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Previous genetic association studies have failed to identify loci robustly associated with sepsis, and there have been no published genetic association studies or polygenic risk score analyses of patients with septic shock, despite evidence suggesting genetic factors may be involved. We systematically collected genotype and clinical outcome data in the context of a randomized controlled trial from patients with septic shock to enrich the presence of disease-associated genetic variants. We performed genomewide association studies of susceptibility and mortality in septic shock using 493 patients with septic shock and 2442 population controls, and polygenic risk score analysis to assess genetic overlap between septic shock risk/mortality with clinically relevant traits. One variant, rs9489328, located in AL589740.1 noncoding RNA, was significantly associated with septic shock (p = 1.05 × 10–10); however, it is likely a false-positive. We were unable to replicate variants previously reported to be associated (p < 1.00 × 10–6 in previous scans) with susceptibility to and mortality from sepsis. Polygenic risk scores for hematocrit and granulocyte count were negatively associated with 28-day mortality (p = 3.04 × 10–3; p = 2.29 × 10–3), and scores for C-reactive protein levels were positively associated with susceptibility to septic shock (p = 1.44 × 10–3). Results suggest that common variants of large effect do not influence septic shock susceptibility, mortality and resolution; however, genetic predispositions to clinically relevant traits are significantly associated with increased susceptibility and mortality in septic individuals.
Geological, geomorphological and soil maps provide important information on the substrate as well as on the past and present physical landscape. For the intensely studied Netherlands coastal plain and Rhine–Meuse delta, many such map datasets have been compiled over the last two centuries. These mapping materials comprise older and younger legacy datasets, often fragmented over regions. They have been compiled within various research traditions and by various parties, involving geologists, soil scientists, geomorphologists and landscape archaeologists. The maps and datasets summarise overwhelming amounts of underlying data accumulated over the last few centuries, and are therefore valuable for reconstructing past landscapes.
Digital-infrastructure developments have enhanced possibilities for recombining existing and new data over the last few decades, e.g. through GIS solutions such as palaeogeographical base maps, from which multiple derived map products can be generated. Integration of thematic information from various source maps and underlying data is needed to use the accumulated data diversity to its full potential and to answer applied and fundamental scientific questions. Using diverse information to compile or update maps, however, requires awareness of legacy surveying strategies and the state of knowledge at the time the original data and maps were produced. This paper reviews the soil, geological and geomorphological mapping traditions. We evaluate their products, underlying data and the reasoning behind their compilation, focusing on their use in conventional and digital palaeogeographical mapping. This helps get the most out of large quantities of legacy and modern data, a major challenge for surface and substrate digital mapping in the big-data era.
Asenapine is indicated in adults for acute treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder with or without psychotic features. We report the safety, tolerability, and efficacy of asenapine in patients with bipolar I disorder completing up to 52 weeks of treatment.
Patients completing either of two 3-week efficacy trials and a 9-week double-blind extension were eligible for this 40-week double-blind extension. Patients in the 3-week trials were randomized to flexible-dose asenapine (5 or 10 mg BID), placebo, or olanzapine (5-20 mg QD; included for assay sensitivity only). Patients entering the extension continued their preestablished treatment; those originally randomized to placebo received flexible-dose asenapine (placebo/asenapine, 5 or 10 mg BID). Safety and tolerability endpoints included adverse events (AEs), extrapyramidal symptoms, laboratory values, and anthropometric measures. Efficacy was measured as the change in Young Mania Rating Scale (YMRS) total score from 3-week trial baseline to week 52; the placebo/asenapine group was included in the safety analyses.
Incidence of treatment-emergent AEs was 71.9%, 86.1%, and 79.4% with placebo/asenapine, asenapine, and olanzapine, respectively. The most frequent AEs included headache and somnolence (placebo/asenapine); insomnia, sedation, and depression (asenapine); and weight gain, somnolence, and sedation (olanzapine). Mean ± SD changes in YMRS score at week 52 among observed cases in the intent-to-treat population were -28.6±8.1 for asenapine and -28.2±6.8 for olanzapine.
In this 52-week study, asenapine was well tolerated and long-term maintenance of efficacy was supported in patients initially presenting with bipolar mania.
People with severe mental illnesses, such as schizophrenia, depression or bipolar disorder, have worse physical health and reduced life expectancy compared to the general population. The excess cardiovascular mortality associated with schizophrenia and bipolar disorder is attributed in part to an increased risk of the modifiable coronary heart disease risk factors; obesity, smoking, diabetes, hypertension, and dyslipidaemia.
Over recent years both national and international groups have developed screening and monitoring guidelines but these are not being routinely implemented in the clinical care of patients. A review of the literature identifies barriers to comprehensive screening, monitoring and treatment of somatic co-morbidities on the level of professionals (both within psychiatry as well as in primary care), patients, health care systems (organisational and financial aspects) and health policies.
Psychiatrists and primary care physicians should play an active role in ensuring that patients with mental illness are not disadvantaged. Measures should include the assessment and management of cardiovascular risk factors and diabetes as part of the care of their psychiatric patients. When indicated, shared care with cardiologists, diabetologists, specialist nurses or other specialists should be established.
The aim of the recent joint statement on cardiovascular disease an diabetes in people with severe mental illness of the EPA, EASD and ESC is to reduce cardiovascular risk and to improve diabetes care in patients with SMI and to improve overall health and well-being of the patients (De Hert et al. 2009). This should reduce the burden of physical illness for patients, their families and healthcare services.
Catechol-O-methyltransferase (COMT) has a central role in brain dopamine, noradrenalin and adrenalin signaling, and has been suggested to be involved in the pathogenesis and pharmacological treatment of affective disorders. The functional single nucleotide polymorphism (SNP) in exon 4 (Val158Met, rs4680) influences the COMT enzyme activity. The Val158Met polymorphism is a commonly studied variant in psychiatric genetics, and initial studies in schizophrenia and bipolar disorder presented evidence for association with the Met allele. In unipolar depression, while some of the investigations point at an association between the Met/Met genotype and others have found a link between the Val/Val genotype and depression, most of the studies cannot detect any difference in Val158Met allele frequency between depressed individuals and controls.
In the present study, we further elucidated the impact of COMT polymorphisms including the Val158Met in MDD. We investigated 1,250 subjects with DSM-IV and/or ICD-10 diagnosis of major depression (MDD), and 1,589 control subjects from UK. A total of 24 SNPs spanning the COMT gene were successfully genotyped using the Illumina HumaHap610-Quad Beadchip (22 SNPs), SNPlex™ genotyping system (1 SNP), and Sequenom MassARRAY® iPLEX Gold (1 SNP). Statistical analyses were implemented using PASW Statistics18, FINETTI (http://ihg.gsf.de/cgi-bin/hw/hwa1.pl), UNPHASED version 3.0.10 program and Haploview 4.0 program.
Neither single-marker nor haplotypic association was found with the functional Val158Met polymorphism or with any of the other SNPs genotyped. Our findings do not provide evidence that COMT plays a role in MDD or that this gene explains part of the genetic overlap with bipolar disorder.
Given the limited knowledge on the long-term outcome of adolescents who receive electroconvulsive therapy (ECT), the study aimed to follow-up adolescents treated with ECT for severe mood disorder. Eleven subjects treated during adolescence with bilateral ECT for psychotic depression (n = 6) or mania (n = 5), and ten psychiatric controls matched for sex, age, school level, and clinical diagnosis, completed at least 1 year after treatment a clinical and social evaluation. Mean duration between time of index episode and time of follow-up evaluation was 5.2 years (range 2–9 years). At follow-up: (1) all patients except two in the control group received a diagnosis of bipolar disorder. (2) Fifteen patients had had more than one episode of mood disorder. (3) The two groups did not differ in social functioning nor school achievement. (4) Impact on school achievement was related to the severity of the mood disorder rather than ECT treatment. The results suggest that adolescents given ECT for bipolar disorder, depressed or manic, do not differ in subsequent school and social functioning from carefully matched controls.
We shall present the development of a cohort of 40 children aged from 6 to 11 who were initially diagnosed with ADHD (T0) and then reassessed after two years of treatment with multimodal treatment in addition to stimulant medication. At the outset of the study (T0) the children underwent a complete assessment which included a child psychiatric examination, a neuropsychological evaluation of attention skills and a psychodynamic psychological assessment using the T.A.T. and Rorschach projective tests interpreted from a psychoanalytic viewpoint. An identical protocol was used for the reassessment of the children two years later (T2).
Clinically, and from a strictly behavioral point of view, it is clear that there was a calming down of the symptoms associated with the ADHD. Can the same be said for the results of the neuro-psychological and projective tests as well as for the overall psychic functioning of the children?
At this point in our research, and taking into account that T 2 just ended, we can affirm that the children who were assessed with neurotic disorders (according to the classification of psychopathological disorders in childhood) were those who showed the clearest signs of improvement. We shall then study in depth the majority of the population who were assessed with borderline personality disorders (BPD). As these children received a multimodal treatment over the two years time of the study which involved either individual, group or family psychotherapy, we shall use brief clinical case studies for a comparative approach to our research results.
According to Oedegaard et al. (2010) the co-morbidity of migraine and bipolar disorder (BPD) is well documented in numerous epidemiological and clinical studies, and there are clear pathophysiological similarities. Interestingly, in a genome-wide scan, Lea et al. (2005) identified a susceptibility locus for a severe heritable form of common migraine on chromosome 3q29. With respect to BPD, a susceptibility region on chromosome 3q29 was identified in a genome-wide linkage scan (Bailer et al. 2002) and follow-up linkage analysis (Schosser et al. 2004). These findings were also supported by further fine-mapping of this region (Schosser et al. 2007). Since 3q29 is among the chromosomal regions implicated in migraine and bipolar linkage studies, the aim of the current study is to test for 3q29 association of migraine in sample of patients with BPD. The sample consists of 463 patients with a diagnosis of BPD (34.63% men, 65.37% women; mean age ± SD: 48.01 ± 11.26), as defined by the Diagnostic and Statistical Manual 4th edition operational criteria (DSM-IV) and the International Classification of Diseases 10th edition operational criteria (ICD-10), derived from the Bipolar Affective Disorder Case Control Study (BACCS). A total of 51 SNPs in the region of the 3q29 were genotyped using Sequenom MassARRAY® iPLEX Gold and tested for association with migraine. The results of this association study investigating the 3q29 region in a sample of patients with BPD will be presented.
Second-generation antipsychotics (SGA) are being used more often than ever before in children and adolescents with psychotic and a wide range of non-psychotic disorders. Several SGA have received regulatory approval for some paediatric indications in various countries, but off-label use is still frequent. The aim of this paper was to perform a systematic review and critically evaluate the literature on cardiometabolic and endocrine side-effects of SGA in children and adolescents through a Medline/Pubmed/Google Scholar search of randomized, placebo controlled trials of antipsychotics in children and adolescents (<18 years old) until February 2010. In total, 31 randomized, controlled studies including 3595 paediatric patients were identified. A review of these data confirmed that SGA are associated with relevant cardiometabolic and endocrine side-effects, and that children and adolescents have a high liability to experience antipsychotic induced hyperprolactinaemia, weight gain and associated metabolic disturbances. Only weight change data were sufficiently reported to conduct a formal meta-analysis. In 24 trials of 3048 paediatric patients with varying ages and diagnoses, ziprasidone was associated with the lowest weight gain (−0.04 kg, 95% confidence interval [CI]: −0.38 to +0.30), followed by aripiprazole (0.79 kg, 95% CI: 0.54 to 1.04], quetiapine (1.43 kg, 95% CI: 1.17 to 1.69) and risperidone (1.76 kg, 95% CI: 1.27 to 2.25) were intermediate, and olanzapine was associated with weight gain the most (3.45 kg, 95% CI: 2.93 to 3.97). Significant weight gain appeared to be more prevalent in patients with autistic disorder who were also younger and likely less exposed to antipsychotics previously. These data clearly suggest that close screening and monitoring of metabolic side effects is warranted and that the least cardiometabolically problematic agents should be used first whenever possible. A good collaboration between child- and adolescent psychiatrists, general practitioners and paediatricians is essential to maximize overall outcomes and to reduce the likelihood of premature cardiovascular morbidity and mortality.
Negative attitudes towards treatment hospitalization of patients with borderline personality disorder (BPD) exist among mental health clinicians. These attitudes could affect the treatment administered to these patients, the length of hospitalization and its cost.
To establish recommendations for health officials regarding the hospitalization and treatment of BPD patients in order to shorten the length of hospitalization of patients with BPD and improve the quality of their treatment.
A thorough examination of the attitudes towards BPD patients among four professions (psychiatrists, psychologists, social workers and nurses) in four hospitals, and of the directors of the hospitals and of several wards, so as to evaluate their policy regarding the admission and the treatment of BPD patients.
We administered questionnaires on explicit and implicit attitudes towards these patients to 710 clinicians in 4 hospitals in Israel, and interviewed the hospitals’ directors and several ward directors. We collected data on the hospitalizations of patients with BPD during the period 2009-2011 and analyzed differences on these measures between professions and hospitals.
Nurses and psychiatrists had the most negative attitudes towards these patients, and differences were noted between hospitals. While hospital D was characterized by more negative attitudes, less negative attitudes were found in hospital A, and accordingly the longer were admissions and hospitalizations’ costs in this hospital.
Nurses and psychiatrists are likely to express negative attitudes towards these patients. Possibly, the directors’ attitudes and policy influenced lengths of the hospitalizations and costs of treatment of BPD patients.
The purpose of this talk is to present a study on risk assessments of female sex offenders. The literature on this issue focuses mainly on male sex offenders. By contrast, the literature on female sex offenders is scarce and mostly recent. Moreover, the law regarding sex offenders does not usually deal with offences committed by females. For example, in Israel section 345 of the criminal code refers solely to male rapists. In recent years we are witnessing a rise in the number females who are brought to justice for committing sex offences. Sex offence assessment is a professional process whereby the probability that a certain behavior will occur within certain terms and in a given range of time is assessed. The assessment takes into account the attributes of both, the assault and the perpetrator. During the last few years much research on risk assessment of male sex offenders has been carried out. However, research on female sex offenders is scanty. As of today, there is no theoretical or data base for assessing sexual recidivism of female sex offenders. Assessment criteria are still unclear, and it is still impossible to ascertain whether the actuarial tools which are commonly used for risk assessment of male sexual offenders are valid for females. In the present study actuarial tools and clinical criteria for assessing female sex offenders were compared. The main finding we found is correlation between actuarial tools and dynamic criteria. The main criticism is that the actuarial tools includes
A substantial proportion of schizophrenia patients also meets DSM-IV criteria for obsessive-compulsive disorder (OCD). Schizophrenia with OCD (“schizo-obsessive”) patients are characterized by distinct clinical characteristics, treatment response and prognosis. Whether schizo-obsessive patients exhibit a distinct pattern of brain activation is yet unknown. To address this question, the present functional magnetic resonance imaging (fMRI) study explicitly compared alterations in brain activation and functional connectivity (FC) underlying a working memory deficit in schizophrenia patients with and without OCD.
fMRI was applied during the N-back working memory (WM) task in three groups: schizo-obsessive (n = 16), schizophrenia (n = 17) and matched healthy volunteers (n = 20). WM-related activation in the right dorsolateral prefrontal cortex (DLPFC) and the right caudate nucleus, brain areas relevant to schizophrenia and OCD, and FC analysis were used for the evaluation.
The two schizophrenia groups with and without OCD exhibited a similar reduction in activation in the right DLPFC and right caudate, as well as decreased FC compared to the healthy controls. Notably, reduced regional brain activation was not related to severity of schizophrenic or OCD symptoms.
Schizo-obsessive patients do not differ from their non-OCD schizophrenia counterparts in brain activation patterns during the N-back WM task. Cognitive paradigms taping alternative neural networks (e.g., orbitofrontal cortex) particularly relevant to OCD, are warranted in the search for potential distinctive brain activation patterns of the schizo-obsessive subgroup.
White matter development during adolescents is crucial for a mature integration of neural networks in the brain. Autism spectrum condition (ASC), characterized by social and communication difficulties and rigid behaviour may interact with white matter development observed during adolescence. Changes in white matter development may link autistic symptoms to its genetic underpinnings and explain a 10-fold increase in susceptibility to ASC among siblings of individuals with ASC.
We used diffusion tensor imaging to study an association between age and white matter integrity measures, fractional anisotropy (FA) and mean diffusivity (MD), in adolescents with ASC, their siblings and age-matched healthy controls. Diffusion-weighted data were acquired with 64-direction protocol with 3mm slices and TR of 6600ms and tract-based spatial statistics analysis was performed.
The control subjects showed robust signs of increase in white matter integrity correlated with age. In contrast, individuals with ASC showed significantly lower negative correlation between MD and age in a broad area centred in the right superior longitudinal fasciculus (rSLF). When the three eigenvalues constituting a tensor ellipsoid were considered separately, siblings of individuals with ASC showed a diminished negative correlation between the second eigenvalue and age also centred in the rSLF.
Adolescents with ASC and their siblings experience alterations in white matter development in comparison to age-matched healthy controls, which are similar in direction yet different in scale for the two affected groups. The alterations are observed in the area associated with flexibility of behaviour and may explain both symptoms of ASC and increased susceptibility to ASC.
Schizophrenia patients in positive symptomatic remission (PSR; n = 39) were assessed using a longitudinal research design. The patients were found to exhibit widespread cognitive impairments that were stable over the three-year follow-up period. The findings support a generalized and stable cognitive impairment profile among schizophrenia patients in partial symptomatic remission.
Little evidence is available on the prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immuno deficiency virus (HIV) in mentally ill populations. In April 2012 routine offering of testing for HBV, HCV and HIV of all individuals admitted at Broadmoor, a maximum secure psychiatric hospital, was introduced.
To elicit screening rates of, and to determine the prevalence of HBV, HCV and HIV in the inpatient population at Broadmoor Hospital.
To critically assess the identification process of blood-borne viruses (BBV) in order to improve patient care.
Retrospective data collection via the electronic patient record (EMIS) ascertained the proportion of the 198 inpatients offered screening and ultimately tested for HBV, HCV and HIV inclusive from April 1st 2012 to September 22nd 2012.
The proportion offered screening for HBV was 95% (189); for HCV was 94.9% (188) and for HIV was 92.9% (184). 129 patients were screened in each hepatitis group and 123 in the HIV group. Within the population of Broadmoor were three cases of HCV, one with HIV and zero with HBV.
This is a group at high risk for BBV infection and with a length of stay of up to five to six years it is important to identify those infected in order to instigate treatment and mitigate risk to both patients and staff. This study demonstrates rigorous screening for BBV is critical and will therefore necessarily impact on planning services for the future.
The heterogeneity in the manifestation of PSTD symptomatology has never been described in a developmental period spanning from middle childhood through adolescence. The examination of developmental influences on PTSD symptomatic expression is a high priority for DSM-V and could inform research on the etiology and treatment of PTSD.
To examine the symptom structure of PTSD across different age, gender, and exposure groups, and in association with impairment and other disorders.
To identify homogeneous latent classes of PTSD symptoms in children and adolescents.
Latent class analysis (LCA) was applied to 6,733 New York City students (4th–12th grades) exposed to 9/11-related potentially traumatic events. LCA was first applied to PTSD symptoms only, stratified by age, gender and empirically defined exposure groups, and then in combination with impairment indicators. The resultant classes were studied in association with other disorders.
LCA identified 4 classes that vary in severity and symptom configuration. Only the most severe profile, qualitatively characterized by the presence of traumatic memories in combination with avoidance and sleep-related problems, showed high levels of impairment and high rates of other disorders. Girls after puberty and subjects indirectly exposed to 9/11 are at increased risk of severe disturbance.
The 4-class model describes quantitative and qualitative differences in the structure of PTSD across age, gender and exposure. These findings support the inclusion of developmental considerations into DSM-V PTSD diagnostic criteria and suggest that also gender and the nature of traumatic exposure inflence PTSD phenomenology in children and adolescents.
The capacity to accumulate information over time is crucial to our functioning in an ever-changing world. Recently, in healthy subjects, we showed that brain uses a distributed and hierarchical network of brain areas to process information over time. Specifically, we revealed hierarchy of information processing over time from early sensory areas toward high order perceptual and cognitive areas. Here, we investigate this issue in first-episode schizophrenia patients.
Previous studies posited that schizophrenia is the result of impairment of hierarchical temporal processing by the brain, claiming for impairment in use of context while being processing information. The hierarchical temporal deficit is a fundamental trait that may be a better target for the study of etiology and pathophysiology of the disease.
We intended to map, in schizophrenia patients, the topographical organization of temporal scales using an ecologically relevant auditory stimulus - a real-life story. In addition, we assumed that studying healthy siblings, who are at high-risk for cognitive dysfunctions, will enable to determine functional neuromarkers of predisposition to disorder.
The fMRI data were analyzed using inter-subject correlation approach. The time-courses within each brain area in schizophrenia patients were estimated against healthy controls and unaffected siblings of the patients.
Among patients, we observed impaired hierarchy with processing intact in low level but disturbed in high level. The sibling group showed an intermediate effect.
Better understanding of the underlying neural circuit involved in information processing in schizophrenia patients may assist in early identification of functional neuromarkers for the disease.
White-matter abnormalities are sometimes associated with mood disorders, and atypical depression may be related with a leukodystrophy.
A case report of a treatment-resistant depression with cognitive deficits and extensive white-matter hyperintensities suggested a literature review on this unattended association.
A 33 yrs. woman was recovered in our psychiatric ward with a recurrent depressive disorder, partially resistant to antidepressant for eleven years. MADRS score was 26 at admission, without significant anxiety or psychotic symptoms. After 12 days, she presented delirium with neurological localisation symptoms. MRI examination put in evidence confluent hypersignal of white matter with demyelinisation, without grey-matter lesion. No biological or enzymatic abnormalities were detected. A severe executive dysfunction with information slowing was detected on neuropsychological assessment. We performed a literature review on the association of depression and leukodystrophy.
The presented case is a probable Childhood Ataxia with Cerebral Hypomyelination (CACH) syndrome lately revealed by treatment-resistant depression. It represents 30% of all causes of leukodystrophy, and as it is described typically in a childhood form, an onset at adulthood has also been reported, sometimes with foreground behavioural and affective disorders. in that form, it may present with a treatment-resistant and atypical depression.
Treatment-resistant depression in young people with an atypical presentation may be related with an extensive white-matter disease, and a complete evaluation including MRI, biological, enzymatic, neuropsychological assessments, is therefore recommended.