Sharon Kim

Regional specificity of hippocampal volume reductions in first-episode schizophrenia

Hippocampal volume reductions are widely observed in schizophrenia. Some studies suggest anterior hippocampal regions are more susceptible and associated with frontal lobe dysfunctions, while others implicate posterior regions. Using high-resolution MR images and novel computational image analysis methods, we identified the hippocampal subregions most vulnerable to disease processes in 62 (45 m/17 f) first-episode schizophrenia patients compared to 60 (30 m/30 f) healthy controls, similar in age. The hippocampi were traced on coronal brain slices and hemispheric volumes were compared between diagnostic groups. Regional structural abnormalities were identified by comparing distances, measured from homologous hippocampal surface points to the central core of each individuals hippocampal surface model, between groups in 3D. CSF concentrations were also compared statistically at homologous hippocampal surface points to localize corresponding gray matter reductions. Significant bilateral hippocampal volume reductions were observed in schizophrenia irrespective of brain size corrections. Statistical mapping results, confirmed by permutation testing, showed pronounced left hemisphere shape differences in anterior and midbody CA1 and CA2 regions in patients. Significant CSF increases surrounding the hippocampus were observed in a similar spatial pattern in schizophrenia. Results confirm that hippocampal volume reductions are a robust neuroanatomical correlate of schizophrenia and are present by first episode. Mid- to antero-lateral hippocampal regions show pronounced volume changes and complementary increases in peri-hippocampal CSF, suggesting that these hippocampal regions are more susceptible to disease processes in schizophrenia. Targeting regional hippocampal abnormalities may help dissociate schizophrenia patients from other groups exhibiting global hippocampal volume changes, and better focus systems-level pathophysiological hypotheses.

Abnormal gyral complexity in first-episode schizophrenia

BACKGROUND Abnormalities in the patterns and frequency of cortical folding might help identify temporal and regionally specific disturbances in normal neurodevelopmental processes that occur in association with schizophrenia. Few studies, however, have investigated gyral complexity in schizophrenia. METHODS High-resolution magnetic resonance images were used to examine differences in gyral complexity, measured three-dimensionally in five separate hemispheric regions covering the entire cortical surface, in patients with first-episode schizophrenia (n = 50) compared with demographically matched healthy comparison subjects (n = 50). The modulating effects of gender and hemisphere were also examined. RESULTS Significant increases in cortical folding were observed in the right superior frontal cortex in male schizophrenic patients compared with male control subjects, but not between female diagnostic groups. Significant main effects of hemisphere were found in frontal, parietal, and occipital regions in directions complementary to cerebral torques. CONCLUSIONS Results support previous findings of right frontal hypergyria in male schizophrenic patients and suggest that these abnormalities predate illness onset and are of neurodevelopmental origin. Therefore, in schizophrenia, sexually dimorphic developmental processes and differences in hemispheric connectivity, which have been shown to influence the organization and/or frequency of cortical folding, seem to be disturbed during gyral formation in utero.

Gastrointestinal and Psychological Mediators of Health-Related Quality of Life in IBS and IBD: A Structural Equation Modeling Analysis

OBJECTIVES:Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are chronic gastrointestinal (GI) syndromes in which both GI and psychological symptoms have been shown to negatively impact health-related quality of life (HRQOL). The objective of this study was to use structural equation modeling (SEM) to characterize the interrelationships among HRQOL, GI, and psychological symptoms to improve our understanding of the illness processes in both conditions.METHODS:Study participants included 564 Rome positive IBS patients and 126 IBD patients diagnosed via endoscopic and/or tissue confirmation. All patients completed questionnaires to assess bowel symptoms, psychological symptoms (SCL-90R), and HRQOL (SF-36). SEM with its two components of confirmatory analyses and structural modeling were applied to determine the relationships between GI and psychological symptoms and HRQOL within the IBS and IBD groups.RESULTS:For both IBD and IBS, psychological distress was found to have a stronger direct effect on HRQOL (−0.51 and −0.48 for IBS and IBD, respectively) than GI symptoms (−0.25 and −0.28). The impact of GI symptoms on psychological distress was stronger in IBD compared with IBS (0.43 vs. 0.22; P<0.05). The indirect effect of GI symptoms on HRQOL operating through psychological distress was significantly higher in IBD than IBS (−0.21 vs. −0.11; P<0.05).CONCLUSIONS:Psychological distress is less dependent on GI symptom severity in IBS compared with IBD even though the degree that psychological distress impacts HRQOL is similar. The findings emphasize the importance of addressing psychological symptoms in both syndromes.

Stratification Based on Language-Related Endophenotypes in Autism: Attempt to Replicate Reported Linkage

The identification of autism susceptibility genes has been hampered by phenotypic heterogeneity of autism, among other factors. However, the use of endophenotypes has shown preliminary success in reducing heterogeneity and identifying potential autism‐related susceptibility regions. To further explore the utility of using language‐related endophenotypes, we performed linkage analysis on multiplex autism families stratified according to delayed expressive speech and also assessed the extent to which parental phenotype information would aid in identifying regions of linkage. A whole genome scan using a multipoint non‐parametric linkage approach was performed in 133 families, stratifying the sample by phrase speech delay and word delay (WD). None of the regions reached suggested genome‐wide or replication significance thresholds. However, several loci on chromosomes 1, 2, 4, 6, 7, 8, 9, 10, 12, 15, and 19 yielded nominally higher linkage signals in the delayed groups. The results did not support reported linkage findings for loci on chromosomes 7 or 13 that were a result of stratification based on the language delay endophenotype. In addition, inclusion of information on parental history of language delay did not appreciably affect the linkage results. The nominal increase in NPL scores across several regions using language delay endophenotypes for stratification suggests that this strategy may be useful in attenuating heterogeneity. However, the inconsistencies in regions identified across studies highlight the importance of increasing sample sizes to provide adequate power to test replications in independent samples.

A Mindful Way Through IBS: Reducing Abdominal Pain And Improving Quality Of Life

highly unlikely to develop cancer. To accomplish this, we need to develop a nonendoscopic screening test to diagnose and risk stratify BE in the population at risk and develop more sophisticated endoscopic evaluations, incorporating advanced imaging techniques and biomarkers that can accurately determine those that need intervention. EAC is a devastating disease and our current approaches for disease prevention seem to be flawed.

Tu1409 Body Mass Index (BMI) is Associated With Gastrointestinal Symptoms in a Racially and Ethnically Diverse IBS Patient Population

Background: Obesity is an increasingly prevalent medical problem that has been linked to variousmedical disorders, including gastroesophageal reflux disease andmetabolic syndrome. Obesity and increased body mass index (BMI) have also been associated with upper and/ or lower gastrointestinal (GI) symptoms in community or managed care populations, which have been primarily Caucasian. There is limited data on whether BMI is associated with irritable bowel syndrome (IBS) and if the association is affected by race. Aims: 1) To compare BMI between IBS patients and healthy controls (HCs) while controlling for demographic variables: age, gender, race/ethnicity and education; 2) To determine if BMI is associated with bowel habit subtypes, GI and somatic symptom ratings and quality of life (QOL) in IBS. Methods: Rome III positive IBS patients and HCs were recruited primarily from advertisement in a racially and ethnically diverse metropolitan community. Subjects completed questionnaires regarding demographics, GI and psychological symptoms including GI symptom-specific anxiety (Visceral Sensitivity Index [VSI]), QOL (SF-12), and non-GI somatic symptom severity (PHQ-12). T tests, Spearmans correlation, Kruskal-Wallis and chi-squared tests were used for bivariate comparisons and linear regression was used to control for demographic variables. Significance was assessed at 0.05. Results: A total of 871 subjects (374 IBS) participated in the study. Demographic and BMI data are shown in the Table 1. Rome III bowel habit subtypes in the IBS patients were: 23% IBS-C, 22% IBS-D and 55% IBS-M. Median BMI significantly differed by race/ethnicity AA: 26.7, Hispanic: 24.7, White: 23.7, Asian: 21.2, Other: 23.9 (p<0.001). Mean BMI was significantly higher in IBS than in HCs (P=0.022), but this difference became non-significant after controlling for demographics (P=0.715). Within the IBS group, BMI significantly differed by bowel habit subtype (P=0.010). After controlling for demographics, BMI in IBS-M was significantly higher than IBS-C with a 2.04 unit increase in BMI in IBS-M relative to IBS-C (P=0.005). In IBS, BMI negatively correlated with physical composite score of QOL (r=-0.27, P<0.001) and positively correlated with abdominal pain ratings (r=0.15, P=0.004) and VSI (r=0.12, P=0.027) but did not correlate with non-GI somatic symptom severity. Significance was maintained after controlling for demographics. Conclusion: BMI differences related to race/ ethnicity can account for BMI differences between IBS and HCs. However in IBS, BMI is significantly associated with bowel habit predominance, abdominal pain, and GI symptomspecific anxiety even after controlling for demographic variables. BMI is not associated with non-GI somatic symptom severity suggesting that BMI has an independent relationship to GI symptoms that is not related to presence of comorbidities. Demographics and BMI of Study Subjects