Julia Moreno

Th2 cytokine response in Major Depressive Disorder patients before treatment

In Major Depressive Disorder (MDD), the neuroendocrine and immune systems interactions are impaired. We investigated the pro/anti-inflammatory Th1/Th2 cytokine balance in MDD patients and in non-depressed control group. The MDD subjects showed higher levels of cortisol and TNF-alpha, increased CD3+CD8+ and NK percentages, diminished B cell counts and no significant variations in CD3+CD4+ lymphocyte. Moreover, higher levels of IL-4 and IL-13 (Th2) and significantly lower measurements of IL-2 and IFN-gamma (Th1) cytokines were also observed in the MDD group. Overall, we propose that all these changes could be related to the elevated cortisol levels seen in the MDD patients. Further studies are necessary to explore these findings and its implication in future therapeutic approach of MDD patients.

Variations in circulating cytokine levels during 52 week course of treatment with SSRI for major depressive disorder

Major depressive disorder (MDD) is a psychiatric condition characterized by hypercortisolism and variations in circulatory cytokines. Previously it has been reported that administration of selective serotonin reuptake inhibitors (SSRI) in MDD patients modify cortisol and cytokine levels but these studies only evaluated changes over a short time period. This work reports the long-term effects of administration of SSRI on the cortisol levels and pro-/anti-inflammatory cytokine profile in a group of MDD patients treated for 52 weeks. A total of 31 patients diagnosed with MDD received anti depressant treatment with SSRI. HDRS and BDI were administered over a year, and levels of interleukin IL-1beta, IL-10, IL-2, IFN-gamma, IL-4, IL-13, and 24-h urine cortisol were determined at weeks (W) 0, 5, 20, 36 and 52 of treatment. Before treatment we found high levels of cortisol, IL-4, IL-13 (Th2) and IL-10 in MDD patients when compared with healthy volunteers. At W20 psychiatric scales indicated a remission of the depressive episode concomitantly with increments in IL-2 and IL-1beta but without changes in cortisol. Towards the end of the treatment (W52) we observed a significant reduction (p<0.01) in cortisol levels, with an increment in IL-1beta and IFN-gamma and a decrease in Th2 cytokines. Our results suggest that depressed patients only reach a partial reestablishment of HPA axis function after the long-term administration of SSRI.

Melatonin attenuates antipsychotic metabolic effects: an eight-week randomized, double-blind, parallel-group, placebo-controlled clinical trial.

Second‐generation antipsychotics (SGAs) are among the first‐line treatments for bipolar disorder and schizophrenia, but have a tendency to generate metabolic disturbances. These features resemble a metabolic syndrome for which a central autonomic imbalance has been proposed that may originate from the hypothalamic suprachiasmatic nuclei. In a clinical trial, we hypothesized that melatonin, a hormone that regulates the suprachiasmatic nucleus, could attenuate SGA‐induced adverse metabolic effects.

Hesperidin produces antinociceptive response and synergistic interaction with ketorolac in an arthritic gout-type pain in rats

Hesperidin occurs in greatest concentration in plants from the Rutaceae and Lamiaceae families. In human nutrition it contributes to the integrity of blood vessels and its deficiency in the diet has been linked to abnormal capillary leakiness as well as pain. In this study, the bioflavonoid hesperidin was identified as an active compound in an ethanol extract of the Rosmarinus officinalis aerial parts tested in the pain-induced functional impairment model in the rat (PIFIR) as an assay of inflammatory and chronic nociception similar to that observed in clinical gout. Hesperidin produced a dose-dependent and significant response with an ED₂₅=1666.72 mg/kg in comparison to an ED₂₅=302.90 mg/kg for the extract or an ED₂₅=0.47 mg/kg for the reference drug ketorolac in the PIFIR model. Although the antinociceptive response of R. officinalis was reverted in presence of the opioid antagonist naloxone (10 mg/kg, s.c.) and the 5HT(1A) antagonist WAY100635 (0.12 mg/kg, s.c.), the hesperidin response was not modified by naloxone (10 mg/kg), WAY100635 (0.12 mg/kg), bicuculline (1 mg/kg, s.c.), flumazenil (10 mg/kg, i.p.) or caffeine (1 mg/kg, s.c.). Nevertheless, it was reduced in presence of capsazepine (10 or 20 mg/kg, s.c.) suggesting the participation of the TRPV1 receptor, which was reinforced when hesperidin significantly reduced the capsaicin-induced nociceptive response. A synergistic interaction was also observed when antinociceptive doses of hesperidin were combined with those of ketorolac producing 15 combinations mainly in additive and supra-additive responses. These results provide evidence for the antinociceptive activity of hesperidin and demonstrate synergistic response when combined with ketorolac, possibly by involvement of the TRPV1 receptor, suggesting their clinical potential in pain therapy.

Increase in nitric oxide levels and mitochondrial membrane potential in platelets of untreated patients with major depression

Alterations in platelet activity have been associated with the onset of major depressive disorder (MDD) and with ischemic cardiovascular events through mechanisms that remain unknown. The present study evaluated nitric oxide (NO) levels, mitochondrial membrane potential (PMMP), and P-selectin expression in platelets from 30 untreated MDD patients and 30 matched controls by flow cytometry. In addition, tryptophan and serotonin concentrations were measured in the whole blood by high performance liquid chromatography. Patients were assessed with the Mini International Neuropsychiatric Interview and the Hamilton Depression Rating Scale. The patients had not had antidepressant treatment or any other pharmacological interventions for at least 1 year. MDD patients significantly differed from controls in levels of major fluorescent platelets for NO, PMMP, and P-selectin compared with those observed in control subjects. Serotonin concentrations in MDD patients did not differ from those in controls These results demonstrate that untreated MDD patients show increased platelet activation, suggesting an alteration in the platelet function.

Helminth Infection Alters Mood and Short-Term Memory as well as Levels of Neurotransmitters and Cytokines in the Mouse Hippocampus

Helminthic infections are important causes of morbidity and mortality in many developing countries, where children bear the greatest health burden. The ability of parasites to cause behavioral changes in the host has been observed in a variety of host-parasite systems, including the Taenia crassiceps-mouse model. In murine cysticercosis, mice exhibit a disruption in the sexual, aggressive and avoidance predator behaviors. Objective: The present study was conducted to characterize short-term memory and depression-like behavior, as well as levels of neurotransmitters and cytokines in the hippocampus of cysticercotic male and female mice. Methods: Cytokines were detected by RT-PCR and neurotransmitters were quantified by HPLC. Results: Chronic cysticercosis infection induced a decrease in short-term memory in both male and female mice, having a more pronounced effect in females. Infected females showed a significant increase in forced swimming tests with a decrease in immobility. In contrast, male mice showed an increment in total activity and ambulation tests. Serotonin levels decreased by 30% in the hippocampus of infected females whereas noradrenaline levels significantly increased in infected males. The hippocampal expression of IL-4 increased in infected female mice, but decreased in infected male mice. Conclusion: Our study suggests that intraperitoneal chronic infection with cysticerci in mice leads to persistent deficits in tasks dependent on the animals hippocampal function. Our findings are a first approach to elucidating the role of the neuroimmune network in controlling short-term memory and mood in T. crassiceps-infected mice.

Ultrastructural changes and immunolocalization of P-selectin in platelets from patients with major depression

Depression is considered an important risk factor in patients with cardiovascular disease (CVD). Although the biological mechanism is unknown, it has been suggested that hyperactivity of platelets may have an important role in the onset and evolution of cardiovascular damage. The goals of this study were to evaluate by transmission electron microscopy and immunohistochemistry the presence of ultra-structural variations in platelets from individuals with recent diagnosis of major depression disease (MDD, patients without previous anti-depressant treatment and from healthy control subjects.). Platelets from depressed patients had a greater proportion of dendritic forms compared with those obtained from control subjects. Morphological changes, such as dilation of open canalicular and dense tubular systems, platelet vacuolization, electrodense pattern of membranes, and a different immunolocalization of P-selectin were observed in the platelets from depressed patients compared with those isolated from healthy subjects. Our results revealed ultra-structural changes in platelets isolated from patients with MDD suggestive of enhanced platelet activation.

Lignans from Leaves of Rollinia mucosa

A new furofuranic lignan named (+)-epimembrine together with known (+)-epieudesmine and (+)-epimagnoline were isolated from leaves of R. mucosa. Their structures were determined by spectroscopic data. Palmitone and a mixture of β-sitosterol and stigmasterol were also isolated.

Gonadal hormone levels and platelet tryptophan and serotonin concentrations in perimenopausal women with or without depressive symptoms.

Abstract Introduction: The etiology of depressive symptoms associated with the transition to menopause is still unknown; hormonal changes, serotonergic system or insomnia, could be a trigger to depressive symptomatology. The aim of the present study was to evaluate gonadal hormonal levels, platelet serotonin concentrations and platelet tryptophan concentrations in a group of depressed perimenopausal women and their healthy counterparts. Methods: A total of 63 perimenopausal women between 45 and 55 years old were evaluated; of these, 44 were depressed patients, and 19 were perimenopausal women without depression. The instruments that were applied included the Center for Epidemiologic Studies Depression Scale (CES-D), the Hamilton Depression Rating Scale (HDRS) and the Green Climacteric Scale (GCS); gonadal hormone levels and platelet tryptophan and serotonin concentrations were measured in all participants. Differences in hormonal levels and tryptophan and serotonin concentrations were evaluated with respect to specific symptoms, such as insomnia, hot flashes, nervousness, depressed mood and loss of interest. Results: No differences between groups were observed with respect to hormonal levels and tryptophan and serotonin concentrations; mean sleep hours and insomnia were significantly correlated with platelet tryptophan concentrations. Conclusions: In this sample, all symptoms of depression could not be explained by platelet tryptophan and serotonin concentrations and hormonal levels; differences were observed only when we evaluated insomnia and hot flashes.

Alterations on the morphology, nitric oxide synthesis and activity of platelets reproduced in rats as possible biomarkers for depression are reversed by fluoxetine.

Biochemical markers associated with the prognosis of depression in humans are being described in the literature, whereas experimental studies in animal models in search for antidepressant strategies are lacking. The aim of this study was to evaluate platelet morphology, platelet activity and nitric oxide (NO) synthesis as possible biomarkers of depressive-like behavior by using FST alone and in the presence of fluoxetine. Naïve rats were compared to those receiving vehicle or fluoxetine at 10mg/kg i.p. in acute, subchronic and chronic administration in the FST. After behavioral assessment, platelets were isolated from blood samples and analyzed by flow cytometry to determine the platelet mitochondrial membrane potential and NO synthesis. In addition, HPLC and electron microscopy were used to examine 5-HT and tryptophan levels and morphology of platelets, respectively. Rats receiving vehicle and exposed to FST showed depressive-like behavior at all the times tested; after chronic FST rats showed a similar pattern of alteration in platelet morphology and in the studied as possible biochemical markers as those previously recognized in depressive humans. Depressive-like behavior in rats exposed to FST was prevented in the presence of fluoxetine administration at all the times tested and associated with the prevention of alterations in platelet morphology, platelet activity and NO synthesis, and/or in 5-HT concentrations. The results of the present study suggest that platelet function and morphology might be relevant markers for the prognosis of depression and the search for functional treatments. Besides, the relevance of FST as model to study this psychiatric illness is reinforced.