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magnetic resonance imaging (FMRI) studies from our laboratory andothers revealed a distributed neural circuitry underlying spatial and IMMUNE CONCOMITANT
non-spatial working memory processes. Accordingly, while posteriorcortical regions differentiated based on stimulus characteristics, dorso- S.E. Keller, S.J. Schleifer, J.A. Bartlett, lateral prefrontal regions were activated across processing domains,consistent with the mapping of the central executive component onto that region. Subsequent fMRI studies employing other tasks, such as theoddball paradigm associated with P300 ERP generation and Stroop tasks, UMDNJ-New Jersey Medical School, Newark, New Jersey provided further evidence of a distinct role of prefrontal regions inexecutive processes underlying the selection of task-appropriate re- Bereavement is a common stressor, with spousal/significant other be- sponses. Our recent fMRI studies also revealed that modulation of reavement one of the major life stressors experienced. Early research on NMDA receptor function in healthy subjects mimics executive function immune modulation by psychosocial processes therefore utilized be- deficits observed in schizophrenia, and preferentially disrupts prefrontal reavement as a stressor when searching for immune alterations. In the executive functions despite targeting widespread cortical regions. Fi- early 1980s several reports documented immune findings following nally, behavioral cognitive studies of working memory functions in spousal or significant other bereavement. Since the most common schizophrenic patients suggested that performance deficits were linked to psychological sequela of bereavement is depression, the depression/ the “executive load” of the task, rather than the memory load or the delay immunity relationship has been pursued since the early studies of of information retention. Thus, working memory impairments in schizo- bereavement and immunity. A number of manuscripts have reported phrenia are associated with deficient executive control processes second- various immune findings associated with adult depression and have been ary to widespread prefrontal cortex dysfunction that is also associated presented in meta-analytic reports. These findings include decreases in T4 cells and mitogen stimulation with increasing age, and a generaldecrease in NKCA. Since the immune system develops with age andsince depression may represent differing entities within differing agegroups, the relation between depression and immunity was exploredacross differing developmental cohorts. First the immune depressionrelationship was examined as separate case/control experiments examin- 204. CLINICAL IMPLICATIONS OF THE
ing children, early adolescents, late adolescents, early adulthood, middle INVERTED U-SHAPED CURVE RELATING
age and elderly. Finally, all of these “separate” studies were combined to D1 STIMULATION AND BEHAVIOR
appreciate the developing relationship along the age dimension. Theimmune depression relation in children and adults have been previouslyreported. We examined a total of 284 adolescents, 32 with MDD and 252 P.S. Goldman-Rakic, S. Castner, G. Williams without current MDD. The percent of T4 cells and T cells were increased,while the percent of NK and B cells were decreased. When age and Yale University School of Medicine, VA Medical Center 116A/2, gender were partialled none of these effects remained significant.
Analysis of Partial Variance revealed lower mitogen response and NKCAin the depressed adolescents. Contextualizing these findings along with Two primate models of experimentally induced dopamine dysfunction those of other age groups and the “seamless” age analyses will be will be described: a chronic neuroleptic (Haldol) model that down- presented. An age immune relational continuum is postulated.
regulates D1 receptors in the prefrontal cortex and an amphetaminesensitization model that presumably enhances D1 stimulation. Bothconditions produce profound but selective impairment in working mem- Recent Advances in Cellular and Structural Basis of
ory tasks. However, a D1 agonist reverses the impairment in the case of Working Memory
D1 down-regulation and D1 antagonist reverses the impairment in the AMPH model. These results reveal the powerful role of the state of theD1 receptor in regulating the cognitive functions of the prefrontal cortex.
Moreover, the effects of limited D1 receptor stimulation/blockade appear to induce long-lasting changes in the circuitry subserving working memory, when D1 acting drugs are withdrawn.



Department of Psychiatry, University of North Carolina at Chapel Hill WORKING MEMORY
Working memory is a complex psychological construct, necessary for theperformance of higher cognitive functions such as language and reason- ing. Numerous studies have demonstrated significant working memorydeficits in schizophrenic patients, across modalities and domains, and Department of Psychiatry, Yale University School of Medicine, VA have generated a need for understanding the psychological, neural and Medical Center 116A/2, West Haven, CT 06516, USA pharmacological bases of these deficits. Cognitive models of workingmemory have described multiple components, including a visuospatial Understanding the mechanistic basis of working memory, the capacity to sketchpad, a phonological loop, and a central executive supervisory hold a representation “on line,” is important for delineating the processes system managing and prioritizing access to the former two systems.
involved in higher cognitive functions and the pathophysiology of Consistent with a multi-component cognitive model, early functional thought disorders. We examined the contribution of glutamate and


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Stroke and the statistics of the aspirin/clopidogrel secondaryprevention trialsGeorge Howard, Leslie A. McClure, John W. Krakauer and Christopher S. CoffeyFour randomized trials have investigated the combination ofClopidogrel versus Aspirin in Patients at Risk of Ischemic Eventsclopidogrel plus aspirin for secondary prevention ofClopidogrel for High Atherothrombotic Risk and Ischemicvascular

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