Atopic disease and adolescent psychotic experiences

I was intrigued to read the paper by Khandaker and colleagues [1] (open-access here) reporting results based on a longitudinal study that suggested: "Childhood atopic disorders increase the risk of psychotic experiences in adolescence".

Bish, bash, Bosch @ Wikipedia 

I've talked about the issue of atopic disease and it's potential overlap with something like neurodevelopment before on this blog (see here) based on the possibility of a neuro-immune interaction (i.e. that our immune system might be involved in many more processes than just fighting infection as per the microglia work) as suggested by Meldrum and colleagues [2]. The recent paper from Chang and colleagues [3] reporting a possible connection between allergic disease and behavioural issues in preschoolers adds to that debate. I very much consider the Khandaker findings to be of a similar ilk in terms of potential mechanisms of effect (accepting though that correlation does not necessarily mean causation).

In brief, Khandaker et al followed several thousand children over the course of their trial (data from the ALSPAC cohort which has just received some good news), detailing the presence of atopic diseases such as asthma and eczema of participants at age 10 and any subsequent psychotic experiences at age 13. Various markers linked to inflammation (C-reactive protein and IL-6) were also assessed at age 9. It was then a case of comparing those with atopic disease, whether present singularly or combinatorially, with those without atopic disease on whether the risk of a psychotic episode (PE) was more or less likely. And it was more likely in the atopic group; although strangely enough those markers of inflammatory processes did not seem to "mediate association between atopy and PEs" bearing in mind that inflammatory markers were not seemingly assessed at the time of the PE.

As per the authors findings, I'm not yet able to provide a specific hypothesis to explain the Khandaker findings. I do hark back to my previous chatter about the 'skin-brain axis' for example (see here) as potentially being important although not specifically related to the psychosis findings. The accompanying literature on psychocutaneous disorders [4] "conditions that are characterized by psychiatric and skin manifestations" may very well be something of a research focus to account for at least the proposed eczema - PE link.

With regards to asthma, well there is the suggestion from Moreno and colleagues [5] that asthma was one of a number of conditions "more frequent in individuals with psychotic symptoms but no psychosis diagnosis" but again, comparatively little to suggest a mechanism of connection outside of individual case reports on steroid medication for example (used for some cases of asthma) being linked to the presence of psychotic episodes [6]. I could be really speculative and talk about physiological mechanisms other than atopy potentially linked to such somatic and psychiatric symptoms such as that encompassed by the body of work looking at dietary elements [7] (and this paper by Faith Dickerson and colleagues [8]) but don't want to get ahead of myself given the lack of testing for such parameters in the Khandaker paper.

What however we can take from the Khandaker results is that a possible connection between somatic and psychiatric symptoms should remain an important area of research particularly with regards to shared genetics, epigenetics or biological markers. Perhaps also that more emphasis should be placed on screening for psychotic episodes and related conditions in cases where atopy is present. The tantalising question of whether treating somatic symptoms might have a potential knock-on effect on psychiatric symptoms or vice-versa also remains, as for example, per the recent update on the use of anti-inflammatory agents for schizophrenia by Sommer and colleagues [9]. There doesn't at the moment appear to be an awful lot of research on the potential usefulness of antihistamines (H1-receptor antagonists) commonly used to treat allergic disorders, in cases of psychosis or conditions manifesting psychosis. When however it comes to H2-receptor antagonists and accepting that these medicines are not generally viewed as antihistamines, I am drawn to the chatter about famotidine and schizophrenia [10] for example, something which I think was also mentioned with regards to autism at one point [11] and seemingly never heard of again. So, with no medical advice given or intended, there's still quite a bit more research to do in this area.

To close, having watched the recent BBC4 documentary about The Doors and really appreciating the musical talent they were, a classic: Riders on the Storm... sit back and enjoy.

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[1] Khandaker GM. et al. A population-based study of atopic disorders and inflammatory markers in childhood before psychotic experiences in adolescence. Schizophr Res. 2013 Nov 21. pii: S0920-9964(13)00520-3. doi: 10.1016/j.schres.2013.09.021.

[2] Meldrum SJ. et al. Allergic disease in the first year of life is associated with differences in subsequent neurodevelopment and behaviour. Early Hum Dev. 2012 Jul;88(7):567-73. doi: 10.1016/j.earlhumdev.2011.12.032.

[3] Chang HY. et al. Allergic diseases in preschoolers are associated with psychological and behavioural problems. Allergy Asthma Immunol Res. 2013 Sep;5(5):315-21.

[4] Al Hawsawi K. & Pope E. Pediatric psychocutaneous disorders: a review of primary psychiatric disorders with dermatologic manifestations. Am J Clin Dermatol. 2011 Aug 1;12(4):247-57.

[5] Moreno C. et al. Psychotic symptoms are associated with physical health problems independently of a mental disorder diagnosis: results from the WHO World Health Survey. World Psychiatry. 2013 Oct;12(3):251-7.

[6] Lee KM. et al. Steroid-induced acute psychosis in a child with asthma: report of one case. Acta Paediatr Taiwan. 2001 May-Jun;42(3):169-71.

[7] Karlsson H. et al. Maternal antibodies to dietary antigens and risk for nonaffective psychosis in offspring. Am J Psychiatry. 2012 Jun;169(6):625-32.

[8] Dickerson F. et al. Markers of gluten sensitivity and celiac disease in recent-onset psychosis and multi-episode schizophrenia. Biol Psychiatry. 2010 Jul 1;68(1):100-4.

[9] Sommer IE. et al. Efficacy of Anti-inflammatory Agents to Improve Symptoms in Patients With Schizophrenia: An Update. Schizophr Bull 2014; 40: 181-191.

[10] Martinez MC. Famotidine in the management of schizophrenia. Ann Pharmacother. 1999 Jun;33(6):742-7.

[11] Linday LA. et al. Famotidine treatment of children with autistic spectrum disorders: pilot research using single subject research design. J Neural Transm. 2001;108(5):593-611.

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Khandaker GM, Zammit S, Lewis G, & Jones PB (2013). A population-based study of atopic disorders and inflammatory markers in childhood before psychotic experiences in adolescence. Schizophrenia research PMID: 24268471