Functional diversity of chemokines and chemokine receptors in response to viral infection of the central nervous system.

Encounters with neurotropic viruses result in varied outcomes ranging from encephalitis, paralytic poliomyelitis or other serious consequences to relatively benign infection. One of the principal factors that control the outcome of infection is the localized tissue response and subsequent immune response directed against the invading toxic agent. It is the role of the immune system to contain and control the spread of virus infection in the central nervous system (CNS), and paradoxically, this response may also be pathologic. Chemokines are potent proinflammatory molecules whose expression within virally infected tissues is often associated with protection and/or pathology which correlates with migration and accumulation of immune cells. Indeed, studies with a neurotropic murine coronavirus, mouse hepatitis virus (MHV), have provided important insight into the functional roles of chemokines and chemokine receptors in participating in various aspects of host defense as well as disease development within the CNS. This chapter will highlight recent discoveries that have provided insight into the diverse biologic roles of chemokines and their receptors in coordinating immune responses following viral infection of the CNS

The impact of substance use on brain structure in people at high risk of developing schizophrenia

Ventricular enlargement and reduced prefrontal volume are consistent findings in schizophrenia. Both are present in first episode subjects and may be detectable before the onset of clinical disorder. Substance misuse is more common in people with schizophrenia and is associated with similar brain abnormalities. We employ a prospective cohort study with nested case control comparison design to investigate the association between substance misuse, brain abnormality, and subsequent schizophrenia. Substance misuse history, imaging data, and clinical information were collected on 147 subjects at high risk of schizophrenia and 36 controls. Regions exhibiting a significant relationship between level of use of alcohol, cannabis or tobacco, and structure volume were identified. Multivariate regression then elucidated the relationship between level of substance use and structure volumes while accounting for correlations between these variables and correcting for potential confounders. Finally, we established whether substance misuse was associated with later risk of schizophrenia. Increased ventricular volume was associated with alcohol and cannabis use in a dose-dependent manner. Alcohol consumption was associated with reduced frontal lobe volume. Multiple regression analyses found both alcohol and cannabis were significant predictors of these abnormalities when simultaneously entered into the statistical model. Alcohol and cannabis misuse were associated with an increased subsequent risk of schizophrenia. We provide prospective evidence that use of cannabis or alcohol by people at high genetic risk of schizophrenia is associated with brain abnormalities and later risk of psychosis. A family history of schizophrenia may render the brain particularly sensitive to the risk-modifying effects of these substances

Subcortical volumes across the lifespan: data from 18,605 healthy individuals aged 3-90 years

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.Education and Child Studie

Brain structure and function changes during the development of schizophrenia: The evidence from studies of subjects at increased genetic risk

This article reviews the evidence for changes in the structure and function of the brain in subjects at high risk of schizophrenia for genetic reasons during the genesis of the disorder. We first highlight the structural and functional abnormalities in schizophrenia and whether any similar or lesser abnormalities are apparent in unaffected relatives. There is good evidence for subtle abnormalities of hippocampal and ventricle volume in relatives that are not as marked as the deficits in schizophrenia. In addition, the functional imaging literature suggests that prefrontal cortex function may deteriorate in those at risk who go on to develop the disorder. We then review the findings from longitudinal imaging studies of those at high risk, particularly the Edinburgh High-Risk Study, which report gray matter density reductions in medial and lateral temporal lobe because people develop schizophrenia, as well as functional abnormalities which precede onset. We conclude by quoting our own and others' imaging studies of the associations of genetic and other risk factors for schizophrenia, including stressful life events and cannabis use, which provide mechanistic examples of how these changes may be brought about. Overall, the literature supports the view that there are measurable changes in brain structure and function during the genesis of the disorder, which provide opportunities for early detection and intervention

Current enhancement with alternating gate voltage in the Coulomb blockade regime of a single wall carbon nanotube

We investigated the current–voltage characteristics of a carbon nanotube in a single electron transistor structure with alternating gate voltage. A continuous current enhancement effect with increasing frequency of the applied gate voltage up to 13 MHz is reported. Assuming that I=nef, more than 1000 electrons are driven to flow across the source–drain channel at VDS=100 mV, 13 MHz of gate voltage (Vp-p=2 V) and T=1.8 K. The continuous current enhancement is explained by the broadening effect of the discrete energy levels of the finite-length carbon nanotube

Orbitofrontal morphology in people at high risk of developing schizophrenia

BACKGROUND: Abnormalities of orbitofrontal cortex (OFC) sulcogyral patterns have been reported in schizophrenia, but it is not known if these predate psychosis. METHODS: Hundred and forty-six subjects at high genetic risk of schizophrenia, 34 first episode of schizophrenia patients (SZ) and 36 healthy controls were scanned and clinically assessed. Utilising the classification system proposed by Chiavaras, we categorised OFC patterns and compared their distribution between the groups, as well as between those high risk subjects who did, and did not develop schizophrenia. The relationship between OFC pattern and schizotypy was explored in high risk subjects. RESULTS: We refined Chiavaras' classification system, with the identification of a previously unreported variant of OFC surface structure. There were significant differences in distribution of OFC patterns between high risk subjects who did or did not develop schizophrenia as well as between the first episode of schizophrenia group and healthy controls. Within the high risk group, possession of OFC Type III was associated with higher ratings on the Structured Inventory for Schizotypy (SIS) psychotic factor. CONCLUSIONS: Our results suggest that OFC Type III is associated with psychotic features before the development of schizophrenia. Characterisation of OFC morphology may have a role in the identification of those at greatest risk of developing schizophrenia