Wednesday, 1 July 2015

Offspring autism risk and advancing parental age (differences)

Parental age at offspring conception/birth in relation to offspring autism risk has been a recurrent theme in autism research circles for quite a few years now. I've covered it more than once on this blog (see here for example) and the various suggestions that advancing parental age in particular, might elevate the risk of offspring autism.

Set in this context, the paper by Sven Sandin and colleagues [1] (open-access) (a name not unfamiliar to this blog) adds to the research evidence based on their analysis of some 5.7 million children born between 1985 - 2004 resident in one of five countries (Denmark, Israel, Norway, Sweden and Western Australia). Including data on some 30,000 children diagnosed with an autism spectrum disorder (ASD): "Parental ages, sex and birth year were obtained from birth or civil registers."

After quite a bit of statistical modelling and controlling for various potentially confounding variables, several findings were reported pertinent to the authors' data being "the strongest evidence to date supporting the hypothesis that advanced parental ages at the time of birth are independently associated with risk for ASD in the offspring." Outside of "no support for any modification by the sex of the child" researchers also noted a "combined parental age effect" whereby there "was a joint effect of maternal and paternal age with increasing risk of ASD for couples with increasing differences in parental ages."

A few of the finer details of this study have been covered elsewhere (see here). I'll draw your attention to one or two statistics unearthed during the study:

  • "relative to fathers aged 20–29 years, fathers 50 years or older had a statistically significantly increased risk for offspring with ASD (RR=1.66 95% CI:1.49–1.85)",
  • "Relative to mothers aged 20–29 years, mothers younger than 20 years had a statistically significantly increased risk for offspring with ASD (RR=1.18 95% CI:1.08–1.29)" and 
  • the "lowest risk corresponded to couples that generated the majority of births, specifically, 29–39-year-old fathers and 25–35-year-old mothers.

Those estimates of relative risk (RR) statistics translate into an estimated 66% increased risk for offspring autism if a dad was over 50 years old compared with a dad in their 20s, an 18% increased risk for offspring autism for teen mums compared to 20-something mums and the lowest statistical risk of offspring autism being reported when dads conceive in their 30s coupled with a mid-20 to mid-30 year old mum. The authors also note that "Similar patterns of association, but with slightly higher RRs for the highest parental ages, were evident for AD [autistic disorder]" so completing the message about older parental ages at conception and differing parental ages being relevant across the autism spectrum.

Accepting that this was a huge study in terms of participant numbers and spanning different geographical locations, the authors rightly offer a few words of caution about their methods and data. So: "we lack information about potentially confounding variables such as SES [socio-economic status] and parental psychiatric history" is something to keep in mind [2]. Further: "We cannot rule out the possibility that other factors associated with parental age (for example, length of marriage or partnership, obstetric complications, gestational age and birth weight) have an important role in explaining our results" and "We did not have individual level information on co-morbid ID [intellectual disability] in ASD cases." I'd also suggest that given the growing emphasis on autism or ASD not existing in some sort of diagnostic vacuum (see here) one might reasonably ask whether other comorbidity outside of ID might also play a role in risk estimates.

As to the possible mechanism(s) of effect, well, the authors go through the usual older parents - older sperm and eggs mantra although perhaps bypassing an emerging area outside of just de novo mutations based on the role of epigenetic mechanisms (see here). They do suggest that the 'difference in parental age' factor might suggest "that the increase in risk is not attributable to advancing parental age per se, and that the risk increase cannot be explained solely by an accumulation of point mutations or other genomic alterations in the parents" but say little more on the basis of their collected data.

I might be wrong but I also didn't seem too much in the way of discussion of how parental nutrition might impact on offspring autism risk as per the proposed factor from other work by authors on the Sandin paper in relation to the inter-pregnancy interval (IPI) and autism risk (see here and see here). Although the idea that parental age might affect autism offspring risk, I'd be minded to suggest that this is only the first stage in a journey towards elucidating the particular mechanisms of any effect.

Music: The Pixies - Gigantic.

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[1] Sandin S. et al. Autism risk associated with parental age and with increasing difference in age between the parents. Mol Psychiatry. 2015 Jun 9.

[2] Lehti V. et al. Maternal socio-economic status based on occupation and autism spectrum disorders: A national case-control study. Nord J Psychiatry. 2015 Mar 3:1-8.

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ResearchBlogging.org Sandin S, Schendel D, Magnusson P, Hultman C, Surén P, Susser E, Grønborg T, Gissler M, Gunnes N, Gross R, Henning M, Bresnahan M, Sourander A, Hornig M, Carter K, Francis R, Parner E, Leonard H, Rosanoff M, Stoltenberg C, & Reichenberg A (2015). Autism risk associated with parental age and with increasing difference in age between the parents. Molecular psychiatry PMID: 26055426

Tuesday, 30 June 2015

Low glycemic index diet reduces symptoms of mouse autism

A quote to begin: "Overall, the manuscript supports the idea that ASD [autism spectrum disorder] results from gene–environment interactions and that in the presence of a genetic predisposition to ASD, diet can make a large difference in the expression of the condition."

The manuscript in question was by Antonio Currais and colleagues [1] reporting some rather interesting results based on the 'dangermouse' that is the BTBR mouse model of autism. Researchers from the Salk Institute for Biological Studies showed that "the dietary glycemic index has a significant impact on the ASD phenotype." The dietary glycemic index (GI) by the way, is concerned with how particular foods / foodgroups affect blood glucose levels and the crux of the research was to see what happened to pregnant mice when fed either a high GI or low GI diet in terms of offspring outcomes. Offspring also followed the same diet diet post weaning.

To quote from the paper and some associated media: "The two groups of animals consumed the same number of calories and were identical in weight. But mice that ate a high-glycemic index diet showed all of the expected behavioral symptoms of autism. Their social interactions were impaired, they repeated actions that served no apparent purpose, and they groomed extensively."

Various other differences were present across the different dieting mice as per the findings that: "diet modulates plasma metabolites, neuroinflammation and brain markers of neurogenesis in a manner that is highly reflective of ASD in humans." This included the finding that "the brains of the high-glycemic index diet mice appeared to have greater numbers of activated microglia, the resident immune cells of the brain" and various inflammation-related genes being more readily expressed in comparison to the low-glycemic index diet mice. Microglia and autism remains a complex topic (see here) but with the advent of recent research findings [2] complete with headlines such as ''Missing link' between brain and immune system discovered' I dare say that we'll be hearing more about this is times to come.

The compound doublecortin also receives a mention in the Currais results as per the suggestion that those mice living on the high-glycemic diet had less of the stuff and the significance of this finding given the link between doublecortin and neurogenesis for example [3]. Bearing in mind the BTBR mouse model of autism might already be more prone to reductions in the levels of doublecortin [4] it might be useful to see how this finding pans out when applied to real people in the real world.

"The new study found that the diet might directly influence the ecosystem of bacteria in the gut." It perhaps goes without saying that any sort of dietary change is likely to affect the composition of those trillions of wee beasties that call our gastrointestinal (GI) tract home. This also applies to mice and probably every other type of animal. "'We were really surprised when we found molecules in the blood that others had reported could only be generated by gut bacteria,' Maher says. 'There were big differences in some of these compounds between the two diets.'" Metabolites of gut bacteria found in general circulation... does this imply intestinal permeability (leaky gut) might be part and parcel of any effect? If so, would that perhaps also tie into the findings reported by Elaine Hsaio and colleagues a while back on leaky mice guts, gut bacteria and autism? Add in also the idea that high glycemic index foods tend to include things like wheat and various other grains and we start to get something looking rather familiar to autism research that may well show some relationship [5].

"The group plans to analyze the gut bacteria, and its potential link with features of autism, more directly. They also hope to better understand the role of inflammation in the ability to generate new neurons." I'm very much looking forward to seeing these results, bearing in mind that mice are mice not people [6] and autism (or rather the autisms) is/are [a] very complicated condition(s).

Music: The Jesus And Mary Chain - Just Like Honey.

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[1] Currais A. et al. Dietary glycemic index modulates the behavioral and biochemical abnormalities associated with autism spectrum disorder. Molecular Psychiatry. 2015. June 9.

[2] Louveau A. et al. Structural and functional features of central nervous system lymphatic vessels. Nature. 2015 Jun 1.

[3] Couillard-Despres S. et al. Doublecortin expression levels in adult brain reflect neurogenesis. Eur J Neurosci. 2005 Jan;21(1):1-14.

[4] Stephenson DT. et al. Histopathologic characterization of the BTBR mouse model of autistic-like behavior reveals selective changes in neurodevelopmental proteins and adult hippocampal neurogenesis. Mol Autism. 2011 May 16;2(1):7.

[5] Lammers KM. et al. Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3. Gastroenterology. 2008 Jul;135(1):194-204.e3.

[6] Wong AH. & Josselyn SA. Caution When Diagnosing Your Mouse with Schizophrenia: The Use and Misuse of Model Animals for Understanding Psychiatric Disorders. Biol Psychiatry. 2015 May 6. pii: S0006-3223(15)00361-3.

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ResearchBlogging.org Currais A, Farrokhi C, Dargusch R, Goujon-Svrzic M, & Maher P (2015). Dietary glycemic index modulates the behavioral and biochemical abnormalities associated with autism spectrum disorder. Molecular psychiatry PMID: 26055422

Monday, 29 June 2015

Fermented foods and social anxiety?

Stumbling across a headline that reads: 'Study Finds Decreased Social Anxiety Among Young Adults Who Eat Fermented Foods' was bound to pique my blogging interest. When I eventually tracked down the source paper behind the headline I became more and more intrigued as today I bring to your attention the study findings reported by Matthew Hilimire and colleagues [1].

Implementing "a cross-sectional approach to determine whether consumption of fermented foods likely to contain probiotics interacts with neuroticism to predict social anxiety symptoms" researchers asked over 700 students - psychology students - to self-report on "fermented food consumption, neuroticism, and social anxiety." Fermented foods by the way, cover a range of foods "that contain probiotics" including yogurt and sauerkraut (a particular favourite of mine). Researchers also enquired about various other variables such as fruit and vegetable intake and the amount of exercise taken over the past 30 days.

Bearing in mind that this was a study based on self-report and that psychology students might not be entirely representative of the population in general, the results of an "interaction model, controlling for demographics, general consumption of healthful foods, and exercise frequency" did seem to suggest that there may be more to see when it comes fermented food consumption and social anxiety: "Fermented foods should be further investigated as an intervention for social anxiety."

I'm not falling hook, line and sinker for these results - correlation is not the same as causation - despite my continuing interest in the science of psychobacteriomics (my word creation) and the idea that those trillions of wee beasties that inhabit our deepest, darkest [gut] recesses might be doing so much more than just helping to digest food and making the odd nutrient or two. I do however think that we need to dedicate quite a few more resources to the idea that psychology and behaviour might not be solely rooted in the grey-pink matter floating in our skull [2] as recent news articles seem to imply.

Finally, and without wishing to make too many sweeping generalisations from the Hilimire results, I did think about whether such findings may be particularly 'useful' for certain groups of people where social anxiety might be over-represented. Autism is an obvious label given the suggestion that at least a quarter of those on the autism spectrum might also fulfil the diagnostic criteria for social anxiety disorder (see here). That such anxiety might also have knock-on effects to the presentation of more core autism symptoms (see here) is also noteworthy bearing in mind that a diet rich in fermented foods might not be for everyone and that social anxiety with or without autism is bound to be a very complicated process.

We await further research in this area.

Music: The Flaming Lips - Do You Realize??

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[1] Hilimire MR. et al. Fermented foods, neuroticism, and social anxiety: An interaction model. Psychiatry Res. 2015; 228: 203-208.

[2] Dinan TG. et al. Collective unconscious: how gut microbes shape human behavior. J Psychiatr Res. 2015 Apr;63:1-9.

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ResearchBlogging.org Hilimire MR, DeVylder JE, & Forestell CA (2015). Fermented foods, neuroticism, and social anxiety: An interaction model. Psychiatry research, 228 (2), 203-8 PMID: 25998000

Saturday, 27 June 2015

Probiotics, schizophrenia and inflammation

I have to say that I was initially pretty interested to read the paper by Jakub Tomasik and colleagues [1] (open-access available here) discussing results examining the "possible immunomodulatory effects of probiotic supplementation in chronic schizophrenia patients."

Interested because not only was this a partnership paper including Robert Yolken and Faith Dickerson on the authorship list (names who have appeared a few times on this blog) but also because of the subject matter extending some research interest into how gastrointesinal (GI) 'functions' may very well have some important implications for at least some cases of schizophrenia (see here) particularly linked to the concept of inflammation. This area of research on a 'gut-brain connection', also links into a body of work with autism in mind (see here) and with that autism connection, mention of one Sabine Bahn as a co-author and some research she has published [2] is also worth noting.

In the current paper, Tomasik et al describe work following on from a previous study by Dickerson and colleagues [3] suggesting that adjuvant probiotic use may "help to prevent severe bowel difficulty in patients with schizophrenia" even if not significantly affecting the behavioural presentation of schizophrenia on that research occasion. With no endorsement given or intended, the probiotic preparation in question was called Bifiform Balance and contained "the probiotic organism L. rhamnosus GG and... colony forming units of the probiotic organism Bifidobacterium animalis subsp. lactis BB12 (Ferrosan).Lactobacillus rhamnosus GG has appeared before on this blog (see here) so I was intrigued as I always am when it comes to gut bacteria and health / behaviour.

Authors describe how blood samples from 58 participants who completed the previous Dickerson trial ("31 in the probiotic arm and 27 in the placebo arm") were collected pre- and post-trial (after 14 weeks) and serum samples analysed by immunoassay "targeting selected inflammatory markers, including cytokines, chemokines, and acute-phase reactants."

Results: "Probiotic add-on treatment significantly reduced levels of von Willebrand factor (vWF) and increased levels of monocyte chemotactic protein-1 (MCP-1), brain-derived neurotrophic factor (BDNF), RANTES, and macrophage inflammatory protein-1 beta (MIP-1) beta with borderline significance (P ≤ 0.08)." Actually, the only significant effect was noted for vWF (p=0.047) for which levels seemed to drop following probiotic use. Also interesting was the finding that within the group taking the placebo (although I'm not altogether sure what this contained) there were significant pre- and post-intervention differences for compounds such as vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1); both showing reductions.

The authors note that the significant reduction in levels of vWF within the context of probiotics as an add-on treatment alongside more commonplace pharmacotherapy for schizophrenia might have some important implications for "certain cardiovascular risk parameters" for example. This statement is rooted in the idea that vWF has some research history when it comes to schizophrenia both outside [4] and inside this connection [5]. Certainly, vWF shows a link to inflammation and with mention of the words adhesion too. In the context of schizophrenia, inflammation is of growing interest...

"We conclude that probiotics have immunomodulatory effects in schizophrenia patients, affecting molecules that do not respond to standard antipsychotic therapy." If one goes by the statistical book, I'm not entirely sure that the current findings are completely in line with that last statement. Yes, vWF showed something of a 'relationship' to the probiotic use but the other results with "borderline significance" and the fact that authors "were not able to detect all targeted cytokines in [their] clinical samples", I'd be a little cautious about saying too much more.

Music: House Of Love - Destroy The Heart.

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[1] Tomasik J. et al. Immunomodulatory Effects of Probiotic Supplementation in Schizophrenia Patients: A Randomized, Placebo-Controlled Trial. Biomark Insights. 2015 Jun 1;10:47-54.

[2] Schwarz E. et al. Sex-specific serum biomarker patterns in adults with Asperger's syndrome. Mol Psychiatry. 2011 Dec;16(12):1213-20.

[3] Dickerson FB. et al. Effect of probiotic supplementation on schizophrenia symptoms and association with gastrointestinal functioning: a randomized, placebo-controlled trial. Prim Care Companion CNS Disord. 2014;16(1). pii: PCC.13m01579.

[4] Hope S. et al. Similar immune profile in bipolar disorder and schizophrenia: selective increase in soluble tumor necrosis factor receptor I and von Willebrand factor. Bipolar Disord. 2009 Nov;11(7):726-34.

[5] Dieset I. et al. Cardiovascular risk factors during second generation antipsychotic treatment are associated with increased C-reactive protein. Schizophr Res. 2012 Sep;140(1-3):169-74.

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ResearchBlogging.org Tomasik J, Yolken RH, Bahn S, & Dickerson FB (2015). Immunomodulatory Effects of Probiotic Supplementation in Schizophrenia Patients: A Randomized, Placebo-Controlled Trial. Biomarker insights, 10, 47-54 PMID: 26052224

Friday, 26 June 2015

Early sex differences are not autism-specific

The title of this post mirrors the title of the paper published by Daniel Messinger and colleagues [1] (open-access available here) that reported on "younger sibling sex differences and proband sex differences on the odds of ASD [autism spectrum disorder] in a large sample of prospectively followed high-risk siblings."

Researchers found that alongside "a three-to-one male:female odds ratio in ASD recurrence... the emergence of ASD symptoms in high-risk siblings—both with and without eventual ASD outcomes—occurs in the context of naturally occurring sex-related variability." Further that their results cast "doubt on a female protective effect among high-risk ASD siblings."

Based on participant data derived from the Baby Siblings Research Consortium (BSRC) [2], a collaborative initiative focused on identifying the earliest signs and symptoms of autism, researchers assessed cognitive functioning and autism symptom severity in over 1800 infants, over 1200 of whom were categorised as 'high risk' insofar as being a "younger sibling of a proband with an ASD diagnosis." Of those 1241 high-risk siblings "252 had ASD outcomes" on the basis of a clinical best estimate diagnosis derived from the various data sources available for each participant.

Results: well, there were quite a few of them as previously discussed but I'm going to pick out a few highlights:

  • "The male rate of ASD recurrence in the high-risk siblings was approximately 1 in 4 (26.7 %) while the female rate was 1 in 10 (10.3 %)." Further: "The overall—combined male and female—ASD recurrence rate of 19.5 % yielded an ASD outcome for approximately one in five high-risk siblings." This is an important addition to the previous research done on sibling recurrence rates (see here) bearing in mind the potential effect of variables such as reproductive stoppage and multiplex status.
  • "Challenging accounts of greater female affectedness, there was no evidence that girls exhibited lower levels of cognitive functioning or higher levels of symptom severity than boys." The idea that there may be a female phenotype of autism has gained significant research traction in recent times (see here) partially based on the idea that it may take 'more genetic issues to trigger autism in girls than boys'. Alongside the idea that females may somehow possess greater protection against autism is the suggestion that autism when it does appear in females, may show differences in terms of severity perhaps as a function of that larger genetic load required. Messinger et al however, report that things might not be so simple.
  • "Boys across all groups exhibited slower growth trajectories and lower levels of cognitive performance than girls in fine motor, visual reception, receptive and expressive language functioning." Harking back to some previous musings on the 'fragile male' (see here) Messinger et al showed small but notable difference across the sexes and across ages suggesting female superiority of somewhere between "1.06 to 3.3 months on age-equivalent scores" compared to males. That's not to say males did not develop - everyone developed - rather that girls seemed to develop skills at a faster rate.
  • "With respect to the ASD symptom severity indices, males exhibited higher levels of repetitive behaviors than females, but there were no sex differences in social affect severity scores." This finding tallies with other research in this area (see here). The indication being that aspects such as stereotyped language, hand and finger mannerisms or complex mannerisms may be quite a bit more prevalent in 'boy autism' compared to 'girl autism'. More than that however, such repetitive behaviours might be more present in boys over girls (taking out the variable of autism diagnosis) "consistent with a male focus on regularity in the behavior of non-social objects and events." 'Boys and their toys' is a phrase that springs to mind.

The authors conclude that their results "suggest that male:female ASD differences are not ASD-specific but instead reflect more general sex differences reflected through a prism of autism-linked symptoms."

These are interesting results that gain some scientific traction as a function of the large participant numbers included for study and the prospective nature of the study initiative. The authors have made quite a bit of the fact that their results provide "no overall evidence of a female protective effect" in their high-risk siblings group but acknowledge the need for further investigations in this area specifically where female autism is present and how "female probands in multiplex families (two or more female siblings) [may] confer greater risk for ASD in successive offspring." I wonder if this might include some further thought on how sex differences in brain plasticity [3] might potentially be linked to autism?

Once again, autism reveals just how complicated a condition it is...

Music: The Slits - Typical Girls.

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[1] Messinger DS. et al. Early sex differences are not autism-specific: A Baby Siblings Research Consortium (BSRC) study. Mol Autism. 2015 Jun 4;6:32.

[2] Messinger D. et al. Beyond autism: a baby siblings research consortium study of high-risk children at three years of age. J Am Acad Child Adolesc Psychiatry. 2013 Mar;52(3):300-308.

[3] Mottron L. et al. Sex differences in brain plasticity: a new hypothesis for sex ratio bias in autism. Molecular Autism. 2015. 6; 33.

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ResearchBlogging.org Messinger DS, Young GS, Webb SJ, Ozonoff S, Bryson SE, Carter A, Carver L, Charman T, Chawarska K, Curtin S, Dobkins K, Hertz-Picciotto I, Hutman T, Iverson JM, Landa R, Nelson CA, Stone WL, Tager-Flusberg H, & Zwaigenbaum L (2015). Early sex differences are not autism-specific: A Baby Siblings Research Consortium (BSRC) study. Molecular autism, 6 PMID: 26045943

Thursday, 25 June 2015

Stalking and 'unexpected subthreshold autism spectrum'

I deliberated for quite a while as to whether or not I should write this post on the back of the findings reported by Liliana Dell’Osso and colleagues [1] detailing the experiences of a "25-year-old man with a diagnosis of delusional disorder, erotomanic type" who was hospitalised when presenting with psychotic symptoms "in the framework of a repeated stalking behavior towards his ex girlfriend." Said man was assessed for "adult autism spectrum symptoms" via the Ritvo Autism and Asperger Diagnostic Scale (RAADS-14) and came out with something approaching autism spectrum symptoms.

My blogging hesitancy was in the most part due to the risk of stigmatising and generalising on the basis of the words 'stalking' and 'autism' appearing in the same sentence even in the context of a case report and not necessarily including a formal diagnosis of autism. I'd like to make it very clear that this is/was not my intention at all. As in previous occasions when science has been covered on this blog that falls into a slightly uncomfortable area (see here and see here) I did however eventually choose to cover this topic on the basis that [peer-reviewed] science is science irrespective of particular emotions around topics.

Stalking - the unwanted or obsessive attention by an individual or group toward another person - is a life-changing experience that has profound effects on its victims. The precise hows and whys of stalking behaviour are still the topic of discussion, although thought to be variably mediated by social and personal factors potentially combining with other, more neurobiological processes [2]. As per the description provided in that last sentence and the use of the word 'obsessive' one might be able to see how such fixative behaviours might 'overlap' with some of the clinical description of autism or 'nearly autism' and particularly the idea that obsessions and compulsions might not be totally unfamiliar to the spectrum [3] including those around certain people.

I first came across discussions about stalking and the autism spectrum following my reading of the excellent overview by Tom Berney [4] (open-access). Describing the possible forensic presentation of Asperger syndrome, Dr Berney talked about "Overriding obsessions [that] can lead to offences such as stalking... Admonition can increase anxiety and consequently a ruminative thinking of the unthinkable that increases the likelihood of action." Anxiety and rumination, I might add, are areas crying out for more focused research with autism in mind (see here).

Other more experimental work looking at stalking in the context of autism has pointed to the possibility of an increased risk of such behaviours as per the findings reported by Stokes and colleagues [5]. They reported that individuals with autism were "more likely to engage in inappropriate courting behaviours... and were more likely to focus their attention upon celebrities, strangers, colleagues, and ex-partners... and to pursue their target longer than controls." All this is set in the context of researcher reporting on a small participant group and being based on parental reports.

Insofar as the possible basis for stalking behaviours and the autism spectrum, the paper from Haskins & Silva [6] offers several opinions external to the involvement of obsessionality centred around the idea that empathy and perspective-taking abilities may also play a role. I'm not exactly a great fan of the exclusivity of concepts such as a lack of Theory of Mind (ToM) when applied to the autism spectrum (see here) but can see the logic in this assumption linked to stalking behaviours. Indeed, with such ideas in mind, the paper from Post et al [7] on possible strategies to prevent and overcome stalking when coincidental to autism make some sense.

Just before I bring this post to a close I'd also like to comment on the idea that psychosis or psychotic behaviour might also be an important part of any link between stalking behaviour and autism. Regular readers of this blog might already know that whilst not necessarily a mainstream opinion, I do perhaps think that autism research was historically a little hasty in burning all the bridges between autism and schizophrenia (see here) particularly when it came to the work of people such as Mildred Creak and colleagues. Science is beginning to recognise that a diagnosis of autism is in no way protective against the development of psychosis (see here) and preferential regular screening might be indicated.

Analysing the possibility of a relationship between stalking behaviour, autistic traits and psychosis sounds like something that might provide some important answers particularly in the context of the recent findings from Ho and colleagues [8] talking about ToM potentially being a trait marker of schizophrenia. Again treading carefully not to stigmatise or generalise, any moves to decreasing the likelihood and impact of stalking behaviour and the often devastating consequences that it can bring should be welcomed.

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[1] Dell'Osso L. et al. Unexpected subthreshold autism spectrum in a 25-year-old male stalker hospitalized for delusional disorder: a case report. Compr Psychiatry. 2015 Apr 14. pii: S0010-440X(15)00054-1.

[2] Marazziti D. et al. Stalking: a neurobiological perspective. Riv Psichiatr. 2015 Jan-Feb;50(1):12-8.

[3] Russell AJ. et al. Obsessions and compulsions in Asperger syndrome and high-functioning autism. Br J Psychiatry. 2005 Jun;186:525-8.

[4] Berney T. Asperger syndrome from childhood into adulthood. Advances in Psychiatric Treatment. Aug 2004, 10 (5) 341-351.

[5] Stokes M. et al. Stalking, and social and romantic functioning among adolescents and adults with autism spectrum disorder. J Autism Dev Disord. 2007 Nov;37(10):1969-86.

[6] Haskins BG. & Silva JA. Asperger's disorder and criminal behavior: forensic-psychiatric considerations. J Am Acad Psychiatry Law. 2006;34(3):374-84.

[7] Post M. et al. Understanding stalking behaviors by individuals with Autism Spectrum Disorders and recommended prevention strategies for school settings. J Autism Dev Disord. 2014 Nov;44(11):2698-706.

[8] Ho KKY. et al. Theory of mind impairments in patients with first-episode schizophrenia and their unaffected siblings. Schizophrenia Res. 2015. June 3.

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ResearchBlogging.org Dell’Osso, L., Dalle Luche, R., Cerliani, C., Bertelloni, C., Gesi, C., & Carmassi, C. (2015). Unexpected subthreshold autism spectrum in a 25-year-old male stalker hospitalized for delusional disorder: a case report Comprehensive Psychiatry DOI: 10.1016/j.comppsych.2015.04.003

Wednesday, 24 June 2015

Infant sleep duration a risk factor for autism spectrum behaviours in girls?

To quote from the study results published by Janet Saenz and colleagues [1] (open-access available here): "less sleep duration in infant girls across a period of 5 days was predictive of higher ASD [autism spectrum disorder] scores on the BITSEA [Brief Infant-Toddler Social and Emotional Assessment] in toddlerhood."

Based on a sample of 47 children - 29 males and 18 females - researchers initially studied sleep patterns for participants at 3-4 months of age using actigraphs to ascertain sleep duration and efficiency and determine whether there was any connection to later BITSEA scores at 18-24 months of age. They reported various results in the most part not significant across genders, sleeping patterns and the subsequent effect on scores of social-emotional problems. In the detail however, they did find a suggestion that "sleep duration was a significant predictor of autism spectrum behaviors" specifically in girls and "after controlling for sleep efficiency, a 1-min decrease in sleep duration resulted in a 0.01 point predicted increase in a child’s autism spectrum behaviors score." This, bearing in mind, that BITSEA scores for autism spectrum behaviours range between 0-17.

I'm not wildly enthusiastic about the results reported by Saenz et al given the relatively small sample size and the snap analysis of two variables (sleep and reported behaviour) separated by over a years worth of development. Correlation is not necessarily causation and all that jazz. Indeed, even the authors concede that their use of a "non-clinical sample" limits the applicability of their results to "the low severity end of the diagnostic spectrums."

That being said, I do wonder if these findings invite quite a bit more investigation specifically when it comes to all those resources being put into the early detection of autism as exemplified in the recent paper by Sacrey and colleagues [2]. Sleep and autism is a research topic not unfamiliar to this blog (see here) and the idea that there may be small but measurable differences in sleep parameters in cases of already diagnosed autism. I'm not aware of too much in the way of experimental research reporting on early sleep patterns as being a 'risk' factor for autism outside of results such as those reported by Humphreys et al [3]. The idea that sleep issues might become more present as a child develops is a theme explored by Sivertsen et al [4] and the behavioural 'issue' link has also been mentioned by others [5].

Finally, it is worth reiterating the focus on female autism spectrum behaviours reported by Saenz et al. As per other work by the authors [6] and findings supporting: "the hypothesis that early infancy may be another critical period for the development of gender-linked behavior" based on their examination of infancy salivary testosterone levels and toddler BITSEA ratings, there may be some important lessons to be learned. Sex differences in behavioural presentation when it comes to autism (see here) is a big talking point at the moment in light of discussions about how the gender ratios for diagnosis might be skewed by either a female autism phenotype or just plain old dogma about autism being a male-dominated label. Again, I've not come across much in the way of peer-reviewed research where sleep has been examined from the perspective of risk of autism or autism linked behaviours taking into account gender differences. Hence, another potential research project presents itself and perhaps even more intriguing: could 'alteration' of early sleep patterns offset the future risk of autism?

Music: Kelis - Caught Out There.

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[1] Saenz J. et al. Sleep in infancy predicts gender specific social-emotional problems in toddlers. Front Pediatr. 2015 May 11;3:42.

[2] Sacrey LA. et al. Can parents' concerns predict autism spectrum disorder? A prospective study of high-risk siblings from 6 to 36 months of age. J Am Acad Child Adolesc Psychiatry. 2015 Jun;54(6):470-8.

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ResearchBlogging.org Saenz J, Yaugher A, & Alexander GM (2015). Sleep in infancy predicts gender specific social-emotional problems in toddlers. Frontiers in pediatrics, 3 PMID: 26029685