Anekal C. Amaresha

Monotherapy with tDCS for Schizophrenia: a case report.

positive response to cTBSmight have been related to the association of risperidonewith cTBS orwas primed bya course of low frequency rTMS completed a month before. However, the fact that this patient who suffered fromchronic persistentAVH responded to cTBSbut not to rTMS in addition to the fact that the improvements in her AHRS scores persisted with maintenance cTBS suggest that observed clinical changes were an effect of stimulation by cTBS. The encouraging findings of this case safely treated in a private practice setting aswell as those of the three previously published cases [8,9,10] should be further investigated and confirmed in sufficiently powered placebo-controlled, double-blind studies.

Expressed Emotion in Schizophrenia: An Overview

The expressed emotion (EE) is considered to be an adverse family environment, which includes the quality of interaction patterns and nature of family relationships among the family caregivers and patients of schizophrenia and other psychiatric disorders. Influence of EE has been found to be one of the robust predictors of relapse in schizophrenia. This review article aims to provide a brief description of the origins and evolution of the EE as a construct from the available literature. The EE is modulated by multiple factors–some of which include certain personality profile, attribution factors by caregivers toward patient symptoms, and patients vulnerability to stress. The psychosocial assessment and interventions specifically focused on family psychoeducation can potentially reduce high EE and relapse of symptoms as well. However, the theory surrounded with EE undermines the caregivers positive attitudes toward the patients. Hence, it is important that the future studies should focus on both protective and vulnerable factors within the construct of EE in schizophrenia to facilitate comprehensive care.

Soluble human leukocyte antigen (sHLA)-G levels may predict early onset of schizophrenia in male patients.

Schizophrenia has been recognized as a highly debilitating neurodevelopmental disorder involving interactions between multiple genetic and environmental factors (1). Although the precise etiology remains elusive, the immunopathogenetic basis of schizophrenia has emerged as one of the widely appreciated underlying mechanisms in recent years (2, 3). Importantly, among the immune-related genes identified by the genome-wide association studies, the major histocompatibility complex (MHC) has become the subject of intense research and remained as one of the persistently well-replicated risk loci of schizophrenia (4). The human leukocyte antigen-G (HLA-G), non-classical MHC class-I molecules having predominant expression and immuno-modulatory functions during pregnancy seems to be of particular interest in the neurodevelopmental origin of schizophrenia. Current understanding suggests that the expression of HLA-G may be induced in other cell types during viral infections as well as in pathological conditions such as cancer and inflammatory disorders (5). During pregnancy, HLA-G exerts its immuno-inhibitory attributes by suppressing the functions of natural killer cells and cytotoxic T lymphocytes and influences the outcome of the pregnancy (6). However, altered expression of HLA-G and certain of its genotypes have been shown to be associated with pregnancy complications like preeclampsia by multiple studies (7). Importantly, maternal immune activation and/or inflammation during pregnancy were found to be associated with preeclampsia, preterm delivery etc., which are known to confer strong risk to schizophrenia in the offspring (8). It was previously hypothesized that perturbation of HLA-G expression during early pregnancy might enhance the risk of schizophrenia in the offspring through cytokine-mediated neurodevelopmental abnormality (9). This understanding led to the hypothesis that HLA-G could be a part of the pathway that mediates the causal link between prenatal immune activation and risk of schizophrenia in the offspring. In this study, we have examined HLA-G 14 bp INDEL polymorphism and its impact on the plasma levels of soluble human leukocyte antigen (sHLA)-G in schizophrenia patients. We recruited 46 schizophrenia patients (age range: 18–45 years) attending Schizophrenia Clinic at National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India, and meeting Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for this study. The diagnosis was established using the Mini International Neuropsychiatric Interview (MINI) Plus. Healthy controls (N = 44) were screened to rule out any psychiatric diagnosis using the MINI plus as well as a comprehensive mental status examination. The subjects (patient/control) did not have recent history of high grade fever/infection within the past 6 weeks or any co-morbid medical disease that can potentially influence immune system; none had co-morbid substance abuse/dependence. The study was conducted after obtaining approval from the institutional ethics committee and written informed consent from the patients and healthy volunteers. The genomic DNA was isolated by spin column method (Qiagen, Inc, Limburg, Netherlands). The 14 bp Insertion/Deletion (INDEL) polymorphism (rs66554220) was genotyped as previously described (10). The genotype profile of the 14 bp INDEL polymorphism in a subset of subjects was further confirmed by direct sequencing using Applied Biosystems 3730xI DNA analyzer (Foster City, CA, USA). Soluble HLA-G was measured using the sHLA-G enzyme-linked immunosorbent assay (ELISA) kits (BioVendor, Brno, Czech Republic). The differences in the levels of sHLA-G in plasma between the groups and between the sexes were analyzed using independent sample t-test. Influence of genotypes on the levels of sHLA-G between the groups was analyzed using analysis of variance test. Further, association between levels of sHLA-G and the clinical parameters was analyzed by Pearson’s correlation analysis. Statistical tests were performed using SPSS software. P-values≤ 0.05 were considered significant. Pearson’s chi-square test showed that the genotype distribution in patients and healthy controls was consistent with Hardy–Weinberg equilibrium (patients: χ2 = 1.34, P= 0.247; controls: χ2 = 0.08, P= 0.765; both the groups combined: χ2 = 1.07, P= 0.299). There were no significant differences in the distribution of HLA-G 14 bp alleles and genotypes between schizophrenia patients and healthy controls. However, a significant difference in plasma levels of sHLA-G was observed between the patient (mean= 69.87± 40.56 U/mL) and control (mean= 100.90± 77.08 U/mL) groups (t= 2.374; df= 64.47; P= 0.021). This finding suggests that low levels of sHLA-G

Clinical correlates of parametric digit-symbol substitution test in schizophrenia

Processing speed deficit, ascertained by digit-symbol substitution test (DSST), is considered as a fundamental impairment in schizophrenia. Clinical correlates of processing speed abnormalities, especially using the parametric version of DSST is yet to be evaluated comprehensively. In this study, we examined schizophrenia patients (N = 66) and demographically matched healthy controls (N = 72) using computer-administered parametric DSST (pDSST) with fixed (pDSSTF) as well as random (pDSSTR) conditions and analysed the relationship between pDSST performance and clinical symptoms. Psychopathology was assessed using Scale for Assessment of Positive Symptoms (SAPS)/Negative Symptoms (SANS) with good inter-rater reliability. In comparison with healthy controls, patients demonstrated significantly lesser number of correct responses (CN) in pDSSTF (t = 8.0; p < 0.001) and pDSSTR (t = 7.8; p < 0.001) as well as significantly prolonged reaction time in pDSSTF (t = 7.1; p < 0.001) and pDSSTR (t = 7.0; p < 0.001). The difference in CN between pDSSTF and pDSSTR [ΔCN] was significantly lesser in patients than healthy controls (t = 2.61; p = 0.01). The pDSST reaction time had significant positive correlation with negative syndrome scores as well as bizarre behaviour score. Significantly greater processing speed deficits in pDSST suggest potential relational memory/visual scanning abnormalities in schizophrenia. Furthermore, pDSST deficits demonstrated a significant association with the psychopathology, especially with the various negative symptoms and bizarre behaviour.

The impact of HLA-G 3′ UTR variants and sHLA-G on risk and clinical correlates of schizophrenia

The Major Histocompatibility Complex (MHC)/Human Leukocyte Antigen (HLA) is known to influence the pathogenesis of several complex human diseases resulting from gene-environmental interactions. Recently, it has emerged as one of the risk determinants of schizophrenia. The HLA-G protein (a non-classical MHC class I molecule), encoded by the HLA-G gene, is shown to play important role in embryonic development. Importantly, its genetic variations and aberrant expression have been implicated in pregnancy complications like preeclampsia, inflammation, and autoimmunity. Converging evidence implicates these phenomena as risk mechanisms of schizophrenia. However, the functional implications of HLA-G in schizophrenia are yet to be empirically examined. The impact of two functional polymorphisms [14bp Insertion/Deletion (INDEL) and +3187 A>G] and soluble HLA-G (sHLA-G) levels on schizophrenia risk was evaluated. In this exploratory study, the Ins/Ins genotype of 14bp INDEL was found to confer a strong risk for schizophrenia. Further, low levels of sHLA-G were shown to have a significant impact on Clinical Global Impression (CGI) severity in people with schizophrenia.

Assessing the needs of siblings of persons with schizophrenia: A qualitative study from India

There is a lack of studies on siblings of persons with schizophrenia (SOPS) in Asia. This study aims to explore the needs of SOPS in India. 15 SOPS participated in this qualitative explorative study. All the interviews were audio recorded and later transcribed. Data analysis was carried out using General Inductive Approach. Five themes emerged from the data: managing illness or socio-occupational functioning; follow up services; informational needs; personal needs; and miscellaneous needs. SOPS in India have some distinctive needs. Identifying these needs might help in developing and designing specific psychosocial interventions for better management.

Short term effects of brief need based psychoeducation on knowledge, self-stigma, and burden among siblings of persons with schizophrenia: A prospective controlled trial

Siblings of persons with schizophrenia are important in providing long-term social support to the patients. Interventions addressing their needs are very sparse. Hence, this study aimed at testing the short-term effects of brief need based psychoeducation on knowledge, self-stigma, and burden among siblings of persons with schizophrenia. In this prospective controlled open label trial, 80 siblings of persons with schizophrenia were allocated in equal numbers to the brief need based psychoeducation group and the treatment-as-usual group. The outcomes were measured at baseline, and after the first and third month post-intervention. RM-ANCOVA was conducted to test the effect of the brief psychoeducation on outcome scores. The groups were similar with respect to socio-demographic, clinical, and outcome scores at the baseline. There was a significant group×time interaction effect on knowledge (F=8.71; p<0.01; ηp2=0.14) and self-stigma scores (F=14.47; p<0.001; ηp2=0.21), wherein the brief psychoeducation group showed a significant increase in knowledge and reduction in self-stigma with medium effect size through baseline to the third month follow-up as compared to the treatment as usual group. We also observed a significant main effect of time; irrespective of the group allocation, there was a significant increase in the knowledge through baseline to third month follow-up (F=5.69; p=0.02; ηp2=0.09). No main or interaction effects of group and time were observed on burden. The findings suggest that brief need based psychoeducation may increase knowledge about the illness and reduce self-stigma. Further systematic studies are warranted to test this intervention for long-term effects.

The impact of IL10 polymorphisms and sHLA-G levels on the risk of schizophrenia

Early life immune aberrations have strongly been associated with the risk of schizophrenia. Amongst them, inflammation induced neurodevelopmental origin has emerged as one of the widely recognized underlying mechanisms. Interleukin-10 (IL-10) is an important anti-inflammatory and immunoregulatory cytokine. It modulates the expression of another immuno-inhibitory molecule, Human Leukocyte Antigen-G (HLA-G), predominantly expressed at the feto-maternal interface. Under physiological conditions, IL-10 and HLA-G molecules regulate the feto-maternal immune homeostasis by limiting the inflammatory states and influence the outcome of pregnancy. The aberrant expression of these molecules can cause pregnancy complications, which are known to confer strong risk to schizophrenia in the offspring. However, there is a considerable lack of information on the effect of the functional interactions between IL-10 and HLA-G on the risk of schizophrenia. We therefore examined the impact of possible correlation between IL-10 genetic variations and the plasma levels of soluble HLA-G (sHLA-G) on schizophrenia risk. Genotyping of IL10 (-592 C>A, -1082 A>G) single nucleotide polymorphisms (SNPs) was performed by PCR-RFLP method in 219 schizophrenia patients and 197 healthy subjects and levels of sHLA-G were estimated by ELISA in 46 patients and 44 healthy subjects. There was no significant difference in the genotype and allele frequencies between the groups for both the IL10 SNPs analyzed. However, we observed a correlation between IL10 genetic variation and plasma levels of sHLA-G in schizophrenia patients. Patients carrying CC genotype of IL10 -592C>A polymorphism had significantly lower sHLA-G levels compared to CA and AA genotypes. Our findings suggest the impact of possible correlation between IL-10 and HLA-G on schizophrenia risk.

Neural Correlates of a Perspective-taking Task Using in a Realistic Three-dimmensional Environment Based Task: A Pilot Functional Magnetic Resonance Imaging Study

Objective Perspective-taking ability is an essential spatial faculty that is of much interest in both health and neuropsychiatric disorders. There is limited data on the neural correlates of perspective taking in the context of a realistic three-dimensional environment. We report the results of a pilot study exploring the same in eight healthy volunteers. Methods Subjects underwent two runs of an experiment in a 3 Tesla magnetic resonance imaging (MRI) involving alternate blocks of a first-person perspective based allocentric object location memory task (OLMT), a third-person perspective based egocentric visual perspective taking task (VPRT), and a table task (TT) that served as a control. Difference in blood oxygen level dependant response during task performance was analyzed using Statistical Parametric Mapping software, version 12. Activations were considered significant if they survived family-wise error correction at the cluster level using a height threshold of p<0.001, uncorrected at the voxel level. Results A significant difference in accuracy and reaction time based on task type was found. Subjects had significantly lower accuracy in VPRT compared to TT. Accuracy in the two active tasks was not significantly different. Subjects took significantly longer in the VPRT in comparison to TT. Reaction time in the two active tasks was not significantly different. Functional MRI revealed significantly higher activation in the bilateral visual cortex and left temporoparietal junction (TPJ) in VPRT compared to OLMT. Conclusion The results underscore the importance of TPJ in egocentric manipulation in healthy controls in the context of reality-based spatial tasks.

Experiences of school teachers on participation in a brief school mental health program: a qualitative inquiry

Abstract Background: School mental health programs (SMHPs) aim to strengthen school teachers’ understanding about issues related to child and adolescent mental health and their management. Many studies have looked at outcomes of such programs quantitatively. However, there is a lack of studies on the qualitative effects of SMHPs. With this in mind, the aim was to explore and evaluate the experiences of school teachers in a corporate social responsibility (CSR) project who participated in a brief SMHP in the suburbs of Bangalore City in India. Materials and methods: Twenty-two school teachers of a CSR project participated in this brief one-day SMHP. The program aimed to orient the teachers about common child and adolescent psychiatric disorders. Data were collected through a semi-structured open-ended questionnaire and by narrative inquiry. The data analysis adopted a general inductive approach. Results: From the qualitative data analysis, five overarching themes have emerged: (i) positive experience of being participants in the program; (ii) lack of knowledge on school mental health issues; (iii) enriched understanding and new learning; (iv) expansion of SMHP to other schools; (v) suggestions for prospective SMHP. Conclusion: The positive experiences and increased knowledge of the participants supports conducting similar programs with systematic methods for people working closely with school children.