Tuesday, 2 September 2014

The epigenetics of Chronic Fatigue Syndrome?

"These data are consistent with evidence of multisystem dysregulation in CFS [Chronic Fatigue Syndrome] and implicate the involvement of DNA modifications in CFS pathology". So said the paper by Wilfred de Vega and colleagues [1] (open-access here) which, I think, represents a bit of a first for CFS with their examination of the possible role of epigenetic modifications in relation to the condition(s) [2].

Ladies first @ Wikipedia 
I have to say that I was really quite excited by the de Vega paper and the fact that someone has actually started to apply the science of epigenetics (see here) to CFS. Indeed, only a few months back I mentioned the dearth of research in this area (see here) on the back of some interesting if preliminary findings in relation to things like HERV expression (see here) in ME (myalgic encephalomyelitis) which may very well be linked to methylation issues [3].

A few details about the de Vega paper might be useful, bearing in mind it is open-access:

  • This was a preliminary study which included 12 participants diagnosed with CFS and 12 asymptomatic controls, all women, and age- and BMI matched. Participants were recruited from the SolveCFS BioBank which also talks a little about this trial on their website (see here). Alongside the donation of a blood sample, participants completed the RAND-36, asking questions about health-related quality of life.  
  • "Methylomes in PBMCs [peripheral blood mononucleated cells] were examined" looking for any differences in methylation patterns between the groups. CpG sites were the analytical target, which as has been discussed in previous posts (see here), are those islands of DNA which can be methylated. Oh, and I should at this point also say that methylation or hypermethylation of specific parts of genes normally means gene silencing [4]. 
  • Alongside looking at any methylation differences between the groups, some analytical time was also devoted to gene ontology (GO) and network analysis with the aim to "identify major enriched biological themes". In other words, to look at the biological functions behind any differentially methylated DNA sites.
  • Results: perhaps unsurprisingly, there were some differences between the groups: "1,192 CpG sites were identified as differentially methylated between CFS patients and healthy control subjects, corresponding to 826 genes". These differences were present "across promoters, gene regulatory elements and within coding regions of genes". Further: "within genic regions, 30% of differentially methylated regions were hypomethylated and 70% were hypermethylated overall".
  • When it came to where in the genome differences were found and what functions might be impacted, well among other things, there was "an overrepresentation of terms related to immune cell regulation". With particular regard for gene regulatory elements, and bearing in mind: "Differential methylation of gene regulatory elements is classically associated with alterations in gene expression", the authors reported "a number" of differentially methylated CpGs in such elements related to the immune response. There is also some chatter about the de Vega data being "consistent with previous observations of a Th1- to Th2-mediated immune response shift in CFS".

As per my previous comment, this was quite a small-scale study which although valuable, only really dips it's toe into the epigenetic waters potentially associated with cases of CFS. The authors also note that their results "do not indicate whether these observed epigenetic differences are a cause or a consequence of CFS".

That being said, and knowing what we are starting to know about methylation and how we might be able to manipulate methylation patterns through for example, the use of DNA methyltransferase inhibitors [5], there may be some scope to explore whether a reversal or inhibition of hypermethylation for example, might exert some effect on the clinical signs and symptoms of at least some CFS. I say this without making any value judgements nor providing anything that looks, sounds or smells like clinical advice.

I'd like to think that the de Vega paper might stimulate further research into a possible role for epigenetics in relation to CFS. I say this acknowledging that genes and gene expression are likely to be only one part of the spectrum of presentations which fall under the CFS banner; not forgetting important areas such as the viral link to cases (see here), the growing emphasis on mitochondrial issues (see here) and even some potential role for those trillions of beasties which call our darkest recesses home (see here).

Music then, and Bill Haley and the Comets. Did you know he has an asteroid named after him?

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[1] de Vega WC. et al. DNA Methylation Modifications Associated with Chronic Fatigue Syndrome. PLoS One. 2014 Aug 11;9(8):e104757.

[2] Whiteley P. et al. Correlates of Overlapping Fatigue Syndromes. J Nutr Environ Med. 2004; 14: 247-259.

[3] Laska MJ. et al. (Some) cellular mechanisms influencing the transcription of human endogenous retrovirus, HERV-Fc1. PLoS One. 2013;8(1):e53895.

[4] Baylin SB. DNA methylation and gene silencing in cancer. Nature Clinical Practice Oncology. 2005; 2: S4-S11.

[5] Goffin J. & Eisenhauer E. DNA methyltransferase inhibitors-state of the art. Ann Oncol. 2002 Nov;13(11):1699-716.

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ResearchBlogging.org de Vega WC, Vernon SD, & McGowan PO (2014). DNA Methylation Modifications Associated with Chronic Fatigue Syndrome. PloS one, 9 (8) PMID: 25111603

Monday, 1 September 2014

Lithium for mood disorder symptoms in autism?

Modern classroom? @ Wikipedia 
The paper published by Matthew Siegel and colleagues [1] talking about some preliminary observations on the use of lithium where symptoms of mood disorder might be present in cases of autism spectrum disorder (ASD) caught my eye recently. Concluding that: "lithium may be a medication of interest for those who exhibit two or more mood disorder symptoms, particularly mania or euphoria/elevated mood" the sentiments of more research-to-do in this area presents some intriguing options. That all being said, side-effects of lithium supplementation may yet scupper any large-scale plans for using this medication option with this cohort as per the authors note that: "Forty-seven percent of patients were reported to have at least one side effect, most commonly vomiting (13%), tremor (10%), fatigue (10%), irritability (7%), and enuresis (7%)".

I had a few thoughts after reading the Siegel paper and their findings based on the use of Clinical Global Impressions - Improvement (CGI-I) ratings that "Forty-three percent of patients who received lithium were rated as "improved"". Mood disorders, or the symptoms of mood disorders, covers quite a bit of diagnostic ground. My recent discussions on bipolar disorder being fairly frequent in cases of Asperger syndrome (see here) coincide with the Siegel findings and particularly the case report by Frazier and colleagues [2] discussing a treatment regime which mentions the use of lithium. Other reports have similarly described the use of lithium as a possible management option where bipolar disorder and autism are comorbid [3]. What this tells me is that Siegel et al were not the first to look at lithium and autism (with comorbidity).

A quick glance at the other peer-reviewed literature in this area suggests that lithium is also finding some favour where less idiopathic types of autism are present. The paper by Luiz & Smith [4] talking about lithium as a promising treatment for Fragile X syndrome represents another potentially important area. The precise mode of action is still the subject of some conjecture but the overview provided by Chiu & Chuang [5] (open-access) gives some indication of what might be going on and could be similarly mapped on to potential biological mechanisms linked to autism and mood disorder if and when comorbid.

Finally, I have to make some mention about the important links being made between the use of lithium and the prevention of suicide in mood disorders [6]. I know it's not exactly a topic which makes great dinner party conversation but the emerging evidence base, alongside other important compounds, could potentially be life-saving for some people. Without trying to brush everyone on the autism spectrum as being at risk from suicide, the growing body of evidence suggesting that suicide ideation (see here) or suicide attempts (see here) might be more frequent for those on the autism spectrum [7] is something that needs to be taken seriously. This may imply that alongside appropriate societal support being provided, lithium might also have some important role to fulfil for some people...

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[1] Siegel M. et al. Preliminary Investigation of Lithium for Mood Disorder Symptoms in Children and Adolescents with Autism Spectrum Disorder. J Child Adolesc Psychopharmacol. 2014 August 5.

[2] Frazier JA. et al. Treating a child with Asperger's disorder and comorbid bipolar disorder. Am J Psychiatry. 2002 Jan;159(1):13-21

[3] Kerbeshian J. et al. Lithium carbonate in the treatment of two patients with infantile autism and atypical bipolar symptomatology. J Clin Psychopharmacol. 1987 Dec;7(6):401-5.

[4] Liu Z. & Smith CB. Lithium: A Promising Treatment for Fragile X Syndrome. ACS Chem Neurosci. 2014 May 15.

[5] Chiu CT. & Chuang DM. Molecular actions and therapeutic potential of lithium in preclinical and clinical studies of CNS disorders. Pharmacol Ther. 2010 Nov;128(2):281-304.

[6] Cipriani A. et al. Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis. BMJ. 2013 Jun 27;346:f3646.

[7] Paquette-Smith M. et al. History of Suicide Attempts in Adults With Asperger Syndrome. Crisis. 2014; 35: 273-277.

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ResearchBlogging.org Siegel M, Beresford CA, Bunker M, Verdi M, Vishnevetsky D, Karlsson C, Teer O, Stedman A, & Smith KA (2014). Preliminary Investigation of Lithium for Mood Disorder Symptoms in Children and Adolescents with Autism Spectrum Disorder. Journal of child and adolescent psychopharmacology PMID: 25093602

Saturday, 30 August 2014

Under-recognised co-occurring conditions in autism

A brief post to direct you to the paper by Nicolaidis and colleagues [1] talking about primary care for adults on the autism spectrum and mention of an issue quite important to this blog: "the recognition of associated conditions".
"When 900 years old you reach, look as good you will not".

Alongside the announcement of what seems like an interesting workshop organised by the US IACC (Interagency Autism Coordinating Committee) titled: "IACC Workshop on Under-Recognized Co-Occurring Conditions in ASD", comorbidity, whether psychiatric or more somatic, appearing alongside a diagnosis of autism seems to be moving up the agenda. The fact that both children and adults with autism are covered in the growing interest in this area is an important point to make, particularly in light of recent discussions on the direction of autism research (see here).

I'll leave you, yet again, with a link to the document produced by the UK group Treating Autism titled: "Medical Comorbidities in Autism Spectrum Disorders" which provides a pretty good overview of the peer-reviewed literature in this area, and importantly, is free to view, download and share.

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[1] Nicolaidis C. et al. Primary Care for Adults on the Autism Spectrum. Med Clin North Am. 2014 Sep;98(5):1169-1191.

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ResearchBlogging.org Nicolaidis C, Kripke CC, & Raymaker D (2014). Primary Care for Adults on the Autism Spectrum. The Medical clinics of North America, 98 (5), 1169-1191 PMID: 25134878

Friday, 29 August 2014

Oxytocin and autism: the hype?

Consider some excerpts from two recent papers looking at oxytocin (OXT) - the "love hormone"(!) - and the autism spectrum disorders (ASDs)...
“It’s not the years, honey. It’s the mileage”

"These findings indicate that dysregulated OXT biology is not uniquely associated with ASD social phenotypes as widely theorized, but instead variation in OXT biology contributes to important individual differences in human social functioning, including the severe social impairments which characterize ASD" according to Karen Parker and colleagues [1]. Some media accompanying this paper can be found here.

and

"Participants who received oxytocin showed no benefit following treatment on primary or secondary outcomes" according to the findings reported by Adam Guastella and colleagues [2].

For those who have followed the autism research scene over the years, you'll know that discussions about some connection between the neuropeptide oxytocin and autism have figured quite prominently. Indeed, I've covered OXT and autism before on this blog (see here). Media headlines like the one from the BBC suggesting that the "Love hormone 'helps autistic brain'" have been quite a regular feature, building up OXT to almost Saintly proportions. Unfortunately, as has often been the case with autism (sorry, the autisms) the science has not exactly followed the hype. Take for example the paper by Dadds and colleagues [3] who, prior to Guastella et al, reported that: "Compared to placebo, intranasal oxytocin did not significantly improve emotion recognition, social interaction skills, or general behavioral adjustment in male youths with autism spectrum disorders".

I'm not saying that all the research on OXT and autism is bunk because that's obviously not true [4]. As per the meta-analysis by Preti and colleagues [5] there may, for example, be some merit in continuing looking at where and when OXT use might be indicated including that related to important comorbidity [6]. The route of administration - intranasal (via the nose) - is for me, also a really interesting drug delivery method which may be applicable to many, many different medicines indicated for autism or peripheral symptoms/conditions.

But what the Parker and Guastella studies do tell us, is that once again, grand over-arching theories of autism seemingly serve no-one well. The study by Bedford and colleagues [7] perhaps said it best with their data arguing: "against cognitive theories of ASD which propose that a single underlying factor has cascading effects across early development leading to an ASD outcome". Replace cognitive theories with biological ones and science seems to be getting a little closer to what looks like the real nature of the autisms, heterogeneity, comorbidity and all... Oh, and then there is some interesting data on how oxytocin might be affecting the "second brain" (gastrointestinal function) as well as the grey-pinkish matter [8]. Move over melatonin (see here)?

Music to close and I'm happy to be stuck with you... (stick with the video, the music does eventually kick in).

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[1] Parker KJ. et al. Plasma oxytocin concentrations and OXTR polymorphisms predict social impairments in children with and without autism spectrum disorder. PNAS. 2014. August 4.

[2] Guastella AJ. et al. The effects of a course of intranasal oxytocin on social behaviors in youth diagnosed with autism spectrum disorders: a randomized controlled trial. J Child Psychol Psychiatry. 2014 August 2.

[3] Dadds MR. et al. Nasal oxytocin for social deficits in childhood autism: a randomized controlled trial. J Autism Dev Disord. 2014 Mar;44(3):521-31.

[4] LoParo D. & Waldman ID. The oxytocin receptor gene (OXTR) is associated with autism spectrum disorder: a meta-analysis. Mol Psychiatry. 2014 August 5.

[5] Preti A. et al. Oxytocin and autism: a systematic review of randomized controlled trials. J Child Adolesc Psychopharmacol. 2014 Mar;24(2):54-68.

[6] Hall SS. et al. Effects of intranasal oxytocin on social anxiety in males with fragile X syndrome. Psychoneuroendocrinology. 2012 Apr;37(4):509-18.

[7] Bedford R. et al. Additive effects of social and non-social attention during infancy relate to later autism spectrum disorder. Dev Sci. 2014 Jul;17(4):612-20.

[8] Welch MG. et al. Oxytocin regulates gastrointestinal motility, inflammation, macromolecular permeability, and mucosal maintenance in mice. Am J Physiol Gastrointest Liver Physiol. 2014 Aug 21. pii: ajpgi.00176.2014.

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ResearchBlogging.org Parker, K., Garner, J., Libove, R., Hyde, S., Hornbeak, K., Carson, D., Liao, C., Phillips, J., Hallmayer, J., & Hardan, A. (2014). Plasma oxytocin concentrations and OXTR polymorphisms predict social impairments in children with and without autism spectrum disorder Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1402236111


ResearchBlogging.org Guastella AJ, Gray KM, Rinehart NJ, Alvares GA, Tonge BJ, Hickie IB, Keating CM, Cacciotti-Saija C, & Einfeld SL (2014). The effects of a course of intranasal oxytocin on social behaviors in youth diagnosed with autism spectrum disorders: a randomized controlled trial. Journal of child psychology and psychiatry, and allied disciplines PMID: 25087908

Thursday, 28 August 2014

Minocycline for schizophrenia?

"Minocycline may improve the psychopathology of schizophrenia, especially the negative symptoms, and seems to be well tolerated".
A Bachelors Drawer (apparently) @ Wikipedia 

That was the finding from the systematic review and meta-analysis undertaken by Oya and colleagues [1] looking at the collected literature on the use of "minocycline augmentation therapy in patients with schizophrenia receiving antipsychotic agents". Augmentation therapy by the way, refers to the addition of minocycline to existing pharmacotherapy for schizophrenia.

I wasn't all that surprised to read the Oya paper given that for some time now, there have been scientific rumblings about how antibiotics might do quite a bit more than just 'killing bacteria' [2]. "Scientists shocked" was how one media report has previously talked about this area of research; which conjures up all-manner of visions of stunned science-types walking around with lab coats on and mouths and eyes wide open in amazement.

The reports that minocycline might act on the negative symptoms of schizophrenia (see here) is also quite an important detail, because these are often the symptoms which affect daily living skills, potentially manifesting as "losing interest and motivation in life and activities, including relationships and sex... [and a] lack of concentration, not wanting to leave the house and changes in sleeping patterns". These are also the symptoms which tend to respond less well to traditional management strategies like medication.

The final question(s) are how and why does minocycline affect cases of schizophrenia? The paper from Zhang and Zhao [3] (open-access) provides quite a good overview of the various hypotheses put forward. Unsurprisingly, some effect on inflammation figures quite strongly in the suggestions put forward. I could go on and on and on about the various research in this area (see here for example) but won't on this occasion. Instead, I'll direct you to a previous post I wrote on minocycline and Fragile X syndrome (see here) which mentions some effect from minocycline on matrix metalloproteinase-9 (MMP-9). I'd like to think that this is a potentially important point because of the tie-in with something like homocysteine (see here), the big H, which has also been mentioned with schizophrenia in mind (see here). Just speculatin' of course.

Music to close. Frank Sinatra and something about a lot of coffee in Brazil?

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[1] Oya K. et al. Efficacy and tolerability of minocycline augmentation therapy in schizophrenia: a systematic review and meta-analysis of randomized controlled trials. Hum Psychopharmacol. 2014 Aug 4.

[2] Levkovitz Y. et al. A double-blind, randomized study of minocycline for the treatment of negative and cognitive symptoms in early-phase schizophrenia. J Clin Psychiatry. 2010 Feb;71(2):138-49.

[3] Zhang L. & Zhao J. Profile of minocycline and its potential in the treatment of schizophrenia. Neuropsychiatr Dis Treat. 2014 Jun 17;10:1103-11.

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ResearchBlogging.org Oya K, Kishi T, & Iwata N (2014). Efficacy and tolerability of minocycline augmentation therapy in schizophrenia: a systematic review and meta-analysis of randomized controlled trials. Human psychopharmacology PMID: 25087702

Wednesday, 27 August 2014

Prenatal SSRI exposure and autistic traits

A quote to start today's post: "Our results suggest an association between prenatal SSRI exposure and autistic traits in children". That was a primary finding reported by Hanan El Marroun and colleagues [1] who looked at whether maternal depressive symptoms or a class of quite commonly used pharmaceutics - the selective serotonin reuptake inhibitors (SSRIs) - used to manage depressive symptoms, during pregnancy might impact on offspring development.
"Everything the light touches is our kingdom" 

Before progressing through some of the details around this area, I'm going to also direct your attention to a couple of important accompanying commentaries on the Marroun findings from Jones & McDonald [2] and Petersen and colleagues [3] (open-access). Both caution about reading too much too soon into the reported association between SSRIs and offspring outcomes, and the very real outcomes that can come about if psychiatric issues such as depression are not properly managed. Something I think most people might have heard about recently.

A few details about the Marroun paper might be useful:

  • Following some previous discussions correlating maternal SSRI use during pregnancy and offspring outcome with autism in mind (see here) including the quite recent papers by Harrington and colleagues [4] and Rai and colleagues [5], the authors looked to "prospectively determine whether intra-uterine SSRI exposure is associated with childhood autistic symptoms in a population-based study". 
  • "A total of 376 children prenatally exposed to maternal depressive symptoms (no SSRI exposure), 69 children prenatally exposed to SSRIs and 5531 unexposed children were included" for study. The commentary from Petersen et al notes how small a group were actually exposed to SSRIs and how "these numbers rapidly dwindled when it came to the measurement of the outcome".
  • The Child Behavior Checklist and Social Responsiveness Scale (SRS) were used to assess "pervasive developmental and affective problems" and "autistic traits" respectively. 
  • Results: aside from an association between prenatal selective serotonin reuptake inhibitor (SSRI) exposure and autistic traits in children, researchers also reported that: "Prenatal exposure to maternal depressive symptoms without SSRIs was related to both pervasive developmental (odds ratio (OR) = 1.44, 95% CI 1.07-1.93) and affective problems (OR = 1.44, 95% CI 1.15-1.81)". The suggested link between maternal depressive symptoms and autistic traits was to some degree weaker than the SSRI exposure correlation.
  • The authors conclude that: "Long-term drug safety trials are needed before evidence-based recommendations are possible" as once again I'll direct you to the Jones and Petersen commentaries.

In the same way that the emerging data on prenatal valproate exposure *might* link into offspring outcome including the presence of autism (see here), so the Marroun paper potentially adds another medicine to the list. I would perhaps temper that last sentence by adding that the valproate story is perhaps a little further along in terms of rodent models of prenatal valproate exposure mimicking some features of autism (see here) and the data providing something like mechanisms to be looked at with further investigations in mind [6]. Still, the CDC Treating for Two initiative might be once again relevant.

The added complication with the SSRI-autism correlation is the discussion about maternal depressive symptoms also potentially mediating any link with offspring autism or autistic traits. The paper by Sørensen and colleagues [7] (open-access here) kinda hinted that this and other important confounding factors might impact on any studies of association, including details like: "paternal antidepressant use during the time of pregnancy was not associated with an increased risk of autism spectrum disorders, except for a 30% increase when the fathers took SSRI". Even more recently Clements and colleagues [8] talked about how maternal "major depression" confounded any medication relationship with offspring presentation. They also talked about a link with ADHD which brings me back to yesterday's post on comorbidity (see here)...

One would do well not to discount such confounding factors at this stage. Indeed, if one assumes that depression might have a physiological link to something like inflammation for example [9] we then start to arrive at the increasingly important research looking at maternal inflammation as being a risk factor for offspring autism (see here). And before you ask, yes, C-reactive protein (CRP) has been linked to depressive symptoms as per the meta-analysis by Valkanova and colleagues [10].

The Marroun results are interesting and add something to an increasing bank of peer-reviewed literature [11] suggestive of a possible link between SSRI use during pregnancy and offspring outcomes. On the basis of the current existing literature and with my blogging caveat of no medical advice given or intended, I would be minded to conclude that there is quite a bit more experimental investigation to be done on this category of medicines. But I don't yet think there is enough clear evidence to conclusively put an elevated risk of offspring autism on the list of potential side-effects of these medicines.

Music then. Scissor Sisters and Laura.

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[1] Marroun HE. et al. Prenatal exposure to selective serotonin reuptake inhibitors and social responsiveness symptoms of autism: population-based study of young children. The British Journal of Psychiatry. 2014; 205: 95-102.

[2] Jones I. & McDonald L. Living with uncertainty: antidepressants and pregnancy. The British Journal of Psychiatry. 2014; 205: 103-104.

[3] Petersen I. et al. Prenatal exposure to selective serotonin reuptake inhibitors and autistic symptoms in young children: another red herring? The British Journal of Psychiatry. 2014; 205: 105-106.

[4] Harrington RA. et al. Prenatal SSRI Use and Offspring With Autism Spectrum Disorder or Developmental Delay. Pediatrics. 2014 Apr 14.

[5] Rai D. et al. Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: population based case-control study. BMJ. 2013 Apr 19;346:f2059.

[6] Bambini-Junior V. et al. Prenatal Exposure to Valproate in Animals and Autism. Comprehensive Guide to Autism. 2014: 1779-1793.

[7] Sørensen MJ. et al. Antidepressant exposure in pregnancy and risk of autism spectrum disorders. Clin Epidemiol. 2013 Nov 15;5:449-59.

[8] Clements CC. et al. Prenatal antidepressant exposure is associated with risk for attention-deficit hyperactivity disorder but not autism spectrum disorder in a large health system. Molecular Psychiatry. 2014. August 26.

[9] Berk M. et al. So depression is an inflammatory disease, but where does the inflammation come from? BMC Med. 2013 Sep 12;11:200.

[10] Valkanova V. et al. CRP, IL-6 and depression: a systematic review and meta-analysis of longitudinal studies. J Affect Disord. 2013 Sep 25;150(3):736-44.

[11] Rais TB. & Rais A. Association Between Antidepressants Use During Pregnancy and Autistic Spectrum Disorders: A Meta-analysis. Innov Clin Neurosci. 2014 May;11(5-6):18-22.

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ResearchBlogging.org Marroun, H., White, T., van der Knaap, N., Homberg, J., Fernandez, G., Schoemaker, N., Jaddoe, V., Hofman, A., Verhulst, F., Hudziak, J., Stricker, B., & Tiemeier, H. (2014). Prenatal exposure to selective serotonin reuptake inhibitors and social responsiveness symptoms of autism: population-based study of young children The British Journal of Psychiatry, 205 (2), 95-102 DOI: 10.1192/bjp.bp.113.127746

Tuesday, 26 August 2014

76% of youths with autism meet ADHD diagnostic criteria?

Autism is not normally a stand-alone diagnosis. I've mentioned that point a few times on this blog, stressing how a clinical diagnosis of autism appears to increase the risk of various other behavioural, psychiatric and somatic diagnoses also [variably] being present over a lifetime. Part of that comorbidity has been talked about in discussions about ESSENCE (see here) and the excellent document produced by Treating Autism on medical comorbidities occurring alongside autism (see here) for example. Prof. Gillberg's recent scientific publication called 'Autism Plus Versus Autism Pure' [1] kinda adds to this notion and his very strongly worded sentiments: "It is high time that the comorbidities, sometimes even more important than the autism, came back on the diagnostic agenda".
Cheeky... @ Wikipedia 

Outside of the more traditional comorbidities mentioned in the same breath as some autism, such as learning disability (intellectual disability) and epilepsy or seizure-type disorders, quite a lot of attention is being focused on the overlap between autism and attention-deficit hyperactivity disorder (ADHD). Indeed, the paper by Gagan Joshi and colleagues [2] very much thrusts ADHD into the autism diagnostic arena with their assertion of: "A high rate of comorbidity with ADHD was observed in psychiatrically referred youth with ASD [autism spectrum disorder], with a clinical presentation typical of the disorder".

The Joshi paper sought to "compare the clinical presentation of ADHD between youth with autism spectrum disorder (ASD) and ADHD and a sample of youth with ADHD only". What they found is something remarkably similar to the typical presentation of ADHD (without autism) insofar as age of onset and "distribution of diagnostic subtypes, the qualitative and quantitative symptom profile, and symptom severity". I might add that their participant group was classified as "High-Functioning" (their words not mine) so one needs to be mindful that only one part of the autism spectrum was surveyed.

What is perhaps slightly worrying from the Joshi results was the finding that: "a significant majority of ASD youth with ADHD failed to receive appropriate ADHD treatment". ADHD treatment, as I've mentioned in previous posts, normally implies pharmacotherapy but can also include other intervention options as per discussions on things like dietary changes potentially being useful for some (see here). Indeed, I've talked about the some of the results from things like the use of a gluten- and casein-free (GFCF) diet when applied to autism and how ADHD-type symptoms might be the more important targets for intervention (see here). The idea also that outside of just affecting ADHD symptom profiles, intervention might also have knock-on effects for other areas as per the review by Daley and colleagues [3] is similarly important.

I don't want to linger further on this issue aside from reiterating that the presentation of autism is, more often than not, part of a complex tapestry of presentation which can cover various other diagnostic categories. ADHD or sub-threshold ADHD-type symptoms are being realised as fairly frequent companions to a diagnosis of autism. The changes to the diagnostic criteria for ADHD (see here) will no doubt further expand the link between autism and ADHD, placing yet more emphasis on how autism is not normally a stand-alone diagnosis.

Music to close. Ray Charles and You Don't Know Me.

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[1] Gillberg C. & Fernell E. Autism Plus Versus Autism Pure. J Autism Dev Disord. 2014 Jun 24.

[2] Joshi G. et al. Symptom Profile of ADHD in Youth With High-Functioning Autism Spectrum Disorder: A Comparative Study in Psychiatrically Referred Populations. J Atten Disord. 2014 Aug 1. pii: 1087054714543368.

[3] Daley D. et al. Behavioral Interventions in Attention-Deficit/Hyperactivity Disorder: A Meta-Analysis of Randomized Controlled Trials Across Multiple Outcome Domains. J Am Acad Child Adolesc Psychiatry. 2014 Aug;53(8):835-847.e5.

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ResearchBlogging.org Joshi G, Faraone SV, Wozniak J, Tarko L, Fried R, Galdo M, Furtak SL, & Biederman J (2014). Symptom Profile of ADHD in Youth With High-Functioning Autism Spectrum Disorder: A Comparative Study in Psychiatrically Referred Populations. Journal of attention disorders PMID: 25085653