Heterogeneity of DSM-IV Major Depressive Disorder as a Consequence of Subthreshold Bipolarity

Zimmermann, Petra; Brückl, Tanja; Nocon, Agnes; Pfister, Hildegard; Lieb, Roselind; Wittchen, Hans‐Ulrich; Holsboer, Florian; Angst, J.

doi:10.1001/archgenpsychiatry.2009.158

Cited by 239 publications

(233 citation statements)

References 50 publications

(90 reference statements)

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“…Indeed it may be that this association is less likely than a longitudinal association with psychotic experiences as, whilst it has been found that chronic immune activation occurs in schizophrenia, previous research has suggested that bipolar disorder is an episode-related inflammatory syndrome, with normal cytokine function between affective episodes (Kunz et al 2011;Stertz et al 2013). Hypomanic symptoms in early adulthood are a risk factor for developing bipolar disorder (Zimmermann et al 2009), but are also associated with increased future risk of non-affective Axis I disorders, personality disorders, mental health service use and psychotropic drug prescribing (Päären et al 2014).…”

Section: Introductionmentioning

confidence: 99%

Childhood interleukin-6, C-reactive protein and atopic disorders as risk factors for hypomanic symptoms in young adulthood: a longitudinal birth cohort study

Hayes¹,

Khandaker²,

Anderson³

et al. 2017

Psychol. Med.

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Background. There are no existing longitudinal studies of inflammatory markers and atopic disorders in childhood and risk of hypomanic symptoms in adulthood. This study examined if childhood: (1) serum interleukin-6 (IL-6) and C-reactive protein (CRP); and (2) asthma and/or eczema are associated with features of hypomania in young adulthood.Method. Participants in the Avon Longitudinal Study of Parents and Children, a prospective general population UK birth cohort, had non-fasting blood samples for IL-6 and CRP measurement at the age of 9 years (n = 4645), and parents answered a question about doctor-diagnosed atopic illness before the age of 10 years (n = 7809). These participants completed the Hypomania Checklist at age 22 years (n = 3361).Results. After adjusting for age, sex, ethnicity, socio-economic status, past psychological and behavioural problems, body mass index and maternal postnatal depression, participants in the top third of IL-6 values at 9 years, compared with the bottom third, had an increased risk of hypomanic symptoms by age 22 years [adjusted odds ratio 1.77, 95% confidence interval (CI) 1.10-2.85, p < 0.001]. Higher IL-6 levels in childhood were associated with adult hypomania features in a dose-response fashion. After further adjustment for depression at the age of 18 years this association remained (adjusted odds ratio 1.70, 95% CI 1.03-2.81, p = 0.038). There was no evidence of an association of hypomanic symptoms with CRP levels, asthma or eczema in childhood.Conclusions. Higher levels of systemic inflammatory marker IL-6 in childhood were associated with hypomanic symptoms in young adulthood, suggesting that inflammation may play a role in the pathophysiology of mania. Inflammatory pathways may be suitable targets for the prevention and intervention for bipolar disorder.

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Section: Introductionmentioning

confidence: 99%

Childhood interleukin-6, C-reactive protein and atopic disorders as risk factors for hypomanic symptoms in young adulthood: a longitudinal birth cohort study

Hayes¹,

Khandaker²,

Anderson³

et al. 2017

Psychol. Med.

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“…[1][2][3][4][5][6][7] In the National Comorbidity Survey Replication (NCS-R) study, a nationally representative, face-to-face, household survey of the U.S. population conducted between February of 2001 and April of 2003, nearly 40% of study participants with a history of MDD had subthreshold hypomania (defined as the presence of three or more manic symptoms). 2 Previous reports suggested that, compared to pure major depression, major depressive disorder with mixed features is associated with greater illness severity, [8][9][10][11] increased frequency of recurrent depressive episodes, 2,11 increased risk of suicide attempts, 2,7,11-13 a high frequency of substance abuse, 2,7,11 and greater functional impairment. 2,6,11 MDD with mixed features has recently been endorsed as a clinically distinct and valid entity by its inclusion in the Diagnostic and Statistical Manual of Mental Disorders, 5h ed.…”

Section: Introductionmentioning

confidence: 99%

“…14 Lurasidone is an atypical antipsychotic agent with high affinity for D 2 , 5-HT 2A , and 5-HT 7 receptors (K i = 1, 0.5, and 0.495 nM, respectively). 15 In animal models, the antidepressant effect of lurasidone has been shown to be mediated in part by antagonist activity at the 5-HT 7 receptor. [16][17] Lurasidone has demonstrated efficacy in the treatment of major depressive episodes associated with bipolar I disorder (bipolar depression), both as a monotherapy and as an adjunctive therapy with lithium or valproate.…”

Section: Introductionmentioning

confidence: 99%

Remission and recovery associated with lurasidone in the treatment of major depressive disorder with subthreshold hypomanic symptoms (mixed features): post-hoc analysis of a randomized, placebo-controlled study with longer-term extension

Goldberg

Ng-Mak

Siu³

et al. 2017

CNS Spectr.

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Objective. This post-hoc analysis assessed rates of symptomatic and functional remission, as well as recovery (combination of symptomatic and functional remission), in patients treated with lurasidone for major depressive disorder (MDD) associated with subthreshold hypomanic symptoms (mixed features).Method. Patients with MDD plus two or three manic symptoms (defined as per the DSM-5 mixed-features specifier) were randomly assigned to flexible-dose lurasidone 20-60 mg/day (n = 109) or placebo (n = 100) for 6 weeks, followed by a 3-month open-label, flexible-dose extension study for U.S. sites only (n = 48). Cross-sectional recovery was defined as the presence of both symptomatic remission (Montgomery-Åsberg Depression Rating Scale score ≤ 12) and functional remission (all Sheehan Disability Scale [SDS] domain scores ≤ 3) at week 6, and at both months 1 and 3 of the extension study ("sustained recovery").Results. A significantly higher proportion of lurasidone-treated patients (31.3%) achieved recovery (assessed crosssectionally) compared to placebo (12.2%, p = 0.002) at week 6. The number of manic symptoms at baseline moderated the effect size for attaining cross-sectional recovery for lurasidone treatment (vs. placebo) (p = 0.028). Sustained recovery rates were higher in patients initially treated with lurasidone (20.8%) versus placebo (12.5%).Conclusions. In this post-hoc analysis of a placebo-controlled study with open-label extension that involved patients with MDD and mixed features, lurasidone was found to significantly improve the rate of recovery at 6 weeks (vs. placebo) that was sustained at month 3 of the extension study. The presence of two (as opposed to three) manic symptoms moderated recovery at the acute study endpoint.

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“…[2][3][4][5][6][7][8][9][10][11][12] In MDD patients without mixed features, the presence of concurrent anxiety has been shown to reduce the likelihood of achieving an adequate antidepressant response. [19][20][21][22][23][24][25][26][27] We report here the results of a post-hoc analysis of a placebo-controlled, 6-week trial of MDD presenting with mixed features and anxiety which found that treatment with lurasidone significantly improved depressive symptoms in a subgroup of patients with moderate-to-severe anxiety at baseline.…”

Section: Lurasidone For Mdd With Mixed Features and Anxiety 241mentioning

confidence: 99%

“…1 The available evidence, largely from clinical study populations, suggests that major depressive disorder (MDD) with mixed features may occur in at least 25% of patients with major depression. [2][3][4][5][6][7][8][9][10][11][12] In patients with a diagnosis of MDD, the estimated lifetime prevalence of an anxiety disorder is greater than 35%. 13,14 The presence of comorbid anxiety in MDD has been found to be associated with greater illness severity, chronicity, and functional impairment.…”

Section: Introductionmentioning

confidence: 99%

Lurasidone for major depressive disorder with mixed features and anxiety: a post-hoc analysis of a randomized, placebo-controlled study

et al. 2017

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Objective. The aim of this post-hoc analysis was to evaluate the efficacy of lurasidone in treating patients with major depressive disorder (MDD) with mixed features who present with mild and moderate-to-severe levels of anxiety.Methods. The data in this analysis were derived from a study of patients meeting the DSM-IV-TR criteria for unipolar MDD, with a Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥26, presenting with two or three protocol-defined manic symptoms, who were randomized to 6 weeks of double-blind treatment with either lurasidone 20-60 mg/day (n = 109) or placebo (n = 100). Anxiety severity was evaluated using the Hamilton Anxiety Rating Scale (HAM-A). To evaluate the effect of baseline anxiety on response to lurasidone, the following two anxiety groups were defined: mild anxiety (HAM-A ≤ 14) and moderate-to-severe anxiety (HAM-A ≥ 15). Change from baseline in MADRS total score was analyzed for each group using a mixed model for repeated measures.Results. Treatment with lurasidone was associated with a significant week 6 change versus placebo in MADRS total score for patients with both mild anxiety (-18.4 vs. -12.8, p < 0.01, effect size [ES] = 0.59) and moderate-to-severe anxiety (-22.0 vs. -13.0, p < 0.001, ES = 0.95). Treatment with lurasidone was associated with a significant week 6 change versus placebo in HAM-A total score for patients with both mild anxiety (-7.6 vs. -4.0, p < 0.01, ES = 0.62), and moderate-to-severe anxiety (-11.4 vs. -6.1, p < 0.0001, ES = 0.91).Conclusions. In this post-hoc analysis of an MDD with mixed features and anxiety population, treatment with lurasidone was associated with significant improvement in both depressive and anxiety symptoms in subgroups with mild and moderate-to-severe levels of anxiety at baseline.

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Heterogeneity of DSM-IV Major Depressive Disorder as a Consequence of Subthreshold Bipolarity

Cited by 239 publications

References 50 publications

Childhood interleukin-6, C-reactive protein and atopic disorders as risk factors for hypomanic symptoms in young adulthood: a longitudinal birth cohort study

Childhood interleukin-6, C-reactive protein and atopic disorders as risk factors for hypomanic symptoms in young adulthood: a longitudinal birth cohort study

Remission and recovery associated with lurasidone in the treatment of major depressive disorder with subthreshold hypomanic symptoms (mixed features): post-hoc analysis of a randomized, placebo-controlled study with longer-term extension

Lurasidone for major depressive disorder with mixed features and anxiety: a post-hoc analysis of a randomized, placebo-controlled study

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