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Targeting suicidal ideation in major depressive disorder with MRI-navigated Stanford accelerated intelligent neuromodulation therapy.

ABSTRACT: High suicide risk represents a serious problem in patients with major depressive disorder (MDD), yet treatment options that could safely and rapidly ameliorate suicidal ideation remain elusive. Here, we tested the feasibility and preliminary efficacy of the Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) in reducing suicidal ideation in patients with MDD. Thirty-two MDD patients with moderate to severe suicidal ideation participated in the current study. Suicidal ideation and depression symptoms were assessed before and after 5 days of open-label SAINT. The neural pathways supporting rapid-acting antidepressant and suicide prevention effects were identified with dynamic causal modelling based on resting-state functional magnetic resonance imaging. We found that 5 days of SAINT effectively alleviated suicidal ideation in patients with MDD with a high response rate of 65.63%. Moreover, the response rates achieved 78.13% and 90.63% with 2 weeks and 4 weeks after SAINT, respectively. In addition, we found that the suicide prevention effects of SAINT were associated with the effective connectivity involving the insula and hippocampus, while the antidepressant effects were related to connections of the subgenual anterior cingulate cortex (sgACC). These results show that SAINT is a rapid-acting and effective way to reduce suicidal ideation. Our findings further suggest that distinct neural mechanisms may contribute to the rapid-acting effects on the relief of suicidal ideation and depression, respectively.

SUBMITTER: Li B

PROVIDER: S-EPMC10781692 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Targeting suicidal ideation in major depressive disorder with MRI-navigated Stanford accelerated intelligent neuromodulation therapy.

Li Baojuan B Zhao Na N Tang Nailong N Friston Karl J KJ Zhai Wensheng W Wu Di D Liu Junchang J Chen Yihuan Y Min Yan Y Qiao Yuting Y Liu Wenming W Shu Wanqing W Liu Min M Zhou Ping P Guo Li L Qi Shun S Cui Long-Biao LB Wang Huaning H

Translational psychiatry 20240110 1

High suicide risk represents a serious problem in patients with major depressive disorder (MDD), yet treatment options that could safely and rapidly ameliorate suicidal ideation remain elusive. Here, we tested the feasibility and preliminary efficacy of the Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) in reducing suicidal ideation in patients with MDD. Thirty-two MDD patients with moderate to severe suicidal ideation participated in the current study. Suicidal ideation and de ...[more]

PMID: 38199983

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Project description:BackgroundSuicide is a leading cause of death in adolescents worldwide. Previous research findings suggest that suicidal adolescents with depression have pathophysiological dorsolateral prefrontal cortex (DLPFC) deficits in γ-aminobutyric acid neurotransmission. Interventions with transcranial magnetic stimulation (TMS) directly address these underlying pathophysiological deficits in the prefrontal cortex. Theta burst stimulation (TBS) is newer dosing approach for TMS. Accelerated TBS (aTBS) involves administering multiple sessions of TMS daily as this dosing may be more efficient, tolerable, and rapid acting than standard TMS.Materials and methodsThis is a randomized, double-blind, sham-controlled trial of sequential bilateral aTBS in adolescents with major depressive disorder (MDD) and suicidal ideation. Three sessions are administered daily for 10 days. During each session, continuous TBS is administered first to the right DPFC, in which 1,800 pulses are delivered continuously over 120 seconds. Then intermittent TBS is applied to the left DPFC, in which 1,800 pulses are delivered in 2-second bursts and repeated every 10 seconds for 570 seconds. The TBS parameters were adopted from prior research, with 3-pulse, 50-Hz bursts given every 200 ms (at 5 Hz) with an intensity of 80% active motor threshold. The comparison group will receive 3 daily sessions of bilateral sham TBS treatment for 10 days. All participants will receive the standard of care for patients with depression and suicidal ideation including daily psychotherapeutic skill sessions. Long-interval intracortical inhibition (LICI) biomarkers will be measured before and after treatment. Exploratory measures will be collected with TMS and electroencephalography for biomarker development.DiscussionThis is the first known randomized controlled trial to examine the efficacy of sequential bilateral aTBS for treating suicidal ideation in adolescents with MDD. Results from this study will also provide opportunities to further understand the neurophysiological and molecular mechanisms of suicidal ideation in adolescents.Trial registrationInvestigational device exemption (IDE) Number: G200220, ClinicalTrials.gov (ID: NCT04701840). Registered August 6, 2020. https://clinicaltrials.gov/ct2/show/NCT04502758?term=NCT04701840&draw=2&rank=1.

Project description:Major depressive disorder (MDD) and suicidal behavior have been associated with structural and functional changes in the brain. However, little is known regarding alterations of brain networks in MDD patients with suicidal ideation. We investigated whether or not MDD patients with suicidal ideation have different topological organizations of white matter networks compared with MDD patients without suicidal ideation. Participants consisted of 24 patients with MDD and suicidal ideation, 25 age- and gender-matched MDD patients without suicidal ideation and 31 healthy subjects. A network-based statistics (NBS) and a graph theoretical analysis were performed to assess differences in the inter-regional connectivity. Diffusion tensor imaging (DTI) was performed to assess topological changes according to suicidal ideation in MDD patients. The Scale for Suicide Ideation (SSI) and the Korean version of the Barrett Impulsiveness Scale (BIS) were used to assess the severity of suicidal ideation and impulsivity, respectively. Reduced structural connectivity in a characterized subnetwork was found in patients with MDD and suicidal ideation by utilizing NBS analysis. The subnetwork included the regions of the frontosubcortical circuits and the regions involved in executive function in the left hemisphere (rostral middle frontal, pallidum, superior parietal, frontal pole, caudate, putamen and thalamus). The graph theoretical analysis demonstrated that network measures of the left rostral middle frontal had a significant positive correlation with severity of SSI (r=0.59, P=0.02) and BIS (r=0.59, P=0.01). The total edge strength that was significantly associated with suicidal ideation did not differ between MDD patients without suicidal ideation and healthy subjects. Our findings suggest that the reduced frontosubcortical circuit of structural connectivity, which includes regions associated with executive function and impulsivity, appears to have a role in the emergence of suicidal ideation in MDD patients.

Project description:ObjectiveSuicidal thoughts and behaviors (STBs) in children are an escalating public health concern. This study focused on 1 understudied candidate risk factor, namely, preschool-onset major depressive disorder (PO-MDD), as a predictor of persistent and emerging STBs from early childhood into preadolescence.MethodParticipants were 137 children 8 to 12 years of age who met criteria for PO-MDD when they were 3 to 6 years of age, and a nondepressed sample of 53 age-, income-, and sex-matched peers. STBs were reported by caregivers (preschool, preadolescence) and children (preadolescence) using age-appropriate diagnostic interviews.ResultsBy preadolescence, children who had PO-MDD were 7.38 times more likely than their peers to have endorsed STBs after early childhood (p < .001; 67.9% vs 22.6%), including 6.71 times more likely to have engaged in suicide behaviors/attempts (p = .012; 21.9% vs 3.8%); they were also 8.98 times more likely to have endorsed STBs over the prior month (p = .005; 26.3% vs 3.8%). Similar findings emerged when limiting the PO-MDD group to children without preschool STBs, and when controlling for externalizing comorbidities, implicating PO-MDD as a unique diagnostic predictive risk factor. However, children who had PO-MDD with STBs were 3.46 times more likely than children who had PO-MDD without STBs to endorse later STBs (p = .018; 83.1% vs 54.2%), indicating substantial continuity of preschool STBs alongside strikingly high rates of emerging STBs into preadolescence.Plain language summaryThis longitudinal study explores preschool onset major depressive disorder (PO-MDD) as a predictor of having suicidal thoughts or attempting suicide by age 12. 137 children aged 8 to 12 years who met criteria for PO-MDD when they were 3 to 6 years of age and 53 non-depressed peers were included in the study. The study found that preadolescents who had experienced preschool-onset depression were 6.14 times more likely to experience active suicidal thoughts and 8.03 times more likely to have made a suicide attempt by age 12 when compared to preadolescents who did not experience preschool depression. Results suggest that children with preschool-onset depression would likely benefit from increased suicide screening, proactive safety planning and early interventions.ConclusionPO-MDD is a strong risk factor for the emergence and persistence of STBs into preadolescence. Children with PO-MDD would likely benefit from increased suicide screening, proactive safety planning, and early interventions.

Dataset Information

Targeting suicidal ideation in major depressive disorder with MRI-navigated Stanford accelerated intelligent neuromodulation therapy.

Publications

Targeting suicidal ideation in major depressive disorder with MRI-navigated Stanford accelerated intelligent neuromodulation therapy.

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