TY - JOUR

T1 - Functional Connectivity Between Auditory and Medial Temporal Lobe Networks in Antipsychotic-Naïve Patients With First-Episode Schizophrenia Predicts the Effects of Dopamine Antagonism on Auditory Verbal Hallucinations

AU - Anhøj, Simon

AU - Ebdrup, Bjørn

AU - Nielsen, Mette Ødegaard

AU - Antonsen, Patrick

AU - Glenthøj, Birte

AU - Rostrup, Egill

N1 - Publisher Copyright: © 2023 The Authors

PY - 2024

Y1 - 2024

N2 - Background: Understanding how antipsychotic medication ameliorates auditory verbal hallucinations (AVHs) through modulation of brain circuitry is pivotal for understanding the pathophysiology of psychosis and for predicting treatment response. Methods: This case-control study included examinations at baseline and at follow-up after 6 weeks. Initially, antipsychotic-naïve patients with first-episode schizophrenia who were experiencing AVHs were recruited together with healthy control participants. Antipsychotic treatment with the relatively selective D2 receptor antagonist amisulpride was administered as monotherapy. Functional connectivity measured by resting-state functional magnetic resonance imaging between networks of interest was used to study the effects of D2 blockade on brain circuitry and predict clinical treatment response. Hallucinations were rated with the Positive and Negative Syndrome Scale. Results: Thirty-two patients experiencing AVHs and 34 healthy control participants were scanned at baseline. Twenty-two patients and 34 healthy control participants were rescanned at follow-up. Connectivity between the auditory network and the medial temporal lobe network was increased in patients at baseline (p =.002) and normalized within 6 weeks of D2 blockade (p =.018). At baseline, the connectivity between these networks was positively correlated with ratings of hallucinations (t = 2.67, p =.013). Moreover, baseline connectivity between the auditory network and the medial temporal lobe network predicted reduction in hallucinations (t = 2.34, p =.032). Conclusions: Functional connectivity between the auditory network and the medial temporal lobe predicted response to initial antipsychotic treatment. These findings demonstrate that connectivity between networks involved in auditory processing, internal monitoring, and memory is associated with the clinical effect of dopamine antagonism.

AB - Background: Understanding how antipsychotic medication ameliorates auditory verbal hallucinations (AVHs) through modulation of brain circuitry is pivotal for understanding the pathophysiology of psychosis and for predicting treatment response. Methods: This case-control study included examinations at baseline and at follow-up after 6 weeks. Initially, antipsychotic-naïve patients with first-episode schizophrenia who were experiencing AVHs were recruited together with healthy control participants. Antipsychotic treatment with the relatively selective D2 receptor antagonist amisulpride was administered as monotherapy. Functional connectivity measured by resting-state functional magnetic resonance imaging between networks of interest was used to study the effects of D2 blockade on brain circuitry and predict clinical treatment response. Hallucinations were rated with the Positive and Negative Syndrome Scale. Results: Thirty-two patients experiencing AVHs and 34 healthy control participants were scanned at baseline. Twenty-two patients and 34 healthy control participants were rescanned at follow-up. Connectivity between the auditory network and the medial temporal lobe network was increased in patients at baseline (p =.002) and normalized within 6 weeks of D2 blockade (p =.018). At baseline, the connectivity between these networks was positively correlated with ratings of hallucinations (t = 2.67, p =.013). Moreover, baseline connectivity between the auditory network and the medial temporal lobe network predicted reduction in hallucinations (t = 2.34, p =.032). Conclusions: Functional connectivity between the auditory network and the medial temporal lobe predicted response to initial antipsychotic treatment. These findings demonstrate that connectivity between networks involved in auditory processing, internal monitoring, and memory is associated with the clinical effect of dopamine antagonism.

KW - Antipsychotic treatment

KW - Auditory verbal hallucinations

KW - Dopamine receptor blockade

KW - Functional connectivity

KW - Resting-state functional magnetic resonance imaging

KW - Schizophrenia

U2 - 10.1016/j.bpsgos.2023.06.003

DO - 10.1016/j.bpsgos.2023.06.003

M3 - Journal article

C2 - 38298804

AN - SCOPUS:85169505246

VL - 4

SP - 308

EP - 316

JO - Biological Psychiatry Global Open Science

JF - Biological Psychiatry Global Open Science

SN - 2667-1743

IS - 1

ER -