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 Cowen^2
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). 

Alice Bertero^1,2, Gergely David², Adam Liska², Alberto Galbusera², Massimo Pasqualetti^1,2, and Alessandro Gozzi^2
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. 

Anouk Schrantee¹, Esther E Bron², Henk-Jan MM Mutsaerts^1,3, Stefan Klein², Wiro Niessen^2,4, Serge ARB Rombouts^5,6, and Liesbeth Reneman^1
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. 

Lijing Xin¹, Philippe Conus², Philipp S. Baumann^2,3, Margot Fournier³, Carina Ferrari^2,3, Luis Alameda^2,3, Raoul Jenni^2,3, Thierry Buclin⁴, Rolf Gruetter^5,6,7, Ralf Mekle⁸, and Kim Q. Do^3
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.

Thomas Mueggler¹, Basil Künnecke¹, Henner Knust¹, Andreas Bruns¹, Rodolfo Gasser¹, Andrew Thomas¹, Maria-Clemencia Hernandez¹, and Markus von Kienlin^1
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.

Stephen J Sawiak¹, Bianca Jupp¹, Tom Taylor¹, Daniele Caprioli¹, T Adrian Carpenter¹, and Jeffrey Dalley^1
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. 

Long-Biao Cui¹, Baojuan Li², Yi-Bin Xi¹, and Hong Yin^1
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.

AmirHussein Abdolalizadeh¹, Bahram Mohajer¹, and Nooshin Abbasi^1
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.

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 Fayad^9
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.

Jyothika Kumar¹, Emma L Hall², Siân E Robson², Carolina Fernandes², Elizabeth B Liddle¹, Matthew J Brookes², Lena Palaniyappan¹, Peter G Morris², and Peter F Liddle^1
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.