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

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