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Masahiro Suzuki,
Sakae Takahashi,
Eisuke Matsushima,
Masahiko Tsunoda,
Masayoshi Kurachi,
Takashi Okada,
Takuji Hayashi,
Yohei Ishii,
Kiichiro Morita,
Hisao Maeda,
Seiji Katayama,
Ryuzou Kawahara, Tatsui Otsuka,
Yoshio Hirayasu,
Mizuho Sekine,
Yoshiro Okubo,
Mai Motoshita,
Katsuya Ohta,
Makoto Uchiyama,
Takuya Kojima
[show abstract]
[hide abstract]
ABSTRACT: In our previous studies, we identified that exploratory eye movement (EEM) dysfunction appears to be specific to schizophrenia.
The availability of a biological marker specific to schizophrenia would be useful for clinical diagnosis of schizophrenia.
Consequently, we performed the discriminant analysis between schizophrenics and non-schizophrenics on a large sample using
the EEM test data and examined an application of the EEM for clinical diagnosis of schizophrenia. EEM performances were recorded
in 251 schizophrenics and 389 non-schizophrenics (111 patients with mood disorders, 28 patients with neurotic disorders and
250 normal controls). The patients were recruited from eight university hospitals and three affiliated hospitals. For this
study with a large sample, we developed a new digital computerized version of the EEM test, which automatically handled large
amounts of data. We measured four parameters: number of eye fixations (NEF), total eye scanning length (TESL), mean eye scanning
length (MESL) and responsive search score (RSS). These parameters of schizophrenics differed significantly from those of the
other three groups. The stepwise regression analysis selected the TESL and the RSS as the valid parameters for discriminating
between schizophrenics and non-schizophrenics. In the discriminant analysis using the RSS and TESL as prediction parameters,
184 of the 251 clinically diagnosed schizophrenics were discriminated as having schizophrenia (sensitivity 73.3%); and 308
of the 389 clinically diagnosed non-schizophrenic subjects were discriminated as non-schizophrenics (specificity 79.2%). Based
on our findings we believe that the EEM measures may be useful for the clinical diagnosis of schizophrenia.
European Archives of Psychiatry and Clinical Neuroscience 04/2012; 259(3):186-194. · 3.49 Impact Factor
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Masahiro Suzuki,
Sakae Takahashi,
Eisuke Matsushima,
Masahiko Tsunoda,
Masayoshi Kurachi,
Takashi Okada,
Takuji Hayashi,
Yohei Ishii,
Kiichiro Morita,
Hisao Maeda,
Seiji Katayama, Tatsui Otsuka,
Yoshio Hirayasu,
Mizuho Sekine,
Yoshiro Okubo,
Mai Motoshita,
Katsuya Ohta,
Makoto Uchiyama,
Takuya Kojima
[show abstract]
[hide abstract]
ABSTRACT: Many psychophysiological tests have been widely researched in the search for a biological marker of schizophrenia. The exploratory eye movement (EEM) test involves the monitoring of eye movements while subjects freely view geometric figures. Suzuki et al. (2009) performed discriminant analysis between schizophrenia and non-schizophrenia subjects using EEM test data; consequently, clinically diagnosed schizophrenia patients were identified as having schizophrenia with high probability (73.3%). The aim of the present study was to investigate the characteristics of schizophrenia patients who were identified as having schizophrenia on EEM discriminant analysis (SPDSE) or schizophrenia patients who were identified as not having schizophrenia on EEM discriminant analysis (SPDNSE).
The data for the 251 schizophrenia subjects used in the previous discriminant-analytic study were analyzed, and the demographic or symptomatic characteristics of SPDSE and SPDNSE were investigated. As for the symptomatic features, a factor analysis of the Brief Psychiatric Rating Scale (BPRS) rating from the schizophrenia subjects was carried out.
Five factors were found for schizophrenia symptoms: excitement/hostility; negative symptoms; depression/anxiety; positive symptoms; and disorganization. SPDSE had significantly higher factor scores for excitement/hostility, negative symptoms and disorganization than SPDNSE. Furthermore, the BPRS total score for the SPDSE was significantly higher than that for the SPDNSE.
SPDSE may be a disease subtype of schizophrenia with severe symptoms related to excitement/hostility, negative symptoms and disorganization, and EEM parameters may detect this subtype. Therefore, the EEM test may be one of the contributors to the simplification of the heterogeneity of schizophrenia.
Psychiatry and Clinical Neurosciences 02/2012; 66(3):187-94. · 2.13 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: The central serotonergic (5-HT) system is closely involved in regulating various mental functions such as mood and emotion. In this system, the serotonin transporter (5-HTT) and the 5-HT(1A) receptor play important roles in the pathophysiology and treatment of mood and anxiety disorders. However, only a few integrated databases have considered the intraindividual relationship between pre- and postsynaptic serotonergic transmission. In the present study, we constructed a database of 5-HTT and 5-HT(1A) receptors using positron emission tomography (PET) with [¹¹C]DASB and [¹¹C]WAY100635, respectively. Seventeen healthy young men participated in this study. After anatomic standardization of original images, BP(ND) was calculated on a voxel-by-voxel basis using reference tissue methods. The highest binding to 5-HTT was observed in the dorsal raphe nucleus, striatum, and thalamus; moderate binding, in the insula and cingulate cortex; and very low binding, in the cerebral neocortex. In contrast, the highest binding to 5-HT(1A) receptors was seen in the hippocampal regions, insula, neocortical regions, and dorsal raphe nucleus, and very low binding was found in the thalamus and basal ganglia. These distribution patterns were in agreement with those reported in human postmortem studies and previous PET investigations. In addition, exploratory analysis indicated significant negative correlations between the BP(ND) values with both radiotracers in certain regions of the brain, such as the cingulate, insula, and frontal, temporal and parietal cortices (Pearson's correlation, P < 0.05). These databases facilitate the understanding of the regional distribution of serotonergic neurotransmission function in the living human brain and the pathophysiology of various neuropsychiatric disorders.
Synapse 07/2011; 65(7):624-33. · 2.94 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: 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.
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.
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.
Our findings suggest that the dorsal midbrain is associated with PD pathophysiology. The midbrain volume increase may reflect PD severity.
Psychiatry and Clinical Neurosciences 06/2011; 65(4):365-73. · 2.13 Impact Factor
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Fumitoshi Kodaka,
Hiroshi Ito,
Harumasa Takano,
Hidehiko Takahashi,
Ryosuke Arakawa,
Michie Miyoshi,
Masaki Okumura, Tatsui Otsuka,
Kazuhiko Nakayama,
Christer Halldin,
Lars Farde,
Tetsuya Suhara
[show abstract]
[hide abstract]
ABSTRACT: The increased proportion of the high-affinity state of dopamine D2/3 receptors (D2,high) is assumed to correlate with dopamine hypersensitivity, implying a relationship with psychotic symptoms observed in psychiatric disorders such as schizophrenia. [11C](R)-2-CH3O-N-n-propylnorapomorphine ([11C]MNPA), which has an agonistic property to dopamine D2 receptors (D2Rs), is expected to bind preferentially to D2,high. The occupancy of dopamine D2Rs by antagonists to receptors has not been investigated using [11C]MNPA. We compared dopamine D2R occupancies by risperidone, an antagonist to receptors, between [11C]MNPA and [11C]raclopride to confirm whether risperidone occupies D2,high and D2,low at almost identical proportions. PET studies were performed on 11 healthy men under resting condition and following oral administration of a single dose of risperidone (0.5-2.0 mg). Striatal receptor occupancy for each radioligand was calculated. The relationship between dose or plasma concentration of risperidone and dopamine D2R occupancy was calculated. Striatal dopamine D2R occupancies measured with [11C]MNPA and [11C]raclopride were 22-65% and 24-69%, respectively. In the striatum, ED50 values measured with [11C]MNPA and [11C]raclopride were 0.98 and 1.03 mg, respectively. The striatal ED50 values as calculated from plasma concentration were 9.15 ng/ml and 8.01 ng/ml, respectively. Almost identical occupancies and ED50 values were observed between the two radioligands, indicating that risperidone bound to D2,high and D2,low at almost identical proportions in a dose-dependent manner.
The International Journal of Neuropsychopharmacology 02/2011; 14(1):83-9. · 4.58 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: The central serotonergic (5-HT) system is closely involved in regulating various mental functions such as mood and emotion. In this system, the serotonin transporter (5-HTT) and the 5-HT1A receptor play important roles in the pathophysiology and treatment of mood and anxiety disorders. However, only a few integrated databases have considered the intraindividual relationship between pre- and postsynaptic serotonergic transmission. In the present study, we constructed a database of 5-HTT and 5-HT1A receptors using positron emission tomography (PET) with [11C]DASB and [11C]WAY100635, respectively. Seventeen healthy young men participated in this study. After anatomic standardization of original images, BPND was calculated on a voxel-by-voxel basis using reference tissue methods. The highest binding to 5-HTT was observed in the dorsal raphe nucleus, striatum, and thalamus; moderate binding, in the insula and cingulate cortex; and very low binding, in the cerebral neocortex. In contrast, the highest binding to 5-HT1A receptors was seen in the hippocampal regions, insula, neocortical regions, and dorsal raphe nucleus, and very low binding was found in the thalamus and basal ganglia. These distribution patterns were in agreement with those reported in human postmortem studies and previous PET investigations. In addition, exploratory analysis indicated significant negative correlations between the BPND values with both radiotracers in certain regions of the brain, such as the cingulate, insula, and frontal, temporal and parietal cortices (Pearson's correlation, P < 0.05). These databases facilitate the understanding of the regional distribution of serotonergic neurotransmission function in the living human brain and the pathophysiology of various neuropsychiatric disorders. Synapse, 2011. © 2010 Wiley-Liss, Inc.
Synapse 01/2011; 65(7):624 - 633. · 2.94 Impact Factor
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Tomohide Roppongi,
Motoaki Nakamura,
Takeshi Asami,
Fumi Hayano, Tatsui Otsuka,
Kumi Uehara,
Akiko Fujiwara,
Takashi Saeki,
Shunsuke Hayasaka,
Takeshi Yoshida,
Reina Shimizu,
Tomio Inoue,
Yoshio Hirayasu
[show abstract]
[hide abstract]
ABSTRACT: 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.
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.
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 (beta = 0.446, F = 6.409, P = 0.020), and absent POS was negatively associated with Trait-Anxiety (beta = -0.394, F = 5.341, P = 0.032) and Neuroticism trait (beta = -0.492, F = 6.989, P = 0.017).
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.
Psychiatry and Clinical Neurosciences 06/2010; 64(3):318-26. · 2.13 Impact Factor
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Hidehiko Takahashi,
Harumasa Takano,
Fumitoshi Kodaka,
Ryosuke Arakawa,
Makiko Yamada, Tatsui Otsuka,
Yoshiyuki Hirano,
Hideyuki Kikyo,
Yoshiro Okubo,
Motoichiro Kato,
Takayuki Obata,
Hiroshi Ito,
Tetsuya Suhara
[show abstract]
[hide abstract]
ABSTRACT: Several animal studies have demonstrated functional roles of dopamine (DA) D1 and D2 receptors in amygdala activity. However, the contribution of DA D1 and D2 receptors to amygdala response induced by affective stimuli in human is unknown. To investigate the contribution of DA receptor subtypes to amygdala reactivity in human, we conducted a multimodal in vivo neuroimaging study in which DA D1 and D2 receptor bindings in the amygdala were measured with positron emission tomography (PET), and amygdala response induced by fearful faces was assessed by functional magnetic resonance imaging (fMRI) in healthy volunteers. We used multimodality voxelwise correlation analysis between fMRI signal and DA receptor binding measured by PET. DA D1 binding in the amygdala was positively correlated with amygdala signal change in response to fearful faces, but DA D2 binding in the amygdala was not related to amygdala signal change. DA D1 receptors might play a major role in enhancing amygdala response when sensory inputs are affective.
Journal of Neuroscience 02/2010; 30(8):3043-7. · 7.11 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Effects of antipsychotic drugs have widely been considered to be mediated by blockade of postsynaptic dopamine D(2) receptors. Effects of antipsychotics on presynaptic functions of dopaminergic neurotransmission might also be related to therapeutic effects of antipsychotics. To investigate the effects of antipsychotics on presynaptic functions of dopaminergic neurotransmission in relation with occupancy of dopamine D(2) receptors, changes in dopamine synthesis capacity by antipsychotics and occupancy of dopamine D(2) receptors were measured by positron emission tomography (PET) in healthy men. PET studies using [(11)C]raclopride and L-[beta-(11)C]DOPA were performed under resting condition and oral administration of single dose of the antipsychotic drug risperidone on separate days. Although occupancy of dopamine D(2) receptors corresponding dose of risperidone was observed, the changes in dopamine synthesis capacity by the administration of risperidone were not significant, nor was the relation between the occupancy of dopamine D(2) receptors and these changes. A significant negative correlation was observed between the baseline dopamine synthesis capacity and the changes in dopamine synthesis capacity by risperidone, indicating that this antipsychotic can be assumed to stabilize the dopamine synthesis capacity. The therapeutic effects of risperidone in schizophrenia might be related to such stabilizing effects on dopaminergic neurotransmission responsivity.
Journal of Neuroscience 10/2009; 29(43):13730-4. · 7.11 Impact Factor
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Miho Shidahara,
Hiroshi Ito, Tatsui Otsuka,
Yoko Ikoma,
Ryosuke Arakawa,
Fumitoshi Kodaka,
Chie Seki,
Harumasa Takano,
Hidehiko Takahashi,
Federico E Turkheimer,
Yuichi Kimura,
Iwao Kanno,
Tetsuya Suhara
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study is to investigate errors in quantitative analysis for estimating dopamine D(2) receptor occupancy of antipsychotics with agonist radioligand [(11)C]MNPA by numerical simulation, with particular attention to the validity of a quantitative approach based on the use of a reference region. Synthetic data were validated using clinical data combined with a bootstrap approach. Time-activity curves (TACs) of [(11)C]MNPA were simulated, and the reliability of binding potential (BP(ND)) and occupancy estimated by nonlinear least square (NLS) fitting and a simplified reference tissue model (SRTM) were investigated for various noise levels and scan durations. In the human positron emission tomography (PET) study with and without antipsychotic, risperidone, the uncertainty of BP(ND) and occupancy estimated by SRTM was investigated using resampled TACs based on bootstrap approach with weighted residual errors of fitting. For both NLS and SRTM, it was possible to have <3% of bias in occupancy estimates of [(11)C]MNPA by 60 mins. However, shortened scan duration degrades the quantification of very small binding potentials, especially in case of SRTM. Observations were replicated on the clinical data. Results showed that dopamine D(2) receptor occupancy by antipsychotics can be estimated precisely in region of interest analysis by SRTM with a longer than 60-min [(11)C]MNPA PET scan duration.
Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 09/2009; 30(1):187-95. · 5.46 Impact Factor
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Michie Miyoshi,
Hiroshi Ito,
Ryosuke Arakawa,
Hidehiko Takahashi,
Harumasa Takano,
Makoto Higuchi,
Masaki Okumura, Tatsui Otsuka,
Fumitoshi Kodaka,
Mizuho Sekine,
Takeshi Sasaki,
Saori Fujie,
Chie Seki,
Jun Maeda,
Ryuji Nakao,
Ming-Rong Zhang,
Toshimitsu Fukumura,
Masayasu Matsumoto,
Tetsuya Suhara
[show abstract]
[hide abstract]
ABSTRACT: Peripheral benzodiazepine receptor (PBR) is upregulated in activated glial cells and is therefore a useful biomarker for inflammation in the brain and neurodegenerative disorders. We developed a new PET radioligand, (11)C-AC-N-benzyl-N-ethyl-2-(7-methyl-8-oxo-2-pheyl-7,8-dihydro-9H-purin-9-yl)acetamide ((11)C-AC-5216), that allows the imaging and quantification of PBRs in monkey and mouse brains. The aim of this study was to evaluate a quantification method of (11)C-AC-5216 binding in the human brain.
A 90-min dynamic PET scan was obtained for each of 12 healthy men after an intravenous injection of (11)C-AC-5216. Regions of interest were drawn on several brain regions. Binding potential, compared with nondisplaceable uptake (BP(ND)), was calculated by a nonlinear least-squares fitting (NLS) method with the 2-tissue-compartment model, and total volume of distribution (V(T)) was estimated by NLS and graphical analysis methods.
BP(ND) was highest in the thalamus (4.6 +/- 1.0) and lowest in the striatum (3.5 +/- 0.7). V(T) obtained by NLS or graphical analysis showed regional distribution similar to BP(ND). However, there was no correlation between BP(ND) and V(T) because of the interindividual variation of K(1)/k(2). BP(ND) obtained with data from a scan time of 60 min was in good agreement with that from a scan time of 90 min (r = 0.87).
Regional distribution of (11)C-AC-5216 was in good agreement with previous PET studies of PBRs in the human brain. BP(ND) is more appropriate for estimating (11)C-AC-5216 binding than is V(T) because of the interindividual variation of K(1)/k(2). (11)C-AC-5216 is a promising PET ligand for quantifying PBR in the human brain.
Journal of Nuclear Medicine 07/2009; 50(7):1095-101. · 6.38 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: While clinical features of panic disorder show significant sexual dimorphism, previous structural MRI studies have not sufficiently controlled for sex when looking at regional brain abnormalities in panic disorder. Using optimized voxel-based morphometry (VBM), regional gray matter volume was compared between 24 patients (male/female: 9/15) with panic disorder and 24 healthy subjects matched for age and sex. Significant gray matter volume reductions were found in the bilateral dorsomedial and right ventromedial prefrontal cortices, right amygdala, anterior cingulate cortex, bilateral insular cortex, occipitotemporal gyrus and left cerebellar vermis in the patients compared with the controls. Among these regions, the VBM revealed significant sexual dimorphism: volume reduction in the right amygdala and the bilateral insular cortex was significantly greater in the males, while reduction in the right superior temporal gyrus was greater in females. Furthermore, a significant reduction in the dorsolateral and ventrolateral prefrontal cortices, thalamus, and parietal cortex was specific to the female patients. The present study demonstrated the morphological changes in extensive brain regions of patients with panic disorder compared with the sex-matched controls. The current results further suggested that the sexually dimorphic clinical phenotypes of panic disorder might have a neurobiological background even at the structural level of the brain.
Psychiatry Research 07/2009; 173(2):128-34. · 2.52 Impact Factor
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Fumi Hayano phd,
phd Motoaki Nakamura md,
phd Takeshi Asami md,
Kumi Uehara md,
phd Takeshi Yoshida md,
Tomohide Roppongi md,
phd Tatsui Otsuka md,
phd Tomio Inoue md,
phd Yoshio Hirayasu md,
Fumi Hayano,
Motoaki Nakamura,
Takeshi Asami,
Kumi Uehara,
Takeshi Yoshida,
Tomohide Roppongi, Tatsui Otsuka,
Tomio Inoue,
Yoshio Hirayasu
[show abstract]
[hide abstract]
ABSTRACT: 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.
Psychiatry and Clinical Neurosciences 05/2009; 63(3):266 - 276. · 2.13 Impact Factor
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Tatsui Otsuka,
Hiroshi Ito,
Christer Halldin,
Hidehiko Takahashi,
Harumasa Takano,
Ryosuke Arakawa,
Masaki Okumura,
Fumitoshi Kodaka,
Michie Miyoshi,
Mizuho Sekine,
Chie Seki,
Ryuji Nakao,
Kazutoshi Suzuki,
Sjoerd Finnema,
Yoshio Hirayasu,
Tetsuya Suhara,
Lars Farde
[show abstract]
[hide abstract]
ABSTRACT: It has been demonstrated in vitro that the dopamine D(2) receptor has 2 interconvertible affinity states for endogenous dopamine, referred to as the high- and the low-affinity states. (11)C-(R)-2-CH(3)O-N-n-propylnorapomorphine ((11)C-MNPA) is a new agonist radioligand for in vivo imaging of the high-affinity state of dopamine D(2) receptors using PET. In the present study, the kinetics of (11)C-MNPA were examined for the first time, to our knowledge, in the human brain and analyzed using quantitative approaches with or without an arterial input function.
A 90-min dynamic PET scan was obtained for 10 healthy men after an intravenous injection of (11)C-MNPA. The binding potential (BP(ND)) was calculated using the indirect kinetic method, a kinetic compartment analysis with a metabolite-corrected arterial input function. BP(ND) was also calculated by the simplified reference tissue model (SRTM) and transient equilibrium methods, both with the cerebellum as the reference brain region. The results of the quantitative methods were compared in a cross-validation approach.
The highest regional radioactivity was observed in the putamen. BP(ND) values obtained by kinetic analysis were 0.82 +/- 0.09, 0.59 +/- 0.11, and 0.28 +/- 0.06, respectively, in the putamen, caudate, and thalamus. BP(ND) values obtained by the SRTM and transient equilibrium methods were in good agreement with those obtained by the indirect kinetic method (r = 0.98 and r = 0.93, respectively). For all quantification methods, the BP(ND) values based on data acquired from 0 to 60 min were in good agreement with those based on data acquired from 0 to 90 min (r = 0.90-0.99).
The regional distribution of (11)C-MNPA binding was in good agreement with previous PET studies of dopamine D(2) receptors in the human brain using antagonist radioligands. The results support routine use of the SRTM and transient equilibrium methods, that is, methods that do not require an arterial input function and need a scan time of only about 60 min. (11)C-MNPA should thus be useful for clinical research on the pathophysiology of neuropsychiatric disorders and estimation of dopamine D(2) receptor occupancy by dopaminergic drugs.
Journal of Nuclear Medicine 05/2009; 50(5):703-10. · 6.38 Impact Factor
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Masahiro Suzuki,
Sakae Takahashi,
Eisuke Matsushima,
Masahiko Tsunoda,
Masayoshi Kurachi,
Takashi Okada,
Takuji Hayashi,
Yohei Ishii,
Kiichiro Morita,
Hisao Maeda,
Seiji Katayama,
Ryuzou Kawahara, Tatsui Otsuka,
Yoshio Hirayasu,
Mizuho Sekine,
Yoshiro Okubo,
Mai Motoshita,
Katsuya Ohta,
Makoto Uchiyama,
Takuya Kojima
[show abstract]
[hide abstract]
ABSTRACT: In our previous studies, we identified that exploratory eye movement (EEM) dysfunction appears to be specific to schizophrenia. The availability of a biological marker specific to schizophrenia would be useful for clinical diagnosis of schizophrenia. Consequently, we performed the discriminant analysis between schizophrenics and non-schizophrenics on a large sample using the EEM test data and examined an application of the EEM for clinical diagnosis of schizophrenia. EEM performances were recorded in 251 schizophrenics and 389 non-schizophrenics (111 patients with mood disorders, 28 patients with neurotic disorders and 250 normal controls). The patients were recruited from eight university hospitals and three affiliated hospitals. For this study with a large sample, we developed a new digital computerized version of the EEM test, which automatically handled large amounts of data. We measured four parameters: number of eye fixations (NEF), total eye scanning length (TESL), mean eye scanning length (MESL) and responsive search score (RSS). These parameters of schizophrenics differed significantly from those of the other three groups. The stepwise regression analysis selected the TESL and the RSS as the valid parameters for discriminating between schizophrenics and non-schizophrenics. In the discriminant analysis using the RSS and TESL as prediction parameters, 184 of the 251 clinically diagnosed schizophrenics were discriminated as having schizophrenia (sensitivity 73.3%); and 308 of the 389 clinically diagnosed non-schizophrenic subjects were discriminated as non-schizophrenics (specificity 79.2%). Based on our findings we believe that the EEM measures may be useful for the clinical diagnosis of schizophrenia.
Archiv f ur Psychiatrie und Nervenkrankheiten 02/2009; 259(3):186-94. · 2.75 Impact Factor
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Hidehiko Takahashi,
Motoichiro Kato,
Harumasa Takano,
Ryosuke Arakawa,
Masaki Okumura, Tatsui Otsuka,
Fumitoshi Kodaka,
Mika Hayashi,
Yoshiro Okubo,
Hiroshi Ito,
Tetsuya Suhara
[show abstract]
[hide abstract]
ABSTRACT: Dopamine D(1) receptors in the prefrontal cortex (PFC) are important for prefrontal functions, and it is suggested that stimulation of prefrontal D(1) receptors induces an inverted U-shaped response, such that too little or too much D(1) receptor stimulation impairs prefrontal functions. Less is known of the role of D(2) receptors in cognition, but previous studies showed that D(2) receptors in the hippocampus (HPC) might play some roles via HPC-PFC interactions. We measured both D(1) and D(2) receptors in PFC and HPC using positron emission tomography in healthy subjects, with the aim of elucidating how regional D(1) and D(2) receptors are differentially involved in frontal lobe functions and memory. We found an inverted U-shaped relation between prefrontal D(1) receptor binding and Wisconsin Card Sorting Test performance. However, prefrontal D(2) binding has no relation with any neuropsychological measures. Hippocampal D(2) receptor binding showed positive linear correlations not only with memory function but also with frontal lobe functions, but hippocampal D(1) receptor binding had no association with any memory and prefrontal functions. Hippocampal D(2) receptors seem to contribute to local hippocampal functions (long-term memory) and to modulation of brain functions outside HPC ("frontal lobe functions"), which are mainly subserved by PFC, via the HPC-PFC pathway. Our findings suggest that orchestration of prefrontal D(1) receptors and hippocampal D(2) receptors might be necessary for human executive function including working memory.
Journal of Neuroscience 12/2008; 28(46):12032-8. · 7.11 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: 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.
Psychogeriatrics 11/2008; 8(4):196 - 198. · 1.21 Impact Factor
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ABSTRACT: The effects of antipsychotic drugs have generally been considered to be mediated by blockade of dopamine D2 receptors. The concept of limbic and cortical selectivity of second-generation antipsychotics, i.e. higher dopamine D2 receptor occupancy in the cerebral cortices than in the striatum, has been suggested to explain their clinical efficacy with lower incidence of extrapyramidal side-effects. In this study, regional distribution of dopamine D2 receptor occupancy by risperidone was determined in order to elucidate the limbic and cortical selectivity of second-generation antipsychotics. Striatal and extrastriatal dopamine D2 receptor binding at baseline and after oral administration of 2 mg risperidone were measured in ten healthy men by positron emission tomography (PET) using different tracers with different affinity for the receptors, [11C]raclopride and [11C]FLB 457, respectively. Striatal and extrastriatal occupancies of dopamine D2 receptors were calculated for each brain region. Occupancies of dopamine D2 receptors were about 70% and 60% in the striatum and extrastriatum, respectively. A simulation study showed that non-negligible specific binding in the reference region (cerebellum), could cause systemic underestimation of occupancy in [11C]FLB 457 PET studies, indicating that occupancies in both the striatum and extrastriatum may not have differed. Among the extrastriatal regions including limbic and neocortical regions, no significant regional differences in dopamine D2 receptor occupancy were observed. Thus, limbic and cortical selectivity was not observed by one of the second-generation antipsychotics, risperidone.
The International Journal of Neuropsychopharmacology 11/2008; 12(5):667-75. · 4.58 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
Psychiatry and Clinical Neurosciences 07/2008; 62(3):322-30. · 2.13 Impact Factor
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ABSTRACT: Obsessive-compulsive disorder (OCD) is often complicated by depression. We report on a patient with treatment-refractory OCD and treatment-refractory major depression who demonstrated a robust response to augmentation of paroxetine with perospirone. Perospirone is a second-generation antipsychotic agent with antagonist effects on both serotonin 5-HT(2A) and dopamine D(2) receptors, as well as a unique agonist effects on serotonin 5-HT(1A) receptors. Future studies would be valuable to elucidate the utility of augmentation therapy of selective serotonin reuptake inhibitors with perospirone in the treatment of refractory OCD with depression.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 04/2007; 31(2):564-6. · 3.25 Impact Factor
