Following ADHD long-term: "a persistence rate of 27.8%"

Studies such as the one published by Michel Lecendreux and colleagues [1] always catch my attention. Research that follows a group of people over a period of years makes for interesting reading; not least because one gets a flavour for what *could* happen when such findings are applied to a larger population.

The Lecendreux findings focused on a few important issues pertinent to a diagnosis of attention-deficit hyperactivity disorder (ADHD) specifically related to (a) the persistence of ADHD, and (b) the idea that signs and symptoms of ADHD not meeting the thresholds for a diagnosis of ADHD might be rather important. Indeed, that they may merit "a subthreshold diagnostic category" of their own.

So, based on a starting participant sample of just over a thousand families including a child in the "6-12 years age range", interviews were conducted covering various aspects of ADHD and beyond: "symptoms of ADHD, conduct disorder, and oppositional defiant disorder as well as family living situation, school performance, sleep disturbance, eating habits, use of supplemental iron, and history of ADHD treatment." Approaching half of the original sample (492 / 1012) were followed up some 9 years later where "the persistence of ADHD and its impairments and the emergence of new conditions were assessed."

Results: "At follow-up, 16.7% of the children diagnosed with ADHD at baseline met full criteria for ADHD and 11.1% met criteria for subthreshold ADHD, yielding a persistence rate of 27.8%." Diagnosis of ADHD was, by the way, based on DSM-5 criteria (see here). That figure of 27.8% in terms of ADHD persistence from childhood to early adulthood is potentially an important one. It tells us that for a majority of children diagnosed with ADHD in childhood, their symptoms of inattention, hyperactivity and impulsivity will reduce to such a degree that they are no longer considered clinically significant or at least not reaching thresholds for a diagnosis of ADHD. Whether such a reduction in symptoms is through processes such as maturation or the timely implementation of intervention/management strategies needs quite a bit more work. Whether also ADHD potentially 'morphs' into something else as people age also needs further exploration (see here).

Another important detail was also mentioned by Lecendreux et al: "Among children not diagnosed with ADHD at baseline, 1.1% met criteria for ADHD at follow-up." Such a figure is important in relation to the concept of adult-onset ADHD [2] and the question of whether ADHD is a diagnosis with foundations always rooted in infancy. The Lecendreux findings suggest that for some people, this might not be the case and opens the door to possible talk about acquired ADHD for examples. This also sounds very familiar (see here).

Insofar as the issue of a possible 'subthreshold diagnostic category' for ADHD, I find myself agreeing with the "dimensional conceptualization" mentioned by the authors. Several other conditions / states / diagnoses have recognised 'lite versions' of the label. In autism for example, one might see this as social communication disorder (SCD) or mention of the broader autism phenotype (BAP). I'm even minded to place the label known as pathological demand avoidance (PDA) in a similar bracket given recent opinions (see here). Such chatter about 'lite' does not and should not downplay the effects of such sub-threshold labels. It merely acknowledges that there may be a wider spectrum of issues / difficulties experienced outside of the receipt of a core diagnosis.

So it should perhaps be the same with ADHD too, given what is beginning to emerge on the long-term 'effects' that a diagnosis of ADHD and subthreshold ADHD might bring (see here and see here).

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[1] Lecendreux M. et al. A 9-Year Follow-Up of Attention-Deficit/Hyperactivity Disorder in a Population Sample. J Clin Psychiatry. 2019 May 7;80(3). pii: 18m12642.

[2] Cooper M. et al. Investigating late-onset ADHD: a population cohort investigation. J Child Psychol Psychiatry. 2018 Oct;59(10):1105-1113.

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Childhood lead (Pb) exposure and "greater psychopathology across the life course"

I've talked about the effects of lead (Pb) on cognition, behaviour and psychology before on this blog (see here and see here for examples). A (heavy) metal with no confirmed biological function, lead represents something that pretty much everyone should be avoiding exposure to, despite it still being used in everything from roofing materials to batteries. The findings reported by Aaron Reuben and colleagues [1] add further to the 'avoid lead' sentiments, and specifically how: "Childhood lead exposure may have long-term consequences for adult mental health and personality."

The aim of the Reuben paper was to conduct "the longest and largest psychiatric follow-up to date in a cohort of adults who were lead exposed and lead tested as children." Participants and their data came from "the Dunedin Multidisciplinary Health and Development Study, a longitudinal investigation of health and behavior in a birth cohort." This study specifically drew on data from over 500 Dunedin study members who were tested for lead exposure around age 11 years and were followed up until their late 30s. A range of psychometric measures were employed in adulthood to complement participants' blood lead test results during childhood, including "(1) repeated clinical interviews assessing psychopathology symptoms across adulthood up to 38 years of age; (2) comprehensive, dimensional measures of psychopathology that account for severity, comorbidity, and reoccurrence; and (3) a broad measure of adult personality (Big Five Personality Inventory)... that did not rely on self-report." Importantly, researchers relied on a sample where "the extent of children's exposure to lead was unrelated to their socioeconomic origins."

Results: most of the cohort (over 90%) had tested blood lead levels above the 5 μg/dL level that the US CDC currently describes as a "reference value for clinical attention." This threshold value replaced the 10 μg/dL level that used to be thought to be important. Indeed within the Reuben cohort: "The mean (SD) blood lead level was 11.08 (4.96) μg/dL."

Researchers also observed that: "After adjusting for covariates, each 5-μg/dL increase in childhood BLL was associated with a 1.34-point increase... in general psychopathology." Covariates included "family socioeconomic status, maternal IQ, and family history of mental illness." This seemingly dose-dependent relationship looked to be quite important.

Onward: "study members with higher BLLs [blood lead levels] at 11 years of age were viewed in adulthood by their informants as more neurotic..., less agreeable..., and less conscientious" than those with lower levels. Personality it seems *might* also be affected by childhood lead exposure (at least partially). These and other factors lead Reuben et al to conclude that: "the association between lead exposure and psychopathology may begin to manifest broadly well before adulthood" and "early-life lead exposure in the era of leaded gasoline experienced by individuals who are currently adults may have contributed to subtle, lifelong differences in emotion and behavior that are detectable at least up to 38 years of age."

I know there are caveats to this type of observational work - "there was only one time point of lead testing" - and even controlling for some potential covariates does not mean that the total spread of covariates has been covered in this study. Personally, I'm not overly enthused by the whole personality types bit either; particularly in light of further revelations about some of the historical proponents of such an idea (see here). But taken as part of a wider series of research on lead exposure and psychopathology, the Reuben work is in line with other results on how an environmental factor can seemingly affect both development and psychopathology. And minus any sweeping generalisations about psychopathology and crime, the so-called 'lead-crime hypothesis' under the guise of biosocial criminology for example, doesn't exactly suffer as a result of the Reuben findings...

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[1] Reuben A. et al. Association of Childhood Lead Exposure With Adult Personality Traits and Lifelong Mental Health. JAMA Psychiatry. 2019. Jan 23.

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Suicide risk and autism: data from "Utah over a 20-year period"

The findings reported by Anne Kirby and colleagues [1] are not for the faint-hearted but continue a vitally important theme in autism research and practice circles looking at suicide risk and autism (see here and see here). The 'value-added' bit to the Kirby results to distinguish them from other study in this area was the reliance on data across a 20-year period from a place that has some important autism research history: Utah in the United States (see here).

So: "Four sources of existing data were utilized for this study: URADD statewide autism surveillance data, statewide suicide surveillance data collected by the Utah Office of the Medical Examiner (OME), the UPDB, and Utah's Indicator‐Based Information System for Public Health (IBIS‐PH)." From such data sources, researchers accessed information for nearly 17,000 people diagnosed with an autism spectrum disorder (ASD) "alive at the beginning of 1998 and at least 5 years of age in 2013." Most were male and most were white. They similarly determined that nearly 9,000 people in their total population - not just those diagnosed with ASD - died by suicide between 1998 and 2017. Again, most were male and most were white. The data were combined and interrogated "to calculate the incidence (in 5‐year intervals) of suicide deaths in people with ASD over a 20‐year period (1998 to 2017) in total, as well as by sex, and compared suicide risk in people with versus without ASD." Researchers also looked at other important variables such as "sex, race, death age, occupational status, marital status, and manner of death" across the groups.

Results: "In the first 15 years of the study (1998–2012), we did not observe differences in suicide cumulative incidences between the ASD and non‐ASD populations." This means that when the groups were compared as a function of death by suicide, the figures for those with autism were not significantly different from those without autism for this time period. By saying that I don't want to belittle the fact that between 1998 and 2012 for example, 2 people out of 5,202 autistic people died by suicide or that 1,671 out of 1,928,484 non-autistic people died. Each of these figures was a person with a life and with a family, and that's something that should never ever be forgotten.

The pattern however changed when researchers looked at the period between 2013 and 2017: "For the most recent time interval (2013–2017), the cumulative incidence of suicide death in the ASD population was 0.17%, which is significantly higher than the non‐ASD population cumulative incidence of 0.11%." This percentage (0.17%) represented 28 deaths from an autistic population of 16,907 and 2,791 deaths from a non-autistic population of 2,630,221. Although a sideline point, I'll also bring to your attention how the autistic population numbers changed over the 5-year blocks of study in the Kirby paper: 1998-2002: 5,202 people; 2003-2007: 8,722 people; 2008-2012: 13,890 people; 2013-2017: 16,907 people.

A few other details were observed by Kirby et al: "In comparison with non‐ASD + suicide cases, ASD + suicide cases had significantly younger average death ages (32.4 years vs. 41.8 years; t = −3.8, P < 0.001)." Also: "Combined, 73% of the ASD + suicide cases used methods for suicide considered to be violent; the remaining 26% used nonviolent methods." This again, is important information.

Researchers also mention how across the 2013-2017 period, another important trend was observed: "suicide risk in females with ASD was over three times higher than in females without ASD (relative risk (RR): 3.42; P < 0.01)." They contrast this with the finding that "there were no documented cases of suicide death among females with ASD during the first 15 years of the surveillance period" and what this could mean when it comes to possible explanations of suicide risk in relation to autism.

There's quite a bit to learn from the Kirby findings. Although there are limitations attached to the study design - "inadequate data on intellectual ability was available to examine the influence ID may have on suicide risk in individuals with ASD" - the study was a good one because of its population-wide focus and the pretty good autism-related resources that Utah has (and has had for many years). It demonstrates once again that the difficult topic of suicide and autism should remain a research priority in order to identify who might be most at risk and why, alongside the ways and means that such risk *might* be mitigated (see here for one example).

And for those who might need someone to text / email / talk to, there are always options (see here for services in the UK or see here for those elsewhere).

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[1] Kirby AV. et al. A 20-year study of suicide death in a statewide autism population. Autism Res. 2019 Jan 21.

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"Anxiety and sleep problems may be an early indicator of autism in young children"

The quote titling this post - "Anxiety and sleep problems may be an early indicator of autism in young children" - comes from the findings reported by Jacqueline Uren and colleagues [1]. Researchers dipped into data derived from the Raine study initiative to investigate any "longitudinal associations between sleep and anxiety at 2 years and sleep and anxiety at 8 years controlling for demographic variables" and also "the additional influence of autistic traits at 2 years on sleep problems and anxiety at 8 years."

The Raine study has produced fodder for this blog before (see here and see here for examples). Described as "one of the largest successful prospective cohorts of pregnancy, childhood, adolescence and now early adulthood to be carried out anywhere in the world", the sample size is not to be sniffed at (~2900 pregnant women). It has provided a number of important longitudinal *associations* of interest.  Mention of the name Andrew Whitehouse on the paper authorship is also kinda expected given his interest in autism-related data derived from the Raine study in particular.

So: "Children's sleep and anxiety at 2 and 8 years and autistic traits at 2 years were measured using the Child Behavior Checklist." The data was crunched to assess for any possible associations. And associations there were, as we are told that: "Sleep problems at 2 years and 8 years, anxiety at 2 years, and autistic traits at 2 years were significantly associated with anxiety at 8 years." Further: "Sleep problems at 2 years and anxiety at 8 years were significantly related to sleep problems at 8 years." Such statements also led to that headline observing that anxiety and sleep issues *may* be an early indicator of childhood autism (with a stress on the *may*).

Of particular interest to me was the suggestion that "early autistic traits may also contribute to anxiety problems later in childhood." I say this because I am becoming more and more interested in how anxiety may be something much more 'core' to autism than many have hitherto believed (see here). Yes, there are those that might disagree (see here); perhaps using the 'social model' pathway and the notion that society shoulders a lot of responsibility for things like anxiety and depression in the context of autism (see here) as evidence for some 'acquired anxiety' effect. But the data is becoming compelling to suggest that for some 'types' of autism at least, anxiety may represent something of a core feature (in line with some previous thoughts on this matter [2]) and is present pretty early on for many. And in this respect, the way that one manages something like anxiety in the context of autism, may very much depend on looking at 'managing' certain other core autistic features...

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[1] Uren J. et al. Sleep problems and anxiety from 2 to 8 years and the influence of autistic traits: a longitudinal study. Eur Child Adolesc Psychiatry. 2019 Jan 19.

[2] Evans B. How autism became autism. Hist Human Sci. 2013 Jul; 26(3): 3–31.

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Yet more evidence suggesting that 'lifelong' is not an accurate description of some autism

The findings reported by Amaria Baghdadli and colleagues [1] didn't really come as a great surprise to me. In their study designed to "investigate the adaptive trajectories and their risk factors in ASD [autism spectrum disorder]", researchers reported that just over 5% of their cohort initially categorised as having autism "fell under the ADOS [Autism Diagnostic Observation Schedule] threshold" at a later point in time. 'Fell under the ADOS threshold' translates as not meeting the criteria for autism on one of the gold-standard assessment instruments (that's assessment, not screening) and by inference, not being autistic. Important too was another statistic from their study: "11.9% converted to atypical autism" and: "Most atypical autism diagnoses were unstable."

The Baghdadli study was quite an extensive one. We are told that participants were "prospectively followed" from childhood to adulthood with assessments (including the Vineland Adaptive Behaviour Scales) covering a period of 15 years. Outside of some participants seemingly exiting the diagnosis of autism, authors also talked about different trajectories noted among their cohort that ties in with lots of other research on this topic (see here and see here). The authors concluded that: "changes in diagnostic, speech, and adaptive status are not uncommon, even for individuals with low measured intelligence or apparent intellectual disability, and are sometimes difficult to predict." It's interesting too that: "One-third of children who are nonverbal at 5 years are verbal within 15 years, mostly before 8 years of age."

Minus any sweeping generalisations, I appreciate that talk about the 'instability' of presented symptoms/traits/characteristics and autism is not well received in some quarters. Despite study after study after study being published in the peer-reviewed science domain suggesting that, for some, autism is not a lifelong condition by diagnostic standards, there is a reluctance for some people to accept such data. I've heard for example, people talking about such a reversal of symptoms in the context that 'they weren't autistic in the first place' as if such commentators have some special insight into often complete strangers that surpasses professionals with years of clinical experience. I also don't doubt that talk about masking and camouflaging of symptoms, whilst legitimate in the context of [some] autism (albeit with a lot more science needed), might also eventually be used as another explanation too if it hasn't already. But please, don't tell me that preschoolers are also masking during their various assessments (see here)...

The fact remains that the peer-reviewed science on this topic is pretty unanimous insofar as autism not being 'lifelong' for everyone (see here). And yet again we need further investigations on this topic to elucidate whether a change in overt symptom profile heading towards asymptomatic also means changes in biological parameters or genetic functions/expression. Whether one day it might even be possible to predict who will fit into such a categorisation. I'm also keen to see further work being carried out around the idea that losing a diagnosis might have some pretty important effects on other quality of life affecting labels/symptoms/states (see here) that seem to be over-represented in relation to autism (see here). And then a final question: what role does intervention potentially play in such unstable behavioural profiles (see here) and I'm not just talking about 'behavioural' intervention either?

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[1] Baghdadli A. et al. Adaptive trajectories and early risk factors in the autism spectrum: A 15‐year prospective study. Autism Research. 2018. Oct 1.

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ATEC (Autism Treatment Evaluation Checklist) still rising

The paper by Shreyas Mahapatra and colleagues [1] (open-access available here) provides the blogging fodder today and some important data relating to an important instrument in autism research circles: the Autism Treatment Evaluation Checklist (ATEC).

I'm a fan of the ATEC. Not only because it was one of the first instruments specifically devised to look at measuring changes to autistic symptom severity but also because it's freely available to use. No royalty payments required; free and open for anyone and everyone to use.

Devised by the late Bernard Rimland and Stephen Edelson of the Autism Research Institute (ARI), the ATEC was born out of the need for researchers and non-researchers alike to measure how autism / autistic features can, on some occasions, fluctuate, specifically in response to intervention. It's perhaps no coincidence that the ARI also holds some important data on parent ratings of how useful certain interventions were reported to be when it comes to autism (see here). Although probably not loved by all, such ratings - derived from those who probably know their children best - provide an important rough-and-ready measure of what intervention options perhaps need a little more investigation and which should probably be avoided. The fact that they're based on the reports of over 27,000 parents also helps matters too...

Anyhow, one thing that did seem to be missing from the increasing interest (see here and see here) in the ATEC is data on "the norms on the longitudinal changes in ATEC in the “treatment as usual population." The Mahapatra paper sought to partially remedy that situation based on an "observational cohort who voluntarily completed ATEC evaluations over the period of four years from 2013 to 2017."

Based on observations for some 2600-odd children (mostly males) all of whom scored 20 or above on the ATEC total score, researchers provided some important baseline data. They for example, show how total ATEC scores, a measure of autism severity, seem to change / fluctuate as children age (see Table 1). They also show how subscale scores - Speech / Language / Communication, Sociability, Sensory / Cognitive awareness, Health / Physical / Behavior - move around as a function of 'starting position' and age too. In short, it provides researchers and non-researchers alike some data on what might be expected to happen to the presentation of autism based on ATEC scoring.

But it's not by any means a perfect start. As the authors point out: "In the selection of participants for inclusion in this study, a baseline of ASD [autism spectrum disorder] diagnosis could not be established as child’s diagnosis is not part of ATEC questionnaire" indicating that not every child who participated might have had a diagnosis of autism or ASD. There were other methodological 'issues' too that need to be kept in mind.

I'm still however happy to talk about the ATEC and its potential usefulness to lots more autism studies aside from that already discussed in the peer-reviewed literature. Assuming also that ATEC has some overlap with other more standardised measures used in autism research [2] I think the future continues to look rather rosy for this rather important instrument.

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[1] Mahapatra S. et al. Autism Treatment Evaluation Checklist (ATEC) Norms: A "Growth Chart" for ATEC Score Changes as a Function of Age. Children (Basel). 2018 Feb 16;5(2). pii: E25.

[2] Geier DA. et al. A Comparison of the Autism Treatment Evaluation Checklist (ATEC) and the Childhood Autism Rating Scale (CARS) for the Quantitative Evaluation of Autism. J Ment Health Res Intellect Disabil. 2013 Oct;6(4):255-267.

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The art of the gut microbiome: 'Excretory Wipings' across 45+ years

Excretory Wipings May 18-October 21, 1970 is a piece of art composed by the artist Billy Apple (more accurately known as Billy Apple®). Due to possible copyright issues et al I don't want to show the actual piece on this blog but will describe to you what it comprises: a conceptual art work including toilet paper with erm, traces of a bowel movement provided during that particular period of 1970.

It's probably not everyone's cup of tea when it comes to art, but believe it or not, it might potentially be a rather important research starting point if say you wanted to characterise the gut microbiome past and present. Indeed, that is exactly what the paper by Thilini Jayasinghe and colleagues [1] describes, as they compared the bacterial colonies present in the 1970 sample(s) with a more up-to-date set of samples provided by the same artist in 2016.

Some media interest in the Jayasinghe results can be seen here. In short, three archived samples sourced from the 1970 art piece were compared with three more recent samples sourced exactly 46 years later (2016). Researchers performed 16SrRNA sequencing to "study bacterial phylogeny and taxonomy" [2] and try and find out whether there were similarities/differences in the types of bacteria present and indeed, whether overall bacterial diversity had reduced/stayed the same/increased between the testing periods.

Following this N=1 study, a few details emerged. So: "We observed that 45% of the microbial species were retained over the 45 year interval." Such a finding has to bear in mind that the artist "was suffering from diverticular disease in 2016" and that such a condition may well impact on the type of gut bacteria that is present and/or predominating. Indeed, the authors talk quite a bit about how "the 2016 microbiomes contained significantly higher level of genus Prevotella... which may be related to the observed diverticular disease by having a negative impact on gut immune system." Interestingly too, the word 'butyrate' appears in the Jayasinghe text, as in lower levels of butyrate-producing bacteria being present in the more recent sample. Butyrate is currently going through a period of bacterial 'sainthood' [3] at the moment...

Next: "The diversity of the microbial species from samples taken when Apple was 80 years of age was lower than that from samples when he was 35." Bacterial diversity is something of real interest these days, as more and more people start talking about gut bacterial diversity (and the loss of it) as potentially being related to all-manner of life-enhancing and life-not-so-enhancing correlations. The recent results are framed by the authors in the context of being "consistent with the idea of a drift towards a core microbiome" where ageing seems to play a role in diversity.

Of course, one shouldn't forget that this was a N=1 study and that gut bacterial populations are subject to all-manner of influences pushing and pulling on what bacteria may or may not be present in a longitudinal sense. These latest results say very little outside of what happened to the bacterial profile of Billy Apple® between the testing occasions.

But I'm still intrigued by such findings and the idea that there may be other resources to 'tap into' when it comes to looking either long-term at gut bacterial profiles or indeed, comparing gut bacterial patterns as a function of time and various ages. Y'know, comparing bacterial profiles of various ages in years gone by with similarly aged participants in more modern times, and trying to determine what various factors linked to modern life might have done (or not) to gut bacterial profiles. I don't doubt that some results might be rather interesting and discussion-provoking...

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[1] Jayasinghe TN. et al. Long-term stability in the gut microbiome over 46 years in the life of Billy Apple®. Human Microbiome Journal. 2017; 5-6: 7-10.

[2] Janda JM. & Abbott SL. 16S rRNA Gene Sequencing for Bacterial Identification in the Diagnostic Laboratory: Pluses, Perils, and Pitfalls . Journal of Clinical Microbiology. 2007;45(9):2761-2764.

[3] Canani RB. et al. Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. World Journal of Gastroenterology : WJG. 2011;17(12):1519-1528.

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'Super-parenting' improves children's autism: headline fail as PACT re-emerges...

The title of this post is partially taken from the BBC take on the findings reported by Andrew Pickles and colleagues [1] detailing a long-term follow up (and slight adjustment to the calculation of behavioural scores) of the Preschool Autism Communication Trial (PACT). PACT by the way, is a strategy based on the important tenet of shared attention where: "The approach aims to help parents adapt their communication style to their child’s impairments and respond to their child with enhanced sensitivity and responsiveness."

OK, just before I get started, use of the term 'super-parenting' in that headline is a bit of a fail by my reckoning and I don't doubt that this will probably change/have changed quite soon. Appreciating that there is as much variability in parenting a child with autism as there is parenting a child who does not have the label, the implication that parents of autistic children are somehow 'not doing it right' made by such a headline is frankly, a little rude. Many parents with children with autism are already 'super-parenting' well beyond what you might imagine to be humanly possible.

The study... well, greeted with quite a fanfare as words like 'breakthrough' are used (see here for example) the findings are basically a longer-term follow-up of the original PACT trial [2] which unfortunately reported at the time: "On the basis of our findings, we cannot recommend the addition of the PACT intervention to treatment as usual for the reduction of autism symptoms." Indeed, allied to some of other quite high-profile unspectacular scientific results based on the analysis of short-term parent-mediated intervention discussed on this blog (see here), there is quite a U-turn seemingly being adopted in this area (see here too). I might also add that even an analysis of the cost of PACT vs treatment as usual (TAU) did "not support the cost-effectiveness of PACT + TAU compared to TAU alone" [3]!

That all being said, the recent results from Pickles and colleagues are not bad at all. Tracking down some 120 participants of the original 150-ish cohort, researchers assessed them [blinded in some cases] "with the ADOS Comparative Severity Score (CSS)" among other things to see whether there were any behavioural presentation differences between those who were in receipt of PACT vs. those assigned to TAU. Differences were noted: "the severity of autism symptoms was significantly lower for children in the intervention group than for children in the treatment-as-usual group." And with that the authors pronounce: "We now show that a 12 month parent-mediated preschool intervention can produce sustained improvement in child autism symptoms and social communication with parents, which remained at nearly 6 years after the end of treatment. These findings support the potential long-term effects and value of early parent-mediated interventions for autism." I might also add: "these results are encouraging and provide evidence that sustained changes in autism symptoms can be possible after early intervention, something that has previously been regarded as difficult to achieve."

Caveats? Well, there are a few, not least the observation: "we cannot be sure how our results would generalise to young children with less severe symptoms." The authors also stress that the word 'cure' is not part and parcel of their results, and when it came to important comorbidities such as anxiety: "our related hypothesis that levels of child anxiety, which are often linked to levels of restricted and repetitive behaviours in autism,would also show a treatment effect at follow-up was refuted." Autism rarely exists in a diagnostic vacuum. Given also the quite long time between original and follow-up, it's not outside of the realms of possibility that other 'interventions' may also have 'chipped in' when it came to contributing to the behavioural outcomes noted or there being some element of natural waxing and waning of symptoms at work for some.

For the scientific sticklers out there (good on yer!), there are also a few details included in the study appendix pertinent to protocol and analysis amendments that were included in the study as it is presented, including dropping the Autism Diagnostic Interview-Revised (ADI-R) from the assessment battery and reported results. Does this mark the beginning of the end for the ADI-R I wonder?

So there you have it. After a slightly shaky start potentially illustrative of only modest short-term effects, early intervention of this type might actually have some more positive longer term effects. Of course, I'd like to see some further independent replication of this study and such behavioural intervention does not disqualify other approaches as also potentially being useful for some on the autism spectrum (see here for example). It's all about getting the right support and strategies in place for each individual person and perhaps getting the timing right too (see here).

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[1] Pickles A. et al. Parent-mediated social communication therapy for young children with autism (PACT): long-term follow-up of a randomised controlled trial. Lancet. 2016. Oct 26.

[2] Green J. et al. Parent-mediated communication-focused treatment in children with autism (PACT): a randomised controlled trial. Lancet. 2010 Jun 19;375(9732):2152-60.

[3] Byford S. et al. Cost-effectiveness analysis of a communication-focused therapy for pre-school children with autism: results from a randomised controlled trial. BMC Psychiatry. 2015 Dec 21;15:316.

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Pickles, A., Le Couteur, A., Leadbitter, K., Salomone, E., Cole-Fletcher, R., Tobin, H., Gammer, I., Lowry, J., Vamvakas, G., Byford, S., Aldred, C., Slonims, V., McConachie, H., Howlin, P., Parr, J., Charman, T., & Green, J. (2016). Parent-mediated social communication therapy for young children with autism (PACT): long-term follow-up of a randomised controlled trial The Lancet DOI: 10.1016/S0140-6736(16)31229-6

The stability of an Asperger syndrome diagnosis continued

"The subsample that no longer fulfilled an autism spectrum disorder had full-time jobs or studies (10/11), independent living (100%), and reported having two or more friends (100%)."

So said the paper by Adam Helles and colleagues [1] continuing a research theme from this authorship group on what happens to autism, or rather Asperger syndrome, in the longer-term (see here). Indeed, if you have the time, the thesis from Helles covering this area of study is well worth a read (see here).

This time around the focus was on the often fuzzy concept called 'quality of life' (see here) in terms of "work, academic success, living situation, relationships, support system" for 50 males "with Asperger syndrome diagnosed in childhood and followed prospectively over two decades." Alongside those 'objective' measures of quality of life (QoL), Helles et al also sought some information about more 'subjective' reports of QoL with the use of the "Sense of Coherence and Short-Form Health Survey-36" schedules.

As per the opening sentence to this post, I've initially focused in on those participants where diagnosis was not stable (i.e. the sub-group who did not continue to fulfil criteria for Asperger syndrome) as providing yet more evidence [2] on how objective outcomes were seemingly improved compared to those who still reached diagnostic thresholds. Allied to other work by other independent research groups (see here), these findings continue to demonstrate just how heterogeneous the autism spectrum is and that dogma about autism being a 'lifelong condition' might not necessarily be applicable to everyone who at one time or another met diagnostic thresholds. I know such a line of thought is not always received well by all, but I am of the opinion that remitting autism is at least as likely and important as remitting schizophrenia or remitting depression for example. As to the mechanisms, well, I don't want to speculate too much at this time but 'autisms' (plural) is a word that springs to mind as a first thought when it comes to such experiences (see here).

When compared to this subgroup of those no longer meeting diagnostic criteria, those who remained within the diagnostic boundaries of Asperger syndrome did not appear to fare so well on those objective measures of QoL: "41% had full-time job or studies, 51% lived independently, and 33% reported two or more friends, and a significant minority had specialized employments, lived with support from the government, or had no friends." I say that bearing in mind the difference in participant numbers falling into one or other grouping.

In terms of those subjective measures of QoL, we are also told that: "Stability of autism spectrum disorder diagnosis was associated with objective but not subjective quality of life" and that "psychiatric comorbidity was associated with subjective but not objective quality of life." This is perhaps not unexpected as per the growing body of research suggesting that various psychiatric comorbidity might be over-represented when a diagnosis of autism is received (see here) and how some of it can be truly disabling (see here). It's not then beyond the realms of possibility that one could have (and hold down) a job for example (objective QoL), but feel that one's subjective QoL is still poor as a result of said comorbidity and its impact on areas of life like employment. Indeed, I'd perhaps forward a research case for how what we term 'comorbidity' might actual be more central to the presentation of various types of autism (see here) outside of being just another add-on diagnosis.

I don't want to come across as being too focused on outcomes around diagnostic instability when it comes to the autism spectrum because for the majority of people the diagnosis, whilst liable to fluctuation with regards to certain facets and skills, is very much a lifelong thing. That also definitions of long-term outcome and QoL say little about important concepts such as happiness and life satisfaction is another important point to make (see here). But the accumulating longitudinal work from Helles and others is providing something of an important window into autism in the long-term and how, wearing the cold, objective spectacles of science, the remittance of core symptoms might not be an unfavourable outcome for some...

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[1] Helles A. et al. Asperger syndrome in males over two decades: Quality of life in relation to diagnostic stability and psychiatric comorbidity. Autism. 2016 May 26. pii: 1362361316650090.

[2] Gillberg IC. et al. Boys with Asperger Syndrome Grow Up: Psychiatric and Neurodevelopmental Disorders 20 Years After Initial Diagnosis. J Autism Dev Disord. 2016 Jan;46(1):74-82.

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Helles A, Gillberg IC, Gillberg C, & Billstedt E (2016). Asperger syndrome in males over two decades: Quality of life in relation to diagnostic stability and psychiatric comorbidity. Autism : the international journal of research and practice PMID: 27233289

The persistence of self-injury in relation to autism

Some behaviours associated with a diagnosis of autism don't make for great dinner table discussion. Self-injurious behaviours (SIBs), as exemplified by head banging, hair pulling and eye gouging must rank as some of the more distressing facets of [some] autism insofar as their potential effect on the person and also the people around them.

These and other types of behaviour commonly headed under the category of so-called 'challenging behaviours' have tended not to be too evident when it comes to the public depiction of autism it has to be said. I can appreciate why, but what this can mean is that such issues tend to get 'brushed under the carpet'. In recent times however, there does seem to be a greater willingness for research to delve into such behaviours [1].

The paper by Caroline Richards and colleagues [2] (open-access) looking at the persistence of such behaviour(s) and the potential correlates associated with their persistence is a welcome piece of research added to the research interest. Highlighting how for a small research sample of 67 children/young adults with autism over three-quarters reported SIB persisting over a 3-year period, the data provide some interesting insights into the nature of this issue and, potentially how it should be screened for and managed.

Based here in Blighty, researchers initially managed to recruit 190 participants, the data for some of whom were previously published [3]. As perhaps one might expect, the follow-up after on average 36.4 months had elapsed was not so well-populated. No mind, various findings are reported including that "the presence, topography and severity of self-injury were persistent and stable over three years" and that "individuals with self-injury were significantly more likely to be non-verbal than those who did not engage in self-injury." Further: "individuals with self-injury were significantly more likely to be less able and non-verbal and to show higher levels of stereotyped behaviour, compulsive behaviour, insistence on sameness, overactivity, impulsivity, repetitive behaviour and impairments in social interaction."

There is quite a bit more to do on this topic including facing up to issues around the small (eventual) participant size and the reliance on 'a questionnaire pack' as the chosen method of assessment. The authors also talk quite a bit about how some of the behaviours observed in connection with self-injury - impaired behavioural inhibition - might overlap with other diagnoses such as attention-deficit hyperactivity disorder (ADHD) but as far as I can see, they did not directly screen for ADHD outside of the use of something called The Activity Questionnaire (TAQ). I might also have liked to have seen a little more information about how parents/professionals had 'tackled' SIB in this cohort and what effect that might have had on results. Investigations remain.

Having said all that, the insights provided by the Richards article are important and provide plenty of food for thought when it comes to SIB and autism. Without trying to generalise SIB to all autism nor to come across as portraying too negative an image of what autism can mean to someone, recognition and management (dare I say treatment) of such behaviours when present should really be a priority [4].

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[1] Maddox BB. et al. Untended wounds: Non-suicidal self-injury in adults with autism spectrum disorder. Autism. 2016 May 12. pii: 1362361316644731.

[2] Richards C. et al. Persistence of self-injurious behaviour in autism spectrum disorder over 3 years: a prospective cohort study of risk markers. Journal of Neurodevelopmental Disorders 2016; 8: 21.

[3] Richards C. et al. Self-injurious behaviour in individuals with autism spectrum disorder and intellectual disability. J Intellect Disabil Res. 2012 May;56(5):476-89.

[4] Lee Y-H. et al. Cataract secondary to self-inflicted blunt trauma in children with autism spectrum disorder. Journal of American Association for Pediatric Ophthalmology and Strabismus. 2016. May 17.

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Richards, C., Moss, J., Nelson, L., & Oliver, C. (2016). Persistence of self-injurious behaviour in autism spectrum disorder over 3 years: a prospective cohort study of risk markers Journal of Neurodevelopmental Disorders, 8 (1) DOI: 10.1186/s11689-016-9153-x

Long terms effects of communication by gesture and autism: a case report

As per previous entries on this blog, I'm not at all adverse to the idea that case reports (the so-called N=1) can offer some important insights into a heterogeneous (dare I say 'plural') condition like autism. Today, I'm once again heading down this route as I bring to your attention the letter from Webster and colleagues [1] talking about a 40 year follow-up note "About a Boy with Autism Taught to Communicate by Gestures when Aged Six."

Harking back to a paper published by some of the authors in 1973 [2] (published in the same journal albeit under a different title name), Webster et al provide some important details on how Geoff, a then 6-year old boy, was taught "a sign-language program" and how "at the time, it seemed to help Geoff and many other children." Fast forward some 40+ years and the authors note that things have changed but at the same time remained pretty much the same for Geoff. So: "Geoff has hung onto the signs taught to him early on" but also: "Geoff now “speaks” as he signs some words. This speech is easier to understand if you see him every day than if you see him only now and then." Indeed his vocabulary, whilst perhaps limited by other standards, does include many important words, mostly signed but some either said verbally or paired verbally with signing. Outside of things like food preferences, I was particularly happy to see that various emotions and states are represented in his vocabulary; never underestimate the power that being able to tell someone that you are 'happy' or 'angry' can bring to a person.

"His communications, both verbal and gestural, are constantly evolving to help him to express his wishes, and he seems very excited when he has made clear his needs or wants and we have understood them." What that sentence tells us is that communication is both a vital bridge and something that should be constantly 'worked on' when it comes to autism [3]. In these days where quite a lot of focus has turned towards the usefulness of early intervention for autism (see here for example), the message that learning is a lifelong thing can often get lost in the noise. I might add that said learning might be made a little easier by the rapid rise in technology [4].

Finally, I think it is important to draw your attention to another aspect of the Webster letter in terms of the use of residential and supported living arrangements and the autism spectrum. In line with the idea that the autism spectrum is truly wide and heterogeneous is the reality that for quite a few people, lifetime residential placement and care are an important part of their lives. Geoff, we are told "adjusted well to the residential setting" and continues to enjoy life in that setting. The authors acknowledge that despite their success in teaching sign to people like Geoff: "we tended to underestimate the long-term services that many of these children, as they grow into adolescence and adulthood, do actually require." I daresay that those sentiments ring as true today as they did 40 years ago.

To close, yet another DC comics film coming soon with an excellent trailer soundtrack...

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[1] Webster CD. et al. Lessons that Linger: A 40-Year Follow-Along Note About a Boy with Autism Taught to Communicate by Gestures when Aged Six. J Autism Dev Disord. 2016. March 28.

[2] Webster CD. et al. Communicating with an autistic boy by gestures. J Autism Child Schizophr. 1973 Oct-Dec;3(4):337-46.

[3] Mulhern T. et al. A systematic review and evaluation of procedures for the induction of speech among persons with developmental disabilities. Dev Neurorehabil. 2016 Apr 8:1-21.

[4] Lorah ER. et al. A Systematic Review of Tablet Computers and Portable Media Players as Speech Generating Devices for Individuals with Autism Spectrum Disorder. J Autism Dev Disord. 2015 Dec;45(12):3792-804.

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Webster, C., Fruchter, D., Dean, J., Konstantareas, M., & Sloman, L. (2016). Lessons that Linger: A 40-Year Follow-Along Note About a Boy with Autism Taught to Communicate by Gestures when Aged Six Journal of Autism and Developmental Disorders DOI: 10.1007/s10803-016-2773-x

Going long: examining psychiatric comorbidity in PDD-NOS

"Psychiatric comorbidities in children with autism spectrum disorder (ASD) are rather a rule than an exception."

That was the opening sentence to the paper by Verheij and colleagues [1] (open-access available here) who charted the stability of such comorbidity in a "7-year follow-up of 74 6-12 year old children with Pervasive Developmental Disorder-Not Otherwise Specified [PDD-NOS]."

Continuing a theme from this research group [2] looking longitudinally at what happened to individuals who "were initially referred for diagnostic evaluation to the Department of Child and Adolescent Psychiatry/Psychology of the Erasmus Medical Center—Sophia Children’s Hospital between July 2002 and September 2004", researchers examined various comorbid psychiatric disorders such as anxiety and mood disorder(s) via the use of the Diagnostic Interview Schedule for Children IV Parent Version (DISC-IV-P) over the course of two testing waves (aged 6-12 years and aged 12-20 years).

They found that: "The rate of comorbid psychiatric disorders dropped significantly from childhood (81 %) to adolescence (61 %)." Specifically, the frequency of anxiety disorders dropped from 55% in wave 1 (6-12 years) to 31% in wave 2 (12-20 years) (based on an average follow-up time between waves of nearly 7 years). The frequency of social phobia also seemed to drop between the testing waves (~11% vs. 1%) as did the frequency of specific phobias (40% vs. 25%); these differences were noted to be significant.

But it was not all good news, as we are told that: "The rates for externalizing (i.e. disruptive) disorders did not significantly change from childhood (i.e. 61 %) to adolescence (i.e. 51 %)"; this categorisation including diagnoses such as attention-deficit hyperactivity disorder (ADHD) (various types) and conduct disorder. Indeed also, when it came to issues such as major depressive disorder, the authors noted a non-significant increase in the frequency of this label examined over the course of the testing waves. Further: "Of the individuals who had no comorbid psychiatric disorder in childhood (n = 14), 50 % (n = 7) stayed free of a comorbid psychiatric disorder in adolescence, whereas 50 % (n = 7) of the individuals developed at least one comorbid psychiatric disorder in adolescence."

In terms of predicting stability across the comorbidity and non-comorbidity groups - "the “persistent presence” group (n = 38) versus the “presence to absence” group (n = 22)" - parent-reported stereotyped behaviours and reduced social interest in childhood as measured on the Children’s Social Behavior Questionnaire (CSBQ) seemed to play something of a role, albeit with the requirement for much further study.

Set within the context of PDD-NOS falling into at least some descriptions of the autism spectrum (newer diagnostic criteria don't mention this category) these are interesting results. That certain psychiatric comorbidity wax and wane as a function of issues such as maturation for example, provides something of a ray of hope that these often disabling comorbidity (yes, anxiety can be utterly disabling) may not always be set in stone. At least that is, with regards to their reaching clinical significance and diagnostic thresholds.

Following a trend in autism research suggesting that the core traits of autism are also probably more dynamic than anyone has hitherto appreciated (see here), I might also advance the idea that where issues such as anxiety wane, so to this might have an effect on the core presentation of autism in terms of things like intervention success for example (see here). I might also refer you back to the idea of optimal outcome (OO) in relation to autism and what this might also mean for the presence of psychiatric comorbidity (see here).

The suggestion that certain psychiatric elements however may not be as likely to retreat when it comes to some autism, such as certain types of ADHD and/or major depressive disorder, remains a worrying prospect. As per the Myriam De-la-Iglesia / José-Sixto Olivar discussion piece [3] (see here for my take) on depression and at least some autism, the often far-reaching effects of depression in conjunction with autism is something that really does need to be tackled, and tackled effectively. Not least because of the "high index of depression in this collective emphasises the need to detect suicidal tendencies." A sad but all too real outcome I'm afraid (see here).

I end with a few caveats to bear in mind about the Verheij data: "Results are based on parental interviews in a relatively small sample of individuals with PDD-NOS with an average to high IQ who were referred to one particular center, thus clinicians should make careful considerations regarding their own specific clients, and further research on samples with more phenotypic variation in ASD severity and cognitive ability using multiple informants is needed." That also there were gaps in important variables such as medication history and other more socially-related variables should also be noted.

Still, this kind of longitudinal research is the kinda thing that autism science really needs to do a lot more of, allied to the idea that psychiatric comorbidity is probably over-represented when it comes to the label of autism [4].

To close, the Japanese trailer for the next Star Wars instalment has some new scenes to tantalise...

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[1] Verheij C. et al. The Stability of Comorbid Psychiatric Disorders: A 7 Year Follow Up of Children with Pervasive Developmental Disorder-Not Otherwise Specified. J Autism Dev Disord. 2015 Oct 12.

[2] Louwerse A. et al. ASD Symptom Severity in Adolescence of Individuals Diagnosed with PDD-NOS in Childhood: Stability and the Relation with Psychiatric Comorbidity and Societal Participation. J Autism Dev Disord. 2015 Sep 22.

[3] De-la-Iglesia M. & Olivar JS. Risk Factors for Depression in Children and Adolescents with High Functioning Autism Spectrum Disorders. ScientificWorldJournal. 2015;2015:127853.

[4] Russell AJ. et al. The mental health of individuals referred for assessment of autism spectrum disorder in adulthood: A clinic report. Autism. 2015 Oct 15. pii: 1362361315604271.

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Verheij C, Louwerse A, van der Ende J, Eussen ML, Van Gool AR, Verheij F, Verhulst FC, & Greaves-Lord K (2015). The Stability of Comorbid Psychiatric Disorders: A 7 Year Follow Up of Children with Pervasive Developmental Disorder-Not Otherwise Specified. Journal of autism and developmental disorders PMID: 26456972

Of vaccines and monkeys

A quote to begin:

"These data indicate that administration of TCVs [thimerosal-containing vaccines] and/or the MMR [measles, mumps, rubella] vaccine to rhesus macaques does not result in neuropathological abnormalities, or aberrant behaviors, like those observed in ASD [autism spectrum disorder]."

Those were the findings reported by Bharathi Gadad and colleagues [1] (open-access available here) and their study providing "a comprehensive analysis of the influence of TCVs on the brain and behavior in a nonhuman primate model."

Giving infant rhesus macaques "the recommended pediatric vaccine schedules from the 1990s and 2008" and various combinations of vaccinations including MMR vaccine and vaccines on an "accelerated schedule" in contrast to saline (placebo) injections, authors reported no significant differences among behavioural or neuropathological parameters inspected as a function of vaccination status.

Although a little late in getting to this research, I believe this study also ties in with other recent results from some of the same authorship group [2] also suggesting that over a 5-year period of inspection, there was "no consistent evidence of neurodevelopmental deficits or aberrant behavior in vaccinated animals." Readers might also like to read an additional paper from the authors talking about the usefulness of animal models when it comes to autism research [3] among other things.

Appreciating that to mention immunisation and autism in the same sentence can stir up some significant emotions (readers may like to read Tom Insel's post on the Four Kingdoms of Autism as a background), I was drawn to blog about the Gadad paper because it is peer-reviewed science. Alongside the growing evidence base suggesting that there probably is no population-wide link between various vaccine administrations and risk of autism (see here) and the important public health message about the value of immunisation, the Gadad data represents some good longitudinal animal science.

If I had to quibble in anyway about the study, it would be that monkeys are monkeys and not humans (similarly applied to other animal models), and that the animal participant numbers were pretty small bearing in mind that said animals were eventually sacrificed for neuropathological inspection. I'd also suggest that whilst there is evidence that autism is correlated with certain brain regions (see here for example), the jury is still out on making any generalised assumptions to the very, very wide autism spectrum complete with added risk of various comorbidity. Others have also similarly mentioned that not all vaccine groups were fully studied and data presented in the current Gadad paper, so maybe there is more to come from this research project.

The use of nonhuman primates as 'subjects' in the debate about any link between vaccination and 'neurodevelopmental outcomes' has had its fair share of twists and turns down the years. Some readers might remember the peculiar case of another paper from Laura Hewitson and colleagues [4] titled: 'Delayed acquisition of neonatal reflexes in newborn primates receiving a thimerosal-containing hepatitis B vaccine: influence of gestational age and birth weight' that is listed as 'withdrawn' under another entry on PubMed [5] albeit published in another journal. On that occasion, researchers suggested that their data pointed to a possible interaction between birth weight and gestational age when it came to hepatitis B vaccination and the presentation of early reflexes in animals. Other papers from this group [6] have similarly proved controversial, insofar as the reported effects of a pediatric vaccine schedule on aspects of opioid ligand binding for example (with others challenging the results [7] and an author reply). This area seems to court controversy.

I will end however by reiterating the findings reported by Gadad et al reporting the lack of adverse effects of the pediatric vaccine schedule on some of our closest cousins in the animal world. This does not mean that continued vigilance should figure any less (even perhaps with certain groups in mind [8] as per other musings) with regards to this aspect of our pharmaceutical armoury nor that other factors around the time of vaccination are necessarily 'off the hook' [9] as potentially being important to [some] autism. But it does provide some important data pertinent to discussions on the risk/benefit ratio of immunisations and their potentially far-reaching benefits [10].

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[1] Gadad BS. et al. Administration of thimerosal-containing vaccines to infant rhesus macaques does not result in autism-like behavior or neuropathology. Proc Natl Acad Sci U S A. 2015 Sep 28. pii: 201500968.

[2] Curtis B. et al. Examination of the Safety of Pediatric Vaccine Schedules in a Non-Human Primate Model: Assessments of Neurodevelopment, Learning, and Social Behavior. Environmental Health Perspectives. 2015;123(6):579-589.

[3] Gadad BS. et al. Neuropathology and Animal Models of Autism: Genetic and Environmental Factors. Autism Research and Treatment. 2013;2013:731935.

[4] Hewitson L. et al. Delayed acquisition of neonatal reflexes in newborn primates receiving a thimerosal-containing hepatitis B vaccine: influence of gestational age and birth weight. J Toxicol Environ Health A. 2010;73(19):1298-313.

[5] Hewitson L. et al. WITHDRAWN: Delayed acquisition of neonatal reflexes in newborn primates receiving a thimerosal-containing Hepatitis B vaccine: Influence of gestational age and birth weight. Neurotoxicology. 2009 Oct 2.

[6] Hewitson L. et al. Influence of pediatric vaccines on amygdala growth and opioid ligand binding in rhesus macaque infants: A pilot study. Acta Neurobiol Exp (Wars). 2010;70(2):147-64.

[7] Novella S. & Hines T. Autism and the amygdala: commentary on Hewitson and coauthors (2010). Acta Neurobiol Exp (Wars). 2011;71(1):178-9; author reply 180-1.

[8] Poling JS. et al. Developmental Regression and Mitochondrial Dysfunction in a Child With Autism. Journal of Child Neurology. 2006;21(2):170-172.

[9] Schultz ST. et al. Acetaminophen (paracetamol) use, measles-mumps-rubella vaccination, and autistic disorder: the results of a parent survey. Autism. 2008 May;12(3):293-307.

[10] Fullerton HJ. et al. Infection, vaccination, and childhood arterial ischemic stroke. Neurology. 2015. Sept 30.

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Gadad BS, Li W, Yazdani U, Grady S, Johnson T, Hammond J, Gunn H, Curtis B, English C, Yutuc V, Ferrier C, Sackett GP, Marti CN, Young K, Hewitson L, & German DC (2015). Administration of thimerosal-containing vaccines to infant rhesus macaques does not result in autism-like behavior or neuropathology. Proceedings of the National Academy of Sciences of the United States of America PMID: 26417083

Fish oils preventing psychosis: long-term effects?

"This is the first study to show, to the best of our knowledge, that a 12-week intervention with omega-3 PUFAs [polyunsaturated fatty acids] prevented transition to full-threshold psychotic disorder and led to sustained symptomatic and functional improvements in young people with an at-risk mental state for 7 years (median)."

So said the quite remarkable findings reported by Paul Amminger and colleagues [1] (open-access available here) who followed up their previous research study [2] looking at the effects of a 12-week supplementation program consisting of either 1.2 grams per day of fish oil or placebo. On that previous occasion, said omega-3 PUFA supplement ("700 mg of eicosapentaenoic acid (20:5n3), 480 mg of docosahexaenoic acid (22:6n3), and 7.6 mg of mixed tocopherol (vitamin E)") reduced the risk of progression to psychotic disorder in individuals at ultra-high risk of psychosis for up to a year post-intervention baseline.

The latest results represent quite an impressive post-intervention follow-up to the original Amminger study. Looking at some of the original cohort of participants and drawing on several types of information including screening / questionnaire data and "rate of prescription of antipsychotic medication", the authors were able to quite confidently conclude that "omega-3 PUFAs may offer a viable longer-term prevention strategy with minimal associated risk in young people at ultrahigh risk of psychosis."

Insofar as the precise hows and whys of omega-3 PUFAs potentially affecting psychosis risk, well, we are left in quite a typical position of speculating. "Omega-3 PUFAs provide a range of neurochemical activities via modulation of neurotransmitter (noradrenaline, dopamine and serotonin) reuptake, degradation, synthesis and receptor binding, as well as anti-inflammatory and anti-apoptotic effects, and the enhancement of cell membrane fluidity and neurogenesis." Take yer pick, bearing in mind there may also be additive and interacting effects within this menu of potential modes of action.

If one assumes however that the possible connection between omega-3 PUFAs and various behavioural and psychiatric labels might have some commonalities (see here and see here for example), one might see a few additional ways and means that 'mode of action' might become a little clearer in the future. One factor, cognitive decline linked to cases of psychosis onset, might not however be the prime factor extrapolating from other recent results [3]...

Music: Felix Jaehn - Ain’t Nobody (Loves Me Better).

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[1] Amminger GP. et al. Longer-term outcome in the prevention of psychotic disorders by the Vienna omega-3 study. Nat Commun. 2015 Aug 11;6:7934.

[2] Amminger GP. et al. Long-chain omega-3 fatty acids for indicated prevention of psychotic disorders: a randomized, placebo-controlled trial. Arch Gen Psychiatry. 2010 Feb;67(2):146-54.

[3] Chew EY. et al. Effect of Omega-3 Fatty Acids, Lutein/Zeaxanthin, or Other Nutrient Supplementation on Cognitive Function. JAMA. 2015; 314: 791-801.

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Amminger GP, Schäfer MR, Schlögelhofer M, Klier CM, & McGorry PD (2015). Longer-term outcome in the prevention of psychotic disorders by the Vienna omega-3 study. Nature communications, 6 PMID: 26263244