Skip to content

Study · Measured the body's own peptide · 2021

5 results

Abnormal levels of mitochondrial proteins in plasma neuronal extracellular vesicles in major depressive disorder.

Goetzl EJ, Wolkowitz OM, Srihari VH, Reus VI, Goetzl L, Kapogiannis D, Heninger GR, Mellon SH

Molecular psychiatry1 Sept 2021Cited by 100 (Europe PMC)

PMID34471251 (opens in a new tab)PMCIDPMC8872999 (opens in a new tab)DOI10.1038/s41380-021-01268-x (opens in a new tab)PepBankPUB-34471251
Download PDFPubMedAsk about this study
Jump to 5 results

Summary

To characterize neuronal mitochondrial abnormalities in major depressive disorder (MDD), functional mitochondrial proteins (MPs) extracted from enriched plasma neuron-derived extracellular vesicles (NDEVs) of MDD participants (n = 20) were quantified before and after eight weeks of treatment with a selective serotonin reuptake inhibitor (SSRI). Pretreatment baseline NDEV levels of the transcriptional type 2 nuclear respiratory factor (NRF2) which controls mitochondrial biogenesis and many anti-oxidant gene responses, regulators of diverse neuronal mitochondrial functions cyclophilin D (CYPD) and mitofusin-2 (MFN2), leucine zipper EF-hand containing transmembrane 1 protein (LETM1) component of a calcium channel/calcium channel enhancer, mitochondrial tethering proteins syntaphilin (SNPH) and myosin VI (MY06), inner membrane electron transport complexes I (subunit 6) and III (subunit 10), the penultimate enzyme of nicotinamide adenine dinucleotide (NAD) generation nicotinamide mononucleotide adenylytransferase 2 (NMNAT2), and neuronal mitochondrial metabolic regulatory and protective factors humanin and mitochondrial open-reading frame of the 12S rRNA-c (MOTS-c) all were significantly lower than those of NDEVs from matched controls (n = 10), whereas those of pro-neurodegenerative NADase Sterile Alpha and TIR motif-containing protein 1 (SARM1) were higher. The baseline NDEV levels of transcription factor A mitochondrial (TFAM) and the transcriptional master-regulator of mitochondrial biogenesis PPAR γ coactivator-1α (PGC-1α) showed no differences between MDD participants and controls. Several of these potential biomarker proteins showed substantially different changes in untreated MDD than those we reported in untreated first-episode psychosis. NDEV levels of MPs of all functional classes, except complex I-6, NRF2 and PGC-1α were normalized in MDD participants who responded to SSRI therapy (n = 10) but not in those who failed to respond (n = 10) by psychiatric evaluation. If larger studies validate NDEV MP abnormalities, they may become useful biomarkers and identify new drug targets.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

No result from this study comes from a test of the peptide.

Natural levels measured5

These results measure the body's own peptide. Nobody was given the peptide. They are not evidence about taking it. They are left out of key results, evidence counts and charts.

  1. 01HumanEndogenous levelObservational studyOther

    In adults with major depressive disorder, MOTS‑c levels in plasma neuron-derived extracellular vesicles were significantly lower than in matched controls at baseline.

    In plain wordsIn adults with depression, the body's own MOTS‑c level in brain-cell vesicles from blood was lower than in healthy people.

    Peptide
    MOTS-c
    Outcome
    DecreaseMOTS-c in plasma neuron-derived extracellular vesicles, MDD versus controls
    Study

    n = 30

    Comparator
    Matched controls
    Outcome group
    Mitochondrial function · Mental health and mood

    Source sentences

    Summary
    humanin and mitochondrial open-reading frame of the 12S rRNA-c (MOTS-c) all were significantly lower than those of NDEVs from matched controls (n = 10)
    1 context sentence
    Summary · context
    functional mitochondrial proteins (MPs) extracted from enriched plasma neuron-derived extracellular vesicles (NDEVs) of MDD participants (n = 20) were quantified before and after eight weeks of treatment with a selective serotonin reuptake inhibitor (SSRI).

    This result measures the body's own MOTS-c. Nobody was given the peptide. It is not evidence about taking it.

  2. 02HumanEndogenous levelObservational studyOther

    In adults with major depressive disorder, baseline humanin levels in neuron-derived extracellular vesicles were significantly lower than in matched controls.

    In plain wordsIn adults with major depression, the body's own humanin levels in neuron-derived vesicles were lower than in matched controls.

    Peptide
    Humanin
    Outcome
    DecreaseBaseline humanin in neuron-derived extracellular vesicles
    Study

    n = 30

    Comparator
    Matched controls
    Outcome group
    Mitochondrial function · Mental health and mood

    Source sentences

    Summary
    neuronal mitochondrial metabolic regulatory and protective factors humanin and mitochondrial open-reading frame of the 12S rRNA-c (MOTS-c) all were significantly lower than those of NDEVs from matched controls (n = 10)
    1 context sentence
    Summary · context
    To characterize neuronal mitochondrial abnormalities in major depressive disorder (MDD), functional mitochondrial proteins (MPs) extracted from enriched plasma neuron-derived extracellular vesicles (NDEVs) of MDD participants (n = 20) were quantified before and after eight weeks of treatment with a selective serotonin reuptake inhibitor (SSRI).

    This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.

  3. 03HumanEndogenous levelObservational studyOther

    In adults with major depressive disorder, MOTS‑c levels in neuron-derived extracellular vesicles were normalized in SSRI responders but not in non-responders.

    In plain wordsIn adults with depression, the body's own MOTS‑c level in blood vesicles returned toward normal in SSRI responders, not in non-responders.

    Peptide
    MOTS-c
    Outcome
    IncreaseMOTS-c in neuron-derived vesicles after SSRI treatment in responders
    Study

    n = 20

    Comparator
    SSRI non-responders
    Outcome group
    Mitochondrial function · Mental health and mood

    Source sentences

    Summary
    NDEV levels of MPs of all functional classes, except complex I-6, NRF2 and PGC-1α were normalized in MDD participants who responded to SSRI therapy (n = 10) but not in those who failed to respond (n = 10) by psychiatric evaluation.
    1 context sentence
    Summary · context
    functional mitochondrial proteins (MPs) extracted from enriched plasma neuron-derived extracellular vesicles (NDEVs) of MDD participants (n = 20) were quantified before and after eight weeks of treatment with a selective serotonin reuptake inhibitor (SSRI).

    This result measures the body's own MOTS-c. Nobody was given the peptide. It is not evidence about taking it.

  4. 04HumanEndogenous levelObservational studyOther

    In SSRI responders with major depressive disorder, neuron-derived vesicle levels of mitochondrial proteins in all functional classes except complex I-6, NRF2 and PGC-1α were normalized after eight weeks of treatment; humanin is not reported separately in the result sentence.

    In plain wordsIn depressed adults who responded to an SSRI, most mitochondrial protein levels in neuron-derived vesicles, possibly including the body's own humanin, returned to normal.

    Peptide
    Humanin
    Outcome
    IncreaseHumanin in neuron-derived vesicles after SSRI, responders
    Study

    n = 10

    Comparator
    Baseline
    Outcome group
    Mitochondrial function · Mental health and mood

    Source sentences

    Summary
    NDEV levels of MPs of all functional classes, except complex I-6, NRF2 and PGC-1α were normalized in MDD participants who responded to SSRI therapy (n = 10) but not in those who failed to respond (n = 10) by psychiatric evaluation.
    2 context sentences
    Summary · context
    neuronal mitochondrial metabolic regulatory and protective factors humanin and mitochondrial open-reading frame of the 12S rRNA-c (MOTS-c) all were significantly lower than those of NDEVs from matched controls (n = 10)
    Summary · context
    To characterize neuronal mitochondrial abnormalities in major depressive disorder (MDD), functional mitochondrial proteins (MPs) extracted from enriched plasma neuron-derived extracellular vesicles (NDEVs) of MDD participants (n = 20) were quantified before and after eight weeks of treatment with a selective serotonin reuptake inhibitor (SSRI).

    This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.

  5. 05HumanEndogenous levelObservational studyOther

    In SSRI non-responders with major depressive disorder, neuron-derived vesicle levels of mitochondrial proteins were not normalized after eight weeks of treatment; humanin is not reported separately in the result sentence.

    In plain wordsIn depressed adults who did not respond to an SSRI, mitochondrial protein levels in neuron-derived vesicles, maybe including the body's own humanin, stayed abnormal.

    Peptide
    Humanin
    Outcome
    No significant changeHumanin in neuron-derived vesicles after SSRI, non-responders
    Study

    n = 10

    Comparator
    Baseline
    Outcome group
    Mitochondrial function · Mental health and mood

    Source sentences

    Summary
    NDEV levels of MPs of all functional classes, except complex I-6, NRF2 and PGC-1α were normalized in MDD participants who responded to SSRI therapy (n = 10) but not in those who failed to respond (n = 10) by psychiatric evaluation.
    2 context sentences
    Summary · context
    neuronal mitochondrial metabolic regulatory and protective factors humanin and mitochondrial open-reading frame of the 12S rRNA-c (MOTS-c) all were significantly lower than those of NDEVs from matched controls (n = 10)
    Summary · context
    To characterize neuronal mitochondrial abnormalities in major depressive disorder (MDD), functional mitochondrial proteins (MPs) extracted from enriched plasma neuron-derived extracellular vesicles (NDEVs) of MDD participants (n = 20) were quantified before and after eight weeks of treatment with a selective serotonin reuptake inhibitor (SSRI).

    This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.

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. Versions 4 to 18Current

    28 Oct 2026, 02:02 UTC

    The same notice was added 15 times, first on 13 Oct 2026, 21:44 UTC. The status did not change between them.

    Study results updated

  2. Version 3

    13 Oct 2026, 16:31 UTC

    Study data updated · source update from Europe PMC

  3. Version 2

    10 Oct 2026, 08:19 UTC

    Study results updated

  4. Version 1

    9 Oct 2026, 02:47 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

PepBank is a research reference. Talk to a doctor before you use any peptide.