Brian Robertson

Genetic variation at the 22q11 PRODH2/DGCR6 locus presents an unusual pattern and increases susceptibility to schizophrenia

The location of a schizophrenia susceptibility locus at chromosome 22q11 has been suggested by genome-wide linkage studies. Additional support was provided by the observation of a higher-than-expected frequency of 22q11 microdeletions in patients with schizophrenia and the demonstration that ≈20–30% of individuals with 22q11 microdeletions develop schizophrenia or schizoaffective disorder in adolescence and adulthood. Analysis of the extent of these microdeletions by using polymorphic markers afforded further refinement of this locus to a region of ≈1.5 Mb. Recently, a high rate of 22q11 microdeletions was also reported for a cohort of 47 patients with Childhood Onset Schizophrenia, a rare and severe form of schizophrenia with onset by age 13. It is therefore likely that this 1.5-Mb region contains one or more genes that predispose to schizophrenia. In three independent samples, we provide evidence for a contribution of the PRODH2/DGCR6 locus in 22q11-associated schizophrenia. We also uncover an unusual pattern of PRODH2 gene variation that mimics the sequence of a linked pseudogene. Several of the pseudogene-like variants we identified result in missense changes at conserved residues and may prevent synthesis of a fully functional enzyme. Our results have implications for understanding the genetic basis of the 22q11-associated psychiatric phenotypes and provide further insights into the genomic instability of this region.

Common mental health problems in historically disadvantaged urban and rural communities in South Africa: prevalence and risk factors

This paper reports on an epidemiological study of common mental health and substance abuse problems in a historically disadvantaged urban and rural community in South Africa. In the rural Limpopo Province of South Africa, and in a peri-urban township near Cape Town, self-report instruments were used in two random population samples and among respondents at primary care and traditional healer settings, to assess common mental health problems, substance abuse problems and associated problems in social functioning. A high prevalence of mental health and substance abuse problems was observed in both communities, with highest rates in the peri-urban township. Even higher prevalences were found among respondents at primary health care or traditional healers. The study shows that mental health and substance abuse problems constitute a considerable burden of disease among disadvantaged communities in South Africa. The study further underscores the integral role of traditional healers in the mental health care system.

Phenotypic characterization and genealogical tracing in an Afrikaner schizophrenia database.

Founder populations hold tremendous promise for mapping genes for complex traits, as they offer less genetic and environmental heterogeneity and greater potential for genealogical research. Not all founder populations are equally valuable, however. The Afrikaner population meets several criteria that make it an ideal population for mapping complex traits, including founding by a small number of initial founders that likely allowed for a relatively restricted set of mutations and a large current population size that allows identification of a sufficient number of cases. Here, we examine the potential to conduct genealogical research in this population and present initial results indicating that accurate genealogical tracing for up to 17 generations is feasible. We also examine the clinical similarities of schizophrenia cases diagnosed in South Africa and those diagnosed in other, heterogeneous populations, specifically the US. We find that, with regard to basic sample descriptors and cardinal symptoms of disease, the two populations are equivalent. It is, therefore, likely that results from our genetic study of schizophrenia will be applicable to other populations. Based on the results presented here, the history and current size of the population, as well as our previous analysis addressing the extent of background linkage disequilibrium (LD) in the Afrikaners, we conclude that the Afrikaner population is likely an appropriate founder population to map genes for schizophrenia using both linkage and LD approaches.

Risk and resilience in orphaned adolescents living in a community affected by AIDS.

The AIDS pandemic has resulted in a dramatic rise in the number of orphans in South Africa. This study was designed to investigate the associations between family, peer, and community factors and resilience in orphaned adolescents. Self-report questionnaires were administered verbally to 159 parentally bereaved adolescents (aged 10-19) in an economically deprived urban area. Questionnaires included measures of depression, anxiety, and self-esteem. The results of a hierarchical multiple regression analysis indicate that cumulative stress exposure, losing a parent to a cause other than HIV and AIDS, and being cared for by a nonrelative were associated with an increased risk of internalizing symptoms. Family regulation and respect for individuality, peer connection, and community connection and regulation were significantly associated with greater emotional resilience. The findings support a main-effects model of resilience in which risk factors and protective factors contribute additively to the prediction of the outcome, without interaction.

A COMMUNITY STUDY OF TAXI VIOLENCE AND DISTRESS SYMPTOMS AMONG YOUTH

Abstract Objectives: To investigate the prevalence of distress symptoms among youth exposed to taxi violence in Khayelitsha, a South African peri-urban settlement. Design: A cross-sectional community study of a stratified sample of youth. Setting & Subjects: Five hundred and four Xhosa speaking youth aged 9–20 years, from 5 primary schools in Khayelitsha; 396 attending 4 schools in close proximity to a taxi rank (site C) and 108 attending a school away from any taxi rank (site B). Outcome Measures: An adapted version of the Survey of Exposure to Community Violence (SECV) was administered to investigate exposure to violence. The Levonn Instrument, a cartoon-based 29-item questionnaire was used to identify distress symptoms. Results: Three hundred and six respondents (61%) reported personal exposure to taxi violence. Overall, 31 (6%) of the youth reported that a family member had been shot and killed while travelling in a taxi and 41 (8%) reported that a family member had been wounded while travelling in a taxi. Exposure to other forms of violence was recorded. Nearly all subjects, 493 (98%), reported the presence of distress symptoms. Three hundred and thirty three (66%) reported feeling sad about people who have died, 328 (65%) reported feeling sad but did not know why, 294 (59%) were scared about something they had seen, and 248 (50%) reported not being able to concentrate in class. Of note, 132 (26%) reported that life was not worth living and wished they were dead. Those who had been in a taxi that was shot at, those who had been at a taxi rank when people were shot, and those who had seen taxi men shooting, had significantly higher levels of distress symptoms than those who did not have such experiences. Conclusion: The results indicate that an alarmingly high percentage of youth living in Khayelitsha are exposed to taxi violence, in addition to other forms of community violence, and that this increases distress symptoms in those already at risk for exposure to high levels of violence. Unacceptably high levels of distress symptoms were found in the study sample.

Systems of Care in Africa

Rapid change against a background of complex diversity is the most prominent feature of Africa today. Threat and promise are engaged in a struggle for supremacy. While nations battle for independence, and revolutionaries cut swathes of instability across the continent, great statesmen rise up to lead the way to peace and prosperity. As countries buckle under poverty and famine, Africa’s leaders forge global alliances to secure equitable opportunities for developing regions of the world. Africa, “the slumbering giant”, is stirring.

Child Mental Health Services in the New South Africa

Health departments in the new South Africa are undergoing major restructuring and, in some cases, severe financial cutbacks as new policies attempt to redress the inequities of the past. A district system is being phased in, with a shift in funding from academic hospitals to secondary and primary level care. The process is being undermined by the current recession, which also affects Welfare and Education facilities, and by widespread poverty, violence, and other adverse conditions. Child mental health services are discussed in the light of current human resources, epidemiological data, the effects of violence and cultural issues, together with some reflections on their future.

No health without mental health: Establishing psychiatry as a major discipline in an African Faculty of Health Sciences

Psychiatry has not always been a major clinical discipline in medical schools. Although the Faculty of Health Sciences of the University of Cape Town (UCT) celebrates its Centenary in 2012, a closely aligned major psychiatric hospital is older than the Medical School, while the Department of Psychiatry is only 50 years old. These differing dates reflect the history of and challenge for psychiatry; mental disorders contribute a major portion of the burden of disease, while appropriate recognition and resourcing of services and training has been delayed. There are ongoing challenges in aligning the visions of an old state-run system that focused on those with severe psychotic illness, a newer governmental vision of the importance of treating mental disorders in the community, the realities of current under-resourcing, and the international aspiration that psychiatry is one of the clinical neurosciences. Nevertheless, considerable strides have been made towards moving psychiatry from the periphery of society and medicine to a central discipline within the Faculty of Health Sciences at UCT.

Treatment of carcinoma of the anal canal at Groote Schuur Hospital

OBJECTIVESnChemoradiation is the treatment of choice for squamous carcinoma of the anal canal, resulting in the same local control rates as surgery but with the advantage of organ function preservation. We aimed to review all cases of anal canal carcinoma treated at Groote Schuur Hospital between 2000 and 2004 and to assess treatement outcome.nnnMETHODSnThe records for 31 patients presenting during this period were reviewed. Patient and tumour characteristics were recorded. Twenty-six patients were treated with chemoradiation. Local failure-free, colostomy-free and overall survival were calculated using the Kaplan-Meier method.nnnRESULTSnCompared with the literature, the median patient age was younger and the stage was more advanced in this study. The complete response rate for all stages with chemoradiation was 80%. The local failure-free survival at 5 years was 60.7%. Colostomy-free and overall survival at 5 years were 59.2% and 65.6%, respectively.nnnCONCLUSIONSnThe patients presented with locally advanced disease. Chemoradiation is effective treatment for this group of patients and the majority avoid a permanent colostomy as they preserve anal sphincter function.