Reduction of Prefrontal Cortex Glucose Metabolism Common to Three Types of Depression

Baxter, Lewis R.; Schwartz, Jeffrey; Phelps, Michael E.; Mazziotta, John C.; Guze, Barry H.; Selin, Carl; Gerner, Robert H.; Sumida, Ron M.

doi:10.1001/archpsyc.1989.01810030049007

Cited by 1,225 publications

(593 citation statements)

References 62 publications

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“…Furthermore, recent data suggest (Heckers et al, 2002) that bipolar disorder is associated with a significant decrease of glutamic acid decarboxylase (GAD) mRNA-positive neurons and of GAD 65 mRNA expression in the hippocampus. Pharmacotherapeutic studies have also reported increased regional activation of the left prefrontal cortex, thalamus, and medial frontal gyrus post-treatment in depressed patients (Baxter et al, 1989;Bench et al, 1995;Buchsbaum et al, 1997;Mayberg et al, 1999;Saxena et al, 2002). Taken together, these findings indicate that there are abnormalities of the limbic system in depressed patients.…”

Section: What Might This Study Tell Us About Ltg's Mechanism Of Actiomentioning

confidence: 92%

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

Tenebäck

Nahas

et al. 2004

Neuropsychopharmacol

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Little is known about how lamotrigine (LTG) works within brain circuits to achieve its clinical effects. We wished to determine whether the new technique of interleaved transcranial magnetic stimulation (TMS)/functional magnetic resonance imaging (fMRI) could be used to assess the effects of LTG on activated motor or prefrontal/limbic circuits. We carried out a randomized, double-blind, crossover trial involving two visits 1 week apart with TMS measures of cortical excitability and blood oxygen level-dependent TMS/fMRI. Subjects received either a single oral dose of 325 mg of LTG or placebo on each visit. In all, 10 subjects provided a complete data set that included interleaved TMS/fMRI measures and resting motor threshold (rMT) determinations under both placebo and LTG conditions. A further two subjects provided only rMT data under the two drug conditions. LTG caused a 14.979.6% (mean7SD) increase in rMT 3 h after the drug, compared with a 0.6710.9% increase 3 h after placebo (t ¼ 3.41, df ¼ 11, po0.01). fMRI scans showed that LTG diffusely inhibited cortical activation induced by TMS applied over the motor cortex. In contrast, when TMS was applied over the prefrontal cortex, LTG increased the TMS-induced activation of limbic regions, notably the orbitofrontal cortex and hippocampus. These results suggest that LTG, at clinically relevant serum concentrations, has a general inhibitory effect on cortical neuronal excitability, but may have a more complex effect on limbic circuits. Furthermore, the interleaved TMS/fMRI technique may be a useful tool for investigating regional brain effects of psychoactive compounds.

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Section: What Might This Study Tell Us About Ltg's Mechanism Of Actiomentioning

confidence: 92%

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

Tenebäck

Nahas

et al. 2004

Neuropsychopharmacol

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“…Second, since the study included only female subjects, findings cannot be generalized to both sexes. However, regional CMRglu differences between men and women have not been consistently reported (Baxter Jr et al, 1989;Miura et al, 1990). Potential gender differences may exist in FEN activation of CMRglu as there is evidence of gender effects in serotonergic brain function, and rates of serotonin synthesis have been shown to differ by gender (Nishizawa et al, 1997).…”

Section: Limitationsmentioning

confidence: 99%

“…Alternatively, the effects of depression in this area may overpower those of impulsivity in BPD as some functional imaging studies have also suggested a role for the orbital prefrontal cortex in the pathophysiology of depression. For example, studies that examined abnormalities during a Major Depressive Episode and after various forms of treatment report normalization of orbitofrontal and anterior cingulate abnormalities with treatment (Baxter Jr et al, 1989;Bench et al, 1995;Brody et al, 1999;Buchsbaum et al, 1997;Mayberg et al, 2000Mayberg et al, , 2002. Indeed, Bremner et al (1997) found that depressed patients who were 6 weeks into a course of antidepressant treatment exhibited decreases in glucose metabolic rates in the orbitofrontal cortex and thalamus after a tryptophan-depletion-induced acute relapse compared to patients without depressive symptoms.…”

Section: Orbitofrontal Cortex In Mdd With Bpd Compared To Mddmentioning

confidence: 99%

Positron Emission Tomography of Regional Brain Metabolic Responses to a Serotonergic Challenge in Major Depressive Disorder with and without Borderline Personality Disorder

Oquendo

Krunic

Parsey

et al. 2005

Neuropsychopharmacol

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Previous neuroimaging studies of major depression have not controlled for the presence of personality disorders characterized by impulsive aggressive behavior, such as borderline personality disorder (BPD). Using positron emission tomography (PET), we studied regional glucose uptake in response to fenfluramine (FEN) in depressed subjects with BPD (n ¼ 11) and depressed patients without Cluster B Axis II disorders (n ¼ 8). Subjects were scanned while medication-free after a single blind placebo administration and after FEN on a second day. Brain responses were measured by PET imaging of [ 18 F]fluorodeoxyglucose (FDG) and serial prolactin levels. Scans were compared at a voxel level using statistical parametric mapping. Correlations of changes in relative regional cerebral uptake (rCMRglu) with clinical measures were assessed. Depressed borderline patients had greater relative activity in parietotemporal cortical regions (BA 40, BA 22, and BA 42) before and after FEN activation compared to those without BPD. They also had less relative uptake in the anterior cingulate cortex (BA 32) at baseline compared to depressed patients without BPD and FEN abolished this difference. Impulsivity was positively correlated with rCMRglu in superior and middle frontal cortex (BA 6 and 44). Hostility was positively correlated with rCMRglu in temporal cortical regions (BA 21 and 22). In conclusions, borderline pathology in the context of a Major Depressive Disorder is associated with altered activity in parietotemporal and anterior cingulate cortical regions. Controlling for the presence of BPD in future imaging studies of mood disorders may elucidate similarities and differences in regional serotonergic function in these two often comorbid disorders.

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“…with seasonal affective disorder, odor identification scores obtained from the right, but not left, side of the nose correlate negatively with 'typical' depression scores on the Hamilton Depression Rating Scale (r = −0.56, p = 0.006) (Postolache et al, 1999), likely reflecting depression-related right hemisphere anomalies (Baxter et al, 1989;Bench et al, 1993).…”

Section: Introductionmentioning

confidence: 96%

Estrogen replacement therapy induces functional asymmetry on an odor memory/discrimination test

2008

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The secondary afferents of the olfactory system largely project to the ipsilateral cortex without synapsing in the thalamus, making unilateral olfactory testing a useful probe of ipsilateral hemispheric activity. In light of evidence that lateralized performance on some perceptual tasks may be influenced by estrogen, we assessed left:right nostril differences in two measures of olfactory function in 14 post-menopausal women receiving estrogen replacement therapy (ERT) and 48 postmenopausal women receiving no such therapy. Relative to women not taking ERT, those receiving ERT exhibited better performance in the left nostril and poorer performance in the right nostril on an odor memory/discrimination test. Similar laterality effects were not observed for an odor detection threshold test employing phenyl ethyl alcohol. These results suggest that estrogen influences the lateralization of an odor memory/discrimination task and that hormone replacement therapy in the menopause may be an excellent paradigm for understanding lateralizing effects of hormones on some sensory processes.

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Reduction of Prefrontal Cortex Glucose Metabolism Common to Three Types of Depression

Cited by 1,225 publications

References 62 publications

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

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

Positron Emission Tomography of Regional Brain Metabolic Responses to a Serotonergic Challenge in Major Depressive Disorder with and without Borderline Personality Disorder

Estrogen replacement therapy induces functional asymmetry on an odor memory/discrimination test

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