Mouse model of focal cerebral ischemia using endothelin-1

Intracerebral injection of the vasoconstrictor peptide, endothelin-1 (ET-1), has been used as a method to induce focal ischemia in rats. The relative technical simplicity of this model makes it attractive for use in mice. However, the effect of ET-1 on mouse brains has not been firmly established. In this study, we determined the ability of ET-1 to induce focal cerebral ischemia in four different mouse strains (CD1, C57/BL6, NOD/SCID, and FVB). In contrast to rats, intracerebral injection of ET-1 did not produce a lesion in any mouse strain tested. A combination of ET-1 injection with either CCA occlusion or N(G)-nitro-l-arginine methyl ester (l-NAME) injection produced only a small infarct and its size was strain-dependent. A triple combination of CCA occlusion with co-injection of ET-1 and l-NAME produced a lesion in all mouse strains tested, and this resulted in a significant motor deficit. However, lesion size was still relatively small and strain-dependent. This study shows that ET-1 has a much less potent effect for producing an infarct in mice than rats.     

Structural and diffusion tensor imaging of the fornix in childhood- and adolescent-onset schizophrenia

ObjectiveThere is emerging evidence that aberrations in the integrity of cerebral white matter tracts, especially those connected to limbic structures, play a role in the pathophysiology of schizophrenia. The fornix is the primary efferent neural pathway of the hippocampus and has been shown to be abnormal in adults with schizophrenia.MethodHigh-resolution structural magnetic resonance imaging and diffusion tensor images were obtained on 15 patients with childhood- and adolescent-onset schizophrenia and 15 age- and sex-matched controls. Measures of cross-sectional area and water diffusion properties were obtained on regions of interest of the fornix performed by a trained radiologist.ResultsThe volume of the fornix was significantly smaller (10.9%) in children and adolescents with schizophrenia compared to controls (Cohen d = 0.87, p = .025). There were no significant differences between the fractional anisotropy or mean diffusivity between the groups.ConclusionsThese findings suggest that the early stages of schizophrenia are associated with a decrease in fornix volume without microstructural white matter changes. The volume differences may reflect an early insult to neighboring brain regions (i.e., hippocampus), that could decrease the number of efferent fibers without necessarily disrupting fiber integrity. J. Am. Acad. Child Adolesc. Psychiatry, 2008; 47(7):826–832.     

Poverty,inequality and the treated incidence of first-episode psychosis

INTRODUCTION: It is now commonly accepted that a range of psychosocial and environmental factors interact with genetic vulnerability in the genesis of psychotic illness. The aim of this study was to investigate whether measures of poverty and income inequality impact upon the treated incidence of first-episode psychosis (FEP) in the District of Umgungundlovu, South Africa. METHODS: Clinical and demographic data was collected from hospital records on all people aged 15-49 years from the District who presented to psychiatric services with FEP (DSM IV criteria) during 2005 (n = 160). All incident cases were grouped by municipality according to their recorded address. Measures of poverty and income inequality were calculated for each of the seven municipalities using data from the Statistics SA online database for the National Census 2001. Correlations were performed using SPSS to determine the relationships between treated incidence of FEP and poverty and inequality indices per municipality. RESULTS: There was a significant positive relationship between treated incidence and Inequality Index (Partial correlation coefficient 0.840; P = 0.036) and a non-significant negative relationship between treated incidence and Poverty Measure per municipality (Partial correlation coefficient -0.660; P = 0.154). These findings remained significant after adjusting for gender, age, ethnicity, urbanicity and employment status. Importantly, these results were not adjusted for individual level poverty. DISCUSSION/CONCLUSION: These findings lend support, in an African context, to increasing evidence that social, economic and political factors such as poverty and income inequality "shape both the landscape of risk for developing (psychosis) and the context in which health-care is provided" (Kelly in Soc Sci Med 61:721-730, 2005). These complex environmental factors appear to impact on the development and course of psychotic illness.     

Clinical and neurocognitive course in early-onset psychosis: a longitudinal study of adolescents with schizophrenia-spectrum disorders

Aim: Adolescents with psychotic disorders show deficits in IQ, attention, learning and memory, executive functioning, and processing speed that are related to important clinical variables including negative symptoms, adaptive functioning and academics. Previous studies have reported relatively consistent deficits with varying relationships to illness status and symptoms. The goals of this study were to examine these relationships in a larger sample at baseline, and also to examine the longitudinal course of these deficits in a smaller subset of adolescents. Method: Thirty‐six subjects, aged 10 to 17 years, were included at baseline. All had Diagnostic and Statistical Manual‐Fourth Edition diagnoses of schizophrenia, schizoaffective disorder, schizophreniform disorder and psychosis – not otherwise specified, as determined by Kiddie‐Schedule for Affective Disorders and Schizophrenia for School‐Age Children structured interviews. Patients were administered a neuropsychological battery, and Positive and Negative Syndrome Scale ratings were completed at baseline and again at 1 year (n = 14). Most participants were inpatients at baseline, and 13 of 14 were on atypical antipsychotic medication during both sessions. Results: At baseline, the patients demonstrated impairments in working memory, processing speed, executive function and verbal learning. No significant cognitive change was detected at 1‐year follow‐up. In contrast, clinical symptoms were variable across 1 year, with an improvement in positive symptoms at 1 year. No relationships between clinical and cognitive symptoms were observed, with the exception of baseline IQ predicting negative symptoms at 1 year. Conclusions: Young patients with schizophrenia‐spectrum disorders displayed neurocognitive impairments at baseline. Despite measurable fluctuations in clinical symptoms over the year, no significant changes were measured in cognition. Lower IQ at baseline was predictive of more negative symptoms at 1 year.     

Parental anxiety and quality of life in children with epilepsy

Parental beliefs and attitudes concerning epilepsy may significantly impact adjustment and quality of life for both the child and family. The purpose of the present study was to examine the relationship between parental anxiety and quality of life in pediatric patients with ongoing epilepsy. Subjects were parents (n=200) of children between the ages of 6 and 16 years who had been diagnosed and treated for epilepsy for at least 1 year. Parents were given quality of life and anxiety questionnaires during the child's clinic visit. A stepwise regression analysis suggested that severity of comorbid conditions, parental anxiety, seizure control, and number of medications were significantly associated with quality of life for these children. Parents with increased anxiety whose children had poorly controlled seizures and a comorbid disability were found to have diminished quality of life.     

Factors Associated with Academic Achievement in Children with Controlled Epilepsy

Children with epilepsy are at risk for academic underachievement. Multiple etiologies for this academic vulnerability have been suggested by past research including lower self-esteem, inattention, memory inefficiency, and lower socioeconomic status. The present study assessed 65 children (mean age = 10 years, 5 months) with well-controlled epilepsy on the four primary factors, as well as academic achievement and intelligence. A stepwise regression analysis was employed with academic achievement as the dependent variable and measures of self-esteem, attention, memory, and socioeconomic status as independent variables. When intelligence was controlled, attention was the only variable associated with achievement scores. Seizure variables including seizure type and duration of epilepsy were not associated with differences in academic performance. Findings support the importance of measuring attention skills in children with epilepsy and suggest that reduced auditory attention skills may be associated with decreased academic performance in these children.     

Validation of a self-report questionnaire version of the Child Activity Limitations Interview (CALI): The CALI-21

The Child Activity Limitations Interview (CALI) is a measure designed to assess functional impairment due to chronic pain in school-age children. In this study, we present a self-report questionnaire version of the CALI (the CALI-21) that extends the original interview measure. The purpose of this study was to provide internal consistency, cross-informant reliability and construct validity of the CALI-21 on a clinical sample of children and adolescents with chronic pain conditions. One hundred fifty-five children and adolescents (65 males, 90 females; ages 8-18 years, M=14.31, SD=2.45) with chronic pain completed questionnaires as part of their clinic intake procedures at their consultation visit in a pediatric pain management clinic. An exploratory factor analysis was conducted to measure latent constructs within the broader domain of functional impairment. Results of the exploratory factor analysis yielded two factors representing limitation in Active and Routine activities on both parent and child reports. Parent and child total CALI scores correlated with measures of pain intensity, however, different patterns of correlations emerged between age, pain intensity, depressive symptoms, and the Active and Routine factors. The CALI-21 showed good internal consistency, high cross-informant reliability, and demonstrated construct validity. The CALI-21 provides increased flexibility via the questionnaire format in the assessment of pain-related activity limitations in children. Factor analysis extends information about specific types of activity limitations experienced by children.     

Neural progenitor cells transplanted into the uninjured brain undergo targeted migration after stroke onset

Endogenous neural stem cells normally reside in their niche, the subventricular zone, in the uninjured rodent brain. Upon stroke, these cells become more proliferative and migrate away from the subventricular zone into the surrounding parenchyma. It is not known whether this stroke-induced behavior is due to changes in the niche or introduction of attractive cues in the infarct zone, or both. A related question is how transplanted neural stem cells respond to subsequent insults, including whether exogenous stem cells have the plasticity to respond to subsequent injuries after engraftment. We addressed this issue by transplanting neural progenitor cells (NPCs) into the uninjured brain and then subjecting the animal to stroke. We were able to follow the transplanted NPCs in vivo by labeling them with superparamagnetic iron oxide particles and imaging them via high-resolution magnetic resonance imaging (MRI) during engraftment and subsequent to stroke. We find that transplanted NPCs that are latent can be activated in response to stroke and exhibit directional migration into the parenchyma, similar to endogenous neural NPCs, without a niche environment.