Evaluation of the activity of CYP2C19 in Gujrati and Marwadi subjects living in Mumbai (Bombay)

BACKGROUND: Inherited differences in the metabolism and disposition of drugs, and genetic polymorphisms in the targets of drug therapy (e.g., receptors), can greatly influence efficacy and toxicity of medications. Marked interethnic differences in CYP2C19 (a member of the cytochrome P-450 enzyme superfamily catalyzing phase I drug metabolism) which affects the metabolism of a number of clinically important drugs have been documented. The present study evaluated the activity of CYP2C19 in normal, healthy Gujrati and Marwadi subjects by phenotyping (a western Indian population). METHODS: All subjects received 20 mg of omeprazole, which was followed by blood collection at 3 hrs to estimate the metabolic ratio of omeprazole to 5-hydroxyomeprazole. The analysis was done by HPLC. RESULTS: It was seen that 10.36% of this population were poor metabolizers(PM) whereas 89.63% were extensive metabolizers(EM). CONCLUSION: A genotyping evaluation would better help in identifying population specific genotypes and thus help individualize drug therapy

Memory development: implications for adults recalling childhood experiences in the courtroom

Adults frequently provide compelling, detailed accounts of early childhood experiences in the courtroom. Judges and jurors are asked to decide guilt or innocence based solely on these decades-old memories using 'common sense' notions about memory. However, these notions are not in agreement with findings from neuroscientific and behavioural studies of memory development. Without expert guidance, judges and jurors may have difficulty in properly adjudicating the weight of memory evidence in cases involving adult recollections of childhood experiences

Breakfast Staple Types Affect Brain Gray Matter Volume and Cognitive Function in Healthy Children

Childhood diet is important for brain development. Furthermore, the quality of breakfast is thought to affect the cognitive functioning of well-nourished children. To analyze the relationship among breakfast staple type, gray matter volume, and intelligence quotient (IQ) in 290 healthy children, we used magnetic resonance images and applied voxel-based morphometry. We divided subjects into rice, bread, and both groups according to their breakfast staple. We showed that the rice group had a significantly larger gray matter ratio (gray matter volume percentage divided by intracranial volume) and significantly larger regional gray matter volumes of several regions, including the left superior temporal gyrus. The bread group had significantly larger regional gray and white matter volumes of several regions, including the right frontoparietal region. The perceptual organization index (POI; IQ subcomponent) of the rice group was significantly higher than that of the bread group. All analyses were adjusted for age, gender, intracranial volume, socioeconomic status, average weekly frequency of having breakfast, and number of side dishes eaten for breakfast. Although several factors may have affected the results, one possible mechanism underlying the difference between the bread and the rice groups may be the difference in the glycemic index (GI) of these two substances; foods with a low GI are associated with less blood-glucose fluctuation than are those with a high GI. Our study suggests that breakfast staple type affects brain gray and white matter volumes and cognitive function in healthy children; therefore, a diet of optimal nutrition is important for brain maturation during childhood and adolescence

Increased Activity Imbalance in Fronto-Subcortical Circuits in Adolescents with Major Depression

BACKGROUND: A functional discrepancy exists in adolescents between frontal and subcortical regions due to differential regional maturational trajectories. It remains unknown how this functional discrepancy alters and whether the influence from the subcortical to the frontal system plays a primacy role in medication naïve adolescent with major depressive disorder (MDD). METHODOLOGY/PRINCIPAL FINDINGS: Eighteen MDD and 18 healthy adolescents were enrolled. Depression and anxiety severity was assessed by the Short Mood and Feeling Questionnaire (SMFQ) and Screen for Child Anxiety Related Emotional Disorders (SCARED) respectively. The functional discrepancy was measured by the amplitude of low-frequency fluctuations (ALFF) of resting-state functional MRI signal. Correlation analysis was carried out between ALFF values and SMFQ and SCARED scores. Resting brain activity levels measured by ALFF was higher in the frontal cortex than that in the subcortical system involving mainly (para) limbic-striatal regions in both HC and MDD adolescents. The difference of ALFF values between frontal and subcortical systems was increased in MDD adolescents as compared with the controls. CONCLUSIONS/SIGNIFICANCE: The present study identified an increased imbalance of resting-state brain activity between the frontal cognitive control system and the (para) limbic-striatal emotional processing system in MDD adolescents. The findings may provide insights into the neural correlates of adolescent MDD

Prefrontal cortex activation and young driver behaviour: a fNIRS study

Road traffic accidents consistently show a significant over-representation for young, novice and particularly male drivers. This research examines the prefrontal cortex activation of young drivers and the changes in activation associated with manipulations of mental workload and inhibitory control. It also considers the explanation that a lack of prefrontal cortex maturation is a contributing factor to the higher accident risk in this young driver population. The prefrontal cortex is associated with a number of factors including mental workload and inhibitory control, both of which are also related to road traffic accidents. This experiment used functional near infrared spectroscopy to measure prefrontal cortex activity during five simulated driving tasks: one following task and four overtaking tasks at varying traffic densities which aimed to dissociate workload and inhibitory control. Age, experience and gender were controlled for throughout the experiment. The results showed that younger drivers had reduced prefrontal cortex activity compared to older drivers. When both mental workload and inhibitory control increased prefrontal cortex activity also increased, however when inhibitory control alone increased there were no changes in activity. Along with an increase in activity during overtaking manoeuvres, these results suggest that prefrontal cortex activation is more indicative of workload in the current task. There were no differences in the number of overtakes completed by younger and older drivers but males overtook significantly more than females. We conclude that prefrontal cortex activity is associated with the mental workload required for overtaking. We additionally suggest that the reduced activation in younger drivers may be related to a lack of prefrontal maturation which could contribute to the increased crash risk seen in this population

Exploring Predictors of Outcome in the Psychosis Prodrome: Implications for Early Identification and Intervention

Functional disability is a key component of many psychiatric illnesses, particularly schizophrenia. Impairments in social and role functioning are linked to cognitive deficits, a core feature of psychosis. Retrospective analyses demonstrate that substantial functional decline precedes the onset of psychosis. Recent investigations reveal that individuals at clinical-high-risk (CHR) for psychosis show impairments in social relationships, work/school functioning and daily living skills. CHR youth also demonstrate a pattern of impairment across a range of cognitive domains, including social cognition, which is qualitatively similar to that of individuals with schizophrenia. While many studies have sought to elucidate predictors of clinical deterioration, specifically the development of schizophrenia, in such CHR samples, few have investigated factors relevant to psychosocial outcome. This review integrates recent findings regarding cognitive and social-cognitive predictors of outcome in CHR individuals, and proposes potential directions for future research that will contribute to targeted interventions and improved outcome for at-risk youth