Early-life exposure to the SSRI paroxetine exacerbates depression-like behavior in anxiety/depression-prone rats.

Selective serotonin reuptake inhibitor (SSRI) antidepressants are the mainstay treatment for the 10-20% of pregnant and postpartum women who suffer major depression, but the effects of SSRIs on their children's developing brain and later emotional health are poorly understood. SSRI use during pregnancy can elicit antidepressant withdrawal in newborns and increase toddlers' anxiety and social avoidance. In rodents, perinatal SSRI exposure increases adult depression- and anxiety-like behavior, although certain individuals are more vulnerable to these effects than others. Our study establishes a rodent model of individual differences in susceptibility to perinatal SSRI exposure, utilizing selectively bred Low Responder (bLR) and High Responder (bHR) rats that were previously bred for high versus low behavioral response to novelty. Pregnant bHR/bLR females were chronically treated with the SSRI paroxetine (10 mg/kg/day p.o.) to examine its effects on offspring's emotional behavior and gene expression in the developing brain. Paroxetine treatment had minimal effect on bHR/bLR dams' pregnancy outcomes or maternal behavior. We found that bLR offspring, naturally prone to an inhibited/anxious temperament, were susceptible to behavioral abnormalities associated with perinatal SSRI exposure (which exacerbated their Forced Swim Test immobility), while high risk-taking bHR offspring were resistant. Microarray studies revealed robust perinatal SSRI-induced gene expression changes in the developing bLR hippocampus and amygdala (postnatal days 7-21), including transcripts involved in neurogenesis, synaptic vesicle components, and energy metabolism. These results highlight the bLR/bHR model as a useful tool to explore the neurobiology of individual differences in susceptibility to perinatal SSRI exposure.

Preliminary images from an adaptive imaging system.

I-ImaS (Intelligent Imaging Sensors) is a European project aiming to produce real-time adaptive X-ray imaging systems using Monolithic Active Pixel Sensors (MAPS) to create images with maximum diagnostic information within given dose constraints. Initial systems concentrate on mammography and cephalography. In our system, the exposure in each image region is optimised and the beam intensity is a function of tissue thickness and attenuation, and also of local physical and statistical parameters in the image. Using a linear array of detectors, the system will perform on-line analysis of the image during the scan, followed by optimisation of the X-ray intensity to obtain the maximum diagnostic information from the region of interest while minimising exposure of diagnostically less important regions. This paper presents preliminary images obtained with a small area CMOS detector developed for this application. Wedge systems were used to modulate the beam intensity during breast and dental imaging using suitable X-ray spectra. The sensitive imaging area of the sensor is 512 x 32 pixels 32 x 32 microm(2) in size. The sensors' X-ray sensitivity was increased by coupling to a structured CsI(Tl) scintillator. In order to develop the I-ImaS prototype, the on-line data analysis and data acquisition control are based on custom-developed electronics using multiple FPGAs. Images of both breast tissues and jaw samples were acquired and different exposure optimisation algorithms applied. Results are very promising since the average dose has been reduced to around 60% of the dose delivered by conventional imaging systems without decrease in the visibility of details.