Although the treatment of unipolar depression most often targets monoamine depletion, no differences exist in serotonin or noradrenalin metabolite levels between patients with unipolar depression and healthy controls.
Based on cerebrospinal fluid (CSF) analysis, patients with unipolar depression have an imbalance in glutamatergic and gamma-aminobutyric acid, increased hypothalamic-pituitary-adrenal axis activity, increased inflammation, and decreased neuroplasticity.
Putting It Into Practice
According to the WHO, depression affects 260 million people worldwide, and the incidence of depression is on the rise, having increased nearly 15% over the past decade.
Missed and incorrect diagnoses, ineffective treatment, and unpredictability of recurrences lead to increased disability and decreased quality of life.
Now, a panel of CSF biomarkers has been identified which can guide the treatment of depression by normalizing the altered pathophysiologic mechanisms.
Why this study matters
It is well-known that < 40% and 60% of depressed patients have remission of symptoms with the first and second medications prescribed, respectively, which may be explained by the multifactorial pathogenesis underlying depression and the complex neurocircuitry involved.
A meta-analysis of 97 published studies involving CSF biomarkers in patients > 18 years of age was undertaken using the PRISMA and MOOSE reporting guidelines.
Results and conclusion
Of 165 CSF biomarkers evaluated, the CSF levels of IL-6, total protein, and cortisol were increased, while the CSF levels of homovanillic acid, γ-aminobutyric acid, somatostatin, brain-derived neurotrophic factor, amyloid-β 40, and transthyretin were lower in patients with unipolar depression compared to healthy controls.
Mousten IV, Sørensen NV, Christensen RHB, Benros ME. Cerebrospinal fluid biomarkers in patients with unipolar depression compared with healthy control individuals: a systematic review and meta-analysis. JAMA Psychiatry. 2022;79(6):571-581.