Abstracts
Brain Phosphorous Metabolism
High energy phosphate metabolism, intracellular pH, and membrane phospholipid metabolism are altered in depressed patients.
"Brain Phosphorous Metabolism in Depressive Disorders Detected by Phosphorous-31 Magnetic Resonance Spectroscopy," Kato, Tadafumi, Journal of Affective Disorders, 1992;26:223-230.
B Vitamin deficiency
B Vitamins
Certain B vitamins are deficient in major depression. Blood levels may not reflect central nervous system vitamin function or the severity of the effective syndromes.
Older depressed subjects do not necessarily have worse B vitamin status than younger depressed patients.
"B Complex Vitamin Patterns In Geriatric and Young Adult Patients With Major Depression", Bell, Iris R., MD, Ph.D., et al, Journal of The American Geriatric Society, 1991;39(3):252-257.
Caffeine & sugar
Depression is accompanied by appetite and weight changes. Those who are treated for depression frequently have an increased appetite for carbohydrates when they become depressed. It has been theorized that this carbohydrate craving is related to carboydrate's effect on serotonin synthesis. Depressed patients tend to have a serotonin deficit and carbohydrate consumption increases serotonin synthesis. The serotonin increase occurs regardless of whether the carbohydrates are simple or complexed. Yet depressed patients have a preferential craving for simple carbohydrates which does not support the serotonin hypothesis because the short term lift which simple sugars give results in usually longer term fatigue.
Elimination of simple sugars decreases depression.
Cerebral activation may be affected by diet. Refined sucrose intake causes the greatest change in brain wave activity. Delta, alpha and theta brain waves are increased post sucrose challenge.
Caffeine elimination improves mood. Elimination of caffeine and sucrose resolves depression in some patients. The Christensen Dietary Distress Inventory helps identify the diet responders. Elimination should be done for at least two weeks. Reintroduction in a blinded fashion can be used to find which agent causes the depression. The dietary response does not occur in everyone and should be used in conjunction with appropriate psychotherapy.
"The Role of Caffeine and Sugar in Depression", Christensen, Larry, Ph.D., The Nutrition Report, March 1991;9(3):17,24.
Plasma cholesterol
Plasma cholesterol reduction may be associated with suicides and violent death.
In men 70 years or older, depression was 3 times more common with low plasma cholesterol than in those with the higher concentrations. The depressive scores correlated significantly and inversely with plasma cholesterol concentrations, even after adjustment for other variables. If cholesterol lowering increases depression, only those with high cardiovascular risk should be treated.
"Plasma Cholesterol and Depressive Symptoms in Older Men", Morgan, Ross E., et al, The Lancet, January 9, 1993;341:75-79.
Chromium picolinate
Depression is often associated with insulin resistance, owing to cortisol overproduction; conversely, many studies suggest that diabetics are at increased risk for depression.
Recent evidence indicates that insulin is transported through the blood-brain barrier and influences brain function via widely distributed insulin receptors on neurons. These receptors are particularly dense on catecholaminergic synaptic terminals, and, while effects are variable dependent on brain region, several studies indicate that insulin promotes central catecholaminergic activity, perhaps by inhibiting synaptic re-uptake of norepinephrine. Additionally, it is well known that insulin enhances serotonergic activity in increasing blood-brain barrier transport of tryptophan.
Since impaired monoaminergic activity in key brain pathways is believed to play an etiological role in depression, techniques which promote effective insulin activity, both centrally and peripherally, may be therapeutically beneficial in this disorder. This may rationalize anecdotal reports of improved mood in clinical depressives and diabetics receiving the insulin-sensitizing nutrient chromium picolinate.
Chromium picolinate - perhaps in conjunction with other insulin-sensitizing measures such as low-fat diet and aerobic exercise training (already shown to be beneficial in depression) - should be tested as an adjuvant for the treatment and secondary prevention of depression.
McCarty MF: Enhancing central and peripheral insulin activity as a strategy for the treatment of endogenous depression--an adjuvant role for chromium picolinate?. Med Hypotheses, 1994 Oct, 43:4, 247-52.
Adequacy of dietary intake
Dietary intake
Assessed the dietary intake of individuals experiencing a current episode of major depression. (3-day food records).
Females, as a group, consumed a diet that provided 100% of the RDA whereas the diet of males was deficient in energy and 4 of 16 nutrients examined. Considerable variation existed in the dietary intake of both males and females with some individuals in both groups consuming a diet containing less than the RDA in one or more nutrients due to a decrease in food intake.
A substantial percentage of the depressed sample consumed less than the RDA of one or more nutrients. This seems to be due to an inadequate food intake rather than a deficient diet.
Christensen L & Somers S: Adequacy of the dietary intake of depressed individuals. J Am Coll Nutr, 1994 Dec, 13:6, 597-600.
Nutritional status
Nutritional status (1)
Dementia, depression, and Parkinson's disease are in themselves challenging problems in old age. Recognition and diagnosis are often suboptimal. In dementia, many contributing factors must be considered, including nutrition, but in all these conditions the effects of the cognitive, attitudinal, and motor changes can produce permanent and severe nutritional compromise.
Yet many simple steps can be taken to prevent poor nutrition in these diseases, and the primary care practitioner is central to this process of recognition and intervention.
Cohen D: Dementia, depression, and nutritional status. Prim Care, 1994 Mar, 21:1, 107-19.
Nutritional status (2)
Many signs and symptoms suggest poor nutritional status, and some have been categorized by consensus of the Nutrition Screening Initiative as "major indicators".
Virtually all of the signs and symptoms of poor nutritional status are nonspecific and may be caused or exacerbated by other medical conditions. However, by categorizing them as major or minor indicators and summarizing them, the hope is that practicing health professionals will more frequently note these commonly observed changes, appreciate their nutritional significance, and implement nutritional interventions to correct the problems thus preventing the increased morbidity and mortality known to occur in the malnourished older individual.
Ham RJ: The signs and symptoms of poor nutritional status. Prim Care, 1994 Mar, 21:1, 33-54.
Folate levels
A relationship between folate and neuropsychiatric disorders has been inferred from clinical observation and from the enhanced understanding of the role of folate in critical brain metabolic pathways.
Depressive symptoms are the most common neuropsychiatric manifestation of folate deficiency. Conversely, borderline low or deficient serum or red blood cell folate levels have been detected in 15-38% of adults diagnosed with depressive disorders.
Recently, low folate levels have been linked to poorer antidepressant response to selective serotonin reuptake inhibitors. Factors contributing to low serum folate levels among depressed patients as well as the circumstances under which folate and its derivatives may have a role in antidepressant pharmacotherapy must be further clarified.
Alpert JE & Fava M: Nutrition and depression: the role of folate. Nutr Rev, 1997 May, 55:5, 145-9.
Hypericum
Contents:
Concentrated hypericum
Overview and meta-analysis (2)
Pharmacological profile
Concentrated hypericum
In a multicenter, placebo-controlled double-blind trial, the effect on depression (ICD 10 F 32.1) of treatment with an innovative highly concentrated hypericum preparation was investigated.
Treatment resulted in an appreciable improvement in the symptoms of depression, and the 70% response rate (n = 43), corresponded to that of chemical antidepressants. The preparation also showed an anxiolytic effect. The substance was extremely well tolerated, and no side-effects were reported by any of the patients.
Witte B et al., [Treatment of depressive symptoms with a high concentration hypericum preparation. A multicenter placebo-controlled double-blind study]. Fortschr Med, 1995 Oct 10, 113:28, 404-8.
Overview and meta-analysis (1)
To investigate if extracts of Hypericum perforatum (St John's wort) are more effective than placebo in the treatment of depression, are as effective as standard antidepressive treatment, and have fewer side effects than standard antidepressant drugs.
[23 randomised trials including a total of 1757 outpatients with mainly mild or moderately severe depressive disorders].
Hypericum extracts were significantly superior to placebo and similarly effective as standard antidepressants. There were two (0.8%) drop outs for side effects with hypericum and seven (3.0%) with standard antidepressant drugs. Side effects occurred in 50 (19.8%) patients on hypericum and 84 (52.8%) patients on standard antidepressants.
There is evidence that extracts of hypericum are more effective than placebo for the treatment of mild to moderately severe depressive disorders. Further studies comparing extracts with standard antidepressants in well defined groups of patients and comparing different extracts and doses are needed.
Linde K et al., St John's wort for depression--an overview and meta-analysis of randomised clinical trials [see comments]. BMJ, 1996 Aug 3, 313:7052, 253-8.
Overview and meta-analysis (2)
Extracts of Hypericum perforatum St. John's wort, have been used since antiquity for the treatment of depressive symptoms.
In 25 controlled clinical trials where hypericum extract was compared with placebo and established antidepressants, improvement was obtained in 61 percent of patients on low-dose treatment (< 1.2 mg hypericum extract), and in 75 percent of patients treated with a higher dose (2.7 mg).
The side effects were mild and occurred at lower frequency than did those of other antidepressants.
Owing to their beneficial effect and low toxicity, preparations containing extracts from H perforatum might furnish an alternative to established therapy, especially among patients concerned about stigmatization or less apprehensive of herbal medication than of synthetic drugs.
Nordfors M & Hartvig P: [St John's wort against depression in favour again]. Lakartidningen, 1997 Jun 18, 94:25, 2365-7.
Pharmacological profile
The methanolic Hypericum extract LI 160 (Jarsin 300) exerts no protective effect against N-methyl-D-aspartate (NMDA-) or gp120- (from the HIV virus) induced cytotoxicity. Moreover, it is established that Hypericum extract causes no activation of arachidonic acid release from neurons activated by gp120; hence it displays no sensitization effect on the NMDA receptor channel.
The main outcome of this study is the finding that Hypericum extract causes a 50% inhibition (IC50 value) of serotonin uptake by rat synaptosomes at a concentration of 6.2 microglml.
Therefore, the antidepressant activity of Hypericum extract is due to an inhibition of serotonin uptake by postsynaptic receptors. Future studies might focus on the effect of Hypericum extract on serotonin binding to neurons, serotonin storage in granules, the rate of synthesis of serotonin, and on the activity of monoamine oxidase.
Perovic S & Müller WE Pharmacological profile of hypericum extract. Effect on serotonin uptake by postsynaptic receptors. Arzneimittelforschung, 1995 Nov, 45:11, 1145-8.
Lithium & Tryptophan Depletion
Lithium & Tryptophan Depletion
In this study, two white women, one white man, and one black man (mean age of 52.5 years) who had manic depression were studied in a double-blind, placebo-controlled trial of an amino acid mixture that was tryptophan-free. All four patients were on lithium monotherapy, maintaining a mean level of 1.0 mEq/L. It was found during tryptophan depletion that the patients remained euthymic. These data do not suggest that serotonin plays a critical role in the antimanic effect of lithium.
Cassidy, Frederick, et al, Tryptophan Depletion in Recently Manic Patients Treated With Lithium, Biological Psychiatry, 1998;43:230-232.
Omega-3 Fatty Acid
Omega-3 Fatty Acid
Oxidative damage to red cell membranes in depressed patients may cause depletion of omega-3 fatty acids and DHA. In 15 depressed patients compared to 15 healthy control subjects, those who were depressed showed significant depletion of total omega-3 fatty acids and in particular docosahexaenoic acid (DHA) in the cell membranes of red blood cells. Depletion of erythrocyte membrane polyunsaturated fatty acids has also been shown in schizophrenic patients. Dietary supplementation with DHA has been shown to reduce stress-induced aggression in students.
Peet, Malcolm, et al: Depletion of Omega-3 Fatty Acid Levels in Red Blood Cell Membranes of Depressive Patients, Biological Psychiatry, 1998;43:315-319.
Acetyl-L-Carnitine & Depression
Acetyl-L-Carnitine
Acetyl-L-carnitine (ALC) may significantly improve clinical and biological efficiency, especially in depression. In a clinical study, ALC therapy for cognitive disorder among elderly people was observed. Their depression may be due to the abnormal cortisol rhythm within the enocrine system. Hence, cortisol mean levels and rhythms as well as depressive symptoms were measured among the participants. As a result, ALC had significantly greater effect than placebo in treating depression. ALC may alleviate depression among the older population.
M Gecele; G Francesetti; A Meluzzi: Acetyl-L-Carnitine in Aged Subjects with Major Depression: Clinical Efficacy and Effects on the Circadian Rhythm of Cortisol, Dementia 1991; 2:333-337
Acetylcarnitine may be an effective treatment for geriatric patients suffering from serious clinical depression. This agent may not have any side effects. As a result, depression was significantly modified among the patients in the study using acetyl-L-carnitine as compared to placebo. However, the agent did not alleviate symptoms of anxiety, asthenia and sleep disturbances.
Tempesta E, Casella L, Pirrongelli C, Janiri L, Calvani M, Ancona L: L-acetylcarnitine in depressed elderly subjects. A cross-over study vs placebo, Drugs Exp Clin Res 1987;13(7):417-23
Brain Size
Brain size
Depression may affect the size of the hippocampus, a part of the brain essential for learning and memory. In a clinical study, 48 women with or without history of depression were compared. Depressed women had 9 to 13% less volume of the hippocampus. Also, magnetic resonance imaging (MRI) revealed that the amygdala, an area of the brain associated with emotions, was much smaller among women with history of depression. Another discovery was that the volume loss of the hippocampus was affected by depression, not by advanced age. Hence, depression may affect the size of the hippocampus as well as cause long-term damage to the brain.
Sheline YI, Sanghavi M, Mintun MA, Gado MH: Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression, J Neurosci 1999 Jun 15;19(12):5034-43
St. John's Wort
St. John's Wort
St. John's wort may achieve the same results as imipramine against depression but with better patient tolerance, according to this randomized, double-blind study conducted on 324 patients with mild to moderate depression. Patients were divided into two groups taking 75 mg imipramine twice daily or 250 mg hypericum extract ZE 117 twice daily, for a total of 6 weeks. Overall decreases in depression symptoms were similar for each group. However, patients taking hypericum reported better tolerability than did patients taking imipramine.
Woelk H: Comparison of St John's wort and imipramine for treating depression: randomised controlled trial, BMJ 2000 Sep 2;321(7260):536-9
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