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Striatal Volume Increase After Six Weeks of Selective Dopamine D2/3 Receptor Blockade in First-Episode, Antipsychotic-Naïve Schizophrenia Patients

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@article{6e75907a00634eb699fc6ffb9909c742,
title = "Striatal Volume Increase After Six Weeks of Selective Dopamine D2/3 Receptor Blockade in First-Episode, Antipsychotic-Na{\"i}ve Schizophrenia Patients",
abstract = "Patients with chronic schizophrenia often display enlarged striatal volumes, and antipsychotic drugs may contribute via the dopamine D2/3 receptor (D2/3R) blockade. Separating the effects of disease from medication is challenging due to the lack of a proper placebo-group. To address this, we conducted a longitudinal study of antipsychotic-na{\"i}ve, first-episode schizophrenia patients to test the hypothesis that selective blockade of D2/3R would induce a dose-dependent striatal volume increase. Twenty-one patients underwent structural magnetic resonance imaging (sMRI), single-photon emission computed tomography (SPECT), and symptom severity ratings before and after six weeks of amisulpride treatment. Twenty-three matched healthy controls underwent sMRI and baseline SPECT. Data were analyzed using repeated measures and multiple regression analyses. Correlations between symptom severity decrease, volume changes, dose and receptor occupancy were explored. Striatal volumes did not differ between patients and controls at baseline or follow-up, but a significant group-by-time interaction was found (p = 0.01). This interaction was explained by a significant striatal volume increase of 2.1% in patients (Cohens d = 0.45). Striatal increase was predicted by amisulpride dose, but not by either D2/3R occupancy or baseline symptom severity. A significant reduction in symptom severity was observed at a mean dose of 233.3 (SD = 109.9) mg, corresponding to D2/3R occupancy of 44.65%. Reduction in positive symptoms correlated significantly with striatal volume increase, driven by reductions in hallucinations. Our data demonstrate a clear link between antipsychotic treatment and striatal volume increase in antipsychotic-na{\"i}ve schizophrenia patients. Moreover, the treatment-induced striatal volume increase appears clinically relevant by correlating to reductions in core symptoms of schizophrenia.",
keywords = "schizophrenia, dopamine receptor, first-episode antipsychotic-naive, striatum, SPECT, sMRI, antipsychotic drug, longitudinal",
author = "Andersen, {Helle G} and Raghava, {Jayachandra M} and Claus Svarer and Sanne Wulff and Johansen, {Louise B} and Antonsen, {Patrick K} and Nielsen, {Mette {\O}} and Egill Rostrup and Vernon, {Anthony C} and Jensen, {Lars T} and Pinborg, {Lars H} and Glenth{\o}j, {Birte Y} and Ebdrup, {Bj{\o}rn H}",
note = "Copyright {\textcopyright} 2020 Andersen, Raghava, Svarer, Wulff, Johansen, Antonsen, Nielsen, Rostrup, Vernon, Jensen, Pinborg, Glenth{\o}j and Ebdrup.",
year = "2020",
month = may,
day = "20",
doi = "10.3389/fnins.2020.00484",
language = "English",
volume = "14",
pages = "484",
journal = "Frontiers in Neuroscience",
issn = "1662-4548",
publisher = "Frontiers Research Foundation",

}

RIS

TY - JOUR

T1 - Striatal Volume Increase After Six Weeks of Selective Dopamine D2/3 Receptor Blockade in First-Episode, Antipsychotic-Naïve Schizophrenia Patients

AU - Andersen, Helle G

AU - Raghava, Jayachandra M

AU - Svarer, Claus

AU - Wulff, Sanne

AU - Johansen, Louise B

AU - Antonsen, Patrick K

AU - Nielsen, Mette Ø

AU - Rostrup, Egill

AU - Vernon, Anthony C

AU - Jensen, Lars T

AU - Pinborg, Lars H

AU - Glenthøj, Birte Y

AU - Ebdrup, Bjørn H

N1 - Copyright © 2020 Andersen, Raghava, Svarer, Wulff, Johansen, Antonsen, Nielsen, Rostrup, Vernon, Jensen, Pinborg, Glenthøj and Ebdrup.

PY - 2020/5/20

Y1 - 2020/5/20

N2 - Patients with chronic schizophrenia often display enlarged striatal volumes, and antipsychotic drugs may contribute via the dopamine D2/3 receptor (D2/3R) blockade. Separating the effects of disease from medication is challenging due to the lack of a proper placebo-group. To address this, we conducted a longitudinal study of antipsychotic-naïve, first-episode schizophrenia patients to test the hypothesis that selective blockade of D2/3R would induce a dose-dependent striatal volume increase. Twenty-one patients underwent structural magnetic resonance imaging (sMRI), single-photon emission computed tomography (SPECT), and symptom severity ratings before and after six weeks of amisulpride treatment. Twenty-three matched healthy controls underwent sMRI and baseline SPECT. Data were analyzed using repeated measures and multiple regression analyses. Correlations between symptom severity decrease, volume changes, dose and receptor occupancy were explored. Striatal volumes did not differ between patients and controls at baseline or follow-up, but a significant group-by-time interaction was found (p = 0.01). This interaction was explained by a significant striatal volume increase of 2.1% in patients (Cohens d = 0.45). Striatal increase was predicted by amisulpride dose, but not by either D2/3R occupancy or baseline symptom severity. A significant reduction in symptom severity was observed at a mean dose of 233.3 (SD = 109.9) mg, corresponding to D2/3R occupancy of 44.65%. Reduction in positive symptoms correlated significantly with striatal volume increase, driven by reductions in hallucinations. Our data demonstrate a clear link between antipsychotic treatment and striatal volume increase in antipsychotic-naïve schizophrenia patients. Moreover, the treatment-induced striatal volume increase appears clinically relevant by correlating to reductions in core symptoms of schizophrenia.

AB - Patients with chronic schizophrenia often display enlarged striatal volumes, and antipsychotic drugs may contribute via the dopamine D2/3 receptor (D2/3R) blockade. Separating the effects of disease from medication is challenging due to the lack of a proper placebo-group. To address this, we conducted a longitudinal study of antipsychotic-naïve, first-episode schizophrenia patients to test the hypothesis that selective blockade of D2/3R would induce a dose-dependent striatal volume increase. Twenty-one patients underwent structural magnetic resonance imaging (sMRI), single-photon emission computed tomography (SPECT), and symptom severity ratings before and after six weeks of amisulpride treatment. Twenty-three matched healthy controls underwent sMRI and baseline SPECT. Data were analyzed using repeated measures and multiple regression analyses. Correlations between symptom severity decrease, volume changes, dose and receptor occupancy were explored. Striatal volumes did not differ between patients and controls at baseline or follow-up, but a significant group-by-time interaction was found (p = 0.01). This interaction was explained by a significant striatal volume increase of 2.1% in patients (Cohens d = 0.45). Striatal increase was predicted by amisulpride dose, but not by either D2/3R occupancy or baseline symptom severity. A significant reduction in symptom severity was observed at a mean dose of 233.3 (SD = 109.9) mg, corresponding to D2/3R occupancy of 44.65%. Reduction in positive symptoms correlated significantly with striatal volume increase, driven by reductions in hallucinations. Our data demonstrate a clear link between antipsychotic treatment and striatal volume increase in antipsychotic-naïve schizophrenia patients. Moreover, the treatment-induced striatal volume increase appears clinically relevant by correlating to reductions in core symptoms of schizophrenia.

KW - schizophrenia

KW - dopamine receptor

KW - first-episode antipsychotic-naive

KW - striatum

KW - SPECT

KW - sMRI

KW - antipsychotic drug

KW - longitudinal

U2 - 10.3389/fnins.2020.00484

DO - 10.3389/fnins.2020.00484

M3 - Journal article

C2 - 32508577

VL - 14

SP - 484

JO - Frontiers in Neuroscience

JF - Frontiers in Neuroscience

SN - 1662-4548

ER -

ID: 61290130