[Clinical Implications and Appropriate Use of Amyloid Imaging with florbetapir (18F) in Diagnosis of Patients with Alzheimer Disease].

florbetapir (18F) is a radiolabeled compound that can be used to visualize amyloid-beta (Aß) plaques in the brains of patients with cognitive dysfunction, who are suspected of having Alzheimer disease (AD). Knowing the status of Aß accumulation in the brain is beneficial to selecting therapeutic strategies or to planning of laboratory examinations, hence amyloid PET imaging is expected to be utilized more often in a clinical setting. Based on the results of a clinical study of florbetapir (18F), this review discusses the usefulness and clinical significance of amyloid PET imaging, and its appropriate use in Japan. (Received Octover 7, 2015; Accepted February 15, 2016; Published October 1, 2016).

Imaging characteristics and safety of florbetapir (¹8F) in Japanese healthy volunteers, patients with mild cognitive impairment and patients with Alzheimer's disease.

OBJECTIVE: The purpose of this study was to evaluate the performance characteristics and safety of florbetapir ((I8)F) positron emission tomography (PET) in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) and cognitively normal (CN) control patients from Japan. METHODS: Florbetapir ((I8)F) PET was obtained in 48 subjects (15 AD patients, 15 MCI patients, and 18 CNs) within a multicenter phase 2/3 study. Amyloid burden was assessed visually and classified as positive or negative for pathologic levels of amyloid aggregation, blind to diagnostic classification. Cerebral to cerebellar standardized uptake value ratios (SUVRs) were determined from the florbetapir ((I8)F) PET images. Safety was assessed by monitoring adverse events, vital signs, clinical laboratory assessments, and electrocardiograms. Demographic variables and cognitive scales were summarized by using descriptive statistics for each group. Fisher's exact test and one-way analysis of variance were used to compare amyloid positivity and mean SUVRs, respectively, between diagnostic groups. RESULTS: Florbetapir ((I8)F) PET was rated visually amyloid positive in 80.0% of AD patients, 33.3% of MCI patients, and 16.7% of CNs. Mean SUVRs were highest in the AD group and lowest in the CN group for each brain region (P < 0.01) and globally (P < 0.05). Kappa statistics showed strong inter-reader agreement (Fleiss' kappa = 0.82) and individual reader's agreement with the majority of readers (kappa ranged from 0.79 to 1.0). Seventeen of the 48 subjects (35.4%) were Apolipoprotein E genotype ε4 positive, which included 10 subjects in the AD group and 7 subjects in the MCI group. A total of 6 subjects (5 of whom were in the CN group) had at least 1 treatment-emergent adverse event (TEAE). CONCLUSIONS: These data indicate that amyloid positivity increased with diagnostic category (CN < MCI < AD) and are consistent with expected rates of amyloid positivity among individuals with clinical diagnoses of AD and MCI. In addition, these results were similar to those obtained in United States studies. Florbetapir ((18)F) was safe and well tolerated. The reliability of both qualitative and quantitative assessments of florbetapir ((18)F) in this study population provides support for potential use in clinical settings in Japan.

The Uncinate Fasciculus as a Predictor of Conversion from Amnestic Mild Cognitive Impairment to Alzheimer Disease.

BACKGROUND AND PURPOSE: Amnestic mild cognitive impairment (aMCI) is associated with the risk of Alzheimer's disease (AD). Although diffusion tensor imaging (DTI)-based fractional anisotropy (FA) analyses have been used to evaluate white matter changes in patients with AD, it remains unknown how FA values change during the conversion of aMCI to AD. This study aimed to elucidate the prediction of conversion to AD and cognitive decline by FA values in uncinate fasciculus (UF) in aMCI patients. METHODS: Twenty-two aMCI patients were evaluated for their UF FA values by a tractography-based method with DTI and cognitive performance by neuropsychological testing at baseline and after a 3-year follow-up. Patients were divided into 2 groups after 3 years: 14 aMCI-stable (aMCI-aMCI) and 8 AD-conversion (aMCI-AD). RESULTS: At baseline, FA values in the right UF were significantly lower in the aMCI-AD group than in the aMCI-aMCI group. These values also showed significant correlations with the neuropsychological scores after a 3-year follow-up. The area under the curve of the receiver operation characteristic curves for predicting conversion to AD was .813. CONCLUSION: These results suggested that FA values in the right UF might be an effective predictor of conversion of aMCI to AD.

Temporal lobe epilepsy with amygdala enlargement: a morphologic and functional study.

BACKGROUND AND PURPOSE: Temporal lobe epilepsy (TLE) with nontumoral amygdala enlargement (AE) has been reported to be a possible subtype of TLE without hippocampal sclerosis (HS). The purpose of this study was to clarify morphologic and functional characteristics of TLE with AE (TLE + AE). METHODS: We evaluated gray matter volume and cerebral glucose hypometabolism using magnetic resonance imaging (MRI) voxel-based morphometry (VBM) and voxel-based statistical analysis of [(18) F]-fluorodeoxyglucose positron emission tomography (FDG-PET) images in 9 patients with TLE + AE as compared with controls. For VBM analysis, we recruited 30 age- and sex-matched healthy volunteers as controls. For the comparison of FDG-PET analysis, 9 patients with definite mesial TLE with HS (MTLE + HS), and 16 age- and sex-matched healthy controls were recruited. RESULTS: In patients with TLE + AE, a significant increase in gray matter volume was found only in the affected amygdala, and no significant decrease in gray matter volume was detected. In addition, significant glucose hypometabolism was observed in the affected amygdala, whereas significant glucose hypometabolism in the hippocampus, a prominent feature of definite MTLE+HS, was not observed. CONCLUSIONS: TLE + AE is different from MTLE + HS from morphologic and functional points of view, and the enlarged amygdala per se is potentially an epileptic focus in patients with partial epilepsy.

Relationship between major depressive disorder and associated painful physical symptoms: analysis of data from two pooled placebo-controlled, randomized studies of duloxetine.

The aim of this study was to evaluate the relationship between painful physical symptoms (PPS) and outcomes in major depressive disorder (MDD). Post-hoc analysis of two identically designed 8-week trials compared the efficacy of 60 mg/day duloxetine (N=523) with that of placebo (N=532) in treating PPS associated with MDD. The Montgomery-Åsberg Depression Rating Scale (MADRS) total score, the Brief Pain Inventory (BPI) average pain score, and the Sheehan Disability Scale global functional impairment score assessed depression symptoms, pain, and functioning, respectively. Remission was defined as a MADRS score of 10 or less, and the BPI response subgroup was defined as a 50% or greater reduction from baseline. Path analyses assessed relationships among variables. Duloxetine-treated patients who had a 50% or greater reduction in BPI score at endpoint had higher rates of remission. Path analysis indicated that 16% of likelihood of remission in depression symptoms was because of the direct effect of treatment, 41% because of pain reduction, and 43% because of functional improvement. Path analysis also indicated that 51% of improvement in functioning was attributed to pain improvement and 43% to mood improvement. Results demonstrate that improvement in pain and mood contributes to functional improvement, and pain reduction and functional improvement increase the likelihood of remission of depressive symptoms with duloxetine treatment in patients with both MDD and PPS at baseline.

Corticolimbic balance shift of regional glucose metabolism in depressed patients treated with ECT.

BACKGROUND: Although the clinical efficacy of electroconvulsive therapy (ECT) has been well established in patients with pharmacotherapy-resistant depression, the physiological mechanism and changes in regional cerebral function after ECT are unclear. METHODS: We recruited 16 depressed patients who underwent ECT, and 11 healthy controls. The change in cerebral glucose metabolism was evaluated before and after a series of ECT using [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET). RESULTS: Before ECT, the patient group showed significant hypometabolism in the superior frontal gyrus, and hypermetabolism in the inferior temporal gyri compared with healthy controls, and these abnormalities remained after ECT. Comparisons between pre- and post-ECT metabolic activity revealed decreased regional metabolism in the frontotemporal neocortical areas after ECT, while increased metabolism was found in the right medial temporal structures including amygdala and pons. In addition, a decrease in glucose metabolism in the fronto-temporo-parietal regions correlated with an increase in glucose metabolism in the right medial temporal regions across subjects. LIMITATIONS: There was considerable variability in the interval between the last ECT and FDG-PET scan. Depressed subjects were maintained on medication. The subjects included both major depressive disorder and bipolar disorder patients, as well as both ECT responders and non-responders. CONCLUSION: Depression refractory to pharmacotherapy might have functional deficits in specific circumscribed frontal and temporal structures. ECT resolves the clinical symptoms without largely affecting these brain metabolic abnormalities. In contrast, ECT shifts the balance of corticolimbic function, which might explain how ECT ameliorates symptoms of depression in patients.

Reduced white matter integrity as a neural correlate of social cognition deficits in schizophrenia.

BACKGROUND: The pathology of schizophrenia is thought to involve multiple gray and white matter regions. A number of studies have revealed impaired social cognition in schizophrenia. Some evidence suggests an association of this social cognition deficit with gray matter reductions in 'social brain' areas. However, no study has yet revealed the association between social cognition abilities and white matter abnormalities in schizophrenia patients. METHODS: Twenty-six schizophrenia patients and 27 healthy controls underwent the Perception of Affect Task (PAT), which consisted of four subtasks measuring different aspects of emotion attribution. Voxelwise group comparison of white matter fractional anisotropy (FA) was performed using tract-based spatial statistics (TBSS). The relation between impaired social cognition ability and FA reduction was examined in patients for each subtask, using simple regression analysis within brain areas that showed a significant FA reduction in patients compared with controls. The same correlational analysis was also performed for healthy controls in the whole brain. RESULTS: Schizophrenia patients showed reduced emotion attribution ability compared with controls in all four subtasks. The facial emotion perception subtask showed a significant correlation with FA reductions in the left occipital white matter region and left posterior callosal region. The correlational analyses in healthy controls revealed no significant correlation of FA with any of the PAT subtasks. CONCLUSIONS: Our voxelwise correlational analysis of white matter provided a potential neural basis for the social cognition impairments in schizophrenia, in support of the disconnection hypothesis.

Correlation between cognitive deficits and glucose hypometabolism in mild cognitive impairment.

BACKGROUND: In patients with mild cognitive impairment (MCI), poor performances on delayed recall and executive function are risk factors of progression to dementia. The aim of the present study was to clarify neural correlates of these neuropsychological deficits. METHODS: Thirty patients with amnestic MCI and 15 control subjects underwent neuropsychological tests including three-word delayed recall, visual delayed recall of Rey complex figure (RCF), and two-relational reasoning of Raven's colored progressive matrices (RCPM) with a (18)F-fluorodeoxyglucose (FDG)-position emission tomography (PET) measurement of resting state. We evaluated a relationship between performance of neuropsychological tests and regional cerebral glucose metabolism using voxel-based analysis. RESULTS: Poor performance in three-word delayed recall was related to glucose hypometabolism in the right medial temporal, right prefrontal, and left superior parietal cortices. The deficit in visual delayed recall of RCF correlated positively with hypometabolism in the bilateral posterior cingulate. The impairment in two-relational reasoning was associated with hypometabolism in the right prefrontal cortex. CONCLUSIONS: The present findings suggest that hypometabolism in the right medial temporal cortex, right prefrontal cortex, left superior parietal cortex, and bilateral posterior cingulate reflects impairments in delayed recall while hypometabolism in the right prefrontal cortex mirrors deficits in executive function in MCI.

Brain volume and dysexecutive behavior in schizophrenia.

OBJECTIVE: Behaviors associated with frontal/executive impairments are common in patients with schizophrenia. Our aim was to reconfirm that morphological brain abnormalities in schizophrenia patients would overlap the areas underpinning frontal systems behavior, and examine whether any specific association exists between abnormalities of brain structures and frontal behavioral deficits in schizophrenia patients. METHOD: Twenty-six schizophrenia patients and 26 matched healthy controls underwent structural magnetic resonance imaging and their frontal function was assessed by a self-rating questionnaire, Frontal Systems Behavior Scale (FrSBe). We applied voxel-based morphometry (VBM) to investigate regional brain volume alternations. RESULT: Compared with healthy controls, schizophrenia patients showed reduced gray matter volume in multiple frontal and temporal structures, namely, the bilateral dorsolateral prefrontal cortices (DLPFC), bilateral medial prefrontal cortices, left ventrolateral prefrontal cortex, bilateral anterior cingulate cortices, and bilateral superior temporal gyri. The scores on the executive dysfunction subscale of the FrSBe were correlated with volume reduction in the bilateral DLPFC in the patient group. CONCLUSION: Our result suggests that pathology of the DLPFC could be the neural basis of real-life dysexecutive behaviors in schizophrenia patients.

Reduced white matter integrity correlated with cortico-subcortical gray matter deficits in schizophrenia.

BACKGROUND: The pathology of schizophrenia is thought to involve multiple brain regions and the connections among them. Although a number of MRI studies have demonstrated gray matter reductions and abnormal white matter integrity in schizophrenia, to date no study has investigated their association in the whole brain. METHODS: Twenty-seven schizophrenia patients and 33 healthy controls were recruited. Voxelwise group comparison of white matter fractional anisotropy (FA) was performed using tract-based spatial statistics (TBSS). Comparison of gray matter concentration (GMC) was performed using voxel-based morphometry (VBM). Voxelwise correlational analyses were performed for patients inside a significant GMC reduction mask created by VBM, using simple regression models with mean FA values of each significant TBSS cluster as explanatory variables. RESULTS: TBSS revealed FA reduction in left prefrontal and occipital regions in the patients. Mean FA values of both areas revealed significant correlation with gray matter reduction in multiple cortical and subcortical areas, with overlapping but different patterns. CONCLUSIONS: Voxelwise correlational analysis of white and gray matter pathology, as performed here, further elucidated the pathophysiology of schizophrenia, and provided a novel view of the "disconnection hypothesis" of schizophrenia.

Social cognition in schizophrenia: similarities and differences of emotional perception from patients with focal frontal lesions.

The structural and functional abnormalities of the frontal lobes, the region implicated in social information processing, have been suspected to underlie social cognitive impairments in schizophrenia. However, multiple structures, including the limbic/paralimbic areas that are also important for social cognition, have been reported to be abnormal in schizophrenia. The aim of this study is to investigate the extent to which the frontal lobe dysfunction accounts for social cognitive impairments in schizophrenia by comparing with patients who have focal frontal lobe injuries. Social cognitive abilities, focusing on affective aspects, were examined by an emotion intensity recognition task, which is sensitive to the amygdala function, and the emotion attribution tasks, which rely mainly on the frontal lobe function. Individuals with schizophrenia were impaired on the emotion intensity recognition task as well as on the emotion attribution tasks as compared with healthy subjects. By contrast, the frontal lobe-damaged group was defective in the emotion attribution tasks but not in the emotion intensity recognition task. Our results indicated that social cognitive impairments observed in schizophrenia can be accounted for partly by their frontal lobe pathology. Other aspects of social cognitive impairments could also be associated with the extra-frontal pathology, such as the amygdala.

Small orbitofrontal traumatic lesions detected by high resolution MRI in a patient with major behavioural changes.

We report a case of a male patient who showed personality changes and marked social problems after a traumatic brain injury. Although suspected to have lesions in the orbitofrontal cortex because of the typical characteristics of his behavioural change, lesions were not apparent using conventional imaging techniques. However, investigation using high-resolution MRI revealed lesions in the orbitofrontal cortex. Our case suggests that standard MRI scanning techniques may have only limited power. Hence, we stress the important role played by qualitative assessments of emotion, personality, and social behaviour in evaluating sequelae of traumatic orbitofrontal injuries.

The role of the uncinate fasciculus in memory and emotional recognition in amnestic mild cognitive impairment.

BACKGROUND: The putative neural bases of affected episodic memory and emotional recognition in early Alzheimer's disease are suspected to be limbic and paralimbic pathological processes. The uncinate fasciculus (UF) is especially considered to be a critical structure. In the present study, we investigated microstructural UF pathology by diffusion tensor imaging in the subjects with amnestic mild cognitive impairment (aMCI), and its association with memory and emotional processing impairment. METHODS: Subjects included 16 patients with aMCI and 16 healthy individuals. Diffusion tensor images were acquired and the fractional anisotropy (FA) of the UF was calculated. In addition, its association with verbal memory and emotional facial recognition was investigated. RESULTS: The FA values of the left UF were significantly lower in aMCI, and strongly correlated with episodic memory performance in aMCI. For the emotional recognition task, the aMCI subjects performed worse in negative emotion recognitions. The FA values of the left UF were correlated with the performance of fearful facial expression recognition in aMCI. CONCLUSION: These results indicated that microstructural alterations of the UF had already occurred in aMCI. In addition, these alterations could be one of the causes of memory and emotional processing impairment in aMCI.

Theory of mind and frontal lobe pathology in schizophrenia: a voxel-based morphometry study.

Impaired ability to infer the mental states of others (theory of mind; ToM) is considered to be a key contributor to the poor social functioning of patients with schizophrenia. Although neuroimaging and lesion studies have provided empirical evidence for the neural basis of ToM ability, including the involvement of several prefrontal and temporal structures, the association between pathology of these structures and ToM impairment in schizophrenia patients is less well understood. To address this issue, we investigated structural brain abnormalities and ToM impairment in patients with schizophrenia, and examined the relationship between them. Twenty schizophrenia patients and 20 age-, sex- and education-matched healthy participants underwent magnetic resonance imaging (MRI) and were examined for ToM ability based on the revised version of the "Reading the Mind in the Eyes" (or Eyes) test [Baron-Cohen, S., Wheelwright, S., Hill, J., Raste, Y., Plumb, I., 2001. The 'Reading the Mind in the Eyes' test revised version: A study with normal adults, and adults with Asperger syndrome or high-functioning autism. J. Child Psychol. Psychiatry 42, 241-251]. Voxel-based morphometry (VBM) was performed to investigate regional brain alterations. Relative to normal controls, schizophrenia patients exhibited gray matter reductions in the dorsomedial prefrontal cortex (DMPFC), left ventrolateral prefrontal cortex (VLPFC), ventromedial prefrontal cortex (VMPFC), anterior cingulate cortex (ACC), right superior temporal gyrus (STG) and right insula. The patients performed poorly on the Eyes test. Importantly, poor performance on the Eyes test was found to be associated with gray matter reduction in the left VLPFC in the patient group. These results suggest that prefrontal cortical reduction, especially in the left VLPFC, is a key pathology underlying the difficulties faced by schizophrenia patients in inferring the mental states of others.

Female specific anterior cingulate abnormality and its association with empathic disability in schizophrenia.

Evidence suggests that impairments of empathy are present in schizophrenia and that such deficits lead to social dysfunction. However, the relationship between brain morphological abnormalities of the disorder and empathic disabilities has not been fully investigated. As the anterior cingulate cortex (ACC) is one of the critical structures for empathy processing, the pathology of this structure might be a major source of social dysfunction, including interpersonal miscommunication in schizophrenia. In addition, as recent studies suggest that different facets of empathic ability depend on different subdivisions of the ACC, pathology of each subdivision would affect the empathic disability of schizophrenia differentially. Structural MRI data were acquired at 3.0 T from 24 schizophrenic patients and 20 healthy participants, and the volumes of ventral and dorsal ACC were measured and compared between the groups. Subjects' empathic abilities were evaluated using a multidimensional questionnaire, the Interpersonal Reactivity Index (IRI). The relationships of structural abnormalities with empathic disabilities were investigated, by correlating ACC subdivisional volumes with each IRI subscale score. Female schizophrenic patients exhibited volume reductions in the ventral ACC bilaterally and in the left dorsal ACC compared with healthy subjects. Schizophrenic patients performed poorly on fantasy and personal distress subscales of the IRI. Furthermore, volumes of the left dorsal ACC were inversely correlated with personal distress subscale scores within female patients with schizophrenia. These results suggest that pathology of specific ACC subdivisions would have an impact on specific empathic disabilities in schizophrenia, with potential gender specificity.

Structural abnormalities of the adhesio interthalamica and mediodorsal nuclei of the thalamus in schizophrenia.

OBJECTIVE: Several studies have suggested the existence of thalamic volume reduction in patients with schizophrenia. However, the precise locus of volume reduction within the thalamus has scarcely been investigated. On the other hand, underdevelopment of the adhesio interthalamica [AI; Danos, P., Baumann, B., Kramer, A., Bernstein, H.G., Stauch, R., Krell, D., Falkai, P., Bogerts, B., 2003. Volumes of association thalamic nuclei in schizophrenia: a post-mortem study. Schizophrenia Res. 60 141-155], which bridges bilateral medial edges of the thalamus, has been reported in patients with schizophrenia. We assessed the volumes of mediodorsal nuclei (MDN) of thalami, level of AI development, and their interrelationship, in patients with schizophrenia. METHOD: A sample of 58 patients with schizophrenia and 44 matched healthy volunteers underwent assessment with high-resolution 1-mm-thick anatomical MRI. Volume measurements of the MDN of the thalamus and whole thalamus were performed by manual tracing. The level of AI development was quantitatively defined as the maximal anterior-to-posterior length of the AI. RESULTS: Schizophrenia patients had significantly smaller volumes of bilateral MDN. AI ratings were twice as high in women than in men among the control subjects; however, no gender difference emerged in the schizophrenia group due to reduced ratings in female patients. No significant correlation was found between MDN volumes and AI ratings among both groups. CONCLUSIONS: These results provide evidence of volume reduction of the MDN, and female-specific underdevelopment of the AI in schizophrenia. As we did not demonstrate a relationship between MDN volume and AI ratings, it is suggested that these two measures of medial thalamic abnormality are manifestations of different neuropathological processes in schizophrenia patients.

Interfrontal commissural abnormality in schizophrenia: tractography-assisted callosal parcellation.

Previous studies have indicated abnormal fiber connectivity of the corpus callosum (CC) in schizophrenia. This study investigated whether the interfrontal commissural region of the CC is decreased in schizophrenia, by partitioning the CC using a function-anatomically relevant internal landmark derived from tractographic analysis of diffusion tensor imaging (DTI). T1 weighted and DTI images were acquired by 3T-MRI. Using tractography, the interfrontal commissural region (anterior part) was partitioned from the rest of the CC in 40 schizophrenia patients and 36 healthy controls. Schizophrenia patients showed smaller anterior/total CC length and area rates. These results suggested interfrontal hypoconnectivity in schizophrenia.

Insular volume reduction in schizophrenia.

Structural and functional abnormalities of the insular cortex have been reported in patients with schizophrenia. Most studies have shown that the insular volumes in schizophrenia patients are smaller than those of healthy people. As the insular cortex is functio-anatomically divided into anterior and posterior subdivisons, recent research is focused on uncovering a specific subdivisional abnormality of the insula in patients with schizophrenia. A recent ROI-based volumetric MRI study demonstrated specific left anterior insular volume reduction in chronic schizophrenia patients (Makris N, Goldstein J, Kennedy D, Hodge S, Caviness V, Faraone S, Tsuang M, Seidman L (2006) Decreased volume of left and total anterior insular lobule in schizophrenia. Schizophr Res 83:155-171). On the other hand, our VBM-based volumetric study revealed a reduction in right posterior insular volume (Yamada M, Hirao K, Namiki C, Hanakawa T, Fukuyama H, Hayashi T, Murai T (2007) Social cognition and frontal lobe pathology in schizophrenia: a voxel-based morphometric study. NeuroImage 35:292-298). In order to address these controversial results, ROI-based subdivisional volumetry was performed using the MRI images from the same population we analyzed in our previous VBM-study. The sample group comprised 20 schizophrenia patients and 20 matched healthy controls. Patients with schizophrenia showed a global reduction in insular gray matter volumes relative to healthy comparison subjects. In a simple comparison of the volumes of each subdivision between the groups, a statistically significant volume reduction in patients with schizophrenia was demonstrated only in the right posterior insula. This study suggests that insular abnormalities in schizophrenia would include anterior as well as posterior parts. Each subdivisional abnormality may impact on different aspects of the pathophysiology and psychopathology of schizophrenia; these relationships should be the focus of future research.

Anterior and posterior cingulum abnormalities and their association with psychopathology in schizophrenia: a diffusion tensor imaging study.

Evidence suggests that a disruption in limbic system network integrity and, in particular, the cingulate gyrus may play a role in the pathophysiology of schizophrenia. The cingulum bundles (CBs; posterior and anterior) are the most prominent white matter tracts in the limbic system, furnishing both input and output to the cingulate gyrus . In previous diffusion tensor imaging (DTI) studies, abnormal integrity has been demonstrated in the anterior CB portion, but not the posterior, in schizophrenia. As well, the relationships between the abnormalities of CB integrity and the psychopathology of schizophrenia remain to be elucidated. Using DTI acquired on a 3 T MRI machine, we examined fractional anisotropy (FA) in the anterior and posterior CBs of 42 patients with schizophrenia and 24 group-matched controls. Moreover, we investigated the relationships between CB abnormalities and the psychopathology of schizophrenia. Bilaterally reduced FA was demonstrated in both anterior and posterior CBs in schizophrenia patients. However, the pattern of FA reduction was different between anterior and posterior CBs: the reduction in FA was left-accentuated in anterior CBs, while no such lateralized abnormality was found in posterior ones. Finally, FA in posterior CBs correlated with positive symptom scores in patients with schizophrenia. These findings suggest that CB abnormalities in schizophrenia are not restricted to the anterior CB, but include the posterior as well. Pathology in the posterior CB would be one of the possible neural underpinnings of positive symptoms in schizophrenia.

Impaired facial emotion recognition and reduced amygdalar volume in schizophrenia.

Structural abnormalities of the amygdala and impaired facial emotion recognition have been reported in schizophrenia. Most studies demonstrated reduced amygdalar volumes in schizophrenia patients, and difficulty in recognizing negative facial emotions has also been reported. However, findings on the deficit in facial emotion recognition have been inconsistent, and the relationships between this impairment and amygdalar volume reduction remain unclear. In this study, we investigated these relationships by performing volumetric analysis of the amygdala and evaluation of facial emotion recognition performance in the same subjects with schizophrenia. The sample group comprised 20 schizophrenia patients and 20 matched healthy controls. We measured the volumes of the amygdalae with high-resolution magnetic resonance imaging (MRI) at 3.0 Tesla. Additionally, we included a task that evaluated the subjects' ability to recognize the intensity of basic facial emotions. We found that impaired facial emotion recognition in schizophrenia patients is emotion-specific (sadness, surprise, disgust, and anger). Moreover, the volume of each amygdala on either side of the brain was reduced. Finally, we found a correlation between left amygdalar volume and the recognition of sadness in facial expressions. This study demonstrated that amygdala dysfunction may contribute to impaired facial emotion recognition in schizophrenia.