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1.
J Affect Disord ; 282: 1153-1160, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33601690

RESUMO

BACKGROUND: Monoamine oxidase inhibitors (MAOIs) were the first class of modern antidepressants; however, they are under-utilized as compared to the newer antidepressants. METHODS: In this systematic review, network meta-analysis was used to investigate the comparative efficacy and acceptability of MAOIs for depressive disorders. Overall, the network meta-analysis included 52 double-blind, randomized controlled trials (RCTs) that compared 14 antidepressants or placebo. Across studies, the mean arm size was n = 58 participants from a total N = 6462 (5309 active drug; 1153 placebo). RESULTS: Except fluvoxamine, all antidepressants demonstrated superior efficacy to placebo, and none demonstrated substantially better or worse all-cause dropout rates. Phenelzine demonstrated superior evidence for efficacy compared to all other treatments, and clomipramine demonstrated superior evidence for acceptability compared to all other treatments. LIMITATIONS: The study is primarily limited by low estimate precision due to a relative paucity of studies for some of the included treatment conditions. Further evidence is required to study the relative efficacy of MAOIs against newer antidepressants. CONCLUSIONS: The results of this analysis largely support the re-evaluation of the use of MAOIs as antidepressant agents in the treatment algorithm of depression.

2.
J Affect Disord ; 282: 1193-1194, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33601695
5.
Transl Psychiatry ; 10(1): 425, 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33293520

RESUMO

It has been difficult to find robust brain structural correlates of the overall severity of major depressive disorder (MDD). We hypothesized that specific symptoms may better reveal correlates and investigated this for the severity of insomnia, both a key symptom and a modifiable major risk factor of MDD. Cortical thickness, surface area and subcortical volumes were assessed from T1-weighted brain magnetic resonance imaging (MRI) scans of 1053 MDD patients (age range 13-79 years) from 15 cohorts within the ENIGMA MDD Working Group. Insomnia severity was measured by summing the insomnia items of the Hamilton Depression Rating Scale (HDRS). Symptom specificity was evaluated with correlates of overall depression severity. Disease specificity was evaluated in two independent samples comprising 2108 healthy controls, and in 260 clinical controls with bipolar disorder. Results showed that MDD patients with more severe insomnia had a smaller cortical surface area, mostly driven by the right insula, left inferior frontal gyrus pars triangularis, left frontal pole, right superior parietal cortex, right medial orbitofrontal cortex, and right supramarginal gyrus. Associations were specific for insomnia severity, and were not found for overall depression severity. Associations were also specific to MDD; healthy controls and clinical controls showed differential insomnia severity association profiles. The findings indicate that MDD patients with more severe insomnia show smaller surfaces in several frontoparietal cortical areas. While explained variance remains small, symptom-specific associations could bring us closer to clues on underlying biological phenomena of MDD.

6.
Mol Psychiatry ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33230205

RESUMO

The importance of tryptophan as a precursor for neuroactive compounds has long been acknowledged. The metabolism of tryptophan along the kynurenine pathway and its involvement in mental disorders is an emerging area in psychiatry. We performed a meta-analysis to examine the differences in kynurenine metabolites in major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ). Electronic databases were searched for studies that assessed metabolites involved in the kynurenine pathway (tryptophan, kynurenine, kynurenic acid, quinolinic acid, 3-hydroxykynurenine, and their associate ratios) in people with MDD, SZ, or BD, compared to controls. We computed the difference in metabolite concentrations between people with MDD, BD, or SZ, and controls, presented as Hedges' g with 95% confidence intervals. A total of 101 studies with 10,912 participants were included. Tryptophan and kynurenine are decreased across MDD, BD, and SZ; kynurenic acid and the kynurenic acid to quinolinic acid ratio are decreased in mood disorders (i.e., MDD and BD), whereas kynurenic acid is not altered in SZ; kynurenic acid to 3-hydroxykynurenine ratio is decreased in MDD but not SZ. Kynurenic acid to kynurenine ratio is decreased in MDD and SZ, and the kynurenine to tryptophan ratio is increased in MDD and SZ. Our results suggest that there is a shift in the tryptophan metabolism from serotonin to the kynurenine pathway, across these psychiatric disorders. In addition, a differential pattern exists between mood disorders and SZ, with a preferential metabolism of kynurenine to the potentially neurotoxic quinolinic acid instead of the neuroprotective kynurenic acid in mood disorders but not in SZ.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33159975

RESUMO

Despite the important advances in the understanding of the pathophysiology of MDD, a large proportion of depressed patients do not respond well to currently available pharmacological agents. The present review focuses on new targets and future directions in the pharmacological treatment of MDD. Novel agents and their efficacy in the treatment of depression are discussed, with a focus on the respectively target pathophysiological pathways and the level of available evidence. Although it is expected that classic antidepressants will remain the cornerstone of MDD treatment, at least for the near future, a large number of novel compounds is currently under investigation as for their efficacy in the treatment of MDD, many of which with promising results.

8.
Mol Psychiatry ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33173193

RESUMO

Abnormalities within frontal lobe gray and white matter of bipolar disorder (BD) patients have been consistently reported in adult and pediatric studies, yet little is known about the neurochemistry of the anterior white matter (AWM) in pediatric BD and how medication status may affect it. The present cross-sectional 3T 1H MRS study is the first to use a multivoxel approach to study the AWM of BD youth. Absolute metabolite levels from four bilateral AWM voxels were collected from 49 subjects between the ages of 8 and 18 (25 healthy controls (HC); 24 BD) and quantified. Our study found BD subjects to have lower levels of N-acetylaspartate (NAA) and glycerophosphocholine plus phosphocholine (GPC + PC), metabolites that are markers of neuronal viability and phospholipid metabolism and have also been implicated in adult BD. Further analysis indicated that the observed patterns were mostly driven by BD subjects who were medicated at the time of scanning and had an ADHD diagnosis. Although limited by possible confounding effects of mood state, medication, and other mood comorbidities, these findings serve as evidence of altered neurochemistry in BD youth that is sensitive to medication status and ADHD comorbidity.

9.
Sci Rep ; 10(1): 17386, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33097754

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

10.
Bipolar Disord ; 2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33098737

RESUMO

BACKGROUND: There has been growing scientific evidence in recent years that bipolar disorder (BD) is associated with alterations in the kynurenine (KYN) pathway. However, many of these studies have been limited by their focus on adults. Thus, this preliminary study investigated differences in the peripheral levels of KYN metabolites in children and adolescents with BD, unaffected offspring of parents with BD, and healthy controls (HCs). METHODS: Plasma samples were collected from 49 youths with BD, 19 bipolar offspring, and 31 HCs. Tryptophan (TRP), KYN, and kynurenic acid (KYNA) were separated using electrospray ionization. RESULTS: One-Way ANCOVA after controlling for age, gender, race, BMI-for-age, and smoking status showed that BD had lower levels of KYN, while unaffected high-risk offspring subjects had lower levels of TRP, KYN, and KYNA when compared to HCs. Moreover, we found that KYN, KYN/TRP, and KYNA/KYN levels predicted the severity of depressive symptoms, while the YMRS score was not associated with any metabolite. CONCLUSIONS: In summary, this preliminary study has shown that KYN metabolites are decreased in both affected and unaffected subjects, strengthening the idea that the KYN pathway might underlie the familial risk of BD shown by high-risk offspring individuals. However, longitudinal studies are needed to examine whether the alterations observed in this study represent early markers of risk for later developing BD.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33040316

RESUMO

The search for brain morphology findings that could explain behavioral disorders has gone through a long path in the history of psychiatry. With the advance of brain imaging technology, studies have been able to identify brain morphology and neural circuits associated with the pathophysiology of mental illnesses, such as bipolar disorders (BD). Promising results have also shown the potential of neuroimaging findings in the identification of outcome predictors and response to treatment among patients with BD. In this chapter, we present brain imaging structural and functional findings associated with BD, as well as their hypothesized relationship with the pathophysiological aspects of that condition and their potential clinical applications.

16.
Neurosci Biobehav Rev ; 118: 514-523, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32853625

RESUMO

Dysregulated kynurenine (KYN) pathway has been implicated in the pathophysiology of depression. In this systematic review, we examined the relationship between kynurenine pathway metabolites (KYN, kynurenic acid KYNA, tryptophan TRP, quinolinic acid QUIN, KYN/TRP ratio) and depression symptoms in the context of pro-inflammatory activation and immune response. Out of 5,082 articles, fifteen studies were suitable; ten studies (N = 315 medically ill patients treated with interferon-alpha IFN-α) reported baseline and post-intervention plasma KYN, TRP and KYN/TRP ratios which were included in quantitative meta-analysis. Data from five studies were summarized (IFN-α, interferon-beta IFN-ß, and lipopolysaccharide LPS). We found that IFN-α treatment in patients with chronic illnesses was associated with decreased TRP, increased levels of KYN and KYN/TRP ratio and depression scores from baseline to follow-up at both 4 and 24 weeks. Our findings suggest that increased risk of depression observed after immune-activating agents in patients with chronic medical illnesses is likely mediated by the kynurenine pathway. Further prospective studies are required to investigate the exact pathophysiology of the KYN pathway in depression.

17.
Hum Brain Mapp ; 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32596977

RESUMO

The ENIGMA group on Generalized Anxiety Disorder (ENIGMA-Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega-analysis of a large number of brain structural scans. In this process, the group was confronted with many methodological challenges related to study planning and implementation, between-country transfer of subject-level data, quality control of a considerable amount of imaging data, and choices related to statistical methods and efficient use of resources. This report summarizes the background information and rationale for the various methodological decisions, as well as the approach taken to implement them. The goal is to document the approach and help guide other research groups working with large brain imaging data sets as they develop their own analytic pipelines for mega-analyses.

18.
J Affect Disord ; 273: 592-596, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32560958

RESUMO

BACKGROUND: Neuropsychiatric disorders have been linked to immune mechanisms. Altered peripheral levels of eotaxin-1/CCL11; a cytokine implicated in allergic reactions and aging process; have been reported in bipolar disorder (BD). Several brain areas, especially the temporal lobe, seem to display volume loss and accelerated aging in BD. This study aimed at exploring potential associations between eotaxins and brain volumes in patients with BD compared to controls. METHODS: Twenty-two euthymic patients with BD and 22 controls were enrolled in this study. Serum levels of eotaxin-1/CCL11, eotaxin-2/CCL24 and eotaxin-3/CCL26 were determined alongside brain volumes. RESULTS: There were no differences in the levels of eotaxins between patients and controls. A negative correlation was found between eotaxin-1/CCL11 levels and left-hemisphere's superior-temporal volume only in BD patients, which persisted with covariate adjusted model. CONCLUSION: This study corroborates the emerging evidence of association between inflammation and brain volumes in BD. Our preliminary results also support the hypothesis of a possible role of eotaxin-1/CCL11 in accelerated brain aging in BD.

19.
Mol Psychiatry ; 2020 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-32467648

RESUMO

Emerging evidence suggests that obesity impacts brain physiology at multiple levels. Here we aimed to clarify the relationship between obesity and brain structure using structural MRI (n = 6420) and genetic data (n = 3907) from the ENIGMA Major Depressive Disorder (MDD) working group. Obesity (BMI > 30) was significantly associated with cortical and subcortical abnormalities in both mass-univariate and multivariate pattern recognition analyses independent of MDD diagnosis. The most pronounced effects were found for associations between obesity and lower temporo-frontal cortical thickness (maximum Cohen´s d (left fusiform gyrus) = -0.33). The observed regional distribution and effect size of cortical thickness reductions in obesity revealed considerable similarities with corresponding patterns of lower cortical thickness in previously published studies of neuropsychiatric disorders. A higher polygenic risk score for obesity significantly correlated with lower occipital surface area. In addition, a significant age-by-obesity interaction on cortical thickness emerged driven by lower thickness in older participants. Our findings suggest a neurobiological interaction between obesity and brain structure under physiological and pathological brain conditions.

20.
Clin Psychopharmacol Neurosci ; 18(2): 279-288, 2020 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-32329308

RESUMO

Objective: Previous studies have indicated a convergent and bidirectional relationship between metabolic syndrome (MetS) and bipolar disorder (BD). As most of these studies focused mainly on adults diagnosed with BD, our study aims to investigate and characterize metabolic disturbances in child-adolescents diagnosed with BD. Methods: We retrospectively examined the medical records of psychiatric hospitalizations with admitting diagnosis of BD in child-adolescents (age < 18 years). Body mass index (BMI), lipid profile, fasting blood glucose, and blood pressure were primary variables. National Cholesterol Education Program criteria were used to define MetS. Reference group data was obtained from the National Health and Nutrition Examination Survey study. Statistical analyses included t tests, chi-square tests, and Fisher's exact tests. Results: We identified 140 child-adolescent patients with BD (mean age = 15.12 ± 1.70 years, 53% male). MetS was significantly more common in BD compared to the reference group: 14% (95% confidence interval [95% CI] 8-20) vs. 6.7% (95% CI 4.1-9.2), p = 0.001 with no significant difference by sex. MetS components were higher in the BD group, particularly BMI ≥ 95% (25% vs. 11.8%, p < 0.001) and high blood pressure (17% vs. 8%, p = 0.05). Moreover, female patients had lower odds of high blood pressure (odds ratio = 0.24 [95% CI 0.08-0.69], p = 0.005). Conclusion: Compared with the general child-adolescent population, the prevalence of MetS was significantly higher in patients with BD of same age. This reiterates the notion of an increased risk of MetS in patients diagnosed with BD; and thus, further exploration is warranted.

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