Relationships between subjective or objective symptoms and mortality in schizophrenia: a prospective study on 310 schizophrenic patients with a median follow-up of 8.4 years.

The aim of the study was to explore the relationships between subjective or objective symptoms and mortality in schizophrenia. 310 subjects meeting the ICD-10 criteria for schizophrenia were included in the study between 1998 and 2000. At the initial assessment the following variables were respectively assessed to evaluate subjective and objective symptoms: the Frankfurt Complaints Questionnaire (FCQ) and the Positive and Negative Syndrome Scale (PANSS). In May 2008, information about the subjects were collected in order to know if they are alive or not and if they are deceased to know the date and the causes of their death. Survival analysis was conducted using the Kaplan-Meier product-limit estimator and standardized mortality ratio (SMR) was calculated. A multivariate Cox regression was done to detect predictive factors associated with mortality. Absolute mortality rates were 10.01%, 4.46% and 5.42% for overall mortality, unnatural causes and natural causes, respectively. SMR for overall mortality was 4.73. Cox regression analyses showed that elevated scores of FCQ was significant predictor of deaths from unnatural causes. High levels of subjective symptoms, as rated by the FCQ were independent predictor of mortality by unnatural causes in schizophrenic subjects. There were several limitations: The causes of death were not determined by autopsy and secondly, the duration of the study could be insufficient to detect significant associations between clinical variables and mortality.

Effect of CX516, an AMPA-modulating compound, on cognition and behavior in fragile X syndrome: a controlled trial.

A Phase II, 4-week randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the safety and efficacy of the Ampakine compound CX516 as a potential treatment for the underlying disorder in fragile X syndrome (FXS). After baseline screening, subjects with FXS (n = 49) underwent a 1-week placebo lead-in and then were randomized to study drug or placebo for a 4-week period. Cognitive and behavioral outcome measures were administered prior to treatment, at the end of treatment, and 2 weeks posttreatment. There were minimal side effects, no significant changes in safety parameters, and no serious adverse events. There was a 12.5% frequency of allergic rash in the CX516 group and 1 subject developed a substantial rash. There was also no significant improvement in memory, the primary outcome measure, or in secondary measures of language, attention/executive function, behavior, and overall functioning in CX516-treated subjects compared to placebo. This study did demonstrate that many outcome measures were reproducible in this test-retest setting for the FXS population, yet some were too difficult or variable. Adult subjects with FXS were able to complete an intensive clinical trial, and some valid outcome measures were identified for future FXS trial design. Problems with potency of CX516 in other studies have suggested dosing may have been inadequate for therapeutic effect and thus it remains unclear whether modulation of AMPA-mediated neurotransmission is a viable therapeutic strategy for the treatment of FXS.