A Selective Review of the Excitatory-Inhibitory Imbalance in Schizophrenia: Underlying Biology, Genetics, Microcircuits, and Symptoms

Liu, Yi; Ouyang, Pan; Zheng, Yingjun; Mi, Lin; Zhao, Jingping; Ning, Yuping; Guo, Wenbin

doi:10.3389/fcell.2021.664535

Cited by 37 publications

(32 citation statements)

References 177 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, we demonstrate that MIA can induce methylation changes to known DEGs in schizophrenia brains. The majority of these enriched genes were specific to cortical excitatory and inhibitory neurons, which is in line with the imbalance of excitatory-inhibitory transmission that has long been considered a key feature of schizophrenia (Liu et al, 2021). However, we were unable to detect enrichment of GWAS-associated schizophrenia genes among the DMGs following MIA.…”

Section: Discussionmentioning

confidence: 58%

Maternal immune activation induces methylation changes in schizophrenia genes

Johnson

Handunnetthi

2022

Preprint

View full text Add to dashboard Cite

Susceptibility to schizophrenia is mediated by genetic and environmental risk factors. Infection driven maternal immune activation (MIA) during pregnancy is a key environmental risk factor. However, little is known about how MIA during pregnancy could contribute to adult-onset schizophrenia. In this study, we investigated if maternal immune activation induces changes in methylation of genes linked to schizophrenia. We found that differentially expressed genes in schizophrenia brain were significantly enriched among MIA induced differentially methylated genes in the foetal brain in a cell-type-specific manner. Upregulated genes in layer V pyramidal neurons were enriched among hypomethylated genes at gestational day 9 (fold change = 1.57 , FDR = 0.049) and gestational day 17 (fold change = 1.97 , FDR = 0.0006). We also found that downregulated genes in GABAergic Rosehip interneurons were enriched among hypermethylated genes at gestational day 17 (fold change = 1.62, FDR= 0.03). Collectively, our results highlight a connection between MIA driven methylation changes during gestation and schizophrenia gene expression signatures in the adult brain. These findings carry important implications for early preventative strategies in schizophrenia.

show abstract

Section: Discussionmentioning

confidence: 58%

Maternal immune activation induces methylation changes in schizophrenia genes

Johnson

Handunnetthi

2022

Preprint

View full text Add to dashboard Cite

show abstract

“…NX210c thus presents a therapeutic opportunity to enhance excitatory neurotransmission in different disorders and states where glutamatergic synaptic transmission is impaired, such as schizophrenia [ 14 , 15 ], AD [ 17 , 18 , 20 ], Parkinson’s disease [ 19 , 20 ], unresponsive wakefulness syndrome [ 23 ], and even normal aging [ 24 , 25 ]. In addition, a reduction in glutamatergic system activity is often associated with a reduction in GABAergic system activity to maintain the balance between excitatory and inhibitory transmissions [ 23 , 37 , 38 , 39 ]; the activity of both systems could therefore be enhanced by an exogenous supply of NX210c. One major challenge in treating excitatory synaptic dysfunction is to reach a fast rebalancing of excitation and inhibition within the CNS without promoting excitotoxic neuronal death.…”

Section: Discussionmentioning

confidence: 99%

NX210c Peptide Promotes Glutamatergic Receptor-Mediated Synaptic Transmission and Signaling in the Mouse Central Nervous System

Lemarchant¹,

Sourioux²,

Douce³

et al. 2022

IJMS

View full text Add to dashboard Cite

NX210c is a disease-modifying dodecapeptide derived from the subcommissural organ-spondin that is under preclinical and clinical development for the treatment of neurological disorders. Here, using whole-cell patch-clamp recordings, we demonstrate that NX210c increased α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)- and GluN2A-containing N-methyl-D-aspartate receptor (GluN2A-NMDAR)-mediated excitatory postsynaptic currents in the brain. Accordingly, using extracellular field excitatory postsynaptic potential recordings, an enhancement of synaptic transmission was shown in the presence of NX210c in two different neuronal circuits. Furthermore, the modulation of synaptic transmission and GluN2A-NMDAR-driven signaling by NX210c restored memory in mice chronically treated with the NMDAR antagonist phencyclidine. Overall, by promoting glutamatergic receptor-related neurotransmission and signaling, NX210c represents an innovative therapeutic opportunity for patients suffering from CNS disorders, injuries, and states with crippling synaptic dysfunctions.

show abstract

“…Research now suggests psychological function is driven by an underlying relationship of the two opposing electro-physiological state actions, excitation and inhibition (E/I). Importantly, findings suggest certain behavioral phenotypes or traits may be correlated with E/I balance or imbalance (Liu et al, 2021).…”

Section: State Vs Traitmentioning

confidence: 98%

Wired to Connect: The Autonomic Socioemotional Reflex Arc

Ludwig

Welch

2022

Front. Psychol.

View full text Add to dashboard Cite

We have previously proposed that mothers and infants co-regulate one another’s autonomic state through an autonomic conditioning mechanism, which starts during gestation and results in the formation of autonomic socioemotional reflexes (ASRs) following birth. Theoretically, autonomic physiology associated with the ASR should correlate concomitantly with behaviors of mother and infant, although the neuronal pathway by which this phenomenon occurs has not been elucidated. In this paper, we consider the neuronal pathway by which sensory stimuli between a mother and her baby/child affect the physiology and emotional behavior of each. We divide our paper into two parts. In the first part, to gain perspective on current theories on the subject, we conduct a 500-year narrative history of scientific investigations into the human nervous system and theories that describe the neuronal pathway between sensory stimulus and emotional behavior. We then review inconsistencies between several currently accepted theories and recent data. In the second part, we lay out a new theory of emotions that describes how sensory stimuli between mother and baby unconsciously control the behavior and physiology of both. We present a theory of mother/infant emotion based on a set of assumptions fundamentally different from current theories. Briefly, we propose that mother/infant sensory stimuli trigger conditional autonomic socioemotional reflexes (ASRs), which drive cardiac function and behavior without the benefit of the thalamus, amygdala or cortex. We hold that the ASR is shaped by an evolutionarily conserved autonomic learning mechanism (i.e., functional Pavlovian conditioning) that forms between mother and fetus during gestation and continues following birth. We highlight our own and others research findings over the past 15 years that support our contention that mother/infant socioemotional behavior is driven by mutual autonomic state plasticity, as opposed to cortical trait plasticity. We review a novel assessment tool designed to measure the behaviors associated with the ASR phenomenon. Finally, we discuss the significance of our theory for the treatment of mothers and infants with socioemotional disorders.

show abstract

A Selective Review of the Excitatory-Inhibitory Imbalance in Schizophrenia: Underlying Biology, Genetics, Microcircuits, and Symptoms

Cited by 37 publications

References 177 publications

Maternal immune activation induces methylation changes in schizophrenia genes

Maternal immune activation induces methylation changes in schizophrenia genes

NX210c Peptide Promotes Glutamatergic Receptor-Mediated Synaptic Transmission and Signaling in the Mouse Central Nervous System

Wired to Connect: The Autonomic Socioemotional Reflex Arc

Contact Info

Product

Resources

About