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.

Features of Duration Mismatch Negativity Around the Onset of Overt Psychotic Disorders: A Longitudinal Study.

Reduced amplitude of duration mismatch negativity (dMMN) has been reported in psychotic disorders and at-risk mental state (ARMS); however, few longitudinal MMN studies have examined the amplitude changes during the course of psychosis. We compared dMMN amplitude between ARMS individuals with later psychosis onset and those without, and we longitudinally examined potential dMMN changes around psychosis onset. Thirty-nine ARMS subjects and 22 healthy controls participated in this study. Of the 39 ARMS subjects, 11 transitioned to psychosis (at-risk mental state with later psychosis onset [ARMS-P]) during follow-up and 28 did not (at-risk mental state without later psychosis onset [ARMS-NP]). dMMN was measured twice using an auditory oddball paradigm with a mean interval of 2 years. Follow-up dMMN data were available for all but four ARMS-P subjects. dMMN amplitude at baseline was smaller in ARMS-P subjects compared with control and ARMS-NP subjects. Additionally, ARMS-P subjects displayed a longitudinal decline in dMMN amplitude, which was not present in control and ARMS-P subjects. We also observed a progressive decline in dMMN amplitude during the transition period, suggesting dynamic brain changes associated with the psychosis onset. Our findings implicate dMMN amplitude as a biological predictor of future psychosis onset in high-risk individuals, which may be used for early detection and intervention of psychosis.

Premorbid intellectual ability in schizophrenia influence family appraisal related to cognitive impairments: a cross-sectional study on cognitive impairment and family assessments.

BACKGROUND: Patients with schizophrenia are unaware of their cognitive impairments. Misperception of cognitive impairment is an important factor associated with real-world functional outcomes in patients with schizophrenia. The patient's family member plays a crucial role in detecting patients' cognitive impairments when the patients are unaware of their own cognitive impairments. Previous studies have reported that not only the patient's subjective rating, but also the patient's family members' rating of their cognitive impairment may not be precise. However, it is unclear why family ratings are inaccurate, and which factors impact family ratings. This study investigated whether family ratings differed significantly from the patients' subjective ratings of the patients' cognitive impairments and sought to determine the reason for the differences between the family ratings and the patients' neurocognitive performances. We investigated the relationship between patients' subjective ratings, family ratings for patients' cognitive impairments, neuropsychological performance, and other aspects, including premorbid IQ and clinical symptoms. METHOD: We evaluated 44 patients with schizophrenia for cognitive function using neuropsychological tests; in addition, both the patients and their families rated the patients' cognitive impairments through questionnaires. We used the Mann-Whitney U test to examine whether the family ratings differed significantly from the patients' self-reported ratings of their cognitive impairment. We conducted multiple regression analysis and structural equation modeling to determine why the patients' subjective ratings and the family ratings were not definitively associated with the patients' neurocognitive performances. We performed multiple regression analysis with a stepwise method with neurocognitive performance, premorbid IQ, positive symptoms, and negative symptoms as independent variables and family ratings of patients' cognitive impairments as dependent variables. RESULTS: We found that the family ratings differed significantly from the patients' subjective self-reported ratings of their cognitive impairments. Our results showed that the premorbid IQ of patients is the strongest predictor of family ratings. Furthermore, among the neurocognitive domains, only the processing speed of patients was associated with family ratings. CONCLUSIONS: We found that the family ratings were not consistent with the patients' subjective self-reported ratings and the family ratings were most affected by the patients' premorbid intellectual abilities. These results suggest that the families' current assessments of the patients' current cognitive impairments were affected by the patients' premorbid intellectual ability rather than the patients' current neurocognitive performance. Patients' processing speed predicted family ratings; however, family members' ratings were not related to verbal learning/memory, executive function, and language of patients. Therefore, our findings highlight that patients' family ratings may differ from patients' subjective ratings, results of performance-based neuropsychological tests, and clinician ratings.

Olfactory deficits in individuals at risk for psychosis and patients with schizophrenia: relationship with socio-cognitive functions and symptom severity.

Odor identification deficits are well documented in patients with schizophrenia, but it remains unclear whether individuals at clinical high-risk for psychosis exhibit similar changes and whether their olfactory function is related to social/cognitive functions and symptomatology. In this study, we investigated odor detection sensitivity and identification ability in 32 individuals with at-risk mental state (ARMS), 59 schizophrenia patients, and 169 healthy controls using a T&T olfactometer. The ARMS and schizophrenia subjects were administered the Brief Assessment of Cognition in Schizophrenia (BACS), the Schizophrenia Cognition Rating Scale (SCoRS), and the Social and Occupational Functioning Assessment Scale (SOFAS) to assess their cognitive and social functions, and the Positive and Negative Syndrome Scale (PANSS) for clinical symptoms. Both the ARMS and schizophrenia subjects had lower odor identification ability when compared with healthy controls, while no significant difference was found in the odor detection sensitivity. The lower odor identification ability in the ARMS group correlated with the severity of negative symptoms and weakly correlated with lower performance on the BACS verbal fluency test. The olfactory measures of schizophrenia patients did not correlate with illness duration, medication, symptom severity, and social and cognitive functions. For the ARMS and schizophrenia groups, the olfactory measures did not correlate with the SOFAS and SCoRS scores. These findings suggest that high-risk subjects for psychosis already show odor identification deficits similar to those observed in schizophrenia patients, which probably reflect a biological trait related to vulnerability to psychosis.

Possible relation between olfaction and anxiety in healthy subjects.

AIMS: While olfaction is a sense closely associated with the limbic system and emotions, the relation between emotional status and olfactory functioning has not been well documented. This study aimed to examine the possible effect of anxiety on olfaction in healthy subjects. METHODS: We investigated the effect of state and trait anxiety on the detection and recognition thresholds for five different odors in 124 healthy subjects (62 men and 62 women, mean age = 27.2 years) using a T&T olfactometer. RESULTS: While the influences of age, socioeconomic status, IQ, and smoking history on olfaction were not significant, women had a lower recognition threshold for the odor of sweet fruit and a higher detection threshold for that of rotten food as compared with men. Both state and trait anxiety ratings were significantly associated with reduced olfactory ability, especially for identification of rose odor. CONCLUSIONS: These findings suggest that emotional status affects olfactory functioning in healthy subjects. Our findings may also partly explain the mild olfactory impairment reported in clinical conditions, such as anxiety disorders.

Relationships between erythrocyte membrane mono- and poly- unsaturated fatty acid composition and clinical/cognitive indices in antipsychotic-free schizophrenia patients.

Introduction: Membrane phospholipid abnormalities are considered a pathophysiological background for schizophrenia. The aim of the study was to explore in detail the fatty acid (FA) composition in patients with antipsychotic-free schizophrenia and its association with clinical symptoms and cognitive function. Materials and methods: Erythrocyte membrane FAs were measured in 29 antipsychotic-free patients with schizophrenia (male/female = 11/18; mean [standard deviation] age=26.7 [7.9] years) and age and sex-matched 32 healthy volunteers. Clinical symptoms and cognitive function were assessed using the Positive and Negative Syndrome Scale (PANSS), Brief Assessment of Cognition in Schizophrenia (BACS), and the Schizophrenia Cognition Rating Scale (SCoRS). Results: Eicosapentaenoic acid levels were lower in the schizophrenia group than in the healthy control group. In contrast, arachidonic acid and nervonic acid levels were higher in the schizophrenia group than in the control group. Nervonic acid levels were significantly associated with depression scores as measured by the PANSS. No FA levels were correlated with BACS score; however, oleic acid levels were significantly related to cognitive dysfunction, as measured by the SCoRS. Conclusion: These findings suggest that depressive symptoms along with cognitive dysfunction in daily living in schizophrenia may be linked to the FA composition abnormalities. Further studies will be needed to examine potential longitudinal FA changes during the course of schizophrenia as well as disease specificity.

Nomenclature for psychosis risk in Japan: Survey results from high-risk individuals, caregivers, and mental health professionals.

BACKGROUND: Labeling terms for high-risk state for psychosis, such as 'ultra-high risk' (UHR), 'attenuated psychosis syndrome' (APS), and 'at-risk mental state' (ARMS), have been criticized for their potential to lead to stigma. Hence, mental health service users in Melbourne recently proposed new terms illustrating the at-risk concept ['pre-diagnosis stage' (PDS), 'potential of developing a mental illness' (PDMI), and 'disposition for developing a mental illness' (DDMI)]. We aimed at testing the suitability of these existing and new terms in the clinical settings of early psychiatric intervention in Japan. METHODS: At two centers of early intervention (Toyama and Tokyo), a questionnaire on the understanding and opinion of high-risk terminology was administered to 62 high-risk patients, 44 caregivers, and 64 clinicians. The questionnaire contained the existing and new terms, where the term ARMS was translated into two different Japanese terms ARMS-psychosis and ARMS-kokoro. Participants' opinion on the disclosure of high-risk status was also obtained. RESULTS: ARMS-kokoro was most preferred, least stigmatizing, and best explaining the patients' difficulties for all groups, while UHR and other terms including the Japanese word 'psychosis' (i.e., APS and ARMS-psychosis) were not preferred. New labeling terms were generally not well received. All groups preferred full disclosure of high-risk terms by the psychiatrist with or without the presence of family members. CONCLUSION: The term ARMS-kokoro was commonly accepted as a favorable labeling term for the high-risk state for psychosis in Japan. However, another translation ARMS-psychosis was considered stigmatizing, demonstrating the importance of appropriate translation of high-risk terminology into local languages.

[Early intervention practice in Toyama Prefecture: efforts to improve the clinical service].

We report our activity in the Consultation and Support Service in Toyama (CAST), a clinical service provided by the collaboration of Toyama Prefectural Mental Health Center and University Hospital of Toyama(UHT). About 23% of users diagnosed with at-risk mental state (ARMS), during October 2006 until March 2012, transitioned to overt schizophrenia. More than half of the subjects who continued to visit the specialized clinic in UHT were treated with antipsychotic drugs. We encountered a case of schizophrenia in which early treatment with an atypical psychotic drug was effective in normalizing cognitive function and achieving a good social consequence. The ability of mismatch negativity, an event-related potential, to predict progression to psychosis in subjects with ARMS is discussed. Further efforts should be directed towards improving long-term outcomes, such as social function, for users of the CAST.

Analysis of polyunsaturated fatty acids in antipsychotic-free individuals with at-risk mental state and patients with first-episode schizophrenia.

Introduction: Abnormalities in membrane phospholipids are considered one of the pathophysiological backgrounds for schizophrenia. This study, explores the fatty acid composition of erythrocyte membranes and its association with clinical characteristics in two groups: individuals with an at-risk mental state (ARMS) and patients experiencing their first-episode of schizophrenia (FES). Materials and methods: This study measured erythrocyte membrane fatty acids in 72 antipsychotic-free individuals with ARMS, 18 antipsychotic-free patients with FES, and 39 healthy volunteers. Clinical symptoms and cognitive and social functions were assessed using the Positive and Negative Syndrome Scale (PANSS), Brief Assessment of Cognition in Schizophrenia (BACS), Schizophrenia Cognition Rating Scale (SCoRS), and Social and Occupational Functioning Assessment Scale (SOFAS). Results: Eicosapentaenoic and docosapentaenoic acid levels were lower in the ARMS and FES groups than in the healthy control group. In contrast, nervonic acid (NA) levels were markedly higher in the ARMS and FES groups than in the controls, while only the FES group showed higher levels of arachidonic acid. Oleic acid and NA levels were significantly associated with PANSS scores in both the FES and ARMS groups, particularly for the negative and general subscores. However, the patient groups had no significant associations between the fatty acid composition and the BACS, SCoRS, and SOFAS scores. Furthermore, the baseline fatty acid composition did not differ between the ARMS individuals who later developed psychosis (N = 6) and those who were followed for more than 2 years without developing psychosis onset (N = 30). Discussion: The findings suggest that abnormal fatty acid compositions may be shared in the early stages of schizophrenia and the clinical high-risk state for psychosis and may serve as vulnerability markers of psychopathology.

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.

Development and validation of a scale of self-alienation-related attributes for the early diagnosis of schizophrenia.

BACKGROUND: The onset of schizophrenia is often preceded by a prodromal phase. However, it is difficult to predict the future transition to schizophrenia from the prodromal symptoms. Based on the diagnostic significance of Schneider's first rank symptoms (FRS), especially those representing "ego disorders (Ichstörungen)", we developed a scale of self-alienation-related attributes (Self-A) to assess the psychological characteristics associated with ego disorders for the early diagnosis of schizophrenia. METHODS: In total, 153 schizophrenia (Sz) patients, 83 at-risk mental state (ARMS) subjects, and 154 healthy control (HC) subjects participated in this study. The Self-A scale was constructed by items from the Minnesota Multiphasic Personality Inventory (MMPI) based on the differences between schizophrenia patients with and without FRS representing ego-disorders designated as "self-alienation symptoms". The Self-A scale was tested for its reliability and validity in a different sample of schizophrenia patients, and was then applied to different cohorts including first-episode schizophrenia (FES) patients, ARMS individuals, and HC subjects. RESULTS: The Self-A consisting of 27 items exhibited good internal consistency reliability. The validity was well demonstrated by the high correlation of the Self-A scores with the self-alienation symptom scores. The ARMS and FES groups had higher Self-A scores than the HC group. The Self-A score in the ARMS individuals who later developed schizophrenia was higher than that in the ARMS subjects who did not, and was comparable with that in the FES group. CONCLUSIONS: This study suggests that the newly developed Self-A scale assessing the self-alienation-related attributes can improve the early diagnosis of 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.

Membrane fatty acid levels as a predictor of treatment response in chronic schizophrenia.

Abnormal fatty acid composition in neural membranes, that is, the balance between essential polyunsaturated fatty acids (EPUFAs) and saturated fatty acids, has been suggested to be related to the psychotic symptoms and cognitive impairment of schizophrenia. This study was conducted to test the hypothesis that the ability of atypical antipsychotic drugs to ameliorate positive symptoms and cognitive function relevant to daily living would be predicted by baseline EPUFAs concentrations in the erythrocyte membrane in subjects with schizophrenia. A total of 24 actively psychotic patients with schizophrenia participated in the study. After blood drawing, they were treated with olanzapine or perospirone. The Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for Assessment of Negative symptoms (SANS), as well as the script tasks, a measure of event schema recognition, were administered at baseline and 3months after the start of treatment. Erythrocyte membrane fatty acid levels were analysed using a gas chromatography system. Scores of SAPS and SANS, as well as script task performance, were improved during treatment with either antipsychotic drug. Regression analysis indicates baseline EPUFAs concentrations were positively and negatively related with percent improvement of positive symptoms and script task performance, respectively. The results of this study suggest composition of phospholipids in the erythrocyte membrane provide a feasible marker to predict treatment response in patients with schizophrenia.

[Schizophrenia Cognition Rating Scale Japanese version (SCoRS-J) as a co-primary measure assessing cognitive function in schizophrenia].

The assessment of cognitive function is important for patients with schizophrenia because cognitive impairment is a core feature of the disease, and is a major determinant of functional outcome. To implement a practical assessment tool, we previously developed the Japanese-language version of the Brief Assessment of Cognition in Schizophrenia that objectively measures cognitive domains relevant to outcome. Meanwhile, the U.S. Food and Drug Administration took the position that a drug to improve coghition should show changes on an additional measure (a co-primary), in addition to an accepted consensus cognitive performance measure that is considered functionally meaningful. Thus, four potential co-primary measures, two measures of functional capacity and two interview-based measures of cognition, were evaluated for psychometric properties and validity. The Schizophrenia Cognition Rating Scale (SCoRS) is one of the interview-based measures of cognition. It consists of 20 questions to measure attention, memory, reasoning and problem solving, working memory, language production, and motor skills, which are related to day-to-day functioning. University of California at San Diego Performance-Based Skills Assessment (UPSA) is one of the measures of functional capacity. For its clinical application, we developed the Japanese-language version of the SCoRS (SCoRS-J) and UPSA (UPSA-J) through back-translation into English.

Duration Mismatch Negativity Predicts Remission in First-Episode Schizophrenia Patients.

Objective: Remission in schizophrenia patients is associated with neurocognitive, social, and role functioning during both the early and chronic stages of schizophrenia. It is well-established that the amplitudes of duration mismatch negativity (dMMN) and frequency MMN (fMMN) are reduced in schizophrenia patients. However, the potential link between MMN and remission has not been established. In this study, we investigated the relationship between MMNs and remission in first-episode schizophrenia (FES) and their association with neurocognitive and social functioning. Method: dMMN and fMMN were measured in 30 patients with FES and 22 healthy controls at baseline and after a mean of 3 years. Clinical symptoms and cognitive and social functioning in the patients were assessed at the time of MMN measurements by using the Positive and Negative Syndrome Scale (PANSS), modified Global Assessment of Functioning (mGAF), Schizophrenia Cognition Rating Scale (SCoRS), and the Brief Assessment of Cognition in Schizophrenia (BACS). Remission of the patients was defined using the criteria by the Remission in Schizophrenia Working Group; of the 30 patients with FES, 14 achieved remission and 16 did not. Results: Baseline dMMN amplitude was reduced in FES compared to healthy controls. Further, baseline dMMN in the non-remitters had decreased amplitude and prolonged latency compared to the remitters. MMN did not change during follow-up period regardless of parameters, diagnosis, or remission status. Baseline dMMN amplitude in FES was correlated with future SCoRS and PANSS total scores. Logistic regression analysis revealed that dMMN amplitude at baseline was a significant predictor of remission. Conclusions: Our findings suggest that dMMN amplitude may be a useful biomarker for predicting symptomatic remission and improvement of cognitive and social functions in FES.

Prolonged P300 Latency in Antipsychotic-Free Subjects with At-Risk Mental States Who Later Developed Schizophrenia.

We measured P300, an event-related potential, in subjects with at-risk mental states (ARMS) and aimed to determine whether P300 parameter can predict progression to overt schizophrenia. Thirty-three subjects with ARMS, 39 with schizophrenia, and 28 healthy controls participated in the study. All subjects were antipsychotic-free. Subjects with ARMS were followed-up for more than two years. Cognitive function was measured by the Brief assessment of Cognition in Schizophrenia (BACS) and Schizophrenia Cognition Rating Scale (SCoRS), while the modified Global Assessment of Functioning (mGAF) was used to assess global function. Patients with schizophrenia showed smaller P300 amplitudes and prolonged latency at Pz compared to those of healthy controls and subjects with ARMS. During the follow-up period, eight out of 33 subjects with ARMS developed overt psychosis (ARMS-P) while 25 did not (ARMS-NP). P300 latency of ARMS-P was significantly longer than that of ARMS-NP. At baseline, ARMS-P elicited worse cognitive functions, as measured by the BACS and SCoRS compared to ARMS-NP. We also detected a significant relationship between P300 amplitudes and mGAF scores in ARMS subjects. Our results suggest the usefulness of prolonged P300 latency and cognitive impairment as a predictive marker of later development of schizophrenia in vulnerable individuals.

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 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.

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.

Effect of perospirone on P300 electrophysiological activity and social cognition in schizophrenia: a three-dimensional analysis with sloreta.

The purpose of this study was to determine if perospirone, a second generation antipsychotic drug and partial agonist at serotonin-5-HT(1A) receptors, enhances electrophysiological activity, such as event-related potentials (ERPs), in frontal brain regions, as well as cognitive function in subjects with schizophrenia. P300 current source images were obtained by means of standardized low resolution brain electromagnetic tomography (sLORETA) before and after treatment with perospirone for 6 months. Perospirone significantly increased P300 current source density in the left superior frontal gyrus, and improved positive symptoms and performance on the script tasks, a measure of verbal social cognition, while verbal learning memory tended to be improved. There was a significant correlation between the changes in P300 amplitude on the left frontal lead and those in social cognition. These results suggest the changes in three-dimensional distribution of cortical activity, as demonstrated by sLORETA, may mediate some of the actions of antipsychotic drugs. The distinct cognition-enhancing profile of perospirone in patients with schizophrenia may be related to its actions on 5-HT(1A) receptors.