Kugaya A, Sanacora A. Beyond monoamines: Glutamatergic Function in Mood Disorders. CNS Spectrums 10: 808-818

ArticleinCNS spectrums 10(10):808-19 · November 2005with68 Reads
Source: PubMed
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.
    • "Kainate receptors are located either presynaptically at both GABAergic and glutamatergic synapses, where they control neurotransmitter release and are involved in presynaptic plasticity (Schmitz et al., 2001 ), or postsynaptically in several regions deeply involved in epilepsy, including the cortex, hippocampus, and amygdala (Crépel and Mulle, 2015). Few studies thus far have investigated the role of glutamate in aggression (Comai et al., 2012a); however, there is strong evidence of the involvement of glutamate in the pathophysiology and treatment of mood disorders such as depression (Kugaya and Sanacora, 2005; Niciu et al., 2014) that often coexist with aggressive behavior. Support for the glutamate hypothesis of aggression includes the demonstration of a positive relationship between cerebrospinal fluid glutamate levels and measures of impulsive aggression in both healthy human subjects and subjects with personality disorders (Coccaro et al., 2013). "
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    • "Glutamate is nonessential and glucogenic amino acid that can be synthesized by a-ketoglutarate through glutamate dehydrogenase. It has many biological functions, such as GSH synthesis, mood disorders, depression, immune regulation and so on (Kugaya & Sanacora, 2005; Palucha & Pilc, 2005; Whillier et al., 2011; Xue & Field, 2010). Additionally, a decreased in tryptophan level has been observed in SPEPs relative to healthy controls. "
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    • "Taken together, these findings support the view that the brain circuitry and neurobiological mechanisms involved in the regulation of the aggressive behavior and emotion may be differentially affected by different developmental factors (Sandi and Haller, 2015). Anxiety and mood disorders frequently emerge at puberty (Pattwell et al., 2013) and have been related to both decreased GABA (Mohler, 2012; Tzanoulinou et al., 2014a) and altered glutamatergic transmission (Kugaya and Sanacora, 2005). In agreement with those findings, we found that the iS rats have elevated levels of Glu and low levels of GABA in the LS. "
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