Thursday, 8 November 2012

Schizophrenia, central canal and particles?

Canals, we have quite a few of them here in Blighty. People cruise them on their canal boats to slowly take in the rich countryside and reminisce over their important role in our Industrial past. Venice has also quite a few canals, as was wrongly believed about Mars quite a few years ago.
Canals not camels @ Wikipedia 

A very different kind of canal is the topic of today's post, the central canal, an important part of our body given that it houses cerebrospinal fluid (CSF), the stuff our brains float around in. Just as a matter of interest, you might be interested to read about the lateral ventricles ("the chambers that hold cerebrospinal fluid") of Temple Grandin's brain as per some quite recent news.

Anyway, I'm no expert on the central canal and CSF, but someone close to me has advised me that it's a very important system and not to be tampered with too much as per the cautions which follow intrathecal compounding and administration of drugs, including baclofen, a previous resident on this blog.

I don't know if it specifically relevant but the recent outbreak of fungal meningitis in the United States thought due to contaminated epidural steroid injections might also serve as a reminder of how delicate this region of the body really is.

As a diagnostic medium, CSF is also pretty useful. And whilst getting to CSF is quite invasive (lumbar puncture), there have been more than a few suggestions of some potentially important CSF findings in cases of autism.

With all this in mind, I was very interested in the findings reported by Johansson and colleagues* (open-access) on the presence of microscopic particles detected in quite a few samples of CSF from people diagnosed with schizophrenia, schizoaffective disorder or bipolar disorder. Interested because particles like this really ought not to be in CSF, which is a sterile environment, given the juicy medium of glucose and protein that would be more than conducive for pathogen growth.

Back to those microscopic particles, this is not the first time that such an observation has been reported. Wetterberg and colleagues** reported on micrometre sized particles in quite a few CSF samples from participants with schizophrenia (compared with only 2/38 controls). Båve and colleagues*** similarly reported on spherical and thread-like particles being present in CSF samples in over 75% of their cohort diagnosed with bipolar disorder (compared with no such findings in controls).

A few points from the Johansson paper:

  • One hundred and two participants in total; 65 healthy controls, 21 monozygotic and 16 dizygotic twins variably diagnosed with schizophrenia, schizoaffective disorder or bipolar disorder.
  • Blood and CSF samples were collected. The CSF samples were collected in such a way that two samples were available for examination by scanning electron microscopy (SEM) post-sample size exclusion filtering and coating.
  • Results: well, the particles were detected and "strongly associated with schizophrenia and bipolar disorder" whereas being comparatively rarely detected in controls. Being a co-twin seemed to be an important factor; that and the fact that medication status, alcohol abuse, anxiety disorders, body mass index (BMI) and inflammatory markers were not seemingly associated with findings.

So, what are these particles and what do they potentially represent? Good question and at the moment, its more speculation than fact. In true Bruce Forsyth fashion (its a Brit thing), higher than a protein, lower than a cell (you get nothing for a pair... not in this game) size-wise.

A long quote from the authors: "The mainly spherical form points to a high lipid content of the particles, which may reflect an intense apoptosis of lipid rich cell membranes not being cleared rapidly enough by the immune mechanism in the central nervous system". Issues with apoptosis (programmed cell death) eh? Makes you wonder whether they might want to look as those executioner molecules, the caspases in these cohorts. OK, the literature already has to some degree as per articles like this one and this one with some potentially relevant findings reported.

I've a feeling that this won't be the last time we hear about peculiar microscopic particles in CSF. The question is outside of the cases of schizophrenia, bipolar disorder and indeed amyotrophic lateral sclerosis (ALS) examined, whether the hole gets any deeper for particles in CSF?


* Johansson V. et al. Microscopic particles in two fractions of fresh cerebrospinal fluid in twins with schizophrenia or bipolar disorder and in healthy controls. PLoS One. 2012 ;7: e45994.

** Wetterberg L. et al. Micrometer-sized particles in cerebrospinal fluid (CSF) in patients with schizophrenia. Neurosci Lett. 2002; 329: 91-95.

*** Båve U. et al. Micrometer-sized thread-like and/or spherical particles in the first fraction of cerebrospinal fluid in patients with bipolar disorder. Bipolar Disord. 2010; 12: 298-305.

---------- Johansson V, Nybom R, Wetterberg L, Hultman CM, Cannon TD, Johansson AG, Ekman CJ, & Landén M (2012). Microscopic particles in two fractions of fresh cerebrospinal fluid in twins with schizophrenia or bipolar disorder and in healthy controls. PloS one, 7 (9) PMID: 23049916