Wednesday, 31 August 2016

Filicide and autism

"The choice of the victim was in line with emerging evidence indicating that children with disabilities in general and with autism in particular are frequent victims of filicide-suicide."

The case report presented by Declercq and colleagues [1] reflects yet another uncomfortable topic discussed on this blog and how the 'deliberate act of murdering ones own child' is something unfortunately not unfamiliar when it comes to the label of autism. Declercq et al provide quite a raw account of paternal filicide and how circumstances and state of mind may have been important variables in determining the eventual outcome. Not least is the intersection between "schizoid personality disorder and homicide and violence" that appears to have been linked to such an act (minus any sweeping generalisations).

This is not the first time that the words 'filicide' and 'autism' have appeared together in the peer-reviewed science domain as per other examinations of media reporting of such acts [2] that have revealed a disturbing trend when it comes to "disabled children as victims of filicide-suicide." The fact that some authors have even gone as far as talking about "prevention strategies" [3] specifically with filicide in families with autistic children should tell you that despite being an uncomfortable discussion, this is not something that can be just brushed under the carpet.

Having read about quite a few accounts of filicide-suicide where autism has figured down the years and the many and varied responses to such acts (see here and see here for example), it's clear that there are a number of different viewpoints when it comes to this emotive topic. Murder is murder and that point should never be forgotten; made all the more harrowing by the fact that it was a parent and a trusted caregiver who carried out such a heinous act. Irrespective of circumstances, the murdered child is the victim; let us not forget that.

I also believe that it is right to research and question how and why such acts come about. In the same way that the motives of autistic people who themselves kill a parent (although rare) need to be understood, so one needs to know what might drive a parent to kill their child with autism. Such questioning does not condone such actions; neither does it or should it lessen the impact of such actions. It merely highlights the idea that to know why such acts occur can potentially prevent further instances happening in other cases. If such knowledge saves only one child, it will be worthwhile.

I'm not going to venture further into the possible reasons why parents murder their children - whether with autism or not - because they are likely to be complex and variable from case to case bearing in mind that becoming a parent does not automatically make a bad person into a good person. What I will reiterate is that murder is murder and if there is even the slightest hope that science can identify factors that might place a child at risk, resources aplenty should be poured into looking.


[1] Declercq F. et al. A Case Study of Paternal Filicide-Suicide: Personality Disorder, Motives, and Victim Choice. J Psychol. 2016 Aug 18:1-13.

[2] Coorg R. & Tournay A. Filicide-suicide involving children with disabilities. J Child Neurol. 2013 Jun;28(6):745-51

[3] Palermo MT. Preventing filicide in families with autistic children. Int J Offender Ther Comp Criminol. 2003 Feb;47(1):47-57.

---------- Declercq F, Meganck R, & Audenaert K (2016). A Case Study of Paternal Filicide-Suicide: Personality Disorder, Motives, and Victim Choice. The Journal of psychology, 1-13 PMID: 27537187

Tuesday, 30 August 2016

A prenatal 'unhealthy' diet and offspring ADHD?

'Scientists study link between unhealthy pregnancy diet and ADHD' went one media headline covering the paper by Jolien Rijlaarsdam and colleagues [1].

The name of the research game was again to draw on data derived from ALSPAC (Avon Longitudinal Study of Parents and Children) (yes, again) to look-see "the degree to which prenatal high-fat and -sugar diet might relate to ADHD [attention-deficit hyperactivity disorder] symptoms via IGF2 DNA methylation for early-onset persistent (EOP) versus low CP [conduct problems] youth." In other words: "Experts examine how a diet high in fat and sugar could alter baby’s DNA in a way that might cause behavioural problems."

To do this meant looking at around 80 youth presenting with early-onset conduct problems compared with around 80 youths who didn't have the same magnitude of issues. Data on maternal nutrition captured for the two groups (ALSPAC did a lot of data collecting!) was cross-referenced with group status and also epigenetic - methylation - status of the insulin-like growth factor 2 gene (IGF2). IGF2 is a gene that seems to be pretty active during the nine months that made us but less so as we enter the big, wide world. As the name suggests it seems to have a 'growth' role which is probably why issues with this gene have also been associated with the development of a number of cancers.

Results: "Prenatal ‘unhealthy diet’ was positively associated with IGF2 methylation at birth for both the EOP and low CP youth." Minus any 'blame', such results suggest that maternal diet might be important for the developing child. I know this is it not exactly a shock, but in these days of more and more research and clinical focus on the special time called pregnancy, the idea that particular epigenetic changes might come from a chosen diet is a potentially important one.

Further: "For EOP only: (a) higher IGF2 methylation predicted ADHD symptoms; and (b) prenatal ‘unhealthy diet’ was associated with higher ADHD symptoms indirectly via higher IGF2 methylation." The higher IGF2 methylation - higher ADHD symptoms is an interesting association. Methylation - the addition of a methyl group - is normally taken to mean gene silencing suggesting that a malfunction of the the IGF2 gene and/or lower levels of its protein product might have some important implications. At this point I might add that whilst there is a bit of a research gap when it comes to IGF2 and behaviour specifically linked to ADHD, there is some interesting animal research looking at mice engineered to show low levels of the protein product in terms of behaviours such as anxiety [2] alongside "a role for the placenta in long-term programming of emotional behaviour." Cutting edge stuff to be sure.

"At present, this is not a study that would change my clinical practice, but if intervention studies resulting from this work show nutritional support in pregnancy can have an effect then we should take any opportunity we can to help." That was one comment from a physician discussing the results of the Rijlaarsdam study that I would agree with. The fact that the study focuses on just one gene in amongst the thousands potentially linked to conduct problems and ADHD is something to bear in mind.

Set however within the context that food can seemingly also affect behaviour and psychiatry as well as physiology (see here for example) I'd like to think that more studies on nutrition during pregnancy would be forthcoming and quickly on this important topic.

To close, thanks to Gene for the laughter...


[1] Rijlaarsdam J. et al. Prenatal unhealthy diet, insulin-like growth factor 2 gene (IGF2) methylation, and attention deficit hyperactivity disorder symptoms in youth with early-onset conduct problems. J Child Psychol Psychiatry. 2016 Aug 18.

[2] Mikaelsson MA. et al. Placental programming of anxiety in adulthood revealed by Igf2-null models. Nat Commun. 2013;4:2311.

---------- Rijlaarsdam J, Cecil CA, Walton E, Mesirow MS, Relton CL, Gaunt TR, McArdle W, & Barker ED (2016). Prenatal unhealthy diet, insulin-like growth factor 2 gene (IGF2) methylation, and attention deficit hyperactivity disorder symptoms in youth with early-onset conduct problems. Journal of child psychology and psychiatry, and allied disciplines PMID: 27535767

Monday, 29 August 2016

The ketogenic diet and the BTBRT+Tf/J mouse model of autism

I was rather interested to read the findings reported by Richelle Mychasiuk & Jong Rho [1] suggesting that the expression of certain genes might be affected by adoption of a ketogenic diet in one of the more familiar mouse models of autism (the BTBRT+Tf/J 'dangermouse').

The ketogenic diet (KD), consisting of "a high-fat low-carbohydrate anti-seizure and neuroprotective diet" has been of some interest to autism research over the years (see here). Its potential usefulness has also been explored in mouse models of autism including the BTBR mouse model (see here) and this latest research should be viewed in that context.

The name of the research game this time around was to investigate "changes in mRNA [messenger RNA] and gene expression in the BTBR mouse model of ASD [autism spectrum disorder] that may contribute to the behavioral phenotype" including what happened to said gene expression following the use of a KD. Looking in mouse brains, researchers found a few genes that seemed to be differentially expressed in the BTBR mice compared to controls. Perhaps more important to this post however was the observation that following the use of a KD, there were some potentially important changes: "brain regions demonstrated improvements in ASD deficits associated with myelin formation and white matter development."

Bearing in mind mice are mice not people, this is interesting work. It does not imply that use of a ketogenic diet is going to be for everyone with autism in terms of 'altering' gene expression and onwards positively affecting the presentation of the condition. What it does imply is further exploration is required into how use of something like a KD might have quite a few effects that could explain why for some people it is a life-changer (see here). The idea that we don't all walk around with our genes in the 'on' position is also reiterated and potentially provides a roadmap for looking at gene expression when it comes to lots more different intervention options used with autism in mind...


[1] Mychasiuk R. & Rho JM. Genetic modifications associated with ketogenic diet treatment in the BTBRT+Tf/J mouse model of autism spectrum disorder. Autism Res. 2016 Aug 16. 

---------- Mychasiuk R, & Rho JM (2016). Genetic modifications associated with ketogenic diet treatment in the BTBRT+Tf/J mouse model of autism spectrum disorder. Autism research : official journal of the International Society for Autism Research PMID: 27529337

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?


[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.

---------- 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).


[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.

---------- 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...


[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

---------- 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.


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

---------- 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).


[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.

---------- 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."


[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).

---------- 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).


[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.

---------- 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

Friday, 19 August 2016

Childhood inflammation and hypomanic symptoms in young adulthood?

"Higher levels of systemic inflammatory marker IL-6 in childhood were associated with hypomanic symptoms in young adulthood, suggesting that inflammation may play a role in the pathophysiology of mania."

That was the conclusion reached by Joseph Hayes and colleagues [1] (open-access available here) who drew on data derived from the excellent resource that is ALSPAC ("Charting the health of 14,500 families in the Bristol area to improve the health of future generations"). I'll be talking about other ALSPAC-derived data in upcoming posts too.

Based on a cohort of some 4600 children who provided blood samples (analysable blood samples no less) at aged 9 years old and "who completed the Hypomania Checklist (HCL-32)" at aged 22 years, researchers looked at how blood levels of C-reactive protein (CRP) and IL-6 might link in with later self-reported hypomanic symptoms.

Bearing in mind the focus on "immune activity in healthy individuals" (quite a few participants were excluded from the study as a result of reporting an infection in the week before samples were taken), researchers reported some interesting associations. As per the opening sentence: "Higher IL-6 levels in childhood were associated with adult hypomania features in a dose-response fashion." That being said: "Higher serum IL-6 levels at age 9 years were associated with female sex, non-white British ethnicity, lower SES, higher past psychological and behavioural problems and higher BMI" too. When it comes to BMI (body mass index), the observation that various immune system markers might be elevated is not necessarily a new idea.

Although childhood IL-6 levels were associated with later hypomanic symptoms (even when adjusted for the various potentially confounding variables), blood levels of CRP did not seem to show the same kind of relationship: "There was no evidence of an association between CRP levels and hypomanic symptoms." Similarly, when authors looked at the possibility of an association between the presence of atopic disease and hypomanic symptoms based on the inclusion of a parent-response question when their child participant was 10 years old - "Has a doctor ever actually said that your study child has asthma or eczema?" - the authors reported little indication of any connection.

At least one of the co-authors on the Hayes paper has some prior interest in the possible psychiatric manifestations of childhood inflammation as per other entries on this blog (see here). As much as I am intrigued by this area of research, you don't have to be a rocket scientist to understand the potential flaws in such a study where one or two biological variables are mapped on to a self-report questionnaire quite a few years later potentially excluding a myriad of factors not readily taken into account in a study like this. It would for example, be preferable to have seen multiple measures of CRP and/or IL-6 during childhood (say, every year) to see if any potential association between childhood inflammation and hypomanic symptoms holds. That also only IL-6 seemed to show some sort of connection maybe also implies that the generalised idea that 'inflammation' might tie into later psychiatric symptoms is perhaps a little bit too generalised. I could go on i.e. CRP is not the only pentraxin, IL-6 is not necessarily just a pro-inflammatory cytokine, etc.

In short, some interesting observations and yes "immunological understanding of major mental illness could potentially lead to novel approaches to diagnosis, prevention and treatment" but I think we need a lot more quality data on this topic.


[1] Hayes JF. et al. Childhood interleukin-6, C-reactive protein and atopic disorders as risk factors for hypomanic symptoms in young adulthood: a longitudinal birth cohort study. Psychol Med. 2016 Aug 1:1-11.

---------- Hayes JF, Khandaker GM, Anderson J, Mackay D, Zammit S, Lewis G, Smith DJ, & Osborn DP (2016). Childhood interleukin-6, C-reactive protein and atopic disorders as risk factors for hypomanic symptoms in young adulthood: a longitudinal birth cohort study. Psychological medicine, 1-11 PMID: 27476619

Thursday, 18 August 2016

Mercury and autism: where the science currently stands

Yes, I know that on the 'hot potato' scale, to talk about mercury and autism still moves the needle up to somewhere approaching furnace level for some people despite discussions on this heavy metal still figuring in several quarters. This is however a blog based on peer-reviewed science (for the most part) and so with mucho, mucho caveats included I want to draw your attention to the review paper by Janet Kern and colleagues [1] (open-access available here) and the observation that: "The preponderance of the evidence indicates that mercury exposure is causal and/or contributory in ASD [autism spectrum disorder]." I might add that this authorship group are no strangers to this particular topic (see here).

As per the 'review' heading accompanying the Kern paper, this was an analysis (inventory) of the up-to-date - "1999 to February 2016" - peer-reviewed studies done around the topic of mercury and autism. The authors present the data based on tissue type, ASD vs. not-ASD and various other parameters detailing the back-and-forth of relationship and no relationship that seems to percolate through the autism research scene. They conclude that "the vast majority (74%) of those studies suggest that mercury is a risk factor for ASD" and that any effect is likely to consist of "both direct and indirect effects of mercury exposure." This direct and indirect effects explanation is accompanied by a graphic highlighting the many and varied ways that mercury exposure might be linked to cases of autism. They also direct readers to a similar paper on this topic [2] that "also found that 74% of studies support a link between mercury exposure and ASD."

Without courting controversy as to the sources of and relative role that mercury might have on cases of autism I was drawn to a particular conclusion made by the authors that "children with ASD are more susceptible to mercury than typically developing children." I've seen and blogged about enough autism research down the years to understand that for some people on the autism spectrum, behavioural 'symptoms' can be accompanied by various genetic and biological 'issues' linked to the handling of various toxicants and other environmental agents. I'm not yet convinced with the argument that universally people diagnosed with autism are somehow preferentially exposed to greater levels of mercury than the rest of the population but I am warming to the idea that their 'handling' of such a heavy metal (and others) might to some extent be 'impaired' and that this could have some impact on body burden levels as well as clinical presentation.

Obviously, more research is implied.


[1] Kern JK. et al. The relationship between mercury and autism: A comprehensive review and discussion. J Trace Elem Med Biol. 2016 Sep;37:8-24.

[2] Desoto MC. & Hitlan RT. Sorting out the spinning of autism: heavy metals and the question of incidence. Acta Neurobiol Exp (Wars). 2010;70(2):165-76.

---------- Kern JK, Geier DA, Sykes LK, Haley BE, & Geier MR (2016). The relationship between mercury and autism: A comprehensive review and discussion. Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS), 37, 8-24 PMID: 27473827

Wednesday, 17 August 2016

76% of youths with autism meet ADHD diagnostic criteria? No, more like 59%

"In a population of children diagnosed with ASD [autism spectrum disorder], the rate of ADHD [attention-deficit hyperactivity disorder] + ASD was 42% and the rate of ADHD + ASD + ID [intellectual disability] was 17%, resulting in a 59% total comorbidity rate of ADHD and ASD."

That was one of the important findings reported by Tara Stevens and colleagues [1] who using data from the Survey of Pathways to Diagnosis and Services (Pathways), a US initiative that has previously been discussed on this blog (see here), threw their research hat into an increasingly important part of the autism research and practice landscape.

I mentioned the percentage figure of 76% in the title of this post with reference to other, smaller scale, findings previously talked about on this blog (see here) based on the work published by Joshi and colleagues [2] and their observation of a: "high rate of comorbidity with ADHD... in psychiatrically referred youth with ASD, with a clinical presentation typical of the disorder."

The Stevens data is based on a larger sample cohort and whilst not necessarily carrying the same sort of diagnostic clout as the Joshi data ("Diagnostic interviews were administered by highly trained and closely supervised psychometricians with bachelor’s or master’s degrees in psychology or a related field") does benefit from those larger numbers included and indeed, the more naturalistic setting of data collection. That Stevens et al report that: "Average age at diagnosis was over 6 years for children with ASD + ADHD but close to 2.5 years for children with ASD only" also provides some welcome information about the experiences of a dual diagnosis of autism plus ADHD.

In these days of autism plus [3] (ESSENCE even) further focus on the idea that the label of autism rarely exists in some sort of diagnostic vacuum (see here) represents an important step towards offering appropriate - preferential - screening when autism is mentioned and also focusing minds on how comorbidity can in some cases be even more disabling than the core diagnosis of autism (see here). Although one has to be quite careful not to 'big up' the relationship between autism and ADHD, particularly in these days where a very vocal group of people talk about over-diagnosis of ADHD, I'd be minded to suggest that as per the example with other comorbidity over-represented when it comes to autism, tackling something like ADHD when it is present/diagnosed might have some important repercussions for the presentation of core autism itself and its impact on quality of life...


[1] Stevens T. et al. The comorbidity of ADHD in children diagnosed with autism spectrum disorder. Research in Autism Spectrum Disorders. 2016; 31: 11–18.

[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] Gillberg C. & Fernell E. Autism plus versus autism pure. J Autism Dev Disord. 2014 Dec;44(12):3274-6.

---------- Stevens, T., Peng, L., & Barnard-Brak, L. (2016). The comorbidity of ADHD in children diagnosed with autism spectrum disorder Research in Autism Spectrum Disorders, 31, 11-18 DOI: 10.1016/j.rasd.2016.07.003

Tuesday, 16 August 2016

Group A Streptococcal infections and paediatric neuropsychiatric disorders: Taiwan style

There they go again. Taiwan and their 'big data' publishing, yet again, some rather interesting population-based research trends derived from data from the National Health Insurance Research Database (NHIRD).

This time around it is the paper by Han-Cheng Wang and colleagues [1] and the hypothesis to evaluate the "association between group A streptococcal (GAS) infections and the risks of developing tic disorders, obsessive-compulsive disorder (OCD), and attention-deficit/hyperactivity disorder (ADHD)." For those in the know, the relationship between Strep infection and those neuropsychiatric labels brings us into the realm of PANDAS and PANS (and no, not the fluffy black-and-white kind of panda either).

Based on a not insignificant participant number - "2,596 patients and 25,960 controls" - researchers set about looking at under-18 year olds newly diagnosed with a GAS infection and their subsequent risk of receiving one or more of those neuropsychiatric labels.

Compared to controls, the incidence of neuropsychiatric disorder in the GAS group was higher (60.42 per 10,000 person-years vs. 49.32 per 10,000 person-years) particularly when it came to the presentation of a tic disorder. If said GAS infection was serious enough to put someone in hospital, the risk of neuropsychiatric disorder was even higher compared with than those who did not have a GAS infection. The authors conclude: "Our results confirmed an association between previous group A streptococcal infection and neuropsychiatric disorders."

Set within the growing research base suggesting that various infections can very much lead to behavioural outcomes (see here for another example) as well as physical ones, there is some interesting science still to be done on the hows and whys. Whether said infection meets us during the nine months that made us (see here) or some time after provides some intriguing insights on how timing and infection type might show differential effects for a person. The question of whether (a) we can prevent certain infections or (b) offset their primary effects via the use of agents affecting immune function or immune response perhaps represent some of the more important avenues for further investigations in this area.


[1] Wang HC. et al. Group A Streptococcal Infections Are Associated With Increased Risk of Pediatric Neuropsychiatric Disorders: A Taiwanese Population-Based Cohort Study. J Clin Psychiatry. 2016 Jul;77(7):e848-54.

---------- Wang, H., Lau, C., Lin, C., Chang, A., & Kao, C. (2016). Group A Streptococcal Infections Are Associated With Increased Risk of Pediatric Neuropsychiatric Disorders The Journal of Clinical Psychiatry DOI: 10.4088/JCP.14m09728

Monday, 15 August 2016

Offending behaviour and ADHD

"Although some associations between ADHD [attention-deficit hyperactivity disorder] and offending may be accounted for by co-morbidity with substance use disorders, early onset of offending and repeated violent offending appear to be directly related to ADHD."

That was the conclusion reached by Jan Román-Ithier and colleagues [1] reporting on their study designed to "examine correlates of childhood ADHD symptoms among prisoners." Based on a sample adult prison population (N=1179) where self-reported "retrospective measures of ADHD and a diagnostic interview for substance use disorders" were coupled with data on offending behaviour(s), researchers reported that there may be more to see when it comes to self-reported ADHD and offending behaviour not necessarily just due to substance abuse. Indeed: "Self-reported ADHD was associated with age of first arrest, a number of violent and non-violent offences and re-offending."

Of course you'd be right if you highlighted a few methodological issues with the current data insofar as the use of self-report and indeed, retrospective self-report when it comes to ADHD or ADHD-type symptoms. I might even throw in the idea that feigning ADHD is not something unheard of in the peer-reviewed literature either (see here) bearing in mind one might expect some special treatment or accommodation for prisoners who might meet diagnostic thresholds. There is more [controlled] research to be done in this area for sure.

But set within the idea that there may be something of an over-representation of ADHD in the prison population (see here), the Román-Ithier results add further weight to the idea that screening (including preferential screening for some) and treating ADHD early in life might be something to seriously think about from a population health and wellbeing perspective. Yes, one has to be careful about sweeping generalisations when it comes to ADHD and 'adverse outcomes' (see here) including the idea that ADHD persistence might not be uniform [2] and I don't doubt that some might be slightly adverse to the idea of some of the currently indicated treatment measure for ADHD when it comes to medication for example (see here). But as with many things in life, the pros and cons of tackling such issues need to be weighed up on an individual basis assuming for example, that a life of offending and re-offending is probably not to be helpful to anyone. I might also throw the findings by Chorniya & Kitashimab [3] into this post and how substance abuse disorder and other 'risky behaviours' might also decline as and when ADHD is appropriately managed.

And outside of just pharmacotherapy for ADHD, there are other management options to potentially consider (see here and see here and see here for example)...

To close, fair-dos to Gary Lineker...


[1] Román-Ithier JC. et al. Attention deficit hyperactivity disorder symptoms, type of offending and recidivism in a prison population: The role of substance dependence. Crim Behav Ment Health. 2016 Jul 26.

[2] McAuley T. et al. Clinical, Sociobiological, and Cognitive Predictors of ADHD Persistence in Children Followed Prospectively Over Time. J Abnorm Child Psychol. 2016 Jul 29.

[3] Chorniya A. & Kitashimab L. Sex, drugs, and ADHD: The effects of ADHD pharmacological treatment on teens' risky behaviors. Labour Economics. 2016. July 5.

---------- Román-Ithier, J., González, R., Vélez-Pastrana, M., González-Tejera, G., & Albizu-García, C. (2016). Attention deficit hyperactivity disorder symptoms, type of offending and recidivism in a prison population: The role of substance dependence Criminal Behaviour and Mental Health DOI: 10.1002/cbm.2009

Saturday, 13 August 2016

Inflammation is part of Gulf War Syndrome

Although mostly trying to avoid any politics-talk on this blog I am going to make some reference to it in this post set in the context of the Persian Gulf War otherwise known at the First Iraq War.

The recent publication of the Chilcot report describing the case for the UK's involvement in the 2003 Iraq War (the second Iraq War) has further lit up an already illuminating year in British politics, by perhaps adding fuel to the notion that 'finishing the job' might have been an important link between the two conflicts...

Operation Desert Storm - the combat phase of the First Gulf War (1991) - described by some as 'the most toxic war in history' left a mark not just on the region where it was fought and its people but also on many of the returning service personnel, some of whom came back in a pretty poor state of health. Their various symptoms known collectively as Gulf War Syndrome or Illness, are still the topic of discussions and debate to this day despite increasing evidence that they are 'real' symptoms (see here) and not just some psychosomatic manifestation of combat stress for example, as advocated by some quite prominent figures. The possible reasons for illness are varied (see here) but when one uses the words 'sarin' in the context of potential exposures for example you get a flavour for what might have been involved [1] and their potential contributions to health or rather ill-health.

The paper by Gerhard Johnson and colleagues [2] (open-access) adds further credence to the idea that Gulf War Illness (GWI) is indeed a real phenomenon and specifically: "that inflammation is a component of the pathobiology of GWI." Based on the examination of a relatively small number of veterans (85 out of 500 deployed veterans who were invited to participate), researchers undertook a "structured interview" that "assessed their health status, and blood samples were obtained." They managed to divide veterans up into GWI+ (n=57) and GWI- (n=28) groupings dependent on whether or not they reached the Fukuda criteria [3] for a "a chronic multisymptom condition" linked to deployment to the Gulf War.

Results: over 80 specific analytes were assayed for from the blood samples provided by participants. Many compounds had an immunological slant in terms of being cytokines or being other markers of immune system (specifically inflammatory) 'activation'. "The results of the current study provide evidence of alterations in a number of blood parameters that are readily measurable in routine clinical laboratories" was the headline as six specific compounds, all with inflammation in mind, were ripe for further independent study: plasma C-reactive protein (CRP), leptin, brain-derived neurotrophic factor (BDNF), and matrix metalloproteinase-9 (MMP-9)  = higher in the GWI+ group. Heart-type fatty acid binding protein (H-FABP) and matrix metalloproteinase-2 (MMP-2) = lower in the blood of GWI+ subjects. Alongside "the distributions of peripheral blood lymphocyte, monocyte, neutrophil, and platelet counts were higher in GWI+ subjects" compared with GWI- participant data leading researchers to observe that "a model utilizing three readily measurable biomarkers [lymphocytes, monocytes, and C reactive protein]... appears to significantly augment the symptom-based case definition of GWI."

"The limitations of the study include small sample size, restricted geographic, ethnic, and sex composition of the study subjects, assay of blood parameters only once, some plasma protein assays, including cytokines, considered inevaluable due to a high percentage of assays below the level of detection, overlap of biomarker distributions within the normal range, absence of correction for multiple comparisons, a limited number of blood proteins found to be positively related to GWI+ status, and the absence of a confirmation cohort study." Apologies for just grafting a large chunk of text from the Johnson paper into this post, but when it comes to the limitations of their work, the authors do a pretty good job of cautioning against any over-hype and providing a roadmap to 'where next?'

And as part of that 'where next?' it appears that we might be talking quite soon about some findings if an associated entry is anything to go by (see here) on the use of 'delayed-release prednisone' with this group. I say this without making any value judgements or providing anything that looks, sounds or smells like medical or clinical advice.

We wait and see.

And to close: "all is as the Force wills it" apparently...


[1] Proctor SP. et al. Effects of sarin and cyclosarin exposure during the 1991 Gulf War on neurobehavioral functioning in US army veterans. Neurotoxicology. 2006 Dec;27(6):931-9.

[2] Johnson GJ. et al. Blood Biomarkers of Chronic Inflammation in Gulf War Illness. PLoS ONE 11(6): e0157855.

[3] Fukuda K. et al. Chronic multisymptom illness affecting Air Force veterans of the Gulf War. JAMA. 1998 Sep 16;280(11):981-8.

---------- Johnson GJ, Slater BC, Leis LA, Rector TS, & Bach RR (2016). Blood Biomarkers of Chronic Inflammation in Gulf War Illness. PloS one, 11 (6) PMID: 27352030