Background: Bipolar disorder is associated with a wide range of neurocognitive deficits including impairment of attention, executive functions, visuospatial processing, and verbal learning and memory (1). Cognitive impairment is not solely associated with manic and depressive episodes, but often persists during the euthymic phases of the illness (2). Previous studies suggest that subsyndromal symptomatology during remission periods may be associated with the maintenance of cognitive impairments (3). Additionally, research suggests that cognitive deficits are more pronounced in individuals with a more severe history of bipolar disorder; e.g. alongside frequency or duration of manic and/or depressive episodes, or number of hospitalisations (4). Neuropsychological deficits are in turn linked to difficulties with psychosocial and vocational functioning (5), and subsequently reduced quality of life (6). The primary aim of this study was to elucidate the influence of subthreshold symptoms of mania or depression on cognitive and psychosocial functioning, in patients with bipolar disorder not currently meeting criteria for a mood episode. It was hypothesised that a higher degree of subsyndromal symptoms would be associated with greater cognitive and functional impairments. The secondary aim was to explore variables related to the course of illness in association with cognitive and psychosocial functioning. Methods: This cross-sectional study recruited 40 participants, aged 18-65, with a diagnosis of bipolar disorder meeting criteria for euthymia, i.e. scoring ≤7 on the Hamilton Depression Rating Scale (HDRS; 7) and Young Mania Rating Scale (YMRS; 8) at a screening interview. Demographic and clinical information were collected in a structured interview. Participants underwent an extensive neuropsychological battery, comprising measures of current IQ (WASI two-subtests Vocabulary and Matrix Reasoning; 9), verbal learning and memory (WMS Verbal Paired Associates VPA I 10), working memory (WAIS-IV Digit Span; 11), attention and processing speed (WAIS-IV Coding 11), phonemic verbal fluency (Delis-Kaplan FAS; 12), and executive functions (Hotel Test; 13). The results of these individual measures were amalgamated into a composite score, serving as an indication of overall cognitive performance. Severity of depression and mania (HDRS and YMRS scores) were assessed alongside daily life functioning (FAST; 14). Participants were divided into two groups based on the intensity of their subthreshold symptoms, using Berk et al.’s (15) criteria for a psychometric distinction between complete and symptomatic remission in bipolar disorder (subsyndromal group = HDRS and/or YMRS≥4; asymptomatic group = HDRS and YMRS≤3). To address the study’s primary aim, independent samples t-tests were used to compare subsyndromal versus asymptomatic groups’ current cognitive performance and psychosocial functioning. Cohen’s d effect sizes were calculated post-hoc to estimate the magnitude of the difference between groups (computed as the mean group difference divided by the pooled standard deviation). Secondly, the association between cognitive outcomes, current mood measures, and prior course of illness measures (i.e. age of onset; illness chronicity; number of episodes; number of hospitalisations; previous pharmacological and psychological therapies) were explored using Pearson correlations. Results: Asymptomatic (n=13) and subsyndromal (n=27) groups did not significantly differ in age, years of education, occupational status, premorbid IQ, age of onset, illness chronicity, number of past depressive or manic episodes, previous hospitalisations, length of current euthymia, medications previously or currently prescribed, and psychological therapies undertaken (Table 1). The sample was predominantly female (77% of asymptomatic, 63% of subsyndromal participants), with a bipolar type I, as opposed to type II, diagnosis (92.3% of asymptomatic, 70.4% of subsyndromal group). Group comparisons of neuropsychological performance revealed a significant advantage for asymptomatic patients in visuospatial processing (Matrix Reasoning; d=1.45; p<0.001), processing speed (Coding; d=0.68; p=0.039), and the composite cognitive score (d=0.75; p=0.036). All other group differences, albeit not significant, consistently demonstrated higher performance in asymptomatic participants (Table 2). However, both groups performed poorly in the Hotel Test of executive function, compared with healthy controls in the test validation study (13). The asymptomatic group also appeared less functionally impaired than the subsyndromal group (FAST; d=1.61; p<0.001). When separating by type of subthreshold symptoms, depression severity (M=4.63; HDRS range: 0-11) was moderately associated with reduced current IQ (WASI; r=-0.368; p=0.037), working memory (Digit Span; r=-0.331; p=0.02), and everyday life functioning (FAST; r=0.557; p<0.001). Subthreshold manic symptoms (M=2.43; YMRS range: 0-9) were marginally correlated with reduced functioning only (FAST; r=0.314; p=0.048). A younger age of mood symptom onset was negatively associated with processing speed (Coding; r=-0.321; p=0.044), verbal fluency (FAS; r=-0.396; p=0.012), and the composite cognitive score (r=-0.367; p=0.02). Number of current psychiatric medications was correlated with deficits in delayed verbal memory recall (VPA II; r=-0.322; p=0.043) and processing speed (Coding; r=-0.41; p=0.009). In contrast, participants who had previously undertaken more psychological therapies showed better at multitasking and time-management skills (Hotel Test; r=-0.388; p=0.013). Conclusions: Despite ostensibly being in recovery from mood episodes, participants in this study exhibited more deficits in several neuropsychological measures if experiencing subthreshold symptoms of depression and/or mania, specifically in the domains of processing speed and perceptual reasoning. Additionally, functional difficulties were more pronounced in the presence of symptomatology, which highlights the existence of a close relationship between cognition and functioning. Both groups performed poorly on an executive function task, potentially suggesting a trait vulnerability in this domain in bipolar disorder that is at least partially independent of mood state. However, exploratory analyses suggest that depressive symptoms were overall more strongly associated with poorer neuropsychological performance than manic symptom severity (16). Subthreshold depressive symptomatology was more frequent (72.5% of participants experienced predominantly depressive symptoms, while only 17.5% presented primarily with manic subsyndromal symptoms) and depression scores varied more widely than for mania; these factors may have minimised potential associations between mood elevation symptoms and cognition. While our results do not demonstrate a causal relationship, we suggest that more conscientious management of subsyndromal depression may enhance patients’ cognition and improve their everyday lives. Our findings may indicate an argument for tightening the definition of euthymia, as patients reporting symptoms in the subthreshold range may in fact be experiencing untreated illness. While causes of neurocognitive dysfunction are likely multi-factorial, both pharmacological and non-pharmacological strategies have the potential to enhance cognition and functioning in people with bipolar disorder.
Strawbridge et al. (Fri,) studied this question.
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