Psychiatric effects of childhood inflammation?

"Higher levels of the systemic inflammatory marker IL-6 [interleukin 6] in childhood are associated with an increased risk of developing depression and psychosis in young adulthood". So said the paper by Golam Khandaker and colleagues [1] looking at the growing link between inflammation and psychiatry.

The bright light of Autumn @ Wikipedia 

The name Khandaker has appeared before on this blog (see here and see here), most recently with research looking at a possible link between the presence of a neurodevelopmental disorder and subsequent reports of psychotic experiences [2]. It's all rather fascinating research.

With the most recent investigation in mind...

• Two inflammatory markers, IL-6 and C-Reactive Protein (CRP), were the variables of choice as per their inflammatory link (see here and see here). Said inflammatory markers were analysed in blood samples from quite a nice cohort (~4500) of 9-year olds who took part in the ALSPAC initiative. 
• When their cohort were 18 years old, their mental health was assessed for things like depression and psychotic experiences (PEs) using various questionnaires and semi-structured interviews.
• Results: depending on whether participants fell into groups suggestive of low, medium or high inflammation on the basis of inflammatory markers seemed to have some effect on their mental health almost a decade later. So: "participants in the top third of IL-6 values compared with the bottom third at age 9 years were more likely to be depressed... at age 18 years". This finding was reported after correction for various potentially interfering variables.
• Additionally: "Risks of PEs and of psychotic disorder at age 18 years were also increased with higher IL-6 levels at baseline".
• The authors conclude: "Higher IL-6 levels in childhood were associated with subsequent risks of depression and PEs in a dose-dependent manner".

There is, as one might expect, some accompanying media interest in these results (see here). I was interested to see that Judy Van de Water commented on the Khandaker results. Regular readers of the autism research scene will probably already known about Dr Van de Water's interest in immune function (including inflammation) and autism previously talked about on this blog (see here for example). She is quoted talking about: "kids who get fevers more often and for longer periods of time may also have higher levels of inflammation". Mmm...

Whilst the Khandaker results are very interesting, as always, I do think there is more to do in this area. Aside from correlating spot analyses of inflammatory markers with events almost a decade later, IL-6 is portrayed as the bad guy in this scenario based on it's connection to systemic inflammation. But things are rarely so straight-forward as per the paper by Scheller and colleagues [3] (open-access) on the two faces of IL-6. To boil depression and PEs solely down to childhood inflammation also does little to say how complex such conditions are; something which Dr Khandaker's other research has also hinted at. I've also talked about other correlates and things like depression including vitamin D levels (see here), certain bacteria (see here) and possibly even something like dietary components (see here) showing potential involvement. It's complicated as I said.

Oh and headlines like 'Could aspirin and ibuprofen help fight depression?' are perhaps a little premature at this time... but at least they didn't suggest paracetamol.

Music to close. MAGIC! and Rude (Marry that Girl!).

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[1] Khandaker GM. et al. Association of Serum Interleukin 6 and C-Reactive Protein in Childhood With Depression and Psychosis in Young Adult Life. JAMA Psychiatry. 2014. August 13.

[2] Khandaker GM. et al. A population-based longitudinal study of childhood neurodevelopmental disorders, IQ and subsequent risk of psychotic experiences in adolescence. Psychol Med. 2014 Apr 25:1-10.

[3] Scheller J. et al. The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 2011; 1813: 878-888.

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Golam M. Khandaker, Rebecca M. Pearson, Stanley Zammit, Glyn Lewis, & Peter B. Jones (2014). Association of Serum Interleukin 6 and C-Reactive Protein in Childhood With Depression and Psychosis in Young Adult Life JAMA Psychiatry : doi:10.1001/jamapsychiatry.2014.1332