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Critically evaluate the claim that biochemical factors may be important in the aetiology of depression

Introduction

Depression is characterised by reduced feeling and motivation, along with disorders in sleep, appetite and motivation. Many cases of depression arise for poorly understood reasons so much research is undertaken to pinpoint any biological changes common to depressed individuals. If biological changes are apparent this provides the opportunity for drug treatment or some other form of therapy. Depression can also result as a side effect of drug treatment, so the altered biological systems in these instances can also be used as a starting point.

Functional imaging

Gross anatomical changes were not consistent between depressed patients, with some showing reduced brain mass in areas such as the amydala and frontal cortex, whilst others showed no changes. However functional imaging results appear to be more consistent, with underactivity in the dorsal brain region, and overactivity in the ventral brain region accounting for the apathetic and hypermanic symptoms respectively (Gupta, Elheis, & Pansari, 2004). PET scanning results indicate increased activity in the amygdala and orbitofrontal cortex, whilst MRI scans show reduced dopamine levels. This latter finding correlates with the fact that Parkinson’s disease, a disorder characterised by reduced dopamine levels, is very often associated with depression.

Monoamines

The monoamine hypothesis of depression states that ‘depression is caused by a functional deficit of monoamine transmitters at certain sites in the brain, whilst mania results from a functional excess’ (Rang, Dale, & Ritter, 1999). The theory came about when it was seen that drugs that depleted monoamines could lead to depression (Ressler & Nemeroff, 2000). The principle monoamines implicated in depression are serotonin (5-HT) and noradrenaline.
5-HT is the most oft cited biochemical factor altered during depression, and underlies the use of Selective Serotonin Reuptake Inhibitors (SSRIs) in drug treatment.

Whilst it is generally accepted that 5-HT levels are reduced during depression the actual evidence is not as clear-cut as this acceptance should require. It is possible to measure serotonin levels via several methods and these each produce different results. Whilst there are reductions in platelet serotonin levels in some studies, others show no change at all (Lestra, d’ Amato, Ghaemmaghami, Perret-Liaudet, Broyer & Renaud, 1998). Similarly the method of measuring the monoamine deficit affects the results, in that metabolism measurements provide different results to investigation of receptor numbers (Rang, Dale & Ritter, 1999), although both should provide a similar measure of any changes in overall transmitter amounts.
It is interesting to note that 5-HT levels vary with age; in that levels measured in non-depressed post-mortem brains at age 90 are approximately 1/3 of those measured at age 60 (Gottfries, 2001).

It has been shown that the dopaminergic system is dysregulated in depression, with receptor numbers being increased (Dailly, Chenu, Renard, & Bourin, 2004). Whether this is as compensation to reduced dopamine levels or causative of manic symptoms is not clear.
All of this would indicate that, whilst monoamines, and 5-HT in particular, do have a role in depression, it is not a simple case of altered neurotransmitter levels causing the disease; there are more factors in play. Indeed many authors bemoan the strategy of viewing depression as a univariate disorder including McNeal & Cimbolic (1986), Schiepers, Wichers & Maes (2005) and Ressler & Nemeroff (2000).
Neuroendocrine factors
The IRS model of depression, also known as the cytokine or macrophage theory, implicates an association between depression and abnormal activation of the inflammatory response system (Schiepers, Wichers & Maes, 2005). The theory can be logically applied as the behaviours exhibited during times of immune activation are similar to those exhibited during depression – eg appetite loss, fatigue, depressed mood and general disinclination towards activities, all of which disappear when the immune activation is over (Schiepers, Wichers & Maes, 2005). The bi-directional nature of the connection between the CNS and immune system means that when soluble mediators of immune responses are released they have an effect upon the CNS (Leonard, 2000). Hypersecretion of cortisol is an oft observed endocrine change associated with depression, along with increased secretion of prostaglandins (Leonard, 2000) and increased plasma concentrations of proinflammatory cytokines such as interleukin-1 and 6 (Schiepers, Wichers & Maes, 2005). It is believed that immune changes may cause depression via an effect upon the hypothalamo-hypophyseal axis, which produces the majority of hormones.

Folic acid

A negative association between folic acid and depression was first suggested in 1962 (Paul, McDonnell, & Kelly, 2004) , and gained a lot of support since. However, as with monoamines, results vary significantly depending on the method of measuring folic acid levels. Reduced folic acid levels were found in depressed study participants in a number of studies in Australia (Sachdev, Parslow, Lux, Salonikas, Wen & Naidoo 2005) Finland (Tolmunen et al., 2003) and Norway (Bjelland, Tell, Vollset, Refsum, & Ueland, 2003). However, not all results were statistically significant, put down to selection bias often precluding the most depressed patients, who would not take part in any study that involved choosing to respond (Bjelland, Tell, Vollset, Refsum, & Ueland, 2003). In general the more significant results are associated with the more severely depressed patients (Paul, McDonnell & Kelly, 2004).
Supportive evidence is obtained from the findings that depression has a very low incidence in Hong Kong and Taiwan, both areas with very high levels of folic acid in the normal diet (Coppen & Bolander-Gouaille, 2005).
Folic acid is involved, via the one-carbon cycle, in the metabolism of homocysteine to form methionine, the main brain methyl donor (Bottiglieri, Laundy, Crellin, Toone, Carney & Reynolds 2000). Many studies have associated a raised homocysteine level with depression (Reynolds, 2002).
However as folic acid is obtained via the diet, and loss of appetite is a cardinal feature of depression, it cannot easily be ascertained whether the reduced folic acid levels are a cause or effect of depression.

Conclusion

There are a number of biochemical factors that have been implicated in depression but thus far evidence has not shown whether the altered levels are a cause or consequence of the disorder. Likewise the wide variety of methods of obtaining study participants, measuring depression and biochemical markers also greatly affects results. Much evidence is still obtained by assessing the effects of drugs that alleviate symptoms and concluding that they must be restoring abnormal biochemical factors. It would help understanding to see more longitudinal studies which investigated lifetime aetiology of depression and highlighted any biochemical associations.

References

Bjelland, I., Tell, G. S., Vollset, S. E., Refsum, H., & Ueland, P. M. (2003). Folate, vitamin B12, homocysteine, and the MTHFR 677C->T polymorphism in anxiety and depression: The hordaland homocysteine study. Archives of General Psychiatry, 60(6), 618-626.
Bottiglieri, T., Laundy, M., Crellin, R., Toone, B. K., Carney, M. W., & Reynolds, E. H. (2000). Homocysteine, folate, methylation, and monoamine metabolism in depression. Journal of Neurology, Neurosurgery, and Psychiatry, 69(2), 228-232.
Coppen, A., & Bolander-Gouaille, C. (2005). Treatment of depression: Time to consider folic acid and vitamin B12. Journal of Psychopharmacology (Oxford, England), 19(1), 59-65.
Dailly, E., Chenu, F., Renard, C. E., & Bourin, M. (2004). Dopamine, depression and antidepressants. Fundamental & Clinical Pharmacology, 18(6), 601-607.
Gottfries, C. G. (2001). Late life depression. European Archives of Psychiatry and Clinical Neuroscience, 251 Suppl 2, II57-61.
Gupta, A., Elheis, M., & Pansari, K. (2004). Imaging in psychiatric illnesses. International Journal of Clinical Practice, 58(9), 850-858.
Leonard, B. (2000). Stress, depression and the activation of the immune system. World J.Biol.Psychiatry., 1(1), 17-25.
Lestra, C., d’ Amato, T., Ghaemmaghami, C., Perret-Liaudet, A., Broyer, M., & Renaud, B. et al. (1998). Biological parameters in major depression: Effects of paroxetine, viloxazine, moclobemide, and electroconvulsive therapy. relation to early clinical outcome. Biological Psychiatry, 44(4), 274-280.
McNeal, E. T., & Cimbolic, P. (1986). Antidepressants and biochemical theories of depression. Psychological Bulletin, 99(3), 361-374.
Paul, R. T., McDonnell, A. P., & Kelly, C. B. (2004). Folic acid: Neurochemistry, metabolism and relationship to depression. Hum.Psychopharmacol., 19(7), 477-488.
Rang, H. P., Dale, M. M., & Ritter, J. M. (1999). Drugs used in affective disorders. In H. P. Rang, M. M. Dale & J. M. Ritter (Eds.), Pharmacology (Fourth ed.) (pp. 550-565). Edinburgh: Churchill Livingstone.
Ressler, K. J., & Nemeroff, C. B. (2000). Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders. Depression and Anxiety, 12 Suppl 1, 2-19.
Reynolds, E. H. (2002). Folic acid, ageing, depression, and dementia. BMJ (Clinical Research Ed.), 324(7352), 1512-1515.
Sachdev, P. S., Parslow, R. A., Lux, O., Salonikas, C., Wen, W., & Naidoo, D. et al. (2005). Relationship of homocysteine, folic acid and vitamin B12 with depression in a middle-aged community sample. Psychological Medicine, 35(4), 529-538.
Schiepers, O. J., Wichers, M. C., & Maes, M. (2005). Cytokines and major depression. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 29(2), 201-217.
Tolmunen, T., Voutilainen, S., Hintikka, J., Rissanen, T., Tanskanen, A., & Viinamaki, H. et al. (2003). Dietary folate and depressive symptoms are associated in middle-aged finnish men. The Journal of Nutrition, 133(10), 3233-3236.