J.L. Roos

Assessment of the frequency of the 22q11 deletion in Afrikaner schizophrenic patients.

A hemizygous deletion of the q11 band on chromosome 22 occurs in 1 of every 5,950 live births (0.017%). The deletion is mediated by low copy repeats (LCRs) flanking this locus. Presence of the deletion is associated with variable phenotypic expression, which can include distinctive facial dysmorphologies, congenital heart disease and learning disabilities. An unusually high percentage of individuals with this deletion (25–30%) have been described to develop schizophrenia or schizoaffective disorder. In previous studies, the prevalence of the 22q11 deletion in patients with schizophrenia was found to be approximately 2% in Caucasian adults and 6% in childhood‐onset cases. Both these frequencies represent a dramatic increase from the prevalence of the deletion in the general population. In this study, we investigate the occurrence of the 22q11 deletion in an independent sample of schizophrenic patients of Afrikaner origin. We first ascertained a sample of 85 patients who meet full diagnostic criteria for schizophrenia for presence of two or more of the clinical features associated with presence of the 22q11 deletion. A group of six patients (7%) met these criteria. This group was subjected to fluorescent in situ hybridization (FISH) and presence of the 22q11 deletion was confirmed for two subjects. Our study therefore confirms the previously reported rate of 2% frequency of the 22q11 deletion in adult schizophrenic patients and provides a two‐stage screening protocol to identify these patients.

Clinical Characteristics of an Afrikaner Founder Population Recruited for a Schizophrenia Genetic Study

The clinical characteristics of an Afrikaner founder population sample recruited for a schizophrenia genetic study are described. Comparisons on several clinical characteristics between this sample and a U.S. sample of schizophrenia patients show that generalization of findings in a founder population to the population at large is applicable. The assessment of the frequency of the 22q11 deletion in Afrikaner schizophrenia patients is approximately 2%, similar to findings in a U.S. sample. Results of analysis of early non‐psychotic deviant behavior in subjects under the age of 10 years in the Afrikaner population broadly replicated findings in a U.S. sample. Approximately half of male schizophrenia patients and a quarter of female patients in the Afrikaner schizophrenia database used or abused cannabis. Male users of cannabis with severe early deviant behavior had the lowest mean age of criteria onset, namely 18.4 years. These findings confirm previous findings, indicating that early deviance is linked to later outcome of disease. The clinical characteristics and premorbid variables in 12 childhood‐onset Afrikaner schizophrenia patients thus far recruited in this study compare favorably with what is known about childhood‐onset schizophrenia in a U.S. sample. The prevalence of co‐morbid OCD/OCS in this Afrikaner schizophrenia founder sample was 13.2% which is in keeping with that of co‐morbid OCD in schizophrenia, estimated at 12.2% by the U.S. National Institute of Mental Health. These findings confirm that the clinical characteristics of a schizophrenia sample drawn from the Afrikaner founder population can be generalized to the schizophrenia population at large when compared to findings reported in the literature.

Phenotypic features of patients with schizophrenia carrying de novo gene mutations : a pilot study

Genome-wide scans have revealed a significant role for de novo copy number variants (CNVs) and Single Nucleotide variants (SNVs) in the genetic architecture of schizophrenia. The present study attempts to parse schizophrenia based on the presence of such de novo mutations and attempts genotype-phenotype correlation. We examined phenotypic variables across three broad categories: clinical presentation, premorbid function, disease course and functional outcome and compared them in individuals with schizophrenia carrying either a de novo CNV, a de novo SNV, or no de novo mutation. Work skills were worst affected in patients carrying de novo CNVs. More learning disabilities were found in subjects carrying de novo SNVs. Patients with either mutation had older parents at birth and worse functional outcome as measured by SLOF scores. We found no relation between treatment resistance and the presence of de novo mutations. The combined consideration of the functional outcome scores and early deviant behaviours was found to have higher predictive value for underlying genetic vulnerability. Due to the rare nature of the de novo mutations the sample sizes studied here were small. Despite this, valuable phenotypic characteristics were identified in schizophrenia patients carrying de novo mutations and studying larger samples will be of interest.

Psychiatric and other contributing factors in homicide-suicide cases, from northern Gauteng, South Africa over a six-year period

ABSTRACT Homicide committed by a person who subsequently commits suicide within one week of the homicide is a relatively rare event. The current study used an explanatory sequential design, including psychological autopsies, to identify psychiatric and other contributing factors in 35 homicide-suicide cases in northern Gauteng Province, South Africa. This research highlighted the complex multifactorial nature of these events. Identification of high-risk individuals and delineation of contributing factors is important. Early recognition and effective treatment of psychiatric illness, particularly depression and substance use problems, in people experiencing relationship issues (with pending/recent separations) and financial stressors, is an essential component in the prevention of homicide-suicide incidents. Evaluations should always include direct questioning about suicidal and homicidal ideations. Mental health practitioners have a definite role to play in offering comfort, support, and treatment to all those who remain behind after these devastating events. Urgent attention needs to be given to the availability of support and treatment for investigating police officers and surviving family and friends.

S189. CARVING A MORE SPECIFIC SUBTYPE OF SCHIZOPHRENIA FOR GENETIC STUDIES: SPORADIC SCHIZOAFFECTIVE BIPOLAR TYPE

Abstract Background Schizophrenia is a heterogeneous group of disorders. The familial-sporadic distinction has been considered under a range of genetic models. Research supports a strong association of de novo copy mutations with sporadic schizophrenia. The aim of the study was to determine a more homogenous phenotype for genetic research via comparison of various clinical and socio-demographic variables in familial and sporadic schizophrenia. Methods A cross-sectional observational design was used. This study included 384 participants with schizophrenia/schizoaffective disorder from an Afrikaner founder population in South Africa that previously participated in genetic research. A comprehensive data capturing sheet was completed from a pre-existing database that contains information obtained from the Diagnostic Interview for Genetic Studies, chronological clinical summary reports and additional sources of information. The study protocol was approved by the Research Ethics Committee from the Faculty of Health Sciences at the University of Pretoria. Logit models were fitted using the backward elimination procedure to investigate relationships where the dependent variable was binary. Odds ratio estimates were calculated for independent variables that were significant in the model. The Kruskal-Wallis test was conducted to compare the means of groups. For cases where there were significant differences a post-hoc test with a Bonferroni correction was done to determine which groups differ significantly. Results There were 214 familial and 170 sporadic subjects. 279 had a diagnosis of schizophrenia, 66 schizoaffective, bipolar type and 39 schizoaffective disorder, depressive type. 242 were male and 142 female. The age at onset of the primary psychiatric diagnosis, season of birth, co-morbid diagnoses, symptomatology, suicidality history and marital status weren’t significantly different when considering the combined schizophrenia/schizoaffective disorder group and its relationship to familiality. Early deviant behaviour was however decreased in the sporadic group. These findings were replicated when analysing schizophrenia independently from schizoaffective disorder. The sporadic schizoaffective disorder, bipolar type did however have a significantly lower age at onset (mean 20.18 versus 25.07 years), 8.8 times more hallucinations, 6.6 times more odd behaviour before the age of 10 and were 2.8 times more likely to be single. The bipolar type also had 2.9 times more suicide attempts as opposed to ideation. This finding wasn’t statistically significant. The sporadic schizoaffective group overall was 2.2 times more likely to abuse substances. The depressive type didn’t differ significantly with regards to age at onset, season of birth, co-morbidities, early deviant behaviour, symptomatology, suicidality or marital status. Discussion The combined schizophrenia/schizoaffective group didn’t differ significantly, nor did schizophrenia and schizoaffective disorder depressive type when analysed independently. The sporadic schizoaffective bipolar type differed significantly on multiple important variables that suggest a poorer prognosis and increased disease severity. The sporadic schizoaffective bipolar type forms a more homogenous group, with genetic studies hinting at relatively specific genetic risk factors. Studies elucidating the genetic architecture of this group could prove invaluable in clarifying the aetiology of schizophrenia.

Increased risk of suicide in schizophrenia patients with linkage to chromosome 13q

We link schizophrenia in families from the genetically isolated South African Afrikaner population to chromosome 13q (n =51), 1p (n =23) and combined 13q & 1p (n =18). Patients with linkages to chromosome 13q were 4.16 times more likely to meet diagnostic criteria for schizoaffective disorder compared to patients with linkage to 1p. A third of patients with linkage to both 13q &1p met diagnostic criteria for SAD. There was a significant positive relationship between suicidality and a diagnosis of schizoaffective disorder. Identifying linkage to chromosome 13q may be informative in identifying suicide risk early and prevent morbidity and mortality in schizophrenia patients.

Methodological limitations to a study on interpersonal therapy

Studies comparing pharmaco- v. psychotherapy in HIV-positive patients with depression are of great importance. These are vulnerable patients, both in a psychological sense and because of potential drug interactions. Psychotherapy should play an important role in the treatment of these patients.

Suicide risk in schizophrenia - a follow-up study after 20 years Part 1: Outcome and associated social factors

Objective. This study re-evaluated, after a period of 20 years, a cohort of patients with schizophrenia who had been considered to be at high risk for suicide. The outcome and social factors associated with their suicide risk were investigated over the two decades. Method. Subjects were contacted and interviewed face to face using a questionnaire devised for this purpose. The Beck Hopelessness Scale (BHS) was administered and ratings were compared with those from the original study. The Calgary Depression Scale for Schizophrenia (CDSS) was administered. Cross-tabulations were performed to identify factors associated with increased suicide risk. A psychological autopsy was performed for those subjects who had committed suicide since the original study. Results. Fourteen of the original 33 high-suicide-risk schizophrenia patients were traced. Three subjects had committed suicide during the 20-year period. Among the living subjects, risks for suicide were found to be lower than those 20 years earlier. Male gender, poor social support, early age of illness onset, current admission to or recent discharge from hospital, and a higher level of education were all factors associated with increased suicide risk. Conclusion. Demographic factors and those related to illness course found to be associated with suicide risk in patients with schizophrenia in this study are in accord with those reported in the literature.

Can we close the barn door before the horses get out? A case study of high genetic loading and subsequent development of psychosis.

We would like to report on a 10 year old girl who was referred to a genetic study of schizophrenia in the Afrikaner population because of a high familial genetic loading. This patient subsequently at the age of 16 years was diagnosed with a psychotic disorder. The initial presentation at 10 years of age as well as the course of illness until the diagnosis of psychosis was made will be reported on. Possible predictors of the ultimate development of psychosis will be highlighted and the continuous follow-up of a high-risk case is emphasized.

Depression Later in Life – an Approach for the Family Practitioner

Abstract Depressive disorder is the most common mental health problem in older people. Health professionals mainly come into contact with those who are most susceptible to depression, including older people who live in residential facilities and the frail with acute or chronic physical illness. Quite often, such individuals also exhibit multiple pathology. Under these circumstances, health professionals may have an exaggerated view of the extent of depression among the elderly, causing them to overlook depressive disorders that they may have developed. Organic factors, including alcohol and iatrogenic drugs, must be ruled out in the aetiology. Physical ill health must receive optimum treatment. The choice of antidepressant drug is based on the side-effect profiles and potential drug-drug interactions, rather than on the degree of therapeutic efficacy. Treatment should be multimodal and multidisciplinary, with the aim of complete recovery and not simple improvement. By using a range of treatments, most patients will recover, though keeping patients well is more difficult. Treatment should be continued for at least 12 months. Many patients who could benefit from long-term maintenance therapy do not receive it. With optimum management the prognosis is at least as good as that for any other stage of adult life.