Well-being in patients with schizophrenia, mood and personality disorders attending psychiatric services in the community. A controlled study

Background: Poor attention is paid by recent research to the prevalence of mental well-being in psychiatric patients and the comparison between groups with different diagnoses. Data suggest that the presence of mental illness does not necessarily mean the absence of well-being, particularly in stable outpatients. Methods: A consecutive series of 375 patients attending two community mental health centers was given the Mental Health Continuum Short Form (MHC-SF) and the Clinical Global Impression – Severity scale. Diagnoses were made after the MINI Neuropsychiatric Interview and a chart review of all relevant clinical information. The flourishing category and the three components of MHC-SF were used to rate well-being. A total of 274 controls were taken from the employees at a local firm. Results: The rates of flourishing mental health were: 33.1% schizophrenia, 36.6% bipolar disorder, 23.3% unipolar depression, 24.4% cluster B personality disorder, and 53.3% controls (p < 0.001). The comparison of the three MHC components across diagnostic groups found that unipolar depression and cluster B personality patients had significantly lower scores compared to bipolar and schizophrenia patients. Flourishing mental health was detected more often in males than females (34.9% vs. 24.1% - p < 0.05). For schizophrenia patients indices of well-being were better in those on depot medications. Conclusions: Psychiatric outpatients with major mental illness have lower rates of well-being compared to controls, although about one-third is flourishing. Patients with unipolar depression and cluster B personality disorder may deserve special attention when planning intervention for fostering well-being. Keywords: Well-being, Flourishing, Mental health, Schizophrenia, MHC-SF, Depressio

Erratum to "Ziprasidone vs clozapine in schizophrenia patients refractory to multiple antipsychotic treatments: The MOZART study" [Schizophrenia Research 113 (2009) 112–121]

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Exome sequencing in schizophrenic patients with high levels of homozygosity identifies novel and extremely rare mutations in the GABA/glutamatergic pathways

Inbreeding is a known risk factor for recessive Mendelian diseases and previous studies have suggested that it could also play a role in complex disorders, such as psychiatric diseases. Recent inbreeding results in the presence of long runs of homozygosity (ROHs) along the genome, which are also defined as autozygosity regions. Genetic variants in these regions have two alleles that are identical by descent, thus increasing the odds of bearing rare recessive deleterious mutations due to a homozygous state. A recent study showed a suggestive enrichment of long ROHs in schizophrenic patients, suggesting that recent inbreeding could play a role in the disease. To better understand the impact of autozygosity on schizophrenia risk, we selected, from a cohort of 180 Italian patients, seven subjects with extremely high numbers of large ROHs that were likely due to recent inbreeding and characterized the mutational landscape within their ROHs using Whole Exome Sequencing and, gene set enrichment analysis. We identified a significant overlap (17%; empirical p-value = 0.0171) between genes inside ROHs affected by low frequency functional homozygous variants (107 genes) and the group of most promising candidate genes mutated in schizophrenia. Moreover, in four patients, we identified novel and extremely rare damaging mutations in the genes involved in neurodevelopment (MEGF8) and in GABA/glutamatergic synaptic transmission (GAD1, FMN1, ANO2). These results provide insights into the contribution of rare recessive mutations and inbreeding as risk factors for schizophrenia. ROHs that are likely due to recent inbreeding harbor a combination of predisposing low-frequency variants and extremely rare variants that have a high impact on pivotal biological pathways implicated in the disease. In addition, this study confirms that focusing on patients with high levels of homozygosity could be a useful prioritization strategy for discovering new high-impact mutations in genetically complex disorders

Epidemiology and economic impact of moderate and severe neurotrophic keratopathy in Italy

Neurotrophic keratopathy is a rare corneal disease caused by impaired corneal innervation. There is a paucity of published evidence on neurotrophic keratopathy with no published studies on the economics of neurotrophic keratopathy in the Italian or international literature. This cost analysis aimed at assessing the economic impact of moderate (persistent epithelial defect) and severe (corneal ulcer without perforation) neurotrophic keratopathy from the perspective of the National Health Service and patients in Italy. Treatment algorithm and health resource use information were collected from a panel of nine experts from Italian centres specialized in ocular/corneal conditions. National ambulatory and inpatient hospital tariffs were applied to units of service, and Agenzia Italiana del Farmaco (AIFA) published prices to pharmaceuticals. Mean annual per patient cost was derived as an average cost weighted by the proportion of patients on each respective treatment and length of the treatment. The National Health Service + patient perspective additionally included patients' out-of-pocket expenses. The mean annual estimated National Health Service cost of treatment was €5167 (persistent epithelial defect) and €10,885 (corneal ulcer without perforation) per patient. Costs were largely driven by ambulatory visits and hospital interventions. The mean annual estimated National Health Service + patient cost was €5731 (persistent epithelial defect) and €11,478 (corneal ulcer without perforation) per patient, including cost of out-of-pocket expenses for pharmaceuticals and therapeutic contact lenses. Mean annual cost of neurotrophic keratopathy in Italy doubles with disease severity. Further research is warranted to provide more insight especially into societal costs

New Copy Number Variations in Schizophrenia

Genome-wide screenings for copy number variations (CNVs) in patients with schizophrenia have demonstrated the presence of several CNVs that increase the risk of developing the disease and a growing number of large rare CNVs; the contribution of these rare CNVs to schizophrenia remains unknown. Using Affymetrix 6.0 arrays, we undertook a systematic search for CNVs in 172 patients with schizophrenia and 160 healthy controls, all of Italian origin, with the aim of confirming previously identified loci and identifying novel schizophrenia susceptibility genes. We found five patients with a CNV occurring in one of the regions most convincingly implicated as risk factors for schizophrenia: NRXN1 and the 16p13.1 regions were found to be deleted in single patients and 15q11.2 in 2 patients, whereas the 15q13.3 region was duplicated in one patient. Furthermore, we found three distinct patients with CNVs in 2q12.2, 3q29 and 17p12 loci, respectively. These loci were previously reported to be deleted or duplicated in patients with schizophrenia but were never formally associated with the disease. We found 5 large CNVs (>900 kb) in 4q32, 5q14.3, 8q23.3, 11q25 and 17q12 in five different patients that could include some new candidate schizophrenia susceptibility genes. In conclusion, the identification of previously reported CNVs and of new, rare, large CNVs further supports a model of schizophrenia that includes the effect of multiple, rare, highly penetrant variants

Self-ordered pointing and visual conditional associative learning tasks in drug-free schizophrenia spectrum disorder patients

<p>Abstract</p> <p>Background</p> <p>There is evidence of a link between schizophrenia and a deficit of working memory, but this has been derived from tasks not specifically developed to probe working memory per se. Our aim was to investigate whether working memory deficits may be detected across different paradigms using the self-ordered pointing task (SOPT) and the visual conditional associative learning task (VCALT) in patients with schizophrenia spectrum disorders and healthy controls. The current literature suggests deficits in schizophrenia spectrum disorder patients versus healthy controls but these studies frequently involved small samples, broad diagnostic criteria, inclusion of patients on antipsychotic medications, and were not controlled for symptom domains, severity of the disorder, etc. To overcome some of these limitations, we investigated the self-monitoring and conditional associative learning abilities of a numerically representative sample of healthy controls and a group of non-deteriorated, drug-free patients hospitalized for a schizophrenia spectrum disorder with florid, mainly positive psychotic symptoms.</p> <p>Methods</p> <p>Eighty-five patients with a schizophrenia spectrum disorder (DSM-IV-TR diagnosis of schizophrenia (<it>n </it>= 71) or schizophreniform disorder (<it>n </it>= 14)) and 80 healthy controls entered the study. The clinical picture was dominated by positive symptoms. The healthy control group had a negative personal and family history of schizophrenia or mood disorder and satisfied all the inclusion and exclusion criteria other than variables related to schizophrenia spectrum disorders.</p> <p>Results</p> <p>Compared to controls, patients had worse performances on SOPT, VCALT and higher SOPT/VCALT ratios, not affected by demographic or clinical variables. ROC curves showed that SOPT, VCALT, and SOPT/VCALT ratio had good accuracy in discriminating patients from controls. The SOPT and VCALT scores were inter-correlated in controls but not in patients.</p> <p>Conclusion</p> <p>The selection of a clinically homogeneous group of patients, controlled for a number of potential confounding factors, and the high level of significance found in the different analyses confirm the presence of SOPT and VCALT abnormalities in a large preponderance of patients with schizophrenia spectrum disorder with positive symptoms. SOPT, VCALT, and SOPT/VCALT ratio showed good accuracy in discriminating patients from healthy controls. These conclusions cannot be extended to schizophrenia spectrum disorder patients with a different clinical profile from our patient population.</p

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection