Understanding the Molecular Mechanisms Underpinning Gene by Environment Interactions in Psychiatric Disorders: The FKBP5 Model – Biological Psychiatry


This is a very interesting article which puts it together (genes and environment) for bipolar, depression, and schizophrenia.
Adds to literature on glucocorticoid receptors, heat shock protein, and epigenetic methylation of DNA.

FKBP5 is a gene common to all persons which mediates the interaction between stress/adversity and many different psychiatric disorders.  This model offers a common pathway which is “TRANSDIAGNOSTIC” and a target for universal treatment.  It involves the stress system.  Basically early adversity leads to less methylation and altered epigenetic, leading FKBP5 increased responsively (and higher FKBP5 evels) to future stressors.  It is the molecular model of stress induction, a transdiagnostic notion.   Now, certain FKBP5 genetic variants are more susceptible that others to this effect, with some variants causing high cortisol levels more than others.  It is  viscious circle:  higher cortisol leads to more demethylation of glucorticoid related DNA, leading to more responsiveness, etc.  The measurement of rising FKBP5 is diagnostic of this process.  The rising FKBP5 and higher cortisol leads to lasting changes in brain anatomy and structure, leading to more psychiatric illness.  FKBP5 is a biomarker. Treatment with FKBP51 antagonists is on the horizon.



Biological Psychiatry 2018,Vol 83. May.

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