Depression and cerebral blood flow.
Maybe a benefit will arise from the current debate about the usefulness of antidepressants in depression, if it draws attention to the published studies concerning reduced regional cerebral blood flow in depression which have failed to influence clinical opinion. Perhaps the relevance of such information can be appreciated by reference to the study by Lucey et al. (1) They showed that in patients with panic disorder with agoraphobia, obsessive compulsive disorder and post traumatic stress disorder, there were regional reductions in cerebral blood flow, but in each disorder in different regions of the brain.
It is proposed that depression is the dysfunctional state arising from inadequate rates of blood flow to deliver the necessary oxygen and nutrient substrates to sustain normal tissue function in specific regions of the brain. This means that the condition would be reversible when there were adequate rates of blood flow.
In 1990, Sackheim et al (2) critically examined what had been written about regional cerebral blood flow in mood disorders. An important contribution was made by Bench et al (3) who reported their findings in a study in which previously scanned patients were rescanned on remission. They concluded, "Thus, recovery from depression is associated with increases in regional cerebral blood flow in the same area in which focal decreases in regional cerebral blood flow are described in the depressed state, in comparison with normal subjects." Similar findings were reported in another paper (4) which reported that the reduced rate of blood flow in the left frontal region which had been observed during depression, returned to normal during remission. The lack of attention given to such findings probably reflects the current antipathy to reports which imply a role for the flow properties of blood (blood rheology).
It is possible to interpret such changes in blood flow in terms of the effects of poorly deformable red cells, which reflect change in their environment by a reduction in fluidity of the the cell membrane. Normalisation of the cell environment restores normal levels of deformability. So it is not surprising that depression is a frequent problem in chronic disorders which are known to have altered blood rheology manifested as increased blood viscosity and poorly deformable red cells, such as in diabetes for example.
Kamada et al (5) in 1986 reported that sardine oil so increased the fluidity of the membranes of diabetic red cells that they were unable to distinguish such cells from those of non-diabetics. Ten years later Maes et al (6) noted that, " Major depressed subjects had significantly lower C18-3 omega-3 in cholesteryl esters than normal controls. Major depressed subjects showed significantly lower total omega-3 polyunsaturated fatty acids... than minor depressed subjects and healthy controls." A later study of the omega-3 fatty acid content in the diet and in red cell membranes of depressed patients (7) noted that, "Lower red blood cell membrane n-3 polyunsaturated fatty acids are associated with the severity of depression," and concluded, "The findings raise the possibility that depressive symptoms may be relieved by n-3 polyunsaturated fatty acid supplementation."
Ten years later there is no indication that the significance of such findings have been recognised and therapy for depression has been based upon antidepressants rather that omega-3 rich fish oil which might correct the primary problem. Possibly, if the current debate leads to a more public recognition of the problems of cerebral blood flow in depression, then maybe those who suffer from depression will explore the potential benefits of taking 2 x 1000mg capsules of fish oil, three times daily. Many studies have used 10 capsules daily, and one study reported that the maximal tolerable dose was twenty grams daily. Because of the need for the enzyme delta-6-desaturase to be functional in order to utilise the plant derived alphalinolenic acid, it is safer to use fish oil as a source of omega-3 fatty acids. An alternative would be to increase the dietary intake of omega-3 fatty acids by including sardines or oily fish in meals on a daily basis.
In addition, because regular light exercise has been shown to reduce blood viscosity, an activity such as walking or dancing should be part of the daily programme. A good example was an Australian study involving "pram pushing" which was shown to be beneficial for women with post-partum depression.
1. Lucey JV, Costa DC, Adshead G, et al. Brain blood flow in anxiety disorders: OCD, panic disorder with agoraphobia and post traumatic stress disorder. Br J Psychiatry 1997;171:346-50.
2. Sackheim HA, Prohovnik I, Moeller JR, et al. Regional cerebral blood flow in mood disorders. Arch Gen Psychiatry 1990;47:60-70.
3. Bench CJ, Frackowiak RS, Dolan RJ. Changes in regional cerebral blood flow on recovery from depression. Psychol Med 1995;25:247-61.
4. Navarro V, Gasto C, Lomena F, et al. Normalisation of frontal cerebral perfusion in remitted elderly major depression: a 12-month follow-up SPECT study. Neuroimage 2002;16:781-7.
5. Kamada T, Yamashita T, Baba Y, et al. Dietary sardine oil increases erythrocyte membrane fluidity in diabetic patients. Diabetes 1986;35:604- 11.
6. Maes M, Smith R, Christophe A, et al. Fatty acid composition in major depression: decreased omega-3 fractions in cholesteryl esters and increased C20:4 omega-6/C20:5 omega-3 ratio in cholesteryl esters and phospholipids. J Affect Disord 1996;38:35-46.
7. Edwards R, Peet M, Shay J, et al. Omega-3 polyunsaturated fatty acid levels in the diet and in red blood cell membranes of depressed patients. J Affect Disord 1998;48:149-55.
Competing interests: None declared
Competing interests: No competing interests