"NMDAR-antibody encephalitis might best be described as a mixed mood-psychosis syndrome"

Every once in a while a paper comes along with the potential to 'really shift opinions'. I'm gonna place the publication by Adam Al-Diwani and colleagues [1] in that category, and their (pre-registered) systematic review around the topic of N-methyl-D-aspartate receptor (NMDAR)-antibody encephalitis.

NMDAR-antibody encephalitis reflects a condition characterised by the immune system failing to identify self as self. For whatever reason, the immune system starts treating specific cells of the body as 'enemy' and mounts an immune attack against them. This results in the formation of specific antibodies - "against the NR1 subunit of the NMDA receptor" [2] - also typically resulting in "psychiatric features before progressing to seizures, a complex movement disorder, autonomic dysfunction, and hypoventilation." The book and film 'Brain on Fire' is about as good an education as you might need on the personal costs and effects of NMDAR-antibody encephalitis.

As Al-Diwani et al mention, things are getting rather interesting for NMDAR-antibody encephalitis in psychiatric circles. Awareness of the condition is growing, albeit with further 'flesh on the bones' required in terms of clinical features to look out for which could accompany the biological testing for the condition. Researchers sought to do just that: "the psychopathology of NMDAR-antibody encephalitis needs to be clearly defined to encourage accurate clinical identification and prompt treatment."

They trawled the peer-reviewed scientific literature looking for mention of NMDAR-antibody encephalitis, and eventually settled on over 300 records describing 1100 people in total. Over 460 of those people were identified with "definite NMDAR-antibody encephalitis according to consensus criteria" and their psychiatric features were examined. "The authors extracted 50 lower-level psychiatric features reported in these 464 patients, defined their frequency, and grouped them into eight higher-level features." Further comparisons were made leading to them assessing "whether individual patients were best described by one or by several psychiatric diagnoses" used as comparators.

Various features were potentially important: "The most common higher-level features were behaviour (316 [68%]), psychosis (310 [67%]), mood (219 [47%]), catatonia (137 [30%]), and sleep disturbance (97 [21%]), and these features frequently coexisted in individual patients." Various interesting graphs and figures are presented by the authors to illustrate their findings. The end result was the description of NMDAR-antibody encephalitis as "polymorphic and not to respect traditional psychiatric classifications." That being said, the notion of a "mixed mood-psychosis syndrome" represents as good a description as any based on the Al-Diwani findings.

Other details? "Overall, the age and sex distribution centred around young women, and the frequency of cases was greatly reduced after 40 years of age." Important information there about a potentially vulnerable group. Also: "139 (30%) of 464 cases were associated with ovarian teratoma, seven (2%) with previous herpes simplex virus encephalitis, and 24 (5%) with pregnancy." Ovarian teratoma is described as a rare cancer categorised as a 'germ cell tumour'. The *link* between ovarian teratoma and NMDAR-antibody encephalitis is something that has been of interest for a few years [3] and perhaps provides a clue for further investigation.

I do stand by my 'game-changer' type comment of the Al-Diwani paper. There is of course more to do in this area (including examining a curious link between NMDAR-antibody encephalitis and 'an autistic-like regression' in some children which is becoming all the more prominent in the research literature [4]). Putting all the various features identified by the authors into a useful set of diagnostic criteria is also a next step...

----------

[1] Al-Diwani A. et al. he psychopathology of NMDAR-antibody encephalitis in adults: a systematic review and phenotypic analysis of individual patient data. The Lancet Psychiatry. 2019. Feb 11.

[2] Finke C. A transdiagnostic pattern of psychiatric symptoms in autoimmune encephalitis. The Lancet Psychiatry. 2019. Feb 11.

[3] Acién P. et al. Ovarian teratoma-associated anti-NMDAR encephalitis: a systematic review of reported cases. Orphanet J Rare Dis. 2014;9:157.

[4] Khundakji Y. et al. Anti-NMDA receptor encephalitis in a toddler: A diagnostic challenge. International Journal of Pediatrics and Adolescent Medicine. 2018; 5: 75-77.

----------

"Psychotic experiences are important clinical markers of risk for future suicidal behavior"

The quote titling this post - "Psychotic experiences are important clinical markers of risk for future suicidal behavior" - comes from the systematic review and meta-analysis findings reported by Kathryn Yates and colleagues [1].

Authors posed the research question: "Are psychotic experiences associated with an increased risk of later suicidal ideation, suicide attempt, and/or suicide death?" and looked to the existing peer-reviewed research literature to try and answer it. Based on the combined results from ten studies that "reported on 84 285 participants from 12 different samples and 23 countries" and met the inclusion criteria of their review, Yates et al made some important conclusions.

"Individuals who reported psychotic experiences had an increase in the odds of future suicidal ideation (5 articles; n = 56 191; odds ratio [OR], 2.39 [95% CI,1.62-3.51]), future suicide attempt (8 articles; n = 66 967; OR, 3.15 [95% CI, 2.23-4.45]), and future suicide death (1 article; n = 15 049; OR, 4.39 [95% CI, 1.63-11.78])." These are important statistics. They translate into some important details insofar as "individuals who reported PEs [psychotic experiences] had 2-fold increased odds of subsequent suicidal ideation, 3-fold increased odds of subsequent suicide attempt, and 4-fold increased odds of subsequent suicide death." Some further nifty statistical analysis from the authors looking into something called the population-attributable fraction (PAF), defined as "the proportion of incidents in the population that are attributable to the risk factor", suggested that the percentage figure for "PEs for suicide attempts and suicide deaths combined was 24.7%." That is also something rather important.

Should anyone be surprised by these results? Well, yes and no. Yes, because the magnitude of the association between PEs and suicidal behaviours was probably a lot more pronounced than many would have perhaps expected. No, because other literature has talked about psychosis in depression for example, as being potentially important to the development and presentation of suicidal behaviour (see here). Having said all that, I will reiterate that suicidal behaviours are very complicated.

Aside from the important issue of potentially expanding screening for suicidal behaviours when PEs are present, there are other factors to consider. Not least that: "The mechanisms explaining the association between PEs and suicidal behavior are potentially manifold." I was particularly interested in one theory put forward by the authors, suggesting that: "In the context of high stress and poorer communication skills, this might adversely affect the individual’s ability to formulate logical plans to manage perceived challenges and instead increase the likelihood of turning to suicide." Such an idea is based on other findings observing that there may be cognitive 'challenges' accompanying PEs that may impair problem-solving skills. Y'know, not having the skills to stop molehills from turning into mountains? Perhaps further research in this area might also turn to looking at some of the underlying biology behind such issues as well as the psychology. How, for example, inflammatory processes and the immune system *might* show some important involvement (see here and see here) for at least some people? One future avenue of research attention at least.

The data from Yates and colleagues is particularly poignant at the time of writing this post as the US CDC release figures suggesting that suicide mortality in the United States has climbed and climbed and climbed over the past few decades (see here). Again, the reasons are probably going to be complicated but that shouldn't stop people from continually asking 'why?' and 'what can we do about them?'

I close this post with some important contact details should anyone need someone to talk to (see here)...

----------

[1] Yates K. et al. Association of Psychotic Experiences With Subsequent Risk of Suicidal Ideation, Suicide Attempts, and Suicide Deaths. JAMA Psychiatry. 2018. Nov 28.

----------

1 in 5 adults with autism diagnosed with non-affective psychotic disorder (NAPD) before the age of 35?

The quote heading this post - "1 in 5 adults with autism diagnosed with non-affective psychotic disorder (NAPD) before the age of 35?" - comes from the findings reported by Schalbroeck and colleagues [1] continuing a research theme from this authorship group [2] on how autism rarely appears in some sort of diagnostic vacuum.

Relying on longitudinal data from the Netherlands ("from Dutch psychiatric case registers"), authors sought to capitalise on their previous findings from Sweden to "to assess the risk of NAPD or BD [bipolar disorder] among individuals with ASD [autism spectrum disorder], and compared the results to those obtained for the Dutch population in earlier studies." NAPD in this case refers to a grouping of labels covering schizophrenia, delusional disorder and acute and transient psychotic disorder. Bipolar disorder was previously called manic depression, reflecting mood swings between depression and mania. Both labels have some research history when it comes to autism (see here and see here for examples).

Based on the longitudinal analysis of participant records in the thousands, over 17,000, all diagnosed with ASD, researchers set about calculating the risk of NAPD and BD in their cohort. They observed that: "Of the individuals with ASD, 23.50%... were diagnosed with NAPD and 3.79%... with BD before age 35 years." Such percentages contrasted with general population figures of 0.9% and 0.1% for NAPD and BD respectively. Further study based on around 8,000 people "diagnosed with ASD before age 16 years" also showed elevated levels of NAPD and BD being diagnosed before 25 years of age (1.8% and 0.5% respectively) compared with general population figures (0.6% and 0.1%); albeit to a lesser extent.

Aside from concluding that the risk of NAPD and BD in relation to autism "is likely not the result of diagnostic or selection bias", the Schalbroeck findings reiterate again that autism seemingly rarely exists in some sort of diagnostic vacuum (see here). They reiterate that psychiatric comorbidity, some of which can often be both serious and quality-of-life destroying, is not uncommon in the context of the label of autism. They also reiterate that timely screening, diagnosis and yes, treatment for such comorbidity, are basic human rights that are as relevant to someone with autism as they are to someone not on the autism spectrum.

Oh, and given the quite significant overlap between autism and such psychiatric comorbidity, it is perhaps all the more reason to keep on studying a group where autistic and psychiatric issues seemingly were but are no more (see here)...

----------

[1] Schalbroeck R. et al. Risk of non-affective psychotic disorder or bipolar disorder in autism spectrum disorder: a longitudinal register-based study in the Netherlands. Psychol Med. 2018 Nov 21:1-8.

[2] Selten JP. et al. Risks for nonaffective psychotic disorder and bipolar disorder in young people with autism spectrum disorder: a population-based study. JAMA Psychiatry. 2015 May;72(5):483-9.

----------

Psychosis in depression linked to an increased risk of completed suicide

The results of the systematic review and meta-analysis published by Rossetos Gournellis and colleagues [1] provide the blogging fodder today, discussing an important topic on "whether psychotic features increase the risk of completed suicides in unipolar depression." The authors' conclusion was that yes: "The presence of psychosis in major depression should alert clinicians for the increased risk of completed suicide", something that may potentially have implications for various different 'scenarios' where psychosis (psychotic features), depression and suicide risk intersect. I'll come back to this shortly.

So, the name of the research games was systematic review and meta-analysis focused on both the peer-reviewed and 'gray' literature for studies "providing data on completed suicides in PMD [unipolar psychotic major depression] compared to non-PMD." Psychotic major depression by the way, is pretty much what the name suggests: depression or a depressive episode with the addition of psychotic symptoms such as hallucinations or delusions. Boiling down the pertinent research literature from thousands of articles to just nine articles covering "33,873 patients, among them 828 suicides", authors began their analyses.

Results: As already mentioned, the data pointed to the idea that psychosis might be an important part of suicide risk: "PMD patients manifest elevated risk of suicide even when they are compared with non-PMD patients who suffer from severe depression." Authors also concluded that: "This [suicide] risk is elevated in both the acute phase of the disorder and lifetime" and: "The data are inconclusive on the contribution of age, mood congruence, comorbidity, and suicide method on PMD’s suicide risk." The bottom line is that psychosis or the presence of symptoms of psychosis could be an important screening variable for risk of suicide in depression and also a target for intervention/prevention...

Before I go, I just want to head back to that previous sentence about these results perhaps having significance for 'different scenarios' where depression, psychosis and risk of suicide mix. I speak of course about the core topic of this blog - autism - and the on-going efforts to understand the complicated hows-and-whys of suicide risk in relation to autism (see here and see here). Acknowledging that the paths that take someone towards suicidality are often complex (see here), there is already some recognition in the peer-reviewed science domain that psychosis alongside autism might be a risk factor for suicide (see here). This, on the basis that psychosis and conditions manifesting psychosis might be 'over-represented' in relation to the autism spectrum (see here and see here) and depression is also not something unfamiliar (see here). It strikes me as eminently sensible that psychosis as well as depression could perhaps be screened more routinely as and when a diagnosis of autism is received. Both conditions/states are manageable...

----------

[1] Gournellis R. et al. Psychotic (delusional) depression and completed suicide: a systematic review and meta-analysis. Annals of General Psychiatry. 2018;17, 39.

----------

"psychiatric diagnoses, psychiatric care and psychotropic medication" in older age adults with autism

Is 55 years old still considered older age?

Well, according to the findings reported by Lena Nylander and colleagues [1] it represents the lower end cut-off point for their study looking at "the pattern of coexistent psychiatric diagnoses and the utilisation of psychiatric care and psychotropic medication among any individuals found to have ASD [autism spectrum disorder] diagnoses." Said individuals were aged between 55 and 96 in 2012 and "had a registered diagnosis of any ASD—defined as an ICD-10 code."

Those individuals 'found to have ASD' were located via some of those very useful Scandinavian population registries, this time based in Sweden. As a function of their registration for 'municipal services' researchers were also able to access other collected records and subsequently mined data on "gender, other psychiatric diagnoses, psychiatric care utilisation and psychotropic medication [use]" for a group of increasing research and clinical importance in the context of autism (see here).

The results proved interesting. Of the 600 people included for study, most had received a diagnosis of childhood autism (~40%), most had not received a concomitant intellectual disability (ID) diagnosis (~60%) and quite a few had received more than one 'type' of autism diagnosis (~15%).

When it came to the receipt of other psychiatric diagnoses such as affective disorder, personality disorder, anxiety or psychotic disorder, several notable observations were made. As a function of the total group, including everyone whether diagnosed with an ID or not, around 50% of participants had received at least one psychiatric diagnosis. A nebulous category defined as "other psychiatric diagnosis" was most frequently mentioned, but when it came to a named class of condition(s), affective disorders led the way in terms of frequency irrespective of the presence of ID or not. Affective disorders covers quite a bit of diagnostic ground but typically includes labels/conditions such as depression and/or bipolar disorder; conditions that are no stranger to autism (see here and see here respectively). Anxiety and psychotic disorders were also mentioned as being present among this cohort too; again not for the first time (see here and see here).

With regards to 'psychiatric care utilisation', it was more typical to see psychiatric care used than not used as nearly two-thirds of the cohort had used some kind of psychiatric care over the period included for study examination. Most were categorised as "general adult psychiatric care" and: "The group with Asperger’s syndrome had the highest number of people who had spent time as psychiatric inpatients" reflected in the odds ratio (OR) generated from the study for this group (OR: 6.87, 95% CI 3.80–12.43).

Finally, on the topic of psychotropic medication use, researchers observed that "63% of patients without registered ID diagnosis and as many as 84% of those with ID in combination with ASD had been prescribed antipsychotic medication." Antipsychotics were the most frequent medication mentioned in records, closely followed by anxiolytics (to manage anxiety) and antidepressants. Around 1 in 5 participants received more than one type of medication (irrespective of the presence of ID or not).

An important picture emerges from the Nylander findings. A picture suggesting that psychiatric diagnoses feature fairly prominently in the clinical profile of many older age adults with autism, and their identification and intervention need to be more clearly recognised. Nylander also pointed out that certain sub-groups within the autism spectrum should perhaps be more closely followed in relation to their achieving and maintaining good mental health. So, without trying to focus too much attention on one label: "It seems that the group with Asperger’s syndrome, or ASD without ID, is especially vulnerable to psychiatric disorders" on the basis that: "Only 15 individuals, or 11%, of the group with Asperger’s syndrome had not been in contact with psychiatric care, and 43% had been psychiatric in-patients, which may be interpreted as a sign of vulnerability in these individuals." That word again  - vulnerability - arises in the context of autism (see here and see here for other examples). And here is yet another example (see here) illustrating that phrases like 'high-functioning' in the context of the autism spectrum, really don't do justice to the lived experience of autism and the effects of it's important add-ons.

And on the topic of ageing and autism, and specifically ageing well, there are the findings reported by Ye In Hwang and colleagues [2] to consider, and specifically: "A very small proportion (3.3%) of autistic adults were found to be aging well."

----------

[1] Nylander L. et al. Older Adults with Autism Spectrum Disorders in Sweden: A Register Study of Diagnoses, Psychiatric Care Utilization and Psychotropic Medication of 601 Individuals. J Autism Dev Disord. 2018. April 16.

[2] Hwang YI. et al. Aging Well on the Autism Spectrum: An Examination of the Dominant Model of Successful Aging. J Autism Dev Disord. 2018. May 2.

----------

Low grade inflammation in acute psychiatric inpatients

I was interested to read the findings reported by Emanuele Osimo and colleagues [1] (open-access available here) recently, and their observation that: "Evidence of low-grade inflammation was present in all major diagnostic groups, with prevalences ranging from 12 to 40% depending on the measure."

'Major diagnostic groups' included in the Osimo paper, included "acutely unwell psychiatric inpatients from all major ICD-10 diagnostic groups" covering labels such as psychotic disorder, schizophrenia, mood disorders, personality disorders and organic mental disorders.

Authors - including the notable name of Golam Khandaker who has published work previously covered on this blog (see here and see here for examples) - conducted an "anonymised search of the electronic patient records" for those hospitalised in a specialist mental health department for the treatment of a mental health / psychiatric condition between 2013 and 2016. Alongside, they had to have "a blood test result for CRP [C-reactive protein] or for WBC [total white cell count] [that] had been recorded on the electronic medical notes system within 14 days of admission" yielding almost 600 participants. In effect, a blood test pertinent to the measurement of compounds reflective of immune system processes such as inflammation.

As per the opening sentences to this post, and using CRP and/or WBC as a measure of inflammation, authors identified some quite notable prevalences of low-grade inflammation in their patient group. So: "The prevalence of inflammation in the major ICD-10 diagnostic groups of psychotic disorders (F20–29), mood disorders (F30–39), neurotic disorders (F40–48) and personality disorders (F60–69) was 32%, 21%, 22% and 42%, respectively." Various other variables also seemed to be *associated* with the presence of such inflammation too. Authors note for example that: "Patients with medical comorbidities were more likely to be inflamed" alongside various other factors also potentially exerting an effect: "older age, black ethnicity, being single, self-harm, diagnoses of schizophrenia, bipolar disorder, current treatments with antidepressants, [and] benzodiazepines" were all associated with low-grade inflammation.

Such findings add to the ever-growing amount of research that suggests a role for the immune system in relation to various psychiatric / behavioural diagnoses (see here). Further, that with a little more focus on the somatic as well as the psychiatric (see here) when it comes to such conditions, potentially relevant clues may emerge pertinent to treatment options. I might finally also draw your attention to some work previously discussed on this blog dealing with the idea that inflammation *might* have the ability to affect social cognitive processing (see here). Such a finding, focused on symptoms rather than labels, could offer a few alternative directions for intervention given the widespread nature of social cognitive issues across a wide variety of psychiatric conditions.

----------

[1] Osimo EF. et al. Prevalence and correlates of low-grade systemic inflammation in adult psychiatric inpatients: An electronic health record-based study. Psychoneuroendocrinology. 2018 Mar 1. pii: S0306-4530(17)31581-0.

----------

ADHD and non-suicidal self-injury (NSSI)

I've covered the growing literature observing a link between a diagnosis of attention-deficit hyperactivity disorder (ADHD) and risk of unintentional injury a few times on this blog (see here and see here). The quite consistent picture emerging from that body of peer-reviewed research is that yes, a diagnosis of ADHD does seem to increase the risk of injury for whatever reason(s). Further, that pharmacotherapy utilising some of the various medicines indicated for ADHD, seems to have something of a 'reducing' effect on that elevated injury risk (see here).

Today I'm extending that ADHD-injury risk work to include the findings reported by Judit Balázs and colleagues [1] who concluded that: "ADHD symptoms are associated with an increased risk of NSSI [non-suicidal self-injury] in adolescents." Further that: "the symptoms of affective disorders and alcohol abuse/dependence psychotic symptoms" seem to be important 'mediators' of that risk of NSSI in the context of ADHD symptoms.

Based on the examination of adolescents who "were inpatients in the Vadaskert Child and Adolescent Psychiatric Hospital and Outpatient Clinic, Budapest, Hungary between 25.02.2015 and 09.05.2016", researchers reported that some 50 adolescents met the full criteria for ADHD and a further 70-odd "showed symptoms of ADHD at the subthreshold level." They employed the "Hungarian version of the modified Mini International Neuropsychiatric Interview Kid" to assess for various psychiatric symptoms, alongside the Deliberate Self-Harm Inventory (DSHI) to provide details on self-injury and some further questioning on suicidality. The aim was to investigate rates of NSSI in their cohort but also "how the symptoms of comorbid psychiatric conditions influence this [relationship], and whether there is a difference between girls and boys at this age."

Results: alongside the finding that at the very least, ADHD or ADHD symptoms are not protective against non-suicidal self-injury (NSSI), authors also observed that "people with ADHD have a higher risk than those without of developing comorbid psychiatric problems, both externalizing and internalizing ones" and "there is no direct association between the symptoms of ADHD and the prevalence of NSSI in a clinical sample of adolescents in any sex." On that last point, authors further opine that: "Comorbidities fully mediate the association between these conditions." In other words, clinicians should be screening for various psychiatric comorbidities - major depressive episode, dysthymic disorder, hypo/manic episode, psychotic disorders, substance-related dependence/abuse - and treating said comorbidities to potentially offset the risk of NSSI appearing alongside ADHD or subclinical ADHD.

In these days of ESSENCE - Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations - where the rule seems to be that various labels do not appear in some sort of diagnostic vacuum (see here for example), the Balázs findings fit well. The implication being that before grand associations are made on the basis of one variable = one condition/label/diagnosis (see here for example), one should perhaps consider a wider clinical picture. Indeed, to further extend the Balázs findings talking about NSSI, and based on the idea that autism and ADHD seem to be an important clinical combination (see here), I would perhaps encourage a greater depth of screening in future research (see here). That also might apply to the delicate issue of suicidality too (see here)...

----------

[1] Balázs J. et al. Attention-deficit hyperactivity disorder and nonsuicidal self-injury in a clinical sample of adolescents: the role of comorbidities and gender. BMC Psychiatry. 2018; 18:34.

----------

On treating psychosis in the context of autism

"This report describes the successful improvement in symptoms and quality of life in a young man with psychosis and ASD [autism spectrum disorder], who had previously tried numerous medical interventions."

So said the findings published by Victoria Bell and colleagues [1] (open-access available here) providing some discussion not only about how a diagnosis of autism is seemingly not protective against the development of something like psychosis (see here) but also how psychosis in this context can be successfully managed with a little bit of [clinical] thought. I'll also draw your attention to some other quite recent research that has conversely talked about how difficult it can be to treat psychosis when an autism diagnosis is also in the frame (see here).

Bell et al discuss a case report of a young man (HP) who came to clinical attention in his mid-teens. School examinations seemed to be a possible trigger for episodes of vomiting after eating, leading to hospitalisation. Other symptoms also appeared - "a lowering of mood and poor sleep, and weight loss" - leading to more clinical contact. Bullying was also a feature; as we are told that: "a group of boys had made videos of him, including him being flash mobbed, which had been placed on YouTube; they had also made a persecutory Facebook page." I can think of a few choice words to describe such boys and their antics but won't.

As time progressed, he had "an in-patient admission to a Child and Adolescent Mental Health Services ward, for over a year" where a diagnosis of Asperger syndrome was made alongside "dissociative disorder, and a severe depressive episode with psychotic features." Lots more followed including him becoming "increasingly non-communicative and episodically aggressive toward his parents" culminating in him returning to an in-patient setting.

What is rather refreshing to see is the clinical work-up that this young man received. So: "magnetic resonance imaging (MRI) scans, electroencephalograms (EEGs), anti-NMDA antibodies, as well as B12, folate and thyroid function tests were repeatedly normal." Some critical thinking eventually led clinicians to discount the idea that his symptoms 'were just part of his autism' - "differentiating between psychotic catatonia and autism-related catatonia" - and instead look to a comorbid diagnosis of psychosis. Further: "this was adopted as our working diagnosis for treatment."

Treatment came in the form of various pharmacotherapy and some 'psychological input' bearing in mind "HP remained selectively mute throughout his admission." His clinical management wasn't exactly helped by the fact that another 'very disruptive patient' was admitted at the same time as HP and, on more than one occasion, physically attacked him. But eventually the 'number of days out' increased and symptoms such as vomiting, incontinence and aggression decreased as the "symptom-based approach" adopted seemed to work.

What lessons can be learned from this case report? Well, several. Not least that as well as not existing in some sort of diagnostic vacuum (see here), a diagnosis of autism can and does raise the risk of various psychiatric comorbidity potentially appearing. And sometimes it's hard to see where autism ends and said comorbidity starts (see here for example); assuming that is, that you see comorbidity as comorbidity and not something rather more core.

There is also a positive message from the Bell findings in relation to the 'treatability' of various comorbidity over-represented alongside autism. Yes, it takes time and resources to diagnose and rule things in or out, but quality of life can be improved for the person and those around them. Indeed the authors add: "The level of violence upon admission concerned our team and his parents... if psychotic symptoms were ignored, violence may have continued and led to long-term placements in a more secure environment." Indeed.

----------

[1] Bell V. et al. A symptom-based approach to treatment of psychosis in autism spectrum disorder in October 2017. BJPsych Open. 2018 Jan;4(1):1-4.

----------

"Social cognitive deficits are present in a wide range of clinical conditions"

Happy New Year!

Welcome to Questioning Answers 2018-style. Let's continue...

Today I'm bringing to your attention the findings reported by Jack Cotter and colleagues [1] who concluded that: "social cognitive deficits appear to be a core cognitive phenotype of many clinical conditions."

Social cognitive issues defined as "mental operations that underlie social interactions" and "includes a range of cognitive processes that help individuals to understand how others think and feel" are something not unknown to the core subject of this blog: autism. Indeed, Cotter et al mention how the "most heavily researched aspects of social cognition are emotion recognition and theory of mind (ToM)." Right or wrong, ToM in particular, has had quite a significant influence on autism research and thought down the years (see here).

Cotter and colleagues "sought to collate existing meta-analytic data on social cognitive performance among individuals with a range of clinical conditions" on the basis that whilst the label of autism has received the lion's share of research interest, social cognitive issues perhaps span a far wider range of labels/conditions. They scoured the peer-reviewed literature and identified some 31 meta-analyses published that "examined performance on facial emotion recognition (24 papers) and/or ToM tasks (24 papers) among 30 different clinical populations relative to controls." The sorts of clinical populations identified ranged from psychiatric disorders such as psychosis and schizophrenia, to neurological disorders such as epilepsy and traumatic brain injury to developmental disorders such as attention-deficit hyperactivity disorder (ADHD) and intellectual (learning) disability.

Their conclusions: "Though these results do not provide directly comparable estimates between clinical conditions, they provide a robust indication that social cognitive deficits appear to be a core cognitive phenotype of many developmental, neurological and psychiatric disorders." The authors go on to discuss how, on the basis of their findings, social cognitive issues (impairment) might be "a general biomarker indicative of neurological abnormality" more generally; also, in some contexts, providing information on the 'progression' of a particular condition.

In these days of ever-blurring labels and conditions, where comorbidity is proving to be the rule rather than the exception [2] (see here also), there is common sense in the Cotter findings. Sense, insofar as the idea that no one diagnostic label has generally got a monopoly on a particular behaviour and/or symptom and that social cognitive issues might be 'core' to quite a few conditions. A greater appreciation of such an idea could potentially impact, in many different ways, on what we think about many seemingly different psychiatric, developmental and neurological labels. A few stand-out points include: (a) a reiteration of how nonsensical the term 'neurotypical' is from a social cognitive perspective when describing 'not-autism' (see here); (b) a further illustration of the value of a professional assessment as and when something like autism is suspected, rather than just a reliance on brief 'are you autistic?' questionnaires that tend to rely heavily on social cognition as a 'symptom' (see here); and (c) investigation into whether or not important biological 'issues' thought to accompany social cognitive 'issues' could also be quite wide-ranging among many conditions/labels (see here for some discussion on the concept of inflammation for example).

And since we're on the topic of grand, sweeping psychological concepts spanning different conditions, how about the idea that executive function issues might also cross labels [3] too...

Stay tuned for more in 2018.

----------

[1] Cotter J. et al. Social cognitive dysfunction as a clinical marker: A systematic review of meta-analyses across 30 clinical conditions. Neuroscience & Biobehavioral Reviews. 2018; 84: 92-99.

[2] Posserud M. et al. Autism traits: The importance of “co-morbid” problems for impairment and contact with services. Data from the Bergen Child Study. Research in Developmental Disabilities. 2018; 72: 275-283.

[3] Carter Leno V. et al. Testing the specificity of executive functioning impairments in adolescents with ADHD, ODD/CD and ASD. Eur Child Adolesc Psychiatry. 2017 Dec 9.

----------

Various symptoms cluster around psychosis but...

The findings reported by Abigail Livny and colleagues [1] provide some [brief] blogging fodder today. Looking to "characterize the symptoms of patients later hospitalized for psychotic disorders in primary mental health outpatient settings" researchers found several variables seemed to be *correlated* in their target population (N=1092).

So: "thought disorder, perceptual abnormalities, poor orientation, and suicidality was associated with an increased risk for hospitalization for nonaffective psychotic disorder" as a function of various time periods. The hazard ratios (HRs) produced were not to be sniffed at. The authors concluded however that: "Despite the increased risk, the positive predictive values of this symptom cluster were low" suggesting that looking for such a symptom cluster does not necessarily guarantee prediction of "later hospitalization for nonaffective psychotic disorder."

It remains the holy grail of psychiatry to be able to 'predict' who might go on to develop something like a clinical diagnosis of psychosis or other related condition and onward, target those vulnerable groups/people with appropriate screening and other required services. Whilst there is seemingly no end of potential 'behaviours to watch for' (indeed, conditions/labels to watch for too), the fact of the matter is that we still don't [reliably] know who will or won't go to develop psychosis. And I doubt that position will change very much without some greater focus on biological 'risk' markers also added to the mix (see here and see here for examples)...

----------

[1] Livny A. et al. A Population-Based Longitudinal Study of Symptoms and Signs Before the Onset of Psychosis. Am J Psychiatry. 2017 Nov 28: appiajp201716121384.

----------

Vitamin D for schizophrenia? No but...

The results published by Amir Krivoy and colleagues [1] talking about "no significant effect of vitamin D on psychotic, depressive or metabolic parameters" in a cohort of people diagnosed with schizophrenia, make for interesting reading.

Interesting, not only because authors reported very little effect of supplementation on the symptoms of schizophrenia, but also because such 'negative' findings kinda follow a theme in vitamin D - psychiatric research circles: low levels of vitamin D (insufficiency and/or deficiency) being associated with a condition (see here) yet little [experimental] evidence that supplementation does anything more than correct the vitamin D availability issues (see here for another example). Certainly the quite significant speculation that vitamin D might have lots and lots of 'extra-bone' related actions do not yet seem to have been borne out by the currently available experimental data in this area...

Krivoy et al describe the methodology and results of their "eight-week, randomized, double-blind, placebo-controlled clinical trial" focused on some 47 patients "age between 18 and 65 years old, diagnosis of schizophrenia according to DSM-IV-TR criteria confirmed by two senior psychiatrists, treated with clozapine for at least 18 weeks and being on a stable clozapine dose for at least four weeks prior to enrollment, serum 25(OH) vitamin D level below 75 nmol/L (30 ng/ml) and total severity of psychopathology score, as measured by the Positive and Negative Symptom Scale (PANSS) total score above 70." Vitamin D supplementation - 14,000 IU [international units] per week - was pitted against a placebo formulation, although I can't seem to find what exactly the placebo contained (N=24 vs. N=23 respectively). Various outcome measures were used to determine any effect or not.

Results: as per the opening line of this post, there was little to see between the vitamin D and placebo receiving groups when compared on the basis of PANSS scores. Both groups showed a trend towards a decreasing total and sub-scale psychopathology scores over the course of the experimental period indicative of some modest improvement in psychiatric symptoms. At the same time, authors report that vitamin D levels did change amongst those in receipt of the vitamin D supplement: "The 25(OH) vitamin D serum levels increased significantly in the drug group... while essentially unchanged in the placebo group" so we can be pretty sure that there was both compliance with the experimental regime and that vitamin levels were increasing in the supplemented group as expected.

There was one small 'ray of hope' when it came to supplementation that has been hinted at in the research literature previously: "A beneficial effect of vitamin D supplementation was noted on cognitive performance, as reflected in an increase in MoCA [Montreal Cognitive Assessment] total score." I say 'hinted at' because although it is a little premature to talk about vitamin D as a nootropic (cognitive enhancer), there is evidence that low levels of the stuff *might* under certain circumstances, negatively affect certain cognitive abilities (see here for example). Whether supplementation with vitamin D is a more general cognitive 'affector' remains to be seen but the Krivoy results suggest further inspection is indicated.

There is more to do in this area before the vitamin D - schizophrenia link is branded completely spurious. The authors mention the relatively small sample sizes included for study and how the nature of schizophrenia as a condition potentially means that "patients with extreme presentation are less likely to consent to participate in a randomized controlled trial due to their paranoid and suspicious attitudes" as being something important. It's also interesting that at least one of the supplemented participants seemed to show little response to vitamin D in a physiological levels sense: "This patient, despite attending all assessments and dosing visits, showed vitamin D level of 22 nmol/L at baseline and 17 nmol/L at endpoint due to unclear reasons." Assuming that vitamin D testing was accurate i.e. using something like mass spectrometric methods over older, potentially less reliable assays (see here) I wonder if there could be other components required in future studies in this area, such as also looking at the genetics of vitamin D metabolism as per other, unrelated research (see here).

----------

[1] Krivoy A. et al. Vitamin D Supplementation in Chronic Schizophrenia Patients Treated with Clozapine: A Randomized, Double-Blind, Placebo-controlled Clinical Trial. EBioMedicine. 2017. Nov 29.

----------

On antipsychotic treatment failure when both psychosis and autism present together

"Children with first-episode psychosis and comorbid autism spectrum disorders at first presentation are less likely to have a beneficial response to antipsychotics."

So said the results reported by Johnny Downs and colleagues [1] based on their analysis of historical health records for over 630 children and young adults "referred to mental health services in South London, United Kingdom" between 2008 and 2014. Researchers looked for evidence of "multiple treatment failure" (MTF) - defined as "the initiation of a third trial of a novel antipsychotic due to insufficient response, intolerable adverse effects, or nonadherence to prior antipsychotic treatment" - among their cohort as a function of a diagnosis of an autism spectrum disorder (ASD) and other neurodevelopmental labels such as "hyperkinetic disorders (ICD-10 F90) and intellectual disability (ICD-10 F70–9)." The hypothesis being that those with at least one mention of psychosis in their health records alongside comorbid ASD "would be more likely to experience treatment failure" as a consequence of other findings talking about "psychopharmacologic effectiveness [being] lower in populations with coexisting ASD." The reasoning for that hypothesis seemingly comes from other research such as that from Politte and colleagues [2] and is set in the context of the NICE guidance here in Blighty on the subject of antipsychotics and 'core' autism (see here).

Results: 114 of the 638 participants (~18%) studied also had a diagnosis of ASD. This kinda reiterates that psychosis and other conditions characterised by psychosis are probably not strangers when it comes to the clinical profile of [some] autism (see here and see here). Some 20% of their total cohort developed MTF during the study follow-up period. After adjusting for various potentially confounding variables researchers observed that: "ASD comorbidity was associated with a 2-fold increased risk of MTF" and further: "28% of those with comorbid ASD compared to 11% of non-ASD children had a persistently insufficient response to antipsychotics." Autism or possibly something about autism or linked to autism, seemed to potentially affect response to antipsychotics where psychosis was present.

There are a couple of other observations to make about the Downs data. When comparing the ASD - first episode psychosis (FEP) group with the not ASD - FEP group, the former showed an increased frequency of both hyperkinetic disorders a.k.a attention-deficit hyperactivity disorder (ADHD) and intellectual (learning) disability. This tallies with quite a bit of other research looking at other over-represented labels in the context of autism (see here and see here respectively). Also: "Children with ASD showed higher rates of the “persistent insufficient response” or the “insufficient response–adverse effect” trajectory but lower rates of adherence-related reasons relative to those without ASD." The adherence bit kinda suggests that for example, not taking the antipsychotic medicine when required to, was not a core reason for MTF where ASD is mentioned.

Insofar as the important questions of 'how and why' in relation to the Downs results, the authors pop into 'speculating mode'. They talk for example, about how findings "may be explained by specific neurobiological profiles related to psychosis-ASD comorbidity" mentioning things like dopamine as being important. Equally as speculative, I might add in a few ideas that could also be pertinent. The first is that some effect on immune function could be a complementary pathway in relation to the action of specific antipsychotics (see here). The second is another 'sexy' area of research with a proposed 'epigenetic' action (see here); antipsychotics potentially acting on targets linked to gene expression for example. Both areas - immune function and/or epigenetics - have some 'research form' in both psychosis and autism investigations (see here for example). Both areas require a lot more investigation in this context.

I'm going to finish with another important quote from the Downs paper: "Our results are consistent with the evidence that shows psychotic illness experienced by children and adults with ASD may be different from non-ASD samples." I think the authors might be on to something here as per other observations on important psychiatric comorbidity in relation to autism such as the presentation of bipolar disorder (see here) for example. The idea being that such 'atypical' psychosis presentation and seemingly poor(er) response to recognised treatments for such psychiatric issues could denote that either a novel phenotype may be at work or indeed, that alongside anxiety and depression (see here and see here) being present in cases of autism, psychotic and other symptoms might be seen as more 'core' features of some autism? Once again, I hark back to the [sadly forgotten] writings of Mildred Creak and colleagues [3] as a possible framework for further study...

----------

[1] Downs JM. et al. The Association Between Comorbid Autism Spectrum Disorders and Antipsychotic Treatment Failure in Early-Onset Psychosis. Journal of Clinical Psychiatry. 2017.

[2] Politte LC. et al. Psychopharmacological interventions in autism spectrum disorder. Harv Rev Psychiatry. 2014 Mar-Apr;22(2):76-92.

[3] Evans B. How autism became autism: The radical transformation of a central concept of child development in Britain. Hist Human Sci. 2013 Jul;26(3):3-31.

----------

Can a bone marrow transplant really affect psychotic symptoms in schizophrenia?

"Though BMT [bone marrow transplantation] may not be a cure for all cases of schizophrenia, it definitely possesses the potential to manage overall disease severity and improve the quality of life, and this case report is a preliminary demonstration of the safety and efficacy of BMT in treatment-resistant schizophrenia."

So said the findings reported by Tsuyoshi Miyaoka and colleagues [1] (open-access available here) discussing a case report of a young man initially diagnosed with paranoid schizophrenia which was eventually deemed 'treatment-resistant' on the basis of his lack of [positive] response to anti-psychotic medication(s) given for "his auditory hallucinations, suspiciousness, active social avoidance, persecutory delusion, and deterioration in the level of social functioning."

Things unfortunately got worse for this young man we are told, as he was subsequently diagnosed with acute myeloid leukemia - cancer of the white blood cells - setting in motion the initially daunting task of treatment via a bone marrow transplant. As the name suggests, BMT involves the transplantation of bone marrow where stem cells are made. Stem cells are those wonderful cells that give rise to the various types of blood cells we all have among other things. The idea being that a kinda of reboot of white blood cells in this case could potentially treat his leukemia.

Although Miyaoka et al don't actually say how successful the BMT was for his leukemia (the patient was alive 8 years after BMT so I assume successful), they do talk about what happened to his psychotic symptoms following the BMT. So: "Thirty days later, his psychotic symptom had almost disappeared. He was sustained without any neuroleptic treatment and need for any other administration." Indeed, this didn't appear to be any short-term effect neither as "8 years after BMT, the improvements of somatic and psychiatric symptoms are continued, and the patient is very well and there are no residual psychiatric symptoms." In short, things were still going well for this young man both in terms of his past leukemia diagnosis and also psychotic symptoms.

There is always the possibility of "spontaneous improvement without any treatment" as accounting for the psychiatric results presented by the authors. Indeed, I also note that various immunosuppressive medicines were also administered around the time of the BMT to "avoid graft versus host disease (GVHD)" which might also have played some role in light of other research suggestions [2]. One has to be careful not to jump to too many conclusions particularly on the basis of single case reports.

But... it is a potentially important coincidence that use of a BMT came at the same time as the symptom changes noted. I'll also draw your attention to a 'call for case histories' on the topic of "BMT in patients with coincident schizophrenia" made by Sommer and van Bekkum [3] on the back of other work from these authors in relation to "the possibility that schizophrenia may be transmitted" where "a patient... developed severe psychosis after receiving a BM transplant from his schizophrenic brother" [4]. It seems that there may be a two-way process potentially at work when it comes to immune function and schizophrenia.

This is interesting stuff. Framed alongside the idea that schizophrenia might not be a homogeneous condition - think 'the schizophrenias' -  and that at least one 'type' of schizophrenia might have a significant 'immune' component to it (see here for example), one could envisage further investigations on the potential use of BMT in certain cases. I do have to mention safety and the possible side-effects of BMT outside of just GVHD (see here) as being important considerations; added to the invasiveness of BMT.

And whilst we're on this topic, I'd also direct you to some chatter about mice and bone marrow transplants in the context of autism some years back (see here) minus any sweeping generalisations but again, interesting...

----------

[1] Miyaoka T. et al. Remission of Psychosis in Treatment-Resistant Schizophrenia following Bone Marrow Transplantation: A Case Report. Front Psychiatry. 2017 Sep 21;8:174.

[2] Knight JG. et al. Rationale for a trial of immunosuppressive therapy in acute schizophrenia. Mol Psychiatry. 2007 May;12(5):424-31.

[3] Sommer IE, van Bekkum DW. Call for case histories of BMT in patients with coincident schizophrenia. Bone Marrow Transplantation. 2013;48(6):880.

[4] Sommer IE. et al. Severe chronic psychosis after allogeneic SCT from a schizophrenic sibling. Bone Marrow Transplantation. 2015;50(1):153-154.

----------

Insomnia having "a causal role in the occurrence of certain psychotic experiences"

The findings reported by Sarah Reeve and colleagues [1] (open-access available here) observing that: "Sleep loss resulted in moderate to large effect size increases in paranoia, hallucinations, and cognitive disorganization as compared to standard sleep" are not typical fodder for this blog. In the context however, that (a) sleep issues are something potentially important to some people on the autism spectrum (see here and see here) and that (b) at least some 'types' of autism might be more readily 'prone' to psychosis and/or psychotic experiences (see here), there is merit in me covering the Reeve findings. Even more so when one considers that some of the over-represented comorbidity potentially appearing alongside autism (see here) might also have some connection(s) to sleep (see here) and onward too, enhanced future risk of the presentation of psychosis (see here). Possibly...

Reeve et al specifically focused on how sleep loss may tie into the presentation of certain psychotic experiences based on clinical examination following a period of  'restricted sleep'. Participants with a previous history of 'good quality sleep', no history of psychiatric disorder and with no "requirement to drive, cycle, or operate heavy machinery during the study(!)" were randomly allocated to either a restricted sleep cycle (4 h sleep a night for 3 nights) or a control sleep cycle (standard sleep). Alongside the use of wrist actigraphy to provide an objective monitor of sleep-wake patterns (bravo!), researchers also describe how "automated hourly text (SMS) messages" were sent to would-be sleep deprived participants to ensure they were awake. Various measures relating to reported psychotic experiences and things like depression and anxiety levels were also delivered over the course of the study.

Results: well those 'are you awake?' text messages seemed to have done the trick as over 98% of them were answered within the required 15 minute window. Sleep times between the groups were also different as would be expected too. Then: "in comparison to the control condition, the sleep loss condition was associated with significant increases in hallucinations, paranoia, and cognitive disorganization." Also: "Highly significant and large effect size increases were found for depression, anxiety, and stress following the sleep loss condition, as compared with the control condition." Sleep loss, it appears, is not great for people even over a relatively short period of time.

Interestingly, following further 'mediation analysis' of their data, the authors reported some potentially important variables that might account for their findings. So: "negative affect is by far the most relevant factor in explaining the effect of sleep disruption on psychotic experiences." Negative affect covers things like depression, anxiety and stress. Paranoia in particular, seemed to be particularly tied into negative affect as a function of sleep deprivation. Going back to autism research, I note that paranoia is a feature for some people on the spectrum (see here) and minus any grand judgements, do wonder whether sleep issues could be a feature when presented in that context?

The authors do caution about certain elements of their study, specifically: "Psychotic experiences were generally endorsed at a low level in our sample, and all changes remained in the nonclinical range." They add also that this was research conducted with a "psychologically healthy" group with only mild and quite short-term sleep restriction used. But: "it could be hypothesized that the effect of sleep disruption on psychotic experiences in a more vulnerable group might be correspondingly more severe." Perhaps.

Then to possible intervention(s) and how about the findings reported by Freeman and colleagues [2] (and other authors on the Reeve paper) providing further evidence "that insomnia is a causal factor in the occurrence of psychotic experiences and other mental health problems" and how "digital cognitive behavioural therapy (CBT) for insomnia" seemed to do the trick in terms of levels of paranoia and hallucinations? Does this also open the door to other, more medication-type strategies, also positively impacting on sleep potentially having a possible 'anti-psychotic' effect too? And whilst we're on the topic of sleep deprivation and its effects, the recent paper from Deliens and colleagues [3] talking about visual perspective taking as being affected by sleep loss is something else important too and how "visual perspective taking should be viewed as partially state-dependent, rather than a wholly static trait-like characteristic"...

To close and related to today's chatter about psychosis and psychotic experiences, the British Psychological Society has recently released an updated version of its 'Understanding Psychosis' document. As expected, old 'psychological' habits on causation due to 'life events and trauma' continue to figure and continue to be put in their place by rightly sceptical minds...

----------

[1] Reeve S. et al. Disrupting Sleep: The Effects of Sleep Loss on Psychotic Experiences Tested in an Experimental Study With Mediation Analysis. Schizophr Bull. 2017 Aug 4.

[2] Freeman D. et al. The effects of improving sleep on mental health (OASIS): a randomised controlled trial with mediation analysis. Lancet Psychiatry. 2017 Oct;4(10):749-758.

[3] Deliens G. et al. The impact of sleep deprivation on visual perspective taking. J Sleep Res. 2017 Oct 11.

----------

Colliding spectrums: autism and schizophrenia (meta-analysed)

Consider this post talking about the findings reported by Jorge Lugo Marín and colleagues [1] an extension of previous chatter on this blog about the possibility of overlapping spectrums when it comes to autism and schizophrenia (see here).

I appreciate that there is some 'history' when it comes to moves to separate autism and schizophrenia [2] but the evidence being produced more recently perhaps questions whether the historical 'eagerness' to compartmentalise the labels as separate and independent was more of a socio-political thing over and above a true reflection of the state of any relationship (see here and see here for examples). Indeed, when [peer-reviewed] science for example, starts talking about a possible 'subtype of autism linked to psychosis' (see here) you know that the connections are perhaps not to be under-estimated...

Lugo Marín et al report results following a meta-analysis of the relevant peer-reviewed science done on this topic. Ten papers fulfilled their inclusion criteria. They report that: "The pooled prevalence of SSD [schizophrenia spectrum disorder] in the total ASD [autism spectrum disorder] sample was close to 6%, pointing to a high co-occurrence of the two conditions." Further, that more research is required about the specific hows-and-whys of SSD or symptoms of SSD appearing alongside [some] autism (and vice-versa) and onward, the possibility of preferential screening and intervention.

I've thought about the relationship between autism and schizophrenia quite a bit over the years. Not only because in my own area of research interest - gluten- and casein-free diets and autism - there is history linking autism and schizophrenia (see here) but also because the relationship down the years seemingly plays into the stigmatisation of a label i.e. move autism 'away' from schizophrenia because of the perceived 'dangerousness' connotations attached to schizophrenia for example (see here for a more recent example of this in action [3]). On that point, the evidence is getting clearer that whilst the diagnosis of schizophrenia (plus other factors) is by no means preventative of 'dangerous' acts being committed, people diagnosed with the condition are seemingly far more likely to be victims of something like crime than perpetrators (see here). Sounds familiar doesn't it?

Then also there is the 'identity' perspective to consider when talking about autism and schizophrenia in the same breath. Schizophrenia is considered to be a mental health issue; autism by contrast is primarily viewed as a developmental condition, which, although increasing the risk of developing a mental health issue (see here for example), is not itself described as such per se. I say this acknowledging that support for schizophrenia as being a 'neurodevelopmental disorder' is also growing [4] as words like 'prodrome' become more frequently discussed. Also important in this context, are the possible effects of certain comorbidity being 'over-represented' in cases of autism potentially also impacting on the subsequent risk of a diagnosis of schizophrenia (see here).

Keeping the theme of 'identity' going when discussing autism and schizophrenia, there is another angle to consider in terms of 'ownership' of the labels and perceptions around such a concept. I speak of the movement towards use of terms like 'autistic person' over 'person with autism' preferentially considered by some (see here) and how such a move is seemingly at odds with identity in terms of schizophrenia. The term 'schizophrenic' is considered unsuitable in this day and age (see here - "A person is not the sum total of the symptoms") alongside other 'label-first' terms such as 'manic depressive' and 'psychotic' for example. You can perhaps see how labelling someone as 'autistic' whilst at the same time labelling them has 'having schizophrenia' under circumstances where the two spectrums collide, presents a quandary when it comes to language and identity and perhaps serves to reiterate the gulf between the labels/conditions in terms of perceived stigma for example.

What we can say on the back of the Lugo Marín findings is that, in these days of ESSENCE (see here) and RDoC (see here) the possible reunification of the autism and schizophrenia spectrums in specific cases, should not be seen as something detrimental to either label and could provide some important insights into the genetic and biological nature of both spectrums (see here). I have my views about where the two spectrums might meet on a biological level [5] but no doubt there will be lots of other intersections too. Indeed, once again harking back to the [sadly forgotten] writings of Mildred Creak and colleagues and their "9 key features of ‘schizophrenic syndrome in childhood’", their description is uncannily pertinent to large parts of the autism spectrum when taking into account inclusion of diagnostic items such as "abnormal perceptual experience", "distortion in motility patterns" and "acute, excessive and seemingly illogical anxiety" and the often pronounced effects that such symptoms can have on quality of life.



To close, a picture relevant to today...

----------

[1] Lugo Marín J. et al. Prevalence of Schizophrenia Spectrum Disorders in Average-IQ Adults with Autism Spectrum Disorders: A Meta-analysis. J Autism Dev Disord. 2017 Oct 4.

[2] Evans B. How autism became autism: The radical transformation of a central concept of child development in Britain. Hist Human Sci. 2013 Jul;26(3):3-31.

[3] Sasson NJ. & Morrison KE. First impressions of adults with autism improve with diagnostic disclosure and increased autism knowledge of peers. Autism. 2017 Oct 1:1362361317729526.

[4] Owen MJ. et al. Neurodevelopmental hypothesis of schizophrenia. The British Journal of Psychiatry. 2011;198(3):173-175.

[5] Prata J. et al. Bridging Autism Spectrum Disorders and Schizophrenia through inflammation and biomarkers - pre-clinical and clinical investigations. J Neuroinflammation. 2017 Sep 4;14(1):179.

----------

Toxoplasma infection may be a risk factor for manifestation of psychotic-like symptoms

It's been a while since I last talked about Toxoplasma gondii on this blog (see here). All the initial research excitement from a few years back on how T. gondii exposure might correlate with various psychiatric symptoms/conditions seems to have been toned down in recent times. Still, I continue to be fascinated with the idea that at least for some, exposure to T. gondii might be more than just a somatic thing...

The findings reported by Lindgren and colleagues [1] illustrate how my interest in the gondii remains justified as per their conclusion: "Toxoplasma infection may be a risk factor for manifestation of psychotic-like symptoms." Based on data from Finland - "Health 2000, a large cross-sectional health survey of the Finnish general population aged 30 and above" - the authorship team included on the Lindgren paper contain some names familiar to the T. gondii research scene: namely Faith Dickerson and Robert Yolken.

So, the presence of lifetime psychotic-like symptoms via "section G of the Composite International Diagnostic Interview, Munich version (M-CIDI)" were analysed alongside seropositivity to Toxoplasma "defined as a cutoff of 50IU/ml of IgG antibodies" in nearly 6000 participants. Various other potentially interfering variables - "age, gender, education, region of residence, cat ownership, and C-reactive protein measuring inflammation" - were also thrown into the statistical mix. Cat ownership by the way, refers to the [disputed] research hypothesis that some cats might be unwitting hosts for the gondii with potential onward implications for owners (see here).

Results: "T. gondii seropositivity was significantly associated with clinically relevant psychotic-like symptoms... and with the number of psychotic-like symptoms." That being said, presenting with an immune profile suggestive of some contact with T. gondii did not show any significant connection with diagnosed conditions with a psychotic element to them such as schizophrenia. The authors however, felt confident enough to say that psychotic symptoms might not be totally unrelated to T. gondii exposure.

Accepting that there may be various reasons why someone might present with clinically-relevant psychotic-like symptoms [2] I find good reason to continue with the research agenda looking at T. gondii exposure and human behaviour on the basis of results such as those from Lindgren. The spectrum of labels - behavioural/psychiatric - potentially *associated* with T. gondii exposure is not to be sniffed at [3]. Even if only a proportion of cases are found to be *associated* with gondii exposure, there are treatments readily available (see here) to manage the infection. Whether such intervention(s) might also provide some relief of psychiatric symptoms alongside, is something too that needs more investigation...

----------

[1] Lindgren M. et al. The association between toxoplasma and the psychosis continuum in a general population setting. Schizophr Res. 2017 Jul 12. pii: S0920-9964(17)30391-2.

[2] Cosgrave J. et al. The interaction between subclinical psychotic experiences, insomnia and objective measures of sleep. Schizophr Res. 2017 Jul 12. pii: S0920-9964(17)30397-3.

[3] de Barros JL. et al. Is there any association between Toxoplasma gondii infection and bipolar disorder? A systematic review and meta-analysis. J Affect Disord. 2017 Feb;209:59-65.

----------