Characterizing psychosis risk traits in Africa: A longitudinal study of Kenyan adolescents

AbstractThe schizophrenia prodrome has not been extensively studied in Africa. Identification of prodromal behavioral symptoms holds promise for early intervention and prevention of disorder onset. Our goal was to investigate schizophrenia risk traits in Kenyan adolescents and identify predictors of psychosis progression.135 high-risk (HR) and 142 low-risk (LR) adolescents were identified from among secondary school students in Machakos, Kenya, using the structured interview of psychosis-risk syndromes (SIPS) and the Washington early recognition center affectivity and psychosis (WERCAP) screen. Clinical characteristics were compared across groups, and participants followed longitudinally over 0-, 4-, 7-, 14- and 20-months. Potential predictors of psychosis conversion and severity change were studied using multiple regression analyses.More psychiatric comorbidities and increased psychosocial stress were observed in HR compared to LR participants. HR participants also had worse attention and better abstraction. The psychosis conversion rate was 3.8%, with only disorganized communication severity at baseline predicting conversion (p=0.007). Decreasing psychotic symptom severity over the study period was observed in both HR and LR participants. ADHD, bipolar disorder, and major depression diagnoses, as well as poor occupational functioning and avolition were factors relating to lesser improvement in psychosis severity.Our results indicate that psychopathology and disability occur at relatively high rates in Kenyan HR adolescents. Few psychosis conversions may reflect an inadequate time to conversion, warranting longer follow-up studies to clarify risk predictors. Identifying disorganized communication and other risk factors could be useful for developing preventive strategies for HR youth in Kenya

Mutations in SLC20A2 are a major cause of familial idiopathic basal ganglia calcification

Familial idiopathic basal ganglia calcification (IBGC) or Fahr's disease is a rare neurodegenerative disorder characterized by calcium deposits in the basal ganglia and other brain regions, which is associated with neuropsychiatric and motor symptoms. Familial IBGC is genetically heterogeneous and typically transmitted in an autosomal dominant fashion. We performed a mutational analysis of SLC20A2, the first gene found to cause IBGC, to assess its genetic contribution to familial IBGC. We recruited 218 subjects from 29 IBGC-affected families of varied ancestry and collected medical history, neurological exam, and head CT scans to characterize each patient's disease status. We screened our patient cohort for mutations in SLC20A2. Twelve novel (nonsense, deletions, missense, and splice site) potentially pathogenic variants, one synonymous variant, and one previously reported mutation were identified in 13 families. Variants predicted to be deleterious cosegregated with disease in five families. Three families showed nonsegregation with clinical disease of such variants, but retrospective review of clinical and neuroimaging data strongly suggested previous misclassification. Overall, mutations in SLC20A2 account for as many as 41 % of our familial IBGC cases. Our screen in a large series expands the catalog of SLC20A2 mutations identified to date and demonstrates that mutations in SLC20A2 are a major cause of familial IBGC. Non-perfect segregation patterns of predicted deleterious variants highlight the challenges of phenotypic assessment in this condition with highly variable clinical presentation

Mutations in SLC20A2 are a major cause of familial idiopathic basal ganglia calcification

Familial idiopathic basal ganglia calcification (IBGC) or Fahr's disease is a rare neurodegenerative disorder characterized by calcium deposits in the basal ganglia and other brain regions, which is associated with neuropsychiatric and motor symptoms. Familial IBGC is genetically heterogeneous and typically transmitted in an autosomal dominant fashion. We performed a mutational analysis of SLC20A2, the first gene found to cause IBGC, to assess its genetic contribution to familial IBGC. We recruited 218 subjects from 29 IBGC-affected families of varied ancestry and collected medical history, neurological exam, and head CT scans to characterize each patient's disease status. We screened our patient cohort for mutations in SLC20A2. Twelve novel (nonsense, deletions, missense, and splice site) potentially pathogenic variants, one synonymous variant, and one previously reported mutation were identified in 13 families. Variants predicted to be deleterious cosegregated with disease in five families. Three families showed nonsegregation with clinical disease of such variants, but retrospective review of clinical and neuroimaging data strongly suggested previous misclassification. Overall, mutations in SLC20A2 account for as many as 41 % of our familial IBGC cases. Our screen in a large series expands the catalog of SLC20A2 mutations identified to date and demonstrates that mutations in SLC20A2 are a major cause of familial IBGC. Non-perfect segregation patterns of predicted deleterious variants highlight the challenges of phenotypic assessment in this condition with highly variable clinical presentation