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Gitte M Knudsen - One of the best experts on this subject based on the ideXlab platform.
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identification of a serotonin 2a receptor subtype of schizophrenia spectrum disorders with pimavanserin the sub sero proof of concept trial protocol
Frontiers in Pharmacology, 2020Co-Authors: Olga B Baltzersen, Vibe Gedsoe Frokjaer, Jayachandra Mitta Raghava, Lone Baandrup, Christian H Fibiger, Birte Glenthøj, Birgitte Fagerlund, Gitte M KnudsenAbstract:Background: All current approved antipsychotic drugs against schizophrenia spectrum disorders share affinity for the dopamine receptor (D2R). However, up to one-third of these patients respond insufficiently, and in some cases, side-effects outweigh symptom reduction. Previous data have suggested that a subgroup of antipsychotic-naive patients will respond to serotonin 2A receptor (2AR) blockade. Aims: This investigator-initiated, translational, proof-of-concept study has overall two aims; 1) To test the Clinical effectiveness of monotherapy with the newly approved drug against Parkinson's disease psychosis, pimavanserin, in antipsychotic-free patients with first-episode schizophrenia spectrum disorders; 2) To characterize the neurobiological profile of responders to pimavaserin. Materials and Equipment: Forty patients will be enrolled in this 6-week open label, one-armed trial with the selective serotonin 2AR antagonist (pimavanserin 34 mg/day). At baseline, patients will undergo: positron emission tomography (PET) imaging of the serotonin 2AR using the radioligand [¹¹C]Cimbi-36; structural magnetic resonance imaging (MRI); MR spectroscopy of cerebral glutamate levels and diffusion tensor imaging; cognitive and psychopathological examinations; electrocardiogram, and blood sampling for genetic- and metabolic analyses. Outcome Measures: The primary Clinical endpoint will be reduction in the Positive and Negative Syndrome Scale (PANSS) positive score. Secondary Clinical endpoints comprise multiple Clinical ratings (positive and negative symptoms, depressive-, obsessive-compulsive symptoms, quality of life, social functioning, sexual functioning, and side-effects). PET, MRI, and cognitive parameters will be used for in-depth neuropsychiatric characterization of pimavanserin response. Anticipated Results: Clinically, we expect pimavanserin to reduce psychotic symptoms with similar effect as observed with conventional antipsychotics, for which we have comparable historical data. We expect pimavanserin to induce minimal side-effects. Neurobiologically, we expect psychotic symptom reduction to be most prominent in patients with low frontal serotonin 2AR binding potential at baseline. Potential pro-cognitive and brain structural effects of pimavanserin will be explored. Perspectives: Sub-Sero will provide unique information about the role serotonin 2AR in antipsychotic-free, first-episode psychosis. If successful, Sub-Sero will aid identification of a "serotonergic subtype" of schizophrenia spectrum patients, thereby promoting development of precision medicine in Clinical Psychiatry. Clinical Trial Registration: ClinicalTrials, identifier NCT03994965.
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identification of a serotonin 2a receptor subtype of schizophrenia spectrum disorders with pimavanserin the sub sero proof of concept trial protocol
Frontiers in Pharmacology, 2020Co-Authors: Olga B Baltzersen, Vibe Gedsoe Frokjaer, Jayachandra Mitta Raghava, Lone Baandrup, Christian H Fibiger, Birte Glenthøj, Birgitte Fagerlund, Gitte M KnudsenAbstract:Background: All current approved antipsychotic drugs against schizophrenia spectrum disorders share affinity for the dopamine receptor (D2R). However, up to one-third of these patients respond insufficiently, and in some cases, side-effects outweigh symptom reduction. Previous data have suggested that a subgroup of antipsychotic-naive patients will respond to serotonin 2A receptor (2AR) blockade. Aims: This investigator-initiated, translational, proof-of-concept study has overall two aims; 1) To test the Clinical effectiveness of monotherapy with the newly approved drug against Parkinson's disease psychosis, pimavanserin, in antipsychotic-free patients with first-episode schizophrenia spectrum disorders; 2) To characterize the neurobiological profile of responders to pimavaserin. Materials and Equipment: Forty patients will be enrolled in this 6-week open label, one-armed trial with the selective serotonin 2AR antagonist (pimavanserin 34 mg/day). At baseline, patients will undergo: positron emission tomography (PET) imaging of the serotonin 2AR using the radioligand [¹¹C]Cimbi-36; structural magnetic resonance imaging (MRI); MR spectroscopy of cerebral glutamate levels and diffusion tensor imaging; cognitive and psychopathological examinations; electrocardiogram, and blood sampling for genetic- and metabolic analyses. Outcome Measures: The primary Clinical endpoint will be reduction in the Positive and Negative Syndrome Scale (PANSS) positive score. Secondary Clinical endpoints comprise multiple Clinical ratings (positive and negative symptoms, depressive-, obsessive-compulsive symptoms, quality of life, social functioning, sexual functioning, and side-effects). PET, MRI, and cognitive parameters will be used for in-depth neuropsychiatric characterization of pimavanserin response. Anticipated Results: Clinically, we expect pimavanserin to reduce psychotic symptoms with similar effect as observed with conventional antipsychotics, for which we have comparable historical data. We expect pimavanserin to induce minimal side-effects. Neurobiologically, we expect psychotic symptom reduction to be most prominent in patients with low frontal serotonin 2AR binding potential at baseline. Potential pro-cognitive and brain structural effects of pimavanserin will be explored. Perspectives: Sub-Sero will provide unique information about the role serotonin 2AR in antipsychotic-free, first-episode psychosis. If successful, Sub-Sero will aid identification of a "serotonergic subtype" of schizophrenia spectrum patients, thereby promoting development of precision medicine in Clinical Psychiatry. Clinical Trial Registration: ClinicalTrials, identifier NCT03994965.
Olga B Baltzersen - One of the best experts on this subject based on the ideXlab platform.
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identification of a serotonin 2a receptor subtype of schizophrenia spectrum disorders with pimavanserin the sub sero proof of concept trial protocol
Frontiers in Pharmacology, 2020Co-Authors: Olga B Baltzersen, Vibe Gedsoe Frokjaer, Jayachandra Mitta Raghava, Lone Baandrup, Christian H Fibiger, Birte Glenthøj, Birgitte Fagerlund, Gitte M KnudsenAbstract:Background: All current approved antipsychotic drugs against schizophrenia spectrum disorders share affinity for the dopamine receptor (D2R). However, up to one-third of these patients respond insufficiently, and in some cases, side-effects outweigh symptom reduction. Previous data have suggested that a subgroup of antipsychotic-naive patients will respond to serotonin 2A receptor (2AR) blockade. Aims: This investigator-initiated, translational, proof-of-concept study has overall two aims; 1) To test the Clinical effectiveness of monotherapy with the newly approved drug against Parkinson's disease psychosis, pimavanserin, in antipsychotic-free patients with first-episode schizophrenia spectrum disorders; 2) To characterize the neurobiological profile of responders to pimavaserin. Materials and Equipment: Forty patients will be enrolled in this 6-week open label, one-armed trial with the selective serotonin 2AR antagonist (pimavanserin 34 mg/day). At baseline, patients will undergo: positron emission tomography (PET) imaging of the serotonin 2AR using the radioligand [¹¹C]Cimbi-36; structural magnetic resonance imaging (MRI); MR spectroscopy of cerebral glutamate levels and diffusion tensor imaging; cognitive and psychopathological examinations; electrocardiogram, and blood sampling for genetic- and metabolic analyses. Outcome Measures: The primary Clinical endpoint will be reduction in the Positive and Negative Syndrome Scale (PANSS) positive score. Secondary Clinical endpoints comprise multiple Clinical ratings (positive and negative symptoms, depressive-, obsessive-compulsive symptoms, quality of life, social functioning, sexual functioning, and side-effects). PET, MRI, and cognitive parameters will be used for in-depth neuropsychiatric characterization of pimavanserin response. Anticipated Results: Clinically, we expect pimavanserin to reduce psychotic symptoms with similar effect as observed with conventional antipsychotics, for which we have comparable historical data. We expect pimavanserin to induce minimal side-effects. Neurobiologically, we expect psychotic symptom reduction to be most prominent in patients with low frontal serotonin 2AR binding potential at baseline. Potential pro-cognitive and brain structural effects of pimavanserin will be explored. Perspectives: Sub-Sero will provide unique information about the role serotonin 2AR in antipsychotic-free, first-episode psychosis. If successful, Sub-Sero will aid identification of a "serotonergic subtype" of schizophrenia spectrum patients, thereby promoting development of precision medicine in Clinical Psychiatry. Clinical Trial Registration: ClinicalTrials, identifier NCT03994965.
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identification of a serotonin 2a receptor subtype of schizophrenia spectrum disorders with pimavanserin the sub sero proof of concept trial protocol
Frontiers in Pharmacology, 2020Co-Authors: Olga B Baltzersen, Vibe Gedsoe Frokjaer, Jayachandra Mitta Raghava, Lone Baandrup, Christian H Fibiger, Birte Glenthøj, Birgitte Fagerlund, Gitte M KnudsenAbstract:Background: All current approved antipsychotic drugs against schizophrenia spectrum disorders share affinity for the dopamine receptor (D2R). However, up to one-third of these patients respond insufficiently, and in some cases, side-effects outweigh symptom reduction. Previous data have suggested that a subgroup of antipsychotic-naive patients will respond to serotonin 2A receptor (2AR) blockade. Aims: This investigator-initiated, translational, proof-of-concept study has overall two aims; 1) To test the Clinical effectiveness of monotherapy with the newly approved drug against Parkinson's disease psychosis, pimavanserin, in antipsychotic-free patients with first-episode schizophrenia spectrum disorders; 2) To characterize the neurobiological profile of responders to pimavaserin. Materials and Equipment: Forty patients will be enrolled in this 6-week open label, one-armed trial with the selective serotonin 2AR antagonist (pimavanserin 34 mg/day). At baseline, patients will undergo: positron emission tomography (PET) imaging of the serotonin 2AR using the radioligand [¹¹C]Cimbi-36; structural magnetic resonance imaging (MRI); MR spectroscopy of cerebral glutamate levels and diffusion tensor imaging; cognitive and psychopathological examinations; electrocardiogram, and blood sampling for genetic- and metabolic analyses. Outcome Measures: The primary Clinical endpoint will be reduction in the Positive and Negative Syndrome Scale (PANSS) positive score. Secondary Clinical endpoints comprise multiple Clinical ratings (positive and negative symptoms, depressive-, obsessive-compulsive symptoms, quality of life, social functioning, sexual functioning, and side-effects). PET, MRI, and cognitive parameters will be used for in-depth neuropsychiatric characterization of pimavanserin response. Anticipated Results: Clinically, we expect pimavanserin to reduce psychotic symptoms with similar effect as observed with conventional antipsychotics, for which we have comparable historical data. We expect pimavanserin to induce minimal side-effects. Neurobiologically, we expect psychotic symptom reduction to be most prominent in patients with low frontal serotonin 2AR binding potential at baseline. Potential pro-cognitive and brain structural effects of pimavanserin will be explored. Perspectives: Sub-Sero will provide unique information about the role serotonin 2AR in antipsychotic-free, first-episode psychosis. If successful, Sub-Sero will aid identification of a "serotonergic subtype" of schizophrenia spectrum patients, thereby promoting development of precision medicine in Clinical Psychiatry. Clinical Trial Registration: ClinicalTrials, identifier NCT03994965.
David H Brendel - One of the best experts on this subject based on the ideXlab platform.
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reductionism eclecticism and pragmatism in Psychiatry the dialectic of Clinical explanation
Journal of Medicine and Philosophy, 2003Co-Authors: David H BrendelAbstract:Explanatory models in Psychiatry reflect what clinicians deem valuable in rendering people’s behavior intelligible and thus help guide treatment choices for mental illnesses. This article outlines some key scientific and ethical principles of Clinical explanation in twenty-first century Psychiatry. Recent work in philosophy of science, Clinical Psychiatry, and psychiatric ethics are critically reviewed in order to elucidate conceptual underpinnings of contemporary explanatory models. Many explanatory models in Psychiatry are reductionistic or eclectic. The former restrict options for diagnostic and therapeutic paradigm choice, while the latter lack a well-defined theoretical basis. These two methodological approaches stand in a dialectical relation to one another insofar as clinicians often move from one approach to its antithesis, ultimately seeking a synthesis of the two approaches that satisfies Clinical needs. Pragmatic considerations can help to transcend the reductionism/eclecticism dialectic. In th...
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reductionism eclecticism and pragmatism in Psychiatry the dialectic of Clinical explanation
Journal of Medicine and Philosophy, 2003Co-Authors: David H BrendelAbstract:Explanatory models in Psychiatry reflect what clinicians deem valuable in rendering people's behavior intelligible and thus help guide treatment choices for mental illnesses. This article outlines some key scientific and ethical principles of Clinical explanation in twenty-first century Psychiatry. Recent work in philosophy of science, Clinical Psychiatry, and psychiatric ethics are critically reviewed in order to elucidate conceptual underpinnings of contemporary explanatory models. Many explanatory models in Psychiatry are reductionistic or eclectic. The former restrict options for diagnostic and therapeutic paradigm choice, while the latter lack a well-defined theoretical basis. These two methodological approaches stand in a dialectical relation to one another insofar as clinicians often move from one approach to its antithesis, ultimately seeking a synthesis of the two approaches that satisfies Clinical needs. Pragmatic considerations can help to transcend the reductionism/eclecticism dialectic. In the absence of a completed science of mental disorders, psychiatrists must tolerate ambiguity and uncertainty as they strive to integrate diverse explanatory concepts in a rigorous and evidence-based fashion. A pragmatic explanatory model in Clinical Psychiatry must focus on favorable treatment outcomes for patients by respecting the pluralistic, participatory, and provisional nature of psychiatric explanation.
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philosophy of mind in the clinic the relation between causal and meaningful explanation in Psychiatry
Harvard Review of Psychiatry, 2000Co-Authors: David H BrendelAbstract:Conceptual dichotomies between mind and brain, psychology and neuroscience, meaning and causation, and fact and value confound thinking in philosophy of mind, Clinical Psychiatry, and psychiatric ethics. Paul Churchland's theory of eliminative materialism highlights these dichotomies, stating that advances in neuroscience have restricted, and eventually will eliminate, any need for psychology. The core principles of this theory are questionable, because psychiatrists still need psychology and perhaps always will. The main argument in this essay is that even in cases of well-defined brain pathology (where eliminative materialism seems most plausible), psychological concepts remain critical. Thus, philosophers and psychiatrists should generate conceptual models that lead not to eliminativism but to explanatory pluralism, which is the pragmatic integration of diverse concepts toward the end of better handling Clinical challenges. The contributions of Karl Jaspers in opposition to eliminative materialism and ...
Birgitte Fagerlund - One of the best experts on this subject based on the ideXlab platform.
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identification of a serotonin 2a receptor subtype of schizophrenia spectrum disorders with pimavanserin the sub sero proof of concept trial protocol
Frontiers in Pharmacology, 2020Co-Authors: Olga B Baltzersen, Vibe Gedsoe Frokjaer, Jayachandra Mitta Raghava, Lone Baandrup, Christian H Fibiger, Birte Glenthøj, Birgitte Fagerlund, Gitte M KnudsenAbstract:Background: All current approved antipsychotic drugs against schizophrenia spectrum disorders share affinity for the dopamine receptor (D2R). However, up to one-third of these patients respond insufficiently, and in some cases, side-effects outweigh symptom reduction. Previous data have suggested that a subgroup of antipsychotic-naive patients will respond to serotonin 2A receptor (2AR) blockade. Aims: This investigator-initiated, translational, proof-of-concept study has overall two aims; 1) To test the Clinical effectiveness of monotherapy with the newly approved drug against Parkinson's disease psychosis, pimavanserin, in antipsychotic-free patients with first-episode schizophrenia spectrum disorders; 2) To characterize the neurobiological profile of responders to pimavaserin. Materials and Equipment: Forty patients will be enrolled in this 6-week open label, one-armed trial with the selective serotonin 2AR antagonist (pimavanserin 34 mg/day). At baseline, patients will undergo: positron emission tomography (PET) imaging of the serotonin 2AR using the radioligand [¹¹C]Cimbi-36; structural magnetic resonance imaging (MRI); MR spectroscopy of cerebral glutamate levels and diffusion tensor imaging; cognitive and psychopathological examinations; electrocardiogram, and blood sampling for genetic- and metabolic analyses. Outcome Measures: The primary Clinical endpoint will be reduction in the Positive and Negative Syndrome Scale (PANSS) positive score. Secondary Clinical endpoints comprise multiple Clinical ratings (positive and negative symptoms, depressive-, obsessive-compulsive symptoms, quality of life, social functioning, sexual functioning, and side-effects). PET, MRI, and cognitive parameters will be used for in-depth neuropsychiatric characterization of pimavanserin response. Anticipated Results: Clinically, we expect pimavanserin to reduce psychotic symptoms with similar effect as observed with conventional antipsychotics, for which we have comparable historical data. We expect pimavanserin to induce minimal side-effects. Neurobiologically, we expect psychotic symptom reduction to be most prominent in patients with low frontal serotonin 2AR binding potential at baseline. Potential pro-cognitive and brain structural effects of pimavanserin will be explored. Perspectives: Sub-Sero will provide unique information about the role serotonin 2AR in antipsychotic-free, first-episode psychosis. If successful, Sub-Sero will aid identification of a "serotonergic subtype" of schizophrenia spectrum patients, thereby promoting development of precision medicine in Clinical Psychiatry. Clinical Trial Registration: ClinicalTrials, identifier NCT03994965.
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identification of a serotonin 2a receptor subtype of schizophrenia spectrum disorders with pimavanserin the sub sero proof of concept trial protocol
Frontiers in Pharmacology, 2020Co-Authors: Olga B Baltzersen, Vibe Gedsoe Frokjaer, Jayachandra Mitta Raghava, Lone Baandrup, Christian H Fibiger, Birte Glenthøj, Birgitte Fagerlund, Gitte M KnudsenAbstract:Background: All current approved antipsychotic drugs against schizophrenia spectrum disorders share affinity for the dopamine receptor (D2R). However, up to one-third of these patients respond insufficiently, and in some cases, side-effects outweigh symptom reduction. Previous data have suggested that a subgroup of antipsychotic-naive patients will respond to serotonin 2A receptor (2AR) blockade. Aims: This investigator-initiated, translational, proof-of-concept study has overall two aims; 1) To test the Clinical effectiveness of monotherapy with the newly approved drug against Parkinson's disease psychosis, pimavanserin, in antipsychotic-free patients with first-episode schizophrenia spectrum disorders; 2) To characterize the neurobiological profile of responders to pimavaserin. Materials and Equipment: Forty patients will be enrolled in this 6-week open label, one-armed trial with the selective serotonin 2AR antagonist (pimavanserin 34 mg/day). At baseline, patients will undergo: positron emission tomography (PET) imaging of the serotonin 2AR using the radioligand [¹¹C]Cimbi-36; structural magnetic resonance imaging (MRI); MR spectroscopy of cerebral glutamate levels and diffusion tensor imaging; cognitive and psychopathological examinations; electrocardiogram, and blood sampling for genetic- and metabolic analyses. Outcome Measures: The primary Clinical endpoint will be reduction in the Positive and Negative Syndrome Scale (PANSS) positive score. Secondary Clinical endpoints comprise multiple Clinical ratings (positive and negative symptoms, depressive-, obsessive-compulsive symptoms, quality of life, social functioning, sexual functioning, and side-effects). PET, MRI, and cognitive parameters will be used for in-depth neuropsychiatric characterization of pimavanserin response. Anticipated Results: Clinically, we expect pimavanserin to reduce psychotic symptoms with similar effect as observed with conventional antipsychotics, for which we have comparable historical data. We expect pimavanserin to induce minimal side-effects. Neurobiologically, we expect psychotic symptom reduction to be most prominent in patients with low frontal serotonin 2AR binding potential at baseline. Potential pro-cognitive and brain structural effects of pimavanserin will be explored. Perspectives: Sub-Sero will provide unique information about the role serotonin 2AR in antipsychotic-free, first-episode psychosis. If successful, Sub-Sero will aid identification of a "serotonergic subtype" of schizophrenia spectrum patients, thereby promoting development of precision medicine in Clinical Psychiatry. Clinical Trial Registration: ClinicalTrials, identifier NCT03994965.
Vibe Gedsoe Frokjaer - One of the best experts on this subject based on the ideXlab platform.
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identification of a serotonin 2a receptor subtype of schizophrenia spectrum disorders with pimavanserin the sub sero proof of concept trial protocol
Frontiers in Pharmacology, 2020Co-Authors: Olga B Baltzersen, Vibe Gedsoe Frokjaer, Jayachandra Mitta Raghava, Lone Baandrup, Christian H Fibiger, Birte Glenthøj, Birgitte Fagerlund, Gitte M KnudsenAbstract:Background: All current approved antipsychotic drugs against schizophrenia spectrum disorders share affinity for the dopamine receptor (D2R). However, up to one-third of these patients respond insufficiently, and in some cases, side-effects outweigh symptom reduction. Previous data have suggested that a subgroup of antipsychotic-naive patients will respond to serotonin 2A receptor (2AR) blockade. Aims: This investigator-initiated, translational, proof-of-concept study has overall two aims; 1) To test the Clinical effectiveness of monotherapy with the newly approved drug against Parkinson's disease psychosis, pimavanserin, in antipsychotic-free patients with first-episode schizophrenia spectrum disorders; 2) To characterize the neurobiological profile of responders to pimavaserin. Materials and Equipment: Forty patients will be enrolled in this 6-week open label, one-armed trial with the selective serotonin 2AR antagonist (pimavanserin 34 mg/day). At baseline, patients will undergo: positron emission tomography (PET) imaging of the serotonin 2AR using the radioligand [¹¹C]Cimbi-36; structural magnetic resonance imaging (MRI); MR spectroscopy of cerebral glutamate levels and diffusion tensor imaging; cognitive and psychopathological examinations; electrocardiogram, and blood sampling for genetic- and metabolic analyses. Outcome Measures: The primary Clinical endpoint will be reduction in the Positive and Negative Syndrome Scale (PANSS) positive score. Secondary Clinical endpoints comprise multiple Clinical ratings (positive and negative symptoms, depressive-, obsessive-compulsive symptoms, quality of life, social functioning, sexual functioning, and side-effects). PET, MRI, and cognitive parameters will be used for in-depth neuropsychiatric characterization of pimavanserin response. Anticipated Results: Clinically, we expect pimavanserin to reduce psychotic symptoms with similar effect as observed with conventional antipsychotics, for which we have comparable historical data. We expect pimavanserin to induce minimal side-effects. Neurobiologically, we expect psychotic symptom reduction to be most prominent in patients with low frontal serotonin 2AR binding potential at baseline. Potential pro-cognitive and brain structural effects of pimavanserin will be explored. Perspectives: Sub-Sero will provide unique information about the role serotonin 2AR in antipsychotic-free, first-episode psychosis. If successful, Sub-Sero will aid identification of a "serotonergic subtype" of schizophrenia spectrum patients, thereby promoting development of precision medicine in Clinical Psychiatry. Clinical Trial Registration: ClinicalTrials, identifier NCT03994965.
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identification of a serotonin 2a receptor subtype of schizophrenia spectrum disorders with pimavanserin the sub sero proof of concept trial protocol
Frontiers in Pharmacology, 2020Co-Authors: Olga B Baltzersen, Vibe Gedsoe Frokjaer, Jayachandra Mitta Raghava, Lone Baandrup, Christian H Fibiger, Birte Glenthøj, Birgitte Fagerlund, Gitte M KnudsenAbstract:Background: All current approved antipsychotic drugs against schizophrenia spectrum disorders share affinity for the dopamine receptor (D2R). However, up to one-third of these patients respond insufficiently, and in some cases, side-effects outweigh symptom reduction. Previous data have suggested that a subgroup of antipsychotic-naive patients will respond to serotonin 2A receptor (2AR) blockade. Aims: This investigator-initiated, translational, proof-of-concept study has overall two aims; 1) To test the Clinical effectiveness of monotherapy with the newly approved drug against Parkinson's disease psychosis, pimavanserin, in antipsychotic-free patients with first-episode schizophrenia spectrum disorders; 2) To characterize the neurobiological profile of responders to pimavaserin. Materials and Equipment: Forty patients will be enrolled in this 6-week open label, one-armed trial with the selective serotonin 2AR antagonist (pimavanserin 34 mg/day). At baseline, patients will undergo: positron emission tomography (PET) imaging of the serotonin 2AR using the radioligand [¹¹C]Cimbi-36; structural magnetic resonance imaging (MRI); MR spectroscopy of cerebral glutamate levels and diffusion tensor imaging; cognitive and psychopathological examinations; electrocardiogram, and blood sampling for genetic- and metabolic analyses. Outcome Measures: The primary Clinical endpoint will be reduction in the Positive and Negative Syndrome Scale (PANSS) positive score. Secondary Clinical endpoints comprise multiple Clinical ratings (positive and negative symptoms, depressive-, obsessive-compulsive symptoms, quality of life, social functioning, sexual functioning, and side-effects). PET, MRI, and cognitive parameters will be used for in-depth neuropsychiatric characterization of pimavanserin response. Anticipated Results: Clinically, we expect pimavanserin to reduce psychotic symptoms with similar effect as observed with conventional antipsychotics, for which we have comparable historical data. We expect pimavanserin to induce minimal side-effects. Neurobiologically, we expect psychotic symptom reduction to be most prominent in patients with low frontal serotonin 2AR binding potential at baseline. Potential pro-cognitive and brain structural effects of pimavanserin will be explored. Perspectives: Sub-Sero will provide unique information about the role serotonin 2AR in antipsychotic-free, first-episode psychosis. If successful, Sub-Sero will aid identification of a "serotonergic subtype" of schizophrenia spectrum patients, thereby promoting development of precision medicine in Clinical Psychiatry. Clinical Trial Registration: ClinicalTrials, identifier NCT03994965.