"his sudden interest in changing gender may have been another of his autistic obsessions"

A recent (online) newspaper report from here in Blighty included the quote used in the title of this post: "his sudden interest in changing gender may have been another of his autistic obsessions" (see here).

The report describes how a male - born biologically male - teenager diagnosed with autism expressed an opinion that "he believed he was female" and how his opinion was received by his parents and other professionals. Differences in the reception and perception of that opinion eventually led to some 'frustration' and, worryingly, the eventual intervention of social (child) services.

I decided to blog about this report primarily because (a) it ties in with some important peer-reviewed science discussions about gender identity and autism (see here and see here), and (b) there is a distinct possibility that the headline accompanying the report - "Social services threaten to take autistic boy into care after his parents refuse to let doctors give him powerful sex-change drugs" - is likely to be replicated again. Such a headline also taps into some wider debates about an increasing number of children talking about their gender and the decision-making rights and abilities of children both on and off the autism spectrum.

First things first, I know there are lots of strong opinions about sex and gender and 'what's right for children' these days. I don't offer an opinion either way nor do I claim to be an expert on issues such as gender dysphoria - "where a person experiences discomfort or distress because there's a mismatch between their biological sex and gender identity" - or gender reassignment or related issues. As mentioned, I'm interested in the science behind such discussions because autism has been discussed, on more than one occasion, as being potentially 'over-represented' among those with gender dysphoria [1] and/or wanting to/going through gender reassignment services. I say 'potentially over-represented' but wouldn't want anyone to think that any scientific debates have been settled at the current time: they haven't [2] (see here). I'm also interested in this topic because, aside from any gender reassignment issues, autism not so long ago was faced with something called the 'Lupron protocol'. Then leuprorelin, a drug sometimes used to 'delay puberty', was touted as something important to autism for very, very different reasons. I might add that the story of such a 'protocol' did not end well, as words like 'chemical castration' were banded around (see here).

I selected the quote that heads this post because it strikes me that there are some 'unique' issues that arise in the context of autism being mentioned alongside gender dysphoria and/or reassignment. Issues that don't seem to have been properly considered at the time of writing. Indeed, when I first tweeted about the source article for this post, a couple of response summed up the positions taken. First: "That child is not a boy. She is a girl and she needs the medical transition that will treat her dysphoria and allow her to live her best life." Another response was from someone who is themselves autistic and mentioned an important word: 'impulsivity'. Indeed, the article itself also mentions some similarly important phrases which require consideration. So: "they [his parents] suspected his abrupt decision to change sex was a result of his autism" and "All we were doing was trying to get him to pause and think about his actions" and "The school and social workers took what our child said as gospel. But considering he has autism, his perception of social scenarios is seen through an autism lens." An autism lens?

As you can see, a lot of those quotes/opinions focus on the idea that the traits that stem from or follow autism are potentially important to this debate. Minus any 'pity me' sentiments, they imply for example, that autism confers some specific 'vulnerability' that cannot simply be brushed under the carpet particularly when a person makes, or wants to make, important, potentially life-changing, decisions. I've talked about the issue of vulnerability and autism before on this blog (see here and see here) with some equally life-changing issues in mind. The topics differ but the sentiments remain the same. It's highly likely that the parents discussed in that news report know a little a bit about such vulnerability and autism purely in the context of raising their offspring.

Such vulnerability does however have to be balanced with individual rights; that is the rights of an individual to make important decisions that affect them. Such decisions might not always be 'the correct ones' or the ones that significant others necessarily want them to make but nonetheless, still need to be valued particularly within the context of assumed competence (see here). Indeed I get the impression that it's the possibility that the child has expressed an opinion with future consequences - "My biggest worry as a mum is my child gets pushed down this route, becomes a woman, goes through the surgery, then gets to 25 and says, “I’ve made a mistake.”" - that seems to worry the parents in the news report more than anything else. The use of the word 'surgery', implying the degree of 'invasiveness' needed and potentially also inferring 'irreversibility', is perhaps also an important part of their response.

What else? Well, without heading too far into scientifically unexplored territory I think there are other issues that come into play in such a scenario. Going back to the comment on impulsivity and the 'abrupt decision' talked about in the article, another important (and contentious) issue is potentially introduced: rapid-onset gender dysphoria (ROGD) [3]. ROGD is something that is not well-liked in some quarters (see here) and still remains a topic of some (heated) discussion (see here). It defines a state whereby "teens and young adults who did not have symptoms of gender dysphoria during childhood but who were observed by their parents to rapidly develop gender dysphoria symptoms over days, weeks or months during or after puberty." I don't make any comment on the rights or wrongs of something like ROGD but would encourage further study. Specifically with autism in mind and on the basis of the case being reported, questions like: 'how abrupt was the decision?' (or was the decision taken many moons ago but just communicated recently?) are important. Whether those who are diagnosed with autism or present with significant autistic traits are 'over-represented' among cases of ROGD is another research question that perhaps needs considering. And then there's the possible question of why?

Ultimately there are no easy answers to the issue described in today's post despite some significant strength of feeling. What will help however, is research; good quality research that is not afraid to test difficult hypotheses. And whilst individuals should always be empowered to make decisions for themselves, there should always be an appreciation that decision-making typically does not occur in a vacuum...

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[1] Janssen A. et al. Gender Variance Among Youth with Autism Spectrum Disorders: A Retrospective Chart Review. Transgend Health. 2016 Feb 1;1(1):63-68.

[2] Nobili A. et al. Autistic Traits in Treatment-Seeking Transgender Adults. J Autism Dev Disord. 2018. April 13.

[3] Littman L. Rapid-onset gender dysphoria in adolescents and young adults: A study of parental reports. PLoS One. 2018 Aug 16;13(8):e0202330.

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High frequency of (self-reported) ADHD symptoms in eating disorders

"There is a high frequency of ADHD [attention-deficit hyperactivity disorder] symptoms in patients with binge eating/purging eating disorders that motivates further studies."

That was the conclusion reached in the study by Nils Erik Svedlund and colleagues [1] (open-access) who, among other things, set out to "explore the prevalence and types of self-reported ADHD symptoms in a large, unselected group of ED [eating disorder] patients assessed in a specialized ED clinic." Participants (over 1100 of them) were "seeking help at the Stockholm Centre for Eating Disorders (SCED) from 4 February 2013 through 18 September 2015" and as well as being confirmed to have an eating disorder were also screened for ADHD-type behaviours using the WHO ADHD Self-Rating Scale for Adults (ASRS-screener). Notice the 'self-rated' part of that last sentence...

Based on a ASRS screener score of 14 or above, researchers reported that some 30% of females (N=1094) self-reported 'issues' associated with a diagnosis of ADHD. Some 34% of men included for study (N=47) reported similar ADHD traits (31.3% of the total group including those diagnosed with 'Eating Disorder Not Otherwise Specified (EDNOS) type 5' were on or above the ASRS screener score of 14).

Bearing in mind the presence of various types of different eating disorders in their cohort, researchers also looked at how those self-reported ADHD traits might correlate with sub-groupings. They report that: "The highest frequency of possible ADHD was found in BN [Bulimia Nervosa] and in AN-BP [Anorexia Nervosa bingeing/purging subtype], respectively." They also noted that specific symptoms of ED correlated with the ASRS-screener scores: binge eating, purging, loss of control over the eating and BMI [body mass index] > 17.5. I might add that based on responses to another schedule - the Comprehensive Psychiatric [Psychopathological] Rating Scale (CPRS) - included as part of the study, authors noted something of a link between the ASRS trait scores and "the CPRS scales for depression..., anxiety... and obsession-compulsion." But: "Psychiatric comorbidity correlated to ADHD symptoms without explaining the differences between eating disorder diagnoses."

Keeping in mind that answering 6 questions on a screener questionnaire does not an ADHD diagnosis make, I am rather interested in these and other findings. I am by no means an expert on eating disorder but I have previously been interested in the suggestion that autistic traits may be 'over-represented' when it comes to ED (see here). Combined with the idea that autism and [diagnosed] ADHD might not also be unstrange diagnostic bedfellows (see here) and you can perhaps see that there is potentially more research to do in this area in these times of overlap and ESSENCE. And speaking of ESSENCE [2]...

With a word or two of caution, I note the authors also talked about potential 'treatment' options given the overlap between ADHD traits (self-reported) and ED. So: "This motivates further randomized trials with stimulant treatment for bingeing/purging ED-patients with and without a concomitant ADHD diagnosis." Certain stimulants have quite a good track record when it comes to ADHD (see here) but the authors rightly note that 'appetite suppression' is a potential side-effect of such pharmacotherapy and something perhaps not ideal if someone is already underweight. More studies are indicated to disentangle what is linked to what.

And while I'm on the topic, the link between autism traits and anorexia nervosa might actually be a little more tenuous that you perhaps think [3]...

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[1] Svedlund NE. et al. Symptoms of Attention Deficit Hyperactivity Disorder (ADHD) among adult eating disorder patients. BMC Psychiatry. 2017; 17: 19.

[2] Karjalainen L. et al. Eating disorders and eating pathology in young adult and adult patients with ESSENCE. Compr Psychiatry. 2016 Apr;66:79-86.

[3] Postorino V. et al. Investigation of Autism Spectrum Disorder and Autistic Traits in an Adolescent Sample with Anorexia Nervosa. J Autism Dev Disord. 2017. Jan 24.

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Svedlund, N., Norring, C., Ginsberg, Y., & von Hausswolff-Juhlin, Y. (2017). Symptoms of Attention Deficit Hyperactivity Disorder (ADHD) among adult eating disorder patients BMC Psychiatry, 17 (1) DOI: 10.1186/s12888-016-1093-1

Impulsivity and uric acid

A few years back I posted about an interesting body of research on purine metabolism in relation to the autism spectrum disorders (ASDs) and how some work from the likes of Mary Coleman and Ted Page had reported high levels of uric acid to be coincidentally present in cases of ASD.

The gout @ Wikipedia  

As with other research angles, the initial interest in this finding of hyperuricosuria - elevated urinary uric acid - and autism did not seem to last. Just like the dusty research doll that is sulphation (sulfation) and autism, uric acid came to find itself under the autism research bed listening to the tune of 'when somebody loved me'. Sulphation, I might add with autism in mind, has started to see something of a renaissance recently but only a small one (see here).

Enter then an intriguing paper by Angelina Sutin and colleagues* reporting on an association between elevated levels of uric acid and impulsivity as a trait in both human and mice. As per another recent paper which was discussed on this blog on ADHD and solar intensity, the publishing journal was Biological Psychiatry which is fast becoming a real favourite journal of mine. Reading through Dr Sutin's profile page it is interesting to note that she has some interest in how personality might be associated with physical and mental health. Her latest paper therefore continues this interesting theme.

A few details from the Sutin paper are in order:

• This was a study drawing on both human and mouse model data to ascertain whether the findings of elevated uric acid in behavioural and psychiatric conditions "characterized by high impulsivity" might actually be specifically related to the impulsivity trait.
• Human participants (N=6883) derived from two cohorts - SardiNIA and the Baltimore Longitudinal Study of Aging - completed the Revised NEO Personality Inventory which aims to characterise the Big Five personality traits (openness, conscientiousness, extraversion, agreeableness, neuroticism) via self-report.
• They also provided fasting blood samples which were screened for uric acid both at time of schedule completion and at follow-up (some 3-5 years later).
• A second study was also reported looking at the behaviour of mice "urate oxidase null" = bred to show elevations in uric acid, compared with wild-type controls. 
• Results: lots of them, but a few of the more interesting findings included (i) impulsiveness and excitement seeking individuals were more likely to have higher levels of uric acid (albeit mediated by factors such as BMI and smoking which themselves pose some interesting questions), and (ii) "homozygous urate oxidase-deficient mice" (high uric acid) showed a lot more exploratory and "emotional" behaviour. 
• In short, the two experiments reported "supports the hypothesis that impulsivity is associated with higher levels of uric acid".
• Another quote from the paper sums up where this kind of research could potentially lead: "The identification of biological markers of impulsivity may lead to a better understanding of the physiological mechanisms involved in impulsivity and may suggest potential targets for therapeutic intervention".

Very interesting stuff I'm sure you'll agree. Indeed the participant numbers for the human part of the study are certainly impressive and indeed across the two geographically distinct cohorts too, even more impressive.

But with my science-hat on, lets take a step back and point out some important limitations of this work. First and foremost is the assumption that the personality trait impulsivity measured by only one personality inventory is the only potential correlate here, at least among the human participants. It isn't. And indeed one should always be mindful that just because investigators test for something like a personality trait or a specific cognitive skill or even a specific condition/state/disease does not mean they have excluded all other potentially important variables** (indeed if this is even possible). Next is the assumption that self-report responses on a five-point Likert scale are going to be true and honest. No-one can be totally assured of that, particularly if responses are to some of the more less desirable personality traits that we would all like to put to one side. Finally is the interpretation of a mouse model of high uric acid showing the impulsivity trait based on their novelty-seeking and exploratory behaviours during field tests. I've talked mouse models before with autism in mind and how behavioural animal models are always subject to some degree of interpretation until such time that we can talk to the animals (and they talk back).

Having said all that I do find myself still very interested in the Sutin findings in terms of how the work was done, the results obtained and where it could lead. Without giving anything that looks or sounds like medical or clinical advice, one has to wonder (as the authors have done) whether 'adjusting' levels of uric acid might have a knock-on effect on certain behaviours particularly where uric acid might be seen in more behaviourally or psychiatrically defined conditions. I'm not saying everyone should be taking something like allopurinol or anything like that but perhaps further investigation is at least warranted.

Finally, on a similar note to the Sutin study I also recently came across a study by Soto-Insuga and colleagues*** which reported some very preliminary findings from treating iron deficiency in cases of attention-deficit hyperactivity disorder (ADHD). To quote: "Treatment with iron supplements can be an effective alternative to treat patients with ADHD and iron deficiency, especially the inattentive subtype". By 'treatment' I take it to mean that not only were the authors resolving the iron deficiency but also in specific cases of ADHD identified by that inattentive subtype**** they were talking about the management of behavioural symptoms too.

Example evidence that the psychosomatic or somatopsychological relationship should definitely remain near the top of the research agenda?

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* Sutin AR. et al. Impulsivity is associated with uric acid: evidence from humans and mice. Biol Psychiatry. April 2013.

** Cerecero P. et al. Association between serum uric acid levels and cardiovascular risk among university workers from the State of Mexico: a nested case--control study. BMC Public Health 2013; 13: 415.

*** Soto-Insuga V. et al. Role of iron in the treatment of attention deficit-hyperactivity disorder. An Pediatr (Barc). April 2013.

**** Solanto MV. The predominantly inattentive subtype of attention-deficit/hyperactivity disorder. CNS Spectr. 2000; 5: 45-51.

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Sutin AR, Cutler RG, Camandola S, Uda M, Feldman NH, Cucca F, Zonderman AB, Mattson MP, Ferrucci L, Schlessinger D, & Terracciano A (2013). Impulsivity is Associated with Uric Acid: Evidence from Humans and Mice. Biological psychiatry PMID: 23582268