Mismatch Negativity in Socially Withdrawn Children Yair Bar-Haim, Peter J. Marshall, Nathan A. Fox, Efrat A. Schorr, and Sandra Gordon-Salant Background: Individual differences in auditory process- ing have been associated with social withdrawal, intro- version, and other forms of dysfunction in social engage- ment. The goal of this study was to investigate the characteristics of an electrophysiologic response that is seen to index early cortical auditory processing (mismatch negativity, MMN) among socially withdrawn and more sociable control children. Methods: Auditory event-related potentials to standard and deviant tone stimuli were computed for 23 socially withdrawn children and 22 control subjects. We calcu- lated MMN difference waveforms for frontal, central, and parietal electrode sites. Results: Socially withdrawn children had smaller MMN amplitude and longer MMN latencies compared with more sociable control children. Conclusions: The findings point to the involvement of individual differences in early cortical auditory process- ing in childhood social withdrawal. Reduced MMN am- plitude and delayed latency may index a component of social withdrawal seen in socially withdrawn children and in depressed and schizophrenic patients. The existence of a secondary MMN generator in the frontal cortex may provide a link between the hypothesized frontal lobe involvement in childhood social withdrawal, schizophre- nia, and depression and the MMN reductions seen in these conditions. Biol Psychiatry 2003;54:17–24 © 2003 So- ciety of Biological Psychiatry Key Words: Mismatch negativity, social withdrawal, temperament, evoked response potential, children, audi- tory Introduction S ocial withdrawal and other forms of dysfunction in social engagement are defining features in a variety of psychiatric disorders, including mood and anxiety disor- ders and schizophrenia. For this reason, researchers of human development have extensively examined factors that may contribute to the consistent display of social withdrawal during childhood, as well as the consequences of childhood social withdrawal for the later development of psychopathology (for a review, see Rubin and Stewart 1996). Childhood social withdrawal can be broadly defined as the consistent disposition to display solitary behavior when encountering peers in social contexts. There may be different circumstances underlying individual differences in children’s tendencies to exhibit social withdrawal, one of the most extensively studied being the possibility of a biological disposition. Most theorizing on the biological basis of stable individual differences in social withdrawal in early childhood centers on Kagan’s (1994) concept of behavioral inhibition to the unfamiliar. Behavioral inhibi- tion is typically viewed as a temperamental construct reflecting relatively stable individual differences in behav- ioral style (e.g., Goldsmith et al 1987). Behaviorally inhibited children are characteristically watchful and quiet in new situations, including social interactions with unfa- miliar people (Kagan et al 1984). It is now widely accepted that the prefrontal cortex (PFC) and the amygdala are two key structures in the central circuitry of emotion and emotion regulation (for reviews, see Davidson 2002; Davidson et al 2000). Indi- vidual differences in the functioning of both the PFC and amygdala are thought to play a key role in individual differences in the propensity for behavioral inhibition and social withdrawal. Kagan and coworkers have proposed that the contrast in reactions to novelty of inhibited and uninhibited children arises from variation in the excitabil- ity of neural circuits of the limbic system (e.g., Kagan and Snidman 1991). This model focuses on the central nucleus of the amygdala, which is the primary source of projec- tions from the amygdala to subcortical sites that modulate behavioral and physiologic responses to a threatening stimulus (e.g., Davis 1992; LeDoux et al 1990). Increased activity of the central nucleus of the amygdala would be expected to result in specific patterns of activity of response systems that are influenced by the central nu- cleus. Indeed, evidence suggesting that inhibited children differ from uninhibited children in their autonomic and neuroendocrine profiles has been used to support the From the Department of Psychology (YB-H), Tel-Aviv University, Ramat Aviv, Tel-Aviv, Israel; Departments of Human Development (PJM, NAF, EAS) and Hearing and Speech Sciences (SG-S), University of Maryland, College Park, Maryland. Address reprint requests to Yair Bar-Haim, Department of Psychology, Tel-Aviv University, Ramat Aviv, Tel-Aviv 69978, Israel. Received October 16, 2002; revised January 19, 2003; accepted January 24, 2003. © 2003 Society of Biological Psychiatry 0006-3223/03/$30.00 doi:10.1016/S0006-3223(03)00175-6