Abstract:
:We conducted a systematic review and meta-analysis of randomized controlled trials that compared second-generation antipsychotic (SGA) drugs with placebo in schizophrenic patients and which considered 13 different outcome measures. Thirty-eight randomized controlled trials with 7323 participants were included. All SGA drugs were more effective than placebo, but the pooled effect size (ES) for overall symptoms (primary outcome) was moderate (-0.51). The absolute difference (RD) in responder rates was at 18% (41% responded to drug compared with 24% to placebo, number needed to treat=6). Similar ESs were found for the other efficacy parameters: negative symptoms (ES=-0.39), positive symptoms (ES=-0.48), depression (ES=-0.26), relapse (RD 20%) and discontinuation due to inefficacy (RD 17%). Curiously, the efficacy of haloperidol for negative and depressive symptoms was similar to that of the SGA drugs. In contrast to haloperidol, there was no difference in terms of EPS between any SGA drugs and placebo, and there was also no difference in terms of dropouts due to adverse events. Meta-regression showed a decline in treatment response over time, and a funnel plot suggested the possibility of publication bias. We conclude that the drug versus placebo difference of SGA drugs and haloperidol in recent trials was moderate, and that there is much room for more efficacious compounds. Whether methodological issues account in part for the relatively low efficacy ESs and the scarcity of adverse event differences compared with placebo needs to be established.
journal_name
Mol Psychiatryjournal_title
Molecular psychiatryauthors
Leucht S,Arbter D,Engel RR,Kissling W,Davis JMdoi
10.1038/sj.mp.4002136subject
Has Abstractpub_date
2009-04-01 00:00:00pages
429-47issue
4eissn
1359-4184issn
1476-5578pii
4002136journal_volume
14pub_type
杂志文章,meta分析,评审abstract::The G-protein coupled metabotropic glutamate receptors (GRMs/mGluRs) have been implicated in the aetiology of schizophrenia as they modulate the NMDA response and that of other neurotransmitters including dopamine and GABA.(1-3) Electrophysiological studies in GRM subtype 5 knockout mice reveal, in one study, a sensor...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4000848
更新日期:2001-05-01 00:00:00
abstract::After psychological trauma, recurrent intrusive visual memories may be distressing and disruptive. Preventive interventions post trauma are lacking. Here we test a behavioural intervention after real-life trauma derived from cognitive neuroscience. We hypothesized that intrusive memories would be significantly reduced...
journal_title:Molecular psychiatry
pub_type: 杂志文章,随机对照试验
doi:10.1038/mp.2017.23
更新日期:2018-03-01 00:00:00
abstract::With the fast advance of connectome imaging techniques, we have the opportunity of mapping the human brain pathways in vivo at unprecedented resolution. In this article we review the current developments of diffusion magnetic resonance imaging (MRI) for the reconstruction of anatomical pathways in connectome studies. ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2017.92
更新日期:2017-09-01 00:00:00
abstract::Identifying biomarkers in schizophrenia during the first episode without the confounding effects of treatment has been challenging. Leveraging these biomarkers to establish diagnosis and make individualized predictions of future treatment responses to antipsychotics would be of great value, but there has been limited ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-018-0106-5
更新日期:2020-04-01 00:00:00
abstract::This corrects the article DOI: 10.1038/mp.2016.107. ...
journal_title:Molecular psychiatry
pub_type: 杂志文章,已发布勘误
doi:10.1038/mp.2017.203
更新日期:2018-01-01 00:00:00
abstract::Several lines of evidence have suggested altered functions of the brain-derived neurotrophic factor (BDNF) in the pathogenesis of neurodegenerative diseases including Alzheimer's disease (AD). In the search for polymorphisms in the 5'-flanking and 5'-noncoding regions of the BDNF gene, we found a novel nucleotide subs...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4000792
更新日期:2001-01-01 00:00:00
abstract::It is believed that genetic factors play a large role in the development of many cognitive and neurological processes; however, epidemiological evidence for the genetic basis of childhood neurodevelopment is very limited. Identification of the genetic polymorphisms associated with early-stage neurodevelopment will hel...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-018-0205-3
更新日期:2020-11-01 00:00:00
abstract::Among the most consistent results of studies of post-mortem brain tissue from schizophrenia patients (SZP) is the finding that in this disease, several genes expressed by GABAergic neurons are downregulated. This downregulation may be caused by hypermethylation of the relevant promoters in affected neurons. Indeed, in...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001954
更新日期:2007-04-01 00:00:00
abstract::A common polymorphism of the gene encoding acyl-coenzyme A: cholesterol acyltransferase 1 (SOAT1), which is involved in the regulation of beta-amyloid peptide generation, is associated with low brain amyloid load (P=0.03) and with low cerebrospinal fluid levels of cholesterol (P=0.005). This polymorphism of SOAT1 is a...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001296
更新日期:2003-06-01 00:00:00
abstract::Serotonergic (5HT) neurons exert diverse and widespread functions in the brain. Dysfunction of the serotonergic system gives rise to a variety of mental illnesses including depression, anxiety, obsessive compulsive disorder, autism and eating disorders. Here we show that human primary fibroblasts were directly convert...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2015.101
更新日期:2016-01-01 00:00:00
abstract::Posttranscriptional regulation of gene expression plays an important role in the maturation, transport, stability and translation of coding and noncoding RNAs. RNA-binding protein (RBP) is a key factor of the regulation. Regulator of calcineurin 1 (RCAN1) is a multifunctional protein involved in neurodegeneration, mit...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-019-0487-0
更新日期:2019-08-27 00:00:00
abstract::Although schizophrenia is generally considered to occur as a consequence of multiple genes that interact with one another, very few methods have been developed to model epistasis. Phenotype definition has also been a major challenge for research on the genetics of schizophrenia. In this report, we use novel statistica...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2011.108
更新日期:2012-11-01 00:00:00
abstract::We endeavored to identify objective blood biomarkers for pain, a subjective sensation with a biological basis, using a stepwise discovery, prioritization, validation, and testing in independent cohorts design. We studied psychiatric patients, a high risk group for co-morbid pain disorders and increased perception of p...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-018-0345-5
更新日期:2019-04-01 00:00:00
abstract::Translin-associated protein X (TRAX) is a scaffold protein with various functions and has been associated with mental illnesses, including schizophrenia. We have previously demonstrated that TRAX interacts with a Gsα protein-coupled receptor, the A2A adenosine receptor (A2AR), and mediates the function of this recepto...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-017-0007-z
更新日期:2018-12-01 00:00:00
abstract::The glutamate hypothesis of schizophrenia derived from evidence that phencyclidine, a noncompetitive N-methyl-D-aspartate (NMDA) antagonist, produces schizophrenia-like symptoms in healthy humans. Sensorimotor gating, measured by prepulse inhibition (PPI), is a fundamental form of information processing that is defici...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001404
更新日期:2004-01-01 00:00:00
abstract::Although few studies dispute that there are gender differences in depression, the etiology is still unknown. In this review, we cover a number of proposed factors and the evidences for and against these factors that may account for gender differences in depression. These include the possible role of estrogens at puber...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:10.1038/mp.2009.94
更新日期:2010-01-01 00:00:00
abstract::Microdeletions of chromosomal region 2q23.1 that disrupt MBD5 (methyl-CpG-binding domain protein 5) contribute to a spectrum of neurodevelopmental phenotypes; however, the impact of this locus on human psychopathology has not been fully explored. To characterize the structural variation landscape of MBD5 disruptions a...
journal_title:Molecular psychiatry
pub_type: 杂志文章,多中心研究
doi:10.1038/mp.2013.42
更新日期:2014-03-01 00:00:00
abstract::Previous studies suggested that risk for Autism Spectrum Disorder (ASD) may be increased in children exposed to antidepressants during the prenatal period. The disease specificity of this risk has not been addressed and the possibility of confounding has not been excluded. Children with ASD or attention-deficit hypera...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2014.90
更新日期:2015-06-01 00:00:00
abstract::Converging advances in the fields of molecular biology, molecular genetics, cellular biology and embryology have given researchers the tools for the targeted delivery and stable germline transmission of foreign genes (transgenes) in the mouse. In the realm of neuropsychiatry, this so-named transgenic technology has be...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:
更新日期:1996-05-01 00:00:00
abstract::An increase in corticotropin-releasing factor (CRF) is a putative factor in the pathophysiology of stress-related disorders. As CRF expression in the central nucleus of the amygdala (CeA) is important in adaptation to chronic stress, we hypothesized that unrestrained synthesis of CRF in CeA would mimic the consequence...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2008.91
更新日期:2009-01-01 00:00:00
abstract::The serotonergic neurons of the dorsal raphe (DR) nucleus in the CNS are involved in fear, anxiety and depression. Depression and anxiety occur quite frequently in postmenopausal women, but estrogen replacement to correct these CNS disorders is at present not favored because estrogen carries with it an increased risk ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2012.62
更新日期:2013-06-01 00:00:00
abstract::The hippocampus is critical to healthy cognition, yet results in the current study show that action video game players have reduced grey matter within the hippocampus. A subsequent randomised longitudinal training experiment demonstrated that first-person shooting games reduce grey matter within the hippocampus in par...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2017.155
更新日期:2018-07-01 00:00:00
abstract::The urocortin (Ucn) family of neuropeptides is suggested to be involved in homeostatic coping mechanisms of the central stress response through the activation of corticotropin-releasing factor receptor type 2 (CRFR2). The neuropeptides, Ucn1 and Ucn2, serve as endogenous ligands for the CRFR2, which is highly expresse...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2009.115
更新日期:2010-04-01 00:00:00
abstract::APAF1, encoding the protein apoptosis protease activating factor 1 (Apaf-1), has recently been established as a chromosome 12 gene conferring predisposition to major depression in humans. The molecular phenotypes of Apaf-1 variants were determined by in vitro reconstruction of the apoptosome complex in which Apaf-1 ac...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001755
更新日期:2006-01-01 00:00:00
abstract::Positron emission tomography (PET) studies suggest opioidergic system dysfunction in morbid obesity, while evidence for the role of the dopaminergic system is less consistent. Whether opioid dysfunction represents a state or trait in obesity remains unresolved, but could be assessed in obese subjects undergoing weight...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2015.153
更新日期:2016-08-01 00:00:00
abstract::We conducted a 10 centimorgan (cM) linkage genome scan in a set of American extended pedigrees ascertained through probands with panic disorder. Several anxiety disorders segregate in these families. In this article, we describe results for simple phobia from 14 of these families (including 129 subjects of whom 57 are...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001224
更新日期:2003-01-01 00:00:00
abstract::Familial and twin studies have suggested that anorexia nervosa (AN) is a multifactorial disorder with a substantial genetic contribution. The hSKCa3 potassium channel gene, which contains polymorphic CAG repeats in the coding region and is involved in the regulation of neuronal activity, may be a candidate gene for AN...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4000931
更新日期:2002-01-01 00:00:00
abstract::Stress and exposure to glucocorticoids (GC) during early life render individuals vulnerable to brain disorders by inducing structural and chemical alterations in specific neural substrates. Here we show that adult rats that had been exposed to in utero GCs (iuGC) display increased preference for opiates and ethanol, a...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2011.126
更新日期:2012-12-01 00:00:00
abstract::Previous studies have implicated DTNBP1 as a schizophrenia susceptibility gene and its encoded protein, dysbindin, as a potential regulator of synaptic vesicle physiology. In this study, we found that endogenous levels of the dysbindin protein in the mouse brain are developmentally regulated, with higher levels observ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2009.58
更新日期:2010-02-01 00:00:00
abstract::Acetylcholinesterase (AChE), the enzyme involved in the hydrolysis of the neurotransmitter acetylcholine, has been implicated in non-cholinergic actions which may play a role in neurodegenerative diseases such as Alzheimer's disease. To study the potential cytotoxicity of brain AChE, the effects of affinity purified A...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4000383
更新日期:1998-05-01 00:00:00