Altered interactions of tryptophan metabolites in first-episode neuroleptic-naive patients with schizophrenia.

Schizophrenia is characterized by complex and dynamically interacting perturbations in multiple neurochemical systems. In the past, evidence for these alterations has been collected piecemeal, limiting our understanding of the interactions among relevant biological systems. Earlier, both hyper- and hyposerotonemia were variously associated with the longitudinal course of schizophrenia, suggesting a disturbance in the central serotonin (5-hydroxytryptamine (5-HT)) function. Using a targeted electrochemistry-based metabolomics platform, we compared metabolic signatures consisting of 13 plasma tryptophan (Trp) metabolites simultaneously between first-episode neuroleptic-naive patients with schizophrenia (FENNS, n=25) and healthy controls (HC, n=30). We also compared these metabolites between FENNS at baseline (BL) and 4 weeks (4w) after antipsychotic treatment. N-acetylserotonin was increased in FENNS-BL compared with HC (P=0.0077, which remained nearly significant after Bonferroni correction). N-acetylserotonin/Trp and melatonin (Mel)/serotonin ratios were higher, and Mel/N-acetylserotonin ratio was lower in FENNS-BL (all P-values<0.0029), but not after treatment, compared with HC volunteers. All three groups had highly significant correlations between Trp and its metabolites, Mel, kynurenine, 3-hydroxykynurenine and tryptamine. However, in the HC, but in neither of the FENNS groups, serotonin was highly correlated with Trp, Mel, kynurenine or tryptamine, and 5-hydroxyindoleacetic acid (5HIAA) was highly correlated with Trp, Mel, kynurenine or 3-hydroxykynurenine. A significant difference between HC and FENNS-BL was further shown only for the Trp-5HIAA correlation. Thus, some metabolite interactions within the Trp pathway seem to be altered in the FENNS-BL patients. Conversion of serotonin to N-acetylserotonin by serotonin N-acetyltransferase may be upregulated in FENNS patients, possibly related to the observed alteration in Trp-5HIAA correlation. Considering N-acetylserotonin as a potent antioxidant, such increases in N-acetylserotonin might be a compensatory response to increased oxidative stress, implicated in the pathogenesis of schizophrenia.

Fruit and vegetable intake and knowledge increased following a community-based intervention in older adults in Georgia senior centers.

Our purpose was to evaluate a community-based fruit and vegetable intervention conducted in rural and urban areas of Georgia. Participants were a convenience sample from Georgia senior centers that completed a pre-test, the intervention, and a post-test (N = 558, mean age = 75, 83% female, 47% white, 53% black). The 4-month intervention had eight sessions focused on practical ways to increase intake of fruits and vegetables at meals and snacks and included physical activity. Pre- and post-tests examined self-reported intakes of fruits and vegetables at breakfast, lunch, the evening meal, and snacks, knowledge of recommended intakes, and barriers to intake. Following the intervention, the number of participants reporting consumption of at least 7 servings of fruits and vegetables daily increased by 21-percentage points (P < or = 0.001), knowledge that 7 to 10 servings of fruits and vegetables are recommended daily (for 1,600 to 2,200 calories) increased from 7% to 57% (P < or = 0.001), and three barriers to fruit and vegetable intake decreased (P < or = 0.05): "difficulties with digestion," "too many are recommended," and "too much trouble." Regression analyses indicated that increased intake following the intervention was independently associated with living in more urban rather than rural areas, improved knowledge of intake recommendations, decrease in perception of cost as a barrier, and increase in digestive problems as a barrier (P < or = 0.05). These results provide an evidence base for the effectiveness of this community intervention for improving knowledge and intake and decreasing barriers to fruit and vegetable intake in older adults.

Oxidative damage and schizophrenia: an overview of the evidence and its therapeutic implications.

Free radicals are highly reactive chemical species generated during normal metabolic processes. which in excess can lead to membrane damage. Elaborate antioxidant defence systems exist to protect against oxidative stress. There is accumulating evidence of altered antioxidant capacity in schizophrenia. Membrane dysfunction can be secondary to free radical-mediated pathology, and may contribute to specific aspects of schizophrenic symptomatology and complications of its treatment. Specifically, free radical-mediated abnormalities may contribute to the development of a number of clinically significant consequences, including prominent negative symptoms, tardive dyskinesia, neurological 'soft' signs and parkinsonian symptoms. Our previous results showing altered membrane dynamics and antioxidant enzyme activities in schizophrenia, and findings from other investigators, are consistent with the notion of free radical-mediated neurotoxicity in schizophrenia. These findings provide a theoretical basis from which the development of novel therapeutic strategies such as fatty acid and antioxidant supplementation can occur in the future.

Membrane phospholipid abnormalities in postmortem brains from schizophrenic patients.

Previous studies in schizophrenia have shown alterations in membrane phospholipids and polyunsaturated fatty acids. However, these studies have primarily examined peripheral (non-neuronal) cell types. The purpose of the present study was to examine whether the membrane deficits seen in peripheral tissues are also observed in the brain. The caudate was the primary region of interest for this study. Using high-pressure liquid chromatography in conjunction with an evaporative light-scattering detector, we first measured the level of various membrane phospholipids (PL) in schizophrenic (n=11) and control groups with (n=7) and without (n=14) other mental disorders. Polyunsaturated fatty acids (PUFAs) were then determined by capillary gas chromatography. Within groups, there are no significant correlations between membrane PL levels and other collection and demographic parameters including age, postmortem interval, storage time and brain weight. Significantly lower amounts of phosphatidylcholine and phosphatidylethanolamine were found in postmortem brain tissue from schizophrenic patients than in those from control groups, even after accounting for potential confounds. In addition, strong reductions of total PUFAs and saturated fatty acids were found in schizophrenic brains, relative to control brains. Specifically, the reduced PUFAs were largely attributable to decreases in arachidonic acid (AA) and, to a lesser extent, its precursors, linoleic and eicosadienoic acids. There are no significant differences between the control groups with and without other mental disorders. The present findings suggest that deficits identified in peripheral membranes may also be present in the brain from schizophrenic patients. Such a deficit in membrane AA may contribute to the many biological, physiological, and clinical phenomena observed in schizophrenia.

Human plasma glutathione peroxidase and symptom severity in schizophrenia.

BACKGROUND: Previous studies have shown impaired antioxidant defense system in schizophrenia, including alterations in glutathione peroxidase (GSH-Px) activity in erythrocytes. There exists a related enzyme, human plasma GSH-Px (hpGSH-Px), that has not been previously examined in schizophrenia. METHODS: An enzyme-linked immunoassay was used to determine hpGSH-Px levels in male schizophrenic patients (n = 39), using a within-subject, on-off haloperidol (HD) treatment design, compared with age- and gender-matched normal control subjects (n = 37). RESULTS: hpGSH-Px was not significantly different between normal control subjects and patients, consistent with our previous findings in erythrocyte GSH-Px. There were no significant treatment effects. hpGSH-Px was significantly and positively correlated with psychosis rating scores in patients both on and off HD treatment. CONCLUSIONS: Although not different from normal controls, hpGSH-Px levels in patients may reflect oxidative stress associated with greater psychosis severity. The present findings thus suggest that schizophrenic patients, without obvious increase of endogenous antioxidant enzymes (e.g., hpGSH-Px), may be at risk for oxidative damage.

Free radical pathology in schizophrenia: a review.

There is evidence that free radicals are involved in membrane pathology, and may play a role in schizophrenia. Free radicals are reactive chemical species generated during normal metabolic processes, and, in excess, can damage lipids, proteins, and DNA. Regions of high oxygen consumption, lipid content, and transition metals are at particular risk. Hence, neuronal membranes are uniquely vulnerable to radical-mediated damage. Elaborate antioxidant defense systems exist to protect against oxidative stress. In schizophrenia there is evidence for dysregulation of free radical metabolism, as detected by abnormal activities of critical antioxidant enzymes and other indices of lipid peroxidation in plasma, red blood cells, and cerebrospinal fluid. Such abnormalities have been associated with tardive dyskinesia, negative symptoms, neurological signs, poor premorbid function, and CT scan abnormalities. Studies to date have generally been exploratory. Further elucidation of the role of free radicals and antioxidants in schizophrenia and its treatment will require systematic investigation.