Prefrontal cortex and depression.
01 Jan 2022-Neuropsychopharmacology (Springer Science and Business Media LLC)-Vol. 47, Iss: 1, pp 225-246
TL;DR: The prefrontal cortex (PFC) has emerged as one of the regions most consistently impaired in major depressive disorder (MDD), and although functional and structural PFC abnormalities have been reported in both individuals with current MDD as well as those at increased vulnerability to MDD, this information has not translated into better treatment and prevention strategies as discussed by the authors.
About: This article is published in Neuropsychopharmacology.The article was published on 2022-01-01. It has received 88 citations till now. The article focuses on the topics: Prefrontal cortex.
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TL;DR: The author first summarizes the extant knowledge about the pathophysiology of anhedonia, which may provide a road map toward novel treatment and prevention strategies, and then highlights several priorities to facilitate clinically meaningful breakthroughs.
Abstract: Anhedonia-the loss of pleasure or lack of reactivity to pleasurable stimuli-remains a formidable treatment challenge across neuropsychiatric disorders. In major depressive disorder, anhedonia has been linked to poor disease course, worse response to psychological, pharmacological, and neurostimulation treatments, and increased suicide risk. Moreover, although some neural abnormalities linked to anhedonia normalize after successful treatment, several persist-for example, blunted activation of the ventral striatum to reward-related cues and reduced functional connectivity involving the ventral striatum. Critically, some of these abnormalities have also been identified in unaffected, never-depressed children of parents with major depressive disorder and have been found to prospectively predict the first onset of major depression. Thus, neural abnormalities linked to anhedonia may be promising targets for prevention. Despite increased appreciation of the clinical importance of anhedonia and its underlying neural mechanisms, important gaps remain. In this overview, the author first summarizes the extant knowledge about the pathophysiology of anhedonia, which may provide a road map toward novel treatment and prevention strategies, and then highlights several priorities to facilitate clinically meaningful breakthroughs. These include a need for 1) appropriately controlled clinical trials, especially those embracing an experimental therapeutics approach to probe target engagement; 2) novel preclinical models relevant to anhedonia, with stronger translational value; and 3) clinical scales that incorporate neuroscientific advances in our understanding of anhedonia. The author concludes by highlighting important future directions, emphasizing the need for an integrated, collaborative, cross-species, and multilevel approach to tackling anhedonic phenotypes.
17 citations
TL;DR: Zhang et al. as discussed by the authors found that there was a significant increase in TRPV4 in the hippocampus in a depression mouse model induced by LPS, and they considered that the nonselective cation channel transient receptor potential vanilloid 4 has an important role in contributing to the depression-like behavior following LPS-induced systemic inflammation.
16 citations
TL;DR: In this article , the authors compared brain 5-HT release capacity in patients experiencing a major depressive episode (MDE) to that of healthy control subjects (HCs) without depression.
13 citations
TL;DR: Wang et al. as discussed by the authors used ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) and qualitatively identified the major active ingredients in the LBRD standard decoction, respectively.
Abstract: Lily Bulb and Rehmannia Decoction (LBRD), is a traditional Chinese formula that has been shown to be safe and effective against depression; however, its material basis and pharmacological mechanisms remain unknown. Here, ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) and high-performance liquid chromatography (HPLC) were used to identify the chemical spectrum and qualitatively identify the major active ingredients in the LBRD standard decoction, respectively. Subsequently, we assessed the behavior, neuronal function and morphology, neurotransmitter levels, hypothalamic–pituitary–adrenal (HPA)-axis associated hormones, inflammatory cytokine levels, and miRNA/mRNA expression alterations in an in vitro/vivo depression model treated by the LBRD standard decoction. Finally, miRNA/mRNA regulatory networks were created through bioinformatics analysis, followed by functional experiments to verify its role in LBRD standard decoction treatment. A total of 32 prototype compounds were identified in the LBRD standard decoction, and the average quality of verbascoside in the fresh lily bulb decoction, fresh raw Rehmannia juice, and the LBRD standard decoction were 0.001264%, 0.002767%, and 0.009046% (w/w), respectively. Administration of the LBRD standard decoction ameliorated chronic unpredictable mild stress (CUMS)-induced depression-like phenotypes and protected PC12 cells against chronic corticosterone (CORT)-induced injury. The levels of neurotransmitter, cytokine, stress hormones and neuronal morphology were disrupted in the depression model, while LBRD standard decoction could work on these alterations. After LBRD standard decoction administration, four differentially expressed miRNAs, rno-miR-144-3p, rno-miR-495, rno-miR-34c-5p, and rno-miR-24-3p, and six differentially expressed mRNAs, Calml4, Ntrk2, VGAT, Gad1, Nr1d1, and Bdnf overlapped in the in vivo/vitro depression model. Among them, miR-144-3p directly mediated GABA synthesis and release by targeting Gad1 and VGAT, and miR-495 negatively regulated BDNF expression. The LBRD standard decoction can reverse the above miRNA/mRNA network-mediated GABA and BDNF expression in the in vivo/vitro depression model. Collectively, the multi-components of the LBRD standard decoction altered a series of miRNAs in depression through mediating GABAergic synapse, circadian rhythm, and neurotrophic signaling pathway etc., thereby abolishing inhibitory/excitatory neurotransmitter deficits, recovering the pro-/anti-inflammatory cytokine levels and regulating the HPA-axis hormone secretion to achieve balance of the physiological function of the whole body.
7 citations
TL;DR: In this paper , the authors developed new approaches to characterize brain networks to potentially contribute to a better understanding of mechanisms involved in depression, and found significant differences in functional connectivity (FC) between depressed patients vs. healthy controls.
Abstract: Aim: This study aims to develop new approaches to characterize brain networks to potentially contribute to a better understanding of mechanisms involved in depression. Method and subjects: We recruited 90 subjects: 49 healthy controls (HC) and 41 patients with a major depressive episode (MDE). All subjects underwent clinical evaluation and functional resting-state MRI. The data were processed investigating functional connectivity network measures across the two groups using Brain Connectivity Toolbox. The statistical inferences were developed at a functional network level, using a false discovery rate method. Linear discriminant analysis was used to differentiate between the two groups. Results and discussion: Significant differences in functional connectivity (FC) between depressed patients vs. healthy controls was demonstrated, with brain regions including the lingual gyrus, cerebellum, midcingulate cortex and thalamus more prominent in healthy subjects as compared to depression where the orbitofrontal cortex emerged as a key node. Linear discriminant analysis demonstrated that full-connectivity matrices were the most precise in differentiating between depression vs. health subjects. Conclusion: The study provides supportive evidence for impaired functional connectivity networks in MDE patients.
6 citations
References
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TL;DR: Results presented below indicate that immobility is reduced by different treatments known to be therapeutic in depression including three drugs, iprindole, mianserin and viloxazine which although clinically active show little or no ‘antidepressant’ activity in the usual animal tests.
Abstract: A MAJOR problem in the search for new antidepressant drugs is the lack of animal models which both resemble depressive illness and are selectively sensitive to clinically effective antidepressant treatments. We have been working on a new behavioural model in the rat which attempts to meet these two requirements. The method is based on the observation that a rat, when forced to swim in a situation from which there is no escape, will, after an initial period of vigorous activity, eventually cease to move altogether making only those movements necessary to keep its head above water. We think that this characteristic and readily identifiable behavioural immobility indicates a state of despair in which the rat has learned that escape is impossible and resigns itself to the experimental conditions. This hypothesis receives support from results presented below which indicate that immobility is reduced by different treatments known to be therapeutic in depression including three drugs, iprindole, mianserin and viloxazine which although clinically active1–3 show little or no ‘antidepressant’ activity in the usual animal tests4–6.
4,172 citations
TL;DR: A novel test procedure for antidepressants was designed in which a mouse is suspended by the tail from a lever, the movements of the animal being recorded, and the test can separate the locomotor stimulant doses from antidepressant doses.
Abstract: A novel test procedure for antidepressants was designed in which a mouse is suspended by the tail from a lever, the movements of the animal being recorded. The total duration of the test (6 min) can be divided into periods of agitation and immobility. Several psychotropic drugs were studied: amphetamine, amitriptyline, atropine, desipramine, mianserin, nomifensine and viloxazine. Antidepressant drugs decrease the duration of immobility, as do psychostimulants and atropine. If coupled with measurement of locomotor activity in different conditions, the test can separate the locomotor stimulant doses from antidepressant doses. Diazepam increases the duration of immobility. The main advantages of this procedure are the use of a simple, objective test situation, the concordance of the results with the validated "behavioral despair" test from Porsolt and the sensitivity to a wide range of drug doses.
3,139 citations