Intranasal Insulin for Improved Mood and Cognition

  

This post follows on the previous one that raised the issue of brain-specific insulin sensitivity being a common feature of neurological diseases/disorders.

It appears to be much more than just a rare possibility.   There have been numerous studies and even more are ongoing.

Intranasal insulin has even been tried one single-gene type of autism (Phelan-McDermid Syndrome) and in autism’s big brothers, bipolar and schizophrenia.

I did look for trials in children with Down Syndrome, since here is a direct link to Alzheimer’s, but there is just a trial in adults in progress.

There was an early trial in typical adults which is interesting since it found not only a cognitive improvement but also improved mood, so perhaps it should be trialed in adults with depression.  In the US, interestingly, T3 thyroid hormone is sometimes given off-label for depression and some antidepressants increase the conversion of the pro-hormone T4 to T3 in the brain.  I think central hypothyroidism is likely a feature of some neurological disorders, as I proposed in an earlier post.

I think it would be well worth trialing intranasal insulin in idiopathic Autism and, separately, idiopathic Asperger’s.  I am surprised nobody has done it. I really think Autism and Asperger’s  should be separated, since while we sometimes see the same therapy helps in both, sometimes there are Asperger-specific therapies, like Baclofen.

A small number of readers of this blog do follow the science and engage in some experimentation at home.  I think given what some people have already tried, intranasal insulin is not at all far fetched, you just need a metered dose nasal spray, insulin and the correct amount of dilutant/diluent, as in the trials.

Insulin and IGF-1 (insulin-like growth factor 1)

There are autism trials underway using subcutaneous injections of IGF-1 and also oral IGF-1 analogs.

IGF-1 is a primary mediator of the effects of growth hormone (GH). Growth hormone is made in the anterior pituitary gland, is released into the blood stream, and then stimulates the liver to produce IGF-1. IGF-1 then stimulates systemic body growth, and has growth-promoting effects on almost every cell in the body,

Insulin levels affect levels of growth hormone (GH) and IGF-1.

We know that various growth factors (NGF, BDNF, IGF-1 etc.) in people with autism can be disturbed, but there is both hypo and hyper.

We also know that the level of hormones measured in the blood can be very different to those in the brain/CNS.  This means that having blood tests indicating  high serotonin, thyroid T3, IGF-1 etc. does not tell you anything about the level within the brain.  Quite possibly they may be the opposite.

It would seem to be hugely preferable to target the brain directly, rather than the whole body.

The lack of side effects in the numerous studies of intranasal insulin is very encouraging.

Healthy Neurotypical Adults

Intranasal insulin improves memory in humans

Declarative memory in humans without causing systemic side effects like hypoglycaemia. The improvement of memory in the eighth week of treatment corroborates previous findings of improved memory function following acute intravenous administration of the peptide both in healthy subjects (Kern et al., 2001) and in patients with Alzheimer’s disease (Craft et al., 1999). In addition, intranasal insulin positively affected mood in our subjects. The improving effect of subchronic intranasal insulin administration appeared to be specific for hippocampus dependent declarative memory.

Our subjects in the insulin group also expressed enhanced mood. Acute intranasal intake of insulin enhanced the feelings of well-being and self-confidence, which is in accordance with previous results (Kern et al., 1999).

In summary our data indicate that prolonged intranasal intake of insulin improves both consolidation of words and general mood. These beneficial findings suggest intranasal administration of insulin as a potential treatment in patients showing memory deficits in conjunction with a lack of insulin, such as in Alzheimer’s disease

Adults with Schizophrenia

No effect of adjunctive, repeated-dose intranasal insulin treatment on psychopathology and cognition in patients with schizophrenia.

Abstract

OBJECTIVE:

This study examined the effect of adjunctive intranasal insulin therapy on psychopathology and cognition in patients with schizophrenia.

METHODS:

Each subject had a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of schizophrenia or schizoaffective disorder and been on stable antipsychotics for at least 1 month. In an 8-week randomized, double-blind, placebo-controlled study, subjects received either intranasal insulin (40 IU 4 times per day) or placebo. Psychopathology was assessed using the Positive and Negative Syndrome Scale and the Scale for Assessment of Negative Symptoms. A neuropsychological battery was used to assess cognitive performance. The assessment for psychopathology and cognition was conducted at baseline, week 4, and week 8.

RESULTS:

A total of 45 subjects were enrolled in the study (21 in the insulin group and 24 in the placebo group). The mixed model analysis showed that there were no significant differences between the 2 groups at week 8 on various psychopathology and cognitive measures (P > 0.1).

CONCLUSIONS:

Adjunctive therapy with intranasal insulin did not seem to be beneficial in improving schizophrenia symptoms or cognition in the present study. The implications for future studies were discussed.

Adults with Bipolar

A randomized, double-blind, controlled trial evaluating the effect of intranasal insulin on neurocognitive function in euthymic patients with bipolar disorder.

 

Abstract

BACKGROUND:

Neurocognitive deficits are prevalent, persistent, and implicated as mediators of functional impairment in adults with bipolar disorder. Notwithstanding progress in the development of pharmacological treatments for various phases of bipolar disorder, no available treatment has been proven to be reliably efficacious in treating neurocognitive deficits. Emerging evidence indicates that insulin dysregulation may be pertinent to neurocognitive function. In keeping with this view, we tested the hypothesis that intranasal insulin administration would improve measures of neurocognitive performance in euthymic adults with bipolar disorder.

METHODS:

Sixty-two adults with bipolar I/II disorder (based on the Mini International Neuropsychiatric Interview 5.0) were randomized to adjunctive intranasal insulin 40 IU q.i.d. (n = 34) or placebo (n = 28) for eight weeks. All subjects were prospectively verified to be euthymic on the basis of a total score of ≤ 3 on the seven-item Hamilton Depression Rating Scale (HAMD-7) and ≤ 7 on the 11-item Young Mania Rating Scale (YMRS) for a minimum of 28 consecutive days. Neurocognitive function and outcome was assessed with a neurocognitive battery.

RESULTS:

There were no significant between-group differences in mean age of the subjects {i.e., mean age 40 [standard deviation (SD) = 10.15] years in the insulin and 39 [SD = 10.41] in the placebo groups, respectively}. In the insulin group, n = 27 (79.4%) had bipolar I disorder, while n = 7 (21.6%) had bipolar II disorder. In the placebo group, n = 25 (89.3%) had bipolar I disorder, while n = 3 (10.7%) had bipolar II disorder. All subjects received concomitant medications; medications remained stable during study enrollment. A significant improvement versus placebo was noted with intranasal insulin therapy on executive function (i.e., Trail Making Test-Part B). Time effects were significant for most California Verbal Learning Test indices and the Process Dissociation Task-Habit Estimate, suggesting an improved performance from baseline to endpoint with no between-group differences. Intranasal insulin was well tolerated; no subject exhibited hypoglycemia or other safety concerns.

CONCLUSIONS:

Adjunctive intranasal insulin administration significantly improved a single measure of executive function in bipolar disorder. We were unable to detect between-group differences on other neurocognitive measures, with improvement noted in both groups. Subject phenotyping on the basis of pre-existing neurocognitive deficits and/or genotype [e.g., apolipoprotein E (ApoE)] may possibly identify a more responsive subgroup

Children with Phelan-McDermid Syndrome 

22q13 deletion syndrome is a genetic disorder caused by deletions or rearrangements on the q terminal end (long arm) of chromosome 22. Any abnormal genetic variation in the q13 region that presents with significant manifestations typical of a terminal deletion should be diagnosed as 22q13 deletion syndrome. 22q13 deletion syndrome is often placed in the more general category of Phelan-McDermid Syndrome (abbreviated PMS), which includes some mutations and microdeletions. 

Physical

·         Absent to severely delayed speech: 99%

·         Normal to accelerated growth: 95%

·         High tolerance to pain: 77%

·         Hypotonia (poor muscle tone): 75%

·         Dysplastic toenails: 73%

·         Long eyelashes: 73%

·         Poor thermoregulation: 68%

·         Prominent, poorly formed ears: 65%

·         Large or fleshy hands: 63%

·         Pointed chin: 62%

·         Dolichocephaly (elongated head): 57%

·         Ptosis (eyelid) (droopy eyelids): 57%

·         Gastroesophageal reflux: 42%

·         Epileptic seizures: 27%

·         Kidney problems: 26%

·         Delayed ability to walk: 18%

Behavioral

·         Chewing on non food items: 85%

·         Delayed or unreliable toileting: 76%

·         Impulsive behaviors: 47%

·         Biting (self or others): 46%

·         Problems sleeping: 46%

·         Hair pulling: 41%

·         Autistic behaviors: 31%

·         Episodes of non-stop crying before age 5: 30%

·         Teeth grinding: (unknown) %

Intranasal insulin to improve developmental delay in children with 22q13 deletion syndrome: an exploratory clinical trial.

 

BACKGROUND:

The 22q13 deletion syndrome (Phelan-McDermid syndrome) is characterised by a global developmental delay, absent or delayed speech, generalised hypotonia, autistic behaviour and characteristic phenotypic features. Intranasal insulin has been shown to improve declarative memory in healthy adult subjects and in patients with Alzheimer disease.

AIMS:

To assess if intranasal insulin is also able to improve the developmental delay in children with 22q13 deletion syndrome.

METHODS:

We performed exploratory clinical trials in six children with 22q13 deletion syndrome who received intranasal insulin over a period of 1 year. Short-term (during the first 6 weeks) and long-term effects (after 12 months of treatment) on motor skills, cognitive functions, or autonomous functions, speech and communication, emotional state, social behaviour, behavioural disorders, independence in daily living and education were assessed.

RESULTS:

The children showed marked short-term improvements in gross and fine motor activities, cognitive functions and educational level. Positive long-term effects were found for fine and gross motor activities, nonverbal communication, cognitive functions and autonomy. Possible side effects were found in one patient who displayed changes in balance, extreme sensitivity to touch and general loss of interest. One patient complained of intermittent nose bleeding.

CONCLUSIONS:

We conclude that long-term administration of intranasal insulin may benefit motor development, cognitive functions and spontaneous activity in children with 22q13 deletion syndrome.

For intranasal administration, insulin (40 IU/ml; Actrapid, Novo Nordisk, Mainz, Germany) was diluted with 0.9% saline solution to a concentration of 20 IU/ml so that each 0.1 ml puff with the nasal atomizer (Aero Pump, Hochheim, Germany) contained a dose of 2 IU insulin. Subjects received one dose of 2 IU insulin per day during the first 3 days according to the standard subcutaneous insulin therapy in children with type 1 diabetes mellitus. In three-day intervals, administration was increased gradually, until the final dosage of about 0.5-1.5 IU/kg/d (TID)

As with idiopathic autism there is interest in using the related IGF-1 as a therapy.

A pilot controlled trial of insulin-like growth factor-1 in children with Phelan-McDermid syndrome

Background

Autism spectrum disorder (ASD) is now understood to have multiple genetic risk genes and one example is SHANK3. SHANK3 deletions and mutations disrupt synaptic function and result in Phelan-McDermid syndrome (PMS), which causes a monogenic form of ASD with a frequency of at least 0.5% of ASD cases. Recent evidence from preclinical studies with mouse and human neuronal models of SHANK3 deficiency suggest that insulin-like growth factor-1 (IGF-1) can reverse synaptic plasticity and motor learning deficits. The objective of this study was to pilot IGF-1 treatment in children with PMS to evaluate safety, tolerability, and efficacy for core deficits of ASD, including social impairment and restricted and repetitive behaviors.

Methods

Nine children with PMS aged 5 to 15 were enrolled in a placebo-controlled, double-blind, crossover design study, with 3 months of treatment with IGF-1 and 3 months of placebo in random order, separated by a 4-week wash-out period.

Results

Compared to the placebo phase, the IGF-1 phase was associated with significant improvement in both social impairment and restrictive behaviors, as measured by the Aberrant Behavior Checklist and the Repetitive Behavior Scale, respectively. IGF-1 was found to be well tolerated and there were no serious adverse events in any participants.

Conclusions

This study establishes the feasibility of IGF-1 treatment in PMS and contributes pilot data from the first controlled treatment trial in the syndrome. Results also provide proof of concept to advance knowledge about developing targeted treatments for additional causes of ASD associated with impaired synaptic development and function.

Drug administration

IGF-1 (Increlex; Ipsen Biopharmaceuticals, Inc) is an aqueous solution for injection containing human insulin-like growth factor-1 (rhIGF-1) produced by recombinant DNA technology. Placebo consisted of saline prepared in identical bottles by the research pharmacy at Mount Sinai. We received an Investigational New Drug exemption from the Food and Drug Administration (#113031) to conduct this trial in children with PMS. Based on the package insert for Increlex, dose titration was initiated at 0.04 mg/kg twice daily by subcutaneous injection, and increased, as tolerated, every week by 0.04 mg/kg per dose to a maximum of 0.12 mg/kg twice daily. This titration was justified based on our preclinical data, which indicated that 0.24 mg/kg/day is effective in reversing electrophysiological deficits whereas 0.12 mg/kg/day was not as effective[21]. We aimed to reach the therapeutic dose as quickly as is safe and tolerated in order to allow maximum time for clinical improvement. Doses could be decreased according to tolerability by 0.04 mg/kg per dose. Medication was administered twice daily with meals, and preprandial glucose monitoring was performed by parents prior to each injection throughout the treatment period. Parents were carefully trained in finger stick monitoring, symptoms of hypoglycemia, and medication administration.

Down Syndrome

The ongoing Down Syndrome trial is in adults.  As mentioned earlier, a feature of the syndrome is the likely early onset of Alzheimer’s, so not surprisingly if intranasal insulin helps people with Alzheimer’s it makes sense to trial it on people with Down Syndrome.

I think it makes sense to trial it on young people with Down Syndrome, prior to the onset of Alzheimer’s.

Investigation of the Safety of Intranasal Glulisine in Down Syndrome

This study is a single center, randomized, double-blind, placebo-controlled, cross-over pilot study designed to assess the safety of intranasally (IN) delivered glulisine versus placebo in patients with DS. Subjects will be randomized into this cross-over study and within subject comparisons conducted between single treatment of intranasal insulin glulisine and single treatment of intranasal placebo

The SNIFF (Study of Nasal Insulin in the Fight against Forgetfulness) Trials

The large clinical trials all relate to Alzheimer’s.  The big trial, SNIFF INI, will last for 18 months, but they are also making shorter trials using different types of insulin.  There is  SNIFF Quick to test fast acting insulin and SNIFF long to test the long acting type.

SNIFF Quick

SNIFF Long

SNIFF INI

The big 18 month study.

Conclusion

I think in a couple of decade’s time, it will be widely recognized that various physiological states exist in many complex diseases and while it may not be possible to cure those conditions, you can treat those altered physiological states.

In the case of autism those states might include:-

·        Oxidative stress

·        Mitochondrial stress

·        Microglial activation

·        Central hormonal dysfunction

·        Reduced brain insulin sensitivity

·        Impaired remyelination

·        Faulty GABA switch

These altered states are in addition to the specific channelopathies and other dysfunctions a particular person might have.

By applying what is learnt from other diseases we can then better treat the autism variants.  So what eventually develops from MS research in regard to remyelination can be translated to some autism variants, quite possibly that of Hannah Poling (mitochondrial disease, triggered by vaccination).

Reduced brain insulin sensitivity, where present, appears very treatable today.  I suspect some variants of autism do indeed feature reduced brain insulin sensitivity, but others will not.  There is no clever way to predict this, but it looks simple to test.

Autism Biology, Comorbidity, Mortality and Better use of Existing Research

Karolinska Institutet, the Medical University of Stockholm, viewed from garden next door

It is sometimes disappointing how the level of understanding of Autism, even among supposed experts, is so very low.

As readers of this blog are aware there is already a vast wealth of research in autism, highlighting many biological differences and comorbid medical conditions.  Not surprisingly this is reflected in life expectancy.

Autistica, a UK Autism charity, is trying to raise $15 million to fund five years of research into why there is premature death in autism.

This would be a complete waste of money, since the answers already exist in the literature if this “Autism Research” charity employed people who actually could/did read the research.

This subject dates back to a Swedish study from last year that is languishing behind a pay wall, so no open access to it.


The rather skimpy abstract:

Premature mortality in autism spectrum disorder.

  
The rather underwhelming press release from the Karolinska Institute:-

People with autism run a higher risk of premature death

Courtesy of SFARI we have this graphic and highlights.

Large Swedish study ties autism to early death

·        Autistic adults with a learning disability were found to die more than 30 years before non-autistic people.

·        The study found that on average people with autism died over 18 years earlier than non-autistic people.

·        Autistic adults with a learning disability are 40 times more likely to die prematurely due to a neurological condition, with epilepsy the leading cause of death

·        Autistic adults without a learning disability are 9 times more likely to die from suicide

 Autistica did produce a report that is based on the Swedish study:-

Personal tragedies, public crisis - The urgent need for a national response to early death in autism

Is there anything new here?

Epilepsy

People might rather not discuss it, but there are numerous examples of well-known people who had a child with severe autism, MR/ID and epilepsy, and it all ended pretty much as suggested in the Swedish Study.  A fatal seizure (SUDEP), or an accident like drowning following a seizure.

The logical thing to do is to prevent epilepsy developing in the first place, which some readers of this blog are already endeavoring to do.   This is not fantasy, just hard to prove it worked.

Suicide

We have seen that anxiety can be a key problem for people with Asperger’s. 

We heard from a UK pediatrician who found an off-label treatment, Baclofen, which was effective in most cases.  We also were told why he/she did not want to continue prescribing it do to the lack of any clinical trials supporting its use.

We saw how Prozac, the anti-anxiety pill frequently prescribed in autism has the known side effect of increasing suicidal thoughts.

We saw a long time ago in my hypothesis on TRH, that the US military is developing a TRH nasal spray to reduce the suicide rate in soldiers returning from combat.  A homemade version of this nasal spray was used for years by a US doctor/author to treat various neurological disorders.

We do not need to worry about suicide and people with Strict Definition Autism (SDA), but they are highly prone to accidents like drowning, caused by a combination of being allowed to wander off unsupervised and not knowing how to swim confidently.

Medical Comorbidities

Autism has a long list of known medical comorbidities and not surprisingly they will show up as a cause of death.

By accurately treating a person’s autism, you will at the same time be treating some of their comorbid conditions.

For example, if you have a problem with calcium channels (like Cav1.2) in your brain, you should not be surprised to have problems in other parts of the body where they are heavily expressed, so the heart and pancreas for Cav1.2.

The medical comorbidities are indeed a valuable tool to identify the possible biological dysfunctions underlying a person’s autism.  Then you can treat them at the same time, with the same drug.

Bipolar and Schizophrenia

In the case of autism’s adult-onset big brothers, namely bipolar and schizophrenia, there is a reduction in life expectancy of 10-20 years.

By comparison, type 1 diabetes on average reduces life expectancy by 20 years.  But you do not have to be Mr/Ms Average; if you control your condition well and also improve insulin sensitivity (ALA, NAC, Cinnamon, Sulforaphane, Cocoa flavanols etc.) the future can be bright.

People with Bipolar or Schizophrenia have a high suicide risk, in common with Asperger’s, but they also have high levels of substance abuse, starting with smoking and alcohol and going up the scale.

The core biological dysfunctions in both Bipolar and Schizophrenia are studied and some evidence-based therapies exist, lying forgotten in the literature.


Sweden as a Model

The autism mortality statistics in this post are based on Swedish data.  Sweden is not typical.  Sweden is possibly the best country in the world to live in if you have a physical or mental disability.  It is remarkable inclusive and the less able are well looked after.  So if the data existed for other countries, it would very likely look even worse. 

Conclusion

I think quasi-science organizations, like Autistica, are not helping and just add to the public misunderstanding of autism.  It is highly complex, but a great deal is already understood.  

Better use should be made of what is already known. It cannot be adequately explained in tabloid TV, or a few sound bites.

Why don’t researchers/Institutes like the Karolinska Institute, Stockholm, pay up a couple of thousand dollars and make their excellent research open access? 

As we saw when we looked at Down Syndrome, life expectancy is a case of out of sight is out of mind.

What do Autistica think the age at death of someone with autism+MR/ID +epilepsy was in 1960?

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445685/figure/F2/

In the Down Syndrome chart above, you just had to stop locking them up in institutions as babies, for them to have a better prognosis.

Since the 1970s, society no longer locks up toddlers with autism either, so now they live longer.  To live as long as other people, they need some help from science.

If you treat the underlying dysfunctions in people with autism, bingo they will live longer.  You do not need $15 million to figure that out.  You do need an open mind.

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.

  

Abstract

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).

Understanding Cognitive Impairments in Bipolar Disorder and Psychosis

  

“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.

Sodium Butyrate For Improving Cognitive Function In Schizophrenia

Epigenetic mechanisms in schizophrenia

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

Conclusion

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.