Influence of birth cohort on age of onset cluster analysis in bipolar I disorder

PURPOSE: Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database. METHODS: The database includes 4037 patients with a diagnosis of bipolar I disorder, previously collected at 36 collection sites in 23 countries. Generalized estimating equations (GEE) were used to adjust the data for country median age, and in some models, birth cohort. Model-based clustering (mixture analysis) was then performed on the age of onset data using the residuals. Clinical variables in subgroups were compared. RESULTS: There was a strong birth cohort effect. Without adjusting for the birth cohort, three subgroups were found by clustering. After adjusting for the birth cohort or when considering only those born after 1959, two subgroups were found. With results of either two or three subgroups, the youngest subgroup was more likely to have a family history of mood disorders and a first episode with depressed polarity. However, without adjusting for birth cohort (three subgroups), family history and polarity of the first episode could not be distinguished between the middle and oldest subgroups. CONCLUSION: These results using international data confirm prior findings using single country data, that there are subgroups of bipolar I disorder based on the age of onset, and that there is a birth cohort effect. Including the birth cohort adjustment altered the number and characteristics of subgroups detected when clustering by age of onset. Further investigation is needed to determine if combining both approaches will identify subgroups that are more useful for research

The pharmacodynamic properties of lurasidone and their role in its antidepressant efficacy in bipolar disorder

The treatment of bipolar depression is one of the most challenging issues in contemporary psychiatry. Currently only quetiapine, the olanzapine-fluoxetine combination and recently lurasidone are officially FDA-approved against this condition. The neurobiology of bipolar depression and the possible targets of bipolar antidepressant therapy remain elusive. The current study investigated whether the pharmacodynamic properties of lurasidone fit to a previously developed model which was the first to be derived on the basis of the strict combination of clinical and preclinical data with no input from theory or opinion. The authors performed a complete and systematic review of the literature to identify the pharmacodynamic properties of lurasidone. The original model suggests that a constellation of effects on different receptors are necessary but the serotonin reuptake inhibition does not seem to play a significant role for bipolar depression. On the contrary norepinephrine activity seems to be very important. Probably the early antidepressant effect can be achieved through an agonistic activity at 5HT-1A and antagonism at alpha1 noradrenergic and 5-HT2A receptors, but the presence of a norepinephrine reuptake inhibition is essential in order to sustain it. Overall the properties of lurasidone fit well the model and add to its validity. A point that needs clarification is norepinephrine reuptake inhibition which is not yet studied for lurasidone. © 2014 Elsevier B.V. and ECNP

Validating a two-dimensional bipolar spectrum model integrating DSM-5's mixed features specifier for Major Depressive Disorder

Introduction The literature on DSM-5's ‘Major Depressive Disorder with lifetime mixed features’ (MDD-MF) is limited. This study investigated MDD-MF's potential inclusion into a bipolar spectrum. Methods We recruited 287 patients with Bipolar I disorder (BD-I), BD-II, MDD-MF or ‘MDD without lifetime mixed features’ (MDD-noMF); most (N = 280) were stabilized for at least one year on medication. Sixteen validators (clinical features, psychiatric family history, temperament, stabilizing treatment) were compared across groups and subjected to trend analyses. Two discriminant function analyses (DFA; primary and secondary), excluding or including, respectively, treatment-related predictors, explored latent dimensions maximizing between-group discrimination; mahalanobis distances between group ‘centroids’ were calculated. Results Eleven validators differed significantly across groups; nine varied monotonically along a bipolar diathesis gradient with significant linear trends; two peaked at MDD-MF and displayed significant quadratic trends. In the primary DFA, apart from a classic bipolarity dimension, correlating with hospitalizations, early age at onset, lifetime psychosis and lower anxious temperament scores, on which groups ranked along a bipolar propensity gradient, a second dimension was also significant, peaking at BD-II and MDD-MF (challenging the classic bipolar ranking), which correlated with lifetime psychiatric comorbidities, suicidality, lower lifetime psychosis rates, female gender, higher cyclothymic and lower depressive temperament scores; MDD-MF was equipoised amidst BD-II and MDD-noMF. After including treatment-related predictors (secondary DFA), discrimination improved overall but BD-II and MDD-MF were closest than any other pair, suggesting similar treatment patterns for these two groups at this naturalistic setting. Conclusions To our knowledge, this is the first time a two-dimensional bipolar spectrum based on classic external validators is proposed, fitting the data better than a unidimensional model. Additional predictors are warranted to improve BD-II/MDD-MF discrimination. © 2017 Elsevier Inc

Comorbidity of obsessive-compulsive disorder in bipolar spectrum disorders: Systematic review and meta-analysis of its prevalence

Background: Obsessive-compulsive disorder (OCD) is often comorbid with Bipolar Disorder (BD), complicating its presentation and management. OCD prevalence rates in BD vary widely across studies and recent meta-analyses. Objective: We performed a comprehensive systematic review and meta-analysis of studies reporting cross-sectional or lifetime OCD prevalence in BD, assessed by meta-regression various determinants of estimated prevalence and compared it with major depressive disorder (MDD) patients and general population subjects included in extracted studies. Methods: Relevant articles published up to January 2019 in PubMed/MEDLINE were retrieved. Prevalence rates underwent Freeman–Tukey double arcsine transformation before meta-analysis. Results: We included 29 studies reporting cross-sectional prevalence (N = 6109) and 39 studies reporting lifetime prevalence (N = 8205); eight studies reported both. The pooled lifetime and cross-sectional prevalence of comorbid OCD in BD was estimated at 10.9% (95% CI: 7.8–14.4%) and 11.2% (7.6–15.3%), respectively, in the random-effects model. Respective estimates in the general population were 2.5% and 1.6%. Study setting (epidemiological or clinical), diagnostic criteria and procedures, gender, BD subtype and remission status could not explain heterogeneity of prevalence estimates in meta-regressions. Age had a small yet significant negative correlation with lifetime prevalence. OCD prevalence in BD was not significantly different than in MDD. Limitations: Search was limited to English-language literature. Conclusions: Lifetime OCD prevalence in BD was 4.4 times higher than in the general population. Cross-sectional prevalence was as high as lifetime, suggesting that OCD in BD is more chronic/ persistent than in the general population, where cross-sectional stands at about two thirds the lifetime prevalence. © 201

Depression and anxiety in epilepsy: The association with demographic and seizure-related variables

Background: Depression and anxiety are common psychiatric symptoms in patients with epilepsy, exerting a profound negative effect on health-related quality of life. Several issues, however, pertaining to their association with psychosocial, seizure-related and medication factors, remain controversial. Accordingly, the present study was designed to investigate the association of interictal mood disorders with various demographic and seizure-related variables in patients with newly-diagnosed and chronic epilepsy. Methods: We investigated 201 patients with epilepsy (51.2% males, mean age 33.2 ± 10.0 years, range 16-60) with a mean disease duration of 13.9 ± 9.5 years. Depression and anxiety were assessed in the interictal state with the Beck Depression Inventory, 21-item version (BDI-21) and the state and trait subscales of the State-Trait Anxiety Inventory (STAI-S and STAI-T), respectively. The association of mood disorders with various variables was investigated with simple and multiple linear regression analyses. Results: High seizure frequency and symptomatic focal epilepsy (SFE) were independent determinants of depression, together accounting for 12.4% of the variation of the BDI-21. The STAI-S index was significantly associated with the type of epilepsy syndrome (SFE). Finally, high seizure frequency, SFE and female gender were independent determinants of trait anxiety accounting for 14.7% of the variation of the STAI-T. Conclusion: Our results confirm the prevailing view that depression and anxiety are common psychological disorders in epileptics. It is additionally concluded that female gender, high seizure frequency and a symptomatic epilepsy syndrome are independent risk factors for the development of anxiety and/or depression. © 2007 Kimiskidis et al; licensee BioMed Central Ltd

Increased plasma homocysteine levels in patients with multiple sclerosis and depression

Background: The aim of the study was to assess the plasma levels of homocysteine in patients with multiple sclerosis (MS) and to investigate whether an association with depression exists. Methods: Plasma homocysteine (Hcy), vitamin B12 and plasma folate were measured in 65 moderately disabled patients with relapsing/remitting MS (RR-MS) and 60 healthy controls. All subjects were assessed with the Beck Depression Inventory (BDI). Results: Hcy levels were significantly increased in MS patients compared to controls (13.5 ± 4.7 μmol/l vs 8.5 ± 3.1, p < 0.001). A significant correlation was found between Hcy levels and BDI scores (Pearson r = 0.3025, p < 0.05). Plasma Hcy was not related to Extended Disability Status Scale (EDSS) score, age, disease duration or vitamin B12 and folate. Conclusion: Moderately disabled MS patients with elevated Hcy levels are particularly prone to develop depressive symptomatology. Further study is warranted in order to elucidate the prognostic and therapeutic implications of this novel finding. © 2008 Triantafyllou et al; licensee BioMed Central Ltd

Corrigendum to “Self-reported changes in anxiety, depression and suicidality during the COVID-19 lockdown in Greece”. [J Affect Disord. 2020 Nov 2;279:624-629] (Journal of Affective Disorders (2021) 279 (624–629), (S0165032720329062), (10.1016/j.jad.2020.10.061))

The authors regret that because of a typo, in table 2 the percentages concerning the answers to question O11 concerning suicidal thoughts were presented incorrectly. The correct table is as follows The authors would like to apologise for any inconvenience caused. © 2020 Elsevier Lt

General and comparative efficacy and effectiveness of antidepressants in the acute treatment of depressive disorders: A report by the WPA section of pharmacopsychiatry

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Executive summary of the report by the WPA section on pharmacopsychiatry on general and comparative efficacy and effectiveness of antidepressants in the acute treatment of depressive disorders

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