Socio-economic status, functioning and cognition in young versus adult patients newly diagnosed with bipolar disorder and their unaffected relatives; results from a cross-sectional study.

BACKGROUND: Bipolar disorders (BD) figures on top of the World Health Organization classification of disabling disorders. It is unclear if there are socioeconomic, functioning, and cognition differences in young patients newly diagnosed with BD and whether these are different for young and adult patients newly diagnosed with BD. Understanding these differences is important for tailored treatment and support. METHODS: Participant groups included 401 patients newly diagnosed with BD, 145 of their unaffected first-degree relatives (UR) and 209 healthy control individuals (HC). First, we compared socio-economic status, functioning and cognition between young patients newly diagnosed with BD (150), UR (61) and HC (92) (15-25 years) and adult patients newly diagnosed with BD (251), UR (84) and HC (117) (>25 years), respectively. Second, within patients, we compared functioning and cognition between young and adult patients newly diagnosed with BD. RESULTS: In both participant groups, patients newly diagnosed with BD, and to a lesser degree UR, had lower socio-economic status and impaired functioning and cognition compared with HC. Further, young patients newly diagnosed with BD were less functionally impaired, than adults newly diagnosed with BD, whereas cognition did not differ between groups. LIMITATIONS: Applied tools for assessments of functioning and cognition are not validated below age 18. CONCLUSIONS: Overall, lower socio-economic status and impaired functioning and cognition were found both in young and adult patients newly diagnosed with BD and their UR compared with young and adult HC, respectively. Young patients were less functionally impaired than adults, but cognition was similarly impaired.

Assessment of the validity and feasibility of a novel virtual reality test of emotion regulation in patients with bipolar disorder and their unaffected relatives.

BACKGROUND: Emotion dysregulation has been suggested as an endophenotype of bipolar disorder (BD). Neuroimaging studies show aberrant neural activity during emotion regulation in remitted patients with BD and their unaffected first-degree relatives (UR) compared to healthy controls (HC). However, behavioural studies produce conflicting - generally negative findings - possibly due to limited sensitivity and ecological validity of current behavioural paradigms. METHODS: This study aimed to explore emotion regulation in BD (n = 30) and UR (n = 26) relative to HC (n = 47) by using a novel emotion regulation task in virtual reality (VR). Participants were instructed to either react naturally to, or dampen, their emotional response to highly positive or highly negative scenarios presented in first-person 360-degree spherically camera-recorded VR environments. Participants also completed a more traditional computerised task of emotion regulation for comparison purposes. RESULTS: Patients with BD exhibited difficulties with down-regulating their negative emotions in the VR paradigm compared to HC and UR (ps ≤ .04), whereas UR did not differ from HC (p = .97). There was no emotion regulation difference between groups in the more traditional computerised task (ps ≥ .40). LIMITATIONS: The small sample size limits generalisability. CONCLUSIONS: The results suggest trait-related reduced ability to down-regulate negative emotions in BD patients compared to HC in the VR paradigm, but not in the more traditional task of emotion regulation. This may indicate that VR provides a more sensitive measure relative to traditional paradigms. The findings provided no support for aberrant emotional regulation as an endophenotype of BD given the normal emotion regulation performance in UR.

Can magnetic resonance imaging enhance the assessment of potential new treatments for cognitive impairment in mood disorders? A systematic review and position paper by the International Society for Bipolar Disorders Targeting Cognition Task Force.

BACKGROUND: Developing treatments for cognitive impairment is key to improving the functioning of people with mood disorders. Neuroimaging may assist in identifying brain-based efficacy markers. This systematic review and position paper by the International Society for Bipolar Disorders Targeting Cognition Task Force examines the evidence from neuroimaging studies of pro-cognitive interventions. METHODS: We included magnetic resonance imaging (MRI) studies of candidate interventions in people with mood disorders or healthy individuals, following the procedures of the Preferred Reporting Items for Systematic reviews and Meta-Analysis 2020 statement. Searches were conducted on PubMed/MEDLINE, PsycInfo, EMBASE, Cochrane Library, and Clinicaltrials.gov from inception to 30th April 2021. Two independent authors reviewed the studies using the National Heart, Lung, Blood Institutes of Health Quality Assessment Tool for Controlled Intervention Studies and the quality of neuroimaging methodology assessment checklist. RESULTS: We identified 26 studies (N = 702). Six investigated cognitive remediation or pharmacological treatments in mood disorders (N = 190). In healthy individuals, 14 studies investigated pharmacological interventions (N = 319), 2 cognitive training (N = 73) and 4 neuromodulatory treatments (N = 120). Methodologies were mostly rated as 'fair'. 77% of studies investigated effects with task-based fMRI. Findings varied but most consistently involved treatment-associated cognitive control network (CCN) activity increases with cognitive improvements, or CCN activity decreases with no cognitive change, and increased functional connectivity. In mood disorders, treatment-related default mode network suppression occurred. CONCLUSIONS: Modulation of CCN and DMN activity is a putative efficacy biomarker. Methodological recommendations are to pre-declare intended analyses and use task-based fMRI, paradigms probing the CCN, longitudinal assessments, mock scanning, and out-of-scanner tests.

Socio-economic status and functioning in patients newly diagnosed with bipolar disorder and their unaffected siblings - Results from a cross-sectional clinical study.

BACKGROUND: Few studies have reported socio-economic status and functioning in patients newly diagnosed with bipolar disorder (BD) and their unaffected siblings (US). METHODS: Socio-economic status and functioning were compared in a cross-sectional clinical study including 382 patients newly diagnosed with BD, 129 of their US, and 200 healthy control individuals (HC). RESULTS: Socio-economic status was lower in patients newly diagnosed with BD compared with HC within educational achievement, employment status, workability and relationship status (p < 0.001, OR between 0.02 and 0.53). Regarding US and HC, US had lower educational achievement (p < 0.001, OR = 0.27 [0.16; 0.46]), as the only affected socio-economic outcome. Functioning was substantially impaired according to the Functional Assessment Short Test (FAST) (p < 0.001, Cohen's d = 2.12) and Work and Social Adjustment Scale (WSAS) (p < 0.001, Cohen's d = 2.76) in patients newly diagnosed with BD compared with HC. US expressed the same pattern with impaired overall functioning. Within patients, the impaired functioning was associated with a longer illness duration. LIMITATIONS: Patients had an illness duration of 10.5 [IQR: 6.1; 16.2] years, even though they were included shortly after a diagnosis of BD (0.3 [IQR: 0.1; 0.7] years), highlighting the obstacles of research in illness onset of BD. CONCLUSIONS: Patients newly diagnosed with BD, and to a lesser degree their US, exhibit lower socio-economic status and impaired overall functioning. These findings emphasise the importance of early diagnosis, treatment and focus on functional recovery and stress that intervention strategies and further research in high-risk individuals are needed.

Cognition in older adults with bipolar disorder: An ISBD task force systematic review and meta-analysis based on a comprehensive neuropsychological assessment.

OBJECTIVES: We aim to characterize the cognitive performance in euthymic older adults with bipolar disorder (OABD) through a comprehensive neuropsychological assessment to obtain a detailed neuropsychological profile. METHODS: We conducted a systematic search in MEDLINE/Pubmed, Cochrane, and PsycInfo databases. Original studies assessing cognitive function in OABD (age ≥50 years ) containing, at a minimum, the domains of attention/processing speed, memory, and executive functions were included. A random-effects meta-analysis was conducted to summarize differences between patients and matched controls in each cognitive domain. We also conducted meta-regressions to estimate the impact of clinical and socio-demographic variables on these differences. RESULTS: Eight articles, providing data for 328 euthymic OABD patients and 302 healthy controls, were included in the meta-analysis. OABD showed worse performance in comparison with healthy controls, with large significant effect sizes (Hedge's g from -0.77 to -0.89; p < 0.001) in verbal learning and verbal and visual delayed memory. They also displayed statistically significant deficits, with moderate effect size, in processing speed, working memory, immediate memory, cognitive flexibility, verbal fluency, psychomotor function, executive functions, attention, inhibition, and recognition (Hedge's g from -0.52 to -0.76; p < 0.001), but not in language and visuoconstruction domains. None of the examined variables were associated with these deficits. CONCLUSIONS: Cognitive dysfunction is present in OABD, with important deficits in almost all cognitive domains, especially in the memory domain. Our results highlight the importance of including a routine complete neuropsychological assessment in OABD and also considering therapeutic strategies in OABD.

Cognition Assessment in Virtual Reality: Validity and feasibility of a novel virtual reality test for real-life cognitive functions in mood disorders and psychosis spectrum disorders.

There is a pressing need for measures of real-life cognitive functioning in patients with mood or psychotic disorders in clinical settings and treatment trials targeting cognition. We developed the first immersive virtual reality cognition assessment tool, the Cognition Assessment in Virtual Reality (CAVIR), which assesses verbal memory, processing speed, attention, working memory and planning skills in an interactive virtual reality kitchen scenario. This study investigates the sensitivity and validity of the CAVIR for cognitive impairments in mood and psychotic disorders and its association with functioning and neuropsychological performance. Symptomatically stable patients with mood disorders (MD; n = 40) or psychosis spectrum disorders (PSD; n = 41) and healthy control participants (HC; n = 40) completed the CAVIR and standard neuropsychological tests and were rated for clinical symptoms and daily functioning. We found that the CAVIR was sensitive to cognitive impairments across MD and PSD with large effect sizes (MD: F(73) = 11.61, p < .01, ηp2 = 0.14; PSD: F(72) = 18.24, p < .001, ηp2 = 0.19). There was a moderate to strong positive correlation between performance on the CAVIR and on neuropsychological tests (r(121) = 0.58, p < .001), which prevailed after adjustment for age, years of education and verbal IQ (B = 0.67, p < .001). Lower CAVIR scores correlated moderately with more observer-rated and performance-based functional disability (r(121) = -0.30, p < .01 and r(68) = 0.44, p < .001, respectively), also after adjustment for age, years of education and verbal IQ (B = 0.03, p < .001). In conclusion, the CAVIR is a sensitive and valid instrument for measuring real-life cognitive impairments in mood and psychotic disorders. After further psychometric assessments, the CAVIR can be implemented in clinical settings and trials targeting cognition.

Virtual reality assessment of daily life executive functions in mood disorders: associations with neuropsychological and functional measures.

BACKGROUND: Mood disorders are often accompanied by cognitive difficulties that impede patients' functional capacity. However, neuropsychological tests provide limited insight into patients' ability to tackle daily life cognitive challenges. To address this challenge, we investigated the sensitivity and validity of the Jansari assessment of Executive Functions (JEF©) virtual reality test in patients with mood disorders and its associations with functional capacity. METHODS: In total, 21 patients with bipolar disorder or unipolar disorder in full or partial remission and 29 healthy control participants were recruited for the study. Participants attended one test session during which they underwent diagnostic assessments, mood ratings and assessments with JEF©, a battery of standard neuropsychological tests (RAVLT, Trial Making A and B, Fluency tests, letter-number sequencing and RBANS digit span and coding tests) and functional capacity measures (UPSA-B and FAST). RESULTS: Patients showed impaired executive functions on JEF© compared to the control group. Relative to the control group, patients were also impaired on neuropsychological sub-composite scores of executive function, verbal memory and processing speed as well as on a global cognition composite score. In addition, JEF© scores predicted performance on a global cognition composite based on neuropsychological tests, and a performance-based measure of functional capacity. LIMITATIONS: This study had a relatively small sample size and included a mixed group of patients with unipolar or bipolar disorder. CONCLUSIONS: JEF© is a sensitive and valid measure of daily life executive impairments in patients with mood disorders that is associated with functional capacity.

[Assessment and treatment of cognitive impairments in patients with affective disorders].

Many patients with affective disorders have cognitive impairments during remission, which impede their functional recovery and quality of life. The International Society for Bipolar Disorders Targeting Cognition Task Force recommends that clinicians screen for cognitive impairments, when patients are in remission using subjective and objective screening tools. Clinicians should evaluate, whether any impairments are secondary to comorbidity, medication or unhealthy lifestyle. Information to patients and their relatives about how to tackle cognitive impairments can improve daily life functioning.

The Internet-Based Cognitive Assessment Tool: System Design and Feasibility Study.

BACKGROUND: Persistent cognitive impairment is prevalent in unipolar and bipolar disorders and is associated with decreased quality of life and psychosocial dysfunction. The screen for cognitive impairment in psychiatry (SCIP) test is a validated paper-and-pencil instrument for the assessment of cognition in affective disorders. However, there is no digital cognitive screening tool for the brief and accurate assessment of cognitive impairments in this patient group. OBJECTIVE: In this paper, we present the design process and feasibility study of the internet-based cognitive assessment tool (ICAT) that is designed based on the cognitive tasks of the SCIP. The aims of this feasibility study were to perform the following tasks among healthy individuals: (1) evaluate the usability of the ICAT, (2) investigate the feasibility of the ICAT as a patient-administered cognitive assessment tool, and (3) examine the performance of automatic speech recognition (ASR) for the assessment of verbal recall. METHODS: The ICAT was developed in a user-centered design process. The cognitive measures of the ICAT were immediate and delayed recall, working memory, and psychomotor speed. Usability and feasibility studies were conducted separately with 2 groups of healthy individuals (N=21 and N=19, respectively). ICAT tests were available in the English and Danish languages. The participants were asked to fill in the post study system usability questionnaire (PSSUQ) upon completing the ICAT test. Verbal recall in the ICAT was assessed using ASR, and the performance evaluation criterion was word error rate (WER). A Pearson 2-tailed correlation analysis significant at the .05 level was applied to investigate the association between the SCIP and ICAT scores. RESULTS: The overall psychometric factors of PSSUQ for both studies gave scores above 4 (out of 5). The analysis of the feasibility study revealed a moderate to strong correlation between the total scores of the SCIP and ICAT (r=0.63; P=.009). There were also moderate to strong correlations between the SCIP and ICAT subtests for immediate verbal recall (r=0.67; P=.002) and psychomotor speed (r=0.71; P=.001). The associations between the respective subtests for working memory, executive function, and delayed recall, however, were not statistically significant. The corresponding WER for English and Danish responses were 17.8% and 6.3%, respectively. CONCLUSIONS: The ICAT is the first digital screening instrument modified from the SCIP using Web-based technology and ASR. There was good accuracy of the ASR for verbal memory assessment. The moderate correlation between the ICAT and SCIP scores suggests that the ICAT is a valid tool for assessing cognition, although this should be confirmed in a larger study with greater statistical power. Taken together, the ICAT seems to be a valid Web-based cognitive assessment tool that, after some minor modifications and further validation, may be used to screen for cognitive impairment in clinical settings.

Expert Consensus on Screening and Assessment of Cognition in Psychiatry.

During the past two decades, it has been amply documented that neuropsychiatric disorders (NPDs) disproportionately account for burden of illness attributable to chronic non-communicable medical disorders globally. It is also likely that human capital costs attributable to NPDs will disproportionately increase as a consequence of population aging and beneficial risk factor modification of other common and chronic medical disorders (e.g., cardiovascular disease). Notwithstanding the availability of multiple modalities of antidepressant treatment, relatively few studies in psychiatry have primarily sought to determine whether improving cognitive function in MDD improves patient reported outcomes (PROs) and/or is cost effective. The mediational relevance of cognition in MDD potentially extrapolates to all NPDs, indicating that screening for, measuring, preventing, and treating cognitive deficits in psychiatry is not only a primary therapeutic target, but also should be conceptualized as a transdiagnostic domain to be considered regardless of patient age and/or differential diagnosis.

An ethnographic study of the effects of cognitive symptoms in patients with major depressive disorder: the IMPACT study.

BACKGROUND: The manifestation of major depressive disorder (MDD) may include cognitive symptoms that can precede the onset of MDD and persist beyond the resolution of acute depressive episodes. However, little is known about how cognitive symptoms are experienced by MDD patients and the people around them. METHODS: In this international (Brazil, Canada, China, France, and Germany) ethnographic study, we conducted semi-structured interviews and observations of remitted as well as symptomatic MDD patients (all patients self-reported being diagnosed by an HCP and self-reported being on an antidepressant) aged 18-60 years with self-reported cognitive symptoms (N = 34). In addition, participating depressed patients' close family or friends (N = 31) were interviewed. Separately recruited from depressed participants, work colleagues (N = 21) and healthcare providers (HCPs; N = 13) of depressed individuals were interviewed. RESULTS: Key insights were that: (1) patients were generally unaware that their cognitive symptoms were linked to their depression and, instead, attributed these symptoms to negative aspects of their person (e.g., age, separate disease, laziness, exhaustion); (2) cognitive symptoms in MDD appeared to negatively impact patients' social relationships and patients' ability to handle daily tasks at work and at home; (3) patients' cognitive symptoms also impacted relationships with family members and coworkers; (4) patients' cognitive symptoms increased stress and feelings of failure, which in turn seemed to worsen the cognitive symptoms, thereby creating a destructive cycle; and (5) although HCPs recommended that patients re-engage in everyday activities to help overcome their depression, cognitive symptoms seemed to impede such functional recovery. CONCLUSIONS: Taken together, these findings highlight a negative impact of patients' cognitive symptoms on their social functioning, work performance, and quality of life on the people close to them, and consequently on the degree of functional recovery after depression.

Assessment of subjective and objective cognitive function in bipolar disorder: Correlations, predictors and the relation to psychosocial function.

Cognitive dysfunction is prevalent in bipolar disorder (BD). However, the evidence regarding the association between subjective cognitive complaints, objective cognitive performance and psychosocial function is sparse and inconsistent. Seventy seven patients with bipolar disorder who presented cognitive complaints underwent assessment of objective and subjective cognitive function and psychosocial functioning as part of their participation in two clinical trials. We investigated the association between global and domain-specific objective and subjective cognitive function and between global cognitive function and psychosocial function. We also identified clinical variables that predicted objective and subjective cognitive function and psychosocial functioning. There was a correlation between global subjective and objective measures of cognitive dysfunction but not within the individual cognitive domains. However, the correlation was weak, suggesting that cognitive complaints are not an assay of cognition per se. Self-rated psychosocial difficulties were associated with subjective (but not objective) cognitive impairment and both subjective cognitive and psychosocial difficulties were predicted by depressive symptoms. Our findings indicate that adequate assessment of cognition in the clinical treatment of BD and in drug trials targeting cognition requires implementation of not only subjective measures but also of objective neuropsychological tests.