Low dopamine transporter binding in the nucleus accumbens in geriatric patients with severe depression

Moriya, Hiroki; Tiger, Mikael; Tateno, Amane; Sakayori, Takeshi; Masuoka, Takahiro; Kim, Woochan; Arakawa, Ryosuke; Okubo, Yoshiro

doi:10.1111/pcn.13020

Cited by 23 publications

(23 citation statements)

References 67 publications

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“…Studies of D2/D3 receptor binding using PET in young or midlife populations are mixed, with some finding increased receptor availability in MDD, potentially reflecting decreased dopaminergic activity and homeostatic receptor upregulation [ 20 – 22 ], while others report no differences [ 23 – 25 ]. In contrast, PET and postmortem studies of adult MDD [ 26 , 27 ] and PET studies in geriatric LLD [ 28 ] consistently demonstrate lower dopamine transporter (DAT) availability in the putamen, NAc, ventral tegmental area, and superior midbrain. This reduction in DAT availability has been interpreted as possible compensatory downregulation due to low dopamine signaling.…”

Section: Dopaminergic System Changes Seen In Depression and The Effec...mentioning

confidence: 99%

Influences of dopaminergic system dysfunction on late-life depression

et al. 2021

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Deficits in cognition, reward processing, and motor function are clinical features relevant to both aging and depression. Individuals with late-life depression often show impairment across these domains, all of which are moderated by the functioning of dopaminergic circuits. As dopaminergic function declines with normal aging and increased inflammatory burden, the role of dopamine may be particularly salient for late-life depression. We review the literature examining the role of dopamine in the pathogenesis of depression, as well as how dopamine function changes with aging and is influenced by inflammation. Applying a Research Domain Criteria (RDoC) Initiative perspective, we then review work examining how dopaminergic signaling affects these domains, specifically focusing on Cognitive, Positive Valence, and Sensorimotor Systems. We propose a unified model incorporating the effects of aging and low-grade inflammation on dopaminergic functioning, with a resulting negative effect on cognition, reward processing, and motor function. Interplay between these systems may influence development of a depressive phenotype, with an initial deficit in one domain reinforcing decline in others. This model extends RDoC concepts into late-life depression while also providing opportunities for novel and personalized interventions.

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Section: Dopaminergic System Changes Seen In Depression and The Effec...mentioning

confidence: 99%

Influences of dopaminergic system dysfunction on late-life depression

et al. 2021

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“…SLC6A3 (a dopamine transporter gene) affects the function of the dopamine nerve system. In geriatric patients with severe major depressive disorder, a low level of dopamine transporter binding was found in the region of the nucleus accumbens and putamen ( Moriya et al, 2020 ). Alteration of dopamine transporter density in depressed patients with anhedonia showed reduced dopamine concentration in the synaptic cleft ( Sarchiapone et al, 2006 ).…”

Section: Discussionmentioning

confidence: 99%

Integrated Network Pharmacology and GC-MS–Based Metabolomics to Investigate the Effect of Xiang-Su Volatile Oil Against Menopausal Depression

Yang

Chen

et al. 2021

Front. Pharmacol.

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Menopausal depression perplexes a great number of women in later life. Xiangfu-Zisu (Xiang-Su), a traditional Chinese herbal pair composed of rhizomes of Cyperus rotundus L. (Xiangfu) and leaves of Perilla frutescens (L.) Britt. (Zisu), is frequently reported with antidepressant-like effects. The volatile oil from Xiangfu and Zisu has shown good antidepressant action, but its mechanism is still unclear. This study aimed to investigate the pharmacological mechanism of Xiang-Su (XS) volatile oil against menopausal depression through gas chromatography–mass spectrometry (GC-MS)-based network pharmacology and metabolomics. First, ADME screening was performed on actual detected components of XS volatile oil to obtain active constituents, and then duplicates of active constituent–related targets and menopausal depression–related targets were collected. These duplicates were considered as targets for XS volatile oil against menopausal depression, followed by GO and KEGG enrichment analyses. It showed that a total of 64 compounds were identified in XS volatile oil, and 38 active compounds were screened out. 42 overlapping genes between 144 compound-related genes and 780 menopausal depression–related genes were obtained. Results showed that targets of SLC6A4 and SLC6A3, regulation of serotonergic and dopaminergic synapses, were involved in the antidepressant mechanism of XS volatile oil. Next, antidepressant-like effect of XS volatile oil was validated in menopausal rats by ovariectomy (OVX) combined with chronic unpredictable mild stress (CUMS). Behavioral tests, biochemical analysis, and GC-MS–based non-targeted plasma metabolomics were employed to validate the antidepressant effect of XS volatile oil. Experimental evidence demonstrated that XS volatile oil reversed behavioral parameters in the sucrose preference test (SPT), open-field test (OFT), forced swim test (FST), and serum estradiol levels in OVX rats. Furthermore, results of metabolomics indicated that XS volatile oil mainly acts on regulating metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, tyrosine metabolism, and tryptophan metabolism, which were corresponding with the above-predicted results. These data suggest that network pharmacology combined with metabolomics provides deep insight into the antidepressant effect of XS volatile oil, which includes regulating key targets like SLC6A4 and SLC6A3, and pathways of serotonergic and dopaminergic synapses.

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“…Besides aripiprazole, it is also possible to hypothesize that the typical antagonism action on 5-HT2A of CAR might be usefu,l even in other antipsychotic-induced akathisia, as seen for mirtazapine, a 5-HT2A antagonist drug. 10 In the present case, we did not consider an ARI-LAI dose reduction based on the current clinical response, the previous failed treatments, and the fact the 300 mg might often not be suitable for severe patients. In conclusion, CAR is safe and useful, but further studies are required.…”

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confidence: 93%

“…A recent study using [ 18 F] FE-PE2I for positron emission tomography, which has high affinity and selectivity for DAT, revealed that geriatric patients with severe MDD showed significantly lower DAT binding in the nucleus accumbens than the controls. 10 However, it remains unclear whether the finding represents functional consequence or early dopaminergic neurodegeneration. Assessment of regional DAT availability in the striatum might provide data allowing the identification of a specific pattern of dopaminergic alteration possibly related to prodromal DLB.…”

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confidence: 99%