Monday, 19 March 2018

One more time... ADHD is over-represented in cases of epilepsy

"Among the 73 children with epilepsy, 23% (n = 17) had comorbid ADHD [attention-deficit hyperactivity disorder], of whom 59% (n = 10) had predominantly inattentive type, 35% (n = 6) combined type, and 6% (n = 1) predominantly hyperactive-impulsive type."

So said the findings reported by Anita Choudhary and colleagues [1] adding to an ever growing body of peer-reviewed research literature suggesting that a diagnosis of epilepsy may, for whatever reason(s), elevate the risk of ADHD being diagnosed or, at the very least, the symptoms of ADHD occurring (see here).

This time around, Choudhary et al focused on data derived from a children's neurology service where epilepsy was "defined as two or more unprovoked seizures occurring 24 hours apart after four weeks of age, with at least one epileptic seizure in the previous five years, regardless of AED [anti epileptic drugtreatment, based on International League Against Epilepsy definitions."

As per the opening sentence, some 73 children aged 6-12 years old met their study eligibility criteria; being part of a larger trial where data on behavioural comorbidity in the context of epilepsy had already been published [2]. Importantly for this latest study, the authors excluded those who "had an intellectual disability or comorbid chronic systemic disease" which seems to be rather relevant to the clinical picture emerging with regards to epilepsy in the context of a condition 'over-represented' in ADHD, autism (see here). Alongside a behavioural/psychiatric evaluation based first on parent/caregiver ratings and if required, followed up with a more professional consultation, researchers also carried out assessments related to cognitive functions and reviewed health records.

Aside from noting that ADHD seemed to be over-represented among their cohort with epilepsy, authors also talked about a couple of variables that also seemed to be important to the presentation of ADHD in those with epilepsy. So: "Children with both epilepsy and ADHD had lower IQ scores and were significantly less likely to be attending school, with epilepsy being the primary reason." That point about the presence of epilepsy *correlating* with lower IQ scores is not necessarily something prevalent across the research in this area, but some authors have talked about a "subgroup of about 10–25% of children that shows a clinically significant intellectual decline" [3] which could potentially be relevant.

Pertinent biological mechanisms crossing both epilepsy and ADHD? Well similar to the last blogging occasion, one has to mention that epilepsy does affect various brain functions (see here) so that is something to consider as also impacting the likelihood of ADHD. Whether this means affecting something structural or something like connectivity, we just don't know at present. I'm also minded to highlight the possibility of genetic overlaps too; drawing on work in autism where autism genes are not just genes for autism (see here) so one might consider a similar scenario pertained for at least some with the epilepsy-ADHD diagnostic combination...


[1] Choudhary A. et al. Childhood epilepsy and ADHD comorbidity in an Indian tertiary medical center outpatient population. Sci Rep. 2018 Feb 8;8(1):2670.

[2] Choudhary A. et al. Behavioral comorbidity in children and adolescents with epilepsy. J Clin Neurosci. 2014 Aug;21(8):1337-40.

[3] Vingerhoets G. Cognitive effects of seizures. Seizure. 2006; 15: 221-226.


Saturday, 17 March 2018

"specificity for diagnosis was relatively low": the psychometric properties of autism diagnostic measures

The quote accompanying this fairly brief post - "specificity for diagnosis was relatively low" - comes from the findings reported by Sarah Wigham and colleagues [1] who undertook a systematic review of various "structured questionnaires and diagnostic measures" used in the assessment of autism in adults.

Their conclusions, based on some 20 studies identified in the current peer-reviewed literature, suggest that 'could do better' is a phrase best suited to various measures currently used to identify adults with autism, particularly in the context of an often complicated clinical picture (see here).

Similar things have already been discussed on this blog (see here for one example). In particular, how individual self-report 'are you autistic?' screening instruments whilst making good 'pop psychology' (see here) are absolutely no match for a thorough professional clinical assessment, save other important diagnoses/conditions being overlooked and going unmanaged (see here and see here). I know this puts the concept of 'self-diagnosis' as a result of the use of such instruments in some hot water, but as in many other branches of medicine and psychiatry, professionals and the assessments they conduct are there for a very good reason. Whether you can access such assessments in a timely fashion is an entirely different issue...

When I first tweeted about this paper being published, I emphasised one author on the Wigham paper in particular: Dr Tom Berney. The reasoning behind this was because of his involvement/link to research that has looked at how we identify adults with autism here in Blighty on the back of some headlines a few years back on estimating how many adults have autism here (see here). He, alongside some other notable authors who highlighted that '1% of adults with autism' figure, also talked about how some of the screening/assessment instruments used in that study weren't really cutting the epidemiological mustard [2]. It appears they might have been right.

So what lessons can be learned from this recent review? Well first, that whilst autism-related behavioural dimensions are vitally important to a diagnosis of autism, they are not universally specific to a diagnosis of autism, is important. Second is the need to perhaps move away from often very brief autism screening instruments that seem to provide a 'quick snapshot' to something rather more far-reaching and comprehensive. I know we all want a 'quick answer' that uses as few finite resources as possible, but sometimes, to get something right, you need to spend time and resources looking at it carefully. And diagnosing professionals also need to be mindful of notions of 'frank autism' too (see here). Finally, I'd like to re-emphasise that autism plus [3] does seem to be more typical these days, over autism appearing in some sort of diagnostic vacuum. As Wigham et al opine: "Robust autism spectrum disorder assessment tools specifically for use in adult diagnostic health services in the presence of co-occurring mental health and neurodevelopmental disorders are a research priority." Indeed they are.


[1] Wigham S. et al. Psychometric properties of questionnaires and diagnostic measures for autism spectrum disorders in adults: A systematic review. Autism. 2018 Feb 1:1362361317748245.

[2] Brugha TS. et al. Validating two survey methods for identifying cases of autism spectrum disorder among adults in the community. Psychol Med. 2012 Mar;42(3):647-56.


Friday, 16 March 2018

Carefully: effect of SSRI use on "rating-scale-assessed suicidality in adults with depression"

I stress the word 'carefully' in the title of this post discussing the findings reported by Jakob Näslund and colleagues [1] because it covers the very sensitive idea that "selective serotonin reuptake inhibitors (SSRIs) have been claimed to elicit or aggravate suicidal ideation."

I think it's sensible to begin this post by stressing that (a) NO medical or clinical advice is given or intended on this blog, and (b) anyone with concerns about their taking this class of medicines really needs to speak to their physician BEFORE making any changes to their prescribed medication routine. I know that point (b) sounds like me giving medical / clinical advice but it's common sense to talk to your medical professional first who's spent years studying and probably years practising medicine, rather than tinker around yourself...

There is always a balancing act to consider when discussing research such as this. A medicine indicated for various clinical conditions, that is taken by many, many people, and quite successfully treating / treated (nay, very successfully [2]) a condition that can, without treatment, have life-limiting consequences. No-one wants to rock the boat and scare or deter people from accessing such a treatment. At the same time however, one needs to know everything about that medicine; not least whether for some, there may be side-effects to possibly consider...

It's been a quite a long running saga talking about the possible additional effects of SSRI use for some (see here). It's drawn heavily on often harrowing individual stories and perspectives and not also been helped by the seeming (in)actions of some of the manufacturers of such medicines (see here). Näslund et al decided to approach this delicate topic from the point of view of analysing "the effect of [SSRI] treatment on rating-scale-assessed suicidal ideation in individual patients." This is distinct from other work that has focused on actual suicides or "suicide-related adverse events" that have been carried out before. The authors suggested that their approach might have the advantages of measuring the "net influence of treatment on suicidality at a group level" as well as the ability to "detect individual cases of emergence or aggravation of suicidal ideation." To this end, scores on the Hamilton Rating Scale for Depression (HRSD) particularly focused on "item 3 of the HRSD" covering suicidal ideation/attempts, was a core feature of their study covering "young adults (18–24) (n = 537) and adults (≥25) (n = 7725)." Said participants were derived from "all industry-sponsored, HRSD-based, FDA-registered placebo-controlled studies undertaken to explore the effects of citalopram, paroxetine or sertraline in major depression in adults."

Results: "In patients above the age of 24, SSRIs were found to reduce the mean rating of the HRSD suicidality item from week 1 until study end-point and also to reduce the risk for aggravation of suicidal ideation and emergent suicidal behaviour." This is very good news. It provides "strong support for the view that the net effect of SSRI treatment is beneficial rather than harmful" when it comes to suicide ideation/contemplation bearing in mind the specific focus on on item on the HRSD. I will again link to the recent findings by Cipriani and colleagues [2] reporting that: "All antidepressants were more efficacious than placebo in adults with major depressive disorder." It doesn't, as Näslund et al suggest, rule out rare cases of 'adverse effects', but does suggest that any such extreme side-effects are not likely to be encountered by most people who take such medicines.

When however it came to those younger adults (aged 18-24 years), the results were a little less straight-forward. So: "In young adults, those given an SSRI were at enhanced risk for worsening of suicidal ideation (in the unadjusted analysis) or emergent suicidality (loose but not strict definition) during the late (weeks 3–6) but not the early phase (weeks 1–2) of treatment." You'll see from the number of brackets used in that last quote that the authors provide some caveats to such findings; but this shouldn't take away from the trends observed. Indeed, bearing in mind such findings and also that "both SSRIs and placebo resulted in an end-point rating of suicidality equal to that observed in adults given an SSRI and lower than that observed in adults given placebo" you kinda get the impression that further investigations are needed to ascertain for example, whether depression and/or suicidality in the 25 and overs is somehow 'different' from depression in the younger age group. At least, different insofar as what treatment choices might be primarily made available. No, I'm not saying that this is evidence enough that SSRIs should have some sort of age restriction, just that cost/benefit ratios might perhaps have to be a little more 'age-sensitive' as well as individual-sensitive.

And, if anyone needs someone to talk to, there are resources available.


[1] Näslund J. et al. Effects of selective serotonin reuptake inhibitors on rating-scale-assessed suicidality in adults with depression. Br J Psychiatry. 2018 Feb 5:1-7.

[2] Cipriani A. et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018. Feb 21.


Thursday, 15 March 2018

Childhood ADHD and vitamin D meta-analysed

The results of the systematic review and meta-analysis published by Yadollah Khoshbakht and colleagues [1] (open-access available here) make for interesting, if not totally unexpected, reading.

Covering the existing peer-reviewed research literature (up to June 2017) on the topic of vitamin D status and attention-deficit hyperactivity disorder (ADHD), researchers concluded that: "The present review provides evidence supporting the relation between vitamin D deficiency and ADHD."

Vitamin D and ADHD is a topic already covered on this blog (see here). The general direction of findings so far have kinda mirrored that seen in other developmental diagnoses such as autism, insofar as vitamin D deficiency / insufficiency as measured by concentrations of 25-hydroxyvitamin D, tending to be pretty over-represented alongside the label (see here). It's perhaps also pertinent to mention that the diagnostic combination of autism and ADHD seems to be quite widespread (see here); particularly in these days of ESSENCE or autism plus (see here). This could very well have a bearing on any observations obtained as per other examples in other areas (see here).


Khoshbakht et al looked at various studies and aspects of studies as part of their analyses. They also pre-registered their intention to undertake some research on vitamin D and ADHD as per a PROSPERO entry (see here) containing some details on hows-and-whys.

From various 'retrieved articles' numbering in the thousands, authors eventually settled on 13 studies ("9 case-control or cross-sectional studies and 4 prospective studies") that examined "the association between vitamin D concentration and the risk of ADHD." The final cumulative study participant number was not bad at all: "3484 patients with ADHD (2183 from the case-control and cross-sectional studies, 1301 from the prospective studies) and 11,837 healthy children (8151 from the case-control and cross-sectional studies, 3686 from the prospective studies) aged between 5 and 18 y were included." Authors also noted that various methods were used to measure 25-hydroxyvitamin D - 25(OH)D - ranging from the gold-standard that is liquid chromatography tandem mass spectrometry (LC-MS/MS) to something perhaps a little less accurate e.g. high-performance liquid chromatography (HPLC) minus the mass spec bit. All-in-all however, most studies were judged to be of moderate or high quality.

Results: "we found modest but significant lower serum vitamin D concentrations in children and adolescents with ADHD compared with healthy control subjects." Based on 9 studies where "the mean ± SD vitamin D concentrations in subjects with and without ADHD" was reported, authors concluded that "children with ADHD had 6.93 ng/mL lower serum vitamin D concentrations compared with healthy controls." And that wasn't all, as authors also looked at prospective studies where for example, vitamin D was measured in maternal serum or umbilical cord blood and then mapped onto risk of ADHD in offspring. With this type of study in mind, they observed that: "lower maternal or cord serum vitamin D concentrations increase the risk of developing ADHD in childhood or adolescence by 40%" albeit with some statistical caveats.

Khoshbakht and colleagues provide some possible pointers about how vitamin D *might* influence the pathophysiology of ADHD. They for example, mention an enzyme that I've been pretty interested in down the years - tryptophan hydroxylase 2 (TPH2) - and how the starting gene for this enzyme has been both linked to ADHD [2] in some studies (but not others). Further: "The TPH2 gene is activated by vitamin D hormone through its vitamin D response element." Personally, I find this interesting but not intellectually satisfying enough to provide an authoritative explanation for any effects of vitamin D deficiency on ADHD. Going also back to the vitamin D story with autism in mind, I'd like to think lessons could be learned about more particular vitamin D genetics (see here) and what role they might also play with regards to ADHD too. There are no doubt other pertinent mechanisms too.

There is still more research to do when it comes to vitamin D and ADHD of that there is no doubt. Again, going back to the relationship between ADHD and autism, I'm wondering whether more focus needs to be on this diagnostic combination (and perhaps other overlaps too) to ascertain whether one condition / label over another shows any stronger relationship with vitamin D levels. In light also of other meta-analysis work talking about lower vitamin D levels being linked to 'poorer cognition' (see here) for example, one might also reasonably suggest that an even broader research agenda might need to be followed.

And then there's the question of supplementation (see here) to consider and whether it may / may not do more than just raise vitamin D levels [3]? Oh wait, and there's more [4]...


[1] Khoshbakht Y. et al. Vitamin D Status and Attention Deficit Hyperactivity Disorder: A Systematic Review and Meta-Analysis of Observational Studies. Adv Nutr. 2018 Jan 1;9(1):9-20.

[2] Park TW. et al. Association between TPH2 gene polymorphisms and attention deficit hyperactivity disorder in Korean children. Genet Test Mol Biomarkers. 2013 Apr;17(4):301-6.

[3] Elshorbagy HH. et al. The Impact of Vitamin D Supplementation on Attention-Deficit Hyperactivity Disorder in Children. Ann Pharmacother. 2018 Feb 1:1060028018759471.

[4] Sahin N. et al. Vitamin D and vitamin D receptor levels in children with attention-deficit/hyperactivity disorder. Neuropsychiatr Dis Treat. 2018 Feb 19;14:581-585.


Wednesday, 14 March 2018

Bullying and autism: not always originating from where you might expect...

There is something rather uncomfortable about the findings reported by Imar Toseeb and colleagues [1] but, at the same time, they do raise an important issue that needs to be openly discussed. Specifically their findings on: "sibling bullying, and the associated psychopathological adversities, in children with and without ASD [autism spectrum disorder]" deserve some airtime.

Bullying and autism is quite a regular talking point in the peer-reviewed research literature (see here) and beyond. Although a diagnosis of autism is by no means protective of someone becoming a bully or being involved in what could be considered bullying behaviour, it is far more typical that those with autism are going to be a victim of bullying rather than perpetrator (see here). Indeed, I reluctantly use the word 'vulnerable' yet again on this occasion but...

When one thinks about bullying in any context including that with autism in mind I would imagine that the school bully who name calls or becomes physical aggressive towards someone - usually smaller and quieter than them - probably first springs to mind. Siblings by contrast, conjure up an image of being caring, supportive and again, with autism in mind, often very protective of their brother(s) and/or sister(s) given their important role, present and probably future. And indeed, many, many siblings are just that (see here).

But real life is rarely so clear-cut or 'homogeneous' as many parents, whether with children diagnosed with autism or not, will attest. Siblings argue, fight and probably because of how well they 'know each other', often know all the right buttons to press to get their required reaction. And yes, behaviour sometimes can spill over to what would be considered bullying under any other circumstance...

Toseeb et al started with the hypothesis that: "children with ASD (child has ASD but their sibling does not) would experience higher levels of sibling bullying compared to those without ASD (child and sibling do not have ASD)." They arrived at this hypothesis on the basis of various factors such as a role for the social-communicative issues that follow autism, the possible effect of the 'broader autism phenotype' (BAP) on siblings, and issues such as a greater frequency of aggression - "reactive aggression" - accompanying particularly boys with autism.

They relied on data from the Millennium Cohort Study (MCS) (a resource that has been mentioned before on this blog) and eventually included data from nearly 500 children with autism alongside over 13,000 not-autism controls. The question(s) on sibling bullying were asked at 11 years of age and went: "he/she was asked to respond to two questions on a six-point scale (never, less often, every few months, approximately once a month, approximately once a week, most days): “how often do your brothers or sisters hurt you or pick on you on purpose?” (victimization) and “how often do you hurt or pick on your brothers or sisters on purpose?” (perpetration)." Responses were coded according to who did what and how often. Various other measures were also examined as part of the MCS and used in the Toseeb paper: socio-demographic data (single parent status, birth order, number of siblings, household incomes), parenting style, psychopathology and cognition.

Results: children diagnosed with autism or ASD were more likely to be bullied by their non-autistic sibling compared with those who did not have autism. This finding held "even after controlling for socio-demographic and family level variables" and "was associated with adverse psychopathologies." Further: "having ASD, being a girl, of White ethnicity, having more siblings, and experiencing harsher parenting were all associated with increased odds of being bullied by a sibling." Whilst we're on the topic of 'adverse psychopathologies, it's perhaps pertinent to mention the findings reported by Dantchev and colleagues [2] observing a possible connection between sibling bullying receipt and psychotic disorder. Yes, it is quite an extreme example, but nonetheless demonstrates the effects bullying can have long-term. I might also refer you back to some discussion arising from the ICF core sets development with autism in mind too (see here).

I digress. I note also that authors discuss sibling bullying as a two-way street: "Our findings indicate that children with ASD are specifically at increased risk of sibling victimization as a bully-victim."

As I said at the beginning of this post, this all makes for uncomfortable reading. If it's not bad enough that a child may be being bullied at school to also then potentially learn that there is little respite from such behaviour at home, makes for an uncomfortable (intolerable?) situation all-round. The question then arises minus any sweeping generalisations: what can be done about sibling bullying for the good of all concerned? And please, don't just solely suggest 'coping strategies' for the bullying victim either.


[1] Toseeb U. et al. The Prevalence and Psychopathological Correlates of Sibling Bullying in Children with and without Autism Spectrum Disorder. J Autism Dev Disord. 2018 Feb 8.

[2] Dantchev S. et al. Sibling bullying in middle childhood and psychotic disorder at 18 years: a prospective cohort study. Psychological Medicine. 2018. Feb 12.


Tuesday, 13 March 2018

Regression in autism: the rule rather than the exception?

"Declining trajectories of development, consistent with a regressive onset pattern, are common in children with ASD [autism spectrum disorder] and may be more the rule than the exception."

So said the findings reported by Sally Ozonoff and colleagues [1] who reported results based on a study of developmental / behavioural regression in autism, and specifically: "how rates of regression differed by measurement method."

Regression in relation to autism is a topic I've covered a few times on this blog (see here and see here for examples). I've followed the [peer-reviewed] story from where behavioural and/or developmental regression was initially thought to be a figment of the [parental] imagination, right up to these days where regression is pretty much accepted as being part and parcel of quite a few cases of autism. The road has not been a smooth one; but the question of whether autism is universally something inborn and hereditary for everyone is slowly starting to be answered: no, it is probably not. The reason(s) for regression still remain fertile grounds for discussion / debate / argument, but there are some important clues in the science literature (see here and see here for examples) with the caveats that autism is a very heterogeneous condition and onset patterns are likely to be influenced by all-manner of different variables. Think different phenotypes in the context of autism (see here) for example; and that's outside of the label previously known as Heller's syndrome.

Anyhow, Ozonoff et al report results for infants "with (n = 147) and without a family history of ASD (n = 83)" who were "seen prospectively for up to 7 visits in the first three years of life." Various different ways and means of assessing reports of symptom onset were collected, "that systematically varied the informant (examiner vs. parent), the decision type (categorical [regression absent or present] vs. dimensional [frequency of social behaviors]), and the timing of the assessment (retrospective vs. prospective)."

Depending on who said what and how they said it, patterns of regression in skills were noted in quite a large proportion of the Ozonoff cohort. So: "A majority of the sample was classified as having a regressive onset using either examiner (88%) or parent (69%) prospective dimensional ratings." The authors suggest that their observations highlight how quite a few more resources (and cautions) need to go into looking at symptom onset patterns in relation to autism.

For quite a few people, the findings reported by Ozonoff et al are 'catch-up' rather than something novel. I can think of quite a few instances where parents / guardians have had their important observations - very important observations - described as being 'talked down' when it came to reporting a regression in previously acquired skills in the context of autism. This should no longer be the case; particularly when also set in the context of the increasing pluralisation of the label of autism (see here) and perhaps even, the changing face of autism (see here) compared with yesteryear.

Then to the next important questions: how and why? I've already alluded to a role for infection in relation to the onset of regressive autism for some, but much more data is required on the specific details and mechanisms. There is also the issue of what *might* potentially be done to minimise factors linked to regression in autism too. Minus any sweeping generalisations, I'd also direct your attention to other mentions of regressive autism in the peer-reviewed science literature [2] and where, minus any hype, there could be some important clues for some. The important point once again, is that the diagnosis of autism should be the start of further investigations, not the finishing line.

To close, don't ask me how or why but one of my brood has started watching and enjoying an old staple part of the weekend TV quiz scene in 1980s Blighty... BFH by the way, is most classically referred to as your 'bus fare home'.


[1] Ozonoff S. et al. Onset patterns in autism: Variation across informants, methods, and timing. Autism Res. 2018 Mar 10.

[2] Poling JS. et al. Developmental regression and mitochondrial dysfunction in a child with autism. J Child Neurol. 2006 Feb;21(2):170-2.


Monday, 12 March 2018

"A pilot study of high-dose intravenous immunoglobulin 5% for autism"

Intravenous immunoglobulin (IVIG), the treatment of choice for "patients with antibody deficiencies" [1] has some research history when it comes to autism (see here).

Quite a few years back, I remember some chatter about the use of IVIG for at least a subset of children/adults diagnosed with autism [2]. Interest in IVIG subsequently waxed and waned, partly as a result of some politics 'accompanying' research but also because of things like the cost of such an intervention.

Judging by the recent results published by Isaac Melamed and colleagues [3] however, it looks however, like IVIG *might* be coming back into research fashion...

So: "we investigated the efficacy and tolerability of intravenous immunoglobulin (IVIG) infusion in children with ASD [autism spectrum disorder]." The words "immune dysregulation" and "neuroinflammation" are mentioned a few times in the Melamed paper so you can probably work out the reason(s) why IVIG was examined. I might add that this study appears to have been registered with too (see here).

This was a pilot study so, of course, one always needs to be a little bit cautious when it comes to the study and any findings. But, from what I can see, the authors put in place quite a few 'primary' and 'secondary' endpoints covering various aspects of behaviour - "Children's Communication Checklist [CCC-2], Social Responsiveness Scale [SRS], Aberrant Behavior Checklist [ABC], Clinical Global Impressions-Severity [CGI-S] and -Improvement [CGI-I], Autism Diagnostic Observation Schedule [ADOS], and Peabody Picture Vocabulary Test [PPVT]" - and also some 'experimental' biomarkers of immune function in this study. That's quite a comprehensive battery all-in-all.

Based on the use of a "high-dose intravenous immunoglobulin" (1g/kg dose of Gammaplex 5%) for ten 21-day treatment cycles with some 14 research participants diagnosed with autism, researchers reported some signs of 'effect'. Behaviourally speaking, they talk about significant improvements in core areas such as reciprocal social interaction, communication and repetitive and/or stereotyped behaviours being observed. This, alongside significant reductions in "numerous secondary outcomes of immunological biomarkers indicative of neuroinflammation." In short, IVIG seemed to show effects and, importantly: "no subjects withdrew due to an adverse event" providing some well needed 'first, do no harm' data.

One study - an open label study at that - does not an evidence base make. Not even close, and that's despite other open label studies also being published [3] in this area. One also needs to bear in mind that IVIG is a blood product typically derived from more than one donor which, although screened for various infectious diseases, might still leave some people a little nervous about its use.

But... results such as the ones from Melamed cannot be easily ignored. Not least set within the context of a growing interest in immune function being *related* to some autism (see here for example) and specifically where 'regression' seems to be part and parcel of symptom onset (see here and see here), further [controlled] investigations are required. And that includes what happens to any behavioural / immunological gains / changes as and when IVIG intervention is stopped too...


[1] Jolles S. et al. Clinical uses of intravenous immunoglobulin. Clinical and Experimental Immunology. 2005;142(1):1-11.

[2] Gupta S. Treatment of children with autism with intravenous immunoglobulin. J Child Neurol. 1999 Mar;14(3):203-5.

[3] Melamed IR. et al. A pilot study of high-dose intravenous immunoglobulin 5% for autism: Impact on autism spectrum and markers of neuroinflammation. Autism Res. 2018 Feb 10.

[4] Boris M. et al. Improvement in children with autism treated with intravenous gamma globulin. Journal of Nutritional & Environmental Medicine. 2005; 15.