Saturday, 1 August 2015

Methylphenidate: a repairer of the 'oxidative balance' in ADHD?

A fairly quick post for you today based on the findings reported by Esra Guney and colleagues [1] who examined whether markers of oxidative stress - an imbalance "between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage" - might be something to look at when it comes to cases of attention-deficit hyperactivity disorder (ADHD).

They concluded that, based on a small-ish sample size, there may be more to see when it comes to oxidative metabolism with ADHD in mind. Their findings are not a million miles away from other work in this area [2] bearing in mind the need for further investigations. I might add that given the quite strong links being put forward between autism and issues with oxidative stress (see here) and the quite consistent overlap between autism and ADHD (see here), future work might need to take quite a broad view of any relationship.

Of particular note to me in the Guney paper was mention of how differences in the oxidative stress index before and after intervention (i.e. medication) in their cohort might offer some new ideas about how certain types of medicines 'work' on cases of ADHD. So: "It was also determined that methylphenidate repairs the oxidative balance by increasing antioxidant defence mechanisms."

Methylphenidate (MPH) (known as Concerta or Ritalin) is a medication of choice for many people diagnosed with ADHD. Although by no means an expert on the whys and wherefores of how MPH works, discussions have always been a little unclear as to how something that looks chemically like an amphetamine (a stimulant) seems to have such a calming effect on some of the characteristics of ADHD. As a nootropic (so-called smart drug) the idea that MPH might work as a performance enhancer offers some clues as to how it might impact on ADHD type symptoms but still curiosity remains on it's important effects.

The idea that MPH might, in amongst its various proposed actions, also impact on processes pertinent to oxidative stress is an interesting one. Animal studies have previously suggested that administration of MPH might affect key compounds related to oxidative stress [3] in particular, related to oxidative defences. That being said, evidence has also been produced to suggest that MPH might do more to induce oxidative stress [4] than to solve any issues, so one has to be a little guarded about making too many sweeping generalisations. That drug dose might also be an important factor is something to take on board too.

Assuming further work is forthcoming to further elucidate any role for MPH in relation to the processes of oxidative stress, some intriguing prospects may lie on the research horizon.

Music: Dream Academy - Life In A Northern Town.


[1] Guney E. et al. Attention Deficit Hyperactivity Disorder and oxidative stress: A short term follow up study. Psychiatry Res. 2015 Jul 8. pii: S0165-1781(15)00448-5.

[2] Joseph N. et al. Oxidative Stress and ADHD: A Meta-Analysis. J Atten Disord. 2013 Nov 14.

[3] Schmitz F. et al. Chronic methylphenidate administration alters antioxidant defenses and butyrylcholinesterase activity in blood of juvenile rats. Mol Cell Biochem. 2012 Feb;361(1-2):281-8.

[4] Martins MR. et al. Methylphenidate treatment induces oxidative stress in young rat brain. Brain Res. 2006 Mar 17;1078(1):189-97.

---------- Guney, E., Cetin, F., Alisik, M., Tunca, H., Tas Torun, Y., Iseri, E., Isik Taner, Y., Cayci, B., & Erel, O. (2015). Attention Deficit Hyperactivity Disorder and oxidative stress: A short term follow up study Psychiatry Research DOI: 10.1016/j.psychres.2015.07.003

Friday, 31 July 2015

Careful now: oral colostrum MAF and Chronic Fatigue Syndrome?

I should perhaps begin this slightly longer than usual post by reiterating my well-trodden caveat on this blog about not giving anything that looks, sounds or smells like medical or clinical advice during my musings. This is a blog [mainly] about peer-reviewed science, nothing more. Added to that, I'm not your Dr Ross and you are not my patient.

So... I've been seeing quite a bit about Gc-MAF (Gc Macrophage Activating Factor) in the news recently. The various headlines about autism and Gc-MAF (see here and see here) have made up the bulk of media coverage but other reports of scientific retractions (see here) have similarly filled some column inches in recent times.

Whilst treading carefully in this area, Gc-MAF has cropped up on this blog a few times based on some of the peer-reviewed literature with autism in mind (see here and see here for further information including what Gc-MAF is). Even Drs Hornig & Lipkin have mentioned Gc-MAF and its precursors in other non peer-reviewed literature (see here). Indeed, given the straddling of autism research and studies on Chronic Fatigue Syndrome (CFS) by Drs Hornig and Lipkin, it is timely that I discuss the paper from Toshio Inui and colleagues [1] (open-access available here) detailing a few case studies suggesting that: "oral colostrum MAF can be used for serious infection and chronic fatigue syndrome (CFS) without adverse effects."

OK. First things first. Oral colostrum MAF is, we are told, a "new form of macrophage-activating factor (MAF) made from colostrum in collaboration with the Tokushima University." Macrophages are known as the 'big eaters' of the immune system getting rid of various molecular debris including viruses, bacteria and the odd 'worn out cell'. The Star Wars version (yes, you heard/read me right) of the role of macrophages can be read in this article [2] by Debra Laskin. Gc-MAF as the name implies is an 'activating factor' for macrophages, also seemingly affected by something called nagalase.

"This new form, referred to as colostrum MAF, is manufactured using bovine colostrum instead of human serum. It is administered orally in an acid-resistant enteric capsule to activate macrophages in the gut-associated lymphoid tissue (GALT) and as a powder in the mouth to activate macrophages in the lymphoid tissue of the mouth and throat."

Given the immune system / macrophage slant to colostrum MAF, the authors moved into the area of CFS and the idea that: "infections and immune dysfunction are thought to play a critical role in the development of the disease." I'll chip in here and reiterate that science does seem to be moving closer to the idea that CFS (and myalgic encephalomyelitis, ME) has origins in organic disease albeit still a little undecided as to what factors are involved. On that basis, two of the three case reports detailed in the Inui paper are on adults with CFS and their experiences of colostrum MAF.

Focusing on those two case reports - both females - they were reported to show some pretty interesting effects concurrent to the use of colostrum MAF. Statements like "reduced malaise" and "being able to do her usual work with more energy like most other people do" are included in the text, even accompanied by "improvements in hair growth on her head." The authors attempt to link such changes to increased phagocytosis. They suggest further work is needed to "elucidate the mechanisms by which MAF has beneficial effects."

These are interesting results but I'm afraid that I need a little more convincing on safety and efficacy yet. Case reports, as I've mentioned in the context of autism (a heterogeneous condition), can provide some really informative data about a specific person diagnosed with a particular condition as a starting point for further investigations more generalised to more people in those specific circumstances. That same logic applies to the Inui findings and the need for further controlled studies on the potential effects of colostrum MAF including specific measures of fatigue and other symptom changes as a result of any intervention(s). This also includes the need for a little more information about the biology behind any reported changes and longer-term, what any effects might be bearing in mind where it comes from. Without casting aspersions, one needs to remember how powerful even a placebo can be (see here).

Insofar as the comments about hair regrowth in relation to CFS, whilst I have heard that hair loss is not uncommon (see here) I can't yet find anything in the peer-reviewed domain specifically about this phenomenon. This doesn't mean that co-occurring issues alongside a diagnosis of CFS might not involve such a symptom but as far as I am aware, it is not a primary part of the [current] diagnostic criteria. In order to avoid any mis-interpretations about colostrum MAF being the next hair growth agent of choice, in future studies I would like to see a little more 'controlled' scientific engagement over such processes.

It is as easy to get carried away with the Inui results as it is to pooh-pooh the findings, particularly in light of all that media coverage of Gc-MAF recently. Throughout the whole history of this compound and now colostrum MAF, there has been a tendency to make some pretty big claims often at the expense of really methodologically sound objective science. Given however the ways and means that a condition like CFS can impact on a person - disable a person - I would suggest that this might be an occasion where sound independent research can come take a lead and put some scientific flesh on the bones on any effect or not.

Music: Carly Rae Jepsen - Call Me Maybe.


[1] Inui T. et al. Oral Colostrum Macrophage-activating Factor for Serious Infection and Chronic Fatigue Syndrome: Three Case Reports. Anticancer Res. 2015 Aug;35(8):4545-9.

[2] Laskin DL. Macrophages and inflammatory mediators in chemical toxicity: a battle of forces. Chem Res Toxicol. 2009 Aug;22(8):1376-85.

---------- Inui T, Kubo K, Kuchiike D, Uto Y, Nishikata T, Sakamoto N, & Mette M (2015). Oral Colostrum Macrophage-activating Factor for Serious Infection and Chronic Fatigue Syndrome: Three Case Reports. Anticancer research, 35 (8), 4545-9 PMID: 26168499

Thursday, 30 July 2015

Inflammatory bowel disease and autism: increased prevalence

A quote to begin today's post:

"Across each population with different kinds of ascertainment, there was a consistent and statistically significant increased prevalence of IBD [inflammatory bowel disease] in patients with ASD [autism spectrum disorder] than their respective controls and nationally reported rates for pediatric IBD."

That was the conclusion reached in the paper published by Finale Doshi-Velez and colleagues [1] including one very notable name on the authorship list, Isaac Kohane (he of comorbidity clusters and autism research fame).

Drawing on data from various sources - "rates of IBD among patients with and without ASD were measured in 4 study populations with distinct modes of ascertainment: a health care benefits company, 2 pediatric tertiary care centers, and a national ASD repository" - researchers set about establishing whether there were any differences between those with autism and those without autism in terms of IBD frequency. IBDs by the way, were characterised using ICD-9-CM codes and primarily included diagnoses of Crohn's disease and/or ulcerative colitis.

Researchers reported that "the rates of IBD-related ICD-9-CM codes for patients with ASD were significantly higher than that of their respective controls" despite the actual numbers diagnosed with an IBD being quite low (23 out of a cumulative population of nearly 10,000 participants). For those 23 people on the autism spectrum however, formal diagnosis of an inflammatory bowel disease is probably a very real thing to them and their families.

As mentioned in previous discussions on this blog, to talk about inflammatory bowel disease and autism can stir up some quite intense emotions and debates (see here) despite the fact that a diagnosis of autism is seemingly not protective against presenting with such issues (see here). Alongside the acceptance that more functional bowel issues such as constipation and diarrhoea are quite a frequent feature for quite a few cases of autism (see here), research attention needs to turn towards the underlying reasons why such functional bowel problems present and whether they may be reflective of something more pathological than just as a consequence of poor eating habits (see here) or any psychological / behavioural comorbidity (see here).

I'd wager that there is a lot more to see in this area of research particularly in light of ideas about the gut-brain axis being something potentially important to [some] autism (see here) alongside the idea that there may be specific neurological consequences of IBDs (see here). The idea that parental experiences of IBDs may also not be associated with offspring autism risk (see here) invites some interesting research discussing the ways and means that IBD risk comes to be heightened in relation to autism...

Music and have you heard that bird is the word?


[1] Doshi-Velez F. et al. Prevalence of Inflammatory Bowel Disease Among Patients with Autism Spectrum Disorders. Inflamm Bowel Dis. 2015 Jul 25.

---------- Doshi-Velez F, Avillach P, Palmer N, Bousvaros A, Ge Y, Fox K, Steinberg G, Spettell C, Juster I, & Kohane I (2015). Prevalence of Inflammatory Bowel Disease Among Patients with Autism Spectrum Disorders. Inflammatory bowel diseases PMID: 26218138

Wednesday, 29 July 2015

Gluten psychosis

"The present case-report confirms that psychosis may be a manifestation of NCGS [non-coeliac gluten sensitivity], and may also involve children; the diagnosis is difficult with many cases remaining undiagnosed."

Elena Lionetti and colleagues [1] (open-access) provide an interesting read in today's post on how diet and psychiatry might once again be linked. Presenting a case report of a 14-year old girl coming to the attention of clinical services "for psychotic symptoms that were apparently associated with gluten consumption", the authors describe the experiences of an otherwise well child quite quickly developing various psychiatric symptoms. Although initially thought to be autoimmune encephalitis (see here) it became apparent that dietary gluten might be a culprit behind the psychiatric presentation and not necessarily because of the classical gluten-related autoimmune condition called coeliac (celiac) disease (CD) either.

"To our knowledge, this is the first description of a pre-pubertal child presenting with a severe psychotic manifestation that was clearly related to the ingestion of gluten-containing food and showing complete resolution of symptoms after starting treatment with the gluten-free diet." Well actually, it's not; as previous ramblings on this blog come to mind (see here) albeit not with the same serological profile as discussed in the Lionetti paper. Interestingly however is the 'autoimmune' link noted in the paper by Eaton and colleagues [2] potentially overlapping with the Lionetti case report: "The only abnormal parameters were anti-thyroglobulin and thyroperoxidase antibodies (103 IU/mL, and 110 IU/mL; v.n. 0–40 IU/mL)." In light of other 'psychiatric' manifestations correlating with autoimmune issues with thyroid function in mind (see here) I'm beginning to wonder whether there might be a few research studies to do in this area...

Hopefully without plagiarising the Lionetti report, another long quote is coming up: "In our case report, the correlation of psychotic symptoms with gluten ingestion and the following diagnosis of NGCS were well demonstrated; the girl was, indeed, not affected by CD, because she showed neither the typical CD-related autoantibodies (anti-tTG and EMA) nor the signs of intestinal damage at the small intestinal biopsy. Features of an allergic reaction to gluten were lacking as well, as shown by the absence of IgE or T-cell-mediated abnormalities of immune response to wheat proteins. The double-blind gluten challenge, currently considered the gold standard for the diagnosis of NCGS, clearly showed that the elimination and reintroduction of gluten was followed by the disappearance and reappearance of symptoms." I might add that mention of 'leaky gut' in the Lionetti paper might offer a further expansion for the role of intestinal hyperpermeability in psychiatry (see here).

Need I say any more aside from: (i) this being further evidence that Dohan might have been on to something and (ii) more scientifically controlled research is most definitely warranted. Oh, and that the spectrum of possible behavioural and/or psychiatric effects from gluten in some people may be expanding...

Music: Shake Some Action.


[1] Lionetti E. et al. Gluten Psychosis: Confirmation of a New Clinical Entity. Nutrients. 2015;7(7): 5532-5539.

[2] Eaton WW. et al. Improvement in Psychotic Symptoms After a Gluten-Free Diet in a Boy With Complex Autoimmune Illness. Am J Psychiatry. 2015; 172: 219-221.

---------- Lionetti, E., Leonardi, S., Franzonello, C., Mancardi, M., Ruggieri, M., & Catassi, C. (2015). Gluten Psychosis: Confirmation of a New Clinical Entity Nutrients, 7 (7), 5532-5539 DOI: 10.3390/nu7075235

Tuesday, 28 July 2015

Adult outcomes following childhood psychiatric problems

A long quote to begin:

"If the goal of public health efforts is to increase opportunity and optimal outcomes, and to reduce distress, then there may be no better target than the reduction of childhood psychiatric distress—at the clinical and subthreshold levels."

That was the bottom line reported by William Copeland and colleagues [1] (open-access) who set out to test whether psychiatric problems presenting in childhood can "adversely affect adult functioning even if the problems themselves do not persist." The Copeland study also has an accompanying editorial in the publishing journal [2].

Based on data derived from a prospective study of nearly 1500 participants "from 11 predominantly rural counties of North Carolina" researchers looked for the presence of "common psychiatric diagnoses and subthreshold psychiatric problems" by means of structured assessments during childhood (9-16 years of age). "The common childhood psychiatric disorders assessed included anxiety disorders (separation anxiety, generalized anxiety, social phobia, specific phobia, agoraphobia, panic disorder, obsessive-compulsive disorder, and posttraumatic stress disorder), mood disorders (major depression, dysthymia, mania, and hypomania), conduct disorder, oppositional defiant disorder, attention-deficit/hyperactivity disorder, and substance disorders."

Just over 1200 of these research participants were then followed into adulthood - young adulthood - and assessed "for adverse outcomes related to health, the legal system, personal finances, and social functioning." This included responses on the the Young Adult Psychiatric Assessment (YAPA) and accessing official criminal records.

Results: of the original childhood cohort, just over a quarter of children/young adults "met criteria for a common behavioral or emotional disorder at some point in childhood/adolescence (9-16 years of age)." Whilst this might sound a lot, other studies have reached similar conclusions (see here). Added to that, about a third of participants at this stage of development "displayed subthreshold psychiatric problems only."

For those followed into adulthood: "Participants with a childhood disorder had 6 times higher odds... of at least 1 adverse adult outcome (ie, indicator) compared with those with no history of psychiatric problems." In more detail: "41.5% of participants who were subthreshold cases only and 59.5% of participants who were psychiatric cases reported an adult outcome" where an 'adult outcome' was classified as one of those 'adverse outcomes' in the areas inspected. "Psychiatric and subthreshold cases made up close to 80% of participants with an adult indicator (42.3% of psychiatric cases, 35.7% of subthreshold cases, and 22.0% of noncases) and close to 90% of participants with 2 or more such indicators (48.2% of psychiatric cases, 39.4% of subthreshold cases, and 12.3% of noncases)."

Drilling down into the details of what diagnosis or subthreshold diagnosis specifically translated into adverse adult outcomes, the authors reported that "childhood depression and conduct disorder were associated with a higher likelihood of having an adverse outcome, and only conduct disorder predicted having 2 or more adverse outcomes." These results held true even when various covariates were taken into account such as low socio-economic status, unstable family structure and maltreatment.

The accompanying editorial does make a case for not jumping to too many conclusions on the basis of the Copeland findings in terms of their meaning. "It is possible that some or all of the causes of psychopathology across the lifespan operate early in life" is one sentiment expressed. Being careful not to make any sweeping generalisations, I would tend to suggest that the evidence does seem to be pointing to early life psychopathology as expressing quite a effect when it comes to later life outcome. Taking for example the idea that a neurodevelopmental disorder might for example, influence the risk of psychosis in later life (see here) is one area where supporting peer-reviewed evidence has been produced. A possible link between the diagnosis of autism (Asperger syndrome) and an elevated risk of bipolar disorder (see here) in adult life is another.

Irrespective of the hows and whys, the data from Copeland adds to the idea that significantly more efforts are perhaps required to 'tackle' childhood psychopathology with the hope of reducing adverse adult outcomes and improving quality of life across the lifespan. Accepting that societal factors might also need some inspection alongside the idea that economics might enter into the equation at some point [3], questions remain about the best way to achieve this aim and how one goes about providing an evidence-based approach to analysing the success or not of any approach to this matter.

Music: LCD Soundsystem - Someone Great.


[1] Copeland WE. et al. Adult Functional Outcomes of Common Childhood Psychiatric Problems: A Prospective, Longitudinal Study. JAMA Psychiatry. 2015. July 15.

[2] Lahey BB. Why Are Children Who Exhibit Psychopathology at High Risk for Psychopathology and Dysfunction in Adulthood? JAMA Psychiatry. 2015. July 15.

[3] Chorozoglou M. et al. Preschool hyperactivity is associated with long-term economic burden: evidence from a longitudinal health economic analysis of costs incurred across childhood, adolescence and young adulthood. Journal of Child Psychology and Psychiatry. 2015. June 13.

---------- Copeland WE, Wolke D, Shanahan L, & Costello EJ (2015). Adult Functional Outcomes of Common Childhood Psychiatric Problems: A Prospective, Longitudinal Study. JAMA psychiatry PMID: 26176785

Monday, 27 July 2015

Incontinence and paediatric autism

Urinary incontinence - "the unintentional passing of urine" - is a fairly common issue affecting millions of people of all ages worldwide. Achieving full bladder and bowel control is seen as a typical part of growing up but for some children, particularly those diagnosed with a behavioural or developmental condition, issues with incontinence can persist much later into life [1].

The findings reported by Alexander von Gontard and colleagues [2] bring the issue of incontinence into the autism research spotlight with their observations that: "children with ASD [autism spectrum disorder] are at a greater risk of being affected by different forms of incontinence and LUTS [lower urinary tract symptoms]."

Based on responses to a questionnaire "referring to incontinence and the International Consultation on Incontinence Questionnaire-Pediatric LUTS (ICIQ-CLUTS)" researchers were able to compare results for 40 children diagnosed with ASD (mean age 11 years) with 43 aged-matched asymptomatic controls. Assessing various different types of incontinence, results suggested that nearly a third of participants with ASD showed nocturnal enuresis (night-time urinary incontinence) and nearly a quarter with daytime urinary incontinence. Control responses were 0% and ~5% respectively. Presentation of lower urinary tract symptoms (LUTS) in general were more frequently noted in the ASD group including "urgency and postponement".

Given that psychological symptoms can to some extent also overlap with incontinence issues, researchers also reported that "children with ASD showed higher rates of clinically relevant psychological symptoms (externalizing and internalizing symptoms), and according to the psychiatric interview, they had higher rates of comorbid psychological disorders." The conclusion: "children with ASD are at a greater risk of being affected by different forms of incontinence and LUTS. Therefore, screening for incontinence and, if indicated, treatment of these disorders is recommended."

This is not the first time that incontinence issues have been reported as occurring alongside a diagnosis of autism. Geier and colleagues [3] observed a fairly high number of their cohort with autism (mean age ~ 6 years) as also presenting with incontinence issues. Other studies have suggested a connection between certain medication use and the onset of incontinence in cases of autism [4]. Incontinence has tended to be something of unspoken issue in autism research and practice down the years as reports of children 'still in nappies' have circulated. I can't say for sure why such issues seemed to have been just left as part of the expected outcome for children with 'special needs' as the earlier article from von Gontard [1] described them, but it strikes me that we should perhaps be doing more to tackle such issues when present. The idea that continence problems might also have specific presentation profile(s) when noted in cases of autism is also interesting in light of other work [5] suggesting that screening for autism in case of "functional defecation disorders" might be indicated. Added to research on slow bowel transit time and autism (see here) and the closer inspection of general incontinence issues allied to autism is very much indicated.

Music: The Beatles - Hello Goodbye. Well, make up your mind...


[1] von Gontard A. Urinary incontinence in children with special needs. Nat Rev Urol. 2013 Nov;10(11):667-74.

[2] von Gontard A. et al. Incontinence in children with autism spectrum disorder. Journal of Pediatric Urology. 2015. May 22.

[3] Geier DA. et al. A prospective Cross-sectional Cohort Assessment of Health, Physical, and Behavioral Problems in Autism Spectrum Disorders. Maedica (Buchar). 2012 Sep;7(3):193-200.

[4] Kumazaki H. et al. Risperidone-associated urinary incontinence in patients with autistic disorder with mental retardation. J Clin Psychopharmacol. 2014 Oct;34(5):624-6.

[5] Peeters B. et al. Autism spectrum disorders in children with functional defecation disorders. J Pediatr. 2013 Sep;163(3):873-8.

---------- von Gontard A, Pirrung M, Niemczyk J, & Equit M (2015). Incontinence in children with autism spectrum disorder. Journal of pediatric urology PMID: 26052001

Saturday, 25 July 2015

Medical comorbidity and adult autism (again)

Regular readers are probably tired of reading blog titles like the one for today on this site. It's not as if the idea that a diagnosis of autism might predispose someone to quite a few more comorbid conditions (see here and see here) hasn't been discussed on quite a few occasions.

But just in case the message hasn't got through, I draw your attention to the paper by Kyle Jones and colleagues [1] concluding that: "Adults in this cohort of autism spectrum disorder first ascertained in the 1980s experience a high number of chronic medical conditions, regardless of intellectual ability."

The cohort in question was part of the 1980s Utah/UCLA autism epidemiologic study and some further follow-up of some of the people who participated in this quite early research foray into the epidemiology of autism. I say 'some' of the cohort because, as has been discussed previously on this blog (see here), sadly not everyone has survived over the years. Part and parcel of that 'excess mortality' in this cohort discussed by Bilder and colleagues [2] was thought due to "the presence of comorbid medical conditions" among other things.

The recent Jones paper "queried medical symptoms, disorders, hospitalizations, surgeries, and medication use" for 92 participants from the original cohort, mostly aged in their mid-30s. The found that: "The most common medical conditions were seizures, obesity, insomnia, and constipation." Further: "The median number of medical conditions per person was 11." Interestingly, researchers suggested that various factors might further increase the risk of such medical comorbidity including gender (females over males) and the presence of obesity. I say that bearing in mind the relatively small participant numbers included for study (69 of the 92 participants were male).

What's more to say on the basis of these and other findings? Well, the need for greater appreciation that autism seems to go much further than the presentation of core symptoms might be one thing (see here). As per my various ramblings on physical health and activity with the autism spectrum in mind (see here) tackling issues such as obesity might be another thing (see here) bearing in mind how various eating/feeding issues for example, might complicate matters when it comes to autism and obesity (see here). The same also goes for sleep (see here).

In the words of Jones et al: "Understanding of these conditions commonly experienced should direct community-based and medical primary care for this population." Once again, I cannot disagree with such sentiments.

Music: Glen Campbell - Wichita Lineman.


[1] Jones KB. et al. A description of medical conditions in adults with autism spectrum disorder: A follow-up of the 1980s Utah/UCLA Autism Epidemiologic Study. Autism. 2015. July 10.

[2] Bilder D. et al. Excess mortality and causes of death in autism spectrum disorders: a follow up of the 1980s Utah/UCLA autism epidemiologic study. J Autism Dev Disord. 2013 May;43(5):1196-204.

---------- Jones, K., Cottle, K., Bakian, A., Farley, M., Bilder, D., Coon, H., & McMahon, W. (2015). A description of medical conditions in adults with autism spectrum disorder: A follow-up of the 1980s Utah/UCLA Autism Epidemiologic Study Autism DOI: 10.1177/1362361315594798