Glutamate and corticotropin releasing hormone (CRH) are pro-stress neurotransmitters and may be altered in the plasma and cerebrospinal fluid (CSF) of persons with major depressive disorder (MDD). The goal of this study was to compare the CSF levels of glutamate, glutamine and CRH between patients with depression and healthy controls.

Eighteen patients with MDD and 25 healthy controls underwent a lumbar puncture (LP); CSF samples were withdrawn and assays were done for glutamine, glutamate, and CRH. Patients with MDD underwent 8 weeks of treatment with the antidepressant venlafaxine and then had a repeat LP post treatment.

Patients had higher baseline scores on depression and suicide rating scales and those scales improved significantly post-treatment. Higher suicidal ratings at baseline were correlated with higher glutamate levels (p=0.016). There were no significant differences between the control and patient group in any baseline CSF measures of glutamate (p=0.761), glutamine (p=0.226) or CRH (p=0.675). Despite no significant change in glutamate (p=0.358) and CRH (p=0.331) in the treatment group, there was a post-treatment decrease in glutamine (p=0.045) in patients.

There was a small sample size, age discordance between patients and controls, lack of a follow-up LP in controls, absence of dexamethasone suppression testing, and fluctuating sample sizes among various measures.

Although no significant differences were noted between patients and controls at baseline there was an association of high CSF glutamate and suicidal ideation and lower glutamine post-treatment which may be correlated with attenuation of dysfunction in the glutamatergic system after antidepressant treatment.