Suicidal Ideation In Major Depressive Disorder Research Articles

C-reactive protein in anhedonia among patients with major depressive disorder and its relation to suicidal ideation

BackgroundThere is evidence that major depressive disorder (MDD) with its cardinal symptoms, anhedonia and suicide, are linked with raised inflammatory markers like C-reactive protein (CRP). This case–control study investigated the correlation between high sensitive CRP (Hs-CRP), anhedonia, suicidal ideation, and depression severity in MDD patients.MethodsForty-one MDD patients and 47 healthy controls were recruited. MDD diagnosis was confirmed using DSM-5 criteria. Depression severity, anhedonia, and suicidal ideation were assessed using standardized scales. Serum Hs-CRP levels were measured as an inflammatory marker.ResultsMDD cases had significantly greater Hs-CRP levels compared to controls. Additionally, Hs-CRP levels were positively correlated with both anhedonia and suicidal ideation in MDD cases. Depression severity was significantly linked with both anhedonia and suicidal ideation.ConclusionThis study suggests a link between inflammation, anhedonia, suicidal ideation, and depression severity in MDD patients. Additional research is necessary to find out the principal mechanisms.

Differences in resting-state brain activity in first-episode drug-naïve major depressive disorder patients with and without suicidal ideation.

Despite altered brain activities being associated with suicidal ideation (SI), the neural correlates of SI in major depressive disorder (MDD) have remained elusive. We enrolled 82 first-episode drug-naïve MDD patients including 41 with SI and 41 without SI, as well as 41 healthy controls (HCs). Resting-state functional and structural MRI data were collected. The measures of fractional amplitude of low-frequency fluctuation (fALFF) and grey matter volume (GMV) were calculated and compared. Compared with HCs, patients with SI exhibited increased fALFF values in the right rectus gyrus and left medial superior frontal gyrus, middle frontal gyrus and precuneus. Decreased GMV in the right parahippocampal gyrus, insula and middle occipital gyrus and increased GMV in the left superior frontal gyrus were detected in patients with SI. In addition, patients without SI demonstrated increased fALFF values in the right superior frontal gyrus and decreased fALFF values in the right postcentral gyrus. Decreased GMV in the left superior frontal gyrus, right medial superior frontal gyrus, opercular part of inferior frontal gyrus, postcentral gyrus, fusiform gyrus and increased left supplementary motor area, superior occipital gyrus, right anterior cingulate gyrus and superior temporal gyrus were revealed in patients with SI. Moreover, in comparison with patients without SI, increased fALFF values were identified in the left precuneus of patients with SI. However, no significant differences were found in GMV between patients with and without SI. These findings might be helpful for finding neuroimaging markers predicting individual suicide risk and detecting targeted brain regions for effective early interventions.

Relationship between biological rhythm dysregulation and suicidal ideation in patients with major depressive disorder

BackgroundAlthough the disturbance of circadian rhythms represents a significant clinical feature of major depressive disorder (MDD), the relationship between biological rhythm disturbances and the severity of suicidal ideation in individuals with MDD remains unclear. We aimed to explore the characteristics of different biological rhythm dimensions in MDD and their association with the severity of depressive symptoms and suicidal ideation.MethodsA total of 50 MDD patients and 50 healthy controls were recruited and their general information was collected. The severity of depressive symptoms was assessed with the 17-item Hamilton Depression Rating Scale (HDRS17). The intensity of suicidal ideation was evaluated with the Beck Scale for Suicide Ideation (BSS). The Chinese version of the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) scale was utilized to assess the participants’ biological rhythm dysregulation. Multiple logistic regression analysis was conducted to explore the relationship between biological rhythm and the risk of MDD. Multiple linear regression analysis was performed in the MDD group to investigate the relationship between different biological rhythm dimensions and suicide ideation.ResultsSignificant differences were observed between the MDD group and the control group in total BRIAN score (Z=-5.41, P < 0.001) as well as scores for each dimension. After adjusting for confounding factors, multiple logistic regression analysis revealed a significant association between total BRIAN score and the presence of MDD (OR = 1.20, 95% CI = 1.10–1.29, P < 0.001), as well as between scores in different BRIAN dimensions and the presence of MDD (activity: OR = 1.47, 95% CI = 1.24–1.74, P < 0.001; sleep: OR = 1.52, 95% CI = 1.28–1.79, P < 0.001; social: OR = 1.80, 95% CI = 1.32–2.46, P < 0.001; eating pattern: OR = 1.34, 95% CI = 1.12–1.60, P = 0.001). In patients with MDD, linear regression analysis demonstrated a positive relationship between BSS scores and BRIAN eating pattern scores (β = 0.34, P = 0.022), even after adjusting for demographic factors and the severity of depression.ConclusionsPatients with MDD exhibited significantly higher levels of dysregulation in all four biological rhythm dimensions compared to healthy controls and the degree of dysregulation was associated with the severity of depression. More importantly, dysregulation of eating pattern may increase the intensity of suicidal ideation in MDD, thus elevating the risk of suicide.

Volumetric alterations of the hippocampal subfields in major depressive disorder with and without suicidal ideation

Major depressive disorder (MDD) is often accompanied with suicidal ideation (SI). Previous studies suggested that MDD patients who experienced suicidal attempts (SA) exhibited smaller hippocampal volume than those without SA. The hippocampus consists of several subfields that are histologically and functionally unique respectively. However, few studies have been designed to investigate the relationship between suicide and volumetric changes of the hippocampal subfields in MDD. A total of 92 participants, including 24 MDD patients with SI (MDD-SI), 30 MDD patients without SI (MDD-nSI), and 38 healthy controls (HC) were recruited in this study. High-resolution structural magnetic resonance images (MRI) were obtained and analyzed by using the automated hippocampal substructure module in FreeSurfer 7.3.2 Analyses of variance (ANOVA) were performed to obtain hippocampal subfields with significant differences among three groups and then post hoc tests were calculated for inter-group comparisons. Finally, the relationships between volumes of the hippocampal subfields and clinical characteristics were assessed using correlation analyses. The ANOVA revealed significant volumetric differences of the hippocampal subfields among three groups in the bilateral cornu ammonis (CA) 1 head, CA4 body, granule cell layer of the dentate gyrus (GC-ML-DG), molecular layer (ML), the right hippocampus-amygdala transition area (HATA), the right subiculum (Sub) body, and the left CA4 head. Relative to HC, both groups of MDD showed decreased volumes in the CA1 head, CA4, GC-ML-DG head, ML head, and whole hippocampal head of the left hippocampus, the right HATA, and bilateral whole hippocampal body, and whole hippocampus. Meanwhile, the MDD-SI group further exhibited diminished volume in the CA1 head, GC-ML-DG head, ML head, CA4 body, Sub body, and whole hippocampal head of the right hippocampus, as well as bilateral GC-ML-DG body and ML body. Additionally, the MDD-SI group also showed decreased volumes in the right GC-ML-DG body, ML body, and Sub body when compared to MDD-nSI group. However, no significant association was observed between hippocampal subfield volumes and clinical features in MDD. The present findings suggested that SI in MDD might be attributed to subfield abnormalities in the subiculum and DG-dominant circuit of the right hippocampus.

Resting State MRI Amplitude of Low Frequency Fluctuations Associated With Suicidal Ideation in Bipolar Depression.

Objective: Suicidal ideation (SI) is a risk factor for completed suicide. Our previous resting state functional magnetic resonance imaging (fMRI) study found that higher amplitude of low frequency fluctuation (ALFF) in right hippocampus and thalamus was associated with SI in major depressive disorder (MDD). The present study aimed to evaluate that association in participants with bipolar disorder (BD).Methods: Thirty depressed, adult participants with a DSM-IV diagnosis of BD had resting state fMRI scans. Region-of-interest (ROI) analyses used ALFF values within areas that were previously associated with SI in MDD. Spearman rank correlation and ordinal regression analyses were performed to assess associations between ALFF values and the SI item of the Montgomery-Asberg Depression Rating Scale. Exploratory whole-brain analyses identified regions where ALFF was associated with SI.Results: Within the right hippocampus region, SI was positively associated with ALFF (Spearman R = 0.490, P = .0060). Ordinal regression analysis indicated that for every 0.1-unit increase in ALFF in that region, the odds of having higher SI were increased by 35% (odds ratio = 1.35; 95% confidence interval, 1.08-1.73; P = .012). Within the previously identified thalamus cluster, SI was associated with ALFF only at a trend level (Spearman R = 0.310, P = .069). Whole-brain analyses identified 3 clusters of positive association between SI and ALFF, 1 of which was located in the right hippocampus.Conclusions: This study found that our previous finding of positive association between SI and ALFF in the right hippocampus extended to bipolar depression. Future studies should examine the clinical utility of this association, and the role of the hippocampus in SI.Trial Registration: Data used for this secondary analysis came from studies with ClinicalTrials.gov identifiers NCT02239094 (January 2015 through September 2016) and NCT02473250 (January 2015 through December 2019).

Reduced orbitofrontal-thalamic functional connectivity related to suicidal ideation in patients with major depressive disorder

Despite recent developments in neuroimaging, alterations of brain functional connectivity in major depressive disorder (MDD) patients with suicidal ideation are poorly understood. This study investigated specific changes of suicidal ideation in functional connectivity of MDD patients. Whole brain functional connectivity in 46 patients with MDD (23 with suicidal ideation and 23 without) and 36 age- and gender- matched healthy controls were compared using resting-state functional Magnetic Resonance Imaging (fMRI) analyzed with network-based statistics (NBS) and graph-theoretical methods. Decreased functional connectivity in a characterized sub-network was observed in patients with MDD and suicidal ideation (FDR-adjusted p < 0.05). The sub-network included the regions of the fronto-thalamic circuits in the left hemisphere. The network measures of the left superior frontal gyrus, pars orbitalis (r = −0.40, p = 0.009), left thalamus (r = −0.41, p = 0.009), and right thalamus (r = −0.51, p = −0.002) were shown, through graph theoretical analysis, to be significantly negatively correlated with severity of suicidal ideation. The reduced functional connectivity in left orbitofrontal-both thalamic regions with suicidal ideation in MDD were inversely proportional to the severity of suicidality independent from depression severity. These findings suggest problems with decision-making and information integration in MDD patients with suicidal ideation.

Neurophysiological correlates of suicidal ideation in major depressive disorder: Hyperarousal during sleep

BackgroundSuicide is a major public health concern, and a barrier to reducing the suicide rate is the lack of objective predictors of risk. The present study considers whether quantitative sleep electroencephalography (EEG) may be a neurobiological correlate of suicidal ideation. MethodsParticipants included 84 (45 female, mean age=26.6) adults diagnosed with major depressive disorder (MDD). The item that measures thoughts of death or suicide on the Quick Inventory of Depressive Symptomatology (QIDS) was used to classify 47 participants as low suicidal ideation (24 females, mean age=26.1) and 37 as high suicidal ideation (21 females, mean age=27.3). Data were obtained from archival samples collected at the University of Michigan and University of Texas Southwestern Medical Center between 2004 and 2012. Sleep EEG was quantified using power spectral analysis, and focused on alpha, beta, and delta frequencies. ResultsResults indicated that participants with high compared to low suicidal ideation experienced 1) increased fast frequency activity, 2) decreased delta activity, and 3) increased alpha-delta sleep after adjusting for age, sex, depression, and insomnia symptoms. LimitationsLimitations include the exclusion of imminent suicidal intent, a single suicidal ideation item, and cross-sectional archival data. ConclusionsThis is one of the first studies to provide preliminary support that electrophysiological brain activity during sleep is associated with increased suicidal ideation in MDD, and may point toward central nervous system (CNS) hyperarousal during sleep as a neurobiological correlate of suicidal ideation.

Suicidal ideation is associated with reduced prefrontal activation during a verbal fluency task in patients with major depressive disorder

BackgroundDespite the known relationship between prefrontal function and increased suicidality during major depressive episodes, the links between prefrontal function and suicidality remain unclear in major depressive disorder (MDD). Suicidal ideation usually precedes a suicide attempt. If prefrontal cortex (PFC) activity is a biomarker for suicidal ideation in depression, monitoring it could be useful for suicide prevention. Therefore, in this study, we assessed the association between prefrontal function and suicidal ideation in MDD. MethodsPrefrontal function in 67 patients with MDD (31 with suicidal ideation and 36 without) and 67 age-, gender-, and intelligence quotient-matched healthy controls (HCs) was evaluated using near-infrared spectroscopy (NIRS) during a verbal fluency task (VFT). Suicidal ideation was assessed using item 3 of the Hamilton Depression Rating Scale (HAMD). ResultsRegional hemodynamic changes were significantly smaller in patients with MDD than in HCs in prefrontal and temporal regions. Hemodynamic changes in the right dorsolateral PFC (DLPFC), orbitofrontal cortex (OFC), and right frontopolar cortex (FPC) regions in patients with MDD with suicidal ideation were significantly smaller than in those without suicidal ideation. In addition, hemodynamic changes correlated negatively with the severity of suicidal ideation in the DLPFC, OFC, and FPC in patients with MDD. LimitationsFurther studies with a larger sample size are required to verify our findings. ConclusionsThese results suggest that the DLPFC, OFC, and FPC are brain substrates of suicidal ideation in depressive states in patients with MDD, and that NIRS data can be employed as a clinically useful biomarker for the assessment of suicide risk.

Positron emission tomography quantification of serotonin(1A) receptor binding in suicide attempters with major depressive disorder.

Serotonergic system dysfunction has been associated with increased lethal suicide attempts and suicide. Dysfunction includes higher binding of serotonin(1A) autoreceptor in the brainstem raphe of individuals who die by suicide. To determine the relationships between brain serotonin(1A) binding and suicidal behavior in vivo in major depressive disorder (MDD) using positron emission tomography and the serotonin(1A) antagonist radiotracer carbon C 11 [11C]-labeled WAY-100635. Cross-sectional positron emission tomography study at an academic medical center from 1999 through 2009. We compared serotonin(1A) binding between individuals with MDD who did not attempt suicide (nonattempters) (n = 62) and those who attempted suicide (attempters) (n = 29). We subdivided the attempters into those with lower (n = 16) and higher (n = 13) levels of lethality. The binding potential (BPF) of [11C]WAY-100635 (calculated as the number of receptors available divided by affinity) in the prefrontal cortex (PFC) and brainstem, estimated by kinetic modeling with an arterial input function; the severity of suicidal behaviors, including lethality and intent of suicide attempts; and suicidal ideation. Using a linear mixed-effects model, we found no difference between attempters and nonattempters with MDD in serotonin(1A) BPF in the PFC regions (F1,88 = 0.03; P = .87) or in the raphe nuclei (F1,88 = 0.29; P = .59). Raphe nuclei serotonin(1A) BPF was 45.1% greater in higher-lethality attempters compared with lower-lethality attempters (F1,25 = 7.33; P = .01), whereas no difference was observed in the PFC regions (F1,25 = 0.12; P = .73). Serotonin(1A )BPF in the raphe nuclei of suicide attempters was positively correlated with the lethality rating (F1,25 = 10.56; P = .003) and the subjective lethal intent factor (F1,25 = 10.63; P = .003; R2 = 0.32) based on the most recent suicide attempt. Suicide ideation in participants with MDD was positively correlated with serotonin(1A) BPF in the PFC regions (F1,88 = 5.19; P = .03) and in the raphe nuclei (F1,87 = 7.38; P = .008; R2 = 0.12). Higher brainstem raphe serotonin(1A)BPF observed in higher-lethality suicide attempters with MDD is in agreement with findings in suicide studies and also with the finding of low cerebrospinal fluid levels of 5-hydroxyindoleacetic acid in higher-lethality suicide attempters. Higher brainstem raphe serotonin(1A) BPF would be consistent with lower levels of serotonin neuron firing and release and supports a model of impaired serotonin signaling in suicide and higher-lethality suicidal behavior. Severity of suicidal ideation in MDD is related to brainstem and prefrontal serotonin(1A) BPF, suggesting a role for both regions in suicidal ideation. Lower levels of serotonin release at key brain projection sites, such as the prefrontal regions, may favor more severe suicidal ideation and higher-lethality suicide attempts.

Brain functional changes (QEEG cordance) and worsening suicidal ideation and mood symptoms during antidepressant treatment

Antidepressant medications are efficacious overall; however, some individuals experience worsening mood symptoms and increased suicidal ideation (SI) during treatment. We examined the quantitative electroencephalographic (QEEG) cordance biomarker of brain function biomarker in relation to treatment-emergent symptom worsening. Seventy-two major depressive disorder (MDD) subjects were treated with fluoxetine 20 mg (n = 13), venlafaxine 150 mg (n = 24), or placebo (n = 35) under double-blind conditions. Behavioral ratings determined whether each subject demonstrated worsening of depressed mood, anxiety, or SI during treatment. QEEG cordance data were analyzed to determine whether symptom worsening was associated with neurophysiological changes. Antidepressant treatment-emergent SI (13.5%) was associated with a large transient decrease in midline-and-right-frontal (MRF) cordance 48 h after start of medication. Hypothesis-generating results suggest a pattern of functional changes in midline and right frontal brain regions associated with antidepressant treatment-emergent SI in MDD.

Indicators of pretreatment suicidal ideation in adults with major depressive disorder

In order to evaluate the presence of treatment emergent suicidal ideation (SI), it becomes necessary to identify those patients with SI at the onset of treatment. The purpose of this report is to identify sociodemographic and clinical features that are associated with SI in major depressive disorder (MDD) patients prior to treatment with a selective serotonin reuptake inhibitor. This multisite study enrolled 265 out-patients with non-psychotic MDD. Sociodemographic and clinical features of participants with and without SI were compared post hoc. Social phobia, bulimia nervosa, number of past depressive episodes, and race were independently associated with SI by one or more SI measure. Concurrent social phobia and bulimia nervosa may be potential risk factors for SI in patients with non-psychotic MDD. Additionally, patients with more than one past depressive episode may also be at increased risk of SI.