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William Nikolic: Homocysteine as a Mentalhealth Signal
May 4, 2026, 17:48

William Nikolic: Homocysteine as a Mentalhealth Signal

William Nikolic, Associate Director MSL at Alfasigma USA, shared a post on LinkedIn about a recent article by Fatemeh Moradi published in European Journal of Clinical Investigation, adding:

“Homocysteine is not just a cardiovascular marker. It’s a mentalhealth signal!

Here’s what large meta-analyses show about hyperhomocysteinemia and depression:

  • Depressed individuals show 2.53 µmol/L higher homocysteine vs. healthy controls.
  • Elevated homocysteine equal to 34% higher pooled risk of depression.
  • High homocysteine in later life equal to 70% higher odds of depression, and each 1 µmol/L increase raises risk by nearly 4%.

Neurovascular injury plus metabolic stress equal to compounded vulnerability.

Homocysteine sits at the center of the one-carbon cycle, methylation, neurotransmitter synthesis, and oxidative stress regulation.

When it rises, something upstream is often off:

  • Folate metabolism
  • B12 status
  • Methylation capacity
  • Inflammatory load

Depression is not just psychological.

It is biological.

And metabolism is part of the story.”

Title: The association between serum homocysteine and depression: A systematic review and meta-analysis of observational studies

Authors: Fatemeh Moradi, Keyhan Lotfi, Maryam Armin, Cain C T Clark, Gholamreza Askari, Mohammad Hossein Rouhani

William Nikolic

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