Neurocognitive functions in euthymic bipolar patients

Objective: Meta‐analytic findings support the hypothesis of specific neurocognitive deficits for bipolar patients in the domains of attention, processing speed, memory and executive functions. This study aims to show neurocognitive impairment in euthymic patients with bipolar I disorder compared with healthy controls while detailing the impact of medication side‐effects or illness characteristics on neuropsychological test performance. Method: Forty euthymic patients with bipolar I disorder were compared with 40 healthy controls in a cross‐sectional design. Clinical features and neuropsychological measures of IQ, psychomotor speed, verbal fluency, learning and memory, executive functions and attention were assessed. Results: Patients without antipsychotic drug use did not differ significantly from healthy controls in any neuropsychological measure. Yet patients treated with antipsychotics showed significant underperformance in the domains of semantic fluency, verbal learning and recognition memory as well as executive functions related to planning abilities, even when clinical features were controlled for. Conclusion: The impact of antipsychotic medication needs to be further clarified for euthymic bipolar patients and should be considered when neuropsychological test performance is interpreted.     

The neurocognitive performance of drug‐free and medicated euthymic bipolar patients do not differ

Objective: Although it is established that euthymic bipolar patients have neurocognitive deficits, the influence of medication on their cognitive performance is uncertain and requires investigation. Method: Neuropsychological tests of executive function, memory and attention were performed on 44 prospectively verified, euthymic bipolar I patients, 22 of whom were drug‐free. Residual mood symptom effects were controlled statistically using ancova . Results: Drug‐free and medicated patients differed only in delayed verbal recall (Rey AVLT list A7, drug‐free > medicated), and perseverations during the five‐point test (drug‐free > medicated). When residual mood symptoms were controlled statistically, differences between drug‐free and medicated subjects became insignificant. Medication effect sizes were modest. Significant correlations were found between residual depression scores and measures of verbal learning. Conclusion: Medications did not have any significant influence on neurocognitive performance, suggesting that neurocognitive deficits are an integral part of bipolar disorder.     

Impact of neurocognitive function on academic difficulties in pediatric bipolar disorder: A clinical translation.

BACKGROUND: Previous research has demonstrated that academic and neuropsychological functions are compromised in pediatric bipolar disorder (PBD). Investigation of the degree to which neuropsychological deficits might contribute to those academic problems is needed to aid in the recognition and intervention for school achievement difficulties in PBD. METHODS: A sample of 55 children and adolescents with PBD with and without attention-deficit/hyperactivity disorder (ADHD) (PBD group, n = 28; PBD+ADHD group, n = 27) were tested with a computerized neurocognitive battery and standardized neuropsychological tests. Age range of subjects was 7-17 years, with the mean age of 11.97 (3.18) years. Parents completed a structured questionnaire on school and academic functioning. RESULTS: Logistic regression analyses indicated that executive function, attention, working memory, and verbal memory scores were poorer in those with a history of reading/writing difficulties. A separate logistic regression analysis found that attentional dysfunction predicted math difficulties. These relationships between neuropsychological function and academic difficulties were not different in those with PBD+ADHD than in those with PBD alone. CONCLUSIONS: In PBD neuropsychological deficits in the areas of attention, working memory, and organization/problem solving skills all contribute to academic difficulties. Early identification and intervention for these difficulties might help prevent lower academic achievement in PBD.     

Neuropsychological deficits and functional impairment in bipolar depression, hypomania and euthymia

OBJECTIVE: To examine whether patients with bipolar disorder (BD) have subtle neuropsychological deficits that manifest clinically as cognitive and functional compromise, and this study attempted to determine the pattern of such cognitive deficits and their functional impact across all three phases of BD. We hypothesised that euthymia does not equate with normal neuropsychological function and that each phase has a characteristic pattern of deficits, with disturbance in attention and memory being common across all phases of the illness: (i) bipolar depression - psychomotor slowing and impairment of memory; (ii) hypomania by frontal-executive deficits and (iii) euthymia - a mild disturbance of attention, memory and executive function. METHODS: Twenty-five patients with a diagnosis of bipolar I disorder underwent neuropsychological testing over a period of 30 months in the natural course of their illness while hypomanic and/or depressed and/or euthymic. The results from these assessments were compared with findings from neuropsychological tests conducted on 25 healthy controls matched for age, sex, education and handedness. RESULTS: Initial analyses revealed modest impairment in executive functioning, memory and attention in both hypomanic and depressed bipolar patients, with additional fine motor skills impairment in the latter. Memory deficits, also noted in euthymic patients, were non-significant after controlling for confounding variables, although bipolar depressed patients remained significantly impaired on tests of verbal recall. Bipolar depressed and hypomanic patients differed with respect to the nature of their memory impairment. Depressed patients were more impaired as compared with euthymic patients on tests of verbal recall and fine motor skills. Psychosocial functioning was impaired across all three patient groups, but only in depressed and hypomanic patients did this correlate significantly with neuropsychological performance. CONCLUSIONS: The mood-state-related cognitive deficits in both bipolar depression and hypomania compromise psychosocial function when patients are unwell. In euthymic patients, subtle impairments in attention and memory suggest that an absence of symptoms does not necessarily equate to 'recovery'. The possibility of persistent cognitive deficits in BD is an issue of profound clinical and research interest that warrants further investigation; however, future research needs to adopt more sophisticated neuropsychological probes that are able to better define state and trait deficits and determine their functional impact.     

Neuropsychological functioning in youth with bipolar disorder.

BACKGROUND: Little is known about the neuropsychological status of youth with bipolar disorder (BPD) or whether cognitive deficits in this population are accounted for by comorbidity with attention deficit/hyperactivity disorder (ADHD). We compared neuropsychological and academic functioning of youth with and without DSM-IV BPD, controlling for effects of comorbid ADHD. METHODS: Fifty-seven youth with BPD and 46 healthy control subjects were assessed on a battery of clinical neuropsychological measures including subtests from the Wechsler Intelligence Scales for Children and Adults (Third Editions), the Stroop, the Wisconsin Card Sorting Test, the Rey-Osterreith Complex Figure, an auditory working memory Continuous Performance Test, a measure of verbal learning, and the Wide Range Achievement Test-Third Edition. RESULTS: Bipolar disorder was associated with impairments on subtests reflecting sustained attention, working memory, and processing speed after controlling for ADHD. Additionally, decrements of moderate effect sizes were found for measures of interference control, abstract problem solving, and verbal learning but did not meet criteria for statistical significance. CONCLUSIONS: After controlling for ADHD, youth with BPD show neuropsychological deficits similar to impairments found in adults with the disorder. Further studies are needed to understand the clinical implications of these impairments as well as their role in the underlying risk for pediatric BPD.     

Neurocognitive impairment in euthymic young adults with bipolar spectrum disorder and recurrent major depressive disorder

OBJECTIVE: Patients with remitted major depressive disorder (MDD) and bipolar disorder have persistent impairments in executive function and verbal memory that may represent endophenotypic abnormalities. In this study, we examine neurocognitive function in a sample of euthymic young adults with bipolar spectrum disorder (BSD) (Can J Psychiatry 2002; 47: 125-134) and compare this to well-matched samples of young adults with recurrent MDD and controls. METHOD: Twenty-one euthymic young adult patients with BSD were compared with 42 young adult patients with MDD and 33 controls on a neuropsychological battery assessing attention, executive function and verbal memory. RESULTS: Patients with BSD were significantly more impaired than MDD patients and controls on tests of executive function and verbal memory. MDD patients did not differ significantly from controls on verbal memory function but performed less well on a test of executive function. CONCLUSION: Euthymic young adults with BSD had greater impairment on neurocognitive measures associated with prefrontal and hippocampal function than MDD patients and controls. This is a reflection of a strong bipolar diathesis in the BSD group rather than being a consequence of a more severe unipolar illness.     

Neurocognitive function in clinically stable men with bipolar I disorder or schizophrenia and normal control subjects.

BACKGROUND: Patients with bipolar disorder and schizophrenia have been shown to have neurocognitive deficits when compared with control subjects. The degree and pattern of impairment between psychiatric groups have rarely been compared, especially when subjects are psychiatrically stable. METHODS: Using a standard neurocognitive battery, we compared euthymic outpatients with bipolar disorder (n = 40), stable patients with schizophrenia (n = 20), and subjects with no psychiatric disorder (n = 22). The neurocognitive domains assessed included executive functioning, verbal memory, visual memory, procedural learning, visuoconstructive ability, and language functions. Effect sizes were calculated for each cognitive domain across groups. RESULTS: Stable schizophrenic subjects demonstrated a generalized cognitive impairment across most domains compared with control subjects, with average effect sizes of .9. Euthymic bipolar subjects were significantly impaired compared with control subjects only in executive functioning (Wisconsin Card Sorting Task) and verbal memory (California Verbal Learning Test) domains (effect sizes in the .8-.9 range). Performance on the executive function measures was bimodal among bipolar subjects, suggesting two subgroups: one with relatively normal and one with impaired executive functioning. No significant differences between the bipolar patient group and control subjects were observed in visuoconstructive ability, procedural learning, or language function. CONCLUSIONS: Both euthymic bipolar subjects and relatively stable schizophrenic subjects differed from control subjects in neurocognitive function. Among schizophrenic subjects, a generalized cognitive impairment was observed, and the degree of impairment was greater in the schizophrenic compared with the bipolar subjects. Subjects with bipolar disorder were impaired in two specific domains (verbal memory and executive function). Furthermore, within the bipolar group there was a subset with relatively normal executive functioning and a subset with significant impairment. Possible reasons for the persistence of these neurocognitive deficits in some subjects with bipolar disorder during periods of euthymia are reviewed.     

Neuropsychological profile in bipolar disorder: a preliminary study of monotherapy lithium-treated euthymic bipolar patients evaluated at a 2-year interval

Objective: To investigate the cognitive impairment of a sample of euthymic bipolar patients treated with lithium monotherapy at baseline in a 2‐year longitudinal study. Method: Fifteen DSM‐IV‐TR bipolar out‐patients and 15 healthy‐matched controls were cognitively assessed twice over a 2‐year follow‐up. All patients underwent lithium monotherapy on the first evaluation, and they were euthymic in both evaluations. Cognitive assessment was performed by means of a neuropsychological test battery tapping into the main cognitive domains (executive function, attention, processing speed, verbal memory and visual memory). Results: Repeated measures multivariate analysis of variance showed that the bipolar disorder group was cognitively impaired in the executive domain, attention and processing speed, and such deficits were maintained over time. Conclusion: Our results showed that executive dysfunction is the main long‐term neuropsychological deficit of bipolar disorder. Also, the persistence of these deficits did not seem to be influenced by any clinical or pharmacological variables.     

Cognitive features in euthymic bipolar patients in old age

Objectives:  Studies of cognition in bipolar disorder (BD) have reported impairments in processing speed, working memory, episodic memory, and executive function, but they have primarily focused on young and middle-aged adults. In such studies, the severity of cognitive deficits increases with the duration of illness. Therefore, one would expect more pronounced deficits in patients with longstanding BD. The first aim of the present study was to determine the pattern and the magnitude of cognitive impairment in older euthymic BD patients. The second aim was to explore the interrelationship between these cognitive deficits and determine whether they reflect a single core impairment or the co-occurrence of independent cognitive deficits.
Methods:  Twenty-two euthymic elderly BD patients and 22 controls, matched for gender, age, and education, underwent a comprehensive neuropsychological assessment.
Results:  Compared to controls, BD patients had significantly reduced performance in processing speed, working memory, verbal fluency, and episodic memory, but not in executive function. Hierarchical regression analyses showed that verbal fluency and working memory impairments were fully mediated by changes in processing speed. This was not the case for the episodic memory dysfunction.
Conclusion:  The cognitive profile in older euthymic BD cases is similar to the one described in younger BD cohorts. Our results further suggest that impaired processing speed plays a major role in the cognitive changes observed in BD patients except for deficits in episodic memory, thus providing strong evidence that processing speed and episodic memory are two core deficits in elderly BD patients.     

Impaired verbal memory in young adults with unipolar and bipolar depression

Aim: Early stages of severe mood disorders may be accompanied by neurocognitive changes. Specifically, deficits in verbal memory have been linked to depression in young people. This study examined whether young adults with unipolar compared with bipolar depression showed similar neurocognitive deficits. Methods: A total of 57 young adults (16–32 years) were assessed in this study. Twenty with unipolar and 20 with bipolar depression, all currently depressed, were compared with 17 healthy controls. Neuropsychological assessment included psychomotor speed, attention for routine mental operations, attentional switching, executive control and verbal learning and memory. Results: Both unipolar and bipolar subjects showed significant impairments in verbal memory and attentional switching compared with controls. Both mood disorder groups showed no impairments in psychomotor speed, attention for routine mental operations and executive control. Effects size calculations show that the unipolar and bipolar groups do not differ from each other across a range of neurocognitive measures. Conclusion: Neurocognitive deficits in young adults with current depressive syndromes appear to differ from those typically seen in older patients. In early adulthood, both unipolar and bipolar depression may be distinguished by poor verbal memory, despite intact speed of processing, attention and executive functions. This study suggests that there is utility in neuropsychological testing for young adults in the early stages of severe mood disorders. In order to prevent neurobiological changes inherent to the disease, pharmacological and non-pharmacological interventions that target verbal memory deficits may be optimally delivered early in the disease course.     

Early-onset bipolar disorder: how about visual-spatial skills and executive functions?

Early-onset bipolar disorder is an impairing condition that is strongly associated with genetic inheritance. Neurocognitive deficits are core traits of this disorder which seem to be present in both young and adult forms. Deficits in verbal memory and attention are persistent within euthymic phases in bipolar adults, adolescents, and children. In younger samples, including type I or II and not otherwise specified patients, executive functions are not widely impaired and the existence of visual-spatial deficits remains unclear. The main aim of this study was to compare the neurocognitive performance in young stabilized type I or II bipolar patients and healthy controls. Fifteen medicated adolescents with bipolar disorder and 15 healthy adolescents, matched in age and gender, were compared on visual-spatial skills (reasoning, memory, visual–motor accuracy) and executive functioning (attention and working memory, set-shifting, inhibition) using t-tests and MANCOVA. Correcting for verbal competence, MANCOVA showed that patients performed significantly worse than controls in letters and numbers sequencing (P = 0.003), copy (P < 0.001) and immediate recall (P = 0.007) of the Rey Complex Figure Test, interference of the Stroop Color-Word Test (P = 0.007) and non-perseverative errors on the Wisconsin Card Sorting Test (P = 0.038). Impaired cognitive performance was found in young bipolar patients in working memory, visual-motor skills, and inhibitory control.     

Neurocognitive Function in Pediatric Bipolar Disorder: 3-Year Follow-up Shows Cognitive Development Lagging Behind Healthy Youths

ObjectiveLongitudinal follow-up of neurocognitive functioning in people with pediatric bipolar disorder (PBD) was conducted to characterize the developmental trajectory of cognitive disabilities in this disorder.MethodPatients with PBD (n = 26) and controls (HC; n = 17; mean age 11.66 ± 2.70 years) completed cognitive testing at baseline and then again at a 3-year follow-up. Groups were matched at baseline on age, sex, race, parental socioeconomic status, general intelligence, and single-word reading ability. The PBD group received treatment guided by a standardized medication algorithm during the 3-year period. A battery of neuropsychological tests was administered to assess attention, executive function, working memory, verbal memory, visual memory, and visuospatial perception at baseline and follow-up.ResultsAt baseline and follow-up, the patients showed deficits in all of the examined domains. At 3-year follow-up, developmental progress in executive functions and verbal memory was significantly less in the patients with PBD than in the HC. Improvement on attention, working memory, visual memory, and visuospatial perception tasks in the patients with PBD was comparable to that of the HC, but the patients with PBD remained impaired in all domains relative to the HC.ConclusionsThe developmental delay in some neurocognitive functioning in PBD suggests that the illness disrupts cognitive development with potential lifelong implications for reduced functional ability. Treating bipolar symptoms does not seem to prevent the lag in cognitive development. This dysmaturation may be a direct effect of the illness on brain function, or it may represent indirect consequences of psychopathology or medications on cognitive development.     

Cognitive impairment in schizoaffective disorder: a comparison with non-psychotic bipolar and healthy subjects

Objective: Only a few studies have examined specifically the neuropsychological performance of schizoaffective patients. Method: The sample consisted of 34 euthymic DSM‐IV schizoaffective patients, who were compared with 41 euthymic bipolar patients without history of psychotic symptoms and 35 healthy controls. Euthymia was defined by a score of 6 or less at the Young Mania Rating Scale and a score of 8 or less at the Hamilton Depression Rating Scale for at least 6 months. Patients were compared with several clinical, occupational, and neuropsychological variables such as executive function, attention, verbal and visual memory and the two groups were contrasted with 35 healthy controls on cognitive performance. The three groups were compared using mancova after checking the potential role of several co‐variables. Results: Schizoaffective patients showed greater impairment than controls and bipolar patients, in several domains, including verbal memory, executive function, and attentional measures. Bipolar patients without history of psychosis performed similar to the controls except for verbal fluency. Conclusion: Schizoaffective disorder carries more neurocognitive impairment than non‐psychotic bipolar disorder and more occupational difficulties.     

Cognitive functioning in elderly patients with early onset bipolar disorder

BACKGROUND: Very little is known about the long term cognitive sequelae of bipolar disorder. AIM: To investigate neuropsychological functioning in older euthymic persons with early onset bipolar disorder. METHOD: Fifteen older patients (age >60) with an early onset (<50 years) bipolar-I disorder in a euthymic mood were tested using a comprehensive neuropsychological test battery. Neuropsychological functioning was compared with that of a sex, age and education-matched group of 15 comparison subjects without mood disorders or memory complaints. RESULTS: Bipolar subjects scored lower than comparison subjects on selective attention, verbal memory, verbal fluency and mental effort tests. CONCLUSIONS: The findings suggest that euthymic bipolar patients are impaired across a range of cognitive domains. This could represent a trait-like cognitive disability related to the disease, as the impairments are comparable with those found in younger bipolar patients.     

Neuropsychological functioning in euthymic bipolar disorder: a meta-analysis

OBJECTIVE: Although cognitive deficits are prominent in symptomatic patients with bipolar disorder, the extent and pattern of cognitive impairment in euthymic patients remain uncertain. METHOD: Neuropsychological studies comparing euthymic bipolar patients and healthy controls were evaluated. Across studies, effect sizes reflecting patient-control differences in task performance were computed for the 15 most frequently studied cognitive measures in the literature. RESULTS: Across the broad cognitive domains of attention/processing speed, episodic memory, and executive functioning, medium-to-large performance effect size differences were consistently observed between patients and controls, favoring the latter. Deficits were not observed on measures of vocabulary and premorbid IQ. CONCLUSION: Meta-analytic findings provide evidence of a trait-related neuropsychological deficit in bipolar disorder involving attention/processing speed, memory, and executive function. Findings are discussed with regard to potential moderators, etiologic considerations, limitations, and future directions in neuropsychological research on bipolar disorder.     

Neuropsychological functioning in early onset psychotic disorders

This paper examines whether neuropsychological profiles of youth with early onset psychotic disorders predicted diagnostic or clinical status. Youth with schizophrenia (n=27), bipolar disorder (n=22), and psychosis NOS (n=20) were included. Subjects received an extensive neuropsychological evaluation, including measures of general cognition, attention, memory, and executive functioning. Medication status was not controlled. No statistically significant neurocognitive differences across diagnostic groups were found. Compared to standardized norms, youth with schizophrenia demonstrated deficits in general cognition, verbal learning, recall, sustained effort, and social knowledge. Subjects with bipolar disorder and psychosis NOS exhibited deficits on measures of verbal learning, recall, and sustained effort similar to those of youth with schizophrenia. Neurocognitive deficits in memory and attention appeared to be common among youth with psychotic illnesses, regardless of diagnosis. Those with schizophrenia may have greater global cognitive deficits and problems with social knowledge. Across diagnoses, subjects demonstrated relative strengths on tests that provided them with immediate feedback, and performed most poorly on tests requiring delayed recall.     

Neuropsychological dysfunction in bipolar affective disorder: a critical opinion

Data from the imaging literature have led to suggestions that permanent structural brain changes may be associated with bipolar disorder. Individuals diagnosed with bipolar disorder display deficits on a range of neuropsychological tasks in both the acute and euthymic phases of illness, and correlations between experienced number of affective episodes and task performance are commonly reported. These findings have renewed interest in the neuropsychological profile of individuals with bipolar disorder, with deficits of attention, learning and memory, and executive function, asserted to be present. This paper critically reviews five different potential causes of neurocognitive dysfunction in bipolar disorder: (i) iatrogenic, (ii) acute functional changes associated with depression or mania, (iii) permanent structural lesions of a neurodegenerative origin, (iv) permanent structural lesions that are neurodevelopmental in origin, and (v) permanent functional changes that are most likely genetic in origin. Although the potential cognitive effects of residual symptomatology and long-term medication use cannot be entirely excluded, we conclude that functional changes associated with genetically driven population variation in critical neural networks underpin both the neurocognitive and affective symptoms of bipolar disorder. The philosophical implications of this conclusion for neuropsychology are briefly discussed.     

Cognitive functioning in euthymic bipolar I and bipolar II patients

Objective: There is growing evidence of cognitive impairment as a trait factor in bipolar disorder. The generalizability of this finding is limited because previous studies have either focussed exclusively on bipolar I disorder or have analysed mixed patient groups. Thus, it is still largely unknown whether bipolar II patients perform differently from bipolar I patients on measures of cognitive functioning. Methodology: A total of 65 patients with bipolar I disorder, 38 with bipolar II disorder, and 62 healthy controls participated in the study. Patients had to be euthymic for at least one month. Clinical and demographic variables were collected in a clinical interview and with the Structured Clinical Interview for DSM‐IV. Cognitive functioning was assessed using a neuropsychological battery. Univariate and multivariate analyses of variance were conducted for analyzing possible differences between the groups. Results: The multivariate analysis of covariance (MANCOVA) indicated overall differences in neuropsychological performance between the three groups (Pillai Spur: F 1.96, p = 0.003). Post hoc comparisons revealed that patients with bipolar I disorder showed significantly lower scores in psychomotor speed, working memory, verbal learning, delayed memory, and executive functions than healthy controls. Patients with bipolar II disorder showed significant deficits in psychomotor speed, working memory, visual/constructional abilities, and executive functions compared to controls, but not on verbal learning and delayed memory. The two patient groups did not differ significantly from each other on any domain tested. Conclusion: These results support a similar pattern of cognitive deficits in both subtypes of bipolar disorder.     

Neurocognitive impairments and their relationship with psychosocial functioning in euthymic bipolar II disorder

The aim of this study was to compare neurocognitive functioning between euthymic patients with bipolar I disorder (BDI), bipolar II disorder (BDII), and healthy controls. An additional aim was to estimate the relationship between neurocognitive impairments and psychosocial functioning. Eighty-seven patients with BDI (n = 48) or BDII (n = 39) and 39 healthy controls were included. All subjects completed an extensive neurocognitive battery. Psychosocial functioning was assessed using the General Assessment of Functioning. Patients with BDII performed more poorly than did the controls in measures of psychomotor speed, verbal memory, and executive functioning. Patient groups did not show differences in any of the cognitive measures assessed. The performance in trail-making test B was the only independent predictor of psychosocial functioning in both patient groups. Patients with BDII have cognitive impairments, and this has a negative influence on their functional outcome. Our results bring additional support to the notion that BDII disorder is not a merely mild type of BDI.     

Facial emotion processing in acutely ill and euthymic patients with pediatric bipolar disorder

OBJECTIVE: Past investigations indicate facial emotion-processing abnormalities in pediatric bipolar disorder (PBD) subjects. However, the extent to which these deficits represent state- and trait-related factors is unclear. We investigated facial affect processing in acutely ill and clinically stabilized children with PBD and matched healthy subjects. METHOD: Subjects (N = 86) consisted of unmedicated/acutely ill (n = 29) and medicated/clinically stabilized (n = 29) PBD youths and matched healthy subjects (n = 28) who completed tasks of facial affect identification and differentiation. RESULTS: Subjects with PBD, regardless of clinical and treatment status, showed marked impairments in the ability to correctly identify emotionally intense happy and sad facial expressions, with both groups tending to misjudge extreme facial expressions as being moderate to mild in intensity. However, when differentiating subtle variations of happy or sad expressions, only unmedicated/acutely ill PBD patients performed more poorly than healthy subjects. Younger age at onset was associated with more impaired emotion processing only in the PBD sample. PBD subjects with comorbid attention-deficit/hyperactivity disorder (ADHD) performed more poorly than subjects without ADHD when processing sad facial expressions, but not happy ones. CONCLUSIONS: This study found evidence of both state-of-illness and trait-related deficits in emotion processing in PBD. Treatments are needed to better reduce this impairment and to reduce its developmental impact on interpersonal functioning.