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.

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.

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.

Profile of mortality of patients admitted to Weskoppies Psychiatric Hospital in South Africa over a 5-year period (2001-2005).

OBJECTIVE: Mortality in the psychiatric population, both from natural and unnatural causes, is higher than in the general population and this is despite an improvement in the delivery of care and treatment of mental illness in recent years. The study was conducted to determine a profile of mortality and standardized mortality rates within our psychiatric hospital. METHOD: A retrospective clinical case audit was conducted of deaths that occurred at Weskoppies Hospital between 1st January 2001 and 31st December 2005. Direct standardised mortality rates were calculated (gender specific adjusted for age according to the South African population). RESULTS: A total of 164 deaths were observed during this period. The gender-specific all cause mortality rates, standardised to the South African population, were 0.0177 (95% CI 0.0141, 0.0213) and 0.0163 (95% CI 0.0121, 0.0206) for males and females respectively. The all cause mortality rates for the South African male and female population were 0.0188 and 0.0170 respectively (not significantly different as it falls within the 95% confidence interval of the standardised rates). The predominant natural cause of mortality was infection. Ten of the deaths were due to unnatural causes, of these 7 were suicides. The mortality ratio for unnatural causes was 0.47. CONCLUSION: Mortality studies are important tools for determining quality of health care provisions to patients. Studies of this nature assist in making recommendations for optimal clinical practice and aid in developing preventative measures.

Testing the effectiveness of existing psycho-educational material (The Alliance Programme) for patients suffering from schizophrenia in the South African context.

OBJECTIVE: The objective of this study was to test the effectiveness of the existing psycho-educational material (The Alliance Programme) for patients suffering from schizophrenia in the South African context. METHOD: A qualitative research approach was used. Fifteen Setswana speaking participants, with a diagnosis of schizophrenia were exposed to the programme. Semi-structured and screening interviews were used to collect demographic and clinical data. The participants were divided into two groups and were exposed to either the Alliance Programme or on adapted version of the programme. Participatory communication instruments including focus groups, were used to assess comprehension and knowledge retention of the material over time. RESULTS: Participants who were exposed to the original Alliance Programme experienced the contents of the programme to be technical, difficult to read or recall. They were unable to relate their previous symptoms to the psycho-education given. Participants who were exposed to the adapted version faired much better, gained more insight and were able to relate better to their illnesses. Participants preferred booklets with examples and illustrations, video clips and films over formal lectures. CONCLUSION: Psycho-education material given to people suffering from schizophrenia and their caregivers has to be adapted to their context to be effective.

Clinical characteristics and premorbid variables in childhood-onset schizophrenia: a descriptive study of twelve cases from a schizophrenia founder population.

OBJECTIVE: To analyze clinical and demographic data of childhood-onset (12 years and younger) schizophrenia patients collected for a genetic study in schizophrenia, undertaken nationally in South Africa, using multiple parameters. METHOD: Patients with an onset of schizophrenia at 12 years or younger, were included. From the Diagnostic Interview for Genetic Studies (DIGS), patients' information and summary report data was tabulated and analyzed. Specific subgroups were further compared. This sub-population of 12 subjects was further compared with a group of the adult sample. RESULTS: Of the 12 patients recruited, prominent results were: male to female ratio of 1:1; all had insidious onset of psychosis; a third had all 3 multidimensional impairment (MDI) symptoms; all patients that received ADHD treatment had ADHD treatment failure; two thirds had milestone delay; 58% had birth complications; a third were predominantly bottle fed; 42% had family history of schizophrenia; a third had family history of other major psychiatric conditions; all patients had at least one non-psychotic deviant behaviour (NPDB); no patient used cannabis; all delusions were paranoid; 92% had school achievement difficulty and a third had treatment resistance. Gender comparison included: earlier onset of psychosis in females; all females had aggression versus a third of males; more females had school achievement difficulty than males; males had more treatment resistance. Patients with MDI, compared to the sample average had: earlier onset of non-psychotic deviant behaviour; lower school drop-out rate; less social difficulty and no treatment resistance. CONCLUSION: The results compare well to previous research on this topic. The new concepts introduced by the present study require further investigation.

LRRTM1 on chromosome 2p12 is a maternally suppressed gene that is associated paternally with handedness and schizophrenia.

Left-right asymmetrical brain function underlies much of human cognition, behavior and emotion. Abnormalities of cerebral asymmetry are associated with schizophrenia and other neuropsychiatric disorders. The molecular, developmental and evolutionary origins of human brain asymmetry are unknown. We found significant association of a haplotype upstream of the gene LRRTM1 (Leucine-rich repeat transmembrane neuronal 1) with a quantitative measure of human handedness in a set of dyslexic siblings, when the haplotype was inherited paternally (P=0.00002). While we were unable to find this effect in an epidemiological set of twin-based sibships, we did find that the same haplotype is overtransmitted paternally to individuals with schizophrenia/schizoaffective disorder in a study of 1002 affected families (P=0.0014). We then found direct confirmatory evidence that LRRTM1 is an imprinted gene in humans that shows a variable pattern of maternal downregulation. We also showed that LRRTM1 is expressed during the development of specific forebrain structures, and thus could influence neuronal differentiation and connectivity. This is the first potential genetic influence on human handedness to be identified, and the first putative genetic effect on variability in human brain asymmetry. LRRTM1 is a candidate gene for involvement in several common neurodevelopmental disorders, and may have played a role in human cognitive and behavioral evolution.

Dysrhythmogenic potential in acute admissions to psychiatric hospitals and clinics.

UNLABELLED: Co-morbidity between physical disease, especially cardiovascular, and psychological disturbances is well documented. In psychiatric patients, the potential for dysrhythmogenic incidences is increased by the fact that many psychiatric medications influence cardiovascular function. AIM: The aim of the study was to examine the dysrhythmogenic potential of 30 psychiatric patients (group A), irrespective of diagnoses or medication, at admission to psychiatric institutions. METHODS: The dysrhythmogenic potential was determined in terms of heart rate-corrected QT intervals (QTc), heart rate-corrected JT intervals (JTc), QT and JT dispersion (QTcd and JTcd) between leads V1 and V6, and heart rate variability (HRV) as determined from lead V6 of the ECG. Values were compared with 30 age- and gender-matched controls (group B). In the second part of the study the dysrhythmogenic indicators were assessed in a patient group (group C; n = 43) with only psychiatric disorders and compared to a group with psychiatric as well as medical disorders (group D; n = 27). RESULTS: The patient group A had significantly higher values than the control group for mean QTc (V6) (0.4579 +/- 0.0328 vs 0.4042 +/- 0.0326; p = 0.0470), mean JTc (V6) (0.3883 +/- 0.0348 vs 0.3064 +/- 0.0271; p = 0.0287) and mean QT and JT dispersion values (QTcd = 0.0443 +/- 0.0203 vs 0.0039 +/- 0.0053 and JTcd = 0.0546 +/- 0.1075 vs 0.0143 +/- 0.1450, p < 0.05). A statistically significant difference (p < 0.0001) was found between the patients' (group A) HRV and that of the controls (group B). No statistically significant differences were found between the values of the dysrhythmogenic indicators for patients with only psychiatric illness (group C) and those with psychiatric as well as medical disorders (group D). CONCLUSIONS: Psychiatric patients at the point of admission to psychiatric institutions may have an increased dysrhythmogenic potential, not necessarily caused by physical disease. The potential of an augmented risk for cardiovascular incidents in psychiatric patients should be considered when treating such patients.

Prevalence and clinical characteristics of obsessive-compulsive disorder and obsessive compulsive symptoms in Afrikaner schizophrenia and schizoaffective disorder patients.

OBJECTIVE: There is evidence of variation in the prevalence of co-morbid obsessive-compulsive disorder in schizophrenia amongst ethnic groups. This study evaluated the lifetime prevalence and clinical characteristics of obsessive-compulsive disorder (OCD)/ obsessive-compulsive symptoms (OCS) in Afrikaner schizophrenic and schizoaffective disorder patients. METHOD: An ongoing genetic study of schizophrenia is currently being conducted on the Afrikaner founder population. In this cohort of 400 subjects from the original genetic study, we identified 53 subjects with schizophrenia or schizoaffective disorder and co-morbid OCD/OCS (study group). They were matched for gender and age of onset of illness with 59 subjects who do not have OCD/OCS (control group). The diagnostic instrument used in this cohort is the Diagnostic Interview for Genetic Studies (DIGS) version 2, which has been translated into Afrikaans. In addition to the DIGS, information for the relevant clinical characteristics reported in this study was also drawn from a detailed narrative chronological summary report and clinical files. A checklist was completed. RESULTS: The prevalence of co-morbid OCD/OCS amongst 400 subjects with schizophrenia or schizoaffective disorder was 13.2% [n=53] of which 40 were male and 13 female patients. The prevalence of OCD was 10.7% and OCS was 2.5%. Contamination obsessions [n=17] were the most common type of obsession reported, followed by religious obsessions [n=8]. The most prevalent compulsions were repetitive rituals [n=32] followed by checking behaviour [n=22]. Onset of psychotic symptoms was found to be insidious in 86.8% of the study group compared to 24.6% of the control group (p<0.0001). Second-generation antipsychotic use was found to be statistically more prevalent in the study group (77.4%), compared to the control group (45.8%) (p=0.0008). 73% of the study group experienced depressive symptoms compared to 50.8% of the control group. Both groups were found to have a similar incidence of suicidal thoughts and suicide attempts. Substance abuse amongst the control group was significantly higher (35.9%) compared to the study group (19.2%) (p <0.05). Cannabis was most commonly abused in both groups, followed by alcohol. CONCLUSION: The prevalence rate of 13.2% of co-morbid OCD/OCS in Afrikaner schizophrenia and schizoaffective disorder patients differs from findings in other ethnic groups, suggesting the possible role of genetic and cultural factors in the prevalence of co-morbid OCD/OCS. Second-generation antipsychotic use amongst schizophrenia and schizoaffective disorder patients with co-morbid OCD/OCS was found to be significantly higher than in those without co-morbid OCD/OCS. Clinical characteristics of Afrikaner schizophrenics and schizoaffective disorder patients with and without co-morbid OCD/OCS are the same, both groups were associated with significant psychopathology and a poor prognosis.

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.

Personality traits, brief recurrent depression and attempted suicide.

This study investigated the relationship between attempted suicide, personality factors and brief recurrent depression. Over a period of 1 year, the demographic and psychiatric factors of 307 patients who had attempted suicide and subsequently been hospitalised at H. F. Verwoerd Hospital and referred to its Department of Psychiatry were recorded. Their personality traits were evaluated clinically. After 5 years, 205 respondents were traced to complete a follow-up questionnaire and, where possible, a personality assessment was completed on clinical grounds. They were also evaluated for brief recurrent depression. Among the men, antisocial, dependent and histrionic personality traits, in that order, were most commonly noted and among the women, histrionic, dependent and antisocial traits. A clear relationship between suicidal behaviour and the syndrome of brief recurrent depression was established. The latter was also found to be related to histrionic personality traits in women. This underscores the relationship between suicide attempts and histrionic personality traits.

[Suicide in schizophrenic patients]. / Selfmoord by pasiënte met skisofrenie.

Suicide is a serious and extensive problem in the clinical management of schizophrenic patients. A retrospective empirical study was conducted on 33 white schizophrenic patients who committed suicide between 1978 and 1989. 'Psychological autopsy' and psychiatric interviews were used for gathering information. A group of 33 schizophrenic patients with a high suicide risk were used as control group. The two groups were correlated as far as possible with regard to age, duration of illness and sex. A statistical analysis was made of the findings. Risk factors revealed by this study, which may be of use in the clinical situation to help prevent suicide in schizophrenic patients, are discussed and include sociodemographic data, depressive and psychotic symptomatology and the misuse of Cannabis. Suggestions are also made regarding future research on schizophrenia and suicide. It is concluded that the clinician should be conservative in his assumptions when identifying schizophrenic patients with a high risk of suicide and should not overestimate his abilities in this field.

Weskoppies Hospital, founded 1892--the early years.

The Krankzinnigengesticht te Pretoria (Pretoria Lunatic Asylum) was established in 1892 as the first and only psychiatric institution in the Zuid-Afrikaansche Republiek (now the Transvaal). The asylum was later renamed Weskoppies Hospital. The first 10 years of the hospital's history, including the turbulent years of the Anglo-Boer War, are described. Attention is given to the institution's management, the diagnosis and treatment of patients and the effectiveness of such treatment. The hospital's medical director followed an enlightened approach to caring for the mentally ill, in line with the policies of psychiatric hospitals in contemporary Europe. However, his ideals of no restraint and minimal confinement of patients could not be maintained during the war years owing to insufficient accommodation and a lack of suitably trained attendants. It is concluded that the humane care of the institutionalised psychiatric patient was (and is) not guaranteed by enlightened policies, but depends on sufficient resources to put such policies into practice.

[Psychiatric aspects of family killings]. / Psigiatriese aspekte van gesinsmoord.

There has been very little research done on family slayings in the RSA. The concept is defined and a short survey of the literature is provided. Five case studies of patients who were referred to Weskoppies Hospital after being involved in family killings are described; a diagnosis of depression was made in all 5 cases. The clinical implications of manslaughter and depression are discussed, and suggestions are offered for future research into psychiatric factors involved in family killings.