Functional connectivity of the amygdala subregions and the antidepressant effects of repeated ketamine infusions in major depressive disorder.

BACKGROUND: Amygdala subregion-based network dysfunction has been determined to be centrally implicated in major depressive disorder (MDD). Little is known about whether ketamine modulates amygdala subarea-related networks. We aimed to investigate the relationships between changes in the resting-state functional connectivity (RSFC) of amygdala subregions and ketamine treatment and to identify important neuroimaging predictors of treatment outcomes. METHODS: Thirty-nine MDD patients received six doses of ketamine (0.5 mg/kg). Depressive symptoms were assessed, and magnetic resonance imaging (MRI) scans were performed before and after treatment. Forty-five healthy controls underwent one MRI scan. Seed-to-voxel RSFC analyses were performed on the amygdala subregions, including the centromedial amygdala (CMA), laterobasal amygdala (LBA), and superficial amygdala subregions. RESULTS: Abnormal RSFC between the left LBA and the left precuneus in MDD patients is related to the therapeutic efficacy of ketamine. There were significant differences in changes in bilateral CMA RSFC with the left orbital part superior frontal gyrus and in changes in the left LBA with the right middle frontal gyrus between responders and nonresponders following ketamine treatment. Moreover, there was a difference in the RSFC of left LBA and the right superior temporal gyrus/middle temporal gyrus (STG/MTG) between responders and nonresponders at baseline, which could predict the antidepressant effect of ketamine on Day 13. CONCLUSIONS: The mechanism by which ketamine improves depressive symptoms may be related to its regulation of RSFC in the amygdala subregion. The RSFC between the left LBA and right STG/MTG may predict the response to the antidepressant effect of ketamine.

Efficacy and safety of intermittent theta burst stimulation on adolescents and young adults with major depressive disorder: A randomized, double blinded, controlled trial.

BACKGROUND: Intermittent theta burst stimulation (iTBS) is a newer form of Repetitive Transcranial Magnetic Stimulation (rTMS) for depression. However, its efficacy and safety in adolescents and young adults with major depressive disorder (AYA-MDD) have not been well studied, especially when applied with a strategy that combines neuronavigation targeting and accelerated iTBS. METHODS: In this study, ninety patients were randomly assigned to twice-daily (two 600-pulse sessions spaced out by 10 min, n = 31), once-daily (one 600-pulse session, n = 29) or sham iTBS (no pulses, n = 30) groups for 10 treatment days. The primary outcome measure was the change in depression scores on the Hamilton Rating Scale for Depression (HAMD-17). Other clinical symptoms, such as anxiety, were also evaluated. RESULTS: Linear mixed model analysis found that scores on the HAMD-17 and its factors improved in all three groups, but these improvements did not significantly differ among groups. Other clinical symptoms such as anxiety also improved. Response and remission rates were relatively low and did not differ among groups at any time point. The most common adverse event was headache, and the proportion of participants who reported headache in the twice-daily and once-daily groups was significantly higher than that in the sham group. CONCLUSIONS: The current results indicated that twice-daily and once-daily iTBS under neuronavigation are safe and well tolerated in AYA-MDD, but the overall efficacy was not superior to that of sham treatment. We speculated several possible reasons such as the high placebo response of the young population, inadequate iTBS pulses and so on.

Short-term cognitive effects of repeated-dose esketamine in adolescents with major depressive disorder and suicidal ideation: a randomized controlled trial.

BACKGROUND: Ketamine and its enantiomer have rapid and robust effects on depressive symptom and suicidal ideation. Little is known about their cognitive effects in adolescents. We aimed to evaluate the short-term effect of esketamine on cognition in adolescents with major depressive disorder (MDD) and suicidal ideation. METHOD: In this randomized-controlled trial, 51 participants aged 13-18 with MDD and suicidal ideation received three intravenous infusions of either esketamine (0.25 mg/kg) or midazolam (0.02 mg/kg). Four dimensions of the MATRICS Consensus Cognitive Battery (MCCB), including processing speed, working memory, verbal learning and visual learning, were assessed at Days 0, 6 and 12. RESULTS: In the linear mixed model, a significant time main effect (F = 12.803, P < 0.001), drug main effect (F = 6.607, P = 0.013), and interaction effect (F = 3.315, P = 0.041) was found in processing speed. Other dimensions including working memory and verbal learning showed significant time main effect (all P < 0.05), but no significant drug or interaction effect (all P > 0.05). Esketamine group showed improvement in processing speed from baseline to Days 6 and 12, and working memory from baseline to Day 12 (all P < 0.05). The generalized estimation equation showed no significant association between baseline cognition and antidepressant or antisuicidal effect (both P > 0.05). CONCLUSIONS: The present study suggested that three-dose subanesthetic esketamine infusions did not harm cognition among adolescents with MDD and suicidal ideation. Instead, esketamine may be associated with improvement in processing speed. TRIAL REGISTRATION: This trial was registered in the Chinese Clinical Trials Registry ( http://www.chictr.org.cn , ChiCTR2000041232).

Alterations of functional connectivity in young people with depression mediate the relationship between sleep quality and cognitive function.

BACKGROUND: Sleep disturbances is common in young people with depression, and poor sleep quality affects the ability to learn. In this study, we examined possible resting-state functional connectivity abnormalities between regions of interest, and clarified the relationship with depressive symptoms, sleep quality, and cognitive function. METHODS: Resting-state functional magnetic resonance imaging (fMRI) was collected on 42 healthy controls (HCs), 82 youth depressive patients (44 without sleep disturbances (NSD), and 38 with sleep disturbances (SD)). Regions of interest were defined by using Brainnetome Atlas. Functional connectivity was calculated, and its associations with depressive symptoms, sleep quality, and cognitive function were examined using correlation analysis and mediation analysis. RESULTS: The left and right caudal of cingulate gyrus, tongue and larynx region of postcentral gyrus were significant brain regions in NSD versus SD. The average functional connectivity between these regions was associated with poor sleep quality (r = 0.368, p = 0.001) and worse working memory (r = -0.256, p = 0.023) and mediated the relationship between sleep quality and working memory (c = -0.738, c' = -0.500). LIMITATION: Data consistency in this study was not good enough. This study did not monitor sleep rhythms to provide objective sleep-related data. CONCLUSION: The functional connectivity between the left and right caudal of cingulate gyrus with tongue and larynx region of postcentral gyrus may be the neural mechanism by which sleep disturbances affect working memory. This provides an intervention target for clinically improving cognitive function in young people with depression.

Efficacy of repeated intravenous esketamine in adolescents with anxious versus non-anxious depression.

Background: Patients with anxious major depressive disorder (MDD) are more likely to have poorer outcomes than those with non-anxious MDD. However, the effect of esketamine on adolescents with anxious versus non-anxious MDD has remained unknown. Aims: We compared the efficacy of esketamine in adolescents with MDD and suicidal ideation, both anxious and non-anxious. Methods: Fifty-four adolescents with anxious (n=33) and non-anxious (n=21) MDD received three infusions of esketamine 0.25 mg/kg or active-placebo (midazolam 0.045 mg/kg) over 5 days, with routine inpatient care and treatment. Suicidal ideation and depressive symptoms were assessed using the Columbia Suicide Severity Rating Scale and the Montgomery-Åsberg Depression Rating Scale. Multiple-sample proportional tests were used to compare the differences between groups on treatment outcomes 24 hours after the final infusion (day 6, primacy efficacy endpoint) and throughout the 4-week post-treatment (days 12, 19 and 33). Results: In subjects who received esketamine, a greater number of patients in the non-anxious group than the anxious group achieved antisuicidal remission on day 6 (72.7% vs 18.8%, p=0.015) and day 12 (90.9% vs 43.8%, p=0.013), and the non-anxious group had a higher antidepressant remission rate compared with the anxious group on day 33 (72.7% vs 26.7%, p=0.045). No significant differences in treatment outcomes were observed between the anxious and non-anxious groups at other time points. Conclusions: Three infusions of esketamine as an adjunct to routine inpatient care and treatment had a greater immediate post-treatment antisuicidal effect in adolescents with non-anxious MDD than in those with anxious MDD; however, this benefit was temporary and was not maintained over time. Trial registration number: ChiCTR2000041232.

Effect of Repeated Intravenous Esketamine on Adolescents With Major Depressive Disorder and Suicidal Ideation: A Randomized Active-Placebo-Controlled Trial.

OBJECTIVE: Suicide is a major cause of death in adolescents with limited treatment options. Ketamine and its enantiomers have shown rapid anti-suicidal effects in adults with major depressive disorder (MDD), but their efficacy in adolescents is unknown. We conducted an active, placebo-controlled trial to determine the safety and efficacy of intravenous esketamine in this population. METHOD: A total of 54 adolescents (aged 13-18 years) with MDD and suicidal ideation were included from an inpatient setting and randomly assigned (1:1) to receive 3 infusions of esketamine (0.25 mg/kg) or midazolam (0.02mg/kg) over 5 days, with routine inpatient care and treatment. Changes from baseline to 24 hours after the final infusion (day 6) in the scores of the Columbia Suicide Severity Rating Scale (C-SSRS) Ideation and Intensity (primary outcome) and the Montgomery-Åsberg Depression Rating Scale (MADRS, key secondary outcome) were analyzed using linear mixed models. In addition, the 4-week clinical treatment response was a key secondary outcome. RESULTS: The mean changes in C-SSRS Ideation and Intensity scores from baseline to day 6 were significantly greater in the esketamine group than in the midazolam group (Ideation, -2.6 [SD = 2.0] vs -1.7 [SD = 2.2], p = .007; Intensity, -10.6 [SD = 8.4] vs -5.0 [SD = 7.4], p = .002), and the changes in MADRS scores from baseline to day 6 were significantly greater in the esketamine group than in the midazolam group (-15.3 [SD = 11.2] vs -8.8 [SD = 9.4], p = .004). The rates of anti-suicidal and antidepressant responses at 4 weeks posttreatment were 69.2% and 61.5% after esketamine, and were 52.5% and 52.5% after midazolam, respectively. The most common adverse events in the esketamine group were nausea, dissociation, dry mouth, sedation, headache, and dizziness. CONCLUSION: These preliminary findings indicate that 3-dose intravenous esketamine, added to routine inpatient care and treatment, was an effective and well-tolerated therapy for treating adolescents with MDD and suicidal ideation. CLINICAL TRIAL REGISTRATION INFORMATION: The efficacy and safety of esketamine combined with oral antidepressants in the treatment of major depressive disorder with suicidal ideation. http://www.chictr.org.cn. Chinese Clinical Trial Registry: ChiCTR2000041232. DIVERSITY & INCLUSION STATEMENT: We worked to ensure that the study questionnaires were prepared in an inclusive way. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. We actively worked to promote sex and gender balance in our author group.

Pain mediates the improvement of social functions of repeated intravenous ketamine in patients with unipolar and bipolar depression.

OBJECTIVE: Previous research has shown that ketamine can improve social functions. In addition, evidence also suggests that ketamine can alleviate pain. Herein, we propose that ketamine-induced improvements in pain and depression are partially mediated by a reduction in pain. We aimed to determine whether improvements in pain-mediated changes in psychological function were associated with ketamine treatment. METHOD: This trial included unipolar or bipolar patients (n = 103) who received 6 intravenous infusions (0.5 mg/kg) of ketamine over 2 weeks. The severity of current depressive symptoms and social function were evaluated by the Montgomery-Åsberg Depression Scale (MADRS), Self-Rating Depression Scale (SDS) and Global Assessment Function (GAF), respectively, at baseline and on day 13 and day 26. At the same time points, the three dimensions of pain, including the sensory index, affective index and present pain intensity (PPI), were measured by the Simple McGill Pain Scale (SF-MPQ). RESULTS: The mixed model results showed that ketamine plays an important role in improving the psychosocial functioning of patients. There was a significant decrease from baseline to the day 13 and day 26, indicating that the pain index of the patient improved significantly. Mediation analysis showed that for SDS score (coef = -5.171, 95 % CI[-6.317, -4.025]) and GAF score (coef = 1.021, 95 % CI[0.848, 1.194]), the overall effect of ketamine was observable. The overall indirect and direct effects of ketamine on social functioning were significant (SDS: direct: coef = -1949 to -2114; total indirect: from 0.594 to 0.664; GAF: from 0.399 to 0.427; total indirect: coef = 0.593 to 0.664). The MADRS total score and emotional index were important mediators of the association between ketamine treatment and improvements in subjective and objective social functioning. CONCLUSION: Depressive symptom severity and the affective index of pain partially mediated improvements in social function after six repeated ketamine treatments among patients with bipolar or unipolar depressive disorder.

Functional connectivity of the amygdala and the antidepressant and antisuicidal effects of repeated ketamine infusions in major depressive disorder.

Background: Dysfunction of the amygdala is the core pathogenesis of major depressive disorder (MDD). However, it remains unclear whether ketamine treatment could modulate characteristics of amygdala-related networks. We aimed to explore the relationship between changes in the resting-state functional connectivity (RSFC) of the amygdala and the treatment of ketamine in MDD patients and to identify important neuroimaging predictors of treatment outcome. Methods: Thirty-nine MDD patients received six subanesthetic dose infusions of ketamine. Depressive and suicidal symptoms were assessed and magnetic resonance imaging (MRI) scans were performed before and after six ketamine infusions. Forty-five healthy controls also underwent once MRI scans. Seed-based RSFC analyses were performed, focusing on the bilateral amygdala. Results: After ketamine treatment, the RSFC between the left amygdala (LA) and the left medial superior frontal gyrus (mSFG) of MDD patients enhanced significantly, and this change was positively correlated with the reduction in depressive symptoms (r = 0.40, p = 0.012). The combination baseline RSFC of LA - right putamen and right amygdala (RA) - right putamen was related to the antidepressant and antisuicidal effects of ketamine. The combination baseline RSFC of LA - right putamen and RA - right putamen could predict the ineffective antidepressant (AUC = 0.739, p = 0.011) and antisuicidal effects of ketamine (AUC = 0.827, p = 0.001). Conclusion: Ketamine can regulate the relevant circuits of amygdala and mSFG, and the baseline RSFC between bilateral amygdala and right putamen may be a predictor of the response of ketamine's antidepressant and antisuicidal treatment. Clinical trial registration: https://www.chictr.org.cn/showproj.aspx?proj=20875, identifier ChiCTR-OOC-17012239.

Ketamine-induced hippocampal functional connectivity alterations associated with clinical remission in major depression.

OBJECTIVE: Hippocampal functional connectivity (FC) alterations, which may happen following ketamine treatment, play a key role in major depression remission. This study aims to investigate the resting-state FC changes of the hippocampus associated with clinical remission after repeated ketamine infusions. METHODS: Forty-four major depressive patients received six intravenous ketamine (0.5 mg/kg) infusions in 12 days. The FC change of the hippocampus subregions following ketamine treatment was compared between remitters (MADRS score ≤ 10 post-treatment) and nonremitters. We also investigated whether baseline hippocampus FC predicted the antidepressant efficiency of ketamine using Receiver Operating Characteristic Curve analyses. RESULTS: Thirty-nine patients were included in the analysis. There were significant differences in change of left rostral hippocampus FC with the right angular gyrus (the key node of the default mode network, DMN), left inferior parietal cortex and the right superior parietal cortex (parts of the dorsal attention network, dAN) between remitters and nonremitters following ketamine treatment. Specifically, while the remitters showed significantly less negative hippocampus FC than the nonremitters at baseline, the FC significantly decreased in remitters but increased in nonremitters after ketamine injections. Moreover, baseline hippocampus FC with the above three regions predicted the antidepressant effect of ketamine, with the highest predictive strength identified in the hippocampus-right angular gyrus FC (Area-Under-Curve = 0.8179, p < 0.05). CONCLUSION: Ketamine treat depression by modulating the left rostral hippocampus resting-state FC with the DMN and dAN. The FC between the hippocampus and parts of the DMN and dAN may show promising potential in predicting remission after ketamine treatment in MDD.

Abnormal amygdala functional connectivity in MDD patients with insomnia complaints.

BACKGROUND: Insomnia is one of the major symptom relevant factors in major depressive disorder (MDD), but the neurological mechanisms underlying the multiple effect between insomnia and depression have not been well interpreted. This study aimed at exploring the potential mechanisms between insomnia and depression based on amygdala-based resting-state functional connectivity (RSFC). METHODS: In total 56 MDD patients with low insomnia (MDD-LI) patients, 46 MDD patients with high insomnia (MDD-HI) patients, and 57 healthy controls (HCs) were employed and underwent a resting-state functional magnetic resonance imaging (fMRI) scan. ANOVA test was performed on RSFC value for three groups. Correlation analysis was conducted to evaluate the relationship between abnormal RSFC values and clinical features. RESULTS: We found that MDD-HI mainly showed increased RSFC in (bilateral superior temporal gyrus (STG), and decreased RSFC in left supplementary motor area (SMA) and bilateral postcentral gyrus (PoCG) compared with MDD-LI. Correlation analysis indicated that RSFC of the bilateral amygdala with STG were positively associated with the sleep disturbance score and adjust HAMD score. CONCLUSION: Our findings suggest that RSFC in temporal lobe and other specifically activated regions may be associated with neural circuits involved with insomnia in MDD. These provide new evidence for understanding the potential mechanisms of major depression and insomnia from the perspective of functional connectivity.

The efficacy and safety of esketamine in the treatment of major depressive disorder with suicidal ideation: study protocol for a randomized controlled trial.

BACKGROUND: Major depressive disorder (MDD) is a high risk factor for suicide, with up to 20% of MDD patients attempting suicide during their lifetime. Current treatments for MDD are slow onset of action, low efficiency, and the inability to control suicidal behaviors quickly and effectively. Intravenous ketamine has been shown to have a rapid but transient antidepressant effect, but there is still lack evidence on the efficacy and safety of intravenous esketamine in reducing suicidal ideation and depressive symptoms in MDD patients with suicidal ideation. We designed a study to investigate the effect of short-term repeated intravenous infusion of esketamine three times in MDD patients with suicidal ideation. METHODS: This study features a randomized, double-blind, placebo-controlled trial (RCT) comparing short-term repeated intravenous infusions of esketamine with placebo as a supplement to conventional antidepressants with an intervention period of 6 days and one infusion every other day, followed by 4 weeks of follow-up. These methods support the examination of the efficacy, safety, tolerability, and mechanism of action of short-term repeated intravenous infusions of esketamine in MDD patients with suicidal ideation. DISCUSSION: This is the first RCT to explore the efficacy and safety of short-term repeated infusion of esketamine on suicidal ideation and depressive symptoms in MDD patients with suicidal ideation. If proven effective and tolerated, it will provide evidence for rapid and effective treatment of suicidal ideation and depressive symptoms in MDD individuals with suicidal ideation. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR2000041232 . Registered 22 December 2020.

The functional connectivity of the middle frontal cortex predicts ketamine's outcome in major depressive disorder.

Background: Ketamine, a robust antidepressant, has promising potential in the treatment of major depressive disorder (MDD). However, it does not work for all MDD patients, and the mechanism underlying its anti-depressive effects is unclear. Researchers have explored the mechanisms of ketamine action in MDD patients through MRI, a technique that measures brain activity intuitively. Notably, many MRI results were inconsistent because they selected different brain regions as seeds, particularly with respect to functional connectivity (FC) analysis. To eliminate the influence of prior seeds as much as possible, we used the significantly different results in degree centrality (DC) analysis as seeds to explore the FC changes in MDD patients to identify an imaging biomarker of ketamine's effect. Methods: Forty-four MDD patients and 45 healthy controls (HCs) were included in the study. Patients, aged 18-65, received six intravenous ketamine injections over 12 days. Depressive symptoms were estimated and MRI scans were performed at baseline and the day after the sixth infusion. We estimated FC differences between responders, non-responders and HCs using the region that showed significant differences between responders and non-responders in DC analysis as the seed. The correlation between the MADRS changes and zFC values was performed, and the potential of zFC values to be a neuroimaging biomarker was explored using the receiver operating characteristic curve. Result: Compared with non-responders, responders had significantly decreased DC values in the right middle frontal gyrus (MFG). In the analysis of FC using the region that showed significant differences in DC as a seed, there was a significant difference in the region of the right supplementary motor area (SMA) among responders, non-responders, and HCs. This region also overlapped with the bilateral median cingulate gyrus. In post hoc analysis, responders had higher FC than non-responders and HCs, and non-responders had lower FC than HCs. Importantly, the FC between the MFG and SMA (overlapping bilateral median cingulate gyrus) was correlated with the improvement of symptoms, which was estimated by the Mongomery-Asberg Depression Scale (MADRS). FC has the potential to be an imaging biomarker that can predict the ketamine effect in MDD patients according to the receiver operating characteristic curve analysis. Conclusion: Our results revealed that FC between the SMG and SMA and mACC was highly correlated with depressive symptoms and has the potential to be a neuroimaging biomarker to predict the effect of ketamine in MDD.

Baseline patterns of resting functional connectivity within posterior default-mode intranetwork associated with remission to antidepressants in major depressive disorder.

BACKGROUND: The default mode network (DMN) is implicated in the pathophysiology of major depressive disorder (MDD), and functional connectivity (FC) involved in DMN is suggested to be associated with antidepressant remission. The goal of this study is to recognize relationships between FC within DMN and early amelioration in MDD patients and to further test the capacity of FC to predict early efficacy. METHODS: In total 66 MDD patients and 57 healthy controls were recruited for resting-state functional magnetic resonance imaging scans at baseline. After four weeks of treatment with Escitalopram or Venlafaxine, patients were divided into subgroups with remitters (R, n = 31) and non-remitters (NR, n = 35). Independent component analysis (ICA) was used to compare intranetwork functional connectivity (intra-FC) in DMN between the three groups. RESULTS: Relative to NR-MDD group and HCs, the R-MDD group showed significantly higher intra-FC in the right angular gyrus of DMN, and the intra-FC was positively correlated with the reduction ratio of the depressive symptom scores. The ROC curve analysis revealed that intra-FC exhibited a high diagnostic value for remission. CONCLUSION: These findings indicated that intra-FC related to the DMN is a prognostic marker that can potentially predict early remission of symptoms after antidepressant treatment.

Variability and concordance among indices of brain activity in major depressive disorder with suicidal ideation: A temporal dynamics resting-state fMRI analysis.

OBJECTIVE: The resting-state functional magnetic resonance imaging (rs-fMRI) have been used to explore functional abnormality of the brain in MDD patients with suicidal ideation (SI). However, few studies reported the variability and concordance of alterations of rs-fMRI indices in MDD with SI. In this study, we aimed to explore the variability and concordance of alterations of rs-fMRI indices in MDD with SI. METHODS: A sliding window analysis was performed among 36 MDD patients with SI, 66 MDD patients without SI (NSI), and 50 healthy controls (HCs). Furthermore, the correlation between voxel-wise concordance and cognitive function was examined in the SI group. RESULTS: The SI group had a lower dynamics degree centrality (dDC) value than the NSI group in left inferior occipital gyrus, and a lower voxel mirrored homotopic connectivity (dVMHC) value than the NSI group in the right and left inferior occipital gyrus. The mean values of volume wise concordance of HCs group shown higher than SI group and NSI group. SI group revealed decreased voxel-wise concordance in right cerebellum, left fusiform gyrus, left lingual gyrus, right middle temporal gyrus, left postcentral gyrus, and right supplementary motor area compared to NSI group. Moreover, the voxel-wise concordance of left middle occipital gyrus was negatively correlated with verbal learning and memory and working memory in the SI group. LIMITATION: This is a cross-sectional analysis, limiting causal inferences. CONCLUSIONS: The abnormal voxel-wise concordance of left middle occipital gyrus could be useful in understanding the pathophysiology of MDD patients with SI.

Aberrant Dynamic Functional Connectivity of Posterior Cingulate Cortex Subregions in Major Depressive Disorder With Suicidal Ideation.

Accumulating evidence indicates the presence of structural and functional abnormalities of the posterior cingulate cortex (PCC) in patients with major depressive disorder (MDD) with suicidal ideation (SI). Nevertheless, the subregional-level dynamic functional connectivity (dFC) of the PCC has not been investigated in MDD with SI. We therefore sought to investigate the presence of aberrant dFC variability in PCC subregions in MDD patients with SI. We analyzed resting-state functional magnetic resonance imaging (fMRI) data from 31 unmedicated MDD patients with SI (SI group), 56 unmedicated MDD patients without SI (NSI group), and 48 matched healthy control (HC) subjects. The sliding-window method was applied to characterize the whole-brain dFC of each PCC subregion [the ventral PCC (vPCC) and dorsal PCC (dPCC)]. In addition, we evaluated associations between clinical variables and the aberrant dFC variability of those brain regions showing significant between-group differences. Compared with HCS, the SI and the NSI groups exhibited higher dFC variability between the left dPCC and left fusiform gyrus and between the right vPCC and left inferior frontal gyrus (IFG). The SI group showed higher dFC variability between the left vPCC and left IFG than the NSI group. Furthermore, the dFC variability between the left vPCC and left IFG was positively correlated with Scale for Suicidal Ideation (SSI) score in patients with MDD (i.e., the SI and NSI groups). Our results indicate that aberrant dFC variability between the vPCC and IFG might provide a neural-network explanation for SI and may provide a potential target for future therapeutic interventions in MDD patients with SI.

Resting-state functional connectivity of the amygdala in major depressive disorder with suicidal ideation.

Suicide is a common issue among major depressive disorder (MDD) patients and suicidal ideation (SI) is the first step toward it. There are no definitive objective biomarkers of SI relative to MDD. In this study, a seed-based correlation analysis was performed among 36 MDD patients with SI, 66 MDD patients without SI (NSI), and 57 healthy controls (HCs) using amygdala resting-state functional connectivity (RSFC). Furthermore, the correlation between amygdala RSFC and clinical features was examined in the SI group. When compared to the NSI group, SI group exhibited increased RSFC between the left amygdala seed and left medial superior frontal gyrus (SFGmed) as well as left middle frontal gyrus (MFG). In turn, a decreased RSFC was observed between the left amygdala seed and the following brain regions including the left inferior parietal lobule (IPL), right precentral gyrus (PrCG), and left superior parietal lobule (SPL) in SI group compared to NSI group. Moreover, the SI group exhibited increased RSFC of the right amygdala with left middle temporal gyrus (MTG); In addition, the RSFC of the left amygdala with left MFG was negatively associated with learning and memory (VSM), speed of processing (SOP). The RSFC of the amygdala is distinct between MDD patients with SI and without SI. Our findings reveal the neurobiological characteristics of MDD with respect to SI and provide new clues regarding vulnerability to mental illness. It is necessary to carry out repeated and more longitudinal researches using multimodal approaches on SI in the future.

Long-term outcomes of repeated ketamine infusions in patients with unipolar and bipolar depression: A naturalistic follow-up study.

OBJECTIVE: Ketamine was proven to have short-term antidepressant effects. There is a paucity of studies focused on the long-term outcomes of repeated infusions of ketamine. This study aimed to examine the long-term outcomes of repeated ketamine infusions in patients with unipolar and bipolar depression METHODS: One hundred and eight patients with unipolar and bipolar depression completed the repeated treatment phase (administered ketamine three times weekly over a 12-day) and entered a 9-month naturalistic follow-up phase. Assessments were obtained at week 2, month 6, and month 9 after the repeated treatment phase. The Patient Health Questionnaire-9 (PHQ-9) Scale and the Global Assessment of Functioning (GAF) Scale were used to assess depressive symptoms and global functional status, respectively. RESULTS: Seventy-one (65.7%) of patients completed the 9-month follow-up. On month 9, the response and remission rate were 80.3% and 78.9%, respectively. Among 56 patients who achieved response after the repeated treatment phase, 26 (46.4%) of patients sustained response during 9-month follow-up and their GAF score remained over 70. Sixteen patients relapsed during the 9-month follow-up and 14 (85.7%) of the relapse occurred during the first 2-week follow-up. LIMITATION: The major limitation of this study is the open-label design. CONCLUSIONS: This small sample study suggested that patients with unipolar and bipolar depression who response to repeated treatment with continued oral antidepressant may be a viable treatment option, and their global functional status improved with a follow-up. Relapse of depression tended to occur during the 2 weeks follow-up.