A 6 Week Randomized Double-Blind Placebo-Controlled Trial of Ziprasidone for the Acute Depressive Mixed State

OBJECTIVE: To examine the efficacy of ziprasidone vs. placebo for the depressive mixed state in patients with bipolar disorder type II or major depressive disorder (MDD). METHODS: 73 patients were randomized in a double-blinded, placebo-controlled study to ziprasidone (40-160 mg/d) or placebo for 6 weeks. They met DSM-IV criteria for a major depressive episode (MDE), while also meeting 2 or 3 (but not more nor less) DSM-IV manic criteria. They did not meet DSM-IV criteria for a mixed or manic episode. Baseline psychotropic drugs were continued unchanged. The primary endpoint measured was Montgomery-Åsberg Depression Rating Scale (MADRS) scores over time. The mean dose of ziprasidone was 129.7±45.3 mg/day and 126.1±47.1 mg/day for placebo. RESULTS: The primary outcome analysis indicated efficacy of ziprasidone versus placebo (p = 0.0038). Efficacy was more pronounced in type II bipolar disorder than in MDD (p = 0.036). Overall ziprasidone was well tolerated, without notable worsening of weight or extrapyramidal symptoms. CONCLUSIONS: There was a statistically significant benefit with ziprasidone versus placebo in this first RCT of any medication for the provisional diagnostic concept of the depressive mixed state. TRIAL REGISTRATION: Clinicaltrials.gov NCT00490542

Radiative Transfer Simulations Using Mesoscale Cloud Model Outputs: Comparisons with Passive Microwave and Infrared Satellite Observations for Midlatitudes

Real midlatitude meteorological cases are simulated over western Europe with the cloud mesoscale model Méso-NH, and the outputs are used to calculate brightness temperatures at microwave frequencies with the Atmospheric Transmission at Microwave (ATM) radiative transfer model. Satellite-observed brightness temperatures (TBs) from the Advanced Microwave Scanning Unit B (AMSU-B) and the Special Sensor Microwave Imager (SSM/I) are compared to the simulated ones. In this paper, one specific situation is examined in detail. The infrared responses have also been calculated and compared to the Meteosat coincident observations. Overall agreement is obtained between the simulated and the observed brightness temperatures in the microwave and in the infrared. The large-scale dynamical structure of the cloud system is well captured by Méso-NH. However, in regions with large quantities of frozen hydrometeors, the comparison shows that the simulated microwave TBs are higher than the measured ones in the window channels at high frequencies, indicating that the calculation does not predict enough scattering. The factors responsible for the scattering (frozen particle distribution, calculation of particle dielectric properties, and nonsphericity of the particles) are analyzed. To assess the quality of the cloud and precipitation simulations by Méso-NH, the microphysical fields predicted by the German Lokal-Modell are also considered. Results show that in these midlatitude situations, the treatment of the snow category has a high impact on the simulated brightness temperatures. The snow scattering parameters are tuned to match the discrete dipole approximation calculations and to obtain a good agreement between simulations and observations even in the areas with significant frozen particles. Analysis of the other meteorological simulations confirms these results. Comparing simulations and observations in the microwave provides a powerful evaluation of resolved clouds in mesoscale models, especially the precipitating ice phase.[Completion of this field awaiting access to full-text paper]Peer reviewe

Irregular sleep habits, regional grey matter volumes, and psychological functioning in adolescents

Changing sleep rhythms in adolescents often lead to sleep deficits and a delay in sleep timing between weekdays and weekends. The adolescent brain, and in particular the rapidly developing structures involved in emotional control, are vulnerable to external and internal factors. In our previous study in adolescents at age 14, we observed a strong relationship between weekend sleep schedules and regional medial prefrontal cortex grey matter volumes. Here, we aimed to assess whether this relationship remained in this group of adolescents of the general population at the age of 16 (n = 101; mean age 16.8 years; 55% girls). We further examined grey matter volumes in the hippocampi and the amygdalae, calculated with voxel-based morphometry. In addition, we investigated the relationships between sleep habits, assessed with self-reports, and regional grey matter volumes, and psychological functioning, assessed with the Strengths and Difficulties Questionnaire and tests on working memory and impulsivity. Later weekend wake-up times were associated with smaller grey matter volumes in the medial prefrontal cortex and the amygdalae, and greater weekend delays in wake-up time were associated with smaller grey matter volumes in the right hippocampus and amygdala. The medial prefrontal cortex region mediated the correlation between weekend wake up time and externalising symptoms. Paying attention to regular sleep habits during adolescence could act as a protective factor against the emergence of psychopathology via enabling favourable brain development.publishedVersionPeer reviewe

The IMAGEN study: a decade of imaging genetics in adolescents

Imaging genetics offers the possibility of detecting associations between genotype and brain structure as well as function, with effect sizes potentially exceeding correlations between genotype and behavior. However, study results are often limited due to small sample sizes and methodological differences, thus reducing the reliability of findings. The IMAGEN cohort with 2000 young adolescents assessed from the age of 14 onwards tries to eliminate some of these limitations by offering a longitudinal approach and sufficient sample size for analyzing gene-environment interactions on brain structure and function. Here, we give a systematic review of IMAGEN publications since the start of the consortium. We then focus on the specific phenotype 'drug use' to illustrate the potential of the IMAGEN approach. We describe findings with respect to frontocortical, limbic and striatal brain volume, functional activation elicited by reward anticipation, behavioral inhibition, and affective faces, and their respective associations with drug intake. In addition to describing its strengths, we also discuss limitations of the IMAGEN study. Because of the longitudinal design and related attrition, analyses are underpowered for (epi-) genome-wide approaches due to the limited sample size. Estimating the generalizability of results requires replications in independent samples. However, such densely phenotyped longitudinal studies are still rare and alternative internal cross-validation methods (e.g., leave-one out, split-half) are also warranted. In conclusion, the IMAGEN cohort is a unique, very well characterized longitudinal sample, which helped to elucidate neurobiological mechanisms involved in complex behavior and offers the possibility to further disentangle genotype × phenotype interactions