Effect of Body Position and Size of Pleural Effusion on Oxygenation Status in Spontaneously Breathing Patients with Unilateral Pleural Effusion.

Abvims and Dr Rml Hospital, Delhi In unilateral pleural effusion it is necessary to find the best position for unilateral pleural effusion so that recovery can be hastened. There is scarcity of literature on the effect of body positional variations on oxygenation, and current guidelines do not address the necessity. The objective of this study is to assess the effect of body position and size of pleural effusion on oxygenation status in spontaneously breathing patients with unilateral pleural effusion. MATERIAL: This was a hospital based observational cross-sectional study having a sample size of 90 patients of unilateral pleural effusion and on the basis of severity, they were divided into 2 classes- small and large. Ipsilateral and Contralateral oxygenation were analysed separately in small and large effusions using Mann-Whitney and Wilcoxon signed rank test and final analysis was made using SPSS software. OBSERVATION: It was observed that oxygenation was better when patient lies on contralateral side in small effusion (PaO2 82.4±8.83 vs 85.01±8.24 p value <0.0001) while in cases of large effusion, oxygenation was better on ipsilateral side of effusion (82.35±10.4 vs 78.06±9.92, p value<0.0001). No significant difference was noted in case of PaCO2 levels in small and large effusion in ipsilateral and contralateral position. It was also noted that there was a significant difference in oxygen saturation. CONCLUSION: There is significant effect of body position and size of pleural effusion on oxygenation status in spontaneously breathing patient with unilateral pleural effusion.

Greater extracellular free-water in first-episode psychosis predicts better neurocognitive functioning.

Free Water Imaging is a novel diffusion magnetic resonance (MR) imaging method that is able to separate changes affecting the extracellular space from those that reflect changes in neuronal cells and processes. A previous Free Water Imaging study in schizophrenia identified significantly greater extracellular water volume in the early stages of the disorder; however, its clinical and functional sequelae have not yet been investigated. Here, we applied Free Water Imaging to a larger cohort of 63 first-episode patients with psychosis and 70 healthy matched controls to better understand the functional significance of greater extracellular water. We used diffusion MR imaging data and the Tract-Based Spatial Statistics analytic pipeline to first analyze fractional anisotropy (FA), the most commonly employed metric for assessing white matter. This comparison was then followed by Free Water Imaging analysis, where two parameters, the fractional volume of extracellular free-water (FW) and cellular tissue FA (FA-t), were estimated and compared across the entire white matter skeleton between groups, and correlated with cognitive measures at baseline and following 12 weeks of antipsychotic treatment. Our results indicated lower FA across the whole brain in patients compared with healthy controls that overlap with significant increases in FW, with only limited decreases in FA-t. In addition, higher FW correlated with better neurocognitive functioning following 12 weeks of antipsychotic treatment. We believe this is the first study to suggest that an extracellular water increase during the first-episode of psychosis, which may be indicative of an acute neuroinflammatory process, and/or cerebral edema may predict better functional outcome.

Hippocampal subregion volume changes associated with antipsychotic treatment in first-episode psychosis.

BACKGROUND: Hippocampal dysfunction is considered central to many neurobiological models of schizophrenia, yet there are few longitudinal in vivo neuroimaging studies that have investigated the relationship between antipsychotic treatment and morphologic changes within specific hippocampal subregions among patients with psychosis. METHOD: A total of 29 patients experiencing a first episode of psychosis with little or no prior antipsychotic exposure received structural neuroimaging examinations at illness onset and then following 12 weeks of treatment with either risperidone or aripiprazole in a double-blind randomized clinical trial. In addition, 29 healthy volunteers received structural neuroimaging examinations at baseline and 12-week time points. We manually delineated six hippocampal subregions [i.e. anterior cornu ammonis (CA) 1-3, posterior CA1-3, subiculum, dentate gyrus/CA4, entorhinal cortex, and fimbria] from 3T magnetic resonance images using an established method with high inter- and intra-rater reliability. RESULTS: Following antipsychotic treatment patients demonstrated significant reductions in dentate gyrus/CA4 volume and increases in subiculum volume. Healthy volunteers demonstrated non-significant volumetric changes in these subregions across the two time points. We observed a significant quadratic (i.e. inverted U) association between changes in dentate gyrus/CA4 volume and cumulative antipsychotic dosage between the scans. CONCLUSIONS: This study provides the first evidence to our knowledge regarding longitudinal in vivo volumetric changes within specific hippocampal subregions in patients with psychosis following antipsychotic treatment. The finding of a non-linear relationship between changes in dentate gyrus/CA4 subregion volume and antipsychotic exposure may provide new avenues into understanding dosing strategies for therapeutic interventions relevant to neurobiological models of hippocampal dysfunction in psychosis.

Neurocognitive subtypes in patients with bipolar disorder and their unaffected siblings.

BACKGROUND: Our previous work revealed substantial heterogeneity in the cognitive profile of bipolar disorder (BD) due to the presence of three underlying cognitive subgroups characterized as: globally impaired, selectively impaired, or cognitively intact. In an effort to determine whether these subgroups are differentially related to genetic risk for the illness, we investigated whether cognitive deficits were more pronounced in unaffected siblings (UAS) of BD probands within identified clusters. METHODS: Cluster analysis was used to identify cognitive clusters in BD (N = 60). UAS (N = 49) were classified into groups according to their proband sibling's cluster assignment; comparisons were made across all clusters and healthy controls (HCs; N = 71). RESULTS: Three cognitive clusters in BD emerged: a globally impaired (36.7%), a selectively impaired (30%), and a cognitively intact cluster (33.3%). UAS showed a qualitatively similar pattern to their BD siblings; UAS of the globally impaired BD cluster showed verbal memory and general cognitive impairments relative to HCs. In contrast, UAS of the other two clusters did not differ from HCs. CONCLUSIONS: This study corroborates findings from prior work regarding the presence of cognitive heterogeneity in BD. UAS of subjects in the globally impaired BD cluster presented with a qualitatively similar cognitive profile to their siblings and performed worse than all other BD clusters and UAS groups. This suggests that inherited risk factors may be contributing to cognitive deficits more notably in one subgroup of patients with BD, pointing toward differential causes of cognitive deficits in discrete subgroups of patients with the disorder.

Characterizing cognitive heterogeneity on the schizophrenia-bipolar disorder spectrum.

BACKGROUND: Current group-average analysis suggests quantitative but not qualitative cognitive differences between schizophrenia (SZ) and bipolar disorder (BD). There is increasing recognition that cognitive within-group heterogeneity exists in both disorders, but it remains unclear as to whether between-group comparisons of performance in cognitive subgroups emerging from within each of these nosological categories uphold group-average findings. We addressed this by identifying cognitive subgroups in large samples of SZ and BD patients independently, and comparing their cognitive profiles. The utility of a cross-diagnostic clustering approach to understanding cognitive heterogeneity in these patients was also explored. METHOD: Hierarchical clustering analyses were conducted using cognitive data from 1541 participants (SZ n = 564, BD n = 402, healthy control n = 575). RESULTS: Three qualitatively and quantitatively similar clusters emerged within each clinical group: a severely impaired cluster, a mild-moderately impaired cluster and a relatively intact cognitive cluster. A cross-diagnostic clustering solution also resulted in three subgroups and was superior in reducing cognitive heterogeneity compared with disorder clustering independently. CONCLUSIONS: Quantitative SZ-BD cognitive differences commonly seen using group averages did not hold when cognitive heterogeneity was factored into our sample. Members of each corresponding subgroup, irrespective of diagnosis, might be manifesting the outcome of differences in shared cognitive risk factors.

Genome-wide autozygosity is associated with lower general cognitive ability.

Inbreeding depression refers to lower fitness among offspring of genetic relatives. This reduced fitness is caused by the inheritance of two identical chromosomal segments (autozygosity) across the genome, which may expose the effects of (partially) recessive deleterious mutations. Even among outbred populations, autozygosity can occur to varying degrees due to cryptic relatedness between parents. Using dense genome-wide single-nucleotide polymorphism (SNP) data, we examined the degree to which autozygosity associated with measured cognitive ability in an unselected sample of 4854 participants of European ancestry. We used runs of homozygosity-multiple homozygous SNPs in a row-to estimate autozygous tracts across the genome. We found that increased levels of autozygosity predicted lower general cognitive ability, and estimate a drop of 0.6 s.d. among the offspring of first cousins (P=0.003-0.02 depending on the model). This effect came predominantly from long and rare autozygous tracts, which theory predicts as more likely to be deleterious than short and common tracts. Association mapping of autozygous tracts did not reveal any specific regions that were predictive beyond chance after correcting for multiple testing genome wide. The observed effect size is consistent with studies of cognitive decline among offspring of known consanguineous relationships. These findings suggest a role for multiple recessive or partially recessive alleles in general cognitive ability, and that alleles decreasing general cognitive ability have been selected against over evolutionary time.

Targeting the schizophrenia genome: a fast track strategy from GWAS to clinic.

The Psychiatric Genomics Consortium-Schizophrenia Workgroup (PGC-SCZ) has recently published a genomewide association study (GWAS) identifying >100 genetic loci, encompassing a total of 341 protein-coding genes, attaining genomewide significance for susceptibility to schizophrenia. Given the extremely long time (12-15 years) and expense (>$1 billion) associated with the development of novel drug targets, repurposing of drugs with known and validated targets may be the most expeditious path toward deriving clinical utility from these GWAS findings. In the present study, we examined all genes within loci implicated by the PGC-SCZ GWAS against databases of targets of both approved and registered pharmaceutical compounds. We identified 20 potential schizophrenia susceptibility genes that encode proteins that are the targets of approved drugs. Of these, we prioritized genes/targets that are of clear neuropsychiatric interest and that are also sole members of the linkage disequilibrium block surrounding a PGC-SCZ GWAS hit. In addition to DRD2, 5 genes meet these criteria: CACNA1C, CACNB2, CACNA1I, GRIN2A and HCN1. An additional 20 genes coding for proteins that are the targets of drugs in registered clinical trials, but without approved indications, were also identified. Although considerable work is still required to fully explicate the biological implications of the PGC-SCZ GWAS results, pathways related to these known, druggable targets may represent a promising starting point.

The SORL1 gene and convergent neural risk for Alzheimer's disease across the human lifespan.

Prior to intervention trials in individuals genetically at-risk for late-onset Alzheimer's disease, critical first steps are identifying where (neuroanatomic effects), when (timepoint in the lifespan) and how (gene expression and neuropathology) Alzheimer's risk genes impact the brain. We hypothesized that variants in the sortilin-like receptor (SORL1) gene would affect multiple Alzheimer's phenotypes before the clinical onset of symptoms. Four independent samples were analyzed to determine effects of SORL1 genetic risk variants across the lifespan at multiple phenotypic levels: (1) microstructural integrity of white matter using diffusion tensor imaging in two healthy control samples (n=118, age 18-86; n=68, age 8-40); (2) gene expression using the Braincloud postmortem healthy control sample (n=269, age 0-92) and (3) Alzheimer's neuropathology (amyloid plaques and tau tangles) using a postmortem sample of healthy, mild cognitive impairment (MCI) and Alzheimer's individuals (n=710, age 66-108). SORL1 risk variants predicted lower white matter fractional anisotropy in an age-independent manner in fronto-temporal white matter tracts in both samples at 5% family-wise error-corrected thresholds. SORL1 risk variants also predicted decreased SORL1 mRNA expression, most prominently during childhood and adolescence, and significantly predicted increases in amyloid pathology in postmortem brain. Importantly, the effects of SORL1 variation on both white matter microstructure and gene expression were observed during neurodevelopmental phases of the human lifespan. Further, the neuropathological mechanism of risk appears to primarily involve amyloidogenic pathways. Interventions targeted toward the SORL1 amyloid risk pathway may be of greatest value during early phases of the lifespan.

Molecular genetic evidence for overlap between general cognitive ability and risk for schizophrenia: a report from the Cognitive Genomics consorTium (COGENT).

It has long been recognized that generalized deficits in cognitive ability represent a core component of schizophrenia (SCZ), evident before full illness onset and independent of medication. The possibility of genetic overlap between risk for SCZ and cognitive phenotypes has been suggested by the presence of cognitive deficits in first-degree relatives of patients with SCZ; however, until recently, molecular genetic approaches to test this overlap have been lacking. Within the last few years, large-scale genome-wide association studies (GWAS) of SCZ have demonstrated that a substantial proportion of the heritability of the disorder is explained by a polygenic component consisting of many common single-nucleotide polymorphisms (SNPs) of extremely small effect. Similar results have been reported in GWAS of general cognitive ability. The primary aim of the present study is to provide the first molecular genetic test of the classic endophenotype hypothesis, which states that alleles associated with reduced cognitive ability should also serve to increase risk for SCZ. We tested the endophenotype hypothesis by applying polygenic SNP scores derived from a large-scale cognitive GWAS meta-analysis (~5000 individuals from nine nonclinical cohorts comprising the Cognitive Genomics consorTium (COGENT)) to four SCZ case-control cohorts. As predicted, cases had significantly lower cognitive polygenic scores compared to controls. In parallel, polygenic risk scores for SCZ were associated with lower general cognitive ability. In addition, using our large cognitive meta-analytic data set, we identified nominally significant cognitive associations for several SNPs that have previously been robustly associated with SCZ susceptibility. Results provide molecular confirmation of the genetic overlap between SCZ and general cognitive ability, and may provide additional insight into pathophysiology of the disorder.

Empirical evidence for discrete neurocognitive subgroups in bipolar disorder: clinical implications.

BACKGROUND: Recent data suggest trait-like neurocognitive impairments in bipolar disorder (BPD), with deficits about 1 s.d. below average, less severe than deficits noted in schizophrenia. The frequency of significant impairment in BPD is approximately 60%, with 40% of patients characterized as cognitively spared. This contrasts with a more homogeneous presentation in schizophrenia. It is not understood why some BPD patients develop deficits while others do not. METHOD: A total of 136 patients with BPD completed the MATRICS Consensus Cognitive Battery and data were entered into hierarchical cluster analyses to: (1) determine the optimal number of clusters (subgroups) that fit the sample; and (2) assign subjects to a specific cluster based on individual profiles. We then compared subgroups on several clinical factors and real-world community functioning. RESULTS: Three distinct neurocognitive subgroups were found: (1) an intact group with performance comparable with healthy controls on all domains but with superior social cognition; (2) a selective impairment group with moderate deficits on processing speed, attention, verbal learning and social cognition and normal functioning in other domains; and (3) a global impairment group with severe deficits across all cognitive domains comparable with deficits in schizophrenia. CONCLUSIONS: These results suggest the presence of multiple cognitive subgroups in BPD with unique profiles and begin to address the relationships between these subgroups, several clinical factors and functional outcome. Next steps will include using these data to help guide future efforts to target these disabling symptoms with treatment.

Genetic association study between antipsychotic-induced weight gain and the melanocortin-4 receptor gene.

Antipsychotic-induced weight gain (AIWG) may result in the metabolic syndrome in schizophrenia (SCZ) patients. Downstream variants of the melanocortin-4 receptor (MC4R) gene have been associated with obesity in various populations. Thus, we examined single-nucleotide polymorphisms (SNPs) in the MC4R region for association with AIWG in SCZ patients. Four SNPs (rs2229616, rs17782313, rs11872992 and rs8087522) were genotyped in 224 patients who underwent treatment for SCZ and were evaluated for AIWG for up to 14 weeks. We compared weight change (%) across genotypic groups using analysis of covariance for three SNPs (r²≤0.8). European-ancestry patients who were rs8087522 A-allele carriers (AG+AA) on clozapine gained significantly more weight than non-carriers (P=0.027, n=69). These observations were marginal after correction for multiple testing. We performed in vitro electrophoretic mobility-shift assay that suggested that the presence of the A-allele may create a transcription factor-binding site. Further investigation is warranted for both these exploratory findings.

Neurocognitive phenomics: examining the genetic basis of cognitive abilities.

Cognitive deficits are core to the disability associated with many psychiatric disorders. Both variation in cognition and psychiatric risk show substantial heritability, with overlapping genetic variants contributing to both. Unsurprisingly, therefore, these fields have been mutually beneficial : just as cognitive studies of psychiatric risk variants may identify genes involved in cognition, so too can genome-wide studies based on cognitive phenotypes lead to genes relevant to psychiatric aetiology. The purpose of this review is to consider the main issues involved in the phenotypic characterization of cognition, and to describe the challenges associated with the transition to genomewide approaches. We conclude by describing the approaches currently being taken by the international consortia involving many investigators in the field internationally (e.g. Cognitive Genomics Consortium; COGENT) to overcome these challenges.

Pharmacogenetics in psychiatry: translating research into clinical practice.

Pharmacogenetic/pharmacogenomic (PGx) approaches to psychopharmacology aim to identify clinically meaningful predictors of drug efficacy and/or side-effect burden. To date, however, PGx studies in psychiatry have not yielded compelling results, and clinical utilization of PGx testing in psychiatry is extremely limited. In this review, the authors provide a brief overview on the status of PGx studies in psychiatry, review the commercialization process for PGx tests and then discuss methodological considerations that may enhance the potential for clinically applicable PGx tests in psychiatry. The authors focus on design considerations that include increased ascertainment of subjects in the earliest phases of illness, discuss the advantages of drug-induced adverse events as phenotypes for examination and emphasize the importance of maximizing adherence to treatment in pharmacogenetic studies. Finally, the authors discuss unique aspects of pharmacogenetic studies that may distinguish them from studies of other complex traits. Taken together, these data provide insights into the design and methodological considerations that may enhance the potential for clinical utility of PGx studies.

Fine mapping of ZNF804A and genome-wide significant evidence for its involvement in schizophrenia and bipolar disorder.

A recent genome-wide association study (GWAS) reported evidence for association between rs1344706 within ZNF804A (encoding zinc-finger protein 804A) and schizophrenia (P=1.61 × 10(-7)), and stronger evidence when the phenotype was broadened to include bipolar disorder (P=9.96 × 10(-9)). In this study we provide additional evidence for association through meta-analysis of a larger data set (schizophrenia/schizoaffective disorder N=18 945, schizophrenia plus bipolar disorder N=21 274 and controls N=38 675). We also sought to better localize the association signal using a combination of de novo polymorphism discovery in exons, pooled de novo polymorphism discovery spanning the genomic sequence of the locus and high-density linkage disequilibrium (LD) mapping. The meta-analysis provided evidence for association between rs1344706 that surpasses widely accepted benchmarks of significance by several orders of magnitude for both schizophrenia (P=2.5 × 10(-11), odds ratio (OR) 1.10, 95% confidence interval 1.07-1.14) and schizophrenia and bipolar disorder combined (P=4.1 × 10(-13), OR 1.11, 95% confidence interval 1.07-1.14). After de novo polymorphism discovery and detailed association analysis, rs1344706 remained the most strongly associated marker in the gene. The allelic association at the ZNF804A locus is now one of the most compelling in schizophrenia to date, and supports the accumulating data suggesting overlapping genetic risk between schizophrenia and bipolar disorder.

GWA study data mining and independent replication identify cardiomyopathy-associated 5 (CMYA5) as a risk gene for schizophrenia.

We conducted data-mining analyses using the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and molecular genetics of schizophrenia genome-wide association study supported by the genetic association information network (MGS-GAIN) schizophrenia data sets and performed bioinformatic prioritization for all the markers with P-values ≤0.05 in both data sets. In this process, we found that in the CMYA5 gene, there were two non-synonymous markers, rs3828611 and rs10043986, showing nominal significance in both the CATIE and MGS-GAIN samples. In a combined analysis of both the CATIE and MGS-GAIN samples, rs4704591 was identified as the most significant marker in the gene. Linkage disequilibrium analyses indicated that these markers were in low LD (3 828 611-rs10043986, r(2)=0.008; rs10043986-rs4704591, r(2)=0.204). In addition, CMYA5 was reported to be physically interacting with the DTNBP1 gene, a promising candidate for schizophrenia, suggesting that CMYA5 may be involved in the same biological pathway and process. On the basis of this information, we performed replication studies for these three single-nucleotide polymorphisms. The rs3828611 was found to have conflicting results in our Irish samples and was dropped out without further investigation. The other two markers were verified in 23 other independent data sets. In a meta-analysis of all 23 replication samples (family samples, 912 families with 4160 subjects; case-control samples, 11 380 cases and 15 021 controls), we found that both markers are significantly associated with schizophrenia (rs10043986, odds ratio (OR)=1.11, 95% confidence interval (CI)=1.04-1.18, P=8.2 × 10(-4) and rs4704591, OR=1.07, 95% CI=1.03-1.11, P=3.0 × 10(-4)). The results were also significant for the 22 Caucasian replication samples (rs10043986, OR=1.11, 95% CI=1.03-1.17, P=0.0026 and rs4704591, OR=1.07, 95% CI=1.02-1.11, P=0.0015). Furthermore, haplotype conditioned analyses indicated that the association signals observed at these two markers are independent. On the basis of these results, we concluded that CMYA5 is associated with schizophrenia and further investigation of the gene is warranted.

Intralesional immunotherapy with killed Mycobacterium w vaccine for the treatment of ano-genital warts: an open label pilot study.

BACKGROUND: Intralesional immunotherapy with skin test antigens and vaccines has been found to be effective in the management of genital and extragenital warts. OBJECTIVE: To evaluate the efficacy and safety of intralesional Mycobacterium w (Mw) vaccine monotherapy for the treatment of ano-genital warts. PATIENTS AND METHODS: Ten patients clinically diagnosed to have external ano-genital warts, including three with giant ano-genital warts (Buschke Löwenstein tumour), were included in this open-label pilot study. Two patients were human immunodeficiency virus seropositive, and one was on iatrogenic immunosuppression for renal transplantation. Mw vaccine (0.1 mL) was initially injected intradermally in the deltoid region on both the sides, followed 2 weeks later by intradermal intralesional injection into the genital warts. Intralesional injections were repeated weekly until either complete clearance or a maximum of 10 injections was achieved. RESULTS: One patient was lost to follow-up after the first intralesional injection. In 8 out of remaining 9 patients (88.9%), the genital warts cleared completely. In one patient with giant perianal wart, the lesion was reduced to less than 5% of its volume after 10 intralesional injections, which was later electrosurgically excised. The treatment was well tolerated by the majority of the patients. The adverse reactions were noted in four patients, which were reversible. No recurrence was seen after a mean follow-up of 5.1 months. CONCLUSION: Intralesional immunotherapy of ano-genital warts with Mw vaccine seems to be a promising new approach, which needs to be evaluated in the randomized controlled trials.

Cytodiagnosis of extramedullary hematopoiesis in serous effusion: A rare presentation unfolding the underlying etiology.

Extramedullary hematopoiesis (EMH) usually involves reticuloendothelial system. However, it rarely may be present in the serous body effusions. In our case, the fluid cytology of both peritoneal and pleural fluid was diagnostic of the EMH in a patient with an undiagnosed underlying etiology.

Single point mutation on the gene encoding dysbindin results in recognition deficits.

The dystrobrevin-binding protein 1 (DTNBP1) gene is a candidate risk factor for schizophrenia and has been associated with cognitive ability in both patient populations and healthy controls. DTNBP1 encodes dysbindin protein, which is localized to synaptic sites and is reduced in the prefrontal cortex and hippocampus of patients with schizophrenia, indicating a potential role in schizophrenia etiology. Most studies of dysbindin function have focused on the sandy (sdy) mice that lack dysbindin protein and have a wide range of abnormalities. In this study, we examined dysbindin salt and pepper (spp) mice that possess a single point mutation on the Dtnbp1 gene predicted to reduce, but not eliminate, dysbindin expression. By western blot analysis, we found that spp homozygous (spp -/-) mutants had reduced dysbindin and synaptosomal-associated protein 25 (SNAP-25) in the prefrontal cortex, but unaltered levels in hippocampus. Behaviorally, spp mutants performed comparably to controls on a wide range of tasks assessing locomotion, anxiety, spatial recognition and working memory. However, spp -/- mice had selective deficits in tasks measuring novel object recognition and social novelty recognition. Our results indicate that reduced dysbindin and SNAP-25 protein in the prefrontal cortex of spp -/- is associated with selective impairments in recognition processing. These spp mice may prove useful as a novel mouse model to study cognitive deficits linked to dysbindin alterations. Our findings also suggest that aspects of recognition memory may be specifically influenced by DTNBP1 single nucleotide polymorphisms or risk haplotypes in humans and this connection should be further investigated.

The relationship between temperament and character and psychotic-like experiences in healthy children and adolescents.

BACKGROUND: Prior work by our group identified personality profiles associated with psychotic-like experiences (PLE's) in healthy adults that were strikingly similar to those found in schizophrenia patients, with the exception of two key differences. Specifically, higher levels of PLE's were linked to higher persistence and cooperativeness, suggesting that these characteristics might represent personality-based resilience factors. Notably, age and personality were significantly correlated in these data, raising questions about whether healthy children and adolescents would show similar results. To date, no study has examined personality profiles associated with both positive and negative PLE's in healthy children and adolescents using Cloninger's Temperament and Character Inventory (TCI). Thus, this study examined the relationship between TCI dimensions and PLE's in healthy children and adolescents. METHOD: The TCI and the Community Assessment of Psychic Experiences (CAPE) were administered to 123 healthy children and adolescents aged 8-18. Multiple regression models were used to examine personality dimensions associated with overall severity of PLE's as well as severity of positive and negative PLE's separately. RESULTS: Positive, negative, and overall PLE severity were all associated with a personality pattern of higher harm avoidance and lower self-directedness. Negative PLE severity was also associated with lower persistence. CONCLUSIONS: Personality correlates of PLE's in healthy children and adolescents were largely consistent with our past work on PLE's in healthy adults. However, our previously identified resilience factors were notably absent in this sample. These findings may suggest that these personality characteristics have not yet crystallized or emerged to aid in coping with PLE's.