Distinguishing Prodromal From First-Episode Psychosis Using Neuroanatomical Single-Subject Pattern Recognition

Background: The at-risk mental state for psychosis (ARMS) and the first episode of psychosis have been associated with structural brain abnormalities that could aid in the individualized early recognition of psychosis. However, it is unknown whether the development of these brain alterations predates the clinical deterioration of at-risk individuals, or alternatively, whether it parallels the transition to psychosis at the single-subject level. Methods: We evaluated the performance of an magnetic resonance imaging (MRI)-based classification system in classifying disease stages from at-risk individuals with subsequent transition to psychosis (ARMS-T) and patients with first-episode psychosis (FE). Pairwise and multigroup biomarkers were constructed using the structural MRI data of 22 healthy controls (HC), 16 ARMS-T and 23 FE subjects. The performance of these biomarkers was measured in unseen test cases using repeated nested cross-validation. Results: The classification accuracies in the HC vs FE, HC vs ARMS-T, and ARMS-T vs FE analyses were 86.7%, 80.7%, and 80.0%, respectively. The neuroanatomical decision functions underlying these discriminative results particularly involved the frontotemporal, cingulate, cerebellar, and subcortical brain structures. Conclusions: Our findings suggest that structural brain alterations accumulate at the onset of psychosis and occur even before transition to psychosis allowing for the single-subject differentiation of the prodromal and first-episode stages of the disease. Pattern regression techniques facilitate an accurate prediction of these structural brain dynamics at the early stage of psychosis, potentially allowing for the early recognition of individuals at risk of developing psychosis.Key words: at-risk mental state, early prediction of psychosis, voxel-based morphometry, multivariate analysis, machine learning, support vector machine     

White matter alterations related to P300 abnormalities in individuals at high risk for psychosis: an MRI-EEG study

Background

Psychosis onset is characterized by white matter and electrophysiologic abnormalities. The relation between these factors in the development of illness is almost unknown. We studied the relation between white matter volumes and P300 in prodromal psychosis.

Methods

We assessed white matter volume (detected using magnetic resonance imaging) and electrophysiologic response during an oddball task (P300) in healthy controls and individuals at high clinical risk for psychosis (with an “at-risk mental state” [ARMS]).

Results

We included 41 controls and 39 patients with an ARMS in our study. A psychotic disorder developed in 26% of the ARMS group within the follow-up period of 2 years. The P300 amplitude was significantly lower in the ARMS group than in the control group. The ARMS group showed reduced volume of white matter underlying the left superior temporal gyrus and the left superior frontal gyrus and increased volume of white matter underlying the right insula and the right angular gyrus compared with controls. Relative to individuals who did not later become psychotic, the subgroup in whom psychosis subsequently developed had a smaller volume of white matter underlying the left precuneus and the right middle temporal gyrus and increased volume in the white matter underlying the right middle frontal gyrus. We observed a significant interaction in the right middle frontal gyrus: white matter volume was negatively associated with P300 amplitude in the ARMS group and positively associated with P300 amplitude in the control group.

Limitations

The voxel-based morphometry method alone cannot determine whether abnormal white matter volumes are due to an altered number of axonal connections or decreased myelination.

Conclusion

P300 abnormalities precede the onset of psychosis and are directly related to white matter alterations, representing a correlate of an increased vulnerability to disease.     

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.     

Brain morphometric abnormalities in geriatric depression: long-term neurobiological effects of illness duration

OBJECTIVE: The authors' goal was to compare regional brain volumes in depressed elderly subjects with those of nondepressed elderly subjects by using voxel-based morphometry. METHOD: They used statistical parametric mapping to analyze magnetic resonance imaging scans from 30 depressed patients 59 to 78 years old and 47 nondepressed comparison subjects 55 to 81 years old. RESULTS: Depressed patients had smaller right hippocampal volume than comparison subjects. The volume of the hippocampal-entorhinal cortex was inversely associated with the number of years since the first lifetime episode of depression. CONCLUSIONS: These data provide further evidence of structural brain abnormalities in geriatric depression, particularly in patients with a longer course of illness.     

Different duration of at-risk mental state associated with neurofunctional abnormalities. A multimodal imaging study

Objectives: Neurofunctional alterations are correlates of vulnerability to psychosis, as well as of the disorder itself. How these abnormalities relate to different probabilities for later transition to psychosis is unclear. We investigated vulnerability‐ versus disease‐related versus resilience biomarkers of psychosis during working memory (WM) processing in individuals with an at‐risk mental state (ARMS). Experimental design: Patients with “first‐episode psychosis” (FEP, n = 21), short‐term ARMS (ARMS‐ST, n = 17), long‐term ARMS (ARMS‐LT, n = 16), and healthy controls (HC, n = 20) were investigated with an n‐back WM task. We examined functional magnetic resonance imaging (fMRI) and structural magnetic resonance imaging (sMRI) data in conjunction using biological parametric mapping (BPM) toolbox. Principal observations: There were no differences in accuracy, but the FEP and the ARMS‐ST group had longer reaction times compared with the HC and the ARMS‐LT group. With the 2‐back > 0‐back contrast, we found reduced functional activation in ARMS‐ST and FEP compared with the HC group in parietal and middle frontal regions. Relative to ARMS‐LT individuals, FEP patients showed decreased activation in the bilateral inferior frontal gyrus and insula, and in the left prefrontal cortex. Compared with the ARMS‐LT, the ARMS‐ST subjects showed reduced activation in the right inferior frontal gyrus and insula. Reduced insular and prefrontal activation was associated with gray matter volume reduction in the same area in the ARMS‐LT group. Conclusions: These findings suggest that vulnerability to psychosis was associated with neurofunctional alterations in fronto‐temporo‐parietal networks in a WM task. Neurofunctional differences within the ARMS were related to different duration of the prodromal state and resilience factors. Hum Brain Mapp 33:2281–2294, 2012. © 2011 Wiley Periodicals, Inc.     

Voxel-based morphometry evaluation of patients with photosensitive juvenile myoclonic epilepsy

We aim to investigate structural brain abnormalities in juvenile myoclonic epilepsy (JME) patients with photosensitivity (PS). Sixty JME patients, 19 (32%) of whom were photosensitive, were submitted to 1.5 T magnetic resonance voxel-based morphometry (VBM). The control group (CTL) consisted of 30 sex-matched healthy volunteers. JME patients with (JME-PS) and without (JME-NPS) PS did not differ in their duration of disease, treatment or seizure control. VBM revealed significantly reduced bilateral gray matter volume (GMV) in thalami, insula cortices and cerebellar hemispheres; while significantly increased GMV was observed in the right superior frontal, orbitofrontal and medial frontal gyri of the JME group compared to CTL. JME-PS had reduced bilateral GMV of visual cortices when compared with CTL; while it was not seen among JME-NPS patients. Reduced left hippocampus and left inferior frontal gyrus volume was observed among JME-PS compared with JME-NPS. This study demonstrates structural abnormalities beyond the limits of the frontal lobes and provides evidence for the role of the occipital cortex in human PS, reinforcing the existence of functional-anatomic ictogenic networks in JME and the concept of ‘system epilepsies’.     

Developmental changes in multivariate neuroanatomical patterns that predict risk for psychosis in 22q11.2 deletion syndrome

The primary objective of the current prospective study was to examine developmental patterns of voxel-by-voxel gray and white matter volumes (GMV, WMV, respectively) that would predict psychosis in adolescents with 22q11.2 deletion syndrome (22q11.2DS), the most common known genetic risk factor for schizophrenia. We performed a longitudinal voxel-based morphometry analysis using structural T1 MRI scans from 19 individuals with 22q11.2DS and 18 typically developing individuals. In 22q11.2DS, univariate analysis showed that greater reduction in left dorsal prefrontal cortical (dPFC) GMV over time predicted greater psychotic symptoms at Time2. This dPFC region also showed significantly reduced volumes in 22q11.2DS compared to typically developing individuals at Time1 and 2, greater reduction over time in 22q11.2DS COMT^Met compared to COMT^Val, and greater reduction in those with greater decline in verbal IQ over time. Leave-one-out Multivariate pattern analysis results (MVPA) on the other hand, showed that patterns of GM and WM morphometric changes over time in regions including but not limited to the dPFC predicted risk for psychotic symptoms (94.7-100% accuracy) significantly better than using univariate analysis (63.1%). Additional predictive brain regions included medial PFC and dorsal cingulum. This longitudinal prospective study shows novel evidence of morphometric spatial patterns predicting the development of psychotic symptoms in 22q11.2DS, and further elucidates the abnormal maturational processes in 22q11.2DS. The use of neuroimaging using MVPA may hold promise to predict outcome in a variety of neuropsychiatric disorders.     

Autism Spectrum Disorder as Early Neurodevelopmental Disorder: Evidence from the Brain Imaging Abnormalities in 2–3 Years Old Toddlers

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that occurs within the first 3 years of life, which is marked by social skills and communication deficits along with stereotyped repetitive behavior. Although great efforts have been made to clarify the underlying neuroanatomical abnormalities and brain-behavior relationships in adolescents and adults with ASD, literature is still limited in information about the neurobiology of ASD in the early age of life. Brain images of 50 toddlers with ASD and 28 age, gender, and developmental quotient matched toddlers with developmental delay (DD) (control group) between ages 2 and 3 years were captured using combined magnetic resonance-based structural imaging and diffusion tensor imaging (DTI). Structural magnetic resonance imaging was applied to assess overall gray matter (GM) and white matter (WM) volumes, and regional alterations were assessed by voxel-based morphometry. DTI was used to investigate the white matter tract integrity. Compared with DD, significant increases were observed in ASD, primarily in global GM and WM volumes and in right superior temporal gyrus regional GM and WM volumes. Higher fractional anisotropy value was also observed in the corpus callosum, posterior cingulate cortex, and limbic lobes of ASD. The converging findings of structural and white matter abnormalities in ASD suggest that alterations in neural-anatomy of different brain regions may be involved in behavioral and cognitive deficits associated with ASD, especially in an early age of 2–3 years old toddlers.     

Multivariate patterns of brain-cognition associations relating to vulnerability and clinical outcome in the at-risk mental states for psychosis

Background: Neuropsychological deficits are a core feature of established psychosis and have been previously linked to fronto‐temporo‐limbic brain alterations. Both neurocognitive and neuroanatomical abnormalities characterize clinical at‐risk mental states (ARMS) for psychosis. However, structure–cognition relationships in the ARMS have not been directly explored using multivariate neuroimaging techniques. Methods: Voxel‐based morphometry and partial least squares were employed to study system‐level covariance patterns between whole‐brain morphological data and processing speed, working memory, verbal learning/IQ, and executive functions in 40 ARMS subjects and 30 healthy controls (HC). The detected structure–cognition covariance patterns were tested for significance and reliability using non‐parametric permutation and bootstrap resampling. Results: We identified ARMS‐specific covariance patterns that described a generalized association of neurocognitive measures with predominantly prefronto‐temporo‐limbic and subcortical structures as well as the interconnecting white matter. In the conversion group, this generalized profile particularly involved working memory and verbal IQ and was positively correlated with limbic, insular and subcortical volumes as well as negatively related to prefrontal, temporal, parietal, and occipital cortices. Conversely, the neurocognitive profiles in the HC group were confined to working memory, learning and IQ, which were diffusely associated with cortical and subcortical brain regions. Conclusions: These findings suggest that the ARMS and prodromal phase of psychosis are characterized by a convergent mapping from multi‐domain neurocognitive measures to a set of prefronto‐temporo‐limbic and subcortical structures. Furthermore, a neuroanatomical separation between positive and negative brain–cognition correlations may not only point to a biological process determining the clinical risk for disease transition, but also to possible compensatory or dysmaturational neural processes. Hum Brain Mapp 33:2104–2124, 2012. © 2011 Wiley Periodicals, Inc.     

Absence of gender effect on children with attention-deficit/hyperactivity disorder as assessed by optimized voxel-based morphometry

Brain abnormalities, as determined by structural magnetic resonance imaging (MRI), have been reported in patients with attention-deficit hyperactivity disorder (ADHD); however, female subjects have been underrepresented in previous reports. In this study, we used optimized voxel-based morphometry to compare the total and regional gray matter volumes between groups of 7- to 17-year-old ADHD and healthy children (total 114 subjects). Fifty-seven children with ADHD (n=57, 35 males and 22 females) and healthy children (n=57) received MRI scans. Segmented brain MRI images were normalized into standardized stereotactic space, modulated to allow volumetric analysis, smoothed and compared at the voxel level with statistical parametric mapping. Global volumetric comparisons between groups revealed that the total brain volumes of ADHD children were smaller than those of the control children. As for the regional brain analysis, the brain volumes of ADHD children were found to be bilaterally smaller in the following regions as compared with normal control values: the caudate nucleus and the cerebellum. There were two clusters of regional decrease in the female brain, left posterior cingulum and right precuneus, as compared with the male brain. Brain regions showing the interaction effect of diagnosis and gender were negligible. These results were consistent with the hypothesized dysfunctional systems in ADHD, and they also suggested that neuroanatomical abnormalities in ADHD were not influenced by gender.     

A multimodal meta-analysis of regional structural and functional brain alterations in type 2 diabetes

Neuroimaging studies have identified brain structural and functional alterations of type 2 diabetes mellitus (T2DM) patients; however, there is no systematic information on the relations between abnormalities in these two domains. We conducted a multimodal meta-analysis of voxel-based morphometry and regional resting-state functional MRI studies in T2DM, including fifteen structural datasets (693 patients and 684 controls) and sixteen functional datasets (378 patients and 358 controls). We found, in patients with T2DM compared to controls, conjoint decreased regional gray matter volume (GMV) and altered intrinsic activity mainly in the default mode network including bilateral superior temporal gyrus/Rolandic operculum, left middle and inferior temporal gyrus, and left supramarginal gyrus; decreased GMV alone in the limbic system; and functional abnormalities alone in the cerebellum, insula, and visual cortex. This meta-analysis identified complicated patterns of conjoint and dissociated brain alterations in T2DM patients, which may help provide new insight into the neuropathology of T2DM.     

Multimodal voxel-based meta-analysis of structural and functional magnetic resonance imaging studies in those at elevated genetic risk of developing schizophrenia

Computational brain-imaging studies of individuals at familial high risk for psychosis have provided interesting results, but interpreting these findings can be a challenge due to a number of factors. We searched the literature for studies reporting whole brain voxel-based morphometry (VBM) or functional magnetic resonance imaging (fMRI) findings in people at familial high risk for schizophrenia compared with a control group. A voxel-wise meta-analysis with the effect-size version of Signed Differential Mapping (ES-SDM) identified regional abnormalities of functional brain response. Similarly, an ES-SDM meta-analysis was conducted on VBM studies. A multi-modal imaging meta-analysis was used to highlight brain regions with both structural and functional abnormalities. Nineteen studies met the inclusion criteria, in which a total of 815 familial high-risk individuals were compared to 685 controls. Our fMRI results revealed a number of regions of altered activation. VBM findings demonstrated both increases and decreases in grey matter density of relatives in a variety of brain regions. The multimodal analysis revealed relatives had decreased grey matter with hyper-activation in the left inferior frontal gyrus/amygdala, and decreased grey matter with hypo-activation in the thalamus. We found several regions of altered activation or structure in familial high-risk individuals. Reliable fMRI findings in the right posterior superior temporal gyrus further confirm that alteration in this area is a potential marker of risk.     

New structural brain imaging endophenotype in bipolar disorder

Neuroimaging studies suggest anterior-limbic structural brain abnormalities in patients with bipolar disorder (BD), but few studies have shown these abnormalities in unaffected but genetically liable family members. In this study, we report morphometric correlates of genetic risk for BD using voxel-based morphometry. In 35 BD type I (BD-I) patients, 20 unaffected first-degree relatives (UAR) of BD patients and 40 healthy control subjects underwent 3?T magnetic resonance scanner imaging. Preprocessing of images used DARTEL (diffeomorphic anatomical registration through exponentiated lie algebra) for voxel-based morphometry in SPM8 (Wellcome Department of Imaging Neuroscience, London, UK). The whole-brain analysis revealed that the gray matter (GM) volumes of the left anterior insula and right inferior frontal gyrus showed a significant main effect of diagnosis. Multiple comparison analysis showed that the BD-I patients and the UAR subjects had smaller left anterior insular GM volumes compared with the healthy subjects, the BD-I patients had smaller right inferior frontal gyrus compared with the healthy subjects. For white matter (WM) volumes, there was a significant main effect of diagnosis for medial frontal gyrus. The UAR subjects had smaller right medial frontal WM volumes compared with the healthy subjects. These findings suggest that morphometric brain abnormalities of the anterior-limbic neural substrate are associated with family history of BD, which may give insight into the pathophysiology of BD, and be a potential candidate as a morphological endophenotype of BD.     

Reduced gray matter volume in ventral prefrontal cortex but not amygdala in bipolar disorder: Significant effects of gender and trait anxiety

Neuroimaging studies in bipolar disorder report gray matter volume (GMV) abnormalities in neural regions implicated in emotion regulation. This includes a reduction in ventral/orbital medial prefrontal cortex (OMPFC) GMV and, inconsistently, increases in amygdala GMV. We aimed to examine OMPFC and amygdala GMV in bipolar disorder type 1 patients (BPI) versus healthy control participants (HC), and the potential confounding effects of gender, clinical and illness history variables and psychotropic medication upon any group differences that were demonstrated in OMPFC and amygdala GMV. Images were acquired from 27 BPI (17 euthymic, 10 depressed) and 28 age- and gender-matched HC in a 3T Siemens scanner. Data were analyzed with SPM5 using voxel-based morphometry (VBM) to assess main effects of diagnostic group and gender upon whole brain (WB) GMV. Post-hoc analyses were subsequently performed using SPSS to examine the extent to which clinical and illness history variables and psychotropic medication contributed to GMV abnormalities in BPI in a priori and non-a priori regions has demonstrated by the above VBM analyses. BPI showed reduced GMV in bilateral posteromedial rectal gyrus (PMRG), but no abnormalities in amygdala GMV. BPI also showed reduced GMV in two non-a priori regions: left parahippocampal gyrus and left putamen. For left PMRG GMV, there was a significant group by gender by trait anxiety interaction. GMV was significantly reduced in male low-trait anxiety BPI versus male low-trait anxiety HC, and in high- versus low-trait anxiety male BPI. Our results show that in BPI there were significant effects of gender and trait-anxiety, with male BPI and those high in trait-anxiety showing reduced left PMRG GMV. PMRG is part of medial prefrontal network implicated in visceromotor and emotion regulation.     

Associations of White Matter Integrity and Cortical Thickness in Patients With Schizophrenia and Healthy Controls

Typical brain development includes coordinated changes in both white matter (WM) integrity and cortical thickness (CT). These processes have been shown to be disrupted in schizophrenia, which is characterized by abnormalities in WM microstructure and by reduced CT. The aim of this study was to identify patterns of association between WM markers and cortex-wide CT in healthy controls (HCs) and patients with schizophrenia (SCZ). Using diffusion tensor imaging and structural magnetic resonance imaging data of the Mind Clinical Imaging Consortium study (130 HC and 111 SCZ), we tested for associations between (a) fractional anisotropy in selected manually labeled WM pathways (corpus callosum, anterior thalamic radiation, and superior longitudinal fasciculus) and CT, and (b) the number of lesion-like WM regions (“potholes”) and CT. In HC, but not SCZ, we found highly significant negative associations between WM integrity and CT in several pathways, including frontal, temporal, and occipital brain regions. Conversely, in SCZ the number of WM potholes correlated with reduced CT in the left lateral temporal gyrus, left fusiform, and left lateral occipital brain area. Taken together, we found differential patterns of association between WM integrity and CT in HC and SCZ. Although the pattern in HC can be explained from a developmental perspective, the reduced gray matter CT in SCZ patients might be the result of focal but spatially heterogeneous disruptions of WM integrity.Key words: cortical thickness, fractional anisotropy, structural MRI, DTI, schizophrenia     

Brain Structure in Neuropsychologically Defined Subgroups of Schizophrenia and Psychotic Bipolar Disorder

Background:

Neuropsychological impairment is heterogeneous in psychosis. The association of intracranial volume (ICV) and total brain volume (TBV) with cognition suggests brain structure abnormalities in psychosis will covary with the severity of cognitive impairment. We tested the following hypotheses: (1) brain structure abnormalities will be more extensive in neuropsychologically impaired psychosis patients; (2) psychosis patients with premorbid cognitive limitations will show evidence of hypoplasia (ie, smaller ICV); and (3) psychosis patients with evidence of cognitive decline will demonstrate atrophy (ie, smaller TBV, but normal ICV).

Methods:

One hundred thirty-one individuals with psychosis and 97 healthy subjects underwent structural magnetic resonance imaging and neuropsychological testing. Patients were divided into neuropsychologically normal and impaired groups. Impaired patients were further subdivided into deteriorated and compromised groups if estimated premorbid intellect was average or below average, respectively. ICV and TBV were compared across groups. Localized brain volumes were qualitatively examined using voxel-based morphometry.

Results:

Compared to healthy subjects, neuropsychologically impaired patients exhibited smaller TBV, reduced grey matter volume in frontal, temporal, and subcortical brain regions, and widespread white matter volume loss. Neuropsychologically compromised patients had smaller ICV relative to healthy subjects, and neuropsychologically normal and deteriorated patient groups, but relatively normal TBV. Deteriorated patients exhibited smaller TBV compared to healthy subjects, but relatively normal ICV. Unexpectedly, TBV, adjusted for ICV, was reduced in neuropsychologically normal patients.

Conclusions:

Patients with long-standing cognitive limitations exhibit evidence of early cerebral hypoplasia, whereas neuropsychologically normal and deteriorated patients show evidence of brain tissue loss consistent with progression or later cerebral dysmaturation.Key words: psychosis, cognition, brain volume, neurodevelopmental, neuroprogressive     

Abnormal Causal Connectivity by Structural Deficits in First-Episode,Drug-Naive Schizophrenia at Rest

Anatomical deficits and resting-state functional connectivity (FC) alterations in prefrontal-thalamic-cerebellar circuit have been implicated in the neurobiology of schizophrenia. However, the effect of structural deficits in schizophrenia on causal connectivity of this circuit remains unclear. This study was conducted to examine the causal connectivity biased by structural deficits in first-episode, drug-naive schizophrenia patients. Structural and resting-state functional magnetic resonance imaging (fMRI) data were obtained from 49 first-episode, drug-naive schizophrenia patients and 50 healthy controls. Data were analyzed by voxel-based morphometry and Granger causality analysis. The causal connectivity of the integrated prefrontal-thalamic (limbic)-cerebellar (sensorimotor) circuit was partly affected by structural deficits in first-episode, drug-naive schizophrenia as follows: (1) unilateral prefrontal-sensorimotor connectivity abnormalities (increased driving effect from the left medial prefrontal cortex [MPFC] to the sensorimotor regions); (2) bilateral limbic-sensorimotor connectivity abnormalities (increased driving effect from the right anterior cingulate cortex [ACC] to the sensorimotor regions and decreased feedback from the sensorimotor regions to the right ACC); and (3) bilateral increased and decreased causal connectivities among the sensorimotor regions. Some correlations between the gray matter volume of the seeds, along with their causal effects and clinical variables (duration of untreated psychosis and symptom severity), were also observed in the patients. The findings indicated the partial effects of structural deficits in first-episode, drug-naive schizophrenia on the prefrontal-thalamic (limbic)-cerebellar (sensorimotor) circuit. Schizophrenia may reinforce the driving connectivities from the left MPFC or right ACC to the sensorimotor regions and may disrupt bilateral causal connectivities among the sensorimotor regions.Key words: first-episode schizophrenia, causal effect, structural deficits, voxel-based morphometry, Granger causality analysis     

Cortical thickness is associated with poor insight in first-episode psychosis

Through conceptualizing poor insight in psychotic disorders as a form of anosognosia (neurological deficit), frontal lobe dysfunction is often ascribed a vital role in its pathogenesis. Whether non-frontal brain regions are important for insight remains to be investigated. We used a multi-method approach to examine the neural morphometry of all cortical regions for insight in first-episode psychosis. Insight was rated in 79 people with a first-episode psychosis with the awareness of illness and awareness of treatment need and efficacy items of the Scale for assessment of Unawareness of Mental Disorder. Participants were assessed with magnetic resonance imaging. Cortical thickness analysis and voxel-based morphometry were utilized to identify the possible neuroanatomical basis of insight. Cortical thickness technique revealed that poorer awareness of illness was associated with regional thinning in left middle frontal and inferior temporal gyri. Poorer awareness of treatment need and efficacy was associated with cortical thinning in left medial frontal gyrus, precuneus and temporal gyri. No significant associations emerged between any insight measure and gray matter density using voxel-based morphometry. The results confirm predictions derived from the anosognosia/neuropsychology account and assert that regional thickness in frontal cortex is associated with awareness of illness in the early phase of psychosis. The fact that prominent thickness reductions emerged in non-frontal regions of the brain in parietal and temporal cortices for both awareness of illness and awareness of treatment need and efficacy suggests that the neural signature of insight involves a network of brain structures, and not only the frontal lobes as previously suggested.     

No change to grey and white matter volumes in bipolar I disorder patients

BACKGROUND: Structural brain imaging is assumed to be a key method to elucidate the underlying neuropathology of bipolar disorder. However, magnetic resonance imaging studies using region of interest analysis and voxel-based morphometry (VBM) revealed quite inconsistent findings. Hence, there is no clear evidence so far for core regions of cortical or subcortical structural abnormalities in bipolar disorder. The aim of this study was to investigate grey and white matter volumes in a large sample of patients with bipolar I disorder. METHODS: Thirty-five patients with bipolar I disorder and 32 healthy controls matched with respect to gender, handedness and education participated in the study. MRI scanning was performed and an optimized VBM analysis was conducted. RESULTS: We could not observe any significant differences of grey or white matter volumes between patients with bipolar disorder and healthy control subjects. Additional analyses did not reveal significant correlations between grey or white matter volume with number of manic or depressive episodes, duration of illness, existence of psychotic symptoms, and treatment with lithium or antipsychotics. CONCLUSIONS: With this VBM study we were not able to identify core regions of structural abnormalities in bipolar disorder.     

Unimpaired social cognition in adult patients with ADHD: brain volumetric and behavioral results

The present study aimed to investigate whether adult patients with attention deficit hyperactivity disorder (ADHD) show deficits in social cognition and to identify the structural neural correlates of social cognitive skills in ADHD. Twenty-six adult patients with ADHD and 26 matched healthy control participants performed the Movie for the Assessment of Social Cognition and underwent a structural magnetic resonance imaging scan. We compared theory of mind (ToM) performance between ADHD patients and healthy controls. Using voxel-based morphometry, we further compared gray matter volumes in regions that are critical for social cognition between the two groups and examined whether ToM performance was correlated with brain morphometry measures. We did not observe any between-group differences in ToM abilities or regional gray matter volumes. Across both groups, performance on affective aspects of ToM correlated positively with gray matter volumes in the medial part of the superior frontal gyri, which is typically involved in social cognition. This study is the first to relate brain structure to social cognitive abilities in adult patients with ADHD. Although our sample was small and heterogeneous, with half of the patients showing mild-to-moderate psychiatric comorbidities, our results may encourage longitudinal studies that relate social cognitive development in childhood and adolescence to brain maturation of ADHD patients.