A neurodevelopment approach for a transitional model of early onset schizophrenia

In the last decades, the conceptualization of schizophrenia has dramatically changed, moving from a neurodegenerative process occurring in early adult life to a neurodevelopmental disorder starting be-fore birth, showing a variety of premorbid and prodromal symptoms and, in relatively few cases, evolving in the full-blown psychotic syndrome. High rates of co-occurring different neurodevelopmental disorders such as Autism spectrum disorder and ADHD, predating the onset of SCZ, and neurobio-logical underpinning with significant similarities, support the notion of a pan-developmental disturbance consisting of impairments in neuromotor, receptive language, social and cognitive development. Con-sidering that many SCZ risk factors may be similar to symptoms of other neurodevelopmental psychi-atric disorders, transition processes from child & adolescent to adult systems of care should include both high risk people as well as subject with other neurodevelopmental psychiatric disorders with different levels of severity. This descriptive mini-review discuss the need of innovative clinical approaches, re-considering specific diagnostic categories, stimulating a careful analysis of risk factors and promoting the appropriate use of new and safer medications

The FDA “black box” warning on antidepressant suicide risk in young adults: More harm than benefits?

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

Socio-demographic and clinical characterization of patients with obsessive-compulsive tic-related disorder (OCTD) : An Italian multicenter study

© Copyright by Pacini Editore SrlIn the DSM-5 a new "tic-related" specifier for obsessive compulsive disorder (OCD) has been introduced, highlighting the importance of an accurate characterization of patients suffering from obsessive-compulsive tic-related disorder ("OCTD"). In order to characterize OCTD from a socio-demographic and clinical perspective, the present multicenter study was carried out. The sample consists of 266 patients, divided in two groups with lifetime diagnoses of OCD and OCTD, respectively. OCTD vs OCD patients showed a significant male prevalence (68.5% vs 48.5%; p < .001), a higher rate of psychiatric comorbidities (69.4 vs 50%; p < .001) - mainly with neurodevelopmental disorders (24 vs 0%; p < .001), a lower education level and professional status (middle school diploma: 25 vs 7.6%; full-Time job 44.4 vs 58%; p < .001). Moreover, OCTD vs OCD patients showed significantly earlier age of OCD and psychiatric comorbidity onsets (16.1 ± 10.8 vs 22.1 ± 9.5 years; p < .001, and 18.3 ± 12.8 vs 25.6 ± 9.4: p < .001, respectively). Patients with OCTD patients were treated mainly with antipsychotic and with a low rate of benzodiazepine (74.2 vs 38.2% and 20.2 vs 31.3%, respectively; p < .001). Finally, OCTD vs OCD patients showed higher rates of partial treatment response (58.1 vs 38%; p < .001), lower rates of current remission (35.5 vs 54.8%; p < .001) and higher rates of suicidal ideation (63.2 vs 41.7%; p < .001) and attempts (28.9 vs 8.3%; p < .001). Patients with OCTD report several unfavorable socio-demographic and clinical characteristics compared to OCD patients without a history of tic. Additional studies on larger sample are needed to further characterize OCTD patients from clinical and therapeutic perspectives.Peer reviewedFinal Published versio

Childhood maltreatment, personality vulnerability profiles, and borderline personality disorder symptoms in adolescents

Adverse childhood experiences are significant risk factors in the development of adolescent borderline personality disorder symptoms (BPDs). Theorists have posited that two personality vulnerabilities factors, self-criticism and dependency, may inform our understanding of this relationship. However, no research has examined the associations between early negative experiences, personality vulnerabilities, and adolescent BPDs. The current study aimed to identify profiles of dependency and self-criticism to examine the associations of these profiles with cumulative forms of childhood maltreatment (CM) and BPDs as well as to explore the mediating and moderating role of vulnerable personality profiles in the relationship between cumulative CM and BPDs. Two hundred and forty-one nonclinical and clinical adolescents participated in the study (Mage = 16.37, SD = 1.84). The findings indicated three different profiles: average dependent profile, dependent and self-critical profile, and self-critical profile. Individuals in the average dependent profile presented lower levels of CM and BPDs. Mediation analyses showed that relative to the average dependent profile, a higher cumulative CM history predicted a higher probability of belonging in the dependent and self-critical profile or the self-critical profile and, in turn, this was associated with higher levels of BPDs. No moderating effects of profiles of dependency and self-criticism were found

The melatonergic system in mood and anxiety disorders and the role of agomelatine: implications for clinical practice

Melatonin exerts its actions through membrane MT1/MT2 melatonin receptors, which belong to the super family of G-protein-coupled receptors consisting of the typical seven transmembrane domains. MT1 and MT2 receptors are expressed in various tissues of the body either as single ones or together. A growing literature suggests that the melatonergic system may be involved in the pathophysiology of mood and anxiety disorders. In fact, some core symptoms of depression show disturbance of the circadian rhythm in their clinical expression, such as diurnal mood and other symptomatic variation, or are closely linked to circadian system functioning, such as sleep-wake cycle alterations. In addition, alterations have been described in the circadian rhythms of several biological markers in depressed patients. Therefore, there is interest in developing antidepressants that have a chronobiotic effect (i.e., treatment of circadian rhythm disorders). As melatonin produces chronobiotic effects, efforts have been aimed at developing agomelatine, an antidepressant with melatonin agonist activity. The present paper reviews the role of the melatonergic system in the pathophysiology of mood and anxiety disorders and the clinical characteristics of agomelatine. Implications of agomelatine in “real world” clinical practice will be also discussed

Gold Nanorods as Radiopharmaceutical Carriers: Preparation and Preliminary Radiobiological In Vitro Tests

Low-energy electrons (Auger electrons) can be produced via the interaction of photons with gold atoms in gold nanorods (AuNRs). These electrons are similar to those emitted during the decay of technetium-99m (99mTc), a radioactive nuclide widely used for diagnostics in nuclear medicine. Auger and internal conversion (IC) electron emitters appropriately targeted to the DNA of tumors cells may, therefore, represent a new radiotherapeutic approach. 99mTc radiopharmaceuticals, which are used for diagnosis, could indeed be used in theragnostic fields when loaded on AuNRs and delivered to a tumor site. This work aims to provide a proof of concept (i) to evaluate AuNRs as carriers of 99mTc-based radiopharmaceuticals, and (ii) to evaluate the efficacy of Auger electrons emitted by photon-irradiated AuNRs in inducing radio-induced damage in T98G cells, thus mimicking the effect of Auger electrons emitted during the decay of 99mTc used in clinical settings. Data are presented on AuNRs’ chemical characterization (with an aspect ratio of 3.2 and Surface Plasmon Resonance bands at 520 and 680 nm) and the loading of pharmaceuticals (after 99mTc decay) on their surface. Spectroscopic characterizations, such as UV-Vis and synchrotron radiation-induced X-ray photoelectron (SR-XPS) spectroscopies, were performed to investigate the drug–AuNR interaction. Finally, preliminary radiobiological data on cell killing with AuNRs are presented

Celecoxib Adjunctive Treatment to Antipsychotics in Schizophrenia: A Review of Randomized Clinical Add-On Trials

Schizophrenia is a severe, chronic and debilitating mental disorder. Past literature has reported various hypotheses about the psychopathology of schizophrenia. Recently, a growing literature has been trying to explain the role of inflammation in the etiopathogenesis of schizophrenia. In the past, numerous immune modulation and anti-inflammatory treatment options have been proposed for schizophrenia, but sometimes the results were inconsistent. Electronic search was carried out in November 2015. PubMed and Scopus databases have been used to find studies to introduce in this review. Only randomized-placebo-controlled add-on trials were taken into account. In this way, six articles were obtained for the discussion. Celecoxib showed beneficial effects mostly in early stages of schizophrenia. In chronic schizophrenia, the data are controversial, possibly in part for methodological reasons

The role of inhaled loxapine in the treatment of acute agitation in patients with psychiatric disorders: A clinical review

Loxapine is a first generation antipsychotic, belonging to the dibenzoxazepine class. Recently, loxapine has been reformulated at a lower dose, producing an inhaled powder that can be directly administered to the lungs to treat the agitation associated with psychiatric disorders, such as schizophrenia and bipolar disorder. Thus, the aim of this narrative and clinical mini-review was to evaluate the efficacy and tolerability of inhaled loxapine in the treatment of acute agitation in patients with psychiatric disorders. The efficacy of inhaled loxapine has been evaluated in one Phase II trial on patients with schizophrenia, and in two Phase III trials in patients with schizophrenia and bipolar disorder. Moreover, there are two published case series on patients with borderline personality disorder and dual diagnosis patients. Inhaled loxapine has proven to be effective and generally well tolerated when administered to agitated patients with schizophrenia and bipolar disorder. Two case series have suggested that inhaled loxapine may also be useful to treat agitation in patients with borderline personality disorder and with dual diagnosis, but further studies are needed to clarify this point. However, the administration of inhaled loxapine requires at least some kind of patient collaboration, and is not recommended in the treatment of severe agitation in totally uncooperative patients. Moreover, the drug-related risk of bronchospasm must always be kept in mind when planning to use inhaled loxapine, leading to a careful patient assessment prior to, and after, administration. Also, the higher costs of inhaled loxapine, when compared to oral and intramuscular medications, should be taken into account when selecting it for the treatment of agitation

Deficiencies in the Quality of Diabetes Care: Comparing Specialist with Generalist Care Misses the Point

The quality of diabetes care delivered to patients falls below the expectations of practice guidelines and clinical trial evidence. Studies in many jurisdictions with varying health care systems have shown that recommended processes of care occur less often than they should; hence, outcomes of care are inadequate. Many studies comparing care between specialists and generalists have found that specialists are more likely to implement processes of care. However, this provides little insight into improving quality of care, as the difference between specialists and generalists in these studies is small compared to the overall deficiency in quality. Therefore, future research should instead focus on ways to implement high quality care, regardless of specialty. To date, few methodologically rigorous studies have uncovered interventions that can improve quality of care. The development of such interventions to help all physicians implement better quality care could greatly benefit people with diabetes