Saturday, 26 May 2018

"CFS symptoms resemble a hypothyroid state" but...

I am a little late getting to the paper published by Begoña Ruiz-Núñez and colleagues [1] observing that, at least for some diagnosed with chronic fatigue syndrome (CFS), clinical findings related to thyroid function might "resemble a mild form of “non-thyroidal illness syndrome” and “low T3 syndrome” experienced by a subgroup of hypothyroid patients receiving T4 monotherapy." But I did get here eventually. Before heading into this paper, I'm gonna link to one of the 'already prepared' discussions on the Ruiz-Núñez findings (see here). My analysis is pretty similar but not entirely the same...

So: "We studied 98 CFS patients (21–69 years, 21 males) and 99 age- and sex-matched controls (19–65 years, 23 males)" was the starting point, as participants provided blood samples and 24-hour urine samples onward to various analyses being carried out. This included: "the measurement of routine hematological parameters [Hb, hematocrit, WBC, red blood cells (RBC), and thrombocytes]" and more specifically: "parameters of thyroid function, low-grade inflammation and gut wall integrity..., together with secondary markers of inflammation." Those 'parameters of thyroid function' included various measures of free and total levels of T3 and T4 required to ascertain the presence of "low-T3 syndrome." I was impressed to see that a measure of gut wall integrity was also on the research menu in the form of plasma zonulin levels being included (albeit analysed via ELISA and bearing in mind the issues that have emerged with that particular method).

Results: "Chronic fatigue syndrome patients exhibited lower FT3, TT4, TT3, %TT3, SPINA-GD, and SPINA-GT, lower ratios of TT3/TT4, FT3/FT4, TT3/FT3, and TT4/FT4; and higher %rT3 and rT3/TT3 ratio." These findings were based on 'group' comparisons with those sex-matched not-CFS controls, and point to some 'issues' with thyroid function in general. Coupled to other thyroid related findings, the Ruiz-Núñez suggest that lower levels of thyroid hormones were detected but "distinct from thyroidal disease" typical levels of thyroid-stimulating hormone (TSH) were also reported. TSH is the stuff that tells the thyroid gland to make thyroid hormone (thyroxine (T4)), where T4 is, in effect, the starting material for T3 (triiodothyronine). Where there are suitable levels of TSH but lower levels of T4 and/or T3, one gets the impression that it's more about what's 'happening' to T3 and T4 over and above issues with their production. Indeed, the collected findings led authors to talk about that 'low T3 [triiodothyronine]syndrome' as being potentially pertinent to their findings in relation to CFS. Going back to those plasma zonulin findings, and there is just a sentence from Ruiz-Núñez and colleagues: "Zonulin, a parameter of intestinal permeability... was lower in CFS patients as compared to controls" but not much else.

I'm not particularly au fait with all the details of low T3 syndrome in the context of CFS or anything else so can't really add too much more. From what I gather, this is not a CFS-exclusive condition but does seemingly tap into talk about CFS being reflective of a "hypometabolic state" (see here). Questions about how to 'treat' such thyroid-related issues in the context of CFS remain unanswered, despite authors talking about "trials with, e.g., T3 and iodide supplements" being potentially indicated. I say this bearing in mind that the focus on biochemistry in the Ruiz-Núñez paper could perhaps, have been complemented by a little more on the presentation of clinical symptoms too.

In short, quite a bit more investigation in this area is indicated...


[1] Ruiz-Núñez B. et al. Higher Prevalence of “Low T3 Syndrome” in Patients With Chronic Fatigue Syndrome: A Case–Control Study. Front. Endocrinol. 2018. Mar 20.


Friday, 25 May 2018

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."


[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.


Thursday, 24 May 2018

"Lonely young adults in modern Britain"

"Lonelier young adults were more likely to experience mental health problems, to engage in physical health risk behaviours, and to use more negative strategies to cope with stress."

Those were some of the conclusions reached in the study published by Timothy Matthews and colleagues [1] who relied on data from the "Environmental Risk (E-Risk) Longitudinal Twin Study, which tracks the development of a birth cohort of 2232 British children" to "examine the profile of loneliness in a prospective, contemporary, nationally representative cohort of 18 year-olds living in the UK." The specific focus was on how loneliness might impact on various domains: "mental health, physical health and health risks, coping and functioning, and career prospects."

Results: first and foremost, when it came to the question(s) of loneliness, and the prevalence of loneliness as measured by the UCLA Loneliness Scale, Version 3, "23–31% of participants reported experiencing any of these feelings ‘some of the time’, and 5–7% reported feeling them ‘often’." Sex/gender and socio-economic status did not seem to show any statistically significant relationship to reports on loneliness.

In terms of possible or actual psychopathology, we are told that: "Lonelier 18 year-olds were more likely to meet diagnostic criteria for depression, anxiety, ADHD [attention-deficit hyperactivity disorder], conduct disorder, alcohol and cannabis dependence, to have self-harmed, and to have attempted suicide." Depression and anxiety came out with the strongest *association* in relation to loneliness, and insofar as the 'attempted suicide' bit, I'm wondering whether it may tie into other recent quite shocking findings (see here). Researchers also noted that: "lonelier individuals engaged in less day-to-day physical activity and were more likely to be daily smokers."

Whilst realising that the various associations mentioned in the context of loneliness do not necessarily tie directly into loneliness (e.g. loneliness does not necessarily 'cause' anxiety and depression or indeed, vice-verse), these are important results. They add to a bank of peer-reviewed research which suggests that loneliness - chronic loneliness - is probably not great for anyone (see here). They also observe that increasing social contact with others, whilst not without benefits, is not necessarily all that can be done to combat this state and it's rather negative correlations.

And it is perhaps timely that at the time of writing this post, loneliness is highlighted as being over-represented when it comes to certain diagnostic labels as part of a package of issues affecting quality of life (see here)...


[1] Matthews T. et al. Lonely young adults in modern Britain: findings from an epidemiological cohort study. Psychological Medicine. 2018. April 24.


Wednesday, 23 May 2018

Pregnancy exposure to paracetamol and offspring developmental outcomes meta-analysed

Yes, I'm yet again talking about pregnancy paracetamol (acetaminophen) use and offspring developmental outcomes on this blog (see here and see here for other discussions on this topic). As I mentioned on another recent blogging occasion, the news regarding pregnancy paracetamol use and offspring outcomes seems to be getting worse and worse, as associations galore keep appearing in the peer-reviewed science arena. Of course one has to be a little cautious about the nature of the studies that are emerging (i.e. observational, not readily designed to look at 'cause-and-effect') but the volume of research is growing at a significant pace potentially suggestive of something to see.

Now we have the results of a "Systematic Review, Meta-Analysis, and Meta-Regression Analysis of Cohort Studies" published by Reem Masarwa and colleagues [1] on the topic of pregnancy paracetamol use and "the risk for attention deficit hyperactivity disorder (ADHD) and autistic spectrum disorder (ASD) in the offspring of women exposed to acetaminophen during pregnancy." All that meta-analysis stuff means that authors boiled down the current, existing peer-reviewed research into some sort of coherent whole. Their paper also comes complete with some lay media attention too (see here).

The findings? Well, taking into account various studies published "up to January 2017" and including some "132,738 mother and child pairs and with a follow-up period of 3-11 years", you probably won't be surprised to here that prolonged paracetamol use during pregnancy did seem to increase the risk of ADHD and/or autism in offspring to the tune of about 20-30% compared with those who did not take such medicine during pregnancy. That's not an unimportant percentage in anyone's book.

Reiterating the observational nature of the studies reviewed and boiled down (in a statistical sense) by Masarwa et al and the need for further investigations on things like possible mechanisms and indeed, whether the conditions for which paracetamol as pain relief was being taken *might* exert an effect on offspring risk, the results add to the concern. Much like other areas where various pregnancy medications are seemingly being implicated in relation to offspring outcome (see here and see here) such findings reiterate the importance of the nine months that made us and the need for much more sound research on this topic...


[1] Masarwa R. et al. Prenatal Exposure to Acetaminophen and Risk for Attention Deficit Hyperactivity Disorder and Autistic Spectrum Disorder: A Systematic Review, Meta-Analysis, and Meta-Regression Analysis of Cohort Studies. American Journal of Epidemiology. 2018. April 24.


Tuesday, 22 May 2018

A poo(p) transplant for depression and anxiety?

Contrary to the title of this post - "A poo(p) transplant for depression and anxiety?" - I don't think we are yet in a position to say that Fecal Microbiota Transplantation (FMT) is ready to go 'mainstream' as an approved treatment for depression and/or anxiety. I do however, think that the findings reported by Shunya Kurokawa and colleagues [1] provide evidence for a further, more controlled, scheme of research on this topic.

Based on their following a small-ish group of patients diagnosed with "either Irritable Bowel Syndrome (IBS), Functional Diarrhea (FDr) or Functional Constipation (FC) who underwent FMT for the treatment of gastrointestinal symptoms and observation of psychiatric symptoms" authors report results before said poo(p) transplant and after 4 weeks based on ratings on various instruments pertinent to the presentation of depression and anxiety. Alongside "intestinal microbiota were measured" with a particular focus on the level of diversity of species that were present in pre- and post-FMT samples. I might also mention at this point, how something like IBS is not without it's own 'psychological' correlates as per other research (see here and see here).

Following an 'open-trial' methodology and including only a "small sample size with no control group", researchers reported some significant improvements in relation to those depression and anxiety symptom scores for some. Importantly too, they noted that potential FMT effects on mood seemed to be independent of effects on "gastrointestinal symptom change." Similarly: "There was a significant correlation between baseline Shannon index and HAM-D [Hamilton Rating Scale for Depression] score, and a correlation between Shannon index change and HAM-D improvement after FMT." This suggests that bacterial diversity might be something to look at as potentially explaining the psychological effects of FMT.

Reiterating that the Kurokawa findings are preliminary and hence, require quite a lot more further (independent) study, I find this topic to be an interesting one. Although there may be some 'consumer resistance' to the idea of FMT, for some people, this type of intervention is nothing short of life-saving (see here). The idea that a similar type of transplant *might* also hold some benefits for conditions/labels outside of something like Clostridium difficile (C. difficile) infection has already been noted in the peer-reviewed science literature (see here and see here for examples), including conditions characterised by behaviour and psychology. This alongside a growing interest in how mood and temperament might have some important connection to those trillions of wee beasties (the gut microbiome) that call us all home (see here). We'll see where this goes...


[1] Kurokawa S. et al. The effect of fecal microbiota transplantation on psychiatric symptoms among patients with irritable bowel syndrome, functional diarrhea and functional constipation: An open-label observational study. J Affect Disord. 2018 Apr 12;235:506-512.


Monday, 21 May 2018

The "experiences and perspectives of people who have severe autism and are minimally verbal"

I'm not going to formulate some sort of mammoth, long-read post on the paper by Christie Welch and colleagues [1] but I did want to bring their findings to your attention. My reasoning: the authors include a quite 'under-represented' group (see here) when it comes to the public view of the autism spectrum: those who "have severe autism and are minimally verbal."

Presenting the results of a qualitative study whereby "three memoirs written by youths who have severe autism and are minimally verbal were examined using inductive thematic analysis", authors observed several important themes emerging. Principal among them: "regarding the youths' concern that the way they are perceived from the outside does not match the people they are on the inside."

"These youths emphasize concepts of embodiment and physical control as central to their experiences of autism" said Welch et al, as the message seems to be that more should be done to 'tackle' these experiences and ensuring that sweeping generalisations about language use or non-use for example, are not seen as a proxy for cognitive and intellectual abilities. Just because someone cannot speak verbally, does not mean that they have nothing to say, and vice-verse.

I'm careful not to fall into the trap of 'autism severity' on the basis of the Welch findings, where terms like 'high' and 'low' functioning unduly simplify people in a binary fashion and seemingly without regard for the complexity of how autism affects various aspects of a person's life. I do however like the idea that more effort needs to go into things like the development of communication systems for those who are minimally verbal; both for clinical and research purposes but perhaps more importantly, day-to-day purposes, given also some catastrophic examples where communication issues have severely impacted on autistic lives (see here and see here).

And to the question of 'how common is 'minimally verbal' in the context of autism', well, another recent paper [2] has come up with an estimate: about a third...


[1] Welch C. et al. Autism inside out: lessons from the memoirs of three minimally verbal youths. Disabil Rehabil. 2018 Apr 23:1-9.

[2] Bacon EC. et al. Naturalistic language sampling to characterize the language abilities of 3-year-olds with autism spectrum disorder. Autism. 2018 May 1:1362361318766241.


Saturday, 19 May 2018

Temporal armchair diagnosing taken to the max: 'How Do We Explain ‛Autistic Traits’ in European Upper Palaeolithic Art?'

Headlines aplenty...
I'm not a great fan of 'armchair diagnosing' also known as 'diagnosing at a distance'. It's speculative, often inaccurate and runs the real risk of ruining lives.

The remote diagnosing of psychiatric and behavioural disorders is a particular bugbear of mine. It's something that autism research and practice in particular has had to endure for quite a few years, as a volley of historical figures for example, were revealed to be supposedly autistic. Such musings also add a temporal aspect to proceedings.

The paper published by Penny Spikins and colleagues [1] takes such temporal armchair diagnosing to the absolute max, with their contribution to the "long standing debate about the existence of ‘autistic traits’ in European Upper Palaeolithic art." Some of the media that followed these findings really went to town, as per headlines such as 'Ice Age cave artists were AUTISTIC' (capital letters were already included in the headline, not added by me - see above) and 'Autism shaped the art of survival'. Wow. All of that information from a few paintings and carvings...

So how did the the authors and the lay media arrive at such a conclusion?

Well, first and foremost Spikins et al did not say that the makers of such early art were 'autistic'. They focused on autistic traits, and in particular the idea of an "extreme local processing bias" or attention to detail trait that seems to accompany the diagnosis of autism (for some). Importantly, they note that: "Local processing bias is common in autism but also seen in individuals without autism" and "‘Autistic traits’ in Upper Palaeolithic art do not necessarily signify the work of an individual with autism." So, from the outset, we can probably do away with that rather sweeping [diagnostic evidence-free] media headline on Ice Age cave artists being autistic.

Quite a lot of the Spikins paper focuses on what's been observed - directly observed - in some of those diagnosed as being on the autism spectrum when it comes to artistic talent, which is then 'extrapolated' to such prehistoric artists. This includes some rather nice pictures drawn by individuals with autism who expressed a "marked local processing bias" compared with age-matched drawings from non-autistic individuals. We're also told that the use of the (very) famous 'are you autistic?' self-report screener that is the Autism Spectrum Quotient (AQ) by the authors, revealed that "individuals with a very high autism quotient (AQ) of 32 or above, which is taken as indicative of an autism spectrum condition within a population sample were statistically much more likely than neurotypical individuals (i.e. those with a lower AQ score) to have an interest in and experience of art outside of any school curriculum." 'Indicative of an autism spectrum condition'? Well, we'll see. And I still have some problems with what comes under the term 'neurotypical' too (see here).

Of course you can perhaps see the issue here. Take one block of 'evidence', some of it based on individual case reports and some of it based on an 'autism' screener that probably picks up an awful lot more than 'just autism' (see here and see here and see here for examples), correlate and correlate some more and hey presto, we reach the conclusion that the art must have been drawn by someone expressing an autistic trait or even someone who was autistic.

A testable hypothesis? No, it's not. We don't know who drew those paintings or made those carvings. We don't know anything about them personally and we certainly don't have any evidence about whether they expressed any significant autistic or any other kind of trait. For all we know, the paintings or carvings could also have been made by more than one person; a family or group effort if you like. We just don't know because, well, those artistic depictions were made thousands and thousands of years ago before the tools that help us record history were even a twinkle in the cosmic eye.

I don't want to come across as poo-pooing such 'observations' stressing how autistic traits are not necessarily a new thing because, in essence, I do think that some autistic traits have probably been with us from our earliest evolutionary times (see here). I say that on the basis that the traits of autism are not some 'magical' behaviours that are completely distant from the human experience; more likely they represent the extremes of what is typically seen in the general population at particular ages and stages and environments. Taking such logic back in an evolutionary sense, one can for example see how something like an 'attention to detail' could be a good survival skill if your life depended on it.

But I do think one has to be very, very cautious about such research and any 'feelgood' factor it might attempt to generate or put forward. Autism, as a clinical definition, only really came about in the last hundred years or so, and for many, any benefits derived from a 'marked local processing bias' have to be balanced with the possible downsides to such directed focus (e.g. increased rumination and anxiety). I'd also add in that the idea that Palaeolithic Art (or indeed, any kind of art) merely comes about as a result of traits that are noted in the context of psychopathology is a pretty dangerous path to take. It risks boiling down human efforts such as creativity and artistic skill to nothing more than diagnostic characteristics and feeds into narratives such as the "creativity is akin to insanity" headlines of not so long ago (see here). As I've said before, people are so much more than the labels they've received or the diagnostic term they identify with.

In short, Palaeolithic art is interesting and adds to our understanding of how we evolved. But it simply cannot provide an accurate window on any states and traits of those who created it...

To close, there's a wedding on today apparently. Best wishes to the happy couple. And not to make light of our Royal Family, but The Windsors TV show is absolute comedy gold (particularly Harry Enfield)...


[1] Spikins P. et al. How Do We Explain ‛Autistic Traits’ in European Upper Palaeolithic Art? Open Archaeology. 2018; 4: 262-279.