Childhood onset schizophrenia: familial neurocognitive measures

OBJECTIVE: Early onset disorders may have more salient familial/genetic etiology. Neurocognitive deficits which are seen in families of adult onset schizophrenic patients were examined in healthy family members of patients with childhood-onset schizophrenia (COS). METHODS: Trail Making Tests (TMT) A and B, Wechsler Intelligence Scale-Revised Digit Span and Vocabulary subtests were administered to 67 parents and 24 siblings of patients with childhood-onset schizophrenia and 114 healthy community controls (CC) comparable in sex, age, and educational level. RESULTS: COS siblings performed significantly more poorly than did controls on Trails Making Test B with a trend for poorer performance evident on Trails Making Test A. COS parents performed more poorly than controls only on Trails Making Test A. CONCLUSIONS: Healthy first-degree relatives of COS probands have subtle deficits in tests involving oculomotor/psychomotor speed, working memory and executive function. This provides further support for continuity between COS and later onset schizophrenia and for a familial/genetic factor associated with the illness.     

Structural brain MRI abnormalities in healthy siblings of patients with childhood-onset schizophrenia

OBJECTIVE: Childhood-onset schizophrenia shows progressive brain magnetic resonance imaging (MRI) changes during adolescence, which follow a back-to-front "wave." The authors' goal was to examine whether healthy siblings of patients with childhood-onset schizophrenia show structural brain abnormalities and the age-related pattern of abnormalities seen in patients with childhood-onset schizophrenia. METHOD: Anatomic brain MRI scans were obtained from 15 psychiatrically healthy full siblings of 15 patients with childhood-onset schizophrenia and from 32 matched community volunteers. Automated measures were used to compare total and regional brain volumes of the siblings and volunteers. RESULTS: Siblings of patients with childhood-onset schizophrenia had smaller total cerebral volume and total, frontal, and parietal gray matter volumes than volunteers. When divided into younger and older groups, younger siblings had smaller parietal gray matter volumes and older siblings showed trends for smaller total and frontal gray matter volumes. CONCLUSIONS: Healthy siblings of patients with childhood-onset schizophrenia share brain MRI abnormalities with the patients that may follow a similar pattern of progression. Developmental brain abnormalities in childhood-onset schizophrenia may thus be genetic trait markers.     

Progressive brain volume loss during adolescence in childhood-onset schizophrenia

OBJECTIVE: Previous reports have documented a striking progressive reduction in cortical gray matter volume during adolescence in patients with childhood-onset schizophrenia. This study examined the rate of loss in cortical gray matter volume in relation to age and clinical status in adolescent patients over a follow-up period of 2-6 years. METHOD: A total of 131 brain magnetic resonance imaging scans were acquired for 60 subjects with childhood-onset schizophrenia (mean age=14.5 years, SD=2.5), and 140 scans were acquired for 64 matched healthy comparison subjects. One or more follow-up scans were acquired at approximately 2-year intervals for 39 subjects with childhood-onset schizophrenia and 43 healthy subjects. Developmental trajectories for total and regional brain volumes were examined in relation to age by using polynomial growth models and data from all available scans. The rate of gray matter reduction in patients with childhood-onset schizophrenia was examined in relation to developmental and clinical measures by using stepwise regression. RESULTS: Rates of brain volume reduction were significantly higher for patients with childhood-onset schizophrenia than for healthy comparison subjects. In childhood-onset schizophrenia, the rate of gray matter reduction was related to premorbid impairment and baseline severity of clinical symptoms but not to gender, ethnicity, or age at onset of the disorder. Unexpectedly, greater clinical improvement was significantly related to a higher rate of gray matter reduction. Longitudinal trajectories suggested that the rate of cortical loss plateaus during adolescence. CONCLUSIONS: Striking loss of cerebral gray matter is seen through adolescence in patients with childhood-onset schizophrenia. The rate of reduction was related to premorbid impairment and baseline symptom severity, but it may also be in part a plastic response to illness.     

Clozapine-induced neutropenia in children: management with lithium carbonate

Clozapine, an atypical antipsychotic, is the most effective medication for treatment-resistant schizophrenia, but its use is limited by the high risk of neutropenia and agranulocytosis. In children, the rate of clozapine-induced neutropenia is even higher than in adults. We report two cases of children 7- and 12-years old diagnosed with very early onset schizophrenia, who developed neutropenia when treated with clozapine. In both cases addition of lithium carbonate elevated the white blood count (WBC) allowing clozapine rechallenge. WBC and total neutrophil count remained stable long-term with coadministration of clozapine (400-425 mg per day) and lithium with the blood level of 0.8-1.1 microg/mL. This report supports the use of adjunct lithium for clozapine-induced neutropenia as a safe and successful strategy in children.     

Comparison of parent and student responses to asthma surveys: students grades 3-12 and their parents from a suburban private school setting

Schools are being called upon to help address asthma, a common problem in school-aged children. School-based asthma programs need information about asthma diagnoses, asthma symptoms, and asthma's impact on school attendance. Parent or student surveys are the most common method of collecting these data. However, medical literature offers little guidance to help schools determine whether parents or students are the most appropriate and effective source of asthma-related information. This study compares student and parent responses to the same set of asthma-related questions. In general, parents and students have a high level of agreement in reporting the absence of an asthma diagnosis or asthma symptoms. When parents and students disagreed, students reported many more asthmalike symptoms, especially symptoms with exercise and symptoms at night, than did their parents. The disparity in student and parent symptom reporting did not vary by age of the student. Students appear to provide the most sensitive measure of asthma-related problems.     

A double-blinded, randomized, vehicle-controlled, multicenter, parallel-group study to assess the safety and efficacy of tretinoin gel microsphere 0.04% in the treatment of acne vulgaris in adults

This double-blinded, randomized, vehicle-controlled, multicenter, parallel-group, 12-week, phase 4 study was conducted in adults with mild to moderate acne vulgaris. Of 178 subjects randomized to be treated, 88 subjects (49%) were treated with tretinoin gel microsphere 0.04% and 90 subjects (51%) were treated with vehicle. Inflammatory lesion counts were statistically significantly reduced at 2 weeks in tretinoin-treated subjects (P = .0110), and reductions in total lesion counts also were noted. The reduction in total lesion counts reached statistical significance at week 4 (P = .0305); at week 12, mean total, inflammatory, and noninflammatory lesion counts were statistically significantly lower in the tretinoin treatment group versus vehicle group (P < .05), and mean percentage reductions in lesion counts were significantly greater in the subjects with noninflammatory lesions treated with tretinoin compared with vehicle (P < .05). Mean percentage reductions in total, inflammatory, and noninflammatory lesion counts were 35.5%, 38.2%, and 33.6%, respectively, at week 12 for the tretinoin treatment group compared with 20.9%, 19.2%, and 20.4%, respectively, for the vehicle group (all P < .05). All adverse events were of mild or moderate intensity with the exception of severe skin irritation in one tretinoin-treated subject. At week 12, there were no statistically significant differences between treatment groups for any measured tolerability parameter.     

Dynamic mapping of cortical development before and after the onset of pediatric bipolar illness

BACKGROUND: There are, to date, no pre-post onset longitudinal imaging studies of bipolar disorder at any age. We report the first prospective study of cortical brain development in pediatric bipolar illness for 9 male children, visualized before and after illness onset. METHOD: We contrast this pattern with that observed in a matched group of healthy children as well as in a matched group of 8 children with 'atypical psychosis' who had similar initial presentation marked by mood dysregulation and transient psychosis (labeled as 'multi-dimensionally impaired' (MDI)) as in the bipolar group, but have not, to date, developed bipolar illness. RESULTS: Dynamic maps, reconstructed by applying novel cortical pattern matching algorithms, for the children who became bipolar I showed subtle, regionally specific, bilaterally asymmetrical cortical changes. Cortical GM increased over the left temporal cortex and decreased bilaterally in the anterior (and sub genual) cingulate cortex. This was seen most strikingly after the illness onset, and showed a pattern distinct from that seen in childhood onset schizophrenia. The bipolar neurodevelopmental trajectory was generally shared by the children who remained with MDI diagnosis without converting to bipolar I, suggesting that this pattern of cortical development may reflect affective dysregulation (lability) in general. CONCLUSIONS: These dynamic trajectories of cortical development may explain age-related disparate findings from cross-sectional studies of bipolar illness, and suggest the importance of mood disordered non-bipolar control group in future studies.     

Detection of BRAF mutation on fine needle aspiration biopsy specimens: a new diagnostic tool for papillary thyroid cancer

Numerous biomolecular markers have been studied to improve the accuracy of fine needle aspiration biopsy (FNAB) in the diagnostic and prognostic evaluation of thyroid tumors, but none of them has yet become clinically useful. The recently discovered BRAF mutation, which occurs specifically in papillary thyroid cancers (PTC) with a high prevalence and is associated with poor clinicopathological outcomes, has the potential to be a useful diagnostic and prognostic marker for PTC. In the present study, we investigated whether detection of BRAF mutation on FNAB specimens was technically possible and could be used as an adjunct diagnostic tool with routine FNAB. Evaluation of a new colorimetric mutation detection method demonstrated 100% sensitivity and 100% specificity in comparison with conventional DNA sequencing as the "gold standard" in a large pool of DNA samples from various primary thyroid tumor specimens and cell lines. We found this novel technique even more sensitive in detecting BRAF mutation on FNAB specimens than conventional sequencing. In a series of 48 patients undergoing thyroidectomy, mostly for thyroid cancer or for suspicion of cancer, we performed preoperative FNAB and, using the colorimetric mutation detection method, identified BRAF mutation on the cytological specimens. Prospective analysis showed that 50% of the nodules that proved to be PTC on surgical histopathology were correctly diagnosed by BRAF mutation analysis on FNAB specimens; there were no false positive findings. Thus, we have demonstrated the usefulness of BRAF mutation detection on FNAB specimens that can help diagnose and identify those PTC patients who may need more aggressive surgical treatment and vigilant clinical monitoring.     

Functional outcomes in patients with right hemisphere brain damage

Background : In this era of accountability in health care, the need to document treatment-related changes in health status is critical. However, few studies report outcomes in people with right cerebral hemisphere damage (RHD). Aims : The objective of this study was to document, in a single population of patients with RHD, selected functional outcomes at the termination of inpatient treatment. Of particular interest were cognitive performance and its influence on motor and overall recovery. Methods & Procedures : Functional outcomes were retrospectively examined in 101 RHD patients, at discharge from an in-patient rehabilitation programme. The Functional Independence Measure (FIM; Center for Functional Assessment Research, 1993) was the measurement tool. The five outcomes examined were: final functional status, amount of gain, efficiency of gain, length of stay (LOS), and discharge placement. FIM scores, produced on an ordinal rating scale, were statistically transformed by the Rasch method (Rasch, 1960) to generate interval-level data for regression analyses. Outcomes & Results : Summary by outcomes: Gains were evident in cognitive and motor realms, with greater and more efficient improvement in the latter. Regression analysis indicated that final functional status was best predicted by age, initial motor severity (FIM motor score), and initial total cognitive severity (FIM cognitive scores); amount of gain was best predicted by age, evidence of previous neurological incident, and gender; efficiency of gain by initial cognitive item scores, initial motor severity (FIM score) and age; LOS by initial motor severity (FIM score); and discharge placement by age, marital status, and initial severity (FIM status). Major predictors tended to be age and the family of cognitive FIM scores, especially Problem Solving (PS). Memory and PS were the most challenging cognitive items for these patients, as indicated by scores on admission and discharge reflecting less than functional ability. A sizeable number of patients began and ended rehabilitation with functional levels of ability in comprehension, expression, and social interaction. Significant differences existed between patients with neglect and those without, but neglect was not a significant predictor of any outcome measure. Low initial cognitive FIM scores, presence of neglect, and older age were associated with poorer performance in motor and cognitive realms. Previous neurological episodes were negatively associated with amount of gain. Number of comorbidities was not statistically associated with outcomes. Conclusions : Initial severity levels and age were the most influential factors on these outcomes. The presence of neglect had a relatively minor impact on most outcomes. Performance on the cognitive items was less impaired than motor items, and registered less gain and less efficient gain than motor items, but did predict various final status and gain-related measurements in overall and motor realms. Analyses in this study revealed that the FIM scale is less sensitive to cognitive change than to motor change.