Meta-Analysis of Regional Brain Volumes in Schizophrenia
01 Jan 2000-American Journal of Psychiatry (American Psychiatric Publishing)-Vol. 157, Iss: 1, pp 16-25
TL;DR: In this article, the authors conducted a systematic search for structural magnetic resonance imaging (MRI) studies of patients with schizophrenia that reported volume measurements of selected cortical, subcortical, and ventricular regions in relation to comparison groups.
Abstract: Objective: The authors’ goal was to determine whether patients with schizophrenia differ from comparison subjects in regional brain volumes and whether these differences are similar in male and female subjects. Method: They conducted a systematic search for structural magnetic resonance imaging (MRI) studies of patients with schizophrenia that reported volume measurements of selected cortical, subcortical, and ventricular regions in relation to comparison groups. They carried out a meta-analysis of the volumes of these regions in the patients with schizophrenia and the comparison subjects using a random effects model; they also used random effects regression analysis to examine the influence of gender on effect sizes. Results: Fifty-eight studies were identified as suitable for analysis; these studies included 1,588 independent patients with schizophrenia. Assuming a volume of 100% in the comparison group, they found that the mean cerebral volume of the subjects with schizophrenia was smaller (98%), but the mean total ventricular volume of the subjects with schizophrenia was greater (126%). Relative to the cerebral volume differences, the regional volumes of the subjects with schizophrenia were 94% in the left and right amygdala, 94% in the left and 95% in the right hippocampus/amygdala, and 93% in the left and 95% in the right parahippocampus. Relative to the global ventricular system differences, the largest differences in ventricular subdivisions were in the right and left body of the lateral ventricle, where the volumes of schizophrenic subjects were 116% and 116%, respectively. For most regions, effect size was not significantly related to gender. Conclusions: Regional structural differences in patients with schizophrenia include bilaterally reduced volume of medial temporal lobe structures. There is a need for greater integration of results from structural MRI studies to avoid redundant research activity. (Am J Psychiatry 2000; 157:16‐25)
Citations
More filters
TL;DR: The 193 peer reviewed MRI studies reported in the current review span the period from 1988 to August, 2000 and have led to more definitive findings of brain abnormalities in schizophrenia than any other time period in the history of schizophrenia research.
2,298 citations
Cites background from "Meta-Analysis of Regional Brain Vol..."
...A possible alternative would have been to provide a meta-analysis that weights each study based on subject N and effect size (e.g. Glass et al., 1981; Gøtzsche 2000; Hunter and Schmidt 1990; Petitti, 1994; Rosenthal and Rubin, 1979, 1982, 1986; Wright et al., 2000)....
[...]
TL;DR: This review critically summarizes the neuropathology and genetics of schizophrenia, the relationship between them, and speculates on their functional convergence via an influence upon synaptic plasticity and the development and stabilization of cortical microcircuitry.
Abstract: This review critically summarizes the neuropathology and genetics of schizophrenia, the relationship between them, and speculates on their functional convergence. The morphological correlates of schizophrenia are subtle, and range from a slight reduction in brain size to localized alterations in the morphology and molecular composition of specific neuronal, synaptic, and glial populations in the hippocampus, dorsolateral prefrontal cortex, and dorsal thalamus. These findings have fostered the view of schizophrenia as a disorder of connectivity and of the synapse. Although attractive, such concepts are vague, and differentiating primary events from epiphenomena has been difficult. A way forward is provided by the recent identification of several putative susceptibility genes (including neuregulin, dysbindin, COMT, DISC1, RGS4, GRM3, and G72). We discuss the evidence for these and other genes, along with what is known of their expression profiles and biological roles in brain and how these may be altered in schizophrenia. The evidence for several of the genes is now strong. However, for none, with the likely exception of COMT, has a causative allele or the mechanism by which it predisposes to schizophrenia been identified. Nevertheless, we speculate that the genes may all converge functionally upon schizophrenia risk via an influence upon synaptic plasticity and the development and stabilization of cortical microcircuitry. NMDA receptor-mediated glutamate transmission may be especially implicated, though there are also direct and indirect links to dopamine and GABA signalling. Hence, there is a correspondence between the putative roles of the genes at the molecular and synaptic levels and the existing understanding of the disorder at the neural systems level. Characterization of a core molecular pathway and a 'genetic cytoarchitecture' would be a profound advance in understanding schizophrenia, and may have equally significant therapeutic implications.
1,879 citations
TL;DR: It is suggested that distinct patterns of structural and functional abnormalities in neural systems important for emotion processing are associated with specific symptoms of schizophrenia and bipolar and major depressive disorder.
1,662 citations
Cites background from "Meta-Analysis of Regional Brain Vol..."
...Other studies have reported decreased insular size in schizophrenic patients (Crespo-Facorro et al 2000; Wright et al 2000)....
[...]
...…Nasrallah et al 1994) and volume reductions (Altshuler et al 2000; Heckers 2001; Lawrie and Abukmeil 1998; Nelson et al 1998; Shenton et al 1992; Wright et al 2000) in these regions, an association between amygdalar lesions and psychotic symptoms (Fudge et al 1998), and an inverse correlation…...
[...]
...…the presence of volume reductions within the prefrontal (Goldman-Rakic and Selemon 1997; Lawrie and Abukmeil 1998; Pearlson and Marsh 1999; Wright et al 2000) and, more specifically, dorsolateral prefrontal cortex in patients with schizophrenia (Zuffante et al 2001), several studies have…...
[...]
TL;DR: Findings implicate interconnected neural circuits in which pathologic patterns of neurotransmission may result in the emotional, motivational, cognitive, and behavioral manifestations of primary and secondary affective disorders.
1,280 citations
TL;DR: Some of the grey-matter abnormalities associated with psychotic disorders predate the onset of frank symptoms, whereas others appear in association with their first expression.
1,272 citations
References
More filters
TL;DR: Funnel plots, plots of the trials' effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials.
Abstract: Objective: Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Design: Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews . Main outcome measure: Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision. Results: In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias. Conclusions: A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution. Key messages Systematic reviews of randomised trials are the best strategy for appraising evidence; however, the findings of some meta-analyses were later contradicted by large trials Funnel plots, plots of the trials9 effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials Funnel plot asymmetry was found in 38% of meta-analyses published in leading general medicine journals and in 13% of reviews from the Cochrane Database of Systematic Reviews Critical examination of systematic reviews for publication and related biases should be considered a routine procedure
37,989 citations
TL;DR: This paper examines eight published reviews each reporting results from several related trials in order to evaluate the efficacy of a certain treatment for a specified medical condition and suggests a simple noniterative procedure for characterizing the distribution of treatment effects in a series of studies.
33,234 citations
TL;DR: New MRI neuroimaging techniques are used to derive volume measurements and three-dimensional reconstructions of temporal-lobe structures in vivo in 15 right-handed men with chronic schizophrenia and 15 matched controls to discover the degree of thought disorder is related to the size of the reduction in volume of the left posterior superior temporal gyrus.
Abstract: Background. Data from postmortem, CT, and magnetic resonance imaging (MRI) studies indicate that patients with schizophrenia may have anatomical abnormalities of the left temporal lobe, but it is unclear whether these abnormalities are related to the thought disorder characteristic of schizophrenia. Methods. We used new MRI neuroimaging techniques to derive (without knowledge of the diagnosis) volume measurements and three-dimensional reconstructions of temporal-lobe structures in vivo in 15 right-handed men with chronic schizophrenia and 15 matched controls. Results. As compared with the controls, the patients had significant reductions in the volume of gray matter in the left anterior hippocampus—amygdala (by 19 percent [95 percent confidence interval, 3 to 36 percent]), the left parahippocampal gyrus (by 13 percent [95 percent confidence interval, 3 to 23 percent], vs. 8 percent on the right), and the left superior temporal gyrus (by 15 percent [95 percent confidence interval, 5 to 25 percent]...
1,159 citations
TL;DR: Cumulative meta-analysis of therapeutic trials facilitates the determination of clinical efficacy and harm and may be helpful in tracking trials, planning future trials, and making clinical recommendations for therapy.
Abstract: Background. The large volume of published randomized, controlled trials has led to a need for meta-analyses to track therapeutic advances. Performing a new meta-analysis whenever the results of a new trial of a particular therapy are published permits the study of trends in efficacy and makes it possible to determine when a new treatment appears to be significantly effective or deleterious. We describe the use of such a procedure, cumulative meta-analysis, to assess therapeutic trials among patients with myocardial infarction. Methods. We performed cumulative meta-analyses of clinical trials that evaluated 15 treatments and preventive measures for acute myocardial infarction. Results. An example of this method is its application to the use of intravenous streptokinase as thrombolytic therapy for acute infarction. Thirty-three trials evaluating this therapy were performed between 1959 and 1988. We found that a consistent, statistically significant reduction in total mortality (odds ratio, 0.74; 95...
1,088 citations
TL;DR: In this article, the authors found that subtle abnormalities of cerebral anatomy (namely, small anterior hippocampi and enlarged lateral and third ventricles) are consistent neuropathologic features of schizophrenia and that their cause is at least in part not genetic.
Abstract: Recent neuroradiologic and neuropathological studies indicate that at least some patients with schizophrenia have slightly enlarged cerebral ventricles and subtle anatomical abnormalities in the region of the anterior hippocampus. Using magnetic resonance imaging (MRI), we studied 15 sets of monozygotic twins who were discordant for schizophrenia (age range, 25 to 44 years; 8 male and 7 female pairs). For each pair of twins, T1-weighted contiguous coronal sections (5 mm thick) were compared blindly, and quantitative measurements of brain structures were made with a computerized image-analysis system. In 12 of the 15 discordant pairs, the twin with schizophrenia was identified by visual inspection of cerebrospinal fluid spaces. In two pairs no difference could be discerned visually, and in one the twin with schizophrenia was misidentified. Quantitative analysis of sections through the level of the pes hippocampi showed the hippocampus to be smaller on the left in 14 of the 15 affected twins, as compared with their normal twins, and smaller on the right in 13 affected twins (both P less than 0.001). In the twins with schizophrenia, as compared with their normal twins, the lateral ventricles were larger on the left in 14 (P less than 0.003) and on the right in 13 (P less than 0.001). The third ventricle also was larger in 13 of the twins with schizophrenia (P less than 0.001). None of these differences were found in seven sets of monozygotic twins without schizophrenia who were studied similarly as controls. We conclude that subtle abnormalities of cerebral anatomy (namely, small anterior hippocampi and enlarged lateral and third ventricles) are consistent neuropathologic features of schizophrenia and that their cause is at least in part not genetic. Further study is required to determine whether these changes are primary or secondary to the disease.
988 citations