Gray Matter Volume Deficits Research Articles

Radiation-induced changes in normal-appearing gray matter in patients with nasopharyngeal carcinoma: a magnetic resonance imaging voxel-based morphometry study

Evidence is accumulating that temporal lobe radiation necrosis in patients with nasopharyngeal carcinoma (NPC) after radiotherapy (RT) could involve gray matter (GM). The purpose of the study was to assess the radiation-induced GM volume differences between NPC patients who had and had not received RT and the effect of time after RT on GM volume differences in those patients who had received RT. We used magnetic resonance imaging voxel-based morphometry (VBM) to assess differences in GM volume between 30 NPC patients with normal-appearing whole-brain GM after RT and 15 control patients with newly diagnosed but not yet medically treated NPC. Correlation analyses were used to investigate the relationship between GM volume changes and time after RT. Patients who had received RT had GM volume decreases in the bilateral superior temporal gyrus, left middle temporal gyrus, right fusiform gyrus, right precentral gyrus, and right inferior parietal lobule (p < 0.001, uncorrected, cluster size >100 voxels). Moreover, the correlation analysis indicated that regional GM volume loss in the left superior temporal gyrus, left middle temporal gyrus, and right fusiform gyrus were negatively related to the mean dose to the ipsilateral temporal lobe, respectively. These results indicate that GM volume deficits in bilateral temporal lobes in patients who had received RT might be radiation-induced. Our findings might provide new insight into the pathogenesis of radiation-induced structural damage in normal-appearing brain tissue. Yet this is an exploratory study, whose findings should therefore be taken with caution.

Frontal Lobe Synaptic Plasticity in Development and Disease: Modulation by the Dopamine D1 Receptor

Synaptic plasticity is now known to occur at glutamate synapses throughout the brain, including the neocortex, and to play a role in neurodevelopment as well as in a broad spectrum of adult neural functions. Here the hypothesis that synaptic plasticity, specifically long term depression, is the neural substrate that mediates adolescent synaptic pruning is re-examined in the context of its ramifications for neuropsychiatric illnesses. Stress, which in part is mediated by dopamine acting via the D1 receptor, may disrupt normal synaptic plasticity in adolescence resulting in excessive synaptic elimination. In this manner elevated dopamine levels due to stress could contribute to deficits in gray matter volume and reduced neural connectivity in diseases such as major depressive disorder and schizophrenia. Attention deficit hyperactivity disorder, another developmental illness associated with cortical gray matter volume deficits, may represent a state of diminished dopamine stimulation that is equally disruptive to normal mechanisms of synaptic plasticity. In post-traumatic stress disorder, long term potentiation necessary for conditioned fear extinction, is thought to be impaired. Recent evidence suggests that genotypes related to dopamine neurotransmission confer vulnerability to post-traumatic stress disorder, perhaps indicating that low dopamine levels are less permissive of the synaptic plasticity that underlies consolidation and retention of fear extinction. Further understanding of the role that dopamine-modulated synaptic plasticity plays in development and, when disrupted, in precipitating neuropsychiatric illness could lead to novel drug treatments, and ultimately to preventative pharmacotherapeutic interventions, for these disorders.

Frontal-insula gray matter deficits in first-episode medication-naïve patients with major depressive disorder

ObjectiveThis study is designed to investigate the gray matter volume (GMV) deficits in patients with first-episode medication-naïve major depressive disorder (MDD). MethodsWe enrolled 38 patients with first-episode medication-naïve MDD and 27 controls in this project. Voxel-based morphometry was used to compare GMV differences between two groups. Besides, the relationship between GMV of patients and the severity of clinical symptoms was estimated to confirm the role of GMV deficits in clinical symptoms. The correlation between total GMV and illness duration was also performed to elucidate the impacts of untreated duration on the GMV. ResultsWe found that first-episode medication-naïve MDD patients had significant GMV deficits in bilateral superior frontal gyri, left middle frontal gyrus, left medial frontal gyrus and left insula. The GMV of patient group was negatively correlated with the severity of clinical symptoms and the illness duration. ConclusionA pattern of GMV deficits in fronto-insula might represent the biomarker for first-episode medication-naïve MDD.

Readiness to change and brain damage in patients with chronic alcoholism

High motivation to change is a crucial triggering factor to patients’ engagement in clinical treatment. This study investigates whether the low readiness to change observed in some alcoholic inpatients at treatment entry could, at least partially, be linked with macrostructural gray matter abnormalities in critical brain regions. Participants comprised 31 alcoholic patients and 27 controls, who underwent 1.5-T magnetic resonance imaging. The Readiness to Change Questionnaire, designed to assess three stages of motivation to change (precontemplation, contemplation and action stages), was completed by all patients, who were then divided into “Action” (i.e. patients in action stage) and “PreAction” (i.e. patients in precontemplation or in contemplation stage) subgroups. The PreAction subgroup, but not the Action subgroup, had gray matter volume deficits compared with controls. Unlike the patients in the Action subgroup, the PreAction patients had gray matter abnormalities in the cerebellum (Crus I), fusiform gyri and frontal cortex. The low level of motivation to modify drinking behavior observed in some alcoholic patients at treatment entry may be related to macrostructural brain abnormalities in regions subtending cognitive, emotional and social abilities. These brain volume deficits may result in impairment of critical abilities such as decision making, executive functions and social cognition skills. Those abilities may be needed to resolve ambivalence toward alcohol addiction and to apply “processes of change”, which are essential for activating the desire to change problematic behavior.

Changes in gray matter volume of remitted first-episode, drug-naïve, panic disorder patients after 6-week antidepressant therapy

ObjectiveThis study aimed to investigate changes in the gray matter volume (GMV) of first-episode, remitted drug-naïve patients under 6 weeks of escitalopram treatment for panic disorder (PD). We also determined any persistent GMV deficits after remission to assess for “state-dependent brain changes” and “trait-like brain changes” for PD. Method3-Tesla magnetic resonance imaging structural scans were performed on 21 PD patients at baseline and in their remitted state at week 6 of the study. To account for the inter-scanner bias, 21 healthy controls were also scanned twice within 6 weeks. All structural images were processed and analyzed to estimate GMV differences between patients and controls. We utilized optimized voxel-based morphometry with global brain volume, age, and gender as covariates. We also estimated the correlation between improvements in clinical rating scale scores and changes in total gray matter volumes to confirm the results of optimized voxel-based morphometry. ResultsRating scales of panic symptoms improved significantly (corrected p < 0.001). Remitted patients showed increased GMV in the left superior frontal gyrus (corrected p < 0.05) after escitalopram therapy. There were significant GMV deficits in the right precentral gyrus (corrected p < 0.05) after remission of PD symptoms. Changes in total GMV after remission were correlated with changes in clinical scores (r = 0.638; Spearman's rho p = 0.002). ConclusionThe left superior frontal gyrus (state-dependent brain changes) and the right precentral gyrus (trait-like brain changes) might be implicated in the underlying pathophysiology of PD.

Macrostructural abnormalities in Korsakoff syndrome compared with uncomplicated alcoholism

To distinguish, in patients with Korsakoff syndrome (KS), the structural brain abnormalities shared with alcoholic patients without KS (AL), from those specific to KS. MRI data were collected in 11 alcoholic patients with KS, 34 alcoholic patients without KS, and 25 healthy control subjects (CS). Gray and white matter volumes were compared in the 3 groups using a voxel-based approach. A conjunction analysis indicated a large pattern of shared gray and white matter volume deficits in AL and KS. There were graded effects of volume deficits (KS < AL < CS) in the medial portion of the thalami, hypothalamus (mammillary bodies), left insula, and genu of the corpus callosum. Abnormalities in the left thalamic radiation were observed only in KS. Our results indicate considerable similarities in the pattern of gray and white matter damage in AL and KS. This finding confirms the widespread neurotoxic effect of chronic alcohol consumption. Only a few cerebral regions, including the medial thalami, mammillary bodies, and corpus callosum, were more severely damaged in KS than in AL. The continuum of macrostructural damage from AL to KS is therefore restricted to key brain structures. Longitudinal investigations are required to determine whether alcoholic patients with medial thalamic volumes that are comparable to those of patients with KS are at increased risk of developing KS.

Impaired Insulin Sensitivity as Indexed by the HOMA Score Is Associated With Deficits in Verbal Fluency and Temporal Lobe Gray Matter Volume in the Elderly

OBJECTIVEImpaired insulin sensitivity is linked to cognitive deficits and reduced brain size. However, it is not yet known whether insulin sensitivity involves regional changes in gray matter volume. Against this background, we examined the association between insulin sensitivity, cognitive performance, and regional gray matter volume in 285 cognitively healthy elderly men and women aged 75 years from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study.RESEARCH DESIGN AND METHODSInsulin sensitivity was calculated from fasting serum insulin and plasma glucose determinations using the homeostasis model assessment of insulin resistance (HOMA-IR) method. Cognitive performance was examined by a categorical verbal fluency. Participants also underwent a magnetic resonance imaging (MRI) brain scan. Multivariate analysis using linear regression was conducted, controlling for potential confounders (sex, education, serum LDL cholesterol, mean arterial blood pressure, and abdominal visceral fat volume).RESULTSThe HOMA-IR was negatively correlated with verbal fluency performance, brain size, and temporal lobe gray matter volume in regions known to be involved in speech production (Brodmann areas 21 and 22, respectively). No such effects were observed when examining diabetic (n = 55) and cognitively impaired (n = 27) elderly subjects as separate analyses.CONCLUSIONSThese cross-sectional findings suggest that both pharmacologic and lifestyle interventions improving insulin signaling may promote brain health in late life but must be confirmed in patient studies.

Brain Structural Abnormalities at the Onset of Schizophrenia and Bipolar Disorder: A Meta-analysis of Controlled Magnetic Resonance Imaging Studies

A number of structural brain imaging studies and meta-analytic reviews have shown that multiple subtle brain abnormalities are consistently found in schizophrenia and bipolar disorder. Several studies suggest that schizophrenia and affective psychoses share a largely common pattern of brain abnormalities. Aim of the present study was to compare, by means of a meta-analytic approach, brain structural abnormalities, as detected by Magnetic Resonance Imaging (MRI), found at the onset of schizophrenia and bipolar disorder in order to address the question of the specificity of brain abnormalities across diagnostic groups. Forty-five studies were identified as suitable for analysis. In both schizophrenic and bipolar patients significant overall effect sizes were demonstrated for intracranial, whole brain, total grey and white matter volume reduction as well as for an increase of lateral ventricular volume at disease onset. Thus, the available literature data strongly indicate that some brain abnormalities are already present in first-episode schizophrenia or bipolar disorder and that there is a significant overlap of brain abnormalities in affective and non-affective psychotic disorders at the onset of the disease. However, whole grey matter volume deficits and lateral ventricular enlargement appear to be more prominent in first-episode schizophrenia whereas white matter volume reduction seems more prominent in bipolar disorder. The common vs specific trajectories of brain pathomorphology in schizophrenia and bipolar disorder are discussed.

Neuroanatomy of auditory verbal hallucinations in schizophrenia: A quantitative meta-analysis of voxel-based morphometry studies

IntroductionVoxel-based morphometry (VBM) studies demonstrate grey matter volume (GMV) deficits in schizophrenia. This method is also applied for detecting associations between specific psychotic symptoms and brain structure, such as auditory verbal hallucinations (AVHs). However, due to differing methodological approaches, the available findings are inconsistent and difficult to integrate. MethodsWe used a novel voxel-based meta-analytical method to provide a robust quantitative review of neuroanatomical abnormalities specifically associated with the hallucinatory phenomenon in the schizophrenic brain. We reviewed all VBM studies of AVHs in schizophrenia published until July 2011 (n = 9). A total of 438 patients with a diagnosis of schizophrenia were included (307 with AVHs). Using a random-effects parametric voxel-based meta-analysis, coordinates of 83 foci reported as significant in the source studies were extracted and computed to estimate the brain locations most consistently associated with AVHs. ResultsSeverity of AVHs was significantly associated with GMV reductions in the left (p = .022) and marginally with the right (p = .062) superior temporal gyri (STGs, including Heschl’s gyri) across studies examining correlations with AVHs severity in patients (n = 8). Analysis of studies categorically comparing patients with and without AVHs did not reveal any significant findings, possibly due to the small number of studies using this approach (n = 3). ConclusionsThis meta-analysis implicates bilateral STG (including Heschl’s gyri) as key areas of structural pathology in AVHs in schizophrenia. These findings support a model postulating that aberrations within neural systems involved at different levels of language processing are critical to AVHs in schizophrenia.

Myelin-Associated Glycoprotein Gene and Brain Morphometry in Schizophrenia

Myelin and oligodendrocyte disruption may be a core feature of schizophrenia pathophysiology. The purpose of the present study was to localize the effects of previously identified risk variants in the myelin-associated glycoprotein (MAG) gene on brain morphometry in schizophrenia patients and healthy controls. Forty-five schizophrenia patients and 47 matched healthy controls underwent clinical, structural magnetic resonance imaging, and genetics procedures. Gray and white matter cortical lobe volumes along with hippocampal volumes were calculated from T1-weighted MRI scans. Each subject was also genotyped for the two disease-associated MAG single nucleotide polymorphisms (rs720308 and rs720309). Repeated measures general linear model (GLM) analysis found significant region by genotype and region by genotype by diagnosis interactions for the effects of MAG risk variants on lobar gray matter volumes. No significant associations were found with lobar white matter volumes or hippocampal volumes. Follow-up univariate GLMs found the AA genotype of rs720308 predisposed schizophrenia patients to left temporal and parietal gray matter volume deficits. These results suggest that the effects of the MAG gene on cortical gray matter volume in schizophrenia patients can be localized to temporal and parietal cortices. Our results support a role for MAG gene variation in brain morphometry in schizophrenia, align with other lines of evidence implicating MAG in schizophrenia, and provide genetically based insight into the heterogeneity of brain imaging findings in this disorder.

From generation of biomarkers to treatment and psychosocial aspects of psychosis

Transcriptome and proteome analyses in psychiatric diseases have furthered the understanding of pathogenesis on a molecular level. However, most of the potential biomarker candidates have not been validated in peripheral fluids such as blood and cerebrospinal fluid (CSF). In schizophrenia, there is a need for biomarkers allowing early diagnosis and prediction of outcome as well as development of treatment options based on neurobiological processes. However, the management and safety of lumbar puncture in schizophrenia patients is under discussion. Kranaster et al. [1] report here for the first time an evaluation of clinical use and safety of CSF diagnosis in 155 patients with first-episode schizophrenia. This study may encourage future investigations of CSF biomarkers in the disease. A further marker of disturbed brain development in schizophrenia is the gyrification index of the brain, which is determined during neurodevelopment and may be under genetic control. In a study in monozygotic and twins and unrelated siblings, Hasan et al. [2] found no effects of genetic background on the gyrification index in several brain regions, suggesting a stronger influence of environmental factors like intrauterine conditions and early postnatal development on this morphological feature. Other structural abnormalities such as ventricular enlargements are among the most consistent findings in schizophrenia. In a combined structural MRI and DTI study, Horga et al. [3] report that ventricular enlargement is globally interrelated with gray matter volume deficits but not with volume loss in the immediately adjacent caudate, putamen, or internal capsule. Oligodendrocytes play a major role in nerve cell propagation and myelination of axons connecting brain regions. Effects of antipsychotic medication on oligodendrocyte degeneration have been investigated by Steiner et al. [4], who found cell protective effects of haloperidol and clozapine in a serum and glucose deprivation model, suggesting that previously reported decreases in oligodendrocyte numbers in schizophrenia are rather disease related than caused by antipsychotic medication. Degner et al. [5] deal with another aspect of atypical antipsychotic treatment, namely EEG alterations in patients under olanzapine treatment, which have been commonly observed and found to be dependent on dosage. Pharmacological treatment in major psychoses should consider medical and psychopathological comorbidities. Altamura et al. [6] give an actual overview on this topic. An important treatment outcome in schizophrenia is the subjective quality of life and psychosocial functioning. They were measured by different rating scales and showed that greater symptom severity and worse insight were associated with worse functioning and stress further investigations on identifying treatment targets to improve social functioning in schizophrenia [7]. In a Brazilian catchment area, a psychosis continuum has been detected in a sample of 1,464 adults in order to identify psychotic symptoms [8]. Different risk factors have been identified influencing the manifestation of psychotic symptoms. Altogether, this issue of EAPCN gives a broad overview on neurobiological, treatment-related and psychosocial aspects of psychosis.

A mathematical formula for prediction of gray and white matter volume recovery in abstinent alcohol dependent individuals

We propose a mathematical formula that predicts the trajectory of the recovery from lobar gray and white matter volume deficits in individuals with sustained abstinence from alcohol. The formula was validated by using MRI-measured volumetric data from 16 alcohol dependent individuals who had brain scans at three time points during abstinence from alcohol. Using the measured volumetric data of each individual from the first two time points, we estimated the individual's gray and white matter volume of the frontal, parietal and temporal lobes for the third time point using the formula. Similarly, using the measured data for the second and third time points, we estimated the first time point data for each individual. The data predicted from the formula were very similar to the experimentally measured data for all lobes and for both gray and white matter. The intra-class correlation coefficients between the measured data and the data estimated from the formula were > 0.95 for almost all the tissues. The formula may also be applicable in other neuroimaging studies of tissue volume changes such as white matter myelination during brain development and white matter demyelination or brain volume loss in neurodegenerative diseases, such as Alzheimer's disease.

Gray matter volume deficits in spinocerebellar ataxia: An optimized voxel based morphometric study

IntroductionSpinocerebellar ataxias (SCA) are a group of autosomal dominant ataxias with varied clinical phenotypes. However there are no unique distinguishing features on routine neuroimaging among the various genetically defined SCAs. Voxel-based morphometry (VBM) provides an automated unbiased analysis of structural MRI scans and gives a comprehensive assessment of anatomical differences throughout the brain. ObjectivesThe aims of this study were to (i) characterize the patterns of atrophy in SCA1, SCA2 and SCA3 using optimized VBM, (ii) demonstrate the characteristic anatomical differences in these genetically distinct SCA subtypes, and (iii) assess the relationship between morphometric measures and the CAG repeat lengths and other attributes of the disease. MethodsThirty-one genetically confirmed patients suffering from SCA (SCA1 – 12, SCA2 – 9, and SCA3 – 10) were studied. High resolution T1-weighted 3-Dimensional Magnetic Resonance Images of 31 patients were analyzed using the optimized VBM procedure. ResultsIn all the three SCAs there was a significant loss of gray matter in both cerebellar hemispheres and vermis. Vermian atrophy was more pronounced in SCA3, while SCA1 and SCA2 had significant white matter atrophy. Pontine white matter atrophy was more pronounced in SCA2. In SCA1, the severity of ataxia strongly correlated with the degree of gray matter atrophy in cerebellar hemispheres. The duration of symptoms and lengths of CAG repeats had no correlation with the degree of atrophy. ConclusionsThis study showed that the different subtypes of SCAs may have morphometric differences in the cerebellum, brainstem and the supratentorial structures.

Gray matter volume deficits are associated with motor and attentional impairments in adolescents with schizophrenia

Cognitive deficits have been well described in adolescents with schizophrenia, but little is known about the neuroanatomical basis of these abnormalities. The authors examined whether neuropsychological deficits observed in adolescents with schizophrenia were associated with cortical gray matter volume deficits. Volumes of the superior frontal gyrus, anterior cingulate gyrus and orbital frontal lobe were outlined manually from contiguous MR images and automatically segmented into gray and white matter in 52 patients and 48 healthy volunteers. Subjects received a comprehensive neuropsychological test battery, assessing five different functional domains: executive, attention, verbal memory, motor and sensory motor. Children and adolescents with schizophrenia were found to have lower total cortical and lower superior frontal gyrus gray matter volumes and lower test scores across all functional domains compared to healthy volunteers. Among patients, the lower total cortical gray matter volume was associated with worse functioning on the attention and motor domains. Our findings point to widespread, perhaps multifocal, pathology as contributing to cognitive dysfunction in adolescents with schizophrenia.

Different gray matter patterns in chronic schizophrenia and chronic bipolar disorder patients identified using voxel-based morphometry

Gray matter (GM) volume deficits have been described in patients with schizophrenia (Sz) and bipolar disorder (BD), but to date, few studies have directly compared GM volumes between these syndromes with methods allowing for whole-brain comparisons. We have used structural magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) to compare GM volumes between 38 Sz and 19 BD chronic patients. We also included 24 healthy controls. The results revealed a widespread cortical (dorsolateral and medial prefrontal and precentral) and cerebellar deficit as well as GM deficits in putamen and thalamus in Sz when compared to BD patients. Besides, a subcortical GM deficit was shown by Sz and BD groups when compared to the healthy controls, although a putaminal reduction was only evident in the Sz patients. In this comparison, the BD patients showed a limited cortical and subcortical GM deficit. These results support a partly different pattern of GM deficits associated to chronic Sz and chronic BD, with some degree of overlapping.

Gray Matter Alterations in Adults with Attention-Deficit/Hyperactivity Disorder Identified by Voxel Based Morphometry

Gray and white matter volume deficits have been reported in many structural magnetic resonance imaging (MRI) studies of children with attention-deficit/hyperactivity disorder (ADHD); however, there is a paucity of structural MRI studies of adults with ADHD. This study used voxel based morphometry and applied an a priori region of interest approach based on our previous work, as well as from well-developed neuroanatomical theories of ADHD. Seventy-four adults with DSM-IV ADHD and 54 healthy control subjects comparable on age, sex, race, handedness, IQ, reading achievement, frequency of learning disabilities, and whole brain volume had an MRI on a 1.5T Siemens scanner. A priori region of interest hypotheses focused on reduced volumes in ADHD in dorsolateral prefrontal cortex, anterior cingulate cortex, caudate, putamen, inferior parietal lobule, and cerebellum. Analyses were carried out by FSL-VBM 1.1. Relative to control subjects, ADHD adults had significantly smaller gray matter volumes in parts of six of these regions at p ≤ .01, whereas parts of the dorsolateral prefrontal cortex and inferior parietal lobule were significantly larger in ADHD at this threshold. However, a number of other regions were smaller and larger in ADHD (especially fronto-orbital cortex) at this threshold. Only the caudate remained significantly smaller at the family-wise error rate. Adults with ADHD have subtle volume reductions in the caudate and possibly other brain regions involved in attention and executive control supporting frontostriatal models of ADHD. Modest group brain volume differences are discussed in the context of the nature of the samples studied and voxel based morphometry methodology.

Association of Frontal and Posterior Cortical Gray Matter Volume With Time to Alcohol Relapse: A Prospective Study

Alcoholism is associated with gray matter volume deficits in frontal and other brain regions. Whether persistent brain volume deficits in abstinence are predictive of subsequent time to alcohol relapse has not been established. The authors measured gray matter volumes in healthy volunteers and in a sample of treatment-engaged, alcohol-dependent patients after 1 month of abstinence and assessed whether smaller frontal gray matter volume was predictive of subsequent alcohol relapse outcomes. Forty-five abstinent alcohol-dependent patients in treatment and 50 healthy comparison subjects were scanned once using high-resolution (T(1)-weighted) structural MRI, and voxel-based morphometry was used to assess regional brain volume differences between the groups. A prospective study design was used to assess alcohol relapse in the alcohol-dependent group for 90 days after discharge from 6 weeks of inpatient treatment. Significantly smaller gray matter volume in alcohol-dependent patients relative to comparison subjects was seen in three regions: the medial frontal cortex, the right lateral prefrontal cortex, and a posterior region surrounding the parietal-occipital sulcus. Smaller medial frontal and parietal-occipital gray matter volumes were each predictive of shorter time to any alcohol use and to heavy drinking relapse. These findings are the first to demonstrate that gray matter volume deficits in specific medial frontal and posterior parietal-occipital brain regions are predictive of an earlier return to alcohol use and relapse risk, suggesting a significant role for gray matter atrophy in poor clinical outcomes in alcoholism. Extent of gray matter volume deficits in these regions could serve as useful neural markers of relapse risk and alcoholism treatment outcome.

Gray matter volume deficits and correlation with insight and negative symptoms in first-psychotic-episode subjects

To determine brain areas reduced in first episode of psychotic subjects and its association with lack of insight and negative symptoms. Twenty-one drug naive first-episode subjects and 20 controls underwent a structural MRI scan and were clinically assessed. Optimized voxel-based-morphometry analysis (VBM) was implemented to find between-group differences and correlations between GM volume and: (i) lack of insight and (ii) negative symptoms. Patients showed GM reduction in prefrontal and left temporal areas. A significant correlation was found between insight and GM volume in the cerebellum (corrected P = 0.01), inferior temporal gyrus (corrected P = 0.022), medial superior frontal gyrus (corrected P < 0.001), and inferior frontal gyrus (corrected P = 0.012), as the insight decreased, the volume decreased. Negative symptoms correlated with decreased GM volume at cerebellum (corrected P = 0.037) and frontal inferior regions (corrected P < 0.001), the more negative symptoms, the less volume. Our findings support an association between prefrontal, temporal, and cerebellar deficits and lack of insight in schizophrenia and confirm previous findings of GM deficits in patients since the first episode of psychosis.

Impulsivity-related brain volume deficits in schizophrenia-addiction comorbidity

Despite a high prevalence of schizophrenia patients with comorbid substance abuse, little is known about possible impacts on the brain. Hence, our goal was to determine whether addicted and non-addicted schizophrenic patients suffer from different brain deficits. We were especially interested to determine if grey matter volumes were affected by impulsivity. We hypothesized that (comorbid) substance abuse would be associated with enhanced impulsivity and that this enhanced impulsivity would be related to grey matter volume deficits in prefrontal areas. We employed a voxel-based morphometry approach as well as neuropsychological assessment of executive functions and trait impulsivity in 51 participants (age range 23-55). The schizophrenia group comprised 24 patients (12 patients with paranoid schizophrenia and 12 with additional comorbid substance use disorders). The comparison group comprised 27 non-schizophrenic individuals, matched by age and education (14 healthy individuals and 13 patients with substance use disorders). Total grey matter volume deficits were found in all patient groups as compared with healthy controls but were largest (~8%) in both addicted groups. While grey matter volume losses in lateral orbitofrontal and temporal regions were affected by schizophrenia, volume decreases of the medial orbitofrontal, anterior cingulate and frontopolar cortex were associated with addiction. Compared with non-addicted schizophrenics, comorbid patients showed significant volume decreases in anterior cingulate, frontopolar and superior parietal regions. Additionally, they showed an increased non-planning impulsivity that was negatively related to grey matter volumes in the same regions, except for parietal ones. The present study indicates severe grey matter volume and functional executive deficits in schizophrenia, which were only partially exacerbated by comorbid addiction. However, the relationship between non-planning impulsivity and anterior cingulate and frontopolar grey matter volumes points to a specific structure-function relationship that seems to be impaired in schizophrenia-addiction comorbidity.

Neuroanatomical correlates of psychopathology in antipsychotic-naïve schizophrenia.

Background:Previous Magnetic Resonance Imaging (MRI) studies using manual techniques reporting significant relationship between psychopathology and gray matter volume in schizophrenia are limited by various confounding factors. None used automated image analysis to examine gray matter volume correlates of psychopathology in antipsychotic-naïve schizophrenia patients.Aim:This study aimed at examining the relationship between psychopathology and gray matter volume abnormalities in antipsychotic-naïve schizophrenia patients.Patients and Methods:MRI of 30 antipsychotic-naïve schizophrenia (DSM-IV) patients and 27 age-, sex- education- and handedness-matched healthy controls were compared for gray matter volume differences using Optimized Voxel-based Morphometry (VBM)-an automated, rapid and unbiased technique. Psychopathology was measured using Positive and Negative Syndrome Scale (PANSS) with good inter-rater reliability. The correlations between PANSS scores and gray matter volume were examined using VBM.Results:Schizophrenia patients had significant gray matter volume deficits in frontal, cingulate, temporal, insula and precuneus cortices; thalamus, caudate and cerebellum. Positive syndrome score had significant negative correlation with left superior temporal gyrus volume. Negative syndrome score had significant inverse correlation with frontal, cingulate and cerebellar gray matter volumes.Conclusions:Cortical and cerebellar gray matter volume deficits and their significant negative correlations with psychopathology scores are supportive of ‘Cognitive Dysmetria’ in schizophrenia.