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

Scientific Session • Monitoring Change & Difference in Psychiatric Disorders

Wednesday 3 June 2015

John Bassett Theatre 102

16:00 - 18:00


Donna J. M. Lang, Ph.D., Natalie M. Zahr, Ph.D.

16:00 0731.   
Utility of MR-Spectroscopy in early drug discovery: characterization of dynamic temporal metabolic changes following psychoactive challenges in the rodent brain
Sakthivel Sekar1, Sankar Seramani1, Joanne Garnell1, and Kishore Kumar Bhakoo1
1Translational Imaging Industrial Lab, Singapore Bioimaging Consortium, Biopolis, Singapore

Our findings exemplify the utility of 1H-MRS in early drug discovery, to non-invasively investigate the dynamic metabolite temporal changes in the brain, to further understand (or corroborate) the behavioral effects of psychoactive compounds [Sekar et al., 2013] and their functional activation(s) observed with other Neuroimaging modalities (fMRI, rs-fMRI, electrophysiology, etc) [Sekar et al., 2010, 2011, 2013]

16:12 0732.   1H MRS Monitoring of GABAergic and Glutamatergic Response to 4 Weeks of Antipsychotic Treatment in Medication-naïve First-episode Psychosis Patients
Camilo de la Fuente-Sandoval1, Francisco Reyes-Madrigal2, Xiangling Mao3, Pablo León-Ortiz4, Oscar Rodríguez-Mayoral5, Helgi Jung-Cook6, Ariel Graff-Guerrero7, Rodolfo Solis-Vivanco8, and Dikoma C Shungu3
1Neuropsychiatry & Laboratory of Experiment Psychiatry, Instituto Nacional de Neurología y Neurocirugía (INNN), Mexico City, Distrito Federal, Mexico,2Laboratory of Experimental Psychiatry, INNN, Mexico City, Mexico, 3Radiology, Weill Cornell Medical College, New York, NY, United States, 4Education, INNN, Mexico City, Mexico, 5Palliative Care Unit, Instituto Nacional de Cancerología, Mexico City, Mexico, 6Laboratory of Neuropsychopharmacology, INNN, Mexico City, Mexico, 7Multimodal Neuroimaging Schizophrenia Group, Centre for Addiction and Mental Health, Toronto, ON, Canada, 8Laboratory of Neuropsychology, INNN, Mexico City, Mexico

Dysregulations of GABA and glutamate are implicated in schizophrenia pathophysiology. Using 1H MRS, GABA and glutamate+glutamine (Glx) levels were measured at baseline and after 4 weeks of antipsychotic treatment in the medial prefrontal cortex (MPFC) and dorsal caudate (DCA) of medication-naive first-episode psychosis (FEP) patients and matched health controls. The results showed higher baseline levels of both GABA and Glx in the MPFC and DCA of FEP subjects than in controls, which normalized in both brain regions after 4 weeks of treatment. These data suggest that schizophrenia is characterized by elevations of GABA and Glx, which normalize with antipsychotic treatment.

16:24 0733.   
MRI and MRS characterization of Crtc1 knock-out mice limbic structures: investigating neurobiology of mood disorders
Antoine Cherix1, Jean-René Cardinaux2,3, Rolf Gruetter1,4, and Hongxia Lei5,6
1Laboratory for functional and metabolic imaging (LIFMET), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Vaud, Switzerland, 2Center for Psychiatric Neuroscience (CNP), Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Vaud, Switzerland, 3Faculty of Medicine, University of Lausanne, Lausanne, Vaud, Switzerland, 4Department of Radiology, University of Lausanne, Lausanne, Vaud, Switzerland, 5Center for Biomedical Imaging (CIBM), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Vaud, Switzerland, 6Department of Radiology, University of Geneva, Geneva, Geneva, Switzerland

MRI and MRS are two techniques that have been extensively used to study mood disorders. However, a lot of discrepancies between the studies reflect the lack of understanding in the pathophysiology of these complex diseases. We have investigated the volumetric and metabolic profile in a mouse model of mood disorders lacking Crtc1 gene. Knock-out animals showed strong regional dysregulations in their brain metabolism together with structural changes as compared to wild-type animals. This study provides a link between a specific gene and its associated metabolic and volumetric alterations and will help understanding further the underlying pathophysiology of mood disorders.

16:36 0734.   Restoration of Abnormal Interconnectivity between Memory and Emotional Processing Circuits in Remitted Late-Life Depression
Wenjun Li1, B. Douglas Ward2, Gang Chen2, Xiaolin Liu2, Jennifer Jones3, Piero Antuono3, Shi-Jiang Li1,2, and Joseph Goveas1
1Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, WI, United States, 2Biophysics, Medical College of Wisconsin, WI, United States, 3Neurology, Medical College of Wisconsin, WI, United States

Although task-based functional MRI and single-seed functional connectivity MRI have been extensively used to study the disease, these methods show limited success in simultaneously analyzing multiple brain circuits. In current study, we use a recently developed method called step-wise connectivity to identify the brain regions that are responsible for the integration of memory encoding and emotional processing networks. We hypothesize abnormal interconnectivity between memory and emotional processing networks that will be seen in LLD will show recovery towards normal patterns remitted patients.

16:48 0735.   Lithium brain absorption in the elderly versus younger patients with bipolar disease.
Maria Otaduy1, Ivan Aprahaiam2, Rodolfo Ladeira2, Rodrigo Machado-Vieira3,4, Claudia Leite5, Wagner Gattaz6, and Orestes Forlenza2
1Laboratory of Magnetic Resonance in Neuroradiology, LIM 44, Institute and Department of Radiology, University of São Paulo, São Paulo, São Paulo, Brazil, 2Laboratory of Neuroscience, LIM 27, Institute and Department of Psychiatry, University of São Paulo, São Paulo, São Paulo, Brazil, 3Laboratory of Neuroscience, LIM 27, Institute and Department of Psychiatry, University of São Paulo, São Paulo, Brazil, 4Department of Health and Human Services, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United States, 5Laboratory of Magnetic Resonance in Neuroradiology, LIM 44, Institute and Department of Radiology, University of São Paulo, Sao Paulo, Brazil, 6Laboratory of Neuroscience, LIM 27, Institute and Department of Psychiatry, University of São Paulo, São Paulo, Sao Paulo, Brazil

In this study we used 7Li-MRS to quantify brain lithium concentration in patients with bipolar disease under lithium treatment. The purpose of this study was to evaluate if lithium brain absorption is different in young (20-40yrs) from elderly (60-80yrs) patients. For that we evaluated the mean brain to plasma lithium ratio for both groups and found it to be the same. Noteworthy, within the younger group we found a negative correlation between brain to plasma lithium ratio and age that was not observed for the elderly group.

17:00 0736.   The Impact of Ebselen Administration on Brain myo-Inositol Concentration
Uzay E Emir1, Nisha Singh2,3, Ann Sharpley3, Charles Masaki3, Sridhar Vasudevan2, Peter Jezzard1, Phil Cowen3, and Grant Churchill2
1University of Oxford, FMRIB Centre, Oxford, Oxfordshire, United Kingdom, 2University of Oxford, Department of Pharmacology, Oxford, Oxfordshire, United Kingdom, 3University of Oxford, Department of Psychiatry, Oxford, Oxfordshire, United Kingdom

Bipolar disorder (BPD) is a relatively common psychiatric disorder for which lithium is the gold standard of treatment but it has a number of side-effects which require careful monitoring of plasma levels of the drug. A drug, ebselen, that mimics the effect of lithium but without its side-effects has been recently reported. In this study, we assessed if ebselen reduces brain inositol levels, compared to placebo using magnetic resonance spectroscopy.

17:12 0737.   
Ketamine Improves Astroglial Metabolic Activity and Neurotransmission in Social Defeat Model of Depression: A 1H-[13C]-NMR Study - video not available
Pravin Kumar Mishra1 and Anant Bahadur Patel1
1Centre for Cellular and Molecular Biology, Hyderabad, India

Astroglia play a major role in recycling and metabolism of neurotransmitters at synapse. The functional characteristics of astroglia is not well understood in depression. Ketamine has been reported to possess rapid anti-depressant activity. The objective of the current study was to evaluate the astroglial metabolic activity, and effects of ketamine in social defeat model of depression. Depression led to reduction in the astroglial metabolic activity. Moreover, sub-anesthetic dose of ketamine was able to restore behavioral phenotypes and astroglial activity in depressed mice.

17:24 0738.   Electroconvulsive Therapy (ECT) induced neurochemical modulation as measured by 1HMRS in Major Depression
Shantanu H Joshi1, Stephanie Njau1, Amber Leaver1, Antonio Marquina2, Roger P Woods1, Randall Espinoza3, and Katherine L Narr1
1Neurology, UCLA, Los Angeles, CA, United States, 2Mathematics, University of Valencia, Valencia, Spain, 3Psychiatry and Behavioral Sciences, UCLA, Los Angeles, CA, United States

Proton magnetic resonance spectroscopy (1HMRS) offers a non-invasive technique for measuring the neurochemical disturbances in cortico-limbic regulatory circuits in depression. Electroconvulsive therapy (ECT) is a rapidly acting treatment for patients with severe depression. While patients with major depression show abnormal neurochemistry, several emerging hypotheses for ECT induced neuroplasticity have led to measuring the ECT driven neuro-metabolite response using 1HMRS. Here, we examined cross-sectional and longitudinal ECT treatment effects on glutamate/glutamine (Glx), N-acetyl aspartate (NAA), creatinine+phospocreatinie (Cr/PCr), and myo-inositol (mI) in the hippocampus, and the dorsal and subgenual cingulate in patients with major depressive disorder (MDD) along with cross-sectional diagnosis effects in metabolites when compared to age and gender matched healthy controls.

17:36 0739.   1H MRS Demonstrates Elevations of Prefrontal Cortex GABA in Major Depressive Disorder after Treatment with Repetitive Transcranial Magnetic Stimulation
Marc J Dubin1, Xiangling Mao2, Samprit Banerjee3, Rebecca Gordon4, Zachary Goodman5, Kyle AB Lapidus6, Guoxin Kang2, Conor Liston1, and Dikoma C Shungu2
1Psychiatry & Brain and Mind Research Institute, Weill Cornell Medical College, New York, NY, United States, 2Radiology, Weill Cornell Medical College, New York, NY, United States, 3Healthcare Policy and Research, Weill Cornell Medical College, New York, NY, United States, 4Psychiatry, Weill Cornell Medical College, New York, NY, United States, 5Johns Hopkins University, Baltimore, MD, United States, 6Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States

Although repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder (MDD), its antidepressant mechanisms are unclear. This study investigated the potential involvement of GABA and glutamate in the antidepressant mechanism of rTMS. Patients with MDD underwent a 5-week treatment of rTMS, with 1H MRS measurements of prefrontal GABA and Glx pre- and post-treatment. After rTMS treatment, prefrontal GABA increased 12.3% in all depressed subjects and 18.3% in subjects with partial or full responses. Glx was unchanged. These results seem to implicate GABAergic and glutamatergic systems in the antidepressant mechanism of action of rTMS.

17:48 0740.   Methylphenidate modulates the connectivity of default mode network in ADHD: a resting-state dynamic causal model analysis
Hongjian He1, Fangfang Xu1, and Jianhui Zhong1
1Center for Brain Imaging Science and Technology, Zhejiang University, Hangzhou, Zhejiang, China

This study is interested in the modulatory effect of Methylphenidate in attention deficit hyperactivity disorder. A dynamic causal model analysis was applied to investigated the effective connectivity within default mode network in resting state. Our preliminary study revealed that the causal connectivity is altered by the dose of MPH, in which the inhibitory link from RIPL to MPFC is significantly enhanced.