Rare copy number variants (CNVs) are associated with risk of neurodevelopmental disorders characterised by varying degrees of cognitive impairment, including schizophrenia, autism spectrum disorder and intellectual disability. However, the effects of many individual CNVs in carriers without neurodevelopmental disorders are not yet fully understood, and little is known about the effects of reciprocal copy number changes of known pathogenic loci.

We aimed to analyse the effect of CNV carrier status on cognitive performance and measures of occupational and social outcomes in unaffected individuals from the UK Biobank.

We called CNVs in the full UK Biobank sample and analysed data from 420 247 individuals who passed CNV quality control, reported White British or Irish ancestry and were not diagnosed with neurodevelopmental disorders. We analysed 33 pathogenic CNVs, including their reciprocal deletions/duplications, for association with seven cognitive tests and four general measures of functioning: academic qualifications, occupation, household income and Townsend Deprivation Index.

Most CNVs (24 out of 33) were associated with reduced performance on at least one cognitive test or measure of functioning. The changes on the cognitive tests were modest (average reduction of 0.13 s.d.) but varied markedly between CNVs. All 12 schizophrenia-associated CNVs were associated with significant impairments on measures of functioning.

CNVs implicated in neurodevelopmental disorders, including schizophrenia, are associated with cognitive deficits, even among unaffected individuals. These deficits may be subtle but CNV carriers have significant disadvantages in educational attainment and ability to earn income in adult life.

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Evidence-based treatment and age-specific services are required to address the needs of trauma-affected older populations. Narrative exposure therapy (NET) may present an appropriate treatment approach for this population since it provides prolonged exposure in a lifespan perspective. As yet, however, no trial on this intervention has been conducted with older adults from Western Europe.

Examining the efficacy of NET in a sample of older adults.

Out-patients with post-traumatic stress disorder (PTSD), aged 55 years and over, were randomly assigned to either 11 sessions of NET (n = 18) or 11 sessions of present-centred therapy (PCT) (n = 15) and assessed on the Clinician-Administered PTSD Scale (CAPS) pre-treatment, post-treatment and at follow-up. Total scores as well as symptom scores (re-experience, avoidance and hyperarousal) were evaluated.

Using a piecewise mixed-effects growth model, at post-treatment a medium between-treatment effect size for CAPS total score (Cohen's d = 0.44) was found, favouring PCT. At follow-up, however, the between-treatment differences were non-significant. Drop-out rates were low (NET 6.7%, PCT 14.3%) and no participant dropped out of the study because of increased distress.

Both NET and PCT appear to be safe and efficacious treatments with older adults: PCT is non-intrusive and NET allows for imaginal exposure in a lifespan perspective. By selectively providing these approaches in clinical practice, patient matching can be optimised.

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