Glutamate/GABA+ ratio is associated with the psychosocial domain of autistic and schizotypal traits

Abstract

BackgroundThe autism and schizophrenia spectra overlap to a large degree in the social and interpersonal domains. Similarly, abnormal excitatory glutamate and inhibitory γ-aminobutyric acid (GABA) neurotransmitter concentrations have been reported for both spectra, with the interplay of these neurotransmitters important for cortical excitation to inhibition regulation. This study investigates whether these neurotransmitter abnormalities are specific to the shared symptomatology, and whether the degree of abnormality increases with increasing symptom severity. Hence, the relationship between the glutamate/GABA ratio and autism and schizophrenia spectrum traits in an unmedicated, subclinical population was investigated.MethodsA total of 37 adults (19 female, 18 male) aged 18-38 years completed the Autism Spectrum Quotient (AQ) and Schizotypal Personality Questionnaire (SPQ), and participated in the resting state proton magnetic resonance spectroscopy study in which sequences specific for quantification of glutamate and GABA+ concentration were applied to a right and left superior temporal voxel.ResultsThere were significant, moderate, positive relationships between right superior temporal glutamate/GABA+ ratio and AQ, SPQ and AQ+SPQ total scores (p<0.05), SPQ subscales Social Anxiety, No Close Friend, Constricted Affect, Odd Behaviour, Odd Speech, Ideas of Reference and Suspiciousness, and AQ subscales Social Skills, Communication and Attention Switching (p<0.05); increased glutamate/GABA+ coinciding with higher scores on these subscales. Only the relationships between glutamate/GABA+ ratio and Social Anxiety, Constricted Affect, Social Skills and Communication survived multiple comparison correction (p< 0.004). Left superior temporal glutamate/GABA+ ratio reduced with increasing restricted imagination (p<0.05).ConclusionThese findings demonstrate evidence for an association between excitatory/inhibitory neurotransmitter concentrations and symptoms that are shared between the autism and schizophrenia spectra.

Social impairments in alternating hemiplegia of childhood

“…The pathophysiology underlying AHC in these animals is related to increased excitability of principal neurons and decreased firing of GABAergic fast‐spiking parvalbumin‐positive interneurons . This increased excitability and reduced GABAergic inhibition, as demonstrated in the temporal lobe, is consistent with recent data about the role of increased glutamate/GABA ratio and of decreased GABAergic inhibition in patients with ASD …”

“…There also has not been an investigation into the range of symptoms of autism spectrum disorder (ASD) that may occur in these patients. In addition, ATP1A3 dysfunction has been shown to result in neuronal, particularly GABAergic, dysfunction in AHC mouse models, and ASD has also been noted to involve GABAergic dysfunction . Finally, there is evidence that the presence of epilepsy can increase the risk of ASD‐type symptoms in patients without AHC .…”

“…In addition, ATP1A3 dysfunction has been shown to result in neuronal, particularly GABAergic, dysfunction in AHC mouse models, 8,9 and ASD has also been noted to involve GABAergic dysfunction. 10,11 Finally, there is evidence that the presence of epilepsy can increase the risk of ASD-type symptoms in patients without AHC. 12 This is of particular interest given that about half of all patients with AHC also have epilepsy.…”

The morphometric co‐atrophy networking of schizophrenia, autistic and obsessive spectrum disorders

“…The neurobiological substrate of these common alterations may involve a neurochemical unbalance, especially an alteration in the ratios of GABA-glutamate on the one hand, and oxytocin-vasopressin on the other, which could be the targets of specific pharmacological therapies (Ford, Nibbs, & Crewther, 2017;LeBlanc & Fagiolini, 2011).…”

The P1 visual-evoked potential, red light, and transdiagnostic psychiatric symptoms

“…For example, administration of the NMDA antagonist ketamine to nonpsychiatric participants acutely increased delusional thought (Stone et al, 2015) and persistent delusional symptoms corresponded with higher frequency of use in chronic ketamine users (Morgan et al, 2010). Furthermore, glutamate/GABA+ ratio was found to be associated with increased SPQ Constricted Affect scores in nonpsychiatric adults (Ford et al, 2017) and administration of ketamine during surgery induced blunted affect more than tramadol - an opioid agonist (Hidayah et al, 2014). Given that both M pathway abnormalities and clinical symptoms have been linked to the NMDA system, dysfunction within this system may be a common underlying mechanism.…”