Neuroimaging alterations and relapse in early-stage psychosis.

BACKGROUND: Recent reports have indicated that symptom exacerbation after a period of improvement, referred to as relapse, in early-stage psychosis could result in brain changes and poor disease outcomes. We hypothesized that substantial neuroimaging alterations may exist among patients who experience relapse in early-stage psychosis. METHODS: We studied patients with psychosis within 2 years after the first psychotic event and healthy controls. We divided patients into 2 groups, namely those who did not experience relapse between disease onset and the magnetic resonance imaging (MRI) scan (no-relapse group) and those who did experience relapse between these 2 timings (relapse group). We analyzed 3003 functional connectivity estimates between 78 regions of interest (ROIs) derived from resting-state functional MRI data by adjusting for demographic and clinical confounding factors. RESULTS: We studied 85 patients, incuding 54 in the relapse group and 31 in the no-relapse group, along with 94 healthy controls. We observed significant differences in 47 functional connectivity estimates between the relapse and control groups after multiple comparison corrections, whereas no differences were found between the no-relapse and control groups. Most of these pathological signatures (64%) involved the thalamus. The Jonckheere-Terpstra test indicated that all 47 functional connectivity changes had a significant cross-group progression from controls to patients in the no-relapse group to patients in the relapse group. LIMITATIONS: Longitudinal studies are needed to further validate the involvement and pathological importance of the thalamus in relapse. CONCLUSION: We observed pathological differences in neuronal connectivity associated with relapse in early-stage psychosis, which are more specifically associated with the thalamus. Our study implies the importance of considering neurobiological mechanisms associated with relapse in the trajectory of psychotic disorders.

Face processing of social cognition in patients with first episode psychosis: Its deficits and association with the right subcallosal anterior cingulate cortex.

The clinical importance of social cognition is well acknowledged in patients with psychosis, in particular those with first episode psychosis (FEP). Nevertheless, its brain substrates and circuitries remain elusive, lacking precise analysis between multimodal brain characteristics and behavioral sub-dimensions within social cognition. In the present study, we examined face processing of social cognition in 71 FEP patients and 77 healthy controls (HCs). We looked for a possible correlation between face processing and multimodal MRI characteristics such as resting-state functional connectivity (rsFC) and brain volume. We observed worse recognition accuracy, longer recognition response time, and longer memory response time in FEP patients when compared with HCs. Of these, memory response time was selectively correlated with specific rsFCs, which included the right subcallosal sub-region of BA24 in the ACC (scACC), only in FEP patients. The volume of this region was also correlated with memory response time in FEP patients. The scACC is functionally and structurally important in FEP-associated abnormalities of face processing measures in social cognition.

Deep vein thrombosis and septic pulmonary emboli with MRSA osteomyelitis in a pediatric patient.

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are relatively rare occurrences in the pediatric population. However, DVT and PE are associated with significant morbidity and mortality to the patient if not promptly diagnosed and treated. We describe the case of a 5-year-old boy that was diagnosed in our emergency department with DVT and PE. The underlying etiology was osteomyelitis of the left tibia caused by community-acquired methicillin-resistant Staphylococcus aureus. The patient had a prolonged hospital course with multiple complications but was eventually discharged in a good condition. In areas with a high prevalence of community-acquired methicillin-resistant S. aureus, it is important for physicians in the emergency department to be aware of the rare, but potentially fatal, complications of infection, including DVT with PE from septic emboli.

Narrowing critical regions and determining penetrance for selected 18q- phenotypes.

One of our primary goals is to help families who have a child with an 18q deletion anticipate medical issues in order to optimize their child's medical care. To this end we have narrowed the critical regions for four phenotypic features and determined the penetrance for each of those phenotypes when the critical region for that feature is hemizygous. We completed molecular analysis using oligo-array CGH and clinical assessments on 151 individuals with deletions of 18q and made genotype-phenotype correlations defining or narrowing critical regions. These nested regions, all within 18q22.3 to q23, were for kidney malformations, dysmyelination of the brain, growth hormone stimulation response failure, and aural atresia. The region for dysmyelination and growth hormone stimulation response failure were identical and was narrowed to 1.62 Mb, a region containing five known genes. The region for aural atresia was 2.3 Mb and includes an additional three genes. The region for kidney malformations was 3.21 Mb and includes an additional four genes. Penetrance rates were calculated by comparing the number of individuals hemizygous for a critical region with the phenotype to those without the phenotype. The kidney malformations region was 25% penetrant, the dysmyelination region was 100% penetrant, the growth hormone stimulant response failure region was 90% penetrant with variable expressivity, and the aural atresia region was 78% penetrant. Identification of these critical regions suggest possible candidate genes, while penetrance calculations begin to create a predictive phenotypic description based on genotype.

Growth hormone benefits children with 18q deletions.

Most individuals with constitutional deletions of chromosome 18q have developmental delays, dysmyelination of the brain, and growth failure due to growth hormone deficiency. We monitored the effects of growth hormone treatment by evaluating 23 individuals for changes in growth, nonverbal intelligence quotient (nIQ), and quantitative brain MRI changes. Over an average of 37 months, the treated group of 13 children had an average nIQ increase of 17 points, an increase in height standard deviation score of 1.7, and significant change in T1 relaxation times in the caudate and frontal white matter. Cognitive changes of this magnitude are clinically significant and are anticipated to have an effect on the long-term outcomes for the treated individuals.

The spectrum of thyroid abnormalities in individuals with 18q deletions.

Chromosome 18q deletions (18q-) are survivable autosomal deletions, having an estimated incidence of one in 40,000 live births. Our long-term goals were to 1) comprehensively define the endocrine phenotype, 2) determine the natural history, and 3) identify key genes leading to particular phenotypes. This report specifically emphasizes the thyroid phenotype. Medical record review and comprehensive clinical assessment(s) were performed on 120 individuals with 18q- at the Chromosome 18 Clinical Research Center, the largest group of individuals with 18q- ever assembled. Affected subjects ranged in age from 6 wk to 32 yr at initial assessment. Due to case reports of thyroid dysfunction in 18q deletions and the well-established association between hypothyroidism and aneusomies, we undertook thyroid testing in all individuals and completed TRH studies on 50 of them. Our studies demonstrated that 12% had hypothyroidism, and the results were consistent with primary thyroidal dysfunction. Furthermore, two individuals progressed from normal to abnormal over the course of 2 yr. Based on these studies, it appears that, as is the case in other aneusomies, annual thyroid testing, using TSH as a primary screening tool, is indicated. The mechanism of the hypothyroidism is not yet known, and the genetic basis has not been delineated.

Molecular characterization of 18p deletions: evidence for a breakpoint cluster.

PURPOSE: To determine the size and parental origin of the deletion in individuals with 18p- syndrome. METHODS: Molecular and fluorescence in situ hybridization analyses of the pericentromeric region of chromosome 18 were performed on genomic DNA and chromosomes from study participants. RESULTS: The majority of the breakpoints were located between markers D18S852 on 18p and D18S1149 on 18q, a distance of approximately 4 Mb. The parental origin of these deletions appears to be equally distributed, half maternally derived and half paternally derived. CONCLUSION: The distributions of both the size and parental origin of the 18p deletions support the presence of a breakpoint cluster in the 18p- syndrome.