Leonardo Emberti Gialloreti

Auditory sensory processing in autism: a magnetoencephalographic study

BACKGROUND Patients with autism show clinical features suggestive of abnormal processing of auditory and other sensory information. We hypothesized that low-functioning autistic subjects present abnormalities in discriminating simple auditory stimuli at sensory system preconscious stages of cortical processing. METHODS To verify our hypothesis, we used magnetoencephalographic measurements of mismatch field (MMF), which reflects the detection of a change in the physical characteristics of a repetitive sound. Fourteen patients (aged 8-32 years) who met DSM-IV diagnostic criteria for autistic disorder participated in an auditory oddball experiment. Ten healthy participants matched for age and gender acted as control subjects. RESULTS Significant differences in cerebral responses between patients and control subjects were recorded. Whereas control subjects showed a clearly identifiable MMF, with distinct generators in the M100 brain wave with regard to latency, position, and strength, no identifiable MMF was present in the autistic group. CONCLUSIONS Our findings suggest that low-functioning autistic subjects present a dysfunction at preconscious stages of cortical auditory discrimination, playing a role in the abnormal processing of auditory sensory afferences. The attention independence of the MMF allows for exclusion of an effect related to impaired attention or task-related responses.

Long-term cognitive and behavioral therapies, combined with augmentative communication, are related to uncinate fasciculus integrity in autism.

Recent evidence points to white-matter abnormalities as a key factor in autism physiopathology. Using Diffusion Tensor Imaging, we studied white-matter structural properties in a convenience sample of twenty-two subjects with low-functioning autism exposed to long-term augmentative and alternative communication, combined with sessions of cognitive and behavioral therapy. Uncinate fasciculus structural properties correlated significantly with therapy length and early onset, as well as to clinical outcome, independently from IQ, age or symptoms severity at therapy onset. Moreover, adherence to therapy was linked with better clinical outcome and uncinate fasciculus structural integrity. The results point to the capability of a long-term rehabilitation of subjects with low-functioning autism to produce white-matter structural modifications, which could thus play a role in the rehabilitative outcome.

Isolated theory of mind deficits and risk for frontotemporal dementia: a longitudinal pilot study

Objective Recent data suggest that theory of mind (ToM) deficits represent an early symptom of the behavioural variant of frontotemporal dementia (bvFTD). However, longitudinal data on the natural history of subjects presenting with isolated ToM deficits are lacking. The aim of the study was to verify if isolated ToM deficits represent an at-risk state for prefrontal dysfunction and bvFTD. Methods A population of healthy subjects (n=4150, age range: 50–60 years) completed a clinical and neuropsychological evaluation including the Reading the Mind in the Eyes Test (RMET), a widely used ToM task. From this group, we recruited a low-RMET group (n=83) including subjects with RMET scores lower than 2 SDs but an otherwise normal neuropsychological evaluation and a control group. All subjects underwent evaluation at baseline and after 2 years. Results Subjects in the low-RMET group showed decline in prefrontal functions at follow-up. Moreover, at follow-up 12 subjects in the low-RMET group presented with findings suggestive of bvFTD. Neuropsychological performance was stable in the control group. Conclusions Our data suggest that isolated ToM deficits could represent an at-risk situation for the development of future prefrontal dysfunction and bvFTD. ToM evaluation should be included in neuropsychological protocols aimed to evaluate the early phases of dementia.

Are caesarean sections, induced labor and oxytocin regulation linked to Autism Spectrum Disorders?

The etiology of Autism Spectrum Disorders (ASDs) continues to be elusive. While ASDs have been shown to be heritable, several environmental co-factors, such as, e.g. pre- or perinatal adverse events, could play a role in the pathogenesis of the disorder as well. Prevalence of ASDs appears to have increased in the last three decades, but the causes of this surge are not fully understood. As perinatal adverse events have increased as well, they have been regarded as logical contributors to the risen prevalence of ASDs. Over the last three decades there has been also a considerable increase in the rates of induced labor and caesarean sections (CS). However, even if a causal association between CS and ASDs increase has been suggested, it has not yet been proven. Nevertheless, we hypothesize here that such an association is actual and that it might help to explain a part of the increase in ASD diagnoses. Our assumption is based on the wider epidemiological picture of ASDs and CS, as well as on the possible biological plausibility of this correlation, by postulating potential epigenetic and neurobiological mechanisms underpinning this relationship. Today, several observations point toward the existence of epigenetic dysregulation in ASDs and this raises the issue of the role of environmental factors in bringing about epigenetic modifications. Epigenetic dysregulations in some brain neuropeptide systems could play a role in the behavioral dysfunctions of ASDs. Particularly, some evidence suggests a dysregulation of the oxytocinergic system in autistic brains. Perinatal alterations of oxytocin (OT) can also have life-long lasting effects on the development of social behaviors. Within the perinatal period, various processes, like pitocin infusion or CS, can alter the OT balance in the newborn; OT dysregulation could then interact with genetic factors, leading ultimately to the development of ASDs. Large long-term prospective studies are needed to identify causal pathways for ASDs and examine whether and how (epi-)genetic susceptibility interacts with obstetric risk factors in the development of ASDs. A better understanding of such a potential interplay could become paradigmatic for a wide range of genetic-environmental interactions in ASDs.

Souvenaid reduces behavioral deficits and improves social cognition skills in frontotemporal dementia: a proof-of-concept study.

Background: Souvenaid™ is a nutraceutical compound thought to positively enhance synaptic function. In line with this mechanism of action, Souvenaid™ has been shown to improve cognitive function in subjects with mild Alzheimers disease in randomized clinical trials. To date, however, the potential of Souvenaid™ to improve cognitive functioning in subjects with other neurodegenerative conditions also characterized by synaptic loss has not been explored. Objective: To evaluate the impact of Souvenaid™ on executive functions, social cognition and behavioral disturbances in subjects with the behavioral variant of frontotemporal dementia (bv-FTD). Methods: Twenty-six subjects with bv-FTD were enrolled in the study and randomized to Souvenaid™ (125 ml/day) or placebo groups. After 12 weeks, subjects were switched between the two groups. All subjects, blinded to treatment, underwent clinical and cognitive evaluations at enrollment, after 12 weeks and after 24 weeks. Results: Treatment with Souvenaid™ was associated with a significant reduction of behavioral symptoms and an increase in Theory of Mind skills compared to placebo, which both returned to baseline when Souvenaid™ was discontinued. Souvenaid™ did not have an effect on executive functions. Conclusions: Our results provide evidence of the potential of Souvenaid™ therapy for the treatment of behavioral disturbances and social cognition skills in FTD.

Amisulpride vs. fluoxetine treatment of Chronic Fatigue Syndrome: A pilot study

Different pharmacologic agents have been evaluated in the treatment of Chronic Fatigue Syndrome (CFS), albeit with moderate efficacy. Among the compounds thought to present with potential to be efficacious in CFS patients stands out low-dose amisulpride, a substituted benzamide that has been shown to be an useful treatment for conditions which exhibit some overlap with CFS such as dysthymia and somatoform disorders. We thus recruited forty non-depressed CFS patients that were randomized to receive either amisulpride 25mg bid, or fluoxetine 20mg uid; all subjects were un-blinded to the treatment regimen. At the time of enrollment in the study and after twelve weeks of treatment, enrolled subjects completed the Krupp Fatigue Severity Scale, the Hospital Anxiety and Depression Scale and a visual analog scale focused on pain and bodily discomfort. Moreover, all subjects were evaluated by a clinician, blinded to the treatment regimen, using the Clinical Global Impression Severity Scale. Our data revealed a significant improvement both in self-report, and observer-based measures for the amisulpride-treated, but not for the fluoxetine-treated patients. Amisulpride-treated subjects also presented with a significant reduction of somatic complaints, while the amisulpride effect on anxiety and mood levels was not significant. Both drugs were equally well tolerated. Summing up, we showed a positive symptomatic effect of amisulpride, compared to SSRI treatment, in a group of non-depressed CSF patients on self-report and on observer-based measures of fatigue and somatic complaints. If confirmed by larger, blinded studies, amisulpride thus could represent an effective approach to this difficult-to-treat condition.

Effectiveness of community-based treatment on clinical outcome in children with autism spectrum disorders: An Italian prospective study

Abstract Objective: Little is known about outcomes of Autism Spectrum Disorders (ASDs) interventions in real-life settings. The main aim of this naturalistic study was to collect real-life data on the actual ASDs treatment practices in Italy. Methods: A cohort of 48 children undergoing community-based interventions was observed in terms of personal and environmental characteristics, treatment typology and outcomes. Results: An earlier start of treatment was associated with an improvement of autistic symptoms, independently from symptoms severity (p < 0.05), but not with improvements in terms of intelligence quotient (p = 0.8). Children belonging to lower socioeconomic status families began treatment later (48.0 months) than those belonging to middle (39.8 months) or upper (39.2 months) classes (p < 0.05), and received less hours of treatment. Conclusion: The study showed that ASDs interventions should be observed not only in experimental settings, but also in naturalistic environments, so to appraise the actual effectiveness of integrating different treatment methods in community settings.

Is total lymphocyte count a reliable predictor of the CD4 lymphocyte cell count in resource-limited settings?

Although the depletion of CD4 T cells remains the most reliable marker for estimating the degree of immunosuppression in HIV-1-infected individuals several authors have investigated the possible prognostic and predictive role offered by total lymphocyte count (TLC) as a surrogate of the CD4 cell count in resource-limited settings (RLS). TLC offers the advantages of being less expensive and less complicated than the CD4 cell count. In addition the equipment needed is already available in most RLS. Despite these potential advantages papers recently published on this issue do not demonstrate that TLC fulfils the rigorous requirements as to sensitivity and specificity particularly needed when methods already proved to be accurate detectors of immunosuppression (such as CD4 cell count) are available. The rapid tests for diagnosing HIV infection in adolescents and adults are an example of this having replaced enzyme-linked immunosorbent assay and Western blot in RLS not only because of their lower cost but also because of their good mean sensitivity and specificity (98.5 and 93.4% respectively). The aim of this study was to assess the impact of considering TLC alone on the introduction of antiretroviral therapy in an asymptomatic HIV-infected African population undergoing regular CD4 lymphocyte controls in the framework of a highly active antiretroviral therapy protocol. Moreover the effectiveness of TLC as a marker of immunosuppression was compared with that of another marker the body mass index (BMI) requiring the simple measurement of the anthropometrical parameters of weight and height. (excerpt)

Determinants of acute hospital care use by elderly patients in Italy from 1996 to 2006.

To determine the trend of elderly hospitalization rates in Italy, following the economic rationalization of health systems in Western countries, and to evaluate which alternatives to acute hospitalization have been developed during the period 1996-2006 an ecological observational study has been carried out. Data from the Italian Hospital-Discharge Registries (HDRs) of the years 1996, 2001, and 2006 have been analyzed in order to assess the variations among the elderly in terms of hospitalization rates, hospital stay, and bed rates. The results were compared with nursing home admission rates and home care offer. Relations among these variables were explored by univariate and multivariate analyses. Elderly hospital admission rates decreased in Italy from 324.2/1000 in 1996, to 258.7 in 2006. Mean hospital stay of elderly patients was 9.4 days in 2006, 9.5 in 2001 and 10.1 in 1996. A multivariate linear regression model was statistically significant in explaining the variations in hospitalization rates (F: 5.68; p=0.004; R(2)=0.77). The main determinants linked to such variations were the bed rate (β=0.67; p=0.004) and the hospital length of stay (β=-0.77; p=0.03). The analysis showed a reduction in hospitalization rates among the elderly, which was not counterbalanced by an increased offer of home care and/or nursing home services, but was mainly linked to a decrease in the supply of acute beds, with possible consequences on the quality of health care.

Prevalence and cognitive underpinnings of isolated apathy in young healthy subjects

BACKGROUND Apathy is well described in neurodegenerative conditions, however to date there is no evidence of significant isolated apathy in subjects free from other neurological and psychiatric co-morbidites. Identifying isolated apathy in subjects free from neuropsychiatric conditions could contribute to refining current concepts of apathy and reevaluate its nosological classification as an independent clinical syndrome. METHODS We assessed apathy and perceived quality of life in a group of 2751 adults (age 19-40 years) free from neuropsychiatric or medical conditions. Subjects with and without elevated apathy were compared on measures of depression, self-efficacy, behavioral inhibition, and behavioral activation. RESULTS Observed prevalence of isolated elevated apathy was 1.45%. Subjects with apathy presented with reduced quality of life and lower behavioral activation compared to apathy-free subjects, while there was no difference between the two groups on measures of depression, self-efficacy, and perceived social skills. LIMITATIONS The main limitation of this study is the use of self-report questionnaires. CONCLUSIONS Isolated, ecologically-relevant apathy can be found in adults independently from the presence of subclinical depression or of concurrent medical conditions. Apathy screening should be considered in the evaluation of young non-depressed subjects with reduced perceived quality of life.