Risk of breast cancer in women with schizophrenia: meta-analysed

"In this meta-analysis of 12 cohort studies that included 125 760 women and in which conventional methods of meta-analysis had been used, schizophrenia in women was associated with an increased breast cancer incidence compared with the general population."

That was a primary findings reported by Chuanjun Zhuo & Patrick Triplett [1] following their survey of the peer-reviewed research literature on the topic of breast cancer risk and schizophrenia up to August 2017. The authors caution however that their review of this topic might not be the last word on it - "it is possible that a future study will show a decreased breast cancer risk in women with schizophrenia compared with the general population" - given "substantial between-study variance" among the research literature they examined. Another very good example of how the currency of science is probability and big sweeping generalisations may not necessarily stand the test of time.

"The status of physical health in patients with schizophrenia has become an important topic in health care management research" introduced the the Zhuo/Triplett paper, and with it, important recognition that diagnoses like schizophrenia can lead to an over-emphasis on the psychiatric often to the detriment of the somatic (see here). This, allied to other findings that have suggested that risk of premature mortality from various somatic complaints / diagnoses / issues is potentially heightened in relation to schizophrenia (see here).

Authors located studies fulfilling their study entry criteria, including "schizophrenia identified as exposure at baseline" and "documented incidence of breast cancer on follow-up" and applied their statistical analyses to results. Importantly: "Studies reporting breast cancer–related mortality rather than incidence were also excluded because the mortality outcome may be affected by many factors other than breast cancer incidence, such as comorbidities and treatments." Most of the included studies/data were found to be methodologically sound based on scores on the Newcastle-Ottawa Scale.

Alongside their finding that women with schizophrenia seemed to be at an elevated risk of breast cancer, authors also suggested that "intensive prevention and treatment against breast cancer are warranted for women with schizophrenia." So yes, this means discussing about potentially modifiable risk factors for breast cancer such as alcohol use and obesity (obesity, at the time of writing, being something of a focus for one large cancer charity here in Blighty). But this also means looking at how schizophrenia and its management might also place someone at elevated risk of something like breast cancer as a result of it sometimes being a "hormone-dependent cancer" and, as the authors note, "a significant positive association between plasma prolactin levels and the risk of breast cancer, has been observed." Minus any scaremongering, prolactin elevations have been noted following the use of certain antipsychotic medicines typically indicated for schizophrenia [2] and other conditions (see here). Any additional risk needs to be managed, and managed well.

I don't think anyone should be unduly alarmed by the Zhuo/Triplett results, but rather more mindful of the fact that a psychiatric diagnosis does not disqualify someone from other risks of more somatic conditions / complaints. The key, yet again, is screening and keeping an open mind...

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[1] Zhou C. & Triplett PT. Association of Schizophrenia With the Risk of Breast Cancer Incidence: A Meta-analysis. JAMA Psychiatry. 2018. March 7.

[2] Wu Chou AI. et al. Female schizophrenia patients and risk of breast cancer: A population-based cohort study. Schizophr Res. 2017 Oct;188:165-171.

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"evidence does not support the validity of pathological demand avoidance as an independent syndrome"

Pathological Demand Avoidance (PDA) mentioned in the title of this post represents "a behaviour profile within the autism spectrum" according to one authoritative source.

As I mentioned in a blogpost a few years back discussing PDA (see here), the label encompasses quite a few characteristics that overlap with facets of autism. Importantly however, it also includes a few other elements, including 'resisting and avoiding the ordinary demands of life' and the 'active use of various strategies to resist demands via social manipulation', not readily associated with autism (see here for further information). The late Prof. Liz Newson talked quite a bit about PDA [1] and I was honoured to see her speak so passionately about this topic on a few occasions.

As per the UK National Autistic Society (NAS) entry on PDA, the label is "increasingly, but not universally, accepted as a behaviour profile that is seen in some individuals on the autism spectrum." Such a description sets the scene for how things stand at the moment with regards to PDA and it's current lack of formal acceptance in the various diagnostic manuals despite relatively common usage, at least here in Blighty. The viewpoint article published by Jonathan Green and colleagues [2] is likely to provoke reactions on both sides of the debate of whether PDA is an "independent syndrome" or merely reflects "an important known range of co-occurring difficulties for many children with autism spectrum disorder." Green et al suggest the latter.

This is a difficult topic to talk about. Not least because there are quite a few children and adults who have been diagnosed with PDA. The idea that these people may have been 'mis-diagnosed' or perhaps even given the label on the basis of a diagnostic 'fad' has the potential to cause quite a bit of distress both to them, their parents / caregivers and various other people who have an interest in their education and development. I make no value judgements on the Green paper aside from looking at the quality of the [current] peer-reviewed science upon which it is based.

On the topic of the peer-reviewed science on PDA, well, the term 'limited in quantity' probably best describes it so far, which is a bit surprising given the increasingly popularity of the label. I daresay that this point probably impacted on the conclusion reached by Green and colleagues, but there are some important things to highlight so far.

The paper by Elizabeth O'Nions and colleagues [3] talking about the possibility of identifying PDA via the use of the DISCO (Diagnostic Interview for Social and Communication Disorder) covered some important issues. First: "the sense that identifying PDA features in individuals within the autism spectrum may serve an important clinical function in providing tailored educational and support strategies" is mentioned. In these times when autism is increasingly being talked about in the plural sense ('the autisms') and rarely as a 'stand-alone' diagnosis (see here), PDA perhaps represents a first important step in categorising or sub-categorising part of the autism spectrum. It's perhaps no coincidence that the name Gillberg also appears on quite a bit of the literature talking about PDA, with his interest in the overlapping concept of ESSENCE including autism (see here). I might add that this is not the first time that efforts have been made with regard to formulating a diagnostic instrument for PDA [4].

Second, O'Nions and colleagues both in their adapting DISCO to diagnosis paper and other peer-reviewed publications [5] make reference to how data suggest that "a number of the traits characteristic of PDA are not very specific to the PDA phenotype and may be relatively common across the autism and problem behaviour phenotypes." They observed for example that: "Outrageous acts and lack of concern for their effects draw parallels with conduct problems and callous-unemotional traits" and even that: "The pathological demand avoidance group displayed comparable levels of autistic traits and peer problems to the autism spectrum disorders group and anti-social traits approaching those seen in the conduct problems and callous-unemotional traits group." This is important in any debate about whether PDA is deserving of a stand-alone diagnosis status or something more 'comorbid'. It should also be viewed alongside the idea that autistic traits are not seemingly just autism-specific (see here) but also occur across various different labels and diagnoses (see here). Going back to the idea for example, that callous-unemotional and anti-social traits seem to be part and parcel of some PDA, I'll draw your attention to a group of conditions where such issues are also seemingly 'over-represented' (see here) and how such conditions are themselves over-represented when it comes to the autism spectrum [6] (see here also). In short, it's [clinically] complicated.

Finally, although by no means a specific gender-linked diagnosis, I note that there are facets of the description of PDA that could 'overlap' with issues that are 'rising' when it comes to autism and in particular, female autism. So, again from the NAS description, the phrase "appears social at first and to be people-orientated" is mentioned in connection to PDA; complemented by observations on the use of 'role-play' with regard to obtaining needs and wants. I've specifically mentioned female autism in this context because of the growing interest in how the female presentation of autism might be subtly different (camouflaged) from the male presentation (see here), bearing in mind the need not to make too many sweeping generalisations (see here).

To reiterate, I remain neutral as to the current position of PDA as a distinct entity or something more 'co-occurring' symptom-wise. I do think the Green findings should be a 'call to action' for more research on this topic in terms of symptom comparisons and importantly, symptom presentation more longitudinally. With my interest in all-things 'comorbidity' in relation to autism (see here) I'd also like to see more investigations done on how the comorbidity profile may be similar/different in relation to more classical presentations of autism. And then there's biology to consider, and whether PDA notably 'differs' across any physiological measure(s) compared with other manifestations of the autism spectrum?

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[1] Newson E. et al. Pathological demand avoidance syndrome: a necessary distinction within the pervasive developmental disorders. Arch Dis Child. 2003 Jul;88(7):595-600.

[2] Green J. et al. Pathological Demand Avoidance: symptoms but not a syndrome. The Lancet Child & Adolescent Health. 2018. March 23.

[3] O'Nions E. et al. Identifying features of 'pathological demand avoidance' using the Diagnostic Interview for Social and Communication Disorders (DISCO). Eur Child Adolesc Psychiatry. 2016 Apr;25(4):407-19.

[4] O'Nions E. et al. Development of the 'Extreme Demand Avoidance Questionnaire' (EDA-Q): preliminary observations on a trait measure for Pathological Demand Avoidance. J Child Psychol Psychiatry. 2014 Jul;55(7):758-68.

[5] O'Nions E. et al. Pathological demand avoidance: exploring the behavioural profile. Autism. 2014 Jul;18(5):538-44.

[6] Gordon-Lipkin E. et al. Anxiety and Mood Disorder in Children With Autism Spectrum Disorder and ADHD. Pediatrics. 2018 Mar 30. pii: e20171377.

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Estimated autism prevalence in Canada in 2015: 1 in 66

"On March 29, 2018, the Public Health Agency of Canada published the first comprehensive review of the prevalence of autism spectrum disorder (ASD) in Canada."

So began the 'what did we find' summary (see here) covering the "Made in Canada" findings detailed in the Canadian National Autism Spectrum Disorder Surveillance System (NASS) 2018 Report (see here) [1]. Pertinent to the year 2015 and including some 88% of the children and young adults living in various participating Provinces and Territory, data was gathered from various sources (education, social services, health) onward to the estimated prevalence of diagnosed autism in Canada.

Their results: "Among children and youth 5–17 years old across seven provinces and territory, the combined prevalence of ASD for the year 2015 is 1 in 66 (15.2 per 1,000)" (bold text added by me).

Details, details, details... Such an estimate applies to children and young adults (youth) diagnosed with autism and does not say anything about the number of adults diagnosed with autism. It only covers those diagnosed with autism based on strict criteria: "The diagnosis of ASD is provided or confirmed by a licensed health care professional(s)... [and] The diagnosis of ASD is based on the clinical criteria in the Diagnostic and Statistical Manual (DSM) for Mental Disorders or the case is identified as ASD in the International Classification for Diseases (ICD)." It does not provide any information on how many people *might* be autistic but not yet in receipt of a diagnosis. Males made up the lion's share of those diagnosed. Most had been diagnosed by the age of 8 years (72%). Oh, and not every Province or Territory showed the same estimated prevalence rate for various potential reasons. And rest.

Also pretty important to the reported findings is the comparison with earlier years estimates: for 3 geographic locations in Canada we see the characteristic 'upward trend' in the estimated prevalence of ASD noted in other sample data from other countries, from around 4-6 per 1,000 in 2003 to between 16-20 per 1,000 in 2015. And when compared with a neighbour to the South (USA) and their estimated autism prevalence stats covering 2012 (see here) coming up with a figure of 1 in 68, the Canadian estimates are not a million miles away,. This, bearing in mind, some differences in the way the different country figures were arrived at and also the time periods covered. That also reminds me, we should be seeing the latest US stats on estimated autism prevalence from the CDC at some point in the (very) near future, and the promise that "the ADDM Network will be able to estimate ASD case status on the basis of both DSM-5 and DSM-IV-TR." Those comparisons should be rather interesting in light of other preliminary data (see here).

What else it there to say? Diagnosed autism is fairly prevalent across Canada (who have some important history in relation to the autism 'numbers game') and I assume we'll be seeing more on their tracking of the diagnosis in future times. Preparation is an important part of the figures being discussed; preparation of education, social and health services to support the numbers of children and young adults being diagnosed now and who, I assume, will eventually be transitioning to adult services. And on the topic of adult services, I'll refer you to Harold Doherty's blog and some of his opinions on adult services in a Canadian setting (see here).

Finally, is the question of 'why' the increase? Well, let's wait and see what those US CDC figures say first and how useful they might be to answering 'why' in the Canadian and other contexts too. I say this accepting that those 'better awareness', 'diagnostic switching' and 'broader criteria' arguments that have long been trumpeted as 'fact' are probably not all there is to see in this area (see here and see here).

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[1] Autism Spectrum Disorder among children and youth in Canada 2018. Public Health Agency of Canada. 2018. March 2018.

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Euthanasia and assisted suicide mentioning autism: inadequate safeguards and 'vulnerability'

By discussing the paper by Irene Tuffrey-Wijne and colleagues [1] (open-access), I'm once again returning to the complex topic of euthanasia and assisted suicide (EAS) where autism is mentioned (see here and see here).

As per my previous blogging entries on some of the peer-reviewed science on this subject, I'll reiterate how sensitive and contentious this topic is. On the one hand is the primary human freedom to choose. On the other, is another human right: the right to live and the sanctity of life. The two viewpoints collide on this topic (see here).

Tuffrey-Wijne et al follow on from the work of Kim and colleagues [2] by focusing on the Netherlands, where EAS is legal. Legal that is, "provided that statutory due care criteria are met, including: (a) voluntary and well-considered request; (b) unbearable suffering without prospect of improvement; (c) informing the patient; (d) lack of a reasonable alternative; (e) independent second physician’s opinion." The authors searched the records of regional review committees (RTE) who provide oversight on "whether the requirements of 'due care' had been observed" in cases of EAS, looking for any mention of intellectual (learning) disability and/or autism spectrum disorder (ASD). They found a small number of people (N=9) who met these diagnostic criteria and set about analysing whether "the EAS due care criteria are applied." Their conclusions: "The Dutch EAS due care criteria are not easily applied to people with intellectual disabilities and/or autism spectrum disorder, and do not appear to act as adequate safeguards."

Authors provide details on the nine cases, including "selected quotes with regards to the patients’ stated characteristics, diagnosis, and due care criteria." I was particularly struck by some of the reports included under the heading 'unbearable suffering without prospect of improvement' which provides not only insight into how lives can be so totally affected by a diagnosis, but also a reflection of how we (society) continue to fail so many people on so many different levels. I know to use the word 'suffering' in the context of autism for example, has the ability to furrow brows in some quarters. But for these nine people there did seem to be genuine misery and suffering. To quote: "For two patients, for whom various psychiatric and somatic conditions were described, the stated suffering appeared to stem from characteristics of autism spectrum disorder itself, rather than from acquired medical conditions." Factors such as a 'loss of control' and the manifestation of issues stemming from autism "that may not be directly understandable to others" are also detailed.

The authors conclude: "particular caution [is required] in cases of EAS requests from people with intellectual disabilities and/or autism spectrum disorder, with the onus on both physicians and the RTE to demonstrate much more clearly how all due care criteria were met." In other words, countries that have legalised EAS need to do quite a bit more to ensure that vulnerable groups are not unfairly disadvantaged and are supported as much as possible when it comes to making such an extreme decision. I'll also say again (see here), vulnerability is too often seen as a 'dirty word' when it comes to autism, despite there being ample evidence that vulnerability manifests widely across many areas of daily living for those diagnosed. I can think of no more 'final' outcome than EAS where the (supposed implied) recognition of vulnerability needs to be paramount to any decision being made.

As per the opening paragraph to this blog entry, there is a balance to be struck between the sanctity of life and personal choice in this area. But that 'choice' needs to be an informed choice; with the requirement to ensure that any "such [EAS] legislation includes sufficient safeguards to protect vulnerable patient groups."

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[1] Tuffrey-Wijne I. et al. Euthanasia and assisted suicide for people with an intellectual disability and/or autism spectrum disorder: an examination of nine relevant euthanasia cases in the Netherlands (2012–2016). BMC Medical Ethics. 2018; 19: 17.

[2] Kim SY. et al. Euthanasia and Assisted Suicide of Patients With Psychiatric Disorders in the Netherlands 2011 to 2014. JAMA Psychiatry. 2016 Apr;73(4):362-8.

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Has the ADHD 'phenotype' become more common over the past decade?

It's a question that continues to prominently figure in ADHD (attention-deficit hyperactivity disorder) circles: Are there more people out there 'developing' ADHD, or is the quite rapid increase in cases being diagnosed due to various other 'artificial' factors?

Far be it from me to come down on either side with any great certainty - as per a similar question being asked with autism in mind - but the findings reported by Mina Rydell and colleagues [1] do provide some important discussion on this question. Authors concluded that: "the increased rates of clinically diagnosed ADHD might reflect changes in diagnostic and treatment practices of ADHD, administrative changes in reporting diagnoses, greater awareness of ADHD, better access to healthcare, or current overdiagnosis, rather than an increase in the ADHD phenotype." But...

The evidence for their conclusion came from their use of an instrument called the A-TAC (Autism-Tics, ADHD and other Comorbidities inventory) and its application to a study initiative called the
Child and Adolescent Twin Study in Sweden (CATSS). Indeed mentioning about a similar question being posed in autism research circles, I'll direct you to a recent blog post where A-TAC and CATSS led researchers - some of the same researchers as on the Rydell paper - to conclude that the autism of today might not necessarily be the same as autism of yesteryear (see here).

As well as assessing ADHD symptoms with the A-TAC (not to be confused with the ATEC) for some 20,000 twins between 2004 and 2014, researchers also "modeled the lifetime prevalence of diagnostic-level and subthreshold ADHD with logistic regression" using data from the National Patient Register (NPR) in Sweden.

Results: well, as I've already indicated, there seemed to be quite an influence of those other 'artificial' factors noted from the Rydell paper. So: "The prevalence of diagnostic-level ADHD based on parent ratings did not differ significantly over time from 2004 to 2014." This refers to data garnered through the CATSS using the A-TAC. By contrast: "Clinically diagnosed ADHD increased more than fivefold from 2004 to 2014" based on data from the NPR. You can perhaps see the difference between the two databases.

Of course the debate is not entirely closed as to what might be going on with the ADHD phenotype and the rise in cases being diagnosed. The authors for example, do report that they found "small increases in normal and subthreshold variations of ADHD-like traits" which could indicate that more children are starting to show more ADHD-related traits as time passed. Harking also back to other previous research by some of the authors [2], I wonder if further investigations into this area might take into account variables such as physical activity / inactivity as being something to consider, in light of other evidence (see here)? I don 't doubt there will be other considerations too (see here and see here and see here)...

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[1] Rydell M. et al. Has the attention deficit hyperactivity disorder phenotype become more common in children between 2004 and 2014? Trends over 10 years from a Swedish general population sample. J Child Psychol Psychiatry. 2018 Feb 27.

[2] Rommel AS. et al. Is Physical Activity Causally Associated With Symptoms of Attention-Deficit/Hyperactivity Disorder? J Am Acad Child Adolesc Psychiatry. 2015 Jul;54(7):565-70.

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World Autism Awareness Day: "individuals with ASD are 4-times more likely to experience depression in their lifetime"

Autistica: number 1 research priority

Today - 2 April - is World Autism Awareness Day.

According to the United Nations, today is a day to "highlight the need to help improve the quality of life of those with autism so they can lead full and meaningful lives as an integral part of society."

I'm sure everyone - those diagnosed with autism, their parents and other family members and those who've devoted their professional lives to autism - will have a different interpretation of how to accomplish that message. I assume however, that all strive for a better life for ALL those on the autism spectrum and perhaps moving the message from 'awareness' to something more like 'actions'.

Quite a big part of 'improving quality of life' means acknowledging that a diagnosis of autism brings about an elevated frequency of certain quality-of-life-draining issues. I've talked quite extensively about some of them on this blog (see here and see here for example) covering both physiological and psychiatric issues / labels / diagnoses. Of all the 'comorbidities' (if I can still call them that) mentioned, one diagnosis and/or constellation of symptoms seems to be particularly frequent and life-changing in the context of autism: depression (see here) in its many forms (see here).

Depression covers a lot of clinical ground and, in some cases, has some important links to some potentially life-limiting outcomes (see here) that have also been mentioned in the context of autism (see here). It's something that needs both screening for and management of (yes, depression is manageable) and can be literally life-transforming when tackled / managed successfully. I might add that alongside pharmacotherapy / talking therapy being indicated, there are various other options to potentially consider when it comes to the management of depression in various contexts (see here and see here and see here and see here) (minus any medical or clinical advice given or intended).

A recent paper by Chloe Hudson and colleagues [1] summarises the collected peer-reviewed literature on the topic of depression and autism, concluding that: "rates of depressive disorders are high among individuals with ASD [autism spectrum disorder]." Also, as per the title of this post, "individuals with ASD are 4-times more likely to experience depression in their lifetime" when compared with the non-autistic population. The authors have also very helpfully written a lay-person summary of their meta-analysis (yet another meta-analysis covering something to do with autism).

I don't think anyone is or should be particularly surprised by the Hudson findings but it does cement the autism-depression link based on the top of the methodological tree hierarchy of peer-reviewed science. I might add that another finding reported by Hudson et al - "Rates [of depression] were also higher in studies that included participants with higher intelligence" - is also worthy of comment (see here). Not least, when it comes to targeted screening for something like depression in the context of autism (and possibly beyond), but also because such a finding seems to add to the idea that being intelligent / cognitively more able does not always mean that life is just fine and dandy (see here). I might also mention that greater research and clinical efforts also need to be focused on screening for something like depression in some of the more 'under-studied' peoples of the autism spectrum too (see here). Y'know, just to ensure that depression being associated with higher intelligence is not simply because those who aren't more cognitively able are being excluded from such investigations...

There is another question that needs comment when it comes to the autism-depression link: why? Some authors have speculated that issues such as 'autism acceptance' could be part-and-parcel of any link (see here). Yes, the social environment probably does play a role for some people, but I'm slightly reluctant to suggest that acceptance plays a solitary role in the development of something like depression. I say that on the basis of some growing interest in how issues such as loneliness begets low self-esteem which *might* then lead into something like an enhanced risk of depression (see here). One also needs to consider that autism rarely appears in some sort of diagnostic or social vacuum (see here) so other labels and/or diagnoses could also elevate the risk of depressive symptoms appearing (see here for example). And then there is biology to also consider (see here). Factors related to the aetiology of depression are likely to be complex and quite individual across different people. Sweeping generalisations are not required.

The take-home message once again, is that the risk of depression is elevated when it comes to a diagnosis of autism, and screening and appropriate management are very much indicated [2]. To move on from just talking about improving quality of life to actually improving quality of life could well be achieved (at least in part) by recognising and tackling depression when it appears in the context of autism. Real quality of life changing stuff...

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[1] Hudson CC. et al. Prevalence of Depressive Disorders in Individuals with Autism Spectrum Disorder: a Meta-Analysis. J Abnorm Child Psychol. 2018 Mar 1.

[2] Sapmaz D. et al. The Clinical Features of Comorbid Pediatric Bipolar Disorder in Children with Autism Spectrum Disorder. J Autism Dev Disord. 2018 Mar 21.

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