Prenatal nicotine exposure (PNE) has been associated with increased prevalence of attention deficit hyperactivity disorder (ADHD), major depressive disorder (MDD) and substance abuse in exposed children and adolescents. Whether these syndromes are caused by nicotine exposure, or genetic and psychosocial adversities associated with maternal smoking is not completely clear. Animal models suggest a direct impact of PNE. However, the fact that nicotine is forcefully administrated in these paradigms raises some questions about the specificity of these findings. Pregnant C57BI/6J mice were allowed to choose drinking saccharin/nicotine solutions or pure water. Controls could choose saccharin solutions or pure water. Offspring were tested in spontaneous locomotion, fear-associated learning (trace conditioning), addictive (conditioned place preference), and depression-like (learned helplessness) behaviors. There was no significant difference in weight or pup number between the prenatal treatment groups. A significant effect of PNE was observed on spontaneous locomotion, preference for a cocaine-associated place, and latency to escape in the learned helplessness paradigm. Surprisingly, PNE mice exhibited an increased learning of trace-conditioned fear-associated cues. The hyperlocomotive behavior reported in animal models of PNE is not likely an artifact of forceful nicotine administration. The increased prevalence of ADHD, MDD and substance abuse observed in PNE children and adolescents is probably caused by direct behavioral teratogenic effects of PNE. The role of PNE as a risk factor of syndromes associated to increased learning of fear-associated cues such as post-traumatic stress disorder (PTSD) warrants further evaluation.

Prenatal ethanol exposure is associated with an increased incidence of depressive disorders in patient populations. However, the mechanisms that link prenatal ethanol exposure and depression are unknown. Several recent studies have implicated reduced brain-derived neurotrophic factor (BDNF) levels in the hippocampal formation and frontal cortex as important contributors to the etiology of depression. In the present studies, we sought to determine whether prenatal ethanol exposure is associated with behaviors that model depression, as well as with reduced BDNF levels in the hippocampal formation and/or medial frontal cortex, in a mouse model of fetal alcohol spectrum disorder (FASD). Compared to control adult mice, prenatal ethanol-exposed adult mice displayed increased learned helplessness behavior and increased immobility in the Porsolt forced swim test. Prenatal ethanol exposure was associated with decreased BDNF protein levels in the medial frontal cortex, but not the hippocampal formation, while total BDNF mRNA and BDNF transcripts containing exon III, IV or VI were reduced in both the medial frontal cortex and the hippocampal formation of prenatal ethanol-exposed mice. These results identify reduced BDNF levels in the medial frontal cortex and hippocampal formation as potential mediators of depressive disorders associated with FASD.

Objective Abnormal 50 and 100ms event-related brain activity derived from paired-click procedures are a well established finding in schizophrenia. There is little agreement on whether ratio score (second click/first click) paired-click group differences reflect an encoding or gating abnormality. In addition, the functional implications of the ratio score deficit remain unclear. In the present study, EEG and MEG were used to examine paired-click measures as well as the cognitive correlates of paired-click activity. Method Electroencephalographic (EEG) Cz and whole-cortex magnetoencephalographic (MEG) data were acquired during the standard paired-click paradigm in 73 controls and 79 patients with schizophrenia. Paired-click ratio scores were obtained at 50ms (P50 at Cz, M50 at left and right superior temporal gyrus, STG) and 100ms (N100 at Cz, M100 at left and right STG). Subjects were administered a cognitive battery assessing attention, working memory, and long-delay memory. An IQ estimate was also obtained. Results Groups differed on ratio score and S1 amplitude measures. 50ms and 100ms ratio and S1 amplitude scores predicted variance in attention (primarily S1 amplitude), working memory, and long-delay memory. The attention findings remained after removing variance associated with general cognitive ability (i.e., IQ). Conclusions Associations between paired-click measures and cognitive performance in patients supports 50ms and 100ms ratio and amplitude scores as clinically significant biomarkers of schizophrenia. In general, cognitive performance was better predicted by the ability to encode auditory information rather than the ability to filter redundant information.