Abstract:
BACKGROUND:Postmortem brain studies have shown that HDAC1-a lysine deacetylase with broad activity against histones and nonhistone proteins-is frequently expressed at increased levels in prefrontal cortex (PFC) of subjects diagnosed with schizophrenia and related disease. However, it remains unclear whether upregulated expression of Hdac1 in the PFC could affect cognition and behavior. METHODS:Using adeno-associated virus, an Hdac1 transgene was expressed in young adult mouse PFC, followed by behavioral assays for working and long-term memory, repetitive activity, and response to novelty. Prefrontal cortex transcriptomes were profiled by microarray. Antipsychotic drug effects were explored in mice treated for 21 days with haloperidol or clozapine. RESULTS:Hdac1 overexpression in PFC neurons and astrocytes resulted in robust impairments in working memory, increased repetitive behaviors, and abnormal locomotor response profiles in novel environments. Long-term memory remained intact. Over 300 transcripts showed subtle but significant changes in Hdac1-overexpressing PFC. Major histocompatibility complex class II (MHC II)-related transcripts, including HLA-DQA1/H2-Aa, HLA-DQB1/H2-Ab1, and HLA-DRB1/H2-Eb1, located in the chromosome 6p21.3-22.1 schizophrenia and bipolar disorder risk locus, were among the subset of genes with a more robust (>1.5-fold) downregulation in expression. Hdac1 levels declined during the course of normal PFC development. Antipsychotic drug treatment, including the atypical clozapine, did not affect Hdac1 levels in PFC but induced expression of multiple MHC II transcripts. CONCLUSIONS:Excessive HDAC1 activity, due to developmental defects or other factors, is associated with behavioral alterations and dysregulated expression of MHC II and other gene transcripts in the PFC.
journal_name
Biol Psychiatryjournal_title
Biological psychiatryauthors
Jakovcevski M,Bharadwaj R,Straubhaar J,Gao G,Gavin DP,Jakovcevski I,Mitchell AC,Akbarian Sdoi
10.1016/j.biopsych.2013.03.020subject
Has Abstractpub_date
2013-11-01 00:00:00pages
696-705issue
9eissn
0006-3223issn
1873-2402pii
S0006-3223(13)00299-0journal_volume
74pub_type
杂志文章abstract:BACKGROUND:Acute ketamine has been shown to model features of schizophrenia such as psychotic symptoms, cognitive deficits and smooth pursuit eye movement dysfunction. There have been suggestions that chronic ketamine may also produce an analogue of the disorder. In this study, we investigated the effect of persistent ...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2008.10.045
更新日期:2009-06-15 00:00:00
abstract::Animal models of social isolation have been suggested to be relevant to several neuropsychiatric disorders; however, social isolation is usually not purely an alteration of social environment, as it often involves such factors as decreased complexity of the environment, loss of tactile stimulation, and increased metab...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(95)00546-3
更新日期:1996-11-01 00:00:00
abstract::The intuitive association between self-focused rumination in major depressive disorder (MDD) and the self-referential operations performed by the brain's default-mode network (DMN) has prompted interest in examining the role of the DMN in MDD. In this article, we present meta-analytic findings showing reliably increas...
journal_title:Biological psychiatry
pub_type: 杂志文章,评审
doi:10.1016/j.biopsych.2015.02.020
更新日期:2015-08-15 00:00:00
abstract::This review describes the strategy of using elementary phenotypes for neurobiological and genetic linkage studies of schizophrenia. The review concentrates on practical aspects of selecting the phenotype and then understanding the confounds in its measurement and interpretation. Examples from the authors' studies of d...
journal_title:Biological psychiatry
pub_type: 杂志文章,评审
doi:10.1016/s0006-3223(99)00085-2
更新日期:1999-07-01 00:00:00
abstract:BACKGROUND:Neurobiologic abnormalities in the thalamus have been implicated in the pathophysiology of obsessive-compulsive disorder. We recently reported increased thalamic volume in treatment-naive pediatric obsessive-compulsive disorder patients versus case-matched healthy comparison subjects that decreased to levels...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0006-3223(00)00902-1
更新日期:2000-08-15 00:00:00
abstract:BACKGROUND:Volumetric imaging research has shown abnormal brain morphology in adults with posttraumatic stress disorder (PTSD) when compared with matched control subjects. In this article, we present brain imaging findings from a study of children with PTSD symptoms. METHODS:Twenty-four children between the ages of 7 ...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/s0006-3223(01)01218-5
更新日期:2001-12-15 00:00:00
abstract:BACKGROUND:Studies in elderly patients demonstrate antipsychotic efficacy and favorable safety profiles for olanzapine. We report results from two placebo-controlled, double-blind studies of olanzapine for treatment of dopamimetic drug-induced psychosis in patients with Parkinson's disease (PD). METHODS:Patients were ...
journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/s0006-3223(02)01392-6
更新日期:2002-09-01 00:00:00
abstract::Patients with chronic hypercortisolemia due to Cushing's syndrome (CS) exhibit cognitive dysfunction. Because glucocorticoid excess is associated with hippocampal damage in animals, and the hippocampus participates in learning and memory, we explored the relationships between hippocampal formation (HF) volume, memory ...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(92)90079-f
更新日期:1992-11-01 00:00:00
abstract::N,N-Dimethyltryptamine (DMT) was given (ip) in different doses (0.25, 0.5, 1.0, 2.0, 4.0, 8.0 mg/kg) in a randomized order to a group of ten rats (Fisher 344/Mai) who were trained to a high, stable base line of conditioned avoidance responding in the shuttlebox. DMT produced dose-dependent disruptive effects, as a sig...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:
更新日期:1977-06-01 00:00:00
abstract::Previous studies have shown an association between low serum cholesterol concentration and suicide; however, conflicting results have also been reported. To examine this potential association, cholesterol levels in 99 patients admitted to an emergency ward following an attempted suicide were compared with those in 74 ...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/S0006-3223(95)00672-9
更新日期:1997-01-15 00:00:00
abstract::The effects of thyrotropin-releasing hormone (TRH) administration on electroconvulsive therapy (ECT)-induced prolactin (PRL) secretion and the duration of the seizure were studied in 14 depressed women. In a balanced order crossover design the patients were given 0.4 mg TRH or placebo intravenously 20 min before ECT d...
journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/0006-3223(95)00198-0
更新日期:1996-03-15 00:00:00
abstract::Tourette syndrome (TS) is thought to involve dopaminergic disturbances, but the nature of those disturbances remains controversial. Existing hypotheses suggest that TS involves 1) supersensitive dopamine receptors, 2) overactive dopamine transporters that cause low tonic but high phasic dopamine, 3) presynaptic dysfun...
journal_title:Biological psychiatry
pub_type: 杂志文章,评审
doi:10.1016/j.biopsych.2018.02.1172
更新日期:2018-09-01 00:00:00
abstract::Previous studies suggest that catecholaminergic overactivity and structural brain damage may contribute to the pathogenesis of tardive dyskinesia (TD). Although dopaminergic (DA) mechanisms, specifically postsynaptic receptor supersensitivity, have been extensively studied, equally plausible noradrenergic (NE) changes...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(86)90245-3
更新日期:1986-07-01 00:00:00
abstract::Several studies have demonstrated that the great majority of Alzheimer's disease (AD) patients suffer "noncognitive" neuropsychiatric symptoms. Depression is one of the most frequent neuropsychiatric comorbidities of AD. Affecting up to 50% of AD patients, depression in AD is associated with serious negative consequen...
journal_title:Biological psychiatry
pub_type: 杂志文章,评审
doi:10.1016/s0006-3223(03)00543-2
更新日期:2003-08-01 00:00:00
abstract::This study evaluated electrophysiological (EEG, ERGs), and cognitive (neuropsychological testing) responses in patients with late luteal phase dysphoric disorder (LLPDD, DSM-III-R) and controls over the menstrual cycle. In both groups, the frequency and stability of electroencephalogram (EEG) alpha activity significan...
journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章
doi:10.1016/0006-3223(95)00183-2
更新日期:1996-04-15 00:00:00
abstract::Research published in the past decade that used quantitative indices to evaluate the waking EEG characteristics of depressed patients is reviewed. Methodological problems that make results of different research laboratories difficult to compare include diagnostic heterogeneity of depressed groups, lack of inclusion of...
journal_title:Biological psychiatry
pub_type: 杂志文章,评审
doi:10.1016/0006-3223(90)90591-o
更新日期:1990-04-01 00:00:00
abstract:BACKGROUND:Binge eating and other forms of disordered eating behavior (DEB) are associated with failed inhibitory control. This study investigated the neural correlates of failed inhibitory control as a potential biomarker for DEB. METHODS:The study used prospective longitudinal data from the European IMAGEN study ado...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2019.01.027
更新日期:2019-06-01 00:00:00
abstract:BACKGROUND:In food-restricted rats, leptin suppresses semistarvation-induced hyperactivity (SIH) and decreases exploratory behavior. Leptin ameliorates anxiety-related movement in ob/ob mice. In this study, we assessed the relationship between leptin and qualities of physical activity and restlessness in acute anorexia...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2005.11.001
更新日期:2006-08-01 00:00:00
abstract:BACKGROUND:Suicide is a major risk for those with bipolar disorder, a risk amplified by comorbid substance abuse in some, but not all, previous studies. To further explore the relationships of substance abuse, suicide, and bipolarity as they present in clinical practice, we analyzed standardized clinical data from a la...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2004.10.003
更新日期:2004-11-15 00:00:00
abstract:BACKGROUND:Increased physical activity is a common feature of anorexia nervosa (AN). Although high activity levels are associated with greater risk of developing AN, particularly when combined with dieting, most individuals who diet and exercise maintain a healthy body weight. It is unclear why some individuals develop...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2020.06.030
更新日期:2020-07-16 00:00:00
abstract:BACKGROUND:Our previous work has shown genetic variation in the human choline transporter gene (CHT1) to be associated with depressive symptoms and autonomic cardiac (cholinergic) dysregulation. Here, functional magnetic resonance imaging (fMRI) was used to examine the relation between a single nucleotide polymorphism ...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2006.03.059
更新日期:2006-11-15 00:00:00
abstract::Direct current potentials measured on the scalp suprajacent to the midline prefrontal cortex appear to monitor the metabolic activity, via CO2 production, of this portion of the cerebrum. Changes in the frontal potential 90 min after oral administration of 2.0 g L-tryptophan and of 50 mg cortisol were studied in group...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:
更新日期:1976-08-01 00:00:00
abstract::To date, there has been little investigation of the neurobiological basis of emotion processing abnormalities in psychiatric populations. We have previously discussed two neural systems: 1) a ventral system, including the amygdala, insula, ventral striatum, ventral anterior cingulate gyrus, and prefrontal cortex, for ...
journal_title:Biological psychiatry
pub_type: 杂志文章,评审
doi:10.1016/s0006-3223(03)00171-9
更新日期:2003-09-01 00:00:00
abstract:BACKGROUND:Difficulty with impulse control is heightened in children with a family history of alcohol use disorders and is a risk factor for later substance problems. Cross-sectional functional magnetic resonance imaging studies have shown altered impulse control processing in adolescents with a positive family history...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2014.03.005
更新日期:2014-11-01 00:00:00
abstract::The relationship between plasma kynurenine (KYN) concentration and anxiety and depression in psychiatric patients was examined. KYN has been reported as a probable endogenous anxiogen in animal models of anxiety. Thirty patients with affective states were studied. The Hamilton Anxiety Scale (HAM-A), Hamilton Depressio...
journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章
doi:10.1016/0006-3223(94)91189-4
更新日期:1994-07-15 00:00:00
abstract:BACKGROUND:Preclinical and clinical evidence indicate that the glutamatergic system might play a role in the pathophysiology of mood disorders. This study was conducted to determine the efficacy and safety of riluzole, a glutamate-modulating agent, in bipolar depression. METHODS:This was an 8-week add-on study of rilu...
journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章
doi:10.1016/j.biopsych.2004.11.023
更新日期:2005-02-15 00:00:00
abstract::In order to evaluate the impact of aging on EEG sleep patterns we investigated the polysomnograms of 74 patients with major depression and 51 healthy volunteers aged 18-65 years. In most of the EEG sleep parameters, age-related changes were obvious in both the depressives and the normals. In the patients, some of thes...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(91)90355-p
更新日期:1991-05-15 00:00:00
abstract:BACKGROUND:Several studies have reported elevated S100B serum levels in schizophrenia. Our study focused on its scavenger, soluble receptor for advanced glycation end products (sRAGE). Given the benefits of sRAGE in metabolic and inflammatory diseases, we hypothesized a similar effect in schizophrenia. METHODS:S100B a...
journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2008.10.044
更新日期:2009-06-15 00:00:00
abstract:BACKGROUND:Impulsive aggression in patients with personality disorders is associated with diminished levels of cerebrospinal fluid (CSF) 5-HIAA, blunted neuroendocrine responses to serotonergic agonists, and decreased glucose utilization in the prefrontal cortex. We tested the hypothesis that impulsive aggression in bo...
journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章
doi:10.1016/s0006-3223(99)00202-4
更新日期:2000-03-15 00:00:00
abstract::Cocaine can cause a variety of neuropsychiatric and neurobehavioral complications; however, it is uncertain whether cocaine causes persistent cerebral structural and neurochemical abnormalities in asymptomatic users. We studied 52 African-American men (26 human immunodeficiency virus-negative asymptomatic heavy cocain...
journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章
doi:10.1016/s0006-3223(97)00135-2
更新日期:1997-12-15 00:00:00