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.

Combination Psychotropic Use for Schizophrenia With Long-Acting Injectable Antipsychotics and Oral Antipsychotics: A Nationwide Real-World Study in Japan.

BACKGROUND: Although several guidelines recommend monotherapy with antipsychotics for the treatment of schizophrenia, patients who receive long-acting injectable antipsychotics (LAIs) are frequently treated with oral antipsychotics (OAPs). In the present study, we investigated the detailed use of psychotropic medications among patients throughout Japan with schizophrenia who received LAIs or OAPs. METHODS: The present study used data from the project for the Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment from 94 facilities in Japan. The LAI group included patients who received any LAI, and the non-LAI group included patients who took only OAP medications at discharge. The participants of this study were 2518 schizophrenia patients (263 in the LAI group and 2255 in the non-LAI group) who received inpatient treatment and had prescription information at discharge between 2016 and 2020. RESULTS: This study revealed significantly higher rates of polypharmacy antipsychotics, number of antipsychotics, and chlorpromazine equivalents in the LAI group than in the non-LAI group. In contrast, the LAI group showed lower rate of concomitant use of hypnotic and/or antianxiety medication than the non-LAI group. CONCLUSIONS: Presenting these real-world clinical results, we want to encourage clinicians to keep monotherapy in mind for the treatment of schizophrenia, especially by reducing concomitant use of antipsychotics in the LAI group and reducing hypnotic and/or antianxiety medication in the non-LAI group.

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.

Change of prescription for patients with schizophrenia or major depressive disorder during admission: real-world prescribing surveys from the effectiveness of guidelines for dissemination and education psychiatric treatment project.

BACKGROUND: Polypharmacy of additional psychotropics alongside the main treatment drug (antipsychotics in schizophrenia and antidepressants in major depressive disorder) is common in Japan. Our goal is to align psychotropic prescription in Japan with international standards, while reducing the differences between facilities. To achieve this goal, we aimed to compare prescriptions at the time of hospital admission and discharge. METHODS: Data on prescriptions at admission and discharge from 2016 to 2020 were collected. We divided the patients into four groups: (1) mono_mono group, monotherapy of the main drug at admission and discharge; (2) mono_poly group, monotherapy at admission and polypharmacy at discharge; (3) poly_poly group, polypharmacy at admission and discharge; and (4) poly_mono group, polypharmacy at admission and monotherapy at discharge. We compared the changes in dosage and number of psychotropics among the four groups. RESULTS: For both schizophrenia and major depressive disorder, the patients who received monotherapy with the main drug at admission were likely to receive main drug monotherapy at discharge and vice versa. For schizophrenia, the polypharmacy was prescribed more often in the mono_poly group than that in the mono_mono group. The prescription was not changed at all for more than 10% of the patients. CONCLUSIONS: It is critical to avoid a polypharmacy regimen to ensure that guideline-compliant treatment is provided. We expect higher rates of monotherapy with the main drug after the EGUIDE lectures. TRIAL REGISTRATION: The study protocol was registered in the University Hospital Medical Information Network Registry (UMIN000022645).

Effects of electroconvulsive therapy on the use of anxiolytics and sleep medications: a propensity score-matched analysis.

AIM: We investigated the association of electroconvulsive therapy (ECT) with anxiolytic and sleep medication use in patients with major depressive disorder (MDD) and schizophrenia (SZ). METHODS: This nationwide observational study analyzed data from 3483 MDD inpatients and 6663 SZ inpatients. Patients with MDD and SZ were classified into those who underwent ECT during hospitalization and those who did not. A propensity score-matching method was performed to adjust for preadmission characteristics and clinical information, which were expected bias between the two groups. Rates of anxiolytic and sleep medication use at discharge were compared in the matched sample. RESULTS: 500 MDD patients were assigned to both groups. In the matched MDD sample, the rate of anxiolytic and sleep medication use at discharge was significantly lower in the ECT group than in the non-ECT group (64.9% vs. 75.8%, P = 1.7 × 10-4 ). In the ECT group, the rate of anxiolytic and sleep medication use at discharge was significantly lower than that prior to admission (64.9% vs. 73.2%, P = 1.2 × 10-14 ). 390 SZ patients were allocated. In the matched SZ sample, the ECT group was not significantly different from the non-ECT group in the rate of anxiolytics and sleep medications use at discharge (61.3% vs. 68.2%, P = 4.3 × 10-2 ). In the ECT group, the rate of anxiolytics and sleep medications use at discharge was significantly lower than that before admission (61.3% vs. 70.5%, P = 4.4 × 10-4 ), although this was not the primary outcome. CONCLUSION: Reduction of anxiolytic and sleep medication use may be considered positively when ECT is indicated for treatment of MDD.

Effect of education regarding treatment guidelines for schizophrenia and depression on the treatment behavior of psychiatrists: A multicenter study.

AIM: This study aims to examine the real-world effectiveness of education regarding clinical guidelines for psychiatric disorders using 'the Effectiveness of guidelines for dissemination and education in psychiatric treatment (EGUIDE)' project. METHODS: The EGUIDE project is a nationwide prospective implementation study of two clinical practice guidelines, i.e., the Guideline for Pharmacological Therapy of Schizophrenia and the Treatment Guidelines for Major Depressive Disorders, in Japan. Between 2016 and 2019, 782 psychiatrists belonging to 176 hospitals with psychiatric wards participated in the project and attended lectures on clinical practice guidelines. The proportions of guideline-recommended treatments in 7405 patients with schizophrenia and 3794 patients with major depressive disorder at participating hospitals were compared between patients under the care of psychiatrists participating in the project and those not participating in the project. Clinical and prescribing data on the patients discharged from April to September each year from participating hospitals of the project were also analyzed. RESULTS: The proportions of three quality indicators (antipsychotic monotherapy regardless of whether other psychotropics medication, antipsychotic monotherapy without other psychotropics and no prescription of anxiolytics or hypnotics) for schizophrenia were higher among participating psychiatrists than among nonparticipating psychiatrists. As similar results were obtained in major depressive disorder, the effectiveness of the project for the dissemination of guideline-recommended treatment has been replicated. CONCLUSION: This strategy of providing education regarding the clinical guidelines for psychiatric disorders was effective in improving the treatment-related behavior of psychiatrists. The use of this education-based strategy might contribute to resolving the mental health treatment gap.

Clozapine Treatment Is Associated With Higher Prescription Rate of Antipsychotic Monotherapy and Lower Prescription Rate of Other Concomitant Psychotropics: A Real-World Nationwide Study.

BACKGROUND: Although clozapine is effective for treatment-resistant schizophrenia (TRS), the rate of clozapine prescription is still low. Whereas antipsychotic monotherapy is recommended in clinical practice guidelines, the rate of antipsychotic polypharmacy is still high. There is little evidence on whether a clozapine prescription influences changes in the rate of monotherapy and polypharmacy, including antipsychotics and other psychotropics. We therefore hypothesized that the rate of antipsychotic monotherapy in patients with TRS who were prescribed clozapine would be higher than that in patients with schizophrenia who were not prescribed clozapine. METHODS: We assessed 8306 patients with schizophrenia nationwide from 178 institutions in Japan from 2016 to 2019. We analyzed the psychotropic prescription data at discharge in patients diagnosed with TRS and with no description of TRS (ND-TRS) based on the diagnosis listed in the discharge summary. RESULTS: The rate of antipsychotic monotherapy in the TRS with clozapine group (91.3%) was significantly higher than that in the TRS without clozapine group (45.9%; P < 2.0 × 10-16) and the ND-TRS without clozapine group (54.7%; P < 2.0 × 10-16). The rate of antipsychotic monotherapy without any other concomitant psychotropics in the TRS with clozapine group (26.5%) was significantly higher than that in the TRS without clozapine group (12.6%; P = 1.1 × 10-6) and the ND-TRS without clozapine group (17.0%; P = 5.9 × 10-6). CONCLUSIONS: Clozapine prescription could be associated with a high rate of antipsychotic monotherapy. Patients will benefit from the correct diagnosis of TRS and thus from proper clozapine prescription.

The characteristics of discharge prescriptions including pro re nata psychotropic medications for patients with schizophrenia and major depressive disorder from the survey of the "Effectiveness of guidelines for dissemination and education in psychiatric treatment (EGUIDE)" project.

BACKGROUND: Several guidelines recommend monotherapy in pharmacotherapy for schizophrenia and major depressive disorder. The content of regular prescriptions has been reported in several studies, but not enough research has been conducted on the content of pharmacotherapy, including pro re nata (PRN) medications. The purpose of this study was to evaluate the content of pharmacotherapy, including PRN medications, and to clarify the relationship with regular prescriptions. METHODS: We used data from the "Effectiveness of Guidelines for Dissemination And Education in psychiatric treatment" (EGUIDE) project to investigate the presence or absence of PRN psychotropic medications at discharge for each drug category. We compared the PRN psychotropic prescription ratio at discharge by diagnosis for each drug category. The antipsychotic monotherapy ratio and no prescription ratio of other psychotropics for schizophrenia at discharge and the antidepressant monotherapy ratio and no prescription ratio of other psychotropics for major depressive disorder at discharge were calculated for each regular prescription, including PRN psychotropic medications, as quality indicators (QIs). Spearman's rank correlation test was performed for QI values of regular prescriptions and the QI ratio between regular prescriptions and prescriptions including PRN medications for each diagnosis. RESULTS: The PRN psychotropic prescription ratio at discharge was 28.7% for schizophrenia and 30.4% for major depressive disorder, with no significant differences by diagnosis. The prescription ratios of PRN antipsychotic medications and PRN antiparkinsonian medications were significantly higher for schizophrenia. The prescription ratios of PRN anxiolytic and hypnotic and PRN antidepressant medications were significantly higher for patients with major depressive disorder. For both schizophrenia and major depressive disorder, the QI was lower for discharge prescriptions, including PRN medications, than for regular prescriptions. QI values for regular prescriptions and the QI ratio were positively correlated. CONCLUSIONS: Considering PRN psychotropic medications, the monotherapy ratio and no prescription ratio of other psychotropics at discharge decreased in pharmacotherapy for schizophrenia and major depressive disorder. A higher ratio of monotherapy and no prescription of other psychotropics on regular prescriptions may result in less concomitant use of PRN psychotropic medications. Further studies are needed to optimize PRN psychotropic prescriptions.

Increased brain gyrification in the schizophrenia spectrum.

AIM: Increased brain gyrification in diverse cortical regions has been reported in patients with schizophrenia, possibly reflecting deviations in early neurodevelopment. However, it remains unknown whether patients with schizotypal disorder exhibit similar changes. METHODS: This magnetic resonance imaging study investigated brain gyrification in 46 patients with schizotypal disorder (29 male, 17 female), 101 patients with schizophrenia (55 male, 46 female), and 77 healthy controls (44 male, 33 female). T1-weighted magnetic resonance images were obtained for each participant. Using FreeSurfer software, the local gyrification index (LGI) of the entire cortex was compared across the groups. RESULTS: Both schizophrenia and schizotypal disorder patients showed a significantly higher LGI in diverse cortical regions, including the bilateral prefrontal and left parietal cortices, as compared with controls, but its extent was broader in schizophrenia especially for the right prefrontal and left occipital regions. No significant correlations were found between the LGI and clinical variables (e.g., symptom severity, medication) for either of the patient groups. CONCLUSION: Increased LGI in the frontoparietal regions was common to both patient groups and might represent vulnerability to schizophrenia, while more diverse changes in schizophrenia patients might be associated with the manifestation of florid psychosis.

Differentiation of schizophrenia using structural MRI with consideration of scanner differences: A real-world multisite study.

AIM: Neuroimaging studies have revealed that patients with schizophrenia exhibit reduced gray matter volume in various regions. With these findings, various studies have indicated that structural MRI can be useful for the diagnosis of schizophrenia. However, multisite studies are limited. Here, we evaluated a simple model that could be used to differentiate schizophrenia from control subjects considering MRI scanner differences employing voxel-based morphometry. METHODS: Subjects were 541 patients with schizophrenia and 1252 healthy volunteers. Among them, 95 patients and 95 controls (Dataset A) were used for the generation of regions of interest (ROI), and the rest (Dataset B) were used to evaluate our method. The two datasets were comprised of different subjects. Three-dimensional T1-weighted MRI scans were taken for all subjects and gray-matter images were extracted. To differentiate schizophrenia, we generated ROI for schizophrenia from Dataset A. Then, we determined volume within the ROI for each subject from Dataset B. Using the extracted volume data, we calculated a differentiation feature considering age, sex, and intracranial volume for each MRI scanner. Receiver-operator curve analyses were performed to evaluate the differentiation feature. RESULTS: The area under the curve ranged from 0.74 to 0.84, with accuracy from 69% to 76%. Receiver-operator curve analysis with all samples revealed an area under the curve of 0.76 and an accuracy of 73%. CONCLUSION: We moderately successfully differentiated schizophrenia from control using structural MRI from differing scanners from multiple sites. This could be useful for applying neuroimaging techniques to clinical settings for the accurate diagnosis of schizophrenia.

Altered brain gyrification in deficit and non-deficit schizophrenia.

BACKGROUND: Patients with the deficit form of schizophrenia (D-SZ) are characterized by severe primary negative symptoms and differ from patients with the non-deficit form of schizophrenia (ND-SZ) in several aspects. No study has measured brain gyrification, which is a potential marker of neurodevelopment, in D-SZ and ND-SZ. METHODS: We obtained magnetic resonance scans from 135 schizophrenia patients and 50 healthy controls. The proxy scale for deficit syndrome (PDS) was used for the classification of D-SZ and ND-SZ. The local gyrification index (LGI) of the entire cortex was measured using FreeSurfer. Thirty-seven D-SZ and 36 ND-SZ patients were included in the LGI analyses. We compared LGI across the groups. RESULTS: SZ patients exhibited hyper-gyral patterns in the bilateral dorsal medial prefrontal and ventromedial prefrontal cortices, bilateral anterior cingulate gyri and right lateral parietal/occipital cortices as compared with HCs. Although patients with D-SZ or ND-SZ had higher LGI in similar regions compared with HC, the hyper-gyral patterns were broader in ND-SZ. ND-SZ patients exhibited a significantly higher LGI in the left inferior parietal lobule relative to D-SZ patients. Duration of illness inversely associated with LGI in broad regions only among ND-SZ patients. CONCLUSIONS: The common hyper-gyral patterns among D-SZ and ND-SZ suggest that D-SZ and ND-SZ may share neurodevelopmental abnormalities. The different degrees of cortical gyrification seen in the left parietal regions, and the distinct correlation between illness chronicity and LGI observed in the prefrontal and insular cortices may be related to the differences in the clinical manifestations among D-SZ and ND-SZ.

Surface morphology of the orbitofrontal cortex in individuals at risk of psychosis: a multicenter study.

Changes in the surface morphology of the orbitofrontal cortex (OFC), such as a fewer orbital sulci and altered sulcogyral pattern of the 'H-shaped' orbital sulcus, have been reported in schizophrenia, possibly reflecting abnormal neurodevelopment during gestation. However, whether high-risk subjects for developing psychosis also exhibit these gross morphologic anomalies is not well documented. This multicenter MRI study from four scanning sites in Japan investigated the distribution of the number of intermediate and posterior orbital sulci, as well as the OFC sulcogyral pattern, in 125 individuals with an at-risk mental state (ARMS) [of whom 22 later developed psychosis (ARMS-P) and 89 did not (ARMS-NP)] and 110 healthy controls. The ARMS group as a whole had a significantly lower number of intermediate and posterior orbital sulci compared with the controls, which was associated with prodromal symptomatology. However, there was no group difference in OFC pattern distribution. The ARMS-P and -NP groups did not differ in OFC surface morphology. These results suggest that gross morphology of the OFC in high-risk subjects may at least partly reflect neurodevelopmental pathology related to vulnerability to psychosis.

Increased Frontal Gyrification Negatively Correlates with Executive Function in Patients with First-Episode Schizophrenia.

Previous neuroimaging studies of gyrification, a possible marker of early neurodevelopment, in schizophrenia patients have reported inconsistent results. In addition, it remains unclear whether aberrant gyrification in schizophrenia patients, if present, is associated with cognitive impairment, which is one of the core features of schizophrenia. Magnetic resonance images were obtained from 62 patients with first-episode schizophrenia and 57 healthy control subjects. Using FreeSurfer software, local gyrification index (LGI) of the entire cortex was compared between the groups. The relationship between LGI and performance in the Wisconsin Card Sorting Test (WCST) was also examined in a subgroup of patients (n= 28). Compared with the controls, the patients showed a significantly higher LGI in a wide range of bilateral frontal regions as well as in the right inferior parietal and bilateral occipital regions. The number of WCST categories archived in patients was negatively correlated with the LGI mainly in the rostral middle frontal and anterior cingulate regions in the right hemisphere. Our findings suggested a widespread hypergyrification pattern in schizophrenia patients, which supported early neurodevelopmental abnormalities. Our results also suggested that executive dysfunction in schizophrenia patients may be at least partly related to aberrant neurodevelopment, especially in the right frontal regions.

Orbitofrontal sulcogyral pattern and olfactory sulcus depth in the schizophrenia spectrum.

Morphological changes in the orbitofrontal cortex (OFC), such as an altered sulcogyral pattern of the 'H-shaped' orbital sulcus and a shallow olfactory sulcus, have been demonstrated in schizophrenia, possibly reflecting deviations in early neurodevelopment. However, it remains unclear whether patients with schizotypal features exhibit similar OFC changes. This magnetic resonance imaging study examined the OFC sulcogyral pattern (Types I, II, III, and IV) and olfactory sulcus morphology in 102 patients with schizophrenia, 47 patients with schizotypal disorder, and 84 healthy controls. The OFC sulcogyral pattern distribution between the groups was significantly different on the right hemisphere, with the schizophrenia patients showing a decrease in Type I (vs controls and schizotypal patients) and an increase in Type III (vs controls) expression. However, the schizotypal patients and controls did not differ in the OFC pattern. There were significant group differences in the olfactory sulcus depth bilaterally (schizophrenia patients < schizotypal patients < controls). Our findings suggest that schizotypal disorder, a milder form of schizophrenia spectrum disorders, partly shares the OFC changes (i.e., altered depth of the olfactory sulcus) with schizophrenia, possibly reflecting a common disease vulnerability. However, altered distribution of the OFC pattern specific to schizophrenia may at least partly reflect neurodevelopmental pathology related to a greater susceptibility to overt psychosis.

Increased pituitary volume in subjects at risk for psychosis and patients with first-episode schizophrenia.

AIM: Enlarged pituitary gland has been reported in schizophrenia, possibly reflecting hypothalamic-pituitary-adrenal hyperactivity. The aim of the present study was to examine whether individuals at risk of psychosis also have similar changes. METHODS: Magnetic resonance imaging was used to examine the pituitary volume in 22 individuals with at-risk mental state (ARMS; 11 male, 11 female), 64 first-episode patients with schizophrenia (FESz; 37 male, 27 female), and 86 healthy controls. The control subjects were divided into age- and gender-matched controls for ARMS (11 male, 11 female) and FESz (37 male, 27 female). RESULTS: Both the ARMS and FESz groups had a larger pituitary volume compared with matched controls, but no difference was found between the ARMS and FESz subjects. There was no association between the pituitary volume and clinical variables (symptommeasures at scanning, daily dosage or duration of antipsychotic medication) in either clinical group. The pituitary volume did not differ significantly between the ARMS individuals who later developed schizophrenia (n = 5) and those who did not (n = 17). The pituitary volume was larger in women than in men for all diagnostic groups. CONCLUSION: The finding of increased pituitary volume in both ARMS and FESz subjects may reflect a common vulnerability to stress in early psychosis. Further work in a larger ARMS sample is required to examine the possible relationship between pituitary volume and emergence of psychosis.

Development of an individual fitness score (IFS) based on the depression treatment guidelines of in the Japanese Society of Mood Disorders.

AIM: Treatment guidelines are designed to assist patients and health care providers and are used as tools for making treatment decisions in clinical situations. The treatment guidelines of the Japanese Society of Mood Disorders establish treatment recommendations for each severity of depression. The individual fitness score (IFS) was developed as a simple and objective indicator to assess whether individual patients are practicing treatment by the recommendations of the depression treatment guidelines of the Japanese Society of Mood Disorders. METHODS: The EGUIDE project members determined the IFS through the modified Delphi method. In this article, the IFS was calculated based on the treatment of depressed patients treated and discharged between 2016 and 2020 at facilities participating in the EGUIDE project. In addition, we compared scores at admission and discharge. RESULTS: The study included 428 depressed patients (mild n = 22, moderate/severe n = 331, psychotic n = 75) at 57 facilities. The mean IFS scores by severity were statistically significantly higher at discharge than at admission with moderate/severe depression (mild 36.1 ± 34.2 vs. 41.6 ± 36.9, p = 0.49; moderate/severe 50.2 ± 33.6 vs. 55.7 ± 32.6, p = 2.1 × 10-3; psychotic 47.4 ± 32.9 versus 52.9 ± 36.0, p = 0.23). CONCLUSION: We developed the IFS based on the depression treatment guideline, which enables us to objectively determine how close the treatment is to the guideline at the time of evaluation in individual cases. Therefore, the IFS may influence guideline-oriented treatment behavior and lead to the equalization of depression treatment in Japan, including pharmacotherapy.

Longitudinal MRI study of the pituitary volume in chronic schizophrenia: a preliminary report.

This longitudinal MRI study investigated the pituitary volume in 17 patients with chronic schizophrenia and 17 matched controls. In contrast to previous findings of pituitary expansion during the first episode of schizophrenia, the chronic patients showed non-significant mild pituitary atrophy, suggesting that the pituitary volume changes differently at different illness stages.

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.