Affective Instability, Childhood Trauma and Major Affective Disorders

BACKGROUND: Affective instability (AI), childhood trauma, and mental illness are linked, but evidence in affective disorders is limited, despite both AI and childhood trauma being associated with poorer outcomes. Aims were to compare AI levels in bipolar disorder I (BPI) and II (BPII), and major depressive disorder recurrent (MDDR), and to examine the association of AI and childhood trauma within each diagnostic group. METHODS: AI, measured using the Affective Lability Scale (ALS), was compared between people with DSM-IV BPI (n=923), BPII (n=363) and MDDR (n=207) accounting for confounders and current mood. Regression modelling was used to examine the association between AI and childhood traumas in each diagnostic group. RESULTS: ALS scores in descending order were BPII, BPI, MDDR, and differences between groups were significant (p<0.05). Within the BPI group any childhood abuse (p=0.021), childhood physical abuse (p=0.003) and the death of a close friend in childhood (p=0.002) were significantly associated with higher ALS score but no association was found between childhood trauma and AI in BPII and MDDR. LIMITATIONS: The ALS is a self-report scale and is subject to retrospective recall bias. CONCLUSIONS: AI is an important dimension in bipolar disorder independent of current mood state. There is a strong link between childhood traumatic events and AI levels in BPI and this may be one way in which exposure and disorder are linked. Clinical interventions targeting AI in people who have suffered significant childhood trauma could potentially change the clinical course of bipolar disorder

Interaction between COMT rs5993883 and second generation antipsychotics is linked to decreases in verbal cognition and cognitive control in bipolar disorder

Abstract Background Second generation antipsychotics (SGAs) are increasingly utilized in Bipolar Disorder (BD) but are potentially associated with cognitive side effects. Also linked to cognitive deficits associated with SGA-treatment are catechol-O-methyltransferase (COMT) gene variants. In this study, we examine the relationship between cognition in SGA use and COMT rs5993883 in cohort sample of subjects with BD. Methods Interactions between SGA-treatment and COMT rs5993883 genotype on cognition was tested using a battery of neuropsychological tests performed in cross-sectional study of 246 bipolar subjects. Results The mean age of our sample was 40.15 years and was comprised of 70 % female subjects. Significant demographic differences included gender, hospitalizations, benzodiazepine/antidepressant use and BD-type diagnosis. Linear regressions showed that the COMT rs5993883 GG genotype predicted lower verbal learning (p = 0.0006) and memory (p = 0.0026) scores, and lower scores on a cognitive control task (p = 0.004) in SGA-treated subjects. Interestingly, COMT GT- or TT-variants showed no intergroup cognitive differences. Further analysis revealed an interaction between SGA-COMT GG-genotype for verbal learning (p = 0.028), verbal memory (p = 0.026) and cognitive control (p = 0.0005). Conclusions This investigation contributes to previous work demonstrating links between cognition, SGA-treatment and COMT rs5993883 in BD subjects. Our analysis shows significant associations between cognitive domains such as verbal-cognition and cognitive control in SGA-treated subjects carrying the COMT rs5993883 GG-genotype. Prospective studies are needed to evaluate the clinical significance of these findings.http://deepblue.lib.umich.edu/bitstream/2027.42/134550/1/40359_2016_Article_118.pd

Dopaminergic Influences on Emotional Decision Making in Euthymic Bipolar Patients

We recently reported that the D2/D3 agonist pramipexole may have pro-cognitive effects in euthymic patients with bipolar disorder (BPD); however, the emergence of impulse-control disorders has been documented in Parkinson\u27s disease (PD) after pramipexole treatment. Performance on reward-based tasks is altered in healthy subjects after a single dose of pramipexole, but its potential to induce abnormalities in BPD patients is unknown. We assessed reward-dependent decision making in euthymic BPD patients pre- and post 8 weeks of treatment with pramipexole or placebo by using the Iowa Gambling Task (IGT). The IGT requires subjects to choose among four card decks (two risky and two conservative) and is designed to promote learning to make advantageous (conservative) choices over time. Thirty-four BPD patients completed both assessments (18 placebo and 16 pramipexole). Baseline performance did not differ by treatment group (F = 0.63; p = 0.64); however, at week 8, BPD patients on pramipexole demonstrated a significantly greater tendency to make increasingly high-risk, high-reward choices across the five blocks, whereas the placebo group\u27s pattern was similar to that reported in healthy individuals (treatment x time x block interaction,

Association between solar insolation and a history of suicide attempts in bipolar I disorder

In many international studies, rates of completed suicide and suicide attempts have a seasonal pattern that peaks in spring or summer. This exploratory study investigated the association between solar insolation and a history of suicide attempt in patients with bipolar I disorder. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area on Earth. Data were collected previously from 5536 patients with bipolar I disorder at 50 collection sites in 32 countries at a wide range of latitudes in both hemispheres. Suicide related data were available for 3365 patients from 310 onset locations in 51 countries. 1047 (31.1%) had a history of suicide attempt. There was a significant inverse association between a history of suicide attempt and the ratio of mean winter solar insolation/mean summer solar insolation. This ratio is smallest near the poles where the winter insolation is very small compared to the summer insolation. This ratio is largest near the equator where there is relatively little variation in the insolation over the year. Other variables in the model that were positively associated with suicide attempt were being female, a history of alcohol or substance abuse, and being in a younger birth cohort. Living in a country with a state-sponsored religion decreased the association. (All estimated coefficients p <0.01). In summary, living in locations with large changes in solar insolation between winter and summer may be associated with increased suicide attempts in patients with bipolar disorder. Further investigation of the impacts of solar insolation on the course of bipolar disorder is needed.Peer reviewe

Cognitive function in adulthood and elderly euthymic bipolar patients: a comparison to test models of cognitive evolution

Objective: Neurocognitive dysfunction is considered as the main predictor of overall outcome of BD. The issue of whether neurocognitive dysfunction in BD is progressive—or not—has become critical in the effort to define staging models for these disorders. Data about cognitive dysfunction evolution are scarce and contradictory. While some studies showed a progressive pattern others have found a stable form of evolution. Methods: Twenty four patients with BD aged 60 years or older (E-BD), 24 patients with BD aged 40 years or younger (Y-BD) and 20 healthy controls matched by the E-BD group were evaluated with traditional clinical instruments and an extensive neuropsychological battery was completed. We used ANOVA and Chi-squared for comparisons. Raw score of neurocognitive tasks was transformed to standardized Z-score from the normative data of each test to avoid the effect of age. In order to decrease the risk of type I errors, one-way multivariate analysis of variance was conducted. Results: Despite having an illness duration that was 4 times longer, E-BD did not differ in terms of key cognitive domains compared to Y-BD. These data do not support the hypothesis of a progression of cognitive dysfunction due to illness chronicity.Fil: Strejilevich, S. A.. Universidad Favaloro. Facultad de Medicina. Instituto de Neurociencias; Argentina. Instituto de Neurología Cognitiva; ArgentinaFil: Martino, Diego Javier. Universidad Favaloro. Facultad de Medicina. Instituto de Neurociencias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Neurología Cognitiva; Argentin

A longitudinal mirror-image assessment of morbidity in bipolar disorder

Background Evidence about the clinical course of bipolar disorder is inconsistent and limited. The aim of this study was to assess changes in morbidity in patients with bipolar disorder along a mean follow-up period of 80 months. Methods Based on a mirror-image design, the follow-up period of each patient was divided into two halves. Then, three measures of morbidity — number of affective episodes, time spent ill, and cycle length — were recorded and compared between each half of the follow-up period. Results On average, there was a trend to a smaller amount of time spent with subclinical symptomatology during the second half of the follow-up period. In contrast, there were no differences in terms of number of episodes, time spent with clinical symptoms, or cycle length between the first and second half of the follow-up period. A subgroup analysis identified 21.9% of patients with consistent data of a worsening during follow-up. Conclusions The results suggest that, on average, there is stability or slight improvement of clinical morbidity over the course of BD. Then, worsening of the clinical course may be a feature of a subgroup of patients rather than an inherent characteristic of the disorder. These subgroups or patient profiles could represent an opportunity for further studies to assess clinical, pathophysiologic, and therapeutic features associated with them.Fil: Martino, Diego Javier. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro; ArgentinaFil: Samame, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro; ArgentinaFil: Marengo, E.. Universidad Favaloro; ArgentinaFil: Igoa, A.. Universidad Favaloro; ArgentinaFil: Scápola, M.. Universidad Favaloro; ArgentinaFil: Strejilevich, S. A.. Universidad Favaloro; Argentina. Instituto de Neurología Cognitiva; Argentin

Are major depression and bipolar disorder neuropsychologically distinct? A meta-analysis of comparative studies

Background: Neuropsychological deficits are present in both major depression and bipolar disorder. So far, however, reports directly comparing these mood disorders with regard to cognitive outcomes have been scant and yielded inconsistent results. This work aims to combine the findings of comparative studies of cognition in major depression and bipolar disorder in order to explore whether these neuropsychiatric conditions present with distinct cognitive features. Methods: The main online databases were extensively searched to retrieve reports assessing neurocognitive functioning in two groups of mood disorder patients, one with major depressive disorder and another with bipolar disorder, both in the same phase of illness. Between-group effect sizes for cognitive variables were obtained from selected studies and pooled by means of meta-analytic procedures. Results: During euthymia, a significant overall effect size (Hedges’g = 0.64, P < 0.001) favoring major depressive disorder was found for verbal memory as assessed with list learning tests, whereas no significant between-group differences were found for the remaining variables analyzed. During depressive episodes, similar cognitive outcomes were observed between groups. Conclusion: At present, it is not possible to postulate specific neuropsychological profiles for major depression and bipolar disorder in light of available evidence. It remains to be ascertained whether the differences found for verbal memory constitute an expression of distinct underlying mechanisms or whether they are best explained by sample characteristics or differential exposure to variables with a negative impact on cognition.Fil: Samame, Cecilia. Universidad Favaloro. Facultad de Medicina. Instituto de Neurociencias; Argentina. Universidad de Buenos Aires. Facultad de Psicología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Szmulewicz, A. G.. Universidad Favaloro. Facultad de Medicina. Instituto de Neurociencias; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Emergencias Psiquiáicas "Torcuato de Alvear"; ArgentinaFil: Valerio, Marina Paula. Gobierno de la Ciudad de Buenos Aires. Hospital de Emergencias Psiquiáicas "Torcuato de Alvear"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Martino, Diego Javier. Universidad Favaloro. Facultad de Medicina. Instituto de Neurociencias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Strejilevich, S. A.. Universidad Favaloro. Facultad de Medicina. Instituto de Neurociencias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; Argentin

Funcionamiento Cognitivo En Los Trastornos Bipolares: Avances, Controversias Y Desafíos.

Fil: Strejilevich, S. A.. Universidad Favaloro. Facultad de Medicina; ArgentinaFil: Martino, Diego Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; Argentin

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Fil: Martino, Diego Javier. Universidad Favaloro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Samame, Cecilia. Universidad Favaloro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Strejilevich, S. A.. Universidad Favaloro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin