Real-time fMRI neurofeedback amygdala training may influence kynurenine pathway metabolism in major depressive disorder

Tsuchiyagaito, Aki; Smith, Jared; El-Sabbagh, Nour; Zotev, Vadim; Misaki, Masaya; Teague, T. Kent; Paulus, Martin P.; Bodurka, Jerzy; Savitz, Jonathan

doi:10.1016/j.nicl.2021.102559

Cited by 23 publications

(32 citation statements)

References 74 publications

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“…Decreased right basolateral amygdala gray matter density was positively correlated with reductions in perceived stress after an 8-week mindfulness-based stress reduction intervention in stressed healthy individuals ( Hölzel et al, 2010 ). More recently, there is growing interest in real-time fMRI amygdala neurofeedback as a clinical tool ( Tsuchiyagaito et al, 2021 , Young et al, 2017 , Zotev and Bodurka, 2020 ), which has been combined with substructural volume analyses. For example, left amygdala real-time fMRI neurofeedback training in Post-Traumatic Stress disorder (PTSD) resulted in volume increases in the left hippocampal CA1 head region ( Misaki et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Amygdala substructure volumes in Major Depressive Disorder

Roddy

Kelly

Farrell

et al. 2021

NeuroImage: Clinical

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Highlights MDD is associated with larger right sided medial nuclei amygdala volumes. MDD is associated with increased right:left whole and substructural volume ratios. MDD cortisol inversely correlated with left corticoamygdaloid transition area. The study implies the potential importance of amygdala substructure volumes in MDD.

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Section: Discussionmentioning

confidence: 99%

Amygdala substructure volumes in Major Depressive Disorder

Roddy

Kelly

Farrell

et al. 2021

NeuroImage: Clinical

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“…Major depressive disorder is a debilitating brain disorder (Tsuchiyagaito et al, 2021 ), which is characterized by impaired cognitive functioning, such as inattention and inability to focus, somatic abnormalities, and neurovegetative symptoms, such as sleep and appetite disturbance (Liu et al, 2021 ; Luo et al, 2021 ). Based on the global burden of a disease report from the World Health Organization, depression is the third rank cause of disability and has been estimated to be the first-rank cause of burden before 2030 (World Health Organization, 2008 ; Ebneabbasi et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Dynamic Functional Connectivity Predicts Treatment Response to Electroconvulsive Therapy in Major Depressive Disorder

Dini

Sendi

Sui

et al. 2021

Front. Hum. Neurosci.

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Background: Electroconvulsive therapy (ECT) is one of the most effective treatments for major depressive disorder. Recently, there has been increasing attention to evaluate the effect of ECT on resting-state functional magnetic resonance imaging (rs-fMRI). This study aims to compare rs-fMRI of depressive disorder (DEP) patients with healthy participants, investigate whether pre-ECT dynamic functional network connectivity network (dFNC) estimated from patients rs-fMRI is associated with an eventual ECT outcome, and explore the effect of ECT on brain network states.Method: Resting-state functional magnetic resonance imaging (fMRI) data were collected from 119 patients with depression or depressive disorder (DEP) (76 females), and 61 healthy (HC) participants (34 females), with an age mean of 52.25 (N = 180) years old. The pre-ECT and post-ECT Hamilton Depression Rating Scale (HDRS) were 25.59 ± 6.14 and 11.48 ± 9.07, respectively. Twenty-four independent components from default mode (DMN) and cognitive control network (CCN) were extracted, using group-independent component analysis from pre-ECT and post-ECT rs-fMRI. Then, the sliding window approach was used to estimate the pre-and post-ECT dFNC of each subject. Next, k-means clustering was separately applied to pre-ECT dFNC and post-ECT dFNC to assess three distinct states from each participant. We calculated the amount of time each subject spends in each state, which is called “occupancy rate” or OCR. Next, we compared OCR values between HC and DEP participants. We also calculated the partial correlation between pre-ECT OCRs and HDRS change while controlling for age, gender, and site. Finally, we evaluated the effectiveness of ECT by comparing pre- and post-ECT OCR of DEP and HC participants.Results: The main findings include (1) depressive disorder (DEP) patients had significantly lower OCR values than the HC group in state 2, where connectivity between cognitive control network (CCN) and default mode network (DMN) was relatively higher than other states (corrected p = 0.015), (2) Pre-ECT OCR of state, with more negative connectivity between CCN and DMN components, is linked with the HDRS changes (R = 0.23 corrected p = 0.03). This means that those DEP patients who spent less time in this state showed more HDRS change, and (3) The post-ECT OCR analysis suggested that ECT increased the amount of time DEP patients spent in state 2 (corrected p = 0.03).Conclusion: Our finding suggests that dynamic functional network connectivity (dFNC) features, estimated from CCN and DMN, show promise as a predictive biomarker of the ECT outcome of DEP patients. Also, this study identifies a possible underlying mechanism associated with the ECT effect on DEP patients.

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“…In mood disorders, antidepressant treatment with an selective serotonin reuptake inhibitor (SSRI) ( 48 ), ketamine ( 48 , 101 ), electroconvulsive therapy (ECT) ( 79 , 102 ) or real time functional magnetic resonance imaging (RT fMRI) neurofeedback training ( 103 ) typically have similar effects on the KP pathway as evidenced by overall lowering of QUINO and 3-HK levels (typically thought to be more neurotoxic in nature), as well as increases in KA, which is seen as neuroprotective. These KP changes, as well as baseline high QUINO and low KA levels were predictive for treatment response or remission ( 48 , 101 , 104 ).…”

Section: Link Between Peripheral Kp Markers and Endo-phenotypical Markers Of Psychiatric Illnessmentioning

confidence: 99%

Brain Versus Blood: A Systematic Review on the Concordance Between Peripheral and Central Kynurenine Pathway Measures in Psychiatric Disorders

et al. 2021

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ObjectiveDisturbances in the kynurenine pathway have been implicated in the pathophysiology of psychotic and mood disorders, as well as several other psychiatric illnesses. It remains uncertain however to what extent metabolite levels detectable in plasma or serum reflect brain kynurenine metabolism and other disease-specific pathophysiological changes. The primary objective of this systematic review was to investigate the concordance between peripheral and central (CSF or brain tissue) kynurenine metabolites. As secondary aims we describe their correlation with illness course, treatment response, and neuroanatomical abnormalities in psychiatric diseases.MethodsWe performed a systematic literature search until February 2021 in PubMed. We included 27 original research articles describing a correlation between peripheral and central kynurenine metabolite measures in preclinical studies and human samples from patients suffering from neuropsychiatric disorders and other conditions. We also included 32 articles reporting associations between peripheral KP markers and symptom severity, CNS pathology or treatment response in schizophrenia, bipolar disorder or major depressive disorder.ResultsFor kynurenine and 3-hydroxykynurenine, moderate to strong concordance was found between peripheral and central concentrations not only in psychiatric disorders, but also in other (patho)physiological conditions. Despite discordant findings for other metabolites (mainly tryptophan and kynurenic acid), blood metabolite levels were associated with clinical symptoms and treatment response in psychiatric patients, as well as with observed neuroanatomical abnormalities and glial activity.ConclusionOnly kynurenine and 3-hydroxykynurenine demonstrated a consistent and reliable concordance between peripheral and central measures. Evidence from psychiatric studies on kynurenine pathway concordance is scarce, and more research is needed to determine the validity of peripheral kynurenine metabolite assessment as proxy markers for CNS processes. Peripheral kynurenine and 3-hydroxykynurenine may nonetheless represent valuable predictive and prognostic biomarker candidates for psychiatric disorders.

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Real-time fMRI neurofeedback amygdala training may influence kynurenine pathway metabolism in major depressive disorder

Cited by 23 publications

References 74 publications

Amygdala substructure volumes in Major Depressive Disorder

Amygdala substructure volumes in Major Depressive Disorder

Dynamic Functional Connectivity Predicts Treatment Response to Electroconvulsive Therapy in Major Depressive Disorder

Brain Versus Blood: A Systematic Review on the Concordance Between Peripheral and Central Kynurenine Pathway Measures in Psychiatric Disorders

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