Elevated Homocysteine Levels in Young Male Patients With Schizophrenia

Ben Gurion University of the Negev, Beersheva, Israel.
American Journal of Psychiatry (Impact Factor: 12.3). 11/2002; 159(10):1790-2. DOI: 10.1176/appi.ajp.159.10.1790
Source: PubMed


Elevated plasma homocysteine has been found to be a risk factor for Alzheimer's disease as well as cerebral vascular disease, suggesting that some risk factors can accelerate or increase the severity of several CNS disease processes. The authors measured plasma homocysteine levels in patients with chronic schizophrenia in their catchment area.
A one-way analysis of covariance with age and sex as covariates was performed on the total plasma homocysteine levels of 193 patients with schizophrenia compared with 762 subjects without the diagnosis of schizophrenia who were evaluated in a screening program for employee health.
The effect of schizophrenia was marked: the mean homocysteine level was 16.3 micro M (SD=11.8) in patients with schizophrenia compared with 10.6 micro M (SD=3.6) in healthy comparison subjects. The difference between groups was almost entirely attributable to the homocysteine levels of young male patients with schizophrenia.
Elevated levels of homocysteine in young male patients with schizophrenia could be related to the pathophysiology of aspects of this illness.

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    • "Although the one-carbon metabolism is a well-studied subject in depression and schizophrenia research (e.g. Bjelland et al., 2003; Kale et al., 2010; Kim et al., 2008; Levine et al., 2002; Muntjewerff et al., 2006), only two studies in PTSD patients exits wherein homocysteine was measured as an indicator of one-carbon metabolism activity. Both studies found higher homocysteine concentrations in male PTSD patients compared to healthy or trauma-exposed controls (Jendricko et al., 2009; Levine et al., 2008). "
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    ABSTRACT: Posttraumatic stress disorder (PTSD) is associated with increased morbidity and mortality through somatic conditions, particularly cardiovascular disease. The one-carbon metabolism in connection with the hypothalamic-pituitary-adrenal (HPA)-axis may be an important mediator of this increased cardiovascular risk. In a mixed-gender sample of 49 PTSD patients and 45 healthy controls we therefore investigated: (1) alterations in the one-carbon metabolism as reflected in fasting plasma concentrations of homocysteine, folate, vitamins B6 and B12, and (2) associations of these one-carbon metabolites with the HPA-axis hormones cortisol, dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S). After correction for confounders, PTSD patients had significantly elevated homocysteine (z=2.963, p=.003) compared to controls, but normal levels of folate, vitamin B6 and B12. Comorbid depression did not explain the observed higher homocysteine levels. Patients showed increased risk for moderate hyperhomocysteinemia (OR=7.0, χ(2)=7.436, p=.006). Additionally, homocysteine was associated with PTSD severity (z=2.281, p=.005). Moreover, all HPA-axis hormones were associated with folate in both patients and controls (all p's≤.011), while DHEA-S influenced folate in patients (z=2.089, p=.037). Our clinical sample is relatively small and therefore small-sized effects may have remained undetected. Our study indicates that: (1) the one-carbon metabolism is altered in PTSD patients, (2) earlier findings of higher homocysteine in male PTSD patients are generalized to female patients, (3) homocysteine is negatively associated with PTSD severity, and (4) HPA-axis alterations are associated with the one-carbon metabolism. Longitudinal studies are needed to determine whether elevated homocysteine levels reflect preexisting risk factors and/or consequences of psychological trauma. Copyright © 2015. Published by Elsevier B.V.
    Journal of Affective Disorders 06/2015; 184:277-285. DOI:10.1016/j.jad.2015.05.062 · 3.38 Impact Factor
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    • "Thus, moderate HHcy has been linked to cognitive impairment (Levine et al., 2002) and to a reduction in neurogenesis in mouse models (Rabaneda et al., 2008). "
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    Hippocampus 07/2014; 24(7). DOI:10.1002/hipo.22274 · 4.16 Impact Factor
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    • "Additionally, Hcy level may positively correlate with duration of untreated psychosis (DUP) (Ayesa-Arriola et al. 2012), the severity of negative symptoms (Goff et al. 2004; Petronijevic et al. 2008; Bouaziz et al. 2010) and cognitive deficits (Levine et al. 2006). Some authors suggest that mainly young schizophrenia males demonstrate elevated Hcy levels (Levine et al. 2002). In the recent study by Geller et al. (2013), it was found that siblings of schizophrenia patients are also characterized by elevated Hcy level. "
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    ABSTRACT: Accumulating evidence indicates that elevated homocysteine (Hcy) level occurs in first-episode schizophrenia (FES) patients. We included 56 FES patients and 53 healthy controls (HC). Plasma level of Hcy was significantly higher in FES patients than HC (p = 0.044). In addition, plasma levels of high-density lipoproteins (HDL) and folate were significantly lower in FES than in HC (p < 0.001). Positive family history of schizophrenia was associated with lower plasma HDL (p = 0.041) and vitamin B12 (p = 0.017), as well as higher level of Hcy (p = 0.017). Patients with FES, who abused cannabis, had higher levels of Hcy (p = 0.017), as well as lower levels of vitamin B12 (p = 0.017) and HDL (p = 0.041). Plasma Hcy negatively correlated with duration of untreated psychosis (r = -0.272, p = 0.042). There was a positive correlation between Hcy level and the severity of negative symptoms (r = 0.363, p = 0.006) and general psychopathology (r = 0.349, p = 0.008) assessed using Positive and Negative Syndrome Scale (PANSS). Vitamin B12 level was negatively associated with the severity of negative symptoms (r = -0.406, p = 0.002), while folate level negatively correlated with general psychopathology score (r = -0.365, p = 0.006) in PANSS. These results indicate that the severity of one-carbon metabolism alterations and HDL deficiency might be associated with family history of schizophrenia and cannabis abuse. Lower vitamin B12 and folate along with elevated Hcy may influence the severity of FES psychopathology.
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