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Item 39. Viruses and Schizophrenia: Implications for Pathophysiology and Treatment(Oxford University Press, 2018-04) Breier, Alan; Psychiatry, School of MedicineOverall Abstract: The viral hypothesis of schizophrenia posits that viral infections disrupts cortical circuits that give rise to schizophrenia psychopathology. Prenatal viral exposure during key neurodevelopmental periods, either through direct effects on fetal brain or exposure to excessive maternal cytokines and other chemokines, have been implicated. In addition, abnormal activation of dormant neuro-viruses have been linked to the pathophysiology of schizophrenia. Activation of dormant viruses has potentially important treatment implication for therapies, such as valacyclovir, that suppress viral activity. Among the viruses that have been mostly frequently associated with schizophrenia include herpes simplex virus type 1 (HSV1) and Epstein-Barr virus (EBV). The purpose of this symposium is to focus on the role of viruses in the pathophysiology of schizophrenia and results of antiviral treatment trials in this illness.Item The Cognitive Change Index as a Measure of Self and Informant Perception of Cognitive Decline: Relation to Neuropsychological Tests(IOS Press, 2016-02-25) Rattanabannakit, Chatchawan; Risacher, Shannon L.; Gao, Sujuan; Lane, Kathleen A.; Brown, Steven A.; McDonald, Brenna C.; Unverzagt, Frederick W.; Apostolova, Liana G.; Saykin, Andrew J.; Farlow, Martin R.; Department of Neurology, IU School of MedicineBACKGROUND: The perception of cognitive decline by individuals and those who know them well ("informants") has been inconsistently associated with objective cognitive performance, but strongly associated with depressive symptoms. OBJECTIVE: We investigated associations of self-report, informant-report, and discrepancy between self- and informant-report of cognitive decline obtained from the Cognitive Change Index (CCI) with cognitive test performance and self-reported depressive symptoms. METHODS: 267 participants with normal cognition, mild cognitive impairment (MCI), or mild dementia were included from a cohort study and memory clinic. Association of test performance and self-rated depression (Geriatric Depression Scale, GDS) with CCI scores obtained from subjects (CCI-S), their informants (CCI-I), and discrepancy scores between subjects and informants (CCI-D; CCI-S minus CCI-I) were analyzed using correlation and analysis of covariance (ANCOVA) models. RESULTS: CCI-S and CCI-I scores showed high internal consistency (Cronbach alpha 0.96 and 0.98, respectively). Higher scores on CCI-S and CCI-I, and lower scores on the CCI-D, were associated with lower performance on various cognitive tests in both univariate and in ANCOVA models adjusted for age, gender, and education. Adjustment for GDS slightly weakened the relationships between CCI and test performance but most remained significant. CONCLUSION: Self- and informant-report of cognitive decline, as measured by the CCI, show moderately strong relationships with objective test performance independent of age, gender, education, and depressive symptoms. The CCI appears to be a valid cross-sectional measure of self and informant perception of cognitive decline across the continuum of functioning. Studies are needed to address the relationship of CCI scores to longitudinal outcome.Item Sex differences in cognitive performance and alcohol consumption in High Alcohol-Drinking (HAD-1) rats(Elsevier, 2020-03-02) Mittal, N.; Fleming, S.M.; Martinez, A.; Thakore, N.; Bell, Richard L.; Maddox, W.T.; Schallert, T.; Duvauchelle, C.L.; Psychiatry, School of MedicineExcessive alcohol (ethanol) consumption negatively impacts social, emotional, as well as cognitive function and well-being. Thus, identifying behavioral and/or biological predictors of excessive ethanol consumption is important for developing prevention and treatment strategies against alcohol use disorders (AUDs). Sex differences in alcohol consumption patterns are observed in humans, primates, and rodents. Selectively bred high alcohol-drinking rat lines, such as the “HAD-1” lines are recognized animal models of alcoholism. The present work examined sex differences in alcohol consumption, object recognition, and exploratory behavior in male and female HAD-1 rats. Naïve male and female HAD-1 rats were tested in an object recognition test (ORT) prior to a chronic 24 h intermittent ethanol access procedure for five weeks. Object recognition parameters measured included exploratory behavior, object investigation, and time spent near objects. During the initial training trial, rearing, active object investigation and amount of time spent in the object-containing section was significantly greater in female HAD-1 rats compared to their male counterparts. During the subsequent testing trial, time spent in the object-containing section was greater in female, compared to male, rats; but active object investigation and rearing did not statistically differ between females and males. In addition, female HAD-1 rats consumed significantly more ethanol than their male counterparts, replicating previous findings. Moreover, across all animals there was a significant positive correlation between exploratory behavior in ORT and ethanol consumption level. These results indicate there are significant sex differences in cognitive performance and alcohol consumption in HAD-1 rats, which suggests neurobiological differences as well.