ISMRM 24th Annual Meeting & Exhibition • 07-13 May 2016 • Singapore

Scientific Session: Psychiatric Disorders: Translational Approaches

Thursday, May 12, 2016
Hall 606
16:00 - 18:00
Moderators: Henry Ka-Fung Mak, Khin Tha

The impact of ebselen administration on neurochemical profiles: A magnetic resonance spectroscopy study at 7 Tesla
Uzay E Emir1, Charles Masaki2, Ann L Sharpley2, Beata R Godlewska2, Adam Berrington1, Tasuku Hashimoto2, Nisha Singh3, Sridhar R Vasudevan3, Grant C Churchill3, and Philip J Cowen2
1FMRIB Centre, University of Oxford, Oxford, United Kingdom, 2Department of Psychiatry, University of Oxford, Oxford, United Kingdom, 3Department of Pharmacology, University of Oxford, Oxford, United Kingdom
Bipolar disorder (BPD) is a relatively common psychiatric disorder for which lithium is the gold standard of treatment. Lithium is an inhibitor of the enzyme inositol monophosphatase (IMPase) , leading to marked decreases in brain myo -inositol (myo -Ins) levels  Recently, it has been reported that ebselen, a drug developed for its antioxidant and inflammatory properties, inhibits IMPase and lowers myo -Ins levels in the human brain.  In this study, it was aimed to replicate this finding using a higher dose of ebselen and at ultra high field strength (7T). 

Default-mode network hypo-connectivity in a mouse model of human chromosome 16p11.2 microdeletion
Alice Bertero1,2, Gergely David2, Adam Liska2, Alberto Galbusera2, Massimo Pasqualetti1,2, and Alessandro Gozzi2
1Department of Biology, Unit of Cell and Developmental Biology, University of Pisa, Pisa, Italy, 2Functional Neuroimaging Lab, Center for Neuroscience and Cognitive Systems, Istituto Italiano di Tecnologia, Rovereto, Italy
Autism spectrum disorder (ASD) has been associated to reduced or aberrant functional brain connectivity as measured with resting state fMRI (rsfMRI). However little is known on the pathophysiological and genetic determinants underlying these alterations. Here we show that mice recapitulating human chromosome 16p11.2 microdeletion, a trait associated with intellectual disability and high ASD penetrance, exhibit reduced connectivity in prefrontal hubs of the mouse default mode network, recapitulating a hallmark neuroimaging finding in ASD. These findings establish a causal link between ASD-associated mutations and connectivity alterations and identify a plausible macroscale substrate for the cognitive impairments associated to 16p11.2 microdeletion. 

Assessing the effects of methylphenidate on human brain development using pharmacological magnetic resonance imaging: a randomized controlled trial
Anouk Schrantee1, Esther E Bron2, Henk-Jan MM Mutsaerts1,3, Stefan Klein2, Wiro Niessen2,4, Serge ARB Rombouts5,6, and Liesbeth Reneman1
1Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands, 2Biomedical Imaging Group Rotterdam, Departments of Medical Informatics and Radiology, Erasmus MC, Rotterdam, Netherlands, 3Sunnybrook Research Institute, Toronto, ON, Canada, 4Imaging Physics, Applied Sciences, Delft University of Technology, Delft, Netherlands, 5Institute of Psychology, Leiden University, Leiden, Netherlands, 6Department of Radiology, LUMC, Leiden, Netherlands
In this randomized clinical trial we studied the effect of methylphenidate exposure on the development of the dopamine system in children and adults with ADHD. Concurrent with preclinical literature, we found an increased DA reactivity using arterial spin labeling pharmacological MRI following four months of treatment with methylphenidate in children with ADHD, but not in adult patients. 

Does N-acetylcysteine elevate brain glutathione levels? : a six-months double-blind randomized controlled study
Lijing Xin1, Philippe Conus2, Philipp S. Baumann2,3, Margot Fournier3, Carina Ferrari2,3, Luis Alameda2,3, Raoul Jenni2,3, Thierry Buclin4, Rolf Gruetter5,6,7, Ralf Mekle8, and Kim Q. Do3
1Animal Imaging and Technology Core (AIT), Center for Biomedical Imaging (CIBM), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, 2Service of General Psychiatry, Department of Psychiatry, Lausanne University Hospital (CHUV), Lausanne, Switzerland, 3Unit for Research in Schizophrenia, Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital (CHUV), Lausanne, Switzerland, 49. Division of clinical pharmacology, Lausanne University Hospital (CHUV), Lausanne, Switzerland, 5Laboratory of Functional and Metabolic Imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, 6Department of Radiology, University of Geneva, Geneva, Switzerland, 7Department of Radiology, University of Lausanne, Lausanne, Switzerland, 82. Physikalisch-Technische Bundesanstalt, Braunschweig and Berlin, Germany
Dysregulation of the glutathione (GSH) metabolism has been implicated in schizophrenia pathophysiology. Boosting GSH levels by N-acetylcysteine (NAC), a precursor of GSH, was hypothesized to be a neuroprotective treatment. The aim of this study was to investigate whether the supplementation of NAC treatment has an impact on cerebral GSH levels and other metabolites in early psychosis patients using  in vivo 1H MRS. A significant increase of mPFC GSH levels was observed in patients with 6-months NAC treatment, however such increase was absent in placebo group.

A GABA-A receptor a5 subtype specific fMRI Signature in the Rat Brain: Negative versus Positive Allosteric Modulation effects
Thomas Mueggler1, Basil Künnecke1, Henner Knust1, Andreas Bruns1, Rodolfo Gasser1, Andrew Thomas1, Maria-Clemencia Hernandez1, and Markus von Kienlin1
1Pharma Research and Early Development, Roche Innovation Center Basel, Hoffmann-La Roche, Basel, Switzerland
The GABA-A α5 subunit-containing receptors are prominently expressed in the hippocampus. There is genetic and pharmacological evidence for a modulatory role in learning and memory positioning the GABA-A α5 subunit-containing receptor as potential target for treatment of cognitive dysfunction. In order to investigate the circuitry engaged by modulation of the GABA-A α5 subtype-containing receptors we performed pharmacological MRI (phMRI) studies in the sedated rat using a selective GABA-A α5 negative (NAM) and a positive allosteric modulator (PAM) and demonstrated a differential neurofunctional response which contrasted to that of the non-selective benzodiazepine agonist diazepam.

MEGAPRESS reveals lower ?-aminobutyric acid ratios in the striatum of highly-impulsive rats
Stephen J Sawiak1, Bianca Jupp1, Tom Taylor1, Daniele Caprioli1, T Adrian Carpenter1, and Jeffrey Dalley1
1University of Cambridge, Cambridge, United Kingdom
Disorders of impulse control are a rising issue in society as diagnosis rates of conditions such as attention deficit and hyperactivity disorder are increasing. In humans, the MEGAPRESS approach to measuring GABA is becoming a standard technique but it has not yet been used much in translational studies. Here, we used it to measure GABA in the striatum of highly-impulsive rats compared to rats with low impulsivity and found significantly reduced levels of this inhibitory neurotransmitter in the impulsive animals. 

Thalamic-Auditory Cortical-Hippocampal Dysconnectivity in First-Episode Schizophrenia Patients with Auditory Verbal Hallucinations
Long-Biao Cui1, Baojuan Li2, Yi-Bin Xi1, and Hong Yin1
1Xijing Hospital, Fourth Mililtary Medical University, Xi'an, China, People's Republic of, 2School of Biomedical Engineering, Fourth Mililtary Medical University, Xi'an, China, People's Republic of
We found hyperconnectivity from the thalamus to auditory cortex and hypoconnectivity from the auditory cortex to the hippocampus in AVHs. The thalamic-auditory cortical-hippocampal circuit seems to be crucial for AVHs in SZ. In SZ patients with AVHs, there is a failure to attenuate the sensitivity of auditory cortex to thalamic inputs with a complementary down-regulation of hippocampal responses to ascending auditory input. These findings are consistent with current thinking about dysconnection syndromes in SZ; particularly the aberrant modulation of neuromodulatory gain control and its role assigning aberrant precision or salience to sensory evidence in conditions like SZ. Our findings might provide support for dysconnectivity hypothesis of AVHs associated with auditory/language-processing regions, default mode regions, and other networks (insula and striatum), as reviewed most recently. Dysconnectivity of this circuit may also serve as a potential diagnostic biomarker and therapeutic target of AVHs in SZ based on the direct evidence in vivo we found.

Functional Dysconnectivity in Autism Spectrum Disorder Revealed by Network-Based Statistics.
AmirHussein Abdolalizadeh1, Bahram Mohajer1, and Nooshin Abbasi1
1Students Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
Since the advent of Connectomics, borders of our knowledge about brain and nervous system have increased tremendously. Thus, novel methods to analyze brain connectivity have always been under focus.  We used Network-based statistics (NBS), to exert a weak control over family-wise error, and discover interconnected networks in 35 Autism Spectrum Disorder (ASD) and 34 age-, sex- matched Typically developing (TD) children. We also used NBS results' nodes for structural connectivity analysis. We respectively showed increased and decreased functional connectivity of fronto-inferior temporal and default-mode networks, in patients with ASD compared to TD.

Relationship between neuropsychological stress and inflammation: a PET and MRI study.
Cheuk Ying Tang1, Victoria X Wang2, Johnny C Ng2, Venkatesh Mani2, Sarah Horn3, James Murrough3, Chloe Solomon2, Willem Mulder2, Valentin Fuster4, Dennis Charney5, Ahmed A Tawakol6, Lisa Shin7, Matthias Nahrendorf8, and Zahi A Fayad9
1Radiology & Psychiatry, Translational and Molecular Imaging Institute at Mount Sinai, New York, NY, United States, 2Radiology, Translational and Molecular Imaging Institute at Mount Sinai, New York, NY, United States, 3Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States, 4Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States, 5Psychiatry, Neuroscience & Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, United States, 6Cardiology, Massachusetts General Hospital, Boston, MA, United States,7Psychology, Tufts University, Medford, MA, United States, 8Center for Systems Biology, Massachusetts General Hospital, Boston, MA, United States, 9Radiology, Medicine & Cardiology, Translational and Molecular Imaging Institute at Mount Sinai, New York, NY, United States
We used both FDG PET and MRI to study the relationship between neuropsychological stress and inflammation in a PTSD population. Significant correlations between white matter fractional anisotropy and inflammation in the carotid as measured using FD-PET. Resting state scans and functional scans correlated with HAMA and MADRS but no relationship was detected with FDG-PET.

Glutathione and Glutamate in Schizophrenia: A 7T MRS Study
Jyothika Kumar1, Emma L Hall2, Siân E Robson2, Carolina Fernandes2, Elizabeth B Liddle1, Matthew J Brookes2, Lena Palaniyappan1, Peter G Morris2, and Peter F Liddle1
1Centre for Translational Neuroimaging, Division of Psychiatry and Applied Psychology, University of Nottingham, Nottingham, United Kingdom, 2Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom
Various theories of neurochemical dysfunction in schizophrenia have been proposed. Using 7T MR spectroscopy, we aim to investigate abnormalities in the antioxidant and glutamatergic systems in patients with schizophrenia and whether there is a relationship between the two. We found reduced levels of glutathione in the anterior cingulate cortex (ACC) in patients with residual schizophrenia indicating a reduction in the brain’s antioxidant defences accompanied by reduced levels of glutamate and glutamine. A positive correlation between glutathione and glutamate was observed in the ACC in all participants indicating a mechanistic link between these two systems.

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