The Danish PET/depression project: PET findings in patients with major depression

Videbech, Poul; Ravnkilde, Barbara; Pedersen, Anya; Egander, A.; Landbo, B.; Rasmussen, N. A.; Andersen, Flemming; Stødkilde-Jørgensen, Hans; Gjedde, Albert; Rosenberg, Raben

doi:10.1017/s0033291701004469

Cited by 80 publications

(65 citation statements)

References 56 publications

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“…In fact, people with cerebellar lesions have displayed characteristics like passivity, blunting of emotion, and disinhibition of restraint similar to the depressed and manic states characteristic of mood disorders (Schmahmann and Sherman, 1998). Imaging studies suggest that a tonic increase in cerebellar activity is characteristic of major depression as determined by positron emission tomography (Videbech et al, 2001) and glucose utilization studies (Kimbrell et al, 2002). Accordingly, successful treatment of depression with venlafaxine has been associated with decreased blood flow to the cerebellum (Davies et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Postmortem Brain Tissue of Depressed Suicides Reveals Increased Gsα Localization in Lipid Raft Domains Where It Is Less Likely to Activate Adenylyl Cyclase

Donati¹,

Dwivedi²,

Roberts³

et al. 2008

J. Neurosci.

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Recent in vivo and in vitro studies have demonstrated that Gs␣ migrates from a Triton X-100 (TX-100)-insoluble membrane domain (lipid raft) to a TX-100-soluble nonraft membrane domain in response to chronic, but not acute, treatment with tricyclic or selective serotonin reuptake inhibitor antidepressants. This migration resulted in a more facile association with adenylyl cyclase. Our hypothesis is that Gs␣ may be ensconced, to a greater extent, in lipid rafts during depression, and that one action of chronic antidepressant treatment is to reverse this. In this postmortem study, we examined Gs␣ membrane localization in the cerebellum and prefrontal cortex of brains from nonpsychiatric control subjects and suicide cases with confirmed unipolar depression. Sequential TX-100 and TX-114 detergent extractions were performed on the brain tissue. In the cerebellum, the ratio of TX-100/TX-114-soluble Gs␣ is ϳ2:1 for control versus depressed suicides. Results with prefrontal cortex samples from each group demonstrate a similar trend. These data suggest that depression localizes Gs␣ to a membrane domain (lipid rafts) where it is less likely to couple to adenylyl cyclase and that antidepressants may upregulate Gs␣ signaling via disruption of membrane microenvironments. Raft localization of Gs␣ in human peripheral tissue may thus serve as a biomarker for depression and as a harbinger of antidepressant responsiveness.

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Section: Discussionmentioning

confidence: 99%

Postmortem Brain Tissue of Depressed Suicides Reveals Increased Gsα Localization in Lipid Raft Domains Where It Is Less Likely to Activate Adenylyl Cyclase

Donati¹,

Dwivedi²,

Roberts³

et al. 2008

J. Neurosci.

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“…Forty-six normal volunteers, mean age 41 AE 11X6 years (range 21±65 years, 16 males/30 females), participated in the study as part of a larger study dealing with affective disorders (Ravnkilde et al, 2001;Videbech et al, 2001aVidebech et al, , 2001bVidebech et al, , 2001c. The subjects were recruited by newspaper advertisement and had an average of 12X4 AE 2X4 years of education.…”

Section: Subjectsmentioning

confidence: 99%

“…All instructions and injections were given by the same two persons. Further details of imaging and statistical methods are described elsewhere (Videbech et al, 2001b).…”

Section: Imaging Proceduresmentioning

confidence: 99%

Putative Tests of Frontal Lobe Function: A PET-Study of Brain Activation During Stroop's Test and Verbal Fluency

Ravnkilde¹,

Videbech²,

Rosenberg³

et al. 2002

Journal of Clinical and Experimental Neuropsychology

107

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Stroop's test and the Verbal Fluency test are commonly argued to be measures of the integrity of the prefrontal cortex. This assumption has only to some degree been con®rmed by lesion studies. In the present study, Positron Emission Tomography (PET) with H 2 15O was used to further validate Stroop's test and the Verbal Fluency as measures of frontal lobe function; both tests were implemented as activation paradigms during scanning of normal middleaged individuals. Stroop interference was found to activate the left anterior cingulate cortex, the supplementary motor cortex, thalamus, and the cerebellum. Although the prominent anterior cingulate activation is in the frontal lobe, it is not prefrontal. Verbal Fluency activated the left inferior frontal cortex and the left dorsolateral prefrontal cortex, the supplementary motor cortex, the anterior cingulate cortex and the cerebellum. These results bring this latter test closer to being a speci®c test of prefrontal function.

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“…Sex differences in depressed populations, however, have not been the primary focus of clinical PET studies. Videbech et al (2001) reported significant sex differences in cerebral blood flow in the parietal lobe (and a trend for sex differences in the temporal lobe) for the entire sample of MDD patients and healthy controls (n ¼ 89, 42 patients including 12 males, 47 controls including 16 males). When regressing out the effects of sex and age, the research revealed increased blood flow to the hippocampus as the main finding in major depression, but no statistically significant correlations were found between any region and the Hamilton Depression Scale (HDS).…”

Section: Evidence For Sex Differencesmentioning

confidence: 96%

Using positron emission tomography to investigate hormone-mediated neurochemical changes across the female lifespan: implications for depression

Zsido

Villringer

Sacher

2017

International Review of Psychiatry

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Ovarian hormones, particularly oestrogen and progesterone, undergo major fluctuations across the female lifespan. These hormone transition periods, such as the transition from pregnancy to postpartum, as well as the transition into menopause (perimenopause), are also known to be times of elevated susceptibility to depression. This study reviews how these transition periods likely influence neurochemical changes in the brain that result in disease vulnerability. While there are known associations between oestrogen/progesterone and different monoaminergic systems, the interactions and their potential implications for mood disorders are relatively unknown. Positron Emission Tomography (PET) allows for the in-vivo quantification of such neurochemical changes, and, thus, can provide valuable insight into how both subtle and dramatic shifts in hormones contribute to the elevated rates of depression during pre-menstrual, post-partum, and perimenopausal periods in a woman's life. As one better understands how to address the challenges of PET studies involving highly vulnerable populations, such as women who have recently given birth, one will gain the insight necessary to design and individualize treatment and therapy. Understanding the precise time-line in younger women when dramatic fluctuations in the hormonal milieu may contribute to brain changes may present a powerful opportunity to intervene before a vulnerable state develops into a diseased state in later life. ARTICLE HISTORY

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The Danish PET/depression project: PET findings in patients with major depression

Abstract: Our main finding is increased blood flow to the hippocampus, even when controlling for a number of confounders. This is in accordance with a rapidly expanding literature suggesting an important role for this structure in major depression.

Cited by 80 publications

References 56 publications

Postmortem Brain Tissue of Depressed Suicides Reveals Increased Gsα Localization in Lipid Raft Domains Where It Is Less Likely to Activate Adenylyl Cyclase

Postmortem Brain Tissue of Depressed Suicides Reveals Increased Gsα Localization in Lipid Raft Domains Where It Is Less Likely to Activate Adenylyl Cyclase

Putative Tests of Frontal Lobe Function: A PET-Study of Brain Activation During Stroop's Test and Verbal Fluency

Using positron emission tomography to investigate hormone-mediated neurochemical changes across the female lifespan: implications for depression

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