Abstract:
BACKGROUND:A novel, high-affinity (.7-2.0 nmol) compound that selectively activates the alpha2, alpha 3, and alpha 5 (but not alpha1) gamma-aminobutyric acid-A (GABA(A)) receptor subtypes, TPA023B (2',6-difluoro-5'-[3-(1-hydroxy-1-methylethyl) imidazo[1,2-b][1,2,4]triazin-7-yl][1,1'-biphenyl]-2-carbonitrile) was pharmacologically characterized and studied by means of positron emission tomography (PET) to determine dynamic occupancies of the benzodiazepine binding site of human brain GABA(A) receptors after a single oral dose. METHODS:Four healthy male volunteers were studied in a double-blind, randomized placebo-controlled study of which three were given a single dose of 1.5 mg TPA023B and the fourth received placebo. The time course of GABA(A) receptor occupancy was determined with multiple dynamic [(11)C]flumazenil PET studies at pre-dose baseline and 5 and 24 hours after dose. Arterial sampling and full kinetic modeling with a two-compartment model was used to calculate parametric maps of receptor availability (distribution volume V(T)) and of occupancy. RESULTS:The GABA(A) receptor occupancy as determined from [(11)C]flumazenil V(T) values in all brain regions was reduced homogeneously, on average by 52.5 +/- 1.2% after 5 hours and 46.4 +/- 6.0% after 24 hours. No serious adverse events were encountered in humans. CONCLUSIONS:Single oral doses of 1.5 mg of TPA023B correspond to average receptor occupancies in neocortical regions of 52% and 46% after 5 and 24 hours, respectively. Provided suitable ligands and quantification methods are available for the appropriate target, quantitative PET offers a unique tool for dynamic in vivo measurement of relevant on-site receptor occupancy.
journal_name
Biol Psychiatryjournal_title
Biological psychiatryauthors
Van Laere K,Bormans G,Sanabria-Bohórquez SM,de Groot T,Dupont P,De Lepeleire I,de Hoon J,Mortelmans L,Hargreaves RJ,Atack JR,Burns HDdoi
10.1016/j.biopsych.2008.01.021subject
Has Abstractpub_date
2008-07-15 00:00:00pages
153-61issue
2eissn
0006-3223issn
1873-2402pii
S0006-3223(08)00133-9journal_volume
64pub_type
杂志文章,随机对照试验abstract:BACKGROUND:This multicenter, randomized, fixed-dose, double-blind, placebo-controlled study evaluated efficacy of extended-release dexmethylphenidate (d-MPH-ER) in adults with attention-deficit/hyperactivity disorder (ADHD). METHODS:Randomized adults with ADHD (n=221) received once-daily d-MPH-ER 20 mg, 30 mg, or 40 m...
journal_title:Biological psychiatry
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.biopsych.2006.07.032
更新日期:2007-06-15 00:00:00
abstract::This article demonstrates methods by which receiver operating characteristics (ROC) analysis may be used to evaluate and improve the Dexamethasone Suppression Test (DST). ROC indices provide a description of nonbinary diagnostic tests that is independent of any particular cutoff and that allows investigators to use ri...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(89)90160-1
更新日期:1989-01-15 00:00:00
abstract::Stable schizophrenic and schizoaffective outpatients underwent abrupt withdrawal from a fixed dose of neuroleptic. Prolactin concentrations were determined preceding and following drug withdrawal. Basal prolactin concentrations were significantly lower 3, 4, or 5 days following drug withdrawal than on subsequent days....
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(89)90016-4
更新日期:1989-06-01 00:00:00
abstract::Posttraumatic stress disorder (PTSD) is a stress-related psychiatric disorder that is thought to emerge from complex interactions among traumatic events and multiple genetic factors. Epigenetic regulation lies at the heart of these interactions and mediates the lasting effects of the environment on gene regulation. An...
journal_title:Biological psychiatry
pub_type: 杂志文章,评审
doi:10.1016/j.biopsych.2015.04.003
更新日期:2015-09-01 00:00:00
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 struc...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2010.11.010
更新日期:2011-05-15 00:00:00
abstract:BACKGROUND:Benzodiazepines modulate γ-aminobutyric acid type A (GABA(A)) receptors throughout the brain. However, it is not fully understood which brain regions within anxiety-related brain circuits are really responsible for their anxiolytic effects and how these regions interact. METHODS:We investigated whether the ...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2012.09.004
更新日期:2013-02-15 00:00:00
abstract:BACKGROUND:Posttraumatic stress disorder (PTSD) is marked by intrusive, chronic, and distressing memories of highly emotional events. Previous research has highlighted the role of the amygdala and its interactions with the hippocampus in mediating the effect of enhanced memory for emotional information in healthy indiv...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2010.07.018
更新日期:2010-12-01 00:00:00
abstract:BACKGROUND:Schizophrenics show deficits in sensorimotor gating, as measured by prepulse inhibition of acoustic startle (PPI). The goal of this investigation is to further characterize PPI and habituation deficits in schizophrenia, and to examine whether differing subgroups of schizophrenics would show comparable PPI de...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0006-3223(99)00148-1
更新日期:2000-04-01 00:00:00
abstract::Cell lines of continuously dividing human olfactory neuroblasts can be propagated using olfactory epithelium obtained from human donors at biopsy or autopsy. The expression of neuronal proteins in these cells, such as neurofilament protein and tau protein, can be increased using a combination of factors including nerv...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(93)90051-e
更新日期:1993-12-15 00:00:00
abstract::Specific electroencephalogram (EEG) changes during clozapine therapy were prospectively studied in a cohort of 50 chronic state hospital patients with schizophrenia who were randomly assigned to one of three nonoverlapping clozapine serum level ranges (50-150 ng/mL, 200-300 ng/mL, and 350-450 ng/mL). EEGs were obtaine...
journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/S0006-3223(96)00298-3
更新日期:1997-07-15 00:00:00
abstract::Conditioned responses to drug-related cues appear to be related to the maintenance of stimulant addiction. These conditioned responses are not blocked by treatments that block the direct effects of stimulants and may contribute to the high rate of relapse of addicts. Rats administered (+)-amphetamine in a specific env...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(92)90159-w
更新日期:1992-06-01 00:00:00
abstract::Drugs with antidepressant properties in patients with severe depression also have various behavioral and neurochemical effects in animals. This has given rise to numerous animal models that have been suggested to be valid for research into the neurobiology of depression and the neurochemical mechanisms of the antidepr...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(85)90156-8
更新日期:1985-07-01 00:00:00
abstract::Ten pedigrees systematically ascertained in Germany were tested for linkage to chromosome 5q11-q13. In order to replicate the previous report by Sherrington et al (1988), families with a bipolar family member were omitted from the lod score calculations, all diagnoses were based upon Research Diagnostic Criteria, and ...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(92)90008-n
更新日期:1992-01-01 00:00:00
abstract:BACKGROUND:Working memory impairments are commonly found in attention-deficit/hyperactivity disorder (ADHD) and often improve with psychostimulant treatment. Little is known about how these medications affect the function of frontoparietal brain regions engaged for working memory. This study used functional magnetic re...
journal_title:Biological psychiatry
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.biopsych.2011.11.011
更新日期:2012-03-01 00:00:00
abstract::The volume of the entorhinal region is significantly reduced in postmortem brains of schizophrenics compared with controls (p less than 0.017). In addition, a significant reduction of neurons (p less than 0.017), but no significant increase in absolute glial cell numbers, is found. These results are consistent with th...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(88)90162-x
更新日期:1988-09-01 00:00:00
abstract:BACKGROUND:Fear learning in stressful situations is highly adaptive for survival by steering behavior in subsequent situations, but fear learning can become disproportionate in vulnerable individuals. Despite the potential clinical significance, the mechanism by which stress modulates fear learning is poorly understood...
journal_title:Biological psychiatry
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.biopsych.2015.02.014
更新日期:2015-12-15 00:00:00
abstract:BACKGROUND:Few studies have examined the involvement of the central dopaminergic system in the pathophysiology of mood disorders. The study of prolactin (PRL) secretion may be an informative indirect method for the assessment of the dopaminergic system in children with major depressive disorder (MDD). METHODS:Plasma P...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0006-3223(99)00005-0
更新日期:1999-08-15 00:00:00
abstract:BACKGROUND:Current neuroimaging perspectives on a variety of mental disorders emphasize dysfunction of the amygdala. The neuropeptide oxytocin (OXT), a key mediator in the regulation of social cognition and behavior, accumulates in cerebrospinal fluid after intranasal administration in macaques and humans and modulates...
journal_title:Biological psychiatry
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.biopsych.2017.04.015
更新日期:2017-12-15 00:00:00
abstract::It has been proposed that the nailfold subpapillary plexus visibility score (PVS) may be a marker of susceptibility to schizophrenia. To further investigate this hypothesis, we evaluated plexus visibility in a sample of 61 chronic schizophrenics, a large sample of first-episode psychotic patients and their first-degre...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(92)90231-n
更新日期:1992-02-15 00:00:00
abstract:BACKGROUND:Structural MRI data indicate schizophrenics have reduced left-sided temporal lobe gray matter volumes, especially in the superior temporal gyrus (STG) and medial temporal lobe. Our data further suggest a specificity to schizophrenia spectrum disorders of STG volume reduction. Interpretation of research studi...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0006-3223(99)00030-x
更新日期:1999-06-01 00:00:00
abstract:BACKGROUND:Cerebral myeloarchitecture shows substantial development across childhood and adolescence, and aberrations in these trajectories are relevant for a range of mental disorders. Differential myelination between intracortical and subjacent white matter can be approximated using signal intensities in T1-weighted ...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2018.09.027
更新日期:2019-03-01 00:00:00
abstract:BACKGROUND:It is widely considered that exposure to maternal cigarette smoking in pregnancy has risk effects on offspring attention-deficit/hyperactivity disorder (ADHD). This view is supported by consistent observations of association. It is, however, impossible to be certain of adequate control for confounding factor...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2009.05.032
更新日期:2009-10-15 00:00:00
abstract:BACKGROUND:Prenatal inflammatory mechanisms may play a role in the pathogenesis of psychiatric disorders and could be relevant for attention-deficit/hyperactivity disorder (ADHD). We investigated maternal chronic somatic diseases with immune components as possible risk factors for ADHD in offspring. METHODS:We perform...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2015.11.024
更新日期:2017-03-01 00:00:00
abstract:BACKGROUND:Attention-deficit/hyperactivity disorder (ADHD) is the most common psychiatric disorder of childhood, with average worldwide prevalence of 5.3%, varying by region. METHODS:We assessed the relationship between the prevalence of ADHD and solar intensity (SI) (kilowatt hours/square meters/day) on the basis of ...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2013.02.010
更新日期:2013-10-15 00:00:00
abstract:BACKGROUND:Intracellular deposition of tau protein is a hallmark lesion of Alzheimer's disease. Although it is known this event is secondary to excessive tau phosphorylation, the mechanisms involved remain unknown. We previously reported that the enzyme 5-Lipoxygenase (5LO) acts as a modulator of Aβ peptides formation ...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2012.12.012
更新日期:2013-09-01 00:00:00
abstract:BACKGROUND:Sleep disturbance is associated with activation of systemic and cellular inflammation, as well as proinflammatory transcriptional profiles in circulating leukocytes. Whether treatments that target insomnia-related complaints might reverse these markers of inflammation in older adults with insomnia is not kno...
journal_title:Biological psychiatry
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.biopsych.2015.01.010
更新日期:2015-11-15 00:00:00
abstract:BACKGROUND:Fatigue is highly prevalent and causes serious disruption in quality of life. Although the underlying biological mechanism is unknown, increases in inflammation have been implicated. This prospective study examined the association between C-reactive protein (CRP), a biomarker of systemic inflammation, and fa...
journal_title:Biological psychiatry
pub_type: 杂志文章,多中心研究
doi:10.1016/j.biopsych.2009.06.008
更新日期:2009-11-01 00:00:00
abstract::Twenty psychiatric patients on lithium medication were examined with 7-Li-magnetic resonance spectroscopy of the brain. Patients on long-term lithium treatment (> 6 months) were compared with a short-term group who had been taking lithium for between 4 and 8 weeks. Patients met DSM-III-R criteria for either recurrent ...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/S0006-3223(96)00330-7
更新日期:1997-04-15 00:00:00
abstract::Short-term reduction in plasma tryptophan (tryptophan depletion) produces a relapse of depressive symptoms in 60% of previously depressed patients recently recovered with serotonin reuptake inhibitor treatment. Tryptophan depletion does not consistently increase depressive symptoms in unmedicated depressed patients or...
journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/S0006-3223(96)00224-7
更新日期:1997-05-01 00:00:00
abstract:BACKGROUND:Experimental animal studies suggest that early glucocorticoid exposure may have lasting effects on the neurodevelopment of the offspring; animal studies also suggest that this effect may be eliminated by positive postnatal rearing. The relevance of these findings to humans is not known. METHODS:We prospecti...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2010.01.002
更新日期:2010-06-01 00:00:00