Nicotine exposure and offspring ADHD (yet again)

The study findings reported by Andre Sourander and colleagues [1] talking about "an association with and a dose-response relationship between nicotine exposure during pregnancy and offspring ADHD [attention-deficit hyperactivity disorder]" continue an important research theme (see here and see here).

What was different about the Sourander results compared with some of the other studies in this area was their focus on the measurement of cotinine levels - cotinine being a biomarker for exposure to tobacco smoke - in mums-to-be as "measured by using quantitative immunoassays from maternal serum specimens collected during the first and second trimesters of pregnancy and archived in the national biobank." Indeed, such a biological marker measurement protocol mimics other research from members of this authorship group when looking at maternal nicotine exposure and offspring risk of schizophrenia for example (see here).

Based on the analyses of samples from over a thousand participants born in the late 1990s and diagnosed with ADHD compared with samples from a similar number of non-ADHD control participants, researchers came to their possible *link* observation. They mention how the relationship between maternal cotinine levels and offspring ADHD diagnosis was statistically significant even when other important, potentially confounding, variables were taken into account. When categorising their maternal cotinine results into bands approximating light to heavy nicotine exposure and the possibility of a link with offspring ADHD diagnosis, researchers also reported something that looked like a dose-response relationship. Ergo, a biomarker of nicotine exposure during pregnancy *looked* to be potentially linked to offspring risk of ADHD.

Although important work, my first thought when reading this research was about how these results are 'set' within the context that historically, smoking rates or tobacco exposure rates during pregnancy were so much larger decades ago than they are now (see here), but ADHD is seemingly showing only quite a recent rise in numbers (see here). Although no expert on pregnancy tobacco consumption during the 20th century, I'm assuming that all those adverts about smoking being 'healthy' in the 1940s and beyond (see here) probably meant that quite a few women smoked during their pregnancy in the belief that it was 'healthy'. At the very least, it probably meant that they were exposed to a lot more second-hand tobacco smoke as a result of smoking being allowed in various public places and also more likely to be observed in the home environment. Surely then we would have seen an explosion of ADHD diagnoses at that point in time if the link was so simple? That is, assuming that the tobacco of today is the same as the tobacco of yesteryear.

I'm also intrigued that within the various potentially confounding variables which Sourander and colleagues adjusted for - "maternal socioeconomic status, maternal age, maternal psychopathology, paternal age, paternal psychopathology, and child’s birth weight for gestational age" - there's another variable that could exert an effect on ADHD risk: relative age (see here and see here). Relative age refers to the observation that the youngest children in the school classroom compared to their older classmates, are more likely to be diagnosed with ADHD. It strikes me that alongside something like tobacco or nicotine exposure, so age and other effects could be important.

I'm not trying to poo-poo the link that Sourander and various other research teams have independently observed. I'm also not trying to downplay the harms that tobacco (nicotine) exposure can have for the unborn child. I merely suggest that with typically falling rates of (reported) tobacco exposure during pregnancy in many countries (see here) and increasing levels of childhood (and adulthood) ADHD being reported, there must be other factors at work in any such relationship (see here for example).

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[1] Sourander A. et al. Prenatal Cotinine Levels and ADHD Among Offspring. Pediatrics. 2019. Feb 25.

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Pigeons, meet cat: "The Hans Eysenck affair: Time to correct the scientific record"

I'm heading off-piste with my musings today, drawing your attention to a paper by Anthony Pelosi [1] and an accompanying editorial by David Marks [2] (both open-access) that are likely to 'put the cat among the pigeons' in some quarters (with thanks to Matthew Dalby for bringing the Pelosi study to my Twitter attention). Indeed, the publishing journal - The Journal of Health Psychology - is no stranger to 'cat among the pigeons' discussions, as per their 2017 special edition [3] on the PACE trial "for patients with myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS)." Perhaps interestingly, there is a 'psychosomatic' connection between the topic covered in the Pelosi paper and those critical musings on how to (or perhaps how not to) treat ME/CFS...

The person at the centre of the Pelosi paper is the late Prof. Hans Eysenck; a figure who anyone with the slightest interest in the discipline called psychology would probably have heard of. Personality was one of the major research interests for Eysenck, and in particular, the proposal of dimensions to personality: extroversion/introversion, neuroticism/stability, psychoticism/socialisation. Perhaps not as famously known about, but still influential, were Eysenck's views relating to "his persistent denial of the carcinogenic effects of tobacco." Indeed, his 'alternative view' that "certain personality traits that lead to smoking also increase the risk of developing cancer" is starting to look decidedly 'shaky' in modern times. More so when there is talk of 'funding' and 'sources of funding' potentially complicating the issue.

Pelosi (and Marks) make a case that the time is right for psychology and various other interconnected disciplines to start looking more critically at the collected published work of Eysenck and some of his colleagues. They argue that claims "about the alleged effectiveness of psychotherapy in preventing cancer" or that "behaviour therapy may be useful in prolonging life, as well as in preventing disease" have little place in modern, evidence-based, science and medicine. Pelosi - who has some important history of being slightly critical of some of Eysenck's findings alongside other notable names - also goes one stage further in suggesting that some of the "widely cited studies" published with Eysenck's name attached "have had direct and indirect influences on some people’s smoking and lifestyle choices." Further: "This means that for an unknown and unknowable number of individual men and women, this programme of research has been a contributory factor in premature illness and death." Strong words indeed.

Marks ends his editorial with open letters to the President and Principal of King's College London and the Chief Executive of the British Psychological Society (BPS) calling for further investigation of the points highlighted in the Pelosi paper. Pelosi has seemingly approached the BPS previously on this matter but apparently did not receive a particularly warm reception to his then request for further investigation of some of the science and conclusions made in this area (see here). Whether such a second request - made in the era of social media - will be acted upon differently this time is a 'wait and see' question. All of this taking into account the moves being made to make psychology a more credible science these days...

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[1] Pelosi AJ. Personality and fatal diseases: Revisiting a scientific scandal. Journal of Health Psychology. 2019. Feb 23.

[2] Marks DF. The Hans Eysenck affair: Time to correct the scientific record. Journal of Health Psychology. 2019. Feb 23.

[3] Marks DF. Special issue on the PACE Trial. Journal of Health Psychology. 2017. July 31..

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"Are women with autism at an increased risk of adverse pregnancy outcomes?"

The paper by Heléne Sundelin and colleagues [1] provides the blogging fodder today, and research pertinent to the question: "Are women with autism at an increased risk of adverse pregnancy outcomes?" The short answer to the question is yes: "Maternal autism is associated with preterm birth, likely due to an increased frequency of medically indicated preterm births, but also with other adverse pregnancy outcomes, suggesting a need for extra surveillance during prenatal care."

It was refreshing to read the results from Sundelin et al (a research group who are no strangers to autism research) because this was a study devoted to looking at women with autism / autistic women and their pregnancy outcomes. It was distinct from other research on maternal pregnancy outcomes and offspring autism more traditionally seen in the peer-reviewed research literature and covered on this blog (see here and see here for examples).

The source material for the Sundelin study was the Swedish Medical Birth Registry (yes, one of those fantastic Scandinavian population registries again) and records of "2,198 births to 1,382 women with autism and 877,742 births to 503,846 women never diagnosed with autism." When comparing the groups across various different measures including preterm delivery ("defined as <37 completed weeks of gestation"), tobacco smoking during pregnancy and the use of various prescription medicines during pregnancy, some interesting trends were observed.

"Women with autism were at an increased risk of preterm birth..., which after stratification, remained for moderately (32 to <37 weeks) preterm birth." Also: "Maternal autism was also linked with an increased risk of elective cesarean delivery in births to women with autism" and "Preeclampsia was more prevalent in mothers with autism."

Although not seemingly affecting many of the 'adverse' pregnancy outcomes examined, researchers also noted that rates of tobacco smoking (light and heavy use) during early pregnancy were elevated in mums with autism, alongside prescription medicine use (antiepileptics, antipsychotics, hypnotics/anxiolytics, antidepressants) being more frequently reported before and during pregnancy compared to non-autistic pregnant mums. Authors reported that "there was no increased risk of adverse pregnancy outcomes except for induction of delivery" but one has to remember that the focus was on pregnancy outcomes - "completed weeks of gestation, mode of delivery, 5-minute Apgar scores, intrauterine growth, stillbirth, and maternal complications (preeclampsia and gestational diabetes)" - and does not say anything about longer term post-pregnancy outcomes. I say this with a few potential 'issues' in mind (see here and see here and see here).

The Sundelin study is by no means perfect - a "limitation is the lack of information on life circumstances" - but does carry the research weight that comes from those extremely well-categorised Scandinavian population registries. The authors conclude that their: "results suggest a need for individual prenatal care for women with autism, weighing pros and cons for continuation of psychotropic medication, with a better understanding of the difficulties related to autism, especially regarding the communication with health care professionals." Who am I to argue with them?

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[1] Sundelin HE. et al. Pregnancy outcomes in women with autism: a nationwide population-based cohort study. Clin Epidemiol. 2018 Nov 30;10:1817-1826.

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"an association between maternal experience of childhood abuse and risk for ADHD in offspring"

As per the title of this post - "an association between maternal experience of childhood abuse and risk for ADHD [attention-deficit hyperactivity disorder] in offspring" - this is another entry about some uncomfortable but potentially important research [1]. Indeed, the findings reported by Andrea Roberts and colleagues continue a theme from this research group (see here and see here) on how maternal exposure to various forms of abuse both in childhood and adulthood *might* have some important repercussions for offspring psychological and developmental health and well being.

The authors begin with the premise that: "Children whose mothers experienced childhood abuse are more likely to suffer various neurodevelopmental deficits" based on quite a lot of their own previous findings [2]. Such abuse - which comes in many different forms - is, they observe, likely to impact various psychological and biological functions; some of those functions *could* also have an inter-generational effect.

So: "We examined the association of maternal experience of childhood abuse with ADHD in offspring, assessed by maternal report of diagnosis and validated with the ADHD Rating Scale-IV in a subsample, in the Nurses' Health Study II (n = 49,497 mothers, N offspring cases = 7,607, N offspring controls = 102,151)." The Nurses' Health Study II seems to be a favourite resource for these researchers, and continues to contribute to many areas of health science and research (see here). Alongside looking at maternal experience of abuse and ADHD diagnosis in offspring, researchers also looked for the presence of various other 'adverse circumstances' that might be important to any enhanced risk of offspring ADHD being diagnosed. This included exposure to tobacco smoking (see here) which has some pretty strong 'observational' evidence on a possible effect.

Results: "Exposure to abuse was associated with greater prevalence of ADHD in offspring." Although important, the nature of the relationship between abuse exposure and offspring ADHD was not exclusive, i.e. ADHD was present in both offspring of mums exposed to abuse and those not exposed to abuse. The percentage difference between abuse exposure vs. no exposure was statistically significant however, and importantly, remained significant even after adjustment for those other adverse circumstances mentioned previously. Ergo, maternal exposure to childhood abuse *might* have an important impact on offspring enhanced risk of a diagnosis of ADHD.

Although requiring further study, these are important findings. A case is made for further inspection of how such a relationship comes about covering important areas such as the effects of childhood abuse on maternal state and behaviour(s) [3] and indeed, whether adverse pregnancy factors such as tobacco smoking may also actually be related to such previous experiences of abuse [4]. I daresay that things are going to be complicated and not straight-forward when it comes to any relationship(s) and so no sweeping generalisations are required from me or anyone else.

The possibility of an 'inter-generational' aspect to the experience of childhood abuse and subsequent offspring ADHD risk is important. It provides evidence that the expression of some childhood developmental disorders may not necessarily be 'hard-wired' in a genetic sense (assuming that is, that exposure to childhood abuse is not able to 'modify' the structure/functioning of the genome [5] for example). It provides evidence for the idea that adverse life experiences may be able to manifest as physical issues (being careful how I use the term 'biopsychosocial' for example). It also might suggest that alongside the continuously important stress on preventing any form of childhood abuse, there may interventions that could eventually be put in place to 'undo' any biological effects that it causes to offspring... Eventually.

I do want to end by reiterating that whilst the experience of childhood abuse may be *associated* with a heightened risk of offspring ADHD, such a relationship does need to be treated with some caution. I'm particularly keen to 'nip in the bud' any idea that every diagnosis of ADHD is somehow an intergenerational product of abuse: it's not.

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[1] Roberts AL. et al. Association of Maternal Exposure to Childhood Abuse With Elevated Risk for Attention Deficit Hyperactivity Disorder in Offspring. Am J Epidemiol. 2018 May 14.

[2] Roberts AL. et al. Maternal exposure to intimate partner abuse before birth is associated with autism spectrum disorder in offspring. Autism. 2016 Jan;20(1):26-36.

[3] Chronis AM. et al. Maternal depression and early positive parenting predict future conduct problems in young children with attention-deficit/hyperactivity disorder. Dev Psychol. 2007 Jan;43(1):70-82.

[4] Pear VA. et al. The Role of Maternal Adverse Childhood Experiences and Race in Intergenerational High-Risk Smoking Behaviors. Nicotine Tob Res. 2017 May 1;19(5):623-630.

[5] Cecil CA. et al. Epigenetic signatures of childhood abuse and neglect: Implications for psychiatric vulnerability. J Psychiatr Res. 2016 Dec;83:184-194.

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Maternal tobacco smoking and offspring ADHD risk again

"ADHD [attention-deficit hyperactivity disorder] and movement disorders were found to be more common in hospitalized children of smoking mothers."

That was one of the details recorded in the research findings published by Gil Gutvirtz and colleagues [1] adding to a growing research 'trend' suggesting that maternal tobacco smoking during pregnancy seemingly does little for mum's health and also probably not a great deal for her offspring's health and wellbeing either (see here).

Based on results analysing "all deliveries of mothers who reported smoking during pregnancy and non-smoking mothers between 1991 and 2014 at a single tertiary medical center" researchers included almost 250,000 children in their study. Quite a small proportion - "2861 (1.2%)" - were children of mothers who smoked during pregnancy. When researchers looked at these children they noted "higher rates of movement, eating and developmental disorders as well as attention deficit hyperactive disorder" as compared with the larger non-smoking group. "Maternal smoking during pregnancy is an independent risk factor for long-term neurological morbidity of the offspring" was the conclusion.

Allowing for the fact that observational studies, even population-based ones, aren't great for 'proving' cause-and-effect, the volume of such studies independently reaching the conclusion that maternal smoking during pregnancy *might* have an important connection to risk of offspring ADHD is growing. Indeed, alongside all the other adverse outcomes seemingly connected to smoking during pregnancy (see here) I don't think it would be out of place for regulators and health-related agencies to start informing the population at large that ADHD or ADHD-related behaviours as an outcome is at least possible; as some agencies seem to be doing (see here)...

Another research step could be some further investigations actually looking at something like cotinine levels (and important marker of tobacco smoke exposure) in both mums and offspring to see whether 'the dose makes the poison' as other recent studies have hinted at [2].

Tobacco smoking ain't good for anyone it seems, and children seem to be particularly vulnerable to its effects.

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[1] Gutvirtz G. et al. Maternal smoking during pregnancy and long-term neurological morbidity of the offspring. Addictive Behaviors. 2018. Aug 16.

[2] Kim KM. et al. Associations between urinary cotinine and symptoms of attention deficit/hyperactivity disorder and autism spectrum disorder. Environ Res. 2018 Jun 26;166:481-486.

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"DNA methylation data from neonatal blood spots can be used to accurately predict age and maternal smoking status"

There were two primary reasons why I wanted to blog about the findings reported by Eilis Hannon and colleagues [1]: first, the focus of the study was "to identify DNA methylation biomarkers of ASD [autism spectrum disorder] detectable at birth", and second, the authors actually "identified robust epigenetic signatures of gestational age and prenatal tobacco exposure, confirming the utility of DNA methylation data generated from neonatal blood spots."

The first reason, looking at DNA methylation biomarkers in relation to autism, follows other similar initiatives down the years (see here for example) on the back of some significant interest in how "epigenetic variation induced by non-genetic exposures" might complement/fill in some gaps left by more traditional genetic studies. Epigenetics by the way, seemingly means different things to different people, but is currently summarised as "the study of heritable changes in gene function that do not involve changes in the DNA sequence." DNA methylation reflects one epigenetic process (there are others). The second reason - robust epigenetic signatures linked to gestational age and prenatal tobacco exposure - actually turned out to be the more important finding, or at least the more significant finding, reported by Hannon et al hence the title of this post...

'Guthrie cards' are mentioned as the starting material for the Hannon paper, and yet another hat-tip to a true medical pioneer, Robert Guthrie (and his team), who has saved multitudes of lives with his cards used to collect and store neonatal blood spots. As well as being used to screen for various potential inborn errors of metabolism (some of which seem to have something of a relationship with some autism), those archived blood spot cards have also proved to be important research fodder too (see here).

Hannon garnered neonatal methylomic data for approaching 1300 individual - "comprising equal numbers of ASD cases and matched controls, 50% male/female" - derived from "the iPSYCH case–control sample" based in Denmark. We are told that: "DNA methylation was quantified across the genome using the Infinium HumanMethylation450k array" bearing in mind this technique/system "only assays ~ 3% of CpG sites in the genome." Alongside: "Matched genome-wide single nucleotide polymorphism (SNP) genotyping data from the same individuals enabled us to undertake an integrated genetic–epigenetic analysis of ASD, exploring the extent to which neonatal methylomic variation at birth is associated with elevated polygenic burden for ASD."

Results: with regards to a neonatal methylomic 'signature' for autism or ASD, nothing significant was detected. Obviously one has to bear in mind the limitations of the assay/method used and the fact that blood from bloodspots represents only one type of tissue (DNA methylation patterns are not necessarily the same across different tissues). I was also interested to see the authors talk about "the chronology of sample collection prior to ASD diagnosis" and the 'plausability' that they were "looking too early on in the disease process." No, autism isn't 'a disease', but this work might provide some support for the idea that the processes and onset of autism is not always set either during conception nor during gestation (see here). Dangerous thinking for some people of a sweeping generalisation ilk...

Having said all that, researchers did talk about a "significant association between increased polygenic burden for autism and methylomic variation at specific loci" but I'd like to see replication of this effect before any big claims are made.

Then to those other findings of "robust epigenetic signatures of gestational age and prenatal tobacco exposure" and what that could mean to several different areas of research, autism and beyond. I'm a little surprised that the authors didn't make more of their 'robust findings' in their discussion of these results. I appreciate that their primary aim to "identify DNA methylation biomarkers of ASD detectable at birth" was not met with startling success but the suggestion of a tell-tale epigenetic sign of exposure to maternal smoking during pregnancy for example is, I would have thought, an important advance. Certainly one that could be at least relevant to various other studies, including those related to an important comorbidity that seems to be 'over-represented' in relation to some autism (see here) and perhaps more.

To close, it's not the first time that the Star Wars universe has been subject to peer-reviewed 'science' but the paper by Hatters Friedman and colleagues is an interesting one...

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[1] Hannon E. et al. Elevated polygenic burden for autism is associated with differential DNA methylation at birth. Genome Med. 2018 Mar 28;10(1):19.

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Chronic kidney disease is over-represented in cases of serious mental illness

The findings reported by Masao Iwagami and colleagues [1] observing that "CKD [chronic kidney disease] is identified more commonly among patients with SMI [serious mental illness] than in the general population" are not entirely novel. I've touched upon this topic before (see here), set within the broader perspective that physical / somatic ailments experienced by those with a psychiatric and/or behavioural diagnosis can sometimes be 'downplayed' in light of their receipt of a 'primary' psychiatric / behavioural label. It stretches across various different labels (see here for example) with sometimes catastrophic outcomes.

Iwagami et al started out with the premise that risk factors for CKD - "a long-term condition where the kidneys don't work as well as they should" - including tobacco smoking and diabetes, are more frequently reported in those diagnosed with an SMI, hence their risk of CKD may be greater. To see if there was any heightened association between SMI and CKD here in Blighty, they relied on data from a resource called the Clinical Practice Research Datalink (CPRD). CPRD allows researchers to access various details from patient records based on the accrual of primary healthcare data. Importantly, as well as containing read codes for SMI, the database also includes laboratory test results pertinent to CKD: "CKD was based on two measurements of estimated glomerular filtration rate <60 mL/min/1.73 m2 separated by 3 months or longer; calculated from serum creatinine." The combined data was analysed and 'adjusted' for various potentially confounding variables including lithium use (lithium can affect kidney function).

From a starting population of some 2.5 million people (records), authors identified a diagnosis of SMI in about 28,000 (~1%). Most of those 28,000 or so diagnosed with a SMI had no history of lithium use (24,101 / 28,396). The prevalence of CKD was 14.6% in those with a SMI and history of lithium use. The prevalence of CKD was 3.3% in those with a SMI and no history of lithium use. This compares with a CKD prevalence rate of 2.1% in the population not diagnosed with a SMI (N=2,387,988). Ergo: "patients with SMI had a greater prevalence of CKD compared to the general population." Authors also mention how risk of renal replacement therapy (RRT) was also increased in those with a SMI.

This is important data. It's not foolproof data insofar as "a greater prevalence of CKD among patients with SMI may, in part, be influenced by surveillance or ascertainment bias. Patients with SMI take medications, such as lithium and other psychotropic drugs, which need regular monitoring." It does however suggest that regular screening for CKD needs to be a priority for those diagnosed with a SMI particularly given that "CKD is strongly and independently associated with mortality and cardiovascular risk" (something else mentioned in the context of certain psychiatric diagnoses). But there is also something rather uncomfortable in the Iwagami results: that possibility of an advanced risk of CKD in cases of SMI with a history of lithium use.

Minus any clinical or medical advice given or intended on this blog, I can see why the authors haven't overplayed the potential effect of lithium use on their results. Lithium, in the context of various psychiatric disorders and beyond, is an important medication, particularly when it comes to its proposed properties as an 'anti-suicidal' agent (see here). It really does save lives. But as with just about every medicine available, there is an important cost-benefit ratio to take into account when prescribing this medication and ensuring regular monitoring is available to minimise any side-effects. I might also add that there are *possibilities* [2] when it comes to potentially reducing some of the effects that lithium use might have on kidney function but I'll leave such discussions to the experts.

For now, we have further evidence that for whatever reason(s), being diagnosed with a SMI has the potential to impact on many areas of health, both mental and physical.

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[1] Iwagami M. et al. Severe mental illness and chronic kidney disease: a cross-sectional study in the United Kingdom. Clin Epidemiol. 2018 Apr 16;10:421-429.

[2] Lodin M. & Dwyer J. The role of amiloride in managing patients with lithium‐induced nephrogenic diabetes insipidus. J Pharmacy Practice & Research. 2017; 47(5): 389-392.

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Exercise may protect against the development of depression

"Available evidence supports the notion that physical activity can confer protection against the emergence of depression regardless of age and geographical region."

So said the findings reported by Felipe Schuch and colleagues [1] who undertook a review of the existing peer-reviewed research literature looking at whether physical activity a.k.a exercise *might* provide some important protection against the development of depression. Such a review took place in the context that NHS Choices, the go-to place for health and medical information here in Blighty, already has an entry called 'exercise for depression'.

The authors - many of whom are quite recognisable names in the area of science looking at the physical and the mental coexisting together - located almost 50 studies labelled as prospective cohort studies including over a quarter of a million participants residing across the globe. They undertook a meta-analysis - combining all the data from the various studies together and coming up with a sort of consensus finding - and concluded that yes, physical activity does seem to have a positive effect on reducing the risk of depression. The level of the decrease in risk of depression from participation in physical activity seemed to vary slightly according to age, amount of exercise and geographical region, but the trend was most definitely in the protective direction across such variables and remained even after potentially important variables such as body mass index (BMI) and tobacco smoking were taken into account. The authors also reported that: "Although significant publication bias was found, adjusting for this did not change the magnitude of the associations" indicating that although there was a tendency for results 'friendly' to the 'physical activity might reduce depression' hypothesis to be published over less positive results, this did not seemingly affect the findings in any particularly meaningful way.

Accepting that there is a further scheme of work required on this topic in terms of things like what physical activities might be 'best' for depression or depressive symptoms (see here), how to measure physical activity more objectively (ahem, actigraphy) and what the mechanism(s) of effect might be, these are important results. I can think of many, many different areas that the Schuch results could be pertinent to; several already covered on this blog (see here and see here). Many of those areas / conditions / labels reflect states where either physical activity seems to be reduced by choice (see here) or through necessity (see here) but the net result could be the same in terms of elevated risk of depression.

Still, the general message emerging from the Schuch paper is: if you can, move more, and perhaps not just for the physical benefits that accompany physical activity.

And just in case you need some more reading material on this topic, you could do a lot worse than the paper by Brett Gordon and colleagues [2] who concluded that: "Resistance exercise training significantly reduced depressive symptoms among adults regardless of health status, total prescribed volume of RET, or significant improvements in strength."

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[1] Schuch FB. et al. Physical Activity and Incident Depression: A Meta-Analysis of Prospective Cohort Studies. Am J Psychiatry. 2018 Apr 25:appiajp201817111194.

[2] Gordon BR. et al. Association of Efficacy of Resistance Exercise Training With Depressive Symptoms. JAMA Psychiatry. 2018. May 9.

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ALSPAC examines... pregnancy risk factors and oppositional-defiant disorder (ODD) and conduct disorder

ALSPAC mentioned in the title of this post refers to the Avon Longitudinal Study of Parent and Children, something of quite a regular feature on this blog by all accounts (see here and see here for examples). On this blogging occasion, I'm talking about ALSPAC in relation to the research paper published by I. Hyun Ruisch and colleagues [1] who reported that: "Common and potentially preventable pregnancy risk factors were independently related to both offspring ODD [oppositional-defiant disorder] and CD [conduct disorder] symptomatology in children from the general population."

ODD and CD represent a couple of the most prevalent 'disruptive behavioural' conditions seen nowadays. Whilst subtly different from one and another both in scope and severity, both represent conditions where control and in particular, self-control in accordance with cultural rules and norms, is perhaps not as it should be. I've mentioned one or other of these conditions in previous posts on this blog (see here for example) and the heightened risk of future adverse outcomes seemingly associated with them.

As with many (nay, all) behavioural and psychiatric conditions, science is still at a bit of a loss as to how they come about, accepting that they all probably [variably] include genetic and non-genetic factors working differently in different people. Ruisch et al set about utilising data from ALSPAC to ascertain if and whether "a broad range of pregnancy factors" might play some [statistically significant] role. Their results are quite revealing...

So: "Higher ODD symptom scores were linked to paracetamol use... and life events stress... during pregnancy." Further: "Higher CD symptom scores were linked to maternal smoking..., life events stress... and depressive symptoms... during pregnancy."

It should be noted that ODD and CD symptoms scores were gathered via the Development and Well-Being Assessment (DAWBA) as per other ALSPAC research occasions (see here). Researchers also quizzed both mothers and teachers of their children; thus providing two potentially different snapshots of functioning and their related factors.

In relation to that sentence on "Common and potentially preventable pregnancy risk factors were independently related to both offspring ODD and CD symptomatology in children" my eye was immediately drawn to two variables reported as being connected to said diagnoses: pregnancy paracetamol use and maternal smoking; both of which have appeared with increasing regularity in relation to adverse offspring developmental outcomes.

First, paracetamol also known as acetaminophen to our cousins across the Pond and other parts of the world. What can I say? It seems to be going from bad to worse for this go-to over-the-counter medicine with regards to pregnancy use *associations* and offspring developmental factors (see here). Yes, I appreciate that more studies need to be done on the possible pregnancy effects of this medicine, but the emerging peer-reviewed science is starting to look quite consistent. And many of the studies pointing the finger at paracetamol, like ALSPAC, are not to be under-estimated in size or power...

Second, maternal tobacco smoking during pregnancy. Again, something that has been talked about before on this blog (see here) in the context of related clinical labels. We can't yet say that 'pregnancy smoking causes offspring CD' because proof of cause-and-effect are rarely established by such observational studies. But much like the paracetamol story, the data is becoming more and more consistent for a possible effect of pregnancy smoking on child development. And for various other reasons, smoking during pregnancy is generally not thought of being a great thing for the developing child.

More investigations are indicated but clues are starting to emerge.

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[1] Ruisch IH. et al. Pregnancy risk factors in relation to oppositional-defiant and conduct disorder symptoms in the Avon Longitudinal Study of Parents and Children. J Psychiatr Res. 2018 Feb 23;101:63-71.

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Maternal tobacco smoking and offspring ADHD risk

"The results showed that either prenatal exposure to MSDP [maternal smoking during pregnancy] or smoking cessation during first trimester was significantly associated with childhood ADHD [attention-deficit hyperactivity disorder] after adjusting for parental psychiatric history and social socioeconomic status."

and:

"With our meta-analysis, we provide evidence for an association between maternal smoking and offspring ADHD but do not solve the causality issues concerning potential confounding by other risk factors."

Those quotes were taken from the findings reported by Tianyu Dong and colleagues [1] and Lan Huang and colleagues [2] respectively, both applying the 'top of the methodological tree' analysis that is a meta-analysis to the collected data looking at whether maternal smoking during pregnancy might impact on offspring risk of a diagnosis of ADHD. Their combined answer: very possibly but...

Having previously covered the non-association between maternal smoking during pregnancy and offspring autism before on this blog (see here), the recent results from Dong and Huang highlight how tobacco smoking during pregnancy is still something to be avoided for the sake of the child(ren). The fact that Huang et al also observed something of a dose-response relationship: "The risk of ADHD was greater for children whose mothers were heavy smokers (OR: 1.75; 95% CI: 1.51-2.02) than for those mothers were light smokers (OR: 1.54; 95% CI: 1.40-1.70)" kinda adds to the strength of their argument for an *association* between smoking during pregnancy and adverse offspring developmental outcome(s).

It's true that even with such meta-analytical prowess, it's still a little difficult to say conclusively that 'smoking causes offspring ADHD'. I'm also minded to state how "different assessment tools of ADHD and a lack of objective biological measures for maternal smoking" were picked up by the authors as other reasons to be cautious about their [collected] findings. I will also direct you to other research published not-so-long-ago that did not find such a strong connection between maternal smoking during pregnancy and offspring ADHD [3] (or at least "indicating that the association between maternal smoking during pregnancy and offspring ADHD is not directly causal, but confounded by unmeasured factors.")

Still, even if maternal smoking during pregnancy represents just one of a number of factors potentially impacting on offspring risk of ADHD, it is worth reducing that risk by nudging mums-to-be (and perhaps even dads-to-be) to quit smoking for the sake of their children. This on top of the myriad of other reasons that parental tobacco smoking during conception, pregnancy and offspring childhood is something that really needs to be stamped out once and for all...

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[1] Dong T. et al. Prenatal Exposure to Maternal Smoking during Pregnancy and Attention-deficit/hyperactivity Disorder in Offspring: A Meta-analysis. Reprod Toxicol. 2017 Dec 30. pii: S0890-6238(17)30599-3.

[2] Huang L. et al. Maternal Smoking and Attention-Deficit/Hyperactivity Disorder in Offspring: A Meta-analysis. Pediatrics. 2018 Jan;141(1). pii: e20172465.

[3] Gustavson K. et al. Smoking in Pregnancy and Child ADHD. Pediatrics. 2017 Feb;139(2). pii: e20162509.

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Tobacco smoking and psychiatric illness

"The prevalence of smoking has remained alarmingly high among individuals with schizophrenia and bipolar disorder, and the disparity with those without psychiatric disorders and with the general population is increasing."

So said the findings reported by Faith Dickerson and colleagues [1] who surveyed nearly 2000 people "about their cigarette smoking at enrollment into a research study for which they were selected without regard to their smoking status." Their findings make for important reading in the context that tobacco smoking is not exactly a healthy activity (see here) and could potentially contribute to some of the health inequalities already recognised when it comes to serious mental illness (SMI) (see here).

The sorts of figures of smoking prevalence observed by Dickerson et al are not to be ignored: "62% of individuals with schizophrenia, 37% with bipolar disorder, and 17% of participants without a psychiatric disorder (control group) reported that they were current smokers." This set in the context of falls in the rates of smoking in the general population. It's also worthwhile noting that being a 'current smoker' with reference to a diagnosis of schizophrenia or bipolar disorder typically meant smoking "more cigarettes per day" than the control cohort.

There are other implications from this work. Without generalising (or stigmatising) if one draws on other work talking about a possible connection between prenatal nicotine exposure and offspring [heightened] risk of schizophrenia for example (see here), a complex pattern of *association* seems to emerge. No, I'm not saying that every woman with schizophrenia who is pregnant will smoke through their pregnancy (despite evidence of some increased risk [2]) but greater focus and education on the need to restrict tobacco smoking during that critical period is perhaps warranted. Such discussions may also have implications for the whole nature-nurture debate with regards to such psychiatric diagnoses too.

Although there are many (many!) good reasons for encouraging those with a SMI to quit smoking, I do feel it is important also to understand why so many are smokers. The findings reported by Li and colleagues [3] offer something of a perspective on this issue where for example: "Smokers had a higher mental QOL [quality of life] than non-smokers... in MDD [major depressive disorder]." Similarly, Mallet and colleagues [4] discussed results that suggested that "some therapeutics may improve daily smoking behavior in smokers" in the context of schizophrenia (as others seemed to be associated with 'not improving' smoking behaviours). In short, the roads that lead to, and perpetuate tobacco smoking in the context of SMI are likely as complex as the ones needed to lead people away from such habits...

And aside from the health reasons to quit smoking particularly among those diagnosed with a SMI, the grand review, meta-analysis and meta-regression paper by Cassidy and colleagues [5] lists tobacco smoking as one potentially important (and modifiable) correlate when it comes to risk factors for suicidality in schizophrenia...

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[1] Dickerson F. et al. Cigarette Smoking by Patients With Serious Mental Illness, 1999-2016: An Increasing Disparity. Psychiatr Serv. 2017 Sep 15:appips201700118.

[2] Nilsson E. et al. Women with schizophrenia: pregnancy outcome and infant death among their offspring. Schizophr Res. 2002 Dec 1;58(2-3):221-9.

[3] Li XH. et al. Prevalence of smoking in patients with bipolar disorder, major depressive disorder and schizophrenia and their relationships with quality of life. Sci Rep. 2017 Aug 16;7(1):8430.

[4] Mallet J. et al. Cigarette smoking and schizophrenia: a specific clinical and therapeutic profile? Results from the FACE-Schizophrenia cohort. Prog Neuropsychopharmacol Biol Psychiatry. 2017 Oct 3;79(Pt B):332-339.

[5] Cassidy RM. et al. Risk Factors for Suicidality in Patients With Schizophrenia: A Systematic Review, Meta-analysis, and Meta-regression of 96 Studies. Schizophr Bull. 2017 Sep 23.

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When grandmothers smoked during pregnancy...

Please, do not smoke during pregnancy

ALSPAC - the Avon Longitudinal Study of Parents and Children - continues to give in research terms as today I want to mention the findings reported by Jean Golding and colleagues [1] (open-access) observing "an association between maternal grandmother smoking in pregnancy and grand daughters having adverse scores in Social Communication and Repetitive Behaviour measures that are independently predictive of diagnosed autism."

The study results have garnered quite a bit of media interest (see here for example) with calls for quite a bit more research to be carried out on this important topic. I might also give a hat-tip to Jill Escher and the Escher Fund for Autism who were instrumental in this study. Indeed, her analysis of the Golding results (see here) will no doubt trump my contribution.

The Golding paper is open-access but a few details are worth mentioning:

• As I noted, ALSPAC provided the source data for the study (as it has on quite a few autism research occasions). This time around researchers looked at autistic traits among some of their 14,000 strong cohort comprising "a social communication score, a speech coherence score, a sociability temperament scale, and a repetitive behaviour score." 
• Mothers and fathers of children involved in ALSPAC also provided information about pregnancy including answering questions on whether mothers themselves were/had smoked during pregnancy and also whether their mother (the child's grandmothers on both sides) smoked during pregnancy.
• The data obtained from the autistic traits measures (delivered at various times of the child's development) and the smoking histories were analysed. Data on some 170 participating children actually diagnosed with an autism spectrum disorder (ASD) were also thrown into the statistical mix.
• Results: "We found that two of the four autistic traits in the grandchild (F2) were increased in prevalence if the maternal grandmother (F0) smoked in pregnancy especially if the mother herself (F1) did not herself smoke." Researchers also noted a particular association between grandmother pregnancy smoking and grand-daughters over grandsons, and several potentially important confounding variables were also taken into account. They also concluded that "diagnosed autism was also associated with the maternal grandmother smoking in pregnancy" but express some caution in light of the smaller numbers included in this part of the analysis.

"These results are intriguing" say the authors. Indeed they are. Accepting the reliance on parental report, acceptance of the myriad of other factors that might affect any relationship and the fact that "sets of trait questions were not designed as measures of autistic traits but rather to identify the child’s performance in regard to a large number of attributes at different ages" as a consequence of researchers not originally expecting the prevalence of autism to be anything like it is today(!), further research is indicated. I say this in the context that research looking at any link between maternal pregnancy smoking and offspring autism risk has not consistently found any correlation (see here).

Then to the question of mechanism of effect. Well, researchers talk about "two plausible candidate mechanisms" to account for results. First is "transmission of damage to mitochondrial DNA (mtDNA)" where mitochondria DNA is subject to 'mutation' as a result of exposure to tobacco smoke. The researchers noted that: "Mitochondrial transmission across the generations is exclusively via the mother, so is compatible with our observed associations between maternal prenatal tobacco exposure and adverse scores on Social Communication and Repetitive Behaviour measures in her granddaughters." The second possible mechanism is that of "epigenetic inheritance from one generation to the next." This builds upon something of a continuing debate where structural DNA issues (i.e. mutations) are put to one side in favour of chemical alterations to genes (e.g. the addition of methyl groups) affecting gene expression. It's a topic that has been talked about quite a bit on this blog with reference to autism (see here for example) but still needs a lot more science done on it specifically on transgenerational epigenetic inheritance. Smoking is known to have effects on DNA methylation (see here) but the suggestion is that these or other epigenetic effects could continue down into future generations.

The potential effects of tobacco smoking during pregnancy in relation to second (or even third generation) autism or autistic traits risk requires quite a bit more study. Importantly, if such results are confirmed in future investigations, it opens up a whole myriad of possibilities in terms of how other previous generational exposures outside of just tobacco smoking during pregnancy might have affected future generations. This research area could get very, very complicated indeed.

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[1] Golding J. et al. Grand-maternal smoking in pregnancy and grandchild's autistic traits and diagnosed autism. Sci Rep. 2017 Apr 27;7:46179.

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Golding J, Ellis G, Gregory S, Birmingham K, Iles-Caven Y, Rai D, & Pembrey M (2017). Grand-maternal smoking in pregnancy and grandchild's autistic traits and diagnosed autism. Scientific reports, 7 PMID: 28448061

Prenatal nicotine exposure and offspring schizophrenia?

"Another reason why pregnant women shouldn’t smoke: schizophrenia" went one media headline reporting on the findings by Solja Niemelä and colleagues [1] who concluded that their results were the "most definitive evidence to date that smoking during pregnancy is associated with schizophrenia."

Analysing data from nearly 1000 people identified with schizophrenia whose information, and that of their mothers, were held in one of two databases - the Finnish Prenatal Study of Schizophrenia and the Finnish Maternity Cohort - researchers embarked on a case-control study. Maternal cotinine levels - a metabolite of nicotine - were analysed from archive serum samples taken during pregnancy ("early- to mid-gestation") and compared across groups based on offspring who did or did not go on to receive a diagnosis of schizophrenia. Authors concluded that: "A higher maternal cotinine level, measured as a continuous variable, was associated with an increased odds of schizophrenia." The increased 'risk' of offspring schizophrenia to those mothers with the highest cotinine levels (highest nicotine exposure) was somewhere in the region of 38% and "were not accounted for by maternal age, maternal or parental psychiatric disorders, socioeconomic status, and other covariates."

Accepting that correlation is not the same as causation and that one has to be slightly careful when analysing just one biomarker, I was intrigued by these latest findings. A quick trawl of the research literature in this area suggests that this is not the first time that maternal smoking behaviour might have implications for offspring risk of schizophrenia [2]. I don't doubt however, that any relationship is likely to be complicated and potentially influenced by various other factors as we are reminded that elevated levels of maternal cotinine indicative of heavy smoking were also reported in nearly 15% of mothers of control (not schizophrenia) participants in the Niemelä study. I might also add that when it comes to other labels not necessarily a million miles away from schizophrenia, the suggestion of a link with smoking during pregnancy is not strong at all (see here).

Where perhaps the latest findings are so interesting is the idea of a possible relationship between a proxy measure for foetal nicotine exposure and risk of schizophrenia. The emphasis is on 'nicotine exposure' and not necessarily the myriad of other toxins that are present when tobacco combusts (although I'm sure they might exert some kind of effect) thus potentially suggesting that quite a bit more research is indicated on other sources of nicotine exposure during pregnancy such as the use of nicotine replacement skin patches or even e-cigarettes. Indeed, having recently watched the ever-intrepid Dr Michael Mosley discuss the question: 'Are e-cigarettes really a menace?', with the Niemelä findings in mind, one might have to conclude, very possibly if used during pregnancy depending on what level of nicotine they might deliver. Just however, to confuse you further, the use of nicotine - "targeting nicotinic and nicotinic receptor subtypes" [3] - as a potential intervention for [some] schizophrenia has to be mentioned although perhaps not necessarily in the long-term.

Irrespective of the plausibility or generalisability of the Niemelä findings, giving up smoking when pregnant to protect the developing foetus from potential schizophrenia or lots of other things, really is a no-brainer...

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[1] Niemelä S. et al. Prenatal Nicotine Exposure and Risk of Schizophrenia Among Offspring in a National Birth Cohort. American Journal of Psychiatry. 2016. May 24.

[2] Stathopoulou A. et al. Prenatal tobacco smoke exposure, risk of schizophrenia, and severity of positive/negative symptoms. Schizophrenia Research. 2013; 148: 105-110.

[3] Featherstone RE. & Siegel SJ. The Role of Nicotine in Schizophrenia. Int Rev Neurobiol. 2015;124:23-78.

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Niemelä, S., Sourander, A., Surcel, H., Hinkka-Yli-Salomäki, S., McKeague, I., Cheslack-Postava, K., & Brown, A. (2016). Prenatal Nicotine Exposure and Risk of Schizophrenia Among Offspring in a National Birth Cohort American Journal of Psychiatry DOI: 10.1176/appi.ajp.2016.15060800

Smoking during pregnancy and autism risk: no association (again)

Question: Does tobacco smoking during pregnancy elevate the risk of offspring autism?

Answer: According to the meta-analysis published by Shiming Tang and colleagues [1] (open-access), probably not.

I have to say that I was interested in the paper from Tang et al. Interested not only because of their findings suggestive that smoking during pregnancy did not seem to elevate the risk of offspring autism, but also that their report seemed to pretty much replicate a previous meta-analysis by Brittany Rosen and colleagues [2] in both design and findings. I've talked previously about the Rosen paper on this blog (see here).

To quote from Tang: "The random-effects model was used to combine results from individual studies." To quote from Rosen et al: "Using a random-effects model, we found no evidence of an association."

Same with the results - from Tang: "The pooled odds ratio (OR) was 1.02 (95% confidence interval (CI): 0.93–1.13) comparing mothers who smoked during pregnancy with those who did not." Figures that weren't a million miles away from those previously published by Rosen et al - "summary OR 1.02, 95 % CI 0.93–1.12."

Tang do make reference to the Rosen meta-analysis in their text and the fact that they: "only searched two databases which missed several eligible studies" also that they "misunderstood the difference between the period of “prenatal” and “pregnancy”, and they inappropriately included studies that only reported smoking during pregnancy but not specified whether it was during the prenatal period or not." That both papers eventually ended up with 15 studies in their final analyses and pretty much identical results should be noted however.

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[1] Tang S. et al. A Meta-Analysis of Maternal Smoking during Pregnancy and Autism Spectrum Disorder Risk in Offspring. Int. J. Environ. Res. Public Health 2015; 12: 10418-10431.

[2] Rosen BN. et al. Maternal Smoking and Autism Spectrum Disorder: A Meta-analysis. J Autism Dev Disord. 2015 Jun;45(6):1689-98.

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Tang, S., Wang, Y., Gong, X., & Wang, G. (2015). A Meta-Analysis of Maternal Smoking during Pregnancy and Autism Spectrum Disorder Risk in Offspring International Journal of Environmental Research and Public Health, 12 (9), 10418-10431 DOI: 10.3390/ijerph120910418

Transdermal nicotine for aggression comorbid to autism?

The paper from Gerrit Van Schalkwyk and colleagues [1] caught my eye recently and a potentially interesting case report on the use of "transdermal nicotine as an adjunctive medication to treat aggression in a hospitalized adolescent with ASD [autism spectrum disorder]."

Transdermal, by the way, refers to passage through the various and complicated layers of the skin, and reflects an important way of getting medicines into the body other than via the more traditional oral route. I'm more than a little interested in the various ways and means that science is coming up with to bypass the mouth - gut - general circulation route as per other discussions on this blog (see here) with some of my own peer-reviewed contributions in mind [2]. In terms of how this might translate into autism and beyond, think about the processes for example, involved in swallowing a tablet or capsule and whether more could be done to 'ease' the mechanics of getting medicines into the body as well as improving things like adherence to a particular regime...

Anyhow, Van Schalkwyk et al reported that transdermal nicotine use - "a 21 mg nicotine patch" - seemed to have something of a positive effect on aggression in their particular case. Said young man presented with various issues with aggression against himself ("headbanging and biting... continuously re-opened old wounds") and others ("violently attacked staff at school") in the context of "a diagnosis of non-verbal ASD... requiring support with each of his activities of daily living." Various behavioural and pharmacological options were tried to alleviate aggression when he was hospitalised with seemingly little effect.

The idea to use a nicotine patch stemmed from some previous research interest from some of this authorship group on a role for nicotinic acetylcholine receptors in relation to mood and anxiety [3]. Their idea that: "smokers may use the nicotine in tobacco products as an attempt to self-medicate symptoms of affective disorders" potentially taps into some interesting research questions on the role of smoking in light of diagnoses where 'affective disorders' may be prominent.

Further research is of course indicated as to whether nicotine patches may be useful for some people and some behaviours associated with the autism spectrum. I say this bearing in mind that the rates of tobacco smoking tend to be quite a bit lower in autism compared with the general population [4] and the desire not to see such figures increase bearing in mind the adverse effects smoking can have for a person. Remember also, that nicotine is classified as addictive...

Music: The Clash - Complete Control.

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[1] Van Schalkwyk GI. et al. Reduction of Aggressive Episodes After Repeated Transdermal Nicotine Administration in a Hospitalized Adolescent with Autism Spectrum Disorder. JADD. 2015. May 16.

[2] Dodou K. et al. Ex vivo studies for the passive transdermal delivery of low-dose naltrexone from a cream; detection of naltrexone and its active metabolite, 6β-naltrexol, using a novel LC Q-ToF MS assay. Pharm Dev Technol. 2014 May 2.

[3] Picciotto MR. et al. Mood and anxiety regulation by nicotinic acetylcholine receptors: A potential pathway to modulate aggression and related behavioral states. Neuropharmacology. 2015 Jan 9. pii: S0028-3908(14)00479-1.

[4] Bejerot S. & Nylander L. Low prevalence of smoking in patients with autism spectrum disorders. Psychiatry Res. 2003 Jul 15;119(1-2):177-82.

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Van Schalkwyk, G., Lewis, A., Qayyum, Z., Koslosky, K., Picciotto, M., & Volkmar, F. (2015). Reduction of Aggressive Episodes After Repeated Transdermal Nicotine Administration in a Hospitalized Adolescent with Autism Spectrum Disorder Journal of Autism and Developmental Disorders DOI: 10.1007/s10803-015-2471-0

Respiratory illness and schizophrenia

"Schizophrenia is associated with impaired lung function and increased risk for pneumonia, COPD [Chronic obstructive pulmonary disease] and chronic bronchitis."

That was the primary conclusion reached in the paper by Krista Partti and colleagues [1] who aimed to "compare the respiratory health of people with psychosis with that of the general population." Their findings, based on data from "a nationally representative sample of 8028 adult Finns" (Finns as in inhabitants of Finland) involved collected data on the frequency of respiratory disease/symptoms as well as measuring lung function via the technique known as spirometry. Tobacco smoking or exposure to smoking, one of the primary causes of respiratory illness in the general population, was "quantified with serum cotinine levels."

"Participants with schizophrenia and other non-affective psychoses had significantly lower lung function values compared with the general population, and the association remained significant for schizophrenia after adjustment for smoking and other potential confounders." Indeed, as per the opening sentence to this post, authors reported some pretty elevated odds ratios (ORs) for various respiratory illnesses related to a diagnosis of schizophrenia compared with asymptomatic controls.

This is not the first time that respiratory diseases have been reported as potentially being more frequently diagnosed in cases of schizophrenia. Schoepf and colleagues [2] reported that in their cohort of those diagnosed with schizophrenia, various physical comorbidity were detected including COPD. As a predictor of "general hospital mortality" both COPD and bronchitis were included in the list of diseases. Other studies have arrived at similar conclusions [3] including data derived from the 'big data' producer that is Taiwan as per the findings from Hsu and colleagues [4].

As per the NHS Choices entry on COPD: "The main cause of COPD is smoking." Tobacco smoking is reported to be more frequently present in cases of schizophrenia [5] albeit with the need for some caution when it comes to making sweeping statements about the overlap [6]. It's therefore not beyond the realms of possibility that smoking habits may very well have a primary role in the association reported by Partti et al particularly in light of their findings on cotinine levels.

That being said, and acknowledging that smoking cessation programmes may be lifesavers for people with schizophrenia as they are for the rest of the population, I'm interested in whether there may be other factors at work when it comes to lung function and schizophrenia. Airway physiology, for example, might be something to consider, particularly in light of other findings when it comes to autism covered previously on this blog (see here). I'm not trying to downplay lifestyle factors [7], just sayin' that we need to cover all the potential bases including looking at whether familial transmission might also be a factor to consider [8].

Music: Song 2 by Blur.

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[1] Partti K. et al. Lung function and respiratory diseases in people with psychosis: population-based study. Br J Psychiatry. 2015 Apr 9.

[2] Schoepf D. et al. Physical comorbidity and its relevance on mortality in schizophrenia: a naturalistic 12-year follow-up in general hospital admissions. Eur Arch Psychiatry Clin Neurosci. 2014 Feb;264(1):3-28.

[3] Hendrie HC. et al. Health outcomes and cost of care among older adults with schizophrenia: a 10-year study using medical records across the continuum of care. Am J Geriatr Psychiatry. 2014 May;22(5):427-36.

[4] Hsu JH. et al. Increased risk of chronic obstructive pulmonary disease in patients with schizophrenia: a population-based study. Psychosomatics. 2013 Jul-Aug;54(4):345-51.

[5] Kelly C. & McCreadie R. Cigarette smoking and schizophrenia. BJPsych Advances. 2000; 6.

[6] Chapman S. et al. Citation bias in reported smoking prevalence in people with schizophrenia. Aust N Z J Psychiatry. 2009 Mar;43(3):277-82.

[7] Filik R. et al. The cardiovascular and respiratory health of people with schizophrenia. Acta Psychiatr Scand. 2006 Apr;113(4):298-305.

[8] Zöller  B. et al. Familial transmission of chronic obstructive pulmonary disease in adoptees: a Swedish nationwide family study. BMJ Open 2015;5:e007310 doi:10.1136/bmjopen-2014-007310

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Partti K, Vasankari T, Kanervisto M, Perälä J, Saarni SI, Jousilahti P, Lönnqvist J, & Suvisaari J (2015). Lung function and respiratory diseases in people with psychosis: population-based study. The British journal of psychiatry : the journal of mental science PMID: 25858177