[teejai]

http://www.medwire-news.md/47/74178/..._patients.html

Pro-inflammatory gene signature found in bipolar patients
By Andrew Czyzewski
09 April 2008
Arch Gen Psychiatry 2008; 65: 395-407

MedWire News: Patients with bipolar disorder show elevated expression of a set of genes involved in the inflammation process, report Dutch researchers who claim that this "proinflammatory gene signature" may be of predictive value in at-risk individuals.

The findings also support the so-called "macrophage-T-cell theory" of mood disorders, where an inflammatory response is postulated to induce the production of cytokines capable of destabilizing brain function and causing major mood disturbances, Hemmo Drexhage (Erasmus Medical Centre, Rotterdam) and colleagues claim.

Previous studies had hinted toward this theory by showing that patients with mood disorders display increased serum, saliva, and cerebral spinal fluid levels of several pro-inflammatory compounds.

To investigate further, the researchers performed gene microarray analysis comparing messenger RNA expression levels in the monocyte cells of five lithium-naïve bipolar patients with six mentally healthy controls.

Drexhage and colleagues found 71 genes that were differentially regulated more than two-fold between patients and controls.

Among these 71 genes was a panel of 19 markers known to be involved in either inflammatory, trafficking, survival, or mitogen-activated protein kinase (MAPK) pathways.

The researchers attempted to validate this putative pro-inflammatory gene signature in an independent cohort of 42 bipolar patients (half of whom were euthymic) and 38 mentally healthy controls.

Twenty-three (55%) of the 42 bipolar patients had a positive signature test result versus seven (18%) of 38 healthy controls.

Interestingly, during a manic episode, the expression of two genes, MAPK6 and chemokine ligand-2, was significantly increased in manic versus euthymic bipolar patients; while during depressive episodes, expression of these genes was raised in addition to that of interleukin-6, pentraxin-related gene-3, epithelial membrane protein- 1, and bcl-2-related protein- A1.

Notably, the expression of 11 genes was reduced in 24 patients who were using lithium and eight who were on antipsychotics, relative to patients who were not using these drugs.

Finally, the researchers tested the pro-inflammatory gene signature in a separate cohort of 54 young adults with a bipolar parent, of whom 13 had a mood disorder themselves and three developed a disorder during a follow-up period.

Eleven (85%) of the 13 affected individuals and all three (100%) of the late-onset bipolar patients were positive for the pro-inflammatory signature, compared with 45% of the non-affected offspring.

"This coherent set of genes opens new avenues for biomarker development with possibilities for disease prediction in individuals genetically at risk and for the subclassification of bipolar patients who could possibly benefit from anti-inflammatory treatment," Drexhage and team conclude.

Free abstract

[RelientK]

Thanks for the post and link.

I believe very strongly in this theory of cytokine immune involvement in mood disorders.

As a BP II patient, I have had quite a few blood tests done. One of them showed that I had an immune response which got more intense over the course of 6 months (while I was in a mood episode). This was a positive titer for ANA.

Another interesting cytokine note involves Green Tea. Green Tea is known to affect the expression of cytokine genes. I drank Green Tea while I was at my lowest and it actually raised my mood rather quickly. Unfortunately, it effect was short lived...but interesting nonetheless. This wasn't a fluke thing. I repeated this several times over the course of a week.

Cheers