ReviewMolecular psychiatry2022
Aberrant maturation and connectivity of prefrontal cortex in schizophrenia-contribution of NMDA receptor development and hypofunction.
Review in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed.
- Thalamofrontal synaptic weakening underlies short-term memory deficits from adolescent NMDAR hypofunction.Science advances · 2026Article
- Schizophrenia: Converging Neurobiological Mechanisms and Emerging Therapeutic Strategies.Biomolecules · 2026Review
- NMDA receptor ablation in medial prefrontal cortex disrupts value updating and reward history integration.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- The Effect of Iclepertin on Hematological Parameters: An Overview of Nonclinical Studies and Clinical Trials in Healthy Volunteers and Patients with Cognitive Impairment Associated with Schizophrenia.Journal of clinical pharmacology · 2026Review
- Common molecular signatures: the role of BDNF, melatonin, and orexin in the ASD-schizophrenia continuum.Molecular biology reports · 2026Review
- Harnessing Proteogenomics to Advance Precision Oncology: From Melanoma and Hepatocellular Carcinoma Perspective.Current oncology reports · 2026Review
- Moderating Role of Cigarette Smoking on the Efficacy of tDCS in the Treatment of Negative and Cognitive Symptoms of Schizophrenia: Results from a Randomized Clinical Trial.Brain sciences · 2026Article
- Abdominal Ultrasound Stimulation Alleviates Negative Symptoms Through Modulation of Serotonin Signaling and Gut Microbiota in the MK-801 Model of Schizophrenia.Schizophrenia bulletin · 2026Article
- GluN2A-NMDA receptor inhibition disinhibits the prefrontal cortex, reduces forced swim immobility, and impairs sensorimotor gating.Acta pharmacologica Sinica · 2026Article
- Reduced serum Klotho in chronic schizophrenia: diagnostic value and association with cognitive impairment.Frontiers in psychiatry · 2026Article
- Bipolar and schizophrenia risk gene AKAP11 encodes an autophagy receptor coupling the regulation of PKA kinase network homeostasis to synaptic transmission.Nature communications · 2025Article
- Unraveling the mysteries of schizophrenia: Insights into prefrontal cortex dysfunction and therapeutic implications.World journal of psychiatry · 2025Review
- Enhancement of hippocampal interneuron excitability by NMDA receptor positive allosteric modulation.The Journal of physiology · 2025Article
- Article
- Transient Inhibition of the Mediodorsal Thalamus During Early Adolescence Induces Hypofrontality and Social Memory Deficits in Young Adulthood.Biological psychiatry global open science · 2025Article
- 16p11.2 duplication shows early male-biased impacts on reward learning, but NMDA receptor antagonism reduces optimal choice selection in both wildtypes and 16p11.2 duplication.bioRxiv : the preprint server for biology · 2025Article
- Early postnatal NMDA receptor ablation in cortical interneurons impairs affective state discrimination and social functioning.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Glutamate-Based Therapeutic Strategies for Schizophrenia: Emerging Approaches Beyond Dopamine.International journal of molecular sciences · 2025Review
- Characterization of Brain Abnormalities in Lactational Neurodevelopmental Poly I:C Rat Model of Schizophrenia and Depression Using Machine-Learning and Quantitative MRI.Journal of magnetic resonance imaging : JMRI · 2025Article
- Exon-variant interplay and multi-modal evidence identify endocrine dysregulation in severe psychiatric disorders impacting excitatory neurons.Translational psychiatry · 2025Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
The neurobiology of schizophrenia involves multiple facets of pathophysiology, ranging from its genetic basis over changes in neurochemistry and neurophysiology, to the systemic level of neural circuits. Although the precise mechanisms associated with the neuropathophysiology remain elusive, one essential aspect is the aberrant maturation and connectivity of the prefrontal cortex that leads to complex symptoms in various stages of the disease. Here, we focus on how early developmental dysfunction, especially N-methyl-D-aspartate receptor (NMDAR) development and hypofunction, may lead to the dysfunction of both local circuitry within the prefrontal cortex and its long-range connectivity. More specifically, we will focus on an "all roads lead to Rome" hypothesis, i.e., how NMDAR hypofunction during development acts as a convergence point and leads to local gamma-aminobutyric acid (GABA) deficits and input-output dysconnectivity in the prefrontal cortex, which eventually induce cognitive and social deficits. Many outstanding questions and hypothetical mechanisms are listed for future investigations of this intriguing hypothesis that may lead to a better understanding of the aberrant maturation and connectivity associated with the prefrontal cortex.
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