Abstract:
BACKGROUND:There is increasing evidence that antipsychotic (APD) may affect brain structure directly. To examine this, we developed a rodent model that uses clinically relevant doses and serial magnetic resonance imaging (MRI), followed by postmortem histopathological analysis to study the effects of APD on brain structures. METHODS:Antipsychotic , haloperidol, and olanzapine were continuously administered to rats via osmotic minipumps to maintain clinic-like steady state levels for 8 weeks. Longitudinal in vivo MRI scanning (T₂-weighted) was carried out at baseline, 4 weeks, and 8 weeks, after which animals were perfused and their brains preserved for ex vivo MRI scanning. Region of interest analyses were performed on magnetic resonance images (both in vivo as well as ex vivo) along with postmortem stereology using the Cavalieri estimator probe. RESULTS:Chronic (8 weeks) exposure to both haloperidol and olanzapine resulted in significant decreases in whole-brain volume (6% to 8%) compared with vehicle-treated control subjects, driven mainly by a decrease in frontal cerebral cortex volume (8% to 12%). Hippocampal, corpus striatum, lateral ventricles, and corpus callosum volumes were not significantly different from control subjects, suggesting a differential effect of APD on the cortex. These results were corroborated by ex vivo MRI scans and decreased cortical volume was confirmed postmortem by stereology. CONCLUSIONS:This is the first systematic whole-brain MRI study of the effects of APD, which highlights significant effects on the cortex. Although caution needs to be exerted when extrapolating results from animals to patients, the approach provides a tractable method for linking in vivo MRI findings to their histopathological origins.
journal_name
Biol Psychiatryjournal_title
Biological psychiatryauthors
Vernon AC,Natesan S,Modo M,Kapur Sdoi
10.1016/j.biopsych.2010.11.010subject
Has Abstractpub_date
2011-05-15 00:00:00pages
936-44issue
10eissn
0006-3223issn
1873-2402pii
S0006-3223(10)01171-6journal_volume
69pub_type
杂志文章abstract::Reduced platelet MAO activity has been previously reported as a biochemical marker for a subgroup of psychiatric patients, including some chronic schizophrenics. As tryptamine metabolism appears to be sensitive to alterations in MAO activity, urinary tryptamine excretion was measured in chronic schizophrenics with low...
journal_title:Biological psychiatry
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journal_title:Biological psychiatry
pub_type: 杂志文章,评审
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2009.02.030
更新日期:2009-07-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2015.03.032
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journal_title:Biological psychiatry
pub_type: 杂志文章
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journal_title:Biological psychiatry
pub_type: 杂志文章
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更新日期:1983-04-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2013.10.012
更新日期:2014-05-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:
更新日期:1982-11-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0006-3223(03)00114-8
更新日期:2003-06-15 00:00:00
abstract:BACKGROUND:QTc interval prolongation can occur as a result of treatment with both conventional and novel antipsychotic medications and is of clinical concern because of its association with the potentially fatal ventricular arrhythmia, torsade de pointes. METHODS:One case is described in which a patient with schizophr...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0006-3223(01)01333-6
更新日期:2002-02-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2011.05.029
更新日期:2011-11-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/0006-3223(88)90022-4
更新日期:1988-03-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2020.06.007
更新日期:2020-06-13 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.biopsych.2012.01.008
更新日期:2012-04-15 00:00:00
abstract::The male bias in autism spectrum disorder incidence is among the most extreme of all neuropsychiatric disorders, yet the origins of the sex difference remain obscure. Developmentally, males are exposed to high levels of testosterone and its byproduct, estradiol. Together these steroids modify the course of brain devel...
journal_title:Biological psychiatry
pub_type: 杂志文章,评审
doi:10.1016/j.biopsych.2016.10.004
更新日期:2017-03-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2006.07.024
更新日期:2007-08-15 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2019.02.006
更新日期:2019-06-15 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0006-3223(97)00476-9
更新日期:1998-12-01 00:00:00
abstract::Male hooded rats were observed for 6 days following implantation with slow-release subcutaneous pellets containing LSD, mescaline, or control vehicle solution. In animals housed in isolation cages, continuous hallucinogen administration resulted in a gradual increase in head twitches and catatonic postures which peake...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:
更新日期:1980-02-01 00:00:00
abstract::Rhesus mother-infant pairs were housed in a playpen apparatus beginning just before the birth of four male infants. The infants were separated from their mothers four times beginning at a mean age of 218 days. In Type A separations (I and IV) the infants were removed and housed away from their familiar environment in ...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:
更新日期:1975-12-01 00:00:00
abstract:BACKGROUND:Obsessive-compulsive disorder (OCD) and tic disorders have phenomenological and familial-genetic overlaps. An OCD family study sample that excludes Tourette's syndrome in probands is used to examine whether tic disorders are part of the familial phenotype of OCD. METHODS:Eighty case and 73 control probands ...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0006-3223(01)01074-5
更新日期:2001-10-15 00:00:00
abstract:BACKGROUND:A parallel downregulation of brain-derived neurotrophic factor (BDNF) and somatostatin (SST), a marker of inhibitory gamma-aminobutyric acid interneurons that target pyramidal cell dendrites, has been reported in several brain areas of subjects with major depressive disorder (MDD). Rodent genetic studies sug...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2018.09.026
更新日期:2019-03-15 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0006-3223(98)00138-3
更新日期:1998-07-15 00:00:00
abstract::Cerebrospinal fluid concentrations of corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH) and somatostatin (SRIF) were measured in 77 female inpatients with moderate to extreme dementia and in 17 elderly female controls. Both multi-infarct (MID) and Alzheimer-type (SDAT) demented patients had eq...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(92)90132-j
更新日期:1992-09-01 00:00:00
abstract:BACKGROUND:Identifying trait markers specific to schizophrenia might uncover mechanisms underlying illness susceptibility. Previous research shows the N2 and P3 event-related potentials are abnormal in schizophrenia; specificity of these potential trait markers has not been well established. METHODS:Electroencephalogr...
journal_title:Biological psychiatry
pub_type: 杂志文章,多中心研究
doi:10.1016/j.biopsych.2007.09.018
更新日期:2008-04-15 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2003.12.015
更新日期:2004-04-15 00:00:00