Paralimbic frontal lobe hypometabolism in depression associated with Huntington's disease

Mayberg, Helen S.; Starkstein, Sergio E.; Peyser, Carol E.; Brandt, Jason; Dannals, R. F.; Folstein, Susan E.

doi:10.1212/wnl.42.9.1791

Cited by 182 publications

(97 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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. A comparable pattern of abnormality in the orbitofrontal cortical region is seen in refractory depressed patients (Mayberg et al, 1997) and in patients with depression associated with neurological disorders (Bromfield et al, 1992;Mayberg et al, 1990Mayberg et al, , 1992. Mayberg et al (1999) suggested that mood provocation in patients with acute and remitted depression resulted in rCBF decrease in the medial orbitofrontal cortex BA 10/11, which was absent in healthy controls.…”

Section: Orbitofrontal Cortex In Mdd With Bpd Compared To Mddmentioning

confidence: 84%

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

View full text Add to dashboard Cite

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.

show abstract

Section: Orbitofrontal Cortex In Mdd With Bpd Compared To Mddmentioning

confidence: 84%

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

View full text Add to dashboard Cite

show abstract

“…Anterior cingulate cortex is involved in emotional responses and in sensory, motor, and cognitive processing (Vogt et al, 1992). Positron emission tomographic studies in patients with HD have revealed impairment of activity in the anterior cingulate cortex as well as the striatum (Mayberg et al, 1992). In R6/1 mice, transplantation of wild-type donor cortex to replace diseased anterior cingulate cortex delays the onset of a specific motor symptom of HD (van Dellen et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Environmental Enrichment Rescues Protein Deficits in a Mouse Model of Huntington's Disease, Indicating a Possible Disease Mechanism

Spires¹,

Grote²,

Varshney³

et al. 2004

J. Neurosci.

334

254

View full text Add to dashboard Cite

Huntington's disease (HD) is a devastating neurodegenerative disorder caused by a CAG repeat expansion encoding an extended polyglutamine tract in the huntingtin protein. Transgenic mice expressing a human huntingtin transgene containing an expanded CAG repeat (R6/1 model) develop a neurodegenerative disorder closely resembling human HD. Previous work demonstrated that environmental enrichment delays the onset of motor symptoms in this mouse model. We confirmed that at 5 months of age, enrichment ameliorates motor symptoms (assessed using the rotarod test) and prevents loss of body weight induced by the HD transgene. We further examined molecular consequences of enrichment by determining changes in protein levels in the neostriatum, hippocampus, and anterior cortex using quantitative Western blot analysis. Non-enriched HD mice have severe reductions in BDNF in the hippocampus and striatum at 5 months, which are entirely rescued by enrichment. BDNF levels are unaltered by HD in the anterior cortex, suggesting that enrichment might prevent HD-induced impairment of anterograde transport of this neurotrophin to the striatum. NGF is unaffected by HD. Nonenriched HD mice also exhibit deficits in dopamine and cAMP-regulated phosphoprotein (32 kDa) in striatum and anterior cortex. Environmental enrichment rescues the cortical but not the striatal deficit at 5 months. These results suggest that environmental enrichment benefits animals at early stages of the disease by rescuing protein deficits, possibly through rescuing transcription or protein transport problems.

show abstract

“…However, this cortical area has been demonstrated to exhibit hypometabolism in patients with HD, studied by a variety of noninvasive functional imaging methods (31). Similarly, neuropathological studies have highlighted this area as one exhibiting prominent neurite pathology in this disease (32,33).…”

Section: Discussionmentioning

confidence: 99%

Nonapoptotic neurodegeneration in a transgenic mouse model of Huntington's disease

Turmaine

Raza²,

Mahal³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

392

266

View full text Add to dashboard Cite

Huntington's disease (HD) is a fatal inherited neurodegenerative disorder characterized by personality changes, motor impairment, and subcortical dementia. HD is one of a number of diseases caused by expression of an expanded polyglutamine repeat. We have developed several lines of mice that are transgenic for exon 1 of the HD gene containing an expanded CAG sequence. These mice exhibit a defined neurological phenotype along with neuronal changes that are pathognomonic for the disease. We have previously observed the appearance of neuronal intranuclear inclusions, but did not find evidence for neurodegeneration. In this study, we report that all lines of these mice develop a late onset neurodegeneration within the anterior cingulate cortex, dorsal striatum, and of the Purkinje neurons of the cerebellum. Dying neurons characteristically exhibit neuronal intranuclear inclusions, condensation of both the cytoplasm and nucleus, and ruffling of the plasma membrane while maintaining ultrastructural preservation of cellular organelles. These cells do not develop blebbing of the nucleus or cytoplasm, apoptotic bodies, or fragmentation of DNA. Neuronal death occurs over a period of weeks not hours. We also find degenerating cells of similar appearance within these same regions in brains of patients who had died with HD. We therefore suggest that the mechanism of neuronal cell death in both HD and a transgenic mouse model of HD is neither by apoptosis nor by necrosis.

show abstract

Paralimbic frontal lobe hypometabolism in depression associated with Huntington's disease

Cited by 182 publications

References 0 publications

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

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

Environmental Enrichment Rescues Protein Deficits in a Mouse Model of Huntington's Disease, Indicating a Possible Disease Mechanism

Nonapoptotic neurodegeneration in a transgenic mouse model of Huntington's disease

Contact Info

Product

Resources

About