Toby Wise1, Matthew J Taylor2, Andres Herane-Vives3, Antonella Marino Gammazza4, Francesco Cappello4, David J Lythgoe5, Steve Cr Williams5, Allan H Young6, Anthony J Cleare6, Danilo Arnone7. 1. Centre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; National Institute for Health Research Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London, UK; Wellcome Trust Centre for Neuroimaging, University College London, London, UK; Max Planck UCL Centre for Computational Psychiatry and Ageing Research, London, UK. Electronic address: toby.wise@kcl.ac.uk. 2. Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. 3. Centre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; Departamento de Clínicas, Facultad de Medicina, Universidad Católica del Norte, Coquimbo, Chile. 4. Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche, Sezione di Anatomia Umana, Università degli Studi di Palermo, Palermo, Italy; Istituto Euro-Mediterraneo di Scienza e Tecnologia, Palermo, Italy. 5. Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. 6. Centre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; National Institute for Health Research Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London, UK; South London and Maudsley NHS Foundation Trust, London, UK. 7. Centre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; South London and Maudsley NHS Foundation Trust, London, UK.
Abstract
BACKGROUND: There is uncertainty as to whether alterations in glutamatergic function in affective disorders differ between unipolar and bipolar disorders and between depressive and euthymic states. Additionally, there are currently no available blood-based markers of central glutamatergic function to support clinical diagnosis and aid brain based investigations. METHODS: In this study, we measured levels of glutamate in the dorsal anterior cingulate cortex in-vivo using 1H-Magnetic Resonance Spectroscopy in medication free unipolar and bipolar patients (n = 29, 20 unipolar and 9 bipolar) experiencing a major depressive episode, in comparison with a group of matched healthy controls (n = 20). We also analysed peripheral glutaminase measured in serum to examine the relationship between central and peripheral measures. RESULTS: Anterior cingulate glutamate levels were reduced in both unipolar and bipolar depression groups relative to healthy controls, although this only reached significance in the unipolar group. Peripheral glutaminase levels did not differentiate bipolar from unipolar depression and a positive correlation with central glutamate levels did not reach statistical significance. LIMITATIONS: The sample of bipolar disorder patients was relatively small due to the difficulties involved in finding medication-free patients experiencing a depressive episode. CONCLUSIONS: These results suggest that glutamatergic hypofunction might represent a state marker for a depressive episode irrespective of diagnosis. Peripheral glutaminase did not index central glutamate levels in this study, which could potentially reflect a small magnitude of the effect requiring larger samples for detection.
BACKGROUND: There is uncertainty as to whether alterations in glutamatergic function in affective disorders differ between unipolar and bipolar disorders and between depressive and euthymic states. Additionally, there are currently no available blood-based markers of central glutamatergic function to support clinical diagnosis and aid brain based investigations. METHODS: In this study, we measured levels of glutamate in the dorsal anterior cingulate cortex in-vivo using 1H-Magnetic Resonance Spectroscopy in medication free unipolar and bipolar patients (n = 29, 20 unipolar and 9 bipolar) experiencing a major depressive episode, in comparison with a group of matched healthy controls (n = 20). We also analysed peripheral glutaminase measured in serum to examine the relationship between central and peripheral measures. RESULTS: Anterior cingulate glutamate levels were reduced in both unipolar and bipolar depression groups relative to healthy controls, although this only reached significance in the unipolar group. Peripheral glutaminase levels did not differentiate bipolar from unipolar depression and a positive correlation with central glutamate levels did not reach statistical significance. LIMITATIONS: The sample of bipolar disorderpatients was relatively small due to the difficulties involved in finding medication-free patients experiencing a depressive episode. CONCLUSIONS: These results suggest that glutamatergic hypofunction might represent a state marker for a depressive episode irrespective of diagnosis. Peripheral glutaminase did not index central glutamate levels in this study, which could potentially reflect a small magnitude of the effect requiring larger samples for detection.
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