Affective dysfunction has been recognized as a major deficit in schizophrenia, and flat affect is a prominent negative symptom, presenting a challenge for treatment. Our efforts in the current project have advanced the understanding of emotion processing deficits in schizophrenia through convergence of clinical, neurobehavioral and structural and functional neuroimaging methods. Our results underscored the importance of flat affect in adversely impacting course and outcome. They suggested that the interaction between limbic and prefrontal regions could underlie both emotion processing and some cognitive deficits. Our current study has also revealed substantial deficits in emotion processing in unaffected first-degree relatives of patients, and the renewal application proposes to study a group of unaffected siblings. Advances in neuroscience provide unprecedented tools to probe the neurobiology of emotion processing in healthy people and reveal with increased precision mechanisms that could be responsible for dysfunction in people with schizophrenia. The goal of the proposed competing renewal application is to build on current findings and focus on functional MRI (fMRI) paradigms to examine emotion processing in people with schizophrenia and their unaffected siblings. In the proposed study we will perform two experiments, both using a sparse event-related design that can isolate neural systems engaged in top-down emotion categorization tasks from those responding to threat related facial affect. In the first experiment we will test the hypothesis that abnormal bottom-up amygdale response to facial affect is especially impaired for fearful expressions, and contributes to misinterpretation and possibly failure to process affectively valenced stimuli. We will confirm our findings that this abnormal amygdala response is strongly associated with severity of flat affect and adversely impacts course and outcome, and examine the effects of gaze direction on limbic activation. The sample size for this experiment is powered to examine potentially modulating effects of anxiety, basal cognitive and emotion processing abilities, sex differences, and ethnicity effects. In the second experiment we will examine variables that could modulate the abnormal amygdala response to threat related facial expressions. We will examine the contribution of stimulus parameters by manipulating information conveyed in facial features. Specifically, we will determine the effects of changes in upper or lower face, and familiarity by using photographs of facial affect displays obtained from people familiar to the participants. In both experiments, incorporation of a recognition task will permit linking limbic response to the likelihood of correct face encoding. The application of a genetic strategy, by studying family members with the neurobehavioral and fMRI paradigms, will permit the integration of two powerful research strategies in schizophrenia - genetics and behavioral neuroscience - needed to assess vulnerability. We expect the results to shed light on mechanisms for affective dysfunction in schizophrenia that can lead to improved identification of vulnerability and treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH060722-10
Application #
7880840
Study Section
Special Emphasis Panel (ZRG1-BDCN-N (02))
Program Officer
Rumsey, Judith M
Project Start
1999-12-01
Project End
2012-05-31
Budget Start
2010-06-01
Budget End
2012-05-31
Support Year
10
Fiscal Year
2010
Total Cost
$510,165
Indirect Cost
Name
University of Pennsylvania
Department
Psychiatry
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Kuo, Susan S; Almasy, Laura; Gur, Ruben C et al. (2018) Cognition and community functioning in schizophrenia: The nature of the relationship. J Abnorm Psychol 127:216-227
van Erp, Theo G M; Walton, Esther; Hibar, Derrek P et al. (2018) Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium. Biol Psychiatry 84:644-654
Radke, Sina; Seidel, Eva-Maria; Eickhoff, Simon B et al. (2016) When opportunity meets motivation: Neural engagement during social approach is linked to high approach motivation. Neuroimage 127:267-276
Keutmann, Michael K; Moore, Samantha L; Savitt, Adam et al. (2015) Generating an item pool for translational social cognition research: methodology and initial validation. Behav Res Methods 47:228-34
Roalf, David R; Gur, Raquel E; Verma, Ragini et al. (2015) White matter microstructure in schizophrenia: associations to neurocognition and clinical symptomatology. Schizophr Res 161:42-9
Kohler, Christian G; Richard, Jan A; Brensinger, Colleen M et al. (2014) Facial emotion perception differs in young persons at genetic and clinical high-risk for psychosis. Psychiatry Res 216:206-12
Dyck, Miriam; Loughead, James; Gur, Ruben C et al. (2014) Hyperactivation balances sensory processing deficits during mood induction in schizophrenia. Soc Cogn Affect Neurosci 9:167-75
Kohn, Nils; Falkenberg, Irina; Kellermann, Thilo et al. (2014) Neural correlates of effective and ineffective mood induction. Soc Cogn Affect Neurosci 9:864-72
Cao, Houwei; Cooper, David G; Keutmann, Michael K et al. (2014) CREMA-D: Crowd-sourced Emotional Multimodal Actors Dataset. IEEE Trans Affect Comput 5:377-390
Roalf, David R; Ruparel, Kosha; Verma, Ragini et al. (2013) White matter organization and neurocognitive performance variability in schizophrenia. Schizophr Res 143:172-8

Showing the most recent 10 out of 88 publications