Reduced glutamate in the anterior cingulate cortex in depression: an in vivo proton magnetic resonance spectroscopy study

Increased Anterior Cingulate/Medial Prefrontal Cortical Glutamate and Creatine in Bipolar Depression

“…In this study, acceptably reliable peaks, as defined by LCModel quality control criteria, were recorded consistently for each of these. Thereby, the Gln resonance was smaller and relatively more variable than Glx and Glu, as has been seen by others (Auer et al, 2000;Rosenberg et al, 2005). Higher field strength may better quantify Gln and separate it from Glu as evidenced by a 4-T study of left anterior cingulate finding reductions in both Glu and Gln in schizophrenia (Theberge et al, 2003).…”

“…Frontal cortex and basal ganglia Glx elevations have also been reported in pediatric bipolar disorder; the acute mood state and Cr levels were not reported (Castillo et al, 2000). In contrast, below-normal anterior cingulate [Glx] has been reported in unipolar depression with (Rosenberg et al, 2005;Mirza et al, 2004) or without (Auer et al, 2000;Pfleiderer et al, 2003) below-normal [Cr]. Despite phenomenologic similarities between bipolar and unipolar depression, the epidemiology, course of illness (age of onset, associated comorbidities), and potential liability of antidepressant treatment suggest that these are in fact, two different disease states (Bowden, 2005).…”

“…It is unclear if the potential for 1 HMRS anterior cingulate glutamate to distinguish bipolar from unipolar depression is related to the different disease state (bipolar glutamate increase/unipolar glutamate decrease) or to the current phenomenologic presentation (atypical glutamate increase/melancholic glutamate decrease). The unipolar studies that reported reduced anterior cingulate [Glx] (Rosenberg et al, 2005;Mirza et al, 2004;Auer et al, 2000;Pfleiderer et al, 2003) did not report glutamate levels based on subtype or pattern of depression.…”

Elevated Levels of the NR2C Subunit of the NMDA Receptor in the Locus Coeruleus in Depression

“…Recently, Sanacora et al (2004) demonstrated increased levels of glutamate in occipital cortex in depressed subjects as compared to healthy controls, utilizing proton magnetic resonance spectroscopy. On the other hand, Auer et al (2000) reported reduced glutamate level in the anterior cingulate cortex associated with depression. Consistent with the hypothesis that depression is associated with elevated glutamatergic transmission, NMDAR antagonists exhibit antidepressant-like potential in rodent antidepressant screening procedures (Moryl et al, 1993;Papp and Moryl, 1994).…”

Interleaved Transcranial Magnetic Stimulation/Functional MRI Confirms that Lamotrigine Inhibits Cortical Excitability in Healthy Young Men

“…The present study in healthy volunteers may not be relevant to drug effects in patients with bipolar disorder, but the surprising observation of limbic activation in the presence of LTG when TMS was applied to the prefrontal cortex is worth considering with the clinical situation in mind. Studies of the neuropathology in familial Major Depressive Disorder have reported changes in morphology and metabolism in selected areas of the limbic system, such as the hippocampus (Auer et al, 2000;Rusch et al, 2001;Thibault et al, 2001), the orbital frontal lobe (Drevets 2000;MacFall et al, 2001), and amygdala (Sheline et al, 1998). Frodl et al (2002) reported smaller hippocampal gray matter volumes in patients with a first episode of major depression compared with healthy subjects.…”