Depression and schizophrenia : cause, consequence or trans-diagnostic issue?

The presence of depression in schizophrenia has been a challenge to the Kraepelinian dichotomy, with various attempts to save the fundamental distinction including evoking and refining diagnoses such as schizoaffective disorder. But the tectonic plates are shifting. Here we put forward a summary of recent evidence regarding the prevalence, importance, possible aetiological pathways and treatment challenges that recognising depression in schizophrenia bring. Taken together we propose that depression is more than co-morbidity and that increased effective therapeutic attention to mood symptoms will be needed to improve outcomes and to support prevention

Mood instability : significance, definition and measurement

Mood instability is common, and an important feature of several psychiatric disorders. We discuss the definition and measurement of mood instability, and review its prevalence, characteristics, neurobiological correlates and clinical implications. We suggest that mood instability has underappreciated transdiagnostic potential as an investigational and therapeutic target

TH17 Cells in Autoimmunity and Immunodeficiency: Protective or Pathogenic?

In 2005 a newly discovered T helper cell subset that secreted interleukin (IL)-17 became the center of attention in immunology. Initial studies painted Th17 cells as the culprit for destruction in many different autoimmune and auto-inflammatory diseases. Subsequently, the discovery of patients with primary immunodeficiencies in the IL-17 pathway taught us that Th17 cells have a critical role in defense against certain fungal and bacterial infections. Moreover, the paradoxical exacerbation of Crohn’s disease in the clinical trials of a Secukinumab (AIN457), a fully human neutralizing antibody to IL-17A, has cast into doubt a universal pro-inflammatory and harmful role for Th17 cells. Evidence now suggests that depending on the environment Th17 cells can alter their differentiation program, ultimately giving rise to either protective or pro-inflammatory cells. In this review we will summarize the evidence from patients with immunodeficiencies, autoimmune, or auto-inflammatory diseases that teaches us how the pro-inflammatory versus protective function of Th17 cells varies within the context of different human diseases

Polymorphisms of MTHFR and MTR genes are not related to susceptibility to childhood ALL in north India

Background:Acute lymphoblastic leukemia (ALL) is the most worldwide common type of childhood cancer. Methylenetetrahydrofolate reductase (MTHFR) and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) participate in folate pathways and are known as critical factors for DNA integrity as well as DNA hypomethylation. The aim of this work is to investigate frequency of MTHFR (677C→T and 1298A→C) and MTR (2756A→G) polymorphisms and their interaction with respect to possible effect on risk of childhood ALL among North Indian population. Procedure: A case control study from has been conducted on bone marrow and peripheral blood samples from 125 ALL patients and 100 sex-age matched healthy controls using PCR-RFLP method. Results: No statistically significant differences were observed for different genotypes between patients and controls (p>0.05). Significant difference for the risk of ALL in individuals having genotype of MTHFR 677TT (OR=0.61, 95% CI=0.21–1.77) and MTHFR 1298CC (OR=0.56, 95% CI=0.18–1.68) was not observed. The correlation of SNP of MTR gene and risk of ALL was not observed, too. Conclusions: The differences in distribution of possible combined genotypes of MTHFR (677C→T, 1298A→C) and MTR (2756A→G) between ALL patients and controls were statistically insignificant

Prevalence of diaphragmatic muscle weakness and dyspnoea in Graves' disease and their reversibility with carbimazole therapy

Objectives: Dyspnoea is a common complaint among patients with thyrotoxicosis. However, its causative mechanisms have not been identified. We assessed the role of thoracic diaphragmatic muscle weakness in dyspnoea among patients with active Graves' disease. Methods: Twenty-seven patients (19 female, 8 male) with active Graves' disease were assessed for the clinical severity of dyspnoea, functional (pressure generating capacity) and anatomical aspects (thickness and excursion) of the diaphragm at presentation. The severity of dyspnoea was assessed using a visual analogue scale (VAS) and the 6 min walk test. Lung function tests, diaphragmatic strength (sniff oesophageal pressure, SniffPoeso), maximum inspiratory and expiratory pressures, diaphragmatic thickness and movements on real time ultrasonography were evaluated during normal and deep respiration. Twenty of the 27 patients were reassessed after achieving euthyroidism with carbimazole therapy at a mean interval of 5±2 months. Results: Reevaluation after carbimazole therapy revealed a significant reduction in dyspnoea on the VAS (59±26 to 23±13%). Patients covered a similar distance during the 6 min walk before and after euthyroidism. Significant improvement was observed in the vital capacity (2.57±0.62 to 2.94±0.60 l), forced expiratory volume in the first second (2.21±0.49 to 2.45±0.47 l), total lung capacity (3.57±1.19 to 4.1±1.12 l), diaphragmatic movement during deep respiration (5.5±1.0 to 6.6±1.1 cm) and SniffPoeso (68.7±23 to 93.1±25.2 cmH2O). There was no significant change in the distance walked in 6 min, tidal volume, lung diffusion capacity and diaphragmatic thickness. There was no significant correlation between the net change in dyspnoea score and net change in lung function tests, diaphragmatic movement and SniffPoeso. Conclusions: Significant functional weakness of diaphragm muscle is present in patients with active Graves' disease. This weakness is more marked during a maximal respiratory manoeuvre, indicating a diminished diaphragmatic reserve which could be the cause of dyspnoea observed on exertion among patients with thyrotoxicosis

Prevalence of psychosis in black ethnic minorities in Britain: analysis based on three national surveys

Purpose A considerable excess of psychosis in black ethnic minorities is apparent from clinical studies, in Britain, as in other developed economies with white majority populations. This excess is not so marked in population surveys. Equitable health service provision should be informed by the best estimates of the excess. We used national survey data to establish the difference in the prevalence of psychosis between black ethnic groups and the white majority in the British general population. Methods Analysis of the combined datasets (N = 26,091) from the British national mental health surveys of 1993, 2000 and 2007. Cases of psychosis were determined either by the use of the Schedules for Clinical Assessment in Neuropsychiatry (SCAN), or from a combination of screening items. We controlled for sex, age, social class, unemployment, design features and other putative confounders, using a Disease Risk Score. Results People from black ethnic minorities had an excess prevalence rate of psychosis compared with the white majority population. The OR, weighted for study design and response rate, was 2.72 (95 % CI 1.3–5.6, p = 0.002). This was marginally increased after controlling for potential confounders (OR = 2.90, 95 % CI 1.4–6.2, p = 0.006). Conclusions The excess of psychosis in black ethnic minority groups was similar to that in two previous British community surveys, and less than that based on clinical studies. Even so it confirms a considerable need for increased mental health service resources in areas with high proportions of black ethnic minority inhabitants

A systematic review of the neurobiological underpinnings of borderline personality disorder (BPD) in childhood and adolescence

Contemporary theories for the aetiology of borderline personality disorder (BPD) take a lifespan approach asserting that inborn biological predisposition is potentiated across development by environmental risk factors. In this review, we present and critically evaluate evidence on the neurobiology of BPD in childhood and adolescence, compare this evidence to the adult literature, and contextualise within a neurodevelopmental framework. A systematic review was conducted to identify studies examining the neurobiological (i.e. genetic, structural neuroimaging, neurophysiological, and neuropsychological) correlates of BPD symptoms in children and adolescents aged 19 years or under. We identified, quality assessed, and narratively summarised 34 studies published between 1980 and June 2016. Similar to findings in adult populations, twin studies indicated moderate to high levels of heritability of BPD, and there was some evidence for gene-environment interactions. Also consistent with adult reports is that some adolescents with BPD demonstrated structural (grey and white matter) alterations in frontolimbic regions and neuropsychological abnormalities (i.e. reduced executive function and disturbances in social cognition). These findings suggest that neurobiological abnormalities observed in adult BPD may not solely be the consequence of chronic morbidity or prolonged medication use. They also provide tentative support for neurodevelopmental theories of BPD by demonstrating that neurobiological markers may be observed from childhood onwards and interact with environmental factors to increase risk of BPD in young populations. Prospective studies with a range of repeated measures are now required to elucidate the temporal unfurling of neurobiological features and further delineate the complex pathways to BPD