Psychotic symptoms are present in a significant subset of individuals with Bipolar Disorder (BD) and carry devastating personal and clinical implications. Most biomedical research on BD has ignored the variable presentation of psychosis possibly overlooking biologically significant heterogeneity in BD; such heterogeneity may cause inconsistencies in the literature by treating BD as a homogenous category 7,18. The expression of psychosis in some BD patients (BD-P) and absence in others (BD-NP) may indicate divergent disease processes of critical nosological and clinical relevance. PARDIP leverages a large sample of BD, a comprehensive battery, and sophisticated analytic tools to establish whether BD-P and BD-NP represent a difference in degree or a difference in kind. Long-term goals: This work will critically impact how BD is classified and studied, provide robust targets for effective future etiological studies, and clarify the utility of available biomarkers o major psychiatric disturbance. PARDIP represents a step toward mechanistically based classification of psychiatric disorders.
Specific Aims : PARDIP will (i) identify the patterns of bo-cognitive disruptions which mark psychosis (BD-P`BD-NP) or mood instability in general (BD`healthy comparisons), (ii) explore how these biomarkers relate to one another and to other dimensions of psychopathology present in BD, and (iii) utilize latent class and cluster analyses of the multivariate dataset to verify taxonicity within BD with regard to psychosis and uncover latent psychiatric subgroups of interest for future genotyping and etiological research. Methods: The three-year PARDIP project will recruit 135 psychotic BD, 135 non-psychotic BD, and 135 psychiatrically healthy comparison subjects (all new recruits), administering a comprehensive battery focused on the psychosis and mania domains of psychopathology. We will obtain measures of neurophysiology, (smooth pursuit eye movements, antisaccades, auditory ERPs), cognition (cognitive battery, response inhibition, spatial working memory), neuroanatomy (structural magnetic resonance imaging [MRI]), emotional processing (ERPs to emotional pictures), intrinsic brain state (resting functional MRI connectivity), and circadian function (Actigraphy). We will compare biomarkers between BD-P, BD-NP, and H groups to determine which track with psychosis and which track with affective disturbance. We will identify common sources of variance among measures with joint-ICA and PCA approaches, and examine how biomarkers and biomarker composites relate to other aspects of clinical heterogeneity. Taxometric procedures (MAXCOV- HITMAX and its multivariate extension MAXEIG-HITMAX and k-means clustering) will be carried out with the multivariate dataset to empirically identify distinct subgroups of subjects. PARDIP will be conducted by 4 experienced research groups (across 3 collection sites) with a long history of close and productive collaboration.

Public Health Relevance

This multisite project built upon and benefiting from the extensive infrastructure of the ongoing BSNIP consortium will collect a comprehensive battery of biological, neuroanatomic, neurophysiologic, cognitive, and clinical measures from a large sample of Bipolar Disorder (BD) patients to determine whether BD patients with psychosis and BD patients without psychosis represent a difference in degree or a difference in kind Multivariate and taxometric analyses will leverage the extensive, comprehensive dataset to i) characterize the overall structure and clinical covariates of identified biomarkers, ii) test the validity of a categorical BD-P vs. BD- NP distinction, and iii) uncover latent psychiatric subgroups. Findings from this work will contribute critically to the development of mechanistically relevant classification systems in psychiatry, a necessary prerequisite for effective treatment development and genealogical research.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Special Emphasis Panel (ZRG1-BDCN-A (64))
Program Officer
Rumsey, Judith M
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University of Texas Sw Medical Center Dallas
Schools of Medicine
United States
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Hudgens-Haney, Matthew E; Ethridge, Lauren E; McDowell, Jennifer E et al. (2018) Psychosis subgroups differ in intrinsic neural activity but not task-specific processing. Schizophr Res 195:222-230
Reilly, James L; Hill, S Kristian; Gold, James M et al. (2017) Impaired Context Processing is Attributable to Global Neuropsychological Impairment in Schizophrenia and Psychotic Bipolar Disorder. Schizophr Bull 43:397-406
Eum, Seenae; Hill, S Kristian; Rubin, Leah H et al. (2017) Cognitive burden of anticholinergic medications in psychotic disorders. Schizophr Res 190:129-135
Braff, David L; Tamminga, Carol A (2017) Endophenotypes, Epigenetics, Polygenicity and More: Irv Gottesman's Dynamic Legacy. Schizophr Bull 43:10-16
Rubin, Leah H; Yao, Li; Keedy, Sarah K et al. (2017) Sex differences in associations of arginine vasopressin and oxytocin with resting-state functional brain connectivity. J Neurosci Res 95:576-586
Sheffield, Julia M; Kandala, Sridhar; Tamminga, Carol A et al. (2017) Transdiagnostic Associations Between Functional Brain Network Integrity and Cognition. JAMA Psychiatry 74:605-613
Hudgens-Haney, Matthew E; Ethridge, Lauren E; Knight, Justin B et al. (2017) Intrinsic neural activity differences among psychotic illnesses. Psychophysiology 54:1223-1238
Du, Yuhui; Pearlson, Godfrey D; Lin, Dongdong et al. (2017) Identifying dynamic functional connectivity biomarkers using GIG-ICA: Application to schizophrenia, schizoaffective disorder, and psychotic bipolar disorder. Hum Brain Mapp 38:2683-2708
Pearlson, Godfrey D; Clementz, Brett A; Sweeney, John A et al. (2016) Does Biology Transcend the Symptom-based Boundaries of Psychosis? Psychiatr Clin North Am 39:165-74
Rubin, Leah H; Connelly, Jessica J; Reilly, James L et al. (2016) Sex and diagnosis specific associations between DNA methylation of the oxytocin receptor gene with emotion processing and temporal-limbic and prefrontal brain volumes in psychotic disorders. Biol Psychiatry Cogn Neurosci Neuroimaging 1:141-151

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