ISMRM 23rd Annual Meeting & Exhibition • 30 May - 05 June 2015 • Toronto, Ontario, Canada

Scientific Session • Biomarkers & Subtyping of Psychiatric Disorders

Tuesday 2 June 2015

Room 701 A

16:00 - 18:00


Hilleke E. Hulshoff Pol, Ph.D., T.B.A.

16:00 0429.   Demyelination versus increased free water in schizophrenia: A pilot study using q-space trajectory imaging
Markus Nilsson1, Filip Szczepankiewicz2, Danielle van Westen3, Cecilia Mattisson4, Mats Bogren4, Ofer Pasternak5, Marek Kubicki5, and Carl-Fredrik Westin5,6
1Lund University Bioimaging Center, Lund University, Lund, Sweden, 2Dept. of Medical Radiation Physics, Lund University, Lund, Sweden, 3Diagnostic Radiology, Lund University, Lund, Sweden, 4Clinical Sciences, Psychiatry, Lund University, Lund, Sweden, 5Brigham and Women’s Hospital, Harvard Medical School, MA, United States, 6Dept. of Biomedical Engineering, Linköping University, Linköping, Sweden

In this work, we estimate the second and fourth moments, i.e. the mean (2nd order tensor) and the covariance (4th order tensor) of a distribution of tensors. Estimation of the covariance tensor is not possible with conventional diffusion encoding, but was enabled by q-space trajectory imaging (QTI). We compare novel invariant scalar quantities of the 4th order tensor between schizophrenia patients and healthy controls, and conclude that the changes observed in schizophrenia are not well explained by elevated radial diffusivity, e.g. cellular pathology such as demyelination, but very well by increased levels of free water, e.g. axonal loss or atrophy.

16:12 0430.   Dissecting Myelin and Axon Abnormalities in Schizophrenia and Bipolar disorder Patients using Novel MRI Approaches - permission withheld
Fei Du1, Eve Lewandowski1, Jackie Goldbatch1, and Dost Ongur1
1McLean Hospital, Harvard Medical School, Belmont, MA, United States

Schizophrenia (SZ) and Bipolar disorders (BD) are associated with brain tissue microstructure changes especially in the white matter (WM), which was commonly quantified by DTI. However, DTI is difficult to distinguish abnormalities between axonal and myelin. In this study, we examined WM integrity using two complementary MR-based techniques: MTR to probe myelin content and diffusion tensor spectroscopy (DTS) of NAA to probe axonal geometry. Our findings suggest SZ and BD have the distinct different abnormality: SZ is associated with abnormalities of amount of myelin and the structure of axons, whereas WM abnormalities in BD may be specific to myelin.

16:24 0431.   
Diffusion spectrum imaging connectomics: a biomarker for staging in psychotic disorders
Alessandra Griffa1,2, Philipp S Baumann3,4, Carina Ferrari3,4, Tanja Eric3,4, Philippe Conus3,4, Kim Q Do3,4, Jean-Philippe Thiran1,2, and Patric Hagmann1,2
1Signal Processing Laboratory 5 (LTS5), École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland, 2Department of Radiology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland, 3Service of General Psychiatry and Center for Psychiatric Neuroscience, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland, 4Naional Center of Competence in Research (NCCR) “SYNAPSY - The Synaptic Bases of Mental Diseases”, Switzerland

Schizophrenia is a severe psychiatric disorder hypothesized to result from brain connectivity impairment. According to the concept of clinical staging in psychotic disorders, brain connectivity might by more abnormal in more severe stages of the pathology, and altered connectivity measures might show progressive changes from prodromal to chronic phase. In this diffusion spectrum imaging (DSI) study we identify possible network-based biomarkers of pathology progression from early psychosis to chronic schizophrenia stage, compared to healthy subjects.

16:36 0432.   
Topology of structural connectomes in healthy carriers of common gene variants associated with schizophrenia
Mark Drakesmith1,2, Thomas Lancaster2, Sonya Foley1,2, Lisa Brindley1,2, Derek K Jones1,2, and David Linden1,2
1CUBRIC, Cardiff University, Cardiff, Wales, United Kingdom, 2Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, Wales, United Kingdom

Graph theory has been used to explore the topology of structural connectomes in psychiatric illnesses. However, no studies have yet looked at topology in carriers of high-risk genotypes. Here, the effects of two common schizophrenia-risk SNPs, ZNF804A and CACNA1C, on network topology are examined in 85 healthy participants. Results show differences similar to schizophrenia in carriers of the high-risk allele of CACNA1C and several regional deficits, including the precuneus, a core network hub. These differences may be due to downstream effects of synaptic dysfunction. This study is the first to show topological network differences in healthy carriers of high-risk genotypes.

16:48 0433.   Identification of a Schizophrenia-Related Disease Pattern using Resting State fMRI
An Vo1, Ivana De Lucia1, Delbert G Robinson2,3, Juan A Gallego2,3, Peter B Kingsley4, Miklos M Argyelan2,3, Anil K Malhotra2,3, Aziz M Ulug1,5, and Philip R Szeszko2,3
1Center for Neurosciences, Feinstein Institute for Medical Research, Manhasset, New York, United States, 2Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, New York, United States, 3Psychiatry Research, Zucker Hillside Hospital, North Shore-LIJ Health System, Glen Oaks, New York, United States, 4Radiology, North Shore University Hospital, Manhasset, New York, United States, 5Institute of Biomedical Engineering, Bogazici University, Istanbul, Turkey

Psychosis is a chronic and often lifelong illness associated with significant disability. In this study we report the identification of a psychosis related disease pattern (PDP) using resting state fMRI from multivariate data analysis. The PDP was identified initially in first-episode patients with psychosis (training dataset) and then replicated in an independent cohort of first-episode psychosis patients and a second independent replication dataset of chronic psychosis patients. Our findings may be indicative of a trait-related biomarker for the identification of psychosis.

17:00 0434.   
GluCEST in the olfactory cortex as a marker of heightened clinical risk for schizophrenia
Ravi Prakash Reddy Nanga1, David R. Roalf2, Hari Hariharan1, Mark A. Elliott1, Karthik Prabhakaran2, Megan Quarmley2, Paul J. Moberg2, Ravinder Reddy1, and Bruce I. Turetsky2
1Radiology, University of Pennsylvania Health Systems, Philadelphia, Pennsylvania, United States, 2Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, United States

In vivo measurement of glutamate neurotransmitter levels in brain structures implicated in neuropsychiatry disorders may provide insight into the role of these structures play in the manifestation of symptoms and potentially lead to improvements in therapy. Recent, studies with methods based on glutamate chemical exchange saturation transfer (GluCEST) in animal models and humans suggest that GluCEST mapping may serve as a biomarker of brain glutamate distribution, in vivo. Here, we use GluCEST to map glutamate distributions, within olfactory cortex, in healthy individuals (HC) and individuals at clinical risk for developing schizophrenia (CR).

17:12 0435.   
Characterization of Hemodynamic Alterations in Autism using Resting State fMRI
Wenjing Yan1 and Gopikrishna Deshpande1,2
1AU MRI Research Center,Department of Electrical and Computer Engineering, Auburn University, Auburn, Alabama, United States, 2Department of Psychology, Auburn University, Alabama, United States

Functional MRI studies of Autism attribute all changes in the fMRI signal to underlying neural activity, assuming an unaltered hemodynamic response function (HRF) in Autism. However, recent evidence from molecular/cellular approaches indicates that some neurovascular alterations may exist in the autistic brain. Therefore, we hypothesized that voxel-wise HRF derived from blind deconvolution of resting state fMRI will be altered in the autistic brain. We found significant group differences in HRF parameters in the frontal, temporal and motor areas, indicating that alterations based on the fMRI signal in Autism cannot be entirely attributed to underlying neural activity.

17:24 0436.   Relationship Between Structure and Function of the Auditory System is Altered in 16p11.2 Deletion and Duplication
Jeffrey I Berman1,2, Julian Jenkins1, Darina Chudnovskaya1, Srikantan Nagarajan3, Pratik Mukherjee3, Randy Buckner4, John E Spiro5, Wendy K Chung6, Elliott H Sherr7, and Timothy PL Roberts1,2
1Radiology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States, 2Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States, 3Radiology, University of California San Francisco, California, United States, 4Psychology, Harvard University, Boston, Massachusetts, United States, 5Simons Foundation, New York, United States, 6Pediatrics and Medicine, Columbia University Medical Center, New York, United States, 7Neurology, University of California San Francisco, California, United States

Deletion and duplication of chromosome 16p11.2has been associated with developmental disorders such as autism spectrum disorders (ASD). This multimodal study hypothesizes that the relationship between auditory radiation microstructure and the timing of the auditory evoked response (M100) is altered in children with 16p11.2 deletions and duplications. Diffusion MR and MEG were performed on 39 controls, 30 deletion carriers, and 9 duplication carriers. In the controls, low M100 was significantly correlated with low diffusivity. In the deletion and duplication populations, no significant correlation between DTI metrics and M100 was observed. This multimodal study indicates varying gene doses may similarly have an abnormal structure-function relationship.

17:36 0437.   Symptom-based subtypes of major depressive disorder manifest distinct nucleus accumbens hemodynamic responses to reward and punishment
Masaya Misaki1, Teresa Victor1, Hideo Suzuki1, Kent Teague2, Brett McKinney3, Jonathan Savitz1,4, Wayne Drevets1,5, and Jerzy Bodurka1,6
1Laureate Institute for Brain Research, Tulsa, OK, United States, 2Dept. of Surgery, University of Oklahoma College of Medicine, OK, United States, 3Tandy School of Computer Science, Dept. of Mathematics, University of Tulsa, OK, United States, 4Dept. of Medicine, Tulsa School of Community Medicine, University of Tulsa, OK, United States, 5Janssen Pharmaceuticals, LLC, of Johnson & Johnson, Inc., Titusville, NJ, United States, 6College of Engineering, University of Oklahoma, OK, United States

Distinct patterns of hemodynamic responses of the nucleus accumbens (NAcc) to gains and losses exist in healthy and depressed subjects. We identified associations between subtypes of reward- and punishment-related responses in NAcc and specific depressive symptoms. Linear discriminant analysis was performed on individual symptom ratings from the HAM-A, HAM-D and MADRS. Lower hemodynamic activity in NAcc correlated with more severe symptoms in ‘Depersonalization and Derealization’, ‘Suicidal thoughts’, and ‘Anxiety Somatic’ items. Elevated NAcc activity correlated with more severe symptoms in ‘Depressed mood’ and ‘Inability to feel’ domains. Patients with normal NAcc responses (most healthy subjects) manifested no or mild symptoms.

17:48 0438.   The long-term effects of marijuana use on the brain
Sina Aslan1,2, Vince Calhoun3, Jeffrey Spence2, and Francesca Filbey2
1Advance MRI, LLC, Frisco, Texas, United States, 2University of Texas at Dallas, Dallas, TX, United States, 3The Mind Research Network, Albuquerque, New Mexico, United States

Chronic marijuana use is associated with complex neuroadaptive processes.