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Study · Randomized controlled trial · n = 30 · 2024

6 results

Altered oxidative neurometabolic response to methylene blue in bipolar disorder revealed by quantitative neuroimaging.

Russo A, Örzsik B, Yalin N, Simpson I, Nwaubani P, Pinna A, De Marco R, Sharp H, Kartar A, Singh N, Blockley N, Stone AJL and 6 more

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Turkheimer FE, Young AH, Cercignani M, Zelaya F, Asllani I, Colasanti A

Journal of affective disorders15 Jul 2024Cited by 4 (Europe PMC)

PMID39019231 (opens in a new tab)DOI10.1016/j.jad.2024.07.029 (opens in a new tab)PepBankPUB-39019231
Publisher pagePubMedAsk about this study
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Summary

BackgroundCerebral mitochondrial and hemodynamic abnormalities have been implicated in Bipolar Disorder pathophysiology, likely contributing to neurometabolic vulnerability-leading to worsen clinical outcomes and mood instability. To investigate neurometabolic vulnerability in patients with BD, we combined multi-modal quantitative MRI assessment of cerebral oxygenation with acute administration of Methylene Blue, a neurometabolic/hemodynamic modulator acting on cerebral mitochondria.MethodsFifteen euthymic patients with chronic BD-type 1, and fifteen age/gender-matched healthy controls underwent two separate MRI sessions in a single-blinded randomized cross-over design, each after intravenous infusion of either MB (0.5 mg/kg) or placebo. MRI-based measures of Cerebral Blood Flow and Oxygen Extraction Fraction were integrated to compute Cerebral Metabolic Rate of Oxygen in Frontal Lobe, Anterior Cingulate, and Hippocampus-implicated in BD neurometabolic pathophysiology. Inter-daily variation in mood rating was used to assess mood instability.ResultsA decrease in global CBF and CMRO2 was observed after acutely administrating MB to all participants. Greater regional CMRO2 reductions were observed after MB, in patients compared to controls in FL (mean = -14.2 ± 19.5 % versus 2.3 ± 14.8 %), ACC (mean = -14.8 ± 23.7 % versus 2.4 ± 15.7 %). The effects on CMRO2 in those regions were primarily driven by patients with longer disease duration and higher mood instability.LimitationsSample size; medications potentially impacting on response to MB.ConclusionsAn altered neurometabolic response to MB, a mitochondrial/hemodynamic modulator, was observed in patients, supporting the hypothesis of vulnerability to neurometabolic stress in BD. Integrating quantitative imaging of cerebral oxygen metabolism with a mitochondrial-targeting pharmacological challenge could provide a novel biomarker of neurometabolic and cerebrovascular pathophysiology in BD.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

6 results from studies that gave the peptide. 6 results from people.

  1. 01HumanRandomized controlled trialMechanism

    In bipolar patients and healthy controls, acute methylene blue reduced global cerebral blood flow.

    In plain wordsMethylene blue reduced global brain blood flow in bipolar patients and healthy controls.

    Peptide
    Methylene blue
    Outcome
    DecreaseGlobal cerebral blood flow
    Study

    n = 30

    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    0.5 mg/kg · intravenousAs given in this study (human).

    Source sentences

    Summary
    A decrease in global CBF and CMRO2 was observed after acutely administrating MB to all participants.
    1 context sentence
    Summary · context
    Fifteen euthymic patients with chronic BD-type 1, and fifteen age/gender-matched healthy controls underwent two separate MRI sessions in a single-blinded randomized cross-over design, each after intravenous infusion of either MB (0.5 mg/kg) or placebo.
  2. 02HumanRandomized controlled trialMechanism

    In bipolar patients and healthy controls, acute methylene blue reduced global cerebral oxygen metabolic rate.

    In plain wordsMethylene blue reduced global brain oxygen metabolism in bipolar patients and healthy controls.

    Peptide
    Methylene blue
    Outcome
    DecreaseGlobal cerebral oxygen metabolic rate
    Study

    n = 30

    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    0.5 mg/kg · intravenousAs given in this study (human).

    Source sentences

    Summary
    A decrease in global CBF and CMRO2 was observed after acutely administrating MB to all participants.
    1 context sentence
    Summary · context
    Fifteen euthymic patients with chronic BD-type 1, and fifteen age/gender-matched healthy controls underwent two separate MRI sessions in a single-blinded randomized cross-over design, each after intravenous infusion of either MB (0.5 mg/kg) or placebo.
  3. 03HumanRandomized controlled trialMechanism

    After methylene blue, bipolar patients showed greater frontal lobe oxygen metabolism reductions than healthy controls.

    In plain wordsAfter methylene blue, frontal lobe oxygen metabolism decreased more in bipolar patients than healthy controls.

    Peptide
    Methylene blue
    Outcome
    DecreaseFrontal lobe oxygen metabolism
    Study

    n = 30

    Comparator
    Healthy controls receiving MB
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    0.5 mg/kg · intravenousAs given in this study (human).

    Measurements

    CMRO2 change
    −14.2%
    bipolar patients
    CMRO2 change
    2.3%
    healthy controls

    Source sentences

    Summary
    Greater regional CMRO2 reductions were observed after MB, in patients compared to controls in FL (mean = -14.2 ± 19.5 % versus 2.3 ± 14.8 %), ACC (mean = -14.8 ± 23.7 % versus 2.4 ± 15.7 %).
    1 context sentence
    Summary · context
    Fifteen euthymic patients with chronic BD-type 1, and fifteen age/gender-matched healthy controls underwent two separate MRI sessions in a single-blinded randomized cross-over design, each after intravenous infusion of either MB (0.5 mg/kg) or placebo.
  4. 04HumanRandomized controlled trialMechanism

    After methylene blue, bipolar patients showed greater anterior cingulate oxygen metabolism reductions than healthy controls.

    In plain wordsAfter methylene blue, anterior cingulate oxygen metabolism decreased more in bipolar patients than healthy controls.

    Peptide
    Methylene blue
    Outcome
    DecreaseAnterior cingulate oxygen metabolism
    Study

    n = 30

    Comparator
    Healthy controls receiving MB
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    0.5 mg/kg · intravenousAs given in this study (human).

    Measurements

    CMRO2 change
    −14.8%
    bipolar patients
    CMRO2 change
    2.4%
    healthy controls

    Source sentences

    Summary
    Greater regional CMRO2 reductions were observed after MB, in patients compared to controls in FL (mean = -14.2 ± 19.5 % versus 2.3 ± 14.8 %), ACC (mean = -14.8 ± 23.7 % versus 2.4 ± 15.7 %).
    1 context sentence
    Summary · context
    Fifteen euthymic patients with chronic BD-type 1, and fifteen age/gender-matched healthy controls underwent two separate MRI sessions in a single-blinded randomized cross-over design, each after intravenous infusion of either MB (0.5 mg/kg) or placebo.
  5. 05HumanRandomized controlled trialOther

    In bipolar patients, greater regional oxygen metabolism reductions after methylene blue were associated with longer disease duration.

    In plain wordsIn bipolar patients, longer disease duration was linked to greater regional brain oxygen metabolism reductions after methylene blue.

    Peptide
    Methylene blue
    Outcome
    Not applicableDisease duration and regional oxygen response
    Study

    n: not reported in source

    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    0.5 mg/kg · intravenousAs given in this study (human).

    Source sentences

    Summary
    The effects on CMRO2 in those regions were primarily driven by patients with longer disease duration and higher mood instability.
    1 context sentence
    Summary · context
    Fifteen euthymic patients with chronic BD-type 1, and fifteen age/gender-matched healthy controls underwent two separate MRI sessions in a single-blinded randomized cross-over design, each after intravenous infusion of either MB (0.5 mg/kg) or placebo.
  6. 06HumanRandomized controlled trialOther

    In bipolar patients, greater regional oxygen metabolism reductions after methylene blue were associated with higher mood instability.

    In plain wordsIn bipolar patients, higher mood instability was linked to greater regional brain oxygen metabolism reductions after methylene blue.

    Peptide
    Methylene blue
    Outcome
    Not applicableMood instability and regional oxygen response
    Study

    n: not reported in source

    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    0.5 mg/kg · intravenousAs given in this study (human).

    Source sentences

    Summary
    The effects on CMRO2 in those regions were primarily driven by patients with longer disease duration and higher mood instability.
    1 context sentence
    Summary · context
    Fifteen euthymic patients with chronic BD-type 1, and fifteen age/gender-matched healthy controls underwent two separate MRI sessions in a single-blinded randomized cross-over design, each after intravenous infusion of either MB (0.5 mg/kg) or placebo.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    14 Oct 2026, 05:02 UTC

    Study results updated

  2. Version 1

    14 Oct 2026, 01:46 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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