Unfortunately there have been lot of problems with "antipsychotic" drugs. Weight gain and other side effects have been seen. These are discussed in Ref. 2 and 3. Because of these side effects the patient and the clinician should take an interest in nutrition even if these drugs are the treatment. A good diet can counteract the weight gain side effect. Such a diet would be high in fiber with possibly fiber supplements.
One of the worst side effects of the atypical "antipsychotics" is diabetes, which is a terrible disease that can cause blindness, death, loss of toes, loss of legs, etc. This is discussed in Ref. 4. Again nutrition is important because one of the treatments for diabetes is diet.
"Our findings suggest brain-specific alterations in glucoregulatory processes in the CSF of drug-naïve patients with first-onset schizophrenia, implying that these abnormalities are intrinsic to the disease, rather than a side effect of antipsychotic medication." Holmes et al (2006) This quote is from Ref. 6. "Results from 1H NMR spectroscopy showed significantly elevated glucose concentrations in CSF samples from drug-naïve patients with first-onset schizophrenia, as compared to the demographically matched control group, with a relative increase in concentration of 6.5% (p = 0.04; calculated from a distinct resonance signal at 3.68-3.72 ppm)." Holmes et al (2006) The UK group postulated slowed brain glucose metabolism to explain the results.
Ref. 13 reported abnormal glucose tolerance tests in "drug-naive" patients with schizophrenia. This suggest that there is a glucose abnormality that is not caused by the medication. The medication may cause a different kind of glucose abnormality. Ref. 14 reports a case of glucose-6-phosphatase deficiency, which can present with psychiatric symptoms. This inherited disease gives us an important clue. It appears that almost any impairment of brain glucose metabolism results in psychiatric symptoms. In this disease the brain burns lactate, which can come from amino acids.
Compromised Brain Metabolism
Ref. 15 reports "mitochondrial dysfunction" and "compromised brain metabolism" in schizophrenia. But what causes this compromised brain metabolism? Are dietary factors involved? My theory is that the answer is "Yes". Increased lactate has been reported in the cerebrospinal fluid (Ref. 22). This increased lactate may be coming from amino acids.
The authors of Ref. 22 reported the following:
"Cerebrospinal fluid (CSF) concentration of lactate, a product of extra-mitochondrial glucose metabolism, is commonly elevated in individuals with mitochondrial disorders, especially those with neuropsychiatric symptoms."
They suggested "mitochondrial pathology" in schizophrenia and bipolar disorder.
In my theory amino acids are flooding the brain cells in the various forms of mental disease including bipolar disorder, schizophrenia, etc. A diet very low in protein is suggested.
The highest sources of protein are in fish and meat. Certain plant foods are also high in protein including spinach, tofu, mustard greens, crimini mushrooms, soybeans, etc. According to the World's Healthiest Foods website, collard greens, cauliflower and many legumes including lentils, split peas, kidney beans, black beans, pinto beans and garbanzo beans are "good" sources of protein. Another good website on this matter is orthomolecular.org.
The USDA has calculated a lot of this data and has its own website. My guess is that the other websites may have gotten their information from the USDA (Dept. of Agriculture). I prefer the health foods websites because they also give clinical information.
A diet low in protein is suggested. There may be other factors including flavonoids. Flavonoids may be helpful. They are found in fruits and fruit juices, which have little protein. There also may be other bad factors. It seems that a lot of sugar causes insulin release. This results in more tryptophan being pumped into the brain, which already has too much of it in these diseases.
1. The World Health Report, Mental Health: New understanding, new hope. Geneva: World Health Organisation (WHO); 2001.
2. Sevy S, Nathanson K, Schlecter C, Fulop G. Contingency Valuation and Preferences of Health States Associated With Side Effects of Antipsychotic Medications in Schizophrenia. Schizophrenia Bulletin. 2001;27:643-651.
3. Brixner DI, Said Q, Corey-Lisle PK, Tuomari AV, L'Italien GJ, Stockdale W, Oderda GM. Naturalistic Impact of Second-Generation Antipsychotics on Weight Gain. Annals of Pharmacotherapy. 2006;40:626-632. doi: 10.1345/aph.1G564.
4. Koro CE, Fedder DO, L'Italien GJ, Weiss SS, Magder LS, Kreyenbuhl J, et al. Assessment of independent effect of olanzapine and risperidone on risk of diabetes among patients with schizophrenia: population based nested case-control study. BMJ. 2002;325:243. doi: 10.1136/bmj.325.7358.243.
5. Sevy S, Nathanson K, Schlecter C, Fulop G. Contingency Valuation and Preferences of Health States Associated With Side Effects of Antipsychotic Medications in Schizophrenia. Schizophrenia Bulletin. 2001;27:643-651.
6. Metabolic Profiling of CSF: Evidence That Early Intervention May Impact on Disease Progression and Outcome in Schizophrenia Elaine Holmes, Tsz M Tsang, Jeffrey T.-J Huang, F. Markus Leweke, Dagmar Koethe, Christoph W Gerth, Brit M Nolden, Sonja Gross, Daniela Schreiber, Jeremy K Nicholson, and Sabine BahnPLoS Med. 2006 August; 3(8): e327. Published online 2006 August 22. doi: 10.1371/journal.pmed.0030327. PMCID: PMC1551919
7. Disease Biomarkers in Cerebrospinal Fluid of Patients with First-Onset Psychosis Jeffrey T.-J Huang, F. Markus Leweke, David Oxley, Lan Wang, Nathan Harris, Dagmar Koethe, Christoph W Gerth, Brit M Nolden, Sonja Gross, Daniela Schreiber, Benjamin Reed, and Sabine BahnPLoS Med. 2006 November; 3(11): e428. Published online 2006 November 7. doi: 10.1371/journal.pmed.0030428. PMCID: PMC1630717
8. Henderson DC, Ettinger ER. Schizophrenia and diabetes. Int Rev Neurobiol. 2002;51:481-501.
9. Newcomer JW. Abnormalities of glucose metabolism associated with atypical antipsychotic drugs. J Clin Psychiatry. 2004;65((Suppl 18)):36-46.
10. White LR, Garseth M, Aasly J, Sonnewald U. Cerebrospinal fluid from patients with dementia contains increased amounts of an unknown factor. J Neurosci Res. 2004;78:297-301.
11. Iwamoto K, Bundo M, Kato T. Altered expression of mitochondria-related genes in postmortem brains of patients with bipolar disorder or schizophrenia, as revealed by large-scale DNA microarray analysis. Hum Mol Genet. 2005;14:241-253.
12. Karry R, Klein E, Ben Shachar D. Mitochondrial complex I subunits expression is altered in schizophrenia: A postmortem study. Biol Psychiatry. 2004;55:676-684.
13. Ryan MC, Collins P, Thakore JH. Impaired fasting glucose tolerance in first-episode, drug-naive patients with schizophrenia. Am J Psychiatry. 2003;160:284-289.
14. Fernandes J, Berger R, Smit GP. Lactate as energy source for brain in glucose-6-phosphatase deficient child. Lancet. 1982;1:113.
15. Prabakaran S, Swatton JE, Ryan MM, Huffaker SJ, Huang JT, et al. Mitochondrial dysfunction in schizophrenia: Evidence for compromised brain metabolism and oxidative stress. Mol Psychiatry. 2004;9:684-697. 643.
16. Regenold WT, Phatak P, Kling MA, Hauser P. Post-mortem evidence from human brain tissue of disturbed glucose metabolism in mood and psychotic disorders. Mol Psychiatry. 2004;9:731-733.
17. Thaker GK, Carpenter WT., Jr Advances in schizophrenia. Nat Med. 2001;7:667-671. 18. Brain metabolite abnormalities in the white matter of elderly schizophrenic subjects: implication for glial dysfunction Linda Chang, Joseph Friedman, Thomas Ernst, Kai Zhong, Nicholas D. Tsopelas, and Kenneth DavisBiol Psychiatry. Author manuscript; available in PMC 2008 December 15. PMCID: PMC2222890 Published in final edited form as: Biol Psychiatry. 2007 December 15; 62(12): 1396-1404. Published online 2007 August 13. doi: 10.1016/j.biopsych.2007.05.025.
19. Davis K, Stewart D, Friedman J, Buchsbaum M, Harvey P, Hof P, et al. White matter changes in schizophrenia: evidence for myelin-related dysfunction. Archives of General Psychiatry. 2003;60:443-456.
20. Uranova N, Vostrikov V, Orlovskaya D, Rachmanova V. Oligodendroglial density in the prefrontal cortex in schizophrenia and mood disorders: a study from the Stanley Neuropathology Consortium. Schizophrenia Research. 2004;67:269-275.
21. "Increased lactate levels and reduced pH in postmortem brains of schizophrenics: Medication confounds.(Author abstract)(Report). ." Journal of Neuroscience Methods. 169.1 (March 30, 2008): 208(6). Health Reference Center Academic. Gale. Needham Free Public Library. 4 Feb. 2009
Regenold WT, Phatak P, Marano CM, Sassan A, Conley RR, Kling MA.
Biol Psychiatry. 2009 Mar 15;65(6):489-94. Epub 2008 Dec 21.
PMID: 19103439 [PubMed - in process]