Persistent Maternal Mental Health Disorders and Toddler Neurodevelopment at 18 Months: Longitudinal Follow-up of a Low-Income South African Cohort.

One of the biggest threats to early childhood development in Africa is poor maternal mental health. The present study reports on the relationships between clinical diagnoses of persistent maternal mental health disorders (at 3- and/or 6- and 18-month post-term age) and toddler neurodevelopment at 18 months of age. Eighty-three mother-toddler dyads from low socio-economic status settings in Cape Town, South Africa, were included. At the 3-, 6- and 18-month postnatal visits, clinician-administered structured diagnostic assessments were carried out according to the Diagnostic and Statistical Manual of Mental Disorders-V (DSM-V) criteria. Toddler neurodevelopment at 18 months corrected age was assessed with the Bayley Scales of Infant and Toddler Development (BSID-III). No significant differences (p > 0.05) were found between toddlers with exposure to persistent mood or psychotic disorders in the different BSID-III domains compared to toddlers with no exposure. Toddlers exposed to persistent comorbid anxiety and mood disorders scored significantly higher on the cognitive (p = 0.049), motor (p = 0.013) and language (p = 0.041) domains and attained significantly higher fine motor (p = 0.043) and gross motor (p = 0.041) scaled scores compared to toddlers with no maternal mental health disorder exposure. Future investigations should focus on the role of protective factors to explain the pathways through which maternal mental health status is associated with positive toddler neurodevelopmental outcomes.

Maternal mental health and infant neurodevelopment at 6 months in a low-income South African cohort.

Maternal mental health disorders and the adverse consequences for infant neurodevelopment have received substantial research attention in high-income countries over the past five decades. In Africa, where relatively little work has been done on this topic, researchers have largely focused on infant physical health outcomes. This longitudinal study investigated the neurodevelopment of infants at 6 months post-term with exposure to mothers with a clinical diagnosis of persistent mental health disorders residing in low-income communities in Cape Town, South Africa. Adjusted models revealed no significant differences on the Bayley Scales of Infant and Toddler Development (BSID-III) domains (cognitive, motor, language, socio-emotional, and adaptive behavior) between infants exposed to maternal mental health disorders (n = 62) and the comparison group (n = 35) at 3 and 6 months. Subgroup analyses found no significant differences on the BSID-III domains between infants with exposure to mood disorders (n = 31), as well as infants with exposure to comorbid (i.e., a combination of two or three) mental health disorders (n = 14) and the comparison group. However, infants with exposure to psychotic disorders (n = 14) scored significantly lower on the cognitive and the motor domains and the fine motor subscale. These novel data provide an important contribution to the scientific literature especially in the field of maternal psychotic disorders in Africa.

Los trastornos de la salud mental materna y las consecuencias adversas para el neurodesarrollo del infante han recibido una considerable atención investigativa en países de altos niveles económicos a lo largo de las últimas cinco décadas. En África, donde se ha llevado a cabo relativamente poco trabajo sobre este tema, los investigadores se han enfocado por la mayor parte en los resultados de la salud física del infante. Este estudio longitudinal investigó el neurodesarrollo de infantes a los 6 meses después del término de gestación que habían sido expuestos a madres con un diagnóstico clínico de trastornos de salud mental persistentes quienes residían en comunidades de bajos recursos en Ciudad del Cabo, Sudáfrica. Los ajustados modelos no revelaron significativas diferencias en los dominios de las Escalas Bayley del Desarrollo del Infante y Niños Pequeñitos (BSID-III) (cognitivo, motor, lenguaje, comportamiento socioemocional y de adaptación) entre los infantes que habían estado expuestos a los trastornos de salud mental materna (n = 62) y el grupo de comparación (n = 35) a los 3 y 6 meses. Los análisis de subgrupo no encontraron diferencias significativas en los dominios de BSID-III entre los infantes que habían estado expuestos a los trastornos de estado de ánimo (n = 31), así como los infantes que habían estado expuestos a trastornos de salud mental comórbidos (v.g. una combinación de dos o tres) (n = 14) y el grupo de comparación. Sin embargo, los infantes que habían estado expuestos a trastornos sicóticos (n = 14) tuvieron puntajes significativamente más bajos en los dominios cognitivo y motor, así como en la subescala de las habilidades motoras finas. Estos novedosos datos ofrecen una contribución importante a la literatura científica especialmente en el campo de los trastornos sicóticos maternos en África.

Les troubles de la santé mentale maternelle et les conséquences négatives pour le neurodéveloppement du nourrisson ont reçu l'attention de beaucoup de recherches dans les pays à revenu élevé ces cinquante dernières années. En Afrique où relativement peu de travail a été fait sur ce sujet, les chercheurs se sont en grande partie penchés sur les résultats de la santé physique des nourrissons. Cette étude longitudinale s'est penchée sur le neurodéveloppement de nourrissons à 6 mois après terme avec une exposition aux mères avec un diagnostic clinique de troubles de la santé mentale persistants, résidant dans des communautés défavorisées à Cape Town, en Afrique du Sud. Les modèles ajustés n'ont révélé aucunes différences importantes dans les domaines (cognitif, moteur, langage, comportement socio-émotionnel et comportement adaptif) des Echelles Bayley du Développement du Nourrisson et du Jeune Enfant (BSID-III) entre les nourrissons exposés à des troubles de la santé mentale maternelle (n = 62) et le groupe de comparaison (n-35) à 3 et 6 mois. Les analyses de sous-groupes n'ont trouvé aucunes différences concernant les domaines BSID-III entre les nourrissons avec une exposition à des troubles de l'humeur (n-31), ainsi que des nourrissons avec une exposition à des troubles de santé mentale comorbides (c'est-à-dire une combinaison de deux ou trois) (n-14) et le groupe de comparaison. Cependant, les nourrissons ayant été exposés à des troubles psychotiques (n = 14) ont reçu des scores bien plus bas dans le domaine cognitif, dans le domaine moteur, et à la sous-échelle motrice fine. Ces nouvelles données offrent une contribution importante aux recherches scientifiques, surtout dans le domaine des troubles psychotiques maternels en Afrique.

Early motor behavior of infants exposed to maternal mental health disorders - A South African perspective.

INTRODUCTION: Over the past five decades the bulk of research on exposure to maternal mental health disorders and infant neurodevelopment has been generated in high-income countries. The current study included infants, residing in low-income communities in South Africa, born to mothers with a history of psychiatric disorders. AIM: To assess the motor behavior of 10- to 20-week-old infants exposed to maternal mental health disorders, and a subgroup of infants with prenatal psychotropic medication exposure. METHODS: The present study is a cross-sectional descriptive study, with a longitudinal subgroup analysis. General Movement Assessment (GMA), including the Motor Optimality Score-Revised (MOS-R), was used at 10-20 weeks corrected age to assess infant motor behavior. RESULTS: The study included 112 infants. No significant difference (p = 0.523) was found on the MOS-R between infants exposed to maternal mental health disorders (n = 70) and the comparison group (n = 42). Both the exposed and comparison groups scored within the mildly reduced range on the MOS-R. No significant differences were found in a subgroup of infants with prenatal exposure to multi-class psychotropic medication (n = 17), mono-class psychotropic medication (n = 35) or valproate exposure (n = 10) (p > 0.1). CONCLUSION: No association was found between exposure to maternal mental health disorders or exposure to psychotropic medication and infant motor behavior at 10-20 weeks post-term age on the MOS-R. Future research should focus on the contribution of exposure to specific classes and types of psychotropic medication on neurodevelopmental outcome of infants in larger cohorts.

The Shared Pleasure Paradigm: A study in an observational birth cohort in South Africa.

Mother-infant dyads in low- and middle-income countries (LMICs) may be exposed to a range of factors associated with suboptimal development. Optimal infant development is likely supported by synchronicity in the early mother-infant relationship, but limited corroborative research is available in LMICs. The Drakenstein Child Health Study (DCHS) provided an opportunity to study this synchronicity and its associations in South Africa. A South African birth cohort study investigating early-life determinants of child health in a LMIC context provided participants. The Shared Pleasure (SP) paradigm helped assess early mother-infant synchronicity in videos of a sub-set of 291 mother-infant dyads at their 14-week well baby visit. General linear regression models investigated the relationship between selected maternal and infant characteristics and the presence of Shared Pleasure moments. Out of a possible 291 dyads, 82% (n = 239) yielded Shared Pleasure moments. The mean age of mothers was 27 years, while infant sex distribution comprised 54% females and 46% males. The shortest single Shared Pleasure moment lasted at least 0.5 s and the longest 28 s. Shared Pleasure moments were associated with higher gestation age at delivery (p = 0.008) and higher infant birth weight (p = 0.006), but were not related to mother's mental health and infant health outcomes at 14 weeks. The high frequency of positive Shared Pleasure moments in reciprocal dyadic interactions in this sample suggests that significant disruption in shared pleasure may be present only in extreme cases (e.g. mothers with severe mental disorders). Further work is needed to investigate the mechanisms underlying the associations between early mother-infant synchronicity and better outcomes noted here, and to assess whether SP may serve as a culturally appropriate screen for assessing connectedness.

Maternal Shared Pleasure, Infant Withdrawal, and Developmental Outcomes in a High Risk Setting in South Africa.

Background: Infants in lower middle income countries are often exposed to early adversities which may lead to suboptimal caregiving environments and place them at risk of not achieving their developmental potential. Synchrony and positive engagement in the mother-infant relationship plays a critical role in buffering the impact of early adversity. Shared Pleasure (SP) is considered a marker of high intensity positive interaction and may hold a promise of improving developmental outcomes. Methods: This study was part of a prospective observational study of mothers with and without mental illness in South Africa. Dyadic videos were assessed for SP and infant withdrawal (using the Alarm Distress Baby Scale) at 6 months. Infant developmental outcomes were assessed using the Bayley's Scales for Infant and Toddler Development, third edition at 18 months. Results: Ninety-one dyads were assessed for SP. The occurrence of SP was low (20%). There was no significant association with an EPDS measure of maternal depression (p = 0.571) and SP moments. Infant withdrawal was high (72%) and associated with male infant gender (p = 0.025). There was a significant association between the occurrence of SP and a lower score of infant withdrawal (estimate = -1.29; SE = 0.4; p = 0.0002). The number of SP moments at 6 months was significantly associated with motor (estimate = 2.4; SE = 0.9; p = 0.007) and marginally significant with cognitive scores (estimate = 1.9; SE = 1.0; p = 0.052) at 18 months. Regression modelling differential outcomes showed a greater improvement in cognitive scores at 18 months in infants with an SP moment compared to those without an SP moment [SP average difference (AD) = 7.4 (2.4), no SP AD = 10.4 (1.2); p = 0.012]. Infants without an SP moment experienced a larger decrease in motor scores at 18 months compared to those with an SP moment [SP AD = -3 (3.0); no SP AD = -10.6 (1.5), p = 0.027]. Conclusion: While the occurrence of SP in this sample was low and the rates of infant withdrawal were high, there were promising results suggesting early positive SP interactions may contribute to improvements in subsequent developmental outcomes.

Associations Between Neonatal Cry Acoustics and Visual Attention During the First Year.

It has been suggested that early cry parameters are connected to later cognitive abilities. The present study is the first to investigate whether the acoustic features of infant cry are associated with cognitive development already during the first year, as measured by oculomotor orienting and attention disengagement. Cry sounds for acoustic analyses (fundamental frequency; F0) were recorded in two neonatal cohorts at the age of 0-8 days (Tampere, Finland) or at 6 weeks (Cape Town, South Africa). Eye tracking was used to measure oculomotor orienting to peripheral visual stimuli and attention disengagement from central stimuli at 8 months (Tampere) or at 6 months (Cape Town) of age. Only a marginal positive correlation between fundamental frequency of cry (F0) and visual attention disengagement was observed in the Tampere cohort, but not in the Cape Town cohort. This correlation indicated that infants from the Tampere cohort with a higher neonatal F0 were marginally slower to shift their gaze away from the central stimulus to the peripheral stimulus. No associations between F0 and oculomotor orienting were observed in either cohort. We discuss possible factors influencing the current pattern of results suggesting a lack of replicable associations between neonatal cry and visual attention and suggest directions for future research investigating the potential of early cry analysis in predicting later cognitive development.

Pregnancy outcomes, early separation, and psychiatric relapse experienced by South African women with peripartum psychosis: a descriptive exploration.

The peripartum is associated with increased incidence of severe mental illness (SMI), a greater occurrence of psychotic symptoms and psychiatric admissions. This study aimed to describe the psychiatric, medical and psycho-social risk factors affecting South African mothers who experienced peripartum psychosis. Using a prospective, descriptive design, we conducted a detailed interview and supplementary information was collected by review of clinical records. The study examined the accounts of forty mothers who experienced peripartum psychosis between 6 and 18 months postpartum. Descriptive statistics for demographic and clinical variables were completed with SPSS for Windows, version 25. Pregnancies were predominantly unplanned and more than half of participants reported prenatal substance use. Medical or psychiatric problems during pregnancy were common and the majority of dyads experienced periods of early separation. Socio-demographic factors exacerbated the challenges this group of women at high risk face, in providing nurturing care to their infants. Results highlight the need for close follow-up for women with SMI, with particular attention to substance screening and psychosocial stressors. Integrated maternal and infant mental health services are recommended.

Erratum: The validation of the visual screening tool for anxiety disorders and depression in hypertension and/or diabetes.

No abstract available.

Cross-cultural analysis of attention disengagement times supports the dissociation of faces and patterns in the infant brain.

Infants are slower to disengage from faces than non-face patterns when distracted by novel competing stimuli. While this perceptual predilection for faces is well documented, its universality and mechanisms in relation to other aspects of attention are poorly understood. We analysed attention disengagement times for faces and non-face patterns in a large sample of 6-to 9-month-old infants (N = 637), pooled from eye tracking studies in socioculturally diverse settings (Finland, Malawi, South Africa). Disengagement times were classified into distinct groups of quick and delayed/censored responses by unsupervised clustering. Delayed disengagement was frequent for faces (52.1% of trials), but almost negligible for patterns (3.9% of trials) in all populations. The magnitude of this attentional bias varied by individuals, whereas the impact of situational factors and facial expression was small. Individual variations in disengagement from faces were moderately stable within testing sessions and independent from variations in disengagement times for patterns. These results point to a fundamental dissociation of face and pattern processing in infants and demonstrate that the bias for faces can be robust against distractors and habituation. The results raise the possibility that attention to faces varies as an independent, early-emerging social trait in populations.

Revisiting the African origins of attachment research-50 years on from Ainsworth: A descriptive review.

Culture plays a significant role in the variations observed in the manifestation, expression, and meaning of attachment behaviors. Africa is home to multiple cultures, with distinct organizations of caregiving relationships underlying the development of attachment. This review aims to consolidate knowledge about African attachment by describing studies of infant attachment conducted in Africa since Mary Ainsworth's Ugandan findings in 1967. Electronic databases were searched with the terms "Africa" ("attachment" or "bond") and "infant." Nine studies that assessed infant attachment style with self-report or observation methods were included, but spanned only five countries. The Strange Situation Procedure was most frequently used. Most studies described dyads living in peri-urban or township areas. Multiple socioeconomic factors affecting living conditions were identified, including, unemployment, financial difficulties, limited education, poor housing, single parenthood, lack of partner support, substance abuse, and depression. Overall distributions of attachment classification proportions appear consistent with global attachment-classification patterns. Despite adverse conditions, secure attachment was relatively widespread, and some populations had low rates of avoidant attachment. Relatively high rates of disorganized attachment were found when the category was included. Africa remains an understudied continent regarding infant attachment. The continent's cultural diversity may hold important truths necessary for understanding the complex relationship between infant and attachment figure.

La cultura juega un papel significativo en las variaciones observadas en la manifestación, expresión y significado de los comportamientos de afectividad. África es hogar de múltiples culturas, con distintas organizaciones de relaciones de prestación de cuidados que resaltan el desarrollo de la afectividad. Esta revisión se propone consolidar el conocimiento acerca de la afectividad africana por medio de describir estudios de la afectividad infantil llevados a cabo en África desde los resultados que obtuvo Ainsworth en Uganda. Se buscó en los bancos de información electrónica los términos "África" ("afectividad" o "unión") e "infante." Se incluyeron nueve estudios que evaluaron el estilo de afectividad del infante con métodos de auto-reporte o de observación, pero se cubrió sólo cinco países. El Procedimiento de la Situación Extraña fue usado más frecuentemente. La mayoría de los estudios describieron díadas que vivían en áreas periurbanas o municipalidades. Se identificaron múltiples factores socio-económicos que afectan las condiciones de vida, incluyendo falta de empleo, dificultades financieras, limitada educación, pobres condiciones de vivienda, la soltería del progenitor, falta de apoyo de la pareja, abuso de sustancias y depresión. En general, las distribuciones de las proporciones de clasificación de la afectividad parecen consistentes con los patrones globales de afectividad. A pesar de las condiciones adversas, la afectividad segura estaba relativamente extendida, y algunos grupos de poblaciones tenían bajos puntajes con respecto a evitar la afectividad. Relativamente altos puntajes de afectividad desorganizada se encontraron cuando la categoría fue incluida. África se mantiene como un continente poco estudiado en lo que respecta a la afectividad del infante. La diversidad cultural del continente pudiera contener importantes verdades necesarias para comprender la compleja relación entre el infante y la figura de afectividad.

La culture joue un rôle important dans les variations observées dans la manifestation, l'expression et la signification des comportements d'attachement. L'Afrique est l'hôte et la mère de nombreuses cultures, avec des organisations distinctes de relation de soin sous-tendant le développement de l'attachement. Cette revue a pour but de consolider les connaissances sur l'attachement africain en décrivant des études de l'attachement du nourrisson faites en Afrique depuis les conclusions ougandiennes de Ainsworth. Les bases de données électroniques ont été sondées avec les termes "Afrique", ("attachement" ou "lien") et "nourrisson". Neuf études ayant évalué un style d'attachement du nourrisson au moyen d'une auto-évaluation et de méthodes d'observation ont été inclues mais elles ne portaient que sur seulement cinq pays africains. La Procédure de Situation Etrange était la plus souvent utilisée. La plupart des études ont décrit des dyades vivant dans des zones périurbaines ou dans des villes. Divers facteurs socio-économiques affectant les conditions de vie ont été identifiés, comme par exemple le chômage, les difficultés financières, l'éducation limitée, la pauvreté des logements, le manque de soutien du conjoint, la toxicomanie et la dépression. Les distributions générales des proportions de classification de l'attachement semblent s'aligner avec les patterns globaux de classification de l'attachement. En dépit de conditions adverses, l'attachement sécure était relativement répandu et certaines populations avaient des taux faibles quant à l'attachement d'évitement. Des taux relativement élevés d'attachement désorganisé ont été trouvés quand la catégorie était incluse. La diversité culturelle du continent africain pourrait tenir en elle des vérités importantes nécessaires à la compréhension de la relation complexe entre le nourrisson et la figure d'attachement.

The impact of a psychiatry clinical rotation on the attitude of South African final year medical students towards mental illness.

BACKGROUND: Stigmatising attitudes of health care professionals towards mental illness can impede treatment provided for psychiatric patients. Many studies have reported undergraduate training to be a critical period for changing the attitudes of medical students, and one particularly valuable intervention strategy involves time spent in a clinical psychiatric rotation. In South Africa, medical students are exposed to a clinical rotation in psychiatry but there is no evidence to show whether this has an effect on attitudes toward mental illness. METHODS: This prospective cohort study involved a convenience sample of 112 South African medical students in their 5th or 6th year of undergraduate training. This sample attended a 7-week psychiatry rotation. The Attitudes to Mental Illness Questionnaire (AMIQ) was used to assess students' attitudes toward mental illness before and after the clinical rotation which includes exposure to a number of psychiatric sub-divisions and limited didactic inputs. RESULTS: There was a significant improvement (p < 0.01, t-test) in the students' attitude toward mental illness following the psychiatric rotation. Females displayed a more positive attitude towards mental illness at the end of the rotation compared to males. The participants' attitude significantly deteriorated for the non-psychiatric vignette describing diabetes (< 0.01, t-test). CONCLUSIONS: Our findings suggest that clinical training and exposure to a psychiatric setting impacts positively on medical students' attitude towards mental illness, even when this training does not include any focused, didactic anti-stigma input.

The development of the visual screening tool for anxiety disorders and depression: Addressing barriers to screening for depression and anxiety disorders in hypertension and/or diabetes.

BACKGROUND:  There is a lack of screening tools for common mental disorders that can be applied across cultures, languages and levels of education in people with diabetes and hypertension. Aim: To develop a visual screening tool for depression and anxiety disorders that is applicable across cultures and levels of education. Setting: Participants were purposively recruited from two not-for-profit organisations and two public health facilities - a maternal mental health unit and a primary health care centre. Method: This was a qualitative cross-sectional study. Thirteen drawings based on the Hospital Anxiety and Depression Scale depicting symptoms of anxiety disorders and depression were drawn. Participants described emotions and thoughts depicted in the drawings. Data were analysed through content analysis. Results: Thirty-one women (66%) and 16 men (34%) participated in the development of the visual screening tool. The mean age was 34 (standard deviation [SD] 12.46). There were 32 (68%) black participants, 11 (23%) mixed race participants and 4 (9%) white participants. Two participants (4%) had no schooling, 14 (31%) primary schooling, 8 (18%) senior schooling, 13 (29%) matric qualification and 8 (18%) had post-matric qualification. Participants correctly described 10 out of the 13 visual depiction of symptoms as associated with depression and anxiety disorders, with no differences between levels of education and cultural groups. Conclusion: Ten drawings were appropriate for inclusion in the visual screening tool for anxiety disorders and depression (VISTAD). The VISTAD will be validated against the mini international neuropsychiatric interview (MINI) in a primary care population with hypertension and/or diabetes.

An Attempt to Stem the Tide: Exploring the Effect of a 90-Day Transitional Care Intervention on Readmissions to an Acute Male Psychiatric Unit in South Africa.

INTRODUCTION: Pressure on inpatient beds often results in premature discharges, which may precipitate early readmission. This has prompted an increased interest in transitional care interventions to bridge the gap between in- and outpatient care to reduce such readmissions. Our study aimed to assess the effect of a Transitional Care Service (TCS) on readmission rates in a high pressure inpatient service which utilizes a premature discharge policy to address bed pressures. METHODS: Sixty male patients identified for crisis discharge were offered a TCS for the first ninety days after discharge. Patients received a structured intervention consisting of four phone calls and one home visit, focusing on maintaining adherence, appointment reminders and psychoeducation. The TCS patients were retrospectively compared to a matched control group in terms of readmission after 90days. Data was collected on adherence to medication, attendance of appointments and incidence of substance use. RESULTS: There was no significant difference in readmission rates. Prevalence of substance use was very high (90%), especially methamphetamine use (48%). Adherence dropped from 45% (n=27) at one week post-discharge to 25% (n=15) at 90days. CONCLUSION: Structured telephone-based transitional interventions have no effect on readmission rates in this setting. Prematurely discharged patients require more comprehensive support with focus on comorbid substance use.

The identification of novel genetic variants associated with antipsychotic treatment response outcomes in first-episode schizophrenia patients.

BACKGROUND: Although antipsychotics are integral to the treatment of schizophrenia, drug efficacy varies between patients. Although it has been shown that antipsychotic treatment response outcomes are heritable, our understanding of the genetic factors that are involved remains incomplete. Therefore, this study aims to use an unbiased scan of the genome to identify the genetic variants contributing toward antipsychotic treatment response outcomes. MATERIALS AND METHODS: This study utilized whole-exome sequencing of patients on extreme ends of the treatment response spectrum (n=11) in combination with results from previous antipsychotic studies to design a panel of variants that were genotyped in two well-characterized first-episode schizophrenia cohorts (n=103 and 87). Association analyses were carried out to determine whether these variants were significantly associated with antipsychotic treatment response outcomes. RESULTS: Association analyses in the discovery cohort identified two nonsynonymous variants that were significantly associated with antipsychotic treatment response outcomes (P<2.7 × 10(-5)), which were also significantly associated with the corresponding treatment response outcome in an independent replication cohort. Computational approaches showed that both of these nonsynonymous variants--rs13025959 in MYO7B (E1647D) and rs10380 in MTRR (H622Y)--were predicted to impair the functioning of their corresponding protein products. CONCLUSION: The use of whole-exome sequencing in a subset of patients from a well-characterized cohort of first-episode schizophrenia patients, for whom longitudinal depot treatment response data were available, allowed for (i) the removal of confounding factors related to treatment progression and compliance and (ii) the identification of two genetic variants that have not been associated previously with antipsychotic treatment response outcomes and whose results were applicable across different classes of antipsychotics. Although the genes that are affected by these variants are involved in pathways that have been related previously to antipsychotic treatment outcomes, the identification of these novel genes will play an important role in improving our understanding of the specific variants involved in antipsychotic treatment response outcomes.

Facial affect recognition and exit examination performance in medical students: a prospective exploratory study.

BACKGROUND: Facial affect recognition (FAR) abilities underpin emotional intelligence (EI). The latter is suggested to predict academic success and to be important for clinician-patient interaction. It is therefore of interest to investigate the possible association between FAR and academic performance in undergraduate medical students. METHODS: We assessed the association between the ability to recognize emotions through facial expression and exit examination performance, a measure of clinical proficiency, in undergraduate medical students stratified by gender at a South African tertiary institution using a prospective descriptive design. Data on the perception of facial expressions and exit examination marks were obtained from 144 (61%) females and 93 (39%) males with a mean age of 24.1 ± 1.6 years. Facial affect recognition measures on the Hexagon and Animation tasks were individually correlated with academic performance indicators using Pearson correlation. RESULTS: The perceptual discrimination of anger was associated with improved performance in anaesthetics (r = .24; p = .004) and urology (r = .24; p = .001), while the recognition of happiness was associated with decreased performance in obstetrics (r = -.21, p = .002). Gender was an effect modifier in the relationship between perceptual discrimination of anger and urology performance (p = .03), with a strong positive relationship for males, but a non-significant relationship for females. CONCLUSION: There was no overall correlation between FAR and overall academic performance or with gender. However, subject (specialty) specific findings with recognition of specific emotions and with gender as effect modifier poses interesting questions about EI and FAR and prompts further research into FAR as a useful tool. Being an objective test and offering a more focused assessment makes FAR worthy of further application.

Patterns of variation influencing antipsychotic treatment outcomes in South African first-episode schizophrenia patients.

AIM: Many antipsychotic pharmacogenetics studies have been performed examining candidate genes or known variation; however, our understanding of the genetic factors involved in antipsychotic pharmacogenetic traits remains limited. MATERIALS & METHODS: A well-characterized cohort of first-episode schizophrenia (FES) patients was used to identify a subset of nonresponders and responders to antipsychotic treatment for exome sequencing (n = 11). The variation observed in the responders and nonresponders was subsequently compared and a prioritization strategy was employed to identify variants for genotyping in the entire FES cohort (n = 103) as well as an additional Xhosa schizophrenia cohort (n = 222). RESULTS: Examination of coding variation revealed a potential role for rare loss-of-function variants in treatment response outcomes. One variant, rs11368509, was found to be weakly associated with better treatment outcomes in the FES cohort (p = 0.057) and the Xhosa schizophrenia cohort (p = 0.016). In addition, the majority of the loss-of-function variation that was considered likely to be involved in antipsychotic treatment response was either novel or rare in Asian and European populations. CONCLUSION: This pilot study has highlighted the importance of exome sequencing for antipsychotic pharmacogenomics studies, particularly in African individuals. Furthermore, the results emphasize once again the complexity of antipsychotic pharmacogenomics and the need for future research.

Next-generation sequencing of pharmacogenes: a critical analysis focusing on schizophrenia treatment.

INTRODUCTION: Because of the unmet needs of current pharmacotherapy for schizophrenia, antipsychotic pharmacogenetic research is of utmost importance. However, to date, few clinically applicable antipsychotic pharmacogenomic alleles have been identified. Nonetheless, next-generation sequencing technologies are expected to aid in the identification of clinically significant variants for this complex phenotype. The aim of this study was therefore to critically examine the ability of next-generation sequencing technologies to reliably detect variation present in pharmacogenes. MATERIALS AND METHODS: Candidate antipsychotic pharmacogenes and very important pharmacogenes were identified from the literature and the Pharmacogenomics Knowledgebase. Thereafter, the percentage sequence similarity observed between these genes and their corresponding pseudogenes and paralogues, as well as the percentage low-complexity sequence and GC content of each gene, was calculated. These sequence attributes were subsequently compared with the 'inaccessible' regions of these genes as described by the 1000 Genomes Project. RESULTS: It was found that the percentage 'inaccessible genome' correlated well with GC content (P=9.96×10), low-complexity sequence (P=0.0002) and the presence of pseudogenes/paralogues (P=8.02×10). In addition, it was found that many of the pharmacogenes were not ideally suited to next-generation sequencing because of these genomic complexities. These included the CYP and HLA genes, both of which are of importance to many fields of pharmacogenetics. CONCLUSION: Current short read sequencing technologies are unable to comprehensively capture the variation in all pharmacogenes. Therefore, until high-throughput sequencing technologies advance further, it may be necessary to combine next-generation sequencing with other genotyping strategies.

Association of MB-COMT polymorphisms with schizophrenia-susceptibility and symptom severity in an African cohort.

The catechol-O-methyltransferase (COMT) gene is an attractive schizophrenia candidate gene, encoding a catabolic dopamine enzyme. The enzyme exists as two distinct isoforms, with the membrane bound enzyme (i.e. MB-COMT) being predominantly expressed in the brain. Since African populations remain underrepresented in genetic/genomic research, we performed an association study to determine whether MB-COMT genetic variants are associated with schizophrenia-susceptibility and symptom severity in the South African Xhosa population. Fourteen candidate polymorphisms were selected by means of a literature search and in silico analyses and were subsequently genotyped in a cohort of 238 Xhosa schizophrenia patients and 240 healthy Xhosa controls. Genetic association was tested with schizophrenia-susceptibility as well as symptom severity within the patient group. Polymorphisms of interest were also analysed using functional assays. Two SNPs, rs2020917 (OR=0.54, 95% CI 0.37-0.79; P=0.0011) and rs737865 (OR=0.52, 95% CI 0.36-0.74; P=0.0002), in the P2 promoter region were significantly associated with schizophrenia as well as an increase (increase=11.2%, 95% CI 3.7%-19.2%; P=0.0031) in reporter gene expression. The minor alleles of these SNPs were underrepresented in the schizophrenia cohort, indicating a possible protective effect. The P2 region also formed part of a haplotype found to be associated with the severity of the negative symptoms of the disorder. The data generated by this study indicate that genetic variation of MB-COMT could be associated with schizophrenia and negative symptom severity in the Xhosa population and may therefore be one of the genomic loci contributing towards the disorder in the South African community. Future large-scale studies in other African schizophrenia populations are required to further elucidate the significance of these findings.

Symptom recurrence following intermittent treatment in first-episode schizophrenia successfully treated for 2 years: a 3-year open-label clinical study.

OBJECTIVE: An unanswered question in the management of schizophrenia is how long antipsychotic treatment should be continued after a single psychotic episode. In this study, we assessed the rates of symptom recurrence with intermittent treatment in patients with a first episode of DSM-IV-defined schizophrenia or related illness after 2 years of successful continuous treatment. We also investigated antecedents of recurrence, as well as demographic and baseline clinical predictors of early recurrence, and we compared the psychopathology of the recurrence episode with that of the first episode. METHOD: Outpatients in an academic psychiatric hospital setting (single site) who had responded well in an open-label study with risperidone long-acting injection were recruited for this intermittent treatment trial, and those who participated had their treatment tapered and discontinued over a period of up to 6 weeks, with follow-up for 3 years or until reemergence of symptoms. Open-label treatment with oral risperidone and risperidone long-acting injection was immediately reinstituted in the event of recurrence of symptoms. The study was conducted between February 2004 and March 2010. The primary outcome measure was symptom recurrence rate at 3 years. RESULTS: Participants (N = 33) had a mean age ± SD of 28 ± 7.9 years and a mean baseline Positive and Negative Syndrome Scale total score ± SD of 44.8 ± 7.4 at study entry. Symptom recurrence rates were 79% at 12 months, 94% at 24 months, and 97% at 36 months. Onset of recurrence symptoms was fairly abrupt, and symptom severity returned to levels close to those of the first episode. No significant predictors of early recurrence were identified. CONCLUSIONS: Intermittent antipsychotic treatment, even after 2 years of successful treatment, may not be in the best interest of patients who have experienced a single psychotic episode. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00378092.

Chromosome 22q11 in a Xhosa schizophrenia population.

Chromosome 22q11 aberrations substantially increase the risk for developing schizophrenia. Although micro-deletions in this region have been extensively investigated in different populations across the world, little is known of their prevalence in African subjects with schizophrenia. We screened 110 African Xhosa-speaking participants with schizophrenia for the presence of micro-deletions. As further verification for the presence or absence of 22q11 microdeletions, we screened 238 Xhosa schizophrenia patients and 240 healthy Xhosa individuals from a larger schizophrenia candidate 22q11 gene study using molecular analyses. Data from molecular and cytogenetic analyses confirmed the absence of 22q11 microdeletions in the Xhosa schizophrenia samples. Although the absence of chromosome 22q11 micro-deletions in this group of patients does not exclude the possibility that it may occur in Xhosa schizophrenia patients, we concluded an extremely low prevalence. Our findings suggest that unique susceptibility loci may be present in this group.