A reduced concentration of brain interstitial amino acids is associated with depression in subarachnoid hemorrhage patients

Abstract

The amino-acids tryptophan, phenylalanine and tyrosine seem to play an important role in the pathophysiology of depressive disorders. We measured daily brain extracellular levels of these amino-acids using cerebral microdialysis (CMD) and high performance liquid chromatography in 26 consecutive subarachnoid hemorrhage (SAH) patients and associated them with the presence of depressive disorders. Patients were grouped as follows: medical history of depression (prior to SAH), antidepressant intake 12 months after SAH (but not before), or neither. CMD-tryptophan, CMD-phenylalanine and CMD-tyrosine levels were significantly lower in patients with preexisting depressive disorders compared to those without depression (p\u2009<\u20090.01). Disease severity and SAH-related complications were not associated with amino-acid concentrations. We found a positive correlation between nutritionally administered and brain interstitial levels of tryptophan and phenylalanine in non-depressed patients (R\u2009=\u20090.26 and R\u2009=\u20090.24, p\u2009<\u20090.05), which was not present in patients with preexisting depression (p\u2009>\u20090.1). In conclusion, brain interstitial levels of tryptophan, phenylalanine and tyrosine measured in the context of the clinical management of SAH were significantly decreased in patients with a medical history of depression. This study supports the hypothesis that the availability of these neurotransmitter precursor amino-acids in the human brain may play an important role in the pathophysiology of depressive disorders.