Parsing heterogeneity in white matter integrity along the progression of psychosis

529 

Abstract Submission 

Galya Iseli^1,2, Sarah Ulrich^3,4, Philipp Staempfli^5,6, Erich Studerus⁷, Anita Riecher-Rössler⁸, Philipp Homan⁹, Stefan Kaiser¹⁰, Stefan Borgwardt¹¹, Matthias Kirschner¹⁰, André Schmidt¹²

¹Department of Clinical Research (DKF), University Psychiatric Clinics, Translational Neurosciences, Basel, Switzerland, ²Division of Cognitive Neuroscience, Department of Biomedicine University of Basel, Basel, Switzerland, ³Experimental Clinical Affective Neuroscience Lab (ECANL), Department of Clinical Research (DKF)), Basel, Switzerland, ⁴Center for Affective, Stress and Sleep Disorders, University Psychiatric Clinics (UPK), Basel, Switzerland, ⁵Psychiatric University Hospital Zurich, Zurich, Switzerland, ⁶MR-Center of the Psychiatric Hospital and the Department of Child and Adolescent Psychiatry, University of Zurich, Zürich, Switzerland, ⁷Division of Personality and Developmental Psychology, University of Basel, Basel, Switzerland, ⁸Faculty of Medicine, University of Basel, Basel, Switzerland, ⁹Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric University Hospital Zurich, Basel, Switzerland, ¹⁰Division of Adult Psychiatry, Department of Psychiatry, Geneva University Hospitals, Geneva, Switzerland, ¹¹University of Lübeck, Lübeck, Germany, ¹²University of Basel, Department of Clinical Research (DKF), University Psychiatric Clinics (UPK), Basel, Switzerland

Galya Iseli  
Department of Clinical Research (DKF), University Psychiatric Clinics, Translational Neurosciences|Division of Cognitive Neuroscience, Department of Biomedicine University of Basel
Basel, Switzerland|Basel, Switzerland

Sarah Ulrich  
Experimental Clinical Affective Neuroscience Lab (ECANL), Department of Clinical Research (DKF))|Center for Affective, Stress and Sleep Disorders, University Psychiatric Clinics (UPK)
Basel, Switzerland|Basel, Switzerland

Philipp Staempfli  
Psychiatric University Hospital Zurich|MR-Center of the Psychiatric Hospital and the Department of Child and Adolescent Psychiatry, University of Zurich
Zurich, Switzerland|Zürich, Switzerland

Erich Studerus  
Division of Personality and Developmental Psychology, University of Basel
Basel, Switzerland

Anita Riecher-Rössler  
Faculty of Medicine, University of Basel
Basel, Switzerland

Philipp Homan  
Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric University Hospital Zurich
Basel, Switzerland

Stefan Kaiser  
Division of Adult Psychiatry, Department of Psychiatry, Geneva University Hospitals
Geneva, Switzerland

Stefan Borgwardt  
University of Lübeck
Lübeck, Germany

Matthias Kirschner  
Division of Adult Psychiatry, Department of Psychiatry, Geneva University Hospitals
Geneva, Switzerland

André Schmidt  
University of Basel, Department of Clinical Research (DKF), University Psychiatric Clinics (UPK)
Basel, Switzerland

Psychosis develops along a continuum ranging from subclinical psychotic experiences in healthy volunteers from the general population and individuals at clinical high risk to patients with clinically relevant psychosis. Each stage along the continuum demonstrates heterogeneity in clinical profiles and outcome features. While previous research also indicated structural brain heterogeneity at both ends of the continuum, it remains unknown whether it evolves with disease progression and whether divergence from the norm is associated with more adverse clinical features.

Data of 212 participants collected at three different centers was included in this post-hoc analysis. Samples ranging from five different groups of disease progression were collected at the Department of Psychiatry (UPK) of the University of Basel, the University Hospital of Psychiatry, Bern and the Department of Psychiatry, Psychotherapy and Psychosomatics at the Psychiatric Hospital, University of Zurich: healthy controls (HC, n = 59), schizotypal (SPT, n = 27), at risk mental state (ARMS, n = 35), first episode psychosis (FEP, n = 50), and patients diagnosed with schizophrenia (SZ, n = 41). Structural brain heterogeneity of diffusion tensor imaging (DTI) parameters including fractional anisotropy (FA), mean diffusivity (MD) and fiber density (FD) was computed using the person-based similarity index (PBSI) scores, a novel index that expresses an individual's similarity towards others of the same group. Besides comparing the different DTI PBSIs across groups using the Kruskal-Wallis test, normalized PBSIs were further converted into z-scores (z-nPBSI) indicating deviators to the normative reference. Furthermore, age, sex and diagnostic group adjusted ANCOVAs were performed to determine whether individuals with deviating PBSIs differ in verbal IQ (MWT-B), psychiatric symptoms (BPRS, SANS) and general ability to function (GAF) compared to subjects with non-deviating PBSIs.

Across diagnostic groups significant differences in the PBSI were found for all three diffusion measures FA (H = 51.81, p < 0.001). MD (H = 44.49, p < 0.001), and FD (H = 55.80, p < 0.001) (Figure 1). Group differences in FA heterogeneity were found between ARMS-SPT (U = -2.87, p = 0.04), FEP-SZ (U = -4.04, p = <0.001), ARMS-SZ (U = -6.13, p = <0.001), and HC-SZ (U = -6.25, p = <0.001). For MD significant differences were found between HC-SPT (U = -3.39, p = 0.007), FEP-SPT (U = -3.56, p = 0.003), HC-ARMS (U = -4.02, p = <0.001), ARMS-FEP (U = 4.17, p = <0.001), HC-SZ (U = -4.74, p = <0.001), and FEP-SZ (U = -4.87, p = <0.001). For FD, FEP-SZ (U = -2.91, p = 0.03), FEP-SPT (U = -4.31, p = <0.001), ARMS-SZ (U = -4.81, p = <0.001), HC-SZ (U = -4.51, p = <0.001), HC-SPT (U = -5.67, p = <0.001), and ARMS-SPT (U = -5.88, p = <0.001) differed significantly.
For FA, SZ showed the greatest percentage of deviators (24.390%) followed by SPT (14.815%), HC (8.475%), FEP (8%) and ARMS (2.857%). For MD 22.5% deviators in SZ, 20% in ARMS, 11.111% in SPT 8% in FEP, and 6.780% in HC. And for FD 25.926% in SPT, 14.634% in SZ, followed by 13.793% in HC, 5.714% in ARMS, and 8.0% in FEP.
Across all DTI parameters, the number of deviators differed significantly across the groups (χ^2 = 11.24, df = 1, p = 0.02). Post-hoc comparisons revealed significant differences between the groups HC-SPT (OR = 2.94, p = 0.04), FEP-SZ (OR = 2.8, p = 0.04) and SPT-FEP (OR = 3.64, p = 0.02).
Furthermore, there were statistical trends for lower GAF scores in SZ patients (F (1,1) = 3.61, p = 0.08) and individuals with SPT (F (1,1) = 3.66, p = 0.07) who exhibited deviating PBSIs compared to those with non-deviating PBSIs.

Our results indicate progressive increases in structural brain heterogeneity. Further large-scale studies are encouraged to examine those with marked deviance from normative data reveal more severe clinical features. Such approaches may enable improved prognosis of disease progression and treatment guidance.

Psychiatric (eg. Depression, Anxiety, Schizophrenia) ¹

Diffusion MRI Modeling and Analysis

Anatomy and Functional Systems

White Matter Anatomy, Fiber Pathways and Connectivity

Diffusion MRI ²

Schizophrenia

Tractography

WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC

Other - psychosis continuum, heterogeneity, normative referencing, person-based similarity index