Insulin resistance and depression: cross sectional study
BMJ 2004; 330 doi: https://doi.org/10.1136/bmj.38313.513310.F71 (Published 30 December 2004) Cite this as: BMJ 2004;330:17
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I read with interest the relationship between insulin resistance and depression. It is known that insulin resistance is common in essential hypertension, type 2 diabetes mellitus, coronary heart disease, and hyperlipidemias (metabolic syndrome X). Many with metabolic syndrome X are depressed, though the exact reason for this is not clear. It is also not known whether features of metabolic syndrome X occur first, follow the development of depression or can occur simultaneously. If both metabolic syndrome X and depression are associated with insulin resistance, could there be a common denominator for these two conditions?
Earlier, I and others showed that the concentrations of essential fatty acids (EFAs) and their metabolites are altered in patients with hypertension, type 2 diabetes mellitus, and coronary heart disease (1). There is evidence available to suggest that EFAs and their metabolites such as arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid can alter cell membrane fluidity and modify insulin resistance. Subjects who have low cell membrane content of these fatty acids have higher insulin resistance. Experimental animals fed these fatty acids showed decrease in insulin resistance and increased response to insulin. The low- grade systemic inflammation seen in subjects with metabolic syndrome X in the form of increased plasma concentrations of C-reactive protein, interleukin-6, and tumor necrosis factor-alpha has also been attributed to decreased concentrations of EFAs and their metabolites (2). This is so, since EFAs and their long-chain metabolites can decrease the production of interleukin-6, tumor necrosis factor-alpha and have anti-inflammatory actions. Furthermore, subjects who consume higher amounts of EFAs and their long-chain metabolites in their diet have much lower concentrations of plasma CRP, IL-6 and TNF-alpha (3). These results suggest that insulin resistance and low-grade systemic inflammation seen in metabolic syndrome X could be attributed to lower concentrations of EFAs and their metabolites.
Several studies showed that patients with depression, and schizophrenia have increased plasma concentrations of IL-6 and TNF-alpha and abnormalities of EFA metabolism. The palsma concentrations of eicosapentaneoic acid and docosahexaenoic acid have been found to be low in patients with depression and schizophrenia (4). Thus, there appears to be some common abnormalities in patients with metabolic syndrome X and depression in terms of presence of low-grade systemic inflammation (as evidence by increased plasma concentrations of CRP, IL-6, and TNF-alpha), and an alteration in the metabolism of EFAs.
In view of this, I suggest that an alteration in the metabolism of EFAs may be the underlying cause for both depression and metabolic syndrome X. But, it is not yet certain when the abnormalities in EFAs and cytokines start or what triggers these changes. There is reasonable evidence to believe that these diseases may have their origin during the perinatal period (5). If this is true, perinatal supplementation of EFAs and their metabolites could be of help both in the prevention and treatment of these conditions.
References:
1. Das UN. essnetial fatty acid metabolism in patients with essential hypertension, diabetes mellitus, and coronary heart disease. Prostaglandins Leukot Essen Fatty Acids 1995; 52: 387-391.
2.Das UN. Beneficial effect(s) of n-3 fatty acids in cardiovascular diseases: but, why and how? Prostaglandins Leukot Essen Fatty Acids 2000; 63: 351-362.
3. paschos GK, Rallidis LS, Liakos GK, et al. Background diet infleucnes the anti-inflammatory effect of alpha-linolenic acid in dyslipidemic subjects. Br J Nutr 2004; 92: 649-655.
4. Ranjekar PK, Hinge A, Hegde MV, et al. Decreased antioxidant enzymes and membrane essential polyunsaturated fatty acids in schizophrenia and bipolar mood disorder patients. Psychiatry Res 2003; 121: 109-122.
5. Das UN. A perinatal strategy for preventing adult disease: The role of long-chain polyunaturated fatty acids. Kluwer Academic Publishers, Boston, 2002.
Competing interests: None declared
Competing interests: No competing interests
EDITOR-
The overlap between mood disorders and diabetes is an important area of research because a fuller understanding of the pathophysiology of insulin resistance and how this impacts on mood could lead to new insights and treatments for depression [1]. Timonen and colleagues recently reported a positive correlation between insulin resistance and severity of depressive symptoms that was more marked in patients with impaired glucose tolerance than patients with type 2 diabetes mellitus [2]. However, this finding is tentative and may need to be viewed with caution. The difference between controls and patients with impaired glucose tolerance on Beck Depression Inventory (BDI) scores, although statistically significant, was very small and is of debatable relevance: controls had a median BDI score of 5 and patients had a median score of only 6 [2]. A score of less than 10 on the BDI is within the normal range and a score of 19 is considered the threshold for moderate depression [3].
Even though an attempt was made by the authors to control for factors such as body mass index, smoking, alcohol, exercise and gender, a difference of only one point on the BDI (in subjects aged between 61 and 63) could easily be explained by a number of other important variables, including any current or previous psychiatric illness, comorbid physical illness, current medications, personality factors, or even subtle cognitive impairment.
References
1. Musselman DL, Betan E, Larsen H, Phillips LS. Relationship of depression to diabetes types 1 and 2: epidemiology, biology, and treatment. Biological Psychiatry 2003;54(3):317-329.
2. Timonen M, Laakso M, Jokelainen J, Rajala U, Meyer-Rochow VB, Keinanen-Kiukaanniemi S. Insulin resistance and depression: cross sectional study. BMJ 2005;330(7481):17-18.
3. Beck AT, Ward, CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Archives of General Psychiatry 1961;4:561-571.
Competing interests: None declared
Competing interests: No competing interests
A pedantic statistician writes ...
The authors state "depression is inversely associated with insulin resistance, but positively associated with diabetes". But inverse is not the opposite of positive, negative is the opposite of positive.
An inverse relationship: y = 1/x
A negative relationship: y = -x
Competing interests: None declared
Competing interests: No competing interests