Metabolic Syndrome and Psychiatric ... - Google Book Search
It has long been known that a disproportionately large percentage of patients with diabetes also suffer major depression. The prevalence of major depression in diabetics, regardless of whether their diabetes is type 1 or type 2, is roughly 3 times that seen in the general population. However, the likelihood of depression is often increased in individuals dealing with serious and potentially disabling illnesses. Plus, the significance of the high prevalence of depression in diabetics, and whether it reflects some interaction between the two seemingly disparate conditions has not been entirely clear.
Over recent years it has become apparent that there is a relationship between major depression and metabolic syndrome, which is frequently the precursor of diabetes type 2. Men and women with depression are more likely than those without depression to develop metabolic syndrome. People with depression often have the abdominal obesity, insulin resistance, hypertension, hyperlipidemia, and elevated fasting glucose levels that characterize the syndrome. There is also a strong relationship between depression and insulin resistance. Insulin resistance, a cardinal feature of metabolic syndrome, is four times more likely to occur in depressed individuals. Although Major depression is associated with metabolic syndrome, it is not clear how the two are related. Does depression cause the metabolic syndrome, or do the biochemical changes of metabolic syndrome lead to depression?
Evidence suggests that depression can set the stage for later development of metabolic syndrome. Women who complain of depression, anxiety, and anger are more likely than women without those psychological characteristics to develop metabolic syndrome in subsequent years. Path analyses have shown statistically that the progression from depression to poor health habits to metabolic syndrome is the most likely course of events when depression and metabolic syndrome coexist.
One explanation for how depression might lead to metabolic syndrome is that depression fosters unhealthy lifestyles. Patients with depression often smoke. They are inactive and eat poorly. Although many patients with major depression have poor appetites, some sufferers crave sweets and indulge in "comfort foods" packed with high glycemic index carbohydrates. This is particularly the case in so-called atypical depression. Despite its name, atypical depression may actually be a common form of depression in women. Comorbidity of depression, obesity, and metabolic syndrome occurs more often in women than in men.
Overeating, smoking, drinking, inactivity, and carbohydrate craving are at least partially responsible for the tendency of people with depression to develop metabolic syndrome. However, even when these unhealthy habits are statistically removed from the equation, there is an unexpectedly high incidence of metabolic syndrome among sufferers of major depression. It is possible that some of the same, underlying physiological abnormalities contribute to both major depression and metabolic syndrome.
Insulin resistance and major depression
The insulin resistance of metabolic syndrome may play a role in major depression. Although insulin dramatically affects the way muscle and fat cells take up and metabolize glucose, neuroscientists have come to believe that it had no significant effect on the brains utilization of glucose. However, insulin has subtle, yet potentially important effects on the way the brain uses glucose.
Insulin is actively transported into the brain, and insulin receptors are found in a variety of important areas of the brain. The amount of insulin in the brain is affected by changes in serum insulin levels. Insulin levels in cerebrospinal fluid increase during acute episodes of hyperinsulemia. In chronic hyperinsulinemia, such as occurs in metabolic syndrome, insulin levels in cerebrospinal fluid can decrease. This is likely due to down regulation of the activity of the insulin transport system into the brain. When insulin is reduced to levels below those generally seen during the fasting state in humans, the brain uses less glucose. It is the older areas of the brain, such as the cerebellum and brainstem, that have the highest density of insulin receptors. However, it is the cerebral cortex, where the higher functions of mind reside, that is most strongly affected by the depletion of insulin.
The insulin resistance that defines metabolic syndrome is most clearly seen in muscle, adipose tissue, and liver. Although changes in insulin levels can clearly affect brain activity, there has been a question as to whether the insulin resistance seen in peripheral tissue also occurs in the brain tissue of patients with metabolic syndrome. Recent studies with human subjects have shown that this is the case. When glucose and insulin levels are controlled by clamping techniques, insulin resistant subjects show less cortical excitation than insulin sensitive subject to the same serum levels of insulin. The degree of insulin's affect on cortical activity is in positive correlation with insulin sensitivity as measured by the ability of insulin to stimulate glucose uptake in peripheral tissues. The ability of a specific level of serum insulin to enhance glucose metabolism in the cerebral cortex is also diminished in subjects with peripheral insulin resistance. This resistance to insulin is most apparent in the prefrontal cortex and other areas of the brain involved in motivation and reward.
Perhaps the most compelling evidence of brain tissue becoming resistant to insulin comes from a study in which the response to insulin was evaluated ex viVo using slices of brain removed from hamsters made insulin resistant by feeding them a fructose enriched diet. Direct administration of insulin into brain tissue was less effective in generating insulin induced long-term inhibition in sections from insulin resistant animals than in those for control animals. Existing data do suggest that decreases in insulin activity in the brain, due either to insulin resistance in brain tissue or decreases in the ability of insulin to reach the brain, could play a significant role in the development of major depression.
Consistent with insulin resistance causing depression are findings that chromium, an essential mineral known to enhance the effects of insulin, can help relieve depression. Chromium has been used successfully for treatment of both depression and dysthymia. The latter is a mild but persistent form of depression. Interestingly, the type of depression that may best be helped by chromium is atypical depression. This is the form of depression were commonly seen in women, that is characterized by a depressed mood, lack of motivation, low sex drive, carbohydrate craving, and sleeping too much. The strongest effects of chromium were in countering carbohydrate craving, increased appetite, and decreased sex drive.
Lithium is a medication that has long been used to treat bipolar and affective disorder. It is also used to augment the effects of antidepressants in treatment resistant depression. Lithium mimics several of the effects of insulin in the brain. Both lithium and insulin inhibits the passivity of the increasingly important enzyme, glycogen synthase kinase 3. Moreover, both lithium and insulin stimulates the effects of the enzymes phosphatidylinositol-3-kinase and protein kinase B. it is not known to what degree the benefits of lithium are due to mimicking the effects of insulin. Neither is it known if lithium has any special benefit for patients that suffer both depression and metabolic syndrome or diabetes type 2. Omega-3 deity assets, which have been found to improve some symptoms of both major depression and metabolic syndrome have also been found to enhance the activity of phosphatidylinositol 3 kinase.