Association between plasma homocysteine levels and cognitive deficits in Han Chinese patients with schizophrenia across age groups

Zhou, Sumiao; Huang, Yuanyuan; Feng, Yangdong; Li, Hehua; Wu, Kai; Yang, Mingzhe; Wu, Fengchun; Huang, Xingbing

doi:10.1038/s41598-021-99239-3

Cited by 7 publications

(11 citation statements)

References 27 publications

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“…Interestingly, the SZ, ATPD, ME, and MD groups did not show signi cant intergroup differences in Hcy levels in the omnibus analysis, suggesting that the psychopathophysiologies of these disorders share common neural substrates. Our results showed signi cantly higher serum Hcy levels in patients with SZ, ATPD, ME, and MD, in overall agreement with previous studies [5,6,19,23,24], but prior evidence for the involvement of Hcy in acute and transient psychotic disorders is poor. However, the majority of previous studies [6, 19,23,25] have shown that Hcy levels are elevated in patients with SZ.…”

Section: Sex Effect Of Serum Hcy Levelssupporting

confidence: 92%

“…Our results showed signi cantly higher serum Hcy levels in patients with SZ, ATPD, ME, and MD, in overall agreement with previous studies [5,6,19,23,24], but prior evidence for the involvement of Hcy in acute and transient psychotic disorders is poor. However, the majority of previous studies [6, 19,23,25] have shown that Hcy levels are elevated in patients with SZ.…”

Section: Sex Effect Of Serum Hcy Levelssupporting

confidence: 92%

“…Chinese people [19,23]. Kevere and co-workers observed that mean Hcy levels were elevated in patients with SZ, and patients in the acute phase had higher levels than did those in the remission phase [26].…”

Section: Sex Effect Of Serum Hcy Levelsmentioning

confidence: 99%

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Homocysteine levels in first-episode, drug-naïve patients with psychiatric disorders

Fan

Zhao

Yun

et al. 2023

Preprint

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A high homocysteine (Hcy) level is reportedly a risk factor for schizophrenia, depression, bipolar disorder, and other psychiatric disorders. The purpose of this study was to examine Hcy levels in first-episode, drug-naïve inpatients with psychotic symptoms and a diversity of psychiatric diseases to further investigate the association between Hcy levels and psychiatric disorders. In this study, we enrolled 247 psychiatric patients, aged 18–40year. Seventy-five were diagnosed with schizophrenia, 48 with acute and transient psychotic disorders, 36 with manic episodes with psychosis, 32 with major depressive episodes with psychosis, and 56 healthy controls. Serum Hcy levels were measured by enzyme cycle method. Concentration of Hcy levels > 15 µmol/L was defined as hyperhomocysteinemia. Hcy levels were significantly higher in first-episode and drug-naïve psychotic patients compared to healthy controls (F = 12.778, P < 0.001). In the psychiatric disorder groups, Hcy levels were significantly higher in males and females (P < 0.05) in schizophrenia, acute and transient psychotic disorder, and major depressive disorder, but not in mania (P > 0.05). However, serum Hcy levels were not significantly different among the psychiatric disorder groups (F = 1.549, P = 0.227). The prevalence of hyperhomocysteinemia was 37.3% for schizophrenia, 45.8% for acute and transient psychotic disorders, 66.7% for manic episodes with psychosis, and 37.5% for major depressive episodes with psychosis. Hyperhomocysteinemia was more frequent in manic episodes with psychosis than in the other groups (χ2 = 10.026, P = 0.018). Moreover, binary logistic regression showed that male sex was an independent risk factor for hyperhomocysteinemia (OR = 6,577, 95% CI = 3.398–12.731, P < 0.001). These results suggest that first-episode, drug-naïve patients with the psychiatric disorders studied here have higher Hcy levels than does the general population, and those at greatest risk are men. However, we observed no differences in Hcy levels across different psychotic disorders. It has been suggested that elevated Hcy level contributes to the pathogenesis of psychiatric disorders, and our results clarify that it is likely an unspecific risk factor for psychiatric disorders generally.

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Section: Sex Effect Of Serum Hcy Levelssupporting

confidence: 92%

Section: Sex Effect Of Serum Hcy Levelssupporting

confidence: 92%

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Homocysteine levels in first-episode, drug-naïve patients with psychiatric disorders

Fan

Zhao

Yun

et al. 2023

Preprint

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“…A Mendelian randomisation study also showed that elevated plasma homocysteine levels could increase the risk of schizophrenia ( 15 ). Folate deficiency and hyperhomocysteinemia appears to be more specifically associated with negative symptoms and cognitive alterations in this population ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

Abnormalities in one-carbon metabolism in young patients with psychosis

et al. 2023

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IntroductionFolates, the main actors in one-carbon (C1) metabolism, are involved in synthesising monoamines and maintaining genomic stability. Previous studies support the association between C1 metabolism and schizophrenia. The main purpose of this study was to assess the prevalence of plasma folate, and/or vitamin B12 deficiencies and hyperhomocysteinemia in young patients with psychotic disorders.MethodsWe included young inpatients (15–30 years old) with psychosis between 2014 and 2017 from Sainte-Anne Hospital in Paris. Plasma folate, vitamin B12 deficiency and homocysteinemia dosages were done at admission. Clinical data were extracted retrospectively, and patients diagnosed with a first-episode psychosis (FEP), schizophrenia, schizoaffective disorder, or persistent delusional disorder were retained for the analysis.ResultsAmong the 334 inpatients, 188 (56%) had C1 dosages available (135 males; 53 females). From the 188 patients, 32% had a C1 abnormality. This abnormality reached 38% of FEP patients. The most frequent abnormality was folate deficiency: 21% of all patients and 27% of FEP. Lower levels of folates were found in males compared to females (p = 0.02) and were correlated with more severe disorder, as assessed by Clinical Global Impression – Severity (CGI-S; p = 0.009). Antipsychotic dosage was positively associated with B12 levels (p = 0.013) and negatively with homocysteinemia (p = 0.034).ConclusionOne-carbon metabolism anomalies in young patients with psychotic disorders are highly prevalent, reaching almost half of the patients with FEP. Potential protective effects from females and antipsychotics have emerged. These results spotlight the need for new therapeutic prospects, such as folate supplementation, to achieve personalised medical approaches to the early stages of psychotic disorders.

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“…Moreover, a randomized controlled trial found that plasma Hcy levels decreased significantly after risperidone treatment and PANSS scores decreased significantly in patients with SCZ ( 9 ), suggesting that high Hcy levels may be related to the pathogenesis of SCZ and clinical psychopathology. Besides, an increasing body of evidence suggests increased plasma Hcy levels are associated with an increased prevalence of more severe cognitive impairment in SCZ ( 10 ), MDD ( 11 ), and BD ( 12 ). Moreover, previous clinical trial suggested that serum Hcy levels were significantly decreased in patients with SCZ after risperidone treatment ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

The Effects of Plasma Homocysteine Level on the Risk of Three Major Psychiatric Disorders: A Mendelian Randomization Study

Xue²,

Wang³

et al. 2022

Front. Psychiatry

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BackgroundHigher homocysteine (Hcy) level has been suggested to be associated with major psychiatric disorders (MPDs), such as schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). We investigated the causal relationships between plasma Hcy level and MPDs risks using the Mendelian randomization (MR) method.MethodsWe selected 18 loci associated with plasma Hcy level from a large-scale genome-wide association study (GWAS) as genetic instruments. Genetic associations with SCZ, MDD, BD and BD subtypes (BD-I and BD-II) were extracted from several GWAS datasets from the Psychiatric Genomics Consortium. We used the Generalized Summary-data-based Mendelian Randomization (GSMR) method to estimate the associations of genetically predicted plasma Hcy levels with MPDs risks. We also performed inverse variance-weighted (IVW) analysis to verify the GSMR results and used MR-Egger regression and leave-one-out analysis to test the assumptions for a valid MR analysis.ResultsGenetically predicted plasma Hcy levels were associated with risks of SCZ (odds ratio [OR] = 1.12, PGSMR = 1.73 × 10−3) and BD-I (OR = 1.14, PIVW = 5.23 × 10−3) after Bonferroni correction. These associations were statistically significant when using IVW analysis (SCZ: OR = 1.11, PIVW = 2.74 × 10−3; BD-I: OR = 1.13, PIVW = 9.44 × 10−3). Furthermore, no significant horizontal pleiotropy was found by sensitivity analysis, and leave-one-out analyses showed no specific SNP affected the overall estimate. However, genetically determined plasma Hcy levels were not causally associated with MDD, BD, or BD-II risks.ConclusionOur results suggest that elevated plasma Hcy levels may increase the risk of SCZ or BD-I. Further randomized clinical trials are warranted to validate the MR findings in our study.

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Association between plasma homocysteine levels and cognitive deficits in Han Chinese patients with schizophrenia across age groups

Cited by 7 publications

References 27 publications

Homocysteine levels in first-episode, drug-naïve patients with psychiatric disorders

Homocysteine levels in first-episode, drug-naïve patients with psychiatric disorders

Abnormalities in one-carbon metabolism in young patients with psychosis

The Effects of Plasma Homocysteine Level on the Risk of Three Major Psychiatric Disorders: A Mendelian Randomization Study

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