Abstract: Objective: Structural neuroimaging studies in attention-deficit hyperactivity disorder (ADHD) have been relatively inconsistent and have mainly been conducted with pediatric samples. Furthermore, there is evidence that stimulant medication may have an effect on brain structure. The authors conducted a meta-analysis of voxel-based morphometry studies in children and adults with ADHD and examined the potential effects of age and stimulant medication on regional gray matter volumes. Method: The PubMed, ScienceDirect, Web of Knowledge, and Scopus databases were searched for articles published between 2001 and 2011. Manual searches were also conducted, and authors of studies were contacted for additional data. Coordinates were extracted from clusters of significant gray matter difference between ADHD patients and healthy comparison subjects. Metaregression methods were used to explore potential age and stimulant medication effects. Results: Fourteen data sets comprising 378 patients with ADHD and 344 healthy subjects met inclusion criteria. The ADHD group had global reductions in gray matter volumes, which were robustly localized in the right lentiform nucleus and extended to the caudate nucleus. Both increasing age and percentage of patients taking stimulant medication were found to be independently associated with more normal values in this region. Patients also had slightly greater gray matter volumes in the left posterior cingulate cortex. Conclusions: These findings confirm that the most prominent and replicable structural abnormalities in ADHD are in the basal ganglia. They furthermore suggest that ADHD patients may progressively catch up with their developmental delay with advancing age and that use of stimulant medication may be associated with normalization of structural abnormalities in ADHD, although longitudinal studies are needed to confirm both observations.
Abstract: Despite an increasing number of published voxel based morphometry studies of schizophrenia, there has been no adequate attempt to examine gray (GM) and white matter (WM) abnormalities and the heterogeneity of published findings. In the current article, we used a coordinate based meta-analysis technique to simultaneously examine GM and WM abnormalities in schizophrenia and to assess the effects of gender, chronicity, negative symptoms and other clinical variables. 79 studies meeting our inclusion criteria were included in the meta-analysis. Schizophrenia was associated with GM reductions in the bilateral insula/inferior frontal cortex, superior temporal gyrus, anterior cingulate gyrus/medial frontal cortex, thalamus and left amygdala. In WM analyses of volumetric and diffusion-weighted images, schizophrenia was associated with decreased FA and/or WM in interhemispheric fibers, anterior thalamic radiation, inferior longitudinal fasciculi, inferior frontal occipital fasciculi, cingulum and fornix. Male gender, chronic illness and negative symptoms were associated with more severe GM abnormalities and illness chronicity was associated with more severe WM deficits. The meta-analyses revealed overlapping GM and WM structural findings in schizophrenia, characterized by bilateral anterior cortical, limbic and subcortical GM abnormalities, and WM changes in regions including tracts that connect these structures within and between hemispheres. However, the available findings are biased towards characteristics of schizophrenia samples with poor prognosis.
Abstract: Studies investigating abnormalities of regional gray matter volume in autism spectrum disorder (ASD) have yielded contradictory results. It is unclear whether the current subtyping of ASD into autistic disorder and Asperger disorder is neurobiologically valid.
Abstract: Brain positron emission tomography (PET) is a useful technique for estimating the neuroreceptor occupancy of a drug in vivo. In the absence of a reference region, occupancy can be obtained from an "occupancy plot" with ordinary least squares (OLS) regression. However, OLS has been found to return inefficient occupancy estimations. The aim of this study was to improve the accuracy and precision of occupancy estimations.
Abstract: Meta-analyses are essential to summarize the results of the growing number of neuroimaging studies in psychiatry, neurology and allied disciplines. Image-based meta-analyses use full image information (i.e. the statistical parametric maps) and well-established statistics, but images are rarely available making them highly unfeasible. Peak-probability meta-analyses such as activation likelihood estimation (ALE) or multilevel kernel density analysis (MKDA) are more feasible as they only need reported peak coordinates. Signed-differences methods, such as signed differential mapping (SDM) build upon the positive features of existing peak-probability methods and enable meta-analyses of studies comparing patients with controls. In this paper we present a new version of SDM, named Effect Size SDM (ES-SDM), which enables the combination of statistical parametric maps and peak coordinates and uses well-established statistics. We validated the new method by comparing the results of an ES-SDM meta-analysis of studies on the brain response to fearful faces with the results of a pooled analysis of the original individual data. The results showed that ES-SDM is a valid and reliable coordinate-based method, whose performance might be additionally increased by including statistical parametric maps. We anticipate that ES-SDM will be a helpful tool for researchers in the fields of psychiatry, neurology and allied disciplines.
Abstract: BACKGROUND: We conducted a meta-analysis of voxel-based morphometry (VBM) studies in autism spectrum disorder (ASD) to clarify the changes in regional white-matter volume underpinning this condition, and generated an online database to facilitate replication and further analyses by other researchers.MethodPubMed, ScienceDirect, Web of Knowledge and Scopus databases were searched between 2002 (the date of the first white-matter VBM study in ASD) and 2010. Manual searches were also conducted. Authors were contacted to obtain additional data. Coordinates were extracted from clusters of significant white-matter difference between patients and controls. A new template for white matter was created for the signed differential mapping (SDM) meta-analytic method. A diffusion tensor imaging (DTI)-derived atlas was used to optimally localize the changes in white-matter volume. RESULTS: Thirteen datasets comprising 246 patients with ASD and 237 healthy controls met inclusion criteria. No between-group differences were found in global white-matter volumes. ASD patients showed increases of white-matter volume in the right arcuate fasciculus and also in the left inferior fronto-occipital and uncinate fasciculi. These findings remained unchanged in quartile and jackknife sensitivity analyses and also in subgroup analyses (pediatric versus adult samples). CONCLUSIONS: Patients with ASD display increases of white-matter volume in tracts known to be important for language and social cognition. Whether the results apply to individuals with lower IQ or younger age and whether there are meaningful neurobiological differences between the subtypes of ASD remain to be investigated.
Abstract: Studies on the relationship between climate and unipolar depression rates have yielded mixed results, which could be attributed to the inclusion of heterogeneous clinical samples and the use of admission rather than onset dates. This study aimed to overcome these methodological issues. During an 8-year timeframe, onset rates of unipolar depressive episodes requiring hospitalization from individuals living up to 15 km from a selected meteorological station were stratified by clinical subtypes and modeled as Autoregressive Integrated Moving Average (ARIMA) functions of orthogonal climatic factors obtained by Principal Components Analysis (PCA). For comparison purposes, onset rates stratified by demographic factors and by diagnosis of Seasonal Affective Disorder (SAD) and admission rates were also modeled. The main findings were a negative 1-month delayed relationship between onset rates of episodes with melancholic features and a climatic factor mainly composed of ambient temperature/sunlight, and a negative 1-month delayed relationship between onset rates of episodes with psychotic features and a climatic factor mainly composed of barometric pressure. Results of this study support a climatic-rather than seasonal-influence in specific subtypes of depression. If replicated, they may have nosological and therapeutic implications.
Abstract: [(11)C]NNC112 (8-chloro-7-hydroxy-3-methyl-5-(7-benzofuranyl)-2,3,4,5-tetrahydro-IH-3-benzazepine), a selective positron-emission tomography (PET) ligand for the D(1) receptor (R) over the 5-HT(2A) R in vitro, has shown lower selectivity in vivo, hampering measurement of D(1) R in the cortex. [(11)C]NNC112 PET and intravenous (i.v) ketanserin challenge were used to (1) confirm the previous findings of [(11)C]NNC112 in vivo D(1) R selectivity, and (2) develop a feasible methodology for imaging cortical D(1) R without contamination by 5-HT(2A) R. Seven healthy volunteers underwent [(11)C]NNC112 PET scans at baseline and after a 5-HT(2A) R-blocking dose of ketanserin (0.15 mg/kg, i.v.). Percent BP(ND) change between the post-ketanserin and baseline scans was calculated. Irrespective of the quantification method used, ketanserin pretreatment led to significant decrease of BP(ND) in the cortical (approximately 30%) and limbic regions (approximately 20%) but not in the striatum, which contains a much lower amount of 5-HT(2A) R. Therefore, ketanserin allows D(1) R signal to be detected by [(11)C]NNC112 PET without significant 5-HT(2A) R contamination. These data confirm the presence of a significant 5-HT(2A) R contribution to cortical [(11)C]NNC112 signal, and call for caution in the interpretation of published [(11)C]NNC112 PET findings on cortical D(1) R in humans. In the absence of more selective ligands, [(11)C]NNC112 PET with ketanserin can be used for cortical D(1) R imaging in vivo.
Abstract: Perception of fearful faces is associated with functional activation of cortico-limbic structures, which has been found altered in individuals with psychiatric disorders such as schizophrenia, autism and major depression. The objective of this study was to isolate the brain response to the features of standardized fearful faces by incorporating principal component analysis (PCA) into the analysis of neuroimaging data of healthy volunteers and individuals with schizophrenia. At the first stage, the visual characteristics of morphed fearful facial expressions (FEEST, Young et al., 2002) were classified with PCA, which produced seven orthogonal factors, with some of them related to emotionally salient facial features (eyes, mouth, brows) and others reflecting non-salient facial features. Subsequently, these PCA-based factors were included into the functional magnetic resonance imaging (fMRI) analysis of 63 healthy volunteers and 32 individuals with schizophrenia performing a task that involved implicit processing of FEEST stimuli. In healthy volunteers, significant neural response was found to visual characteristics of eyes, mouth or brows. In individuals with schizophrenia, PCA-based analysis enabled us to identify several significant clusters of activation that were not detected by the standard approach. These clusters were implicated in processing of visual and emotional information and were attributable to the perception of eyes and brows. PCA-based analysis could be useful in isolating brain response to salient facial features in psychiatric populations.
Abstract: Emotions of fear and disgust are related to core symptoms of depression. The neurobiological mechanisms of these associations are poorly understood. This functional magnetic resonance imaging study aimed at examining the Blood oxygenation level dependent (BOLD) response to facial expressions of fear and disgust in patients with major depressive disorder. Nine patients in an episode of major depression and nine healthy controls underwent two functional magnetic resonance imaging experiments where they judged the gender of facial identities displaying different degrees (mild, strong) of fear or disgust, intermixed with non-emotional faces. Compared with healthy controls, patients with depression demonstrated greater activation in left insula, left orbito-frontal gyrus, left middle/inferior temporal gyrus, and right middle/inferior temporal gyrus to expressions of strong disgust. Depressed patients also demonstrated reduced activation in left inferior parietal lobe to mildly fearful faces. Enhanced activation to facial expressions of disgust may reflect an emotion processing bias that suggests high relevance of emotion of disgust to depression.
Abstract: BACKGROUND: Specific cortico-striato-thalamic circuits are hypothesised to mediate the symptoms of obsessive-compulsive disorder (OCD), but structural neuroimaging studies have been inconsistent. AIMS: To conduct a meta-analysis of published and unpublished voxel-based morphometry studies in OCD. METHOD: Twelve data-sets comprising 401 people with OCD and 376 healthy controls met inclusion criteria. A new improved voxel-based meta-analytic method, signed differential mapping (SDM), was developed to examine regions of increased and decreased grey matter volume in the OCD group v. control group. Results No between-group differences were found in global grey matter volumes. People with OCD had increased regional grey matter volumes in bilateral lenticular nuclei, extending to the caudate nuclei, as well as decreased volumes in bilateral dorsal medial frontal/anterior cingulate gyri. A descriptive analysis of quartiles, a sensitivity analysis as well as analyses of subgroups further confirmed these findings. Meta-regression analyses showed that studies that included individuals with more severe OCD were significantly more likely to report increased grey matter volumes in the basal ganglia. No effect of current antidepressant treatment was observed. Conclusions The results support a dorsal prefrontal-striatal model of the disorder and raise the question of whether functional alterations in other brain regions commonly associated with OCD, such as the orbitofrontal cortex, may reflect secondary compensatory strategies. Whether the reported differences between participants with OCD and controls precede the onset of the symptoms and whether they are specific to OCD remains to be established.
