Altered neurotransmitter metabolism in adolescents with high-functioning autism

Abstract

Previous studies have suggested that alterations in excitatory/inhibitory neurotransmitters might play a crucial role in autism spectrum disorder (ASD). Proton magnetic resonance spectroscopy (1H-MRS) can provide valuable information about abnormal brain metabolism and neurotransmitter concentrations. However, few 1H-MRS studies have been published on the imbalance of the two most abundant neurotransmitters in ASD: glutamate (Glu) and gamma-aminobutyric acid (GABA). Moreover, to our knowledge none of these published studies is performed with a study population consisting purely of high-functioning autism (HFA) adolescents. Selecting only individuals with HFA eliminates factors possibly related to intellectual impairment instead of ASD. This study aims to assess Glu and GABA neurotransmitter concentrations in HFA. Occipital concentrations of Glu and GABA plus macromolecules (GABA+) were obtained using 1H-MRS relative to creatine (Cr) in adolescents with HFA (n=15 and n=13 respectively) and a healthy control group (n=17). Multiple linear regression revealed significantly higher Glu/Cr and lower GABA+/Glu concentrations in the HFA group compared to the controls. These results imply that imbalanced neurotransmitter levels of excitation and inhibition are associated with HFA in adolescents.

Working memory network alterations in high‐functioning adolescents with an autism spectrum disorder

“…Fifteen participants with ASD were recruited from the special secondary education school, de Berkenschutse (located in Heeze, the Netherlands), as detailed previously. 22 All high-functioning adolescents with ASD fulfilled established diagnostic criteria according to the DSM-IV, as well as the autism algorithm cut-offs on the Autism Diagnostic Observation Schedule (ADOS). 26 The HC group consisted of 18 normally developing adolescents who were recruited through advertisements in newspapers and most were living in other parts of the country.…”

“…By assessing these two groups, the potential influence of intellectual impairment rather than ASD is removed. 22 Furthermore, adolescents with high-functioning autism are more prone to psychosocial stress than their low-functioning counterparts, as they are more aware of opinions and evaluations of peers. 23,24 It has been suggested that during adolescence, a complex frontoparietal network of brain regions is involved in WM processes (for review, see Barendse et al 17 ).…”

Big GABA: Edited MR spectroscopy at 24 research sites

“…MRS measurements of GABA have been associated with individual differences in hemodynamic and electrophysiological signals (Donahue et al, 2010; Hu et al, 2013; Kapogiannis et al, 2013; Muthukumaraswamy et al, 2009) and a number of measures of cognition (Fujihara et al, 2015; Shibata et al, 2017; Yoon et al, 2016) and behavior (Boy et al, 2011; Greenhouse et al, 2017; Puts et al, 2011; Silveri et al, 2013). Differential levels of GABA have been observed in a number of neuropsychiatric disorders, such as schizophrenia (Kegeles et al, 2012; Öngür et al, 2010; Rowland et al, 2016; Yoon et al, 2010) and depression (Bhagwagar et al, 2008; Hasler et al, 2007; Price et al, 2009), neurodevelopmental disorders such as autism spectrum disorder (Drenthen et al, 2016; Gaetz et al, 2014; Puts et al, 2016) and attention deficit hyperactivity disorder (Bollmann et al, 2015; Edden et al, 2012a), and neurological diseases, such as Parkinson’s disease (Emir et al, 2012), amyotrophic lateral sclerosis (Foerster et al, 2012; Foerster et al, 2013) and diabetic neuropathy (Petrou et al, 2012). …”

The trajectory of cortical GABA levels across the lifespan: An individual participant data meta-analysis of edited MRS studies

“…While this review does not pertain to cognition, an understanding of the relationship between GABA and cognition motivates our initial step towards understanding the relationship between GABA and age. Alterations of GABA levels are seen in neurodevelopmental disorders such as ADHD (Bollmann et al, 2015;Edden et al, 2012), Autism Spectrum Disorder (Cochran et al, 2015;Drenthen et al, 2016;Gaetz et al, 2014;Puts et al, 2017), and Tourette syndrome (Puts et al, 2015), as well as in other neurological and psychiatric disorders including schizophrenia (Rowland et al, 2016;Shaw et al, 2020), depression (Sanacora et al, 1999) and neurofibromatosis (Violante et al, 2013). These associations are reviewed by Puts and Edden (2012) and by Schür et al (2016).…”