From laboratory to the bedside : genetic findings in schizophrenia

Die komplekse genetiese argitektuur van skisofrenie word kortliks omskryf deur na twee kontrasterende (maar konseptueel verbandhoudende) hipoteses te verwys. Bevindings van die lokus van genoomwye assosiasiestudies (GWAS) en die majorhistoversoenbaarheidskompleks (MHK) op chromosoom 6 en skisofrenie word aangehaal. Klassieke aanvullingskaskade verbonde hieraan word betrek in die eliminering, of ‘snoei van sinapse’ as deel van die patogenese van skisofrenie. Daar word nader aan die siekbed van skisofreniepasiënte beweeg deur te kyk na die volgende navorsingsbevindings in pasiënte met skisofrenie in die Afrikanerbevolking: • mikro-uitwissing by die 22q11.2 chromosoom as ’n spesifieke tipe skisofrenie; • fenotipiese kenmerke van skisofreniepasiënte wat spontane geenmutasies dra; • skisofrenie wat verwant is aan die vaderlike ouderdom (VOVS) en sosiale funksionering vroeg en later in die lewe van die pasiënte; • verhoogde selfdoodrisiko in skisofreniepasiënte met koppeling aan chromosoom 13q en hoe mortaliteit in die pasiënte verlaag kan word.The complex genetic architecture of schizophrenia is briefly described with reference to two contrasting (but conceptually related) hypotheses. There is reference to genome-wide association studies (GWAS) and the major histocompatibility complex (MHC) locus on chromosome 6 and schizophrenia. Recent findings regarding structural alleles in the classical complement cascade, related to the MHC and implicated in the elimination and ‘pruning of synapses’, form part of the pathogenesis of schizophrenia. Moving closer to the bedside of schizophrenia patients, the following research findings in the Afrikaner population are discussed: • micro deletion at 22q11.2 chromosome as a specific subtype of schizophrenia; • phenotypical characteristics of schizophrenia patients with spontaneous gene mutations; • paternal age-related schizophrenia (PARS) and social functioning early and later in the lives of these patients; • increased risk of suicide in schizophrenia patients with linkage to chromosome 13q and how mortality rates can be decreased in these patients.http://www.satnt.ac.zaam2018Psychiatr

Genetics of schizophrenia : communicating scientific findings in the clinical setting

The expected identification of susceptibility genes for psychiatric disorders may bring new opportunities and expectations from patients and families for the clinical translation of research findings in psychiatric genetics. In this article information is provided about familial risk of schizophrenia with the theory behind individualizing risk of recurrence highlighted. Recent new findings regarding the new genetic frontier, Copy Number Variations (CNV), are summarized and the genetic architecture of familial and sporadic schizophrenia applicable to the clinical situation is reviewed. A scenario in which genetic testing could be applied in velocardiofacial syndrome (VCFS) type schizophrenia is debated. Referring to genetic discrimination in mental disorders, reference is made to the implementation of the Federal Genetic Information non-discrimination Act (GINA) of 2008 in the USA and the Mental Health Care Act of 2002 in SA

Latest findings in the genetic architecture of schizophrenia : the contribution of genetic studies among Afrikaners

Die genetiese komponent in die etiologie van skisofrenie word reeds ’n geruime tyd al aanvaar. Die onderliggende argitektuur van die genetiese risiko bly ’n punt van bespreking. Vroeë studies oor koppeling en kandidaatverbintenis het grootliks gelei tot onoortuigende of onbesliste resultate. Meer onlangs het kragtige tegnologieë beskikbaar geword. Dít, tesame met groot genoeg toetsgroepe en genoomwye panele van genetiese merkers, het dit moontlik gemaak om sistematiese en agnostiese skandering te doen regdeur die genoom. In agnostiese skandering word tegnologie aangewend om die probleem op te los, sonder enige voorveronderstelling oor waar die genoomrelevante allele gevind sal word. Daar word gesoek na algemene en unieke siektevariante met onderskeidelik klein of groot effek. Die soektog na variante wat nie ’n groot effek het nie, het beperkte sukses gehad. Aan die ander kant het die rol van unieke genetiese gebeure, soos kopienommervariasie (KNV) en uniekepunt-mutasies al hoe belangriker geraak by geenontdekking in geval van skisofrenie. Onlangse navorsing onder Afrikanerpasiënte met skisofrenie, wat bou op vroeëre bevindings van spontane KNV by die 22q11 lokus, het lig gewerp op die spontane mutasieparadigma as ’n groot komponent in die argitektuur van skisofrenie. ’n Oorsig oor onlangse bevindings van hierdie studies word gegee.A genetic component of schizophrenia has been acknowledged for a long time. The underlying architecture of the genetic risk remains a contentious issue. Early linkage and candidate association studies led to largely inconclusive results. More recently powerful technologies became available. This aspect coupled with samples of sufficient sizes, and genome-wide panels of genetic markers facilitated systematic and agnostic scans throughout the genome for either common or rare disease risk variants of small or large effect size, respectively. Although the former had limited success, the role of rare genetic events, such as copy-number variants (CNVs) or rare point mutations, has become increasingly important in gene discovery for schizophrenia. Recent research done among Afrikaner patients with schizophrenia, building upon earlier findings of de novo recurrent CNVs at the 22q11.2 locus, has highlighted a de novo mutational paradigm as a major component of the genetic architecture of schizophrenia. Recent progress in this regard will be reviewed.http://www.satnt.ac.zaam201

Genetic and family counselling for schizophrenia : where do we stand now?

BACKGROUND : Recent genetic findings have led to profound changes in genetic and family counselling for schizophrenia patients and their families. OBJECTIVES : The article gives an overview of the present knowledge regarding the genetic and family counselling for schizophrenia. METHOD : Literature searches were performed on the MEDLINE database (2011–2015) and African Healthline. A current alert service which provides the most recent literature on the topic on a monthly basis was also used in the study. A clinical case example is presented as is experienced in daily psychiatric practice. RESULTS : Genetic risk communication has become the responsibility of the multiprofessional treatment team, moving away from specialists in the field. The treatment team provides information on a daily basis regarding risk predictors in the management of schizophrenia, including risk of relapse, suicide and comorbid substance use. Although genetic information is unique and has implications for blood relatives, genetic risk factors only rarely provide information that is inherently different from that provided by other risk predictors commonly used in healthcare. The common variant common disease and rare variant common disease models as contrasting hypothesis of the genetics of schizophrenia are discussed and debated. An example of a family counselled is given and the place of commercial companies that offer directly to the consumer affordable personal DNA testing for psychiatric illness is discussed. Ethical issues without resolution regarding genetic counselling of schizophrenia are debated. CONCLUSIONS : Recent genetic findings must lead to profound changes in genetic and family counselling in schizophrenia. Exposed attributable risk has immediate effects on genetic counselling of schizophrenia. Psychiatric risk counselling has thus changed from risk estimates based on family history to estimates based on test results in specific individuals.The author is receiving NRF Incentive Funding for Rated Researchers.http://www.sajpsychiatry.orgam2016Psychiatr

Homicide–suicide : practical implications for risk reduction and support services at primary care level

Homicide–suicide (HS) has been defined as homicide committed by a person who subsequently commits suicide within one week of the homicide. In most cases it occurs within 24 hours. HS is a public health problem, victimising not only those directly involved in the act, but also family, friends, acquaintances, colleagues, witnesses and investigators. The literature and findings of recent South African research regarding HS are discussed to highlight the practical implications for risk reduction at primary care level and to address the provision of support services after HS cases. It has been consistently found that depressed men have the highest risk of committing HS, especially if they also abuse alcohol and have problematic personality traits/disorders, in the context of domestic violence or a problematic relationship. Delusional jealousy, although not a frequent finding, is a great risk for HS. The breakdown of an intimate relationship, with a recent or pending separation (real or imagined), has consistently been found to be the most common contributing factor to HS. Primary health care practitioners are likely to be the first contact that these individuals or families might have with the healthcare system. Through a better understanding of risk factors involved in HS, prevention may be enhanced in clinical practice. HS has far-reaching effects and healthcare practitioners can offer support and treatment to people traumatised by these events.https://www.tandfonline.com/loi/ojfp20pm2020Psychiatr

Early deviant behaviour as a dimension trait and endophenotype in schizophrenia

BACKGROUND: In psychiatry, there is still a lack of objective biological diagnostic measurements. It is important to investigate measurements or symptom dimensions that can inform diagnostic assessments and allow for a more personalised approach to patients. AIM: To discuss how early deviant behaviour (EDB) may be seen as a possible continuous symptom dimension trait and endophenotype in schizophrenia. METHODS: Conducting a commentary review by highlighting some important findings from available literature. RESULTS: Findings regarding EDB in schizophrenia in a South African genetic sample point towards EDB as a progressive subtype of schizophrenia, with very early onset of illness (even prior to the psychotic symptomatology) and a genetic form of illness. CONCLUSION: Valuable information can be gained by enquiring into EDB and viewing it as a continuous symptom dimension trait and endophenotype during the psychiatric diagnostic interview.http://www.sajp.org.zadm2022Psychiatr

Ageism, human rights and ethical aspects of end-of-life care for older people with serious mental illness

There are many complex concepts to consider during end-of-life discussions and advance care planning, especially when vulnerable populations such as older individuals with serious mental illness are involved. This article aims to summarize some of these important concepts, such as the eects of ageism, preservation of human rights and dignity, supported or shared decision making and palliative approaches. It emerged from a study that found two thirds of 100 participants 60 years of age and older with serious mental illness had end-of-life decision-making capacity. This finding highlighted the individual and contextual nature of decision-making capacity, the importance of consideration of individual values and protection of human dignity during end-of-life care. Healthcare providers have a duty to initiate end-of-life and advance care discussions, to optimize decision-making capacity, and to protect autonomous decision-making. Chronological age or diagnostic categories should never be used as reasons for discrimination and all patients should receive end-of-life care in keeping with their preferences and values.http://www.frontiersin.org/Psychiatrydm2022Psychiatr

End-of-life care in South Africa : important legal developments

All healthcare practitioners should be aware of ethical principles and legislation relevant to end-of-life care. The aim of this scientific letter is to highlight some important South African legal developments that might be especially important for practitioners taking care of vulnerable populations, such as older patients with serious mental illness. A recent unpublished descriptive, cross-sectional, observational study that was conducted at Weskoppies Psychiatric Hospital, in Gauteng, South Africa, found that two thirds of 100 participants older than 60 years of age and diagnosed with a serious mental illness had end-of-life decision-making capacity. This highlights the importance of initiating advance care discussion with this vulnerable population. With the ongoing and important legal developments in South Africa, this population should not be excluded from access to humane end-of-life care that is in keeping with their preferences and values.http://www.sajp.org.zadm2022Psychiatr

Forensic psychiatry in Africa: prospects and challenges

Forensic Psychiatry has a history that dates back almost two thousand years, and has evolved into a recognised discipline with a robust background of scientific enquiry, mostly because mental health care has always had an important interface with the law. 1 Nevertheless, even in the developed world there are differences between countries with respect to the extent forensic mental health services have developed. This has been exacerbated by the differences in legal systems, resources and priorities in each country. Consequently comparisons and cooperation between forensic psychiatrists internationally has been difficult. 2-4 In Africa, which is the second largest and most populous continent and containing an immense diversity of languages, religious traditions, ethnic groups and sociopolitical systems forensic psychiatry has largely remained underdeveloped within the context of a pervasive neglect in the provision of mental health services. 5 The situation is compounded by the dearth of information about forensic services on the continent. As described by an eminent African psychiatrist, “the practice of forensic psychiatry in Africa is shrouded in both mystery and confusion”. 6 In addition to the lack of appropriate facilities, most countries in Africa have, on average, one psychiatrist per one million inhabitants. Moreover many psychiatrists have migrated to developed countries, leaving a small number of mental health professionals burdened with large numbers of patients. 6 In most countries there are few coordinated initiatives to involve all stakeholders, such as the police, departments of justice, prisons and hospitals, in the development of forensic mental health services