Effects of risperidone monotherapy on the default-mode network in antipsychotic-naïve first-episode schizophrenia: Posteromedial cortex heterogeneity and relationship with the symptom improvements

Duan, Xujun; Hu, Mao‐Lin; Huang, Xiaoping; Dong, Xinghui; Zong, Xiaofen; He, Changchun; Xiao, Jinming; Tang, Jinsong; Chen, Xiaogang; Chen, Huafu

doi:10.1016/j.schres.2020.01.001

Cited by 15 publications

(20 citation statements)

References 49 publications

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“…Additionally, we observed increased fALFF in the precuneus/posterior cingulate over the course of treatment in responders; this change was not observed in non-responders. This finding complements two recent studies reporting that increased connectivity of the posterior cingulate was associated with clinical response to antipsychotic treatment in the first episode of illness 53,54 . This brain region is considered the hub of the default mode network, and is critical to the ability to shift between self-oriented processing and (external) task-oriented function mediated by dorsal prefrontal cortex 73,74 .…”

Section: Discussionsupporting

confidence: 89%

Frontal lobe fALFF measured from resting-state fMRI at baseline predicts acute treatment response in first episode psychosis

Lencz

Moyett

Barber

et al. 2021

Preprint

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While antipsychotic medications have been utilized for decades, many patients experiencing psychosis do not demonstrate a satisfactory positive symptom response, even in the first episode of illness. Resting state functional magnetic resonance imaging (rs-fMRI) has increasingly been studied as a potential biomarker of antipsychotic treatment response, but studies to date remain limited in terms of sample size and brain regions examined. The present study examined fractional amplitude of low frequency fluctuations (fALFF) derived from rs-fMRI to search the whole brain, in a hypothesis-free manner, for regions that might predict response to 12 weeks of treatments with standard antipsychotic medications (risperidone or aripiprazole). To our knowledge, the present study represents the largest first episode psychosis treatment sample studied with rs-fMRI to date (N=126). At baseline, patients who would later meet strict criteria for clinical response demonstrated significantly greater baseline fALFF in bilateral orbitofrontal cortex compared to non-responders. In a subset of 62 patients who were scanned a second time at the end of treatment, responders and non-responders demonstrated significant increases in fALFF in differing brain regions. Specifically, responders demonstrated significant increases in fALFF, from baseline to follow-up, in bilateral dorsal prefrontal cortex; prefrontal changes were not observed in non-responders or in healthy individuals (n=45) scanned at two time points. Thus, spontaneous activity in orbitofrontal cortex may serve as a prognostic biomarker of antipsychotic treatment, while spontaneous activity in the dorsal prefrontal cortex may serve as a critical target of effective medication.

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Section: Discussionsupporting

confidence: 89%

Frontal lobe fALFF measured from resting-state fMRI at baseline predicts acute treatment response in first episode psychosis

Lencz

Moyett

Barber

et al. 2021

Preprint

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“…All additional studies included 9 structural studies ( 16 , 44 , 48 – 54 ) and 8 functional studies ( 17 , 40 – 43 , 45 – 47 ). Finally, a total of 36 longitudinal studies was included in this review with good quality (mean score = 8.78) ( Supplementary Table 1 ), including 21 studies ( 14 – 16 , 27 – 30 , 32 , 33 , 35 – 37 , 39 , 44 , 48 – 54 ) on brain structure and 15 studies ( 17 , 20 , 24 – 26 , 31 , 34 , 38 , 40 – 43 , 45 – 47 ) on brain function ( Figure 1 ).…”

Section: Resultsmentioning

confidence: 99%

“…Among functional MRI studies, six of them measured regional activities of brain regions ( 24 , 31 , 34 , 38 , 43 , 46 ), including those at resting-state and task-based conditions. Seven studies calculated functional connectivity between regions within the brain ( 17 , 25 , 26 , 40 – 42 , 45 ), and two studies involved both functional measures mentioned above ( 20 , 47 ). Antipsychotics could manifest acute effects on brain function after a very short period of antipsychotic treatment, as reported in studies where patients were treated for only 1 week ( 40 , 43 ).…”

Section: Resultsmentioning

confidence: 99%

“…However, the findings are diverse, different patterns of functional changes were showed that might relate to different mechanisms or pathological processes. Several studies have reported that brain abnormalities at baseline, mostly involving the frontal, parietal, and temporal cortices, basal ganglia and limbic system, were normalized or reduced after being treated ( 17 , 20 , 24 – 26 , 34 , 38 , 40 , 41 , 43 , 47 ). These dynamic changes in abnormal brain activation with symptom improvements were observed after treatment, which may indirectly represent the beneficial effects of antipsychotics.…”

Section: Resultsmentioning

confidence: 99%

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The Effects of Antipsychotic Treatment on the Brain of Patients With First-Episode Schizophrenia: A Selective Review of Longitudinal MRI Studies

et al. 2021

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A large number of neuroimaging studies have detected brain abnormalities in first-episode schizophrenia both before and after treatment, but it remains unclear how these abnormalities reflect the effects of antipsychotic treatment on the brain. To summarize the findings in this regard and provide potential directions for future work, we reviewed longitudinal structural and functional imaging studies in patients with first-episode schizophrenia before and after antipsychotic treatment. A total of 36 neuroimaging studies was included, involving 21 structural imaging studies and 15 functional imaging studies. Both anatomical and functional brain changes in patients after treatment were consistently observed in the frontal and temporal lobes, basal ganglia, limbic system and several key components within the default mode network (DMN). Alterations in these regions were affected by factors such as antipsychotic type, course of treatment, and duration of untreated psychosis (DUP). Over all we showed that: (a) The striatum and DMN were core target regions of treatment in schizophrenia, and their changes were related to different antipsychotics; (b) The gray matter of frontal and temporal lobes tended to reduce after long-term treatment; and (c) Longer DUP was accompanied with faster hippocampal atrophy after initial treatment, which was also associated with poorer outcome. These findings are in accordance with previous notions but should be interpreted with caution. Future studies are needed to clarify the effects of different antipsychotics in multiple conditions and to identify imaging or other biomarkers that may predict antipsychotic treatment response. With such progress, it may help choose effective pharmacological interventional strategies for individuals experiencing recent-onset schizophrenia.

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“…Concerning the effect of medications used in the treatment of psychosis, the heterogeneity of findings is significant and also significant seems to be their possible differential effect on different brain regions and the confounding effect of factors including obesity (Chen et al, 2020; Duan et al, 2020; Gurholt et al, 2020; Hidese et al, 2020). The most interesting and difficult to interpret finding is that the increase or preservation of GM volume is accompanied by a decrease in both white matter volume and ventricle and total CSF volume.…”

Section: Discussionmentioning

confidence: 99%

The effect of first- and second-generation antipsychotics on brain morphology in schizophrenia: A systematic review of longitudinal magnetic resonance studies with a randomized allocation to treatment arms

Fountoulakis

Stahl

2022

J Psychopharmacol

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Schizophrenia manifests as loss of brain volume in specific areas in a progressive nature and an important question concerns whether long-term treatment with medications contributes to this. The aim of the current PRISMA systematic review was to search for prospective studies involving randomization to treatment. PROSPERO ID: CRD42020197874. The MEDLINE/PUBMED was searched and it returned 2638 articles; 3 were fulfilling the inclusion criteria. A fourth was published later; they included 359 subjects, of whom 86 were healthy controls, while the rest were first-episode patients, with 91 under olanzapine, 93 under haloperidol, 48 under risperidone, 5 under paliperidone, 6 under ziprasidone, and 30 under placebo. Probably one-third of patients were suffering from a psychotic disorder other than schizophrenia. The consideration of their results suggested that there is no significant difference between these medications concerning their effects on brain structure and also in comparison to healthy subjects. There does not seem to be any strong support to the opinion that medications that treat psychosis cause loss of brain volume in patients with schizophrenia. On the contrary, the data might imply the possible presence of a protective effect for D2, 5-HT2, and NE alpha-2 antagonists (previously called SGAs). However, the literature is limited and focused research in large study samples is essential to clarify the issue, since important numerical differences do exist. The possibility of the results and their heterogeneity to be artifacts secondary to a modification of magnetic resonance imaging (MRI) signal by antipsychotics should not be easily rejected until relevant data are available.

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Effects of risperidone monotherapy on the default-mode network in antipsychotic-naïve first-episode schizophrenia: Posteromedial cortex heterogeneity and relationship with the symptom improvements

Cited by 15 publications

References 49 publications

Frontal lobe fALFF measured from resting-state fMRI at baseline predicts acute treatment response in first episode psychosis

Frontal lobe fALFF measured from resting-state fMRI at baseline predicts acute treatment response in first episode psychosis

The Effects of Antipsychotic Treatment on the Brain of Patients With First-Episode Schizophrenia: A Selective Review of Longitudinal MRI Studies

The effect of first- and second-generation antipsychotics on brain morphology in schizophrenia: A systematic review of longitudinal magnetic resonance studies with a randomized allocation to treatment arms

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