1,293 publications from this institution
There is now evidence that major depression is associated with an up-regulation of the inflammatory response system (IRS). One of the major factors in this IRS activation is the hyperproduction of pro-inflammatory cytokines. Recently, a number of studies examined whether there is a causative role of these inflammatory mediators in the aetiology of major depression. Studies with animal models and cytokine immune therapy in humans suggest that pro-inflammatory cytokines induce depressive symptomatology. Moreover, these depressive symptoms can be effectively reversed by antidepressant treatment. Thus, it may be suggested that antidepressants suppress pro-inflammatory cytokine production and/or action, resulting in improvement of depressive symptoms. The influence of antidepressants on cytokine production has been examined in culture systems in vitro, and in animal models of depression – in which cytokine production is induced by endotoxin administration. Results suggest that antidepressants of several classes decrease the production of pro-inflammatory cytokines such as interferon-γ and tumour necrosis factor-α, and increase that of interleukin-10, an anti-inflammatory cytokine. Further, the effect of antidepressive treatment on cytokine secretion and on plasma levels of cytokines in depressed patients has been studied. Unfortunately, different approaches to examine cytokine production and different techniques to measure cytokines in plasma are used in these studies. Despite this, current data indicate a normalization of cytokine plasma levels and cytokine production after antidepressant treatment. It is clear, however, that more research is warranted and we strongly argue the need for higher standardization in the methodology used to examine the cytokine network in depressed patients.
Neurodevelopmental disorders appear to be rising in prevalence, according to the recent Global Burden of Disease Study. This rise is likely to be multi-factorial, but the role of certain nutrients known to facilitate neurodevelopment should be considered. One possible contributing factor could be attributed to deficits in choline intake, particularly during key stages of neurodevelopment, which includes the first 1000 days of life and childhood. Choline, a key micronutrient, is crucial for optimal neurodevelopment and brain functioning of offspring. The present narrative review discusses the main research, describing the effect of choline in neurodevelopmental disorders, to better understand its role in the etiology and management of these disorders. In terms of findings, low choline intakes and reduced or altered choline status have been reported in relevant population subgroups: pregnancy (in utero), children with autism spectrum disorders, people with attention deficit hyperactivity disorder and those with dyslexia. In conclusion, an optimal choline provision may offer some neuronal protection in early life and help to mitigate some cognitive effects in later life attributed to neurodevelopmental conditions. Research indicates that choline may act as a modifiable risk factor for certain neurodevelopmental conditions. Ongoing research is needed to unravel the mechanisms and explanations.
Olivia May Dean, Michael Maes, Melanie Ashton, Lesley Berk, Buranee Kanchanatawan, Atapol Sughondhabirom, Sookjareon Tangwongchai, Chee Ng, Nathan Dowling, Gin S. Malhi, and MIchael Berk. Clin Psychopharmacol Neurosci 2014;12:180-8. https://doi.org/10.9758/cpn.2014.12.3.180
The aims of this study were to examine whether pindolol, a serotonin (5-hydroxytryptamine [5-HT])-1A receptor antagonist, and mianserin, a 5-HT2A/C and [small alpha, Greek]2-adrenoceptor ([small alpha, Greek]2-AR) antagonist, may augment the clinical efficacy of fluoxetine, a selective serotonin reuptake inhibitor, and shorten the latency of onset of antidepressive activity in the treatment of major and treatment-resistant depression (TRD). Ten days after admission to the hospital, 31 major depressed patients were randomly assigned using a double-blind, controlled design to receive fluoxetine 20 mg daily, fluoxetine 20 mg daily plus pindolol 7.5 mg daily, or fluoxetine 20 mg plus mianserin 30 mg daily for 5 weeks. The 17-item Hamilton Rating Scale for Depression (HAM-D) score was the primary outcome measure. Analysis of efficacy was conducted according to the intent-to-treat analysis principle considering the change from baseline to endpoint. It was found that fluoxetine plus pindolol and fluoxetine plus mianserin were significantly more effective than fluoxetine alone. Using an outcome measure of 50% reduction in the HAM-D, a 60% response rate was found in patients treated with either fluoxetine plus pindolol or fluoxetine plus mianserin compared with a 9% response rate in patients treated with fluoxetine alone. The HAM-D score 1 week after starting fluoxetine plus mianserin decreased more than 4 points and was significantly greater than that obtained by fluoxetine alone. The results suggest that pindolol and mianserin augment the efficacy of fluoxetine in the treatment of TRD and that mianserin, but not pindolol, may significantly shorten the latency of onset of antidepressive action when combined with fluoxetine. (J Clin Psychopharmacol 1999;19:177-182)
Recently, there have been some reports that changes in serum lipid composition may be related to suicide, major depression and immune‐inflammatory responses. Findings from our laboratory suggest that major depression is accompanied by reduced formation of cholesteryl esters and perhaps by impairment of reverse cholesterol transport. The latter is reportedly accompanied by lower serum high‐density lipoprotein cholesterol (HDL‐C). The aim of this study was to examine whether (i) major depression is accompanied by lower serum HDL‐C or by abnormal levels of serum total cholesterol, triglycerides, low‐density lipoprotein‐C (LDL‐C) or vitamin E, (ii) suicidal attempts are related to lower serum HDL‐C and (iii) there are significant associations between serum HDL‐C and immune/inflammatory markers. A total of 36 subjects with major depression, of whom 28 patients showed treatment resistance, as well as 28 normal control subjects, had blood sampled for the assay of the above lipids, serum zinc (Zn), albumin (Alb) and flow cytometric determination of the T‐helper/T‐suppressor (CD4+/ CD8+) T‐cell ratio. In total, 28 depressed subjects had repeated measures of these variables both before and after treatment with antidepressants. Serum HDL‐C and total cholesterol, as well as the HDL‐C/cholesterol ratio, were significantly lower in subjects with major depression than in normal controls. Serum HDL‐C levels were significantly lower in depressed men who had at some time made serious suicidal attempts than in those without such suicidal behaviour. Treatment with antidepressants for 5 weeks did not significantly alter either serum HDL‐C or other lipid variables. Serum HDL‐C levels were significantly and negatively correlated with the (CD4+/CD8+) T‐cell ratio, and positively correlated with serum Alb and Zn. These results suggest that (i) lower serum HDL‐C levels are a marker for major depression and suicidal behaviour in depressed men, (ii) lower serum HDL‐C levels are probably induced by the immune/inflammatory response in depression and (iii) there is impairment of reverse cholesterol transport from the body tissues to the liver.
