Saturday, 27 August 2016

On autism spectrum disorder [research] validity

Today I'm directing your reading attention to a really, really interesting paper by Lynn Waterhouse and colleagues [1] (open-access) whose review findings suggest that: "the ASD [autism spectrum disorder] diagnosis lacks biological and construct validity."

The paper is a bit of a long read but most definitely worth it as the quite complicated subject of exactly what goal the label of autism actually serves is discussed. The results of various questions posed by the authors suggest: "No unitary ASD brain impairment or replicated unitary model of ASD brain impairment exists. ASD core diagnostic symptoms are not uniquely linked and are only very rarely expressed without nondiagnostic symptoms. ASD has no reliable early predictor, no unitary developmental course, no unitary life outcome, no unitary recurrence risk, no unitary pattern of BAP [broader autism phenotype] features, and no standard homogeneous subgroups." They conclude that from a research perspective at least, disbanding the label of autism as it currently stands is the next logical step. Said disbanding "is likely to be reductive and uncomfortable" particularly when it comes to all those grand [sweeping] theories of autism put forward down the years. Feathers would not doubt be ruffled.

The authors do make reference to two important concepts when it comes how we might want to rethink autism: the Research Domain Criteria framework (RDoC) and Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations (ESSENCE). One is an attempt to move away from simple psychiatric labels as somehow denoting homogeneity, the other is the recognition that labels rarely appear in some sort of diagnostic vacuum. Both are in some way the future of autism research and indeed, the future is already now.

I'm impressed with the paper from Waterhouse et al. The authors have done a good job of basically saying that as things stand, one single label covering such a diverse and heterogeneous group is not fit for purpose. To see real progress in autism research, science needs to think more about those 'autisms' (see here) and stop using the label of autism as the starting point for research (see here). I struggle to disagree with both those sentiments and other authors appear to have reached similar conclusions [2]. Exactly what that means for the autism in the future - from both a research and clinical perspective - is still a little up in the air but the label has weathered change before and no doubt will continue to do so.

And if that isn't enough reading material for you, how about the latest instalment from the British Psychological Society here in Blighty when it comes to autism? Perhaps this will need a revision or two as the Waterhouse suggestions start to percolate through the research community?

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[1] Waterhouse L. et al. ASD validity. Review Journal of Autism and Developmental Disorders. 2016. Aug 10.

[2] Geier DA. et al. Examining genotypic variation in autism spectrum disorder and its relationship to parental age and phenotype. Appl Clin Genet. 2016 Jul 28;9:121-9.

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ResearchBlogging.org Waterhouse, L., London, E., & Gillberg, C. (2016). ASD Validity Review Journal of Autism and Developmental Disorders DOI: 10.1007/s40489-016-0085-x

Friday, 26 August 2016

What does the Autism Spectrum Quotient (AQ) actually measure?

"Higher AQ [Autism Spectrum Quotient] scores were associated with higher scores of loneliness, social anxiety, depression, and anxiety, as well as with lower scores of quality of life (QoL)."

Those were some of the key findings reported by Phil Reed and colleagues [1] who used the very popular 'are you autistic?' AQ screening tool to look at the presence of autistic traits "along with depression, anxiety, loneliness, quality of life, and social anxiety" in a University student cohort (N=413).

Finding that among their research population some 8% scored above the cut-offs used by the AQ, researchers also reported those important 'associations' all tied into QofL.

Accepting that I'm probably a little biased when it comes to the 'problematic' use of the AQ as a screening tool for autism (see here and see here), my interpretation of the Reed results plays into the idea that the AQ is certainly picking up something, but exactly what is still the source of some debate (see here). I might for example, point you in the direction of the findings by Kitazoe and colleagues [2] who, based on similar student cohort, talked about "qualitatively different groups" over and above "a single homogeneous group" when it came to high scorers on the AQ.

It is also pretty well accepted that issues such as social anxiety and depression are over-represented when it comes to a diagnosis of autism (see here and see here respectively) and one has to wonder whether the AQ might be tuned into to the features of those labels over and above core autism. Indeed, going back a few years, the findings reported by Kunihira and colleagues [3] kinda signalled as much where personality traits "toward an obsessional personality" were seemingly connected to AQ scores in a non-autistic population as well as "higher depression and anxiety." Such findings might also be 'useful' when it comes to looking at the AQ in the context of eating disorders too [4].

I look forward to seeing more research done on this important topic (something ripe for more University student research projects perhaps).

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[1] Reed P. et al. Loneliness and Social Anxiety Mediate the Relationship between Autism Quotient and Quality of Life in University Students. J Dev Phys Disabil. 2016. Aug 12.

[2] Kitazoe N. et al. Whether the Autism Spectrum Quotient consists of two different subgroups? Cluster analysis of the Autism Spectrum Quotient in general population. Autism. 2016 Apr 30. pii: 1362361316638787.

[3] Kunihira Y. et al. 'Autistic' traits in non-autistic Japanese populations: relationships with personality traits and cognitive ability. J Autism Dev Disord. 2006 May;36(4):553-66.

[4] Mansour S. et al. Emotions mediate the relationship between autistic traits and disordered eating: A new autistic-emotional model for eating pathology. Psychiatry Res. 2016 Aug 8;245:119-126.

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ResearchBlogging.org Reed, P., Giles, A., Gavin, M., Carter, N., & Osborne, L. (2016). Loneliness and Social Anxiety Mediate the Relationship between Autism Quotient and Quality of Life in University Students Journal of Developmental and Physical Disabilities DOI: 10.1007/s10882-016-9504-2

Thursday, 25 August 2016

Hospitalisation for infection and risk of death by suicide

"An increased risk of death by suicide was found among individuals hospitalized with infection in prospective and dose-response relationships. These findings indicate that infections may have a relevant role in the pathophysiological mechanisms of suicidal behavior."

Some intriguing data has been recently reported by Helene Lund-Sørensen and colleagues [1] (open-access) examining the possibility that certain types of infection (or perhaps the biological response to infection) might increase the risk of suicidal behaviour. Some good media coverage about the study can be read here.

If your sticking with my interpretation of the results, Denmark was the the source of the data, as yet again one of those quite amazing Scandinavian population registries provides a starting cohort of around 7 million people "observed for a total of 149 061 786 person-years" from which subsequent results are derived.

Sadly, some 32,000 suicides (completed) were recorded during the study period; around a quarter of such reports were among people who had "previously been diagnosed as having an infection during a hospitalization." Such data was reported in terms of incidence rate ratios (IRRs) and equated to those hospitalised for infection being 42% more likely to die by suicide than those not hospitalised for infection. The 'dose-response' relationship eluded to in that opening sentence refers to the finding that the more serious the infection and/or the longer the hospital stay (treatment), the more likely the risk of death by suicide. Such an association also held when adjustment was made for potential confounding variables such as sex, age and socio-economic status.

Accepting that suicide - whether contemplated, attempted or completed - is a very complicated and often very individual process these are interesting results. Of course one has to be slightly careful in drawing too many conclusions from such data given both the large number of 'infections' included as part of the analyses and the possible "psychological effect of being hospitalized with a severe infection." The Lund-Sørensen data is still data built on association not necessarily 'cause and effect'.

Still, adding to the increasingly popular idea that infections or the biological response to infection at critical periods of development and life can seemingly affect behaviour (see here and see here for a few more potential examples) as well as physiology, the current study makes an important case for further study in this area. Not least because even if only playing a role in a small proportion of suicides, there may be important screening and possible intervention avenues to explore. I'm also wondering what such a possible association might mean with regards to the 'transmission' of certain infections and potential suicide risk? Y'know added to the speculation that some types of depression could perhaps be relabelled as an infectious disease [2] and in light of the strong connection between depression and suicidal behaviours...

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[1] Lund-Sørensen H. et al. A Nationwide Cohort Study of the Association Between Hospitalization With Infection and Risk of Death by Suicide. JAMA Psychiatry. 2016. Aug 10.

[2] Canli T. Reconceptualizing major depressive disorder as an infectious disease. Biology of Mood & Anxiety Disorders. 2014; 4:10

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ResearchBlogging.org Lund-Sørensen H, Benros ME, Madsen T, Sørensen HJ, Eaton WW, Postolache TT, Nordentoft M, & Erlangsen A (2016). A Nationwide Cohort Study of the Association Between Hospitalization With Infection and Risk of Death by Suicide. JAMA psychiatry PMID: 27532502

Wednesday, 24 August 2016

ALSPAC says maybe to link between prenatal paracetamol exposure and childhood behavioural difficulties

ALSPAC - the Avon Longitudinal Study of Parents and Children - continues to give in research terms as today I approach the findings reported by Evie Stergiakouli and colleagues [1]. They observed that: "Children exposed to acetaminophen [paracetamol] prenatally are at increased risk of multiple behavioral difficulties, and the associations do not appear to be explained by unmeasured behavioral or social factors linked to acetaminophen use insofar as they are not observed for postnatal or partner’s acetaminophen use." Some media attention for the study can be found here.

Continuing the research journey on a topic not unfamiliar to this blog (see here and see here for example) that exposure to paracetamol during the nine months that made us might not be a totally benign affair, Stergiakouli et al analysed data for some 7,700 mothers included in the initiative between 1991 and 1992. Questions about paracetamol use at 18 and 32 weeks of pregnancy were asked of mothers and maternal reports of child behaviour problems at 7 years using the Strengths and Difficulties Questionnaire (SDQ) were thrown into the research mix.

Results: those behavioural difficulties potentially associated with maternal paracetamol use at both 18 and 32 weeks of pregnancy included both conduct problems and hyperactivity symptoms. Researchers were also able to record no (significant) connection between post-natal paracetamol use nor partner paracetamol use and childhood behavioural problems. They concluded that "the timing of acetaminophen use might be important" and that "the association between prenatal acetaminophen exposure and childhood behavioral problems is not explained by unmeasured familial factors linked to both acetaminophen use and childhood behavioral problems and that the findings are consistent with an intrauterine effect."

Combined with the various other studies suggesting an association between prenatal exposure to paracetamol and offspring behavioural 'issues' the case for a possible link is growing. ALSPAC has a number of methodological strengths to its design, not least "the availability of prospective information on acetaminophen use during the second and third trimesters of pregnancy and postnatally by the mother and by her partner." The fact that numerous potentially confounding variables were also controlled for is another bonus for the study results: "maternal age at birth, parity, socioeconomic status, smoking and alcohol consumption during pregnancy, prepregnancy body mass index (BMI), maternal self-reported psychiatric illness, and possible indications for acetaminophen use." This is pretty strong data (or at least as strong as the other data published on this topic).

Mechanism(s) of effect? Still something that needs a little more work I'm afraid, before any precise information is revealed. The authors go with some ideas based on the "endocrine-disrupting properties of acetaminophen" for example, but let's wait and see before anyone makes too many sweeping generalisations. I might however suggest that the possibility of a link between paracetamol exposure and asthma (see here) could be important in light of what asthma might mean for the risk of presentation of ADHD (attention-deficit hyperactivity disorder) for example (see here). Just a thought and bearing in mind the evidence linking paracetamol use and asthma is not always all on-way.

Further studies are required on this increasingly important topic. Please also bear in mind no medical or clinical advice is given or intended on this blog. Speak to your physician if you need more information about pain relief during pregnancy.

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[1] Stergiakouli E. et al. Association of Acetaminophen Use During Pregnancy With Behavioral Problems in Childhood. JAMA Pediatrics. 2016. Aug 15.

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ResearchBlogging.org Stergiakouli, E., Thapar, A., & Davey Smith, G. (2016). Association of Acetaminophen Use During Pregnancy With Behavioral Problems in Childhood JAMA Pediatrics DOI: 10.1001/jamapediatrics.2016.1775

Tuesday, 23 August 2016

Autism and/or ADHD in Down's syndrome

"High rates of ASD [autism spectrum disorder] and ADHD [attention-deficit hyperactivity disorder] were found: 17 (42%) and 14 (34%) of the 41 children met DSM criteria for ASD and ADHD respectively."

That was the conclusion reached in the study by Ulrika Oxelgren and colleagues [1] looking at the "prevalence of autism spectrum disorder (ASD) and attention-deficit-hyperactivity disorder (ADHD) in a population-based group of children and adolescents with Down syndrome." The population in this case comprised 60 children and young adults diagnosed with Down's syndrome (Down syndrome if you prefer) and the gold-standards that are the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) were the instruments of choice when arriving at decisions of whether autism might be present or not.

New news? No it's not new news that autism (whether in diagnosis or in traits) may be over-represented when it comes to Down's syndrome (see here and see here for other research-based examples). There has even been a suggestion that regression - a key part of at least some autism - may be part and parcel of some cases of Down's syndrome (see here) too.

Oxelgren et al suggest that the combination of Down's syndrome and the "intellectual disability and medical disorders" that can accompany Down's syndrome added to a possible higher rate of autism potentially make for "a severely disabled group" worthy of far greater attention when it comes to screening and intervention. I don't think anyone would disagree with such sentiments and in particular, how preferential autism screening should once again be added to a growing list of diagnoses and labels. Indeed, such data in particular directs further attention to the link between intellectual (learning) disability and autism (see here and see here).

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[1] Oxelgren UW. et al. Prevalence of autism and attention-deficit-hyperactivity disorder in Down syndrome: a population-based study. Dev Med Child Neurol. 2016 Aug 9.

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ResearchBlogging.org Oxelgren UW, Myrelid Å, Annerén G, Ekstam B, Göransson C, Holmbom A, Isaksson A, Åberg M, Gustafsson J, & Fernell E (2016). Prevalence of autism and attention-deficit-hyperactivity disorder in Down syndrome: a population-based study. Developmental medicine and child neurology PMID: 27503703

Monday, 22 August 2016

"Theory of mind is not theory of emotion"

A rather interesting paper by Beth Oakley and colleagues [1] (open-access might be available here) appeared recently providing a "cautionary note on the Reading the Mind in the Eyes Test" [2], one of the premier assessments thought to offer a performance-based measure "involving mental state attribution and complex facial emotion recognition from photographs where only the eye region of the face is available."

Most people with some knowledge about autism research history will have heard about the proposal that Theory of Mind (ToM) - a term often used to cover that "mental state attribution" - might be affected in cases of autism (see here) and indeed, how careers and reputations have been made on such a generalisation. These days ToM is less and less being talked about as the heterogeneity of the autism spectrum becomes better understood and how specificity in particular, has proved to be an Achilles' heel for the concept (see here).

One of the emerging ideas to account for some of the results obtained using the Reading the Mind in the Eyes test (RMET) in cases of autism is that alexithymia - a construct characterised by an inability to describe or understand emotions - might actually be the more important issue than autism per se. The idea being that alexithymia can co-occur alongside some autism and that for those presenting with that combination, ToM and assessments like RMET might be problematic.

So Oakley et al delved a little deeper into some of the hows and whys of some of the RMET results obtained with autism in mind and whether "the RMET indexes emotion recognition, associated with alexithymia, or ToM, associated with ASD [autism spectrum disorder]." They did it on the basis of examining a small group of participants diagnosed with an ASD (n=19) alongside 24 participants without autism. Alexithymia was assessed using "the 20-item Toronto Alexithymia Scale (TAS–20)." Autism symptoms severity was measured using the Autism Spectrum Quotient (50) (oh dear..) and "current functioning" in the autism group was assessed using the gold-standard that is the Autism Diagnostic Observation Schedule (ADOS) (more like it).

Results: well bearing in mind the small participant numbers and the need for further independent replication of the findings, "Reading the Mind in the Eyes Test (RMET) performance was unaffected by autism spectrum disorder... but was negatively impacted by alexithymia." Indeed, we are told that: "Six ASD and eight control participants met the criterion for severe alexithymia, with a score of 61 or above on the 20-item Toronto Alexithymia Scale (TAS–20)." Further: "in individuals with ASD and comorbid alexithymia, it is alexithymia, rather than ASD per se, that impairs emotion recognition performance."

I probably don't need to say too much more about this line of research and its important implications outside of perhaps the requirement to screen for alexithymia as and when autism is diagnosed. Insofar as the idea of an "alexithymia hypothesis of emotion-related deficits in ASD", this does sound like a tantalising option but again, I'd be slightly reluctant to go all-in with yet another grand theory for autism given the trials and tribulations that psychological theories in particular have faced over the years with autism in mind. As to other potential impacts from work such as this, well, assertions that a lack of empathy might the root of all evil (see here) also made by proponents of ToM might do well to take on board a role for alexithymia in any future judgements...

Minus any charges of plagiarism, I leave you with the general summary from Oakley and colleagues:

"This study suggests that a highly popular test of the ability to detect what someone else is thinking—the Reading the Mind in the Eyes Test—is instead a test of the ability to recognize another person’s emotional expression. This is important because it suggests that patients who perform badly on this test may still be able to understand another person’s mental state and that, conversely, patients who perform well on this test may still have difficulties in mental state understanding."

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[1] Oakley BF. et al. Theory of mind is not theory of emotion: A cautionary note on the Reading the Mind in the Eyes Test. J Abnorm Psychol. 2016 Aug;125(6):818-23.

[2] Baron-Cohen S. et al. The “Reading the Mind in the Eyes” Test: Complete Absence of Typical Sex Difference in ~400 Men and Women with Autism. PLoS ONE. 2015; 10(8).

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ResearchBlogging.org Oakley BF, Brewer R, Bird G, & Catmur C (2016). Theory of mind is not theory of emotion: A cautionary note on the Reading the Mind in the Eyes Test. Journal of abnormal psychology, 125 (6), 818-23 PMID: 27505409

Saturday, 20 August 2016

Polycystic ovary syndrome (PCOS) and risk of psychiatric disorder

"Polycystic ovary syndrome (PCOS) is an endocrine disorder affecting 5-15% of reproductive-aged women and characterized by high levels of circulating androgens."

OK, go on.

"Women with PCOS had higher risks for a range of psychiatric disorders not shown before. Elevated risk in their siblings suggests shared familial factors between PCOS and psychiatric disorders."

So said the findings reported by Carolyn Cesta and colleagues [1] who using Swedish national register data concluded that there may be something more to see when it comes to the presentation of PCOS and risk of receipt of a comorbid psychiatric label. Included under the banner of psychiatric conditions were a variety of different labels: "schizophrenia, bipolar disorder, depressive and anxiety disorders, eating disorders, personality and gender identity disorder, autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), tics, attempted and completed suicide." Personally, I'm not so sure these days that ASD should necessarily be termed a psychiatric condition but that was a decision made by the authors and I'm sure others might disagree with me.

Participant numbers for the Cesta study were in the tens of thousands as one might expect when it comes to research using the various Scandinavian registries ("all women diagnosed with PCOS between 1990 and 2013 (n = 24,385), their full-siblings (n = 25,921), plus matched individuals (1:10/100) from the general population and their full-siblings") and results were presented as odds ratios and adjusted odds ratios (AORs).

One particular part of the Cesta results stood out for me bearing in mind the primary focus of this blog: "Significantly higher AORs were found for ASD in both brothers and sisters of women with PCOS." Added to other research by Sunday Kosidou and colleagues [2] discussed on this blog (see here), these results potentially tap into some history in autism research talking about androgens and autism (minus any sweeping generalisations).

"Health professionals treating women with PCOS should be aware that these patients – as well as their family members – are important targets for mental health care." Yet again the idea that preferential screening for something like autism and other labels appears as further clues potentially emerge as to the risk factors for autism. The familial aspect to the Cesta data also provide some ideas for research directions too and I might, speculatively, suggest at least one course of future investigation (see here).

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[1] Cesta CE. et al. Polycystic ovary syndrome and psychiatric disorders: Co-morbidity and heritability in a nationwide Swedish cohort. Psychoneuroendocrinology. 2016; 73: 196-203.

[2] Kosidou K. et al. Maternal polycystic ovary syndrome and the risk of autism spectrum disorders in the offspring: a population-based nationwide study in Sweden. Mol Psychiatry. 2015 Dec 8.

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ResearchBlogging.org Cesta, C., Månsson, M., Palm, C., Lichtenstein, P., Iliadou, A., & Landén, M. (2016). Polycystic ovary syndrome and psychiatric disorders: Co-morbidity and heritability in a nationwide Swedish cohort Psychoneuroendocrinology, 73, 196-203 DOI: 10.1016/j.psyneuen.2016.08.005