We speculate that our findings of significant positive associations between BDNF and most symptom clusters in non-medicated patients including depression, somatization, anxiety and psychoticism may be explained through the involvement of BDNF in the hypothalamic-pituitary-adrenal (HPA) axis in depression: The psychological stress of depression, causes an upregulated level of BDNF that in turn causes an increase in corticotrophin-releasing hormone leading to glucocorticoid release [19]. Here, BDNF is linked to major depressive disorder.