Silvia Guida

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.

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.

Agomelatine but not melatonin improves fatigue perception: A longitudinal proof-of-concept study

Chronic Fatigue Syndrome (CFS) represents a disabling condition characterized by persistent mental and physical fatigue, bodily discomfort and cognitive difficulties. To date the neural bases of CFS are poorly understood; however, mono-aminergic abnormalities, sleep-wake cycle changes and prefrontal dysfunctions are all thought to play a role in the development and maintenance of this condition. Here we explored in a group of 62 CFS subjects the impact on fatigue levels of agomelatine, an antidepressant with agonist activity at melatonin receptors (MT1 and MT2) and antagonist activity at serotoninergic 2C receptors (5HT2C). To tease out the relative effects of MT-agonism and 5HT2C antagonism on fatigue, we compared agomelatine 50mg u.i.d. with sustained release melatonin 10mg u.i.d. in the first 12-week-long phase of the study, and then switched all melatonin-treated subjects to agomelatine in the second 12-week-long phase of the study. Agomelatine treatment, but not melatonin, was associated with a significant reduction of perceived fatigue and an increase in perceived quality of life. Moreover the switch from melatonin to agomelatine was associated with a reduction of fatigue levels. Agomelatine was well tolerated by all enrolled subjects. Our data, albeit preliminary, suggest that agomelatine treatment could represent a novel useful approach to the clinical care of subjects with CFS.

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.