Abstract
Objective: The neural basis for autistic spectrum disorders is unclear, but abnormalities in the development of limbic areas and of glutamate have been suggested. Proton magnetic resonance spectroscopy (1H-MRS) can be used to measure the concentration of brain metabolites. However, the concentration of glutamate/glutamine in brain regions implicated in autistic spectrum disorders has not yet been examined in vivo.
Method: The authors used 1H-MRS to investigate the neuronal integrity of the amygdala-hippocampal complex and a parietal control region in adults with autistic spectrum disorders and healthy subjects.
Results: People with autistic spectrum disorders had a significantly higher concentration of glutamate/glutamine and creatine/phosphocreatine in the amygdala-hippocampal region but not in the parietal region.
Conclusions: Abnormalities in glutamate/glutamine may partially underpin the pathophysiology of autistic spectrum disorders, and the authors confirm earlier reports that limbic areas are metabolically aberrant in these disorders.
Autistic spectrum disorders, comprising autism, Asperger’s syndrome, and pervasive developmental disorder (not otherwise specified), are highly genetic, neurodevelopmental conditions that are characterized by impaired communication, deficits in social reciprocity, and obsessional/repetitive behavior. These symptoms are associated with considerable burden—the prevalence of autistic spectrum disorders is approximately 60 per 10,000 children (1), and the annual cost exceeds £1 billion in the United Kingdom alone (2). However, the neural basis of autistic spectrum disorders is poorly understood, and although people with these disorders have functional abnormalities in amygdala-hippocampal (limbic) regions (3), the causes of these differences are unknown.
Glutamate is the major excitatory neurotransmitter and is of crucial importance to brain development, leading some to propose that autistic spectrum disorders are caused by abnormalities in glutamate transmission (4). Preliminary genetic studies have reported an association between autistic spectrum disorders and alleles encoding for kainite and metabotropic glutamate receptors (5–7), the mitochondrial aspartate/glutamate carrier (8), and astrocytic glutamate transporter proteins (9). However, we know of only one previous preliminary report (an abstract reporting a study of eight autistic children) that has measured the concentration of glutamate/glutamine in vivo in brain regions implicated in autistic spectrum disorders (10), and there are few in vivo studies of neuronal integrity (defined as neuronal density/mitochondrial metabolism, membrane turnover, and cellular energy metabolism).
Proton magnetic resonance spectroscopy (1H-MRS) can be used to quantify a range of brain metabolites, including glutamine/glutamate (Glu+Gln); N-acetylaspartate (NAA), a marker of neuronal density and/or mitochondrial function; choline-containing compounds (Cho), a measure of membrane synthesis/turnover; creatine and phosphocreatine (Cr+PCr), a measure of cellular energy metabolism; and myo-inositol, a major osmolite and precursor to several brain metabolites. Previous 1H-MRS studies of autistic spectrum disorders have mostly assessed children and were confounded by the inclusion of learning disabled subjects with physical illnesses. In the only previous study of normal intelligence adults with autistic spectrum disorders, Murphy et al. reported a significant increase in frontal (but not parietal) NAA, Cho, and Cr+PCr in adults with Asperger’s syndrome (11). However, to our knowledge there are no prior in vivo studies of the neuronal integrity of amygdala-hippocampal regions or of Glu+Gln in normal-intelligence adults with autistic spectrum disorders.
Method: The authors used 1H-MRS to investigate the neuronal integrity of the amygdala-hippocampal complex and a parietal control region in adults with autistic spectrum disorders and healthy subjects.
Results: People with autistic spectrum disorders had a significantly higher concentration of glutamate/glutamine and creatine/phosphocreatine in the amygdala-hippocampal region but not in the parietal region.
Conclusions: Abnormalities in glutamate/glutamine may partially underpin the pathophysiology of autistic spectrum disorders, and the authors confirm earlier reports that limbic areas are metabolically aberrant in these disorders.
Autistic spectrum disorders, comprising autism, Asperger’s syndrome, and pervasive developmental disorder (not otherwise specified), are highly genetic, neurodevelopmental conditions that are characterized by impaired communication, deficits in social reciprocity, and obsessional/repetitive behavior. These symptoms are associated with considerable burden—the prevalence of autistic spectrum disorders is approximately 60 per 10,000 children (1), and the annual cost exceeds £1 billion in the United Kingdom alone (2). However, the neural basis of autistic spectrum disorders is poorly understood, and although people with these disorders have functional abnormalities in amygdala-hippocampal (limbic) regions (3), the causes of these differences are unknown.
Glutamate is the major excitatory neurotransmitter and is of crucial importance to brain development, leading some to propose that autistic spectrum disorders are caused by abnormalities in glutamate transmission (4). Preliminary genetic studies have reported an association between autistic spectrum disorders and alleles encoding for kainite and metabotropic glutamate receptors (5–7), the mitochondrial aspartate/glutamate carrier (8), and astrocytic glutamate transporter proteins (9). However, we know of only one previous preliminary report (an abstract reporting a study of eight autistic children) that has measured the concentration of glutamate/glutamine in vivo in brain regions implicated in autistic spectrum disorders (10), and there are few in vivo studies of neuronal integrity (defined as neuronal density/mitochondrial metabolism, membrane turnover, and cellular energy metabolism).
Proton magnetic resonance spectroscopy (1H-MRS) can be used to quantify a range of brain metabolites, including glutamine/glutamate (Glu+Gln); N-acetylaspartate (NAA), a marker of neuronal density and/or mitochondrial function; choline-containing compounds (Cho), a measure of membrane synthesis/turnover; creatine and phosphocreatine (Cr+PCr), a measure of cellular energy metabolism; and myo-inositol, a major osmolite and precursor to several brain metabolites. Previous 1H-MRS studies of autistic spectrum disorders have mostly assessed children and were confounded by the inclusion of learning disabled subjects with physical illnesses. In the only previous study of normal intelligence adults with autistic spectrum disorders, Murphy et al. reported a significant increase in frontal (but not parietal) NAA, Cho, and Cr+PCr in adults with Asperger’s syndrome (11). However, to our knowledge there are no prior in vivo studies of the neuronal integrity of amygdala-hippocampal regions or of Glu+Gln in normal-intelligence adults with autistic spectrum disorders.
| Original language | English |
|---|---|
| Pages (from-to) | 2189-2192 |
| Number of pages | 4 |
| Journal | The American Journal of Psychiatry |
| Volume | 163 |
| Issue number | 12 |
| Publication status | Published - Dec 2006 |