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Depression: HELP
Articles by Michele Fornaro
Based on 55 articles published since 2010
(Why 55 articles?)
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Between 2010 and 2020, M. Fornaro wrote the following 55 articles about Depression.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Editorial Inflammatory markers and suicidal attempts in depressed patients: A review. 2016

Marini, Stefano / Vellante, Federica / Matarazzo, Ilaria / De Berardis, Domenico / Serroni, Nicola / Gianfelice, Daniela / Olivieri, Luigi / Di Renzo, Fulvia / Di Marco, Anna / Fornaro, Michele / Orsolini, Laura / Valchera, Alessandro / Iasevoli, Felice / Mazza, Monica / Perna, Giampaolo / Martinotti, Giovanni / Di Giannantonio, Massimo. ·Department of Neurosciences and Imaging, Chair of Psychiatry, University "G. D'Annunzio", Chieti, Italy sfnmarini@gmail.com. · Department of Neurosciences and Imaging, Chair of Psychiatry, University "G. D'Annunzio", Chieti, Italy. · NHS, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital "G. Mazzini", ASL 4 Teramo, Italy. · Department of "Scienze della Formazione", University of Catania, Italy. · United Hospitals, Academic Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Ancona, Italy. · School of Life and Medical Sciences, University of Hertfordshire, Hatfield, Herts, UK. · Villa S. Giuseppe Hospital, Hermanas Hospitalarias, Ascoli Piceno, Italy. · Laboratory of Molecular Psychiatry and Psychopharmacotherapeutics, Section of Psychiatry, Department of Neuroscience, University School of Medicine "Federico II", Naples, Italy. · Department of Health Science, University of L'Aquila, L'Aquila, Italy. · Hermanas Hospitalarias, Department of Clinical Neurosciences, Villa San Benedetto Menni, Albese con Cassano, Como, Italy. · Department of Psychiatry and Behavioral Sciences, Leonard Miller School of Medicine, University of Miami, Florida, USA. · Department of Psychiatry and Neuropsychology, University of Maastricht, The Netherlands. ·Int J Immunopathol Pharmacol · Pubmed #26729403.

ABSTRACT: Major depressive disorder is a chronic and invalidating psychiatric illness and is associated with a greater risk of suicidal behaviors. In recent decades many data have supported a biological link between depressive states and inflammation. Pro-inflammatory cytokines have been found to rise, first of all TNF-α and IL-6. Suicidal behaviors have been consistently associated with increased levels of IL-6 and decreased levels of IL-2. The aim of this review is to investigate the relationship between inflammatory markers in depressed patients with or without suicidal attempts compared to healthy controls.

2 Review Brexpiprazole for treatment-resistant major depressive disorder. 2019

Fornaro, Michele / Fusco, Andrea / Anastasia, Annalisa / Cattaneo, Carlo Ignazio / De Berardis, Domenico. ·Neuroscience, Reproductive Science and Dentistry, Federico II University of Naples , Naples , Italy. · Department of Psychiatry, Villa Camaldoli Alma Mater SpA , Naples , Italy. · Department of Mental Health, ASL NOVARA , Borgomanero , Italy. · National Health Care System, Mazzini Hospital , Teramo , Italy. ·Expert Opin Pharmacother · Pubmed #31431092.

ABSTRACT:

3 Review Novel Pathways in the Treatment of Major Depression: Focus on the Glutamatergic System. 2019

Tomasetti, Carmine / Montemitro, Chiara / Fiengo, Annastasia L C / Santone, Cristina / Orsolini, Laura / Valchera, Alessandro / Carano, Alessandro / Pompili, Maurizio / Serafini, Gianluca / Perna, Giampaolo / Vellante, Federica / Martinotti, Giovanni / Giannantonio, Massimo D / Kim, Yong-Ku / Nicola, Marco D / Bellomo, Antonello / Ventriglio, Antonio / Fornaro, Michele / Berardis, Domenico D. ·NHS, Department of Mental Health ASL Teramo, Psychiatric Service of Diagnosis and Treatment, Hospital "Maria SS dello Splendore", Giulianova, Italy. · Polyedra Research Group, Teramo, Italy. · Department of Psychiatry, University Medical School "Federico II", Naples, Italy. · Department of Neuroscience, Imaging and Clinical Science, University "G. D'Annunzio", Chieti, Italy. · NHS, Department of Mental Health ASUR Marche AV5, Mental Health Unit, Ascoli Piceno, Italy. · School of Life and Medical Sciences, University of Hertfordshire, Hatfield, Herts, United Kingdom. · Villa S. Giuseppe Hospital, Hermanas Hospitalarias, Ascoli Piceno, Italy. · Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital "Madonna Del Soccorso," NHS, San Benedetto del Tronto, Ascoli Piceno, Italy. · Department of Neurosciences, Mental Health and Sensory Organs, Suicide Prevention Center, S. Andrea Hospital, Sapienza University, Rome, Italy. · Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. · Department of Clinical Neurosciences, Hermanas Hospitalarias, Villa San Benedetto Menni Hospital, FoRiPsi, Albese con Cassano, Como, Italy. · Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands. · Department of Psychiatry and Behavioral Sciences, Leonard Miller School of Medicine, Miami University, Miami, United States. · Department of Psychiatry, Korea University College of Medicine, Seoul, Korea. · Institute of Psychiatry and Psychology, Catholic University of Sacred Heart, Rome, Italy. · Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy. · NHS, Department of Mental Health ASL Teramo, Psychiatric Service of Diagnosis and Treatment, Hospital "G. Mazzini", Teramo, Italy. ·Curr Pharm Des · Pubmed #30864501.

ABSTRACT: Depressive disorders represent protean psychiatric illnesses with heterogeneous clinical manifestations and a multitude of comorbidities leading to severe disability. In spite of decades of research on the pathophysiogenesis of these disorders, the wide variety of pharmacotherapies currently used to treat them is based on the modulation of monoamines, whose alteration has been considered the neurobiological foundation of depression, and consequently of its treatment. However, approximately one third to a half of patients respond partially or become refractory to monoamine-based therapies, thereby jeopardizing the therapeutic effectiveness in the real world of clinical practice. Recent scientific evidence has been pointing out the essential role of other biological systems beyond monoamines in the pathophysiology of depressive disorders, in particular, the glutamatergic neurotransmission. In the present review, we will discuss the most advanced knowledge on the involvement of glutamatergic system in the molecular mechanisms at the basis of depression pathophysiology, as well as the glutamate-based therapeutic strategies currently suggested to optimize depression treatment (e.g., ketamine). Finally, we will mention further "neurobiological targeted" approaches, based on glutamate system, with the purpose of promoting new avenues of investigation aiming at developing interventions that overstep the monoaminergic boundaries to improve depressive disorders therapy.

4 Review The emergence of loss of efficacy during antidepressant drug treatment for major depressive disorder: An integrative review of evidence, mechanisms, and clinical implications. 2019

Fornaro, Michele / Anastasia, Annalisa / Novello, Stefano / Fusco, Andrea / Pariano, Riccardo / De Berardis, Domenico / Solmi, Marco / Veronese, Nicola / Stubbs, Brendon / Vieta, Eduard / Berk, Michael / de Bartolomeis, Andrea / Carvalho, André F. ·Neuroscience, Reproductive Science and Odontostomatology Unit, Section of Psychiatry School of Medicine Federico II, Naples, Italy. Electronic address: Dott.Fornaro@gmail.com. · Casa di Cura Alma Mater S.p.A. "Villa Camaldoli", Naples, Italy. Electronic address: Anastasia.Annalisa@gmail.com. · Neuroscience, Reproductive Science and Odontostomatology Unit, Section of Psychiatry School of Medicine Federico II, Naples, Italy. Electronic address: stefano.novello1@gmail.com. · Neuroscience, Reproductive Science and Odontostomatology Unit, Section of Psychiatry School of Medicine Federico II, Naples, Italy. Electronic address: andreafusco1990@gmail.com. · Neuroscience, Reproductive Science and Odontostomatology Unit, Section of Psychiatry School of Medicine Federico II, Naples, Italy. Electronic address: riccardopariano123@gmail.com. · National Health Service, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital "G. Mazzini", Teramo, Italy. Electronic address: dodebera@aliceposta.it. · University of Padua, Neuroscience Department, Psychiatry Unit, Padua, Italy; Padova Neuroscience Center, University of Padua, Italy. Electronic address: marco.solmi83@gmail.com. · National Research Council, Ageing Branch, Padua, Italy. Electronic address: ilmannato@gmail.com. · Physiotherapy Department, South London and Maudsley NHS Foundation Trust, London, SE5 8AZ, UK; Health Service and Population Research Department and the Department of Psychological Medicine, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK. Electronic address: brendon.stubbs@kcl.ac.uk. · Psychiatry and Psychology Department of the Hospital Clinic, Institute of Neuroscience, University of Barcelona, IDIBAPS, CIBERSAM, 170 Villarroel St, 08036, Barcelona, Catalonia, Spain. Electronic address: EVIETA@clinic.cat. · Deakin University, IMPACT Strategic Research Centre, School of Medicine, Barwon Health, Geelong, VIC, Australia; Centre for Youth Mental Health, Orygen, The National Centre of Excellence in Youth Mental Health, Melbourne, VIC, Australia; Department of Psychiatry, The University of Melbourne, Melbourne, VIC, Australia; The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, Australia. Electronic address: mikebe@barwonhealth.org.au. · Neuroscience, Reproductive Science and Odontostomatology Unit, Section of Psychiatry School of Medicine Federico II, Naples, Italy. Electronic address: adebarto@unina.it. · Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Centre for Addiction & Mental Health (CAMH), Toronto, ON, Canada. Electronic address: andre.carvalho@camh.ca. ·Pharmacol Res · Pubmed #30385364.

ABSTRACT: The re-emergence (i.e. 'breakthrough') of depressive symptoms despite maintenance treatment of depression with antidepressant drugs is a complex clinical phenomenon referred to as tolerance. Herein we critically appraise evidence from both pre-clinical and clinical studies, focusing on putative mechanisms as well as clinical correlates and implications of the emergence tolerance during antidepressant treatment for major depressive disorder (MDD). It is firstly unclear to what extent this phenotype reflects a pharmacological effect of an antidepressant, is driven by non-adherence, is a marker of latent bipolarity or another comorbidity, a marker of neuroprogression of the underlying disorder or the intrusion of the impact of psychosocial variables into the clinical course. The operational definitions of tolerance and its related phenomena have also been largely inconsistent. Several protective clinical indicators have been proposed, including a rapid-cycling course and comorbid chronic anxiety, whilst poor treatment adherence, proneness to emotional blunting and sub-threshold bipolarity have been identified as possible correlates of tolerance to antidepressant treatment in MDD. Putative neurobiological underpinnings include adaptations in the hypothalamic-pituitary-adrenal (HPA) axis and the serotonergic system. Due to the clinical and diagnostic challenges imposed by the emergence of tolerance to antidepressants, there is an urgent need for upcoming international guidelines to reach a consensus on operational definitions for this complex clinical phenomenon, thus enabling a more precise appreciation of the incidence and correlates of tolerance to antidepressants. Taken together, the present review underscores the need to cautiously weight benefits and risks prior to considering long-term antidepressant treatment for patients with MDD as tolerance may emerge in a subset of patients.

5 Review Differentiating between bipolar and unipolar depression in functional and structural MRI studies. 2019

Han, Kyu-Man / De Berardis, Domenico / Fornaro, Michele / Kim, Yong-Ku. ·Department of Psychiatry, Korea University College of Medicine, Seoul, Republic of Korea. · Department of Mental Health Psychiatric Service, Diagnosis and Treatment Hospital "G. Mazzini," ASL 4, NHS, Teramo, Italy. · Head and Neck Department, Section of Psychiatry, University School of Medicine "Federico II", Naples, Italy. · Department of Psychiatry, Korea University College of Medicine, Seoul, Republic of Korea. Electronic address: yongku@korea.ac.kr. ·Prog Neuropsychopharmacol Biol Psychiatry · Pubmed #29601896.

ABSTRACT: Distinguishing depression in bipolar disorder (BD) from unipolar depression (UD) solely based on clinical clues is difficult, which has led to the exploration of promising neural markers in neuroimaging measures for discriminating between BD depression and UD. In this article, we review structural and functional magnetic resonance imaging (MRI) studies that directly compare UD and BD depression based on neuroimaging modalities including functional MRI studies on regional brain activation or functional connectivity, structural MRI on gray or white matter morphology, and pattern classification analyses using a machine learning approach. Numerous studies have reported distinct functional and structural alterations in emotion- or reward-processing neural circuits between BD depression and UD. Different activation patterns in neural networks including the amygdala, anterior cingulate cortex (ACC), prefrontal cortex (PFC), and striatum during emotion-, reward-, or cognition-related tasks have been reported between BD and UD. A stronger functional connectivity pattern in BD was pronounced in default mode and in frontoparietal networks and brain regions including the PFC, ACC, parietal and temporal regions, and thalamus compared to UD. Gray matter volume differences in the ACC, hippocampus, amygdala, and dorsolateral prefrontal cortex (DLPFC) have been reported between BD and UD, along with a thinner DLPFC in BD compared to UD. BD showed reduced integrity in the anterior part of the corpus callosum and posterior cingulum compared to UD. Several studies performed pattern classification analysis using structural and functional MRI data to distinguish between UD and BD depression using a supervised machine learning approach, which yielded a moderate level of accuracy in classification.

6 Review Eradicating Suicide at Its Roots: Preclinical Bases and Clinical Evidence of the Efficacy of Ketamine in the Treatment of Suicidal Behaviors. 2018

De Berardis, Domenico / Fornaro, Michele / Valchera, Alessandro / Cavuto, Marilde / Perna, Giampaolo / Di Nicola, Marco / Serafini, Gianluca / Carano, Alessandro / Pompili, Maurizio / Vellante, Federica / Orsolini, Laura / Fiengo, Annastasia / Ventriglio, Antonio / Yong-Ku, Kim / Martinotti, Giovanni / Di Giannantonio, Massimo / Tomasetti, Carmine. ·National Health Service, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, "G. Mazzini" Hospital, p.zza Italia 1, 64100 Teramo, Italy. domenico.deberardis@aslteramo.it. · Department of Neuroscience, Imaging and Clinical Science, Chair of Psychiatry, University "G. D'Annunzio", 66100 Chieti, Italy. domenico.deberardis@aslteramo.it. · Polyedra Research Group, 64100 Teramo, Italy. dott.fornaro@gmail.com. · Department of Neuroscience, Reproductive Science and Odontostomatology, School of Medicine 'Federico II' Naples, 80121 Naples, Italy. dott.fornaro@gmail.com. · Polyedra Research Group, 64100 Teramo, Italy. a.valchera@ospedaliere.it. · Villa S. Giuseppe Hospital, Hermanas Hospitalarias, 63100 Ascoli Piceno, Italy. a.valchera@ospedaliere.it. · Department of Theory, Analysis and Composition, Music Conservatory "L. Canepa", 07100 Sassari, Italy. marilde_cavuto@virgilio.it. · Hermanas Hospitalarias, FoRiPsi, Department of Clinical Neurosciences, Villa San Benedetto Menni, Albese con Cassano, 22032 Como, Italy. pernagp@gmail.com. · Department of Psychiatry and Neuropsychology, University of Maastricht, 6221 Maastricht, The Netherlands. pernagp@gmail.com. · Department of Psychiatry and Behavioral Sciences, Leonard Miller School of Medicine, University of Miami, Coral Gables, FL 33114, USA. pernagp@gmail.com. · Institute of Psychiatry and Psychology, Catholic University of Sacred Heart, 00118 Rome, Italy. marcodinicola.md@gmail.com. · Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, 16132 Genoa, Italy. gianluca.serafini@uniroma1.it. · NHS, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital "Madonna Del Soccorso", A.S.U.R. 12, 63074 San Benedetto del Tronto, Italy. alessandro.carano@gmail.com. · Department of Neurosciences, Mental Health and Sensory Organs, Suicide Prevention Center, Sant'Andrea Hospital, Sapienza University of Rome, 00118 Rome, Italy. maurizio.pompili@uniroma1.it. · Department of Neuroscience, Imaging and Clinical Science, Chair of Psychiatry, University "G. D'Annunzio", 66100 Chieti, Italy. federica.vellante@gmail.com. · Polyedra Research Group, 64100 Teramo, Italy. laura.orsolini@hotmail.it. · Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences, College Lane Campus, University of Hertfordshire, Hatfield SG141LZ, UK. laura.orsolini@hotmail.it. · Polyedra Research Group, 64100 Teramo, Italy. annastasia.fiengo@gmail.com. · NHS, Department of Mental Health ASUR Marche AV5, Mental Health Unit, 63100 Ascoli Piceno, Italy. annastasia.fiengo@gmail.com. · Department of Clinical and Experimental Medicine, University of Foggia, 71121 Foggia, Italy. a.ventriglio@libero.it. · Department of Psychiatry, Korea University College of Medicine, Seoul 08826, Korea. yongku@korea.edu. · Department of Neuroscience, Imaging and Clinical Science, Chair of Psychiatry, University "G. D'Annunzio", 66100 Chieti, Italy. giovanni.martinotti@gmail.com. · Department of Neuroscience, Imaging and Clinical Science, Chair of Psychiatry, University "G. D'Annunzio", 66100 Chieti, Italy. digiannantonio@unich.it. · Polyedra Research Group, 64100 Teramo, Italy. carmine.tomasetti@aslteramo.it. · Department of Neuroscience, Reproductive Science and Odontostomatology, School of Medicine 'Federico II' Naples, 80121 Naples, Italy. carmine.tomasetti@aslteramo.it. ·Int J Mol Sci · Pubmed #30249029.

ABSTRACT: Despite the continuous advancement in neurosciences as well as in the knowledge of human behaviors pathophysiology, currently suicide represents a puzzling challenge. The World Health Organization (WHO) has established that one million people die by suicide every year, with the impressive daily rate of a suicide every 40 s. The weightiest concern about suicidal behavior is how difficult it is for healthcare professionals to predict. However, recent evidence in genomic studies has pointed out the essential role that genetics could play in influencing person's suicide risk. Combining genomic and clinical risk assessment approaches, some studies have identified a number of biomarkers for suicidal ideation, which are involved in neural connectivity, neural activity, mood, as well as in immune and inflammatory response, such as the mammalian target of rapamycin (mTOR) signaling. This interesting discovery provides the neurobiological bases for the use of drugs that impact these specific signaling pathways in the treatment of suicidality, such as ketamine. Ketamine, an

7 Review Pharmacological management of depression in patients with multiple sclerosis. 2018

Carta, Mauro Giovanni / Paribello, Pasquale / Anastasia, Annalisa / De Berardis, Domenico / Nardi, Antonio Egidio / Fornaro, Michele. ·a Department of Health Sciences and Public Health , University of Cagliari , Cagliari , Italy. · b Villa Camaldoli Alma Mater SpA , Naples , Italy. · c National Health Care System , Mazzini Hospital , Teramo , Italy. · d Medical School - Institute of Psychiatry , Federal University of Rio de Janeiro National Academy of Medicine , Rio de Janeiro , Brazil. · e Neuroscience, Reproductive Science and Odontostolmatology , Federico II University of Naples , Naples , Italy. ·Expert Opin Pharmacother · Pubmed #30207800.

ABSTRACT: INTRODUCTION: The pharmacotherapeutic management of depression in patients with multiple sclerosis (MS) is a matter of debate that cannot be decided from the evidence available in the current literature. Therefore, its management essentially relies on the clinical experience of the prescribing clinician rather than on evidence-based approaches. AREAS COVERED: This review provides a clinically oriented critical perspective on the connection between MS and major depressive disorder (MDD) or depression associated with bipolar disorder (BD), focusing on its optimal pharmacotherapy. Both clinical and pharmacological considerations are accounted in order to promote rational pharmacotherapy, both in terms of efficacy and tolerability. EXPERT OPINION: Despite its clinical burden and relatively frequent occurrence, the interplay of MS and depression still requires further controlled trials to better clarify the appropriate pharmacotherapy across varying 'diseases categories' of MS itself, as well as discriminating between depressive symptoms that do not necessarily reach the threshold of either MDD or BD. Additional insight into new mood-tolerated neurological pharmacotherapy for MS is likewise warranted toward a more effective, immune- and patient-tailored pharmacotherapy, while promoting innovation in drug design, with the ultimate goal of enhancing the overall quality life of the affected individual, his/her caregivers, and to reduce the associated economic and social burden.

8 Review The burden of mood-disorder/cerebrovascular disease comorbidity: essential neurobiology, psychopharmacology, and physical activity interventions. 2017

Fornaro, Michele / Solmi, Marco / Veronese, Nicola / De Berardis, Domenico / Buonaguro, Elisabetta Filomena / Tomasetti, Carmine / Perna, Giampaolo / Preti, Antonio / Carta, Mauro Giovanni. ·a Department of Neuroscience, Reproductive Science and Odontostomatology , School of Medicine 'Federico II' Naples , Naples , Italy. · b Department of Psychiatry , Columbia University Medical Center, New York State Psychiatric Institute , New York , NY , USA. · c Neuroscience Department , University of Padua , Padua , Italy. · d Institute for Clinical Research and Education in Medicine, I.R.E.M , Padua , Italy. · e Department of Medicine (DIMED), Geriatrics Division , University of Padova , Padova , Italy. · f Health Service, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment , Hospital 'G. Mazzini' , Teramo , Italy. · g Department of Psychiatry and Neuropsychology , Maastricht University , Maastricht , Netherlands. · h Department of Clinical Neurosciences, FoRiPsi , Hermanas Hospitalarias-Villa San Benedetto Menni Hospital , Albese con Cassano , Como , Italy. · i Department of Psychiatry and Behavioural Sciences, Leonard Miller School of Medicine , University of Miami , Miami , FL , USA. · j Center of Liaison Psychiatry and Psychosomatics , University Hospital, University of Cagliari , Monserrato , Cagliari , Italy. · k Department of Public Health, Clinical and Molecular Medicine , University of Cagliari , Monserrato , Cagliari , Italy. ·Int Rev Psychiatry · Pubmed #28681620.

ABSTRACT: Cardio-vascular diseases (CVDs) and CVD-related disorders (including cerebrovascular diseases; CBVDs) are a major public health concern as they represent the leading cause of mortality and morbidity in developed countries. Patients with CVDs and CBVDs co-morbid with mood disorders, especially bipolar disorder (BD) and major depressive disorder (MDD), suffer reduced quality-of-life and significant disability adjusted for years of life and mortality. The relationship between CVDs/CBVDs and mood disorders is likely to be bidirectional. Evidence for shared genetic risk of pathways involved in stress reaction, serotonin or dopamine signalling, circadian rhythms, and energy balance was reported in genome-wide association studies. There is some evidence of a neuroprotective effect of various antidepressants, which may be boosted by physical exercise, especially by aerobic ones. Patients with CVDs/CBVDs should be routinely attentively evaluated for the presence of mood disorders, with tools aimed at detecting both symptoms of depression and of hypomania/mania. Behavioural lifestyle interventions targeting nutrition and exercise, coping strategies, and attitudes towards health should be routinely provided to patients with mood disorders, to prevent the risk of CVDs/CBVDs. A narrative review of the evidence is herein provided, focusing on pharmacological and physical therapy interventions.

9 Review Current and Future Perspectives on the Major Depressive Disorder: Focus on the New Multimodal Antidepressant Vortioxetine. 2017

Orsolini, Laura / Tomasetti, Carmine / Valchera, Alessandro / Iasevoli, Felice / Buonaguro, Elisabetta Filomena / Fornaro, Michele / Fiengo, Annastasia L C / Martinotti, Giovanni / Vellante, Federica / Matarazzo, Ilaria / Vecchiotti, Roberta / Perna, Giampaolo / Di Nicola, Marco / Carano, Alessandro / Di Bartolomeis, Andrea / De Giannantonio, Massimo / De Berardis, Domenico. ·National Health Service, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, "G. Mazzini" Hospital, p.zza Italia 1, 64100 Teramo,. Italy. ·CNS Neurol Disord Drug Targets · Pubmed #27781949.

ABSTRACT: BACKGROUND: Vortioxetine (VRX) is a multimodal antidepressant that acts as serotonin (5HT) transporter inhibitor as well as 5HT3A and 5HT7 receptors antagonist, 5HT1A and 5HT1B receptors partial agonist. It was recently approved in the US and the EU for the treatment of adult patients with Major Depressive Disorder (MDD). OBJECTIVE: The present article aims at systematically reviewing findings of the published and unpublished research on the pharmacological properties, efficacy, safety and tolerability of oral VRX in the treatment of MDD. METHOD: A systematic review, in accordance with the Cochrane Collaboration and the PRISMA guidelines, was conducted searching the electronic databases MEDLINE, by combining the following keyterms: ((vortioxetine OR LU AA21004 OR brintellix) AND (antidepressant OR depression OR major depressive disorder), without language/time restrictions. Further studies were retrieved from reference listing of relevant articles or manual search. Preclinical and clinical studies (RCT and open label trials) were here retrieved. RESULTS: Several placebo-controlled and active-treatment studies demonstrated the antidepressant efficacy and tolerability of VRX in adult patients affected with MDD. In addition, VRX seems to own procognitive activity. VRX seems generally well tolerated, without significant cardiovascular or weight gain effects. The most common adverse events reported included nausea, vomiting, hyperhidrosis, headache, dizziness, somnolence, diarrhoea and dry mouth. CONCLUSION: Overall, placebo controlled and active treatment trials support that VRX is effective and well tolerated in MDD. Its combined serotonin reuptake inhibition with agonism, partial agonism and antagonism of a number of receptors might provide a broader spectrum of antidepressant activity than currently available agents.

10 Review The Novel Antipsychotic Cariprazine (RGH-188): State-of-the-Art in the Treatment of Psychiatric Disorders. 2016

De Berardis, Domenico / Orsolini, Laura / Iasevoli, Felice / Prinzivalli, Emiliano / de Bartolomeis, Andrea / Serroni, Nicola / Mazza, Monica / Valchera, Alessandro / Fornaro, Michele / Vecchiotti, Roberta / Carano, Alessandro / Sepede, Gianna / Vellante, Federica / Matarazzo, Ilaria / Pompili, Maurizio / Perna, Giampaolo / Conti, Chiara / Segura-García, Cristina / Martinotti, Giovanni / Di Giannantonio, Massimo. ·National Health Service, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, "G. Mazzini" Hospital, p.zza Italia 1, 64100 Teramo, Italy. dodebera@alice.it. ·Curr Pharm Des · Pubmed #27396597.

ABSTRACT: Cariprazine (RGH-188) is a novel antipsychotic drug that exerts partial agonism of dopamine D2/D3 receptors with preferential binding to D3 receptor, antagonism of 5HT2B receptors and partial agonism of 5HT1A. Currently, cariprazine is in late-stage clinical development (phase III clinical trials) in patients with schizophrenia (S) and in patients with bipolar disorder (BD), as well as an adjunctive treatment in patients with Major Depressive Disorder (MDD) and drug-resistant MDD. Cariprazine has completed phase III trials for the acute treatment of schizophrenia and bipolar mania, phase II trials for the bipolar depression and MDD whilst it is undergoing phase III trials as an adjunct to antidepressants. The present review aims at proving a comprehensive summary of the current evidence on the safety, tolerability and efficacy of cariprazine in the treatment of schizophrenia, BD (manic/mixed/ depressive episode) and MDD. A systematic search was conducted on PubMed/Medline/ Scopus and the database on Clinical Trials from inception until April 2015 by typing a set of specified keywords. Available evidence seems to support cariprazine efficacy in the treatment of cognitive and negative symptoms of schizophrenia. Preliminary findings suggest its antimanic activity whilst it is still under investigation its efficacy in the treatment of bipolar depression and MDD. Furthermore, the available data seems not to allow judgements about its antipsychotic potential in comparison with currently prescribed antipsychotics. Further studies should be carried out to better investigate its pharmacodynamic and clinical potential, particularly as alternative to current antipsychotic drugs.

11 Review New advances in the treatment of generalized anxiety disorder: the multimodal antidepressant vortioxetine. 2016

Orsolini, Laura / Tomasetti, Carmine / Valchera, Alessandro / Iasevoli, Felice / Buonaguro, Elisabetta Filomena / Vellante, Federica / Fornaro, Michele / Fiengo, Annastasia / Mazza, Monica / Vecchiotti, Roberta / Perna, Giampaolo / de Bartolomeis, Andrea / Martinotti, Giovanni / Di Giannantonio, Massimo / De Berardis, Domenico. ·a School of Life and Medical Sciences , University of Hertfordshire , Hatfield , UK. · b Villa San Giuseppe Hospital , Hermanas Hospitalarias , Ascoli Piceno , Italy. · c Polyedra Research Group , Teramo , Italy. · d Department of Psychiatry and Neuropsychology , University of Maastricht , Maastricht , The Netherlands. · e NHS, Department of Mental Health ASL Teramo, Psychiatric Service of Diagnosis and Treatment , Hospital 'Maria SS dello Splendore' , Giulianova , Italy. · f Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, Reproductive and Odontostomatogical Sciences , University of Naples 'Federico II' , Napoli , Italy. · g NHS, Department of Mental Health ASL Teramo, Psychiatric Service of Diagnosis and Treatment , Hospital 'G. Mazzini' , Teramo , Italy. · h Department of Neuroscience and Imaging , University 'G. d'Annunzio' , Chieti , Italy. · i New York Psychiatric Institute , Columbia University , New York , NY , USA. · j Department of Life, Health and Environmental Sciences , University of L'Aquila , L'Aquila , Italy. · k Hermanas Hospitalarias, FoRiPsi, Department of Clinical Neurosciences , Villa San Benedetto Menni , Albese con Cassano , Como , Italy. · l Department of Psychiatry and Behavioral Sciences , Leonard Miller School of Medicine, University of Miami , Coral Gables , Florida , USA. ·Expert Rev Neurother · Pubmed #27050932.

ABSTRACT: Generalized Anxiety Disorder (GAD) is a persistent condition characterized by chronic anxiety, exaggerated worry and tension, mainly comorbid with Major Depressive Disorder (MDD). Currently, selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors are recommended as first-line treatment of GAD. However, some patients may not respond to the treatment or discontinue due to adverse effects. Vortioxetine (VRX) is a multimodal antidepressant with a unique mechanism of action, by acting as 5-HT3A, 5-HT1D and 5-HT7 receptor antagonist, partial agonist at the 5-HT1A and 5-HT1B receptors and inhibitor at the 5-HT transporter. Preliminary clinical trials showed contrasting findings in terms of improvement of the anxiety symptomatology and/or cognitive impairment. Here, we aim to systematically review the evidence currently available on the efficacy, safety and tolerability of VRX in the treatment of GAD. The generalizability of results on the efficacy of VRX in patients with anxiety symptomatology and GAD is limited due to few and contrasting RCTs so far available. Only two studies, of which one prevention relapse trial, reported a significant improvement in anxiety symptomatology compared to three with negative findings.

12 Review The prevalence and predictors of obstructive sleep apnea in major depressive disorder, bipolar disorder and schizophrenia: A systematic review and meta-analysis. 2016

Stubbs, Brendon / Vancampfort, Davy / Veronese, Nicola / Solmi, Marco / Gaughran, Fiona / Manu, Peter / Rosenbaum, Simon / De Hert, Marc / Fornaro, Michele. ·Health Service and Population Research Department, Institute of Psychiatry, King's College London, De Crespigny Park, London Box SE5 8AF, United Kingdom; Physiotherapy Department, South London and Maudsley NHS Foundation Trust, Denmark Hill, London SE5 8AZ, United Kingdom. · KU Leuven Department of Rehabilitation Sciences, Tervuursevest 101, B-3001 Leuven, Belgium; University Psychiatric Centre KU Leuven, Kortenberg, KU Leuven Department of Neurosciences, Leuvensesteenweg 517, B-3070 Kortenberg, Belgium. · Department of Medicine, DIMED, University of Padua, Via Gi ustiani, 2, 35128 Padova, Italy. · Department of Neurosciences, University of Padua, Via Giustiniani, 5, 35128 Padova, Italy; Local Health Unit ULSS 17, Mental Health Department, Monselice, Padova, Italy. · National Psychosis Service, South London and Maudsley NHS Foundation Trust, Denmark Hill, London, United Kingdom. · Zucker Hillside Hospital, North Shore - LIJ Health System, 75-59 263rd Street, Glen Oaks, NY 11004, USA. · Musculoskeletal Division, The George Institute for Global Health and School of Public Health, University of Sydney, Sydney, Australia; School of Psychiatry, University of New South Wales, Sydney, Australia. · KU Leuven - University of Leuven, Department of Neurosciences, B-3000 Leuven, Belgium. · New York Psychiatric Institute, Columbia University, NYC, USA. ·J Affect Disord · Pubmed #26999550.

ABSTRACT: BACKGROUND: Obstructive sleep apnea (OSA) is a health hazard since it is associated with neurocognitive dysfunction and cardio-metabolic diseases. The prevalence of OSA among people with serious mental illness (SMI) is unclear. METHOD: We searched major electronic databases from inception till 06/2015. Articles were included that reported the prevalence of OSA determined by polysomnography (PSG) or an apnea-hypopnea index (AHI) >5 events/hr, in people with major depressive disorder (MDD), bipolar disorder (BD) or schizophrenia. A random effects meta-analysis calculating the pooled prevalence of OSA and meta-regression of potential moderators were performed. RESULTS: Twelve articles were included representing 570,121 participants with SMI (mean age=38.3 years (SD=7.5)), 45.8% male (range=32-80.4) and mean body mass index (BMI) 25.9 (SD=3.7). The prevalence of OSA in SMI in clinical studies was 25.7% (95% CI 13.9 to 42.4%, n=1,535). Higher frequencies of OSA were seen in MDD (36.3%, 19.4-57.4%, n=525) than in BD (24.5%, 95% CI 10.6-47.1, n=681) and schizophrenia (15.4%, 95% CI 5.3-37.1%, n=329). The prevalence of OSA in 568,586 people with SMI from population cohort studies was 10.7% (95% CI 2.4-37.0%) and 19.8% (95% CI 2.5-70.0%) in 358,853 people with MDD. Increasing age (β=0.063, 95% CI 0.0005-0.126, p=0.04, N=10) and BMI predicted increased prevalence of OSA (β=0.1642, 95% CI 0.004-0.3701, p=0.04, N=9). CONCLUSION: People with SMI (particularly MDD) have a high prevalence of OSA. Screening for and interventions to manage OSA in SMI including those focused on reducing BMI are warranted.

13 Review A comparative meta-analysis of TEMPS scores across mood disorder patients, their first-degree relatives, healthy controls, and other psychiatric disorders. 2016

Solmi, Marco / Zaninotto, Leonardo / Toffanin, Tommaso / Veronese, Nicola / Lin, Kangguang / Stubbs, Brendon / Fornaro, Michele / Correll, Christoph U. ·Department of Neuroscience, University of Padova, Padova, Italy; Mental Health Department, Local Health Unit ULSS 17, Monselice, Padova, Italy. Electronic address: marco.solmi83@gmail.com. · Department of Biomedical and Neuro-Motor Sciences, University of Bologna, Bologna, Italy. · Local Health Unit ULSS 7, Conegliano, Italy. · Department of Medicine - DIMED, Geriatrics Section, University of Padova, Italy. · Department of Affective Disorder, Guangzhou Brain Hospital, Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. · Physiotherapy Department, South London and Maudsley NHS Foundation Trust, Denmark Hill, London SE5 8AZ, United Kingdom; Health Service and Population Research Department, Institute of Psychiatry, King's College London, De Crespigny Park, Box SE5 8 AF London, United Kingdom. · New York State Psychiatric Institute, Columbia University, NY, USA. · The Zucker Hillside Hospital, Psychiatry Research, North Shore, Glen Oaks, NY, USA; Hofsra North Shore LIJ School of Medicine, Hampstead, NY, USA. ·J Affect Disord · Pubmed #26897455.

ABSTRACT: BACKGROUND: The Temperament Evaluation Memphis, Pisa, Paris and San Diego Auto-questionnaire (TEMPS) is validated to assess temperament in clinical and non-clinical samples. Scores vary across bipolar disorder (BD), major depressive disorder (MDD), attention-deficit/hyperactivity disorder (ADHD), borderline personality disorder (BPD) and healthy controls (HCs), but a meta-analysis is missing. METHODS: Meta-analysis of studies comparing TEMPS scores in patients with mood disorders or their first-degree relatives to each other, or to a psychiatric control group or HCs. RESULTS: Twenty-six studies were meta-analyzed with patients with BD (n= 2025), MDD (n=1283), ADHD (n=56) and BPD (n=43), relatives of BD (n=436), and HCs (n=1757). Cyclothymic (p<0.001) and irritable TEMPS scores (p<0.001) were higher in BD than MDD (studies=12), and in MDD vs HCs (studies=8). Cyclothymic (p<0.001), irritable (p<0.001) and anxious (p=0.03) scores were higher in BD than their relatives, who, had higher scores than HCs. No significant differences emerged between ADHD and BD (studies=3); CONCLUSION: Affective temperaments are on a continuum, with increasing scores ranging from HCs through MDD to BD regarding cyclothymic and irritable temperament, from MDD through BD to HC regarding hyperthymic temperament, and from HC through BD relatives to BD regarding cyclothymic, irritable and anxious temperament. Depressive and anxious temperaments did not differ between BD and MDD, being nonetheless the lowest in HCs. BD did not differ from ADHD in any investigated TEMPS domain. LIMITATIONS: Different TEMPS versions, few studies comparing BD with ADHD or BPD, no correlation with other questionnaires.

14 Review Atypical Antipsychotics in the Treatment of Acute Bipolar Depression with Mixed Features: A Systematic Review and Exploratory Meta-Analysis of Placebo-Controlled Clinical Trials. 2016

Fornaro, Michele / Stubbs, Brendon / De Berardis, Domenico / Perna, Giampaolo / Valchera, Alessandro / Veronese, Nicola / Solmi, Marco / Ganança, Licínia. ·New York Psychiatric Institute, Columbia University, New York City, NY 10032, USA. dott.fornaro@gmail.com. · Health Service and Population Research Department, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK. brendon.stubbs@kcl.ac.uk. · Physiotherapy Department, South London and Maudsley NHS Foundation Trust, London SE5 8AZ, UK. brendon.stubbs@kcl.ac.uk. · National Health Service, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital. Mazzini, ASL 4, Teramo 64100, Italy. dodebera@aliceposta.it. · Department of Clinical Neurosciences, Hermanas Hospitalarias-Villa San Benedetto Menni Hospital, FoRiPsi 22032, Italy. pernagp@gmail.com. · Hermanas Hospitalarias-Villa San Giuseppe, Ascoli Piceno 63100, Italy. a.valchera@ospedaliere.it. · Department of Medicine (DIMED), University of Padua, Padova 35121, Italy. ilmannato@gmail.com. · Department of Neurosciences, University of Padua, Padova 35121, Italy. marco.solmi83@gmail.com. · New York Psychiatric Institute, Columbia University, New York City, NY 10032, USA. lg2733@cumc.columbia.edu. · Departamento de Psiquiatria e Saúde Mental, Faculdade de Medicina, Universidade de Lisboa, Lisbon 1649-035, Portugal. lg2733@cumc.columbia.edu. ·Int J Mol Sci · Pubmed #26891297.

ABSTRACT: Evidence supporting the use of second generation antipsychotics (SGAs) in the treatment of acute depression with mixed features (MFs) associated with bipolar disorder (BD) is scarce and equivocal. Therefore, we conducted a systematic review and preliminary meta-analysis investigating SGAs in the treatment of acute BD depression with MFs. Two authors independently searched major electronic databases from 1990 until September 2015 for randomized (placebo-) controlled trials (RCTs) or open-label clinical trials investigating the efficacy of SGAs in the treatment of acute bipolar depression with MFs. A random-effect meta-analysis calculating the standardized mean difference (SMD) between SGA and placebo for the mean baseline to endpoint change in depression as well as manic symptoms score was computed based on 95% confidence intervals (CI). Six RCTs and one open-label placebo-controlled studies (including post-hoc reports) representing 1023 patients were included. Participants received either ziprasidone, olanzapine, lurasidone, quetiapine or asenapine for an average of 6.5 weeks across the included studies. Meta-analysis with Duval and Tweedie adjustment for publication bias demonstrated that SGA resulted in significant improvements of (hypo-)manic symptoms of bipolar mixed depression as assessed by the means of the total scores of the Young Mania Rating Scale (YMRS) (SMD -0.74, 95% CI -1.20 to -0.28, n SGA = 907, control = 652). Meta-analysis demonstrated that participants in receipt of SGA (n = 979) experienced a large improvement in the Montgomery-Åsberg Depression Rating Scale (MADRS) scores (SMD -1.08, 95% CI -1.35 to -0.81, p < 0.001) vs. placebo (n = 678). Publication and measurement biases and relative paucity of studies. Overall, SGAs appear to offer favorable improvements in MADRS and YMRS scores vs. placebo. Nevertheless, given the preliminary nature of the present report, additional original studies are required to allow more reliable and clinically definitive conclusions.

15 Review A comprehensive review on the efficacy of S-Adenosyl-L-methionine in Major Depressive Disorder. 2016

De Berardis, Domenico / Orsolini, Laura / Serroni, Nicola / Girinelli, Gabriella / Iasevoli, Felice / Tomasetti, Carmine / de Bartolomeis, Andrea / Mazza, Monica / Valchera, Alessandro / Fornaro, Michele / Perna, Giampaolo / Piersanti, Monica / Di Nicola, Marco / Cavuto, Marilde / Martinotti, Giovanni / Di Giannantonio, Massimo. ·National Health Service, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, "G. Mazzini" Hospital, p.zza Italia 1, 64100 Teramo, Italy. dodebera@aliceposta.it. ·CNS Neurol Disord Drug Targets · Pubmed #26295824.

ABSTRACT: OBJECTIVE: To review the antidepressant efficacy of S-Adenosyl-L-Methionine (SAMe) both in monotherapy and/or in augmentation with antidepressants to better understand its potential role in the treatment of patients with Major Depressive Disorder (MDD) and Treatment-Resistant Depression (TRD). DATA SOURCES: A MEDLINE/PubMed search was carried out by using the following set of keywords: ((SAMe OR SAdenosyl- L-Methionine) AND (major depressive disorder OR depression)). Data Selection and Data Extraction: No language or time restrictions were placed on the electronic searches. Randomized controlled trials and open trials involving humans were here included and analyzed. The references of published articles identified in the initial search process were also examined for any additional studies appropriate for the review. DATA SYNTHESIS: SAMe is an important physiologic compound, playing a central role as precursor molecule in several biochemical reactions. Numerous studies have shown that SAMe may affect the regulation of various critical components of monoaminergic neurotransmission involved in the pathophysiology of MDD. Some findings have suggested its antidepressant efficacy in treating MDD. Several randomized controlled trials have supported that the antidepressant efficacy of SAMe in monotherapy is superior to placebo and tricyclic antidepressants. Recent findings have also demonstrated its efficacy in patients nonresponsive to selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. CONCLUSION: Overall, SAMe is a well-tolerated medication, which may offer considerable advantages as an alternative to antidepressant drugs or as an add-on therapy in the treatment of MDD and TRD. More large-scale controlled trials are needed to gain a better understanding of the relative efficacy of this drug.

16 Review Agomelatine beyond borders: current evidences of its efficacy in disorders other than major depression. 2015

De Berardis, Domenico / Fornaro, Michele / Serroni, Nicola / Campanella, Daniela / Rapini, Gabriella / Olivieri, Luigi / Srinivasan, Venkataramanujam / Iasevoli, Felice / Tomasetti, Carmine / De Bartolomeis, Andrea / Valchera, Alessandro / Perna, Giampaolo / Mazza, Monica / Di Nicola, Marco / Martinotti, Giovanni / Di Giannantonio, Massimo. ·National Health Service, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital "G. Mazzini", ASL 4, 64100 Teramo, Italy. dodebera@aliceposta.it. · Department of "Scienze della Formazione", University of Catania, 95121 Catania, Italy. dott.fornaro@gmail.com. · Department of Neuroscience and Imaging, University "G. D'Annunzio", 66013 Chieti, Italy. serroni.nicola@virgilio.it. · Department of Neuroscience and Imaging, University "G. D'Annunzio", 66013 Chieti, Italy. danicampa@virgilio.it. · Department of Neuroscience and Imaging, University "G. D'Annunzio", 66013 Chieti, Italy. gabriella.rapini@aslteramo.it. · National Health Service, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital "G. Mazzini", ASL 4, 64100 Teramo, Italy. luigi.olivieri@yahoo.it. · Sri Sathya Sai Medical Educational and Research Foundation, Medical Sciences Research Study Center, Prasanthi Nilayam, 40-Kovai Thirunagar Coimbatore-641014, 641014 Tamilnadu, India. · Laboratory of Molecular Psychiatry and Psychopharmacotherapeutics, Section of Psychiatry, Department of Neuroscience, University School of Medicine "Federico II", 80131 Naples, Italy. felix_ias@hotmail.com. · Laboratory of Molecular Psychiatry and Psychopharmacotherapeutics, Section of Psychiatry, Department of Neuroscience, University School of Medicine "Federico II", 80131 Naples, Italy. carmine.tomasetti@unina.it. · Laboratory of Molecular Psychiatry and Psychopharmacotherapeutics, Section of Psychiatry, Department of Neuroscience, University School of Medicine "Federico II", 80131 Naples, Italy. adebarto@unina.it. · Hermanas Hospitalarias, FoRiPsi, Villa S. Giuseppe Hospital, 63100 Ascoli Piceno, Italy. alessandrovalchera@gmail.com. · Hermanas Hospitalarias, FoRiPsi, Department of Clinical Neurosciences, Villa San Benedetto Menni, Albese con Cassano, 22032 Como, Italy. pernagp@tin.it. · Department of Neuroscience and Imaging, University "G. D'Annunzio", 66013 Chieti, Italy. giovanni.martinotti@gmail.com. · Department of Neuroscience and Imaging, University "G. D'Annunzio", 66013 Chieti, Italy. digiannantonio@unich.it. ·Int J Mol Sci · Pubmed #25569089.

ABSTRACT: Agomelatine, a melatonergic antidepressant with a rapid onset of action, is one of the most recent drugs in the antidepressant category. Agomelatine's antidepressant actions are attributed to its sleep-promoting and chronobiotic actions mediated by MT1 and MT2 receptors present in the suprachiasmatic nucleus, as well as to its effects on the blockade of 5-HT2c receptors. Blockade of 5-HT2c receptors causes release of both noradrenaline and dopamine at the fronto-cortical dopaminergic and noradrenergic pathways. The combined actions of agomelatine on MT1/MT2 and 5-HT2c receptors facilitate the resynchronization of altered circadian rhythms and abnormal sleep patterns. Agomelatine appeared to be effective in treating major depression. Moreover, evidence exists that points out a possible efficacy of such drug in the treatment of bipolar depression, anxiety disorders, alcohol dependence, migraines etc. Thus, the aim of this narrative review was to elucidate current evidences on the role of agomelatine in disorders other than major depression.

17 Review Could the underestimation of bipolarity obstruct the search for novel antidepressant drugs? 2011

Fornaro, Michele / Aguglia, Eugenio / Dell'Osso, Liliana / Perugi, Giulio. ·University of Catania, Scienze della Formazione, via Teatro Greco 78, Catania, ZIP 94125, Italy. dott.fornaro@gmail.com ·Expert Opin Pharmacother · Pubmed #22098226.

ABSTRACT: INTRODUCTION: Despite the clinical and social relevance of depression, and the availability of numerous antidepressants and non-pharmacological interventions, response rates remain unsatisfactory and novel therapeutic targets are being explored. AREAS COVERED: This review starts with a brief overview of the evolution of the current antidepressant drug scenario and ends with a focus on the potential influence of the underestimation of bipolarity on the exploration of novel antidepressant drugs. EXPERT OPINION: The field of antidepressant drug development has suffered from a relative decline recently and, with the exception of agomelatine, innovative non-monoaminergic antidepressants have yet to be developed. The need for more effective compounds is evident. Clinicians and researchers should pay greater attention to the impact of bipolarity in depression. The ultimate goal of this review is not to discourage the use of antidepressants but rather to encourage judicious prescriptions, and also to solicit a better collaboration between clinicians and preclinical researchers so that more reliable diagnostic criteria can be adopted.

18 Article Understanding the Complex of Suicide in Depression: from Research to Clinics. 2020

Orsolini, Laura / Latini, Roberto / Pompili, Maurizio / Serafini, Gianluca / Volpe, Umberto / Vellante, Federica / Fornaro, Michele / Valchera, Alessandro / Tomasetti, Carmine / Fraticelli, Silvia / Alessandrini, Marco / La Rovere, Raffaella / Trotta, Sabatino / Martinotti, Giovanni / Di Giannantonio, Massimo / De Berardis, Domenico. ·Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK. · Neomesia Mental Health, Villa Jolanda Hospital, Jesi, Italy. · Polyedra, Teramo, Italy. · Department of Neurosciences, Mental Health and Sensory Organs, Suicide Prevention Center, S. Andrea Hospital, Sapienza University, Rome, Italy. · Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. · Department of Clinical Neurosciences/DIMSC, School of Medicine, Section of Psychiatry, Polytechnic University of Marche, Ancona, Italy. · Department of Neuroscience, Imaging and Clinical Science, Chair of Psychiatry, University of "G. D'Annunzio", Chieti, Italy. · Department of Psychiatry, Federico II University, Naples, Italy. · Villa S. Giuseppe Hospital, Hermanas Hospitalarias, Ascoli Piceno, Italy. · Department of Mental Health, National Health Service, Psychiatric Service of Diagnosis and Treatment, Hospital "SS. Annunziata" ASL 4, Giulianova, Italy. · Department of Mental Health, National Health Service, Azienda Sanitaria Locale, Pescara, Italy. · Department of Mental Health, National Health Service, Psychiatric Service of Diagnosis and Treatment, Hospital "G. Mazzini", ASL 4, Teramo, Italy. ·Psychiatry Investig · Pubmed #32209966.

ABSTRACT: OBJECTIVE: Amongst psychiatric disorders, major depressive disorder (MDD) is the most prevalent, by affecting approximately 15-17% of the population and showing a high suicide risk rate equivalent to around 15%. The present comprehensive overview aims at evaluating main research studies in the field of MDD at suicide risk, by proposing as well as a schematic suicide risk stratification and useful flow-chart for planning suicide preventive and therapeutic interventions for clinicians. METHODS: A broad and comprehensive overview has been here conducted by using PubMed/Medline, combining the search strategy of free text terms and exploded MESH headings for the topics of 'Major Depressive Disorder' and 'Suicide' as following: ((suicide [Title/Abstract]) AND (major depressive disorder [Title/Abstract])). All articles published in English through May 31, 2019 were summarized in a comprehensive way. RESULTS: Despite possible pathophysiological factors which may explain the complexity of suicide in MDD, scientific evidence supposed the synergic role of genetics, exogenous and endogenous stressors (i.e., interpersonal, professional, financial, as well as psychiatric disorders), epigenetic, the hypothalamic-pituitary-adrenal stress-response system, the involvement of the monoaminergic neurotransmitter systems, particularly the serotonergic ones, the lipid profile, neuro-immunological biomarkers, the Brain-derived neurotrophic factor and other neuromodulators. CONCLUSION: The present overview reported that suicide is a highly complex and multifaceted phenomenon in which a large plethora of mechanisms could be variable implicated, particularly amongst MDD subjects. Beyond these consideration, modern psychiatry needs a better interpretation of suicide risk with a more careful assessment of suicide risk stratification and planning of clinical and treatment interventions.

19 Article An Update on Glutamatergic System in Suicidal Depression and on the Role of Esketamine. 2020

De Berardis, Domenico / Tomasetti, Carmine / Pompili, Maurizio / Serafini, Gianluca / Vellante, Federica / Fornaro, Michele / Valchera, Alessandro / Perna, Giampaolo / Volpe, Umberto / Martinotti, Giovanni / Fraticelli, Silvia / Di Giannantonio, Massimo / Kim, Yong-Ku / Orsolini, Laura. ·Department of Neuroscience, Imaging and Clinical Science, University of "G. D'Annunzio", Chieti, Italy. · National Health Service, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital "G. Mazzini", ASL 4 Teramo, Italy. · Polyedra, Teramo, Italy. · Department of Psychiatry, Federico II University, Naples, Italy. · NHS, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital "SS. Annunziata", ASL 4 Giulianova, Italy. · Department of Neurosciences, Mental Health and Sensory Organs, Suicide Prevention Center, S. Andrea Hospital, Sapienza University, Rome, Italy. · Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. · Villa S. Giuseppe Hospital, Hermanas Hospitalarias, Ascoli Piceno, Italy. · Department of Clinical Neurosciences, Hermanas Hospitalarias, Villa San Benedetto Menni Hospital, FoRiPsi, Albese con Cassano, Como, Italy. · Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands. · Department of Psychiatry and Behavioral Sciences, Leonard Miller School of Medicine, Miami University, Miami 786, United States. · Department of Clinical Neurosciences/DIMSC, School of Medicine, Section of Psychiatry, Polytechnic University of Marche, Ancona, Italy. · Department of Psychiatry, Korea University College of Medicine, Seoul, Korea. · Department of Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, Herts, United Kingdom. · Neomesia Mental Health, Villa Jolanda Hospital, Maiolati Spontini, Italy. ·Curr Top Med Chem · Pubmed #32003691.

ABSTRACT: BACKGROUND: A research on mood disorder pathophysiology has hypothesized abnormalities in glutamatergic neurotransmission, by suggesting further investigation on glutamatergic N-methyl-Daspartate (NMDA) receptor modulators in treating Major Depressive Disorder (MDD). Esketamine (ESK), an NMDA receptor antagonist able to modulate glutamatergic neurotransmission has been recently developed as an intranasal formulation for treatment-resistant depression (TRD) and for rapid reduction of depressive symptomatology, including suicidal ideation in MDD patients at imminent risk for suicide. OBJECTIVE: The present study aims at investigating recent clinical findings on research on the role of the glutamatergic system and ESK in treating suicidal depression in MDD and TRD. METHODS: A systematic review was here carried out on PubMed/Medline, Scopus and the database on U.S. N.I.H. Clinical Trials (https://clinicaltrials.gov) and the European Medical Agency (EMA) (https://clinicaltrialsregister.eu) from inception until October 2019. RESULTS: Intravenous infusion of ESK is reported to elicit rapid-acting and sustained antidepressant activity in refractory patients with MDD and TRD. In phase II studies, intranasal ESK demonstrated a rapid onset and a persistent efficacy in patients with TRD as well as in MDD patients at imminent risk for suicide. However, some data discrepancies have emerged in phase III studies. CONCLUSION: The U.S. Food and Drug Administration (FDA) granted fast track and Breakthrough Therapy Designation to Janssen Pharmaceuticals®, Inc. for intranasal ESK in 2013 for treatment-resistant depression (TRD) and in 2016 for the treatment of MDD with an imminent risk of suicide. However, further studies should be implemented to investigate the long-term efficacy and safety of intranasal ESK.

20 Article Commentary letter on "Revitalizing monoamine oxidase inhibitors: a call for action". 2019

Cattaneo, Carlo Ignazio / Fornaro, Michele / Ressico, Francesca Vittoria / Perugi, Giulio. ·Department of Mental Health, ASL NOVARA, Novara, Italy. · Neuroscience, Reproductive Science and Odontostolmatology, Section of Psychiatry, University School of Medicine Federico II, Naples, Italy. · Clinica Psichiatrica, Dipartimento di Medicina Sperimentale- Pisa, University of Pisa, Tuscany, Italy. ·CNS Spectr · Pubmed #31663496.

ABSTRACT: -- No abstract --

21 Article Alexithymia, resilience, somatic sensations and their relationships with suicide ideation in drug naïve patients with first-episode major depression: An exploratory study in the "real world" everyday clinical practice. 2019

De Berardis, Domenico / Fornaro, Michele / Valchera, Alessandro / Rapini, Gabriella / Di Natale, Serena / De Lauretis, Ida / Serroni, Nicola / Orsolini, Laura / Tomasetti, Carmine / Bustini, Massimiliano / Carano, Alessandro / Vellante, Federica / Perna, Giampaolo / Core, Laura / Alessandrini, Marco / Fraticelli, Silvia / Martinotti, Giovanni / Di Giannantonio, Massimo. ·NHS, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital "G. Mazzini," ASL 4, Teramo, Italy. · Department of Neurosciences and Imaging, Chair of Psychiatry, University "G. D'Annunzio", Chieti, Italy. · Neuroscience, Reproductive Science and Odontostolmatology, Section of Psychiatry, University School of Medicine Federico II, Naples, Italy. · Polyedra Research Group, Teramo, Italy. · School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK. · Villa S. Giuseppe Hospital, Hermanas Hospitalarias, Ascoli Piceno, Italy. · Laboratory of Molecular Psychiatry and Psychopharmacotherapeutics, Section of Psychiatry, Department of Neuroscience, University School of Medicine "Federico II", Naples, Italy. · NHS, Department of Mental Health, Rieti, Italy. · NHS, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital "Madonna Del Soccorso", San Benedetto del Tronto, Italy. · Hermanas Hospitalarias, FoRiPsi, Department of Clinical Neurosciences, Villa San Benedetto Menni, Albese con Cassano, Italy. · Department of Psychiatry and Neuropsychology, University of Maastricht, Maastricht, The Netherlands. · Department of Psychiatry and Behavioral Sciences, Leonard Miller School of Medicine, University of Miami, Miami, Florida. · NHS, Department of Mental Health, Center of Mental Health, ASL 4, Giulianova, Italy. ·Early Interv Psychiatry · Pubmed #31402575.

ABSTRACT: AIM: The present study is aimed at revaluating alexithymia, somatic sensations, resilience and their relationships with suicide ideation in drug naïve adult outpatients suffering from first episode major depression (MD). METHODS: Data of 103 adult outpatients (49 men, 56 women) with a diagnostic and statistical manual of mental disorders, 4th edition, text revision (DSM-IV-TR) diagnosis of MD were analysed. Alexithymia was measured using the 20-item Toronto Alexithymia Scale (TAS-20) and resilience with the 25 items Connor-Davidson Resilience Scale (CD-RISC) whereas depression was evaluated using the 17-item Hamilton Depression Rating Scale, somatic sensations with the Body Sensations Questionnaire and suicide ideation with Scale of Suicide Ideation (SSI). RESULTS: Gender comparisons between all demographic and clinical variables showed no significant differences in all variables. Subjects who were found positive for alexithymia showed higher scores on all clinical variables controlling for age, gender and duration of the current episode. In a linear regression model, lower scores on CD-RISC and Difficulty in Identifying Feelings dimension of TAS-20 were significantly predictive of higher scores on SSI. CONCLUSIONS: Alexithymia and low resilience were significant predictors of increased suicide ideation in a first MD episode. However, study limitations must be considered and future research needs are being discussed.

22 Article The FDA "Black Box" Warning on Antidepressant Suicide Risk in Young Adults: More Harm Than Benefits? 2019

Fornaro, Michele / Anastasia, Annalisa / Valchera, Alessandro / Carano, Alessandro / Orsolini, Laura / Vellante, Federica / Rapini, Gabriella / Olivieri, Luigi / Di Natale, Serena / Perna, Giampaolo / Martinotti, Giovanni / Di Giannantonio, Massimo / De Berardis, Domenico. ·Neuroscience, Reproductive Science and Odontostolmatology, Section of Psychiatry, University School of Medicine Federico II, Naples, Italy. · Polyedra Research Group, Teramo, Italy. · Alma Mater S.P.A. Villa Camaldoli, Naples, Italy. · Villa S. Giuseppe Hospital, Hermanas Hospitalarias, Ascoli Piceno, Italy. · NHS, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital G. Mazzini, ASL Teramo, Teramo, Italy. · School of Life and Medical Sciences, University of Hertfordshire, Hatfield, Herts, United Kingdom. · Hermanas Hospitalarias, FoRiPsi, Department of Clinical Neurosciences, Villa San Benedetto Menni, Como, Italy. · Department of Neurosciences and Imaging, Chair of Psychiatry, University G. D'Annunzio, Chieti, Italy. ·Front Psychiatry · Pubmed #31130881.

ABSTRACT: The decision made in the year 2004 by the U.S. Food and Drug Administration (FDA) to require a boxed warning on antidepressants regarding the risk of suicidality in young adults still represents a matter of controversy. The FDA warning was grounded on industry-sponsored trials carried one decade ago or earlier. However, within the past decade, an increasing number of reports have questioned the actual validity of the FDA warning, especially considering a decline in the prescription of the antidepressant drugs associated with an increase in the rate of suicidal events among people with severe depression. The present report provides an overview of the FDA black box warning, also documenting two Major Depressive Disorder patients whose refusal to undergo a pharmacological antidepressant treatment possibly led to an increased risk for suicidal behaviors. The concerns raised by the FDA black box warning need to be considered in real-world clinical practice, stating the associated clinical and public health implications.

23 Article The Relationship between Dietary Vitamin K and Depressive Symptoms in Late Adulthood: A Cross-Sectional Analysis from a Large Cohort Study. 2019

Bolzetta, Francesco / Veronese, Nicola / Stubbs, Brendon / Noale, Marianna / Vaona, Alberto / Demurtas, Jacopo / Celotto, Stefano / Cacco, Chiara / Cester, Alberto / Caruso, Maria Gabriella / Reddavide, Rosa / Notarnicola, Maria / Maggi, Stefania / Koyanagi, Ai / Fornaro, Michele / Firth, Joseph / Smith, Lee / Solmi, Marco. ·Medical Department, Geriatric Unit, Azienda ULSS (Unità Locale Socio Sanitaria) 3 "Serenissima", 30031 Dolo-Mirano District, Italy. francesco.bolzetta@gmail.com. · Aging Branch, Neuroscience Institute, National Research Council, 35128 Padua, Italy. ilmannato@gmail.com. · National Institute of Gastroenterlogy, Research Hospital, IRCCS De Bellis, Castellana Grotte, 70013 Bari, Italy. ilmannato@gmail.com. · South London and Maudsley NHS Foundation Trust, Denmark Hill, London SE5 8AZ, UK. brendon.stubbs@kcl.ac.uk. · Faculty of Health, Social care and Education, Anglia Ruskin University, Bishop Hall Lane, Chelmsford CM1 1SQ, UK. brendon.stubbs@kcl.ac.uk. · Institute of Psychiatry, Psychology and Neuroscience (IoPPN) King's College London, De Crespigny Park, London SE5 8AF, UK. brendon.stubbs@kcl.ac.uk. · Aging Branch, Neuroscience Institute, National Research Council, 35128 Padua, Italy. marianna.noale@in.cnr.it. · Primary Care Department, Azienda ULSS20 Verona, 37122 Verona, Italy. aisamaisa@gmail.com. · Primary Care Department, Azienda USL Toscana Sud Est, 58100 Grosseto, Italy. eritrox7@gmail.com. · Primary Care Department, Aziendale AAS3 Alto Friuli ⁻ Collinare ⁻ Medio Friuli, 33013 Udine, Italy. celottostefano@gmail.com. · University of Siena, 53100 Siena, Italy. chiaracacco@gmail.com. · Medical Department, Geriatric Unit, Azienda ULSS (Unità Locale Socio Sanitaria) 3 "Serenissima", 30031 Dolo-Mirano District, Italy. alberto.cester@aulss3.veneto.it. · National Institute of Gastroenterlogy, Research Hospital, IRCCS De Bellis, Castellana Grotte, 70013 Bari, Italy. gabriella.caruso@irccsdebellis.it. · National Institute of Gastroenterlogy, Research Hospital, IRCCS De Bellis, Castellana Grotte, 70013 Bari, Italy. rosa.reddavide@irccsdebellis.it. · National Institute of Gastroenterlogy, Research Hospital, IRCCS De Bellis, Castellana Grotte, 70013 Bari, Italy. maria.notarnicola@irccsdebellis.it. · Aging Branch, Neuroscience Institute, National Research Council, 35128 Padua, Italy. stefania.maggi@in.cnr.it. · Research and Development Unit, Parc Sanitari Sant Joan de Déu, Fundació Sant Joan de Déu, CIBERSAM, 28029 Barcelona, Spain. koyanagi1117@hotmail.com. · New York State Psychiatric Institute, Columbia University, New York, NY 10027, USA. dott.fornaro@gmail.com. · NICM Health Research Institute, University of Western Sydney, Penrith, NSW 2751, Australia. joefirth@gmail.com. · Division of Psychology and Mental Health, University of Manchester, Manchester M13 9PL, UK. joefirth@gmail.com. · The Cambridge Centre for Sport and Exercise Sciences, Department of Life Sciences, Anglia Ruskin University, Cambridge CB1 1PT, UK. Lee.Smith@anglia.ac.uk. · Department of Neuroscience, University of Padova, 35122 Padova, Italy. marco.solmi83@gmail.com. · Padova Neuroscience Center, University of Padova, 35122 Padova, Italy. marco.solmi83@gmail.com. ·Nutrients · Pubmed #30959758.

ABSTRACT: Few studies assessed the associations between dietary vitamin K and depressive symptoms. We aimed to investigate the association between dietary vitamin K and depressive symptoms in a large cohort of North American People. In this cross-sectional analysis, 4,375 participants that were aged 45⁻79 years from the Osteoarthritis Initiative were included. Dietary vitamin K intake was collected through a semi-quantitative food frequency questionnaire and categorized in quartiles. Depressive symptoms were diagnosed using the 20-item Center for Epidemiologic Studies-Depression (CES-D) ≥ 16. To investigate the associations between vitamin K intake and depressive symptoms, logistic regression analysis were run, which adjusted for potential confounders. Overall, 437 (=10%) subjects had depressive symptoms. After adjusting for 11 confounders, people with the highest dietary vitamin K intake had lower odds of having depressive symptoms (OR = 0.58; 95%CI: 0.43⁻0.80). This effect was only present in people not taking vitamin D supplementation. In conclusion, higher dietary vitamin K intake was significantly associated with a lower presence of depressive symptoms, also after accounting for potential confounders. Future longitudinal research is required to explore the directionality of the association.

24 Article Alexithymia, Suicide Ideation and Homocysteine Levels in Drug Naïve Patients with Major Depression: A Study in the "Real World" Clinical Practice 2019

De Berardis, Domenico / Olivieri, Luigi / Rapini, Gabriella / Di Natale, Serena / Serroni, Nicola / Fornaro, Michele / Orsolini, Laura / Valchera, Alessandro / Carano, Alessandro / Vellante, Federica / Varasano, Paola Annunziata / Lucidi Pressanti, Gabriella / Serafini, Gianluca / Pompili, Maurizio / Martinotti, Giovanni / Di Giannantonio, Massimo. ·National Health Service, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital "G. Mazzini". · Department of Neurosciences and Imaging, University "G. D'Annunzio". · Department of Psychiatry, Federico II University. · Polyedra, Teramo. · School of Life and Medical Sciences, University of Hertfordshire, Hatfield. · Villa S. Giuseppe Hospital, Hermanas Hospitalarias. · Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital "Madonna Del Soccorso", National Health Service. · Department of Immunohematology and Transfusional Medicine, "G. Mazzini" Hospital. · Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa. · Department of Neurosciences, Mental Health and Sensory Organs, Suicide Prevention Center, Sant'Andrea Hospital, Sapienza University of Rome. ·Clin Psychopharmacol Neurosci · Pubmed #30905133.

ABSTRACT: Objective: : This study was performed to elucidate relationships between alexithymia, suicide ideation and homocysteine levels in drug-naïve outpatients with major depressive disorder (MDD). Methods: : Sixty seven outpatients with MDD with melancholic features were evaluated by the means of the Hamilton Depression Rating Scale, the Toronto Alexithymia Scale (TAS-20), the Scale of Suicide Ideation, and homocysteine levels. Results: : Alexithymic subjects showed higher scores on all scales and higher homocysteine levels. Regression analysis shown higher homocysteine levels and TAS-20' "Difficulty in Describing Feelings" dimension, in turn being associated with higher suicide ideation. Conclusion: : In conclusion, alexithymic MDD outpatients may characterize for homocysteine dysregulation that may be linked to suicide ideation, regardless depression' severity. However, study limitations are discussed and must be considered.

25 Article Network analysis of the relationship between depressive symptoms, demographics, nutrition, quality of life and medical condition factors in the Osteoarthritis Initiative database cohort of elderly North-American adults with or at risk for osteoarthritis. 2019

Solmi, Marco / Koyanagi, Ai / Thompson, Trevor / Fornaro, Michele / Correll, Christoph U / Veronese, Nicola. ·Neuroscience Department, Psychiatry Unit, University of Padua, Padua, Italy. · Padua University Hospital, Padua, Italy. · Neuroscience Center, University of Padua, Padua, Italy. · Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Monforte de Lemos 3-5 Pabellón 11, Madrid 28029, Spain. · Research and Development Unit, Parc Sanitari Sant Joan de Déu, Universitat de Barcelona, Fundació Sant Joan de Déu, Dr Antoni Pujadas, 42, Sant Boi de Llobregat, Barcelona 0883, Spain. · Faculty of Education and Health, University of Greenwich, London, UK. · Neuroscience Department, Section of Psychiatry, Federico II University of Naples, Naples, Italy. · Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA. · Department of Psychiatry and Molecular Medicine, Hofstra Northwell School of Medicine, Hempstead, NY, USA. · Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany. · Ageing Branch, National Research Council, Padua, Italy. ·Epidemiol Psychiatr Sci · Pubmed #30698512.

ABSTRACT: AIMS: A complex interaction exists between age, body mass index, medical conditions, polypharmacotherapy, smoking, alcohol use, education, nutrition, depressive symptoms, functioning and quality of life (QoL). We aimed to examine the inter-relationships among these variables, test whether depressive symptomology plays a central role in a large sample of adults, and determine the degree of association with life-style and health variables. METHODS: Regularised network analysis was applied to 3532 North-American adults aged ⩾45 years drawn from the Osteoarthritis Initiative. Network stability (autocorrelation after case-dropping), centrality of nodes (strength, M, the sum of weight of the connections for each node), and edges/regularised partial correlations connecting the nodes were assessed. RESULTS: Physical and mental health-related QoL (M = 1.681; M = 1.342), income (M = 1.891), age (M = 1.416), depressive symptoms (M = 1.214) and education (M = 1.173) were central nodes. Depressive symptoms' stronger negative connections were found with mental health-related QoL (-0.702), income (-0.090), education (-0.068) and physical health-related QoL (-0.354). This latter was a 'bridge node' that connected depressive symptoms with Charlson comorbidity index, and number of medications. Physical activity and Mediterranean diet adherence were associated with income and physical health-related QoL. This latter was a 'bridge node' between the former two and depressive symptoms. The network was stable (stability coefficient = 0.75, i.e. highest possible value) for all centrality measures. CONCLUSIONS: A stable network exists between life-style behaviors and social, environmental, medical and psychiatric variables. QoL, income, age and depressive symptoms were central in the multidimensional network. Physical health-related QoL seems to be a 'bridge node' connecting depressive symptoms with several life-style and health variables. Further studies should assess such interactions in the general population.

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