The use of everolimus in the treatment of neurocognitive problems in tuberous sclerosis (TRON): study protocol for a randomised controlled trial.

BACKGROUND: Tuberous sclerosis complex (TSC) is a genetic disorder affecting about 1 in 6000 people and is characterised by the development of tumours in many organs, including the skin and kidneys, and by a range of neurological and neuropsychiatric manifestations. TSC-associated neuropsychiatric disorders (TAND) occur in the majority of those with TSC, and they have a significant impact on patients and their families, given the everyday impact of TAND on education, employment, family and social life. The potential benefits of better treatment for TAND therefore include reduction in health care demands and wider benefits for patients and their carers. METHODS/DESIGN: We have planned a single-centre, two-arm, individually randomised, phase II, double-blind, placebo-controlled trial of everolimus versus placebo in the treatment of neurocognitive problems in patients with tuberous sclerosis. Everolimus is a licensed medicine in this patient group, but for a different target of effect. The present trial is a proof-of-principle study developed to provide effect size estimates which may be used to inform the design of subsequent trials. Forty-eight patients aged 16-60 years with tuberous sclerosis who have an IQ >60 and a significant deficit (at least -2 SD) in one or more primary outcome measures will be randomly allocated in a ratio of 2:1 to receive everolimus or placebo, respectively. Participants will be assessed for eligibility and then be started on study medication 4 weeks later. They will then be randomised and receive placebo or everolimus for 24 weeks. Neurocognitive and safety assessments will be carried out at baseline and weeks 4, 12, 24 and 36. DISCUSSION: This study is designed to determine the effect sizes of treatment with everolimus or placebo for 6 months on specific neurocognitive functions-recall memory (verbal and non-verbal) and executive function-in people affected by TSC who have significant deficits in these functions. These data will provide new evidence to determine whether larger-scale trials are indicated and to explore suitable outcome measures and analytical methods for neurocognitive trial design. TRIAL REGISTRATION: ISRCTN09739757 . Registered on 28 Dec 2011.

Auditory hallucinations in adolescent and adult students: implications for continuums and adult pathology following child abuse.

An auditory hallucination questionnaire was completed by 250 adolescents and 250 adults in the UK to provide data concerning their hallucinatory experiences, which enabled a consideration of nonclinical population auditory hallucination experiences. The data gathered from the adolescent group were almost identical to that of the adult group, suggesting a continuum between child and adulthood. The data also indicated that the UK adult sample was very similar to an established US sample of adults. The current data was combined with previously published data to construct a proposed developmental model that may link child abuse to pathological hallucinations and possible later mental illness issues. New normative data concerning hallucinatory experiences provide important norms, which need to be considered for adolescents or young adults who may be considered for early intervention in psychosis programs. These new norms provide information that should be considered in a variety of therapeutic settings.