Amyotrophic Lateral Sclerosis (ALS) and neuropsychiatric symptoms in kindreds

"Neuropsychiatric symptoms in addition to schizophrenia, including obsessive-compulsive disorder, autism, and alcoholism, occur more frequently in ALS [amyotrophic lateral sclerosis] kindreds than in controls."

So said the findings reported by Margaret O’Brien and colleagues [1] observing something of a curious *association* between ALS (also called Lou Gehrig's disease after the American baseball player and/or motor neuron disease) and behavioural/psychiatric presentation(s) among first- and second-degree relatives.

I have actually talked about ALS before on this blog, with reference to ALS and the finger length ratio (see here) and also how a diagnosis of autism is seemingly not protective against the development of ALS (see here) (and what happens when 'it's their autism' sentiments perhaps interfere with sound medical investigation). But this is the first time I've covered the possibility of a familial link between ALS and autism (and other labels), even if not being the first time that it has been seen in the peer-reviewed domain [2]...

O'Brien et al identified patients diagnosed with ALS from the Irish Register of ALS and included some 130 people into their study. Alongside a roughly equal number of sex- and age-matched non-ALS controls, the frequency of various neuropsychiatric disorders was determined among their first- and second degree relatives.

Results: "A total of 77 patients with ALS (61.4%) and 51 control participants (38.6%) reported at least 1 first-degree or second-degree relative with a history of schizophrenia, psychosis, suicide, depression, alcoholism, or autism." The authors mention that risk was not however uniform across participants with ALS, as two subgroups emerged "based on the number of family members with a neuropsychiatric condition: expected (0-2) and high (≥3)." They also noted that issues with the gene C9orf72 (chromosome 9 open reading frame 72) linked to quite a few cases of ALS did not seemingly explain their findings: "A total of 5 of 29 probands (17.2%) with a strong family history of neuropsychiatric conditions (≥3 first-degree or second-degree relatives) carried the C9orf72 repeat expansion."

There are potentially important points raised by the data from O'Brien and colleagues but one of the first things we need is replication, and replication across different populations given for example, some [seeming] disparity in the prevalence of ALS world-wide [3] and what that could mean for kindred psychopathology. I am also drawn to some comments made by authors on the O'Brien paper in relation to other work on ALS and schizophrenia [4] for example, stressing how "the divide between psychiatry and neurology is a false one." This is perhaps important when one looks at the relationship between autism and epilepsy (see here) for example, and whether one should see epilepsy in such cases as a comorbidity or indeed, something rather more 'integral' to that particular 'type of autism'. I'm favouring the latter in light of the evidence being produced (see here) which could have some important implications for many areas of autism research and practice (see here for one example).

Mechanisms? I don't think we're even able to think about possible mechanisms just yet but...

No-one really knows what causes ALS despite the link being made with the genetics of C9orf72 and some cases. I note that the current CDC information on ALS talks about some studies suggesting "a possible link with exposure to heavy metals (e.g., lead and mercury)" or other environmental stressors. This could be rather interesting to look at from the point of view of exposure not necessarily being the key issue but rather genetic and biological differences in how the body stores/gets rid of such compounds as being important; bearing in mind what seems to be appearing in the autism literature on this topic (see here) for example. Just one thought...

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[1] O'Brien M. et al. Clustering of Neuropsychiatric Disease in First-Degree and Second-Degree Relatives of Patients With Amyotrophic Lateral Sclerosis. JAMA Neurology. 2017. Oct 16.

[2] Goodman AB. et al. A family history study of schizophrenia spectrum disorders suggests new candidate genes in schizophrenia and autism. Psychiatr Q. 1994 Winter;65(4):287-97.

[3] Chiò A. et al. Global Epidemiology of Amyotrophic Lateral Sclerosis: a Systematic Review of the Published Literature. Neuroepidemiology. 2013;41(2):118-130.

[4] McLaughlin RL. et al. Genetic correlation between amyotrophic lateral sclerosis and schizophrenia. Nat Commun. 2017 Mar 21;8:14774.

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Autism and obstacles to medical diagnosis and treatment

The title of this post reflects the title of the paper by Marcia Datlow Smith and colleagues* which was given to me by Natasa (many thanks) a few days back. The paper is from 2012 so I don't think we can consider this a post about new research. Nevertheless the subject matter of the paper is potentially very important: "describing individuals with autism whose catastrophic illnesses were misdiagnosed due, at least partially, to their autism".

@ Wikipedia

It is indeed a pity that the Smith paper is not open-access (at the time of writing anyway) because it contains two very powerful accounts of how symptoms and medical diagnoses were "overlooked and misread" partially as a result of the presentation of autism. I don't say this to somehow 'blame autism' or anything like that; merely that extra vigilance and a greater degree of acceptance that people with autism are just as prone as everyone else to potential issues affecting health and wellbeing, should be an intrinsic part of the message when it comes to ensuring appropriate healthcare coverage. Think person first, autism diagnosis second; a theme which was also part of the recent NICE Quality Standard and another very important document which is well worth a read.

The authors document the lives of two people diagnosed with autism, Dana, a 54-year old man and Shannon, a 27-year old woman. I'm not often moved by the contents of a peer-reviewed 'science' paper with it's focus on cold, hard objectivity, but reading the account of how Dana was subsequently diagnosed with amyotrophic lateral sclerosis (ALS) (also known as Lou Gehrig's disease or motor neurone disease) and his eventual death 3 weeks after receiving his diagnosis was powerful. Likewise the description of how Shannon eventually came to receive a diagnosis of multiple sclerosis (MS) and the difficult path she had to navigate to arrive at that diagnosis makes for some pretty uncomfortable reading.

I'm not going to post all the details of these case reports because (a) that might be tantamount to plagiarism and (b) I don't want this post to turn into some sort of medical spectacle. Suffice to say that for each person, issues such as the "lack of expressive speech" and a "history of occasional bouts of oppositional behavior" did little to aid the art of medicine in arriving a suitable diagnosis for their symptoms. That however the descriptions include certain professionals suggesting that such symptoms were as a result of "major depressive disorder" with accompanying recommendations for "medication adjustment" is however, a slightly worrying trend and brings to mind that issue of the use of antipsychotics in dementia care (see here). Even further that electroconvulsive therapy (ECT) was one of the treatment choices implemented prior to Shannon being diagnosed with MS (and indeed correlated with "two grand mal seizures") is a further worry.

The common theme of these accounts is, in the authors words, one of caution in how: "stories of Dana and Shannon serve to motivate health practitioners to take care before attributing functional decline or other physical symptoms to a patient's mental illness". I think the authors were being quite general in their description of 'mental illness' over and above trying to specifically describe autism with those words. Their implication however on how dogma about autism somehow just being seen as a stand-alone conditions occurring in a diagnostic vacuum alongside how concepts like 'challenging behaviours' have built up over the years, might not necessarily serve people with autism best is an important part of the stories of Dana and Shannon.

I don't want to drag out further discussion about the Smith paper in this post. I would like to think that some readers might themselves try and locate the full-text paper and read about how good modern-day healthcare really should be able to overcome barriers such as a person's lack of language when it comes to a label for their symptoms and onwards any appropriate care if available and required. Think visual issues and autism as one example. Understanding that people with autism may have medical comorbidity and needs which may surpass the presentation of the core behavioural symptoms as per other examples, is also an important part of how we view the spectrum and indeed, how improvements in quality of life may be made by patching up any health inequality.

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* Smith MD. et al. Autism and Obstacles to Medical Diagnosis and Treatment. Focus Autism Other Dev Disabl 2012; 27: 189-195.

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Marcia Datlow Smith, Patrick J. Graveline, & Jared Brian Smith (2012). Autism and Obstacles to Medical Diagnosis and Treatment Focus Autism Other Dev Disabl DOI: 10.1177/1088357612450049