Brain derived neurotrophic factor (BDNF) release from the human brain in patients with type 2 diabetes—possible influence of venous anatomy and comorbid major depressive disorder

Abstract

To the Editor: Krabbe et al. [1] recently examined whether brain-derived neurotrophic factor (BDNF) plays a role in human glucose metabolism. By examining a large cohort of subjects with or without type 2 diabetes in the presence or absence of obesity they concluded that plasma BDNF levels were reduced in patients with type 2 diabetes and were inversely associated with fasting plasma glucose levels. The authors, using direct internal jugular vein blood sampling, extended this observation by apparently demonstrating that elevated blood glucose levels inhibit the release of BDNF from the human brain. While the authors’ observations shed new light into a possible role of BDNF in type 2 diabetes, there are a number of points that require further clarification. The authors propose that decreased BDNF may be a pathogenic factor linking depression and type 2 diabetes, yet, in their study [1], they did not adequately screen their cohort for the comorbid presence of major depressive disorder (MDD). Neurotrophic factors are thought to play an important role in the aetiology of MDD [2, 3]. Given that a substantial proportion of people with major depressive disorder do not receive adequate treatment [4], using ‘current intake of antidepressive medication’ as a surrogate for screening for MDD is inadequate. Indeed, the authors, in their diabetes cohort, document five cases out of 96 as currently taking antidepressants. Given that the presence of diabetes doubles the odds of comorbid MDD [5] the authors may have underestimated the prevalence of MDD. Without recourse to some type of venous scanning methodology it is difficult to reconcile the precise origin of BDNF in the internal jugular venous effluent. Indeed, the cerebral venous sinus drainage is asymmetrical, with the superior sagittal sinus predominantly draining the cerebral hemispheres [6]. As the sinus nears the internal occipital protuberance it deviates to one side or the other and forms the transverse sinus, which in turn, becomes an internal jugular vein. Investigations from our group indicate that the superior sagittal sinus drains into the right internal jugular vein in approximately 50% of individuals [7–9]. Using technetium blood flow scans it is possible to determine the route of drainage of the superior sagittal sinus [7]. Importantly, cerebral neurotransmitter turnover, in some instances, also displays asymmetry [7, 8], making it possibly important to differentiate between cortical and subcortical drainage. Whether internal jugular BDNF overflow is markedly different between cortical and subcortical brain regions is not known. Using percutaneously placed venous sampling catheters positioned high in an internal jugular vein, Krabbe and colleagues state that they measured ‘jugular–arterial (Av) concentration differences’ as an index of brain production. Accordingly, using this formula, positive veno-arterial concentration gradients would indeed indicate an overflow of BDNF from the brain into the circulation. Contrary to the Diabetologia (2007) 50:2027–2028 DOI 10.1007/s00125-007-0756-3