A brief overview of special education law with focus on autism

This article reviews the provisions of Individuals with Disabilities Education Act as they apply particularly to students with autism. It also refers to the antidiscrimination provisions of the Rehabilitation Act Amendments (Sec. 504) and to their relevance to students with autism. It attempts to answer specific questions posed by the National Academy of Science.     

Schizophrenia and viral infection during neurodevelopment: a focus on mechanisms.

The task of defining schizophrenia pathogenesis has fascinated and frustrated researchers for nearly a century. In recent years, unprecedented advances from diverse fields of study have given credence to both viral and developmental theories. This review considers possible mechanisms by which viral and developmental processes may interact to engender schizophrenia. Many of the current controversies in schizophrenia pathogenesis are reviewed in light of the viral hypothesis, including: epidemiological findings and the role of a genetic diathesis, phenotype heterogeneity, abnormalities in excitatory and inhibitory neurotransmitter systems, anomalous cerebral latereralization, and static vs progressive disease. The importance of animal models in elucidating the impact of viral infections on developing neurons is illustrated by recent studies in which neonatal rats are infected with lymphocytic choriomeningitis virus in order to examine alterations in hippocampal circuitry. Finally, consideration is given to a new hypothesis that some cases of schizophrenia could be instigated by a viral infection that disrupts developing inhibitory circuits, consequently unleashing glutamatergic neurotransmission leading to selective excitotoxicity, and a degenerative disease course.     

Emerging and re-emerging epidemic encephalitis: a tale of two viruses

Two major epidemics of viral encephalitis occurred in Asia in 1997 and 1998. The first was a re-emergence of neurovirulent strains of enterovirus 71, which caused severe encephalomyelitis in children in Malaysia, Taiwan and Japan, on a background of hand, foot and mouth disease. Necropsy studies of patients who died of enterovirus 71 infection showed severe perivascular cuffing, parenchymal inflammation and neuronophagia in the spinal cord, brainstem and diencephalon, and in focal areas in the cerebellum and cerebrum. Although no viral inclusions were detected, immunohistochemistry showed viral antigen in the neuronal cytoplasm. Inflammation was often more extensive than neuronal infection, suggesting that other factors, in addition to direct viral cytolysis, may be involved in tissue damage. The second epidemic of viral encephalitis was the result of a novel paramyxovirus called Nipah, which mainly involved pig handlers in Malaysia and Singapore. Pathological evidence suggested that the endothelium of small blood vessels in the central nervous system was particularly susceptible to infection. This led to disseminated endothelial damage and syncytium formation, vasculitis, thrombosis, ischaemia and microinfarction. However, there was also evidence of neuronal infection by the virus and this may also have contributed to the neurological dysfunction in Nipah encephalitis. Some patients who seemed to recover from the acute symptoms have been re-admitted with clinical findings suggestive of relapsing encephalitis. As these two epidemics indicate, the emergence and re-emergence of viral encephalitides continue to pose considerable challenges to the neuropathologist, in establishing the diagnosis and unravelling the pathogenesis of the neurological disease.     

ADHD in adolescence and adulthood, with a special focus on the dopamine transporter and nicotine

The persistence of attention deficit hyperactivity disorder (ADHD) into adolescence and adulthood has now been accepted as a clinical entity. The rate of prevalence among adults is assumed to be from 2% to 4%. With increasing age, a symptom change has to be considered; disturbance of attention becomes more prominent, whereas hyperactivity often diminishes or changes to inactivity. Neuroimaging studies show a high striatal dopamine transporter (DAT) availability in most adults with ADHD; this can be reduced by stimulants. Nicotine seems to have a stimulant-like action on the DAT. In most adults with ADHD, therapy has to be multimodal, combining psychotherapy and medication. Methylphenidate is the first-line drug in adult ADHD; further options are amphetamine and noradrenaline reuptake inhibitors. Nonresponders to methylphenidate seem to have no elevated DAT availability prior to therapy. Combination with other psychiatric disorders occurs frequently in adults with ADHD; in these patients additional pharmacological treatment with special regard to the comorbid disease is recommended.     

A discriminant validity study of negative symptoms with a special focus on depression and antipsychotic medication

If the construct validity of the negative symptom syndrome is to be established, the conceptual and operational overlap between negative symptoms and other syndromes such as depression and the effects of medication must be explained. The author assessed 26 patients with schizophrenia and 21 patients without schizophrenia, most of whom had depression, at the end of an average 2-week drug washout period and after approximately 2 months of psychotropic medication administration. Negative symptoms were remarkably consistent in patients with schizophrenia despite pharmacological intervention. In contrast, the patients without schizophrenia manifested significant decreases in negative symptoms.     

Behavioural consequences of p-glycoprotein deficiency in mice, with special focus on stress-related mechanisms

P‐glycoprotein (P‐gp), an efflux transporter localised in the blood–brain barrier, limits the access of multiple xenobiotics to the central nervous system. Whether it is also implemented in the transport of the endogenous glucocorticoid corticosterone is a matter of debate. The P‐gp knockout mouse model [abcb1a/b (?/?)] has been shown to differ in the functioning of the hypothalamic‐pituitary adrenal (HPA) axis. In the present study, we investigated the behaviour of abcb1a/b (?/?) and wild‐type mice with respect to stress‐related tests and the effects of corticosterone. Behavioural activities were assessed in the open field (OF) test for 4 days, and in the forced swimming test (FST) and tail suspension test (TST) under naïve and stressed conditions. The FST was also conducted after exogenous corticosterone injection (0.25 and 2.5 mg/kg). Moreover, the elevated plus maze test and the RotaRod test (RotaRod Advanced; TSE Systems, Bad Homburg, Germany) were assessed. Brain corticosterone levels were determined by an immunoassay and expression of glucocorticoid receptors by western blot analysis. Abcb1a/1b (?/?) mice showed significantly decreased brain corticosterone levels and elevated glucocorticoid receptor expression. Behavioural analysis revealed a significantly decreased activity in the OF test on the first 2 days in abcb1a/1b (?/?) mice compared to wild‐type mice, although the differences disappeared under habituation. Immobility time in the FST was significantly decreased in abcb1a/1b (?/?) mice under basal and under stressed conditions, whereas immobility in the TST was significantly elevated in these mice under all conditions. Injection of exogenous corticosterone resulted in significant reductions of immobility in the FST in abcb1a/1b (?/?) mice, whereas wild‐type mice did not respond to the same doses. There were no differences in the elevated plus maze test and RotaRod test. The results obtained in the present study demonstrate that a P‐gp deficiency has an impact on the stress‐related behaviour, possibly as a result of differences in HPA axis‐feedback regulation.     

Biological roles of trace elements in the brain with special focus on Zn and Fe

Introduction

Many metals like iron (Fe), copper (Cu) or zinc (Zn) fulfil various essential biological functions and are thus vital for all living organisms. For instance, they play important roles in nervous tissue, participating in a wide range of processes such as neurotransmitter synthesis, myelination or synaptic transmission.

State of the art

As in other tissues, brain cells tightly control the concentration of metals but any excess or deficit can lead to deleterious responses and alter cognitive functions. Of note, certain metals such as Zn, Fe or Cu accumulate in specific brain structures over lifespan and several neurodegenerative diseases are associated with a dysregulation of the homeostatic mechanisms controlling the concentration of these cations.

Conclusion and perspectives

This review will address some of the cellular and molecular processes controlling the entry and distribution of selected metals (mainly Zn and Fe) in the brain, as well as their roles in synaptic transmission, in the pathogenesis of some neurologic diseases such as Parkinson's disease and Alzheimer's disease, and their impact on cognitive functions.     

Chemokines and the inflammatory response to viral infection in the central nervous system with a focus on lymphocytic choriomeningitis virus

Leukocyte migration to the central nervous system (CNS) is a common process with often devastating consequences that follows infection of this tissue compartment with a variety of viruses. The mechanisms underlying this process are poorly defined but, it is hypothesized that chemokines may be important regulatory signals for the cerebral recruitment and extravasation of leukocytes. Here we discuss this hypothesis in the context of different viral infections of the CNS with emphasis on lymphocytic choriomeningitis virus (LCMV). In general, the pattern of chemokine gene expression in these CNS viral infections is dynamic and complex with often overlapping expression of a number of different subclasses of chemokine genes. In the case of CNS infection with LCMV, cerebral chemokine gene expression was observed in euthymic and to a lesser extent athymic mice and preceded increases in cytokine gene expression and in euthymic mice, CNS leukocyte recruitment. These observations together with the finding that CRG-2/IP-10, a prominently expressed chemokine gene in many different CNS viral infections, was expressed by cells intrinsic to the CNS e.g. astrocytes, suggest that activation of chemokine gene expression may be a direct, early and localized host response to viral infection. These findings are consistent with the proposed involvement of chemokines as key signaling molecules for the migration of leukocytes to the CNS following virus infection.     

Current trends in psychiatry care in Finland with special focus on private practice psychiatry and psychotherapy

Several previous reforms decentralized Finnish psychiatric services to a great extent. The Ministry of Social Affairs and Health is outlining a proposal for Health Care Law, which makes an effort to centralize and reorganize healthcare. It is not yet possible to see what this will mean for the psychiatric services. In general, the health status of the Finnish population has improved. Although rates of suicides have declined considerably, rates of alcohol-related deaths have risen. Moreover, disability related to major depression has increased drastically, which has lead to a nationwide project called MASTO, which has the aim to improve early detection and treatment of depression. The Ministry of Social Affairs and Health set up a work group, MIND 2009, to draft local working models for mental health and addiction services. To study the significance of psychotherapy in a private practice psychiatric context, the Finnish Psychiatric Association conducted a survey amongst its members. Most psychiatrists in private practice conduct psychotherapy.     

Primary prevention of child abuse: focus on the special child.

The authors review the literature on child abuse and present evidence demonstrating that children who are born prematurely or who are sickly or handicapped are at high risk for child abuse. The authors describe ways to identify such children and suggest a number of primary prevention techniques that can reduce parental stress and help prevent child abuse. The techniques include day-care programs for handicapped children, mothers' social clubs, and lay health visitors to give support and impart proper maternal attitudes.     

Psychopharmacological treatment and psychiatric morbidity in 390 cases of suicide with special focus on affective disorders.

OBJECTIVE: The aim of this study was, on the basis of data from health-care registers, to describe the adequacy of psychopharmacological treatment in suicides. METHOD: Data on consecutive suicides in a Danish County (Funen) in the period of 1 April 1991-31 December 1995 were identified in the Danish Psychiatric Central Register, the National Patient Register, the National Health Insurance and Odense University Pharmacoepidemiological Database. RESULTS: Twenty-five per cent of the suicides previously hospitalized due to affective disorders and 3% of the suicides without psychiatric hospitalizations at all, received an apparently adequate treatment with antidepressants the month before suicide. CONCLUSION: The most striking finding was the insufficiency of treatment with antidepressants in the group of suicides without psychiatric hospitalization, in particular in light of the fact that depression is assumed to be present in at least 50% of all suicides.     

Cerebral autoregulation: an overview of current concepts and methodology with special focus on the elderly.

Cerebral autoregulation (CA) refers to the properties of the brain vascular bed to maintain cerebral perfusion despite changes in blood pressure (BP). Whereas classic studies have assessed CA during changes in BP that have a gradual onset, dynamic studies quantify the fast modifications in cerebral blood flow (CBF) in relation to rapid alterations in BP. There is a lack of standardization in the assessment of dynamic CA. This review provides an overview of the methods that have been applied, with special focus on the elderly. We will discuss the relative merits and shortcomings of these methods with regard to the aged population. Furthermore, we summarize the effects of variability in BP on CBF in older people. Of the various dynamic assessments of CA, a single sit-to-stand procedure is a feasible and physiologic method in the elderly. The collection of spontaneous beat-to-beat changes in BP and CBF allows estimation of CA using the technique of transfer function analysis. A thorough search of the literature yielded eight studies that have measured dynamic CA in the elderly aged <75 years. Regardless of the methods used, it was concluded from these studies that CA was preserved in this population.     

Deficiency of adenosine deaminase 2; special focus on central nervous system imaging

Purpose

To increase the knowledge of central nervous system (CNS) imaging features in deficiency of adenosine deaminase 2 (DADA2) by examining magnetic resonance imaging (MRI) studies of a relatively large number of patients.