Ylenia Barone
@policlinico.mi.it
Department of Neurosciences and Mental Health, Milan, Italy
Psychiatrist
Scopus Publications
Scopus Publications
Ylenia Barone, Francesco Cuniberti, and Giampaolo Perna
Springer International Publishing
E. Bianciardi, Y. Barone, V. Lo Serro, A. De Stefano, N. Giacchetti, F. Aceti and C. Niolu
PURPOSE
Increased inflammation has been described as consistently associated with depression. Moreover, the pro-inflammatory pattern was found in women with a history of trauma irrespective of major depression diagnosis. In this study, we explored the possible association of inflammatory markers with perinatal depression (PND), measuring serum levels of cytokines (IL-6, TNF-a, IFN-γ), acute phase proteins (CRP), erythrocyte sedimentation rate (ESR), cortisol and brain-derived neurotrophic factor (BDNF) in women at the second trimester of pregnancy. Moreover, we tested whether the biological markers were correlated with the severity of PND, trauma history and resilience level.
METHODS
Seventy-nine women including two groups of patients (women with PND at the second trimester of pregnancy with and without history of trauma) and two healthy control groups (inside and outside the peripartum) were enrolled. Blood sampling were collected for measuring putative biological markers. Clinical interview, Edinburgh Postnatal Depression Scale (EPDS), Inventory of Traumatic experiences (TEC), Connor-Davidson Resilience Scale (CD-RISC) were administered.
RESULTS
Women with PND and trauma reported a higher EPDS (p=0.004) and lower CD-RISC scores compared to other groups (F=34.77; p<0.001). The one-way ANOVA analysis showed lower ERS (F=2.87; p=0.040), CRP (F42=4.05; p=0.010) mean values among PND women without trauma and higher TNF-α mean values (F=6.07; p=0.001) among PND women with trauma history compared to other groups.
CONCLUSIONS
History of trauma was associated with a more severe clinical phenotype of PND and decreased resilience level. The increase of acute phase proteins in women with PND and higher TNF-a level in those with trauma exposure validated the inflammatory theory of PND. Our findings substantiated the need of implementing the screening of pregnant women with the assessment of trauma history. Properly, resilience-enhancing interventions are recommended with the aim of support mothers and mitigate the possible transgenerational transmission of pathology. The biological results are compelling although preliminary.
Giampaolo Perna, Ylenia Barone, and Alessandra Alciati
Springer International Publishing
M. Nosè, I. Bighelli, M. Castellazzi, G. Martinotti, G. Carrà, C. Lucii, G. Ostuzzi, F. Sozzi, C. Barbui, and
Cambridge University Press (CUP)
Aims.In recent years several warnings have been issued by regulatory authorities on the risk of electrocardiogram abnormalities in individuals exposed to psychotropic drugs. As a consequence of these warnings, monitoring of the QT interval corrected for heart rate (QTc) has become increasingly common. This study was conducted to measure the frequency of QTc prolongation in unselected psychiatric patients, and to document the associated factors using a cross-sectional approach.Method.The study was carried out in 35 Italian psychiatric services that are part of the STAR (Servizi Territoriali Associati per la Ricerca) Network, a research group established to produce scientific knowledge by collecting data under ordinary circumstances. During a three-month period, a consecutive unselected series of both in- and out-patients were enrolled if they performed an ECG during the recruitment period and were receiving psychotropic drugs on the day ECG was recorded.Results.During the recruitment period a total of 2411 patients were included in the study. The prevalence of QTc prolongation ranged from 14.7% (men) and 18.6% (women) for the cut-off of 450 ms, to 1.26% (men) and 1.01% (women) for the cut-off of 500 ms. In the multivariate model conducted in the whole sample of patients exposed to psychotropic drugs, female sex, age, heart rate, alcohol and/or substance abuse, cardiovascular diseases and cardiovascular drug treatment, and drug overdose were significantly associated with QTc prolongation. In patients exposed to antipsychotic drugs, polypharmacy was positively associated with QTc prolongation, whereas use of aripiprazole decreased the risk. In patients exposed to antidepressant drugs, use of citalopram, citalopram dose and use of haloperidol in addition to antidepressant drugs, were all positively associated with QTc prolongation.Conclusions.The confirmation of a link between antipsychotic polypharmacy and QTc prolongation supports the current guidelines that recommend avoiding the concurrent use of two or more antipsychotic drugs, and the confirmation of a link between citalopram and QTc prolongation supports the need for routine QTc monitoring. The relatively low proportion of patients with QTc prolongation not only suggests compliance with current safety warnings issued by regulatory authorities, but also casts some doubts on the clinical relevance of QTc prolongation related to some psychotropic drugs.
Giuseppe Carrà, Cristina Crocamo, Francesco Bartoli, Annamaria Lax, Martina Tremolada, Claudio Lucii, Giovanni Martinotti, Michela Nosè, Irene Bighelli, Giovanni Ostuzzi,et al.
Wiley
Corrected QT (QTc) interval prolongation is often associated with use of first‐generation antipsychotics (FGAs). However, other factors require appropriate consideration, including age and gender, the role of other known medications associated with QTc prolongation, and severe comorbid conditions, such as co‐occurring alcohol abuse/dependence. We aimed to study potential mediating roles of different, related, candidate variables on QTc.
Corrado Barbui, Irene Bighelli, Giuseppe Carrà, Mariasole Castellazzi, Claudio Lucii, Giovanni Martinotti, Michela Nosè, Giovanni Ostuzzi, and
Public Library of Science (PLoS)
Antipsychotic (AP) drugs have the potential to cause prolongation of the QT interval corrected for heart rate (QTc). As this risk is dose-dependent, it may be associated with the number of AP drugs concurrently prescribed, which is known to be associated with increased cumulative equivalent AP dosage. This study analysed whether AP dose mediates the relationship between polypharmacy and QTc interval. We used data from a cross-sectional survey that investigated the prevalence of QTc lengthening among people with psychiatric illnesses in Italy. AP polypharmacy was tested for evidence of association with AP dose and QTc interval using the Baron and Kenny mediational model. A total of 725 patients were included in this analysis. Of these, 186 (26%) were treated with two or more AP drugs (AP polypharmacy). The mean cumulative AP dose was significantly higher in those receiving AP polypharmacy (prescribed daily dose/defined daily dose = 2.93, standard deviation 1.31) than monotherapy (prescribed daily dose/defined daily dose = 0.82, standard deviation 0.77) (z = −12.62, p < 0.001). Similarly, the mean QTc interval was significantly longer in those receiving AP polypharmacy (mean = 420.86 milliseconds, standard deviation 27.16) than monotherapy (mean = 413.42 milliseconds, standard deviation 31.54) (z = −2.70, p = 0.006). The Baron and Kenny mediational analysis showed that, after adjustment for confounding variables, AP dose mediates the association between polypharmacy and QTc interval. The present study found that AP polypharmacy is associated with QTc interval, and this effect is mediated by AP dose. Given the high prevalence of AP polypharmacy in real-world clinical practice, clinicians should consider not only the myriad risk factors for QTc prolongation in their patients, but also that adding a second AP drug may further increase risk as compared with monotherapy.
C. Niolu, Y. Barone, E. Bianciardi, M. Ribolsi, C. Marchetta, Camilla Robone, Antonio Ambrosio, Luca Sarchiola, Giorgio Reggiardo, G. Lorenzo and A. Siracusano
AIM
The aim of this study was to assess possible predictors of poor adherence in patients with a diagnosis of schizophrenia-spectrum disorders (SD) or bipolar disorder (BD) and to evaluate the roles of attachment style and caregivers as predictive factors of adherence.
METHODS
The sample was composed of 178 voluntarily hospitalized inpatients: 89 diagnosed with BD (I, II), 89 with SD and other schizophrenia-spectrum disorders. All patients enrolled in the study were assessed for adherence, psychopathology, attachment style, presence of caregiver, subjective well-being during pharmacological treatment with neuroleptics, side effects following therapy, subjective attitude towards drugs, global functioning and quality of life.
RESULTS
In patients with SD, non-adherence was associated with the absence of a caregiver, fewer years of treatment, poor insight and attitude towards drugs and fearful dimensions of attachment. In patients with BD, poor insight, anxious and social avoidant temperament traits, together with a high sense of self efficacy, were related to non-adherence. Diagnosis, type of medication and side effects were not predictive factors of adherence in either group. Interestingly, some temperament traits and dimensions of attachment predict non-adherence, indicating differences between patients with SD and BD.
CONCLUSION
Considering these predictors of non-adherence and assessing adherence at the time of admission for relapse could be useful to plan an early and tailored “treatment adherence”, along with other therapeutic strategies, for patients using these predictive factors. The role of caregiver proved particularly important in relation to the therapeutic alliance. Attachment style may play a key role in predicting adherence through the therapeutic alliance with both patients and caregivers.
Giorgio Di Lorenzo, Andrea Daverio, Fabiola Ferrentino, Emiliano Santarnecchi, Fabio Ciabattini, Leonardo Monaco, Giulia Lisi, Ylenia Barone, Cherubino Di Lorenzo, Cinzia Niolu,et al.
Frontiers Media SA
Despite the increasing body of evidence supporting the hypothesis of schizophrenia as a disconnection syndrome, studies of resting-state EEG Source Functional Connectivity (EEG-SFC) in people affected by schizophrenia are sparse. The aim of the present study was to investigate resting-state EEG-SFC in 77 stable, medicated patients with schizophrenia (SCZ) compared to 78 healthy volunteers (HV). In order to study the effect of illness duration, SCZ were divided in those with a short duration of disease (SDD; n = 25) and those with a long duration of disease (LDD; n = 52). Resting-state EEG recordings in eyes closed condition were analyzed and lagged phase synchronization (LPS) indices were calculated for each ROI pair in the source-space EEG data. In delta and theta bands, SCZ had greater EEG-SFC than HV; a higher theta band connectivity in frontal regions was observed in LDD compared with SDD. In the alpha band, SCZ showed lower frontal EEG-SFC compared with HV whereas no differences were found between LDD and SDD. In the beta1 band, SCZ had greater EEG-SFC compared with HVs and in the beta2 band, LDD presented lower frontal and parieto-temporal EEG-SFC compared with HV. In the gamma band, SDD had greater connectivity values compared with LDD and HV. This study suggests that resting state brain network connectivity is abnormally organized in schizophrenia, with different patterns for the different EEG frequency components and that EEG can be a powerful tool to further elucidate the complexity of such disordered connectivity.
Cinzia Niolu, Emanuela Bianciardi, Giorgio Di Lorenzo, Claudia Marchetta, Ylenia Barone, Nicoletta Sterbini, Michele Ribolsi, Giorgio Reggiardo, and Alberto Siracusano
SAGE Publications
Aim: This study evaluated adherence to treatment, quality of life and subjective well-being in patients with psychosis treated with long-acting injectable risperidone. Subjects enrolled were part of a larger study where patients were observed in an adherence to treatment program of the University of Rome Tor Vergata. Materials and methods: A total of 27 nonadherent patients (21 men, six women; mean age: 36.1 years; range: 23–63 years) were enrolled. Maximum observational period was 30 months. Results: A total of 12 patients were under treatment for 30 months (44.44%) but only nine had a valid 30-month follow up, while the remaining three patients initially treated at our unit continued long-acting risperidone at their local centre. Reductions of monthly mean values of Scale for the Assessment of Positive Symptoms (SAPS) [repeated measures analysis of variance (rm-ANOVA): p < 0.0001] and Scale for Assessment of Negative Symptoms (SANS) ( p < 0.0001), increase of monthly mean values of Subjective Well-Being Under Neuroleptic Treatment Scale (SWN) ( p < 0.0001) and Schizophrenia Quality of Life Scale (S-QoL) ( p < 0.01) were observed. Significant differences with respect to SAPS baseline values from the sixth month, SANS baseline values from the seventh month, SWN baseline values from the eighth month, S-QoL baseline values from the eighteenth month were shown in post hoc tests. Reduction of SAPS mean values was associated with increase of SWN ( p < 0.0001) and S-QoL ( p < 0.0001) mean values as demonstrated by correlation analysis. The same inverse correlation was found between reduction of SANS mean values and increases of SWN ( p < 0.0001) and S-QoL ( p = 0.0001) mean values. Conclusions: Long-term treatment with long-acting risperidone may be associated with improvement to adherence to therapy and quality of life. Patients may show improvement in psychopathological symptoms, subjective well-being and quality of life.
Cherubino Di Lorenzo, Andrea Daverio, Patrizio Pasqualetti, Gianluca Coppola, Ioannis Giannoudas, Ylenia Barone, Gaetano S. Grieco, Cinzia Niolu, Esterina Pascale, Filippo M. Santorelli,et al.
Wiley
Monoamines have an important role in neural plasticity, a key factor in cortical pain processing that promotes changes in neuronal network connectivity. Monoamine oxidase type A (MAOA) is an enzyme that, due to its modulating role in monoaminergic activity, could play a role in cortical pain processing. The X‐linked MAOA gene is characterized by an allelic variant of length, the MAOA upstream Variable Number Tandem Repeat (MAOA‐uVNTR) region polymorphism. Two allelic variants of this gene are known, the high‐activity MAOA (HAM) and low‐activity MAOA (LAM). We investigated the role of MAOA‐uVNTR in cortical pain processing in a group of healthy individuals measured by the trigeminal electric pain‐related evoked potential (tPREP) elicited by repeated painful stimulation. A group of healthy volunteers was genotyped to detect MAOA‐uVNTR polymorphism. Electrical tPREPs were recorded by stimulating the right supraorbital nerve with a concentric electrode. The N2 and P2 component amplitude and latency as well as the N2–P2 inter‐peak amplitude were measured. The recording was divided into three blocks, each containing 10 consecutive stimuli and the N2–P2 amplitude was compared between blocks. Of the 67 volunteers, 37 were HAM and 30 were LAM. HAM subjects differed from LAM subjects in terms of amplitude of the grand‐averaged and first‐block N2–P2 responses (HAM>LAM). The N2–P2 amplitude decreased between the first and third block in HAM subjects but not LAM subjects. The MAOA‐uVNTR polymorphism seemed to influence the brain response in a repeated tPREP paradigm and suggested a role of the MAOA as a modulator of neural plasticity related to cortical pain processing.
Carla Nasca, Dionysios Xenos, Ylenia Barone, Alessandra Caruso, Sergio Scaccianoce, Francesco Matrisciano, Giuseppe Battaglia, Aleksander A. Mathé, Anna Pittaluga, Luana Lionetto,et al.
Proceedings of the National Academy of Sciences
Epigenetic mechanisms are involved in the pathophysiology of depressive disorders and are unique potential targets for therapeutic intervention. The acetylating agent L -acetylcarnitine (LAC), a well-tolerated drug, behaves as an antidepressant by the epigenetic regulation of type 2 metabotropic glutamate (mGlu2) receptors. It caused a rapid and long-lasting antidepressant effect in Flinders Sensitive Line rats and in mice exposed to chronic unpredictable stress, which, respectively, model genetic and environmentally induced depression. In both models, LAC increased levels of acetylated H3K27 bound to the Grm2 promoter and also increased acetylation of NF-ĸB-p65 subunit, thereby enhancing the transcription of Grm2 gene encoding for the mGlu2 receptor in hippocampus and prefrontal cortex. Importantly, LAC reduced the immobility time in the forced swim test and increased sucrose preference as early as 3 d of treatment, whereas 14 d of treatment were needed for the antidepressant effect of chlorimipramine. Moreover, there was no tolerance to the action of LAC, and the antidepressant effect was still seen 2 wk after drug withdrawal. Conversely, NF-ĸB inhibition prevented the increase in mGlu2 expression induced by LAC, whereas the use of a histone deacetylase inhibitor supported the epigenetic control of mGlu2 expression. Finally, LAC had no effect on mGlu2 knockout mice exposed to chronic unpredictable stress, and a single injection of the mGlu2/3 receptor antagonist LY341495 partially blocked LAC action. The rapid and long-lasting antidepressant action of LAC strongly suggests a unique approach to examine the epigenetic hypothesis of depressive disorders in humans, paving the way for more efficient antidepressants with faster onset of action.
Cherubino Di Lorenzo, Giorgio Di Lorenzo, Andrea Daverio, Patrizio Pasqualetti, Gianluca Coppola, Ioannis Giannoudas, Ylenia Barone, Gaetano S. Grieco, Cinzia Niolu, Esterina Pascale,et al.
Elsevier BV
Francesco Matrisciano, Antonella M.E. Modafferi, Giuseppina I. Togna, Ylenia Barone, Graziano Pinna, Ferdinando Nicoletti, and Sergio Scaccianoce
Elsevier BV