Functional connectivity of the raphe nucleus as a predictor of the response to selective serotonin reuptake inhibitors in obsessive-compulsive disorder

Kim, Minah; Kwak, Seo‐Young; Yoon, Youngwoo Bryan; Kwak, Yoo Bin; Kim, Taekwan; Cho, Kang Ik K.; Lee, Tae Young; Kwon, Jun Soo

doi:10.1038/s41386-019-0436-2

Cited by 27 publications

(16 citation statements)

References 50 publications

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“…A total of 39 patients with FEP, 78 subjects at CHR for psychosis, and 110 healthy controls (HCs) participated in this study. Resting-state functional magnetic resonance imaging (rs-fMRI) data from 39 FEP patients and 40 HCs were used in our previous study [ 19 , 20 ], and data from 110 HCs were used in other studies [ 21 , 22 ]. FEP patients and individuals at CHR for psychosis were recruited from the Seoul Youth Clinic (www.…”

Section: Methodsmentioning

confidence: 99%

“…Resting-state functional magnetic resonance imaging (rs-fMRI) data from 39 FEP patients and 40 HCs were used in our previous study, 19,20 and data from 110 HCs were used in other studies. 21,22 FEP patients and individuals at CHR for psychosis were recruited from the Seoul Youth Clinic (www. youthclinic.org) 23 and the Department of Neuropsychiatry at the Seoul National University Hospital (SNUH).…”

Section: Participantsmentioning

confidence: 99%

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Triple-Network Dysconnectivity in Patients With First-Episode Psychosis and Individuals at Clinical High Risk for Psychosis

Kim

et al. 2022

Psychiatry Investig

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Objective In the triple-network model, the salience network (SN) plays a crucial role in switching between the default-mode network (DMN) and the central executive network (CEN). Aberrant patterns of triple-network connectivity have been reported in schizophrenia patients, while findings have been less consistent for patients in the early stages of psychotic disorders. Thus, the present study examined the connectivity among the SN, DMN, and CEN in first-episode psychosis (FEP) patients and individuals at clinical high risk (CHR) for psychosis.Methods Thirty-nine patients with FEP, 78 patients with CHR for psychosis, and 110 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. We compared the SN, DMN, and CEN connectivity patterns of the three groups. The role of the SN in networks with significant connectivity differences was examined by mediation analysis.Results FEP patients showed lower SN-DMN and SN-CEN (cluster-level F=5.83, false discovery rate [FDR] corrected-p=0.001) connectivity than HCs. There was lower SN-DMN connectivity (cluster-level F=3.06, FDR corrected-p=0.053) at a trend level in CHR subjects compared to HCs. Between HCs and FEP patients, mediation analysis showed that SN-DMN connectivity was a mediator between group and SN-CEN connectivity. Additionally, SN-CEN connectivity functioned as a mediator between group and SN-DMN connectivity.Conclusion Aberrant connectivity between the SN and DMN/CEN suggests disrupted network switching in FEP patients, although CHR subjects showed trend-level SN-DMN dysconnectivity. Our findings suggest that dysfunctional triple-network dynamics centered on the SN can appear in patients in the early stages of psychotic disorders.

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Section: Methodsmentioning

confidence: 99%

Section: Participantsmentioning

confidence: 99%

Triple-Network Dysconnectivity in Patients With First-Episode Psychosis and Individuals at Clinical High Risk for Psychosis

Kim

et al. 2022

Psychiatry Investig

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“…However, as opposed to its simple output pattern which is mainly consisted of GABAergic projections, its input patterns are quite complicated, the NAc receives various input projections of many different neurotransmitters from wide brain regions, including dopaminergic, serotonergic, histaminergic, cholinergic, glutamatergic projections and so on. To be specific, the dopaminergic projections to the NAc mainly originate from the VTA ( Figure 1A ) ( Hadley et al, 2014 ; Lammel et al, 2014 ; Cooper et al, 2017 ), the serotonergic projections to the NAc mainly originate from the raphe nuclei (RN) ( Figure 1C ) ( Modell et al, 1989 ; Kiyasova et al, 2011 ; Alonso et al, 2013 ; Kim et al, 2019 ), histaminergic projections to the NAc mainly originate from the tuberomammillary nucleus (TMN) ( Figure 1E ) ( Zhang et al, 2020 ; Manz et al, 2021 ), cholinergic projections to the NAc mainly originate from the basal forebrain (BF) and pontomesencephalo-tegmental complex (PTC) ( Figure 1G ) ( Mark et al, 2011 ; Laurent et al, 2014 ; Luchicchi et al, 2014 ; Gielow and Zaborszky, 2017 ), and glutamatergic projections to the NAc mainly originate from the broad cortex, hippocampus (CA) and basolateral amygdala (BLA) ( Figure 1I ) ( Walaas, 1981 ; Tarazi et al, 1998 ; Saul’skaya and Mikhailova, 2003 ; Zhu et al, 2022 ). Recently, some studies have revealed changes in the levels of these neurotransmitters and relevant receptors in OCD, and it is believed that the disturbances of these substances especially in the regions related to the cortico-striato-thalamico-cortical (CSTC) circuitry are normally considered as the basis of OCD ( Winslow and Insel, 1990 ; Fineberg et al, 2011 ; van Dijk et al, 2012 ; Haleem et al, 2014 ; Pittenger, 2015 ; Ade et al, 2016 ; Vlček et al, 2018 ; Zhan et al, 2020 ; Zai, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Potential therapeutic mechanism of deep brain stimulation of the nucleus accumbens in obsessive-compulsive disorder

Shi

Wang

Xiao

et al. 2023

Front. Cell. Neurosci.

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Deep brain stimulation (DBS) of the nucleus accumbens (NAc) (NAc-DBS) is an effective solution to refractory obsessive-compulsive disorder (OCD). However, evidence for the neurobiological mechanisms of OCD and the effect of NAc-DBS is still lacking. One hypothesis is that the electrophysiological activities in the NAc are modulated by DBS, and another hypothesis is that the activities of neurotransmitters in the NAc are influenced by DBS. To investigate these potential alterations, rats with quinpirole (QNP)- induced OCD were treated with DBS of the core part of NAc. Then, extracellular spikes (SPK) and local field potentials (LFP) in the NAc were recorded, and the levels of relevant neurotransmitters and related proteins were measured. Analysis of SPK revealed that the firing rate was decreased and the firing pattern was changed after NAc-DBS, and analysis of LFP showed that overall power spectral density (PSD) levels were reduced after NAc-DBS. Additionally, we found that the relative powers of the theta band, alpha band and beta band were increased in OCD status, while the relative powers of the delta band and gamma band were decreased. This pathological pattern of power distribution was reformed by NAc-DBS. Furthermore, we found that the local levels of monoamines [dopamine (DA) and serotonin (5-HT)] and amino acids [glutamate (Glu) and gamma-aminobutyric acid (GABA)] in the NAc were increased in OCD status, and that the expression of the two types of DA receptors in the NAc exhibited an opposite change. These abnormalities could be reversed by NAc-DBS. These findings provide a more comprehensive understanding about the function of the NAc in the pathophysiology of OCD and provide more detailed evidence for the potential effect of NAc-DBS.

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“…For now, selective-serotonin-reuptake inhibitors (SSRI's) are the first-line therapy for OCD [20]. These are also used to treat depression and anxiety.…”

Section: Introductionmentioning

confidence: 99%

Smo-Shh Agonist Purmorphamine Prevents Neurobehavioral and Neurochemical Defects in 8-OH-DPAT-Induced Experimental Model of Obsessive-Compulsive Disorder

et al. 2022

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Obsessive-compulsive disorder is a mental disorder characterized by repetitive, unwanted thoughts and behavior due to abnormal neuronal corticostriatal-thalamocortical pathway and other neurochemical changes. Purmorphamine is a smoothened-sonic-hedgehog agonist that has a protective effect against many neurological diseases due to its role in maintaining functional connectivity during CNS development and its anti-inflammatory and antioxidant properties. As part of our current research, we investigated the neuroprotective effects of PUR against behavioral and neurochemical changes in 8-hydroxy-2-(di-n-propylamino)-tetralin-induced obsessive-compulsive disorder in rats. Additionally, the effect of PUR was compared with the standard drug for OCD, i.e., fluvoxamine. The intra-dorsal raphe-nucleus injection of 8-OH-DPAT in rats for seven days significantly showed OCD-like repetitive and compulsive behavior along with increased oxidative stress, inflammation, apoptosis, as well as neurotransmitter imbalance. These alterations were dose-dependently attenuated by long-term purmorphamine treatment at 5 mg/kg and 10 mg/kg i.p. In this study, we assessed the level of various neurochemical parameters in different biological samples, including brain homogenate, blood plasma, and CSF, to check the drug’s effect centrally and peripherally. These effects were comparable to the standard oral treatment withfluvoxamine at 10 mg/kg. However, when fluvoxamine was given in combination with purmorphamine, there was a more significant restoration of these alterations than the individualtreatmentswithfluvoxamine and purmorphamine. All the above findings demonstrate that the neuroprotective effect of purmorphamine in OCD can be strong evidence for developing a new therapeutic target for treating and managing OCD.

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Functional connectivity of the raphe nucleus as a predictor of the response to selective serotonin reuptake inhibitors in obsessive-compulsive disorder

Cited by 27 publications

References 50 publications

Triple-Network Dysconnectivity in Patients With First-Episode Psychosis and Individuals at Clinical High Risk for Psychosis

Triple-Network Dysconnectivity in Patients With First-Episode Psychosis and Individuals at Clinical High Risk for Psychosis

Potential therapeutic mechanism of deep brain stimulation of the nucleus accumbens in obsessive-compulsive disorder

Smo-Shh Agonist Purmorphamine Prevents Neurobehavioral and Neurochemical Defects in 8-OH-DPAT-Induced Experimental Model of Obsessive-Compulsive Disorder

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