Atsuhito Toyomaki

Tone duration mismatch negativity deficits predict impairment of executive function in schizophrenia

Impairment in mismatch negativity (MMN) potentials is a robust finding in schizophrenia. There are few studies which examined the correlation between MMN deficits and neuropsychological performances. The purpose of this study was to investigate the relationship between deficits of tone duration MMN and various neuropsychological measures in schizophrenic patients (n=23). The results demonstrated a significant correlation between low MMN amplitude and poor performances of executive function in Wisconsin Card Sorting Test, Stroop Test and Trail Making Test. Our finding suggests MMN deficits in schizophrenia predict deficits of executive function and might reflect ongoing functional abnormality of fronto-temporal interaction.

The influence of childhood abuse, adult stressful life events and temperaments on depressive symptoms in the nonclinical general adult population.

BACKGROUND Previous studies have shown the interaction between heredity and childhood stress or life events on the pathogenesis of major depression. We hypothesized that childhood abuse, affective temperaments, and adult stressful life events interact and influence depressive symptoms in the general adult population and tested this hypothesis in this study. METHODS The 294 participants from the nonclinical general adult population were studied using the following self-administered questionnaire surveys: the Patient Health Questionnaire-9 (PHQ-9), Life Experiences Survey (LES), Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego auto-questionnaire (TEMPS-A), and Child Abuse and Trauma Scale (CATS). The data were analyzed with single and multiple regressions and structural equation modeling (Amos 20.0). RESULTS Childhood abuse indirectly predicted the severity of the depressive symptoms through affective temperaments measured by TEMPS-A in the structural equation modeling. Four temperaments - depressive, cyclothymic, irritable, and anxious - directly predicted the severity of depressive symptoms and the negative appraisal of life events during the past year. The negative appraisal of life events during the past year mildly, but significantly, predicted the severity of depressive symptoms. LIMITATIONS The subjects of this study were nonclinical. The findings might not be generalized to patients with mood disorders. CONCLUSIONS This study suggests that childhood abuse, especially neglect, indirectly increased depressive symptoms through increased affective temperaments, which, in turn, increase the negative appraisal of stressful life events. An important role of affective temperaments in the effect of childhood abuse and stressful life events on depressive symptoms was suggested.

Neurocognitive impairments and quality of life in unemployed patients with remitted major depressive disorder.

Quality of life (QOL) has been reported to be impaired in patients with major depressive disorder (MDD), even after remission according to symptom rating scales. Although a relationship between QOL and neurocognitive dysfunction has been reported during depressive episodes, little is known about this relationship in remitted MDD patients. The aim of the present study was to investigate the relationship between QOL and neurocognitive dysfunction in patients with remitted MDD while controlling for confounding factors. Forty-three remitted MDD patients were assessed with neuropsychological tests and QOL, which was measured by a short-form 36-item health survey. The neurocognitive performances of the patients were compared with those of 43 healthy controls. We next evaluated the relationships between neurocognitive impairments, clinical factors, and QOL. Remitted MDD patients had poorer neurocognitive performances than healthy controls for psychomotor speed, attention, and verbal memory. Residual depressive symptoms were strongly associated with QOL. Delayed verbal recall was associated with general health perceptions, which are part of the QOL assessment, even after the effects of the residual depressive symptoms were considered. The results may indicate that clinicians should try to detect neurocognitive dysfunctions that may interfere with QOL using neurocognitive assessments in their daily practice.

Estimated cognitive decline in patients with schizophrenia: A multicenter study

Studies have reported that cognitive decline occurs after the onset of schizophrenia despite heterogeneity in cognitive function among patients. The aim of this study was to investigate the degree of estimated cognitive decline in patients with schizophrenia by comparing estimated premorbid intellectual functioning and current intellectual functioning.

Latitude effect on bipolar temperaments.

BACKGROUND Growing evidence points to an association of daily light exposure and both mood and mood disorders. In recent studies, we demonstrated that higher illuminance of daytime may be positively associated with hyperthymic temperament while lower illuminance of daytime may be positively associated with cyclothymic temperament. However, it is not possible to determine whether hyperthymic or cyclothymic temperament induces higher or lower illuminance via heliotropism or non-heliotropism or whether higher or lower illuminance induces hyperthymic or cyclothymic temperament via light effects. METHODS In order to elucidate these questions, we sought to compare bipolar temperaments between residents who live in regions with varying levels of sunshine. Japan has 4 large islands -Hokkaido, Honshu, Shikoku, and Kyushu. Sapporo in Hokkaido and Oita in Kyushu located at 43° and 33° of latitude differ significantly in mean yearly sunshine. We investigated the data of 189 subjects (94 from Sapporo and 95 from Oita) including their data of Temperament Evaluation of Memphis, Pisa, Paris and San Diego-auto questionnaire version (TEMPS-A). RESULTS Multiple regression analyses revealed that latitude (Sapporo or Oita) effect predicted significant variance of hyperthymic temperament, but not of the other temperaments. LIMITATIONS The limitation of the present study was that there was a small but significant difference in age between the subjects of Sapporo and those of Oita. Therefore, we included age in the multiple regression analysis. Second, there were several climate factors other than sunshine which were significantly different between Sapporo and Oita. We cannot exclude these effects completely. Finally, we did not consider other factors such as psychosocial factors which might have affected bipolar temperaments. CONCLUSIONS The present findings suggest that relatively lower latitude (potentially via more sunshine) may induce hyperthymic temperament.

Severity of generalized social anxiety disorder correlates with low executive functioning.

To evaluate neurocognitive functions of patients with social anxiety disorder (SAD) without comorbidity using neuropsychological assessments and to investigate the relation between neurocognitive functions and clinical severity of SAD, this study assessed 30 SAD patients (10 female, 20 male) without comorbidity and 30 healthy subjects matched on gender, education level, and age. The neuropsychological assessment consisted of the Wisconsin card sorting test (WCST), the continuous performance test, the trail-making test, the word fluency test, and the auditory verbal learning test. On the WCST, patients showed lower performance than healthy controls did. The Liebowitz Social Anxiety Scale score correlated significantly with the numbers of perseverative errors of the WCST, although the State anxiety score of State-Trait Anxiety Inventory and the Beck Depression Inventory - Second Edition score showed no correlation with neuropsychological test scores. Results show that the executive functioning of patients with SAD was low and that the low functioning correlates with the SAD symptom severity.

Absent activation in medial prefrontal cortex and temporoparietal junction but not superior temporal sulcus during the perception of biological motion in schizophrenia: a functional MRI study.

Background Patients with schizophrenia show disturbances in both visual perception and social cognition. Perception of biological motion (BM) is a higher-level visual process, and is known to be associated with social cognition. BM induces activation in the “social brain network”, including the superior temporal sulcus (STS). Although deficits in the detection of BM and atypical activation in the STS have been reported in patients with schizophrenia, it remains unclear whether other nodes of the “social brain network” are also atypical in patients with schizophrenia. Purpose We aimed to explore whether brain regions other than STS were involved during BM perception in patients with schizophrenia, using functional magnetic resonance imaging (fMRI). Methods and patients Seventeen patients with schizophrenia, and 17 age- and sex- matched healthy controls, underwent fMRI scanning during a one-back visual task, containing three experimental conditions: (1) BM, (2) scrambled motion (SM), and (3) static condition. We used one-sample t-tests to examine neural responses selective to BM versus SM within each group, and two-sample t-tests to directly compare neural patterns to BM versus SM in schizophrenics versus controls. Results We found significant activation in the STS region when BM was contrasted with SM in both groups, with no significant difference between groups. On the contrary, significant activation in the medial prefrontal cortex (MPFC) and bilateral temporoparietal junction (TPJ) was found only in the control group. When we directly compared the two groups, the healthy controls showed significant greater activation in left MPFC and TPJ to BM versus SM than patients with schizophrenia. Conclusion Our findings suggest that patients with schizophrenia show normal activation to biologically and socially relevant motion stimuli in the STS, but atypical activation in other regions of the social brain network, specifically MPFC and TPJ. Moreover, these results were not due to atypical processing of motion, suggesting that patients with schizophrenia lack in the recruitment of neural circuits needed for the visual perception of social cognition.

Effects of lithium on brain glucose metabolism in healthy men

Lithium is clinically available for the treatment of mood disorders. However, it has remained unclear how lithium acts on the brain to produce its effects. The aim of this study was to evaluate the effects of chronic lithium on human brain activity using positron emission tomography and clarify the correlation between brain activity changes and cognitive functional changes as induced by chronic lithium administration. A total of 20 healthy male subjects (mean age, 32 ± 6 years) underwent positron emission tomographic scans with 18F-fluorodeoxyglucose and a battery of neuropsychological tests at baseline condition and after 4 weeks of lithium administration. Brain metabolic data were analyzed using statistical parametric mapping. Lithium increased relative regional cerebral glucose metabolism (rCMRglc) in the bilateral dorsomedial frontal cortices including the anterior cingulate gyrus and decreased rCMRglc in the right cerebellum and left lingual gyrus/cuneus. There was no difference in any of the variables of cognitive functions between the baseline condition and after chronic lithium administration. There was no correlation between rCMRglc changes in any of the brain regions and individual variable changes in any of the neuropsychological tests. The results suggest that the effects of chronic lithium are associated with increased activity in the bilateral dorsomedial frontal cortices including the anterior cingulate gyrus and decreased activity in the right cerebellum and left lingual gyrus/cuneus.

Cognitive insight and functional outcome in schizophrenia; a multi-center collaborative study with the specific level of functioning scale–Japanese version

The Specific Levels of Functioning Scale (SLOF) has been reported to provide a measure of social function in patients with schizophrenia. The aim of this multi-center study was to determine convergent validity of the Japanese version of SLOF, and if cognitive insight would be associated with social function. Fifty-eight patients with schizophrenia participated in the study. Social function, neurocognition, and daily activity skills were evaluated by the Social Functioning Scale (SFS), Brief Assessment of Cognition in Schizophrenia (BACS) and UCSD Performance-based Skills Assessment-Brief (UPSA-B), respectively. We also assessed cognitive insight with the Beck Cognitive Insight Scale (BCIS). Significant relationships were noted between scores on the SLOF vs. those of the SFS, BACS, UPSA-B, and BCIS. Specifically, the correlation between performance on the UPSA-B and SLOF scores was significantly more robust compared to the correlation between performance on the UPSA-B and scores on the SFS. Similarly, the correlation between scores on the BACS and SLOF tended to be more robust than that between the BACS and SFS. Importantly, while the correlation between scores on the BCIS and SLOF reached significance, it was not so between scores on the BCIS and SFS. The SLOF Japanese version was found to provide a measure of social consequences in patients with schizophrenia. Importantly, this study is the first to indicate the relationship between cognitive insight and social function evaluated by the SLOF. This finding is consistent with the observation that SLOF scores were considerably associated with performances on objective functional measures.

The effects of mental state on assessment of bipolar temperament

BACKGROUND Although the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-auto questionnaire (TEMPS-A) was designed to identify temperaments which derive from traits but not states, there is a possibility that TEMPS-A scores might be affected by mental state in non-clinical populations. For the purpose of clarifying the effects of mental state on TEMPS-A scores, it is worthwhile to examine associations of the full version of the TEMPS-A with various depressive scales and, if possible, mania rating scales. METHODS TEMPS-A data acquired from 314 medical students and staff was used to investigate the association of temperament scores with mental assessment scores such as the Beck Depression Inventory (BDI), the Quick Inventory of Depressive Symptomatology Self-Report Japanese version (QIDS-SR-J), the Patient Health Questionnaire-9 (PHQ-9), the Hamilton Depression rating scale (HAM-D) and the Young Mania Rating Scale (YMRS). RESULTS Depressive state scores were significantly and positively associated with depressive, anxious, cyclothymic, and irritable temperament scores of TEMPS-A whereas sub-threshold hypomanic state scores were significantly and positively associated with irritable temperament of TEMPS-A. There was no association between depressive state or sub-threshold hypomanic state and hyperthymic temperament scores. LIMITATIONS The nature of the present study is cross-sectional, and it is unknown whether depressive and/or sub-threshold hypomanic states may have affected temperament scores or whether temperament scores might have affected depressive and/or sub-threshold hypomanic scores. Other limitations are that the sample may not represent the entire population and that there is no evidence that Japanese findings can be applicable outside Japan. CONCLUSIONS It is worthwhile to consider the effects of mental state on temperament scores of TEMPS-A even in non-clinical population.