Friday, 4 March 2016

Cognitive Impairment in Schizophrenia, Bipolar & Autism

Neurological/neuropsychiatric disorders are often poorly described and poorly treated, but adult-onset conditions have historically been taken much more seriously and so the research is more advanced .  I find myself quite often looking at research on schizophrenia and bipolar; many of the same genes and metabolic dysfunctions common in autism show up in those conditions.

Many people really dislike the term Mental Retardation (MR), which is actually a very accurate descriptive term, meaning that someone is cognitively behind their peers.  Most lay people have no idea what Intellectual Disability (ID) means.

It is interesting that about 90% of people with schizophrenia and 50% of people with bipolar are cognitively behind their peers.  I suspect the figure for autism would also be about 90%, if someone measured it.  Most people with Asperger’s are not top of the class.

Only in extreme cases of being cognitively behind their peers, when their IQ is less than 70, does a person get diagnosed with MR/ID.

So the clinical diagnosis of MR/ID is just an arbitrary cut-off point.  The idea that if IQ is greater than 70 there is no cognitive deficit is entirely flawed.

It seems than in autism, as in schizophrenia and bipolar we should assume that cognitive dysfunction is present; the only question is how much and what to do about it.

Having treated the cognitive dysfunction(s), the person is then in a better place to compensate for the other dysfunctions they might have.

Even though the psychiatrists and psychologists will tell you that autism is all about the triad of impairments, I think they are missing the most important element, which is cognitive dysfunction.

As people with autism age, many find their symptoms associated with the above “triad of impairments” mellow.  The substantial minority who experience untreated flare-ups driven by inflammation caused by things like allergy, GI problems and even juvenile arthritis may not be so lucky.

I imagine that cognitive function in adulthood remains at the level it reached as a teenager.

Cognitive Function as the Therapeutic Target

Since many children with autism do eventually overcome many of their challenges in childhood, perhaps cognitive function really should be given a higher priority in treatment and research.

Many caregivers and educators are mainly focused on minimizing bad/disruptive behaviors (and bruises) rather than the emergence of good behaviors and learning.  This is sad but true.

As the child matures, in many cases these bad/disruptive behaviors may fade without any clever interventions.

So an intervention that stops stereotypy in a toddler, which was blocking learning, may have very much less impact in an adolescent.  Or at least the impact may be much less obvious.

I remember reading about a parent with two children with Fragile-X who was very upset when the Arbaclofen trials were halted, since her kids had responded well.  But two years later in another article it was clear that things were going fine without Arbaclofen.  The son whose violence towards his mother had been controlled by Arbaclofen, was no longer aggressive.  He continued to suffer cognitively, being a male with Fragile-X, the sister was much less affected  (females with fragile X syndrome have two X chromosomes and only one of the chromosomes usually have an abnormal gene, so usually females are less affected).   

The advantage of using cognitive function as a target is that it is much easier to measure than subjective behavioral deficits.  For the majority of people it is likely to be the most important factor in their future success and well-being.

In the substantial minority of cases where there are seizures and/or factors causing autism flare-ups, the behavioral deficits may remain undiminished into adulthood.  These people would also benefit from maximized cognitive function.

Cognitive Deficit in Schizophrenia & Bipolar (BPD)

To most lay people schizophrenia is characterized by abnormal social behavior and failure to recognize what is real. Common symptoms include false beliefs, unclear or confused thinking, hearing voices, reduced social engagement and emotional expression, and a lack of motivation. People often have additional mental health problems such as major depression, anxiety disorders, or substance use disorder. Symptoms typically come on gradually, begin in early adulthood, and last a long time.

Cognitive impairments and psychopathological parameters in patients of the schizophrenic spectrum.



Cognitive impairment is a core feature of schizophrenia and it is considered by many researchers as one of the dimensional components of the disorder. Cognitive dysfunction occurs in 85% of schizophrenic patients and it is negatively associated with the outcome of the disorder, the psychosocial functioning of the patients, and non-compliance with treatment. Many different cognitive domains are impaired in schizophrenia, such as attention, memory, executive functions and speech. Nowadays, it is argued that apart from clinical heterogeneity of schizophrenia, there is probable heterogeneity in the accompanying neurocognitive dysfunction. Recent studies for cognitive dysfunction in schizophrenia employ computerized assessment batteries of cognitive tests, designed to assess specific cognitive impairments. Computerized cognitive testing permits for more detailed data collection (e.g. precise timing scores of responses), eliminates researcher's measurement errors and bias, assists the manipulation of data collected, and improves reliability of measurements through standardized data collection methods. The aims of the present study are: the comparison of cognitive performance of our sample of patients and that of healthy controls, on different specific cognitive tests, and the testing for possible association between patients' psychopathological symptoms and specific cognitive impairments, using the Cogtest computerized cognitive assessment battery. 71 male inpatients diagnosed with schizophrenia or other psychotic spectrum disorders (mean = 30.23 ± 7.71 years of age), admitted in a psychiatric unit of the First Department of Psychiatry, Athens University Medical School, Eginition Hospital (continuous admissions) were studied. Patients were excluded from the study if they suffered from severe neurological conditions, severe visual or hearing impairment, mental retardation, or if they abused alcohol or drugs.

Bipolar disorder, also known as bipolar affective disorder or manic depression, is a mental disorder characterized by periods of depression and periods of elevated mood. The elevated mood is significant and is known as mania or hypomania depending on the severity or whether symptoms of psychosis are present. During mania an individual feels or acts abnormally happy, energetic, or irritable. They often make poorly thought out decisions with little regard to the consequences. The need for sleep is usually reduced. During periods of depression there may be crying, poor eye contact with others, and a negative outlook on life

It also turns out that cognitive deficit is generally present in bipolar disorder (BPD).

“One area that Dr. Burdick is exploring is the frequency of neurocognitive impairment in BPD. Research shows that approximately 90 percent of schizophrenic patients suffer from cognitive deficits compared to only 40 to 60 percent of BPD patients. Understanding why certain patients develop significant cognitive difficulties while others do not is critical in optimizing patients’ quality of life, she says.”

Bipolar is probably not something you would connect with autism.  Being an observational diagnosis you would not tend to look at the biological underpinnings. The biological basis of both bipolar and schizophrenia are far better studied than autism and do significantly overlap with it.

In a recent post I looked at epigenetics and autism, when it comes to schizophrenia and bipolar the role of epigenetics is far more in the mainstream.

There is an approved epigenetic therapy (the HDAC inhibitor Valproate) for Bipolar mania and there is a clinical trial to improve cognitive function in schizophrenia using ather epigenetic therapy (the HDAC inhibitor Sodium Butyrate.)

Butyrate is also showed promise in a mouse model (D-AMPH) of Bipolar.

Epigenetic mechanisms in schizophrenia

Effects of sodium butyrate on oxidative stress and behavioral changes induced by administration of D-AMPH


I think people should be more open to discuss cognitive deficits and not hide behind politically correct terminology.

It seems that in both bipolar and schizophrenia cognitive deficits are recognized to be at the core of the disorder, even though 99% will not have an IQ<70 and so not be labelled with MR/ID.

Autism therapies which clearly improve cognitive function, like Bumetanide and low-dose Clonazepam, should be promoted as such.  Clinical trials should measure the cognitive improvement separately from autism measures.  As the person ages I think the benefit will often be more noticeable/measurable cognitively than behaviorally.


  1. Hi Peter mi son is 6 years old and has a tgd diagnostic. He has also bpd sympotms. The neurolog prescribed risperidone. But Iam afraid for the dependence and the long terms effects. What do you think?

    1. Hi Jose, drugs like risperidone seem to cause lots of problems.

      Verapamil, one of the drugs I give my son in summer when his autism gets worse has been used for many years as an off-label treatment for bipolar disorder. This might be a better/safer choice to trial than risperidone. Unless you are very unlucky, Verapamil will be well tolerated. We had no problems at all with it.

      For other readers TGD is Spanish for PDD (ie autism).

  2. I assume its the Sodium Butyric Acid that is the most helpful for these issues? Is the Butyric Acid that is 2:1 (Calcium/Magnesium) would have a different mechanism? Does that deliver some of the benefits being a short chain fatty acid too? Thanks!

    1. All the butyrate supplements should have same effect of producing butyric acid. This can also be achieved through eating high fiber diet and/or using a probiotic./bacteria like Miyairi 588. The only question is how much is needed and nobody really knows the answer.

  3. Hi Peter. I have just finished reading Dr. Chez's book. In it, he highly endorses Valproic Acid. He says "Overall in the ASD population, Valproic Acid is my drug of choice". He sites an approximate 70% successful response rate in those patients that have abnormal EEG's, bipolar or manic issues, or both. It would be interesting to see if adding Verapamil to Valproic Acid would increase it's effectiveness.

    1. Valproate is widely used in autism, but as one reader commented on in detail it can have troubling side effects. There are several good reasons as to why it should be effective, but I am not sure you should use it unless you really have to, for example to control seizures.

  4. So the Schizophrenia trail has it 6.57 gms a day... that's for an adult... wonder what that would be dosed for a child?

  5. Not to sound like a cheerleader, but I pretty much agree with all of this and this is exactly the strategy I have with my children. My oldest son (most severe of the three) is in an ABAish classroom and I am pretty sure he does not learn a lot there (this is a high quality public school routinely in the top 50 in the country with a very mediocre special education system).

    So unfortunately progress for the teachers is defined as "minimizing behaviors" since my child does not have to take any standardized tests and therefore means the school rankings do not include him and his fellow students in the classroom. I think the teacher tries hard, as do the aides but for politically correct reasons they don't do any "cognitive testing" so really there is no measure from year to year for improvement. I am thinking of home schooling him next year, but that will be super hard and perhaps impractical with the burden of handling my other three children (two of which are in regular classrooms but have an autism diagnosis as well).

    Nevertheless, the question begs as to what interventions are best for "cognitive improvement" in a person with intellectual disability. Unfortunately, this is very hard with autism and comorbid epilepsy because generally speaking at the cellular level learning and intellectual performance in many ways is about laying off the brakes (more excitation relative to inhibition). Unfortunately, hyperexcitation is often a hallmark of autism for a myriad of reasons so "smart drugs" like racetams that function as ampakines could have disastrous side effects such as seizures in some people with autism. Really, cognitive enhancement means dealing with each cellular dysfunction one by one (e.g. bumetanide for chloride levels, NAC and other antioxidants for oxidative stress, as well as interventions to normalize neurotransmitter levels at the synapse), and then after all that is accomplished, then you start trying to treat the brain connectivity problems (which in addition to the type of research discussed on this blog, has been my parallel focus for the last 5 or so years).

    That I think is the best way forward. As many parents already know first hand, pretty much all non-medical autism therapies are useless in a severely autistic child if learning is dysfunctional because of some of the aforementioned reasons. More time in bed sleeping can improve IQ in this population more than extra time at school doing rote ABA drills, though in my personal experience the principal at my son's elementary school and the rest of the staff at his last IEP were so utterly clueless (or else just didn't care) that the principal actually said that there are studies (she didn't cite) showing that children learn best when they show up at school very early in the morning. Apparently, all she cares about is keeping her school rankings up because while tardiness from letting your kid sleep in on nights he has a problem going to bed at a reasonable hour does impact her school rankings, whether my child is cognitively improving does not affect her rankings. Yes this is cynical but nevertheless completely true as we all know how it feels to have school district's treat your kid as a throwaway child where all that matters from their perspectives is keeping your child (and his issues) out of view and telling the parents whatever they want to hear so they don't raise a fuss.

    Well I do raise a fuss and am not politically correct about the reality of what needs to be accomplished for a child with non-trivial autism to have a positive outcome and so while many of the so-called professionals who think therapies and drugs which may acutely improve behavior at the expense of long-term cognitive dampening are the way to go, fortunately my son has two parents who will always put his cognitive well-being before the convenience of using drugs and therapies which merely sedate him.

    1. Hi Tyler,

      I have recently met a few parents whose children are on the severe end of the spectrum, but are all literate. In all but one case, they have been homeschooled by very bright parents or schooled in alternative settings.

      Special education in schools is glorified baby sitting. For another kind of inflammatory, to many sensibilities this time, is this:

      I felt vindicated for despising most special ed teachers. The figures and the statistics tell the story, the article itself can be ignored.

  6. Hi Peter, I just want to let you know that yesterday I trialled Miorel (baclofen) 10mg/tab, cut in half, three times a day, approximately every 5 hours.
    My early results seem to be favourable in many ways. We had a lot of new, more impulsive huge smiles and he even looked at me deeply in my eyes, as if he was trying to investigate my real feelings, and asked "How do you feel?" "I feel great", I told him, "What about you, does this drug make your muscles feel more relaxed?" He said" Yes, now that you ask, it's good."
    My son, ever since he was very small, has been having some kind of autistic dysphoria with his toes (never takes off his socks, suffers when cuts nails, occasional toe walking etc.) which seems to be a "dark forbidden zone" I cannot explain further. Yesterday he told me that he needs a foot specialist to take care of his toes and nails because thay can't be left so messy anymore????
    Peter, you told me that you don't know the dosage, but do you have any other comments on my baclofen trial?
    Thank you

    1. This comment has been removed by the author.

    2. Hi Petra, that is great. I would keep going at this low dosage and see if the effect grows in the coming days. The paediatrician who suggested baclofen for Asperger's found no problems with side effects or tolerance. So if 5mg x 3 works well, it can be a long term therapy. For other purposes much higher doses are used.

    3. Peter, would it be a good idea to combine baclofen with cinnamon capsules?

    4. Petra, I would wait a couple of weeks until you see the full effect of Baclofen before adding anything. If Baclofen works well you can see how dependent the effect is on the dose. You can try slightly more and slightly less, then choose the most effective dose.

      Being a common food ingredient the Ceylon/Sri Lanka type of cinnamon should be very safe (as long as you are not histamine intolerant). While you do not want to use too many pharmaceuticals, neutraceuticals and may be a good way forward.


Post a comment