Neural cell-derived plasma exosome protein abnormalities implicate mitochondrial impairment in first episodes of psychosis.
Goetzl. Edward J EJ; Srihari. Vinod H VH; Guloksuz. Sinan S; Ferrara. Maria M; Tek. Cenk C; Heninger. George R GR
Key Findings
- First‑episode psychosis patients show significantly reduced humanin levels in astrocyte‑ and neuron‑derived exosomes compared to healthy controls
- Other mitochondrial proteins like mitofusin 2, cyclophilin D, and MOTS‑c are also decreased, indicating broader mitochondrial dysfunction
- The authors propose that drugs or mimetics that raise these peptide levels might have therapeutic value in early schizophrenia
Practical Outcomes
- For biohackers, the study flags humanin as a potential mitochondrial health marker in mental‑health contexts, but there’s no direct dosing guidance yet. Until clinical trials emerge, focusing on general mitochondrial support (e.g., exercise, NAD+ precursors, balanced diet) is more evidence‑based, while keeping an eye on future humanin supplement research.
Summary
People experiencing their first episode of psychosis have lower levels of the mitochondrial‑protective peptide humanin (and other related proteins) in brain‑derived tiny particles in their blood, hinting that their mitochondria may be stressed. The authors suggest that boosting these low‑level peptides could become a treatment strategy, but they didn’t test any supplement or drug themselves.
Abstract
Neuroprotective and other functional proteins of mitochondria were quantified in extracts of plasma neural-derived exosomes from ten first-episode psychosis (FP) patients and ten matched psychiatrically normal controls (ctls). Astrocyte-derived extracellular vesicles (ADEVs) and neuron-derived extracellular vesicles (NDEVs) were immunoabsorbed separately from physically precipitated plasma total EVs. Extracted mitochondrial ATP synthase was specifically immunofixed to plastic wells for quantification of catalytic activity based on conversion of NADH to NAD<sup>+</sup> . Other extracted mitochondrial functional proteins were quantified by ELISAs. All protein levels were normalized with EV content of the CD81 exosome marker. FP patient ADEV level but not NDEV level of mitochondrial ATP synthase activity was significantly lower than that of ctls. FP patient ADEV and NDEV levels of the functionally critical mitochondrial proteins mitofusin 2 and cyclophilin D, but not of transcription factor A of mitochondria, and of the mitochondrial short open-reading frame neuroprotective and metabolic regulatory peptides humanin and MOTS-c were significantly lower than those of ctls. In contrast, FP patient NDEV, but not ADEV, level of the mitochondrial-tethering protein syntaphilin, but not of myosin VI, was significantly higher than that of ctls. The distinctively different neural levels of some mitochondrial proteins in FP patients than ctls now should be correlated with diverse clinical characteristics. Drugs that increase depressed levels of proteins and mimetics of deficient short open-reading frame peptides may be of therapeutic value in early phases of schizophrenia.
Study Information
pubmed
2021
10.1096/fj.202002519r