Non-Invasive Evaluation of the GABAergic/Glutamatergic System in Autistic Patients Observed by MEGA-Editing Proton MR Spectroscopy Using a Clinical 3 Tesla Instrument

Abstract

Amino acids related to neurotransmitters and the GABAergic/glutamatergic system were measured using a 3 T-MRI instrument in 12 patients with autism and 10 normal controls. All measurements were performed in the frontal lobe (FL) and lenticular nuclei (LN) using a conventional sequence for n-acetyl aspartate (NAA) and glutamate (Glu), and the MEGA-editing method for GABA. The GABA level and [GABA]/[NAA] ratio were significantly lower (p < 0.01) in the FL, but not the LN, in patients with autism compared to normal controls. The [GABA]/[Glu] ratio in the FL was also significantly lower (p < 0.05) in the patients than in the normal controls, thus suggesting a possible abnormality in the regulation between GABA and Glu.

May GABA transaminase inhibitors improve stereotyped behaviors in Rett syndrome?

“…The GABA level and the ratio of GABA to glutamate in frontal lobe in autism are significantly lower than that of the control group (Harada et al 2011). GABA(A) receptors are reduced in the brain of individuals with autism (Fatemi et al 2009b;Oblak et al 2011).…”

“…Taking into account that the need for providing drugs for treatment of stereotypies (Ghanizadeh 2010(Ghanizadeh , 2011, the role of GABAergic neurons for stereotypies (Chao et al 2010), the hypofunction of GABA system in autism in brain (Harada et al 2011), the role of GABA transaminase in catabolizing GABA (Tolman and Faulkner 2009), it seems reasonable to hypothesize that GABA transaminase inhibitors such as Vigabatrin may improve stereotypies in autism and Rett syndrome. It is worthwhile to conduct clinical experimental studies on animal models of autism.…”

GABA-Based Evaluation of Neurologic Conditions: MR Spectroscopy

“…73,74 Harada et al 75 recently reported the first MR spectroscopy evaluation of GABA in children with autism, which demonstrated significantly reduced GABA concentration in the frontal lobes and in the GABA/Glu ratio, suggesting that GABAergic activity declines while glutamatergic activity is excessive. These reductions in GABA could explain the cognitive impairment and increased seizure risk inherent in autism.…”

Does Fever Relieve Autistic Behavior by Improving Brain Blood Flow?

“…Blood GABA appears high in autistic children (Dhossche et al 2002), brain GABA may be downregulated (Harada et al 2010;Hasler et al 2010); taurine is often depleted (Pangborn 2002). Downregulation of GABA elevates brain temperature therefore blood flow, but fever's elevation of taurine may be more decisive because taurine carries water out of swollen astrocytes (Benarroch 2005).…”