Carlo Caltagirone

Publications (352)1195.31 Total impact

• Article: Letters persistence after physical offset: Visual word form area and left planum temporale. An fMRI study.

  Francesco Barban, Gian Daniele Zannino, Emiliano Macaluso, Carlo Caltagirone, Giovanni A Carlesimo
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  ABSTRACT: Iconic memory is a high-capacity low-duration visual memory store that allows the persistence of a visual stimulus after its offset. The categorical nature of this store has been extensively debated. This study provides functional magnetic resonance imaging evidence for brain regions underlying the persistence of postcategorical representations of visual stimuli. In a partial report paradigm, subjects matched a cued row of a 3 × 3 array of letters (postcategorical stimuli) or false fonts (precategorical stimuli) with a subsequent triplet of stimuli. The cued row was indicated by two visual flankers presented at the onset (physical stimulus readout) or after the offset of the array (iconic memory readout). The left planum temporale showed a greater modulation of the source of readout (iconic memory vs. physical stimulus) when letters were presented compared to false fonts. This is a multimodal brain region responsible for matching incoming acoustic and visual patterns with acoustic pattern templates. These findings suggest that letters persist after their physical offset in an abstract postcategorical representation. A targeted region of interest analysis revealed a similar pattern of activation in the Visual Word Form Area. These results suggest that multiple higher-order visual areas mediate iconic memory for postcategorical stimuli. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.
  Human Brain Mapping 06/2013; 34(6):1282-92. · 5.88 Impact Factor
• Article: Plasma Fatty Acid Lipidomics in Amnestic Mild Cognitive Impairment and Alzheimer's Disease.

  Luigi Iuliano, Antonio Pacelli, Marco Ciacciarelli, Chiara Zerbinati, Sabrina Fagioli, Fabrizio Piras, Maria Donata Orfei, Paola Bossu, Floriana Pazzelli, Gaetano Serviddio, Carlo Caltagirone, Gianfranco Spalletta
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  ABSTRACT: Polyunsaturated fatty acids (PUFA) of the n-3 series have been linked to brain physiology and cognitive decline, but little is known about the other components of the complex fatty acids category. Here, we compared 30 molecular species pertaining to saturated, monounsaturated, polyunsaturated, and trans fatty acids, measured in plasma by gas chromatography, in 14 patients with a diagnosis of amnestic single domain mild cognitive impairment (aMCI), 30 patients with mild Alzheimer's disease (AD), and 30 healthy controls (HC). As no participants showed neuroimaging evidence of cerebrovascular disease, patients could be considered as purely neurodegenerative. We found differences in specific components of almost all fatty acid classes except n-3-polyunsaturated fatty acids. Compared with HC, aMCI and AD patients had higher levels of arachidic (C20:0), erucic (C22:1, n-9), and vaccenic acid (C18:1, n-9) and lower levels of cerotic (C26:0) and linoleic acid (C18:2, n-6). In particular, the decreased level of linoleic acid was associated with an increased level of mead acid, which progressed from HC to aMCI to AD patients. Linoleic and mead acid were also inversely correlated in AD and aMCI patients. In conclusion, we found a previously unrecognized linoleic acid deficiency in the early phase of neurodegeneration that was strongly supported by an increased, compensatory mead acid level. These findings suggest the importance of creating new dietary manipulation strategies to counteract disease progression.
  Journal of Alzheimer's disease: JAD 05/2013; · 3.74 Impact Factor
• Source

  Available from: Margherita Di Paola

  Article: Cerebellar vermis abnormalities and cognitive functions in individuals with Williams syndrome.

  Deny Menghini, Margherita Di Paola, Riccardo Murri, Floriana Costanzo, Carlo Caltagirone, Stefano Vicari, Laura Petrosini
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  ABSTRACT: In Williams syndrome (WS) cerebellar measures were only indirectly related to behavioral outcomes. T1-weighted magnetic resonance images and neuropsychological data were acquired to investigate whether cerebellar vermis differences were present in 12 WS individuals compared with 13 chronological age-matched controls and whether WS cerebellar vermis measures were related to cognitive scores. In WS participants, we observed a significant increase in the volume of the posterior superior cerebellar vermis (lobules VI-VII) and an atypical ratio between width and height of the cerebellar vermis. Furthermore, we found an inverse correlation between cerebellar posterior vermis volume and scores on implicit learning, phonological fluency and the verbal short-term memory tasks. The present study supported a role for the posterior cerebellar vermis in higher cognitive processes and indicated that the cerebellar vermis abnormalities (enlargement) in WS individuals have an effect in worsening the cognitive performance in specific domains.
  Research in developmental disabilities 04/2013; 34(7):2118-2126. · 4.41 Impact Factor
• Article: Hydrochloric acid alters the effect of L-glutamic acid on cell viability in human neuroblastoma cell cultures.

  Nicoletta Croce, Sergio Bernardini, Stefano Di Cecca, Carlo Caltagirone, Francesco Angelucci
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  ABSTRACT: L-glutamic acid (L-glutamate) is used to induce excitotoxicity and to test neuroprotective compounds in cell cultures. However, because L-glutamate powder is almost insoluble in water, in many datasheets it is recommended to reconstitute L-glutamate in Hydrochloric acid (HCl) before successive dilutions. Nevertheless, HCl, even at low concentrations, may alter the pH of cell culture medium and interfere with cell activity. Thus the aim of the study was to evaluate whether reconstitution of L-glutamate powder in HCl alters its capacity to induce neurotoxicity in different human neuroblastoma cell lines. SH-SY5Y, IMR-32 and SK-N-BE(2) cells were exposed to various concentrations of L-glutamate, either reconstituted in HCl (1M) or post re-equilibrated to a pH of the culture medium (7.5). After 24 and 48h of incubation changes in cell viability versus untreated cells were evaluated. The effect of the identical amount of HCl present in L-glutamate dilutions on neuroblastoma cell survival was also investigated. Our data showed that the neurotoxicity of glutamate reconstituted in HCl was comparable to that of HCl alone. Moreover, pH variations induced by glutamate or HCl in the culture medium were parallel. When the pH of glutamate stock solution was re-equilibrated, L-glutamate induced variation in cell viability to a lower extent and after longer incubation time. This study demonstrates that HCl used to reconstitute L-glutamate powder may alter the effect of glutamate itself on neuroblastoma cell cultures. This information may be useful to scientists working with L-glutamate to induce excitotoxicity or to test neuroprotective agents.
  Journal of neuroscience methods 04/2013; · 2.30 Impact Factor
• Source

  Available from: Paola Bossù

  Article: The stimulation of dendritic cells by Amyloid beta 1-42 reduces BDNF production in Alzheimer's disease patients.

  Antonio Ciaramella, Francesca Salani, Federica Bizzoni, Francesco Angelucci, Gianfranco Spalletta, Anna Rita Taddei, Carlo Caltagirone, Paola Bossù
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  ABSTRACT: Dendritic cells (DCs), the main actors of immune responses and inflammation, may play a role in Alzheimer's disease (AD). Recent studies demonstrate that monocyte-derived DCs (MDDCs), generated in vitro in the presence of Amyloid β1-42 peptide (Aβ1-42), show a functional alteration and increased production of inflammatory molecules. Accordingly, MDDCs from AD patients show a more pronounced pro-inflammatory profile than DCs obtained from control subjects. In this study we aimed at further investigating DC role in AD. Thus, we analyzed the in vitro effect of Aβ1-42 treatment on already differentiated DCs from AD patients, as compared to control subjects. We found that Aβ1-42 significantly decrease the expression of brain-derived neurotrophic factor (BDNF) in DCs derived from AD patients but not from control subjects. Thus, possibly due to their Aβ-induced reduction of neurotrophic support to neurons, DCs from AD patients might contribute to brain damage by playing a part in Aβ-dependent neuronal toxicity.
  Brain Behavior and Immunity 04/2013; · 4.72 Impact Factor
• Article: Theta burst stimulation improves visuo-spatial attention in a patient with traumatic brain injury.

  Sonia Bonnì, Chiara Mastropasqua, Marco Bozzali, Carlo Caltagirone, Giacomo Koch
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  ABSTRACT: Recent studies showed that non-invasive brain stimulation methods, such as repetitive transcranial magnetic stimulation (rTMS) can improve the symptoms of neglect in stroke patients. Here, we adopted this approach to improve visuo-spatial deficit in a patient with traumatic brain injury (TBI) that showed important symptoms of visuo-spatial neglect. We found that continuous theta burst stimulation (cTBS) applied over the left posterior parietal cortex (PPC) induced a clinical improvement of cognitive disorder associated to a functional changes of fronto-parietal network as assessed by means of TMS and resting state fMRI.
  Neurological Sciences 03/2013; · 1.32 Impact Factor
• Article: Low Self-Awareness of Individuals With Severe Traumatic Brain Injury Can Lead to Reduced Ability to Take Another Person's Perspective.

  Umberto Bivona, Angela Riccio, Paola Ciurli, Giovanni Augusto Carlesimo, Valentina Delle Donne, Elisa Pizzonia, Carlo Caltagirone, Rita Formisano, Alberto Costa
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  ABSTRACT: Aims of this study were (i) to verify whether a deficit or a lack of self-awareness can lead to difficulties in assuming another person's perspective after a severe traumatic brain injury (TBI); (ii) to verify whether perspective-taking deficits emerge more from performance-based tasks than self-reports; and (iii) to evaluate the possible relationships between perspective-taking difficulties and some clinical, neuropsychological, neuropsychiatric, and neuroimaging variables. The Interpersonal Reactivity Index, Empathy Quotient, first-order false-belief, and faux pas written stories were administered to 28 patients with severe TBI and 28 healthy controls. The Awareness Questionnaire was also administered to TBI patients and their caregivers. Patients were split into 2 groups (impaired self-awareness vs adequate self-awareness) on the basis of the discrepancy Awareness Questionnaire score. Both TBI groups obtained lower scores than healthy controls on the Fantasy subscale of the Interpersonal Reactivity Index, the reality question of the false-belief stories, and the memory questions of the faux pas test. Only impaired self-awareness patients tended to obtain lower scores in first-order false-belief detection. Impaired self-awareness patients also performed significantly worse than both healthy controls and adequate self-awareness patients on the faux pas tasks. The analysis suggests a causal relationship between low self-awareness and perspective-taking difficulties in this population of patients.
  The Journal of head trauma rehabilitation 03/2013; · 2.39 Impact Factor
• Article: Linking novelty seeking and harm avoidance personality traits to basal ganglia: volumetry and mean diffusivity.

  Daniela Laricchiuta, Laura Petrosini, Fabrizio Piras, Debora Cutuli, Enrica Macci, Eleonora Picerni, Chiara Chiapponi, Carlo Caltagirone, Gianfranco Spalletta
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  ABSTRACT: Novelty Seeking (NS) and Harm Avoidance (HA) temperamental traits are related to approaching or avoiding motivational circuits relying on the integrity and functionality of distributed brain areas implicated in arousal and action. The present study verified whether and how macro- and micro-structural variations of basal ganglia are correlated with scores obtained in the NS and HA temperamental scales of the Temperament and Character Inventory by Cloninger. To this aim, 125 healthy adults aged 18-67 years of both sexes completed the Temperament and Character Inventory and underwent a high-resolution T1-weighted magnetic resonance imaging and a diffusion tensor imaging using a 3T scanner. The scores obtained in the temperamental scales were associated with volumes, mean diffusivity and fractional anisotropy measures of basal ganglia of both hemispheres separately, by using linear regression analyses. We found increased bilateral caudate and pallidum volumes associated with higher NS scores, as well as increased mean diffusivity in the bilateral putamen associated with higher HA scores. Macro- and micro-structural variations of basal ganglia regions contribute to explain the biological variance associated with NS or HA personality phenotype. The present findings evidencing some brain-temperament relationships highlight the importance of obtaining macro- and micro-structural measures in relation to individual differences.
  Brain Structure and Function 03/2013; · 5.63 Impact Factor
• Article: Mini mental Parkinson test: standardization and normative data on an Italian sample.

  Alberto Costa, Eriola Bagoj, Marco Monaco, Silvia Zabberoni, Salvatore De Rosa, Ciro Mundi, Carlo Caltagirone, Giovanni Augusto Carlesimo
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  ABSTRACT: The mini mental Parkinson (MMP) is a test built to overcome the limits of the mini mental state examination (MMSE) in the short-time screening of cognitive disorders in individuals with Parkinson's disease (PD). In fact, in this scale, items tapping executive functioning are included to better capture PD-related cognitive changes. Some data sustain the sensitivity and validity of the MMP in the short neuropsychological screening of these individuals. Here, we report normative data on the MMP we collected on a sample of 307 Italian healthy subjects ranging from 40 to 91 years. The results document a detrimental effect of age and an ameliorative effect of education on the MMP total performance score. We provide for correction grids for age and literacy that derive from results of the regression analyses. Moreover, we also computed equivalent scores in order to allow a direct and fast comparison between the performance on the MMP and on other psychometric measures that can be administered to the subjects.
  Neurological Sciences 03/2013; · 1.32 Impact Factor
• Article: Widespread structural brain changes in OCD: A systematic review of voxel-based morphometry studies.

  Federica Piras, Fabrizio Piras, Chiara Chiapponi, Paolo Girardi, Carlo Caltagirone, Gianfranco Spalletta
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  ABSTRACT: The most widely accepted model of obsessive-compulsive disorder (OCD) assumes brain abnormalities in the "affective circuit", mainly consisting of volume reduction in the medial orbitofrontal, anterior cingulate and temporolimbic cortices, and tissue expansion in the striatum and thalamus. The advent of whole-brain, voxel-based morphometry (VBM) has provided increasing evidence that regions outside the "affective" orbitofronto-striatal circuit are involved in OCD. Nevertheless, potential confounds from the different image analysis methods, as well as other factors, such as patients' medication and comorbidity status, may limit generalization of results. In the present paper, we systematically reviewed the whole-brain VBM literature on OCD by focussing specifically on degree of consistency between studies, extent to which findings have been replicated and interrelation between clinical variables and OCD anatomy, a potentially crucial factor that has been systematically examined only in a limited number of studies. The PubMed database was searched through February 2012. A total of 156 studies were identified; 18 of them fulfilled the inclusion/exclusion criteria and included 511 patients and 504 controls. Results support the notion that the brain alterations responsible for OCD are represented at the network level, and that widespread structural abnormalities may contribute to neurobiological vulnerability to OCD. Apart from defects in regions within the classic "affective" circuit, volume reduction of the cortical source of the dorsolateral (DL) prefronto-striatal "executive" circuit (dorsomedial, DL, ventrolateral and frontopolar prefrontal cortices), and of reciprocally connected regions (temporo-parieto-occipital associative areas) is consistently described in OCD patients. Moreover, increased volume of the internal capsule and reduced frontal and parietal white matter volumes may account for altered anatomical connectivity in fronto-subcortical circuitry. Morphometric changes in both "affective" and "executive" parallel the disease clinical course, being at the same time responsible for variation in symptom severity. Thus, OCD mechanisms involve a more widespread network of cerebral dysfunctions than previously thought, which may explain the heterogeneity in clinical manifestations and symptom severity.
  Cortex 02/2013; · 6.08 Impact Factor
• Article: A Meta-Analysis of the Efficacy of Donepezil, Rivastigmine, Galantamine, and Memantine in Relation to Severity of Alzheimer's Disease.

  Simona Gabriella Di Santo, Federica Prinelli, Fulvio Adorni, Carlo Caltagirone, Massimo Musicco
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  ABSTRACT: BACKGROUND: Randomized clinical trials have evaluated the efficacy of acetylcholinesterase inhibitors (AChE-Is) and memantine across a wide range of Alzheimer's disease (AD) severity. However, these drugs are prescribed and reimbursed according to precise upper and lower cut off scores of cognitive tests. OBJECTIVES: To verify whether the efficacy of pharmacological treatment had any dependence on the severity of dementia in AD patients. METHODS: Published English-language randomized, placebo-controlled trials evaluating the efficacy of AChE-Is or memantine at any dose, over any length of time, in patients with any severity of dementia due to AD were included. Cognitive, behavioral, and functional outcomes were extracted from each study and multiple outcomes from the same trial were pooled to obtain a unique indicator of efficacy for cognition, functional impairment, and behavioral and psychological disturbances. The existence of a relationship between size of the treatment effect and severity of dementia, measured with the Mini-Mental State Examination, was determined using parametric and non-parametric correlation analyses. RESULTS: Both AChE-Is and memantine had significant effects on cognition. Functional and psycho-behavioral outcomes were reported less frequently but also showed significant efficacy of treatment. High heterogeneity among studies was found within and between the different drugs. The efficacy of all drugs except memantine was independent from dementia severity in all domains. Memantine effect on functional impairment was better in more severe patients. CONCLUSIONS: The modest beneficial effects of anti-dementia drugs on cognition are independent from dementia severity. Memantine is more effective on functional incompetence only in severe patients.
  Journal of Alzheimer's disease: JAD 02/2013; · 3.74 Impact Factor
• Article: NPY modulates miR-30a-5p and BDNF in opposite direction in an in vitro model of Alzheimer disease: a possible role in neuroprotection?

  Nicoletta Croce, Francesca Gelfo, Maria Teresa Ciotti, Giorgio Federici, Carlo Caltagirone, Sergio Bernardini, Francesco Angelucci
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  ABSTRACT: Using in vitro models of Alzheimer's disease (AD), we found that the toxic effects of amyloid beta 25-35 (Aβ(25-35)) on the neurotrophin brain-derived neurotrophic factor (BDNF) were counteracted by pre-incubation with neuropeptide Y (NPY), a neuropeptide expressed within the central nervous system. Nonetheless, the mechanism of action of NPY on BDNF neuronal production in the presence of Aβ is not known. BDNF expression might be directly regulated by microRNA (miRs), small non-coding DNA fragments that regulate the expression of target genes. Thus, there is the possibility that miRs alterations are present in AD-affected neurons and that NPY influences miR expression. To test this hypothesis, we exposed NPY-pretreated primary rat cortical neurons to Aβ(25-35) and measured miR-30a-5p (a member of the miR-30a family involved in BDNF tuning expression) and BDNF mRNA and protein expression after 24 and 48 h. Our results demonstrated that pre-treatment with NPY decreased miR-30a-5p expression and increased BDNF mRNA and protein expression at 24 and 48 h of incubation with Aβ. Therefore, this study demonstrates that NPY modulates BDNF and its regulating microRNA miR-30a-5p in opposite direction with a mechanism that possibly contributes to the neuroprotective effect of NPY in rat cortical neurons exposed to Aβ.
  Molecular and Cellular Biochemistry 01/2013; · 2.06 Impact Factor
• Article: The right frontopolar cortex is involved in visual-spatial prospective memory.

  Alberto Costa, Massimiliano Oliveri, Francesco Barban, Sonia Bonnì, Giacomo Koch, Carlo Caltagirone, Giovanni A Carlesimo
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  ABSTRACT: The involvement of frontopolar cortex in mediating prospective memory processes has been evidenced by various studies, mainly by means of neuroimaging techniques. Recently, one transcranial magnetic stimulation study documented that transient inhibition of left Brodmann Area (BA) 10 impaired verbal prospective memory. This result raises the issue of whether the BA 10 involvement in prospective memory functioning may be modulated by the physical characteristics of the stimuli used. The present study aimed to investigate the role of the frontopolar cortex in visual-spatial PM by means of the application of inhibitory theta-burst stimulation. Twelve volunteers were evaluated after inhibitory theta-burst stimulation over left BA 10, right BA10 and CZ (control condition). In the prospective memory procedure, sequences of four spatial positions (black squares) each were presented. During the inter-sequence delay, subjects had to reproduce the sequence in the observed order (ongoing task forward) or the reverse order (backward). At the occurrence of a target position, subjects had to press a key on the keyboard (prospective memory score). Recall and recognition of the target positions were also tested. We found that prospective memory accuracy was lower after theta-burst stimulation over right BA10 than CZ (p<0.01), whereas it was comparable in left BA10 and CZ conditions. No significant difference was found among the three conditions on recall and recognition of target positions and on ongoing task performance. Our findings provide a novel strong evidence for a specific involvement of right frontopolar cortex in visual-spatial prospective memory. In the context of previous data providing evidence for left BA 10 involvement in verbal prospective memory, our results also suggest material-specific lateralization of prospective memory processes in BA 10.
  PLoS ONE 01/2013; 8(2):e56039. · 4.09 Impact Factor
• Article: Cerebellar theta burst stimulation modulates short latency afferent inhibition in Alzheimer's disease patients.

  Francesco Di Lorenzo, Alessandro Martorana, Viviana Ponzo, Sonia Bonnì, Egidio D'Angelo, Carlo Caltagirone, Giacomo Koch
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  ABSTRACT: The dysfunction of cholinergic neurons is a typical hallmark in Alzheimer's disease (AD). Previous findings demonstrated that high density of cholinergic receptors is found in the thalamus and the cerebellum compared with the cerebral cortex and the hippocampus. We aimed at investigating whether activation of the cerebello-thalamo-cortical pathway by means of cerebellar theta burst stimulation (TBS) could modulate central cholinergic functions evaluated in vivo by using the neurophysiological determination of Short-Latency Afferent Inhibition (SLAI). We tested the SLAI circuit before and after administration of cerebellar continuous TBS (cTBS) in 12 AD patients and in 12 healthy age-matched control subjects (HS). We also investigated potential changes of intracortical circuits of the contralateral primary motor cortex (M1) by assessing short intracortical inhibition (SICI) and intracortical facilitation (ICF). SLAI was decreased in AD patients compared to HS. Cerebellar cTBS partially restored SLAI in AD patients at later inter-stimulus intervals (ISIs), but did not modify SLAI in HS. SICI and ICF did not differ in the two groups and were not modulated by cerebellar cTBS. These results demonstrate that cerebellar magnetic stimulation is likely to affect mechanisms of cortical cholinergic activity, suggesting that the cerebellum may have a direct influence on the cholinergic dysfunction in AD.
  Frontiers in aging neuroscience. 01/2013; 5:2.
• Article: Depressive symptoms in Parkinson's disease and in non-neurological medical illnesses.

  Francesca Assogna, Sabrina Fagioli, Luca Cravello, Giuseppe Meco, Mariangela Pierantozzi, Alessandro Stefani, Francesca Imperiale, Carlo Caltagirone, Francesco E Pontieri, Gianfranco Spalletta
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  ABSTRACT: Patients with neurological and non-neurological medical illnesses very often complain of depressive symptoms that are associated with cognitive and functional impairments. We compared the profile of depressive symptoms in Parkinson's disease (PD) patients with that of control subjects (CS) suffering from non-neurological medical illnesses. One-hundred PD patients and 100 CS were submitted to a structured clinical interview for identification of major depressive disorder (MDD) and minor depressive disorder (MIND), according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR), criteria. The Hamilton Depression Rating Scale (HDRS) and the Beck Depression Inventory (BDI) were also administered to measure depression severity. When considering the whole groups, there were no differences in depressive symptom frequency between PD and CS apart from worthlessness/guilt, and changes in appetite reduced rates in PD. Further, total scores and psychic and somatic subscores of HDRS and BDI did not differ between PD and CS. After we separated PD and CS in those with MDD, MIND, and no depression (NODEP), comparing total scores and psychic/somatic subscores of HDRS and BDI, we found increased total depression severity in NODEP PD and reduced severity of the psychic symptoms of depression in MDD PD, with no differences in MIND. However, the severity of individual symptom frequency of depression was not different between PD and CS in MDD, MIND, and NODEP groups. Although MDD and MIND phenomenology in PD may be very similar to that of CS with non-neurological medical illnesses, neurological symptoms of PD may worsen (or confound) depression severity in patients with no formal/structured DSM-IV-TR, diagnosis of depressive mood disorders. Thus, a thorough assessment of depression in PD should take into consideration the different impacts of neurological manifestations on MDD, MIND, and NODEP.
  Neuropsychiatric Disease and Treatment 01/2013; 9:389-96. · 1.81 Impact Factor
• Article: Hedonic tone and its mood and cognitive correlates in Parkinson's disease.

  Gianfranco Spalletta, Sabrina Fagioli, Giuseppe Meco, Mariangela Pierantozzi, Alessandro Stefani, Valerio Pisani, Carlo Caltagirone, Francesco E Pontieri, Francesca Assogna
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  ABSTRACT: Anhedonia has been mainly reported as a symptom of depression and cognitive impairment in Parkinson's disease (PD) patients. Here, we investigated whether hedonic tone depends on depression and clarified its relationship with the cognitive performance of PD patients with different mood disorders. In 254 patients, we assessed hedonic tone using the Snaith-Hamilton Pleasure Scale, depression severity using the Beck Depression Inventory, and cognitive performances using the Mental Deterioration Battery. A structural psychiatric interview was used to diagnose major depressive disorder (MDD) and minor depressive disorder (MIND), according to the DSM-IV-TR criteria. PD patients with diagnosis of MDD were more anhedonic than those with MIND and those without depressive disorders. Reduced hedonic tone correlated with depression severity in patients with MDD and no depressive disorders. In multivariate models that consider depression severity and cognitive performances together, anhedonia was related to increased depression severity and episodic memory (auditory-verbal learning) impairment, in patients with MDD and with increased depression severity and attention impairment in patients with no depressive disorders. In patients with MIND, anhedonia did not correlate with depression severity or any cognitive performance score. Our findings suggest that anhedonia is related to depression severity and specific cognitive performances in patients with MDD and with no depressive disorder. By contrast, the reduced hedonic tone in patients with MIND is independent from depression severity and cognition. Thus, anhedonia in PD is a heterogeneous and multidimensional phenomenon and require investigation at different levels.
  Depression and Anxiety 01/2013; 30(1):85-91. · 4.18 Impact Factor
• Article: Parkinsonian patients with deficits in the dysexecutive spectrum are impaired on theory of mind tasks.

  Alberto Costa, Antonella Peppe, Matteo Martini, Katia Coletta, Massimiliano Oliveri, Carlo Caltagirone, Giovanni A Carlesimo
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  ABSTRACT: Understanding the mental states of others entails a number of cognitive processes known as Theory of Mind (ToM). A relationship between ToM deficits and executive disorders has been hypothesized in individuals with Parkinson's disease (PD). The present study was aimed at investigating the effect of dysexecutive deficits on ToM abilities in PD patients without dementia. Participants included 30 PD patients and 30 healthy subjects (HC). PD patients were divided into two groups according to their executive test performance: patients with poor (dysexecutive group; n=15) and normal (executively unimpaired group; n=15) performance. All participants were administered faux pas recognition written stories. The dysexecutive PD patients performed less accurately than both HC and executively unimpaired PD individuals on all faux pas story questions (p< 0.05); the executively unimpaired PD group performed as accurately as the HC group on the ToM tasks. Results of the study clearly demonstrate that PD is not tout court associated with ToM impairments and that these may occur in PD patients as a function of the degree of their executive impairment. Our findings also indirectly confirm previous data on the role of the prefrontal regions in mediating ToM capacities.
  Behavioural neurology 12/2012; · 1.77 Impact Factor
• Source

  Available from: Paola Bossù

  Article: Increased expression of Interleukin-18 receptor in blood cells of subjects with Mild Cognitive Impairment and Alzheimer's disease.

  Francesca Salani, Antonio Ciaramella, Federica Bizzoni, Francesca Assogna, Carlo Caltagirone, Gianfranco Spalletta, Paola Bossù
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  ABSTRACT: Inflammation has been proposed as a leading force in neurodegeneration and Interleukin (IL)-18 is a pro-inflammatory cytokine which is suggested to be implicated in Alzheimer's disease (AD). However, the meaning of the IL-18 participation in this disease is still unclear. Since IL-18 activity is mediated by its heterodimeric receptor complex IL-18Rα/β, we evaluated the presence of both IL-18R chains on peripheral blood cells of AD patients, as well as in individuals with Mild Cognitive Impairment (MCI), at increased risk to develop AD. More specifically, we compared the levels of CD14(+) monocytes and CD3(+) T-lymphocytes bearing IL-18Rα and β chains in the two groups of patients with those in healthy control subjects, both before and after in vitro cell treatment with lipopolysaccharide (LPS). While no differences in the levels of monocytes and T-lymphocytes bearing IL-18Rα chain were found among the three groups, either in untreated and LPS-treated conditions, the IL-18Rβ chain expression appeared differently regulated in MCI and AD patients, as compared to controls. In particular, the amount of IL-18Rβ-bearing monocytes was similar among the three groups at unstimulated conditions, while after LPS treatment it was increased in MCI vs. controls. A significant increase of IL-18Rβ-bearing T-lymphocytes was also observed in MCI and AD vs. controls, both in untreated and LPS-stimulated conditions. Our findings indicate that the expression of IL-18R complex on blood cells is perturbed in AD and even more markedly in its preclinical state of MCI, confirming that an increased peripheral activity of IL-18 may be involved in the early phase of AD pathophysiology.
  Cytokine 11/2012; · 3.02 Impact Factor
• Article: Fronto-thalamic volumetry markers of somatic delusions and hallucinations in schizophrenia.

  Gianfranco Spalletta, Fabrizio Piras, Ivo Alex Rubino, Carlo Caltagirone, Sabrina Fagioli
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  ABSTRACT: Although the psychotic phenomena of schizophrenia have been extensively investigated, somatic delusions and hallucinations have seldom been reported and their mechanisms are substantially unexplored. Here, we aimed to identify the brain structural correlates of somatic psychotic phenomena using combined volumetry and diffusivity structural neuroimaging techniques. Seventy-five individuals with a DSM-IV-TR diagnosis of schizophrenia and 75 healthy controls (HC) underwent a comprehensive clinical assessment, a high-resolution T1-weighted magnetic resonance imaging and a diffusion tensor imaging protocol using a 3T MRI scanner. Voxel-based volumetry and mean diffusivity (MD) of gray matter (GM) and fractional anisotropy (FA) of white matter (WM) of the whole brain were calculated for each subject. Reduced left fronto-insular GM volume was found in patients with somatic delusions compared with patients without somatic delusions and HC. Increased GM volume was found in the bilateral thalami, primarily in the right ventral-anterior thalamic nucleus projecting to the prefrontal-temporal cortices and the bilateral pars triangularis of the inferior frontal lobe, of patients with somatic hallucinations and HC compared with patients without somatic hallucinations. No differences emerged in GM MD and in WM FA between patients with and without psychotic somatic phenomena (i.e. delusions or hallucinations). These findings provide the first evidence that a frontal-thalamic structural perturbation mediates somatic psychotic phenomena in schizophrenia.
  Psychiatry research. 11/2012;
• Article: A non-comparative assessment of tolerability and efficacy of duloxetine in the treatment of depressed patients with Parkinson's disease.

  Ubaldo Bonuccelli, Giuseppe Meco, Giovanni Fabbrini, Alessandro Tessitore, Mariangela Pierantozzi, Fabrizio Stocchi, Roberto Ceravolo, Carlo Caltagirone, Mauro Silvestrini, Francesca Morgante, Stefano Ruggieri, Laura Avanzino, Michele Guadagna, Grazia Dell'agnello, Andrea Rossi, Riccardo Spezia, Michele Mancini
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  ABSTRACT: Objective: Depression is a comorbidity affecting quality of life (QoL) in patients with Parkinson's disease (PD) and requires appropriate treatment. This study evaluated the tolerability, safety, and efficacy of duloxetine 60 mg once daily for 12 weeks in PD patients with major depressive disorder (MDD). Research and design methods: Non-comparative, open-label, multi-center study. Main outcome measures: Tolerability was evaluated by discontinuation rate (acceptable if ≤ 19%) due to treatment-emergent adverse events (TEAEs) and motor symptoms (UPDRS). Safety measures were TEAEs, the UKU side effect rating scale, vital signs, weight, laboratory tests, and ECG. Efficacy measures included HAMD-17, BDI, CGI-S, PGI-I, and pain VAS. QoL was measured by PDQ-39. Results: Of the 151 patients enrolled, 8.6% (95% upper CI: 13.3%) discontinued the study due to TEAEs. Worsening in PD-related tremor and rigidity was not observed, activities of daily living significantly improved and UKU subscales progressively decreased. Clinically significant abnormalities in laboratory findings were limited to four cases of hypercholesterolemia and one increase of total bilirubin, CPK, and fasting glucose. Blood pressure, weight, and ECG did not change from baseline. HAMD-17 and PDQ-39 total score and individual domains, BDI, CGI-S, and PGI-I total scores significantly improved. Conclusions: Duloxetine seems well tolerated and likely effective in the treatment of depression associated with PD, with no detrimental effects in PD signs and symptoms.
  Expert Opinion on Pharmacotherapy 11/2012; 13(16):2269-80. · 3.20 Impact Factor