Sakthivel Sekar¹, Sankar Seramani¹, Joanne Garnell¹, and Kishore Kumar Bhakoo^1
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]

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 Shungu^3
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.

Antoine Cherix¹, Jean-René Cardinaux^2,3, Rolf Gruetter^1,4, and Hongxia Lei^5,6
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.

Wenjun Li¹, B. Douglas Ward², Gang Chen², Xiaolin Liu², Jennifer Jones³, Piero Antuono³, Shi-Jiang Li^1,2, and Joseph Goveas^1
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.

Maria Otaduy¹, Ivan Aprahaiam², Rodolfo Ladeira², Rodrigo Machado-Vieira^3,4, Claudia Leite⁵, Wagner Gattaz⁶, and Orestes Forlenza^2
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.

Uzay E Emir¹, Nisha Singh^2,3, Ann Sharpley³, Charles Masaki³, Sridhar Vasudevan², Peter Jezzard¹, Phil Cowen³, and Grant Churchill^2
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.

Pravin Kumar Mishra¹ and Anant Bahadur Patel^1
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.

Shantanu H Joshi¹, Stephanie Njau¹, Amber Leaver¹, Antonio Marquina², Roger P Woods¹, Randall Espinoza³, and Katherine L Narr^1
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.

Marc J Dubin¹, Xiangling Mao², Samprit Banerjee³, Rebecca Gordon⁴, Zachary Goodman⁵, Kyle AB Lapidus⁶, Guoxin Kang², Conor Liston¹, and Dikoma C Shungu^2
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.

Hongjian He¹, Fangfang Xu¹, and Jianhui Zhong^1
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.