The relationship between gray/white matter contrast and cognitive performance in first-episode schizophrenia.

Previous postmortem brain studies have revealed disturbed myelination in the intracortical regions in patients with schizophrenia, possibly reflecting anomalous brain maturational processes. However, it currently remains unclear whether this anomalous myelination is already present in early illness stages and/or progresses during the course of the illness. In this magnetic resonance imaging study, we examined gray/white matter contrast (GWC) as a potential marker of intracortical myelination in 63 first-episode schizophrenia (FESz) patients and 77 healthy controls (HC). Furthermore, we investigated the relationships between GWC findings and clinical/cognitive variables in FESz patients. GWC in the bilateral temporal, parietal, occipital, and insular regions was significantly higher in FESz patients than in HC, which was partly associated with the durations of illness and medication, the onset age, and lower executive and verbal learning performances. Because higher GWC implicates lower myelin in the deeper layers of the cortex, these results suggest that schizophrenia patients have less intracortical myelin at the time of their first psychotic episode, which underlies lower cognitive performance in early illness stages.

Gross anatomical variations of the insular cortex in first-episode schizophrenia.

BACKGROUND: Magnetic resonance imaging (MRI) studies have revealed gray matter reductions in the insular cortex of schizophrenia patients. Despite large inter-individual anatomical variations in the insular gyri of human brains, the gross anatomical features of the insular cortex and their relationships with clinical characteristics remain largely unknown in schizophrenia. METHODS: The present MRI study investigated variations in the insular gross anatomy (i.e., the development and split patterns of each gyrus and gyrus numbers) and their relationships with clinical variables and insular gray matter volumes in 66 patients with first-episode schizophrenia (FE-Sz) and 66 age- and sex-matched healthy controls. RESULTS: The FE-Sz group had a significantly larger number of insular gyri bilaterally with well-developed accessory, middle short, and posterior long insular gyri than the control group, and this was associated with a younger onset age and severe positive symptoms. The split patterns of major insular gyri did not significantly differ between the groups. The FE-Sz group was also characterized by a smaller gray matter volume in the insular cortex than the control group; however, this was not associated with the insular gross anatomy or clinical characteristics. CONCLUSION: As the insular gyral organization reflects brain development during mid to late gestation, the gross anatomical features of the insular cortex in schizophrenia, which were independent of gray matter volumes, may be used as early neurodevelopmental abnormality markers for the illness.

Anatomical variations in the insular cortex in individuals at a clinical high-risk state for psychosis and patients with schizophrenia.

Introduction: Since the number of insular gyri is higher in schizophrenia patients, it has potential as a marker of early neurodevelopmental deviations. However, it currently remains unknown whether the features of the insular gross anatomy are similar between schizophrenia patients and individuals at risk of psychosis. Furthermore, the relationship between anatomical variations in the insular cortex and cognitive function has not yet been clarified. Methods: The gross anatomical features (i.e., the number of gyri and development pattern of each gyrus) of the insular cortex were examined using magnetic resonance imaging, and their relationships with clinical characteristics were investigated in 57 subjects with an at-risk mental state (ARMS) and 63 schizophrenia patients in comparison with 61 healthy controls. Results: The number of insular gyri bilaterally in the anterior subdivision was higher in the ARMS and schizophrenia groups than in the control group. The schizophrenia group was also characterized by a higher number of insular gyri in the left posterior subdivision. A well-developed right middle short insular gyrus was associated with symptom severity in first-episode schizophrenia patients, whereas chronic schizophrenia patients with a well-developed left accessory gyrus were characterized by less severe cognitive impairments in motor and executive functions. The features of the insular gross anatomy were not associated with clinical characteristics in the ARMS group. Discussion: The features of the insular gross anatomy that were shared in the ARMS and schizophrenia groups may reflect a vulnerability to psychosis that may be attributed to anomalies in the early stages of neurodevelopment. However, the contribution of the insular gross anatomy to the clinical characteristics of schizophrenia may differ according to illness stages.

Resting state hyperconnectivity of the default mode network in schizophrenia and clinical high-risk state for psychosis.

Disrupted functional connectivity (FC) of the default mode network (DMN) may have a pathophysiological role in schizophrenia. However, functional magnetic resonance imaging (fMRI) of the DMN in schizophrenia patients has shown inconsistent results. It also remains unclear whether individuals with at-risk mental state (ARMS) have an altered DMN connectivity and whether it is related to clinical characteristics. This fMRI study examined resting-state FCs of the DMN and its relevance to clinical/cognitive variables in 41 schizophrenia patients, 31 ARMS individuals, and 65 healthy controls. Compared with controls, schizophrenia patients had significantly increased FCs within the DMN and between the DMN and diverse cortical areas, whereas ARMS patients had increased FCs only between the DMN and occipital cortex. FC of the lateral parietal cortex with superior temporal gyrus was positively correlated with negative symptoms in schizophrenia, whereas FC of that with interparietal sulcus was negatively correlated with general cognitive impairment in ARMS. Our findings suggest that increased FCs between the DMN and visual network commonly seen in schizophrenia and ARMS subjects may reflect a network-level disturbance representing a general vulnerability to psychosis. In addition, FC changes related to the lateral parietal cortex may underpin clinical characteristics of ARMS and schizophrenia subjects.

Gross anatomical features of the insular cortex in schizophrenia and schizotypal personality disorder: Potential relationships with vulnerability, illness stages, and clinical subtypes.

Introduction: Patients with schizophrenia have a higher number of insular gyri; however, it currently remains unclear whether the brain characteristics of patients with schizotypal personality disorder (SPD), a mild form of schizophrenia, are similar. It is also unknown whether insular gross anatomical features are associated with the illness stages and clinical subtypes of schizophrenia. Materials and methods: This magnetic resonance imaging study examined gross anatomical variations in the insular cortex of 133 patients with schizophrenia, 47 with SPD, and 88 healthy controls. The relationships between the insular gross anatomy and schizophrenia subgroups (71 first-episode and 58 chronic groups, 38 deficit and 37 non-deficit subtype groups) were also investigated. Results: The number of insular gyri was higher in the schizophrenia and SPD patients than in the controls, where the patients were characterized by well-developed accessory, middle short, and posterior long insular gyri. The insular gross anatomy did not significantly differ between the first-episode and chronic schizophrenia subgroups; however, the relationship between the developed accessory gyrus and more severe positive symptoms was specific to the first-episode group. The prevalence of a right middle short gyrus was higher in the deficit schizophrenia group than in the non-deficit group. Discussion: These findings suggest that schizophrenia and SPD patients may share an altered insular gross morphology as a vulnerability factor associated with early neurodevelopmental anomalies, which may also contribute to positive symptomatology in the early illness stages and clinical subtypes of schizophrenia.

Increased brain gyrification and subsequent relapse in patients with first-episode schizophrenia.

Most schizophrenia patients experience psychotic relapses, which may compromise long-term outcome. However, it is difficult to objectively assess the actual risk of relapse for each patient as the biological changes underlying relapse remain unknown. The present study used magnetic resonance imaging (MRI) to investigate the relationship between brain gyrification pattern and subsequent relapse in patients with first-episode schizophrenia. The subjects consisted of 19 patients with and 33 patients without relapse during a 3-year clinical follow-up after baseline MRI scanning. Using FreeSurfer software, we compared the local gyrification index (LGI) between the relapsed and non-relapsed groups. In the relapsed group, we also explored the relationship among LGI and the number of relapses and time to first relapse after MRI scanning. Relapsed patients exhibited a significantly higher LGI in the bilateral parietal and left occipital areas than non-relapsed patients. In addition, the time to first relapse was negatively correlated with LGI in the right inferior temporal cortex. These findings suggest that increased LGI in the temporo-parieto-occipital regions in first-episode schizophrenia patients may be a potential prognostic biomarker that reflects relapse susceptibility in the early course of the illness.

Different Heschl's Gyrus Duplication Patterns in Deficit and Non-deficit Subtypes of Schizophrenia.

Deficit syndrome schizophrenia is a characteristic subtype defined by persistent negative symptoms and poor functional outcomes; however, the biological mechanisms underlying this specific subtype have not yet been elucidated in detail. The present magnetic resonance imaging study examined the prevalence of duplicated Heschl's gyrus (HG), a potential neurodevelopmental marker, in schizophrenia patients with (N = 38) and without (N = 37) the deficit syndrome. The prevalence of the HG duplication pattern bilaterally was higher in the whole schizophrenia group than in 59 matched healthy controls. Furthermore, the prevalence of right HG duplication was significantly higher in the deficit schizophrenia group than in the non-deficit schizophrenia group. The HG pattern in schizophrenia was not associated with clinical variables, including illness duration, medication, and symptom severity, while right HG duplication correlated with higher scores for Proxy for the Deficit Syndrome. The present results suggest that the prominent neurodevelopmental pathology associated with gyral formation of HG may contribute to enduring negative symptomatology in schizophrenia.

Thalamic and striato-pallidal volumes in schizophrenia patients and individuals at risk for psychosis: A multi-atlas segmentation study.

Despite previous neuroimaging studies demonstrating morphological abnormalities of the thalamus and other subcortical structures in patients with schizophrenia, the potential role of the thalamus and its subdivisions in the pathophysiology of this illness remains elusive. It is also unclear whether similar changes of these structures occur in individuals at high risk for psychosis. In this study, magnetic resonance imaging was employed with the Multiple Automatically Generated Templates (MAGeT) brain segmentation algorithm to determine volumes of the thalamic subdivisions, the striatum (caudate, putamen, and nucleus accumbens), and the globus pallidus in 62 patients with schizophrenia, 38 individuals with an at-risk mental state (ARMS) [4 of whom (10.5%) subsequently developed schizophrenia], and 61 healthy subjects. Cognitive function of the patients was assessed by using the Brief Assessment of Cognition in Schizophrenia (BACS) and the Schizophrenia Cognition Rating Scale (SCoRS). Thalamic volume (particularly the medial dorsal and ventral lateral nuclei) was smaller in the schizophrenia group than the ARMS and control groups, while there were no differences for the striatum and globus pallidus. In the schizophrenia group, the reduction of thalamic ventral lateral nucleus volume was significantly associated with lower BACS score. The pallidal volume was positively correlated with the dose of antipsychotic treatment in the schizophrenia group. These results suggest that patients with schizophrenia, but not those with ARMS, exhibit volume reduction in specific thalamic subdivisions, which may underlie core clinical features of this illness.

Volume Reduction of the Dorsal Lateral Prefrontal Cortex Prior to the Onset of Frank Psychosis in Individuals with an At-Risk Mental State.

Although some individuals with at-risk mental states (ARMS) develop overt psychosis, surrogate markers which can reliably predict a future onset of psychosis are not well established. The dorsal lateral prefrontal cortex (DLPFC) is thought to be involved in psychotic disorders such as schizophrenia. In this study, 73 ARMS patients and 74 healthy controls underwent 1.5-T 3D magnetic resonance imaging scans at three sites. Using labeled cortical distance mapping, cortical thickness, gray matter (GM) volume, and surface area of DLPFC were estimated. These measures were compared across the diagnostic groups. We also evaluated cognitive function among 36 ARMS subjects to clarify the relationships between the DLPFC morphology and cognitive performance. The GM volume of the right DLPFC was significantly reduced in ARMS subjects who later developed frank psychosis (ARMS-P) relative to those who did not (P = 0.042). There was a positive relationship between the right DLPFC volume and the duration prior to the onset of frank psychosis in ARMS-P subjects (r = 0.58, P = 0.018). Our data may suggest that GM reduction of the DLPFC might be a potential marker of future onset of psychosis in individuals with ARMS.

Altered Heschl's gyrus duplication pattern in first-episode schizophrenia.

BACKGROUND: Reduced gray matter volumes in the superior temporal gyrus and its subregions, such as Heschl's gyrus (HG) and the planum temporale (PT), have been reported in schizophrenia (Sz). However, it remains unclear whether patients exhibit an altered sulcogyral pattern on the superior temporal plane. METHODS: This magnetic resonance imaging study examined the distribution of HG duplication patterns [i.e., single HG, common stem duplication (CSD), or complete posterior duplication (CPD)] and their relationships with clinical variables and gray matter volumes in the HG and PT of 64 first-episode (FE) patients with Sz and 64 healthy controls. RESULTS: The prevalence of duplicated HG patterns was significantly higher and gray matter volumes in the HG and PT of both hemispheres were smaller in FESz patients than in healthy controls. The right CPD pattern in the FESz group was associated with less severe positive symptoms. In the FESz and control groups, CSD and CPD patterns correlated with larger volumes in the HG and PT, respectively. CONCLUSION: The present results revealed an altered HG duplication pattern at the earliest phase of Sz, which may reflect early neurodevelopmental anomalies. However, reduced HG and PT volumes in the FESz were not explained by this sulcogyral pattern only, supporting the complex superior temporal pathology of Sz.

Potential contribution of pineal atrophy and pineal cysts toward vulnerability and clinical characteristics of psychosis.

BACKGROUND: Magnetic resonance imaging (MRI) studies reported pineal gland atrophy in schizophrenia patients and individuals at a clinical high risk of developing psychosis, implicating abnormalities in melatonin secretion in the pathophysiology of psychosis. However, it currently remains unclear whether the morphology of the pineal gland contributes to symptomatology and sociocognitive functions. METHODS: This MRI study examined pineal gland volumes and the prevalence of pineal cysts as well as their relationship with clinical characteristics in 57 at risk mental state (ARMS) subjects, 63 patients with schizophrenia, and 61 healthy controls. The Social and Occupational Functioning Assessment Scale (SOFAS), the Schizophrenia Cognition Rating Scale (SCoRS), and the Brief Assessment of Cognition in Schizophrenia (BACS) were used to assess sociocognitive functions, while the Positive and Negative Syndrome Scale was employed to evaluate clinical symptoms in ARMS subjects and schizophrenia patients. RESULTS: Pineal gland volumes were significantly smaller in the ARMS and schizophrenia groups than in the controls, while no significant differences were observed in the prevalence of pineal cysts. Although BACS, SCoRS, and SOFAS scores were not associated with pineal morphology, patients with pineal cysts in the schizophrenia group exhibited severe positive psychotic symptoms with rather mild negative symptoms. CONCLUSION: The present results indicate the potential of pineal atrophy as a vulnerability marker in various stages of psychosis and suggest that pineal cysts influence the clinical subtype of schizophrenia.

Reduced cortical thickness of the paracentral lobule in at-risk mental state individuals with poor 1-year functional outcomes.

Although widespread cortical thinning centered on the fronto-temporal regions in schizophrenia has been reported, the findings in at-risk mental state (ARMS) patients have been inconsistent. In addition, it remains unclear whether abnormalities of cortical thickness (CT) in ARMS individuals, if present, are related to their functional decline irrespective of future psychosis onset. In this multicenter study in Japan, T1-weighted magnetic resonance imaging was performed at baseline in 107 individuals with ARMS, who were subdivided into resilient (77, good functional outcome) and non-resilient (13, poor functional outcome) groups based on the change in Global Assessment of Functioning scores during 1-year follow-up, and 104 age- and sex-matched healthy controls recruited at four scanning sites. We measured the CT of the entire cortex and performed group comparisons using FreeSurfer software. The relationship between the CT and cognitive functioning was examined in an ARMS subsample (n = 70). ARMS individuals as a whole relative to healthy controls exhibited a significantly reduced CT, predominantly in the fronto-temporal regions, which was partly associated with cognitive impairments, and an increased CT in the left parietal and right occipital regions. Compared with resilient ARMS individuals, non-resilient ARMS individuals exhibited a significantly reduced CT of the right paracentral lobule. These findings suggest that ARMS individuals partly share CT abnormalities with patients with overt schizophrenia, potentially representing general vulnerability to psychopathology, and also support the role of cortical thinning in the paracentral lobule as a predictive biomarker for short-term functional decline in the ARMS population.

Heschl's Gyrus Duplication Pattern in Individuals at Risk of Developing Psychosis and Patients With Schizophrenia.

An increased prevalence of duplicated Heschl's gyrus (HG), which may reflect an early neurodevelopmental pathology, has been reported in schizophrenia (Sz). However, it currently remains unclear whether individuals at risk of psychosis exhibit similar brain morphological characteristics. This magnetic resonance imaging study investigated the distribution of HG gyrification patterns [i.e., single HG, common stem duplication (CSD), and complete posterior duplication (CPD)] and their relationship with clinical characteristics in 57 individuals with an at-risk mental state (ARMS) [of whom 5 (8.8%) later developed Sz], 63 patients with Sz, and 61 healthy comparisons. The prevalence of duplicated HG patterns (i.e., CSD or CPD) bilaterally was significantly higher in the ARMS and Sz groups than in the controls, whereas no significant differences were observed in HG patterns between these groups. The left CSD pattern, particularly in the Sz group, was associated with a verbal fluency deficit. In the ARMS group, left CSD pattern was related to a more severe general psychopathology. The present results suggest that an altered gyrification pattern on the superior temporal plane reflects vulnerability factors associated with Sz, which may also contribute to the clinical features of high-risk individuals, even without the onset of psychosis.

Reduced Hippocampal Subfield Volume in Schizophrenia and Clinical High-Risk State for Psychosis.

Magnetic resonance imaging (MRI) studies in schizophrenia demonstrated volume reduction in hippocampal subfields divided on the basis of specific cytoarchitecture and function. However, it remains unclear whether this abnormality exists prior to the onset of psychosis and differs across illness stages. MRI (3 T) scans were obtained from 77 patients with schizophrenia, including 24 recent-onset and 40 chronic patients, 51 individuals with an at-risk mental state (ARMS) (of whom 5 subsequently developed psychosis within the follow-up period), and 87 healthy controls. Using FreeSurfer software, hippocampal subfield volumes were measured and compared across the groups. Both schizophrenia and ARMS groups exhibited significantly smaller volumes for the bilateral Cornu Ammonis 1 area, left hippocampal tail, and right molecular layer of the hippocampus than the healthy control group. Within the schizophrenia group, chronic patients exhibited a significantly smaller volume for the left hippocampal tail than recent-onset patients. The left hippocampal tail volume was positively correlated with onset age, and negatively correlated with duration of psychosis and duration of medication in the schizophrenia group. Reduced hippocampal subfield volumes observed in both schizophrenia and ARMS groups may represent a common biotype associated with psychosis vulnerability. Volumetric changes of the left hippocampal tail may also suggest ongoing atrophy after the onset of schizophrenia.

Increased Heschl's Gyrus Duplication in Schizophrenia Spectrum Disorders: A Cross-Sectional MRI Study.

Duplicated Heschl's gyrus (HG) is prevalent in patients with schizophrenia and may reflect early neurodevelopmental anomalies. However, it currently remains unclear whether patients with schizotypal disorder, a prototypic disorder within the schizophrenia spectrum, exhibit a similar HG gyrification pattern. In this magnetic resonance imaging study, HG gyrification patterns were examined in 47 patients with schizotypal disorder, 111 with schizophrenia, and 88 age- and sex-matched healthy subjects. HG gyrification patterns were classified as single, common stem duplication (CSD), or complete posterior duplication (CPD). The prevalence of the duplicated HG patterns (CSD or CPD) bilaterally was higher in the schizophrenia and schizotypal groups than in healthy controls, whereas no significant difference was observed between the schizophrenia and schizotypal groups. Schizophrenia patients with the right CPD pattern had less severe positive symptoms, whereas the right single HG pattern was associated with higher doses of antipsychotic medication in schizotypal patients. The present study demonstrated shared HG gyrification patterns in schizophrenia spectrum disorders, which may reflect a common biological vulnerability factor. HG patterns may also be associated with susceptibility to psychopathology.

Longitudinal Changes in Brain Gyrification in Schizophrenia Spectrum Disorders.

Previous magnetic resonance imaging (MRI) studies reported increased brain gyrification in schizophrenia and schizotypal disorder, a prototypic disorder within the schizophrenia spectrum. This may reflect deviations in early neurodevelopment; however, it currently remains unclear whether the gyrification pattern longitudinally changes over the course of the schizophrenia spectrum. The present MRI study using FreeSurfer compared longitudinal changes (mean inter-scan interval of 2.7 years) in the local gyrification index (LGI) in the entire cortex among 23 patients with first-episode schizophrenia, 14 with schizotypal disorder, and 39 healthy controls. Significant differences were observed in longitudinal LGI changes between these groups; the schizophrenia group exhibited a progressive decline in LGI, predominantly in the fronto-temporal regions, whereas LGI increased over time in several brain regions in the schizotypal and control groups. In the schizophrenia group, a greater reduction in LGI over time in the right precentral and post central regions correlated with smaller improvements in negative symptoms during the follow-up period. The cumulative medication dosage during follow-up negatively correlated with a longitudinal LGI increase in the right superior parietal area in the schizotypal group, but did not affect longitudinal LGI changes in the schizophrenia group. Collectively, these results suggest that gyrification patterns in the schizophrenia spectrum reflect both early neurodevelopmental abnormalities as a vulnerability factor and active brain pathology in the early stages of schizophrenia.

Structural MRI Study of the Planum Temporale in Individuals With an At-Risk Mental State Using Labeled Cortical Distance Mapping.

Background: Recent studies have demonstrated brain structural changes that predate or accompany the onset of frank psychosis, such as schizophrenia, among individuals with an at-risk mental state (ARMS). The planum temporale (PT) is a brain region involved in language processing. In schizophrenia patients, gray matter volume reduction and lack of normal asymmetry (left > right) of PT have repeatedly been reported. Some studies showed progressive gray matter reduction of PT in first-episode schizophrenia patients, and in ARMS subjects during their development of psychosis. Methods: MRI scans (1.5 T field strength) were obtained from 73 ARMS subjects and 74 gender- and age-matched healthy controls at three sites (University of Toyama, Toho University and Tohoku University). Participants with ARMS were clinically monitored for at least 2 years to confirm whether they subsequently developed frank psychosis. Cortical thickness, gray matter volume, and surface area of PT were estimated using FreeSurfer-initiated labeled cortical distance mapping (FSLCDM). PT measures were compared among healthy controls, ARMS subjects who later developed overt psychosis (ARMS-P), and those who did not (ARMS-NP). In each statistical model, age, sex, intracranial volume, and scanning sites were treated as nuisance covariates. Results: Of 73 ARMS subjects, 18 developed overt psychosis (12 schizophrenia and 6 other psychoses) within the follow-up period. There were no significant group differences of PT measures. In addition, significant asymmetries of PT volume and surface area (left > right) were found in all diagnostic groups. PT measures did not correlate with the neurocognitive performance of ARMS subjects. Discussion: Our results suggest that the previously-reported gray matter reduction and lack of normal anatomical asymmetry of PT in schizophrenia patients may not emerge during the prodromal stage of psychosis; taken together with previous longitudinal findings, such PT structural changes may occur just before or during the onset of psychosis.

Gray Matter Changes in the Insular Cortex During the Course of the Schizophrenia Spectrum.

Progressive gray matter reductions in the insular cortex have been reported in the early phases of schizophrenia (Sz); however, the trajectory of these reductions during the course of the illness currently remains unclear. Furthermore, it has not yet been established whether patients with schizotypal (SzTypal) features exhibit progressive changes in the insular cortex. This follow-up magnetic resonance imaging study examined volume changes in the short and long insular cortices (mean inter-scan interval = 2.6 years) of 23 first-episode (FE) and 17 chronic patients with Sz, 14 with SzTypal disorder, and 21 healthy controls. Baseline comparisons revealed smaller insular cortex volumes bilaterally in Sz patients (particularly in the chronic group) than in SzTypal patients and healthy controls. FESz patients showed significantly larger gray matter reductions in the insular cortex over time (left: -3.4%/year; right: -2.9%/year) than those in healthy controls (-0.1%/year for both hemispheres) without the effect of subregion or antipsychotic medication, whereas chronic Sz (left: -1.5%/year; right: -1.6%/year) and SzTypal (left: 0.5%/year; right: -0.6%/year) patients did not. Active atrophy of the right insular cortex during FE correlated with fewer improvements in positive symptoms in the Sz groups, while mild atrophy of the left insular cortex during the chronic phase was associated with the severity of negative symptoms in the follow-up period. The present results support dynamic volumetric changes in the insular cortex being specific to overt Sz among the spectrum disorders examined and their degree and role in symptomatology appear to differ across the illness stages.

Subcortical Brain Volume Abnormalities in Individuals With an At-risk Mental State.

Previous structural magnetic resonance imaging studies of psychotic disorders have demonstrated volumetric alterations in subcortical (ie, the basal ganglia, thalamus) and temporolimbic structures, which are involved in high-order cognition and emotional regulation. However, it remains unclear whether individuals at high risk for psychotic disorders with minimal confounding effects of medication exhibit volumetric changes in these regions. This multicenter magnetic resonance imaging study assessed regional volumes of the thalamus, caudate, putamen, nucleus accumbens, globus pallidus, hippocampus, and amygdala, as well as lateral ventricular volume using FreeSurfer software in 107 individuals with an at-risk mental state (ARMS) (of whom 21 [19.6%] later developed psychosis during clinical follow-up [mean = 4.9 years, SD = 2.6 years]) and 104 age- and gender-matched healthy controls recruited at 4 different sites. ARMS individuals as a whole demonstrated significantly larger volumes for the left caudate and bilateral lateral ventricles as well as a smaller volume for the right accumbens compared with controls. In male subjects only, the left globus pallidus was significantly larger in ARMS individuals. The ARMS group was also characterized by left-greater-than-right asymmetries of the lateral ventricle and caudate nucleus. There was no significant difference in the regional volumes between ARMS groups with and without later psychosis onset. The present study suggested that significant volume expansion of the lateral ventricle, caudate, and globus pallidus, as well as volume reduction of the accumbens, in ARMS subjects, which could not be explained only by medication effects, might be related to general vulnerability to psychopathology.

Reduced Cortical Thickness in Schizophrenia and Schizotypal Disorder.

Schizotypal disorder is characterized by odd behavior and attenuated forms of schizophrenic features without the manifestation of overt and sustained psychoses. Past studies suggest that schizotypal disorder shares biological and psychological commonalties with schizophrenia. Structural magnetic resonance imaging (MRI) studies have demonstrated both common and distinct regional gray matter changes between schizophrenia and schizotypal disorder. However, no study has compared cortical thickness, which is thought to be a specific indicator of cortical atrophy, between schizophrenia and schizotypal disorder. The subjects consisted of 102 schizophrenia and 46 schizotypal disorder patients who met the International Classification of Diseases, 10th edition criteria and 79 gender- and age-matched healthy controls. Each participant underwent a T1-weighted 3-D MRI scan using a 1.5-Tesla scanner. Cortical thickness was estimated using FreeSurfer. Consistent with previous studies, schizophrenia patients exhibited wide-spread cortical thinning predominantly in the frontal and temporal regions as compared with healthy subjects. Patients with schizotypal disorder had a significantly reduced cortical thickness in the left fusiform and parahippocampal gyri, right medial superior frontal gyrus, right inferior frontal gyrus, and right medial orbitofrontal cortex as compared with healthy controls. Schizophrenia patients had thinner cortices in the left precentral and paracentral gyri than those with schizotypal disorder. Common cortical thinning patterns observed in schizophrenia and schizotypal disorder patients may be associated with vulnerability to psychosis. Our results also suggest that distinct cortical changes in schizophrenia and schizotypal disorder may be associated with the differences in the manifestation of clinical symptoms among these disorders.