What is the clinical significance of hyperhomocysteinemia and psychotic episodes?

By Scott Cunningham, MD, PhD
Published December 5, 2022

Key Takeaways

  • The serum levels of homocysteine were shown to be elevated during the first psychotic episode in patients with schizophrenia who were not taking anti-psychotics.

Putting It Into Practice

Oxidative stress and inflammation are known to be involved in the onset and progression of several psychiatric disorders. Total oxidative stress damages DNA, proteins, and fatty acids, which in turn leads to brain abnormalities in patients with psychoses.

Whether homocysteine is central to the oxidative load or a mediator via the transsulfuration pathway warrants further study. Indeed, it is possible that homocysteine is a potential biomarker for incipient psychoses in patients at risk for schizophrenia.

Why this study matters

The pathophysiology underlying schizophrenia has not been established, although there is evidence that psychotic episodes reflect an oxidative stress imbalance, as has been demonstrated in other neurodegenerative disorders. Homocysteine is a pro-oxidant and a metabolite of methionine that interacts with N-methyl-D-aspartate receptors and inflammatory cytokines.

As shown in the current study, homocysteine levels are elevated in patients with schizophrenia during the first psychotic episode, thus adding support to the complex associations between homocysteine, oxidative stress, and inflammation.

Study design

One hundred nineteen patients with schizophrenia with first psychotic episode and not taking anti-psychotics and 81 healthy controls were enrolled in the study. Homocysteine levels were measured. Symptom severity was determined using the Positive and Negative Syndrome Scale (PANSS).

Results and conclusion

Homocysteine levels were elevated in patients with schizophrenia not taking anti-psychotics during the first psychotic episode; homocysteine levels were higher in males than females. The homocysteine levels correlated with the PANSS general psychopathology subscale and total scores. Elevated homocysteine levels were unrelated to age and body mass index.

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