Evidence map›Paper›PMID 35883465›Full record

SynthesisBiomolecules2022

Rational and Translational Implications of D-Amino Acids for Treatment-Resistant Schizophrenia: From Neurobiology to the Clinics.

Andrea de Bartolomeis, Licia Vellucci, Mark C Austin, Giuseppe De Simone, Annarita Barone

Open access · goldAbstract readSystematic Review
In one paragraph

Synthesis in Biomolecules, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 4 pooled it
5.1field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 4 syntheses or guidelines pooled it, 40 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Article
  6. Article
  7. Article
  8. UntargetedTranslational psychiatry · 2026
    Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Pharmaco-Multiomics: A New Frontier in Precision Psychiatry.International journal of molecular sciences · 2025
    Review
  18. Review
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 2 countries.

Andrea de BartolomeisLaboratory of Translational and Molecular Psychiatry and Unit of Treatment-Resistant Psychosis, Section of Psychiatry, Department of Neuroscience, Reproductive Sciences and Dentistry, University of Naples Federico II, 80131 Naples, Italy.
Licia VellucciLaboratory of Translational and Molecular Psychiatry and Unit of Treatment-Resistant Psychosis, Section of Psychiatry, Department of Neuroscience, Reproductive Sciences and Dentistry, University of Naples Federico II, 80131 Naples, Italy.
Mark C AustinClinical Psychopharmacology Program, College of Pharmacy, Idaho State University, Pocatello, ID 83209, USA.
Giuseppe De SimoneLaboratory of Translational and Molecular Psychiatry and Unit of Treatment-Resistant Psychosis, Section of Psychiatry, Department of Neuroscience, Reproductive Sciences and Dentistry, University of Naples Federico II, 80131 Naples, Italy.ORCID 0000-0003-0422-3415
Annarita BaroneLaboratory of Translational and Molecular Psychiatry and Unit of Treatment-Resistant Psychosis, Section of Psychiatry, Department of Neuroscience, Reproductive Sciences and Dentistry, University of Naples Federico II, 80131 Naples, Italy.ORCID 0000-0002-2751-5683
University of Naples Federico II · ITIdaho State University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Schizophrenia has been conceptualized as a neurodevelopmental disorder with synaptic alterations and aberrant cortical-subcortical connections. Antipsychotics are the mainstay of schizophrenia treatment and nearly all share the common feature of dopamine D2 receptor occupancy, whereas glutamatergic abnormalities are not targeted by the presently available therapies. D-amino acids, acting as N-methyl-D-aspartate receptor (NMDAR) modulators, have emerged in the last few years as a potential augmentation strategy in those cases of schizophrenia that do not respond well to antipsychotics, a condition defined as treatment-resistant schizophrenia (TRS), affecting almost 30-40% of patients, and characterized by serious cognitive deficits and functional impairment. In the present systematic review, we address with a direct and reverse translational perspective the efficacy of D-amino acids, including D-serine, D-aspartate, and D-alanine, in poor responders. The impact of these molecules on the synaptic architecture is also considered in the light of dendritic spine changes reported in schizophrenia and antipsychotics' effect on postsynaptic density proteins. Moreover, we describe compounds targeting D-amino acid oxidase and D-aspartate oxidase enzymes. Finally, other drugs acting at NMDAR and proxy of D-amino acids function, such as D-cycloserine, sarcosine, and glycine, are considered in the light of the clinical burden of TRS, together with other emerging molecules.

Indexed as

Antipsychotic AgentsSchizophreniaAmino AcidsHumansNeurobiologyReceptors, N-Methyl-D-AspartateSchizophrenia, Treatment-ResistantAmino AcidsAntipsychotic AgentsReceptors, N-Methyl-D-AspartateantipsychoticsD-alanineD-amino acid oxidaseD-aspartateD-cysteinedopamineD-serineglutamateNMDAtreatment-resistant schizophrenia

Identifiers

PMID35883465
PMCPMC9312470
OpenAlexW4283702557

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.