Stefania Ucelli Di Nemi

Brain anatomy and development in autism: review of structural MRI studies

Autism is a neurodevelopmental disorder that severely disrupts social and cognitive functions. MRI is the method of choice for in vivo and non-invasively investigating human brain morphology in children and adolescents. The authors reviewed structural MRI studies that investigated structural brain anatomy and development in autistic patients. All original MRI research papers involving autistic patients, published from 1966 to May 2003, were reviewed in order to elucidate brain anatomy and development of autism and rated for completeness using a 12-item check-list. Increased total brain, parieto-temporal lobe, and cerebellar hemisphere volumes were the most replicated abnormalities in autism. Interestingly, recent findings suggested that the size of amygdala, hippocampus, and corpus callosum may also be abnormal. It is conceivable that abnormalities in neural network involving fronto-temporo-parietal cortex, limbic system, and cerebellum may underlie the pathophysiology of autism, and that such changes could result from abnormal brain development during early life. Nonetheless, available MRI studies were often conflicting and could have been limited by methodological issues. Future MRI investigations should include well-characterized groups of autistic and matched healthy individuals, while taking into consideration confounding factors such as IQ, and socioeconomic status.

Low-grade endotoxemia in patients with severe autism

The objective of this study was to examine whether levels of endotoxin and other markers of immuno-inflammatory activation are altered in adult patients with severe autism. We determined circulating serum endotoxin levels, its soluble receptor (sCD14), and markers of immuno-inflammatory activation (IL-1beta, IL-6, and IL-10) in 22 adult patients with severe autism and 28 age- and gender-matched healthy controls. Compared with healthy subjects, serum levels of endotoxin were significantly higher in autistic patients and inversely and independently correlated with Socialization scores on the Vineland Adaptive Behavior Scales (VABS) and ADI-R Domain A score (social). Whether increased endotoxin may contribute to the pathophysiology of inflammation and impaired reciprocal social interaction in autism should be further explored in future studies.

Behavioral effects of omega-3 fatty acid supplementation in young adults with severe autism: an open label study.

BACKGROUND Pilot findings seem to suggest a potential beneficial effect of omega-3 fatty acid (FA) supplementation on behavioral alterations in children with autism. However, data on the potential benefits of omega-3 supplements in young adults with severe autism are lacking. In the present study, we sought to explore this issue in an open label study. METHODS Nineteen young adults with severe autism (CARS >40), aged 18-40 years, received two fish oil capsules per day [0.93 g of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) plus 5 mg of vitamin E to avoid lipid peroxidation] for 6 weeks. Subjects were assessed with an ad hoc caregiver questionnaire, the Rossago Behavioral Checklist, for the assessment of behavioral anomalies. RESULTS No significant improvements were observed with regard to the severity and frequency of problematic behaviors either during the active treatment period or during the post-treatment 6-week observation period. Moreover, no effect on the number of episodes and severity of behavior aberrations was observed. CONCLUSIONS Our negative findings do not point toward a major effect of omega-3 FA supplementation on behavioral abnormalities in adults with severe autism. Further studies on larger sample sizes are warranted to shed more light on this important issue.

Alterations of circulating endogenous secretory RAGE and S100A9 levels indicating dysfunction of the AGE-RAGE axis in autism

An excess accumulation of advanced glycation end products (AGEs) has been reported in autism brains. Through their interaction with their putative receptor RAGE, AGEs can promote neuroinflammation, oxidative stress and neuronal degeneration. To shed more light on the possible alterations of the AGEs-RAGE axis in autism, hereto we measured plasma levels of endogenous secretory RAGE (esRAGE) and its proinflammatory ligand S100A9 in 18 young adults with autistic spectrum disorder (ASD) and 18 age- and gender-matched healthy comparison subjects. The Childhood Autism Rating Scale (CARS) was used to assess the severity of autistic symptoms. Significantly reduced levels of esRAGE (P = 0.0023) and elevated concentrations of S100A9 (P = 0.0012) were found in ASD patients as compared to controls. In autistic patients, there was a statistically significant positive correlation between CARS scores and S100A9 levels (r = 0.49, P = 0.035), but no significant correlation was seen between esRAGE and S100A9 values (r = -0.23, P = 0.34). Our results of a significantly reduced peripheral level of esRAGE coupled with elevated S100A9 point to a subtle but definite dysfunction of the AGEs/RAGE axis in autism that could play a role in the pathophysiology of this disorder.

Serum levels of vascular endothelial growth factor and its receptors in patients with severe autism

OBJECTIVE To study vascular endothelial growth factor (VEGF) and its soluble receptors sVEGFR-1 and -2 in autism. DESIGN AND METHODS We measured serum levels of angiogenic molecules in 22 patients with severe autism and 28 controls. RESULTS Patients and controls had similar sVEGFR-2 levels, but VEGF levels were lower and sVEGFR-1 higher in patients with autism. CONCLUSION The imbalance between VEGF and its receptor sVEGFR-1 may be involved in the pathophysiology of autism.

Increased serum levels of high mobility group box 1 protein in patients with autistic disorder

BACKGROUND High mobility group box 1 (HMGB1) is a highly conserved, ubiquitous protein that functions as an activator for inducing the immune response and can be released from neurons after glutamate excitotoxicity. The objective of the present study was to measure serum levels of HMGB1 in patients with autistic disorder and to study their relationship with clinical characteristics. METHODS We enrolled 22 adult patients with autistic disorder (mean age: 28.1+/-7.7 years) and 28 age- and gender-matched healthy controls (mean age: 28.7+/-8.1 years). Serum levels of HMGB1 were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS Compared with healthy subjects, serum levels of HMGB1 were significantly higher in patients with autistic disorder (10.8+/-2.6 ng/mL versus 5.6+/-2.5 ng/mL, respectively, P<0.001). After adjustment for potential confounders, serum HMGB1 levels were independently associated with their domain A scores in the Autism Diagnostic Interview-Revised, which reflects their impairments in social interaction. CONCLUSIONS These results suggest that HMGB1 levels may be affected in autistic disorder. Increased HMGB1 may be a biological correlate of the impaired reciprocal social interactions in this neurodevelopmental disorder.

Il problema della valutazione psicometrica di soggetti adulti autistici non verbali. Somministrazione del test Leiter-R

L’autismo e un disturbo pervasivo dello sviluppo neurale caratterizzato da un deficit delle interazioni sociali e della comunicazione e da comportamento ripetitivo e stereotipato. Recenti studi hanno evidenziato la presenza di ritardo mentale nel 70% dei soggetti con ASD, di cui il 40% di grado grave. Lo scopo di questo studio e stato quello di trovare un test adeguato per poter misurare le capacita intellettive degli ospiti non verbali di una farm community, Cascina Rossago, che non erano mai stati valutati prima per l’assenza di uno strumento adeguato per poter testare il quoziente intellettivo (IQ) di soggetti adulti autistici non verbali. Si e scelto di utilizzare la scala di valutazione cognitiva Leiter-R per la sua attendibilita nel valutare i soggetti non verbali e per la scarsa influenza degli aspetti socio-culturali e delle competenze scolastiche sui risultati. Questa scala viene comunemente utilizzata per la misurazione dell’IQ di soggetti autistici non verbali con eta inferiore ai 21 anni, ma nel nostro studio abbiamo voluto testare la sua efficacia nel valutare soggetti adulti con eta superiore al limite precedentemente detto.

Autismo ed epilessia nell’adulto: analisi della letteratura

Several studies in literature have pointed out a close relationship between autism and epilepsy, with reported rates of epilepsy in autism varying as result of sample characteristics: age, female gender, intellectual disability and association with other neurological diseases affected this rates. From a literature review, epilepsy appears to be a negative prognostic factor for the outcome of autism in adulthood since autistic adults with epilepsy have more severe cognitive impairment than adults with autism and no epilepsy. Individuals affected have poor social functioning ability, few live independently or are capable of employment, requiring more support throughout their lifetime, both qualitatively and quantitatively.