Abstract:
BACKGROUND:To develop a pharmacokinetic-pharmacodynamic (PK-PD) model using individual-level data of Positive and Negative Syndrome Scale (PANSS) total score to characterize the antipsychotic drug effect taking into account the placebo effect and dropout rate. In addition, a clinical utility (CU) criterion that describes the usefulness of a drug therapy was calculated using the efficacy of the drug and dropout rates. METHODS:Data from 12 clinical trials in schizophrenia patients was used to quantify the effects of the antipsychotic drugs (APs), namely, haloperidol, risperidone, olanzapine, ziprasidone and paliperidone. Compartmental PK models were used to describe the time course of plasma drug concentrations. The combination of an Emax and the Weibull model was used to describe the drug and placebo effects. The steady-state drug concentrations were assumed to be the drivers of the exposure-response relationship. An exponential model was utilized to identify the predictors of probability of dropout. Simulations were performed to check the predictability of the model, and to calculate the CU of the drugs based on PANSS scores and dropout rates. RESULTS:The maximal drug effect (E(max)) was highest for olanzapine whilst it was lowest for ziprasidone. Higher observed PANSS scores resulted in a greater likelihood of dropout. Taking into account the efficacy and the drop-out rate, all APs possessed a comparable CU at the therapeutic doses. The resulting PK-PD model parameters were used to compute the effective concentration and dose required to produce a clinically meaningful 30% drop in PANSS score from the baseline. CONCLUSIONS:The developed PK-PD model and the associated CU score allow the evaluation of the time course of the PANSS scores of the different APs and a proper comparison of their clinically relevant treatments effects.
journal_name
Schizophr Resjournal_title
Schizophrenia researchauthors
Pilla Reddy V,Kozielska M,Suleiman AA,Johnson M,Vermeulen A,Liu J,de Greef R,Groothuis GM,Danhof M,Proost JHdoi
10.1016/j.schres.2013.02.011subject
Has Abstractpub_date
2013-05-01 00:00:00pages
144-52issue
1-3eissn
0920-9964issn
1573-2509pii
S0920-9964(13)00103-5journal_volume
146pub_type
杂志文章abstract::The glutamatergic dysfunction hypothesis of schizophrenia implicates the genes involved in glutamatergic transmission as strong candidates for schizophrenia-susceptibility. Recent linkage and association studies have identified the glutamate receptor, ionotropic, delta 1 gene GRID1 on 10q22 as a strong candidate for s...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2007.03.007
更新日期:2007-07-01 00:00:00
abstract::The purpose of the study was to examine the relationship between social anxiety and social functioning in first episode psychosis, and to determine whether those with psychosis have any maladaptive or irrational beliefs regarding social situations. A sample of 60 first episode patients (41 males, 19 females) participa...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2005.01.001
更新日期:2005-07-15 00:00:00
abstract::The dopamine (DA) hypothesis of schizophrenia stated that increased DA activity is the primary cause of schizophrenia. Recently, even though increased DA activity is in fact involved in psychotic symptoms and antipsychotic drug response, it has become clear that decreased DA activity is present in remitted and chronic...
journal_title:Schizophrenia research
pub_type: 杂志文章,评审
doi:10.1016/0920-9964(91)90032-m
更新日期:1991-03-01 00:00:00
abstract:BACKGROUND:Gamma-aminobutyric acid (GABA) dysfunction and its consequent imbalance are implicated in the pathophysiology of schizophrenia. Reduced GABA production would lead to a disinhibition of glutamatergic neurons and subsequently cause a disruption of the modulation between GABAergic interneurons and glutamatergic...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2017.07.021
更新日期:2018-03-01 00:00:00
abstract::The Wisconsin Card Sorting Test (WCST) is a multifactorial and complex test, and it involves so many different kinds of functions that it is difficult to understand why patients fail. Capacity of 'working memory' is possibly involved in the WCST performance and is considered a relevant factor responsible for the schiz...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/S0920-9964(97)00090-X
更新日期:1997-10-17 00:00:00
abstract::The SELENBP1 gene previously was found to be up-regulated in microarray analysis of both peripheral blood cell and brain tissue samples from schizophrenia patients. Quantitative PCR analysis subsequently corroborated the altered expression of SELENBP1 in schizophrenia brain tissue samples from the Stanley Array Correc...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2009.06.011
更新日期:2009-09-01 00:00:00
abstract:BACKGROUND:Patients with psychotic disorders show impairments in the recognition of emotions in other people. These impairments have been associated with poor social functioning as measured by self-report questionnaires, clinical interviews and laboratory-based tests of social skills. The ecological validity of these t...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2012.10.003
更新日期:2012-12-01 00:00:00
abstract::Glutamate transporters facilitate the buffering, clearance and cycling of glutamate and play an important role in maintaining synaptic and extrasynaptic glutamate levels. Alterations in glutamate transporter expression may lead to abnormal glutamate neurotransmission contributing to the pathophysiology of schizophreni...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2012.12.019
更新日期:2013-03-01 00:00:00
abstract:BACKGROUND:Clozapine is the drug of choice for patients with unsatisfactory response to routine antipsychotic treatment. Polypharmacy is widely used among patients having clozapine-resistant schizophrenia, although no solid evidence exists for any effective augmentation therapy for this patient population. We aimed to ...
journal_title:Schizophrenia research
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.schres.2009.01.002
更新日期:2009-04-01 00:00:00
abstract::Social anhedonia is an important feature of schizophrenia and it is a promising indicator of schizotypy. Although social anhedonia is defined as an affective construct (less pleasure derived from social encounters), little is known about the emotional responsivity and expressivity of individuals with high levels of so...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2010.06.012
更新日期:2010-12-01 00:00:00
abstract::Numerous genetic and postmortem studies link N-methyl-d-aspartate receptor (NMDAR) dysfunction with schizophrenia, forming the basis of the popular glutamate hypothesis. Neuronal NMDAR abnormalities are consistently reported from both basic and clinical experiments, however, non-neuronal cells also contain NMDARs, and...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2020.10.004
更新日期:2020-11-11 00:00:00
abstract::There has been increasing interest in studying the impact of physical activity on the psychological and physical well-being and functioning in patients with first-episode psychosis. The exploration of factors which contribute to physical activity in psychosis may open up opportunities for improvement of functional out...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2013.08.034
更新日期:2013-11-01 00:00:00
abstract::Schizotypal personality disorder, a diagnosis defined partially in terms of a genetic relatedness to schizophrenia, has begun to receive extensive investigative study. While the exact etiologic relationship between schizotypal personality disorder and schizophrenia remains to be determined, three models have been cons...
journal_title:Schizophrenia research
pub_type:
doi:10.1016/s0920-9964(01)00363-2
更新日期:2002-03-01 00:00:00
abstract::Social dysfunction is a hallmark of schizophrenia. Social isolation may increase individuals' risk for psychotic symptom exacerbation and relapse. Monitoring and timely detection of shifts in social functioning are hampered by the limitations of traditional clinic-based assessment strategies. Ubiquitous mobile technol...
journal_title:Schizophrenia research
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.schres.2019.03.014
更新日期:2019-06-01 00:00:00
abstract:OBJECTIVE:This study sought to evaluate levels of insight and change in insight in subjects with schizophrenia and other major psychiatric disorders. This study also evaluated the relationship of insight to acute psychopathology. METHOD:One-hundred and eighty-seven subjects consecutively admitted to an acute care psyc...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/s0920-9964(99)00215-7
更新日期:2000-09-29 00:00:00
abstract::The right shift (RS) theory (Annett, M., 1972. The distribution of manual asymmetry. Br. J. Psychol. 63, 343-358; Annett, M., 1985. Left, Right, Hand and Brain: The Right Shift Theory. Lawrence Erlbaum, London) suggests that the typical pattern of human cerebral and manual asymmetries depends on a single gene (RS+) wh...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/s0920-9964(99)00072-9
更新日期:1999-10-19 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::The present study determined the minimal exposure time (i.e., critical stimulus duration (CSD) necessary for feature registration and recognition by normals and chronic schizophrenics. Our interest was whether the longer exposure times required by schizophrenics than by normals could be attributed to an inability of s...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/0920-9964(92)90049-b
更新日期:1992-07-01 00:00:00
abstract::Negative symptoms can be grouped into the two dimensions of diminished expression and apathy, which have been shown to be dissociable regarding external validators, such as functional outcome. Here, we investigated whether these two dimensions differentially relate to neurocognitive impairment in schizophrenia. 47 pat...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2015.10.032
更新日期:2015-12-01 00:00:00
abstract::Individuals diagnosed with schizophrenia spectrum disorders have significant neuropsychological deficits that have been linked to poor functional outcome. As more treatments are developed and implemented for cognitive impairments, it will be important to consider whether people with schizophrenia have insight into the...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2008.07.007
更新日期:2008-10-01 00:00:00
abstract::Recently, apolipoprotein D (apoD), a protein that is involved in the essential polyunsaturated fatty acid (EPUFA) transport and metabolism, and neuronal growth and regeneration was reported to have increased in the postmortem brain and decreased in the serum of schizophrenia patients. We studied the plasma apoD levels...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/s0920-9964(01)00378-4
更新日期:2002-11-01 00:00:00
abstract::Mental illness stigma may contribute to suicidality and is associated with social isolation and low self-esteem among young people at risk of psychosis. However, it is unclear whether mental illness stigma contributes to suicidality in this population. We therefore examined the associations of self-labeling and stigma...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2016.01.048
更新日期:2016-04-01 00:00:00
abstract::Schizoaffective patients can have neurocognitive deficits and default mode network dysfunction while being acutely ill. It remains unclear to what extent these abnormalities persist when they go into clinical remission. Memory and executive function were tested in 22 acutely ill schizoaffective patients; they also und...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2014.08.017
更新日期:2014-11-01 00:00:00
abstract:OBJECTIVE:The diagnosis of psychotic disorder is associated with a risk of violence. Psychotic-like experiences (PLEs) in the general population may share an etiological background with psychotic disorders. The present study has evaluated the association between PLEs and violent behavior in adolescents. METHODS:PLEs a...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2010.08.028
更新日期:2011-03-01 00:00:00
abstract:BACKGROUND:Recent research has identified impairment in processing speed, measured by the digit-symbol substitution task, as central to the cognitive deficit in schizophrenia. However, the underlying cognitive correlates of this impairment remain unknown. METHODS:A sample of cases (N=125) meeting DSM-IV criteria for s...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2012.08.020
更新日期:2012-12-01 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::Neuroanatomical abnormalities are considered to be related to the pathogenesis of schizophrenia. Reversal or reduction of normal structural cerebral asymmetries in schizophrenia is particularly striking. The current study investigated the alteration of gray matter volume and cerebral asymmetry in early stage of first-...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2013.05.021
更新日期:2013-08-01 00:00:00
abstract::Schizophrenia is a severe psychiatric disorder with lifetime prevalence of ~1% worldwide. A genotyping study was conducted using a custom panel of Illumina 1536 SNPs in 840 schizophrenia cases and 876 controls (351 patients and 385 controls from North India; and 436 patients, 401 controls and 143 familial samples with...
journal_title:Schizophrenia research
pub_type: 杂志文章,meta分析
doi:10.1016/j.schres.2014.12.031
更新日期:2015-03-01 00:00:00
abstract::Patients with schizophrenia and bipolar disorder (BD) shared a significant overlap in genetic susceptibility, pharmacological treatment responses, neuropsychological deficits, and epidemiological features. However, it remains unknown whether these clinical overlaps are mediated by shared or disorder-specific abnormali...
journal_title:Schizophrenia research
pub_type: 杂志文章,meta分析
doi:10.1016/j.schres.2017.01.005
更新日期:2017-07-01 00:00:00
abstract:OBJECTIVE:Following encouraging results in the early detection of psychotic disorders, interest in the early detection of affective, especially bipolar disorders, has recently been renewed. However, the differentiation between affective disorders with and without psychotic features is often missing, although it has bee...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2012.04.001
更新日期:2012-07-01 00:00:00