Journal: Schizophrenia research
The present study examined the validity of psychometrically assessed positive and negative schizotypy in a study of 214 Spanish young adults using interview and questionnaire measures of impairment and psychopathology. Schizotypy provides a useful construct for understanding the etiology and development of schizophrenia and related disorders. Recent interview, laboratory, and experience sampling studies have supported the validity of psychometrically assessed positive and negative symptom dimensions. The present study expands on previous findings by examining the validity of these dimensions in a Spanish sample and employing a widely used interview measure of the schizophrenia prodrome. As hypothesized, the positive schizotypy dimension predicted CAARMS ultra high-risk or psychosis threshold status, and both dimensions uniquely predicted the presence of schizophrenia-spectrum personality disorders. Furthermore, positive schizotypy was associated with psychotic-like, paranoid, schizotypal, and mood symptoms, whereas negative schizotypy was associated with interview ratings of negative and schizoid symptoms. The schizotypy dimensions were also distinguished by their associations with self and other schemas. Positive schizotypy was associated with increased negative self and other schemas, whereas negative schizotypy was associated with decreased positive self and other schemas. The findings provide further construct validation of positive and negative schizotypy and support these dimensions as universal constructs.
Social Recovery Therapy (SRT) is a cognitive behavioural therapy which targets young people with early psychosis who have complex problems associated with severe social disability. This paper provides a narrative overview of current evidence for SRT and reports new data on a 2year follow-up of participants recruited into the Improving Social Recovery in Early Psychosis (ISREP) trial.
It has remained controversial if antipsychotic treatment is associated with increased or decreased mortality among patients with schizophrenia, and if there are any clinically meaningful differences between specific agents and routes of administration.
The watershed-hypothesis of schizophrenia asserts that over 200 different mutations dysregulate distinct pathways that converge on an unspecified common mechanism(s) that controls disease ontogeny. Consistent with this hypothesis, our RNA-sequencing of neuron committed cells (NCCs) differentiated from established iPSCs of 4 schizophrenia patients and 4 control subjects uncovered a dysregulated transcriptome of 1349 mRNAs common to all patients. Data reveals a global dysregulation of developmental genome, deconstruction of coordinated mRNA networks, and the formation of aberrant, new coordinated mRNA networks indicating a concerted action of the responsible factor(s). Sequencing of miRNA transcriptomes demonstrated an overexpression of 16 miRNAs and deconstruction of interactive miRNA-mRNA networks in schizophrenia NCCs. ChiPseq revealed that the nuclear (n) form of FGFR1, a pan-ontogenic regulator, is overexpressed in schizophrenia NCCs and overtargets dysregulated mRNA and miRNA genes. The nFGFR1 targeted 54% of all human gene promoters and 84.4% of schizophrenia dysregulated genes. The upregulated genes reside within major developmental pathways that control neurogenesis and neuron formation, whereas downregulated genes are involved in oligodendrogenesis. Our results indicate (i) an early (preneuronal) genomic etiology of schizophrenia, (ii) dysregulated genes and new coordinated gene networks are common to unrelated cases of schizophrenia, (iii) gene dysregulations are accompanied by increased nFGFR1-genome interactions, and (iv) modeling of increased nFGFR1 by an overexpression of a nFGFR1 lead to up or downregulation of selected genes as observed in schizophrenia NCCs. Together our results designate nFGFR1 signaling as a potential common dysregulated mechanism in investigated patients and potential therapeutic target in schizophrenia.
Overall results from Cognitive Remediation (CR) indicate robust and long-lasting effects with medium effect size on global cognition and functioning, and a small ES on symptoms present at post-treatment but not at follow-up. However, results are not the same in all CR therapies and in some cases no efficacy results are achieved.
The inability to ignore irrelevant environmental noise is a common problem for people with schizophrenia. The purpose of this study was to determine if the neuronal response to distracting noise is related to mechanisms of altered attention observed in the illness.
Recent studies have suggested that neurodegeneration is involved in the pathogenesis of schizophrenia, and some atypical antipsychotics appear to prevent or retard progressive morphological brain changes. However, the underlying molecular mechanisms are largely unknown. Whether changes in intracellular signaling pathways are related to their neuroprotective effects remains undefined. In the present study, we used mouse embryonic prefrontal cortical neurons to examine the neuroprotection of paliperidone against the neuronal damage induced by exposure to the NMDA receptor antagonist, MK-801. Paliperidone inhibited MK-801 induced neurotoxicity both in MTT metabolism assay (p<0.01) and in lactate dehydrogenase (LDH) activity assay (p<0.01). Time course studies reveled that paliperidone effectively attenuated the elevation of intracellular free calcium concentration ([Ca(2+)]i) induced by exposure to MK-801 (p<0.01). Moreover, paliperidone could significantly retard MK-801-mediated inhibition of neurite outgrowth (p<0.01) and reverse MK-801-induced decreases of gene expression and phosphorylation of Akt1 and GSK3β (both p<0.01). Furthermore, these protective effects of paliperidone were blocked by pretreatment with a PI3K inhibitor LY294002. Taking together, our results demonstrated that paliperidone could protect prefrontal cortical neurons from MK-801-induced damages via Akt1/GSK3β signaling pathway.
Command hallucinations are experienced by 33-74% of people who experience voices, with varying levels of compliance reported. Compliance with command hallucinations can result in acts of aggression, violence, suicide and self-harm; the typical response however is non-compliance or appeasement. Two factors associated with such dangerous behaviours are anger and impulsivity, however few studies have examined their relationship with compliance to command hallucinations. The current study aimed to examine the roles of anger and impulsivity on compliance with command hallucinations in people diagnosed with a psychotic disorder. The study was a cross-sectional design and included individuals who reported auditory hallucinations in the past month. Subjects completed a variety of self-report questionnaire measures. Thirty-two people experiencing command hallucinations, from both in-patient and community settings, were included. The tendency to appraise the voice as powerful, to be impulsive, to experience anger and to regulate anger were significantly associated with compliance with command hallucinations to do harm. Two factors emerged as significant independent predictors of compliance with command hallucinations; omnipotence and impulsivity. An interaction between omnipotence and compliance with commands, via a link with impulsivity, is considered and important clinical factors in the assessment of risk when working with clients experiencing command hallucinations are recommended. The data is highly suggestive and warrants further investigation with a larger sample.
Schizophrenia risk has been linked to urbanization, but the underlying mechanism remains unknown. Green space is hypothesized to positively influence mental health and might mediate risk of schizophrenia by mitigating noise and particle pollution exposure, stress relief, or other unknown mechanisms. The objectives for this study were to determine if green space are associated with schizophrenia risk, and if different measures of green space associate differently with risk. We used satellite data from the Landsat program to quantify green space in a new data set for Denmark at 30×30m resolution for the years 1985-2013. The effect of green space at different ages and within different distances from each person’s place of residence on schizophrenia risk was estimated using Cox regression on a very large longitudinal population-based sample of the Danish population (943,027 persons). Living at the lowest amount of green space was associated with a 1.52-fold increased risk of developing schizophrenia compared to persons living at the highest level of green space. This association remained after adjusting for known risk factors for schizophrenia: urbanization, age, sex, and socioeconomic status. The strongest protective association was observed during the earliest childhood years and closest to place of residence. This is the first nationwide population-based study to demonstrate a protective association between green space during childhood and schizophrenia risk; suggesting limited green space as a novel environmental risk factor for schizophrenia. This study supports findings from other studies highlighting positive effects of exposure to natural environments for human health.
Schizophrenia is a debilitating syndrome with high heritability. Genomic studies reveal more than a hundred genetic variants, largely nonspecific and of small effect size, and not accounting for its high heritability. De novo mutations are one mechanism whereby disease related alleles may be introduced into the population, although these have not been leveraged to explore the disease in general samples. This paper describes a framework to find high impact genes for schizophrenia. This study consists of two different datasets. First, whole exome sequencing was conducted to identify disruptive de novo mutations in 14 complete parent-offspring trios with sporadic schizophrenia from Jerusalem, which identified 5 sporadic cases with de novo gene mutations in 5 different genes (PTPRG, TGM5, SLC39A13, BTK, CDKN3). Next, targeted exome capture of these genes was conducted in 48 well-characterized, unrelated, ethnically diverse schizophrenia cases, recruited and characterized by the same research team in New York (NY sample), which demonstrated extremely rare and potentially damaging variants in three of the five genes (MAF<0.01) in 12/48 cases (25%); including PTPRG (5 cases), SCL39A13 (4 cases) and TGM5 (4 cases), a higher number than usually identified by whole exome sequencing. Cases differed in cognition and illness features based on which mutation-enriched gene they carried. Functional de novo mutations in protein-interaction domains in sporadic schizophrenia can illuminate risk genes that increase the propensity to develop schizophrenia across ethnicities.