Showing posts with label CRP. Show all posts
Showing posts with label CRP. Show all posts

Wednesday 8 October 2014

Intermittent Explosive Disorder (IED) + Autism

An altogether different kind of IED, although you may not always feel so.

Many people think that childhood psychiatric disorders, including autism, are grossly over-diagnosed in the US.

This did spring to mind when I came across a reference to “intermittent explosive disorder” and autism.

Before we get into that, I received an interesting graphical presentation of ADHD in the US, from a company called Healthline; they want me to give a link on my post on Clonidine.  It shows many things including how ADHD diagnosis varies wildly by State, just as the CDC’s autism data does.  The difference is remarkable. I don’t think anybody really believes that ADHD is 3 times more prevalent in Kentucky than in Nevada.  It just shows how inconsistent the diagnosis is; perhaps you could correlate the diagnosis with the medical school attended by the doctor/psychiatrist?

Back to Intermittent Explosive Disorder

Intermittent explosive disorder (IED) is a behavioral disorder characterized by explosive outbursts of anger, often to the point of rage, that are disproportionate to the situation at hand.
This is pretty tame stuff to many carers of anyone with autism.  So I thought it odd that anyone bothered to diagnose autism + IED.

The question is usually where the IED is directed, to the carer or to self (Self Injurious Behavior).

So IED is a normal part of autism, but it can be treated, without recourse to the drugs psychiatrists use.  They often cause further problems.

I was curious to find out what the research says about IED in other people.  Rather surprisingly, or maybe not, the mechanism turns out to be the same.

IED in Autism

Regular readers will recall the posts all about inflammatory agents (cytokine IL-6 and histamine) that turned out to trigger the summertime raging in Monty, aged 11 with ASD.

Using Verapamil to stabilize the mast cells and so lower the level of histamine and IL-6, I made the raging and aggression go away.  It really does work.

IED in Everyone Else

"The researchers measured the inflammatory markers CRP (C Reactive Protein) and IL-6 levels in 197 physically healthy volunteer subjects. Sixty-nine of those subjects had been diagnosed with IED, 61 had been diagnosed with psychiatric disorders not involving aggression, and 67 had no psychiatric disorder.

Both CRP and IL-6 levels were higher, on average, in subjects with IED, compared to either psychiatric or normal controls. Average CRP levels, for example, were twice as high for those with IED as for normal healthy volunteers. Both markers were particularly elevated in subjects who had the most extensive histories of aggressive behaviors. Each marker independently correlated with aggression, the authors note, suggesting that "both have unique relations with aggression."

Overall, the findings reported in this new paper suggest that "medications that reduce inflammation may also drive down aggression," Coccaro said. Anti-inflammatories such as Celebrex, or even aspirin, might make a difference for those with IED. Since available treatments bring less than 50 percent of patients into remission, the authors wrote, "additional strategies for the examination and intervention of human impulsive aggression are needed."

Pass the NAC, please

Not surprisingly people with IED also tend to suffer from oxidative stress.

Animal and clinical studies suggest a link between inflammation and oxidative stress. Because oxidative stress is an inherent part of inflammation, and inflammation is associated with behavioral aggression in lower mammals and humans, we hypothesized that markers of oxidative stress would be related to aggression in human subjects. In this case-control study, markers of oxidative stress and aggression were assessed in human subjects with histories of recurrent, problematic, impulsive aggressive behavior and in nonaggressive comparator subjects.
These data suggest a positive relationship between plasma markers of oxidative stress and aggression in human subjects. This finding adds to the complex picture of the central neuromodulatory role of aggression in human subjects.

I had one reader tell me that the most noticeable effect of the antioxidant NAC on her son with autism, was that he stopped biting her.  One less IED to defuse in her house.

ABA is also a potent tool to understand the underlying cause of aggression and SIB; but if you suffer from neuro-inflammation and oxidative stress, even ABA can do with a little extra help.

Wednesday 15 May 2013

By Jupiter! - Satins Part 3

Makes more sense if you have read:-
Statins Part 1
Statins Part 2

For most of you Jupiter is the fifth planet from the Sun, or maybe the largest planet in the Solar System.  To a young boy like Monty, Jupiter is a red fire engine, normally driven by Fireman Sam.

If you are a cardiologist you will have heard of the JUPITER trial. (Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin trial)

It was a huge study looking into the possible benefits of giving statins to older people with low cholesterol.  All the 17,802 subjects had elevated levels of high-sensitivity C-reactive protein (CRP) levels, which is a marker for cardiac (and neuro) inflammation.  Half were given 20mg of a statin and the other half had a placebo.  The study measured their cholesterol, CRP levels and whether they later had a cardiac incident.  The group with the statin lowered their already okay LDL and triglycerides level and also lowered their CRP level by a thumping 37%.

At the time of study termination (median follow up, 1.9 years; maximal follow-up, 5.0 years), 142 first major cardiovascular events had occurred in the statin group, as compared with 251 in the placebo group.

This was interpreted by the authors as evidence that even older people without elevated cholesterol could benefit from statins to reduce their risk of cardiovascular events.


JUPITER and autism

What JUPITER tells me is that statins were highly effective at reducing inflammation as measured by CRP.

Autism and CRP

Now we just need some data on the level of CRP in Autism.  Thanks to those nice people in Iran we have a study called: - The complementary role of high sensitivity C-reactive protein in the diagnosis and severity assessment of autism.

 They concluded:-

► Inflammatory process can play key role in the pathophysiology of autism.
► Higher levels of hs-CRP are detected in autistic children.
► A correlation exists between hs-CRP level and autism severity.
► Hs-CRP can be considered a complementary diagnostic test for autism.
►These findings affirm the role of inflammation in autism.

I guess because Iran is public enemy number two, nobody took much note of this study, except Paul Whiteley of course.
Autism & Statins

So it looks pretty likely that statins will reduce CRP in autistic subjects and if statins can do this, they will reduce both the neuroinflammation and, by inference, the severity of autistic behaviours.

Peter Research

While in the Astra Zeneca-funded JUPITER study there were 17,802 subjects and five years of research; here in the Peter Research Institute we have one subject and one week of research.

As with my Bumetanide research, I am shocked by the almost immediate effect of the drug.  In terms of lowering cholesterol, statins are supposed to take two weeks to reach full effect.  In terms of reducing neuroinflammation the effect appears to be much faster – very encouraging but, to be honest, quite unexpected.  

Back to Cholesterol & Autism

The important thing is that statins appear to reduce autistic behaviours, at least in my subject; it would however also be nice to fully understand why.  The research shows the presence of dyslipidemia (abnormal amounts of lipids) in boys with autism.

The findings were: - LDL normal, HDL low, Triglycerides high, Total cholesterol normal.  The current benchmark used is that Total Cholesterol divided by HDL should be less than 4.5.  With low HDL and high triglycerides, this could put many autistic subjects in the zone of elevated risk.

Also, be aware of the very rare condition called Smith-Lemli-Opitz Syndrome (SLOS), caused by low levels of cholesterol;  it is explained in this open-access paper:-

In one of the studies I read that CRP always drops before the fall in cholesterol.  This would imply that in the case of ASD, the cholesterol issue is just a consequence; it is the precursors that actually matter.  At least to me, that makes a lot of sense.

In case you missed the prequels:

Statins Part 1
Statins Part 2

and now there is Part 4