Dr. Weeks’ Comment: Peer-reviewwed scientific articles declare the causative role of excessive inflammation in mental illness. Why doesn’t your psychiatrist teach you about anti-inflammation diets and taking safe anti-inflammatory remedies like SOUL?
“… A relationship between inflammation and schizophrenia has been supported by abnormal cytokine production and altered antioxidant status…”
Inflammation and Illnesses
Hum Exp Toxicol. 2013 Jul 8. [Epub ahead of print]
Inflammation and schizophrenia: Alterations in cytokine levels and perturbation in antioxidative defense systems.
1Research Centre, Riyadh Military Hospital, Riyadh, Kingdom of Saudi Arabia.
ObjectiveAlthough aeveral theories have been proposed including developmental/neurodegenerative processes, neurotransmitter abnormalities, viral infection, and immune dysfunction, the exact causative factor of schizophrenia is unclear. A relationship between inflammation and schizophrenia has been supported by abnormal cytokine production and altered antioxidant status. This study was aimed to examine the alterations in serum oxidative-antioxidative status and cytokine levels of schizophrenic patients.MethodsA total of 91 schizophrenic patients from Saudi Arabia and 50 age- and sex-matched healthy controls were enrolled in the present study. Fresh blood samples were collected to measure the levels of cytokines and markers of oxidative stress by spectrophotometric assays simultaneously.ResultsWe observed that there was a significant increase in the levels of tumor necrosis factor-Î±, interleukin (IL)-1Î², and IL-6 and a decrease in the levels of interferon-Î³. Lipid peroxides are elevated in serum, while total-sulfhydryl levels were decreased. Also, the activities of superoxide dismutase and glutathione peroxidase were decreased, while the activities of catalase, glutathione reductase, and myeloperoxidase were found to be elevated in serum.ConclusionWe conclude that inflammation resulting from dysregulation of cytokines and altered antioxidant systems may play a critical role in the etiology of schizophrenia.
J Zhejiang Univ Sci B. 2006 Dec;7(12):981-6.
Imbalanced free radicals and antioxidant defense systems in schizophrenia: a comparative study.
Li HC, Chen QZ, Ma Y, Zhou JF.
Department of Psychiatry, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
To examine changes of blood oxidative-antiovidative level in schizophrenic patients and its relationship with clinical symptoms.
Forty-six Chinese patients met DSM-IV (Diagnostic and Statistical Manual of Mental Disorders-IV) criteria for schizophrenia and fifty age- and sex-matched healthy controls were enrolled in the present study. Baseline psychiatric symptom severity was assessed with brief psychiatric rating scale, positive and negative syndrome scale on the blood draw day. Fresh blood samples were collected to measure levels of nitric oxide and lipid peroxide in plasma as well as activities of superoxide dismutase, catalase and glutathione peroxidase in red blood cells by spectrophotometric assays simultaneously.
Comparison of the biochemical parameters indicated that the level of nitric oxide and lipid peroxide increased in patient group, which represented a positive correlation with positive scale scores; while the activities of three critical enzymes decreased and showed a negative linear correlation.
This study showed that there are dysregulation of free radical metabolism and poor activities of the antioxidant defense systems in schizophrenic patients. Excess free radicals formation may play a critical role in the etiology of schizophrenia. Using antioxidants might be an effective therapeutic approach to partially alleviate or prevent the symptoms of schizophrenia.
- 2006 Mar-Apr;32(2 Pt 1):244-52.
[Oxidative stress involvement in schizophrenia pathophysiology: a review].
[Article in French]
Fendri C, Mechri A, Khiari G, Othman A, Kerkeni A, Gaha L.
UnitÃ© de Recherche en SantÃ© mentale (01/UR/08.08), Service de Psychiatrie, Centre hospitalo-universitaire Fattouma Bourguiba de Monastir, rue du 1er juin 5000, Monastir, Tunisie.
Schizophrenia is a devastating psychiatric disorder with a broad range of behavioural and biologic manifestations. There are several clinical characteristics of the illness that have been consistently associated with poor premorbid adjustment, long duration of psychosis prior to treatment and prominent negative symptoms. The etiopathogenic mechanisms of lack of insight in patients with schizophrenia are to date unknown, although several hypotheses have been suggested. A point of convergence for the theoretical models occurs with regard to the neuronal membrane. Neuronal membrane contains a high proportion of polyunsaturated fatty acid and is the site for oxidative stress. Oxidative stress is a state when there is unbalance between the generation of reactive oxygen species and antioxidant defence capacity of the body. It is closely associated with a number of diseases including Parkinson’s disease, Alzheimer-type dementia and Huntington’s chorea. Accumulating evidence points to many interrelated mechanisms that increase production of reactive oxygen or decrease antioxidant protection in schizophrenic patients.
This review aims to summarize the perturbations in antioxidant protection systems during schizophrenia, their interrelationships with the characteristic clinics and therapeutics and the implications of these observations in the pathophysiology of schizophrenia are discussed.
In schizophrenia there is evidence for deregulation of free radical metabolism, as detected by abnormal activity of critical antioxidant enzymes (superoxide dismutase, glutathione peroxidase and catalase). Many studies conclude in the decrease in the activity of key antioxidant enzymes in schizophrenia. A few studies have examined levels of non enzymatic antioxidants such as plasma antioxidant proteins (albumin, bilirubine, uric acid) and trace elements. How showed decreased levels in schizophrenic patients. Others studies have provided evidence of oxidative membrane damage by examining levels of lipid peroxidation products. Such abnormalities have been associated with certain clinical symptoms and therapeutic features. Negative symptoms have been associated with low levels of GSH-Px. Positive symptoms have been positively correlated with SOD activity. Plasma TAS was significantly lower in drug-free and haloperidol treated patients with schizophrenia. A low erythrocyte SOD activity has been found in never-treated patients, but with haloperidol treatment, SOD activity increased.
These results demonstrate altered membrane dynamics and antioxidant enzyme activity in schizophrenia. Membrane dysfunction can be secondary to free a radical-mediated pathology, and may contribute to specific aspects of the schizophrenia symptomatology. Membrane defects can significantly alter a broad range of membrane functions and presumably modify behavior through multiple downstream biological effects. Phospholipid metabolism in the brain may be perturbed in schizophrenia, with reduced amounts of phosphatidylcholins and phosphatidylethanolamine in post-mortem brain tissue from schizophrenic patients, and large amounts of lipofuscin-like materiel in the oligodendrocytes. The existence of these products within cell membranes results in an unstable membrane structure, altered membrane fluidity and permeability and impaired signal transduction. Recent findings suggest that multiple neurotransmitter systems may be faulty. CNS cells are more vulnerable to the toxic effects of free radicals because they have a high rate of catecholamine oxidative metabolic activity. Neurotransmitters, like glutamate, can induce the same metabolic processes that increase free radical production and can lead to impaired dopamine-glutamate balance. These results question the role of this imbalance in the biochemical basis evoked in the etipathogenic mechanisms of schizophrenia, as well as the role of antioxidants in the therapeutic strategy and their implication in preventive and early intervention approaches in populations at risk for schizophrenia.
BMC Psychiatry. 2011 Feb 14;11:26. doi: 10.1186/1471-244X-11-26.
Reduced antioxidant defense in early onset first-episode psychosis: a case-control study.
MicÃ³ JA, Rojas-Corrales MO, Gibert-Rahola J, Parellada M, Moreno D, Fraguas D, Graell M, Gil J, Irazusta J, Castro-Fornieles J, Soutullo C, Arango C, Otero S, Navarro A, Baeza I, MartÃnez-Cengotitabengoa M, GonzÃ¡lez-Pinto A.
Department of Neuroscience, Pharmacology and Psychiatry, School of Medicine, CIBERSAM, Centro de InvestigaciÃ³n BiomÃ©dica en Red de Salud Mental. University of CÃ¡diz, Spain.
Our objective is to determine the activity of the antioxidant defense system at admission in patients with early onset first psychotic episodes compared with a control group.
Total antioxidant status (TAS) and lipid peroxidation (LOOH) were determined in plasma. Enzyme activities and total glutathione levels were determined in erythrocytes in 102 children and adolescents with a first psychotic episode and 98 healthy controls.
A decrease in antioxidant defense was found in patients, measured as decreased TAS and glutathione levels. Lipid damage (LOOH) and glutathione peroxidase activity was higher in patients than controls. Our study shows a decrease in the antioxidant defense system in early onset first episode psychotic patients.
Glutathione deficit seems to be implicated in psychosis, and may be an important indirect biomarker of oxidative stress in early-onset schizophrenia. Oxidative damage is present in these patients, and may contribute to its pathophysiology.
J Psychiatr Res. 2012 Mar;46(3):394-401. doi: 10.1016/j.jpsychires.2011.10.004. Epub 2012 Jan 4.
Plasma antioxidant capacity is reduced in Asperger syndrome.
Parellada M, Moreno C, Mac-Dowell K, Leza JC, Giraldez M, BailÃ³n C, Castro C, Miranda-Azpiazu P, Fraguas D, Arango C.
Child and Adolescent Psychiatry, Department of Psychiatry, Hospital General Universitario Gregorio MaraÃ±Ã³n, Centro de InvestigaciÃ³n en Red de Salud Mental, CIBERSAM, Dr Esquerdo 46, Madrid, Spain. firstname.lastname@example.org
Recent evidence suggests that children with autism have impaired detoxification capacity and may suffer from chronic oxidative stress. To our knowledge, there has been no study focusing on oxidative metabolism specifically in Asperger syndrome (a milder form of autism) or comparing this metabolism with other psychiatric disorders. In this study, total antioxidant status (TAOS), non-enzymatic (glutathione and homocysteine) and enzymatic (catalase, superoxide dismutase, and glutathione peroxidase) antioxidants, and lipid peroxidation were measured in plasma or erythrocyte lysates in a group of adolescent patients with Asperger syndrome, a group of adolescents with a first episode of psychosis, and a group of healthy controls at baseline and at 8-12 weeks. TAOS was also analyzed at 1 year. TAOS was reduced in Asperger individuals compared with healthy controls and psychosis patients, after covarying by age and antipsychotic treatment. This reduced antioxidant capacity did not depend on any of the individual antioxidant variables measured. Psychosis patients had increased homocysteine levels in plasma and decreased copper and ceruloplasmin at baseline. In conclusion, Asperger patients seem to have chronic low detoxifying capacity. No impaired detoxifying capacity was found in the first-episode psychosis group in the first year of illness.