Insight in schizophrenia: a meta-analysis

There has been an increase in the study of insight in schizophrenia in the last 20 years. Insight is operationally defined according to five dimensions which include: the patient's awareness of mental disorder, awareness of the social consequences of disorder, awareness of the need for treatment, awareness of symptoms and attribution of symptoms to disorder. Despite the development of psychometrically sound measurement tools, the results from previous studies have been inconclusive regarding the nature of the relationship between insight and symptomatology. A meta-analysis of 40 published English-language studies was conducted to determine the magnitude and direction of the relationship, or effect size, between insight and symptom domains in schizophrenia and to determine moderator variables that were associated with the variations in effect sizes across studies. Results indicated that there was a small negative relationship between insight and global, positive and negative symptoms. There was also a small positive relationship between insight and depressive symptoms in schizophrenia. Acute patient status and mean age of onset of the disorder moderated the relationship between insight and symptom clusters. The possible reasons for the effect sizes being modest, the examination of the role of moderator variables and directions for future research are provided.     

Mismatch negativity in schizophrenia: a meta-analysis

BACKGROUND: Mismatch negativity (MMN) is an auditory event-related potential that provides an index of automatic context-dependent information processing and auditory sensory memory. Many studies have reported abnormalities in the generation of MMN in schizophrenia. The objective of this study was to assess the magnitude of this deficit and associated factors. METHOD: Studies of MMN in schizophrenia were identified and included in a meta-analysis to estimate the mean effect size. Effects of duration of illness, gender ratio, age of patients, type of MMN (duration versus frequency MMN) and characteristics of the test paradigms (deviant probability, magnitude of standard-deviant difference) on effect size were assessed. RESULTS: Of 62 identified studies 32 met our inclusion criteria. The mean effect size was 0.99 (95% confidence intervals: 0.79, 1.29). Overall, no specific factor was significantly associated with MMN deficits, although MMN to stimuli differing in duration appeared more impaired in schizophrenia than MMN to frequency deviants. In addition, effect sizes of frequency MMN were significantly correlated with duration of illness. CONCLUSIONS: MMN deficits are a robust feature in chronic schizophrenia and indicate abnormalities in automatic context-dependent auditory information processing and auditory sensory memory in these patients. Reports of normal MMN in first-episode schizophrenia and the association of deficits in frequency MMN with illness duration suggest that MMN may index ongoing neuropathological changes in the auditory cortex in schizophrenia.     

Implicit memory in schizophrenia: a meta-analysis

ObjectivePrevious studies examining implicit memory in schizophrenia yielded inconsistent results. The present meta-analysis aimed at determining whether, compared to healthy controls, schizophrenic patients: (a) exhibited reduced priming in the whole set of studies; (b) were differentially impaired in conceptual/perceptual and production/identification tests; and (c) were less efficient in the use of semantic encoding processes.MethodA systematic search in PsycINFO and PubMed led to the selection of 22 critical studies (31 effect sizes), comparing repetition priming in 836 schizophrenic patients and 760 healthy controls. Moderators were assessed by classifying implicit tasks into the perceptual/conceptual and identification/production categories, and by distinguishing between perceptual and conceptual encoding instructions.ResultsOverall, implicit memory was slightly, but significantly, impaired in schizophrenia (d = 0.179). Patients exhibited reduced priming in conceptually-driven tasks (d = 0.447), but intact priming in perceptually-driven tasks (d = 0.080). No significant difference was observed between identification and production priming (d = 0.064 vs. d = 0.243). Finally, priming in schizophrenic patients was significantly lower than that of controls when the encoding task required the analysis of the conceptual properties of the stimuli (d = 0.261).ConclusionResults suggest that schizophrenia is associated with a specific deficit in the use of conceptual processes, both at encoding and at retrieval. In contrast with theoretical expectations, high levels of response competition did not disproportionately impair the patients' performance.     

Longitudinal studies of cognition in schizophrenia: meta-analysis

BACKGROUND: A wide range of cognitive deficits have been demonstrated in schizophrenia, but their longitudinal course remains unclear. AIMS: To bring together all the available information from longitudinal studies of cognitive performance in people with schizophrenia. METHOD: We carried out a meta-analysis of 53 studies. Unlike previous reviewers, we included all studies (regardless of the type of medication), analysed each variable separately and compared results with data from controls. RESULTS: Participants with schizophrenia showed a significant improvement in most cognitive tasks. The available data for controls showed, with one exception (the Stroop test), a similar or greater improvement. Performance in semantic verbal fluency remained stable in both individuals with schizophrenia and controls. CONCLUSIONS: Participants with schizophrenia displayed improvement in most cognitive tasks, but practice was more likely than cognitive remediation to account for most of the improvements observed. Semantic verbal fluency may be the best candidate cognitive endophenotype.     

Minor physical anomalies in schizophrenia: a meta-analysis

Numerous studies report an increased frequency of minor physical anomalies (MPAs) in schizophrenic individuals compared with controls. However, these studies vary considerably regarding the magnitude of the case-control disparity and the topographical distribution of the anomalies. A meta-analysis was carried out on the existing MPA literature in an effort to better understand the relationship between MPAs and schizophrenia. Following a literature search, 13 studies were identified that met our inclusion criteria. Mean total MPA scores were available for 11 of these studies, whereas only seven studies provided regional MPA scores. For both the total MPA and regional MPA analyses, pooled effect sizes (Hedges' g and pooled odds ratios, respectively) were calculated along with tests of heterogeneity. For the total MPA analyses, a meta-regression approach was used to explore the relationship between possible moderator variables (e.g., number of MPA scale items) and effect size heterogeneity. The magnitude of the pooled effect size for the total MPA scores was high (1.131; p<0.001), indicating significantly more overall MPAs in schizophrenic individuals. Significant effect size heterogeneity was present (p<0.001); however, this heterogeneity could not be explained by any of the included moderator variables. The regional MPA analysis revealed significantly increased MPAs in all six anatomical regions (p<0.05), although the pooled odds ratios for these regions did not differ significantly from one another. These results suggest a lack of regional specificity for MPAs in schizophrenia.     

P300 asymmetry in schizophrenia: a meta-analysis

P300 event-related brain potential (ERP) amplitude is smaller in patients with schizophrenia compared to unaffected controls, but whether left temporal component amplitude is also smaller is debated. The present study employed meta-analytical methods to quantitatively assess previous P300 schizophrenia asymmetry findings. All P300 articles on schizophrenia using an auditory oddball paradigm published before January 2000 were obtained by comprehensive literature searches and cross-referencing for related articles. A total of 19 original articles reporting complete midline electrode data and 11 articles reporting lateral asymmetry electrode data were reviewed, which included different independent conditions that yielded 50 independent data sets. P300 amplitude differences between patients with schizophrenia and control subjects from the midline electrodes yielded effect sizes that differed among recording sites, such that Fz was significantly smaller than Pz, with Cz effect sizes smaller than Pz but larger than Fz. Comparison of P300 amplitude from the lateral data for the T3 and T4 electrodes found no reliable effect size difference when these electrodes were analyzed separately. However, comparison of P300 amplitude effect sizes from the TCP1 was significantly larger than that from the TCP2 when these electrodes were analyzed separately. P300 amplitude is smaller overall in patients with schizophrenia compared to control subjects and differs in its effect size topography across the midline and temporal electrode sites, with the strongest effect sizes obtained for the Pz midline and TCP1 lateral electrodes.     

Memory impairment in schizophrenia: a meta-analysis.

OBJECTIVE: Memory impairment is well documented in schizophrenia. Less is known, however, about the exact magnitude, pattern, and extent of the impairment. The effect of potential moderator variables, such as medication status and duration of illness, is also unclear. In this article, the authors presented meta-analyses of the published literature on recall and recognition memory performance between patients with schizophrenia and normal comparison subjects. METHOD: Meta-analyses were conducted on 70 studies that reported measures of long-term memory (free recall, cued recall, and recognition of verbal and nonverbal material) and short-term memory (digit span). Tests of categorical models were used in analyses of potential moderators (clinical variables and study characteristics). RESULTS: The findings revealed a significant and stable association between schizophrenia and memory impairment. The composite effect size for recall performance was large. Recognition showed less, but still significant, impairment. The magnitude of memory impairment was not affected by age, medication, duration of illness, patient status, severity of psychopathology, or positive symptoms. Negative symptoms showed a small but significant relation with memory impairment. CONCLUSIONS: This meta-analysis documented significant memory impairment in schizophrenia. The impairment was stable, wide ranging, and not substantially affected by potential moderating factors such as severity of psychopathology and duration of illness.     

精神分裂症患者血浆同型半胱氨酸水平的Meta分析

目的 探讨精神分裂症患者与健康者血浆同型半胱氨酸(homocysteine,Hcy)水平的差异,为预防精神分裂症提供依据.方法 计算机检索PubMed、EMbase、Cochrane Library、万方数据库、中国知网全文数据库、维普中文期刊数据库以及中国学位论文全文数据库中关于精神分裂症患者血浆Hcy水平的病例对照研究,应用分析软件RevMan 5.1 对Hcy 水平和高同型半胱氨酸血症(hyperhomocysteinemia,HHcy)检出率进行Meta 分析.结果 共有19篇文献纳入分析.Meta分析结果示,精神分裂症组与对照组之间Hcy水平的均数差(mean differ-ence,MD)为4.94μmol/L(95%CI:4.34~5.54),精神分裂症组Hcy水平高于对照组(P＜0.01);精神分裂症组与对照组HHcy 检出率的比值比OR 为6.48(95%CI:4.54~9.25),精神分裂症组HHcy 检出率高于对照组(P＜0.01).结论 精神分裂症患者的Hcy水平高于健康者.     

Sex differences in the risk of schizophrenia: evidence from meta-analysis

BACKGROUND: Sex differences in the risk of a particular disorder can yield important clues regarding its pathogenesis. The evidence for a sex difference in the risk of schizophrenia is inconclusive. The purpose of this study was to integrate results from the published literature and to provide a quantitative index of the male-female ratio for the incidence of schizophrenia. METHODS: The MEDLINE and PsychLIT databases were searched for English-language publications on "incidence and schizophrenia" that appeared during the period between January 1980 and September 2001. Population-based incidence studies using standard clinical diagnostic criteria were included if they reported sex-specific incidence rates. Sex-specific incidence figures were extracted directly from each study. Categorical analyses were conducted on a subset of studies that met specific methodological criteria (to minimize criterion bias, hospital bias, and age bias). Study categorization and data extraction were performed independently by 2 of us (A. A. and J.-P.S.). RESULTS: Log risk ratio meta-analysis was conducted using a random-effects model. The incidence risk ratios for men to develop schizophrenia relative to women were 1.42 (95% confidence interval [CI], 1.30-1.56) when all studies were included in the analysis (49 effect sizes), 1.31 (95% CI, 1.13-1.51) when studies that minimized selection biases were analyzed separately (23 effect sizes), and 1.39 (95% CI, 1.15-1.68) when only high-quality studies were included (11 effect sizes). The sex difference was significantly smaller in studies with sample years before 1980 than those with sample years after 1980. No significant sex differences were reported in studies from developing countries. A final analysis, limited to studies with an age cutoff of 64 years or older (16 effect sizes), yielded a mean risk ratio of 1.32 (95% CI, 1.13-1.55). CONCLUSION: This meta-analysis provides evidence for a sex difference in the risk of developing schizophrenia, as reported in the published literature from the last 2 decades.     

Inhibition of return and schizophrenia: a meta-analysis

Inhibition of return (IOR) is a phenomenon that involves inhibited or delayed orienting to previously cued locations in favor of attending to novel locations. To date, research on IOR in patients with schizophrenia has generated mixed, and seemingly conflicting, results. Some researchers report patients with schizophrenia exhibit blunted or delayed IOR, while other researchers report normal IOR, in terms of time course and magnitude. This meta-analysis summarizes the literature that has employed an IOR task in patients with schizophrenia and with controls while focusing upon a procedural feature, the use of a cue back to fixation, between the cue and target that is known to be important when executive control has been hampered in non-clinical populations. Fifteen experiments were located yielding a total sample of 362 patients with schizophrenia or schizoaffective disorder and 285 controls. Using a meta-analytic approach, results of the present analyses show that patients with schizophrenia demonstrate delayed IOR in the single cue procedure. In the cue back to fixation procedure, the time course of IOR among patients is more consistent with that of controls. Differences in measured IOR between patients with schizophrenia and controls are largely related to a deficit in endogenous disengagement of attention.     

Sleep in untreated patients with schizophrenia: a meta-analysis

The present meta-analysis investigated the characteristics of sleep in patients with schizophrenia without neuroleptic treatment at the time of sleep recording. The 20 selected studies included 652 participants (321 patients with schizophrenia and 331 healthy subjects). Effect sizes were evaluated using d values for the following sleep variables: sleep latency (SL), total sleep time (TST), sleep efficiency index (SEI), total awake time (TAT), stage 2 percentage (S2%), stage 4 percentage, slow-wave-sleep percentage, rapid-eye-movement (REM) percentage, and REM latency. The initial meta-analysis revealed that patients with schizophrenia have the following sleep disorders: increased SL, decreased TST, and decreased SEI. A moderator analysis revealed that these sleep disorders were worse for the neuroleptic-withdrawal group relative to the never-treated group. However, only never-treated patients showed significantly increased TAT and diminished S2%. These results confirm that patients with schizophrenia have sleep disorders that are not necessarily a consequence of neuroleptic treatments, suggesting that sleep disorders are an intrinsic feature of schizophrenia. However, it must be noted that some sleep disorders may be amplified by residual effects of neuroleptic withdrawal, while others appear to be dampened by neuroleptic treatment.     

Semantic priming in schizophrenia: systematic review and meta-analysis

BACKGROUND: Increased semantic priming is an influential theory of thought disorder in schizophrenia. However, studies to date have had conflicting findings. AIMS: To investigate semantic memory in patients with schizophrenia with and without thought disorder. METHOD: Data were pooled from 36 studies comparing patients with schizophrenia and normal controls in semantic priming tasks. Data from 18 studies comparing patients with thought disorder with normal controls, and 13 studies comparing patients with and without thought disorder were also pooled. RESULTS: There was no support for altered semantic priming in schizophrenia as a whole. Increased semantic priming in patients with thought disorder was supported, but this was significant only in comparison with normal controls and not in comparison with patients without thought disorder. Stimulus onset asynchrony (SOA) and general slowing of reaction time moderated the effect size for priming in patients with thought disorder. CONCLUSIONS: Meta-analysis provides qualified support for increased semantic priming as a psychological abnormality underlying thought disorder. However, the possibility that the effect is an artefact of general slowing of reaction time in schizophrenia has not been excluded.     

Platelet monoamine oxidase in schizophrenia: a meta-analysis.

We did a meta-analysis on all publications (English and other languages) concerned with platelet monoamine oxidase (MAO) in schizophrenia. Essentially, when patients were medicated with a neuroleptic, most studies found that schizophrenics had lower platelet MAO levels than controls. Administration of neuroleptic lowers MAO levels. MAO levels in drug-free schizophrenics were similar to controls. Only a minority of studies found drug-free schizophrenics had decreased platelet MAO levels.     

Hypofrontality in schizophrenia: a meta-analysis of functional imaging studies

OBJECTIVE: Hypofrontality is not a well-replicated finding in schizophrenia either at rest or under conditions of task activation. METHOD: Studies comparing whole brain and frontal blood flow/metabolism in schizophrenic patients and normal controls were pooled. Voxel-based studies were also combined to examine the pattern of prefrontal activation in schizophrenia. RESULTS: Whole brain flow/metabolism was reduced in schizophrenia to only a small extent. Resting and activation frontal flow/metabolism were both reduced with a medium effect size. Duration of illness significantly moderated resting hypofrontality, but the moderating effects of neuroleptic treatment were consistent with an influence on global flow/metabolism only. Pooling of voxel-based studies did not suggest an abnormal pattern of activation in schizophrenia. CONCLUSION: Meta-analysis supports resting hypofrontality in schizophrenia. Task-activated hypofrontality is also supported, but there is little from voxel-based studies to suggest that this is associated with an altered pattern of regional functional architecture.     

A meta-analysis of P50 studies in patients with schizophrenia and relatives: differences in methodology between research groups

OBJECTIVE: To determine whether patients with schizophrenia as well as their relatives show deficits in sensory gating reflected by an abnormal P50 ratio and to quantify the differences from controls. METHODS: A systematic search on articles published between 1982 and 2006 was conducted. 28 patient studies that were suitable for analysis including 891 patients and 686 controls were retrieved. Six studies on P50 of relatives of schizophrenic patients were identified, including 317 relatives and 294 controls. RESULTS: In the patient studies we found an P50 effect size of 1.28 (SD=0.72). We confirmed high variability in outcomes across studies. Almost half of the studies included where published by one laboratory of the University of Colorado and these results differed significantly from the results found in studies performed in other laboratories. We found correlations between effect size outcome and sound intensity, filter settings and subjects' position which could be explained by differences between the Colorado laboratory and the other groups. In the relative studies we found a mean P50 effect size of 0.85 (+/-0.42). CONCLUSIONS: The differences in methodology and lack of reported demographics and methodology including raters blinding in some studies makes it hard to compare results across studies and to evaluate the validity and reliability of P50 as a candidate endophenotype for schizophrenia. There are large differences in outcomes from Colorado studies and non-Colorado studies. In contrast to the Colorado studies in the non-Colorado studies P50 suppression would not qualify as an endophenotype for schizophrenia. These differences might be explained by the differences in methodology e.g. lower levels of sound intensity, differences in filter settings and subjects' position. Finally we make some recommendations for future research based on the outcomes of this meta-analysis.     

A meta-analysis of cognitive remediation in schizophrenia

OBJECTIVE: This study evaluated the effects of cognitive remediation for improving cognitive performance, symptoms, and psychosocial functioning in schizophrenia. METHOD: A meta-analysis was conducted of 26 randomized, controlled trials of cognitive remediation in schizophrenia including 1,151 patients. RESULTS: Cognitive remediation was associated with significant improvements across all three outcomes, with a medium effect size for cognitive performance (0.41), a slightly lower effect size for psychosocial functioning (0.36), and a small effect size for symptoms (0.28). The effects of cognitive remediation on psychosocial functioning were significantly stronger in studies that provided adjunctive psychiatric rehabilitation than in those that provided cognitive remediation alone. CONCLUSIONS: Cognitive remediation produces moderate improvements in cognitive performance and, when combined with psychiatric rehabilitation, also improves functional outcomes.     

Infectious agents associated with schizophrenia: a meta-analysis

Schizophrenia is a highly disabling and limiting disorder for patients and the possibility that infections by some microorganisms may be associated to its development may allow prevention and recovery. In the current study we have done a meta-analysis of studies that have assessed the possible association between detection of different infectious agents and schizophrenia. We report results that support the idea that there is a statistically significant association between schizophrenia and infection by Human Herpesvirus 2 (OR=1.34; CI 95%: 1.09-1.70; p=0.05), Borna Disease Virus (OR=2.03; CI 95%: 1.35-3.06; p<0.01), Human Endogenous Retrovirus W (OR=19.31; CI 95%: 6.74-55.29; p<0.001), Chlamydophila pneumoniae (OR=6.34; CI 95%: 2.83-14.19; p<0.001), Chlamydophila psittaci (OR=29.05; CI 95%: 8.91-94.70; p<0.001) and Toxoplasma gondii (OR=2.70; CI 95%: 1.34-4.42; p=0.005). The implications of these findings are discussed and further research options are also explicated.