TY - JOUR
T1 - Excitatory/inhibitory imbalance in autism spectrum disorders
T2 - Implications for interventions and therapeutics
AU - Uzunova, Genoveva
AU - Pallanti, Stefano
AU - Hollander, Eric
N1 - Publisher Copyright:
© 2015 Taylor & Francis.
PY - 2016/4/2
Y1 - 2016/4/2
N2 - Objectives: Imbalance between excitation and inhibition and increased excitatory-inhibitory (E-I) ratio is a common mechanism in autism spectrum disorders (ASD) that is responsible for the learning and memory, cognitive, sensory, motor deficits, and seizures occurring in these disorders. ASD are very heterogeneous and better understanding of E-I imbalance in brain will lead to better diagnosis and treatments. Methods: We perform a critical literature review of the causes and presentations of E-I imbalance in ASD. Results: E-I imbalance in ASD is due primarily to abnormal glutamatergic and GABAergic neurotransmission in key brain regions such as neocortex, hippocampus, amygdala, and cerebellum. Other causes are due to dysfunction of neuropeptides (oxytocin), synaptic proteins (neuroligins), and immune system molecules (cytokines). At the neuropathological level E-I imbalance in ASD is presented as a “minicolumnopathy”. E-I imbalance alters the manner by which the brain processes information and regulates behaviour. New developments for investigating E-I imbalance such as optogenetics and transcranial magnetic stimulation (TMS) are presented. Non-invasive brain stimulation methods such as TMS for treatment of the core symptoms of ASD are discussed. Conclusions: Understanding E-I imbalance has important implications for developing better pharmacological and behavioural treatments for ASD, including TMS, new drugs, biomarkers and patient stratification.
AB - Objectives: Imbalance between excitation and inhibition and increased excitatory-inhibitory (E-I) ratio is a common mechanism in autism spectrum disorders (ASD) that is responsible for the learning and memory, cognitive, sensory, motor deficits, and seizures occurring in these disorders. ASD are very heterogeneous and better understanding of E-I imbalance in brain will lead to better diagnosis and treatments. Methods: We perform a critical literature review of the causes and presentations of E-I imbalance in ASD. Results: E-I imbalance in ASD is due primarily to abnormal glutamatergic and GABAergic neurotransmission in key brain regions such as neocortex, hippocampus, amygdala, and cerebellum. Other causes are due to dysfunction of neuropeptides (oxytocin), synaptic proteins (neuroligins), and immune system molecules (cytokines). At the neuropathological level E-I imbalance in ASD is presented as a “minicolumnopathy”. E-I imbalance alters the manner by which the brain processes information and regulates behaviour. New developments for investigating E-I imbalance such as optogenetics and transcranial magnetic stimulation (TMS) are presented. Non-invasive brain stimulation methods such as TMS for treatment of the core symptoms of ASD are discussed. Conclusions: Understanding E-I imbalance has important implications for developing better pharmacological and behavioural treatments for ASD, including TMS, new drugs, biomarkers and patient stratification.
KW - Autistic disorder
KW - Biomarkers
KW - Electroencephalography
KW - Transcranial magnetic stimulation
KW - Translational medical research
UR - http://www.scopus.com/inward/record.url?scp=84945232126&partnerID=8YFLogxK
U2 - 10.3109/15622975.2015.1085597
DO - 10.3109/15622975.2015.1085597
M3 - Review article
C2 - 26469219
AN - SCOPUS:84945232126
SN - 1562-2975
VL - 17
SP - 174
EP - 186
JO - World Journal of Biological Psychiatry
JF - World Journal of Biological Psychiatry
IS - 3
ER -