bluuebunny/crossref_metadata_2025 huggingface dataset:
Frequency, phenomenology and anatomical–clinical correlates of major post-stroke depression
Authors: Gainotti G. , Azzoni A. , Marra C.
Published: October 2008

Background

The meaning of post-stroke depression is controversial.

Aims

To investigate the hypothesis that major post-stroke depression (PSD) may be due to organic factors (left frontal lesions) immediately after the stroke, but to psychosocial factors in later stages.

Method

We studied 153 consecutive stroke patients, categorised on the basis of time elapsed since stroke, lesion location and presence/absence of major PSD, Fifty-eight were examined in the first two months following the stroke, 52 between two and four months, and 43 after four months or more. The symptom profiles and anatomical–clinical correlates of major PSD were studied in each subgroup. A group of 30 patients affected by a functional form of major depression were also investigated.

Results

The symptom profiles and anatomical–clinical correlates of major PSD were not different in the acute and more chronic stages. Clear symptom differences were, however, observed between major PSD and endogenous major depression. Motivated (reactive) symptoms prevailed in the former, whereas unmotivated symptoms prevailed in the latter.

Conclusions

Our data are more consistent with a psychological than with a neurological model of post-stroke depression.
Group treatment of auditory hallucinations
Authors: Wykes Til , Parr Ann-Marie , Landau Sabine
Published: October 2008

Background

Cognitive–behavioural therapy has been shown to be effective in reducing psychotic symptoms, but few patients have access to these services. Group cognitive treatment may provide a less costly service with similar benefits.

Aims

To explore the effectiveness of group cognitive–behavioural therapy on insight and symptoms, particularly auditory hallucinations.

Method

Twenty-one DSM–IV diagnosed patients with schizophrenia with treatment-resistant, distressing auditory hallucinations were referred to a group programme consisting of six sessions of cognitive treatment following a strict protocol which emphasised individual power and control as well as coping strategies.

Results

There were significant changes in all three main outcome measures following treatment; those changes were maintained at follow-up and were greater than changes over the waiting-list period. Specifically, there were changes in perceived power and distress as well as increases in the number and effectiveness of the coping strategies.

Conclusions

Group treatment for auditory hallucinations needs further investigation but does look promising and may provide a less costly alternative to individual cognitive treatment.
“To see oursels as others see us”
Authors: David Anthony S.
Published: October 2008

Background

This paper takes as its starting point the paper by Aubrey Lewis entitled “The psychopathology of insight” published in 1934, unreferenced.

Aims

To attempt to explore the historical antecedents and consequences of this work.

Method

Speculative review.

Results

Lewis's approach to phenomenology, contemporaneous movements in psychology and Lewis's own life and times – notably the eugenics legislation in Nazi Germany – probably shaped his conclusions. Modern concepts of insight, which emphasise neuropsychology as well as social psychology, were anticipated in Lewis's writings.

Conclusions

The concept of insight has stimulated research into difficult theoretical and practical areas such as self-awareness and treatment compliance, respectively. Concern over a patients capacity for insight has the potential to humanise psychiatry.
Pragmatic randomised controlled trials in psychiatry
Authors: Hotopf Matthew , Churchill Rachel , Lewis Glyn
Published: October 2008

Background

Randomised controlled trials (RCTs) are the most important method of evaluating new treatments and treatment policies. Despite this, there are relatively few large pragmatic RCTs in psychiatry.

Aims

To explore the main advantages of large pragmatic RCTs and the obstacles to performing them in psychiatry.

Method

A narrative review of literature on pragmatic RCTs with examples drawn from psychiatry and other medical specialities.

Results

Obstacles to performing pragmatic RCTs in psychiatry include the complexity of psychiatric interventions, the complexity of outcomes used in psychiatry and the difficulties of blinding subjects and investigators to some psychiatric interventions.

Conclusions

Researchers need to frame questions in a form that is relevant to clinicians and to convince clinicians to cooperate in simple large pragmatic trials.
In vivo occupancy of striatal and temporal cortical D2/D3 dopamine receptors by typical antipsychotic drugs
Authors: Bigliani Valeria , Mulligan Rachel S. , Acton Paul D. , Visvikis Dimitris , Ell Peter J. , Stephenson Caroline , Kerwin Robert W. , Pilowsky Lyn S.
Published: October 2008

Background

The dopamine hypothesis proposes that antipsychotic drugs act primarily through limbic cortical D2/D2-like dopamine receptor blockade.

Aim

To evaluate this hypothesis with the D2/D3-selective SPET probe [123I]-epidepride.

Method

[123I]-epidepride SPETscans were performed on 12 patients with schizophrenia treated with antipsychotics and 11 age-matched healthy controls. [123I]-epidepride specific binding to D2/D3 dopamine receptors was estimated, and relative percentage D2/D3 receptor occupancy by typical antipsychotic drugs determined.

Results

Mean (s.d.) daily dose was 669.12 (516.8) mg chlorpromazine equivalents. Mean percentage D2/D3 receptor occupancy was 81.6 (8.1) and 73.2 (13.9) in the temporal cortex and striatum respectively.

Conclusions

Typical antipsychotic drug treatment is associated with substantial temporal cortical D2/D3 receptor occupancy. The relationship between this and efficacy is poor in patients with treatment-resistant schizophrenia.
Neuropsychological function in euthymic patients with bipolar disorder
Authors: Ferrier I. N. , Stanton Biba R. , Kelly T. P. , Scott Jan
Published: October 2008

Background

The assumption that patients with bipolar disorder make a full inter-episode recovery has been challenged by limited evidence that suggests that neuropsychological dysfunction in bipolar disorder may persist beyond episodes of illness.

Aims

To test the hypothesis that patients with euthymic bipolar disorder show neuropsychological impairment.

Method

A battery of neuropsychological tests (assessed attention, working memory, learning and executive function) was administered to three matched groups of subjects: good-outcome patients with bipolar disorder (n=21); poor-outcome patients with bipolar disorder (n=20); controls (n=20). All patients were clinically euthymic, although some had low levels of depressive symptoms.

Results

Patients performed worse than controls on a number of neuropsychological tests. When age, premorbid IQ and depressive symptoms were controlled for, the results indicated impairment of executive function.

Conclusions

These findings provide good evidence for the existence of neuropsychological impairment in patients with euthymic bipolar disorder, although the possible effect of medication should not be overlooked. This may be of clinical relevance and raises questions about the course and outcome of the illness.
Evaluating mental health policy in England
Authors: Bindman Jonathan , Beck Andrew , Glover Gyles , Thornicroft Graham , Knapp Martin , Leese Morven , Szmukler George
Published: October 2008

Background

The Care Programme Approach (CPA) and supervision register policies in England are intended to prioritise patients to receive specialist mental health care.

Aims

To describe and evaluate the practical application of the policies.

Method

A questionnaire survey of key informants in mental health provider trusts and an analysis of aggregated data collected by health authorities using the Mental Illness Needs Index as a measure of population need.

Results

On average, 1175 per 100 000 total population are subject to the CPA (95% Cl=1055–1309) and 8.6 per 100 000 (95% Cl=7.5–9.9) are on supervision registers. Wide local variations in the number of people subject to the CPA and supervision registers are not explained by variations in population need.

Conclusions

Prioritisation to receive specialist mental health services is carried out inconsistently, and inequitable use of resources may result.
Effectiveness of cognitive therapy for delusions in routine clinical practice
Authors: Jakes Simon , Rhodes John , Turner Trevor
Published: October 2008

Background

Previous studies have suggested that cognitive therapy is effective in modifying delusions.

Aims

To assess the effectiveness of cognitive therapy on patients seen in routine clinical work.

Method

Eighteen patients with chronic delusions were treated using cognitive therapy, after the method of Chadwick and Lowe. A single-case multiple-baseline experimental design was used, including a control treatment. Each subject was used as their own control.

Results

Six patients reduced conviction in their delusions during cognitive therapy and not during the control treatment. Seven patients' conviction ratings did not change. Five patients showed a variable response. Degree of conviction did not fall to zero in any patient. All patients reported that the therapy had been helpful; six spontaneously mentioned changes in psychotic thinking.

Conclusions

One-third of patients with chronic delusions whom we treated responded to delusion modification with a reduction in degree of belief. Change within therapy sessions predicted outcome, as did variation in the conviction during baseline. Cognitive therapy with delusions should aim at reducing distress as well as conviction.
Altered cerebral perfusion measured by SPECT in relatives of patients with schizophrenia
Authors: Blackwood Douglas H. R. , Glabus Mike F. , Dunan Julie , O'Carroll Ronan E. , Muir Walter J. , Ebmeier Klaus P.
Published: October 2008

Background

Genetic studies in schizophrenia are hampered by the complex heterogeneous clinical phenotype. Biological variables identified as trait markers of risk could clarify the mode of inheritance, define clinical subgroups and provide clues about aetiology.

Aims

To use single photon emission computed tomography (SPECT) to compare brain perfusion maps in patients with schizophrenia (n=19), their asymptomatic ‘high-risk’ relatives (n=36) and control subjects (n=34) and to examine the relationships between imaging, memory and P300 event-related potential.

Method

SPECT, memory tests and P300 recording were carried out.

Results

In the patients with schizophrenia and their relatives, perfusion was reduced in left inferior prefrontal and anterior cingulate cortex and increased bilaterally in a subcortical region. Perfusion significantly correlated with verbal memory and P300 amplitude in left inferior prefrontal cortex and with P300 latency in anterior cingulate cortex.

Conclusions

Medication– and symptom-free relatives had altered regional perfusion intermediate between subjects with schizophrenia and controls. Impaired perfusion, verbal memory and P300 appear to be related traits associated with an increased risk of illness.
No evidence for left superior temporal dysfunction in asymptomatic schizophrenia and bipolar disorder
Authors: Dye Stephen , Spence Sean , Bench Christopher , Hirsch Steven , Stefan Martin , Sharma Tonmoy , Grasby Paul
Published: October 2008

Background

Positron emission tomography (PET) studies have revealed functional left superior temporal gyrus (STG) abnormalities in symptomatic schizophrenia during word generation.

Aims

To discover if this dysfunction is present in asymptomatic schizophrenia. To determine whether, without concurrent symptomatology, schizophrenia and bipolar affective disorder (BPD) are distinguishable by differing regional cerebral blood flow (rCBF) patterns during word generation.

Method

A PETverbal fluency protocol was applied to six patients with BPD in remission and six patients with asymptomatic schizophrenia. Analysis included 10 control subjects from a contemporaneous study.

Results

All groups showed relative reduction of rCBF in both superior temporal cortices. There were no quantitative differences in any group comparison. All groups exhibited negative covariation between rCBF in left prefrontal and right (but not left) temporal regions.

Conclusions

Abnormal patterns of left STG function cannot be regarded as a trait marker for schizophrenia. Functional abnormalities may reflect aspects of mental state.
How much English health authorities are allocated for mental health care
Authors: Glover Gyles
Published: October 2008

The authors of the King's Fund report on London's mental health services (Johnson et al, 1997) argued that the formula used by the Department of Health to allocate resources to health authorities fails to meet the needs of inner cities. It is difficult to explore this issue because the principal allocation to district health authorities is set out as a single figure, with no subdivisions for separate clinical areas. This differs from local government finance, where annual allocations are itemised in a report detailing both major components (education, social services and road maintenance), and subdivisions of these (House of Commons, 1998). However, in the process used by the Department of Health to calculate health service allocations, several areas of clinical work, including the care of the mentally ill and learning disabled, receive distinct consideration. An annual publication sets out the detail (NHS Executive, 1998). Slight reworking allows the identification of implied allocations for the following clinical areas: general and acute; mental illness and learning disability; and other community care. This paper outlines the methodology and shows the allocations to health authorities in England for 1990–2000.
Schizophrenia with onset after age 50 years
Authors: Brodaty Henry , Sachdev Perminder , Rose Noelene , Rylands Kylie , Prenter Leanne
Published: October 2008

Background

Schizophrenia occurring for the first time in late life may be a distinct entity or part of a continuum.

Aims

Can late-onset schizophrenia (LOS) and early-onset schizophrenia (EOS) be differentiated by their phenomenology and risk factors to their development?

Method

Convenience samples of 27 DSM–III–R defined LOS subjects, 30 EOS subjects and 34 control subjects were systematically assessed.

Results

Premorbidly, both groups of subjects with schizophrenia had personality traits that were different from controls but not from each other. The EOS subjects had more family members with a history of psychiatric illness or schizophrenia and less hearing impairment than the other two groups, which did not differ from each other. Clinically, LOS and EOS subjects were similar, except that EOS subjects had more negative symptom scores, tended to have more delusions of guilt/sin and of being controlled and more formal thought disorder, and had significantly poorer instrumental activities of daily living.

Conclusions

Phenomenology and risk factors do not distinguish discrete LOS.
Schizophrenia with onset after age 50 years
Authors: Sachdev Perminder , Brodaty Henry , Rose Noelene , Cathcart Stuart
Published: October 2008

Background

Late-onset schizophrenia (LOS) may have a basis in age-related coarse brain disease, but empirical support for this is conflicting.

Aims

Is LOS characterised by more neurological disease than early-onset schizophrenia (EOS)?

Method

DSM–III–R–defined LOS subjects (n=27) were compared with 30 EOS and 34 volunteer control subjects on neurological status, neuropsychological test performance and brain magnetic resonance imaging (MRI)

Results

LOS and EOS groups had more ‘soft’ neurological signs and drug-induced movement abnormalities, and performed more poorly on tests assessing speed of information processing, memory and frontal executive functioning. On MRI, the LOS and EOS groups had greater lateral ventricular size than the control group. The LOS subjects also had more signal hyperintensities in periventricular white matter and subcortical nuclei than controls.

Conclusions

LOS and EOS subjects were very similar on neuropsychological, neurological and structural neuroimaging parameters, except that there were more MRI periventricular hyperintensities in LOS subjects.
Validation of the Hospital Anxiety and Depression Scale for use with adolescents
Authors: White David , Leach Chris , Sims Ruth , Atkinson Michelle , Cottrell David
Published: October 2008

Background

The Hospital Anxiety and Depression Scale (HADS), developed for use with adults, has potential with adolescents.

Aims

To test the HADS's validity with adolescents.

Method

The HADS was given to 248 schoolchildren and to 48 psychiatric outpatients and 38 deliberate self-harm inpatients aged 12–17, and validated against ICD–10 diagnoses for the out-patients.

Results

The HADS has adequate test-retest reliability and factor structure, and discriminates between adolescents diagnosed with depressive or anxiety disorders and those without these diagnoses.

Conclusions

The psychometric properties of the HADS and its shortness make it useful for screening and in clinical settings with adolescents.
Axis I comorbidity in bipolar disorder with psychotic features
Authors: Pini Stefano , Dell'Osso Liliana , Mastrocinque Concettina , Marcacci Giovanni , Papasogli Alessandra , Vignoli Serena , Pallanti Stefano , Cassano Giovanni B.
Published: October 2008

Background

Axis I comorbidities are prevalent among patients with severe bipolar disorder but the clinical and psychopathological implications are not clear.

Aims

To investigate characteristics of four groups of patients categorised as follows: substance abuse only (group I), substance abuse associated with other Axis I disorders (group 2), non-substance-abuse Axis I comorbidity (group 3), no psychiatric comorbidity (group 4)

Method

Consecutive patients with bipolar disorder with psychotic features (n=125) were assessed using the Structured Clinical Interview for DSM–III–R – patient version, and several psychopathological scales.

Results

By comparison with group 4, group I had a higher risk of having mood-incongruent delusions, group 2 had an earlier age at onset of mood disorder, a more frequent onset with a mixed state and a higher risk of suicide, and group 3 had more severe anxiety and a better awareness of illness.

Conclusions

Substance abuse, non-substance-abuse Axis I comorbidity and their reciprocal association are associated with different characteristics of bipolar disorder.
The EPSILON study of schizophrenia in five European countries
Authors: Becker Thomas , Knapp Martin , Knudsen Helle Charlotte , Schene Aart , Tansella Michele , Thornicroft Graham , Vázquez-Barquero José Luis
Published: October 2008

Background

There is a lack of cross-national research on care for people with schizophrenia.

Aims

To produce standardised European versions of five instruments in key areas of mental health service research in five languages, and to compare data from five European countries regarding patients with schizophrenia and mental health care provision and costs.

Method

Five centres, in Amsterdam, Copenhagen, London, Santander and Verona, participated. Instruments assessing needs, service use, informal carer involvement, quality of life, and service satisfaction were subjected to a conversion procedure including translation, back-translation, focus group discussion and reliability assessment. Patients of local mental health services with a Schedules for Clinical Assessment in Neuropsychiatry diagnosis of schizophrenia were interviewed.

Results

Service provision varied between sites; 404 patients were studied. instrument reliability was found to be good.

Conclusions

The instruments developed were reliable across the range of countries, and will facilitate future comparative health service research.
Post-partum depression and the mother-infant relationship in a South African peri-urban settlement
Authors: Cooper Peter J. , Tomlinson Mark , Swartz Leslie , Woolgar Matthew , Murray Lynne , Molteno Christopher
Published: October 2008

Background

Post-partum depression in the developing world has received tittle research attention, and its association with disturbances in the mother–infant relationship is unknown.

Aims

To determine the prevalence of post-partum depression and associated disturbances in the mother–infant relationship in Khayelitsha, a South African peri-urban settlement.

Method

The mental state of 147 women who had delivered two months previously was assessed, and the quality of their engagement with their infants was determined.

Results

The point prevalence of DSM–IV major depression was found to be 34.7%. Maternal depression was associated with poor emotional and practical support from the partner. It was also associated with insensitive engagement with the infants.

Conclusions

The rate of post-partum depression in Khayelitsha was around three times that found in British post-partum samples, and these depressions were strongly associated with disturbances in the mother–infant relationship.
Cetuximab Plus Irinotecan in Heavily Pretreated Metastatic Colorectal Cancer Progressing on Irinotecan: MABEL Study
Authors: Wilke Hansjochen , Glynne-Jones Robert , Thaler Josef , Adenis Antoine , Preusser Peter , Aguilar Enrique Aranda , Aapro Matti S. , Esser Regina , Loos Anja H. , Siena Salvatore
Published: October 2008

Purpose

This large, multinational study aimed to confirm in a community practice setting the efficacy and safety of cetuximab plus irinotecan in patients with epidermal growth factor–expressing metastatic colorectal cancer (mCRC) who had recently failed an irinotecan-containing regimen.

Patients and Methods

The primary objective was to determine the progression-free survival (PFS) rate at 12 weeks. The initial cetuximab dose was 400 mg/m2 and was followed weekly by 250 mg/m2; irinotecan (according to prestudy regimen) was given weekly (125 mg/m2 weekly for 4 of 6 weeks), every 2 weeks (180 mg/m2 each), or every 3 weeks (350 mg/m2 each).

Results

The intention-to-treat/safety population comprised 1,147 treated patients who received irinotecan weekly (n = 93); every 2 weeks (n = 670); every 3 weeks (n = 356); or another dose (n = 28). The PFS rate at 12 weeks was 61%, and the median survival was 9.2 months. Treatment was generally well tolerated. The most common treatment-related grades 3 to 4 adverse events were diarrhea (19%), neutropenia (10%), rash (7%), and asthenia (6%). The rate of grades 3 to 4 infusion-related reactions (IRRs; composite adverse event category) was 1% for patients who received both antihistamine and corticosteroid premedication.

Conclusion

Tolerability (except IRR incidence), PFS rate, and overall survival rate were in line with previous results. At 1%, the rate of IRRs in patients who received prophylactic premedication with both antihistamine and corticosteroid is lower than previously reported. MABEL clearly confirms in a community practice setting the efficacy and safety of cetuximab plus irinotecan in the treatment of mCRC.
New Insights Into the Pathogenesis of Serous Ovarian Cancer and Its Clinical Impact
Authors: Levanon Keren , Crum Christopher , Drapkin Ronny
Published: October 2008

There are only a handful of concepts concerning cancer and carcinogenesis that are currently beyond dispute. One such dogma is the adenoma-carcinoma sequence and that a multistep accumulation of genetic alterations is required for transformation from a benign to a neoplastic tissue. The inevitable derivative of this dogma is that every invasive carcinoma is in fact a missed intraepithelial tumor, and furthermore, a late evolutionary stage in the sequence of development from a precursor lesion. Until fairly recently, high-grade serous ovarian carcinoma seemed to be one of the only known deviants of these concepts. In this article, we discuss the emergence of the fallopian tube fimbria as a field of origin for high-grade serous carcinomas and present a binary model of ovarian cancer pathogenesis that takes into consideration prior epidemiologic, morphologic, and genetic data. With the rise of the fallopian tube secretory epithelial cell as a cell of origin for high-grade pelvic serous carcinomas, the need to develop tools and model systems to characterize the biology and physiology of this cell is recognized.
Polycystic Ovary Syndrome Is Associated with Tissue-Specific Differences in Insulin Resistance
Authors: Ciaraldi Theodore P. , Aroda Vanita , Mudaliar Sunder , Chang R. Jeffrey , Henry Robert R.
Published: October 2008

Objective: The potential differential contributions of skeletal muscle and adipose tissue to whole body insulin resistance were evaluated in subjects with polycystic ovary syndrome (PCOS).

Research Design and Methods: Forty-two PCOS subjects and 15 body mass index-matched control subjects were studied. Insulin action was evaluated by the hyperinsulinemic/euglycemic clamp procedure. Isolated adipocytes and cultured muscle cells were analyzed for glucose transport activity; adipocytes, muscle tissue, and myotubes were analyzed for the expression and phosphorylation of insulin-signaling proteins.

Results: Fifty-seven per cent of the PCOS subjects had impaired glucose tolerance and the lowest rate of maximal insulin-stimulated whole body glucose disposal compared to controls (P < 0.01). PCOS subjects with normal glucose tolerance had intermediate reduction in glucose disposal rate (P < 0.05 vs. both control and impaired glucose tolerance subjects). However, rates of maximal insulin-stimulated glucose transport (insulin responsiveness) into isolated adipocytes were comparable between all three groups, whereas PCOS subjects displayed impaired insulin sensitivity. In contrast, myotubes from PCOS subjects displayed reduced insulin responsiveness for glucose uptake and normal sensitivity. There were no differences between groups in the expression of glucose transporter 4 or insulin-signaling proteins or maximal insulin stimulation of phosphorylation of Akt in skeletal muscle, myotubes, or adipocytes.

Conclusions: Individuals with PCOS display impaired insulin responsiveness in skeletal muscle and myotubes, whereas isolated adipocytes display impaired insulin sensitivity but normal responsiveness. Skeletal muscle and adipose tissue contribute differently to insulin resistance in PCOS. Insulin resistance in PCOS cannot be accounted for by differences in the expression of selected signaling molecules or maximal phosphorylation of Akt.
The computerized object and abstract designs test (COAD): A pilot study of a new test of visual working memory
Authors: Price Jason P.
Published: October 2008

Objectives

To investigate the clinical and theoretical validity of a new computerized test of visual working memory; the computerized object and abstract designs (COAD) test. The COAD test was designed to be consistent with Baddeley's inclusion of the ‘episodic buffer’ in the ‘multicomponent model’ of working memory.

Design and method

A cross‐sectional design was used with two brain lesion groups (left N = 9 and right hemisphere N = 12) and a control group N = 18. The participants had to complete the new test, along with standardized tests of visual working memory in current clinical use (visual patterns test and spatial span test). Differences between groups, as well as between tests were investigated. Correlations were performed across tests. Regression models were used to further evaluate the COAD clinical sensitivity in comparison with the other tests of visual working memory.

Results

Significant differences were observed, as predicted, between groups and between design types. The COAD test was significantly correlated with both the visual patterns Test and the spatial span test. The COAD test also proved to be more sensitive in detecting brain injury resulting in visual working memory deficits, than the standardized tests.

Discussion and conclusion

The results are discussed in relation to the COAD test's potential utility in the early detection of specific degenerative neurological disorders as well as the potential to be used in identifying deficits in visual working memory and in neurorehabilitation. It is concluded that the COAD test is a clinically valid psychometric test and is a more sensitive instrument than current standardized tests of visual working memory in clinical use.
Autism Profiles of Males With Fragile X Syndrome
Authors: Harris Susan W. , Hessl David , Goodlin-Jones Beth , Ferranti Jessica , Bacalman Susan , Barbato Ingrid , Tassone Flora , Hagerman Paul J. , Herman Kristin , Hagerman Randi J.
Published: October 2008

Autism, which is common in individuals with fragile X syndrome, is often difficult to diagnose. We compared the diagnostic classifications of two measures for autism diagnosis, the ADOS and the ADI-R, in addition to the DSM-IV-TR in 63 males with this syndrome. Overall, 30% of the subjects met criteria for autistic disorder and 30% met criteria for PDD-NOS. The classifications on the ADOS and DSM-IV-TR were most similar, whereas the ADI-R classified subjects as autistic much more frequently. We further investigated the relationship of both FMRP and FMR1 mRNA to symptoms of autism in this cohort and found no significant relationship between the measures of autism and molecular features, including FMRP, FMR1 mRNA, and CGG repeat number.
Evidence for Latent Classes of IQ in Young Children With Autism Spectrum Disorder
Authors: Munson Jeffrey , Dawson Geraldine , Sterling Lindsey , Beauchaine Theodore , Zhou Andrew , Koehler Elizabeth , Lord Catherine , Rogers Sally , Sigman Marian , Estes Annette , Abbott Robert
Published: October 2008

Autism is currently viewed as a spectrum condition that includes strikingly different severity levels; IQ is consistently described as one of the primary aspects of the heterogeneity in autism. To investigate the possibility of more than one distinct subtype of autism based on IQ, both latent class analysis and taxometrics methods were used to classify Mullen IQs in a sample of 456 children with autism spectrum disorder. We found evidence for multiple IQ-based subgroups using both methods. Groups differed in level of intellectual functioning and patterns of verbal versus nonverbal ability. Results support the notion of distinct subtypes of autism that differ in severity of intellectual ability, patterns of cognitive strengths and weaknesses, and severity of autism symptoms.
Memory Skills of Boys With Fragile X Syndrome
Authors: Ornstein Peter A. , Schaaf Jennifer M. , Hooper Stephen R. , Hatton Deborah D. , Mirrett Penny , Bailey Donald B.
Published: October 2008

Multiple aspects of memory were examined in 42 boys with fragile X syndrome and a comparison group of 42 typically developing boys matched on MA. Working memory, incidental memory, and deliberate memory were assessed with a battery that included both free-recall and recognition tasks. Findings indicated that boys with fragile X syndrome performed more poorly than their matches on most measures. The exception was free recall, in which their accuracy was equal to that of the control participants. Results from analyses of a subset of boys with fragile X syndrome who exhibit characteristics of autism and their MA matches, though preliminary, support the conclusion that memory deficits are especially marked in boys who have fragile X syndrome and evidence autistic behaviors.
Gatekeepers of Science: Attitudes Toward the Research Participation of Adults With Intellectual Disability
Authors: McDonald Katherine E. , Keys Christopher B. , Henry David B.
Published: October 2008

Researchers and Institutional Review Board (IRB) members' attitudes influence scientific knowledge about individuals with intellectual disability. We recruited 260 intellectual disability researchers and IRB members to develop a measure of attitudes toward the research participation of adults with intellectual disability, the Participation in Research Attitude Scale. Findings suggest three conceptual domains: Opportunity and Choice, Help in Decision Making, and Beneficence. We also examined individual differences in attitudes and the relationships between general and specific attitudes. In general, intellectual disability researchers and those with closer relationships to individuals with disabilities had attitudes consistent with disability-rights principles. Some dimensions of global attitudes toward adults with intellectual disability predicted more specific attitudes toward their research participation. Implications are discussed.
Novel Role for Vascular Endothelial Growth Factor (VEGF) Receptor-1 and Its Ligand VEGF-B in Motor Neuron Degeneration
Authors: Poesen Koen , Lambrechts Diether , Van Damme Philip , Dhondt Joke , Bender Florian , Frank Nicolas , Bogaert Elke , Claes Bart , Heylen Line , Verheyen An , Raes Katrien , Tjwa Marc , Eriksson Ulf , Shibuya Masabumi , Nuydens Rony , Van Den Bosch Ludo , Meert Theo , D'Hooge Rudi , Sendtner Michael , Robberecht Wim , Carmeliet Peter
Published: October 2008

Although vascular endothelial growth factor-B (VEGF-B) is a homolog of the angiogenic factor VEGF, it has only minimal angiogenic activity, raising the question of whether this factor has other (more relevant) biological properties. Intrigued by the possibility that VEGF family members affect neuronal cells, we explored whether VEGF-B might have a role in the nervous system. Here, we document that the 60 kDa VEGF-B isoform, VEGF-B186, is a neuroprotective factor. VEGF-B186protected cultured primary motor neurons against degeneration. Mice lacking VEGF-B also developed a more severe form of motor neuron degeneration when intercrossed with mutant SOD1 mice. Thein vitroandin vivoeffects of VEGF-B186were dependent on the tyrosine kinase activities of its receptor, Flt1, in motor neurons. When delivered intracerebroventricularly, VEGF-B186prolonged the survival of mutant SOD1 rats. Compared with a similar dose of VEGF, VEGF-B186was safer and did not cause vessel growth or blood–brain barrier leakiness. The neuroprotective activity of VEGF-B, in combination with its negligible angiogenic/permeability activity, offers attractive opportunities for the treatment of neurodegenerative diseases.
The Native Coordinate System of Spatial Attention Is Retinotopic
Authors: Golomb Julie D. , Chun Marvin M. , Mazer James A.
Published: October 2008

Visual processing can be facilitated by covert attention at behaviorally relevant locations. If the eyes move while a location in the visual field is facilitated, what happens to the internal representation of the attended location? With each eye movement, the retinotopic (eye-centered) coordinates of the attended location change while the spatiotopic (world-centered) coordinates remain stable. To investigate whether the neural substrates of spatial attention reside in retinotopically and/or spatiotopically organized maps, we used a novel gaze-contingent behavioral paradigm that probed spatial attention at various times after eye movements. When task demands required maintaining a spatiotopic representation after the eye movement, we found facilitation at the retinotopic location of the spatial cue for 100–200 ms after the saccade, although this location had no behavioral significance. This task-irrelevant retinotopic representation dominated immediately after the saccade, whereas at later delays, the task-relevant spatiotopic representation prevailed. However, when task demands required maintaining the cue in retinotopic coordinates, a strong retinotopic benefit persisted long after the saccade, and there was no evidence of spatiotopic facilitation. These data suggest that the cortical and subcortical substrates of spatial attention primarily reside in retinotopically organized maps that must be dynamically updated to compensate for eye movements when behavioral demands require a spatiotopic representation of attention. Our conclusion is that the visual system's native or low-level representation of endogenously maintained spatial attention is retinotopic, and remapping of attention to spatiotopic coordinates occurs slowly and only when behaviorally necessary.
Tumor Suppressor Schwannomin/Merlin Is Critical for the Organization of Schwann Cell Contacts in Peripheral Nerves
Authors: Denisenko Natalia , Cifuentes-Diaz Carmen , Irinopoulou Theano , Carnaud Michèle , Benoit Evelyne , Niwa-Kawakita Michiko , Chareyre Fabrice , Giovannini Marco , Girault Jean-Antoine , Goutebroze Laurence
Published: October 2008

Schwannomin/merlin is the product of a tumor suppressor gene mutated in neurofibromatosis type 2 (NF2). Although the consequences of NF2 mutations on Schwann cell proliferation are well established, the physiological role of schwannomin in differentiated cells is not known. To unravel this role, we studied peripheral nerves in mice overexpressing in Schwann cells schwannomin with a deletion occurring in NF2 patients (P0–SCH–Δ39–121) or a C-terminal deletion. The myelin sheath and nodes of Ranvier were essentially preserved in both lines. In contrast, the ultrastructural and molecular organization of contacts between Schwann cells and axons in paranodal and juxtaparanodal regions were altered, with irregular juxtaposition of normal and abnormal areas of contact. Similar but more severe alterations were observed in mice with conditional deletion of theNf2gene in Schwann cells. The number of Schmidt–Lanterman incisures, which are cytoplasmic channels interrupting the compact myelin and characterized by distinct autotypic contacts, was increased in the three mutant lines. P0–SCH–Δ39–121 and conditionally deleted mice displayed exuberant wrapping of nonmyelinated fibers and short internodes, an abnormality possibly related to altered control of Schwann cell proliferation. In support of this hypothesis, Schwann cell number was increased along fibers before myelination in P0–SCH–Δ39–121 mice but not in those with C-terminal deletion. Schwann cell numbers were also more numerous in mice with conditional deletion. Thus, schwannomin plays an important role in the control of Schwann cell number and is necessary for the correct organization and regulation of axoglial heterotypic and glio-glial autotypic contacts.
Blocking Central Opiate Function Modulates Hedonic Impact and Anterior Cingulate Response to Rewards and Losses
Authors: Petrovic Predrag , Pleger Burkhard , Seymour Ben , Klöppel Stefan , De Martino Benedetto , Critchley Hugo , Dolan Raymond J.
Published: October 2008

Reward processing is linked to specific neuromodulatory systems with a dopaminergic contribution to reward learning and motivational drive being well established. Neuromodulatory influences on hedonic responses to actual receipt of reward, or punishment, referred to as experienced utility are less well characterized, although a link to the endogenous opioid system is suggested. Here, in a combined functional magnetic resonance imaging–psychopharmacological investigation, we used naloxone to block central opioid function while subjects performed a gambling task associated with rewards and losses of different magnitudes, in which the mean expected value was always zero. A graded influence of naloxone on reward outcome was evident in an attenuation of pleasure ratings for larger reward outcomes, an effect mirrored in attenuation of brain activity to increasing reward magnitude in rostral anterior cingulate cortex. A more striking effect was seen for losses such that under naloxone all levels of negative outcome were rated as more unpleasant. This hedonic effect was associated with enhanced activity in anterior insula and caudal anterior cingulate cortex, areas implicated in aversive processing. Our data indicate that a central opioid system contributes to both reward and loss processing in humans and directly modulates the hedonic experience of outcomes.
Composition and Decomposition in Bimanual Dynamic Learning
Authors: Howard Ian S. , Ingram James N. , Wolpert Daniel M.
Published: October 2008

Our ability to skillfully manipulate an object often involves the motor system learning to compensate for the dynamics of the object. When the two arms learn to manipulate a single object they can act cooperatively, whereas when they manipulate separate objects they control each object independently. We examined how learning transfers between these two bimanual contexts by applying force fields to the arms. In a coupled context, a single dynamic is shared between the arms, and in an uncoupled context separate dynamics are experienced independently by each arm. In a composition experiment, we found that when subjects had learned uncoupled force fields they were able to transfer to a coupled field that was the sum of the two fields. However, the contribution of each arm repartitioned over time so that, when they returned to the uncoupled fields, the error initially increased but rapidly reverted to the previous level. In a decomposition experiment, after subjects learned a coupled field, their error increased when exposed to uncoupled fields that were orthogonal components of the coupled field. However, when the coupled field was reintroduced, subjects rapidly readapted. These results suggest that the representations of dynamics for uncoupled and coupled contexts are partially independent. We found additional support for this hypothesis by showing significant learning of opposing curl fields when the context, coupled versus uncoupled, was alternated with the curl field direction. These results suggest that the motor system is able to use partially separate representations for dynamics of the two arms acting on a single object and two arms acting on separate objects.
Supraspinal Glial–Neuronal Interactions Contribute to Descending Pain Facilitation
Authors: Wei Feng , Guo Wei , Zou Shiping , Ren Ke , Dubner Ronald
Published: October 2008

Spinal glial reaction and proinflammatory cytokine induction play an important role in the development of chronic pain states after tissue and nerve injury. The present study investigated the cellular and molecular mechanisms underlying descending facilitation of neuropathic pain with an emphasis on supraspinal glial–neuronal relationships. An early and transient reaction of microglia and prolonged reaction of astrocytes were found after chronic constriction injury (CCI) of the rat infraorbital nerve in the rostral ventromedial medulla (RVM), a major component of brainstem descending pain modulatory circuitry. There were prolonged elevations of cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) after CCI, and they were expressed in RVM astrocytes at 14 d after injury. Intra-RVM injection of microglial and astrocytic inhibitors attenuated mechanical hyperalgesia and allodynia at 3 and 14 d after CCI, respectively. Moreover, TNFR1 and IL-1R, receptors for TNF-α and IL-1β, respectively, were expressed primarily in RVM neurons exhibiting immunoreactivity to the NMDA receptor (NMDAR) subunit NR1. CCI increased TNFR1 and IL-1R levels and NR1 phosphorylation in the RVM. Neutralization of endogenous TNF-α and IL-1β in the RVM significantly reduced CCI-induced behavioral hypersensitivity and attenuated NR1 phosphorylation. Finally, intra-RVM administration of recombinant TNF-α or IL-1β upregulated NR1 phosphorylation and caused a reversible and NMDAR-dependent allodynia in normal rats, further suggesting that TNF-α and IL-1β couple glial hyperactivation with NMDAR function. These studies have addressed a novel contribution of supraspinal astrocytes and associated cytokines as well as central glial–neuronal interactions to the enhancement of descending facilitation of neuropathic pain.
O Sistema de Yalta como condicionante da política internacional do Brasil e dos países do Terceiro Mundo
Authors: Vizentini Paulo G. Fagundes
Published: October 2008

O Sistema de Yalta foi encarado de diferentes maneiras pelos diversos atores do sistema internacional. Este artigo procura explorar como o Sul, ou o Terceiro Mundo, percebeu-o. Yalta não constituía a divisão do mundo, mas da Europa, e a constituição de um conjunto de regras em que o Sul era mantido como periferia do bloco norte-americano, encobrindo portanto uma dimensão de antagonismo Norte-Sul. Contudo, para o Brasil e para a América Latina em geral, o lugar ocupado neste sistema era ainda mais subordinado e periférico que em outras regiões. Isto levou o Brasil e outros países a buscar uma diplomacia mais autônoma através do nacionalismo desenvolvimentista.
Átomos na integração: a aproximação Brasil-Argentina no campo nuclear e a construção do Mercosul
Authors: Vargas Everton Vieira
Published: October 2008

Este trabalho tenciona ser uma reflexão sobre a importância da aproximação entre o Brasil e a Argentina no campo nuclear, na segunda metade da década de 80 e no início dos anos 90, como fundamento para a construção de um relacionamento novo que suplantou uma rivalidade histórica entre ambos. O processo de aproximação encetado com um propósito aparentemente econômico, tinha uma dimensão estratégica. As repercussões desse esforço iam além dos interesses bilaterais imediatos e se refletiram na busca de uma nova inserção internacional dos dois países, num momento de transformações profundas nos planos interno e internacional. Através do programa de integração Brasil-Argentina (que mais tarde também envolveu o Uruguai) e do MERCOSUL buscou-se estabelecer uma arquitetura político-jurídica, que criou uma realidade que extrapola o campo econômico e projeta-se no terreno político.
A Cúpula Mundial sobre o Desenvolvimento Social e os paradoxos de Copenhague
Authors: Alves J. A. Lindgren
Published: October 2008

Este artigo analisa a Cúpula Mundial sobre Desenvolvimento Social, realizada em Copenhague, em 1995, onde foram debatidos os problemas e as possíveis soluções para o desenvolvimento social e do bem-estar humano de todos.
Dilemas e desafios da Proteção Internacional dos Direitos Humanos no limiar do século XXI
Authors: Trindade Antônio Augusto Cançado
Published: October 2008

Balanço dos avanços conceituais e práticos e das limitações ainda existentes, de ordem legal ou política, à proteção universal dos direitos humanos, ressaltando a construção progressiva dos instrumentos disponíveis - as convenções centrais - e o papel das conferências e das cortes regionais de defesa dos direitos humanos.
A Política Externa da Alemanha após a reunificação
Authors: Pfetsch Frank R.
Published: October 2008

Análise das opções abertas à Alemanha no período após a reunificação, enfatizando seu papel internacional, seu protagonismo comunitário e sua função de ponte entre a Europa Ocidental e a Eurásia.