Autism Spectrum Disorders and Schizophrenia: Meta-Analysis of the Neural Correlates of Social Cognition

CONTEXT: Impaired social cognition is a cardinal feature of Autism Spectrum Disorders (ASD) and Schizophrenia (SZ). However, the functional neuroanatomy of social cognition in either disorder remains unclear due to variability in primary literature. Additionally, it is not known whether deficits in ASD and SZ arise from similar or disease-specific disruption of the social cognition network. OBJECTIVE: To identify regions most robustly implicated in social cognition processing in SZ and ASD. DATA SOURCES: Systematic review of English language articles using MEDLINE (1995-2010) and reference lists. STUDY SELECTION: Studies were required to use fMRI to compare ASD or SZ subjects to a matched healthy control group, provide coordinates in standard stereotactic space, and employ standardized facial emotion recognition (FER) or theory of mind (TOM) paradigms. DATA EXTRACTION: Activation foci from studies meeting inclusion criteria (n = 33) were subjected to a quantitative voxel-based meta-analysis using activation likelihood estimation, and encompassed 146 subjects with ASD, 336 SZ patients and 492 healthy controls. RESULTS: Both SZ and ASD showed medial prefrontal hypoactivation, which was more pronounced in ASD, while ventrolateral prefrontal dysfunction was associated mostly with SZ. Amygdala hypoactivation was observed in SZ patients during FER and in ASD during more complex ToM tasks. Both disorders were associated with hypoactivation within the Superior Temporal Sulcus (STS) during ToM tasks, but activation in these regions was increased in ASD during affect processing. Disease-specific differences were noted in somatosensory engagement, which was increased in SZ and decreased in ASD. Reduced thalamic activation was uniquely seen in SZ. CONCLUSIONS: Reduced frontolimbic and STS engagement emerged as a shared feature of social cognition deficits in SZ and ASD. However, there were disease- and stimulus-specific differences. These findings may aid future studies on SZ and ASD and facilitate the formulation of new hypotheses regarding their pathophysiology

The cost of harmful alcohol use in South Africa

Background. The economic, social and health costs associated with alcohol-related harms are important measures with which to inform alcohol management policies and laws. This analysis builds on previous cost estimates for South Africa.Methods. We reviewed existing international best-practice costing frameworks to provide the costing definitions and dimensions. We sourced data from South African costing literature or, if unavailable, estimated costs using socio-economic and health data from secondary sources. Care was taken to avoid possible causes of cost overestimation, in particular double counting and, as far as possible, second-round effects of alcohol abuse.Results. The combined total tangible and intangible costs of alcohol harm to the economy were estimated at 10 - 12% of the 2009 gross domestic product (GDP). The tangible financial cost of harmful alcohol use alone was estimated at R37.9 billion, or 1.6% of the 2009 GDP.Discussion. The costs of alcohol-related harms provide a substantial counterbalance to the economic benefits highlighted by the alcohol industry to counter stricter regulation. Curtailing these costs by regulatory and policy interventions contributes directly and indirectly to social well-being and the economy.Conclusions. Existing frameworks that guide the regulation and distribution of alcohol frequently focus on maximising the contribution of the alcohol sector to the economy, but should also take into account the associated economic, social and health costs. Current interventions do not systematically address the most important causes of harm from alcohol, and need to be informed by reliable evidence of the ongoing costs of alcohol-related harms

Fifty years of porphyria at the University of Cape Town

The porphyrias are a group of disorders resulting from defective haem biosynthesis. One form, variegate porphyria, is common in South Africa as a result of a founder effect. Over the past 50 years, the University of Cape Town Faculty of Health Sciences has built and maintained an international reputation for excellence in the field of porphyria. The porphyria group is respected for its research and for its accumulated experience in the management of these disorders. Equally important has been the comprehensive and holistic care offered to patients with porphyria, and to their families

Violence, alcohol and symptoms of depression and in Cape Town's poorest communities: results of a community survey

Introduction This paper summarises key findings from the first of three household surveys conducted in three high-violence areas in the Cape Town, investigating community members’ experiences of alcohol use, their built environment, violence and symptoms of depression, together with their views on alcohol and other interventions. Methods A stratified random sample of 1500 dwellings, 1200 in Khayelitsha and 300 in Gugulethu and Nyanga (“Gunya”) was selected using GIS address data for formal areas and aerial photography for informal areas. Fieldwork took place from July to November 2013. Responses to questions were summarized by area, gender, age and formal vs. informal settlement type. Results After substitution and data cleaning, 1213 Khayelitsha households and 286 Gunya households were included. In Gunya, 29% of respondents reported that they or their family members had been affected by at least one violent crime (murder, assault, domestic violence, rape) in the past year, compared with 12% in Khayelitsha. Using a CES-D-10 cut-off of 10, 44% of respondents were classified as depressed. More than half the respondents reported having experienced some form of alcohol nuisance. Respondents were supportive of alcohol interventions such as increased taxes and police regulation of outlets, particularly in Gunya (87%) and amongst female respondents (76%). Satisfaction with infrastructure such as street lighting and drainage was generally low. Conclusions The results describe the co-occurring burdens of alcohol and drug use, violence, depression and deprivation in our study populations

Variegate porphyria in South Africa, 1688 - 1996 - new developments in an old disease

Variegate porphyria, an autosomal dominant inherited trait resulting in decreased activity of protoporphyrinogen oxidase, the penuttimate haem biosynthetic enzyme, is characterised clinically by photosensitive skin disease and a propensity to acute neurovisceral crises. The disease has an exceptionally high frequency in South Africa,owing to a founder effect. The specific mutation in the protoporphynnogen oxidase gene sequence which represents this founder gene has been identified. Genetic diagnosis is therefore now possible in families in whom the gene defect is known. However, the exact nature and degree of activity of the porphyria can only be determined by detailed quantitative biochemical analysis of excreted porphyrins. The relative contributions of the acute attack and the skin disease to the total disease burden of patients with variegate porphyria is not static, and in South Africa there have been significant changes over the past 25 years, with fewer patients presenting with acute attacks, leaving a greater proportion to present with skin disease or to remain asymptomatic with the diagnosis being made in the laboratory. The most common precipitating cause of the acute attack of VP is administration of porphyrinogenic drugs. Specific suppression of haem synthesis with intravenous haem arginate is the most useful treatment of a moderate or severe acute attack. Although cutaneous lesions are limited to the sun-exposed areas, management of the skin disease of VP remains inadequate

Author index for volume 103

Coping with unusual experiences for 12–18 year olds (CUES+): SPIRIT Checklist. (DOC 122 kb

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

The role of ethnicity and diagnosis in rates of adolescent psychiatric admission and compulsory detention: a longitudinal case-note study

OBJECTIVES: To explore whether ethnic variations in psychiatric admission and detention reported for adults also apply to adolescents and to establish the influence of diagnosis. DESIGN: A longitudinal, case-note study over a 10-year period. SETTING: An adolescent inpatient psychiatric unit in London. PARTICIPANTS: All adolescents admitted to the unit. MAIN OUTCOME MEASURES: Rates of admission and detention under the Mental Health Act, according to catchment area population. RESULTS: Young Black people were nearly six times more likely than the White group to be admitted with psychosis but showed no increase in admission for non-psychotic conditions. Young people in the Other group were over three times more likely to be admitted with psychosis but showed only a modest increase in admission with non-psychotic conditions. Young Asians were over twice as likely to be admitted with psychosis but were only one-third as likely to be admitted with non-psychotic conditions. Young people with psychosis in the Black and Other groups were around three times more likely to have been detained, but there were no significant differences for non-psychotic conditions. CONCLUSIONS: Significant ethnic variation was found in the rates of admission and detention for adolescents. However, diagnosis was also an important consideration and must be taken into account when examining for evidence of ethnic bias in the use of mental health services by young people. Further investigation is required to establish whether adolescent care pathways are providing a safe and appropriate level of inpatient care for all ethnic groups