No wait... C-sections are NOT linked to autism

A quote to begin: "There was no association between planned CS [Caesarean section] and ASD [autism spectrum disorder]... or ADHD [attention-deficit hyperactivity disorder]." And further: "There was no association between mode of delivery and ASD or ADHD in this cohort."

Those were the conclusions reached in the paper by Eileen Curran and colleagues [1] who sought to look at whether the route of entry into the world may influence offspring risk of autism or ADHD. Based on data derived from The Millennium Cohort Study (MCS), a longitudinal survey covering the birth period and "including 13,141 children", researchers dived into the treasure trove of collected information to see whether "birth by Cesarean section (CS) and induction of labor (IOL)" correlated with later childhood outcomes. Probably not was the answer coming back, or at least not in any generalisable sense. Indeed, other recent research has also suggested similar things [2].

This is interesting research. Not least because I've discussed other work from this research group on this topic before on this blog (see here) based on their systematic review and meta-analysis of the available data up to February 2014 [3]. Up until then, the message was a cautious: "Delivery by CS is associated with a modest increased odds of ASD, and possibly ADHD, when compared to vaginal delivery."

At this point I'd also like to introduce another recent paper from this authorship group [4] further adding to this debate about birth method and offspring risk (or not) of autism. Based on data derived from the "Swedish Medical Birth Register and the Swedish National Patient Register" providing information on perinatal factors and ASD diagnosis respectively, the authors concluded that whilst "children born by CS are approximately 20% more likely to be diagnosed as having ASD", this association dwindled somewhat when "using sibling controls." Ergo, the correlation between birth by C-section and autism diagnosis is likely "confounding by genetic and/or environmental factors." A good write-up of the study can be seen here.

So, based on two pretty large (participants in the thousands) studies, geographically separate (UK vs. Sweden), the suggestion that birthing method might affect autism risk turns out to be not as strong as originally suggested and with it a reminder that meta-analyses are only as strong as the data they include. I know most people with their eyes and ears to the autism research scene probably won't be shocked by these results and the almost pantomime-like state ('oh yes it is, oh no it's not') of various aspects of autism research. As has been noted on some occasions, autism research seems to have a reproducibility crisis of its own to contend with.

But in all of that a few reminders: autism is a very heterogeneous condition (remember the autisms) and just because there is not population-wide effect does not mean that variable A, B or C is all bunk when it comes to 'some' autism (see here). Oh, and baby and bathwater - as in, don't throw them both out - should also be remembered [5]...

And now... Star Wars.

----------

[1] Curran EA. et al. Obstetrical Mode of Delivery and Childhood Behavior and Psychological Development in a British Cohort. J Autism Dev Disord. 2015 Sep 28.

[2] Robson SJ. et al. Childhood Health and Developmental Outcomes After Cesarean Birth in an Australian Cohort. Pediatrics. 2015. October 12.

[3] Curran EA. et al. Research review: Birth by caesarean section and development of autism spectrum disorder and attention-deficit/hyperactivity disorder: a systematic review and meta-analysis. J Child Psychol Psychiatry. 2015 May;56(5):500-8.

[4] Curran EA. et al. Association Between Obstetric Mode of Delivery and Autism Spectrum Disorder: A Population-Based Sibling Design Study. JAMA Psychiatry. 2015 Sep 1;72(9):935-42.

[5] Chien LN. et al. Risk of autism associated with general anesthesia during cesarean delivery: a population-based birth-cohort analysis. J Autism Dev Disord. 2015 Apr;45(4):932-42.

----------

Curran, E., Cryan, J., Kenny, L., Dinan, T., Kearney, P., & Khashan, A. (2015). Obstetrical Mode of Delivery and Childhood Behavior and Psychological Development in a British Cohort Journal of Autism and Developmental Disorders DOI: 10.1007/s10803-015-2616-1

Higher cognitive 'level' = more vulnerability to depression alongside autism?

Regular readers of this blog probably know that I don't like sweeping generalisations when it comes to autism.

Y'know, all those ideas and theories that have been put forward down the years about the exclusivity and total generalisability of this, that and t'other to autism, which have inevitably fallen by the wayside as science truly starts to understand why autism is called a heterogeneous condition or even conditions (plural).

First it was issues with Theory of Mind (ToM) (see here) and now executive function issues has been given the 'cross-disorder' treatment [1]. I foresee the complicated issue of brain connectivity (hypo- or hyper-?) and autism heading the same way in the near future...

With all that in mind I'm cautiously bringing the review paper by Myriam De-la-Iglesia & José-Sixto Olivar [2] (open-access available here) to your attention today and a topic that can very much affect a person's quality of life in the context of autism: depression.

OK, to start I should perhaps be a little careful with using the word 'depression' as if denoting some singular, universal condition. It's not. Indeed, some people have suggested that depression or depressive illness is but one aspect of a 'cloud' of conditions (somatic and/or psychological) all interacting together, so one needs to be aware of the blurriness of any diagnosis. With autism in mind, depressive illness is a research topic in the ascendancy in terms of how it interacts with autism (see here) (including potentially interacting with other somatic comorbidity too) and what might be the key components of depression present alongside autism (see here). That certain types of depression might be over-represented when it comes to autism is a key issue too (see here).

De-la-Iglesia & Olivar took on quite a wide topic in their review article: "to examine, discuss, and provide proposals on diagnostic comorbidity of depression in children and adolescents with high functioning autism spectrum disorder (HFASD)" in relation to various aspects (prevalence, factors linked to vulnerability, risk of suicide and how to assess symptoms). I might add that their focus on "high functioning autism spectrum disorder" reflects their terminology and not mine and perhaps suggests further caution with regards to 'generalisability'.

Their review is open-access so it doesn't need any grand discussions from me, but I will pull out a few important points made in the article.

First: "Depression is common in prevalence in ASD." I don't need to say much more to that aside from forwarding the idea that preferential screening for depression in cases of autism might need to be more widespread than it currently is. This may also require some artistic medicine in terms of making screening more appropriate to the very heterogeneous target population.

Then: "children with autism that have depression are more likely to have a family history of depression." Being careful not to fall into yet more over-generalisation traps, there is some peer-reviewed evidence to suggest that issues with depression do indeed run deep in families where autism features. The potentially complicated relationship between anti-depressant medication use during pregnancy and offspring autism outcomes provides some of the clearest evidence of a relationship (see here).

Continuing: "the majority of the studies on children with autism show that the older the child and the greater the intelligence quotient (IQ), the greater the incidence of depression." Harking back to the title of this post, I think this is perhaps one of the most important features of depression when discussed in the context of autism. One could follow the De-la-Iglesia / Olivar line that: "The majority of higher functioning individuals with ASD are aware of their social difficulties and this awareness may in turn lead to greater pathology and the development of comorbid psychiatric problems" as accounting for the elevated risk of psychopathology but I'd be tempted to suggest that this might not be the only relevant factor. I do however also wonder whether 'awareness' of difficulties, might also account for other issues seemingly over-represented in autism such as certain types of anxiety too?

Then: "it is possible that the feeling of loneliness, fuelled by the poor social relationships that individuals with ASD have, contributes to greater levels of depression." I don't think that anyone would disagree with the idea that a person's environment could be contributory to their mood and onwards risk of something like depression. As per the findings reported by Schmidt et al [3]: "Participating in society was identified as the only factor predicting life satisfaction in individuals with ASD." Add to that also the idea that: "Negative events such as parents getting divorced, illnesses, death, frequent parental discord, or changing residences have been related to clinical depression, both in children and in adults" and one sees how many variables can combine to bring someone to the label.

Although perhaps not great dinner party conversation, I want to finish on the point made by De-la-Iglesia & Olivar regarding how depression manifesting in autism might tie into discussions about suicide (either ideation or completion).

There is a realisation that suicide ideation in the context of depression in autism is something we need to talk a lot more about (see here). This also taps into the quite disturbing trend of euthanasia requests where autism is mentioned (see here). The authors provide an interesting summary table of factors associated with risk of suicide in relation to autism (see here) which I found to be perhaps one of the most descriptive so far in the autism research literature. Indeed, the implication of 'affecting' one or more of the pathways listed to reduce any risk of suicide perhaps offers some important fodder for future research and practice in this area?

----------

[1] McGrath LM. et al. Extending the 'cross-disorder' relevance of executive functions to dimensional neuropsychiatric traits in youth. J Child Psychol Psychiatry. 2015 Sep 28.

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

[3] Schmidt L. et al. Psychosocial Functioning and Life Satisfaction in Adults With Autism Spectrum Disorder Without Intellectual Impairment. J Clin Psychol. 2015 Sep 25.

----------

De-la-Iglesia M, & Olivar JS (2015). Risk Factors for Depression in Children and Adolescents with High Functioning Autism Spectrum Disorders. TheScientificWorldJournal, 2015 PMID: 26413564

Societal inclusion and adult autism

"Participating in society was identified as the only factor predicting life satisfaction in individuals with ASD [autism spectrum disorder]."

That was the primary finding reported by Lilly Schmidt and colleagues [1] following their report examining "psychosocial functioning and life satisfaction in adults with autism spectrum disorder" and importantly "identifying areas of functioning that are most predictive for life satisfaction in individuals with ASD."

Based on responses to the World Health Organization Disability Assessment Schedule 2.0 part of the ICF framework I believe (see here), researchers quizzed 43 adults diagnosed with autism "without intellectual impairment" and 44 asymptomatic controls.

"Individuals with ASD reported significant functional impairments and less life satisfaction compared with nonclinical individuals in many areas of life" is perhaps not an unexpected finding in light of what autism can mean to someone and its impact on various areas pertinent to quality of life (see here). That being said: "daily living skills (e.g., getting around, self-care, and household) were not different from nonclinical participants" indicating that certain functional aspects of this cohort at least were intact.

Then back to that headline sentence about societal inclusion and participation being not only an important issue but 'the' most important issue when predicting life satisfaction among participants (this cohort at least) with autism. It's perhaps a sad reflection of today's society that something as simple as enabling a person to become an active member of society is seemingly something that we fail at when it comes to the autism spectrum. I know that 'participating in society' is quite a fluffy term and can cover lots of areas such as employment and friendships through to concepts such as social responsibilities, but surely there must be ways and means that aspects of inclusion can be engineered into plans as and when someone is diagnosed on the autism spectrum?

Aside from big national initiatives to tackle social inclusion and participation, I'd like to think that local communities are perhaps at the coalface when it comes to this issue. Accepting that it might not be everyone's cup of tea, something like local sports and related pursuits could be a good starting point in terms of social participation and how such leisure activities might also reduce some of the health inequalities that are becoming very apparent when autism is mentioned (see here). The paper by Müller and colleagues [2] mentioned this angle together with various other social supports - "external supports (e.g. activities based on shared interests, highly structured or scripted social activities, and small groups or dyads); communication supports (e.g. alternative modes of communication, explicit communication, and instruction in interpreting and using social cues); and self-initiated strategies for handling social anxiety (e.g. creative/improvisational outlets, physical activity, spiritual practice/organized religion, and time spent alone)" - that may also be worthy of consideration. Potential solutions are seemingly not hard to find.

Music: Kaiser Chiefs - I Predict A Riot.

----------

[1] Schmidt L. et al. Psychosocial Functioning and Life Satisfaction in Adults With Autism Spectrum Disorder Without Intellectual Impairment. J Clin Psychol. 2015 Sep 25.

[2] Müller E. et al. Social challenges and supports from the perspective of individuals with Asperger syndrome and other autism spectrum disabilities. Autism. 2008 Mar;12(2):173-90.

----------

Schmidt L, Kirchner J, Strunz S, Broźus J, Ritter K, Roepke S, & Dziobek I (2015). Psychosocial Functioning and Life Satisfaction in Adults With Autism Spectrum Disorder Without Intellectual Impairment. Journal of clinical psychology PMID: 26406481

Autism in blind children: 30 times greater prevalence?

An intriguing paper by Rubin Jure and colleagues [1] cropped up on my autism research radar recently. Detailing the results of a study looking at how autism "affected 19 of 38 unselected children at a school for the blind in Cordoba, Argentina", the authors highlight some potentially interesting factors that may be applicable to autism in the general population.

Building on previous work looking at the manifestation of autism in blind* children [2] (*hopefully that is the correct terminology to use), the Jure paper provides scope for much greater research inspection in this area. That autism was detected at "≥30 times greater prevalence than in sighted children" is quite a startling point made, as authors talk about "a distinct pathogenesis" being involved, potentially providing further evidence for the plurality of autism: the autisms.

One further point stands out from the Jure paper: "Autism "recovery," had occurred in 4 verbal children." I know this takes us into some potentially 'choppy' waters with regards to the idea of optimal outcome (OO) being a facet of at least some autism (see here for example) but I'm intrigued at the possible implications here. Particularly so when other research [3] had suggested that "subjects with blindness plus autism have greater neurological impairment (as suggested by the presence of lower intellectual level and cerebral palsy), and more severe visual impairment than the subjects with blindness only" coupled to the idea that language skills might be key to membership of that OO grouping [4] (see here)...

Music: Coldplay - Paradise.

----------

[1] Jure R. et al. Autism Spectrum Disorders (ASD) in Blind Children: Very High Prevalence, Potentially Better Outlook. J Autism Dev Disord. 2015 Sep 25.

[2] Hobson RP. et al. Autism and congenital blindness. J Autism Dev Disord. 1999 Feb;29(1):45-56.

[3] Mukaddes NM. et al. Autism in visually impaired individuals. Psychiatry Clin Neurosci. 2007 Feb;61(1):39-44.

[4] Mukaddes NM. et al. Characteristics of children who lost the diagnosis of autism: a sample from Istanbul, Turkey. Autism Res Treat. 2014;2014:472120.

----------

Jure R, Pogonza R, & Rapin I (2015). Autism Spectrum Disorders (ASD) in Blind Children: Very High Prevalence, Potentially Better Outlook. Journal of autism and developmental disorders PMID: 26408327

Pregnancy folic acid and offspring autism risk: just one minute...

So: "We did not find any evidence to corroborate previous reports of a reduced risk for autism spectrum disorders in offspring of women using folic acid supplements in early pregnancy."

The findings reported by Jasveer Virk and colleagues [1] prove once again that when it comes to autism, universal 'truths' are very much few and far between.

Actually, I'm not particularly surprised that Virk et al found what they did when it came to the idea that "early folic acid supplementation during pregnancy prevents diagnosis of autism spectrum disorders in offspring" (their words, not mine). As I've indicated before on this blog, the buzz about how folic acid intake during the nine months (plus) that made us might reduce the risk of offspring autism has not been all one way traffic (see here). Even recent meta-analyses have agreed on this point (see here).

Based on data derived from some familiar registries (Denmark does it again) researchers "estimated risk ratios for autism spectrum disorders for children whose mothers took folate or multivitamin supplements from 4 weeks prior from the last menstrual period through to 8 weeks after the last menstrual period (-4 to 8 weeks) by three 4-week periods." They concluded that there wasn't too much to see when it came to early folate or multivitamin intake in terms of offspring autism outcomes or not compared with women reporting no supplement use during the same period.

That all being said, I don't think it is yet time to trash the whole idea that pregnancy folic acid supplementation might not show some relationship to offspring outcomes with autism in mind. Bearing in mind other data in this area (see here) including the idea that genetic factors might intersect with things like folate availability and utility (see here) I'd be minded to suggest that there is still quite a bit more science to do in this area. Oh, and that issues with folate receptors in relation to some autism, might extend a lot further than just pregnancy (see here) also needs to be kept in mind...

Music: George Ezra - Listen to the Man (in this case, Magneto).

----------

[1] Virk J. et al. Preconceptional and prenatal supplementary folic acid and multivitamin intake and autism spectrum disorders. Autism. 2015 Sep 25. pii: 1362361315604076.

----------

Virk J, Liew Z, Olsen J, Nohr EA, Catov JM, & Ritz B (2015). Preconceptional and prenatal supplementary folic acid and multivitamin intake and autism spectrum disorders. Autism : the international journal of research and practice PMID: 26408631

Even more vitamin D - depression study results...

I'm starting to sound like a broken record (those 'plastic circle things that used to play music' for the younger crowd) when it comes to the topic of vitamin D and depression on this blog. The idea that there may be an important 'correlation' between the presentation of depression, at least some types of depression, and lower levels of circulating vitamin D is something I've covered a few times in previous entries (see here and see here).

Continuing the theme, I'm bringing the paper by Roland von Känel and colleagues [1] (open-access available here) to your attention today and findings that: "Low vitamin D levels are frequent in hospitalized patients with a current episode of depression." Further: "Especially 25-OH D levels <50 nmol/l were associated with cognitive/affective depressive symptoms, and anhedonia symptoms in particular." Anhedonia, as per another mention on this blog (see here), can be an important part of depression insofar as the inability to derive pleasure from activities usually found pleasurable.

OK, so researchers "aimed to examine the association of vitamin D levels with the severity and dimensions of depressive symptoms in hospitalized patients with a current episode of depression taking into account confounding variables." To do this, some 380 inpatients at a clinic in Switzerland were probed in relation to their presentation of depression whilst also having their functional vitamin D levels measured via analysis of of serum levels of 25-hydroxyvitamin D3 (25-OH D). They were subsequently grouped into categories: "25-OH D concentrations >75 nmol/l were considered sufficient vitamin D. Levels between 50 and 75 nmol/l and <50 nmol/l of 25-OH D were defined insufficient and deficient vitamin D levels, respectively." Data on various other 'covariates' were also collected and measured including psychiatric comorbidity and levels of C-reactive protein (CRP), an important marker of systemic inflammation.

Results: well, aside from depression, psychiatric comorbidity was present in quite a proportion of participants. About a quarter of the cohort also met criteria for anxiety disorder and about 7% could be diagnosed with post-traumatic stress disorder (PTSD). Also: "32.6% were obese." Over 50% of participants fell into the vitamin D deficiency grouping and only 12% were described as vitamin D sufficient.

And the primary finding: "We found that vitamin D deficiency was significantly associated with increased levels of depressive symptoms in patients hospitalized with a depressive episode." That and the very specific link/correlation suggested with anhedonia symptoms led authors to conclude that there may be quite a bit more investigation to do in this area including whether: "it might be prudent to supplement this patient population with at least 800 I.U. [international units] daily of vitamin D."

These are interesting data despite the fact that this was an observational study and as the authors themselves noted, did not adjust for factors such as physical activity levels nor actual exposure to vitamin D sources (outside of supplementation). One also has to bear in mind that this was another study of correlation over and above actual causation, so we can't get too carried away with things.

But... in the context of quite a few other 'correlation' type studies including further data on a temporal association with depressive symptoms [2] I'd be minded to suggest that this is an emerging area in psychiatry. I know that vitamin D has been 'linked' to quite a few extraskeletal conditions in recent times (see here) and there is always the risk that it might be seen as something too generalised to be relevant. But in these days of increasing focus on reducing health inequalities in relation to psychiatry (see here), I'd be minded to suggest that one shouldn't lose sight of deficiency as and when it occurs and whether tackling said deficiency might not have other important repercussions...

Music: Choral Stimulation's rendition of 'Addicted To Love' - The Naked Choir.

----------

[1] von Känel R. et al. Vitamin D Deficiency and Depressive Symptomatology in Psychiatric Patients Hospitalized with a Current Depressive Episode: A Factor Analytic Study. PLoS One. 2015 Sep 23;10(9):e0138550.

[2] Kerr DC. et al. Associations between vitamin D levels and depressive symptoms in healthy young adult women. Psychiatry Res. 2015 May 30;227(1):46-51.

----------

von Känel R, Fardad N, Steurer N, Horak N, Hindermann E, Fischer F, & Gessler K (2015). Vitamin D Deficiency and Depressive Symptomatology in Psychiatric Patients Hospitalized with a Current Depressive Episode: A Factor Analytic Study. PloS one, 10 (9) PMID: 26397113