Regionally localized thinning of the cerebral cortex in schizophrenia

BACKGROUND: Schizophrenia is characterized by small reductions in cortical gray matter volume, particularly in the temporal and prefrontal cortices. The question of whether cortical thickness is reduced in schizophrenia has not been addressed using magnetic resonance imaging (MRI) techniques. Our objectives were to test the hypothesis that cortical thinning in patients with schizophrenia (relative to control subjects) is greater in temporal and prefrontal regions of interest (ROIs) than in control ROIs (superior parietal, calcarine, postcentral, central, and precentral cortices), and to obtain an unbiased estimate of the distribution of cortical thinning in patients (relative to controls) by constructing mean and statistical cortical thickness difference maps. METHODS: Participants included 33 right-handed outpatients receiving medication and meeting DSM-IV criteria for schizophrenia and 32 healthy volunteers, matched on age and parental socioeconomic status. After high-resolution MRI scans, models of the gray-white and pial surfaces were generated for each individual's cortex, and the distance between these 2 surfaces was used to compute cortical thickness. A surface-based averaging technique that aligned the main cortical folds across individuals allowed between-group comparisons of thickness within ROIs, and at multiple, uniformly sampled loci across the cortical ribbon. RESULTS: Relative to controls, patients showed greater cortical thinning in temporal-prefrontal ROIs than in control ROIs, as revealed by a significant (P<.009) interaction between group and region type. Cortical thickness difference maps revealed significant (at P<.05, corrected) thinning within the orbitofrontal cortices bilaterally; the inferior frontal, inferior temporal, and occipitotemporal cortices on the left; and within the medial temporal and medial frontal cortices on the right. Superior parietal and primary somatosensory and motor cortices were relatively spared, even at subthreshold significance levels. CONCLUSIONS: Patients with chronic schizophrenia showed widespread cortical thinning that particularly affected the prefrontal and temporal cortices. This thinning might reflect underlying neuropathological abnormalities in cortical structure.     

Regional thinning of the cerebral cortex in schizophrenia: effects of diagnosis, age and antipsychotic medication

Morphological abnormalities of the cerebral cortex have been reported in a number of MRI-studies in schizophrenia. Uncertainty remains regarding cause, mechanism and progression of the alterations. It has been suggested that antipsychotic medication reduces total gray matter volumes, but results are inconsistent. In the present study differences in regional cortical thickness between 96 patients with a DSM-IV diagnosis of schizophrenia (n=81) or schizoaffective disorder (n=15) and 107 healthy subjects (mean age 42 years, range 17-57 years) were investigated using MRI and computer image analysis. Cortical thickness was estimated as the shortest distance between the gray/white matter border and the pial surface at numerous points across the entire cortical mantle. The influence of age and antipsychotic medication on variation in global and regional cortical thickness was explored. Thinner cortex among patients than controls was found in prefrontal and temporal regions of both hemispheres, while parietal and occipital regions were relatively spared. Some hemispheric specificity was noted, as regions of the prefrontal cortex were more affected in the right hemisphere, and regions of the temporal cortex in the left hemisphere. No significant interaction effect of age and diagnostic group on variation in cortical thickness was demonstrated. Among patients, dose or type of antipsychotic medication did not affect variation in cortical thickness. The results from this hitherto largest study on the topic show that prefrontal and temporal cortical thinning in patients with schizophrenia compared to controls is as pronounced in older as in younger subjects. The lack of significant influence from antipsychotic medication supports that regional cortical thinning is an inherent feature of the neurobiological disease process in schizophrenia.     

Volumetric abnormalities predating the onset of schizophrenia and affective psychoses: an MRI study in subjects at ultrahigh risk of psychosis

It remains unclear whether brain structural abnormalities observed before the onset of psychosis are specific to schizophrenia or are common to all psychotic disorders. This study aimed to measure regional gray matter volume prior to the onset of schizophreniform and of affective psychoses. We investigated 102 subjects at ultrahigh risk (UHR) of developing psychosis recruited from the Personal Assessment and Crisis Evaluation Clinic in Melbourne, Australia. Twenty-eight of these subjects developed psychosis subsequent to scanning: 19 schizophrenia, 7 affective psychoses, and 2 other psychoses. We examined regional gray matter volume using 1.5 mm thick, coronal, 1.5 Tesla magnetic resonance imaging and voxel-based morphometry methods of image analysis. Subjects were scanned at presentation and were followed up clinically for a minimum of 12 months, to detect later transition to psychosis. We found that both groups of subjects who subsequently developed psychosis (schizophrenia and affective psychosis) showed reductions in the frontal cortex relative to UHR subjects who did not develop psychosis. The subgroup that subsequently developed schizophrenia also showed smaller volumes in the parietal cortex and, at trend level, in the temporal cortex, whereas those who developed an affective psychosis had significantly smaller subgenual cingulate volumes. These preliminary findings suggest that volumetric abnormalities in UHR individuals developing schizophrenia vs affective psychoses comprise a combination of features that predate both disorders and others that may be specific to the nature of the subsequent disorder.     

Cortical thinning in cingulate and occipital cortices in first episode schizophrenia.

BACKGROUND: Postmortem studies examining discrete regions show reduced cortical thickness in schizophrenia. Computational image analysis methods allow spatially detailed cortical thickness measurements across the entire cortex in 3D, but have not addressed thickness changes in cingulate or other cortices bordering the medial walls of the cerebral hemispheres in first episode schizophrenia. METHODS: Magnetic resonance images and cortical pattern matching methods were used to compare gray matter thickness, measured at sub-voxel resolution at thousands of spatially equivalent locations on the medial hemispheric surfaces, between 72 (51m/21f) first episode schizophrenia patients and 78 (37m/41f) healthy controls similar in age. Group differences were mapped in 3D, and their overall significance was confirmed by permutation testing. RESULTS: Patients with little or no prior antipsychotic medication treatment showed significant cortical thinning within cingulate, occipital and frontopolar cortices with no significant increases in any cortical location. Regional sex differences were observed with pronounced thinning in the left paracentral lobule and right posterior cingulate in male and female patients respectively compared to same sex controls. CONCLUSIONS: Cortical thinning may correspond to cytoarchitectural and neurochemical abnormalities observed in similar anatomic locations and may underlie systems-wise disturbances that include heteromodal association cortices, where cortical thinning has been previously observed in first episode schizophrenia.     

Hippocampal and anterior cingulate morphology in subjects at ultra-high-risk for psychosis: the role of family history of psychotic illness

BACKGROUND: While structural brain imaging abnormalities have been identified in schizophrenia and related disorders, it is unclear when they arise. Some appear to predate the illness and may be genetic in origin, while others are associated with the onset of the disorder. METHODS: We examined the hippocampal volumes and anterior cingulate morphology from the MRI scans of 79 male subjects at ultra-high-risk (UHR) for developing psychosis, 35 of whom had a family history of schizophrenia, and compared them with 49 healthy male volunteers. RESULTS: Analysis of covariance demonstrated that left hippocampal volumes were significantly smaller in the UHR group without a family history of schizophrenia, when compared to the UHR group with such history. A similar pattern was found for the left anterior cingulate region, both in terms of reduced paracingulate folding and cingulate sulcus interruptions, although this did not reach significance. CONCLUSIONS: We found that a family history of schizophrenia was not associated with a greater degree of structural brain abnormalities in an ultra-high-risk group, and in fact it was those UHR patients without such history who displayed greater abnormalities, although this only reached significance for the left hippocampus. Thus, it appears that the mechanisms that result in gross morphological anomalies in the hippocampus and anterior cingulate in psychosis are driven more by environmental than genetic factors.     

Abnormalities of cortical thickness in postictal psychosis

Postictal psychosis (PIP), the occurrence of psychotic episodes following a seizure, is a common and serious comorbidity in patients with epilepsy. Yet, the anatomical correlates remain poorly defined. Here, we used quantitative MRI morphometry to identify structural abnormalities in the cortex of patients with PIP relative to patients with epilepsy without PIP and age- and gender-matched normal healthy controls. Comparison of patients with epilepsy and PIP with patients with epilepsy without PIP revealed increased cortical thickness in the right lateral prefrontal cortex, right anterior cingulate cortex, and right middle temporal gyrus. The PIP group was distinguished from the EC and NC groups by thicker cortex in the right rostral anterior cingulate cortex and thinner cortex in the right angular gyrus and the left middle temporal region. Findings indicate that PIP is associated with thickening of the right anterior cingulate cortex, which may serve as a marker for patients at risk for developing PIP.     

Prefrontal cortical thickness in first-episode psychosis: a magnetic resonance imaging study.

BACKGROUND: Findings from postmortem studies suggest reduced prefrontal cortical thickness in schizophrenia; however, cortical thickness in first-episode schizophrenia has not been evaluated using magnetic resonance imaging (MRI). METHODS: Prefrontal cortical thickness was measured using MRI in first-episode schizophrenia patients (n = 17), first-episode affective psychosis patients (n = 17), and normal control subjects (n = 17); subjects were age-matched within 2 years and within a narrow age range (18-29 years). A previous study using the same subjects reported reduced prefrontal gray matter volume in first-episode schizophrenia. Manual editing was performed on those prefrontal segmentations before cortical thickness was measured. RESULTS: Prefrontal cortical thickness was not significantly different among groups. Prefrontal gray matter volume and thickness were, however, positively correlated in both schizophrenia and control subjects. The product of boundary complexity and thickness, an alternative measure of volume, was positively correlated with volume for all three groups. Finally, age and age at first medication were negatively correlated with prefrontal cortical thickness only in first-episode schizophrenia. CONCLUSIONS: This study demonstrates the potential usefulness of MRI for the study of cortical thickness abnormalities in schizophrenia. Correlations between cortical thickness and age and between cortical thickness and age at first medication suggest that the longer the schizophrenic process has been operative, the thinner the prefrontal cortex, although this needs confirmation in a longitudinal study.     

Associations between urban upbringing and cortical thickness and gyrification

Urbanicity has been linked to several psychiatric disorders, especially schizophrenia. Recent studies suggest effects of urban upbringing and stress on brain structure and function. Here, we used surface-based and voxel-based morphometry to study the effects of urban upbringing in different environments on variation in brain structure in a non-clinical sample. We recruited 85 young and healthy individuals from the community and recorded urban vs. rural background in their first 15 years of live. All participants underwent T1-weighted 3T MRI, which were then processed via CAT12 toolbox (in SPM12) to analyse cortical volume, thickness and gyrification. These parameters were correlated with an established measure of cumulative childhood and adolescence exposure to urban environments. We found significant (p < 0.05, FWE-corrected) negative correlations of cortical thickness with higher index of urban upbringing in the left dorsolateral prefrontal cortex, bilateral medial prefrontal cortices, as well as temporal cortices including the left superior temporal and left parahippocampal cortex. In contrast, results for volume and gyrification (incl. left posterior cingulate cortex) did not survive correction for multiple comparisons. We show a strong association of early-life urbanicity with cortical thickness in several areas, which are also impaired in schizophrenia patients. Along with other findings, these results converge on the dorsolateral prefrontal cortex as an area mediating this environmental risk.     

A randomized controlled trial of cognitive behavioral therapy for individuals at clinical high risk of psychosis

Background

Symptomatic and functional outcomes in schizophrenia are associated with the duration of untreated psychosis. However, no candidate biomarkers have been adopted in clinical settings. Multichannel near-infrared spectroscopy (NIRS), which can easily and noninvasively measure hemodynamics over the prefrontal cortex, is a candidate instrument for clinical use.

Aims

We intended to explore prefrontal dysfunction among individuals at different clinical stages, including ultra-high-risk (UHR), first-episode psychosis (FEP), and chronic schizophrenia (ChSZ), compared to healthy subjects.

Method

Twenty-two UHR subjects, 27 patients with FEP, 38 patients with ChSZ, and 30 healthy subjects participated. We measured hemodynamic changes during a block-designed letter fluency task using multichannel NIRS instruments.

Results

We found that the activations of the bilateral ventrolateral prefrontal cortex, and the fronto-polar and anterior parts of the temporal cortical regions in the UHR group were lower than those of the controls, but similar to those of the FEP and ChSZ groups. However, the activations in the bilateral dorsolateral prefrontal cortex regions decrease with advancing clinical stage.

Conclusions

To the best of our knowledge, this is the first study directly comparing differences in hemodynamic changes with respect to the 3 clinical stages of psychosis. Furthermore, this study also demonstrates different patterns of impairment according to the progression of clinical stages using NIRS instruments. NIRS measurements for UHR and FEP individuals may be candidate biomarkers for the early detection of the clinical stages of psychosis.     

Subgenual prefrontal cortex volumes in major depressive disorder and schizophrenia: diagnostic specificity and prognostic implications

OBJECTIVE: A variety of findings have implicated the portion of the anterior cingulate cortex ventral to the corpus callosum in the pathophysiology of familial depressive disorder. There are, as yet, few data to address the specificity of these abnormalities to depressive disorders or to characterize their stability over time. METHOD: The authors studied 10 subjects who were judged to have had major depressive disorder with psychotic features, who underwent magnetic resonance imaging (MRI) protocols, and who participated in a longitudinal study of recent-onset psychosis. These were group-matched to 10 subjects with schizophrenia and to 10 well comparison subjects. Volumetric measures were made of the posterior and anterior portions of the subgenual prefrontal cortex for these 30 subjects. Follow-up scans done an average of 4 years after intake were available for seven subjects with major depressive disorder, nine subjects with schizophrenia, and five well comparison subjects. RESULTS: Volumes of the left side of the posterior subgenual prefrontal cortex differed significantly by group and were smallest for the group with psychotic major depressive disorder. Volumes of the anterior subgenual prefrontal cortex did not differ significantly by group. Patients with major depressive disorder were more likely to show increases in posterior subgenual prefrontal cortex volume on follow-up than were comparison subjects or patients with schizophrenia. CONCLUSIONS: These findings add to the evidence that abnormalities in the subgenual region of the anterior cingulate play a role in at least some types of mood disorder.     

Regional cerebral cortical thinning in bipolar disorder

OBJECTIVE: This study was conducted to explore differences in cortical thickness between subjects with bipolar disorder and healthy comparison subjects using cortical surface-based analysis. METHODS: Brain magnetic resonance images were acquired from 25 subjects with bipolar disorder and 21 healthy comparison subjects. Cortical surface-based analysis was conducted using the Freesurfer application. Group differences in cortical thickness, defined by the distance from gray/white boundary to the pial surface, were assessed using statistical difference maps. RESULTS: Subjects with bipolar disorder exhibited significantly decreased cortical thickness in left cingulate cortex, left middle frontal cortex, left middle occipital cortex, right medial frontal cortex, right angular cortex, right fusiform cortex and bilateral postcentral cortices, relative to healthy comparison subjects (all p < 0.001). Duration of illness in bipolar subjects was inversely correlated with the cortical thickness of the left middle frontal cortex. CONCLUSIONS: Cortical thinning was present in multiple prefrontal cortices in bipolar disorder. There was also cortical thinning in sensory and sensory association cortices, which has not been reported in previous studies using region-of-interest or voxel-based morphometry methods. Cortical thinning observed in the current study may be related to impairment of emotional, cognitive, and sensory processing in bipolar disorder but longitudinal studies will be necessary to test this hypothesis.     

Automated MRI parcellation study of regional volume and thickness of prefrontal cortex (PFC) in antipsychotic-naïve schizophrenia

Objective: Prefrontal cortical dysfunction is considered to be critical in the pathogenesis of schizophrenia. However, structural magnetic resonance imaging (MRI) studies on the PFC have yielded inconsistent results because of various confounding factors. Method: In this study we examined the volume and thickness abnormalities of the PFC in antipsychotic‐naïve schizophrenia patients (n = 51) in comparison with age‐, sex‐, and handedness‐matched (as a group) healthy comparison subjects (n = 47) using a newly described automated MRI parcellation analysis. Results: Schizophrenia patients showed i) significant volume deficits in bilateral lateral orbitofrontal and left medial orbitofrontal cortices as well as bilateral pars triangularis; and ii) significant thickness deficit in bilateral medial orbitofrontal cortices. Negative syndrome score had a significant negative correlation with the thickness of the left medial orbitofrontal cortex. Conclusion: The study findings emphasize that prefrontal deficit in schizophrenia is differential and involves primarily the regions essential for ‘social cognition’.     

Dynamically spreading frontal and cingulate deficits mapped in adolescents with schizophrenia

CONTEXT: We previously detected a dynamic wave of gray matter loss in childhood-onset schizophrenia that started in parietal association cortices and proceeded frontally to envelop dorsolateral prefrontal and temporal cortices, including superior temporal gyri. OBJECTIVE: To map gray matter loss rates across the medial hemispheric surface, including the cingulate and medial frontal cortex, in the same cohort studied previously. DESIGN: Five-year longitudinal study. SETTING: National Institute of Mental Health, Bethesda, Md.Subjects Twelve subjects with childhood-onset schizophrenia, 12 healthy controls, and 9 medication- and IQ-matched subjects with psychosis not otherwise specified. INTERVENTIONS: Three-dimensional magnetic resonance imaging at baseline and follow-up. MAIN OUTCOME MEASURES: Gyral pattern and shape variations encoded by means of high-dimensional elastic deformation mappings driving each subject's cortical anatomy onto a group average; changes in cortical gray matter mapped by computing warping fields that matched sulcal patterns across hemispheres, subjects, and time. RESULTS: Selective, severe frontal gray matter loss occurred bilaterally in a dorsal-to-ventral pattern across the medial hemispheric surfaces in the schizophrenic subjects. A sharp boundary in the pattern of gray matter loss separated frontal regions and cingulate-limbic areas. CONCLUSION: Frontal and limbic regions may not be equally vulnerable to gray matter attrition, which is consistent with the cognitive, metabolic, and functional vulnerability of the frontal cortices in schizophrenia.     

Widespread cortical morphologic changes in juvenile myoclonic epilepsy: evidence from structural MRI

Purpose: Atypical morphology of the surface of the cerebral cortex may be related to abnormal cortical folding (gyrification) and therefore may indicate underlying malformations of cortical development (MCDs). Using magnetic resonance imaging (MRI)–based analysis, we examined cortical morphology in patients with juvenile myoclonic epilepsy (JME). Methods: MRI data was collected for 24 patients with JME and 40 demographically matched healthy controls. FreeSurfer, an automated cortical surface reconstruction method, was applied to compare cortical morphology between patients and controls. Areas of anomalous cortical morphology were defined as regions of interest (ROIs) to contrast regional cortical parameters, such as surface area, average thickness, and mean curvature between patients and controls. Key Findings: In patients with JME, changes to cortical morphology were detected in several regions. In the left hemisphere, these were in insular and cingulate cortices, occipital pole, and middle temporal and fusiform gyri. In the right hemisphere, changes were detected in insular cortex, inferior temporal gyrus, and precuneus. Further analysis of ROIs revealed that these changes are related to differences in surface area rather than average cortical thickness. In addition, mean curvature abnormalities were detected in the insula bilaterally, the left cingulate cortex, and right inferior temporal gyrus. Significance: The morphologic findings in this study suggest that structural abnormalities in JME extend beyond mesial frontal lobe regions of the brain. These may be indicative of areas of subtle cortical folding abnormality related to early disruption of cortical development.     

Structural abnormalities in language circuits in genetic high-risk subjects and schizophrenia patients

Schizophrenia is a severe psychiatric disorder with a strong genetic predisposition. Structural and functional brain deficits throughout the cerebral cortex, particularly in the language-processing associated brain regions, are consistently reported. Recently, increasing evidence from magnetic resonance imaging (MRI) studies suggests that healthy relatives of schizophrenia patients also show structural brain abnormalities in cortical gray matter (GM) volume and thickness, suggesting that this may be associated with an unexpressed genetic liability for the disorder. Unfortunately, the findings are not consistent, which may be caused by different age ranges of the cohorts studied. In the present study, we examined the voxel-based whole brain cortical thickness, area, GM volume densities, and regional cortical thickness-related laterality indices in 14 bilateral regions of interest (ROIs) from known language-processing circuits in 20 schizophrenia patients, 21 young non-psychotic subjects with heightened genetic risk for schizophrenia at the peak ages for development of the disorder, and 48 matched controls. The results showed widespread significant reductions in cortical thickness, cortical GM volume density, and scattered decreases in cortical surface area in the schizophrenia patients compared with those in the high-risk subjects and normal controls. Moreover, the genetic high-risk subjects showed significantly increased regional cortical thickness in 7 of the 14 ROIs in the language-processing pathway when compared with controls. They also had increased GM volume density in scattered regions associated with language-processing when compared with the normal controls. Laterality analyses showed that the spatial distribution of abnormal cortical thickness in the schizophrenia patients, as well as in the high-risk subjects, contributes to a decrease of the normal left-greater-than-right anatomical asymmetry in the inferior orbital frontal area, and a increased left-greater-than-right pattern in the inferior parietal and occipital regions. Together with the existing findings in the literature, the results of the present study suggest that developmental disruption of the anatomical differentiation of the hemispheres provides a basis for understanding the language impairment and symptoms of psychosis, and that these may arise because of abnormal left-right hemispherical communications that interrupt the normal flow of information processing. The early structural deficits in language-processing circuits may precede the appearance of psychotic symptoms and may be an indicator of an increased risk of developing schizophrenia.     

Regional cortical thinning in subjects with violent antisocial personality disorder or schizophrenia

Violent behavior is associated with antisocial personality disorder and to a lesser extent with schizophrenia. Neuroimaging studies have suggested that several biological systems are disturbed in schizophrenia, and structural changes in frontal and temporal lobe regions are reported in both antisocial personality disorder and schizophrenia. The neural substrates that underlie violent behavior specifically and their structural analogs, however, remain poorly understood. Nor is it known whether a common biological basis exists for aggressive, impulsive, and violent behavior across these clinical populations. To explore the correlates of violence with brain structure in antisocial personality disorder and schizophrenia, the authors used magnetic resonance imaging data to investigate for the first time, to the authors' knowledge, regional differences in cortical thickness in violent and nonviolent individuals with schizophrenia and/or antisocial personality disorder and in healthy comparison subjects. Subject groups included right-handed men closely matched for demographic variables (total number of subjects=56). Violence was associated with cortical thinning in the medial inferior frontal and lateral sensory motor cortex, particularly in the right hemisphere, and surrounding association areas (Brodmann's areas 10, 11, 12, and 32). Only violent subjects with antisocial personality disorder exhibited cortical thinning in inferior mesial frontal cortices. The biological underpinnings of violent behavior may therefore vary between these two violent subject groups in which the medial frontal cortex is compromised in antisocial personality disorder exclusively, but laminar abnormalities in sensorimotor cortices may relate to violent behavior in both antisocial personality disorder and schizophrenia.     

Age-related cortical thinning in schizophrenia

Although the effects of aging on the neural correlates of schizophrenia have been researched for many years, no clear conclusion has been reached. While some studies have demonstrated progressive age-related gray matter reductions in schizophrenia, other studies have not found evidence of progression. Moreover, it remains unclear whether the influence of aging on global or regional cortical thickness differs between schizophrenia patients and healthy controls. This study aimed to confirm previous reports of reduced cortical thickness in schizophrenia, and to investigate the effects of age on global and regional cortical thickness. Eighty-three patients with schizophrenia (six first-episode patients and 77 chronic patients; age range=18-55 years) and 90 age-, gender- and education-matched healthy controls (age range=19-56 years) underwent structural magnetic resonance imaging (MRI) using a 3-Tesla scanner. Surface-based analysis was applied to assess cortical thickness in the whole brain. The patient group exhibited both global and regional cortical thinning in regions including the prefrontal and temporal cortices. The correlation between age and cortical thickness showed a similar pattern in patients and controls, both globally and regionally. These results suggest that the reduction of cortical thickness in schizophrenia might not be progressive over the course of the illness, indicating that pathological processes occur in a relatively limited period of time around the onset of illness.     

Neuroanatomical Maps of Psychosis Onset: Voxel-wise Meta-Analysis of Antipsychotic-Naive VBM Studies

Background: Despite impressive advancements in early interventions in psychosis, there is an urgent need of robust neurobiological markers to improve the predictive value of psychosis transition. Available structural imaging literature in the field is undermined by several methodological caveats and a number of confounders such as exposure to antipsychotic treatment. Methods: Fourteen voxel-based morphometry studies of antipsychotic-naive subjects at enhanced clinical risk for psychosis (high risk [HR]) or experiencing a first-episode psychosis (FEP) were included. Formal meta-analysis of effect sizes and “signed differential mapping” voxel-based meta-analysis were combined to control the results for sample sizes, strength of individual findings, and confounding variables. Results: Formal effect size meta-analysis indicated consistent gray matter (GM) reductions both in subjects at enhanced clinical risk for psychosis and in first-episode subjects when compared with control groups. Voxel-based meta-analysis showed GM reductions in the temporal, limbic prefrontal cortex within the HR group and in the temporal insular cortex and cerebellum within the FEP group. Psychosis onset was characterized by GM decreases in temporal, anterior cingulate, cerebellar, and insular regions. GM alterations in the temporal regions directly related to severity of psychotic symptoms. There was no publication bias. Heterogeneity across studies was low. Sensitivity analyses confirmed robustness of the above results. Conclusions: Vulnerability to psychosis is associated with consistent GM decreases in prefrontal and temporolimbic areas. The onset of full disease is accompanied by temporoinsular, anterior cingulate, and cerebellar GM reductions. Neuroanatomical alterations in temporal regions may underlie the clinical onset of psychotic symptoms.     

Age effects on cerebral grey matter and their associations with psychopathology,cognition and treatment response in previously untreated schizophrenia patients

The diagnosis of schizophrenia lacks a broadly accepted biological basis and its heterogeneity may well represent a group of disorders with different etiologies. Even so, brain imaging can map and quantify structural brain abnormalities in vivo as an intermediate (or endo-) phenotype of the disorder. Brain structural abnormalities occur in the prodromal phase and progress in the course of illness, and patterns of grey matter deficits appear to determine the clinical phenotype, thus addressing some of the diagnostic heterogeneity. Here we examined cerebral grey matter with cortical pattern matching in MRI scans from 18 previously untreated patients meeting DSM-IV diagnostic criteria for schizophrenia by employing a three-dimensional spoiled gradient recalled (SPGR) pulse sequence at 1.5 T. Data were compared to 18 pair-wise age and sex-matched healthy volunteers from the patient communities. We found widespread cerebral grey matter deficits in schizophrenia. Grey matter deficits in the right dorsolateral prefrontal cortex were the strongest predictor of diagnosis. Symptom severity and treatment response were associated with regional grey matter deficits in older patients with a longer history of untreated illness, while significant structure/function associations with cognitive impairment in prefrontal and temporal cortices were found across all ages. Quantitative brain maps are useful for assessing disease burden in schizophrenia, and for understanding its heterogeneity, including its changing clinical characteristics as the illness progresses.     

Cigarette smoking is associated with thinner cingulate and insular cortices in patients with severe mental illness

Background

Magnetic resonance imaging (MRI) studies show reduced cortical thickness in patients with schizophrenia and bipolar disorder. These subtle brain abnormalities may provide insight into illness mechanisms. However, environmental and lifestyle-related factors, such as cigarette smoking, may contribute to brain structure changes. Cigarette smoking is highly prevalent in patients with severe mental illness. In nonpsychiatric samples, smoking has been associated with reduced thickness in the anterior (ACC) and posterior cingulate cortices, the insular cortex (INS), the dorsolateral prefrontal cortex and the orbitofrontal cortex.

Methods

We examined MRI scans from patients with schizophrenia, other psychotic disorders or bipolar disorder and healthy controls using FreeSurfer.

Results

We included 506 patients (49% smokers) and 237 controls (20% smokers) in our study. We found reduced cortical thickness in the left rostral ACC and the left INS in smoking patients compared with nonsmoking patients, but this difference was not found among healthy controls. No dose–response relationship was found between amount of smoking and cortical thickness in these regions. Among patients, maps of thickness along the whole cortical surface revealed reduced insular thickness but no effects in other regions. Among healthy controls, similar analyses revealed increased age-related cortical thinning in the left occipital lobe among smokers compared with nonsmokers.

Limitations

The causal direction could not be determined owing to the cross-sectional design and lack of detailed data on smoking addiction and smoking history.

Conclusion

The effect of cigarette smoking should be considered in MRI studies of patients with severe mental illness.