Article

Beyond monoamines: Glutamatergic function in mood disorders

Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
CNS spectrums (Impact Factor: 1.3). 11/2005; 10(10):808-19.
Source: PubMed

ABSTRACT The monoamine theory has implicated abnormalities in serotonin and norepinephrine in the pathophysiology of major depression and bipolar illness and contributed greatly to our understanding of mood disorders and their treatment. Nevertheless, some limitations of this model still exist that require researchers and clinicians to seek further explanation and develop novel interventions that reach beyond the confines of the monoaminergic systems. Recent studies have provided strong evidence that glutamate and other amino acid neurotransmitters are involved in the pathophysiology and treatment of mood disorders. Studies employing in vivo magnetic resonance spectroscopy have revealed altered cortical glutamate levels in depressed subjects. Consistent with a model of excessive glutamate-induced excitation in mood disorders, several antiglutamatergic agents, such as riluzole and lamotrigine, have demonstrated potential antidepressant efficacy. Glial cell abnormalities commonly associated with mood disorders may at least partly account for the impairment in glutamate action since glial cells play a primary role in synaptic glutamate removal. A hypothetical model of altered glutamatergic function in mood disorders is proposed in conjunction with potential antidepressant mechanisms of antiglutamatergic agents. Further studies elucidating the role of the glutamatergic system in the pathophysiology of mood and anxiety disorders and studies exploring the efficacy and mechanism of action of antiglutamatergic agents in these disorders, are likely to provide new targets for the development of novel antidepressant agents.

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    • "Res. (2014), http://dx.doi.org/10.1016/j.schres.2014.11.012 brain regions such as the anterior cingulate cortex (Goff and Coyle, 2001; Clinton and Meador-Woodruff, 2004; Kugaya and Sanacora, 2005; Javitt et al., 2012). Specifically, schizophrenia patients have exhibited increased concentrations of glutamatergic metabolites if the patients were in a first-episode and conversely, decreased concentrations if the patients had a chronic disease (Ohrmann et al., 2005; Ohrmann et al., 2008; Marsman et al., 2013; Schwerk et al., 2014). "
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    • "The data gathered during recent years suggests that abnormalities within glutamatergic transmission, especially NMDA (N-methyl- D-aspartate) receptor overactivation, are associated with more generalized mechanisms of brain dysfunction that may underlie various psychiatric disorders, including major depressive disorder. The accumulated evidence demonstrated that the functional and structural pathology of excitatory neurotransmitters have been observed in animal models of depression and clinical trials (Hansen et al., 1983; Kugaya and Sanacora 2005; Petrie et al., 2000; Sanacora et al., 2003; Zarate et al., 2002; Hashimoto, 2009; Pilc et al., 2013). Furthermore, there is evidence that NMDA receptor ligands (functional antagonists ) interacting with different components of the NMDA receptor– ionophore complex produced antidepressant-like effects (Lopes et al., 1997; Panconi et al., 1993; Poleszak et al., 2007; Przegalinski et al., 1998; Trullas and Skolnick, 1990; Szewczyk et al., 2012). "
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    Journal of Affective Disorders 08/2013; 151(3). DOI:10.1016/j.jad.2013.08.009 · 3.71 Impact Factor
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    • "In particular, their effect on glutamate clearance may be relevant for the pathogenesis of MDD, because an excess of this neurotransmitter potentially exerts neurotoxic effects (Hynd et al., 2004; Mattson, 2007). Therefore, ADs may act both on astrocytes and neurons to re-establish a properly functional astrocyte–neuronal network, thereby restoring physiological glutamate homeostasis (Kugaya and Sanacora, 2005; Sanacora et al., 2012). "
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    Neuroscience 12/2012; 232. DOI:10.1016/j.neuroscience.2012.11.061 · 3.33 Impact Factor
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