Huntington's disease (HD) is a neuropsychiatric disorder characterized by choreiform movement of the limbs, cognitive disability, psychosis and dementia. It is untreatable, incurable, and ultimately fatal. HD is invariably associated with an abnormally long CAG expansion within the IT15 gene on human chromosome 4. Although the mutant huntingtin protein (mHtt) is ubiquitously expressed in HD patients, cellular degeneration occurs only in neurons within the striatum and cerebral cortex. The Ras homolog Rhes is expressed very selectively in the precise brain areas affected by HD. Recent work using cultured cells suggests that Rhes may be a co-factor with mHtt in cell death. However, there is controversy as to whether cell death underlies the symptoms of HD. We used a validated transgenic mouse model of HD crossed with Rhes knockout mice to show that the behavioral symptoms of HD are regulated by Rhes. HD/Rhes-/- mice showed greatly delayed expression of HD-like symptoms in this in vivo model. Drugs that block or inhibit the actions of Rhes may be useful as the first treatments for HD.

Huntington’s disease (HD) is a heritable, neurodegenerative disorder characterized by motor, cognitive, and psychiatric disturbances. The progressive disease is caused by an unstable CAG expansion within the gene that normally encodes for the huntingtin protein (Htt). The expanded mutant form of Htt (mHtt) is expressed ubiquitously throughout patients’ bodies; however, neuronal degeneration is prominent only in the corpus striatum and, to a lesser extent, the cortex. The Ras homolog Rhes is also preferentially localized to the striatum. The putative co-factor Rhes has been shown to act with mHtt to cause neuronal death. Simvastatin, a lipid lowering drug, and zoledronate, a nitrogen bisphosphonate, act on the mevalonate pathway, which gives both Rhes and its target cells, binding sites. The current study aimed to interrupt the mevalonate pathway and inactivate, via de-prenylation, Rhes in CD-1 mice exposed to 3-nitroproprionic acid, a neurotoxin that mimics HD mitochondrial dysfunction and striatal degeneration. Results suggest that drug treatment does not rescue motor impairments and may potentiate 3-NP damage. The persistent motor deficits are discussed in relation to possible Rhes de-prenylation.

While a correlation between suffering from psychosis and an increased risk of engaging in aggressive behaviours has been established, many factors have been explored which may contribute to increasing this risk. Patients with a diagnosis of psychosis have been shown to have significant difficulties in facial affect recognition (FAR) and some authors have proposed that this may contribute to increasing the risk of displaying aggressive or violent behaviours. A systematic review of the current evidence regarding the links between facial affect recognition and aggression was conducted. Results were varied with some studies providing evidence of a link between emotion recognition difficulties and aggression, while others were unable to establish such an association. Results should be interpreted with some caution as the quality of included studies was poor due to small sample sizes, insufficient power and limited reporting of results. Adequately powered, randomised controlled studies using appropriate blinding procedures and validated measures are therefore required. There is a substantial evidence base demonstrating difficulties in emotional perception in patients with psychosis, with evidence suggesting a relationship with reduced social functioning, increased aggression and more severe symptoms of psychosis. In this review we aim to review this field to assess if there is a causal link between facial affect recognition difficulties and psychosis. The Bradford Hill criteria for establishing a causal relationship from observational data were used to generate key hypotheses, which were then tested against existing evidence. Where a published meta-analysis was not already available, new meta-analyses were conducted. A large effect of FAR difficulties in those with a diagnosis of psychosis, with a small to moderate correlation between FAR problems and symptoms of psychosis was found. Evidence was provided for the existence of FAR problems in those at clinical high risk of psychosis, while remediation of psychosis symptoms did not appear to impact FAR difficulties. There appears to be good evidence of the existence of facial affect recognition difficulties in the causation of psychosis, though larger, longitudinal studies are required to provide further evidence of this.

Children with social skills deficits in verbal and nonverbal communication can face a variety of social challenges in many aspects of their lives. Given the increasing social needs of many students in today's classrooms, there is a need for increased social skills instruction and support in public schools. Inclusion opportunities in public schools can have a positive impact on the development of social skills and can increase peer understanding and empathy for students with special needs. Although there is research in the area of inclusion and its benefits, there is little known about the impact of the instructional setting on the ability of children to generalize social skills to other school settings. Based on social development theory and social learning theory, this quantitative study used secondary data (N = 129) from 2 primary schools in Connecticut to determine whether elementary age children are more likely to generalize social skills if they are taught social skills in the general education classroom setting compared to those who are taught social skills in the resource room setting or receive no instruction in social skills controlling for natural social skills growth. The result of an ANCOVA revealed that children who were taught social skills in the general education setting were more likely to generalize social skills across settings. The results of this study contribute to positive social change by helping inform school administrators and teachers about how to best support children with social deficits in reaching their academic and social potential. The findings may also help to create an environment that is more accepting of the varying needs of students and as a result can help to create a positive school climate and increase acceptance and friendships among elementary age students that can last into adulthood.

Cognitive theories of depression have long posited automatic interpretation biases (AIB) as a central contributor to depressed mood. The current study was first to examine AIB in a clinically defined depressed sample. While assessing AIB using a semantic association paradigm, pupillary reactivity was simultaneously recorded to build insight into the AIB process. A total of 53 individuals (25 depressed and 28 healthy control) completed the Word Sentence Association Paradigm for Depression (WSAP-D) while pupillary reactivity was recorded. Results revealed the depressed group was significantly more likely to endorse negative AIB and less likely to endorse benign AIB compared to healthy controls. The depressed group demonstrated a modest effect size difference indicating they were faster to endorse negative AIB compared to the healthy controls, but did not differ in endorsing benign AIB or in rejecting either valence. Pupillary reactivity was found to differentiate behaviorally defined AIB type from a natural processing condition when counter to theorized, group relevant AIB. The depressed group demonstrated greater initial pupillary constriction during initial presentation of ambiguous information and comparatively less pupillary dilation during and after endorsing a benign AIB. Taken together, the results suggest that theorized negative AIB and lack of benign AIB are characteristic of depression, that greater cognitive effort is required to reject interpretations consistent with theorized biases consistent with reinterpretation processes, and that depressed individuals are less engaged with benign AIB compared to healthy controls, possibly associated with hedonic deficits. Theoretical implications and future directions are discussed.

Dementia is a syndrome characterized by multiple cognitive deficits, that are sufficient to interfere with daily living and social and occupational functioning (Gabrowski & Damasio, 2004). Alzheimer’s Dementia (AD) is the most common cause of dementia in adults and the risk of developing the disease increases with age. Alzheimer’s Dementia is a disease that is misunderstood in Nigeria because of the nature and time of onset of the condition; memory loss associated with Alzheimer’s Dementia is assumed to be a normal part of aging. This report investigates the quality of care that is provided to older adults with Alzheimer’s Dementia in Nigeria and offers recommendations for improved rehabilitation services / text

This report provides an overview of the adverse effects of the antiepileptic drug topiramate. Specifically, it evaluates the negative cognitive-communication effects of topiramate on individuals with epilepsy and postulates that treating these deficits is within the scope of practice of speech-language pathologists. It begins with a discussion on epilepsy, description of seizures, and the mechanism of action for antiepileptic drugs. It then provides an overview of cognitive communication deficits caused by antiepileptic drugs, including: memory problems, impairments in attention, and executive dysfunction. The final section provides an outline of potentially beneficial treatments a speech-language pathologist may provide to patients experiencing adverse effects from topiramate and how continued research can expand this area of practice. / text

While the consequences of political distortions on fiscal cyclicality have been thoroughly analyzed, there are few studies that specify which political variables create these distortions. In this paper I use political-economy theories of the deficit as a basis as to why fiscal cyclicality deviates from what is predicted by tax-smoothing and Keynesian models. Specifically, I examine the effects of political polarization, the years an incumbent has been in office, party affiliation, and fiscal federalism to partition how political characteristics affect fiscal responses to changes in GDP growth. I find that governments tend to be more responsive to changes in GDP growth further away from elections, left leaning governments are more responsive than right leaning governments, mixed results for political polarization, and that unitary governments are more responsive than federalist governments.

Thesis (doctoral)--Rijksuniversiteit Groningen, 1991. / Summary in Dutch. Includes bibliographical references (p. 218-230).

Thesis (Ph. D.)--University of Missouri-Columbia, 1998. / Typescript. Vita. Includes bibliographical references (leaves 157-163). Also available on the Internet.