Problems in Psychiatric Research

Introduction
Unfortunately there have been severe problems with psychiatric drugs (1, 2).
"There is an association between use of antipsychotic drugs and risk of venous thromboembolism in a large primary care population. The increased risk was more marked among new users and those prescribed atypical antipsychotic drugs." Parker et al (2)
Biological Markers
Ref. 3 deals with biological markers. The search for these markers has been frustrating 4, 5).
Depression
Ref. 7 reports positive findings in depression. Refs. 8 & 9 confirm Ref. 7. There is a serotonin theory for depression (10). Serotonin is a metabolite of tryptophan. The original hypothesis was that serotonin was supposed to be low in depression. However, actual measurements of serotonin do not support this. Nevertheless serotonin is an important neurotransmitter. Kynurenine is another metabolite of tryptophan that has been suspected. It is in a different pathway than the serotonin pathway.
Ref. 11 reported an animal model of depression.
Protein Abnormalities
Protein abnormalities have been reported for decades in schizophrenia, particularly in the plasma proteins (4).
"As it can be seen, many protein differences have statistical significance well above the highly conservative Bonferroni correction threshold (represented by the vertical line, i.e. a p-value threshold of 5% significance level corrected for multiple testing), in particular for schizophrenia." Domenici E et al (4)
One has to be careful here because psychiatric drugs can cause metabolic abnormalities. In particular, atypical "antipsychotics" can even cause diabetes. Thus an insulin abnormality could be a drug side effect.
Insulin Resistance
Ref. 12 reported "insulin resistance". Refs. 13-15 support this. However, Ref. 15's "comorbidity" coulod be a drug artifact since atypical "antipsychotics" can cause diabetes. Then again, many depressives are treated with "antidepressants" including SSRI drugs. The possibility exists that depression might be a diabetes of the brain.
Conclusions
My own theory integrates much of this data as pieces of the jigsaw puzzle. My theory is that tryptophan is flooding the brain cells. This would cause metabolic problems in the brain including the burning of tryptophan for fuel instead of glucose. Other amino acids might also be involved. But what causes tryptophan to flood the cells? The answer might be the abnormal plasma protein. There could be more than one abnormal plasma protein. These proteins could be neurotoxins.
But what is the treatment? The treatment could be a low-tryptophan diet supplemented with niacin to avoid pellagra.
References
1. Incidence and costs of cardiometabolic conditions in patients with schizophrenia treated with antipsychotic medications. Jerrell JM, McIntyre RS, Tripathi A. Clin Schizophr Relat Psychoses. 2010 Oct;4(3):161-8.

2. Antipsychotic drugs and risk of venous thromboembolism: nested case-control study. Parker C, Coupland C, Hippisley-Cox J. BMJ. 2010 Sep 21;341.

3. Extended morphological processing: a practical method for automatic spot detection of biological markers from microscopic images. Kimori Y, Baba N, Morone N. BMC Bioinformatics. 2010 Jul 8;11:373.

4. Plasma protein biomarkers for depression and schizophrenia by multi analyte profiling of case-control collections. Domenici E, Willé DR, Tozzi F, Prokopenko I, Miller S, McKeown A, Brittain C, Rujescu D, Giegling I, Turck CW, Holsboer F, Bullmore ET, Middleton L, Merlo-Pich E, Alexander RC, Muglia P. PLoS One. 2010 Feb 11;5(2):e9166.

5. Connor TJ, Leonard BE. Preskorn SH, Feighner JP, Stanga C, Ross R, editors. Biological markers for Depression. 2004. pp. 117-148. Handbook of Experimental Pharmacology. Antidepressants. Past, Present and Future (Volume 157). Springer, New York.

6. Domenici E, Muglia P. The search for peripheral markers in psychiatry by genomic and proteomic approaches. Exp Opin Med Diagn. 2007;1:235-251.

7. Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2006;27:24-31.

8. Miller AH, Maletic V, Raison CL. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry. 2009;65:732-741.

9. Simon NM, McNamara K, Chow CW, Maser RS, Papakostas GI, et al. A detailed examination of cytokine abnormalities in Major Depressive Disorder. Eur Neuropsychopharmacol. 2008;18:230-233.

10. Tryptophan kynurenine metabolism as a common mediator of genetic and environmental impacts in major depressive disorder: the serotonin hypothesis revisited 40 years later. Oxenkrug GF. Isr J Psychiatry Relat Sci. 2010;47(1):56-63.

11. Central administration of lipopolysaccharide induces depressive-like behavior in vivo and activates brain indoleamine 2,3 dioxygenase in murine organotypic hippocampal slice cultures. Fu X, Zunich SM, O'Connor JC, Kavelaars A, Dantzer R, Kelley KW. J Neuroinflammation. 2010 Aug 2;7:43.

12. Okamura F, Tashiro A, Utumi A, Imai T, Suchi T, et al. Insulin resistance in patients with depression and its changes during the clinical course of depression: minimal model analysis. Metabolism. 2000;49:1255-1260.

13. Tashiro A, Hongo M, Ota R, Utsumi A, Imai T. Hyper-insulin response in a patient with depression. Changes in insulin resistance during recovery from depression. Diabetes Care. 1997;20:1924-1925.

14. Winokur A, Maislin G, Phillips JL, Amsterdam JD. Insulin resistance after oral glucose tolerance testing in patients with major depression. Am J Psychiatry. 1988;145:325-330.

15. Katon WJ. The comorbidity of diabetes mellitus and depression. Am J Med. 2008;121:S8-15.