Cerebrospinal fluid depression

Both norepinephrine (NE) and serotonin play important roles in depression, with increased levels of NE and its metabolites commonly found in the plasma, cerebrospinal fluid, and urine of patients with MDD (Lake, Pickar, Ziegler etal., 1982 ... 

DeBellis, M., Geracioti, T. Altemus, M. (1993). Cerebrospinal fluid monoamine metabolites in fluoxetine treated patients with major depression and in healthy volunteers. Biol. Psychiatry, 33, 636-41. 

Roy, A., Pickar, D., Dejong, J., Karoum, F. Linnoila, M. (1998). Norepinephrine and its metabolites in cerebrospinal fluid, plasma and urine. Relationship to hypothalamic-pituitary-adrenal axis function in depression. Arch. Gen. Psychiatry, 45, 849-57. 

Mann, J. J., Malone, K. M., Sweeney, J. A. et al. Attempted suicide characteristics and cerebrospinal fluid amine metabolites in depressed inpatients. Neuropsychopharm. 15 576-586,1996. 

Uzunova V, Sheline Y, David JM, Rasmusson A, Uzunov DP, et al. 1998. Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar major depression who are receiving fluoxetine or fluvo amine. Proc Natl... 

Changes in cerebrospinal fluid (CSF) concentrations of amine metabolites from patients with depression. 

The role of serotonin (5-hydroxytryptamine, 5-HT) has also been extensively studied in depressed patients. Whereas the overall psycho-physiological effects of noradrenaline in the CNS appear to be linked to drive and motivation, 5-HT is primarily involved in the expression of mood. It is not surprising therefore to find that the serotonergic system is abnormal in depression. This is indicated by a reduction in the main 5-HT metabolite, 5-hydroxy indole acetic acid (5-HIAA), in the cerebrospinal fluid of severely depressed patients and a reduction in 5-HT and 5-HIAA in the limbic regions of the brain of suicide victims. The 5-HT receptor function also appears to be abnormal in depression. This is indicated by an increase in the density of cortical 5-HT2a receptors in the brains of suicide victims and also on the platelet membrane of depressed patients. Platelets may be considered as accessible models of the nerve terminal. 

Thus when the results of the studies on platelets, lymphocytes, changes in cerebrospinal fluid metabolites of brain monoamines and the post-mortem studies are taken into account it may be concluded that a major abnormality in both noradrenergic and serotonergic function occurs in depression, and that such changes could be causally related to the disease process. 

Stress is frequently a trigger factor for depression in vulnerable patients. There is clinical evidence to show that CRT is elevated in the cerebrospinal fluid of untreated depressed patients, which presumably leads to the hypercortisolaemia that usually accompanies the condition. One of the consequences of elevated plasma glucocorticoids is a suppression of some aspects of cellular immunity. It is now established that many cellular (for example, natural killer cell activity, T-cell replication) and non-cellular (for example, raised acute phase proteins) aspects are abnormal in the untreated depressed patient. Such observations could help to explain the susceptibility of depressed patients to physical ill health. 

Head injury and increased intracranial pressure The possible respiratory depressant effects and the potential of potent analgesics to elevate cerebrospinal fluid pressure may be markedly exaggerated in the presence of head injury, intracranial lesions, or a preexisting increase in intracranial pressure. 

C. Pyrazinamide is known to cause hyperuricemia and precipitate gouty arthritis. Pyrazinamide-induced gouty arthritis does not respond to uricosuric therapy with probenecid but may respond to acetylsalicylic acid. Cycloserine (A) can cause headaches, confusion, tremors, and seizures, possibly secondary to low levels of magnesium in the cerebrospinal fluid cycloserine should be avoided in patients with epilepsy and mental depression. It is not associated with hyperuricemia. Thiacetazone (B) is an antibiotic that is rarely used in tuberculosis. The most common adverse reactions are general rashes and GI intolerance. Its use is not associated with hy-... 

Nemeroff, C.B., Bissette, G., Akil, H., and Fink, M. (1991) Neuropeptide concentrations in the cerebrospinal fluid of depressed patients treated with electroconvulsive therapy. Corticotrophin-releasing factor, beta-endorphin and somatostatin. Br J Psychiatry 158 59-63. 

D. C., Tonnai, T.P., Chrousos, G.P., and Gold, P.W. (1987b) Elevated cerebrospinal fluid levels of immunoreactive corticotropinreleasing hormone in anorexia nervosa relation to state of nutrition, adrenal function, and intensity of depression. J Clini Endocrinol Metab 64 203-208. 

Barkai et al. (1978) reported that cerebrospinal fluid levels of inositol were lower in patients with depression than in psychiatrically healthy subjects. We hypothesized that inositol may be deficient in some brain systems in depression. This does not contradict the concept that Li reduces inositol levels and that Li" is an antidepressant, because the PI cycle serves as a second messenger for several balancing and mutually interactive neurotransmitters. Li+ could alleviate depression by reducing inositol and a primary hyperactivity of one hypothetical brain system low inositol levels in another system could cause second messenger dysfunction and thereby depression. 

The most consistent finding in clinical studies has been decreased turnover of DA in patients with depressive disorders, as measured by cerebrospinal fluid [CSF] levels and urinary output of its principal metabolite homovanillic acid [HVA] [A. S. Brown and Gershon 1993 Kapur and Mann 1992). Patients... 

Berrettini WH, Nurnberger JI Jr, Chan JS, et al Pro-opiomelanocortin-related peptides in cerebrospinal fluid a study of manic-depressive disorder. Psychiatry Res 16 287-302, 1985b... 

Carroll BJ, Curtis GC, Mendels J Cerebrospinal fluid and plasma free cortisol concentration in depression. Psychol Med 6 235-244, 1976a... 

Post RM, Kotin J, Goodwin FK, et al Psychomotor activity and cerebrospinal fluid amine metabolites in affective illness. Am J Psychiatry 130 67-72, 1973 Post RM, Stoddard FJ, Gillin JC, et al Alterations in motor activity, sleep, and biochemistry in a cycling manic-depressive patient. Arch Gen Psychiatry 34 470-477, 1977... 

Post RM, Ballenger JC, Hare TA, et al Cerebrospinal fluid GABA in normals and patients with affective disorders. Brain Res Bull 5 (suppl 2 755-759, 1980 Post RM, Uhde TW, Ballenger JC, et al Prophylactic efficacy of carbamazepine in manic-depressive illness. Am J Psychiatry 140 1602-1604, 1983 Post RM, Ballenger JC, Uhde TW, et al Efficacy of carbamazepine in manic-depressive illness implications for underlying mechanisms, in Neurobiology of Mood Disorders. Edited by Post RM, Ballenger JC. Baltimore, MD, Williams Wilkins, 1984, pp 777-816... 

Patient 1. This 24-year-old male university student was brought to the emergency department at 1600 h by his roommate. He was delirious and had a depressed level of consciousness. Although he had been well the previous day, that morning he had complained of a fever, severe headache, severe neck and back stiffness, nausea, and vomiting. He had become progressively unwell over 7-8 hours. On physical examination he was acutely ill with a temperature of 40°C. He was delirious and had neck rigidity with severe resistance to any attempt to passively flex his neck. A CT scan of his brain was normal. A spinal tap was performed and cerebrospinal fluid (CSF) was removed it was cloudy. 

Serotonin and its metabolites are reduced in the cerebrospinal fluid of some depressive patients, which suggests reduced serotoninergic activity in the brain of these individuals. 

Anorectic patients often suffer from complications such as hypotension, hypothermia, and abnormal ECGs, all of which are consistent with starvation. In women, amenorrhea is common with this syndrome. Like patients with depression, they also have high cerebrospinal fluid concentrations of corticotropin-releasing hormone. 

Fluman studies seem to support the animal data on the role of neurotrophic factors in stress states. Depression appears to be associated with a drop in BDNF levels in the cerebrospinal fluid and serum as well as with a decrease in tyrosine kinase receptor activity. Conversely, administration of antidepressants increases BDNF levels in clinical trials and may be associated with an increase in hippocampus volume in some patients. 

Studies of depressed patients have sometimes shown an alteration in monoamine function. For example, some studies have found evidence of alteration in serotonin receptor numbers (5-HT1A and 5-HT2c) or norepinephrine (k2) receptors in depressed and suicidal patients, but these findings have not been consistent. A reduction in the primary serotonin metabolite 5-hydroxyindoleacetic acid in the cerebrospinal fluid is associated with violent and impulsive behavior, including violent suicide attempts. However, this finding is not specific to major depression and is associated more generally with violent and impulsive behavior. 

Morphine releases histamine and may cause peripheral vasodilation and orthostatic hypotension (Figure 47.7). The cutaneous blood vessels dilate around the blush areas such as the face, neck, and upper thorax. Morphine causes cerebral vasodilation (due to increased carbon dioxide retention secondary to respiratory depression), and hence, it increases the cerebrospinal fluid pressure. Therefore, morphine should be used cautiously in patients with either meningitis or a recent head injury. When given subcutaneously, morphine is absorbed poorly whenever there is either traumatic or hemorrhagic shock. 

Salomon RM, Ripley B, Kennedy JS, Johnson B, Schmidt D, Zeitzer JM, Nishino S, Mignot E (2003) Diurnal variation of cerebrospinal fluid hypocretin-1 (Qrexin-A) levels in control and depressed subjects. Biol Psychiatry 54 96-104... 

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