom that provided mostly nurturing environments.

Early childhood deprivation is associated with higher rates of neurodevelopmental and mental disorders in adulthood. The impact of childhood deprivation on the adult brain and the extent to which structural changes underpin these effects are currently unknown. To investigate these questions, we utilized MRI data collected from young adults who were exposed to severe deprivation in early childhood in the Romanian orphanages of the Ceaușescu era and then, subsequently adopted by UK families; 67 Romanian adoptees (with between 3 and 41 mo of deprivation) were compared with 21 nondeprived UK adoptees. Romanian adoptees had substantially smaller total brain volumes (TBVs) than nondeprived adoptees (8.6% reduction), and TBV was strongly negatively associated with deprivation duration. This effect persisted after covarying for potential environmental and genetic confounds. In whole-brain analyses, deprived adoptees showed lower right inferior frontal surface area and volume but greater right inferior temporal lobe thickness, surface area, and volume than the nondeprived adoptees. Right medial prefrontal volume and surface area were positively associated with deprivation duration. No deprivation-related effects were observed in limbic regions. Global reductions in TBV statistically mediated the observed relationship between institutionalization and both lower intelligence quotient (IQ) and higher levels of attention deficit/hyperactivity disorder symptoms. The deprivation-related increase in right inferior temporal volume seemed to be compensatory, as it was associated with lower levels of attention deficit/hyperactivity disorder symptoms. We provide compelling evidence that time-limited severe deprivation in the first years of life is related to alterations in adult brain structure, despite extended enrichment in adoptive homes in the intervening years.









Conclusion

Extreme lack of nurture was shown by the US researchers in the Bucharest Early Intervention Project (BEIP) to lead to life-long disorders including autism, something that got Kanner into trouble for, when he suggested it.

Nurture is the simplest way to improve brain development and has most impact in very early childhood.

It would seem that those starting life with neurological dysfunctions need intense nurture, even when they appear to show no desire for it. This nurture is probably most effective in the years before any medical diagnosis.

Very early intervention programs are clearly a form of intense nurture, but you do not need a big budget to provide intense nurture, just a lot of someone’s time and effort.

Most very young children who will be diagnosed with autism often self-exclude themselves from the very nurture they need.

Genetics certainly can stack the odds against someone, but the power of nurture should not be underestimated.






1 comment:

  1. Speaking of the genetics front there is some new research suggesting RAS proteins might be very important in the long-term storage of memory:

    Press Release:

    https://www.sciencedaily.com/releases/2020/01/200113153330.htm

    Paper:

    https://www.pnas.org/content/early/2020/01/09/1819925117

    You have discussed RASopathies quite extensively on this blog, so I thought this might be of interest since in autism you seem to have both the situation of very poor learning where short-term learned gains don't stick (i.e. poor procedural memory), as well as the other extreme where some people with autism have much higher than average recall when it comes to long-term memories.

    This study was in fruit flies, but it likely applies in a related fashion in vertebrates as well. The researchers also speculate that dopamine buildup is what triggers the RAS-RAF pathway which causes intermediate-term memories to be converted into long-term memories.

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