A double-blind dose-finding pilot study of docosahexaenoic acid (DHA) for major depressive disorder.

We examined the antidepressant efficacy and dose-response pattern of the n-3 docosahexaenoic acid (DHA). Thirty-five depressed adult outpatients (46% women; mean age 42+/-14 years) with a 17-item Hamilton-Depression Scale (HAM-D-17) score of >or=18 were randomized into one of three double-blind dosing arms for 12 weeks. Group A (n=14): 1 g/day of oral DHA; Group B (n=11): 2 g/day; and Group C (n=10): 4 g/day. We measured HAM-D-17 scores, plasma DHA, eicosapentaenoic acid (EPA), and n-6/n-3 ratio. Completer response rates (>or=50% decrease in HAM-D-17 score) were 83% for Group A, 40% for Group B, and 0% for Group C; Groups A and B had significant decreases in HAM-D-17 scores (p<0.05). For completers and intent-to-treat subjects, plasma DHA increased significantly (p<0.05), EPA had little change (p>0.05), and n-6/n-3 decreased significantly (p<0.05). DHA may be effective for depression at lower doses.

Residual cognitive impairments in remitted depressed patients.

Depressive disorders are associated with various cognitive impairments. Studies on whether or not these impairments persist into the euthymic phase have shown conflicting results, due to differences in test versions and in study samples. In this paper, we aimed to compare the cognitive performance of remitted depressed patients with that of age- and gender-matched healthy volunteers across a wide range of cognitive domains. In two studies, we found few differences on neutral as well as emotional information processing tests. The findings indicate that remitted depressed patients who use antidepressant medication still show an increased recognition of facial expression of fear compared to healthy controls. Patients also performed worse on a test of recognition of abstract visual information from long-term memory. No other residual cognitive impairments were found. These results indicate that most of the cognitive impairments associated with depression resolve with recovery through medication, even when recovery is incomplete. Considering the finding that remitted depressed patients have higher levels of cognitive reactivity, future studies may investigate the possibility that these cognitive impairments have not resolved but have become latent, and may therefore easily be triggered by small changes in mood state.

The effects of serotonin manipulations on emotional information processing and mood.

BACKGROUND: Serotonin is implicated in both mood and cognition. It has recently been shown that antidepressant treatment has immediate effects on emotional information processing, which is much faster than any clinically significant effects. This review aims to investigate whether the effects on emotional information processing are reliable, and whether these effects are related to eventual clinical outcome. Treatment-efficiency may be greatly improved if early changes in emotional information processing are found to predict clinical outcome following antidepressant treatment. METHODS: Review of studies investigating the short-term effects of serotonin manipulations (including medication) on the processing of emotional information, using PubMed and PsycInfo databases. RESULTS: Twenty-five studies were identified. Serotonin manipulations were found to affect attentional bias, facial emotion recognition, emotional memory, dysfunctional attitudes and decision making. The sequential link between changes in emotional processing and mood remains to be further investigated. LIMITATIONS: The number of studies on serotonin manipulations and emotional information processing in currently depressed subjects is small. No studies yet have directly tested the link between emotional information processing and clinical outcome during the course of antidepressant treatment. CONCLUSIONS: Serotonin function is related to several aspects of emotional information processing, but it is unknown whether these changes predict or have any relationship with clinical outcome. Suggestions for future research are provided.

Diet rich in alpha-lactalbumin improves memory in unmedicated recovered depressed patients and matched controls.

Depression is associated with reduced brain serotonin (5-hydroxytryptamine; 5-HT) function and with cognitive dysfunctions. A diet rich in alpha-lactalbumin protein has been found to increase the ratio tryptophan /large neutral amino acids (Trp/SigmaLNAA), and to improve cognitive functioning in individuals with high neuroticism scores. Since cognitive dysfunctions sometimes persist after remission of depression, the present study investigated the effects of alpha-lactalbumin-enriched diet on cognition in recovered depressed patients. Twenty-three recovered depressed patients and 20 healthy matched controls without a history of depression consumed meals rich in alpha-lactalbumin or casein protein in a double-blind crossover design. Mood, cognitive function and plasma amino acids were assessed at both sessions before and after dietary intake. Alpha-lactalbumin protein had no effect on mood, but improved abstract visual memory and impaired simple motor performance. These effects were independent of history of depression. Supplements of lactalbumin may be useful for nutrition research in relation to age- or disease-related memory decline. The present findings should be further examined in different (e.g. medicated) samples. The long-term effects of alpha-lactalbumin should also be investigated.

Somatic symptoms in outpatients with major depressive disorder treated with fluoxetine.

Among patients with major depressive disorder (MDD), physical and somatic symptoms are associated with a high degree of disability and healthcare utilization. However, little is known regarding the treatment of these symptoms with standard pharmacotherapy. To measure somatic symptoms of depression, the authors administered The Symptom Questionnaire (Kellner) before and after 8 weeks of open-label treatment with fluoxetine, 20 mg/day, in 170 MDD outpatients (mean age: 40.4 years). Somatic symptom scores decreased significantly after fluoxetine treatment. The degree of reduction in somatic symptoms was significantly and positively correlated with the degree of improvement in depressive symptoms as measured by the 17-item Hamilton Rating Scale for Depression (Ham-D). Somatic symptom scores at baseline did not predict the degree of reduction in Ham-D scores during treatment. However, fluoxetine-remitters had significantly lower somatic symptom scores at end-point than responders who did not remit. Taken together, these findings suggest that developing treatment strategies that successfully target somatic symptoms of depression may further improve the ability to treat depression to remission.

The effects of a diet enriched with alpha-lactalbumin on mood and cortisol response in unmedicated recovered depressed subjects and controls.

Alpha-lactalbumin is a tryptophan-rich protein fraction. A diet enriched with alpha-lactalbumin increases the ratio of tryptophan to the other large neutral amino acids, which may in turn increase brain serotonin content. In stress-vulnerable individuals, alpha-lactalbumin improved mood and attenuated the cortisol response after experimental stress. The aim of the present study was to investigate the effects of an alpha-lactalbumin-enriched diet on mood and stress response in recovered depressed subjects and healthy controls. Forty-three subjects (twenty-three recovered depressed and twenty healthy subjects) received alpha-lactalbumin and casein (placebo) on separate days, in a double-blind randomised crossover design. On both occasions, subjects underwent a stress test (an unsolvable mental arithmetic task with loud noise). The stress test affected mood in both conditions. Although the alpha-lactalbumin diet led to the expected rises in tryptophan and tryptophan:large neutral amino acids ratio, only minimal effects were found on mood and cortisol response to experimental stress. The results were the same for recovered depressed patients and controls. A 1 d diet enriched with alpha-lactalbumin is not sufficient to prevent a stress-induced mood deterioration or a cortisol response in unmedicated, recovered depressed subjects. Future studies may investigate the effects of longer-term diets or may investigate different samples (e.g. medicated patients).

Serum cholesterol in treatment-resistant depression.

OBJECTIVE: Patients with major depressive disorder (MDD) may have significant differences in cholesterol levels compared with healthy controls. A previous study by our group reported that depressed patients with elevated cholesterol levels (>or=200 mg/dl) were significantly more likely to be nonresponders to fluoxetine treatment than depressed patients with nonelevated cholesterol levels. However, very little is known regarding cholesterol in patients with treatment-resistant depression (TRD). The purpose of this study was to compare cholesterol levels at baseline between depressed patients with and without TRD and to test whether cholesterol levels at baseline can predict clinical response in patients with TRD treated with open-label nortriptyline (NT). METHODS: Ninety-two patients with TRD entered a 6-week open trial of NT. Baseline cholesterol levels were randomly collected for 59 of these patients. Controlling for age and gender, we compared baseline cholesterol and triglyceride levels for 35 patients with TRD who did not respond to NT with 205 non-TRD patients who responded to an 8-week open trial of fluoxetine. Furthermore, with the use of logistic regression, we tested whether baseline cholesterol levels predicted clinical response to NT in the patients with TRD. RESULTS: Patients with TRD had higher triglyceride levels at baseline compared with depressed patients without TRD. Cholesterol defined as a dichotomous variable being elevated if equal to or greater than 200 mg/dl, predicted poor response to a 6-week open trial of NT in patients with TRD. CONCLUSIONS: The results of this study confirm the relationship between hypercholesterolemia and poor outcome in the treatment of MDD for patients with TRD.