541. Deficits in and Compensation for Engagement of Social Cognition Areas in Schizophrenia during Naturalistic Viewing

Biological Psychiatry

Friday Abstracts

likely to mediate deficient synchronization of extrinsically-driven gamma oscillations. Supported By: AstraZeneca, P50 AA012870/AA/NIAAA NIH, R01 MH058262/MH/NIMH NIH, UL1 RR024139/RR/ NCRR NIH Keywords: Schizophrenia, Ketamine, NMDAR hypofunction, Gamma oscillation

540. Effects of N-methyl-D-aspartate Glutamate Receptor Disruption and Nicotinic Acetylcholine Enhancement on Mismatch Negativity Holly Hamilton1, Naomi Kort2, Judith Ford1, Brian Roach3, Handan Gunduz-Bruce4, John Krystal4, Judith Jaeger5, Robert Reinhart6, and Daniel Mathalon7 1

San Francisco VA Health Care System & University of California, San Francisco, 2University of California, San Francisco, 3Northern California Institute for Research and Education & University of California, San Francisco, 4Yale University School of Medicine, 5Albert Einstein College of Medicine, 6Boston University, 7University of California, San Francisco & San Francisco VA Health Care System Background: N-methyl-D-aspartate glutamate receptor (NMDAR) hypofunction has been implicated in the pathophysiology of schizophrenia, including auditory processing abnormalities reflected by the mismatch negativity (MMN) eventrelated potential component. Evidence from animal models and healthy individuals suggesting cognitive benefits from nicotine administration, as well as the high rate of cigarette use in patients with schizophrenia, has stimulated interest in whether nicotine modulates NMDAR hypofunction in schizophrenia. Accordingly, we examined the interactive effects of ketamine, an NMDAR antagonist that produces transient schizophrenia-like behavioral and neurophysiological effects, and nicotine, a nicotinic acetylcholine receptor (nAChR) agonist, in healthy volunteers in order to determine whether nicotine prevents or attenuates MMN abnormalities. Methods: Of 30 healthy volunteers enrolled, 27 participants completed four test days, during which they received ketamine and nicotine in a double-blind, counterbalanced design. Each test day involved two infusions, one either ketamine or placebo, and the other either nicotine or placebo. On each test day, MMN to several types of deviant sounds (intensity, pitch, duration, and pitch1duration double deviants) was assessed. Results: Ketamine significantly decreased MMN amplitude for intensity-, pitch-, and double-deviant MMN. In contrast, nicotine significantly increased MMN amplitude, particularly for the doubledeviant MMN. A significant ketamine x nicotine interaction indicated that while nicotine alone increased MMN, it failed to attenuate the decrease in MMN associated with ketamine. Conclusions: These results demonstrate differential effects of nAChR and NMDAR systems on MMN, and further suggest that the detrimental effects of NMDAR blockade dominate when combined with the enhancing effects of nAChR augmentation. Supported By: AstraZeneca, P50 AA012870/AA/NIAAA NIH, R01 MH058262/MH/NIMH NIH, UL1 RR024139/RR/NCRR NIH, VA OAA Advanced Fellowship in Mental Illness Research and Treatment,

Keywords: Schizophrenia, NMDAR hypofunction, Ketamine, Nicotine, Mismatch Negativity

541. Deficits in and Compensation for Engagement of Social Cognition Areas in Schizophrenia during Naturalistic Viewing Gaurav Patel1, Sophie Arkin1, Casimir Klim1, Javier LopezCalderon1, Antigona Martinez1, Rebecca Berman2, David Leopold2, and Daniel Javitt1 NYSPI/Columbia, 2NIMH

1

Background: Social communication deficits are a major cause of psychosocial disability in schizophrenia patients (SzP). Studies of SzP have demonstrated potential differences in the multiple networks underlying social communication, but the interaction of these networks in naturalistic scenarios remains unclear. We recorded brain activity evoked by a cinematic movie in SzP vs. healthy controls (HC) to study these interactions. Methods: 14 SzP and 14 HC underwent fMRI while watching 15 minutes of a movie, as well as task fMRI for localization of visual, face-processing, attention, and theory of mind areas, and resting state to measure connectivity of these areas. The timecourse for each voxel of BOLD activity evoked in each subject by the movie was correlated with the average timecourse of the HCs (intersubject synchronization). Results: Inter-subject synchronization maps were grossly similar in the two populations. Contrasting SzP and HC maps revealed reduced synchronization of visual and posterior STS faceemotion and theory of mind areas. Resting state connectivity of these areas was also reduced in SzP, resulting in a disconnection of visual and theory of mind areas. However, SzP demonstrated increased synchronization of dorsal attention areas as compared to HC, indicating that use of these areas was increased in SzP. Conclusions: This study demonstrates the utility of naturalistic viewing paradigms to simultaneously evaluate the functioning of multiple networks in Sz. We find deficits in the engagement of visual and face-emotion processing areas that mirror the deficits in connectivity. Increased engagement of attention networks may represent compensation for the visual/face-emotion processing deficits. Supported By: NIMH, Leon Levy Foundation, American Psychiatric Foundation Keywords: BOLD fMRI, Resting state functional connectivity, Social Cognition, emotional face processing, attention

542. Cannabis Use and Neurocognitive Functioning in the Psychosis Spectrum J. Cobb Scott1, Jason Jones2, Tyler Moore2, David Roalf2, Monica Calkins2, Daniel Wolf2, Theodore Satterthwaite2, Kosha Ruparel2, Chad Jackson2, Raquel Gur2, and Ruben Gur2 1

Perelman School of Medicine University of Pennsylvania, University of Pennsylvania

2

Background: Schizophrenia is characterized by significant neurocognitive deficits. Meta-analyses suggest that individuals

Biological Psychiatry May 15, 2017; 81:S140–S276 www.sobp.org/journal

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