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Oral ketamine effects on dynamics of functional network connectivity in patients treated for chronic suicidality.

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Title: Oral ketamine effects on dynamics of functional network connectivity in patients treated for chronic suicidality.
Authors: Shan, Zack Y. (AUTHOR), Can, Adem T. (AUTHOR), Mohamed, Abdalla Z. (AUTHOR), Dutton, Megan (AUTHOR), Hermens, Daniel F. (AUTHOR), Calhoun, Vince D. (AUTHOR), Williams, Leanne M. (AUTHOR), Bennett, Maxwell (AUTHOR), Lagopoulos, Jim (AUTHOR)
Source: European Archives of Psychiatry & Clinical Neuroscience. Aug2025, Vol. 275 Issue 5, p1347-1357. 11p.
Subjects: Ketamine, Suicidal ideation, Neural pathways, Suicide prevention, Suicide risk assessment, Cognitive flexibility, Functional connectivity
Abstract: The underlying brain mechanisms of ketamine in treating chronic suicidality and the characteristics of patients who will benefit from ketamine treatment remain unclear. To address these gaps, we investigated temporal variations of brain functional synchronisation in patients with suicidality treated with ketamine in a 6-week open-label oral ketamine trial. The trial's primary endpoint was the Beck Scale for Suicide Ideation (BSS). Patients who experienced greater than 50% improvement in BSS scores or had a BSS score less than 6 at the post-treatment and follow-up (10 weeks) visits were considered responders and persistent responders, respectively. The reoccurring and transient connectivity pattern (termed brain state) from 29 patients (45.6 years ± 14.5, 15 females) were investigated by dynamic functional connectivity analysis of resting-state functional MRI at the baseline, post-treatment, and follow-up. Post-treatment patients showed significantly more (FDR-Q = 0.03) transitions among whole brain states than at baseline. We also observed increased dwelling time (FDR-Q = 0.04) and frequency (FDR-Q = 0.04) of highly synchronised brain state at follow-up, which were significantly correlated with BSS scores (both FDR-Q = 0.008). At baseline, persistent responders had higher fractions (FDR-Q = 0.03, Cohen's d = 1.39) of a cognitive control network state with high connectivities than non-responders. These findings suggested that ketamine enhanced brain changes among different synchronisation patterns and enabled high synchronisation patterns in the long term, providing a possible biological pathway for its suicide-prevention effects. Moreover, differences in cognitive control states at baseline may be used for precise ketamine treatment planning. [ABSTRACT FROM AUTHOR]
Copyright of European Archives of Psychiatry & Clinical Neuroscience is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Oral ketamine effects on dynamics of functional network connectivity in patients treated for chronic suicidality.
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  Data: <searchLink fieldCode="AR" term="%22Shan%2C+Zack+Y%2E%22">Shan, Zack Y.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Can%2C+Adem+T%2E%22">Can, Adem T.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Mohamed%2C+Abdalla+Z%2E%22">Mohamed, Abdalla Z.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Dutton%2C+Megan%22">Dutton, Megan</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Hermens%2C+Daniel+F%2E%22">Hermens, Daniel F.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Calhoun%2C+Vince+D%2E%22">Calhoun, Vince D.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Williams%2C+Leanne+M%2E%22">Williams, Leanne M.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Bennett%2C+Maxwell%22">Bennett, Maxwell</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Lagopoulos%2C+Jim%22">Lagopoulos, Jim</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22European+Archives+of+Psychiatry+%26+Clinical+Neuroscience%22">European Archives of Psychiatry & Clinical Neuroscience</searchLink>. Aug2025, Vol. 275 Issue 5, p1347-1357. 11p.
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  Data: <searchLink fieldCode="DE" term="%22Ketamine%22">Ketamine</searchLink><br /><searchLink fieldCode="DE" term="%22Suicidal+ideation%22">Suicidal ideation</searchLink><br /><searchLink fieldCode="DE" term="%22Neural+pathways%22">Neural pathways</searchLink><br /><searchLink fieldCode="DE" term="%22Suicide+prevention%22">Suicide prevention</searchLink><br /><searchLink fieldCode="DE" term="%22Suicide+risk+assessment%22">Suicide risk assessment</searchLink><br /><searchLink fieldCode="DE" term="%22Cognitive+flexibility%22">Cognitive flexibility</searchLink><br /><searchLink fieldCode="DE" term="%22Functional+connectivity%22">Functional connectivity</searchLink>
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  Data: The underlying brain mechanisms of ketamine in treating chronic suicidality and the characteristics of patients who will benefit from ketamine treatment remain unclear. To address these gaps, we investigated temporal variations of brain functional synchronisation in patients with suicidality treated with ketamine in a 6-week open-label oral ketamine trial. The trial's primary endpoint was the Beck Scale for Suicide Ideation (BSS). Patients who experienced greater than 50% improvement in BSS scores or had a BSS score less than 6 at the post-treatment and follow-up (10 weeks) visits were considered responders and persistent responders, respectively. The reoccurring and transient connectivity pattern (termed brain state) from 29 patients (45.6 years ± 14.5, 15 females) were investigated by dynamic functional connectivity analysis of resting-state functional MRI at the baseline, post-treatment, and follow-up. Post-treatment patients showed significantly more (FDR-Q = 0.03) transitions among whole brain states than at baseline. We also observed increased dwelling time (FDR-Q = 0.04) and frequency (FDR-Q = 0.04) of highly synchronised brain state at follow-up, which were significantly correlated with BSS scores (both FDR-Q = 0.008). At baseline, persistent responders had higher fractions (FDR-Q = 0.03, Cohen's d = 1.39) of a cognitive control network state with high connectivities than non-responders. These findings suggested that ketamine enhanced brain changes among different synchronisation patterns and enabled high synchronisation patterns in the long term, providing a possible biological pathway for its suicide-prevention effects. Moreover, differences in cognitive control states at baseline may be used for precise ketamine treatment planning. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of European Archives of Psychiatry & Clinical Neuroscience is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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              Text: Aug2025
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