Аспирин снижает риск депрессии у людей с повышенным уровнем гомоцистеина

High total plasma homocysteine (tHcy) is associated with increased risk of cardiovascular events and depression. Consumption of B-vitamins (B6, B9 and B12) reduces tHcy by about 15%, but has equivocal effects on these health outcomes, suggesting that this relationship is either not causal or is confounded by other factors. The results of recent randomized trials suggest that antiplatelet therapy may confound these associations. This cross-sectional study assessed 3687 men aged 69–87 years for history of clinically significant depression (Geriatric Depression Scale 15 items 7) or a recorded diagnosis of depression in the Western Australian Data Linkage System, and collected information on the use of aspirin, B-vitamins and antidepressant medication, along with age, education, living arrangements, smoking history and medical comorbidity as assessed by the Charlson index. Participants donated a blood sample for the measurement of tHcy, and concentrations15 μmol l−1 were considered high. Five hundred and thirteen (13.9%) men showed evidence of depression, and of those 31.4% had high tHcy, 41.5% were using aspirin, 6.8% were consuming B-vitamins. Multivariate logistic regression showed that high tHcy was associated with increased odds of depression (odds ratio (OR)=1.60, 95% confidence interval (CI)=1.20–2.14), as was the use of B-vitamins (OR=1.95, 95% CI=1.21–3.13). There was a significant interaction between high tHcy and aspirin use (OR=0.57, 95% CI=0.36–0.91), but not between high tHcy and B-vitamin use (OR=0.80, 95% CI=0.26–2.46). The analyses were adjusted for smoking status, Charlson index and use of antidepressants. The results of this study indicate that older men with high tHcy who use aspirin have lower risk of depression, and suggest that antiplatelet therapy may be an effective preventive or management strategy for these cases. Randomized trials are required to confirm the antidepressant effect of aspirin in people with high tHcy.

Aspirin decreases the risk of depression in older men with high plasma homocysteine

Гомоцистеин и депрессия

Objective: Elevated serum levels of the amino acid homocysteine (HCY) are associated with a variety of diseases. To resolve conflicting findings in studies that suggest a relationship between elevated serum HCY levels and depression, we examined the relationship between HCY levels and depressive symptoms in the largest sample studied to date.
Method: We conducted a cross-sectional study of 11,757 participants (68.9% men) aged 20 to 90 years who completed preventive health examinations at the Cooper Clinic, Dallas, Texas, from 2007 to 2010. Currently experiencing depression was defined as a 10-item Center for Epidemiologic Studies Depression Scale (CES-D) score of ≥ 10. Serum HCY levels were obtained. Data were analyzed in a multiple logistic regression model of CES-D score of ≥ 10.
Results: When controlling for age, sex, body mass index, exercise, education, smoking, antidepressant use, creatinine level, alcohol use, and chronic medical conditions, elevated HCY was associated with 26% greater odds of currently experiencing depressive symptoms (P = .007) as defined by CES-D score.
Conclusions: In the largest sample examined to date, we found a significant positive relationship between elevated serum HCY levels and currently experiencing depressive symptoms. Given the cross-sectional nature of the study, it is not possible to determine the direction of the relationship or whether lowering HCY levels will ameliorate depressive symptoms. Thus, longitudinal studies are needed.

Relationship Between Serum Homocysteine Levels and Depressive Symptoms: The Cooper Center Longitudinal Study

Фолаты могут ослаблять негативную симптоматику у некоторых больных шизофренией

Folate supplementation appears to improve negative symptoms in schizophrenia patients, but only among those with a genetic variant of a folate-metabolizing enzyme, study results show.

It follows an earlier study by the same group showing that schizophrenia patients with low serum folate levels who were also homozygous for the 677C>T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene had severe negative symptoms.

Folate may improve negative symptoms in some schizophrenia patients

Альтернативные методы лечения шизофрении

Outside of India, however, Sen and Bose's observations on the use of rauwolfia for psychotic disorders were generally ignored. It was not until 1954, when Nathan Kline2 reported that both whole root rauwolfia extract and reserpine—a purer preparation—seemed to be somewhat more effective than placebo in more than 400 inpatients with neuropsychiatric conditions, that clinicians in the West took notice. Although it soon became apparent that phenothiazines were generally more tolerable than reserpine, and even after our enthusiastic embrace of clozapine, a respected 1991 review3 still listed reserpine as 1 of 8 reasonable, evidence-based treatment options for persons affected with the refractory symptoms of schizophrenia.

Two essential omega-3 fatty acids were compared in a 3-month, double-blind pilot study that found that augmentation with eicosapentaenoic acid (EPA) was superior to docosahexaenoic acid (DHA) or placebo in significantly reducing Positive and Negative Syndrome Scale (PANSS) scores; a second study using EPA suggested that supplementation with omega-3 for extended periods can benefit some patients even without antipsychotics.

On the other hand, a 16-week trial in 87 patients that compared 3 g/d of e-EPA with placebo found no difference in positive, negative, mood, or cognitive symptoms of schizophrenia.26 Noting that both the active and placebo groups had improvements in their PANSS ratings, these investigators evaluated the placebo response in 37 study participants and found that the 9.5% improvement in the PANSS total score usually occurred by the end of the first 2 weeks of participation, which argues for the value of a placebo run-in phase for future studies.27

Revisiting the initial findings of plasma membrane abnormalities, a 24-hour dietary recall in 146 community-dwelling patients with schizophrenia found little difference in dietary fatty acid and antioxidant intake from controls.28 However, a more elaborate evaluation of 72 subjects with schizophrenia found that the previously reported membrane lipid abnormalities could be explained by the fact that many of the subjects were smokers and had a significantly different omega-3 dietary intake from that of the controls.

Sitting between mainstream and alternative therapies are amino acid treatments, derived from the recognition that phencyclidine (PCP) psychosis was a better model for schizophrenia than the previous model of amphetamine psychosis. Among other observations, those with PCP intoxication presented with negative as well as positive symptoms. The mechanism of PCP's action was eventually elucidated; it specifically blocked the ion channel in NMDA (N-methyl-d-aspartate) glutamate receptors in the brain. An allosteric modulatory site on this complex receptor has been referred to as the "glycine" site, and its endogenous ligands plausibly may be the amino acids glycine, d-serine, and d-alanine (the latter 2 unusual d-forms present in the brain because of a racemizing enzyme).

A meta-analysis of short-term clinical trials found that treatment augmented with the agonists glycine and d-serine moderately reduced negative symptoms, while partial agonist d-cycloserine was less efficacious.35 These agents do not appear helpful for patients treated with clozapine, although glycine and d-serine may be effective for those being treated with olanzapine or risperidone.

High homocysteine levels have been found to interfere with NMDA receptors in animal studies. Neeman and coauthors46 reported finding lower plasma glycine levels and higher homocysteine levels in patients with schizophrenia compared with controls, and glycine levels correlated with increased negative symptoms. Findings of higher homocysteine levels in patients with schizophrenia may often involve folate-deficient dietary choices, obesity, or cigarette smoking, but one study found that these variables explained relatively little of the high homocysteine levels

Oxidative stress/free radical damage has been proposed as mediating pathology in various neuropsychiatric disorders, including schizophrenia. Small initial trials failed to shed adequate light on the value of ascorbic acid (vitamin C) in the treatment of schizophrenia,49,50 although a recent 8-week study reported significant improvement in Brief Psychiatric Rating Scale scores for those receiving an adjunctive 500 mg/d dosage of vitamin C.51 In addition, one study25 with positive findings used adjunctive omega-3 with vitamins C and E. Additional studies are needed to evaluate this approach.

Another putative adjunctive antioxidant strategy in schizophrenia involves the addition of EGb, a standardized Ginkgo biloba extract. Although several studies have shown fairly consistent preliminary results,52-54 larger and more definitive studies are still needed.

The higher rates of schizophrenia in those born in winter or spring, and the reported association between prenatal exposure to the 1945 famine of the "Dutch Hunger Winter" and later development of schizophrenia in offspring may be rationalized by the hypothesis that schizophrenia is more prevalent in those who have had vitamin D deficiency during the first year of life. The results of a 1966 study of a Finnish-birth cohort lend support to this theory.63 However, as there were very few children not given the then-recommended vitamin D supplement, and since not receiving the supplement may have been associated with other plausible risk factors, this single study provides only weak support for this interesting idea.

Treatment Resistance in Schizophrenia: The Role of Alternative Therapies