Publications by authors named "Francesco Catapano"

40 Publications

Duration of untreated illness predicts 3-year outcome in patients with obsessive-compulsive disorder: A real-world, naturalistic, follow-up study.

Psychiatry Res 2021 May 15;299:113872. Epub 2021 Mar 15.

Department of Psychiatry, University of Campania "L. Vanvitelli", Naples, Italy.

Duration of untreated illness (DUI) is a predictor of outcome in psychotic and affective disorders. The few available data on the effect of DUI in obsessive-compulsive disorder (OCD) suggest an association between longer DUI and poorer response to treatments. This is a real-world, naturalistic, follow-up study evaluating the impact of DUI on long-term clinical outcomes. The sample consists of 83 outpatients with OCD with a mean DUI of 7.3 (5.8) years. Patients with symmetry/ordering cluster symptoms were younger at onset of the disease (20.4 ± 7.9 vs. 27.8 ± 10.6; p<.05, d = 0.79), had a longer duration of the illness (10.1 ± 4.6 vs. 6.8 ± 4.6, p<.05; d = 0.53) and a longer DUI (7.9 ± 6.5 vs. 5.4 ± 3.6, p<.05, d = 0.49) compared to patients not presenting with those symptoms. Fifty-nine patients completed the follow-up, and 33.9% (N = 20) met the criteria for partial remission, scoring <15 at the Y-BOCS for at least eight weeks. Patients in partial remission for more than 40% of the follow-up were defined as "good outcome" and they had a significantly shorter DUI compared to patients with "poor outcome". Access to adequate treatments is highly delayed in patients with OCD. DUI is strongly associated with poor treatment outcomes. Therefore, strategies to ensure an early diagnosis and treatment are needed.
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http://dx.doi.org/10.1016/j.psychres.2021.113872DOI Listing
May 2021

Bioinspired artificial exosomes based on lipid nanoparticles carrying let-7b-5p promote angiogenesis in vitro and in vivo.

Mol Ther 2021 Jul 18;29(7):2239-2252. Epub 2021 Mar 18.

Bristol Heart Institute, University of Bristol, Bristol BS2 8ED, UK; National Heart and Lung Institute, Imperial College London, London W12 0NN, UK. Electronic address:

MicroRNAs (miRNAs) regulate gene expression by post-transcriptional inhibition of target genes. Proangiogenic small extracellular vesicles (sEVs; popularly identified with the name "exosomes") with a composite cargo of miRNAs are secreted by cultured stem cells and present in human biological fluids. Lipid nanoparticles (LNPs) represent an advanced platform for clinically approved delivery of RNA therapeutics. In this study, we aimed to (1) identify the miRNAs responsible for sEV-induced angiogenesis; (2) develop the prototype of bioinspired "artificial exosomes" (AEs) combining LNPs with a proangiogenic miRNA, and (3) validate the angiogenic potential of the bioinspired AEs. We previously reported that human sEVs from bone marrow (BM)-CD34 cells and pericardial fluid (PF) are proangiogenic. Here, we have shown that sEVs secreted from saphenous vein pericytes and BM mesenchymal stem cells also promote angiogenesis. Analysis of miRNA datasets available in-house or datamined from GEO identified the let-7 family as common miRNA signature of the proangiogenic sEVs. LNPs with either hsa-let-7b-5p or cyanine 5 (Cy5)-conjugated Caenorhabditis elegans miR-39 (Cy5-cel-miR-39; control miRNA) were prepared using microfluidic micromixing. let-7b-5p-AEs did not cause toxicity and transferred functionally active let-7b-5p to recipient endothelial cells (ECs). let-7b-AEs also improved EC survival under hypoxia and angiogenesis in vitro and in vivo. Bioinspired proangiogenic AEs could be further developed into innovative nanomedicine products targeting ischemic diseases.
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http://dx.doi.org/10.1016/j.ymthe.2021.03.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261169PMC
July 2021

The altered expression of neurofilament in mouse models and patients with spinal muscular atrophy.

Ann Clin Transl Neurol 2021 04 8;8(4):866-876. Epub 2021 Mar 8.

NIHR Great Ormond Street Hospital Biomedical Research Centre, London, United Kingdom.

Objectives: To investigate the levels of neurofilaments (NFs) in transgenic mice and patients with spinal muscular atrophy (SMA), and to evaluate their efficacy as a biomarker in SMA.

Methods: The levels of NF mRNA transcripts were measured by quantitative real-time PCR in spinal cord from SMA mice. Blood levels of NF heavy chain (NfH) from mice and patients were measured by an in-house ELISA method. The response of NFs to therapeutic intervention was analysed in severe SMA mice treated with morpholino antisense oligonucleotides.

Results: Significant changes in NF transcript and protein in spinal cord and protein levels in blood were detected in SMA mice with severe or mild phenotypes, at different time points. A decrease in blood levels of NfH after antisense oligonucleotide treatment was only transient in the mice, despite the persistent benefit on the disease phenotype. A drastic reduction of over 90% in blood levels of NfF was observed in both control and SMA mice during early postnatal development. In contrast, blood levels of NfH were found to be decreased in older SMA children with chronic disease progression.

Interpretation: Our results show that blood NfH levels are informative in indicating disease onset and response to antisense oligonucleotides treatment in SMA mice, and indicate their potential as a peripheral marker reflecting the pathological status in central nervous system. In older patients with chronic SMA, however, the lower NfH levels may limit their application as biomarker, highlighting the need to continue to pursue additional biomarkers for this group of patients.
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http://dx.doi.org/10.1002/acn3.51336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045929PMC
April 2021

The administration of antisense oligonucleotide golodirsen reduces pathological regeneration in patients with Duchenne muscular dystrophy.

Acta Neuropathol Commun 2021 01 6;9(1). Epub 2021 Jan 6.

Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, 30 Guilford St, London, WC1N 1EH, UK.

During the last decade, multiple clinical trials for Duchenne muscular dystrophy (DMD) have focused on the induction of dystrophin expression using different strategies. Many of these trials have reported a clear increase in dystrophin protein following treatment. However, the low levels of the induced dystrophin protein have raised questions on its functionality. In our present study, using an unbiased, high-throughput digital image analysis platform, we assessed markers of regeneration and levels of dystrophin associated protein via immunofluorescent analysis of whole muscle sections in 25 DMD boys who received 48-weeks treatment with exon 53 skipping morpholino antisense oligonucleotide (PMO) golodirsen. We demonstrate that the de novo dystrophin induced by exon skipping with PMO golodirsen is capable of conferring a histological benefit in treated patients with an increase in dystrophin associated proteins at the dystrophin positive regions of the sarcolemma in post-treatment biopsies. Although 48 weeks treatment with golodirsen did not result in a significant change in the levels of fetal/developmental myosins for the entire cohort, there was a significant negative correlation between the amount of dystrophin and levels of regeneration observed in different biopsy samples. Our results provide, for the first time, evidence of functionality of induced dystrophin following successful therapeutic intervention in the human.
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http://dx.doi.org/10.1186/s40478-020-01106-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789286PMC
January 2021

Novel free-circulating and extracellular vesicle-derived miRNAs dysregulated in Duchenne muscular dystrophy.

Epigenomics 2020 11 20;12(21):1899-1915. Epub 2020 Nov 20.

The Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health, 30 Guildford Street, London, WC1N 1EH, United Kingdom.

To perform cross-sectional and longitudinal miRNA profiling in plasma from Duchenne muscular dystrophy (DMD) subjects and find non-invasive biomarkers in DMD. Plasma was collected from 14 age and sex matched controls and 46 DMD subjects. Free-circulating and extracellular vesicle (EV)-derived miRNA expression was measured by RT-qPCR. Free-circulating and EVs derived miR-29c-3p and miR-133a-3p are dysregulated in DMD subjects. Free-circulating and EV-derived miR-29c-3p are reduced in DMD subjects undergoing daily corticosteroid treatment. Free-circulating miR-1-3p and miR-122-5p are longitudinally upregulated in ambulant DMD subjects. We detected novel free-circulating and EV-derived dysregulated miRNAs in plasma from DMD subjects and characterized the longitudinal profile of free-circulating miRNA on plasma from DMD subjects.
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http://dx.doi.org/10.2217/epi-2020-0052DOI Listing
November 2020

A hypothesis on Cotard's syndrome as an evolution of obsessive-compulsive disorder.

Int Rev Psychiatry 2021 Feb-Mar;33(1-2):23-28. Epub 2020 Oct 5.

Department of Psychiatry, University of Campania "Luigi Vanvitelli", Naples, Italy.

Cotard's syndrome usually presents as combined symptoms occurring in a broad series of neurological, psychiatric, and medical disorders, being severe depression the most frequent. The syndrome is not classified as a distinct clinical entity in the nosological systems but appears solely as a clinical condition in case reports. Thus, the diagnosis of Cotard's syndrome mainly centres on the psychiatric interview and the ability of the clinician to recognise specific symptoms due to the absence of both clinical instruments and diagnostic criteria. Cotard's syndrome has never been described to date in patients with a history of obsessive-compulsive disorder (OCD). We report a case of a 49-year-old woman presenting obsessive symptoms and related compulsions for more than 30 years. Cotard's syndrome appeared after 3 years from a tragic event that had caused a psychological trauma. Such an occurrence may have contributed to worsening OCD and leading to a second major depressive episode followed by a suicidal attempt. Since then, the subject of our patient's obsessive thoughts changed, and the belief of being dead appeared. The repetitive and stereotyped thoughts caused severe distress, and accompanied the compulsive nature of reassurance seeking, temporarily beneficial to the anxiety arousing. The transition from obsession to delusion occurred when resistance was abandoned, and insight was lost. Once Cotard's syndrome had stabilised, OCD was no longer present. Additional distinctive features were the absence of psychiatric family history and the persistent nature of the affective psychosis. We concluded that Cotard's syndrome represented the evolution of the initial obsessive-compulsive disorder. Furthermore, we differentiated the clinical condition of our patient from other psychiatric diseases with similar clinical features. Larger-scale research is needed to consider topics other than comorbidity and also to explore significant elements of the patient's clinical history to discover what may influence the evolution and/or the persistence of the diseases.
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http://dx.doi.org/10.1080/09540261.2020.1810425DOI Listing
October 2020

Abnormal bodily experiences detected by Abnormal Bodily Phenomena questionnaire are more frequent and severe in schizophrenia than in bipolar disorder with psychotic features.

Eur Psychiatry 2020 05 14;63(1):e49. Epub 2020 May 14.

Department of Psychiatry, University of Campania "Luigi Vanvitelli", Naples, Italy.

Background: Patients with schizophrenia display experiential anomalies in their feelings and cognitions arising in the domain of their lived body. These abnormal bodily phenomena (ABP) are not part of diagnostic criteria for schizophrenia. One of the reasons is the difficulty to assess specific ABP for schizophrenia spectrum disorders. The present study aimed to explore the presence in patients with schizophrenia of specific ABP.

Methods: We used a semistructured interview-the Abnormal Bodily Phenomena questionnaire (ABPq), an instrument devised to detect and measure ABP specific to patients with schizophrenia. Fifty-one outpatients affected by schizophrenia and 28 euthymic outpatients affected by bipolar disorder type I with psychotic features (BD-pf-e) were recruited. Before assessing the specificity for schizophrenia of the observed ABP, we tested the internal consistency and the convergent validity of the ABPq in patients with schizophrenia. Specificity was assessed by examining potential differences in ABPq among the patients with schizophrenia in remission (SCZ-r) and BD-pf-e.

Results: The ABPq shows strong internal consistency and convergent validity. As to the specificity, ABP measured by ABPq were more frequent and severe in SCZ-r than in BD-pf-e. In particular, all ABPq dimensions, except "Coherence," had at least mild severity in over 50% of SCZ-r, while dimensions with at least mild severity were observed in 5-10% of the BD-pf-e.

Conclusions: These findings can contribute to establish more precise phenomenal boundaries between schizophrenia and bipolar disorder, to explore the borders between nonpsychotic and psychotic forms of ABP, between ABP and negative and disorganized symptoms, and to enlighten core aspects of schizophrenia.
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http://dx.doi.org/10.1192/j.eurpsy.2020.49DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355172PMC
May 2020

Novel Applications of Mesenchymal Stem Cell-derived Exosomes for Myocardial Infarction Therapeutics.

Biomolecules 2020 05 2;10(5). Epub 2020 May 2.

National Heart and Lung Institute, Imperial College London, London W12 0NN, UK.

Cardiovascular diseases (CVDs) are the leading cause of mortality and morbidity globally, representing approximately a third of all deaths every year. The greater part of these cases is represented by myocardial infarction (MI), or heart attack as it is better known, which occurs when declining blood flow to the heart causes injury to cardiac tissue. Mesenchymal stem cells (MSCs) are multipotent stem cells that represent a promising vector for cell therapies that aim to treat MI due to their potent regenerative effects. However, it remains unclear the extent to which MSC-based therapies are able to induce regeneration in the heart and even less clear the degree to which clinical outcomes could be improved. Exosomes, which are small extracellular vesicles (EVs) known to have implications in intracellular communication, derived from MSCs (MSC-Exos), have recently emerged as a novel cell-free vector that is capable of conferring cardio-protection and regeneration in target cardiac cells. In this review, we assess the current state of research of MSC-Exos in the context of MI. In particular, we place emphasis on the mechanisms of action by which MSC-Exos accomplish their therapeutic effects, along with commentary on the current difficulties faced with exosome research and the ongoing clinical applications of stem-cell derived exosomes in different medical contexts.
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http://dx.doi.org/10.3390/biom10050707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277090PMC
May 2020

A high-throughput digital script for multiplexed immunofluorescent analysis and quantification of sarcolemmal and sarcomeric proteins in muscular dystrophies.

Acta Neuropathol Commun 2020 04 17;8(1):53. Epub 2020 Apr 17.

Department of Neurodegenerative Diseases, UCL Queen Square Institute of Neurology, London, UK.

The primary molecular endpoint for many Duchenne muscular dystrophy (DMD) clinical trials is the induction, or increase in production, of dystrophin protein in striated muscle. For accurate endpoint analysis, it is essential to have reliable, robust and objective quantification methodologies capable of detecting subtle changes in dystrophin expression. In this work, we present further development and optimisation of an automated, digital, high-throughput script for quantitative analysis of multiplexed immunofluorescent (IF) whole slide images (WSI) of dystrophin, dystrophin associated proteins (DAPs) and regenerating myofibres (fetal/developmental myosin-positive) in transverse sections of DMD, Becker muscular dystrophy (BMD) and control skeletal muscle biopsies. The script enables extensive automated assessment of myofibre morphometrics, protein quantification by fluorescence intensity and sarcolemmal circumference coverage, colocalisation data for dystrophin and DAPs and regeneration at the single myofibre and whole section level. Analysis revealed significant variation in dystrophin intensity, percentage coverage and amounts of DAPs between differing DMD and BMD samples. Accurate identification of dystrophin via a novel background subtraction method allowed differential assessment of DAP fluorescence intensity within dystrophin positive compared to dystrophin negative sarcolemma regions. This enabled surrogate quantification of molecular functionality of dystrophin in the assembly of the DAP complex. Overall, the digital script is capable of multiparametric and unbiased analysis of markers of myofibre regeneration and dystrophin in relation to key DAPs and enabled better characterisation of the heterogeneity in dystrophin expression patterns seen in BMD and DMD alongside the surrogate assessment of molecular functionality of dystrophin. Both these aspects will be of significant relevance to ongoing and future DMD and other muscular dystrophies clinical trials to help benchmark therapeutic efficacy.
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http://dx.doi.org/10.1186/s40478-020-00918-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165405PMC
April 2020

Exosomes Could Offer New Options to Combat the Long-Term Complications Inflicted by Gestational Diabetes Mellitus.

Cells 2020 03 10;9(3). Epub 2020 Mar 10.

National Heart and Lung Institute, Imperial College London, London W12 0NN, UK.

Gestational diabetes Mellitus (GDM) is a complex clinical condition that promotes pelvic floor myopathy, thus predisposing sufferers to urinary incontinence (UI). GDM usually regresses after birth. Nonetheless, a GDM history is associated with higher risk of subsequently developing type 2 diabetes, cardiovascular diseases (CVD) and UI. Some aspects of the pathophysiology of GDM remain unclear and the associated pathologies (outcomes) are poorly addressed, simultaneously raising public health costs and diminishing women's quality of life. Exosomes are small extracellular vesicles produced and actively secreted by cells as part of their intercellular communication system. Exosomes are heterogenous in their cargo and depending on the cell sources and environment, they can mediate both pathogenetic and therapeutic functions. With the advancement in knowledge of exosomes, new perspectives have emerged to support the mechanistic understanding, prediction/diagnosis and ultimately, treatment of the post-GMD outcomes. Here, we will review recent advances in knowledge of the role of exosomes in GDM and related areas and discuss the possibilities for translating exosomes as therapeutic agents in the GDM clinical setting.
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http://dx.doi.org/10.3390/cells9030675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140615PMC
March 2020

Exosomes: From Potential Culprits to New Therapeutic Promise in the Setting of Cardiac Fibrosis.

Cells 2020 03 2;9(3). Epub 2020 Mar 2.

National Heart and Lung Institute, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.

Fibrosis is a significant global health problem associated with many inflammatory and degenerative diseases affecting multiple organs, individually or simultaneously. Fibrosis develops when extracellular matrix (ECM) remodeling becomes excessive or uncontrolled and is associated with nearly all forms of heart disease. Cardiac fibroblasts and myofibroblasts are the main effectors of ECM deposition and scar formation. The heart is a complex multicellular organ, where the various resident cell types communicate between themselves and with cells of the blood and immune systems. Exosomes, which are small extracellular vesicles, (EVs), contribute to cell-to-cell communication and their pathophysiological relevance and therapeutic potential is emerging. Here, we will critically review the role of endogenous exosomes as possible fibrosis mediators and discuss the possibility of using stem cell-derived and/or engineered exosomes as anti-fibrotic agents.
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http://dx.doi.org/10.3390/cells9030592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140485PMC
March 2020

Myostatin inhibition in combination with antisense oligonucleotide therapy improves outcomes in spinal muscular atrophy.

J Cachexia Sarcopenia Muscle 2020 06 7;11(3):768-782. Epub 2020 Feb 7.

The Dubowitz Neuromuscular Centre, Developmental Neurosciences Research and Teaching Department, Great Ormond Street Institute of Child Health, University College London, London, UK.

Background: Spinal muscular atrophy (SMA) is caused by genetic defects in the survival motor neuron 1 (SMN1) gene that lead to SMN deficiency. Different SMN-restoring therapies substantially prolong survival and function in transgenic mice of SMA. However, these therapies do not entirely prevent muscle atrophy and restore function completely. To further improve the outcome, we explored the potential of a combinatorial therapy by modulating SMN production and muscle-enhancing approach as a novel therapeutic strategy for SMA.

Methods: The experiments were performed in a mouse model of severe SMA. A previously reported 25-mer morpholino antisense oligomer PMO25 was used to restore SMN expression. The adeno-associated virus-mediated expression of myostatin propeptide was used to block the myostatin pathway. Newborn SMA mice were treated with a single subcutaneous injection of 40 μg/g (therapeutic dose) or 10 μg/g (low-dose) PMO25 on its own or together with systemic delivery of a single dose of adeno-associated virus-mediated expression of myostatin propeptide. The multiple effects of myostatin inhibition on survival, skeletal muscle phenotype, motor function, neuromuscular junction maturation, and proprioceptive afferences were evaluated.

Results: We show that myostatin inhibition acts synergistically with SMN-restoring antisense therapy in SMA mice treated with the higher therapeutic dose PMO25 (40 μg/g), by increasing not only body weight (21% increase in male mice at Day 40), muscle mass (38% increase), and fibre size (35% increase in tibialis anterior muscle in 3 month female SMA mice), but also motor function and physical performance as measured in hanging wire test (two-fold increase in time score) and treadmill exercise test (two-fold increase in running distance). In SMA mice treated with low-dose PMO25 (10 μg/g), the early application of myostatin inhibition prolongs survival (40% increase), improves neuromuscular junction maturation (50% increase) and innervation (30% increase), and increases both the size of sensory neurons in dorsal root ganglia (60% increase) and the preservation of proprioceptive synapses in the spinal cord (30% increase).

Conclusions: These data suggest that myostatin inhibition, in addition to the well-known effect on muscle mass, can also positively influence the sensory neural circuits that may enhance motor neurons function. While the availability of the antisense drug Spinraza for SMA and other SMN-enhancing therapies has provided unprecedented improvement in SMA patients, there are still unmet needs in these patients. Our study provides further rationale for considering myostatin inhibitors as a therapeutic intervention in SMA patients, in combination with SMN-restoring drugs.
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http://dx.doi.org/10.1002/jcsm.12542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296258PMC
June 2020

A new patient-derived iPSC model for dystroglycanopathies validates a compound that increases glycosylation of α-dystroglycan.

EMBO Rep 2019 11 30;20(11):e47967. Epub 2019 Sep 30.

Centre for Genomics and Child Health, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

Dystroglycan, an extracellular matrix receptor, has essential functions in various tissues. Loss of α-dystroglycan-laminin interaction due to defective glycosylation of α-dystroglycan underlies a group of congenital muscular dystrophies often associated with brain malformations, referred to as dystroglycanopathies. The lack of isogenic human dystroglycanopathy cell models has limited our ability to test potential drugs in a human- and neural-specific context. Here, we generated induced pluripotent stem cells (iPSCs) from a severe dystroglycanopathy patient with homozygous FKRP (fukutin-related protein gene) mutation. We showed that CRISPR/Cas9-mediated gene correction of FKRP restored glycosylation of α-dystroglycan in iPSC-derived cortical neurons, whereas targeted gene mutation of FKRP in wild-type cells disrupted this glycosylation. In parallel, we screened 31,954 small molecule compounds using a mouse myoblast line for increased glycosylation of α-dystroglycan. Using human FKRP-iPSC-derived neural cells for hit validation, we demonstrated that compound 4-(4-bromophenyl)-6-ethylsulfanyl-2-oxo-3,4-dihydro-1H-pyridine-5-carbonitrile (4BPPNit) significantly augmented glycosylation of α-dystroglycan, in part through upregulation of LARGE1 glycosyltransferase gene expression. Together, isogenic human iPSC-derived cells represent a valuable platform for facilitating dystroglycanopathy drug discovery and therapeutic development.
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http://dx.doi.org/10.15252/embr.201947967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832011PMC
November 2019

Comorbidity of Obsessive-Compulsive Disorder and Schizotypal Personality Disorder: Clinical Response and Treatment Resistance to Pharmacotherapy in a 3-Year Follow-Up Naturalistic Study.

Front Psychiatry 2019 17;10:386. Epub 2019 Jun 17.

Department of Psychiatry, University of Campania "Luigi Vanvitelli", Naples, Italy.

The present study aims to analyze the clinical and socio-demographic characteristics of patients with obsessive-compulsive disorder (OCD) in comorbidity with schizotypal personality disorder (SPD), as well as the response rate to pharmacological treatments. OCD+SPD patients had a younger age at onset, a higher probability to have more severe obsessive-compulsive symptoms, a higher rate of schizophrenia spectrum disorders in their first-degree relatives, and a poorer insight compared to OCD patients. During the 3-year follow-up period, these patients showed a lower rate of recovery, thus requiring augmentation with different psychotropic medications, including low doses of antipsychotics. Our findings suggest that the comorbidity of OCD and SPD causes a poor treatment response, and a reduced probability to recover using standard pharmacological treatment strategies. Further investigations are needed to identify alternative strategies, including psychoeducation and cognitive behavioral therapy, to manage such frequent comorbidity in clinical practice.
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http://dx.doi.org/10.3389/fpsyt.2019.00386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589899PMC
June 2019

The unmasking of hidden severe hyponatremia after long-term combination therapy in exacerbated bipolar patients: a case series.

Int Clin Psychopharmacol 2019 07;34(4):206-210

Department of Psychiatry, University of Campania 'Luigi Vanvitelli', Naples, Italy.

Hyponatremia is occasionally unmasked in psychiatric patients during hospitalization after routine blood and urinary tests, and correlates in most cases with an inappropriate secretion of antidiuretic hormone, mainly due to iatrogenic factors. Only a few studies have regarded the combination of psychotropic drugs as triggers of chronic, asymptomatic hyponatremia in bipolar patients, who require to be hospitalized because of the exacerbation of their mental illness. We presented three clinical cases of patients affected by a long-term psychiatric disorder and under polypharmacotherapy for several months. After excluding other potential factors, we hypothesized that pharmacological treatment with a mood stabilizer (oxcarbazepine) associated with a benzodiazepine (delorazepam), a second-generation antipsychotic (olanzapine) or an antidepressant (fluvoxamine), triggered severe hyponatremia ([Na+] ≤125 mEq/L), serum hypo-osmolarity, and elevated inappropriate urine osmolarity added to more diluted sodium concentration. When we discontinued the treatment, clinical conditions of our patients improved, despite the previous administration of hypertonic saline jointly with water restriction. Psychiatrists should consider that bipolar patients on long-term polypharmacotherapy may present a higher risk of severe hyponatremia not clinically detectable. Consequently, routine laboratory tests should be periodically repeated as they represent the only available tool to unmask such electrolyte imbalances.
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http://dx.doi.org/10.1097/YIC.0000000000000265DOI Listing
July 2019

The clinical spectrum of -related myopathy.

Neurology 2018 10 26;91(17):e1629-e1641. Epub 2018 Sep 26.

From the Neuromuscular Center (C.S., C.B., L.B., B.P., F.G., S.V., B.F.G., G.S., E.P.), Department of Neurosciences, and Departments of Cardiac, Thoracic and Vascular Sciences (M.P., C.C.), Biomedical Sciences (G.M., S.C.E.T.), and Medicine (R.S.), Section of Radiology, University of Padova, Italy; Dubowitz Neuromuscular Centre (Developmental Neuroscience Programme) (F.C.), UCL Great Ormond Street Institute of Child Health, University College London, UK; Neuromuscular and Rare Disease Unit (I.C., M.M.), Department of Neuroscience, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan; Department of Biomedical and Neuromotor Sciences (G.C., V.P.), University of Bologna; and CNR Institute of Neuroscience (S.C.E.T.), Padova, Italy.

Objective: To identify and characterize patients with calsequestrin 1 ()-related myopathy.

Methods: Patients selected according to histopathologic features underwent genetic screening. mutated patients were clinically evaluated and underwent muscle MRI. Vacuole morphology and vacuolated fiber type were characterized.

Results: Twenty-two -mutated patients (12 families) were identified, 21 sharing the previously described founder mutation (p.Asp244Gly) and 1 with the p.Gly103Asp mutation. Patients usually presented in the sixth decade with exercise intolerance and myalgias and later developed mild to moderate, slowly progressive proximal weakness with quadriceps atrophy and scapular winging. Muscle MRI (n = 11) showed a recurrent fibrofatty substitution pattern. Three patients presented subclinical cardiac abnormalities. Muscle histopathology in patients with p.Asp244Gly showed vacuoles in type II fibers appearing empty in hematoxylin-eosin, Gomori, and nicotinamide adenine dinucleotide (NADH) tetrazolium reductase stains but strongly positive for sarcoplasmic reticulum proteins. The muscle histopathology of p.Gly103Asp mutation was different, showing also NADH-positive accumulation consistent with tubular aggregates.

Conclusions: We report the clinical and molecular details of the largest cohort of -mutated patients. A possible heart involvement is presented, further expanding the phenotype of the disease. One mutation is common due to a founder effect, but other mutations are possible. Because of a paucity of symptoms, it is likely that mutations may remain undiagnosed if a muscle biopsy is not performed.
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http://dx.doi.org/10.1212/WNL.0000000000006387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205688PMC
October 2018

How to improve clinical practice on forced medication in psychiatric practice: Suggestions from the EUNOMIA European multicentre study.

Eur Psychiatry 2018 10 15;54:35-40. Epub 2018 Aug 15.

Department of Psychiatry, University of Campania "L. Vanvitelli", Naples, Italy. Electronic address:

Background: The decision to adopt forced medication in psychiatric care is particularly relevant from a clinical and ethical viewpoint. The European Commission has funded the EUNOMIA study in order to develop European recommendations for good clinical practice on coercive measures, including forced medication.

Methods: The recommendations on forced medication have been developed in 11 countries with the involvement of national clinical leaders, key-professionals and stakeholders' representatives. The national recommendations have been subsequently summarized into a European shared document.

Results: Several cross-national differences exist in the use of forced medication. These differences are mainly due to legal and policy making aspects, rather than to clinical situations. In fact, countries agreed that forced medication can be allowed only if the following criteria are present: 1) a therapeutic intervention is urgently needed; 2) the voluntary intake of medications is consistently rejected; 3) the patient is not aware of his/her condition. Patients' dignity, privacy and safety shall be preserved at all times.

Conclusion: The results of our study show the need of developing guidelines on the use of forced medication in psychiatric practice, that should be considered as the last resort and only when other therapeutic option have failed.
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http://dx.doi.org/10.1016/j.eurpsy.2018.07.002DOI Listing
October 2018

Downregulation of miRNA-29, -23 and -21 in urine of Duchenne muscular dystrophy patients.

Epigenomics 2018 07 22;10(7):875-889. Epub 2018 Mar 22.

The Dubowitz Neuromuscular Centre, Molecular Neurosciences Section, Developmental Neurosciences Programme, UCL Great Ormond Street Institute of Child Health, 30 Guildford Street, London WC1N 1EH, UK.

Aim: To study the signature of 87 urinary miRNAs in Duchenne muscular dystrophy (DMD) patients, select the most dysregulated and determine statistically significant differences in their expression between controls, ambulant (A) and nonambulant (NA) DMD patients, and patients on different corticosteroid regimens. Patients/materials & methods: Urine was collected from control (n = 20), A (n = 31) and NA (n = 23) DMD patients. miRNA expression was measured by reverse transcription-quantitative PCR.

Results: miR-29c-3p was significantly downregulated in A DMD patients while miR-23b-3p and miR-21-5p were significantly downregulated in NA DMD patients compared with age-matched controls.

Conclusion: miR-29c-3p, miR-23b-3p and miR-21-5p are promising novel noninvasive biomarkers for DMD, and miR-29c-3p levels are differentially affected by different steroid regimens, supporting the antifibrotic effect of steroid therapy.
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http://dx.doi.org/10.2217/epi-2018-0022DOI Listing
July 2018

Clozapine versus other antipsychotics during the first 18 weeks of treatment: A retrospective study on risk factor increase of blood dyscrasias.

Psychiatry Res 2017 10 20;256:275-282. Epub 2017 Jun 20.

Department of Psychiatry, University of Naples-SUN, Naples, Italy.

Blood dyscrasias excluding agranulocytosis received limited attention in antipsychotic-treated patients during the first 18 weeks of therapy, although severe clinical conditions have been reported in a few cases. We extracted data records of 285 Caucasian patients after 18 weeks of antipsychotic treatments to investigate risk factors of blood dyscrasias. We observed a higher risk to develop both transient and persistent anemia, neutrophilia and eosinophilia in clozapine-treated patients, whereas in those treated with other atypical antipsychotics when compared to a reference group under typical antipsychotics, emerged an increased risk for transient neutrophilia and eosinophilia. Male patients revealed a higher risk of persistent eosinophilia, neutrophilia, and leukocytosis. Concomitant treatments with mood stabilizers or benzodiazepines proved to be risk factors for transient anemia, antidepressants for transient eosinophilia. Severe complications emerged in 3 cases of agranulocytosis. Cross-tabulation analysis showed a higher probability of a poor response in clozapine-treated patients with persistent anemia and a positive with persistent neutrophilia and eosinophilia. Our data evidenced that emerging blood dyscrasias were not associated with critical adverse effects, and only agranulocytosis required a treatment interruption. Other atypical antipsychotics might represent a viable alternative to potentially harmful clozapine and typical antipsychotics at the onset of life-threatening haematological alterations.
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http://dx.doi.org/10.1016/j.psychres.2017.06.068DOI Listing
October 2017

Brain Natriuretic Peptide as a Biomarker of Asymptomatic Clozapine-Related Heart Dysfunction: A Criterion for a More Cautious Administration.

Clin Schizophr Relat Psychoses Winter 2019;12(4):185-188. Epub 2016 Dec 20.

Clozapine-related pericarditis is a rare side effect of the drug. We reported the clinical cases of two women, aged 22 and 28 years, affected by schizophrenia with pericarditis symptoms related to clozapine treatment of 200 mg/day. Clozapine was discontinued in both patients, resulting in normalization of the ECG changes, and echocardiography confirmed the progressive disappearance of the pericardial effusion. Interestingly, while inflammatory indices and pro-brain natriuretic peptide (pro-BNP) plasma levels were high in both patients, only one of them showed tachycardia, subjective chest pain, shortness of breath and dyspnea, with a clinical symptomatology suggesting a cardiac involvement. BNP is a vasoactive peptide synthetized by the ventricular myocardium which splits in two fragments: BNP and the N-terminal (pro-BNP). Both are considered valuable biomarkers in clinical practice for the prediction of disease state and prognosis in patients with suspected heart failure. Pro-BNP acts as a key regulator in the homeostasis of water and salt excretion and in the maintenance of blood pressure, mainly by inhibiting the renin-angiotensin-aldosterone axis and blocking the sympathetic nervous activity. In our cases, pro-BNP plasma levels proved to be a profitable way to identify subjects with asymptomatic cardiac impairment who could benefit from a therapy preventing progression to heart failure.
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http://dx.doi.org/10.3371/CSRP.PRMO.112316DOI Listing
April 2019

How do relatives cope with eating disorders? Results from an Italian multicentre study.

Int J Eat Disord 2017 05 29;50(5):587-592. Epub 2016 Sep 29.

Department of Psychiatry, University of Naples SUN, Naples, Italy.

Objective: This paper aims to: (1) describe coping strategies in relatives of patients with eating disorders (EDs); (2) analyze coping strategies according to the different EDs; (3) identify correlations between patients' clinical characteristics, relatives' socio-demographic characteristics and coping strategies.

Methods: Patients and their relatives consecutively attending three outpatient units for EDs at the Universities of Naples SUN, Salerno and Catanzaro were recruited. Coping strategies were assessed through the Family Coping Questionnaire for Eating Disorders (FCQ-ED). It consists of 32 items, grouped into two factors: problem-oriented ("seek for information", "positive communication") and emotion-focused ("avoidance," "collusion," "coercion") strategies, plus one item on seeking for spiritual help.

Results: Seventy-two patients and 127 relatives were recruited. The most frequently reported coping strategies by relatives were seeking for information, positive communication, seeking for spiritual help; the first two coping strategies were positively correlated with the level of education of both patients and relatives. Mothers reported avoidance less frequently than other relatives. Relatives of patients with BN reported collusion and coercion more frequently compared to relatives of patients with AN.

Discussion: This report represents an initial attempt to understand the complex relationship among clinical, social and personal variables involved in the development of coping strategies. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:587-592).
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http://dx.doi.org/10.1002/eat.22632DOI Listing
May 2017

Altered Levels of MicroRNA-9, -206, and -132 in Spinal Muscular Atrophy and Their Response to Antisense Oligonucleotide Therapy.

Mol Ther Nucleic Acids 2016 Jul 5;5(7):e331. Epub 2016 Jul 5.

Dubowitz Neuromuscular Centre and Developmental Neuroscience Programme, Institute of Child Health, University College London, London, UK.

The identification of noninvasive biomarkers to monitor the disease progression in spinal muscular atrophy (SMA) is becoming increasingly important. MicroRNAs (miRNAs) regulate gene expression and are implicated in the pathogenesis of neuromuscular diseases, including motor neuron degeneration. In this study, we selectively characterized the expression of miR-9, miR-206, and miR-132 in spinal cord, skeletal muscle, and serum from SMA transgenic mice, and in serum from SMA patients. A systematic analysis of miRNA expression was conducted in SMA mice with different disease severities (severe type I-like and mild type III-like) at different disease stages (pre-, mid-, and late-symptomatic stages), and in morpholino antisense oligonucleotide-treated mice. There was differential expression of all three miRNAs in spinal cord, skeletal muscle and serum samples in SMA mice. Serum miRNAs were altered prior to the changes in spinal cord and skeletal muscle at the presymptomatic stage. The altered miR-132 levels in spinal cord, muscle, and serum transiently reversed to normal level after a single-dose morpholino antisense oligomer PMO25 treatment in SMA mice. We also confirmed a significant alteration of miR-9 and miR-132 level in serum samples from SMA patients. Our study indicates the potential of developing miRNAs as noninvasive biomarkers in SMA.
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http://dx.doi.org/10.1038/mtna.2016.47DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5014531PMC
July 2016

[Critical evaluation of current diagnostic classification systems in psychiatry: the case of DSM-5].

Riv Psichiatr 2016 May-Jun;51(3):116-21

Dipartimento di Psichiatria, Università di Napoli SUN.

Since its first edition, the Diagnostic and Statistical manual of Mental disorders (DSM) has had a great impact on the scientific community and the public opinion as well. In 2013, the American Psychiatric Association released the fifth edition of the manual and - as for the previous versions - several criticisms raised. In particular, the persistence of the categorical approach to mental disorders represents one of the main debated topics, as well as the introduction of new diagnostic syndromes, which are not based on an adequate evidences. Moreover, the threshold of diagnostic criteria for many mental disorders has been lowered, with the consequence that the boundaries between "normality" and "pathology" is not so clear. In this paper, we will: 1) report the historical development of the DSM from the publication of its first edition; 2) describe the main changes introduced in the DSM-5; 3) discuss critical elements in the DSM-5. The current debate regarding the validity of diagnostic manuals and its criteria is threatening the psychiatric discipline, but a possible solution should be represented by the integration of diagnostic criteria with the in-depth description of patient's psychopathological experiences.
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http://dx.doi.org/10.1708/2304.24798DOI Listing
September 2017

[Drug safety warnings in psychiatry: adverse drug reactions' signaling from 2002 to 2014].

Riv Psichiatr 2016 May-Jun;51(3):96-103

Dipartimento di Salute Mentale e Fisica e Medicina Preventiva, Università di Napoli SUN.

Objective: Monitoring drug-related side effects in psychiatric patients is highly recommended. In fact, frequent exposure to long-term polipharmacotherapy, poor compliance to pharmachological treatment and comorbidity with organic illnesses requiring the prescription of other drugs are causes of pharmacokinetic/pharmacodynamic interactions. These vulnerability factors result in a certain increase in adverse drug reactions (ADRs).

Methods: This study performes an analysis of Italian Medicine Agency data, in the section "signal analysis", to attempt an assessment of the safety warnings among the different psychotropic drug classes, belonging to the ATC class: N03 (antiepileptics), N05 (antipsychotics), N06 (psycho-analectic drugs). Then we analysed, in a descriptive way, the different association between the drug and the related ADR, evaluating the different safety profiles, in relation to experimental studies, supporting the importance of the signal.

Results: In the last years, among the new 25 ADRs, 10 were related to antidepressant drugs (8 SSRI, 1 mirtazapine, 1 agomelatine). In relation to antipsychotic drugs, 6 new correlations were found between drug and ADR onset, mainly among atypical antispychotics. Other correlations (6 above all) were found among antiepileptic drugs. Among benzodiazepines, a signal linked to rabdomylysis onset was found. It is also recommended an evaluation of safety profile in relation to zolpidem prescription.

Discussion: The results of our systematic review are a motivational input, considering the continuous increase of safety warnings, to attentively monitor drug's prescription. Spontaneous ADRs' signaling is a classical system to provide the required attention in relation to a potential risk. The clinician in charge must report this because he is the key figure in the drugs' safety process.

Conclusions: In psychiatry, in which a long-term pharmachological therapy is frequent, clinicians are requested to find and signal ADRs to the competent authority.
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http://dx.doi.org/10.1708/2304.24792DOI Listing
September 2017

Histopathological Defects in Intestine in Severe Spinal Muscular Atrophy Mice Are Improved by Systemic Antisense Oligonucleotide Treatment.

PLoS One 2016 10;11(5):e0155032. Epub 2016 May 10.

Dubowitz Neuromuscular Centre, Institute of Child Health, University College London, London, United Kingdom.

Gastrointestinal (GI) defects, including gastroesophageal reflux, constipation and delayed gastric emptying, are common in patients with spinal muscular atrophy (SMA). Similar GI dysmotility has been identified in mouse models with survival of motor neuron (SMN) protein deficiency. We previously described vascular defects in skeletal muscle and spinal cord of SMA mice and we hypothesized that similar defects could be involved in the GI pathology observed in these mice. We therefore investigated the gross anatomical structure, enteric vasculature and neurons in the small intestine in a severe mouse model of SMA. We also assessed the therapeutic response of GI histopathology to systemic administration of morpholino antisense oligonucleotide (AON) designed to increase SMN protein expression. Significant anatomical and histopathological abnormalities, with striking reduction of vascular density, overabundance of enteric neurons and increased macrophage infiltration, were detected in the small intestine in SMA mice. After systemic AON treatment in neonatal mice, all the abnormalities observed were significantly restored to near-normal levels. We conclude that the observed GI histopathological phenotypes and functional defects observed in these SMA mice are strongly linked to SMN deficiency which can be rescued by systemic administration of AON. This study on the histopathological changes in the gastrointestinal system in severe SMA mice provides further indication of the complex role that SMN plays in multiple tissues and suggests that at least in SMA mice restoration of SMN production in peripheral tissues is essential for optimal outcome.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0155032PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862622PMC
July 2017

Social contacts and loneliness in people with psychotic and mood disorders.

Compr Psychiatry 2016 Apr 7;66:59-66. Epub 2016 Jan 7.

Unit for Social and Community Psychiatry, (WHO Centre for Mental Health Service Development), Queen Mary University of London. Newham Centre for Mental Health, London, E13 8SP, United Kingdom. Electronic address:

Background: Social relations can be measured through: a) objective indicators, i.e. the number of social contacts in a given time interval or b) subjective indicators, i.e. feelings of loneliness. Comparing subjective and objective indicators in patients with psychotic and mood disorders may help to understand whether diagnosis-specific interventions should be designed for increasing their social relations. In this study we assessed social contacts outside home, work environments and mental health services, which may be increased by these interventions. We also explored feelings of loneliness which could influence readiness of patients to participate in interventions.

Methods: 100 patients in outpatient mental health care were asked to: a) list their social contacts; b) report their feelings of loneliness on a validated five point Likert scale. Multiple logistic regression models were used to test associations of diagnostic categories with: a) having more than one social contact in the previous week; b) reporting at least moderate feelings of loneliness.

Results: Patients had on average 1.7 (SD=1.7) social contacts in the previous week (median=1.0); 77 patients reported at least moderate feelings of loneliness. Patients with psychotic disorders (n=30) showed a statistical trend towards having just one or no contacts in the week before the assessment (Odds ratio, OR=2.246, p=.087). Patients with mood disorders were more likely to report at least moderate feelings of loneliness (OR=2.798; p<.05).

Conclusions: Patients with psychotic disorders, compared to those with mood disorders, may be less likely to report feeling lonely although they tend to have less social contacts. Strategies to enhance social relations of people with psychotic disorders may include approaches to increase patients' drive to establish new social contacts and to emotionally support them in this process.
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http://dx.doi.org/10.1016/j.comppsych.2015.12.008DOI Listing
April 2016

Olanzapine Is Faster than Haloperidol in Inducing Metabolic Abnormalities in Schizophrenic and Bipolar Patients.

Neuropsychobiology 2015 ;72(1):29-36

The effects of olanzapine and haloperidol on metabolic parameters in bipolar patients have been evaluated much less comprehensively than in schizophrenic patients. Therefore, in this study, medical records of 343 schizophrenic and bipolar patients treated with haloperidol or olanzapine for 1 year were retrospectively reviewed and metabolic outcomes were evaluated. After 12 months of follow-up, 25.9% of patients showed ≥3 metabolic abnormalities with a point prevalence of 27.2% in the bipolar and 24.9% in the schizophrenic group: 22.0% of the schizophrenic patients treated with haloperidol and 29.8% of those treated with olanzapine achieved ≥3 metabolic alterations; in bipolar patients, these percentages were 15.8% of those treated with haloperidol and 37.8% of those treated with olanzapine (p < 0.0001). Significant changes were reported over time in fasting glucose, triglycerides and cholesterol blood levels, systolic and diastolic blood pressure, body weight, and BMI. Overall, a significant number of schizophrenic and bipolar patients treated with olanzapine showed ≥3 metabolic alterations in the first month of treatment when compared to those treated with haloperidol. Moreover, the number of olanzapine-treated patients developing metabolic changes in the first month was significantly higher in both diagnostic groups when compared to those who reached metabolic abnormal values in the subsequent 11 months. These data suggest that both antipsychotics could increase the metabolic risk in schizophrenic and bipolar patients with a higher prevalence in olanzapine-treated patients. On the other hand, olanzapine-treated patients seem to achieve metabolic abnormalities faster than haloperidol-treated subjects in both diagnostic groups.
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http://dx.doi.org/10.1159/000437430DOI Listing
July 2016

[Shall psychiatry change its target? Reflections on the evolving role of psychiatry].

Riv Psichiatr 2015 Jan-Feb;50(1):3-7

In this paper we will describe cultural, social and scientific changes occurred in psychiatry in the last years, identifying the new target for mental health professionals. Groups of young psychiatrists from the Italian Psychiatric Association, the European Psychiatric Association and the World Psychiatric Association have established an international network that launched a debate on the future role of psychiatry. In a rapidly changing world, there is the need to: 1) adapt training in psychiatry to the modern world; 2) identify the new target of mental health professionals; 3) enhance the image of psychiatry in the society; 4) overcome stigma towards people with mental disorders. In recent years, socio-cultural and scientific changes have had a significant impact on the psychiatrists' clinical practice. Mental health professionals should deal with these changes appropriately in order to overcome the current "crisis" of psychiatry, which should be considered as a developmental phase rather than a conceptual one. From time to time psychiatry is criticized both from inside and outside the profession. The current crisis was unavoidable due to the recent socio-cultural changes, but it should be considered an opportunity to adapt the profession to modern times.
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http://dx.doi.org/10.1708/1794.19524DOI Listing
December 2016

The role of relatives in pathways to care of patients with a first episode of psychosis.

Int J Soc Psychiatry 2015 Nov 21;61(7):631-7. Epub 2015 Jan 21.

Department of Psychiatry, University of Naples SUN, Naples, Italy.

Aims: To explore the role of relatives in pathways to care of patients with a recent onset of psychosis.

Methods: A total of 34 consecutive patients and their relatives from the Department of Psychiatry of the University of Naples SUN participated in the study. Pathways to care were retrospectively evaluated by administering the Pathways to Care Form and the Nottingham Onset Schedule (NOS) to patients, relatives and treating physicians. Relatives were addressed with the Family Involvement in Pathways to care Schedule (FIPS).

Results: Duration of untreated illness (DUI) and duration of untreated psychosis (DUP) were 145.4 (±141.9) and 33.3 (±54.0) weeks, respectively. Help-seeking delay was 17.6 (±45.0) weeks. The first request for help was made by relatives in 76% of cases. Among health professionals, general practitioners were those most frequently contacted, followed by psychiatrists, neurologists or psychologists. Stigma and wrong attribution of psychotic symptoms were the main reasons for help-seeking delays.

Conclusions: Relatives play a crucial role in pathways to care of patients with psychosis. DUI and DUP could be reduced by interventions aimed at increasing knowledge of early symptoms in the general population, and by the provision of psychiatric consultations in non-stigmatizing settings for young people with psychological distress.
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http://dx.doi.org/10.1177/0020764014568129DOI Listing
November 2015

Use of coercive measures in mental health practice and its impact on outcome: a critical review.

Expert Rev Neurother 2014 Feb 2;14(2):131-41. Epub 2014 Jan 2.

Department of Psychiatry, University of Naples SUN, Naples, Italy.

Although coercive measures have always been part of the psychiatric armamentarium, the ethical dilemma between the use of a "therapeutic" coercion and the loss of patients' dignity is one of the major controversial issues in mental health research and practice. The aims of the present review are to explore the existing literature on predictors of use of coercive measures and to explore the relationship between coercive measures and patient outcome. A literature search was conducted using MEDLINE, PsychyINFO, Scopus, Web of Knowledge and the Cochrane Database. In all selected papers, references were cross-checked to identify other possible eligible papers. The use of coercive measures was predicted by patients' clinical and socio-demographic features, staff characteristics and ward-related factors. Coercive measures have only a limited impact on patients' clinical and social outcome. At the current level of knowledge, coercion is still a controversial issue in mental health practice. Only few studies with a solid methodology have been carried out. Large multicenter and rigorous studies, with long-term follow-ups, are highly needed.
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http://dx.doi.org/10.1586/14737175.2014.874286DOI Listing
February 2014
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