Increased white matter metabolic rates in autism spectrum disorder and schizophrenia

Abstract

Both autism spectrum disorder (ASD) and schizophrenia are often characterized as disorders of white matter integrity. Multimodal investigations have reported elevated metabolic rates, cerebral perfusion and basal activity in various white matter regions in schizophrenia, but none of these functions has previously been studied in ASD. We used fluorodeoxyglucose positron emission tomography to compare white matter metabolic rates in subjects with ASD (n = 25) to those with schizophrenia (n = 41) and healthy controls (n = 55) across a wide range of stereotaxically placed regions-of-interest. Both subjects with ASD and schizophrenia showed increased metabolic rates across the white matter regions assessed, including internal capsule, corpus callosum, and white matter in the frontal and temporal lobes. These increases were more pronounced, more widespread and more asymmetrical in subjects with ASD than in those with schizophrenia. The highest metabolic increases in both disorders were seen in the prefrontal white matter and anterior limb of the internal capsule. Compared to normal controls, differences in gray matter metabolism were less prominent and differences in adjacent white matter metabolism were more prominent in subjects with ASD than in those with schizophrenia. Autism spectrum disorder and schizophrenia are associated with heightened metabolic activity throughout the white matter. Unlike in the gray matter, the vector of white matter metabolic abnormalities appears to be similar in ASD and schizophrenia, may reflect inefficient functional connectivity with compensatory hypermetabolism, and may be a common feature of neurodevelopmental disorders.

Deviation from normative brain development is associated with symptom severity in autism spectrum disorder

“…Within the Advanced group, ASD was associated with higher regional FA values compared with typically development, whereas, lower FA values were present in the Delayed group. Both groups had FA differences in the brain regions previously reported in ASD, such as internal capsule [93][94][95][96], external capsule [97,98], and inferior temporal gyrus [99] in the Advanced group, corpus callosum [95,97,[100][101][102][103], cerebellar peduncle [95,97,104], and inferior frontooccipital fasciculus [98,100] in the Delayed group, and cingulum [100,[105][106][107] in both groups. Notably, the regions that showed significant differences were not same for the subgroups.…”

Vascular endothelial growth factor (VEGF) expression and neuroinflammation is increased in the frontopolar cortex of individuals with autism spectrum disorder

“…Overexpressing VEGF-A 165 also increases blood-brain barrier (BBB) permeability [62]. Consistent with the consequences of VEGF-A overexpression observed in rodents, ASD patients have increased neurogenesis in the frontal cortex [63,64], persistent angiogenesis [65], increased white matter metabolic rates in the frontal lobes [66], and apparent altered BBB permeability [67,68].…”

Sympathetic, Metabolic Adaptations, and Oxidative Stress in Autism Spectrum Disorders: How Far From Physiology?

“…Conversely, these neurotransmitters alterations could explain also the sleep disorders such as nocturnal awakenings, insomnia, and parasomnias (Bramanti et al, 2012 ; Precenzano et al, 2017 ) and food selectivity in ASD children (Chistol et al, 2017 ; Li et al, 2017 ; Suarez, 2017 ). In this context may be explained the cerebral metabolism increasing (Mitelman et al, 2017 ) and the autonomic hyperfunctioning in ASD (Avola et al, 2004 ; Goodman, 2016 ; Parisi et al, 2017 ) sustained by high Orexin A levels (Messina et al, 2013 , 2014 , 2015 ; Kohyama, 2016 ; Messina A. et al, 2016 ; Messina G. et al, 2016 ).…”