Who Gets Autism?

According to a major new report from Australia, social and family factors associated with autism are associated with a lower risk of intellectual disability - and vice versa. But why?

The paper is from Leonard et al and it's published in PLoS ONE, so it's open access if you want to take a peek. The authors used a database system in the state of Western Australia which allowed them to find out what happened to all of the babies born between 1984 and 1999 who were still alive as of 2005. There were 400,000 of them.

The records included information on children diagnosed with either an autism spectrum disorder (ASD), intellectual disability aka mental retardation (ID), or both. They decided to only look at singleton births i.e. not twins or triplets.

In total, 1,179 of the kids had a diagnosis of ASD. That's 0.3% or about 1 in 350, much lower than more recent estimates, but these more recent studies used very different methods. Just over 60% of these also had ID, which corresponds well to previous estimates.

There were about 4,500 cases of ID without ASD in the sample, a rate of just over 1%; the great majority of these (90%) had mild-to-moderate ID. They excluded an additional 800 kids with ID associated with a "known biomedical condition" like Down's Syndrome.

So what did they find? Well, a whole bunch, and it's all interesting. Bullet point time.

  • Between 1984 to 1999, rates of ID without ASD fell and rates of ASD rose, although there was a curious sudden fall in the rates of ASD without ID just before the end of the study. In 1984, "mild-moderate ID" without autism was by far the most common diagnosis, with 10 times the rate of anything else. By 1999, it was exactly level with ASD+ID, and ASD without ID was close behind. Here's the graph; note the logarithmic scale:

  • Boys had a much higher rate of autism than girls, especially when it came to autism without ID. This has been known for a long time.
  • Second- and third- born children had a higher rate of ID, and a lower rate of ASD, compared to firstborns.
  • Older mothers had children with more autism - both autism with and without ID, but the trend was bigger for autism with ID. But they had less ID. For fathers, the trend was the same and the effect was even bigger. Older parents are more likely to have autistic children but less likely to have kids with ID.

  • Richer parents had a strongly reduced liklihood of ID. Rates of ASD with ID were completely flat, but rates of ASD without ID were raised in the richer groups, though it was not linear (the middle groups were highest. - and effect was small.)
To summarize: the risk factors for autism were in most cases the exact opposite of those for ID. The more “advantaged” parental traits like being richer, and being older, were associated with more autism, but less ID. And as time went on, diagnosed rates of ASD rose while rates of ID fell (though only slightly for severe ID).

Why is this? The simplest explanation would be that there are many children out there for whom it's not easy to determine whether they have ASD or ID. Which diagnosis any such child gets would then depend on cultural and sociological factors - broadly speaking, whether clinicians are willing to give (and parents willing to accept) one or the other.

The authors note that autism has become a less stigmatized condition in Australia recently. Nowdays, they say, a diagnosis of ASD may be preferable to a diagnosis of "just" "plain old" ID, in terms of access to financial support amongst other things. However, it is also harder to get a diagnosis of ASD, as it requires you to go through a more extensive and complex series of assessments.

Clearly some parents will be better able to achieve this than others. In other countries, like South Korea, autism is still one of the most stigmatized conditions of childhood, and we'd expect that there, the trend would be reversed.

The authors also note the theory that autism rates are rising because of some kind of environmental toxin causing brain damage, like mercury or vaccinations. However, as they point out, this would probably cause more of all neurological/behavioural disorders, including ID; at the least it wouldn't reduce the rates of any.

These data clearly show that rates of ID fell almost exactly in parallel with rates of ASD rising, in Western Australia over this 15 year period. What will the vaccine-vexed folks over at Age of Autism make of this study, one wonders?

ResearchBlogging.orgLeonard H, Glasson E, Nassar N, Whitehouse A, Bebbington A, Bourke J, Jacoby P, Dixon G, Malacova E, Bower C, & Stanley F (2011). Autism and intellectual disability are differentially related to sociodemographic background at birth. PloS one, 6 (3) PMID: 21479223

Peripheral Nervous System (PNS)

The peripheral nervous system connects the central nervous system with the rest of the body. All motor, sensory and autonomic nerve cells and fibers outside the CNS are generally considered part of the PNS. Specifically, the PNS comprises the ventral (motor) nerve roots, dorsal (sensory) nerve roots, spinal ganglia, and spinal and peripheral nerves, and their endings, as well as a major portion of the autonomic nervous system (sympathetic trunk). The first two cranial nerves (the olfactory and optic
nerves) belong to the CNS, but the remainder belong to the PNS.

Peripheral nerves may be purely motor or sensory but are usually mixed, containing variable fractions of motor, sensory, and autonomic nerve fibers (axons). A peripheral nerve is made up of multiple bundles of axons, called fascicles, each of which is covered by a connective tissue sheath (perineurium). The connective tissue lying between axons within a fascicle is called endoneurium, and that between fascicles is called epineurium. Fascicles contain myelinated and unmyelinated axons, endoneurium, and capillaries. Individual axons are surrounded by supportive cells called Schwann cells. A single Schwann cell surrounds several axons of unmyelinated type. Tight winding of the Schwann cell membrane around the axon produces the myelin sheath that covers myelinated axons. The Schwann cells of a myelinated axon are spaced a small distance from one another; the intervals between them are called nodes of Ranvier. The nerve conduction velocity increases with the thickness of the myelin sheath. The specialized contact zone between a motor nerve fiber and the muscle it supplies is called the neuromuscular junction or motor end plate. Impulses arising in the sensory receptors of the skin, fascia, muscles, joints, internal organs, and other parts
of the body travel centrally through the sensory (afferent) nerve fibers. These fibers have their cell bodies in the dorsal root ganglia (pseudounipolar cells) and reach the spinal cord by way of the dorsal roots.

Which regions of the brain lack a significant blood-brain barrier?

Brain regions that lack a significant blood-brain barrier tend to be midline structures located
near ventricular spaces. They include the area postrema, median eminence of the
hypothalamus, and neurohypophysis.

Blood-brain Barrier Components?

The blood-brain barrier is not a single barrier, but a composite of many systems that act to
control the entry of substances from the blood to the brain:
1. Capillary endothelial cells linked by tight junctions and expressing specialized uptake
systems for particular metabolic substrates (e.g., glucose, amino acids)
2. A prominent basement membrane between endothelia and adjacent cells
3. Pericapillary astrocytes with end-feet adjacent to capillaries
A similar system exists for the choroidal epithelium (blood-cerebrospinal fluid [CSF]

Understanding the molecular and cellular mechanisms, it's so important, why?

1. Enhancement of diagnostic possibilities and treatment options
2. More appropriate selection of diagnostic tests and interpretation of test results
3. Prediction of drug side effects and interactions
4. Selection of optimal drug regimens
5. Aid to critical review of novel concepts and therapies
6. Understanding of the rationale for current clinical trials
7. Provision of a background for communicating information to patients and families

First Fish, Now Cheese, Get Scanned

Here at Neuroskeptic we have closely followed the development of fMRI scanning on fish.

But a new study has taken it to the next level by scanning... some cheese.

OK, this is not quite true. The study used NMR spectroscopy to analyze the chemistry of some cheeses, in order to measure the effects of different kinds of probiotic bacteria on the composition of the cheese. NMR is the same technology as MRI, and indeed you can use an MRI scanner to gather NMR spectra.

In fact, NMR is Nuclear Magnetic Resonance and MRI is Magnetic Resonance Imaging; it was originally called NMRI, but they dropped the "N" because people didn't like the idea of being scanned by a "nuclear" machine. However, this study didn't actually involve putting cheese into an MRI scanner.

But the important point is that they could have done it by doing that. And if you did that, what with the salmon and now the cheese, you could get a nice MRI-based meal going. All we need is for someone to scan some vegetables, some herbs, and a slice of lemon, and we'd have a delicious dataset. Mmm.

How to cook it? Well, it's actually possible to heat stuff up with an MRI scanner. When scanning people, you set it up to make sure this doesn't happen, but the average fMRI experiment still causes mild heating. It's unavoidable.

I'm not sure what the maximum possible heating effect of an average MRI scanner would be. I doubt anyone has gone out of their way to try and maximize it, but maybe someone ought to look into it. Think of the possibilites.

You've just finished a hard day's scanning and you're really hungry, but the microwave at the MRI building is broken. Not to worry! Just pop your fillet of salmon in probiotic cheese sauce in the magnet, and scan it 'till it's done. You could inspect the images and the chemical composition of the meal before you eat it, to make sure it's just right.

Just make sure you don't use a steel saucepan...

ResearchBlogging.orgRodrigues D, Santos CH, Rocha-Santos TA, Gomes AM, Goodfellow BJ, & Freitas AC (2011). Metabolic Profiling of Potential Probiotic or Synbiotic Cheeses by Nuclear Magnetic Resonance (NMR) Spectroscopy. Journal of agricultural and food chemistry PMID: 21443163

BBC: Something Happened, For Some Reason

According to the BBC, the British recession and spending cuts are making us all depressed.

They found that between 2006 and 2010, prescriptions for SSRI antidepressants rose by 43%. They attribute this to a rise in the rates of depression caused by the financial crisis. OK there are a few caveats, but this is the clear message of an article titled Money woes 'linked to rise in depression'. To get this data they used the Freedom of Information Act.

What they don't do is to provide any of the raw data. So we just have to take their word for it. Maybe someone ought to use the Freedom of Information Act to make them tell us? This is important, because while I'll take the BBC's word about the SSRI rise of 43%, they also say that rates of other antidepressants rose - but they don't say which ones, by how much, or anything else. They don't say how many fell, or stayed flat.

Given which it's impossible to know what to make of this. Here are some alternative explanations:

  • This just represents the continuation of the well-known trend, seen in the USA and Europe as well as the UK, for increasing antidepressant use. This is my personal best guess and Ben Goldacre points out that rates rose 36% during the boom years of 2000-2005.
  • Depression has not got more common, it's just that it's more likely to be treated. This overlaps with the first theory. Support for this comes from the fact that suicide rates haven't risen - at least not by anywhere near 40%.
  • Mental illness is no more likely to be treated, but it's more likely to be treated with antidepressants, as opposed to other drugs. There was, and is, a move to get people off drugs like benzodiazepines, and onto antidepressants. However I suspect this process is largely complete now.
  • Total antidepressant use isn't rising but SSRI use is because doctors increasingly prescribe SSRIs over opposed to other drugs. This was another Ben Goldacre suggestion and it is surely a factor although again, I suspect that this process was largely complete by 2007.
  • People are more likely to be taking multiple different antidepressants, which would manifest as a rise in prescriptions, even if the total number of users stayed constant. Add-on treatment with mirtazapine and others is becoming more popular.
  • People are staying on antidepressants for longer meaning more prescriptions. This might not even mean that they're staying ill for longer, it might just mean that doctors are getting better at convincing people to keep taking them by e.g. prescribing drugs with milder side effects, or by referring people for psychotherapy which could increase use by keeping people "in the system" and taking their medication. This is very likely. I previously blogged about a paper showing that in 1993 to 2005, antidepressant prescriptions rose although rates of depression fell, because of a small rise in the number of people taking them for very long periods.
  • Mental illness rates are rising, but it's not depression: it's anxiety, or something else. Entirely plausible since we know that many people taking antidepressants, in the USA, have no diagnosable depression and even no diagnosable psychiatric disorder at all.
  • People are relying on the NHS to prescribe them drugs, as opposed to private doctors, because they can't afford to go private. Private medicine in the UK is only a small sector so this is unlikely to account for much but it's the kind of thing you need to think about.
  • Rates of depression have risen, but it's nothing to do with the economy, it's something else which happened between 2007 and 2010: the Premiership of Gordon Brown? The assassination of Benazir Bhutto? The discovery of a 2,100 year old Japanese melon?
Personally, my money's on the melon.

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