Dataset Information

Antisuicidal Response Following Ketamine Infusion Is Associated With Decreased Nighttime Wakefulness in Major Depressive Disorder and Bipolar Disorder.

ABSTRACT: OBJECTIVE:Insomnia and disrupted sleep are associated with increased risk of suicide. The N-methyl-d-aspartate antagonist ketamine has been associated with reduced suicidal thoughts, but the mechanism of action is unknown. This study sought to evaluate differences in nocturnal wakefulness in depressed individuals who did and did not have an antisuicidal response to ketamine. METHODS:Thirty-four participants with baseline suicidal ideation diagnosed with either DSM-IV major depressive disorder (n = 23) or bipolar depression (n = 11) between 2006 and 2013 completed nighttime electroencephalography (EEG) the night before and the night after a single ketamine infusion (0.5 mg/kg over 40 minutes). Suicidal ideation was assessed at baseline and the morning after ketamine infusion via several measures, including the Hamilton Depression Rating Scale suicide item, the suicide item of the Montgomery-Asberg Depression Rating Scale, and the first 5 items of the Scale for Suicide Ideation. A generalized linear mixed model evaluated differences in nocturnal wakefulness, as verified by EEG, between those who had an antisuicidal response to ketamine and those who did not, controlling for baseline nocturnal wakefulness. Results were also compared to the sleep of healthy controls (n = 22). RESULTS:After analyses adjusted for baseline sleep, participants with an antisuicidal response to ketamine showed significantly reduced nocturnal wakefulness the night after ketamine infusion compared to those without an antisuicidal response (F?,?? = 5.04, P = .04). Level of nocturnal wakefulness after antisuicidal response to ketamine did not differ significantly from nocturnal wakefulness in the control sample but did differ at a trend level (F?,?? = 3.15, P = .08). CONCLUSIONS:Reductions in wakefulness following ketamine may point to a biological mechanism underlying the effect of ketamine on suicidal ideation. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT00088699.

SUBMITTER: Vande Voort JL

PROVIDER: S-EPMC5641476 | biostudies-literature | 2017 Sep/Oct

REPOSITORIES: biostudies-literature

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Antisuicidal Response Following Ketamine Infusion Is Associated With Decreased Nighttime Wakefulness in Major Depressive Disorder and Bipolar Disorder.

Vande Voort Jennifer L JL Ballard Elizabeth D ED Luckenbaugh David A DA Bernert Rebecca A RA Richards Erica M EM Niciu Mark J MJ Park Lawrence T LT Machado-Vieira Rodrigo R Duncan Wallace C WC Zarate Carlos A CA

The Journal of clinical psychiatry 20170901 8

<h4>Objective</h4>Insomnia and disrupted sleep are associated with increased risk of suicide. The N-methyl-d-aspartate antagonist ketamine has been associated with reduced suicidal thoughts, but the mechanism of action is unknown. This study sought to evaluate differences in nocturnal wakefulness in depressed individuals who did and did not have an antisuicidal response to ketamine.<h4>Methods</h4>Thirty-four participants with baseline suicidal ideation diagnosed with either DSM-IV major depress ...[more]

PMID: 27929610

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Project description:Objective: Clinically, it is very difficult to distinguish between major depressive disorder (MDD) and bipolar disorder (BD) in the period of depression. Increasing evidence shows that the insula plays an important role in depression. We aimed to compare the resting-state functional connectivity (rsFC) of insular subregions in patients with MDD and BD in depressive episodes (BDD), who had never experienced manic or hypomanic episodes when they were scanned to identify biomarkers for the identification of two diseases. Methods: We recruited 21 BDD patients, 40 MDD patients and 70 healthy controls (HC). Resting-state functional magnetic resonance imaging (rs-fMRI) was performed. BDD patients had never had manic or hypomanic episodes when they were scanned, and the diagnoses were determined by follow-up. We divided the insula into three parts including the ventral anterior insular cortex (v-AIN), dorsal anterior insular cortex (d-AIN), and posterior insula (PI). The insular-based rsFC was compared among the three groups, and an analysis of the correlation between the rsFC value and Hamilton depression and anxiety scales was carried out. Results: BDD and MDD patients demonstrated decreased rsFC from the v-AIN to the left superior/middle frontal gyrus compared with the HC group. Versus MDD and HC groups, BDD patients exhibited decreased rsFC from the v-AIN to the area in the left orbital frontal gyrus and left superior temporal gyrus (included temporal pole), from the PI to the right lateral postcentral gyrus and from all three insular subregions to the somatosensory and motor cortex. Meanwhile, a correlation between the rsFC value of the PI-right lateral postcentral gyrus and anxiety score was observed in patients. Conclusion: Our findings show BDD and MDD patients have similar decreases in insular connectivity in the dorsal lateral frontal regions, and BDD patients have specific decreased insular connectivity, especially in the somatosensory and motor cortex, which may be used as imaging evidence for clinical identification.

Project description:Family and genetic studies indicate overlapping liability for major depressive disorder and bipolar disorder. The purpose of the present study was to determine whether this shared genetic liability influences clinical presentation.A polygenic risk score for bipolar disorder, derived from a large genome-wide association meta-analysis, was generated for each subject of European-American ancestry (n = 1,274) in the Sequential Treatment Alternatives to Relieve Depression study (STAR*D) outpatient major depressive disorder cohort. A hypothesis-driven approach was used to test for association between bipolar disorder risk score and features of depression associated with bipolar disorder in the literature. Follow-up analyses were performed in two additional cohorts.A generalized linear mixed model including seven features hypothesized to be associated with bipolar spectrum illness was significantly associated with bipolar polygenic risk score [F = 2.07, degrees of freedom (df) = 7, p = 0.04]. Features included early onset, suicide attempt, recurrent depression, atypical depression, subclinical mania, subclinical psychosis, and severity. Post-hoc univariate analyses demonstrated that the major contributors to this omnibus association were onset of illness at age ? 18 years [odds ratio (OR) = 1.2, p = 0.003], history of suicide attempt (OR = 1.21, p = 0.03), and presence of at least one manic symptom (OR = 1.16, p = 0.02). The maximal variance in these traits explained by polygenic score ranged from 0.8% to 1.1%. However, analyses in two replication cohorts testing a five-feature model did not support this association.Bipolar genetic loading appeared to be associated with bipolar-like presentation in major depressive disorder in the primary analysis. However, the results were at most inconclusive because of lack of replication. Replication efforts were challenged by different ascertainment and assessment strategies in the different cohorts. The methodological approach described here may prove useful in applying genetic data to clarify psychiatric nosology in future studies.

Project description:Background: Major Depressive Disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of non-medicated subjects (MDD patients and controls) to select genes of which expression is predictive for disease status. To reveal blood gene expression changes related to MDD disease, we applied a powerful ex vivo stimulus to the blood, i.e. incubation with lipopolysaccharide (LPS; 10 ng/ml blood). Results: Based on LPS-stimulated blood gene expression using whole-genome microarrays in 42 subjects (primary cohort; 21 MDD patients (mean age 42.3 years), 21 healthy controls (mean age 41.9 years)), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated for the primary cohort using an independent quantitative PCR method (P = 0.007). The difference between depressive patients and controls was confirmed (P = 0.019) in a replication cohort of 13 patients with MDD (mean age 42.8 years) and 14 controls (mean age 45.6 years). The MDD-signature score comprised of expression levels of 7 genes could discriminate depressive patients from controls with sensitivity of 76.9% and specificity of 71.8%. Conclusions: We show for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of MDD. In total, 33 MDD patients and 34 healthy controls were analyzed using basal gene expression in whole blood, and gene expression from whole blood that was stimulated with LPS for 5-6 h, using microarrays. Patients were arbitrarily selected from all patients to serve as primary cohort (nMDD = 21 (MDD01-MDD21); nControls = 21 (Con01-Con21)), or replication cohort (nMDD = 12 (MDD22-MDD35); nControls = 13 (Con22-Con37)) using microarrays. This submission does not include Samples CON21_LPS or CON30_LPS.

Dataset Information

Antisuicidal Response Following Ketamine Infusion Is Associated With Decreased Nighttime Wakefulness in Major Depressive Disorder and Bipolar Disorder.

Publications

Antisuicidal Response Following Ketamine Infusion Is Associated With Decreased Nighttime Wakefulness in Major Depressive Disorder and Bipolar Disorder.

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