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AIM Repetitive transcranial magnetic stimulation (rTMS) has been applied as a treatment for patients with treatment-resistant depression in recent years, and a large body of evidence has demonstrated its therapeutic efficacy through stimulating neuronal plasticity. The aim of this study was to investigate structural alterations in the hippocampus (HIPP) and amygdala (AM) following conventional rTMS in patients with depression. METHODS Twenty-eight patients with depression underwent 10 daily 20-Hz left prefrontal rTMS over 2 weeks. The left dorsolateral prefrontal cortex (DLPFC) was identified using magnetic resonance imaging (MRI)-guided neuronavigation prior to stimulation. MRI scans were obtained at baseline and after the completion of rTMS sessions. The therapeutic effects of rTMS were evaluated with the 17-item Hamilton Depression Rating Scale (HAM-D17), and the volumes of the HIPP and AM were measured by a manual tracing method. RESULTS Statistical analyses revealed a significant volume increase in the left HIPP (+3.4%) after rTMS but no significant volume change in the AM. No correlation was found between the left HIPP volume increase and clinical improvement, as measured by the HAM-D17. CONCLUSION The present study demonstrated that conventional left prefrontal rTMS increases the HIPP volume in the stimulated side, indicating a remote neuroplastic effect through the cingulum bundle.

Aim Numerous reports have described differences in the distribution of orbitofrontal cortex (OFC) sulcogyral patterns between patients with schizophrenia (SZ patients) and healthy controls (HC). Alterations in OFC morphology are also observed in those at high risk for developing SZ and in first-episode SZ, suggesting that genetic associations may be extant in determining OFC sulcogyral patterns. We investigated the association between single nucleotide polymorphisms (SNP) in NRG1 and OFC sulcogyral patterns. Methods A total of 59 Japanese patients diagnosed with SZ and 60 HC were scanned on a 1.5-T magnet. Patients were also assessed clinically. OFC sulcogyral patterns were evaluated for each participant, and genotyping was performed for four SNP in NRG1 ( SNP8NRG243177 , SNP8NRG221533 , SNP8NRG241930 , and rs1081062 ). Results There were significant differences in the distribution of OFC sulcogyral patterns between SZ patients and HC (χ2 = 6.52, P = 0.038). SZ patients showed an increase in the frequency of Type III expression, which was associated with an earlier age of disease onset (β = −0.302, F = 4.948, P = 0.030). Although no difference was found in genotype frequencies between SZ patients and HC, an NRG1 SNP, SNP8NRG243177, was associated with Type II expression in SZ patients (β = 0.237, F = 4.120, P = 0.047). Conclusion Our results suggest that OFC sulcogyral pattern formation in schizophrenia may be associated with NRG1 allele frequency, which is closely related to neurodevelopment.

Background and Aim Major depressive disorder (MDD) is an important public health problem, and it is often comorbid with many chronic diseases. The purpose of this study was to identify the clinical features of non-alcoholic fatty liver disease (NAFLD) patients comorbid with MDD and to investigate the influence of MDD on the effect of treatment in patients with NAFLD. Methods A total of 258 patients with biopsy-proven NAFLD were included. MDD was diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision. The patients were followed up for 48 weeks under standard care for NAFLD, which consisted mainly of lifestyle modification. Results There were 32 patients comorbid with MDD. They were characterized by more severe histological steatosis and higher NAFLD activity score, and also significantly higher levels of serum aminotransferase, γ-glutamyl transpeptidase and ferritin, than age-and-sex-matched NAFLD patients without MDD. Moreover, NAFLD patients with MDD showed poor response to the standard care for NAFLD, in body weight loss and in other parameters. Particularly, NAFLD patients with unstable MDD (not in full/partial remission) showed severe resistance to the treatment. Conclusion This is the first study to demonstrate the clinical features and response to therapy of NAFLD patients comorbid with MDD. The comorbid state of MDD was associated with more severe histological liver steatosis and worse treatment outcomes in patients with NAFLD. Further investigations are required to develop new lifestyle modification programs that enable NAFLD patients with MDD to achieve the treatment goal.

The patient was a 72-year-old Japanese woman. At the age of 57, she started having difficulty performing daily work and developed agraphia. She also exhibited restlessness and loss of interest, and began to speak less. Thereafter, stereotypical behavior, gait disturbance and dysphagia were noted. CT scan demonstrated left-dominant frontal and temporal lobe atrophy. She died at the age of 72, about 16 years after the onset of symptoms. Neuropathologically, the brain weighed 867 g, and showed remarkable cerebral atrophy with degeneration of the white matter, predominantly in the left dorsal frontal lobe and anterior temporal lobe. Microscopically, severe neuronal loss and gliosis with rarefaction were found in the cerebral cortex, and severe destruction of myelin and axons was observed in the cerebral white matter. Moderate neuronal loss with gliosis was also found in the pallidum and substantia nigra. Gallyas-Braak staining and tau immunostaining revealed pretangle neurons, NFTs, ballooned neurons and astrocytic plaques in the cerebral cortex, subcortical nuclei and brainstem, and argyrophilic threads and coiled bodies in the subcortical white matter. Tau isoform-specific immunostaining revealed that most tau-immunoreactive structures were positive for 4-repeat (4R) tau, but some of the NFTs were positive for 3-repeat (3R) tau in the cerebral neocortex. Immunoblotting demonstrated an accumulation of 4R tau in the cerebral cortex and subcortical white matter. The patient was pathologically diagnosed as having corticobasal degeneration. Her long survival course likely accounts for the severe white matter degeneration and accumulation of 3R tau in NFTs.

Objectives It is well known that Alzheimer's disease (AD)-type pathology is commonly present in dementia with Lewy bodies (DLB) brains and that the degree of AD-type pathology has an influence on the clinical characteristics of DLB. Although significant hypometabolism in the temporoparietal/precuneus on [18F]fluoro-d-glucose (18F-FDG) positron emission tomography (PET) scans is considered to support a diagnosis of AD, some DLB patients also exhibit this metabolic pattern. The clinical significance of the metabolic pattern on DLB remains unknown. Methods Twenty-three DLB patients, 10 AD patients, and 11 controls underwent 18F-FDG PET scans. According to the degree of hypometabolism in the parietal/precuneus regions, representing the AD-like metabolic pattern, 12 patients were placed in the DLB-AD(+) group and 11 patients were placed in the DLB-AD(−) group. The demographics and clinical variables were compared among the four groups. Results In addition to the parietal/precuneus regions, the DLB-AD(+) group exhibited significantly greater posterior cingulate hypometabolism than the DLB-AD(−) group, although occipital metabolism did not differ. The prevalence of visual hallucinations and extracampine hallucinations, and the Bender–Gestalt test score were significantly higher in the DLB-AD(+) group than the DLB-AD(−) group, although there were no differences in the demographics and other examined clinical variables between the two DLB groups. These clinical differences were absent in the DLB-AD(−) group, AD group, and controls. Conclusions Parietal/precuneus hypometabolism may be associated with clinical characteristics in DLB patients. Further multiple imaging modalities that are sensitive to AD-type pathology are needed to reveal the neurobiological basis of the AD-like metabolic pattern. Copyright © 2014 John Wiley & Sons, Ltd.

We report here an autopsy case of concurrent Huntington's disease (HD) and neurofibromatosis type 1 (NF1), also known as von Recklinghausen's disease. The patient was a Japanese woman with a significant hereditary burden: seven of her family members within four generations were affected by either NF1 or concurrent HD and NF1. She was diagnosed as having NF1 at age 24. At age 40, she showed signs of irritability, aggressive and childish behaviour, which became progressively worse. At age 48, rigidity and spastic gait were observed. One year later, choreoathetoid involuntary movements became apparent. Diagnosis of HD was made by identification of the abnormally expanded cytosine-adenine-guanine repeats in the Huntington's disease gene. Her condition deteriorated gradually to an apallic state and she died at age 60. Post-mortem examination revealed extensive brain atrophy, which was particularly severe in the frontal and temporal cortices and the striatum. The degree of neurodegenerative change seemed to correspond to grade IV. Polyglutamine positive inclusions were seen frequently in all layers of the cerebral cortex and in the amygdala and hippocampus. Inclusions were also present in the striatum, but there were fewer than in the cortex. Remarkably, neuronal intranuclear inclusions were present in the cerebellum, although they are usually not seen in HD. Features associated with the central nervous system involvement of NF1 were not found in the brain, but HD pathology might have been accelerated by the concurrence of NF1. This is the third report of a case with concurrent HD and NF1 in the world, and the first study in which occurrence of polyglutamine inclusions was confirmed on post-mortem examination.

Aim Significant glucose hypometabolism in the primary visual cortex (PVC) is considered to support a diagnosis of dementia with Lewy bodies (DLB), but its relationship to the clinical features remains unknown. The purpose of this study was to assess the association between the metabolic pattern and clinical variables in DLB. Methods A total of 27 DLB patients who underwent [18F]fluoro-d-glucose (18F-FDG) positron emission tomography scans were examined. Demographics and clinical variables were compared between patients with and without glucose hypometabolism in the PVC. The correlations between the cerebral metabolic rate of glucose in the PVC and clinical variables were also investigated. Results Only the onset age of probable rapid eye movement sleep behavior disorder (RBD) was significantly different between patients with and withoutglucose hypometabolism in the PVC, being younger in patients with the metabolic pattern; there were no other differences in clinical variables. The onset age of probable RBD was significantly correlated with the cerebral metabolic rate of glucose in the PVC. Conclusions Glucose hypometabolism in the PVC provides a potential mechanism for the link between antecedent RBD and the subsequent development of dementia in DLB patients. Glucose hypometabolism in the PVC may represent the effect of the pathophysiological process of DLB on RBD rather than a distinct condition in the disease progression. The physiological aspects of the link between this metabolic pattern and the onset of RBD remain unclear.

Suicide attempt is a risk factor for suicide. To investigate trait impulsivity among suicide attempters, 93 attempters admitted to an emergency department and 113 healthy controls were evaluated using the Japanese version of the Barratt Impulsiveness Scale (BIS-11J). Impulsivity was analyzed in relation to clinical data in the attempters. Total BIS-11J, attention impulsiveness, and motor impulsiveness scores were significantly higher in the attempters than in the controls. Both total BIS-11J and non-planning impulsiveness scores were significantly higher in attempters with schizophrenia and other psychotic disorders among the diagnostic groups. Control of impulsivity should be considered as one of the targets for suicide prevention.

Progressive nonfluent aphasia (PNFA) is a clinical subtype of frontotemporal lobar degeneration (FTLD). FTLD with tau accumulation (FTLD-tau) and FTLD with TDP-43 accumulation (FTLD-TDP) both cause PNFA. We reviewed clinical records of 29 FTLD-TDP cases in the brain archive of our institute and found only one case of PNFA. The patient was an 81-year-old male at death. There was no family history of dementia or aphasia. He presented with slow, labored and nonfluent speech at age 75. Behavioral abnormality and movement disorders were absent. MRI at age 76 demonstrated atrophy of the perisylvian regions, including the inferior frontal gyrus, insular gyrus and superior temporal gyrus. The atrophy was more severe in the left hemisphere than the right. On post mortem examinations, neuronal loss was evident in these regions as well as in the substantia nigra. There were abundant TDP-43-immunoreactive neuronal cytoplasmic inclusions and round or irregular-shaped structures in the affected cerebral cortices. A few dystrophic neurites and neuronal intranuclear inclusions were also seen. FTLD-TDP showing PNFA seems to be rare but does exist in Japan, similar to that in other countries.

Aim: The sulcogyral pattern of the orbitofrontal cortex (OFC) is characterized by a remarkable inter-individual variability that likely reflects neurobehavioral traits and genetic aspects of neurodevelopment. The aim of the present study was to evaluate the OFC sulcogyral pattern of patients with schizophrenia (SZ) and healthy controls (HC) to determine group differences in OFC sulcogyral pattern as well as gender differences between groups. Methods: Forty-seven SZ patients (M/F, 23/24) and forty-seven HC (M/F, 17/30), matched on age and gender, were analyzed using magnetic resonance imaging. The sulcogyral pattern was classified into type I, II, or III based on the guidelines set by Chiavaras and Petrides in a previous paper. Chi-squared analysis was used to investigate group and gender differences in the sulcogyral pattern distribution, and categorical regression was used to explore clinical correlations. Results: The distribution of OFC sulcogyral pattern in HC replicated the results found in the previous study (left, χ2 = 0.02, P = 0.989; right, χ2 = 0.97, P = 0.616), in that there were no gender differences. Moreover, the distribution in SZ-M was in accordance with that in the previous study (left, χ2 = 1.59, P = 0.451; right, χ2 = 0.14, P = 0.933). Additionally, within SZ-M, patients with the type III pattern had a higher total positive and negative syndrome scale score (β = 0.902, F = 14.75, P = 0.001). In contrast, the distribution in the right hemisphere in the SZ-F group differed significantly from that observed in SZ-M (χ2 = 6.017, P = 0.046), but did not differ from HC (χ2 = 2.557, P = 0.110). Conclusion: OFC sulcogyral pattern is altered in SZ-M but not in SZ-F, possibly reflecting gender differences in early neurodevelopment.

Aim: Although recent studies suggest abnormalities of the cerebral cortex, limbic structures, and brain stem regions in panic disorder (PD), the extent to which the midbrain is associated with PD pathophysiology is unclear. The aim of this study was to investigate structural abnormalities of the midbrain using magnetic resonance imaging and to determine if there is a clinical correlation between midbrain volume and clinical measurements in patients with PD. Methods: Thirty-eight patients with PD (PD group) and 38 healthy controls (HC group) participated in this study. The midbrain was measured with a manual tracing method with high spatial resolution magnetic resonance imaging. The Panic Disorder Severity Scale and Global Assessment of Functioning were used to examine the correlation between volume abnormality and clinical symptoms and functioning in the PD group. Results: Relative midbrain volume was larger in the PD group than in the HC group. The relative volume of the dorsal midbrain was larger in the PD group, while the volume of the ventral midbrain was not. We found a significant positive correlation between relative dorsal midbrain volume and total Panic Disorder Severity Scale score, and a significant negative correlation between relative dorsal midbrain volume and Global Assessment of Functioning score in the PD group. Conclusions: Our findings suggest that the dorsal midbrain is associated with PD pathophysiology. The midbrain volume increase may reflect PD severity.

Nasu-Hakola disease is an autosomal recessively inherited disease characterized by lipomembranous polycystic osteodysplasia and sclerosing leukoencephalopathy. While white matter lesions prominent in the brain have been reported in the literature, gray matter lesions have not received particular attention. In this study, we examined three autopsy cases of Nasu-Hakola disease in order to focus specifically on gray matter lesions. The ages at onset of the three cases were 20, 23 and 29 years, and the disease durations were 29, 19 and 8 years, respectively. In addition to characteristic degeneration in the cerebral white matter, such as demyelination with conspicuous fibrillary gliosis and axonal changes, all three cases showed overt pathology in the gray matter. Neuronal loss with gliosis in the thalamus (particularly in the dorsomedial nucleus and anterior nucleus), caudate nucleus, putamen and substantia nigra was prominent in all cases, and the severity corresponded to the disease duration. The cerebral cortices were relatively preserved in all cases. One case showed neuronal loss and gliosis in the gray matter of the hippocampus, possibly due to repeated episodes of epileptic convulsions. These gray matter pathologies are considered to be responsible for some of the clinical manifestations of the disease, including extrapyramidal symptoms.

Aims: The posterior region of the orbitofrontal cortex (OFC), which forms its sulcogyral pattern during neurodevelopment, receives multisensory inputs. The purpose of the present study was to assess the relationship between posterior OFC sulcogyral pattern and OFC volume difference in patients with panic disorder. Methods: The anatomical pattern of the posterior orbital sulcus (POS) was classified into three subtypes (absent POS, single POS, double POS) using 3-D high-spatial resolution magnetic resonance images obtained from 28 patients with panic disorder and 28 age- and gender-matched healthy controls. Optimized voxel-based morphometry (VBM) was performed to assess OFC volume differences between the two groups by subtype. Categorical regression analysis was applied to examine the association of POS subtypes with State–Trait Anxiety Inventory and Revised Neuroticism-Extraversion-Openness Personality Inventory scores. Results: No significant difference was found in POS subtype distribution between control subjects and patients with panic disorder. VBM, however, indicated volume reduction in the right posterior–medial OFC region in panic disorder patients with absent POS and single POS. Single POS was positively associated with Trait-Anxiety (β = 0.446, F = 6.409, P = 0.020), and absent POS was negatively associated with Trait-Anxiety (β = −0.394, F = 5.341, P = 0.032) and Neuroticism trait (β = −0.492, F = 6.989, P = 0.017). Conclusions: POS subtypes may be relevant to volume reduction in OFC and the anxiety trait in patients with panic disorder. These findings suggest that volume reduction in OFC in panic disorder may be associated with neurodevelopment.

Aims: Anxiety a core feature of panic disorder, is linked to function of the amygdala. Volume alterations in the brain of patients with panic disorder have previously been reported, but there has been no report of amygdala volume association with anxiety. Methods: Volumes of hippocampus and amygdala were manually measured using magnetic resonance imaging obtained from 27 patients with panic disorder and 30 healthy comparison subjects. In addition the amygdala was focused on, applying small volume correction to optimized voxel-based morphometry (VBM). State–Trait Anxiety Inventory and the NEO Personality Inventory Revised were also used to evaluate anxiety. Results: Amygdala volumes in both hemispheres were significantly smaller in patients with panic disorder compared with control subjects (left: t = −2.248, d.f. = 55, P = 0.029; right: t = −2.892, d.f. = 55, P = 0.005). VBM showed that structural alteration in the panic disorder group occurred on the corticomedial nuclear group within the right amygdala (coordinates [x,y,z (mm)]: [26,−6,−16], Z score = 3.92, family-wise error-corrected P = 0.002). The state anxiety was negatively correlated with the left amygdala volume in patients with panic disorder (r = −0.545, P = 0.016). Conclusions: These findings suggested that the smaller volume of the amygdala may be associated with anxiety in panic disorder. Of note, the smaller subregion in the amygdala estimated on VBM could correspond to the corticomedial nuclear group including the central nucleus, which may play a crucial role in panic attack.

AIMS: To identify profiles associated with treatment retention in Japanese patients with methamphetamine use disorder. METHODS: The study used a retrospective design based on clinical records. The subjects were 101 patients at the Kanagawa Psychiatric Center, Serigaya Hospital, who were diagnosed as having methamphetamine use disorder. They were divided in two groups, namely those who remained in treatment 3 months after the initial assessment, and those who did not. The primary analysis compared patient profiles between the two groups to detect discriminating variables, which were then submitted for secondary analysis using logistic regression to determine the most relevant predictor of retention. RESULTS: Primary analysis indicated that older age, having psychotic symptoms, receiving public assistance, and history of incarceration were associated with treatment retention after 3 months. Secondary analysis showed that positive history of incarceration was the most significant predictor of the outcome. CONCLUSIONS: History of incarceration had the most significant treatment-retention effect on Japanese patients with methamphetamine use disorder. The development and introduction of integrated programs that link methamphetamine-dependent offenders to drug treatment is recommended in outpatient treatment for Japanese patients with methamphetamine user disorder. Language: en

Aim: The goal of the current study was to determine the anxiety level and prevalence of psychiatric disorders among patients awaiting surgery for ovarian tumors. Also analyzed were the predictive factors for psychiatric disorders and changes after surgical diagnosis. Methods: Patients who underwent surgery for ovarian tumors were examined before and after surgery with the MINI International Neuropsychiatric Interview, the Spielberger State-Trait Anxiety Inventory (STAI) and the Mausley Personality Inventory (MPI). Participants diagnosed with cancer were examined a third time after being given an explanation about whether or not adjuvant chemotherapy was required. Results: Twenty-seven participants completed the study and were analyzed. Nine (33.3%) of these 27 participants were diagnosed as having adjustment disorder. There were no differences in the demographic data, STAI trait anxiety score and MPI score between the participants with or without adjustment disorder. At the pre-surgical interview, the STAI state anxiety score of the participants was high (49.5 ± 10.30). After pathological examination of the tumors, it was found that 12 patients had cancer (malignant group) and 15 patients had a benign tumor (benign group). At pre-surgery, the prevalence of adjustment disorder and the level of anxiety in the benign group were similar to those in the malignant group. There was a second surge of anxiety in patients who needed chemotherapy. Conclusion: The above findings demonstrate that patients with suspected ovarian cancer experience a high level of anxiety. Physicians should be aware of the risk of adjustment disorder in these patients. Additionally, ovarian cancer patients need psychological assessment during the course of treatment.

Aim: Recent neuroimaging studies have suggested that the anterior cingulate cortex (ACC) has an important role in the pathology of panic disorder. Despite numerous functional neuroimaging studies that have elucidated the strong relationship between functional abnormalities of the ACC and panic disorder and its symptoms and response to emotional tasks associated with panic disorder, there has been no study showing volumetric changes of the ACC or its subregions. Methods: To clarify the structural abnormalities of ACC and its subregions, the combination of region of interest (ROI) and optimized voxel-based morphometry (VBM) methods were performed on 26 patients with panic disorder, and 26 age and sex-matched healthy subjects. In the ROI study, ACC was divided into four subregions: dorsal, rostral, subcallosal and subgenual ACC. Results: The results of the manually traced ROI volume comparison showed significant volume reduction in the right dorsal ACC. VBM also showed a volume reduction in the right dorsal as well as a part of the rostral ACC as a compound mass. Conclusions: Both manual ROI tracing and optimized VBM suggest a subregion-specific pattern of ACC volume deficit in panic disorder. In addition to functional abnormalities, these results suggest that structural abnormalities of the ACC contribute to the pathophysiology of panic disorder.

Japan has one of the highest suicide rates in the world. Suicides numbered 32,863 in 1998 and have exceeded 30,000 in every subsequent year. Education of those involved in general and psychosocial patient care can contribute greatly to suicide prevention. The authors administered a brief knowledge and attitude assessment questionnaire concerning suicide to students in their first, third, and fifth years at a Japanese medical school. Participants numbered 160 (94 men with a mean age of 21.8 years, SD = 3.01, and 66 women with a mean age of 21.2 years, SD = 2.64); 59 first year, 52 third year, and 49 in their fifth year. The questionnaire consists of eight multiple-choice questions asking knowledge of suicide and one open-ended question asking attitude. In the knowledge part, only about half of the items were answered correctly (mean score was 4.21, SD = 1.28). A significant difference was observed in prevalence of attitudes as categorical variables between student years (P = 0.001). Sympathetic comments increased along with student years, while critical comments decreased. Given the frequent and interventional opportunities of primary-care medical contacts, poor understanding of suicide from the medical viewpoint was of concern. Moreover, judgmental attitudes were common, especially in earlier school years. Better informed, more understanding physicians and other health professionals could contribute greatly to prevention.

The effects of cerebrovascular lesions on DLB are not yet fully understood, whereas the development of Alzheimer's disease (AD) is known to be associated with cerebrovascular lesions. In this study, we investigated the frequency of concomitant cerebrovascular pathologies in autopsy-proven DLB cases (n = 25) in comparison with AD cases (n= 63). We also investigated the correlation between cerebrovascular pathologies and the clinical features of DLB cases. On gross inspection, five cases of DLB and seven cases of AD were complicated by cerebral hemorrhages and the difference was significant; most of the lesions in DLB were subdural hemorrhages, possibly related to trauma. Nine cases of DLB and 25 cases of AD had grossly identified infarctions, but no significant difference was observed. Three cases of DLB and four cases of AD had concomitant hemorrhages, while 10 cases of DLB and 43 cases of AD had infarcts on microscopic inspection. There was a significant difference in the frequency of microscopic infarcts between DLB and AD, whereas no significant difference was noted in the frequency of microscopic hemorrhages. In DLB cases without vascular complications, memory disturbance was common as the initial symptom, while parkinsonism was more common in those with vascular complications. However, no significant difference was observed between DLB cases with and without vascular complications with respect to the frequency of individual clinical symptoms over the whole clinical course. These findings suggest that grossly identified hemorrhages are more common in DLB because of trauma, while microinfarcts are less common in DLB than AD, although the reason remains unclear. Such vascular complications might affect the clinical manifestations, in particular, the initial symptom, of DLB.

Background: Improved management of elderly psychiatric patients requires further identification of their special needs and problems. Methods: We analyzed the characteristics of 1333 consecutive patients admitted to the Psychiatric Center of Yokohama City University Medical Center, a general hospital psychiatric unit, from January 2000 to December 2003. Patients 65 years old or older (the elderly group) accounted for 12.3% of all patients. Results: The duration of admission in elderly patients was significantly longer than in younger patients (less than 65 years old). Admission history and admission type were significantly different between these two groups. Prevalence of dementia or delirium as a primary or secondary diagnosis was significantly greater in the elderly group. About three-quarters of elderly patients were diagnosed as having a mood disorder (47.6%), or an organic mental disorder (31.1%). A significantly smaller fraction of patients were placed in seclusion in the elderly group than in the younger group, although the fraction of patients who were restrained did not differ between the two groups. A significantly higher fraction of elderly patients was transferred to general medical or surgical wards in the hospital to continue treatment for physical illness. In the elderly group, physical and mental prognoses were poorest in patients with organic mental disorders. Conclusions: Compared with the younger patients, the elderly psychiatric patients showed peculiar features. They were thought to require the treatments that were adapted to meet their needs.

Neuroleptic malignant syndrome (NMS) is a potentially fatal adverse reaction to psychopharmacologic treatment. Reported herein are two NMS patients with schizophrenia who were found to possess a CYP2D6 gene deletion allele (CYP2D6*5). The deletion results in decreased CYP2D6 activity, possibly leading to drug accumulation. Both patients with NMS had been treated with neuroleptics, including CYP2D6 substrates. Polymerase chain reaction (PCR) followed by restriction fragment length polymorphism analyses and long PCR were performed to detect CYP2D6 genotype. One patient was found to possess *5/*10; the other had a *1/*5 genotype. The present preliminary report suggests that pharmacokinetic factors cannot be excluded and the CYP2D6 polymorphism is possibly associated with the etiology of NMS.

The purpose of this study is to clarify the relationship between childhood tendencies of attention deficit/hyperactivity disorder (AD/HD) and illicit drug abuse in Japanese prisoners, and to clarify whether drug abusers with AD/HD prefer methamphetamine (MAP) more than other illicit drugs. The Japanese version of the Wender Utah Rating Scale (WURS), which is a self-reporting instrument to retrospectively identify childhood tendencies of AD/HD tendencies, was carried given to 413 prisoners without a drug addiction and 282 prisoners with a drug addiction (192, MAP; 53, toluene; and 37, cannabis). WURS scores were compared between prisoners with and without a drug addiction, and between MAP, toluene, and cannabis abusers. Consequently, prisoners with a drug addiction showed significantly higher WURS scores than those without the addiction (P < 0.001). Toluene abusers showed significantly higher WURS scores than cannabis abusers (P < 0.001), and included a higher proportion with scores over cut-off than MAP or cannabis abusers (P = 0.005). In conclusion, a close relationship existed between illicit drug abuse and childhood AD/HD tendencies. Drug-abusing prisoners with AD/HD tendencies were not prone to choose MAP over other illicit drugs.

P300 amplitude reduction in schizophrenia is, according to previous studies, partially recovered by treatment with neuroleptics. However, whether this medication-induced P300 recovery is associated with duration of untreated psychosis (DUP) remains unreported; the present study is a preliminary examination of this question. Auditory P300 was recorded from 18 drug-naive and first-episode schizophrenia patients, among whom 10 were identified as short DUP, and eight as long DUP. Follow-up event-related potential tests were carried out after treatment with haloperidol or bromperidol for approximately 2 months. Recovery of P300 amplitude was replicated after neuroleptic medication was administered. A significant interaction was found between DUP and the medication effect in P300 amplitude over the left temporo-parietal area; a significant P300 recovery was seen in short DUP but not in long DUP. These results suggest that first-episode schizophrenia patients with long DUP might have severe impairments in the left temporal structures, supporting DUP as a key variable in future neurobiological studies of first-episode schizophrenia.

Summary: Purpose: To test the validity of a hypothesis that kindling-induced enduring kindling inhibition of the homotopic secondary site is not a primate species-specific effect but occurs also in feline species. Methods: Five mature male cats were kindled at the anterior (AC) and posterior (PC) cingulate cortex followed by secondary-site kindling and primary-site retest. Results: Kindling was characterized by a marked seizure-stage instability and a progressive afterdischarge threshold elevation in all the animals. A protracted nonconvulsive seizure stage was followed by convulsive evolution and rapid generalization. At the secondary site, positive transfer effect was absent, and kindling did not occur. Primary-site retest activated kindled seizure within three stimulations. Recurrent spontaneous seizures, identical to the primary-site kindled seizure, occurred in two AC-kindled animals. Subsequent to this, a markedly elevated afterdischarge threshold also was found at some distant cortical and subcortical sites, to which the afterdischarge propagated. Kindling of the amygdala ipsilateral to the kindled AC or PC was tardy, with no positive transfer effect. However, it was associated with afterdischage threshold reduction. Conclusions: Cingulate kindling-induced enduring kindling inhibition at a homotopic secondary site is not a primate species-specific effect and occurs also in feline species. It is not limited to a homotopic site and represents a lasting secondary antiepileptogenesis, presumably due to enhanced intrinsic inhibitory mechanism(s) available to the mammalian brain. A selective afterdischarge threshold elevation concurrently observed is suspected to be a feline species-specific effect.

Frontal hypoperfusion and frontal dysfunction have been reported in patients with major depression. It was also found that frontal hypoperfusion correlated with frontal dysfunction evaluated by neuropsychological tests in depressive patients aged 60 or over. These findings suggested that depression may cause frontal dysfunction and frontal hypoperfusion, and that these pathophysiological changes are manifested as psychomotor retardation. We performed single photon emission computed tomography and Modified Stroop Test on 35 patients with depression aged 25-83 to investigate association of depressive symptoms and psychological tests with cerebral blood perfusion. Additionally, we divided the patients into a younger (less than 60 years old) and an older (60 or over) group to examine the effect of age. Significant correlations were found between frontal perfusion, interference measure on Modified Stroop Test, and psychomotor retardation in all patients. These correlations were also found in the younger group. There was no significant difference on frontal perfusion, interference measure of the Modified Stroop Test, and psychomotor retardation between the two groups. The present findings suggest that frontal hypoperfusion, frontal dysfunction, and psychomotor retardation were associated with one another in not only the old but also the young patients with depression.

Zonisamide (ZNS) add-on administration was used to treat parkinsonian symptoms in three cases of dementia with Lewy bodies (DLB). ZNS was added after doses of the anti-Parkinson's disease drugs were fixed for at least 4 weeks. A total of 25 mg of ZNS produced mild-moderate improvement of parkinsonian symptoms in two cases, but it did not affect the cognitive functions and behavioral or psychological symptoms. Caregiver burdens were decreased in two cases. Although dizziness and drowsiness were detected, these were improved by decreasing the dose. ZNS may be useful for the treatment of motor symptoms in DLB patients.

Tardive dyskinesia (TD) is a neurological disorder caused by the prolonged administration of dopamine antagonists, usually antipsychotics and especially first-generation antipsychotics. Herein, we report on an elderly patient suffering from TD with depression induced by amoxapine, an antidepressant that antagonizes dopamine receptors. This case report demonstrates the therapeutic effect of donepezil even for TD due to amoxapine, corroborating the view that donepezil is beneficial for the treatment of TD induced by dopamine antagonists. A randomized placebo-controlled double-blind trial is required to confirm the usefulness of donepezil in the treatment of dopamine antagonist-induced TD.

Pathophysiology has remained unknown in schizophrenia. Recent neuroimaging advances have enabled us to find structural volume reduction in cortical structures, including the superior temporal gyrus which is associated with auditory information processing and language. These structures also change over time in the clinical course of patients with schizophrenia.

Event-related potentials (ERP) were recorded during auditory oddball tasks for a patient prior to and soon after left anterior temporal lobectomy. The N100 amplitude decreased bilaterally although the latency did not change after the lobectomy. The P300 amplitude decreased in the left hemisphere at 1 and 2 weeks after surgery, then recovered to the pre-operative level at 4 weeks. These findings suggest that the medial temporal structure participates in the generating system of P300.

Summary The effect on limbic kindling of N-methyl-D- aspartate (NMDA) injection into the midline thalamus of rats was investigated. Repeated injection of 25 nmol/0.5 pl NMDA (experimental group) into the massa intermedia (MI), particularly into the reuniens nucleus, caused tonic and/or clonic generalized convulsion associated with temporal limbic EEG seizure discharge. This did not occur after injection of phosphate-buffered saline (PBS, control group). When the animals were subjected to sub-sequent kindling at either the hippocampus (HP) or the amygdala (AM), only the experimental group showed a significant facilitation of kindling rate. The results suggest that an NMDA receptor in the reuniens nucleus participates in modulation of temporal limbic excitability and seizure development.

Summary: Guanidino compounds are intrinsic chemo-convulsants. We investigated the regional and time-dependent changes of these compounds in the amygdala (AM) of kindled rats versus electroconvulsive shock (ECS) seizures using high-performance liquid chromatography (HPLC). Twenty-eight days after the last AM-kindled seizure, guanidinoacetic acid (GAA) and methylguanidine (MG) levels were significantly increased in the bilateral AM as compared with those of control rats, which had been implanted with electrodes but were not stimulated. Both compounds, however, tended to decrease in the bilateral AM after ECS seizure. In addition, we measured these compounds after induction of one af-terdischarge (AD) in the AM. These compounds increased significantly 7 days after AD was induced in the ipsilateral AM. We suggest that the increase of these compounds is coincident with AD generation and specific to AM kindling and the kindled state. RESUME Les composes guanidiniques sont des substances convulsi-vantes intrinseques. Les auteurs ont etudie les modifications regionales de ses composes et leur chronologie au niveau de ľamygdale (AM) de rats ayant subi un kindling par comparaison avec les crises par electrochoc (ECS), au moyen de la chromatographic liquide a haute performance (HPLC). Vingt-huit jours apres la derniere crise amygdalienne par kindling, ils ont constate que les taux d'acide guanidinoacetique et de methyl-guanindine etaient significativement eleves au niveau des AM bilaterales par comparaison avec les rats controles, qui avaient subi une implantation d'electrodes sans stimulation. Les deux composes cependant diminuaient au niveau des 2 AM apres crise par electrochoc. De plus, ils ont mesureces composes apres ľinduction d'une postdecharge (PD) au niveau de ľAM. La concentration de ces composes a augmente significativement 7 jours apres induction de PD au niveau de ľAM ipsilaterale. Ces donnees suggerent que ľaugmentation de ces composes coincide avec la generation de la PD, et est spieifique du kindling amygdalien et de ľetat de kindling. RESUME Se sabe que los compuestos derivados del guanidino pueden ser quimio-convulsivos. Hemos investigado los cambios region-ales, dependientes del tiempo, de estos compuestos en la amigdala (AM) de ratas “condicionadas” (kindled) compareandolos con ataques inducidos por electroshock (ECS) utilizando cro-matografia de liquidos de alta resolution. A los 28 dias despues del ultimo ataque “condicionado” de la AM se observi que los niveles de acido guanidino-acetico y la metilguanidina estaban significativamente incrementados en ambos AM compareandolocon los de las ratas control a las que se habia implantado con un electrodo sin estimulacion. Sin embargo, ambos compuestos mostraron una tendencia a disminuir en ambas AM bilaterales despues del ataque de ECS. Ademas, hemos medido estos compuestos tras la induccion de una post-descarga (AD) en la AM. Estos compuestos se incrementan significativamente a partir del 7o dia despues de que la AD fuese inducida en la AM ipsilateral. Se sugiere que el incremento de estos compuestos coincide con la generateon de AD y “kindling” especifico de la AM y del estado de “condicionamiento.” ZUSAMMENFASSUNG Guanidin-Bestandteile sind als intrinsische Chemokonvulsiva bekannt. Wir untersuchten ihre regionalen und zeitabhangigen Veranderungen im Mandelkern (AM) von gekindelten Ratten im Vergleich zu Elektroschockanfallen (ECS) mittels Flus-sigkeitschromatographie. 28 Tage nach dem letzten AM gekindelten Anfall fanden wir Spiegel fur Guanidinacetat und Meth-ylguanidin in den bilateralen Amygdala signifikant erhoht vergli-chen mit den Kontrolltieren, bei denen eine Elektrode implantiert war, die jedoch nicht stimuliert wurden. Beide Komponenten zeigten nach ECS-Anfallen eine abnehmende Tendenz in beiden Amygdala. Wir masen diese Bestandteile zusatzlich nach Erzeugung einer Nachentladung im AM. 7 Tage nach Erzeugung von Nachentladungen im ipsilateralen AM waren die Komponenten signifikant erhoht. Es wird vermutet, das die Erhohung dieser Substanzen mit der Erzeugung von Nachentladungen einhergeht und spezifisch fur das AM-Kindling und den Kindlingstatus ist.