Abstract:
:Atypical antipsychotic drugs (AAPDs) are widely used in children and adolescents to treat a variety of psychiatric disorders. However, little is known about the long-term effects of AAPD treatment before the brain is fully developed. Indeed, we and others have previously reported that treatment of adolescent rats with olanzapine (OLA; a widely prescribed AAPD) on postnatal days 28-49, under dosing conditions that approximate those employed therapeutically in humans, causes long-term behavioral and neurobiological perturbations. We have begun to study the mechanisms of these effects. Dopamine (DA) and serotonin (5HT) regulate many neurodevelopmental processes. Currently approved AAPDs exert their therapeutic effects principally through their DAergic activities, although in schizophrenia (SZ) and some other diseases for which AAPDs are prescribed, DAergic dysfunction is accompanied by abnormalities of glutamatergic (GLUergic) and γ-aminobutyric acidergic (GABAergic) transmission. Here, we use proton magnetic resonance spectroscopy ((1)H MRS) to investigate the effects of adolescent OLA administration on GABA and GLU levels. We found that the treatment caused long-term reductions in the levels of both GLU and GABA in the nucleus accumbens (NAc) of adult rats treated with OLA during adolescence. The NAc is a key node in the brain's "reward" system, whose function is also disrupted in schizophrenia. Further research into potential, OLA-induced changes in the levels of GLU and GABA in the NAc and other brain areas, and the dynamics and mechanisms of those changes, are an essential step for devising new adjunct therapies for existing AAPDs and for designing new drugs that increase therapeutic effects and reduce long-term abnormalities when administered to pediatric patients.
journal_name
Schizophr Resjournal_title
Schizophrenia researchauthors
Xu S,Gullapalli RP,Frost DOdoi
10.1016/j.schres.2014.10.034subject
Has Abstractpub_date
2015-02-01 00:00:00pages
452-7issue
2-3eissn
0920-9964issn
1573-2509pii
S0920-9964(14)00603-3journal_volume
161pub_type
杂志文章abstract::The dopamine hypothesis of schizophrenia was formulated 30 years ago and postulates that the symptoms of schizophrenia are related to an increased central dopaminergic neurotransmission. The two fundamental assumptions that underlay the dopamine hypothesis of schizophrenia have received support from brain imaging stud...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/s0920-9964(97)00121-7
更新日期:1997-12-19 00:00:00
abstract::Abnormalities of cerebellar structure and function, long recognized as a hallmark of chronic alcohol abuse, have also occasionally been noted in patients with schizophrenia. We used a four-point rating scale to assess clinical signs of cerebellar dysfunction in men meeting DSM-IV criteria for schizophrenia (N=34) and ...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/s0920-9964(01)00300-0
更新日期:2002-10-01 00:00:00
abstract::Prospective, double-blind, randomized trials comparing atypical antipsychotic drugs (APDs) to typical APDs, such as haloperidol, indicate that atypical APDs provide a modest benefit to cognitive function in schizophrenia. However, the validity of this inference has been contested by suggestions that the cognitive impr...
journal_title:Schizophrenia research
pub_type: 杂志文章,meta分析
doi:10.1016/j.schres.2006.08.021
更新日期:2007-01-01 00:00:00
abstract::Around 1 in 5 children under 13 years old experience sub-clinical psychotic experiences (PEs) like hallucinations and delusions. While PEs in childhood are a significant risk factor for adult psychotic disorders, the majority of those experiencing childhood PEs do not develop a psychotic disorder. Individual differenc...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2019.08.022
更新日期:2020-01-01 00:00:00
abstract::Classifications of psychotic disorders are moving towards utilizing dimensional symptom domains as the preferred mechanism for describing psychotic symptomatology. The ICD-11 has proposed six symptom domains (Positive symptoms, Negative symptoms, Depressive symptoms, Manic symptoms, Psychomotor symptoms, and Cognitive...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2018.07.006
更新日期:2018-12-01 00:00:00
abstract::The aim of this study was to test the validity of the CHR state by focusing on the course of psychosis spectrum symptoms, depression and global functioning in converters and non-converters. A total of 188 CHR-positive subjects (60.2% men) aged between 13 and 35years (mean=20.5) at study outset were assessed five times...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2017.01.040
更新日期:2017-11-01 00:00:00
abstract::In 1873 Skeffington Lutwidge, a Lunacy Commission inspector of asylums in England, was killed by an asylum patient. Lutwidge was the uncle and close friend of Charles Lutwidge Dodgson, also known as Lewis Carroll. One year later, Carroll began writing The Hunting of the Snark, a poem whose meaning has mystified Carrol...
journal_title:Schizophrenia research
pub_type: 传,历史文章,杂志文章
doi:10.1016/j.schres.2014.10.001
更新日期:2014-12-01 00:00:00
abstract::Many neuropsychological studies have described deficits of memory and executive functions in patients with schizophrenia, and the severity of these deficits seems to be determinant in predicting the community outcome of these patients [Schizophr. Bull. 26 (2000) 119]. However, neuropsychological evaluation does not pr...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2003.07.005
更新日期:2004-08-01 00:00:00
abstract:BACKGROUND:A definition of clinical remission in schizophrenia has recently been proposed. However, it is also known that neuropsychological (NP) impairments may be better predictors of functional outcomes than clinical symptoms. Understanding the relationship between clinical remission and cognitive improvement may be...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2006.12.032
更新日期:2007-08-01 00:00:00
abstract::Glutamate cycling is critically important for neurotransmission, and may be altered in schizophrenia. The excitatory amino acid transporters (EAATs) facilitate the reuptake of glutamate from the synaptic cleft and have a key role in glutamate cycling. We hypothesized that expression of the EAATs and the EAAT regulatin...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2008.06.012
更新日期:2008-09-01 00:00:00
abstract::Prior studies of mRNA expression, protein expression, and pathway metabolite levels have implicated dysregulation of the kynurenine pathway in the etiology of schizophrenia and bipolar disorder. Here we investigate whether genes involved in kynurenine pathway regulation might interact with genes that respond to kynure...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2009.05.014
更新日期:2009-09-01 00:00:00
abstract::Eleven acutely psychotic patients with schizophrenia or schizoaffective disorder underwent a 5-7 day drug-washout period (with lorazepam allowed) prior to participating in a 6-week controlled dose haloperidol trial. Patients were evaluated longitudinally with clinical ratings and with plasma measures of the catecholam...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/0920-9964(93)90074-s
更新日期:1993-06-01 00:00:00
abstract::Few studies have been conducted examining cytokines in cerebrospinal fluid of patients compared to healthy volunteers. The goals of this study were: 1) to report original data detailing cytokine levels in the cerebrospinal fluid (CSF) of 10 patients with a schizophrenia spectrum disorder (SSD) diagnosis and 10 healthy...
journal_title:Schizophrenia research
pub_type: 杂志文章,meta分析
doi:10.1016/j.schres.2018.07.019
更新日期:2018-12-01 00:00:00
abstract:BACKGROUND:Despite the effectiveness of anti-psychotic pharmacotherapy, residual hallucinations and delusions do not completely resolve in some medicated patients. Additional cognitive behavioral therapy (CBT) seems to improve the management of positive symptoms. Despite promising results, the efficacy of CBT is still ...
journal_title:Schizophrenia research
pub_type: 杂志文章,meta分析
doi:10.1016/j.schres.2005.02.018
更新日期:2005-09-01 00:00:00
abstract:BACKGROUND:Pharmaceutical companies conduct clinical trials to show the efficacy and safety of new medications for the treatment of schizophrenia. After the new medications are marketed, clinicians treating patients with schizophrenia discover that a considerable number of patients do not respond to these new medicatio...
journal_title:Schizophrenia research
pub_type: 杂志文章,评审
doi:10.1016/j.schres.2017.03.020
更新日期:2017-12-01 00:00:00
abstract::Evidence validating the influence of the cytochrome P450 (CYP) 2D6 and 2C19 enzymes genetic polymorphisms in the response to antipsychotics is scarce. We examined the hypothesis that a higher prevalence of CYP2D6 and/or CYP2C19 ultra rapid metabolizers might be found among refractory schizophrenia patients. Three grou...
journal_title:Schizophrenia research
pub_type: 信件
doi:10.1016/j.schres.2015.08.002
更新日期:2015-10-01 00:00:00
abstract::The positive and negative syndrome scale (PANSS) is widely used in psychiatric research. Reflecting this common use, considerable attention has been applied to the psychometric properties of this instrument. However, despite the publication of numerous studies and analyses, it remains uncertain how best data from the ...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/s0920-9964(02)00295-5
更新日期:2003-05-01 00:00:00
abstract::Grey matter brain networks are disrupted in schizophrenia, but it is still unclear at which point during the development of the illness these disruptions arise and whether these can be associated with behavioural predictors of schizophrenia. We investigated if single-subject grey matter networks were disrupted in a sa...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2015.08.025
更新日期:2015-10-01 00:00:00
abstract::Long-stay patients constitute a small proportion of all patients with schizophrenia, but in both VA and state psychiatric systems these patients account for a majority of the costs associated with treatment of the illness. VA and state patients would be expected to differ in several respects, including age at onset an...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/s0920-9964(99)00182-6
更新日期:2000-05-25 00:00:00
abstract::Epidemiological studies often use age-of-first-admission from psychiatric case registers to estimate age-of-onset in schizophrenia. Retrospective, interview-based methods have shown that there is a delay between onset of symptoms and eventual contact with psychiatric services, and that this delay can vary both among i...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/0920-9964(95)00087-9
更新日期:1996-05-01 00:00:00
abstract:INTRODUCTION:Contextual factors representing chronic stressors, such as neighborhood crime characteristics, have been repeatedly linked to compromised mental and physical health, and may contribute to the pathologizing of normative/non-clinical experiences. However, the impact of such structural factors has seldom been...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2019.11.024
更新日期:2020-01-01 00:00:00
abstract::Schizophrenia is a multifactorial disease in both clinical and molecular terms. Thus, depicting the molecular aspects of the disease will contribute to the understanding of its biochemical mechanisms and consequently may lead to the development of new treatment strategies. The protein phosphorylation/dephosphorylation...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2016.03.022
更新日期:2016-11-01 00:00:00
abstract:BACKGROUND:In recent years, schizophrenia has increasingly been recognized as a neurocognitive disorder, which has led to a growing literature on cognitive rehabilitation, and suggested several potential enhancements to cognitive function. For instance, it has been shown that executive functioning deficits as measured ...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2008.08.005
更新日期:2008-12-01 00:00:00
abstract:BACKGROUND:Evidence indicating that symptoms of non-clinical psychosis (NCP) occur in 6-8% of the general population suggests that psychosis may occur across a continuum. Although a number of studies have examined environmental contributors, to date there have been few investigations of biological/genetic factors in th...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2012.06.018
更新日期:2012-09-01 00:00:00
abstract::Studies of neurocognitive function in patients with schizophrenia use widely variable assessment techniques. Clinical trials assessing the cognitive enhancing effect of new medications have used neurocognitive assessment batteries that differed in content, length and administration procedures. The Brief Assessment of ...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2003.09.011
更新日期:2004-06-01 00:00:00
abstract::Patients with schizophrenia did not take significantly more trials than normal controls to learn to use a visual warning signal to avoid a non-aversive stimulus on a simple computer-administered avoidance learning task. When the stimulus to be avoided was aversive (i.e., a loud buzzer), however, the schizophrenic grou...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/s0920-9964(98)00181-9
更新日期:1999-07-27 00:00:00
abstract::Speech deficits, notably those involved in psychomotor retardation, blunted affect, alogia and poverty of content of speech, are pronounced in a wide range of serious mental illnesses (e.g., schizophrenia, unipolar depression, bipolar disorders). The present project evaluated the degree to which these deficits manifes...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2014.10.032
更新日期:2014-12-01 00:00:00
abstract::Schizophrenia is characterized by increased mortality for which suicidality is the decisive factor. An analysis of cortical thickness and folding to further elucidate neuroanatomical correlates of suicidality in schizophrenia has not yet been performed. We searched for relevant brain regions with such differences betw...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2016.08.010
更新日期:2016-10-01 00:00:00
abstract::Omega-3 treatment studies for multi-episode schizophrenia or clinical high risk for conversion to psychosis states have had variable, and often negative, results. To examine adjunctive omega-3 treatment for recent onset psychosis, participants aged 15-40 years with recent onset schizophrenia-spectrum (n = 46) or bipol...
journal_title:Schizophrenia research
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.schres.2018.09.006
更新日期:2019-02-01 00:00:00
abstract::Elevated serum levels of Interleukin-3 (IL-3), a major component of the cytokines, have been observed in chronic and medicated patients with schizophrenia, but this elevation may reflect either or both medication and illness chronicity effects. Thus, we compared serum IL-3 levels in first-episode drug-naive (FEDN) to ...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2016.05.010
更新日期:2016-10-01 00:00:00