Schizophrenia rather than Fragile-X and Retts Syndrome, as a Reference for ASD

You may, like me, have wondered why so much autism research seems to mention Fragile-X syndrome and Retts syndrome.  

Both Fragile-X and Retts are caused by the mutation of single genes, FMR1 and MECP2 respectively.  Autism can be caused by very many, seemingly unrelated things, both genetic and environmental.

When you look at it objectively, there is a much closer comparison for autism, it is schizophrenia.  

I know from the research I am reading that in fact autism and schizophrenia are intertwined and there is no boundary were one stops and the other starts.  Most likely some of the individual biological dysfunctions in autism are present in a greater/lesser degree in schizophrenia and vice versa.  This will be developed in later posts.

For those interested in learning more about schizophrenia here is a nice PowerPoint presentation.

https://files.itslearning.com/data/1512/469/SCHIZO%20PP.pptx

Here are some excerpts:-

·        A biological disorder of the brain which causes disturbances in thinking, speech, perception of reality, emotion (mood), and behavior.

·        Approximately 1% of the population develops schizophrenia during their lifetime.

·        Although schizophrenia affects men and women with equal frequency, the disorder often appears early in men (usually late teens), than women (generally late twenties/early thirties).

The most ASD-like sub-type is called disorganized schizophrenia; and it principal features are:-

•      Confusion and Incoherence

•      Severe deterioration of adaptive behavior

–     Lack of social skills

–     Poor personal hygiene & self-care

•      Behavior appears silly and/or child-like

•      Highly  inappropriate emotional responses

It is not hard to see the potential overlap between ASD and Disorganized Schizophrenia.

We even have a researcher suggesting a very similar strategy for Schizophrenia, to that I am proposing/developing for autism.

Phenotype of schizophrenia: a review and formulation

The discovery of the pathophysiology(ies) for schizophrenia is necessary to direct rational treatment directions for this brain disorder. Firm knowledge about this illness is limited to areas of phenomenology, clinical electrophysiology, and genetic risk; some aspects of dopamine pharmacology, cognitive symptoms, and risk genes are known. Basic questions remain about diagnostic heterogeneity, tissue neurochemistry, and in vivo brain function. It is an illness ripe for molecular characterization using a rational approach with a confirmatory strategy; drug discovery based on knowledge is the only way to advance fully effective treatments. This paper reviews the status of general knowledge in this area and proposes an approach to discovery, including identifying brain regions of dysfunction and subsequent localized, hypothesis-driven molecular screening.

For psychiatrists, the main difference between autism and schizophrenia seems to be when is the onset of symptoms.  Autism strikes at the age of two or three, whereas schizophrenia occurs much older.  Whether in fact some of the same biological mechanisms might be at work does not seem to be relevant to psychiatrists.  Not surprisingly, they have not made much progress treating either condition.

In the days before the autism was so widely diagnosed, there were many more cases of childhood schizophrenia reported, now it is very rarely diagnosed condition, it became autism.

I did look for some statistics that included autism and schizophrenia, but those clever psychiatrists seem to have separated them, so autism is with developmental disabilities and schizophrenia is not.

But I did find some interesting statistics about developmental disabilities.

When you look at the US statistics (1997 – 2008), based on parent-reported developmental disabilities.

Source:  http://pediatrics.aappublications.org/content/early/2011/05/19/peds.2010-2989.full.pdf+html

You can see that about 15% of kids have some kind of developmental disability.  Cases of autism increase from 0.2% to  0.7% over the ten years, but those with a learning disability is pretty flat at around 7% and mental retardation (MR) / intellectual disability is also pretty flat at 0.7%.

You also see that the incidence of seizures remains flat at about 0.7%.

According to the medical research, about 30% of people with autism will also have seizures; you would expect to see a seizure “epidemic’, if there had been an autism “epidemic”.  Whereas diagnosing autism is highly subjective, recognizing most types of seizure is not.

So clearly the numbers do not add up.  Perhaps now only 10% of people with autism have seizures?  Or perhaps only 30% of people with autism, really have it?   

The same is true with the incidence of mental retardation (intellectual disability) it remains flat at 0.7%.  According to the WHO, 50% of people with autism also have MR.  So, if there had been a big increase in new people with autism, you would expect an increase in MR.  If the level of MR remains flat it would seem that some people with MR have just been given an additional diagnosis of autism.  Either that, or the 50% figure is now much lower in the US, (which is what I expect is the reality).

With even the most basic figures not adding up, is it really surprising how little progress has been made in the hard part – actually finding treatments?

Autism has changed and now means entirely different things, to different people.  In particular, comparisons across countries are completely meaningless.

Schizophrenia

Schizophrenia has also changed and is now considered as a family or spectrum of disorders.

Like autism, nobody really knows what causes schizophrenia and most likely many things do, like autism.  There is no single gene, like with Fragile-X or Retts, and there is no cure.

When researchers compared the mixture of genetic dysfunctions in schizophrenia and autism, they found a clear overlap.  This is interesting and perhaps should not have come as a surprise.

In some ways Fragile-X and Retts are actually the opposite of autism.  For example in the case of Retts, the very important substance, Nerve Growth Factor (NGF), is almost at zero, whereas in autism levels tend to be elevated.

Just as we can learn from the comorbidities of autism, I think we can learn a thing or two from the existing research in Schizophrenia.  Indeed I already have.

MR

If anyone was seriously researching treating Mental Retardation (MR), in physically “normal” people, who have not suffered from a brain infection, toxic exposure, malnutrition or any kind of pre-natal or natal problem, we would have another great resource.  It would probably show that, in some cases, MR is caused by a partially-reversible imbalance in the actions of various neurotransmitters, ion channels, hormones etc.  Some of these imbalances will also exist in numerous cases of autism.

According to the well-known expert, Professor Howlin, only about 20% of people with ASD have an IQ in the normal range (i.e. above 70) and 50% have moderate or greater MR (i.e. IQ less than 50).  It would seem that the missing 30% must have mild MR (i.e. an IQ 50 to 70).

I suspect that the cognitive improvement found by treating some types of autism could be replicated in some cases of MR, without ASD.  If there were any clever therapies for treating MR, I would think they would likely be beneficial in autism.  In most countries, as many children have MR as have ASD, so it is strange nobody is looking how to treat it.  They assume the “defects” are hard-wired into the brain; I looks to me that some are not.

Clinical Trials

Even though ASD is a lifelong condition, nearly all the clinical trials are in children, and most often, in quite young children.  Assessing such people is doubly difficult.  Working with adults should be much easier and provide better quality data.

Other neurological conditions like schizophrenia and bi-polar disorder are regarded as adult conditions, so hopefully the quality of the research data is better.  We will see.

Plenty of adults have ASD and the ones with Asperger’s will have no difficulty articulating the effects of any intervention, so it is a pity they are rarely involved in research. 

   

Conclusion

On a happier note, I believe that if you can tune the autistic brain to its optimal performance, you will see a marked improvement in cognitive ability and, by implication, in measured IQ.  

I have no doubt that a well executed, intensive ABA program, over a few years, could also show a marked improvement in measured IQ, in many cases.  ABA is also a kind of retuning of the brain, but it has to be done right to be effective.

Biological tuning plus ABA should yield the best results.

As for schizophrenia, the biological "overlap" with autism does indeed exist. Two such areas are dysfunctional calcium channels and indeed the glutamate receptor mGluR5.  This will be developed later.

Long Term Bumetanide Use in Autism

This blog started life after I read about a clinical trial of the diuretic bumetanide to treat autism.  In the following 12 months the authors of that study, Ben-Ari and Lemmonier, have been busy building up their scientific case.  They published two further papers:-

 

 

Treating Fragile X syndrome with the diuretic bumetanide: a case report. 

We report that daily administration of the diuretic NKCC1 chloride co-transporter, bumetanide, reduces the severity of autism in a 10-year-old Fragile X boy using CARS, ADOS, ABC, RDEG and RRB before and after treatment. In keeping with extensive clinical use of this diuretic, the only side effect was a small hypokalaemia. A double-blind clinical trial is warranted to test the efficacy of bumetanide in FRX.

This single case report showed an improvement of the scores of each test used after 3 months of treatment. Double-blind clinical trials are warranted to test the efficacy of bumetanide in FRX.

 

Improving emotional face perception in autism with diuretic bumetanide: A proof-of-concept behavioral and functional brain imaging pilot study.

 

Clinical observations have shown that GABA-acting benzodiazepines exert  paradoxical excitatory effects in autism, suggesting elevated intracellular chloride (Cl-)i and excitatory action of GABA. In a previous double-blind randomized study, we have shown that the diuretic NKCC1 chloride importer  antagonist bumetanide, that decreases (Cl-)i and reinforces GABAergic  inhibition, reduces the severity of autism symptoms. Here, we report results from an open-label trial pilot study in which we used functional magnetic  esonance imaging and neuropsychological testing to determine the effects of 10 months bumetanide treatment in adolescents and young adults with autism. We show that bumetanide treatment improves emotion recognition and  enhances the activation of  brain regions involved in social and emotional perception during the perception of emotional faces. The improvement of emotion processing by bumetanide reinforces the usefulness of bumetanide as a promising treatment to improve social interactions in autism.

 

My experience after 12 months of Bumetanide

Bumetanide continues to have a positive effect on Monty, aged 10 with ASD, which I would summarize as a marked increase in awareness or “presence” or a lack of “absence” from the world.  Improved social interactions may have followed, but are secondary.

My own impression is that the effect peaks and then reduces somewhat.  This also appears to be the case with NAC and Atorvastatin.  I think the body is adjusting to the new treatments, via feedback loops.  This is inevitable, it is just a matter of human physiology.  If the above MRI study shows a long term change in brain function, then great.

I hope that my future therapies will be more disease changing, this does look to be possible.  Early signs are promising. 

 

My experience of 12 months blogging

My doctor mother asked me over Christmas how many people have been reading my blog and acting on it.  The answer is about 6,000 page views a month, but I suspect less than 10 people have even tried Bumetanide, nobody has tried Atorvastatin, and a few tens have tried NAC.

I think people are frightened of drugs.  Supplements are OK and any kind of unusual diet is great.

I think if I proposed a diet of baked beans, fried eggs and bacon I would have a much bigger following. Luckily that was not my objective.

With the advent of the internet, simple drugs like diuretics are as easy to buy as supplements like NAC; I doubt you are going to get into trouble for having an unauthorized diuretic in the bathroom cabinet.

Supplements are not subject to the same manufacturing standards as drugs and there are pretty strange things sold as “supplements”.

I will continue to develop my own therapy for classic early onset autism and when I finish, I will patent it and produce it as an orphan drug.  Orphan drugs are for rare diseases, where there is no other treatment.  They have less daunting regulatory requirements, meaning you do not need $25 million to develop them. In the EU you need a serious condition affecting fewer than 5 in 10,000 people; across the EU that equates to 250,000 people.  If you narrowly define my target autism phenotype, with biomarkers you end up within this limit.

Unfortunately, if you want to patent something, you have to keep it secret.  I did discuss all this with the venture capital firm that commercializes the intellectual property of my old university plus that of Cambridge, Oxford and UCL. The conclusion was to either give it to the world for free, or to commercialize it.  Giving it for free clearly has zero impact, so it has to be Plan B.

So the blog continues, but it will not contain all the clever stuff.

Next steps

I have also been busy in the last twelve months, having taken my inspiration from the Frenchmen, Ben-Ari and Lemmonier.  I have had my own “breakthroughs”, by applying the research and some imagination.

While you cannot totally cure genuine autism, you can go a long way, far further than I would have dared to believe possible.

You can treat the most difficult issues such as absence, anxiety, aggression and SIB.  Odd behavioural traits like obsessions and compulsions can be greatly reduced.  The combined effect is definitely a much happier person.

I think there is much more possible in areas like mood, confidence, creativity, sociability and indeed cognitive performance.

Bumetanide was a very important first step, but in itself it is far from a “cure”.  In combination with some other safe drugs, the result will indeed be remarkable.

The final element will be time itself.  The human brain does not come ready programmed; the first few years of childhood are used to establish full brain function.  In autism, during these important first few years the brain was running in “safe mode”, all sorts of important connections were never made and some were lost.  The brain does remain plastic throughout life and so it has the potential to make some of these missing connections.

The drug treatment has to deal with oxidative stress, neuro-inflammation, several ion channel/transporter dysfunctions and the tricky area of central hormonal hypofunction/dysfunction.

Note that not all people with autism respond to Bumetanide. Only a large clinical trial will show what percentage are responders.  In the same way, I expect only a minority of those diagnosed with ASD by current psychiatric measures will respond to my drug; but it would be possible to identify them based on biomarkers and case histories. 


 

It’s a Small World – IGF-1 and NNZ-2566 in Autism

You may or may not believe in fate, but some strange things have been happening related to Australia, growth hormones and TBI.

Last week I took Monty, aged 10 with ASD, to have his IGF-1 (insulin-like growth factor) measured.  At the time, this had nothing to do with autism, rather just what the Endocrinologist had requested.  Then I start doing my research on hormones and autism and found, surprisingly, there is an ongoing clinical trial in autism using IGF-1.  Then I start looking again at TBI (Traumatic Brain Injury), which I see as having much in common with ASD.  I looked for similarities in hormone disruptions found in TBI and ASD; I found there are many and they are mainly related to GH (growth hormone) and IGF-1.  The problem with IGF-1 therapy is that it is intravenous; I had told the Endocrinologist that I was not going to measure IGF-1, because I was not very keen on giving Monty intravenous drugs.  In the end, I did the test anyway and I am glad I did.

As I researched TBI, I saw a great deal of interest in using GH as a therapy and the US military is providing a great deal of funding to develop therapies.

Today the postman brings me my first post from Australia in several years.  It contains some children books for Monty (Thank you Lisa).

Now I come across NNZ-2566;  it is a synthetic analogue of a naturally occurring neurotropic peptide derived from IGF-1.   NNZ-2566 is being developed both in intravenous and oral formulations for a range of acute and chronic conditions including TBI, Fragile X and Retts syndrome.  NNZ-2566 exhibits a wide range of important effects including inhibiting neuroinflammation, normalizing the role of microglia and correcting deficits in synaptic function.  NNZ-2566 is being developed guess where? Australia, by Neuren Pharmaceuticals.

Just 10 days ago the company made the following announcement:-

Melbourne, Australia, 18 October 2013: Neuren Pharmaceuticals (ASX: NEU) announced today that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for Neuren’s programme to develop NNZ-2566 for Fragile X Syndrome. Fast Track designation is designed to expedite the development and review of important new medicines that are intended to treat serious diseases and meet unmet medical needs.

A different group of researchers are poised to begin clinical trials of IGF-1 in children with autism early next year. Because IGF-1 is already approved in the United States for use in children with short stature, the U.S. Food and Drug Administration is allowing the researchers to proceed directly to clinical trials for its use as an autism treatment.

What a lot of coincidences.

For those scientists among you, here are more details.

First of all it has been shown that in autism there are elevated levels of growth hormones.  Here is an American study.

Elevated levels of growth-related hormones in autism and autism spectrum disorder

 The Australians quote research from Finland that looks to me to contradict the above paper.  One difference is that the US researchers were testing blood and the Finns were testing spinal fluid.  What is clear is that in autism IGF-1 is not normal.

Neurotrophic Factors in the Pathogenesis of Rett Syndrome

Abstract

Rett syndrome is characterized by disruption of a period of vigorous brain growth with synapse development. Neurotrophic factors are important regulators of neuronal growth, differentiation, and survival during early brain development. The aims of this study were to study the role of neurotrophic factors in Rett syndrome, specifically whether Rett syndrome has abnormal levels of specific neurotrophic factors in serum and cerebrospinal fluid and whether the changes differ from other neuropediatric patients, for example, those with infantile autism. Four neurotrophic factors were measured: nerve growth factor, brain-derived neurotrophic factor, glial cell line—derived neurotrophic factor, and insulin-like growth factor 1 from the frozen cerebrospinal fluid and from serum (except glial cell line—derived neurotrophic factor) by enzyme-linked immunosorbent assay and cerebrospinal fluid glutamate and aspartate by high-performance liquid chromatography (HPLC) method in patients with Rett syndrome. Insulin-like growth factor 1 was measured from the cerebrospinal fluid of patients with infantile autism. We found low concentrations of cerebrospinal fluid nerve growth factor in patients with Rett syndrome compared with control patients. The serum levels and other cerebrospinal fluid neurotrophic factor levels of the patients did not differ from the controls. Patients with Rett syndrome had high cerebrospinal fluid glutamate levels. Patients with infantile autism had low cerebrospinal fluid insulin-like growth factor 1 levels. Nerve growth factor acts especially on cholinergic neurons of the basal forebrain, whereas insulin-like growth factor 1 acts on cerebellar neurons. In Rett syndrome, the forebrain is more severely affected than the other cortical areas. In autism, many studies show hippocampal or cerebellar pathology. Our findings are in agreement with the different morphologic and neurochemical findings (brain growth, affected brain areas, neurotransmitter metabolism) in the two syndromes. Impairment in dendritic development in Rett syndrome could be the consequence of cholinergic deficiency and of neurotrophic factor/glutamate imbalance. Cholinergic gene expression might be influenced by the Rett syndrome gene directly or via the neurotrophic factor system.

 Then we have research showing GH/IGF-1 has secondary functions beyond those in the text books.  Lots of nice words like neuroprotective, regenerative etc.

Role of the Growth Hormone/Insulin-Like GrowthFactor 1 Axis in Neurogenesis

Abstract

The growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis is not only involved in brain growth, development and myelination, but also in brain plasticity as indexed by neurogenesis. This may have links to various cognitive effects of GH and IGF-1. GH and IGF-1 affect the genesis of neurons, astrocytes, endothelial cells and oligodendrocytes. Specifically, IGF-1 increases progenitor cell proliferation and numbers of new neurons, oligodendrocytes, and blood vessels in the dentate gyrus of the hippocampus. In the adult cerebral cortex IGF-1 only affects oligodendrogenesis. Recently, GH therapy has also been shown to induce cell genesis in the adult brain. The profile of effects by GH therapy may be somewhat different than that of IGF-1. In addition, GH secretagogues (GHS) also have neuroprotective and cell regenerative effects per se in the brain. Finally, transgenic disruptions in GH signaling pathways affect neuron and astrocyte cell numbers during development and during adulthood. Altogether, data suggest that both exogenous and endogenous GH and/or IGF-1 may be used as agents to enhance cell genesis and neurogenesis in the adult brain. Theoretically these substances could be used to enhance recovery after brain injuries. However, further experiments with specific animal models for brain injuries are needed before clinical trials can be started. 

For those of you that like mice studies:

Growth factor improves autism symptoms in mice

Now back down under to let the Aussies make their case:

The Case for IGF-1 and IGF-1 (1-3) Glypromate in Autism

Courtesy of our friends “down under” you can read a presentation explaining the likely merits of both IGF-1 and its “terminal tripeptide” IGF-1 (1-3) as therapeutic agents in autism.  The clever Aussies have gone one better and produced NNZ-2566.  It is an analog of and IGF-1 (1-3).  This means it has that the molecule has been very slightly modified.  In this case this has been done to allow it to be orally available (i.e. not by injection) and to better cross the blood brain barrier (BBB). 

NNZ-2566 rationale for use in Autism Spectrum Disorders

Mount Sinai Hospital Clinical trial of IGF-1

Mount Sinai Hospital is a leading US teaching hospital in New York; they are carrying out a trial of IGF-1 in autism.  They are starting with a sub type with a genetic deficiency called SHANK3, but they will then look at the benefit in other types of ASD. 

http://clinicaltrials.gov/ct2/show/NCT01525901 

"In an important test of one of the first drugs to target core symptoms of autism, researchers at Mount Sinai School of Medicine are undertaking a pilot clinical trial to evaluate insulin-like growth factor (IGF-1) in children who have SHANK3 deficiency (also known as 22q13 Deletion Syndrome or Phelan-McDermid Syndrome), a known cause of autism spectrum disorder (ASD).

The seven-month study, which begins this month, will be conducted under the leadership of the Seaver Autism Center Clinical Director Alex Kolevzon, MD, and will utilize a double-blind, placebo-controlled crossover design in children ages 5 to 17 years old with SHANK3 deletions or mutations. Patients will receive three months of treatment with active medication or placebo, separated by a four-week washout period. Future trials are planned to explore the utility of IGF-1 in ASD without SHANK3 deficiency."

 

Conclusion

For a change, my conclusion is that further study is needed (by me).  Probably all the hormonal disruptions in autism need to be looked at together (serotonin, T3 etc) before any wild conclusions are drawn.


 

Statins for Neuroprotection in Autism - Part 2

I suggest you start by reading Part 1.  Click here for Part 1



Choice of Statin
 

Some statins are soluble in fats/lipids (lipophilic) and some are more soluble in water.  In order to cross the blood brain barrier (BBB) to reach the cerebellum and the Purkinje Cell Layer (PCL) a lipophilic statin will be required.  There is a choice of three: - atorvastatin, lovastatin, and simvastatin.  These are also among the most commonly prescribed for cholesterol reduction and so are widely available and inexpensive.

I chose atorvastatin.  Some statins are derived from fungi, but atorvastatin is synthetic.  Lovastatin and simvastatin are pro-drugs, whereas atorvastatin is already in an active form straight out of the box. Absorption of atorvastatin decreases when taken with food.  Due to its long half-life, atorvastatin can be administered at any time of day.

Atorvastatin is approved for use in children as young as 10 and in the US is prescribed to children as young as 5.

Atorvastatin, originally made by Pfizer under name Lipitor, is the best-selling drug in the history of the pharmaceutical industry.  It came off patent recently and so the price has collapsed to a very reasonable level.

In some countries the low dose forms are available over the counter, without a prescription.

 

More Related Research

The research effort into degenerative conditions like Alzheimer’s disease (AD) is far more prolific than into autism.  The closest research to my hypothesis that statins will “perk up the Purkinje cells” is this study:-

Atorvastatin and pitavastatin protect cerebellar Purkinje cells in AD model mice and preserve the cytokines MCP-1 and TNF-α.

  

Fragile X syndrome

Fragile X syndrome is a genetic syndrome that leads to autistic behaviours.  About 5% of the cases defined as autism are due to this genetic flaw.  It also results in certain physical differences, namely:-

• Large, protruding ears (one or both)
• Long face (vertical maxillary excess)
• High-arched palate (related to the above)
• Hyper extensible finger joints
• Hyper extensible ('Double-jointed') thumbs
• Flat feet
• Soft skin
• Hypotonia (low muscle tone)
• single palm crease (crease goes across entire palm)

 At MIT researchers have found that the statin Lovastatin “can correct Fragile X syndrome”.

 

I presume what is actually happening, is that in Fragile X there is also neuroinflammation and this has been reduced by the statin, rather than correcting the syndrome.

  

Retts Syndrome

Retts syndrome is another genetic disorder that causes regression and autism-like behaviours.  It affects mainly girls, because male fetuses with the disorder rarely survive to term.  The prognosis is not good.

Research is underway with statins and currently shows that statins improve symptoms of Rett syndrome in mice.

 

Statins and depression

A large study of patients with heart disease examined the difference between those on statins and those not.  Very interesting was the finding that those on statins had better mental health (i.e. less depression).

Statins: Mechanisms of neuroprotection

A very thorough presentation of the effect of statins and their possible mechanisms along with a review of their use in Alzheimer’s, Parkinson’s, Multiple Sclerosis and strokes, is in the excellent paper:-  Statins: Mechanisms of neuroprotection

 The anti-oxidant effect of statins

A study called The anti-oxidant effect of statins, looks very interesting, but only the abstract is freely available.  Here is the summary:-  

"A number of recent reports have shown that statins may also have important anti-inflammatory effects, in addition to their effects on plasma lipids. Since inflammation is closely linked to the production of reactive oxygen species (ROS), the molecular basis of the observed anti-inflammatory effects of statins may relate to their ability block the production and/or activity of ROS. In this review, we will discuss both the inhibition of ROS generation by statins, through interference with NAD(P)H oxidase expression and activity, and the actions of statins that serve to blunt the damaging effects of these radicals, including effects on antioxidant enzymes, lipid peroxidation, LDL cholesterol oxidation and nitric oxide synthase. These antioxidant effects of statins likely contribute to their clinical efficacy in treating cardiovascular disease as well as other chronic conditions associated with increased oxidative stress in humans."

 

Conclusion

 
Given the minimal side effects, that was more than enough evidence for me to start some primary research of my own. Step one was to try atorvastatin myself. 

My hypothesis is that atorvastatin will reduce autistic behaviours and that the mechanism is the reduction of neuroinflammation in the cerebellum and particularly in the Purkinje Cell Layer (PCL).  I believe that this will be valid regardless of the type of autism. 

The beneficial secondary effect will be reduction in LDL cholesterol, which is typically elevated in cases of autism.

 

Click here for  -  Statins Part 3