Association of Typical versus Atypical Antipsychotics with Symptoms and Quality of Life in Schizophrenia

BACKGROUND: Several reports on patients with chronic schizophrenia suggest that atypical versus typical antipsychotics are expected to lead to better quality of life (QOL) and cognitive function. Our aim was to examine the association of chronic treatment with typical or atypical antipsychotics with cognitive function, psychiatric symptoms, QOL, and drug-induced extrapyramidal symptoms in long-hospitalized patients with schizophrenia. METHODOLOGY AND PRINCIPAL FINDINGS: The Hasegawa Dementia Scale-Revised (HDS-R), Brief Psychiatric Rating Scale (BPRS), the Schizophrenia Quality of Life Scale, translated into Japanese (JSQLS), and the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) were used to evaluate cognitive function, psychiatric symptoms, QOL, and drug-induced extrapyramidal symptoms. We examined the correlation between the dose of antipsychotics and each measure derived from these psychometric tests. The student t-test was used to compare scores obtained from psychometric tests between patients receiving typical and atypical antipsychotics. Results showed significant correlations between chlorpromazine (CPZ)-equivalent doses of typical antipsychotics and atypical antipsychotics, and the total BPRS score and BPRS subscale scores for positive symptoms. CPZ-equivalent doses of typical antipsychotics were correlated with the JSQLS subscale score for dysfunction of psycho-social activity and DIEPSS score. Furthermore, the total BPRS scores, BPRS subscale score for positive symptoms, the JSQLS subscale score for dysfunction of psycho-social activity, and the DIEPSS score were significantly higher in patients receiving typical antipsychotics than atypical antipsychotics. CONCLUSION AND SIGNIFICANCE: These findings suggest that long-term administration of typical antipsychotics has an unfavorable association with feelings of difficulties mixing in social situations in patients with chronic schizophrenia

Decreased cerebral blood flow in the limbic and prefrontal cortex using SPECT imaging in a cohort of completed suicides

Suicide has a high comorbidity with impulsivity and depression, and finding imaging biomarkers indicative of patients at high risk for suicidal behavior is invaluable to the clinician. Using single-photon emission computed tomography (SPECT) imaging, we have previously reported regional cerebral blood flow (rCBF) decreases in the medial prefrontal cortex, ventral tegmental area and subgenual cingulate cortex (Brodmann area 25 (BA 25)), a region found to be hypoperfused with treatment-resistant depression. From 2007 to 2010, we have extended our analysis to include nine additional completed suicides. In all, 27 healthy, age- and gender-matched subjects from a previously acquired healthy brain study served as controls to our 21 completed suicides. All 21 suicides had been previously diagnosed with depression according to Diagnostic and Statistical Manual of Mental Disorder-IV criterion. Voxel-by-voxel analyses were performed using statistical parametric mapping to compare the differences in technetium-99m hexamethylpropylene amine oxime brain uptake between the groups. Factor analysis of the data identified the top 10 regions of hypoperfusion in the suicidal group, including the bilateral superior frontal lobes, the right precuneus, the rolandic operculum, postcentral gyrus, left caudate and insular cortex. We also demonstrate more focal decreases in rCBF in the subgenual cingulate cortex (BA 25) in 18 subjects, supporting our previous hypothesis that hypoperfusion of BA 25 may be a risk factor for suicide in depressed patients. This work suggests that SPECT might be useful in predicting risk for suicide completion in subjects with depression or treatment-resistant depression. Further investigation of this work is necessary to better understand the predictive value of this finding

A randomized controlled multicenter trial of post-suicide attempt case management for the prevention of further attempts in Japan (ACTION-J)

<p>Abstract</p> <p>Background</p> <p>A previous suicide attempt is a potent risk factor for suicide later on. Crisis intervention, psychiatric and psychosocial evaluation at emergency medical facilities, and follow-up care for suicide attempters are considered important components for suicide prevention. The Japanese Multimodal Intervention Trials for Suicide Prevention (J-MISP) includes a randomized, controlled, multicenter trial of post-suicide attempt case management for the prevention of further attempts (ACTION-J) to address the continuing increase in suicides in Japan. The primary aim of ACTION-J is to examine the effectiveness of an extensive intervention for suicide attempters in prevention of recurrent suicidal behavior, as compared with standard intervention. This paper describes the rationale and protocol of the ACTION-J trial.</p> <p>Methods/Design</p> <p>In this clinical trial, case management intervention will be provided at 19 emergency medical facilities in Japan. After crisis intervention including psychiatric evaluation, psychosocial assessment, and psychological education, subjects will be randomly assigned to either a group receiving continuous case management or a control group receiving standard care. Suicidal ideation, depressive symptoms, and general health condition will be evaluated as secondary measures. The intervention was initiated in July 2006. By December, 2009, 842 subjects will be randomized. Subject follow-up will continue for 1.5 to 5 years.</p> <p>Discussion</p> <p>Suicide is a complex phenomenon that encompasses multiple factors. Case management by multi-sector collaboration is needed. ACTION-J may provide valuable information on suicide attempters and may develop effective case management to reduce future risk for suicide attempters.</p> <p>Trial registration</p> <p>UMIN Clinical Trials Registry number, UMIN000000444. ClinicalTrials.gov number, NCT00736918.</p

Subacute Sclerosing Panencephalitis: Results of the Canadian Paediatric Surveillance Program and review of the literature

BACKGROUND: Subacute Sclerosing Panencephalitis (SSPE) is so rare in developed countries with measles immunization programs that national active surveillance is now needed to capture sufficient number of cases for meaningful analysis of data. Through the Canadian Paediatric Surveillance Program (CPSP), the SSPE study was able to document a national incidence and determine the epidemiology of affected Canadian children. METHODS: Between 1997 and 2000, the CPSP surveyed monthly 1978 to 2294 Canadian pediatricians and sub-specialists for SSPE cases. The response rate varied from 82–86% over those years. RESULTS: Altogether, four SSPE cases were reported to the CPSP: one case before, two during and one after the study period. The incidence of SSPE in Canadian children was 0.06/million children/year. Of the four cases, diagnosed between ages four and 17 years, three children had measles infection in infancy. All children showed a progressive course of dementia, loss of motor skills and epilepsy. Two children were treated with isoprinosine and intraventricular interferon but died in less than three years from disease onset. One child did not have any treatment and died after seven years of illness. One child received intraventricular ribavirin and remains alive, but markedly impaired, nine years following diagnosis. CONCLUSION: The CPSP has demonstrated that Canadian paediatricians and paediatric neurologists may encounter cases of SSPE. This report highlights the clinical course of affected Canadian children and provides a review of the disease and its management

Impact of the AHI1 Gene on the Vulnerability to Schizophrenia: A Case-Control Association Study

BackgroundThe Abelson helper integration-1 (AHI1) gene is required for both cerebellar and cortical development in humans. While the accelerated evolution of AHI1 in the human lineage indicates a role in cognitive (dys)function, a linkage scan in large pedigrees identified AHI1 as a positional candidate for schizophrenia. To further investigate the contribution of AHI1 to the susceptibility of schizophrenia, we evaluated the effect of AHI1 variation on the vulnerability to psychosis in two samples from Spain and Germany.Methodology/Principal Findings29 single-nucleotide polymorphisms (SNPs) located in a genomic region including the AHI1 gene were genotyped in two samples from Spain (280 patients with psychotic disorders; 348 controls) and Germany (247 patients with schizophrenic disorders; 360 controls). Allelic, genotypic and haplotype frequencies were compared between cases and controls in both samples separately, as well as in the combined sample. The effect of genotype on several psychopathological measures (BPRS, KGV, PANSS) assessed in a Spanish subsample was also evaluated. We found several significant associations in the Spanish sample. Particularly, rs7750586 and rs911507, both located upstream of the AHI1 coding region, were found to be associated with schizophrenia in the analysis of genotypic (p = 0.0033, and 0.031, respectively) and allelic frequencies (p = 0.001 in both cases). Moreover, several other risk and protective haplotypes were detected (0.006<p<0.036). Joint analysis also supported the association of rs7750586 and rs911507 with the risk for schizophrenia. The analysis of clinical measures also revealed an effect on symptom severity (minimum P value = 0.0037).Conclusions/SignificanceOur data support, in agreement with previous reports, an effect of AHI1 variation on the susceptibility to schizophrenia in central and southern European populations

Psychiatric assessment of suicide attempters in Japan: a pilot study at a critical emergency unit in an urban area

<p>Abstract</p> <p>Background</p> <p>The incidence of suicide has increased markedly in Japan since 1998. As psychological autopsy is not generally accepted in Japan, surveys of suicide attempts, an established risk factor of suicide, are highly regarded. We have carried out this study to gain insight into the psychiatric aspects of those attempting suicide in Japan.</p> <p>Methods</p> <p>Three hundred and twenty consecutive cases of attempted suicide who were admitted to an urban emergency department were interviewed, with the focus on psychosocial background and DSM-IV diagnosis. Moreover, they were divided into two groups according to the method of attempted suicide in terms of lethality, and the two groups were compared.</p> <p>Results</p> <p>Ninety-five percent of patients received a psychiatric diagnosis: 81% of subjects met the criteria for an axis I disorder. The most frequent diagnosis was mood disorder. The mean age was higher and living alone more common in the high-lethality group. Middle-aged men tended to have a higher prevalence of mood disorders.</p> <p>Conclusion</p> <p>This is the first large-scale study of cases of attempted suicide since the dramatic increase in suicides began in Japan. The identification and introduction of treatments for psychiatric disorders at emergency departments has been indicated to be important in suicide prevention.</p

Thymic Alterations in GM2 Gangliosidoses Model Mice

BACKGROUND: Sandhoff disease is a lysosomal storage disorder characterized by the absence of β-hexosaminidase and storage of GM2 ganglioside and related glycolipids. We have previously found that the progressive neurologic disease induced in Hexb(-/-) mice, an animal model for Sandhoff disease, is associated with the production of pathogenic anti-glycolipid autoantibodies. METHODOLOGY/PRINCIPAL FINDINGS: In our current study, we report on the alterations in the thymus during the development of mild to severe progressive neurologic disease. The thymus from Hexb(-/-) mice of greater than 15 weeks of age showed a marked decrease in the percentage of immature CD4(+)/CD8(+) T cells and a significantly increased number of CD4(+)/CD8(-) T cells. During involution, the levels of both apoptotic thymic cells and IgG deposits to T cells were found to have increased, whilst swollen macrophages were prominently observed, particularly in the cortex. We employed cDNA microarray analysis to monitor gene expression during the involution process and found that genes associated with the immune responses were upregulated, particularly those expressed in macrophages. CXCL13 was one of these upregulated genes and is expressed specifically in the thymus. B1 cells were also found to have increased in the thy mus. It is significant that these alterations in the thymus were reduced in FcRγ additionally disrupted Hexb(-/-) mice. CONCLUSIONS/SIGNIFICANCE: These results suggest that the FcRγ chain may render the usually poorly immunogenic thymus into an organ prone to autoimmune responses, including the chemotaxis of B1 cells toward CXCL13

Acoustic Oddball during NREM Sleep: A Combined EEG/fMRI Study

Background: A condition vital for the consolidation and maintenance of sleep is generally reduced responsiveness to external stimuli. Despite this, the sleeper maintains a level of stimulus processing that allows to respond to potentially dangerous environmental signals. The mechanisms that subserve these contradictory functions are only incompletely understood. Methodology/Principal Findings: Using combined EEG/fMRI we investigated the neural substrate of sleep protection by applying an acoustic oddball paradigm during light NREM sleep. Further, we studied the role of evoked K-complexes (KCs), an electroencephalographic hallmark of NREM sleep with a still unknown role for sleep protection. Our main results were: (1) Other than in wakefulness, rare tones did not induce a blood oxygenation level dependent (BOLD) signal increase in the auditory pathway but a strong negative BOLD response in motor areas and the amygdala. (2) Stratification of rare tones by the presence of evoked KCs detected activation of the auditory cortex, hippocampus, superior and middle frontal gyri and posterior cingulate only for rare tones followed by a KC. (3) The typical high frontocentral EEG deflections of KCs were not paralleled by a BOLD equivalent. Conclusions/Significance: We observed that rare tones lead to transient disengagement of motor and amygdala responses during light NREM sleep. We interpret this as a sleep protective mechanism to delimit motor responses and to reduce the sensitivity of the amygdala towards further incoming stimuli. Evoked KCs are suggested to originate from a brain state wit

Genome-Wide Association Study SNPs in the Human Genome Diversity Project Populations: Does Selection Affect Unlinked SNPs with Shared Trait Associations?

Genome-wide association studies (GWAS) have identified more than 2,000 trait-SNP associations, and the number continues to increase. GWAS have focused on traits with potential consequences for human fitness, including many immunological, metabolic, cardiovascular, and behavioral phenotypes. Given the polygenic nature of complex traits, selection may exert its influence on them by altering allele frequencies at many associated loci, a possibility which has yet to be explored empirically. Here we use 38 different measures of allele frequency variation and 8 iHS scores to characterize over 1,300 GWAS SNPs in 53 globally distributed human populations. We apply these same techniques to evaluate SNPs grouped by trait association. We find that groups of SNPs associated with pigmentation, blood pressure, infectious disease, and autoimmune disease traits exhibit unusual allele frequency patterns and elevated iHS scores in certain geographical locations. We also find that GWAS SNPs have generally elevated scores for measures of allele frequency variation and for iHS in Eurasia and East Asia. Overall, we believe that our results provide evidence for selection on several complex traits that has caused changes in allele frequencies and/or elevated iHS scores at a number of associated loci. Since GWAS SNPs collectively exhibit elevated allele frequency measures and iHS scores, selection on complex traits may be quite widespread. Our findings are most consistent with this selection being either positive or negative, although the relative contributions of the two are difficult to discern. Our results also suggest that trait-SNP associations identified in Eurasian samples may not be present in Africa, Oceania, and the Americas, possibly due to differences in linkage disequilibrium patterns. This observation suggests that non-Eurasian and non-East Asian sample populations should be included in future GWAS