We studied 63 patients with epileptiform seizure with computerized tomography (CT, EMI-1000) duri... more We studied 63 patients with epileptiform seizure with computerized tomography (CT, EMI-1000) during the past eight months. I n the neurological, electroencephalographical and CT examinations, one case each of brain tumor, arterio-venous malformation and tuberous sclerosis were excluded from the diagnosis of epilepsy. The other 60 patients were further diagnosed in accordance with the Classification of the International League Against Epilepsy. The relationship between the type of epilepsy and the CT and EEG findings is summarized in Table 1. Significance of the anterior horn size on CT in epileptic patients was studied photometrically. The anterior horn perimeter was copied on tracing paper squared by millimeter and this size was measured by the square counting method. The results were
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 1988
1. In schizophrenic patients, a good drug response was associated with a small cerebellar vermis ... more 1. In schizophrenic patients, a good drug response was associated with a small cerebellar vermis brain ratio (CVBR). 2. It was possible to predict drug response with a higher statistical significance based on CVBR, especially in nonfamilial patients with schizophrenia.
The population of monoaminergic synaptic vesicles in the rat caudate nucleus remained unchanged o... more The population of monoaminergic synaptic vesicles in the rat caudate nucleus remained unchanged or slightly decreased 3 h after chlorpromazine (CP) administration, and clearly increased after 24 h. The diameter of synaptic vesicles became smaller when the vesicles increased. These findings suggest that CP causes presynaptic blocking in part of its actions and leads to a condition in which neural transmission is inactive. In the control animals, population of the vesicles tended to fluctuate following the circadian rhythm.
Background Anxious-depressive attack (ADA) is a symptom complex that comprises sudden intense fee... more Background Anxious-depressive attack (ADA) is a symptom complex that comprises sudden intense feelings of anxiety or depression, intrusive rumination of regretful memories or future worries, emotional distress due to painful thoughts, and coping behaviors to manage emotional distress. ADA has been observed trans-diagnostically across various psychiatric disorders. Although the importance of ADA treatment has been indicated, a scale to measure the severity of ADA has not been developed. This study aimed to develop an Anxious-Depressive Attack Severity Scale (ADAS) to measure the severity of ADA symptoms and examine its reliability and validity. Methods A total of 242 outpatients responded to a questionnaire and participated in an interview, which were designed to measure the severity of ADA, depressive, anxiety, anxious depression, and social anxiety symptoms. Based on the diagnostic criteria for ADA, 54 patients were confirmed to have ADA and were included in the main study analyses...
The present study investigated oxygenated ([oxy-Hb]) and deoxygenated ([deoxy-Hb]) hemoglobin con... more The present study investigated oxygenated ([oxy-Hb]) and deoxygenated ([deoxy-Hb]) hemoglobin concentration changes during the performance of a word fluency task in the frontal region of five drug-naive patients with panic disorder with or without agoraphobia and in 33 age-, sex-, and task performance-matched healthy volunteers by using multi-channel near-infrared spectroscopy (NIRS). The left inferior frontal [oxy-Hb] changes during performance of the task in patients with panic disorder were significantly smaller than those of healthy controls. This pilot study suggests the possibility that the left frontal lobe, required for cognitive function, is impaired in patients with panic disorder.
Plasma glutamate decarboxylase (GAD) activity was measured in patients with endogenous psychoses ... more Plasma glutamate decarboxylase (GAD) activity was measured in patients with endogenous psychoses and neurologic diseases. Unmedicated schizophrenic patients showed no difference in plasma GAD levels compared to controls. Administration of neuroleptics together with anticholinergic agents increased plasma GAD activity in schizophrenic patients. Compared to controls, patients with major depression and bipolar illness showed significantly lower GAD activity. No effect of antidepressants and minor tranquilizers on plasma GAD activity was found. Relatively lower GAD activity was shown in neurotic patients. The enzyme activity in plasma of patients with Huntington's chorea (HC) was lower than control levels. The plasma GAD concentrations correlated with cerebrospinal fluid concentrations in five HC patients.
Transient global amnesia (TGA) is a well-recognized clinical entity, but its pathophysiology and ... more Transient global amnesia (TGA) is a well-recognized clinical entity, but its pathophysiology and prognosis have remained arguable. We reported that a 63-year-old woman with scleroderma developed two TGA episodes. The patient sometimes suffered from headaches when Raynaud's phenomenon appeared in her fingers, but she did not experience further cerebrovascular events. This case suggests that the unique clinical presentation of this syndrome may result from an ischemic event, possibly triggered by a vasospastic mechanism like Raynaud's phenomenon.
Cultural factors influence both the expression of social anxiety and the interpretation and funct... more Cultural factors influence both the expression of social anxiety and the interpretation and functioning of social anxiety measures. This study aimed to test the measurement equivalence of two commonly used social anxiety measures across two sociocultural contexts using individuals with social anxiety disorder (SAD) from Australia and Japan. Scores on the straightforwardly-worded Social Interaction Anxiety Scale (S-SIAS) and the Social Phobia Scale (SPS) from two archival datasets of individual with SAD, one from Australia (n = 201) and one from Japan (n = 295), were analysed for measurement equivalence using a multigroup confirmatory factor analysis (CFA) framework. The best-fitting factor models for the S-SIAS and SPS were not found to be measurement equivalent across the Australian and Japanese samples. Instead, only a subset of items was invariant. When this subset of invariant items was used to compare social anxiety symptoms across the Australian and Japanese samples, Japanese ...
Major depressive disorder is a common psychiatric disorder that is thought to be triggered by bot... more Major depressive disorder is a common psychiatric disorder that is thought to be triggered by both genetic and environmental factors. Depressive symptoms are an important public health problem and contribute to vulnerability to major depression. Although a substantial number of genetic and epigenetic studies have been performed to date, the detailed etiology of depression remains unclear and there are no validated biomarkers. DNA methylation is one of the major epigenetic modifications that play diverse roles in the etiology of complex diseases. In this study, we performed an epigenome-wide association study (EWAS) of DNA methylation on subjects with (N = 20) or without (N = 27) depressive symptoms in order to examine whether different levels of DNA methylation were associated with depressive tendencies. Employing methylation-array technology, a total of 363,887 methylation sites across the genomes were investigated and several candidate CpG sites associated with depressive symptoms...
Panic disorder (PD) is characterized by recurrent and unexpected panic attacks, subsequent antici... more Panic disorder (PD) is characterized by recurrent and unexpected panic attacks, subsequent anticipatory anxiety, and phobic avoidance. Recent epidemiological and genetic studies have revealed that genetic factors contribute to the pathogenesis of PD. We performed whole-exome sequencing on one Japanese family, including multiple patients with panic disorder, which identified seven rare protein-altering variants. We then screened these genes in a Japanese PD case-control group (384 sporadic PD patients and 571 controls), resulting in the detection of three novel single nucleotide variants as potential candidates for PD (chr15: 42631993, T>C in GANC; chr15: 42342861, G>T in PLA2G4E; chr20: 3641457, G>C in GFRA4). Statistical analyses of these three genes showed that PLA2G4E yielded the lowest p value in gene-based rare variant association tests by Efficient and Parallelizable Association Container Toolbox algorithms; however, the p value did not reach the significance threshol...
Panic disorder (PD) is considered to be a multifactorial disorder emerging from interactions amon... more Panic disorder (PD) is considered to be a multifactorial disorder emerging from interactions among multiple genetic and environmental factors. To date, although genetic studies reported several susceptibility genes with PD, few of them were replicated and the pathogenesis of PD remains to be clarified. Epigenetics is considered to play an important role in etiology of complex traits and diseases, and DNA methylation is one of the major forms of epigenetic modifications. In this study, we performed an epigenome-wide association study of PD using DNA methylation arrays so as to investigate the possibility that different levels of DNA methylation might be associated with PD. The DNA methylation levels of CpG sites across the genome were examined with genomic DNA samples (PD, N = 48, control, N = 48) extracted from peripheral blood. Methylation arrays were used for the analysis. β values, which represent the levels of DNA methylation, were normalized via an appropriate pipeline. Then, β...
The quality of life of individuals with panic disorder and agoraphobia can be improved by the all... more The quality of life of individuals with panic disorder and agoraphobia can be improved by the alleviation of agoraphobia. In other words, examining panic disorder in terms of whether agoraphobia is present is crucial. The current study examined panic disorder from this perspective. Subjects were 253 patients who met the diagnostic criteria for panic disorder (lifetime) according to the Mini International Neuropsychiatric Interview (MINI). Of those patients, 179 had agoraphobia and 74 did not. Statistical analysis was used to examine gender differences in the presence (or absence) of agoraphobia, comorbidities, and the effects of the presence of agoraphobia (severity, assessment of depression, assessment of anxiety, and personality) in these patients. Results indicated gender differences in the presence (or absence) of agoraphobia. Compared to patients without agoraphobia, significantly more patients with agoraphobia were female (p<.001), and had a higher prevalence of comorbidities. Patients with agoraphobia had a higher suicide risk (p<.05), more hypomanic episodes (current) (p<.05), and more frequent episodes of social phobia (p<.05). In addition, patients with agoraphobia had more severe panic disorder and a higher level of neuroticism, sensitivity to anxiety, and trait anxiety [PDSS-J, P&A, NEO-N: p<.01, ASI, STAI (Trait Anxiety): p<.05]. The current findings suggest that when treating a panic disorder, diagnosing the presence of agoraphobia is extremely important.
We studied 63 patients with epileptiform seizure with computerized tomography (CT, EMI-1000) duri... more We studied 63 patients with epileptiform seizure with computerized tomography (CT, EMI-1000) during the past eight months. I n the neurological, electroencephalographical and CT examinations, one case each of brain tumor, arterio-venous malformation and tuberous sclerosis were excluded from the diagnosis of epilepsy. The other 60 patients were further diagnosed in accordance with the Classification of the International League Against Epilepsy. The relationship between the type of epilepsy and the CT and EEG findings is summarized in Table 1. Significance of the anterior horn size on CT in epileptic patients was studied photometrically. The anterior horn perimeter was copied on tracing paper squared by millimeter and this size was measured by the square counting method. The results were
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 1988
1. In schizophrenic patients, a good drug response was associated with a small cerebellar vermis ... more 1. In schizophrenic patients, a good drug response was associated with a small cerebellar vermis brain ratio (CVBR). 2. It was possible to predict drug response with a higher statistical significance based on CVBR, especially in nonfamilial patients with schizophrenia.
The population of monoaminergic synaptic vesicles in the rat caudate nucleus remained unchanged o... more The population of monoaminergic synaptic vesicles in the rat caudate nucleus remained unchanged or slightly decreased 3 h after chlorpromazine (CP) administration, and clearly increased after 24 h. The diameter of synaptic vesicles became smaller when the vesicles increased. These findings suggest that CP causes presynaptic blocking in part of its actions and leads to a condition in which neural transmission is inactive. In the control animals, population of the vesicles tended to fluctuate following the circadian rhythm.
Background Anxious-depressive attack (ADA) is a symptom complex that comprises sudden intense fee... more Background Anxious-depressive attack (ADA) is a symptom complex that comprises sudden intense feelings of anxiety or depression, intrusive rumination of regretful memories or future worries, emotional distress due to painful thoughts, and coping behaviors to manage emotional distress. ADA has been observed trans-diagnostically across various psychiatric disorders. Although the importance of ADA treatment has been indicated, a scale to measure the severity of ADA has not been developed. This study aimed to develop an Anxious-Depressive Attack Severity Scale (ADAS) to measure the severity of ADA symptoms and examine its reliability and validity. Methods A total of 242 outpatients responded to a questionnaire and participated in an interview, which were designed to measure the severity of ADA, depressive, anxiety, anxious depression, and social anxiety symptoms. Based on the diagnostic criteria for ADA, 54 patients were confirmed to have ADA and were included in the main study analyses...
The present study investigated oxygenated ([oxy-Hb]) and deoxygenated ([deoxy-Hb]) hemoglobin con... more The present study investigated oxygenated ([oxy-Hb]) and deoxygenated ([deoxy-Hb]) hemoglobin concentration changes during the performance of a word fluency task in the frontal region of five drug-naive patients with panic disorder with or without agoraphobia and in 33 age-, sex-, and task performance-matched healthy volunteers by using multi-channel near-infrared spectroscopy (NIRS). The left inferior frontal [oxy-Hb] changes during performance of the task in patients with panic disorder were significantly smaller than those of healthy controls. This pilot study suggests the possibility that the left frontal lobe, required for cognitive function, is impaired in patients with panic disorder.
Plasma glutamate decarboxylase (GAD) activity was measured in patients with endogenous psychoses ... more Plasma glutamate decarboxylase (GAD) activity was measured in patients with endogenous psychoses and neurologic diseases. Unmedicated schizophrenic patients showed no difference in plasma GAD levels compared to controls. Administration of neuroleptics together with anticholinergic agents increased plasma GAD activity in schizophrenic patients. Compared to controls, patients with major depression and bipolar illness showed significantly lower GAD activity. No effect of antidepressants and minor tranquilizers on plasma GAD activity was found. Relatively lower GAD activity was shown in neurotic patients. The enzyme activity in plasma of patients with Huntington's chorea (HC) was lower than control levels. The plasma GAD concentrations correlated with cerebrospinal fluid concentrations in five HC patients.
Transient global amnesia (TGA) is a well-recognized clinical entity, but its pathophysiology and ... more Transient global amnesia (TGA) is a well-recognized clinical entity, but its pathophysiology and prognosis have remained arguable. We reported that a 63-year-old woman with scleroderma developed two TGA episodes. The patient sometimes suffered from headaches when Raynaud's phenomenon appeared in her fingers, but she did not experience further cerebrovascular events. This case suggests that the unique clinical presentation of this syndrome may result from an ischemic event, possibly triggered by a vasospastic mechanism like Raynaud's phenomenon.
Cultural factors influence both the expression of social anxiety and the interpretation and funct... more Cultural factors influence both the expression of social anxiety and the interpretation and functioning of social anxiety measures. This study aimed to test the measurement equivalence of two commonly used social anxiety measures across two sociocultural contexts using individuals with social anxiety disorder (SAD) from Australia and Japan. Scores on the straightforwardly-worded Social Interaction Anxiety Scale (S-SIAS) and the Social Phobia Scale (SPS) from two archival datasets of individual with SAD, one from Australia (n = 201) and one from Japan (n = 295), were analysed for measurement equivalence using a multigroup confirmatory factor analysis (CFA) framework. The best-fitting factor models for the S-SIAS and SPS were not found to be measurement equivalent across the Australian and Japanese samples. Instead, only a subset of items was invariant. When this subset of invariant items was used to compare social anxiety symptoms across the Australian and Japanese samples, Japanese ...
Major depressive disorder is a common psychiatric disorder that is thought to be triggered by bot... more Major depressive disorder is a common psychiatric disorder that is thought to be triggered by both genetic and environmental factors. Depressive symptoms are an important public health problem and contribute to vulnerability to major depression. Although a substantial number of genetic and epigenetic studies have been performed to date, the detailed etiology of depression remains unclear and there are no validated biomarkers. DNA methylation is one of the major epigenetic modifications that play diverse roles in the etiology of complex diseases. In this study, we performed an epigenome-wide association study (EWAS) of DNA methylation on subjects with (N = 20) or without (N = 27) depressive symptoms in order to examine whether different levels of DNA methylation were associated with depressive tendencies. Employing methylation-array technology, a total of 363,887 methylation sites across the genomes were investigated and several candidate CpG sites associated with depressive symptoms...
Panic disorder (PD) is characterized by recurrent and unexpected panic attacks, subsequent antici... more Panic disorder (PD) is characterized by recurrent and unexpected panic attacks, subsequent anticipatory anxiety, and phobic avoidance. Recent epidemiological and genetic studies have revealed that genetic factors contribute to the pathogenesis of PD. We performed whole-exome sequencing on one Japanese family, including multiple patients with panic disorder, which identified seven rare protein-altering variants. We then screened these genes in a Japanese PD case-control group (384 sporadic PD patients and 571 controls), resulting in the detection of three novel single nucleotide variants as potential candidates for PD (chr15: 42631993, T>C in GANC; chr15: 42342861, G>T in PLA2G4E; chr20: 3641457, G>C in GFRA4). Statistical analyses of these three genes showed that PLA2G4E yielded the lowest p value in gene-based rare variant association tests by Efficient and Parallelizable Association Container Toolbox algorithms; however, the p value did not reach the significance threshol...
Panic disorder (PD) is considered to be a multifactorial disorder emerging from interactions amon... more Panic disorder (PD) is considered to be a multifactorial disorder emerging from interactions among multiple genetic and environmental factors. To date, although genetic studies reported several susceptibility genes with PD, few of them were replicated and the pathogenesis of PD remains to be clarified. Epigenetics is considered to play an important role in etiology of complex traits and diseases, and DNA methylation is one of the major forms of epigenetic modifications. In this study, we performed an epigenome-wide association study of PD using DNA methylation arrays so as to investigate the possibility that different levels of DNA methylation might be associated with PD. The DNA methylation levels of CpG sites across the genome were examined with genomic DNA samples (PD, N = 48, control, N = 48) extracted from peripheral blood. Methylation arrays were used for the analysis. β values, which represent the levels of DNA methylation, were normalized via an appropriate pipeline. Then, β...
The quality of life of individuals with panic disorder and agoraphobia can be improved by the all... more The quality of life of individuals with panic disorder and agoraphobia can be improved by the alleviation of agoraphobia. In other words, examining panic disorder in terms of whether agoraphobia is present is crucial. The current study examined panic disorder from this perspective. Subjects were 253 patients who met the diagnostic criteria for panic disorder (lifetime) according to the Mini International Neuropsychiatric Interview (MINI). Of those patients, 179 had agoraphobia and 74 did not. Statistical analysis was used to examine gender differences in the presence (or absence) of agoraphobia, comorbidities, and the effects of the presence of agoraphobia (severity, assessment of depression, assessment of anxiety, and personality) in these patients. Results indicated gender differences in the presence (or absence) of agoraphobia. Compared to patients without agoraphobia, significantly more patients with agoraphobia were female (p<.001), and had a higher prevalence of comorbidities. Patients with agoraphobia had a higher suicide risk (p<.05), more hypomanic episodes (current) (p<.05), and more frequent episodes of social phobia (p<.05). In addition, patients with agoraphobia had more severe panic disorder and a higher level of neuroticism, sensitivity to anxiety, and trait anxiety [PDSS-J, P&A, NEO-N: p<.01, ASI, STAI (Trait Anxiety): p<.05]. The current findings suggest that when treating a panic disorder, diagnosing the presence of agoraphobia is extremely important.
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