Reduced mitochondrial respiration in T cells of patients with major depressive disorder

Converging evidence indicates that major depressive disorder (MDD) and metabolic disorders might be mediated by shared (patho)biological pathways. However, the converging cellular and molecular signatures remain unknown. Here, we investigated metabolic dysfunction on a systemic, cellular, and molecular level in unmedicated patients with MDD compared with matched healthy controls (HC). Despite comparable BMI scores and absence of cardiometabolic disease, patients with MDD presented with significant dyslipidemia. On a cellular level, T cells obtained from patients with MDD exhibited reduced respiratory and glycolytic capacity. Gene expression analysis revealed increased carnitine palmitoyltransferase IA (CPT1a) levels in T cells, the rate-limiting enzyme for mitochondrial long-chain fatty acid oxidation. Together, our results indicate metabolic dysfunction in unmedicated, non-overweight patients with MDD on a systemic, cellular, and molecular level. This evidence for reduced mitochondrial respiration in T cells of patients with MDD provides translation of previous animal studies regarding a putative role of altered immunometabolism in depression pathobiology

Cognitive function in older adults with major depression: effects of mineralocorticoid receptor stimulation

Memory and executive function are often impaired in older adults with major depression. Mineralocorticoid receptors (MR) are abundantly expressed in the hippocampus and in the prefrontal cortex, brain areas critical for memory and executive function. In both aging and depression, MR expression in the brain is reduced. Therefore, diminished MR function could contribute to impaired cognition in older adults with depression and might be a promising target for pharmacological intervention. Twenty-three older adults with major depression (mean age 61.6 yrs +/- 8.1, n = 13 women) without medication and 24 age-, sex- and education-matched healthy participants received the MR-agonist fludrocortisone (0.4 mg) or placebo in a randomized, double-blind, within-subject cross-over design. We measured psychomotor speed, executive function, verbal learning and memory, and visuospatial memory. Compared to controls, depressed patients performed worse in psychomotor speed (group effect p = 0.01), executive function (group effect p < 0.01), verbal learning (group effect p = 0.02), and verbal memory (group effect p < 0.01) but not in visuospatial memory. There were no significant treatment effects. However, we found a group x treatment interaction in verbal learning (p = 0.04) and visuospatial memory (p = 0.02) indicating that depressed patients performed worse after fludrocortisone whereas controls performed better after fludrocortisone. Our data suggest that -in contrast to younger depressed patients-older adults with depression do not benefit from MR stimulation but deteriorate in cognitive function

Preparation of polyfunctional heterocycles using highly functionalized aminated arylmagnesium reagents as versatile scaffolds

Functionalized Grignard reagents, derived from readily available o-iodoaniline derivatives and obtained via a straightforward iodine−magnesium exchange, can be used to prepare a wide range of polyfunctional indoles, quinolines, and quinazolinones

Cognitive and emotional empathy after stimulation of brain mineralocorticoid and NMDA receptors in patients with major depression and healthy controls

Mineralocorticoid receptors (MR) are predominantly expressed in the hippocampus and prefrontal cortex. Both brain areas are associated with social cognition, which includes cognitive empathy (ability to understand others’ emotions) and emotional empathy (ability to empathize with another person). MR stimulation improves memory and executive functioning in patients with major depressive disorder (MDD) and healthy controls, and leads to glutamate-mediated N-methyl-D-aspartate receptor (NMDA-R) signaling. We examined whether the beneficial effects of MR stimulation can be extended to social cognition (empathy), and whether DCS would have additional beneficial effects. In this double-blind placebo-controlled single-dose study, we randomized 116 unmedicated MDD patients (mean age 34 years, 78% women) and 116 age-, sex-, and education years-matched healthy controls to four conditions: MR stimulation (fludrocortisone (0.4 mg) + placebo), NMDA-R stimulation (placebo + D-cycloserine (250 mg)), MR and NMDA-R stimulation (both drugs), or placebo. Cognitive and emotional empathy were assessed by the Multifaceted Empathy Test. The study was registered on clinicaltrials.gov (NCT03062150). MR stimulation increased cognitive empathy across groups, whereas NMDA-R stimulation decreased cognitive empathy in MDD patients only. Independent of receptor stimulation, cognitive empathy did not differ between groups. Emotional empathy was not affected by MR or NMDA-R stimulation. However, MDD patients showed decreased emotional empathy compared with controls but, according to exploratory analyses, only for positive emotions. We conclude that MR stimulation has beneficial effects on cognitive empathy in MDD patients and healthy controls, whereas NMDA-R stimulation decreased cognitive empathy in MDD patients. It appears that MR rather than NMDA-R are potential treatment targets to modulate cognitive empathy in MDD

Teores de ácidos graxos em ovos comerciais convencionais e modificados com ômega-3 Fatty acids levels in conventional and designer omega-3 commercial eggs

Objetivou-se comparar os teores de ácidos graxos em ovos comerciais convencionais e em ovos modificados com ômega-3. Foram utilizadas 864 poedeiras da linhagem Isa Brown aleatoriamente distribuídas em dois grupos, de modo que cada gaiola com quatro aves foi considerada uma repetição, totalizando 216 repetições. No grupo para produção de ovos convencionais, as aves foram alimentadas durante toda a vida produtiva com ração à base de milho e farelo de soja, enquanto, no grupo para produção de ovos modificados, foram alimentadas, a partir da 22ª semana de idade, com ração contendo 1,5% de substrato de algas marinhas e 1,8% de óleo de peixe. Foram coletados, aleatoriamente, 180 ovos de cada grupo de poedeira (totalizando 360 ovos), que foram distribuídos em delineamento de blocos ao acaso, considerando cada ovo uma repetição. Os ovos modificados com ômega-3 apresentaram menores de índice de gema, mas não diferiram dos ovos convencionais quanto aos demais parâmetros de qualidade. As médias de ácidos graxos poliinsaturados ômega-3 e de ácidos graxos monoinsaturados foram mais altas nos ovos modificados. As relações entre ácidos graxos poliinsaturados e saturados e entre ômega-6 e ômega-3 nos ovos modificados foram próximas ao ideal estimado para alimentação humana. As médias de ácidos graxos poliinsaturados da série ômega-6 e de ácidos graxos saturados nos ovos convencionais foram significativamente maiores que dos ovos modificados com ômega-3.<br>The objective of this work was to compare the levels of fatty acids between conventional commercial eggs and designer omega-3 eggs. It was used 864 Isa Brown line laying hens randomly distributed in two groups, so each cage with four birds was considered a replicate, totalizing 216 repetitions. In the group for production of conventional eggs, birds were fed corn- and soybean-based rations during the entire productive life while in the group for production of designer eggs, they were fed, from the 22nd week of age, rations with 1.5% of marine algae substrate and 1.8% fish oil. A total of 180 eggs was randomly collected from each group of the laying hens (totalizing 360 eggs), which were distributed in a randomized block design, considering each egg a replicate. Designer omega-3 eggs showed the lowest yolk index, but they did not differ from the conventional eggs regarded to the other parameters of quality. Means of omega-3 polyunsaturated fatty acids and monounsaturated fatty acids were higher for designer eggs. The relationships between polyunsaturated and saturated fatty acids and among omega-6 and omega-3 in designer eggs were close to the ideal estimated for human consumption. Means of the polyunsaturated fatty acids from the omega-6 series and of saturated fatty acids were significantly higher than omega-3 designer eggs