Interrogating Associations Between Polygenic Liabilities and Electroconvulsive Therapy Effectiveness

Background: Electroconvulsive therapy (ECT) is the most effective treatment for severe major depressive episodes (MDEs). Nonetheless, firmly established associations between ECT outcomes and biological variables are currently lacking. Polygenic risk scores (PRSs) carry clinical potential, but associations with treatment response in psychiatry are seldom reported. Here, we examined whether PRSs for major depressive disorder, schizophrenia (SCZ), cross-disorder, and pharmacological antidepressant response are associated with ECT effectiveness. Methods: A total of 288 patients with MDE from 3 countries were included. The main outcome was a change in the 17-item Hamilton Depression Rating Scale scores from before to after ECT treatment. Secondary outcomes were response and remission. Regression analyses with PRSs as independent variables and several covariates were performed. Explained variance (R 2) at the optimal p-value threshold is reported. Results: In the 266 subjects passing quality control, the PRS-SCZ was positively associated with a larger Hamilton Depression Rating Scale decrease in linear regression (optimal p-value threshold = .05, R 2 = 6.94%, p < .0001), which was consistent across countries: Ireland (R 2 = 8.18%, p = .0013), Belgium (R 2 = 6.83%, p = .016), and the Netherlands (R 2 = 7.92%, p = .0077). The PRS-SCZ was also positively associated with remission (R 2 = 4.63%, p = .0018). Sensitivity and subgroup analyses, including in MDE without psychotic features (R 2 = 4.42%, p = .0024) and unipolar MDE only (R 2 = 9.08%, p < .0001), confirmed the results. The other PRSs were not associated with a change in the Hamilton Depression Rating Scale score at the predefined Bonferroni-corrected significance threshold. Conclusions: A linear association between PRS-SCZ and ECT outcome was uncovered. Although it is too early to adopt PRSs in ECT clinical decision making, these findings strengthen the positioning of PRS-SCZ as relevant to treatment response in psychiatry

Associations between cognitive functioning, mood symptoms and coping styles in older age bipolar disorder

Background: Older age patients with bipolar disorder (OABD) have often passive coping styles, generally considered as detrimental for functioning. The aim of the current study is to identify the contribution of cognitive functioning, subjective cognitive complaints and mood symptoms to passive and active coping styles in older age BD. Methods: In 90 euthymic patients (age > 60) with BD I or II, we examined coping, neuropsychological profile including memory, attention, executive function and fluency, subjective cognitive complaints and mood symptoms. Results: Better executive functioning and fewer depressive symptoms were associated with more active coping (p =.02 and p =.001 respectively). Associations between executive functioning and coping styles turned nonsignificant when combined with depressive symptoms in one model, indicating the importance of mood on coping styles. No associations were found between subjective cognitive complaints and coping styles. Limitations: Cross-sectional data were used and no conclusions about causality can be made. Conclusions: Even in euthymic patients, subclinical depressive symptoms may influence active coping negatively. Subjective cognitive complaints and objectified cognitive functioning seem to be of less importance for coping styles. Important implications are on the one hand optimizing treatment on reducing depressive symptoms and on the other hand focusing therapeutic interventions on coping in bipolar patients

Physical comorbidity in Older-Age Bipolar Disorder (OABD) compared to the general population - a 3-year longitudinal prospective cohort study

Background: The aim of this study was to examine the accumulation of chronic physical diseases in Older-Age Bipolar Disorder (OABD) as well as in individuals from the general aging population over a 3-year period. Methods: This prospective longitudinal study compared 101 patients with OABD receiving outpatient care (DOBi cohort) with 2545 individuals from the general aging population (LASA cohort). The presence of eight major chronic diseases was asked at baseline and 3-year follow-up. Total number of diseases was the main outcome measure. Self-rated health (SRH, scale 1-5) was examined as a secondary outcome. Multilevel linear modelling of change was performed to estimate and test the observed change in both samples. Results: At baseline, the number of chronic diseases was lower (b= -0.47, p<0.01) and self-rated health comparable (b=0.27, p=0.13) in DOBi than in LASA. Over 3 years the number of chronic diseases increased faster in DOBi than in LASA (b=0.51 versus b=0.35, p(interaction)=0.03). When corrected for employment, depressive symptoms, waist circumference, smoking, and alcohol use, this difference was no longer significant. SRH decreased faster in DOBi than in LASA (b=-0.24 versus b=-0.02, p(interaction)=0.04). Limitations: Information on chronic diseases was collected using self-report. Conclusions: A faster accumulation of chronic physical diseases and a faster decline in health perception was observed in OABD than in participants from the general population. The observed differences could partly be attributed to baseline differences in psychosocial, lifestyle, and health behaviour factors. Our findings urgently call for the use of integrated care in BD

Long-term outcome following electroconvulsive therapy for late-life depression : five-year follow- up data from the MODECT study

Objective: Electroconvulsive therapy (ECT) is the most effective treatment for late-life depression (LLD). Research addressing long-term outcome following an acute course of ECT for LLD is limited. We aimed to describe relapse, cognitive impairment and survival 5 years after a treatment with ECT for severe LLD, and assess the association of clinical characteristics with all three outcome measures. Methods: This cohort study was part of the Mood Disorders in Elderly treated with ECT (MODECT) study, which included patients aged 55 years and older with major depressive disorder. Data regarding clinical course, cognitive impairment and mortality were collected 5 years after the index ECT course. We used multivariable Cox proportional hazards models and logistic regression models to assess the association of clinical characteristics with relapse and survival, and cognitive impairment, respectively. Results: We studied 110 patients with a mean age of 72.9 years. 67.1% of patients who showed response at the end of the index ECT course relapsed, and the included clinical characteristics were not significantly associated with the risk of relapse. 38.8% of patients with available data showed cognitive impairment at five-year follow-up. 27.5% were deceased; higher age and a higher number of previous psychiatric admissions were significantly associated with increased risk of mortality. Conclusions: Five-year outcome after a course of ECT for severe LLD seems to be in line with long-term outcome following other acute treatments for severe LLD in terms of relapse, cognitive impairment and survival. Additional studies aimed at improving long-term outcome in severe LLD are warranted

Self-reported cognitive complaints in elderly bipolar patients

BACKGROUND: Patients with bipolar disorder are at risk to develop cognitive decline in the course of their illness. This may affect their ability to monitor and detect their own cognitive functioning (anosognosia). The aim of this study was to determine whether subjective cognitive complaints were associated with objective neuropsychologic performance and to consider the role of frontal lobe dysfunction in the awareness of cognitive impairment. METHOD: A total of 101 euthymic elderly bipolar patients and 74 healthy comparison subjects were assessed using a comprehensive neuropsychologic battery. The Cognitive Failure Questionnaire was used to determine subjective cognitive complaints. RESULTS: Elderly bipolar patients had no more subjective cognitive complaints than comparison subjects, whereas they showed less cognitive functioning in several domains. Having few subjective cognitive complaints was associated with poorer attentional and executive functioning. CONCLUSIONS: Impaired awareness of cognition might be a reflection of cognitive deterioration and could influence treatment. Evaluation of cognitive functioning in elderly bipolar patients should be part of the treatment program regardless of subjective complaints. © 2012 American Association for Geriatric Psychiatry