Genomic sister-disorders of neurodevelopment: an evolutionary approach

Genomic sister-disorders are defined here as diseases mediated by duplications versus deletions of the same region. Such disorders can provide unique information concerning the genomic underpinnings of human neurodevelopment because effects of diametric variation in gene copy number on cognitive and behavioral phenotypes can be inferred. We describe evidence from the literature on deletions versus duplications for the regions underlying the best-known human neurogenetic sister-disorders, including Williams syndrome, Velocardiofacial syndrome, and Smith–Magenis syndrome, as well as the X-chromosomal conditions Klinefelter and Turner syndromes. These data suggest that diametric copy-number alterations can, like diametric alterations to imprinted genes, generate contrasting phenotypes associated with autistic-spectrum and psychotic-spectrum conditions. Genomically based perturbations to the development of the human social brain are thus apparently mediated to a notable degree by effects of variation in gene copy number. We also conducted the first analyses of positive selection for genes in the regions affected by these disorders. We found evidence consistent with adaptive evolution of protein-coding genes, or selective sweeps, for three of the four sets of sister-syndromes analyzed. These studies of selection facilitate identification of candidate genes for the phenotypes observed and lend a novel evolutionary dimension to the analysis of human cognitive architecture and neurogenetic disorders

Cognitive behaviour therapy for schizophrenia: relationship between anxiety symptoms and therapy

Aims To explore the relationship between symptoms of anxiety and cognitive behaviour therapy (CBT) in patients with schizophreniaDesign Separate subanalyses of two randomized controlled trials comparing CBT for schizophrenia against befriending in the London Newcastle (LN) study, and against treatment as usual in the insight into schizophrenia (IS) study.Main outcome measures: Assessment of anxiety symptoms using the Brief Scale for Anxiety (BSA) derived from the Comprehensive Psychopathological Rating Scale (CPRS), at baseline, end of therapy and follow-up.Results In both studies, anxiety symptoms positively correlated with overall psychopathology, hallucinations and depression. In the LN study, patients with persecutory delusions and with distress due to akathisia and incapacity due to abnormal movements scored significantly higher on the BSA. In the IS study, anxiety scores were also positively correlated with; delusions, negative symptoms, relationship problems and problems with activities of daily living, living conditions, occupation and activities. Both subanalyses showed CBT had beneficial effects on anxiety symptoms compared with the control groups. Overall prognosis was found to be better in those with low anxiety in the LN study.Conclusions CBT improves anxiety symptoms in psychosis. We did not find an association between anxiety symptoms at baseline and outcome of cognitive therapy in this group of patients with schizophrenia