Dorsal striatal hypoconnectivity predicts antipsychotic medication treatment response in first‐episode psychosis and unmedicated patients with schizophrenia

Abstract

Introduction:The dorsal striatum, comprised of the caudate and putamen, is implicated in the pathophysiology of psychosis spectrum disorders. Given the high concentration of dopamine receptors in the striatum, striatal dopamine imbalance is a likely cause in cortico-striatal dysconnectivity. There is great interest in understanding the relationship between striatal abnormalities in psychosis and antipsychotic treatment response, but few studies have considered differential involvement of the caudate and putamen. This study's goals were twofold. First, identify patterns of dorsal striatal dysconnectivity for the caudate and putamen separately in patients with a psychosis spectrum disorder; second, determine if these dysconnectivity patterns were predictive of treatment response.Methods: Using resting state functional connectivity, we evaluated dorsal striatal connectivity using separate bilateral caudate and putamen seed regions in two cohorts of subjects: a cohort of 71 medication-naïve first episode psychosis patients and a cohort of 42 unmedicated patients with schizophrenia (along with matched controls).Patient and control connectivity maps were contrasted for each cohort. After receiving 6 weeks of risperidone treatment, patients' clinical response was calculated. We used regression analyses to determine the relationship between baseline dysconnectivity and treatment response.Results: This dysconnectivity was also predictive of treatment response in both cohorts.Discussion: These findings suggest that the caudate may be more of a driving factor than the putamen in early cortico-striatal dysconnectivity.

fMRI connectivity as a biomarker of antipsychotic treatment response: A systematic review

“…After screening and eligibility assessment 28 studies were included. In one study ( Nelson et al, 2022 ) we identified two distinct cohorts, which we subsequently referred to as Nelson 2022a and Nelson2022b in our study. A total of 952 patients were investigated of which 551 with FE psychosis, 220 with two or more episodes or chronic psychosis, and 181 patients with unknown state of disease.…”

“…Study characteristics are shown in Table 1a , Table 1b , Table 1c . Q1) seventeen studies reported on baseline fMRI-FC and AP-R at follow-up ( Anticevic et al, 2015 , Blazer et al, 2022 , Cadena et al, 2019 , Deng et al, 2022 , Doucet et al, 2020 , Hadley et al, 2014 , Han et al, 2020 , Kraguljac et al, 2016 , Kraguljac et al, 2016 , Li et al, 2020 , Maximo et al, 2021 , Nelson et al, 2022 , Sarpal et al, 2016 , Wang et al, 2019 , Zhang et al, 2019 , Blessing et al, 2020 , Zong et al, 2019 ), Q2) eighteen studies investigated associations between changes in fMRI-FC characteristics before and after treatment related to AP-R ( Anticevic et al, 2015 , Blazer et al, 2022 , Cadena et al, 2019 , Chopra et al, 2021 , Deng et al, 2022 , Duan et al, 2020 , Hadley et al, 2014 , Hadley et al, 2016 , Han et al, 2020 , Kraguljac et al, 2016 , Li et al, 2016 , Li et al, 2020 , Liu et al, 2022 , Sarpal et al, 2015 , Shan et al, 2021 , Wang et al, 2019 , Blessing et al, 2020 , Zong et al, 2019 ), Q3) nine studies investigated the prediction of AP-R based on fMRI-FC ( Cao et al, 2018 , Li et al, 2020 , Li et al, 2020 , Liu et al, 2022 , Sarpal et al, 2016 , Shan et al, 2021 , Zhu et al, 2018 , Blessing et al, 2020 , Nejad et al, 2013 ).…”

“…On the y-axis the total points given to the studies are shown. We considered the study Nelson et al ( Nelson et al, 2022 ) (nelson a and b) as one study for the ROB tool. …”

Functional magnetic resonance imaging in schizophrenia: current evidence, methodological advances, limitations and future directions

“…Cross‐validation of resting state functional connectivity patterns predictive of treatment response in patients with different clinical characteristics and environments is important to test the stability of the predictor. Accordingly, striatal resting state functional connectivity was explored in two cohorts of patients scanned on different MRI platforms: a cohort of medication‐naïve first‐episode patients and a cohort of unmedicated patients with schizophrenia 261 . In both cohorts, striatal resting state functional connectivity was predictive of subsequent treatment response to antipsychotic medication.…”

“…Other functional networks have been studied in relation to their potential to predict antipsychotic treatment response. Functional connectivity of the DMN 262 has been investigated in the above mentioned two cohorts 261 . In both of them, resting state functional connectivity of the hippocampus, one of the principal regions of the DMN, was predictive of subsequent treatment response.…”