M. Reite

Neurobiological theories of schizophrenia and related psychoses have increasingly emphasized impaired neuronal coordination (i.e., dysfunctional connectivity) as central to the pathophysiology. Although neuroimaging evidence has mostly corroborated these accounts, the basic mechanism(s) of reduced functional connectivity remains elusive. In this study, we examine the developmental trajectory and underlying mechanism(s) of dysfunctional connectivity by using gamma oscillatory power as an index of local and long-range circuit integrity. An early-onset psychosis group and a matched cohort of typically developing adolescents listened to monaurally presented click-trains, as whole-head magnetoencephalography data were acquired. Consistent with previous work, gamma-band power was significantly higher in right auditory cortices across groups and conditions. However, patients exhibited significantly reduced overall gamma power relative to controls, and showed a reduced ear-of-stimulation effect indicating that ipsi- versus contralateral presentation had less impact on hemispheric power. Gamma-frequency oscillations are thought to be dependent on gamma-aminobutyric acidergic interneuronal networks, thus these patients' impairment in generating and/or maintaining such activity may indicate that local circuit integrity is at least partially compromised early in the disease process. In addition, patients also showed abnormality in long-range networks (i.e., ear-of-stimulation effects) potentially suggesting that multiple stages along auditory pathways contribute to connectivity aberrations found in patients with psychosis.

The immediate behavioral and immunological consequences of a single 2-week maternal separation experience were studied in socially housed 7-month old bonnet and pigtail macaques. Maternal separation was associated with species dependent behavioral changes. Both species showed significant increases in ingestive behaviors associated with separation. Separated and matched controls showed an increase in disturbance behaviors (vocalization, startles, shaking, temper-tantrums) that subsided after 24-36 hours in control subjects, but continued, albeit with species-dependent patterns, in the separated monkeys. Allomaternal care of the separated bonnet infants but not the pigtail infants was associated with a progressive reduction of these disturbance behaviors during the separation period. Following a period of agitation, pigtail infants showed a depressive phase characterized by slouched, withdrawn postures and reduced motor activity. As a group, the separated infants of both species were not different from controls with respect to lymphocyte activation by mitogens, a measure of immunocompetence. However, when individual behavioral responses were considered, the change in lymphocyte activation during separation was significantly related to behavioral responses which reflected disturbance, such that the change in lymphocyte activation following in vitro stimulation with the mitogens phytohemagglutinin and Concanavalin A (markers of the immunocompetence of T lymphocytes) was related to levels of vocalization and time spent in slouched postures. The activation of B lymphocytes by pokeweed mitogen was not influenced by the separation experience nor was it associated with specific behavioral responses to separation. The importance of assessing the affective consequences of stressor is discussed.