Markus Nilsson¹, Filip Szczepankiewicz², Danielle van Westen³, Cecilia Mattisson⁴, Mats Bogren⁴, Ofer Pasternak⁵, Marek Kubicki⁵, and Carl-Fredrik Westin^5,6
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.

Fei Du¹, Eve Lewandowski¹, Jackie Goldbatch¹, and Dost Ongur^1
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.

Alessandra Griffa^1,2, Philipp S Baumann^3,4, Carina Ferrari^3,4, Tanja Eric^3,4, Philippe Conus^3,4, Kim Q Do^3,4, Jean-Philippe Thiran^1,2, and Patric Hagmann^1,2
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.

Mark Drakesmith^1,2, Thomas Lancaster², Sonya Foley^1,2, Lisa Brindley^1,2, Derek K Jones^1,2, and David Linden^1,2
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.

An Vo¹, Ivana De Lucia¹, Delbert G Robinson^2,3, Juan A Gallego^2,3, Peter B Kingsley⁴, Miklos M Argyelan^2,3, Anil K Malhotra^2,3, Aziz M Ulug^1,5, and Philip R Szeszko^2,3
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.

Ravi Prakash Reddy Nanga¹, David R. Roalf², Hari Hariharan¹, Mark A. Elliott¹, Karthik Prabhakaran², Megan Quarmley², Paul J. Moberg², Ravinder Reddy¹, and Bruce I. Turetsky^2
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).

Wenjing Yan¹ and Gopikrishna Deshpande^1,2
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.

Jeffrey I Berman^1,2, Julian Jenkins¹, Darina Chudnovskaya¹, Srikantan Nagarajan³, Pratik Mukherjee³, Randy Buckner⁴, John E Spiro⁵, Wendy K Chung⁶, Elliott H Sherr⁷, and Timothy PL Roberts^1,2
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.

Masaya Misaki¹, Teresa Victor¹, Hideo Suzuki¹, Kent Teague², Brett McKinney³, Jonathan Savitz^1,4, Wayne Drevets^1,5, and Jerzy Bodurka^1,6
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.

Sina Aslan^1,2, Vince Calhoun³, Jeffrey Spence², and Francesca Filbey^2
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.