Integrating genomic variants and developmental milestones to predict cognitive and adaptive outcomes in autistic children.

Although the first signs of autism are often observed as early as 18-36 months of age, there is a broad uncertainty regarding future development, and clinicians lack predictive tools to identify those who will later be diagnosed with co-occurring intellectual disability (ID). Here, we developed predictive models of ID in autistic children (n=5,633 from three cohorts), integrating different classes of genetic variants alongside developmental milestones. The integrated model yielded an AUC ROC=0.65, with this predictive performance cross-validated and generalised across cohorts. Positive predictive values reached up to 55%, accurately identifying 10% of ID cases. The ability to stratify the probabilities of ID using genetic variants was up to twofold greater in individuals with delayed milestones compared to those with typical development. These findings underscore the potential of models in neurodevelopmental medicine that integrate genomics and clinical observations to predict outcomes and target interventions.

Perspective on clinical high-risk for psychosis in Africa.

Clinical High Risk for Psychosis has evolved in recent years as a conceptual and clinical entity, representing a shift in focus from the syndromal psychosis state to a recognition of the pre-psychotic state as a period of potential preventive intervention. Much existing evidence has been generated from well-resourced countries, with a more limited body of literature available from Africa and other Majority World countries. Against a backdrop of prevailing systemic challenges, it is necessary to appraise the state of knowledge on Clinical High Risk for Psychosis in Africa. In this perspective article, we cover epidemiology, risk factors, predictors of psychosis conversion, as well as an overview of sociocultural factors, notably stigma, and the barriers to mental health services in African settings. We discuss existing and promising assessment approaches and reflect on preventive and early intervention strategies. We conclude with recommendations including the need for more clinical, longitudinal, and collaborative research anchored in an integrative transdisciplinary approach. We highlight the need for more culturally valid assessment tools and strategies to improve access to and utilization of services while also reducing stigma.

Genetic architecture of schizophrenia: a review of major advancements.

Schizophrenia is a severe psychiatric disorder with high heritability. Consortia efforts and technological advancements have led to a substantial increase in knowledge of the genetic architecture of schizophrenia over the past decade. In this article, we provide an overview of the current understanding of the genetics of schizophrenia, outline remaining challenges, and summarise future directions of research. World-wide collaborations have resulted in genome-wide association studies (GWAS) in over 56 000 schizophrenia cases and 78 000 controls, which identified 176 distinct genetic loci. The latest GWAS from the Psychiatric Genetics Consortium, available as a pre-print, indicates that 270 distinct common genetic loci have now been associated with schizophrenia. Polygenic risk scores can currently explain around 7.7% of the variance in schizophrenia case-control status. Rare variant studies have implicated eight rare copy-number variants, and an increased burden of loss-of-function variants in SETD1A, as increasing the risk of schizophrenia. The latest exome sequencing study, available as a pre-print, implicates a burden of rare coding variants in a further nine genes. Gene-set analyses have demonstrated significant enrichment of both common and rare genetic variants associated with schizophrenia in synaptic pathways. To address current challenges, future genetic studies of schizophrenia need increased sample sizes from more diverse populations. Continued expansion of international collaboration will likely identify new genetic regions, improve fine-mapping to identify causal variants, and increase our understanding of the biology and mechanisms of schizophrenia.

A 12 year chart review of childhood and adolescent onset psychosis at a Nigerian tertiary mental health facility.

OBJECTIVES: To review the profile of children and adolescents presenting with psychosis at a specialist mental health facility, and to compare childhood with adolescent onset psychosis. METHOD: Hospital records of all children and adolescents over a 12-year period (1999-2010) were perused to identify those falling under the categories of psychotic disorders. Clinical, socio-demographic, obstetric, and developmental information was extracted. RESULTS: Mean age of the children ((n = 409)) was 15.9 years, with 8.1% aged 12 years or less. The most frequent diagnoses were schizophrenia (40.8%), brief psychotic disorder (25.9%), mood disorder with psychosis (15.2%), and organic psychosis (7.8%). Family history of mental illness was reported among 22.5%. Subjects with childhood onset were significantly less likely than those with adolescent onset to have a family history of mental illness (p = 0.016), more likely to report maternal illness during pregnancy (p = 0.005) and illness during infancy (p = 0.010), and more likely to have a diagnosis of psychotic disorder due to another general medical condition (p < 0.001). CONCLUSION: The study suggests that antenatal/obstetric factors and illness during infancy may be particularly relevant in psychosis of childhood onset. Family history of mental illness may however be of greater relevance in adolescent onset psychosis.

Maternal depression and child psychopathology among Attendees at a Child Neuropsychiatric Clinic in Abeokuta, Nigeria: a cross sectional study.

BACKGROUND: Children with recognized, diagnosable mental and neurological disorders are in addition prone to emotional and behavioral problems which transcend their specific diagnostic labels. In accessing care, these children are almost invariably accompanied by caregivers (usually mothers) who may also have mental health problems, notably depression. The relationship between child and maternal psychopathology has however not been sufficiently researched especially in low and middle income countries. METHODS: Mothers (n = 100) of children receiving care at the Child and Adolescent Clinic of a Neuropsychiatric Hospital in Abeokuta, Nigeria took part in the study. To each consenting mother was administered a sociodemographic questionnaire and the Patient Health Questionnaire, while information regarding their children (n = 100) was obtained using the Strengths and Difficulties Questionnaire. Data analysis was done with the Statistical Package for Social Sciences (SPSS) version 16. RESULTS: The mean ages of the mothers and children were 40.4 years (SD 4.7) and 11.6 years (SD 4.1), respectively. Among the children, 63 % had a main diagnosis of seizure disorder. Regardless of main diagnosis, 40 % of all the children had a comorbid diagnosis. Among the mothers, 23 % had major depressive disorder. A quarter (25 %) of the children had abnormal total SDQ scores. A diagnosis of major depressive disorder in mothers was associated with poor total SDQ scores and poor scores in all SDQ domains except the emotional domain for the children. Major depressive disorder among the mothers was associated with not being married (p = 0.004; OR = 0.142, 95 % CI 0.037-0.546) and longer duration of the child's illness (p = 0.039, OR = 1.165, 95 % CI 1.007-1.346). CONCLUSION: The study showed notable rates of depressive illness among mothers of children with neuropsychiatric disorders. Marked rates of emotional and behavioral disorders were also found among the children. Associations were found between maternal and child psychopathology. Mothers of children with neuropsychiatric disorders should be screened for depressive illness.

Morbidity profile of first-degree relatives of probands with schizophrenia: a comparison with mood disorder and healthy control.

PURPOSE: There is a paucity of data on heritability of psychotic disorders in Africa. The study aimed to investigate morbid risk of schizophrenia and mood disorder among first-degree relatives of schizophrenia probands, compared with mood disorder and healthy controls. METHODS: The study examined 330 first-degree relatives of probands with schizophrenia (n = 50), 350 first-degree relatives of probands with mood disorder (n = 50) and 387 first-degree relatives of healthy control (n = 50). The Schedules for Clinical Assessment in Neuropsychiatry, SCAN was used to ascertain diagnosis in ill subjects. To each subject, a socio-demographic questionnaire was administered. Family history was obtained using the Family History Schedule. Morbid risk estimates were calculated using the Weinberg shorter method. RESULTS: There was a significant difference between the mean age of relatives of schizophrenia probands compared to mood disorder (p = 0.01, 95 % CI 1.34-9.61) and healthy control (p < 0.01, 95 % CI 1.53-9.84). There were also significant differences between the number of children of schizophrenia probands and the number of children of normal control (p < 0.01, 95 % CI -2.0 to -3.9), as well as the number of deceased first-degree relatives of schizophrenia probands compared to normal control (p = 0.04, 95 % CI 0.01-0.94). Finally, there was a significant difference between the number of first-degree relatives of schizophrenia probands compared to the number of first-degree relatives of healthy control who were below the age of risk for schizophrenia (p = 0.01, 95 % CI -0.12 to -1.27). Morbid risks of 4.38 and 0.39 were obtained for schizophrenia among first-degree relatives of probands with schizophrenia and mood disorder, while first-degree relatives of probands with schizophrenia, mood disorder and healthy control had morbid risks for mood disorder of 0.42, 3.82 and 0.35, respectively. CONCLUSION: The study revealed excess mortality among first-degree relatives of schizophrenia patients. First-degree relatives of probands with schizophrenia and mood disorder also had higher morbid risks for these psychotic conditions than healthy control with some measure of overlap between the two diagnostic categories.

Prodromal psychotic symptoms and psychological distress among secondary school students in Abeokuta, Nigeria.

OBJECTIVE: This study aimed to investigate the relationship between prodromal psychotic symptoms and psychological distress among Nigerian adolescents. METHOD: Students (n=508) were randomly selected from secondary schools in Abeokuta, Nigeria. A socio-demographic questionnaire, the Prodromal Questionnaire-Brief Version (PQ-B) and the Strengths and Difficulties Questionnaire (SDQ) were administered to each student. RESULTS: The mean age of the students was 15.4 years (SD 1.3), with most (63%) being female. More than half (55.3%) reported having had a lifetime experience of major life event (20.9% in the preceding 6 months) while 13.9% had experienced bullying or abuse (5.1% in the preceding 6 months). The prevalence of prodromal symptoms was 20.9% (95% CI 0.174-0.244). Abnormal scores in emotional and conduct problems were seen in 11.8% and 6% respectively, while 7.3% had abnormal scores in each of the hyperactivity and peer problems subscales of the SDQ. Abnormality in prosocial behaviour was found in 1.8% of students, with overall abnormality in 4.9%. Regression analysis showed that prodromal symptoms were predicted by female sex, lifetime and 6 month history of major life event, and lifetime and 6 month history of bullying or abuse. Prodromal symptoms were also predicted by higher total SDQ scores and higher scores in all domains of psychological distress except the prosocial domain. CONCLUSION: The study showed a relationship between reported prodromal symptoms and the occurrence of psychological distress. It also showed that early childhood trauma may be a predisposing factor to the early stages of development of psychosis, with female children being especially prone in the years of adolescence.

Summaries of oral sessions at the XXI World Congress of Psychiatric Genetics, Boston, Massachusetts, 17-21 October 2013: state of the field.

The XXI World Congress of Psychiatric Genetics (WCPG), sponsored by the International Society of Psychiatric Genetics (ISPG), took place in Boston, Massachusetts, on 17-21 October 2013. Approximately 900 participants gathered to discuss the latest findings in this rapidly advancing field. The following report was written by student travel awardees. Each was assigned one or more sessions as a rapporteur. This manuscript represents topics covered in most, but not all of the oral presentations during the conference, and contains some of the major notable new findings reported.

Cognitive functioning among patients with schizophrenia in a Nigerian hospital: a comparison with mood disorder.

OBJECTIVE: The study aimed to investigate correlates of cognition among patients with schizophrenia. METHODS: Over a three month period, in-patients diagnosed with schizophrenia (n = 50) and mood disorders (n = 50) were recruited into the study. Both groups of patients were assessed using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN), the Annett Hand Preference Questionnaire (AHPQ) and the Global Assessment of Function Scale (GAF). Patients with schizophrenia were further assessed using the Positive and Negative Syndromes Scale, PANSS and the Clinical Global impression (CGI). The cognitive screen section of SCAN (comprising Verbal Trails Test and Mini Mental State examination, MMSE) and the cognitive factor of PANSS were used to assess cognitive function. RESULTS: No differences were found in the cognitive profile of patients with schizophrenia and mood disorder. Among patients with schizophrenia, poor verbal performance was associated with the negative or mixed syndrome (p = 0.004), left or mixed handedness (p = 0.013), greater illness severity (p = 0.030) and lower GAF scores (p = 0.039). Poor performance on MMSE correlated with higher total PANSS score (p = 0.022) and was also associated with the negative or mixed syndrome (p = 0.003) and lack of clinical improvement (p = 0.035). CONCLUSION: Patients with the negative or mixed schizophrenia syndrome may suffer more cognitive deficit. Poor verbal performance among patients with schizophrenia may be associated with left or mixed handedness, more severe illness and poor functioning.

Comparison of catatonia presentation in patients with schizophrenia and mood disorders in lagos, Nigeria.

OBJECTIVE: To compare the clinical profile and pattern of catatonic symptoms of patients with schizophrenia and mood disorder. METHOD: Records of 13,968 patients seen between 1983-1985 and 2003-2005 were reviewed for symptoms of catatonia by resident doctors in psychiatry. Cases in which the diagnosis were schizophrenia or mood disorder were then noted. Socio-demographic and clinical features were described for each diagnosis. RESULTS: There were a total of 98 cases with catatonia out of the 13,968 case notes reviewed. Schizophrenia accounted for 82.5% and 53.4% in the two periods, while the proportion associated with mood disorders increased from 10% to 20.7%. Male to female ratio was 1.2:1 in schizophrenia and 1:3 in mood disorder. Those with schizophrenia were younger and with an earlier age of onset of symptoms than those with mood disorders. CONCLUSION: Catatonia associated with mood disorder was found to be increasing over the years when compared with schizophrenia. Differences were observed in socio-demographic characteristics and number of predominant catatonic symptoms. Having a separate category for catatonia due to the mood disorders in the current diagnostic guidelines (10(th) edition of the International Classification of Diseases and the 4(th) edition of the Diagnostic and Statistical Manual) will help in better diagnosis of catatonia.

Prevalence and correlates of poor medication adherence amongst psychiatric outpatients in southwestern Nigeria.

OBJECTIVE: The aim of this study was to assess the rate of adherence to medications amongst psychiatric outpatients in Nigeria and examine factors associated with medication nonadherence amongst this group. METHOD: Psychiatric outpatients (n=342) from three centres were assessed for medication adherence using the Morisky Medication Adherence Questionnaire. Details regarding sociodemographic variables (age, sex, education, religion, marital status, employment, income, medication cost), illness related variables (diagnosis, duration, number of episodes/admissions, insight, severity of symptoms, mental state, functional status), medication related variables (type, mode of administration, side effect, attitude to medication) and perception related variables (self-stigma, perceived causation and prognosis) were also obtained. RESULTS: There were 76 participants (22.2%) with good medication adherence, 102 (29.8%) with moderate adherence and 164 (48.0%) with poor adherence. The significant independent correlates of poor medication adherence included being employed [odds ratio (OR) 3.42, 95% confidence interval (95% CI) 2.17-5.39], poor social support (OR 5.86, 95% CI 2.87-12.17), high self-stigma (OR 4.70, 95% CI 2.24-9.96) and perceived spiritual causation of mental illness (OR 3.74, 95% CI 1.87-7.74). CONCLUSIONS: The majority of psychiatric outpatients in southwestern Nigeria had poor medication adherence. Our findings stressed the importance of patients' perception and social environment in determining treatment adherence and the necessity of educating the patient. Clinicians' attention to psychological barriers early in treatment may improve medication adherence and ultimately affect the course of illness.