LANGUAGE, ACCULTURATION, AND FUNCTIONAL CAPACITYASSESSMENT IN SCHIZOPHRENIA

Elizabeth W. Twamley, Brent T. Mausbach, Jesus Bucardo,Thomas L. PattersonUniversity of California, San Diego, CA, USA

The effects of language and acculturation on measurement offunctional capacity in schizophrenia are not yet fully understood. Weassessed functional capacity using the UCSD Performance-Based SkillsAssessment (UPSA), Social Skills Performance Assessment (SSPA), andMedication Management Ability Assessment (MMAA) in English-speaking (n=210) and monolingual Spanish-speaking (n=29)individuals with schizophrenia-spectrum disorders. The two groupsdid not differ on age, severity of positive, negative, and depressivesymptoms, of Global Assessment of Functioning scores. However, theSpanish-speaking sample had less education, later age of onset ofpsychosis, lower Dementia Rating Scale scores, and lower dosages ofantipsychotics; they were also more likely to be female, to haveschizoaffective disorder (vs. schizophrenia), and to be married. TheSpanish-speaking group performed better than did English speakerson theMMAA, butworse on the UPSA. The groups did not differ on theSSPA. In a multiple hierarchical regression controlling for groupdifferences, DRS score (p<.001) and language (p=.008) predictedUPSA performance (R=.74). Within the Spanish-speaking sample,higher levels of education and acculturationwere both associatedwithbetter UPSA performance (rs=.61, .78, ps<.001), but did not explainvariance in UPSA performance beyond that accounted for by DRSperformance. These results suggest that measurement of functionalskills can be strongly affected by language of test administration.Although acculturation is associated with functional capacity amongmonolingual Spanish-speakers with schizophrenia, it does not predictperformance once cognitive performance is considered.

doi:10.1016/j.schres.2010.02.154

Symposium 28RISK FACTORS IN THE DEVELOPMENT OF PSYCHOSIS:COMMON PATHOPHYSIOLOGICAL VARIABLES PROVIDE ANINSIGHT INTO THE ETIOLOGY AND TREATMENT OFSCHIZOPHRENIACo-Chairpersons: Anthony A. Grace, Patrick D. McGorryWednesday, 14 April, 2010 - 10:30 am - 12:30 pm

Overall Abstract: Risk factors in the development of psychosis:Common pathophysiological variables provide an insight into theetiology and treatment of schizophreniaThe etiology of schizophreniais believed to revolve around genetic and environmental risk factorsthat determine whether an individual will transition to psychosis.These risk factors can encompass a number of dimensions; however,recent studies suggest that these factors may have commonpathophysiological actions on the nervous system that negativelyimpact dopamine system regulation. Thiswill be explored in a series oftalks that bridge development and vulnerability in animalmodels andin human patients. Jim Van Os will begin by talking about gene-environment interactions as risk factors for schizophrenia using newneuroimaging and momentary assessment approaches of GxE insamples at psychometric risk, samples at genetic risk and patientsamples. The concept of stress as a risk factorwill be further developedby Pat McGorry, who will present data that demonstrate an impairedhormonal response to stress in first episode psychotic patients.Moreover, his group showed that patients experiencing their firstepisode of psychosis showenhanced cortisol suppression, indicative ofHPA axis dysfunction. These data are consistentwith stress and trauma

as risk factors for psychosis. Anthony Grace will present work derivedfrom a developmental disruption model of schizophrenia, showingthat loss of parvalbumin interneurons in the ventral subiculum of thehippocampus leads to an overdrive of tonic dopamine neuron firing.Moreover, he will show that stress will lead to a similar hyperdopa-minergic state and hyper-responsivity to amphetamine. In contrast,administration of a benzodiazepine anti-anxiety agent peripubertallywill prevent the induction of the hyperdopaminergic state indevelopmentally disrupted rats, showing a role for stress in the onsetof psychosis. Finally, Robin Murray will integrate the focus back intothe patient by exploring whether the epidemiology of schizophreniacan be explained by a pathophysiology in the dopamine system. Thiswill include data showing that, as in animals, many of the risk factorsassociated with schizophrenia also impact the dopamine system,including genes regulating the dopamine transporter, COMT, obstetricevents, abuse of amphetamines and cannabis, and social defeat. Thepanelwill then integrate the various risk factors into amodel system inwhich multiple risk factors all exert common pathophysiologicaldisruptions via a final common action on dopamine system respon-sivity. This will also have important implications for designing noveltreatments that rely on affecting dopamine system regulation up-stream from the dopamine synapse. Discussant: Elaine Walker willbring together topics of stress, risk factors, and susceptibility toschizophrenia, within the context of neurodevelopmental models ofbrain changes that occur in adolescence/early adulthood, the criticalperiod for the emergence of psychosis.

doi:10.1016/j.schres.2010.02.155

SEEING IS BELIEVING: A STRUCTURAL NEUROIMAGINGPARADIGM OF GENE-ENVIRONMENT INTERACTIONS INSCHIZOPHRENIA

Petra HabetsMaastricht University, Maastricht, The Netherlands

The study of gene-environment interactions is complicatedbecause of the difficulty measuring environmental exposures. Devel-opmental trauma and cannabis have been associated with schizo-phrenia risk, but reporting bias may play a role, causing spuriousassociations. We designed a new paradigm, using structural neuroi-maging measures, to investigate GxE in schizophrenia in whichreporting bias cannot impact on the findings. Neuroimagingmeasuresin schizophrenia represent expression of genetic risk or better, giventhat genetic risk moderates environmental sensitivity, gene-environ-ment interactions. Given the fact that biased measures of environ-mental exposures cannot impact on the brain, the use of neuroimagingphenotypes in studies of GxE may provide direct proof for environ-mental impact. We hypothesized that if GxE plays a role in the brainalterations in schizophrenia, a direct effect of developmental traumaand cannabis should be present in cases (as they carry schizophreniagenes causing differential sensitivity to environmental exposures) butnot in controls. We used the measure of cortical thickness, arguablymost sensitive for this purpose, to test these hypotheses in a sample ofaround 80 cases and 80 controls. For each person, 70 measures ofcortical thickness were available. Analysis of the data revealed thatboth developmental trauma and cannabis impacted on corticalthickness in the cases, but not in the controls, strongly suggestingunconfounded and unbiased contributions of environmental expo-sures to GxE underlying brain alterations in schizopohrenia.

doi:10.1016/j.schres.2010.02.156

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