Brain Network Function improved by Higher BDNF relative to Klotho Variant Status

Here in abstract below is the evidence for the Klotho gene variant rs1207568 homozygous requiring highest levels of BDNF, the absence of Klotho gene variant requiring intermediate levels of BDNF and the heterozygous Klotho variant require lower levels of BDNF to have normal mood (and cognition.)

"we confirmed a significant improvement of depressive symptoms after treatment in patients carrying at least one minor allele at rs1207568 and a worse response in patients homozygous for the minor allele at rs9536314. Our results were the first that suggested a possible role of KL in the complex pathway of SSRI response in late-life MDD."

Klotho polymorphism affects SSRI response in late life depression.

GT. high response.

TT  normal response

GG. Low response.

Klotho gene /normal gene as heterozygous pair amplifies BDNF effect via GluN2b receptor increase.  Absence of this amplifier status for BDNF then requires more BDNF to achieve an antidepressant response in TT homozygous normal gene and even higher BDNF levels for homozygous GG.

Hence my statement,  all patients need BDNF but some need it more is confirmed.  Depression is a low BDNF state.  SSRI work to increase BDNF levels.  Response to SSRI is therefore a function of Klotho variant gene status and BDNF level achieved with treatment.

The addition of lifestyle to optimally raise BDNF will improve response rates above SSRI alone.  Higher BDNF levels further improve mood, memory and metabolism.

http://link.springer.com/article/10.1007/s12035-016-9711-y