Go to ... Help | Logoff

Accession Number

BACD199900010618

Author/Editor/Inventor

Ongur Dost. Drevets Wayne C. Price Joseph L [a].

Institution

[a] Dep. Anatomy Neurobiol., Washington Univ. Sch. Med., 660 South Euclid
Ave., St. Louis, MO 63110 USA.

Title

Glial reduction in the subgenual prefrontal cortex in mood disorders.

Source

Proceedings of the National Academy of Sciences of the United States of
America. 95(22). Oct. 27, 1998. 13290-13295.

Abstract

Mood disorders are among the most common neuropsychiatric illnesses, yet little is known about their neurobiology. Recent neuroimaging studies have found that the volume of the subgenual part of Brodmann's area 24 (sg24) is reduced in familial forms of major depressive disorder (MDD) and bipolar disorder (BD). In this histological study, we used unbiased stereological techniques to examine the cellular composition of area sg24 in two different sets of brains. There was no change in the number or size of neurons in area sg24 in mood disorders. In contrast, the numbers of glia were reduced markedly in both MDD and BD. The reduction in glial number was most prominent in subgroups of subjects with familial MDD (24%, P = 0.01) or BD (41%, P = 0.01). The glial reduction in subjects without a clear family history was lower in magnitude and not statistically significant. Consistent with neuroimaging findings, cortical volume was reduced in area sg24 in subjects with familial mood disorders. Schizophrenic brains studied as psychiatric controls had normal neuronal and glial numbers and cortical volume. Glial and neuronal numbers also were counted in area 3b of the somatosensory cortex in the same group of brains and were normal in all psychiatric groups. Glia affect several processes, including regulation of extracellular potassium, glucose storage and metabolism, and glutamate uptake, all of which are crucial for normal neuronal activity. We thus have identified a biological marker associated with familial mood disorders that may provide important clues regarding the pathogenesis of these common psychiatric conditions.

Accession Number

BIOA199800325569

Author/Editor/Inventor

Drevets W C [a]. Ongur D. Price J L.

Institution

[a] B 938, Presbyterian Univ. Hosp., Univ. Pittsburgh Med. Cent., 200
Lothrop St., Pittsburgh, PA 15213 USA.

Title

Neuroimaging abnormalities in the subgenual prefrontal cortex: Implications
for the pathophysiology of familial mood disorders.

Source

Molecular Psychiatry. 3(3). May, 1998. 220-226.

Abstract

The prefrontal cortex (PFC) ventral to the genu of the corpus callosum has been implicated in the modulation of visceral responses to stressful and emotionally provocative stimuli, based upon analysis of lesion effects involving this area in humans and experimental animals. In a recent magnetic resonance imaging (MRI) study of familial mood disorders, we demonstrated that the mean grey matter volume of this cortex is abnormally reduced in subjects with major depressive disorder (MDD) and bipolar disorder, irrespective of their treatment status or current mood state. Moreover, in preliminary histopathological assessments of subgenual PFC tissue taken post mortem from subjects with MDD and bipolar disorder we obtained results suggesting that this decrement in grey matter volume is associated with a reduction in glia without an equivalent loss of neurons. The potential functional significance of these neuroimaging and microscopic abnormalities is discussed with respect to evidence that subgenual PFC dysfunction may disturb stress-related autonomic and neuroendocrine responses and reward-related mesolimbic dopamine function. These data may thus hold important implications for the development of neural models of mood disorders that can account for the abnormal hedonic, motivational, neuroendocrine, and autonomic manifestations evident in these idiopathic conditions.

Accession Number

BIOA199799555989

Author/Editor/Inventor

Drevets Wayne C [a]. Price Joseph L. Simpson Joseph R, Jr. Todd Richard D. Reich Theodore. Vannier Michael. Raichle Marcus E.

Institution

[a] Dep. Psychiatry, Division Radiol. Sci., Mallinckrodt Inst. Radiol.,
Washington Univ. Sch. Med., St. Louis, MO 63110 USA.

Title

Subgenual prefrontal cortex abnormalities in mood disorders.

Source

Nature (London). 386(6627). 1997. 824-827.

Abstract

Pathological disturbances of mood may follow a 'bipolar' course, in which normal moods alternate with both depression and mania, or a 'unipolar' course, in which only depression occurs. Both bipolar and unipolar disorders can be heritable illnesses associated with neurochemical, neuroendocrine and autonomic abnormalities. The neurobiological basis for these abnormalities has not been established'. Using positron emission tomographic (PET) images of cerebral blood flow and rate of glucose metabolism to measure brain activity, we have now localized an area of abnormally decreased activity in the prefrontal cortex ventral to the genu of the corpus callosum in both familial bipolar depressives and familial unipolar depressives. This decrement in activity was at least partly explained by a corresponding reduction in cortical volume, as magnetic resonance imaging (MRI) demonstrated reductions in the mean grey matter volume in the same area of 39 and 48% in the bipolar and unipolar samples, respectively. This region has previously been implicated in the mediation of emotional and autonomic responses to socially significant or provocative stimuli, and in the modulation of the neurotransmitter systems targeted by antidepressant drugs.

Accession Number

BIOA199598148641

Author/Editor/Inventor

Drevets Wayne C [a]. Burton Harold. Videen Tom O. Snyder Abraham Z. Simpson Joseph R, Jr. Raichle Marcus E.

Institution

[a] Div. Radiation Sci., Mallinckrodt Inst. Radiol., Washington Univ. Sch.
Med., St. Louis, MO 63110 USA.

Title

Blood flow changes in human somatosensory cortex during anticipated
stimulation.

Source

Nature (London). 373(6511). 1995. 249-252.

Abstract

Positron emission tomography (PET) measurements of brain blood flow were used to monitor changes in the human primary and secondary somatosensory cortices during the period when somatosensory stimuli were expected. In anticipation of either focal or innocuous touching, or localized, painful shocks, blood flow decreased in parts of the primary somatosensory cortex map located outside the representation of the skin area that was the target of the expected stimulus. Specifically, attending to an impending stimulus to the fingers produced a significant decrease in blood flow in the somatosensory zones for the face, whereas attending to stimulation of the toe produced decreases in the zones for the fingers and face. Decreases were more prominent in the side ipsilateral to the location of the expected stimulus. No significant changes in blood flow occurred in the region of the cortex representing the skin locus of the awaited stimulation. These results are concurrent with a model of spatial attention in which potential signal enhancement may rely on generalized suppression of background activity.

Accession Number

BIOA199598038748

Author/Editor/Inventor

Drevets Wayne C.

Institution

Dep. Psychiatry, Washington Univ. Sch. Med., 4940 Children's Place, Box 8134,
St. Louis, MO 63110-1093, USA.

Title

Geriatric depression: Brain imaging correlates and pharmacologic
considerations.

Source

Journal of Clinical Psychiatry. 55(9 SUPPL. A). 1994. 71-81.

Abstract

The clinical approach to geriatric major depression involves a variety of special etiopathophysiologic, pharmacokinetic, and pharmacodynamic considerations. In regard to pathophysiology, modern brain imaging and postmortem assessments are elucidating neuropathologic changes in elderly depressives that challenge the notion that geriatric depression is simply a functional brain disorder. These data suggest (but do not yet establish) that many patients who experience depression onset at a late age may acquire affective disease on an arteriosclerotic basis. In contrast, elderly depressives who experience depression onset at an early age are more likely to have acquired depression due to genetic factors but may nevertheless develop degenerative neuropathologic changes over time. The presence of these neuropathologic changes appears to increase elderly patients' risk for developing the adverse central nervous system (CNS) effects of antidepressant treatments. They thereby add another level of complexity to the management of an age group in which pharmacokinetic and pharmacodynamic changes already contribute to the likelihood of adverse drug reactions. Fortunately, the last decade of antidepressant drug development has produced several new agents (including the scrotonin selective reuptake inhibitors and more recently, venlafaxine and nefazodone) with substantially reduced CNS and cardiovascular toxicity that facilitate effective treatment of geriatric depression.

Accession Number

BIOA199396081829

Author/Editor/Inventor

Moss Lori E. Neppe Vernon M. Drevets Wayne C [a].

Institution

[a] Washington Univ. Sch. Med., Dep. Psychiatry, 4940 Audubon Ave., St.
Louis, MO 63110 USA.

Title

Buspirone in the treatment of tardive dyskinesia.

Source

Journal of Clinical Psychopharmacology. 13(3). 1993. 204-209.

Abstract

Eight patients with mild to severe tardive dyskinesia (TD) were treated for 12 weeks with buspirone in dosages of up to 180 mg/day in an open-label study. Changes in TD severity were assessed by the Abnormal Involuntary Movement Scale. The rater was blind to buspirone dosage. Buspirone was well tolerated by most subjects. A within-subjects comparison of pretreatment and post-treatment Abnormal Involuntary Movement Scale scores revealed a mean improvement of 4.4 (p lt 0.01). Improvement was also observed in neuroleptic-induced extrapyramidal side effects such as parkinsonism and akathisia. Scores on the Hamilton Rating Scale for Anxiety and the Brief Psychiatric Rating Scale did not change during the 12-week study. The results of this open-label pilot study suggest that relatively high doses of buspirone may be efficacious in the treatment of TD.

Accession Number

094137008

Authors

Drevets W C. Videen T O. Price J L. Preskorn S H. Carmichael S T. Raichle M E.

Institution

DEP. PSYCHIATRY, WASHINGTON UNIV. SCH. MED., 4940 AUDUBON, ST. LOUIS, MO.
63110.

Title

A FUNCTIONAL ANATOMICAL STUDY OF UNIPOLAR DEPRESSION.

Source

Journal of Neuroscience 12 (9). 1992. 3628-3641.

Abstract

The functional neuroanatomy of unipolar major depression was investigated using positron emission tomography to measure differences in regional cerebral blood flow (BF). A relatively homogeneous subject group was obtained using criteria for familial pure depressive disease (FPDD), which are based upon family history as well as upon symptoms and course. Because of the absence of certain knowledge about the pathophysiology of mood disorders and their underlying functional neuroanatomy, we used data obtained from the subtraction of composite images from one-half of depressed and control subjects to identify candidate regions of interest. The major cortical region defined in this manner was statistically tested on a second set of subjects. Using this strategy, we found increased BF in an area that extended from the left ventrolateral prefrontal cortex onto the medial prefrontal cortical surface. Based upon the connectivity between these portions of the prefrontal cortex and the amygdala and evidence that the amygdala is involved in emotional modulation, activity was measured in the left amygdala and found to be significantly increased in the depressed group. A separate group of subjects with FPDD who were currently asymptomatic were also imaged to determine whether these findings represented abnormalities associated with the depressed state, or with a trait difference that might underlie the tendency to become depressed. Only the depressed group had increased activity in the left prefrontal cortex, suggesting that this abnormality represents a state marker of FPDD. Both the depressed and the remitted groups demonstrated increased activity in the left amygdala, though this difference achieved significance only in the depressed group. This suggests that the abnormality involving the left amygdala may represent a trait marker of FPDD, though further assessment in a larger sample size is necessary to establish this. These data along with other evidence suggest that a circuit involving the prefrontal cortex, amygdala, and related parts of the striatum, pallidum, and medial thalamus is involved in the functional neuroanatomy of depression.