Can we predict a "tsunami"? Symptomatic and syndromal density, mood instability and treatment intensity in people with bipolar disorders under a strict and long lockdown.

BACKGROUND: Converging evidence supports the involvement of circadian rhythm disturbances in the course and morbidity of bipolar disorders (BD). During 2020, lockdown measures were introduced worldwide to contain the health crisis caused by the COVID-19 pandemic. As a result, chronobiological rhythms were critically disrupted and illness outcomes were expected to worsen. The current study aimed to explore changes in morbidity among BD patients living under lockdown. METHODS: Ninety BD outpatients under naturalistic treatment conditions were followed from March to September 2020 using a mood chart technique. Different treatment and illness variables, including mood instability, were assessed and compared with the outcomes obtained during the same 28-week period in 2019. RESULTS: For most clinical variables, no significant differences were observed between time periods. A slight decrease was found in symptom intensity (from 15.19 ± 20.62 to 10.34 ± 15.79, FDR-adjusted p = 0.04) and in the number of depressive episodes (from 0.39 ± 0.74 to 0.22 ± 0.63, FDR-adjusted p = 0.03), whereas the intensity of pharmacological treatment remained unchanged. Previous illness course predicted mood outcomes during the confinement. LIMITATIONS: Follow-up periods were relatively short. Further, actigraphy or other methods capable of ensuring significant changes in physical activity were not used. CONCLUSIONS: In line with other studies, our findings show no worsening in the clinical morbidity of BD patients during lockdown. This conspicuous contrast between our initial predictions and the observed findings highlights the fact that we are still far from being able to provide accurate predictive models for BD.

Efficacy of cognitive remediation in bipolar disorder: systematic review and meta-analysis of randomized controlled trials.

A significant percentage of people with bipolar disorder (BD) exhibit suboptimal functional adjustment, even when appropriately treated and after symptomatic recovery is achieved. Given that cognitive impairment is one of the strongest correlates of socio-occupational outcomes and quality of life in BD, cognitive remediation (CR) is currently acknowledged as a promising treatment that could help bridge the gap between symptomatic and full functional recovery. The aim of this review was to explore the efficacy of CR approaches in improving cognitive and functional outcomes in BD patients. PubMed, PsycINFO, and CENTRAL were searched from inception to November 2022. Randomized controlled trials exploring the effects of CR on cognition and/or functional adjustment in adult BD patients were eligible. Ten studies based on seven independent trials (n = 586) were included. Change-score effect sizes (Hedges' g) were obtained for efficacy outcome measures and combined by means of meta-analytic procedures. Small but significant overall effects were observed for working memory (g = 0.32, 95% CI 0.11-0.52), planning (g = 0.30, 95% CI 0.03-0.56), and verbal learning (g = 0.40, 95% CI 0.15-0.66). However, CR was not found to exert any significant effects on functional outcomes at treatment completion or at follow-up assessment. Although CR may modestly enhance the cognitive performance of BD patients, this effect does not translate into an improvement at the functional level. The current data do not support the inclusion of CR as a treatment recommendation in clinical practice guidelines for the management of BD.

The long-term course of cognition in bipolar disorder: a systematic review and meta-analysis of patient-control differences in test-score changes.

Neuropsychological impairment represents a key aspect of bipolar disorder (BD) that is evident even in early-course patients and is a strong predictor of functional outcomes among those affected. Previous meta-analyses of longitudinal studies suggest that BD-related cognitive deficits may not progress along the course of the disorder. However, short test-retest periods were used in most primary studies and comparisons with healthy controls were limited. The aim of this review was to synthesize the findings of research reports comparing long-term neurocognitive trajectories between BD patients and healthy individuals. PubMed, PsycINFO, and Scopus databases were searched from inception through July 2021. Publications were considered for inclusion if they reported cognitive test scores of BD patients and healthy controls at two different time points, with a minimum test-retest interval of 5 years. Fifteen studies compared the long-term course of cognition in BD patients with that of healthy controls. Ten of these were included in the quantitative analysis and involved 540 BD patients and 644 healthy individuals (mean follow-up period: 8.9 years). Patient-control effect sizes (standardized mean differences) were calculated for test-score changes in 24 neuropsychological variables and combined by means of meta-analytic procedures. No significant differences were found between patients and controls regarding long-term cognitive outcomes. These findings are consistent with previous shorter-term longitudinal meta-analyses and do not provide evidence for progressive cognitive deterioration in most bipolar individuals. Future studies should address the longitudinal course of cognition in different subgroups of BD patients and its prognostic and therapeutic value.

Claiming the validity of scientific evidence in post-truth times.

This letter is written in response to a review recently published in the journal. The aim is to highlight a potential methodological limitation common to many studies comparing bipolar patients with few previous episodes versus those with multiple episodes, and in which the results are interpreted as indicating the longitudinal course of the illness.

Functional Outcome in the Middle Course of Bipolar Disorder: A Longitudinal Study.

The aim of this study was to assess the long-term functional outcome of patients with bipolar disorder (BD). At baseline and after a follow-up period of at least 48 months, three measures of functioning were administered: psychosocial functioning (GAF), employment status (full-time, part-time, and unemployment/disability), and a self-reported measure of functional recovery. At baseline, patients with more than five previous affective episodes exhibited poorer outcomes on all measures of functioning than patients with less than five previous episodes. However, along a mean follow-up period of 77 months, measures of functioning tended to remain stable or improved slightly. These results highlight the limitation of studies comparing measures of functioning between patients with many and few episodes to evaluate functional outcome. Likewise, these preliminary results do not support the hypothesis that functional outcome deteriorates over the course of BD.

Neuropsychological profiles of major depressive disorder and bipolar disorder during euthymia. A systematic literature review of comparative studies.

Bipolar disorder and major depressive disorder have been shown to be associated with neurocognitive abnormalities during periods of clinical remission. However, at present, there is no consensus on whether these disorders have distinctive cognitive profiles. The aim of this study was to provide an updated systematic review of studies comparing neuropsychological functioning between bipolar disorder and major depressive disorder during remission. Main findings included the following: 1) no differences regarding performances in measures of attention and processing speed, executive functions and theory of mind were found between both patient groups and 2) regarding verbal memory, preliminary evidence points towards a more defective performance in patients with bipolar disorder than those with major depressive disorder. However, several variables with negative impact on cognition (medication status, age at onset, premorbid IQ, bipolar subtype, among others) were not adequately controlled in most studies. In conclusion, evidence from studies exploring neuropsychological profiles in bipolar disorder and major depressive disorder could not provide clues to differentiate these mood disorders. Larger studies with adequate control of confounding variables would be necessary to elucidate if the finding of more defective verbal memory performance in bipolar disorder is truly explained by distinct underlying mechanisms.

Stability of facial emotion recognition performance in bipolar disorder.

The aim of this study was to assess the performance in emotional processing over time in a sample of euthymic patients with bipolar disorder (BD). Performance in the facial recognition of the six basic emotions (surprise, anger, sadness, happiness, disgust, and fear) did not change during a follow-up period of almost 7 years. These preliminary results suggest that performance in facial emotion recognition might be stable over time in BD.

Behavioral and emotional adverse events of drugs frequently used in the treatment of bipolar disorders: clinical and theoretical implications.

BACKGROUND: Behavioral and emotional adverse events induced by drugs commonly prescribed to patients with bipolar disorders are of paramount importance to clinical practice and research. However, no reviews on the topic have been published so far. METHODS: An extensive search was performed. Reports were reviewed if they described behavioral side effects related to pharmacological treatments for bipolar disorders in healthy subjects or patients with different neuropsychiatric disorders. For this review, lithium, antipsychotics, anticonvulsants and selective serotonin reuptake inhibitors were included. RESULTS: Apathy or emotional blunting, diminished sexual desire, and inability to cry were reported to be associated with exposure to selective serotonin reuptake inhibitors. Neuroleptic-induced deficit syndrome/emotional detachment and obsessive-compulsive symptomatology and decision-making modifications. A lithium-related amotivational syndrome was also reported in the literature. Furthermore, hypersexuality and obsessive-compulsive symptoms have been noted in subjects treated with lamotrigine. LIMITATIONS: Primary studies on drug-related adverse events are scant so far and most of the data currently available derive from case reports. Moreover, most of the evidence reviewed is based on studies performed on healthy subjects and patients with neuropsychiatric conditions other than bipolar disorders. DISCUSSION: There is a remarkable dearth of data on behavioral adverse events of pharmacological treatment for bipolar disorders. However, the pieces of evidence available at present, though scant and scattered, suggest that different behavioral adverse events may be related to pharmacological treatment for these disorders. The implications of these findings for research and management of patients with mood disorders are discussed.

An updated review on the neuropsychological profile of subjects with bipolar disorder

Abstract Background In recent years, growing interest in the neuropsychology of bipolar disorder has emerged, giving rise to the accumulation of a robust body of evidence on this topic and to several related questions. Objective To provide a state-of-the-art overview of the neuropsychological profile of bipolar disorder. Method A thorough literature search was performed. Published research evidence was summarized and organized along three key pathways: findings from cross-sectional studies of cognition in bipolar patients, cognitive heterogeneity among affected subjects, and trajectory of neuropsychological deficits. Results At least two thirds of bipolar patients display neuropsychological deficits, even in euthymia. Although bipolar disorder was found to be associated with an increased risk of dementia, data from elderly subjects and longitudinal research do not support a worsening of cognitive performance over time. Discussion Cognitive dysfunctions are part of the clinical conceptualization of bipolar illness. However, they may not be present in all affected subjects and their course appears to be stable in most cases. Available evidence may be highlighting the fact that bipolar disorder is characterized by remarkable heterogeneity regarding cognitive outcomes. Different variables may be related to such heterogeneity and should be the focus of therapeutic approaches and further research.

The trajectory of neuropsychological dysfunctions in bipolar disorders: a critical examination of a hypothesis.

OBJECTIVE: The hypothesis of a progressive nature of neuropsychological deficits in bipolar disorders is often accepted as an axiom by many clinicians and researchers in the field. However, contradictory pieces of data and a number of methodological concerns put it under debate. METHOD: We reviewed findings from three different approaches to the study of the trajectory of cognitive features in bipolar disorders: longitudinal evaluation of cognition in affected subjects, cross-sectional neuropsychological assessment of patients belonging to different age groups, and exploration of the risk of dementia in bipolar subjects. RESULTS: An increased risk of developing dementia was found in bipolar subjects. However, evidence from cross-sectional studies did not show more severe cognitive deficits in patients with longer illness duration. Furthermore, longitudinal studies revealed that bipolar subjects׳ cognitive performance did not change between different points in time. CONCLUSIONS: After a thorough discussion of these findings and the limitations of the different approaches, we argue that, at present, there is no consistent evidence supporting that bipolar disorders, as a group, have a progressively deteriorating course of cognitive functions. Furthermore, we highlight the possible influence of psychotropic agents and metabolic factors on neuropsychological outcomes. Finally, we discuss the clinical implications of these findings and propose targets for forthcoming research.

Neurocognitive functioning in the premorbid stage and in the first episode of bipolar disorder: a systematic review.

It is well known that patients with bipolar disorder (BD) have cognitive impairments even during periods of euthymia. However, to date it remains unclear the moment when these deficits onset. Therefore, the aim of this study was to review the evidence focusing on the cognitive status of patients with BD in their premorbid stage and in their first episode. An extensive search was conducted through the online databases Pubmed/PsychInfo, covering the period between 1980 and 2014. A total of 23 studies were selected for the review (nine studies explored premorbid stage of people who lately develop BD and 14 examined first-episodes in bipolar patients). There is evidence that general intelligence is not impaired in the premorbid stage. Impairments in verbal memory, attention, and executive functions tend to be present during and after the first episode. Preliminary evidence suggests that these deficits in specific cognitive domains might precede the onset of illness.

An individual task meta-analysis of social cognition in euthymic bipolar disorders.

OBJECTIVE: Social cognition has been shown to be affected in bipolar disorders, even during euthymia. However, the social cognitive profile of this group of disorders remains to be ascertained, given that such a broad neuropsychological construct has not been systematically examined in bipolar subjects across different tasks. The aim of this study was to quantify the magnitude of patient-control differences for distinct social cognition assessment instruments: the Hinting Task, the Eyes Test, Faux Pas, the Mayer-Salovey-Caruso Emotional Intelligence Test, and emotional labeling using visual stimuli. METHOD: Effect sizes were extracted from studies chosen according to more stringent criteria than previously used in systematic reviews on the topic and pooled by means of meta-analytical procedures. RESULTS: No significant patient-control differences were found for the recognition of three basic emotions (happiness, sadness, and anger). Small but significant effect sizes favoring healthy controls (Hedges׳ g<0.5) were noted for emotional intelligence, the Hinting Task, the Eyes Test, and the recognition of fear, disgust, and surprise. A medium effect size (Hedges' g=0.58) was noted for the Faux Pas Test. LIMITATIONS: The possible effects of other neurocognitive impairments on social cognitive performance could not be explored. CONCLUSION: On average, small-to-moderate differences may exist between euthymic bipolar disorder subjects and healthy controls regarding social cognitive performance, with mental state decoding being more preserved than mental state reasoning. The influence of clinical and neurocognitive variables, which may play an important role in the social cognitive outcomes of these patients, deserves further clarification.