Cushing's Syndrome and Depression: A New Theory

Cushing's syndrome is a disease of the pituitary gland, which is part of the brain. The disease was named after Dr. Harvey Cushing, a brilliant American neurosurgeon. Depression is seen as a symtom (1, 2). According to Ref. 2, tryptophan is thought to be involved.

"Depression was the main psychiatric diagnosis made by the CATEGO programme after Present State Examinations. Patients with active Cushing's syndrome were significantly more depressed (Hamilton Rating Scores), than were the other patients." Kelly WF, Checkley SA, Bender DA (2)

Ref. 3 gives further information on tryptophan.

Depression

But why does Cushing's disease cause depression? The answer is that in Cushing's disease there are hormonal changes that cause metabolic errors. These metabolic errors cause the depression symptomatology. This supports the medical model for depression. Depression is organic.

There are various theories of depression. One theory, and perhaps more, involve tryptophan. Ref. 4 reports depressive symptoms as the result of interferon, a drug used to treat cancer.

Drugs

Information about drugs is given in Ref. 5.

Tryptophan and Depression

There are studies linking depression with abnormal tryptophan metabolism (6). It seems that the interferon side effect of depression is associated with altered tryptophan metabolism (7). Interferon appears to be causing tryptophan to enter the cells. This is reflected by decreased serum tryptophan concentrations (7).

Alcoholism

Ref. 8 reports an interesting theory for alcoholism. My view is that this theory may be valid for many forms of mental illness. The brain depends very heavily on glucose metabolism for its energy. Any disturbance in this metabolism can wreak havoc on the brain. Too much glucose in the brain as sometimes seen in diabetes can cause you to pass out. Too little causes psychiatric symptoms.

Roger Williams, one of the authors of Ref. 8, was a brilliant nutrition expert. Unfortunately he is now deceased. Williams' theory might even explain the psychiatric symptoms seen in Cushing's disease because certain hormones regulate glucose metabolism. Cushing's disease is an endocrine disease.

Bipolar Disorder

Ref. 9 discusses bipolar disorder. Kynurenic acid is a metabolite of tryptophan. The fact that it is elevated in bipolar disorder suggests increased brain trypophan metabolism. This would happen if tryptophan were flooding the brain cells. This result does not support the popular serotonin deficiency theory. If tryptophan were flooding the brain cells, then there would be too much serotonin. The brilliant scientists who wrote Ref. 9 were from the prestigious Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden. The Karolinska Institute awards the Nobel prizes in medicine.

Schizophrenia

The same Stockholm group had previously reported elevated kynurenic acid in the cerebrospinal fluid of male patients with schizophrenia (10). This strongly suggests that schizophrenia and bipolar disorder are related. Both appear to be disorders of tryptophan metabolism.

Conclusions

There is a great deal of evidence that tryptophan metabolism is excessive in various mental disorders. Roger Williams' theory (8) that inadequate brain glucose metabolism causes alcoholism is consistent with my tryptophan theory. If excessive tryptophan is flooding the brain cells, then the brain is likely to burn the excessive tryptophan for fuel instead of glucose to keep the cells from blowing up like balloons and bursting. One variation on my theory is that more than one amino acid are involved. Several amino acids could be flooding the brain cells.

This is tremendously important because this points towards orthomolecular treatment since amino acids are found in the diet. The diet would be low in tryptophan. This diet should be supplemented with niacin to avoid pellagra because niacin is a metabolite of tryptophan.

References

1. Cushing's syndrome and depression--a prospective study of 26 patients. Kelly WF, Checkley SA, Bender DA, Mashiter K. Br J Psychiatry. 1983 Jan;142:16-9.

2. Cushing's syndrome, tryptophan and depression. Kelly WF, Checkley SA, Bender DA. Br J Psychiatry. 1980 Feb;136:125-32.

3. Biochemistry of tryptophan in health and disease. Bender DA. Mol Aspects Med. 1983;6(2):101-97.

4. Capuron L, Gumnick JF, Musselman DL, Lawson DH, Reemsnyder A, Nemeroff CB, et al. Neurobehavioral effects of interferon-alpha in cancer patients: phenomenology and paroxetine responsiveness of symptom dimensions. Neuropsychopharmacology. 2002;26(5):643-52.

5. WorstPills.org

6. Widner B, Laich A, Sperner-Unterweger B, Ledochowski M, Fuchs D. Neopterin production, tryptophan degradation, and mental depression--what is the link? Brain Behav Immun. 2002;16(5):590-5.

7. Capuron L, Ravaud A, Neveu PJ, Miller AH, Maes M, Dantzer R. Association between decreased serum tryptophan concentrations and depressive symptoms in cancer patients undergoing cytokine therapy. Mol Psychiatry. 2002;7(5):468-73.

8. Williams, RJ, Roach, MK, "Impaired and inadequate glucose metabolism in the brain as an underlying cause of alcoholism--an hypothesis.", Proc Natl Acad Sci U S A. 1966 August; 56(2): 566-571.

9. Elevated levels of kynurenic acid in the cerebrospinal fluid of patients with bipolar disorder. Olsson SK, Samuelsson M, Saetre P, Lindström L, Jönsson EG, Nordin C, Engberg G, Erhardt S, Landén M. J Psychiatry Neurosci. 2010 May;35(3):195-9.

10. Schizophr Res. 2005 Dec 15;80(2-3):315-22. Epub 2005 Aug 25. Elevated levels of kynurenic acid in the cerebrospinal fluid of male patients with schizophrenia. Nilsson LK, Linderholm KR, Engberg G, Paulson L, Blennow K, Lindström LH, Nordin C, Karanti A, Persson P, Erhardt S.