Poster #S107 DIMENSIONS OF DELUSIONS AND SELF-SERVING BIAS ALONG THE CONTINUUM OF PSYCHOSIS

Abstract

Background: Adolescence is a period of acting out and emotional instability. This may be due to an imbalance between the subcortical areas and the prefrontal cortex. Subcortical areas are thought to be more fully developed already early in adolescence, while cortical areas reach their mature state only at the very end of this period. Adolescence is also the time of onset of psychiatric disorders such as Schizophrenia (SZ) and Bipolar Disorder (BD). These disorders are characterized by impairments in networks involving subcortical and frontal brain regions. We hypothesize that these impairments are already present during adolescent development, prior to the overt manifestation of the disorder. Here, we investigate the development of limbic subcortical regions and the frontal cortex during emotion processing in offspring of SZ and BD patients compared to control subjects. These offspring have a ten-fold increased risk to develop a psychotic disorder themselves, and about 70% will develop non-specific psychopathology. Methods: Fourteen offspring of schizophrenia patients (mean age 12.9, 11 females), twenty nine offspring of bipolar patients (mean age 14.1, 12 females) and 31 control offspring (mean age 13.7, 17 females) viewed and rated neutral, negative, and positive pictures (IAPS), while being scanned with functional MRI (2D-EPI, TR = 1.6s, TE = 23ms). All pictures were presented for 2 seconds, with another 2 second period for subjects to respond. Only those trials in which there was a match between the subjects’ response and the IAPS rating were included. Activation during the presentation of negative pictures was contrasted against activity during the neutral pictures. Changes in activity levels with age were investigated using regression analyses in four a priori regions (amygdala, hippocampus, ventrolateral prefrontal cortex (vlPFC), and the orbitofrontal cortex (OFC)). In addition, psychophysiological interaction (PPI) analyses were performed to reveal changes in functional coupling with age between the areas involved in the emotion network. Results: There were no differences in task performance (reaction time, accuracy) between the groups. Compared to the control group, activation in the amygdala and hippocampus was decreased in the SZ offspring, but not in the BD offspring when processing emotional salient stimuli. In contrast, activation in the vlPFC activity increased with age. Moreover, and in line with previous research (Vink et al., submitted), activation in these limbic subcortical regions decreased with age in the controls but not in the offspring groups. These changes in activation were paralleled by an increase in functional connectivity between the amygdala and vlPFC in controls. No such increase was observed in the offspring groups. Discussion: In sum, we found, using a simple emotion task, that SZ offspring already show impaired brain development during adolescence compared to controls. These findings of reduced limbic subcortical and frontal functioning are consistent with findings in adult patients (Aleman & Kahn, 2005). Remarkably, these deficits occur before the manifestation of the illness. Surprisingly, we did not observed differences between BD offspring and controls. These data provide evidence in support of the notion that psychiatric illnesses have their origin in early adolescence. We plan to follow these groups longitudinally to We plan to follow these groups longitudinally, so that we can identify how the familial risk for SZ and BD impacts individual developmental trajectories.