OBJECTIVES/GOALS: Development of interventions that improve social functioning (SF) in first episode psychosis (FEP) is hindered by a poor understanding of the neural mechanisms underlying SF deficits. This research aims to identify neural correlates of social functioning in FEP, and to evaluate whether this substrate is malleable in response to cognitive training. METHODS/STUDY POPULATION: This is a secondary data-analysis of participants in an ongoing randomized clinical trial investigating whether 12 weeks of targeted cognitive training is neuroprotective in FEP, versus treatment as usual. Baseline and post-training assessments include a brain MRI, three measures of SF, and a neurocognitive battery. Healthy controls complete MRI only. Differences in cortical thickness (CTh) and gray matter volume (GMV) in regions of interest between FEP and controls will be determined with ANCOVA. Multiple linear regression will be used to determine the relationship between neural substrate and SF in FEP. Linear mixed models will be used to examine the relationship between change in CTh and GMV and change in SF. Data collection is ongoing for this study. RESULTS/ANTICIPATED RESULTS: In preliminary data including 12 FEP and 9 healthy controls, FEP demonstrated cortical loss in the right superior frontal cortex and the right isthmus-posterior cingulate. Greater cortical thickness in the posterior cingulate cortex was associated with better social functioning across multiple measures when controlling for global cognition. Gray matter volume in the parahippocampal gyrus was also associated with better social functioning. Preliminary results evaluating whether targeted cognitive training is neuroprotective in these regions of interest in a manner that is associated with improved social functioning will also be presented. DISCUSSION/SIGNIFICANCE OF IMPACT: Preliminary results link the posterior cingulate and parahippocampal gyrus to SF in FEP. Further research will investigate the contribution of changes in these brain regions to improved SF. The identification of biological treatment targets for SF may lead to development and optimization of novel interventions to alleviate SF deficits in FEP.

Borderline personality disorder (BPD) is a paradigmatic disorder of adult attachment, with high rates of antecedent childhood maltreatment. The neurocognitive correlates of both attachment disturbance and maltreatment are both presently unknown in BPD. This study evaluated whether dimensional adult attachment disturbance in BPD is related to specific neurocognitive deficits, and whether childhood maltreatment is related to these dysfunctions. An outpatient BPD group (n = 43) performed nearly 1 SD below a control group (n = 26) on short-term recall, executive, and intelligence functions. These deficits were not affected by emotionally charged stimuli. In the BPD group, impaired recall was related to attachment–anxiety, whereas executive dysfunction was related to attachment–avoidance. Abuse history was correlated significantly with executive dysfunction and at a trend level with impaired recall. Neurocognitive deficits and abuse history exhibited both independent and interactive effects on adult attachment disturbance. These results suggest that (a) BPD patients' reactivity in attachment relationships is related to temporal–limbic dysfunction, irrespective of the emotional content of stimuli, (b) BPD patients' avoidance within attachment relationships may be a relational strategy to compensate for the emotional consequences of frontal-executive dysregulation, and (c) childhood abuse may contribute to these neurocognitive deficits but may also exert effects on adult attachment disturbance that is both independent and interacting with neurocognitive dysfunction.

In this paper, we present a review of semantic priming experiments in schizophrenia. Semantic priming paradigms show utility in assessing the role of deficits in semantic memory network access in the pathology of schizophrenia. The studies are placed in the context of current models of information processing. In this review we include all English-language reports (from peer-reviewed journals) of single-word semantic priming studies involving participants with schizophrenia. The studies to date show schizophrenic patients to exhibit variable semantic priming effects under automatic processing conditions, and consistent impairments under controlled0attentional conditions. We also describe associations with other neurocognitive dysfunction, neurochemical and electrophysiological disturbances, and clinical manifestations (such as thought disorder).

To evaluate the clinical and ecological validity of affect recognition (AR) measures in a sample of community-dwelling schizophrenic outpatients (N = 40), we analyzed the relation of facial and vocal AR to intellectual, symptomatic, and quality-of-life criteria. Facial and vocal AR showed virtually identical patterns of association with these criteria, suggesting that both modalities of AR draw on the same underlying heteromodal capacity. Specifically, AR was correlated with a subset of intellectual abilities (verbal–semantic, executive–attentional), but was unrelated to age, education, or neuroleptic dose. In terms of clinical and ecological criteria, AR errors correlated with more severe psychotic symptoms (positive and disorganized) and with lower quality of life (relationships, community participation, and richness of intrapsychic experience). Even after controlling for subjects' intellectual abilities and illness severity, inaccurate AR was associated with bizarre behaviors (involving sociosexual interactions, clothing, appearance) and with impoverished interpersonal relations. Thus, while difficulty identifying basic affective cues is related to general cognitive and illness-severity factors, it appears to have specific functional implications that do not depend on generalized impairment. Assessment of AR may identify a subgroup of schizophrenic patients who have a central defect in the heteromodal monitoring of emotional-social displays, associated with dysregulation of social behaviors and disruption of interpersonal relations. (JINS, 2000, 6, 649–658.)