ORCID

https://orcid.org/https://orcid.org/0000-0002-0280-3101

Date of Award

Summer 8-15-2018

Author's School

Graduate School of Arts and Sciences

Author's Department

Psychology

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

Cognitive impairment occurs across the psychosis spectrum. However it is unknown whether these shared manifestations of cognitive dysfunction also reflect shared neurobiological mechanisms, or whether the source of impairment differs. One common feature of cognitive impairment across psychotic disorders is that the impairments are often ҧeneralizedӬ indicating deficits in a range of cognitive domains, including executive functioning, processing speed, memory, and attention. The goal of the current study was to determine whether the similar generalized cognitive deficit observed across psychotic disorders is also associated with a shared putative mechanism of functional brain network integrity. To address this question, we estimated resting-state functional network integrity of the cingulo-opercular and fronto-parietal networks -- two networks widely implicated in cognitive ability -- in 201 healthy controls, 143 schizophrenia, 103 schizoaffective, and 129 bipolar disorder with psychosis participants from the Bipolar and Schizophrenia Network on Intermediate Phenotypes (BSNIP1) consortium. Cognitive ability was measured using the Brief Assessment of Cognition in Schizophrenia (BACS), and generalized cognitive ability was estimated as the first factor (54% variance explained) in a principal axis factor analysis of all BACS subtests. Graph theory algorithms were used to estimate the global and local efficiency of the whole brain, cingulo-opercular network (CON), fronto-parietal network (FPN), and the auditory network (AUD), as well as participation coefficient of the anterior insula, dorsal anterior cingulate cortex, and dorsolateral prefrontal cortex. We observed significantly reduced CON global efficiency in schizophrenia and psychotic bipolar patients compared to healthy controls (pճ<.01), but none of the clinical groups differed from one another (pճ>.21). All psychotic disorders had significantly reduced CON local efficiency (pճ<.03), but the clinical groups did not differ from one another. CON global efficiency was significantly associated with general cognitive ability across all groups (_=.099, p=.009), and significantly mediated the relationship between psychotic disorder status and general cognition (p<.05). Exploratory analyses revealed that global efficiency of the subcortical network was also significantly reduced in psychotic disorders (p=.007), and positively predicted cognitive ability (_=.094, p=.009). These findings provide evidence of a role for reduced CON and subcortical network efficiency in the generalized cognitive deficit observed across the psychosis spectrum. They also support the hypothesis that a shared neurobiological mechanism underlies the dimension of cognitive impairment in psychotic disorders.

Language

English (en)

Chair and Committee

Deanna M. Barch

Committee Members

Ryan Bogdan, Todd Braver, Thomas Oltmanns, Nico Dosenbach,

Comments

Permanent URL: 2018-08-15

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