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Lars Farde - One of the best experts on this subject based on the ideXlab platform.

  • PET, and Dopamine D2 Receptors in the Human
    2015
    Co-Authors: Nancy C. Andreasen, Lars Farde, Mirko Dlkslc, Alan Evans, Albert Gjedde, Samarthjl Lai, Qoran Sedvall, Larry Tune, Dean Wong
    Abstract:

    Recently, two research groups pub-lished numbers for D2 receptor sites in the neostriatum of drug-naive schizophrenic patients, obtained in vivo by positron emission tomogra-phy (PET). One study appeared to confirm the increase of D, receptor numbers, while the other study did not. A workshop was convened in Montreal to examine the reasons for the discrepancy between the results obtained by the two groups. The workshop considered patient popu-lations, PET instrumentation and scanning methods, pharmacology, and modeling. The workshop iden-tified differences between the ap-proaches of the two groups that could contribute to the divergent results, including age and chronici-ty of the patient samples, brain region selected for study, metabolism of the different radio-ligands in blood and brain, reversibility of binding, PET instrumentation, and complexity of data analysis. The workshop con-cluded that these initial efforts had made considerable progress in es-tablishing the role of PET in the un-derstanding of the biochemical processes underlying mental ill-ness. In particular, the unique abili-ty to quantify regional neuroreceptor density at different stages in the evolution of the dis-ease has been implemented. At the same time, the work so far and this conference served to identify the main sources contributing to the different findings from the two centers. This information will be important in designing the next phase of the research which will build upon and reconcile these ap-parent discrepancies. The Dopamine Hypothesis is at present the most widely accepted theory concerning the neurochemi-cal abnormalities that may occur in schizophrenia. It postulates that pa-tients suffering from schizophrenia have an apparent overactdvity of Dopaminergic mechanisms in crucial brain regions. The Dopamine Hypothesis is supported by several lines of evidence, including the mechanisms of action of neuroleptic drugs and the fact that Dopamine agonists tend to exacerbate the symptoms of schizophrenia (Anden e

  • Dopamine d2 receptor binding in drug naive patients with schizophrenia examined with raclopride c11 and positron emission tomography
    Psychiatry Research-neuroimaging, 2006
    Co-Authors: Mirjam Talvik, Christer Halldin, Anna-lena Nordström, Yoshiro Okubo, Hans Olsson, Jacqueline Borg, Lars Farde
    Abstract:

    Abstract The aim was to test the Dopamine Hypothesis of schizophrenia in a further analysis of D 2 -like Dopamine binding using the radioligand [ 11 C]raclopride and high resolution 3-dimensional (3D) PET. Eighteen drug-naive patients with schizophrenia and seventeen control subjects were examined. The D 2 binding potential (BP) in the putamen, the caudate and the thalamus was calculated using the simplified reference tissue model. The volume of regions of interest was controlled for by MRI. Symptoms were rated with the Positive and Negative Syndrome Scale for Schizophrenia (PANSS). No significant group differences were found for D 2 BP in the putamen or in the caudate and there was no significant hemispheric difference for any region. In the right thalamus the D 2 BP was significantly lower in patients as compared to control subjects, whereas a numerical difference did not reach statistical significance for the left thalamus. There was no significant correlation between D 2 BP and total PANSS score in any region. There was a highly significant age effect in the caudate and in the putamen, but not in the thalamus. In this relatively large PET study of exclusively drug-naive schizophrenic patients, a lower D 2 BP in the right thalamus was found in the patient group. This finding is in agreement with two previous studies in Sweden and in Japan using the high-affinity radioligand [ 11 C]FLB 457 and provide further support for a role of Dopamine in the thalamus related to the pathophysiology of schizophrenia.

  • Dopamine d2 receptor binding in drug naive patients with schizophrenia examined with raclopride c11 and positron emission tomography
    Psychiatry Research-neuroimaging, 2006
    Co-Authors: Mirjam Talvik, Christer Halldin, Anna-lena Nordström, Yoshiro Okubo, Hans Olsson, Jacqueline Borg, Lars Farde
    Abstract:

    Abstract The aim was to test the Dopamine Hypothesis of schizophrenia in a further analysis of D 2 -like Dopamine binding using the radioligand [ 11 C]raclopride and high resolution 3-dimensional (3D) PET. Eighteen drug-naive patients with schizophrenia and seventeen control subjects were examined. The D 2 binding potential (BP) in the putamen, the caudate and the thalamus was calculated using the simplified reference tissue model. The volume of regions of interest was controlled for by MRI. Symptoms were rated with the Positive and Negative Syndrome Scale for Schizophrenia (PANSS). No significant group differences were found for D 2 BP in the putamen or in the caudate and there was no significant hemispheric difference for any region. In the right thalamus the D 2 BP was significantly lower in patients as compared to control subjects, whereas a numerical difference did not reach statistical significance for the left thalamus. There was no significant correlation between D 2 BP and total PANSS score in any region. There was a highly significant age effect in the caudate and in the putamen, but not in the thalamus. In this relatively large PET study of exclusively drug-naive schizophrenic patients, a lower D 2 BP in the right thalamus was found in the patient group. This finding is in agreement with two previous studies in Sweden and in Japan using the high-affinity radioligand [ 11 C]FLB 457 and provide further support for a role of Dopamine in the thalamus related to the pathophysiology of schizophrenia.

  • central d2 Dopamine receptor occupancy in relation to antipsychotic drug effects a double blind pet study of schizophrenic patients
    Biological Psychiatry, 1993
    Co-Authors: Anna-lena Nordström, Lars Farde, Christer Halldin, Frits-axel Wiesel, Kaj Forslund, Stefan Pauli, Gunilla Uppfeldt
    Abstract:

    Abstract The relationship between central D2-Dopamine receptor occupancy and antipsychotic drug effects was examined in a double-blind study. Raclopride was the compound used to induce a selective occupancy of the D2-Dopamine receptors. In addition, 11 C-labeled raclopride was the radioligand used to measure occupancy by positron emission tomography (PET). Seventeen schizophrenic patients were randomly assigned to one of three parallel groups treated for 4 weeks with daily doses of 2, 6, or 12 mg of raclopride. D2-receptor occupancy was determined by PET at steady-state conditions in 13 patients who completed the study. A statistically significant relationship was demonstrated between antipsychotic effect and degree of D2-receptor occupancy ( p p = 0.02). The finding of a relationship between selective occupancy of the D2-Dopamine receptors and clinical effects in schizophrenic patients principally provides new support for the Dopamine Hypothesis of antipsychotic drug action.

Noriyuki Tomiyama - One of the best experts on this subject based on the ideXlab platform.

  • Neuromelanin Magnetic Resonance Imaging Reveals Increased Dopaminergic Neuron Activity in the Substantia Nigra of Patients with Schizophrenia
    2016
    Co-Authors: Yoshiyuki Watanabe, Hisashi Tanaka, Akio Tsukabe, Yuki Kunitomi, Mitsuo Nishizawa, Ryota Hashimoto, Hidenaga Yamamori, Michiko Fujimoto, Masaki Fukunaga, Noriyuki Tomiyama
    Abstract:

    Purpose: The Dopamine Hypothesis suggests that excessive Dopamine release results in the symptoms of schizophrenia. The purpose of this study was to elucidate the Dopaminergic and noradrenergic neurons using 3-T neuromelanin magnetic resonance imaging (MRI) in patients with schizophrenia and healthy control subjects. Methods: We prospectively examined 52 patients with schizophrenia (M: F = 27:25, mean age, 35 years) and age- and sex-matched healthy controls. Using a 3T MRI unit, we obtained oblique T1-weighted axial images perpendicular to the brainstem. We measured the signal intensity and area for the substantia nigra (SNc), midbrain tegmentum, locus ceruleus (LC), and pons. We then calculated the contrast ratios (CR) for the SNc (CRSN) and LC (CRLC), which were compared between patients and healthy controls using unpaired t-tests. Results: The SNc and LC were readily identified in both patients and healthy controls as areas with high signal intensities in the posterior part of the cerebral peduncle and in the upper pontine tegmentum. The CRSN values in patients were significantly higher than those in healthy controls (10.8962.37 vs. 9.662.36, p,0.01). We observed no difference in the CRLC values between the patients and healthy controls (14.2163.5 vs. 13.4463.37, p = 0.25). Furthermore, there was no difference in area of the SNc and LC between schizophrenia patients and controls. Conclusions: Neuromelanin MRI might reveal increased signal intensity in the SNc of patients with schizophrenia. Ou

  • neuromelanin magnetic resonance imaging reveals increased Dopaminergic neuron activity in the substantia nigra of patients with schizophrenia
    PLOS ONE, 2014
    Co-Authors: Yoshiyuki Watanabe, Hisashi Tanaka, Akio Tsukabe, Yuki Kunitomi, Mitsuo Nishizawa, Ryota Hashimoto, Hidenaga Yamamori, Michiko Fujimoto, Masaki Fukunaga, Noriyuki Tomiyama
    Abstract:

    Purpose The Dopamine Hypothesis suggests that excessive Dopamine release results in the symptoms of schizophrenia. The purpose of this study was to elucidate the Dopaminergic and noradrenergic neurons using 3-T neuromelanin magnetic resonance imaging (MRI) in patients with schizophrenia and healthy control subjects. Methods We prospectively examined 52 patients with schizophrenia (M: F = 27∶25, mean age, 35 years) and age- and sex-matched healthy controls. Using a 3T MRI unit, we obtained oblique T1-weighted axial images perpendicular to the brainstem. We measured the signal intensity and area for the substantia nigra (SNc), midbrain tegmentum, locus ceruleus (LC), and pons. We then calculated the contrast ratios (CR) for the SNc (CRSN) and LC (CRLC), which were compared between patients and healthy controls using unpaired t-tests. Results The SNc and LC were readily identified in both patients and healthy controls as areas with high signal intensities in the posterior part of the cerebral peduncle and in the upper pontine tegmentum. The CRSN values in patients were significantly higher than those in healthy controls (10.89±2.37 vs. 9.6±2.36, p<0.01). We observed no difference in the CRLC values between the patients and healthy controls (14.21±3.5 vs. 13.44±3.37, p = 0.25). Furthermore, there was no difference in area of the SNc and LC between schizophrenia patients and controls. Conclusions Neuromelanin MRI might reveal increased signal intensity in the SNc of patients with schizophrenia. Our results indicate the presence of excessive Dopamine products in the SNc of these patients.

Anna-lena Nordström - One of the best experts on this subject based on the ideXlab platform.

  • Dopamine d2 receptor binding in drug naive patients with schizophrenia examined with raclopride c11 and positron emission tomography
    Psychiatry Research-neuroimaging, 2006
    Co-Authors: Mirjam Talvik, Christer Halldin, Anna-lena Nordström, Yoshiro Okubo, Hans Olsson, Jacqueline Borg, Lars Farde
    Abstract:

    Abstract The aim was to test the Dopamine Hypothesis of schizophrenia in a further analysis of D 2 -like Dopamine binding using the radioligand [ 11 C]raclopride and high resolution 3-dimensional (3D) PET. Eighteen drug-naive patients with schizophrenia and seventeen control subjects were examined. The D 2 binding potential (BP) in the putamen, the caudate and the thalamus was calculated using the simplified reference tissue model. The volume of regions of interest was controlled for by MRI. Symptoms were rated with the Positive and Negative Syndrome Scale for Schizophrenia (PANSS). No significant group differences were found for D 2 BP in the putamen or in the caudate and there was no significant hemispheric difference for any region. In the right thalamus the D 2 BP was significantly lower in patients as compared to control subjects, whereas a numerical difference did not reach statistical significance for the left thalamus. There was no significant correlation between D 2 BP and total PANSS score in any region. There was a highly significant age effect in the caudate and in the putamen, but not in the thalamus. In this relatively large PET study of exclusively drug-naive schizophrenic patients, a lower D 2 BP in the right thalamus was found in the patient group. This finding is in agreement with two previous studies in Sweden and in Japan using the high-affinity radioligand [ 11 C]FLB 457 and provide further support for a role of Dopamine in the thalamus related to the pathophysiology of schizophrenia.

  • Dopamine d2 receptor binding in drug naive patients with schizophrenia examined with raclopride c11 and positron emission tomography
    Psychiatry Research-neuroimaging, 2006
    Co-Authors: Mirjam Talvik, Christer Halldin, Anna-lena Nordström, Yoshiro Okubo, Hans Olsson, Jacqueline Borg, Lars Farde
    Abstract:

    Abstract The aim was to test the Dopamine Hypothesis of schizophrenia in a further analysis of D 2 -like Dopamine binding using the radioligand [ 11 C]raclopride and high resolution 3-dimensional (3D) PET. Eighteen drug-naive patients with schizophrenia and seventeen control subjects were examined. The D 2 binding potential (BP) in the putamen, the caudate and the thalamus was calculated using the simplified reference tissue model. The volume of regions of interest was controlled for by MRI. Symptoms were rated with the Positive and Negative Syndrome Scale for Schizophrenia (PANSS). No significant group differences were found for D 2 BP in the putamen or in the caudate and there was no significant hemispheric difference for any region. In the right thalamus the D 2 BP was significantly lower in patients as compared to control subjects, whereas a numerical difference did not reach statistical significance for the left thalamus. There was no significant correlation between D 2 BP and total PANSS score in any region. There was a highly significant age effect in the caudate and in the putamen, but not in the thalamus. In this relatively large PET study of exclusively drug-naive schizophrenic patients, a lower D 2 BP in the right thalamus was found in the patient group. This finding is in agreement with two previous studies in Sweden and in Japan using the high-affinity radioligand [ 11 C]FLB 457 and provide further support for a role of Dopamine in the thalamus related to the pathophysiology of schizophrenia.

  • central d2 Dopamine receptor occupancy in relation to antipsychotic drug effects a double blind pet study of schizophrenic patients
    Biological Psychiatry, 1993
    Co-Authors: Anna-lena Nordström, Lars Farde, Christer Halldin, Frits-axel Wiesel, Kaj Forslund, Stefan Pauli, Gunilla Uppfeldt
    Abstract:

    Abstract The relationship between central D2-Dopamine receptor occupancy and antipsychotic drug effects was examined in a double-blind study. Raclopride was the compound used to induce a selective occupancy of the D2-Dopamine receptors. In addition, 11 C-labeled raclopride was the radioligand used to measure occupancy by positron emission tomography (PET). Seventeen schizophrenic patients were randomly assigned to one of three parallel groups treated for 4 weeks with daily doses of 2, 6, or 12 mg of raclopride. D2-receptor occupancy was determined by PET at steady-state conditions in 13 patients who completed the study. A statistically significant relationship was demonstrated between antipsychotic effect and degree of D2-receptor occupancy ( p p = 0.02). The finding of a relationship between selective occupancy of the D2-Dopamine receptors and clinical effects in schizophrenic patients principally provides new support for the Dopamine Hypothesis of antipsychotic drug action.

Christer Halldin - One of the best experts on this subject based on the ideXlab platform.

  • Dopamine d2 receptor binding in drug naive patients with schizophrenia examined with raclopride c11 and positron emission tomography
    Psychiatry Research-neuroimaging, 2006
    Co-Authors: Mirjam Talvik, Christer Halldin, Anna-lena Nordström, Yoshiro Okubo, Hans Olsson, Jacqueline Borg, Lars Farde
    Abstract:

    Abstract The aim was to test the Dopamine Hypothesis of schizophrenia in a further analysis of D 2 -like Dopamine binding using the radioligand [ 11 C]raclopride and high resolution 3-dimensional (3D) PET. Eighteen drug-naive patients with schizophrenia and seventeen control subjects were examined. The D 2 binding potential (BP) in the putamen, the caudate and the thalamus was calculated using the simplified reference tissue model. The volume of regions of interest was controlled for by MRI. Symptoms were rated with the Positive and Negative Syndrome Scale for Schizophrenia (PANSS). No significant group differences were found for D 2 BP in the putamen or in the caudate and there was no significant hemispheric difference for any region. In the right thalamus the D 2 BP was significantly lower in patients as compared to control subjects, whereas a numerical difference did not reach statistical significance for the left thalamus. There was no significant correlation between D 2 BP and total PANSS score in any region. There was a highly significant age effect in the caudate and in the putamen, but not in the thalamus. In this relatively large PET study of exclusively drug-naive schizophrenic patients, a lower D 2 BP in the right thalamus was found in the patient group. This finding is in agreement with two previous studies in Sweden and in Japan using the high-affinity radioligand [ 11 C]FLB 457 and provide further support for a role of Dopamine in the thalamus related to the pathophysiology of schizophrenia.

  • Dopamine d2 receptor binding in drug naive patients with schizophrenia examined with raclopride c11 and positron emission tomography
    Psychiatry Research-neuroimaging, 2006
    Co-Authors: Mirjam Talvik, Christer Halldin, Anna-lena Nordström, Yoshiro Okubo, Hans Olsson, Jacqueline Borg, Lars Farde
    Abstract:

    Abstract The aim was to test the Dopamine Hypothesis of schizophrenia in a further analysis of D 2 -like Dopamine binding using the radioligand [ 11 C]raclopride and high resolution 3-dimensional (3D) PET. Eighteen drug-naive patients with schizophrenia and seventeen control subjects were examined. The D 2 binding potential (BP) in the putamen, the caudate and the thalamus was calculated using the simplified reference tissue model. The volume of regions of interest was controlled for by MRI. Symptoms were rated with the Positive and Negative Syndrome Scale for Schizophrenia (PANSS). No significant group differences were found for D 2 BP in the putamen or in the caudate and there was no significant hemispheric difference for any region. In the right thalamus the D 2 BP was significantly lower in patients as compared to control subjects, whereas a numerical difference did not reach statistical significance for the left thalamus. There was no significant correlation between D 2 BP and total PANSS score in any region. There was a highly significant age effect in the caudate and in the putamen, but not in the thalamus. In this relatively large PET study of exclusively drug-naive schizophrenic patients, a lower D 2 BP in the right thalamus was found in the patient group. This finding is in agreement with two previous studies in Sweden and in Japan using the high-affinity radioligand [ 11 C]FLB 457 and provide further support for a role of Dopamine in the thalamus related to the pathophysiology of schizophrenia.

  • central d2 Dopamine receptor occupancy in relation to antipsychotic drug effects a double blind pet study of schizophrenic patients
    Biological Psychiatry, 1993
    Co-Authors: Anna-lena Nordström, Lars Farde, Christer Halldin, Frits-axel Wiesel, Kaj Forslund, Stefan Pauli, Gunilla Uppfeldt
    Abstract:

    Abstract The relationship between central D2-Dopamine receptor occupancy and antipsychotic drug effects was examined in a double-blind study. Raclopride was the compound used to induce a selective occupancy of the D2-Dopamine receptors. In addition, 11 C-labeled raclopride was the radioligand used to measure occupancy by positron emission tomography (PET). Seventeen schizophrenic patients were randomly assigned to one of three parallel groups treated for 4 weeks with daily doses of 2, 6, or 12 mg of raclopride. D2-receptor occupancy was determined by PET at steady-state conditions in 13 patients who completed the study. A statistically significant relationship was demonstrated between antipsychotic effect and degree of D2-receptor occupancy ( p p = 0.02). The finding of a relationship between selective occupancy of the D2-Dopamine receptors and clinical effects in schizophrenic patients principally provides new support for the Dopamine Hypothesis of antipsychotic drug action.

Mirjam Talvik - One of the best experts on this subject based on the ideXlab platform.

  • Dopamine d2 receptor binding in drug naive patients with schizophrenia examined with raclopride c11 and positron emission tomography
    Psychiatry Research-neuroimaging, 2006
    Co-Authors: Mirjam Talvik, Christer Halldin, Anna-lena Nordström, Yoshiro Okubo, Hans Olsson, Jacqueline Borg, Lars Farde
    Abstract:

    Abstract The aim was to test the Dopamine Hypothesis of schizophrenia in a further analysis of D 2 -like Dopamine binding using the radioligand [ 11 C]raclopride and high resolution 3-dimensional (3D) PET. Eighteen drug-naive patients with schizophrenia and seventeen control subjects were examined. The D 2 binding potential (BP) in the putamen, the caudate and the thalamus was calculated using the simplified reference tissue model. The volume of regions of interest was controlled for by MRI. Symptoms were rated with the Positive and Negative Syndrome Scale for Schizophrenia (PANSS). No significant group differences were found for D 2 BP in the putamen or in the caudate and there was no significant hemispheric difference for any region. In the right thalamus the D 2 BP was significantly lower in patients as compared to control subjects, whereas a numerical difference did not reach statistical significance for the left thalamus. There was no significant correlation between D 2 BP and total PANSS score in any region. There was a highly significant age effect in the caudate and in the putamen, but not in the thalamus. In this relatively large PET study of exclusively drug-naive schizophrenic patients, a lower D 2 BP in the right thalamus was found in the patient group. This finding is in agreement with two previous studies in Sweden and in Japan using the high-affinity radioligand [ 11 C]FLB 457 and provide further support for a role of Dopamine in the thalamus related to the pathophysiology of schizophrenia.

  • Dopamine d2 receptor binding in drug naive patients with schizophrenia examined with raclopride c11 and positron emission tomography
    Psychiatry Research-neuroimaging, 2006
    Co-Authors: Mirjam Talvik, Christer Halldin, Anna-lena Nordström, Yoshiro Okubo, Hans Olsson, Jacqueline Borg, Lars Farde
    Abstract:

    Abstract The aim was to test the Dopamine Hypothesis of schizophrenia in a further analysis of D 2 -like Dopamine binding using the radioligand [ 11 C]raclopride and high resolution 3-dimensional (3D) PET. Eighteen drug-naive patients with schizophrenia and seventeen control subjects were examined. The D 2 binding potential (BP) in the putamen, the caudate and the thalamus was calculated using the simplified reference tissue model. The volume of regions of interest was controlled for by MRI. Symptoms were rated with the Positive and Negative Syndrome Scale for Schizophrenia (PANSS). No significant group differences were found for D 2 BP in the putamen or in the caudate and there was no significant hemispheric difference for any region. In the right thalamus the D 2 BP was significantly lower in patients as compared to control subjects, whereas a numerical difference did not reach statistical significance for the left thalamus. There was no significant correlation between D 2 BP and total PANSS score in any region. There was a highly significant age effect in the caudate and in the putamen, but not in the thalamus. In this relatively large PET study of exclusively drug-naive schizophrenic patients, a lower D 2 BP in the right thalamus was found in the patient group. This finding is in agreement with two previous studies in Sweden and in Japan using the high-affinity radioligand [ 11 C]FLB 457 and provide further support for a role of Dopamine in the thalamus related to the pathophysiology of schizophrenia.