Left <scp>DLPFC</scp> activity is associated with plasma kynurenine levels and can predict treatment response to escitalopram in major depressive disorder

Kamishikiryo, Toshiharu; Okada, Go; Itai, Eri; Masuda, Yoshikazu; Yokoyama, Satoshi; Takamura, Masahiro; Fuchikami, Manabu; Yoshino, Atsuo; Mawatari, Kazuaki; Numata, Shusuke; Takahashi, Akira; Ohmori, Tetsuro; Okamoto, Yasumasa

doi:10.1111/pcn.13373

Cited by 8 publications

(2 citation statements)

References 83 publications

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“…The decrease of plasma kynurenine level may indicate the therapeutic response of escitalopram, suggesting that it may participate in the pathophysiological response of severe depression caused by escitalopram treatment. 705 Metabolic signatures of cholangiocarcinoma patients showed that the TCA cycle was reversed, which was obviously manifested by the increase in the level of amino acid and citric acid as intermediate products of TCA cycle and have the ability to predict patients' response to chemotherapy. 706 Stratification of methotrexate efficacy identified significant alterations to various metabolites such as phosphatidylcholines, glucosylceramides, sphingomyelins, hypoxanthine, etc, involved in nucleotide, energy, fatty acid/lipid metabolism.…”

Section: Efficacy Evaluationmentioning

confidence: 99%

Small molecule metabolites: discovery of biomarkers and therapeutic targets

Qiu

Cai

et al. 2023

Sig Transduct Target Ther

240

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Metabolic abnormalities lead to the dysfunction of metabolic pathways and metabolite accumulation or deficiency which is well-recognized hallmarks of diseases. Metabolite signatures that have close proximity to subject’s phenotypic informative dimension, are useful for predicting diagnosis and prognosis of diseases as well as monitoring treatments. The lack of early biomarkers could lead to poor diagnosis and serious outcomes. Therefore, noninvasive diagnosis and monitoring methods with high specificity and selectivity are desperately needed. Small molecule metabolites-based metabolomics has become a specialized tool for metabolic biomarker and pathway analysis, for revealing possible mechanisms of human various diseases and deciphering therapeutic potentials. It could help identify functional biomarkers related to phenotypic variation and delineate biochemical pathways changes as early indicators of pathological dysfunction and damage prior to disease development. Recently, scientists have established a large number of metabolic profiles to reveal the underlying mechanisms and metabolic networks for therapeutic target exploration in biomedicine. This review summarized the metabolic analysis on the potential value of small-molecule candidate metabolites as biomarkers with clinical events, which may lead to better diagnosis, prognosis, drug screening and treatment. We also discuss challenges that need to be addressed to fuel the next wave of breakthroughs.

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Section: Efficacy Evaluationmentioning

confidence: 99%

Small molecule metabolites: discovery of biomarkers and therapeutic targets

Qiu

Cai

et al. 2023

Sig Transduct Target Ther

240

View full text Add to dashboard Cite

show abstract

“…Specifically, remitters showed a greater reduction in DLPFC activation during cognitive tasks than nonremitters. 11 Resting-state fMRI (rsfMRI) research 13 , 14 has also examined the effects of SSRI treatment on regional activity (eg, fractional amplitude of low-frequency fluctuations) in the DLPFC during the resting state. After SSRI treatment, regional DLPFC activity during the resting state increased in responders but not in nonresponders.…”

Section: Introductionmentioning

confidence: 99%

Measures of Connectivity and Dorsolateral Prefrontal Cortex Volumes and Depressive Symptoms Following Treatment With Selective Serotonin Reuptake Inhibitors in Adolescents

et al. 2023

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ImportanceSelective serotonin reuptake inhibitors (SSRIs) are considered a first-line pharmacological treatment for adolescent depression with moderate or higher levels of symptom severity. Thus, it is important to understand neurobiological changes related to SSRIs during the course of treatment for adolescents with depression.ObjectiveTo examine neurobiological changes associated with SSRI treatment in adolescents with major depressive disorder (MDD) by measuring longitudinal changes in volume and resting-state functional connectivity (rsFC) in the dorsolateral prefrontal cortex (DLPFC), a core region of cognitive control.Design, Setting, and ParticipantsThis cohort study was conducted with an open-label design. Adolescents with MDD and healthy controls were recruited at the Seoul National University Hospital (Seoul, South Korea). Adolescents with MDD were treated with escitalopram for 8 weeks. Data analysis was conducted between April 2021 and February 2022.Main Outcomes and MeasuresDepressive symptoms were assessed using the Children’s Depression Rating Scale–Revised. The outcome measure was defined as the change in Children’s Depression Rating Scale–Revised scores from week 0 (before treatment) to week 8 (after treatment) or upon termination. Participants completed structural and resting-state functional magnetic resonance imaging (rsfMRI) assessments before (week 0) and after (week 8) SSRI treatment. Repeated measures analysis of variance and liner mixed model analyses were used to examine the longitudinal associations of SSRI treatment with DLPFC volume and rsFC between responders who showed at least a 40% decrease in depressive symptoms and nonresponders who did not.ResultsNinety-five adolescents with MDD and 57 healthy controls were initially recruited. The final analyses of volume included 36 responders (mean [SD] age, 15.0 [1.6] years; 25 girls [69.4%]) and 26 nonresponders (mean [SD] age, 15.3 [1.5] years; 19 girls [73.1%]). Analyses of rsFC included 33 responders (mean [SD] age, 15.2 [1.5] years; 21 girls [63.6%]) and 26 nonresponders (mean [SD] age, 15.3 [1.5] years; 19 girls [73.1%]). The longitudinal associations of SSRI treatment were more evident in responders than in nonresponders. Responders showed significantly increased right DLPFC volume, decreased bilateral DLPFC rsFC with the superior frontal gyri, and decreased left DLPFC rsFC with the ventromedial PFC after treatment compared with before treatment. Furthermore, increased right DLPFC volume was correlated with decreased rsFC between the right DLPFC and superior frontal gyri after SSRI treatment.Conclusions and RelevanceThe preliminary results of this cohort study suggest that the DLPFC volumetric and rsFC changes may serve as potential neurobiological treatment markers that are associated with symptom improvement in adolescents with MDD.

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Local brain abnormalities in emotional disorders: Evidence from resting state fMRI studies

Jia,

Li,

Wang

et al. 2024

WIRES Cognitive Science

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Emotional disorders inflict an enormous burden on society. Research on brain abnormalities implicated in emotional disorders has witnessed great progress over the past decades. Using cross‐sectional and longitudinal designs, resting state functional magnetic resonance imaging (rs‐fMRI) and its analytic approaches have been applied to characterize the local properties of patients with emotional disorders. Additionally, brain activity alterations of emotional disorders have shown frequency‐specific. Despite the gains in understanding the roles of brain abnormalities in emotional disorders, the limitation of the small sample size needs to be highlighted. Lastly, we proposed that evidence from the positive psychology research stream presents it as a viable discipline, whose suggestions could be developed in future emotional disorders research. Such interdisciplinary research may produce novel treatments and intervention options.This article is categorized under: Psychology > Brain Function and Dysfunction

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Left DLPFC activity is associated with plasma kynurenine levels and can predict treatment response to escitalopram in major depressive disorder

Cited by 8 publications

References 83 publications

Small molecule metabolites: discovery of biomarkers and therapeutic targets

Small molecule metabolites: discovery of biomarkers and therapeutic targets

Measures of Connectivity and Dorsolateral Prefrontal Cortex Volumes and Depressive Symptoms Following Treatment With Selective Serotonin Reuptake Inhibitors in Adolescents

Local brain abnormalities in emotional disorders: Evidence from resting state fMRI studies

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