Molecular biomarkers for vascular cognitive impairment and dementia:the current status and directions for the future

Dementia is a syndrome with various underlying pathologies acting independently or in concert to cause cognitive dysfunction.The development of disease-specific treatments and targeted prevention strategies requires precise clinical sub-typing via etiology and pathophysiological processes.Furthermore,recent research advances in biomarkers,especially for Alzheimer's disease(AD)diagnosis,have improved diagnostic precision for dementia.

Disorders of the brain-gut interaction and eating disorders

BACKGROUND Eating disorders(ED)involve both the nervous system and the gastrointestinal tract.A similar double involvement is also found in disorders of the brain-gut interaction(DGBI)and symptoms are sometimes similar.AIM To find out where there is an association and a cause-effect relationship,we looked for the comorbidity of DGBI and ED.METHODS A systematic review was undertaken.A literature search was performed.Inclusion criteria for the articles retained for analysis were:Observational cohort population-based or hospital-based and case-control studies,examining the relationship between DGBI and ED.Exclusion criteria were:Studies written in other languages than English,abstracts,conference presentations,letters to the Editor and editorials.Selected papers by two independent investigators were critically evaluated and included in this review.RESULTS We found 29 articles analyzing the relation between DGBI and ED comprising 13 articles on gastroparesis,5 articles on functional dyspepsia,7 articles about functional constipation and 4 articles on irritable bowel syndrome.CONCLUSION There is no evidence for a cause-effect relationship between DGBI and ED.Their common symptomatology requires correct identification and a tailored therapy of each disorder.

The prevalence of depression amongst outpatients with multimorbidity

Objectives: Depression may be under-diagnosed and under-treated amongst older adults with multiple chronic illnesses. The current study explores the prevalence of depression diagnosis and Geriatric Depression Scale (GDS) symptoms amongst older multimorbid outpatients, and agreement between GDS scores and doctor-diagnosed depression. Method: Deidentified data from the files of 452 patients aged over 64, with chronic conditions present in two or more organ domains, were extracted from the clinical database of a tertiary referral hospital multidisciplinary outpatient clinic in South Australia between 2005 and 2011. Frequency calculations determined the prevalence of depression diagnosis and GDS categories. Logistic regression, cross-tabulation, kappa and ROC graphs explored relationships between variables. Results: A depression diagnosis had been recorded for 71 (15.7%) patients. Using the recommended cut-off scores for the GDS, 225 (49.8%) patients met criteria for mild-severe depressive symptoms, and 96 (21.3%) met criteria for moderate-severe symptoms. Poor agreement was found between doctor diagnosis of depression and a positive screen for depression using a GDS cut-off score of either 5, k = 0.112 (p = 0.001), or 9, k = 0.189 (p < 0.001), although logistic regression found an association between severity of depression and depression diagnosis, OR = 1.15, p < 0.001 (CI = 1.08 - 1.22). Con-clusion: A much higher proportion of patients with multimorbidities reported threshold level depression symptoms than had a recorded diagnosis of depression, suggesting that although likelihood of diagnosis increases with symptom severity, depression often goes undetected in this population. Depressions’ negative impact on prognosis calls for further investigation of the barriers to screening and diagnosis of depression in multimorbid patients.

Psychiatry Trainees’ Attitudes towards Psychotherapy

Background: Psychotherapy education is one of the essential components of specialist training in psychiatry according to the Royal College of Physicians of Canada. How psychiatry trainees perceive psychotherapy has major implications for how trainees will learn about psychotherapy during training, how they will utilize it in their future practice, and how they will integrate it into their professional identity. Methods: The study involved the distribution of questionnaires to psychiatry residents at an Atlantic Canadian Medical School. The survey consisted of Likert-scaled items which assessed residents’ attitudes towards being a psychotherapist and their future study and practice plans in psychotherapy. Results: Surveys were completed by 18 out of 25 residents (72% response rate). Half of participants indicated that conducting psychotherapy was highly rewarding and the majority of residents planned to incorporate psychotherapy into their future practice. Several mean differences were also noted between those residents who completed their undergraduate medical education in Canada versus at International locations. Conclusion: Despite the recent changes in psychotherapy training requirements and concerns about psychotherapy’s role in psychiatry, many residents perceive psychotherapy skills as being important for competent psychiatry practice and plan to incorporate their psychotherapy training into their future practice. Additional implications for teaching, future research, and practice are discussed.

Long-Term Clinical Outcome of Patients Using Risperidone Long-Acting Injectable: The Romanian e-STAR Database

The objectives of e-STAR Romania (NCT00283517) were to collect clinical outcome data of Romania schizophrenia or schizo-affective disorder patients;prospectively to assess the reasons of treatment initiation, medication usage patterns;to document (long-term) clinical efficacy;and to collect safety data, as well as recording 2-year corresponding retrospective data. In total, 378 eligible subjects were enrolled who were initiated either on risperidone long-acting injectable (RLAI) (290) or on an oral antipsychotic (OA) (88) at baseline as required by the local Summary of the Product Characteristics. Data were collected from per patient both retrospectively and prospectively over a 24-month period at 3-month intervals after starting treatment. The results indicated that subjects suffering from schizophrenia or schizo-affective disorder initiated on RLAI were less likely to be hospitalized within the first 24 months after the initiation of treatment. Moreover, subjects treated with RLAI experienced significant improvements in their illness severity and functioning. Discontinuation rates for RLAI were low and doses were stable throughout the 24 months following the initiation of treatment. In addition, the necessity for supplementary concomitant medication was reduced. Adverse events were reported in 20.3% (RLAI) and 11.4% (OA) of the subjects. In general, patients initiated on RLAI and OA at baseline both clinically improved on all assessed parameters but a larger improvement was observed for patients on RLAI. Incidences of reported AEs during the use of RLAI in a naturalistic setting are comparable with those described in clinical studies;however, the incidence of extrapyramidal signs and weight gain was lower than expected.

Calibrating violence risk assessments for uncertainty

Psychiatrists and other mental health clinicians are often tasked with assessing patients’risk of violence.Approaches to this vary and include both unstructured(based on individual clinicians’judgement)and structured methods(based on formalised scoring and algorithms with varying scope for clinicians’judgement).The end result is usually a categorisation of risk,which may,in turn,reference a probability estimate of violence over a certain time period.Research over recent decades has made considerable improvements in refining structured approaches and categorising patients’risk classifications at a group level.The ability,however,to apply these findings clinically to predict the outcomes of individual patients remains contested.In this article,we review methods of assessing violence risk and empirical findings on their predictive validity.We note,in particular,limitations in calibration(accuracy at predicting absolute risk)as distinct from discrimination(accuracy at separating patients by outcome).We also consider clinical applications of these findings,including challenges applying statistics to individual patients,and broader conceptual issues in distinguishing risk and uncertainty.Based on this,we argue that there remain significant limits to assessing violence risk for individuals and that this requires careful consideration in clinical and legal contexts.

Exploring the link between brain topological resilience and cognitive performance in the context of aging and vascular risk factors:A cross-ethnicity population-based study

Brain aging is typically associated with a significant decline in cognitive performance.Vascular risk factors(VRF)and subsequent atherosclerosis(AS)play a major role in this process.Brain resilience reflects the brain’s ability to withstand external perturbations,but the relationship of brain resilience with cognition during the aging process remains unclear.Here,we investigated how brain topological resilience(BTR)is associated with cognitive performance in the face of aging and vascular risk factors.We used data from two cross-ethnicity community cohorts,PolyvasculaR Evaluation for Cognitive Impairment and Vascular Events(PRECISE,n=2220)and Sydney Memory and Ageing Study(MAS,n=246).We conducted an attack simulation on brain structural networks based on k-shell decomposition and node degree centrality.BTR was defined based on changes in the size of the largest subgroup of the network during the simulation process.Subsequently,we explored the negative correlations of BTR with age,VRF,and AS,and its positive correlation with cognitive performance.Furthermore,using structural equation modeling(SEM),we constructed path models to analyze the directional dependencies among these variables,demonstrating that aging,AS,and VRF affect cognition by disrupting BTR.Our results also indicated the specificity of this metric,independent of brain volume.Overall,these findings underscore the supportive role of BTR on cognition during aging and highlight its potential application as an imaging marker for objective assessment of brain cognitive performance.

Predictors of the placebo response in a nutraceutical randomized controlled trial for depression

Objective The placebo response in depression studies is the change in symptoms amongst those who receive an inactive treatment.Many well-designed randomized controlled trials(RCTs)of depression have a high proportion of placebo responders,with little understanding as to why.The present study assesses characteristics associated with the placebo response in a nutraceutical trial with a large proportion of placebo responders.Methods This is a secondary analysis of a nutraceutical depression RCT which identified no overall treatment benefit relative to placebo(n=69 in placebo group).We investigated participant characteristics such as socio-demographics,clinical features,and recruitment methods,and their association with the placebo response.Monoaminergic genetic polymorphisms were also assessed.Placebo response was measured based on change in Montgomery-Asberg Depression Rating Scale score.The association of these hypothesis-driven variables of interest and the placebo response was examined using linear mixed effects models.Results Greater levels of education,particularly pursuing post-high school education,better self-reported general health,marriage/de facto,greater improvement in the first trial week,and more failed antidepressant therapies in the current depressive episode were associated with greater placebo response.An increased placebo response was not found in those recruited via social media nor in those with concomitant antidepressant therapy.Single nucleotide polymorphisms from the tryptophan hydroxylase 1(TPH1)gene(A779C and A218C)were weakly associated with greater placebo response,although the evidence was attenuated after accounting for multiple comparisons.Conclusion This is,to our knowledge,the first study within nutraceutical research for depression to assess the association between participant characteristics and variation in the placebo response.Several variables appeared to predict the placebo response.Such findings may encourage future trial designs which could dampen placebo response,improve assay sensitivity,and allow for treatment effects to be potentially more detectable.

Depression, anxiety, and cardiac morbidity outcomes after coronary artery bypass surgery： a contemporary and practical review

Research to date indicates that the number of coronary artery bypass graft （CABG） surgery patients affected by depression （i.e., major, minor, dysthymia） approximates between 30% and 40% of all cases. A longstanding empirical interest on psychosocial factors in CABG surgery patients highlights an association with increased risk of morbidity in the short and longer term. Recent evidence suggests that both depression and anxiety increase the risk for mortality and morbidity after CABG surgery independent of medical factors, although the behavioral and biological mechanisms are poorly understood. Though neither depression nor anxiety seem to markedly affect neuropsy- chological dysfunction, depression confers a risk for incident delirium. Following a comprehensive overview of recent literature, practical advice is described for clinicians taking into consideration possible screening aids to improve recognition of anxiety and depression among CABG surgery patients. An overview of contemporary interventions and randomized, controlled trials are described, along with suggestions for future CABG surgery research.

Regulation and postsynaptic binding of neurexins - drug targets for neurodevelopmental and neuropsychiatric disorders

Neurexins （NRXNs） have been linked to neurodevelopmental and neuropsychiatric disorders and have become attractive drug targets. They are transmembrane neuronal adhesion molecules and play important roles in the formation and differentiation of synapses and synaptic activity. Many postsynaptic binding partners of NRXNs have been identified. The interactions between NRXNs and postsynaptic binding partners can be regulated by alternative splicing, synaptic activity, and RNA binding proteins. The postsynaptic interactive partners may compete with each other for NRXN binding. The expression of NRXNs can also be regulated transcriptionally and post-transcriptionally. Genetic polymorphism may affect the function and expression of NRXNs. In this review, we will summarize the recent advance in these areas. Understanding the biology of neurexin signaling is essential for developing neurexin-based drugs.