This is a competitive renewal of a Research Scientist Award. Major research programs are planned in two areas. Primate separation studies will determine if treatment with the MAO-A inhibitor clorgyline will prevent immunological consequences otherwise seen in separated pigtail monkeys, and whether measures of innate "temperament", as determined by heart rate (HR) measures (after Kagan), measures of CNS amine metabolism, and measures of security of mother-infant (M-I) attachment, will predict which individuals will respond favorably. We will also determine if bonnet infants with more restricted social networks (1) experience greater changes in HR and body temperature (BT) circadian rhythms, sleep patterns, and immunological measures in response to separation, (2) whether such animals exhibit alterations in development of CNS norepinephrine (NE) systems in response to altered rearing conditions, and (3) whether such alterations predict individual differences in the response to separation. Finally, we will determine if bonnet infants who are provided with social support during separation exhibit a less pronounced physiological (HR, BT, sleep) and immunological response to separation, and whether such differences might be predicted by individual temperament as reflected by measures of HR variability, or by security of attachment in the mother-infant relationship.

Physiological data (HR, BT, sleep, circadian rhythms) will be obtained with multichannel implantable biotelemetry. Basal HR, HR reactivity, HR variability, and autonomic (parasympathetic/sympathetic) contributions to HR control will be assessed by means of low frequency analysis of the HR interval spectrum. Immunological assessments will include measures of natural cytotoxicity, generation of specific antibodies to KLH, and in vitro Con-A-stimulated IL-2 production. Development of CNS amine systems, and their response to altered rearing environments and separation stress will be measured with cisternal CSF samples analyzed for NE, dopamine, serotonin, MHPG, HVA, 5-HIAA, DOPAC, and DHBA, using HPLC with electrochemical detection.

In the second research area, multichannel MEG evoked field (EF) recordings will be used to estimate 3-D location, depth, orientation, and strength of temporal lobe auditory sources in normal and schizophrenic males and females, in children and relatives of schizophrenics, and in normal monozygotic (MZ) twins and MZ twins discordant for schizophrenia. High resolution magnetic resonance (MR) imaging will identify neuroanatomic structures associated with MEG sources, and identify associated temporal lobe anatomical abnormalities. Auditory sources will also be localized with multichannel EEG evoked potential (EP) based Brain Electrical Source Activity (BESA) analysis, for comparison of EF and EP accuracy. MEG EF recordings and surface and depth EP recordings will be used in primate models to compare EF and EP subcortical localization techniques and accuracy.

Professional development will include formal and informal training in MR imaging and MR spectroscopy theory and techniques.

K05MH046335

1981-07-01

1998-01-31