E. Stella

Metabolic issues in patients affected by schizophrenia: clinical characteristics and medical management

Patients affected by psychotic disorders are more likely to develop high rates of co-morbidities, such as obesity, type 2 diabetes, dyslipidemias, hypertension, metabolic syndrome, myocardial infarction, stroke etc., in the long-term. These morbidities have a significant impact on the life-expectancy of these patients. Patients with chronic psychoses show a 2–3-fold increased risk of death mostly from cardiovascular and metabolic diseases. Although there may be an independent link, between schizophrenia and metabolic conditions the cardio-metabolic risk is mostly related to an unhealthy lifestyle and the usage of antipsychotic agents (especially Second Generation Antipsychotics or atypical) even when these remain effective treatments in the management of major psychoses. Recently, many international organizations have developed screening and monitoring guidelines for the control of modifiable risk factors in order to reduce the rate of co-morbidity and mortality among patients affected by schizophrenia. This paper is a review of current knowledge about the metabolic issues of patients affected by schizophrenia and describes clinical characteristics and medical management strategies for such conditions.

Suicide in the Early Stage of Schizophrenia.

Suicide is a relevant leading cause of death among patients affected by schizophrenia. Even if suicidal ideation may be present in different stages of disease, some differences have been described between the risk of suicide in patients experiencing first episode of psychosis and those with long-term schizophrenia. It is particularly higher during the first year of illness and reaches a steady decline over the following years. Suicidal ideation and attempts may also be common among subjects with subthreshold psychotic experiences. Factors associated with the risk of suicide in the early phase of schizophrenia are previous suicidal attempts and social aspects: the lack of social support and stable relationships, social drift after the first episode, and social impairment. Also, several psychotic symptoms (suspiciousness, paranoid delusions, mental disintegration and agitation, negative symptoms, depression and hopelessness, and command hallucinations) and substance abuse are associated with higher risk of suicide. It has been described that perfectionism and good levels of insight among individuals who have recently developed psychotic symptoms are significantly associated with higher numbers of suicidal attempts. Moreover, recent evidences show that prefrontal cortex-based circuit dysfunction may be related to suicide in the early stage of schizophrenia. This narrative review summarizes available evidences on suicide in the early stage of schizophrenia and deals with issues to be further studied and discussed.

Psychiatry meets pharmacogenetics for the treatment of revolving door patients with psychiatric disorders

ABSTRACT Introduction: Therapeutic failures (TFs) and adverse drug reactions (ADRs), together with the recurring nature of the clinical course of psychiatric disorders, mainly bipolar disorders (BDs), strongly contributed to the prevalence and frequency of hospital readmissions observed in these patients. This is the revolving door (RD) condition, dramatically rising costs for the management of these patients in psychiatric settings. Areas covered: We searched in the medical literature until May 2016 to review the role of functional variants in the cytochrome P450 (CYP) 2D6 gene on observed ADRs and TFs in RD patients with BDs, conferring a different capacity to metabolize psychotropic drugs. Expert commentary: CYP2D6 functional polymorphisms might directly contributed to the prevalence and frequency of the RD condition, commonly observed in BD patients. Although several environmental and socio-demographic/diagnostic variables such as alcohol/drug abuse, and medication non-compliance accounted for a significant proportion of the ability to predict RD prevalence and frequency, the pharmacogenetics of CYP, particularly CYP2D6, may help to identify BD patients at risk for ADRs and TFs. These patients may be addressed towards alternative treatments, thus improving their quality of life, and reducing RD prevalence and frequency and the overall costs for their management.

Pharmacogenetics of neurological and psychiatric diseases at older age: has the time come?

ABSTRACT Introduction: In recent years, a number of pharmacological approaches for treating neuropsychiatric conditions at older age have proven to be inadequate. The resulting increased prevalence of therapeutic failures (TF) and a worsening of clinical symptoms often linked to adverse reactions (ADRs), are perhaps among the major causes of the increasing rate of hospitalizations and institutionalizations observed in these patients. Areas covered: This review underlines the importance of pharmacogenetic data to fingerprint the pharmacological treatment of neuropsychiatric late-life conditions throughout the analysis of metabolizing enzymes and transporters of psychotropic drugs, mainly those of the cytochrome P450 (CYP) family. Pharmacodynamic response measures as treatment effects mediated through targets (i.e., receptors in the brain) may also contribute to this image. Expert opinion: CYP genetics is the basis of a continuum on which environmental and physiological factors act, modeling the phenotype observed in clinical practice with advancing age. Furthermore, other specific polymorphic genes influence drug response through differential effects of their functional genetic variants. The known genotypes associated with an altered metabolizer status and drug transporters may help clinical decision-making to avoid concomitant treatments, reduce therapeutic attempts and increase drug safety in neuropsychiatric conditions in older age, after controlling for other clinical variables.

Empathy and attitudes towards mental illness among Italian medical students

ABSTRACT There is a growing interest regarding the attitudes of medical students towards people with mental illness, since discrimination and stigma may affect healthcare workers and education should be aimed to improve empathy and attitudes at medical school level. A cross-sectional study was conducted at medical schools in Rome and Foggia (Italy). We recruited 339 medical students who completed an anonymous self-report questionnaire including sociodemographic data, the 40-item Community Attitudes toward the Mentally Ill scale (CAMI) and the 60-item Baron Cohen’s Empathy Quotient. The questionnaires were administered before and after the yearly academic course of psychiatry. This study shows a significant improvement in some CAMI items and total score after the yearly academic course of psychiatry among medical students, especially among those who had personal experience with mentally ill people (including the training in a psychiatric ward). Female students reported higher empathy quotient and CAMI scores. Students who preferred medical disciplines to surgical ones seemed to be less stigmatizing towards mental illness. Our results confirm evidence from the scientific literature about medical students’ attitudes towards mental illness and highlight that the improvements in the attitudes increased improving students’ psychiatric knowledge, both theoretical and practical.

Innovative biomarkers in psychiatric disorders: a major clinical challenge in psychiatry

ABSTRACT Introduction: Currently, the diagnosis of psychiatric illnesses is based upon DSM-5 criteria. Although endophenotype-specificity for a particular disorder is discussed, the identification of objective biomarkers is ongoing for aiding diagnosis, prognosis, or clinical response to treatment. We need to improve the understanding of the biological abnormalities in psychiatric illnesses across conventional diagnostic boundaries. The present review investigates the innovative post-genomic knowledge used for psychiatric illness diagnostics and treatment response, with a particular focus on proteomics. Areas covered: This review underlines the contribution that psychiatric innovative biomarkers have reached in relation to diagnosis and theragnosis of psychiatric illnesses. Furthermore, it encompasses a reliable representation of their involvement in disease through proteomics, metabolomics/pharmacometabolomics and lipidomics techniques, including the possible role that gut microbiota and CYP2D6 polimorphisms may play in psychiatric illnesses. Expert opinion: Etiologic heterogeneity, variable expressivity, and epigenetics may impact clinical manifestations, making it difficult for a single measurement to be pathognomonic for multifaceted psychiatric disorders. Academic, industry, or government’s partnerships may successfully identify and validate new biomarkers so that unfailing clinical tests can be developed. Proteomics, metabolomics, and lipidomics techniques are considered to be helpful tools beyond neuroimaging and neuropsychology for the phenotypic characterization of brain diseases.

Psychotropic drugs and CYP2D6 in late-life psychiatric and neurological disorders. What do we know?

ABSTRACT Introduction: Late-life psychiatric and neurological disorders (LLPND) are interesting models to understand the potential role of pharmacogenetics in drug management, since several pharmacological approaches for treating LLPND have proven to be ineffective or deleterious, thus resulting in therapeutic failures (TF) and adverse drug reactions (ADR). Common variants in the genes encoding the cytochrome P450 (CYP) enzyme system, the ‘engine room’ of drug metabolism, together with well-known age-related increased polypharmacy also contributed to the prevalence of TF and ADR observed in these patients, also rising number and time of hospital readmissions and rate of institutionalizations. Areas covered: The genetics of CYP and how it may be used for the management of the outcomes of the most frequent drugs (antidepressants, antipsychotics, anticholinesterase inhibitors, and anxiolytics) used in LLPND. Expert opinion: Tailored CYP-based pharmacological treatments of LLPND will reduce TFs and ADRs, improving patient’s life, reducing number and dosage of administered drugs, and the number and duration of hospital readmissions, saving costs for clinical management of LLPND. Pharmacokinetic interactions are less predictable than pharmacodynamic ones and several requests are made to regulatory organisms for the pharmacological management of frail older patients affected by LLPND.

The pharmacogenetic road to avoid adverse drug reactions and therapeutic failures in revolving door patients with psychiatric illnesses: focus on the CYP2D6 isoenzymes

ABSTRACT Introduction: A periodical hospital readmission caused by therapeutic failures (TFs) and a worsening of clinical symptoms most often linked to adverse drug reactions (ADRs) are probably the major causes for the so-called revolving door condition in psychiatric illnesses. This review underlined the importance that pharmacogenetic data on cytochrome P450 (CYP), particularly CYP2D6 polymorphisms, may offer for the finger printing of the pharmacological treatment of psychiatric illnesses, given the relevance of this enzyme in metabolizing psychotropic drugs. Areas covered: We searched in the medical literature until July 2016 to review the role of functional variants in the CYP2D6 gene on observed ADRs and TFs in revolving door psychiatric patients. Expert commentary: CYP2D6 gene variants could in part explain the revolving door condition in patients attending a psychiatric setting. The preemptive known CYP genotypes associated to a reduced metabolizer status may help clinical decision-making to avoid concomitant treatments, increasing drug safety, so reducing therapeutic attempts, hospital admission, and the overall costs for the national health services. However, CYP2D6 gene is only a part of a complex mechanism in which genetic and non-genetic factors may take part. A possible role of the intrinsic variability of pharmacodynamics and imponderable environmental factors influencing the revolving door condition cannot be excluded.

Migration, violence, and the role of psychiatry in Italy

Abstract Immigration to Italy has been increasing exponentially in the last decades due to the international political changes and conflicts in the Middle East. The relationship between immigration and crimes is a debated issue, and violent radicalization of second or third generations of migrants is under increased scrutiny. Consequently, many politicians and political parties use nationalist and xenophobic language. Inevitably, this will have an impact on reactions of the larger population, as well as that of migrants. Psychiatry can have a major role in dealing with immigrants’ health needs, and also assessing risk and preventing violent behaviours due to mental disorders. It is possible to prevent some radicalization by employing strategies of education, leading to better integration of immigrants in the community (based on education, housing, work, etc.). However, often specialist services for migrants are lacking, and mental healthcare professionals may remain poorly trained. Italy is one of the major countries in Southern Europe with a large number of illegal and legal migrants; thereby, creating a major pressure on the resources. It is important to understand the links between globalization, migration, and violence in Italy, in order to prevent future radicalization. It is also useful for psychiatrists to act as advocates for migrants to help reduce xenophobia and discrimination supported by some national cultural and political movements. Ethno-psychiatric facilities should be promoted, as well as policies of support, integration, and prevention should be employed to promote legal migration through the European countries.

Acculturation and Migration: Language- Proficiency Among Immigrant Psychiatric Patients in Italy

Aim This study tested the associations between Language-proficiency (LP) and clinical, therapeutic characteristics among hospitalized immigrants to study how LP may influence the presentation and the outcome of mental disorders. Background According to our previous evidences, lack of cultural adaptation may risk or worsen mental illness among immigrants, and interfere with assessment and treatment. Also, LP seems essential for access to foreign environments. In this study further considerations were made regarding LP on a larger sample of immigrant patients and longer period of observation. Method We reviewed clinical records of immigrant psychiatric patients hospitalized at the University of Foggia in 2004–2012 (N=153), and compared characteristics of patients with adequate versus inadequate language proficiency (LP). Results Subjects were 80 men and 73 women, aged 35.2±10.3 years, 50.3% emigrated from other European countries. Many were diagnosed with a DSM-IV adjustment disorder (31.3%) or depressive disorder (28.1%), and 69.9% were in first-lifetime episodes. Average comprehension and spoken language-proficiency (LP) was considered adequate in 62.7% and inadequate in 37.3%. Adequate-LP was more prevalent among women (p Conclusion Findings support an expected importance of LP among immigrant psychiatric inpatients, and encourage language-assessment and training as part of comprehensive support of such patients, especially men.