An investigation of organic factors in the neuropsychological functioning of patients with borderline personality disorder

The hypothesis to be tested in this study was that the cognitive deficits that have been documented in patients with Borderline Personality Disorder (BPD) are largely the consequence of organic insult, either developmental or acquired. Using a cross-sectional design, 80 subjects (males and females) who met the criteria for BPD participated in the study. They completed a battery of neuropsychological tests and a comprehensive interview assessing organic status as well as measures of the potentially confounding factors of current levels of depression and anxiety. It was expected that BPD-patients with a probable history of organic insult would perform significantly worse than would BPD patients without such a history. Analyses of the results provided partial support for the hypothesis. Subjects with both BPD and a history of organic insult were significantly more impaired on several measures including measures of attention than were BPD only subjects. The results suggested that the impaired cognitive performance of persons diagnosed with BPD may, in part, be attributed to organic factors.

The mismatch negativity (MMN) response to complex tones and spoken words in individuals with aphasia

Background: The mismatch negativity (MMN) is a fronto-centrally distributed event-related potential (ERP) that is elicited by any discriminable auditory change. It is an ideal neurophysiological tool for measuring the auditory processing skills of individuals with aphasia because it can be elicited even in the absence of attention. Previous MMN studies have shown that acoustic processing of tone or pitch deviance is relatively preserved in aphasia, whereas the basic acoustic processing of speech stimuli can be impaired (e.g., auditory discrimination). However, no MMN study has yet investigated the higher levels of auditory processing, such as language-specific phonological and/or lexical processing, in individuals with aphasia. Aims: The aim of the current study was to investigate the MMN response of normal and language-disordered subjects to tone stimuli and speech stimuli that incorporate the basic auditory processing (acoustic, acoustic-phonetic) levels of non-speech and speech sound processing, and also the language-specific phonological and lexical levels of spoken word processing. Furthermore, this study aimed to correlate the aphasic MMN data with language performance on a variety of tasks specifically targeted at the different levels of spoken word processing. Methods M Procedures: Six adults with aphasia (71.7 years +/- 3.0) and six healthy age-, gender-, and education-matched controls (72.2 years +/- 5.4) participated in the study. All subjects were right-handed and native speakers of English. Each subject was presented with complex harmonic tone stimuli, differing in pitch or duration, and consonant-vowel (CV) speech stimuli (non-word /de:/versus real world/deI/). The probability of the deviant for each tone or speech contrast was 10%. The subjects were also presented with the same stimuli in behavioural discrimination tasks, and were administered a language assessment battery to measure their auditory comprehension skills. Outcomes O Results: The aphasic subjects demonstrated attenuated MMN responses to complex tone duration deviance and to speech stimuli (words and non-words), and their responses to the frequency, duration, and real word deviant stimuli were found to strongly correlate with performance on the auditory comprehension section of the Western Aphasia Battery (WAB). Furthermore, deficits in attentional lexical decision skills demonstrated by the aphasic subjects correlated with a word-related enhancement demonstrated during the automatic MMN paradigm, providing evidence to support the word advantage effect, thought to reflect the activation of language-specific memory traces in the brain for words. Conclusions: These results indicate that the MMN may be used as a technique for investigating general and more specific auditory comprehension skills of individuals with aphasia, using speech and/or non-speech stimuli, independent of the individual's attention. The combined use of the objective MMN technique and current clinical language assessments may result in improved rehabilitative management of aphasic individuals.

Cognitive disorders and neurogenesis deficits in Huntington's disease mice are rescued by fluoxetine

Huntington's disease (HD) is a neurodegenerative disorder caused by an expanded CAG trinucleotide repeat encoding an extended polyglutamine tract in the huntingtin protein. Affected individuals display progressive motor, cognitive and psychiatric symptoms (including depression), leading to terminal decline. Given that transgenic HD mice have decreased hippocampal cell proliferation and that a deficit in neurogenesis has been postulated as an underlying cause of depression, we hypothesized that decreased hippocampal neurogenesis contributes to depressive symptoms and cognitive decline in HD. Fluoxetine, a serotonin-reuptake inhibitor commonly prescribed for the treatment of depression, is known to increase neurogenesis in the dentate gyrus of wild-type mouse hippocampus. Here we show that hippocampal-dependent cognitive and depressive-like behavioural symptoms occur in HD mice, and that the administration of fluoxetine produces a marked improvement in these deficits. Furthermore, fluoxetine was found to rescue deficits of neurogenesis and volume loss in the dentate gyrus of HD mice.

Cognitive deficits associated with cancer: A model of subjective and objective outcomes

Cancer and its treatment can affect many different aspects of quality of life. As a construct measured subjectively, quality of life shows an inconsistent relationship with objective outcome measures. That is, sometimes subjective and objective outcomes correspond with each other and sometimes they show little or no relationship. In this article, we propose a model for the relationship between subjective and objective outcomes using the example of cognitive function in people with cancer. The model and the research findings on which it is based help demonstrate that, in some circumstances, subjective measures of cognitive function correlate more strongly with psychosocial variables such as appraisal, coping, and emotions than with objective cognitive function. The model may provide a useful framework for research and clinical practice in quality of life for people with cancer.

Attention deficit disorder: not just for children

Attention deficit/hyperactivity disorder (ADHD) has long been described in children who demonstrate developmentally inappropriate symptoms of inattention, impulsivity and motor restlessness. In adults, symptoms are known to persist and the validity of adult ADHD as an entity is now recognized. There is an associated high proportion of other serious psychiatric comorbidities, especially substance abuse, mood and anxiety disorders. Advances have been made into the aetiology and management of ADHD. Many of these focus on the dopamine and noradrenaline pathways.

The association between early minor motor difficulties in extreme low birth weight infants and school age attentional difficulties

Introduction: Extremely premature infants of normal intellectual ability have an increased prevalence of motor and attentional difficulties. Knowledge of the relationship between early motor difficulties and measures of attention at school age would enhance understanding of these developmental pathways, their interrelationship and opportunities for intervention. Objective: This study examines whether an association exists between early findings of minor motor difficulties and school age clinical and psychometric measures of attention. Methodology: 45/60 eligible ELBW(1000 g) or preterm (< 27/40 gestation) infants born at the Mater Mother's Hospital were assessed at 12 and 24 months for minor motor deficits (using NSMDA) and at 7-9 years for attention, using clinical (Conners and Du Paul Rating Scales) and psychometric (assessing attention span, selective and divided attention) measures. Results: NSMDA at 12 months was only associated with the psychometric measures of verbal attention span. It was not associated with later clinical measures of attention. NSMDA at 24months was strongly associated with specific clinical measures of attention at school age, independent of biological and social factors. It was not associated with psychometric measures of attention. Conclusion: The major finding of this study is that motor difficulties in ELBW infants at 2 years are associated with later clinical measures of attention. Possible mechanisms underlying this relationship are considered. Crown Copyright (c) 2005 Published by Elsevier Ireland Ltd. All rights reserved.

An integrated biopsychosocial approach to understanding awareness deficits in Alzheimer's disease and brain injury

Considerable emphasis has been placed upon cognitive neuropsychological explanations of awareness disorders in brain injury and Alzheimer's disease (AD), with relatively few models acknowledging the role of psychosocial factors. The present paper explores clinical presentations of unawareness in brain injury and AD, reviews the evidence for the influence of psychosocial factors alongside neuropsychological changes, and considers a number of key issues that theoretical models need to address, before going on to discuss some recently-developed models that offer the potential for developing a comprehensive biopsychosocial account. Building on these developments, we present a framework designed to assist clinicians to identify the specific factors contributing to an individual's presentation of unawareness, and illustrate its application with a case example.

Apnea diving: Long-term neurocognitive sequelae of repeated hypoxemia

This article examines the neurocognitive sequelae of repeated exposure to hypoxemia in apnea (breath-hold) divers. A brief review of the literature on the physiological and neurological adaptations involved in the human diving reflex is presented. The results from a neuropsychological investigation of N = 21 elite apnea divers are evaluated. Standard neuropsychological tests, with known sensitivity to mild brain insults, included speed of visuo-motor responding, speed of language comprehension, response inhibition, and visual and verbal attention and recall tasks. Results indicated that the breath-hold divers performed tasks within the average range compared to norms on all tests, suggesting that 1-20 years of repeated exposure to hypoxemia including multiple adverse neurological events did not impact on performance on standard neuropsychological tasks. The results are discussed in relation to implications for clinical conditions such as sleep apnea, respiratory disorders, altitude sickness, and recreational apnea activities.

The influence of dopamine on semantic activation in Parkinson's disease: Evidence from a multipriming task

Research has suggested that semantic processing deficits in Parkinson's disease (PD) are related to striatal dopamine deficiency. As an investigation of the influence of dopamine on semantic activation in PD, 7 participants with PD performed a lexical-decision task when on and off levodopa medication. Seven healthy controls matched to the participants with PD in terms of sex, age, and education also participated in the study. By use of a multipriming paradigm, whereby 2 prime words were presented prior to the target word, semantic priming effects were measured across stimulus onset asynchronies (SOAs) of 250 Ins and 1,200 Ins. The results revealed a similar pattern of priming across SOAs for the control group and the PD participants on medication. In contrast, within-group comparisons revealed that automatic semantic activation was compromised in PD participants when off medication. The implications of these results for the neuromodulatory influence of dopamine on semantic processing in PD are discussed.

mu O-conotoxin MrVIB selectively blocks Na(v)1.8 sensory neuron specific sodium channels and chronic pain behavior without motor deficits

The tetroclotoxin-resistant voltage-gated sodium channel (VGSC) Na(v)1.8 is expressed predominantly by damage-sensing primary afferent nerves and is important for the development and maintenance of persistent pain states. Here we demonstrate that mu O-conotoxin MrVIB from Conus marmoreus displays substantial selectivity for Na(v)1.8 and inhibits pain behavior in models of persistent pain. In rat sensory neurons, submicromolar concentrations of MrVIB blocked tetroclotoxin-resistant current characteristic of Na(v)1.8 but not Na(v)1.9 or tetroclotoxin-sensitive VGSC currents. MrVIB blocked human Nav1.8 expressed in Xenopus oocytes with selectivity at least 10-fold greater than other VGSCs. In neuropathic and chronic inflammatory pain models, allodynia and hyperalgesia were both reduced by intrathecal infusion of MrVIB (0.03-3 nmol), whereas motor side effects occurred only at 30-fold higher doses. In contrast, the nonselective VGSC blocker lignocaine displayed no selectivity for allodynia and hyperalgesia versus motor side effects. The actions of MrVIB reveal that VGSC antagonists displaying selectivity toward Na(v)1.8 can alleviate chronic pain behavior with a greater therapeutic index than nonselective antagonists.

An n-of-1 trial service in clinical practice: Testing the effectiveness of stimulants for attention-deficit/hyperactivity disorder

OBJECTIVE. We sought to describe the clinical use of n-of-1 trials for attention-deficit/hyperactivity disorder in publicly and privately funded family and specialized pediatric practice in Australia. METHODS. We used a within-patient randomized, double-blind, crossover comparison of stimulant (dexamphetamine or methylphenidate) versus placebo or alternative stimulant using 3 pairs of treatment periods. Trials were conducted from a central location using mail and telephone communication, with local supervision by the patients' clinicians. PATIENTS. Our study population included children with clinically diagnosed attention-deficit/ hyperactivity disorder who were aged 5 to 16 years and previously stabilized on an optimal dose of stimulant. They were selected because treatment effectiveness was uncertain. MAIN OUTCOME MEASURES. Our measures included number of patients recruited, number of doctors who used the service, geographic spread, completion rates, response rate, and post-n-of-1 trial decisions. RESULTS. Forty-five doctors across Australia requested 108 n-of-1 trials, of which 86 were completed. In 69 drug-versus-placebo comparisons, 29 children responded better to stimulant than placebo. Immediately posttrial, 19 of 25 drug-versus-placebo responders stayed on the same stimulant, and 13 of 24 nonresponders ceased or switched stimulants. In 40 of 63 for which data were available, posttrial management was consistent with the trial results. For all types of n-of-1 trials, management changed for 28 of 64 children for whom information was available. DISCUSSION. Attention-deficit/hyperactivity disorder n-of-1 trials can be implemented successfully by mail and telephone communication. This type of trial can be valuable in clarifying treatment effect when it is uncertain, and in this series, they had a noticeable impact on short-term management.

Responding to interpersonal and physically provoking situations in classrooms: emotional intensity in children with attention deficit hyperactivity disorder

The present research investigated the emotional functioning of children with and without Attention Deficit Hyperactivity Disorder (ADHD), in order to examine the relationships between emotional intensity and classroom-based responses to physically and interpersonally provoking situations. Seventy children (35 with ADHD and 35 without ADHD) in Years 3–8 participated and were matched on age, gender, grade, and school class. Each child was observed individually in the classroom over two 20-min periods. The Responses to Interpersonal and Physically Provoking Situations Observation Schedule was used to record the frequency and severity of responses and the triggers for these during the observational periods. Children later rated their emotional intensity in response to hypothetical scenarios on the Emotional Intensity Scale for Children. Results revealed children with ADHD displayed significantly more frequent and severe challenging and solitary off-task behaviours, and significantly more frequent vocalisations and severe interactional off-task behaviours. For triggers, environmental and teacher-initiated distractions were significantly more frequently observed in children with ADHD. There were no differences in ratings of emotional intensity between children with and without ADHD, although a number of significant and meaningful correlations were observed between positive emotional intensity scores and responses and triggers.

Comparison of the clinical efficacy of twice-daily Ritalin and once-daily Equasym XL with placebo in children with Attention Deficit/Hyperactivity Disorder

Objective To compare the efficacy and safety of two methylphenidate (MPH) formulations—once-daily modified-release MPH (EqXL, Equasym™ XL) and twice-daily immediate-release methylphenidate (MPH-IR, Ritalin®)—and placebo in children with Attention Deficit/Hyperactivity Disorder (ADHD). Methods Children aged 6–12 years on a stable dose of MPH were randomized into a double-blind, three-arm, parallel-group, multi-center study and received 3 weeks of EqXL (20, 40, or 60 mg qd), MPH-IR (10, 20, or 30 mg bid) or placebo. Non-inferiority of EqXL to MPH-IR was assessed by the difference in the inattention/overactivity component of the overall teacher’s IOWA Conners’ Rating Scale on the last week of treatment (per protocol population). Safety was monitored by adverse events, laboratory parameters, vital signs, physical exam, and a Side Effect Rating Scale. Results The lower 97.5% confidence interval bound of the difference between MPH groups fell above the non-inferiority margin (−1.5 points) not only during the last week of treatment but during all three treatment weeks. Both MPH-treatment groups experienced superior benefit when compared to placebo during all treatment weeks (P < 0.001). All treatments were well tolerated. Conclusions EqXL given once-daily was non-inferior to MPH-IR given twice-daily. Both treatments were superior to placebo in reducing ADHD symptoms.