Gender influences the detection of spatial working memory deficits in bipolar disorder

Objective:  Despite evidence that gender may influence neurocognitive functioning, few studies have examined its effects in bipolar disorder (BD) a priori . The aim of this study was to examine how gender influences executive-type functions, which are potentially useful as endophenotypes for BD.
Methods:  The performance of 26 euthymic patients (12 males, 14 females) with DSM-IV BD (20 BD type I and six BD type II) was compared to that of 26 controls (12 males, 14 females) on tests of executive function. Controls were matched to patients on an individual basis for sex, age and premorbid IQ. Tests assessed spatial working memory (SWM), planning, attentional set-shifting and verbal fluency.
Results:  Overall, patients showed deficits in SWM strategy (p < 0.001) and made more SWM errors relative to controls (p < 0.001). These deficits were more apparent in male-only comparisons (both p < 0.001) than in female-only comparisons (both p < 0.05). When examined in isolation, male controls were significantly better at performing the SWM task than female controls (both p < 0.05). This pattern was not observed in the patient cohort: male patients had poorer strategy scores than female patients (p < 0.05), but made a similar number of SWM errors.
Conclusions:  These findings provide evidence that gender can influence the detection of SWM deficits in the euthymic phase of BD, as the sex-related disequilibrium in SWM identified in healthy controls was disrupted in BD.     

Clinical predictors of functional outcome of bipolar patients in remission

Objectives:  A number of studies have now shown that subjects with bipolar disorder (BD) have significant psychosocial impairment during interepisode intervals. This study was carried out to assess the level of functioning as well as to identify potential predictors of functioning in a well-defined, euthymic bipolar sample.
Methods:  The study included 71 euthymic bipolar patients and 61 healthy controls. The Functioning Assessment Short Test (FAST) was used to assess multiple areas of functioning such as autonomy, occupational functioning, cognitive functioning, interpersonal relationships, financial issues, and leisure time. Multivariate analysis was used to determine the global and specific clinical predictors of outcome.
Results:  Sixty percent (n = 42) of the patients had overall functional impairment (defined as a FAST total score > 11) compared to 13.1% (n = 8) of the control group (p = 0.001). Bipolar patients showed a worse functioning in all the areas of the FAST. Only four variables—older age, depressive symptoms, number of previous mixed episodes, and number of previous hospitalizations—were associated with poor functioning, on a linear regression model, which accounted for 44% of the variance ( F  =   12.54, df = 58, p < 0.001).
Conclusions:  A substantial proportion of bipolar patients experience unfavorable functioning, suggesting that there is a significant degree of morbidity and dysfunction associated with BD, even during remission periods. Previous mixed episodes, current subclinical depressive symptoms, previous hospitalizations, and older age were identified as significant potential clinical predictors of functional impairment.     

Impaired verbal memory and otherwise spared cognition in remitted bipolar patients on monotherapy with lithium or valproate

Objectives:  Patients with bipolar disorder have been reported to have neurocognitive deficits; however, it is not known whether the cognitive dysfunctions are state-dependent or a stable trait. Lithium and valproate, 2 of the most widely used mood stabilizers in the treatment of bipolar disorder, have also been associated with cognitive impairment. However, the degree and pattern of neurocognitive impairment in euthymic bipolar patients on either monotherapy with lithium or valproate have not been compared before in depth.
Methods:  We compared 17 euthymic outpatients with bipolar disorder (BD) on lithium monotherapy to 11 euthymic outpatients with BD on valproate monotherapy and 29 comparison subjects using tests measuring immediate verbal memory and executive functions in addition to 3 subtests of the Wechsler Adult Intelligence Scale Revised. The groups were similar in terms of level of education, duration and severity of illness, and gender distribution. Patients on lithium monotherapy were older than patients on valproate and healthy controls. Mood symptoms as assessed by standardized scales were mild to non-existent in both patient groups.
Results:  Immediate verbal memory was impaired in both patient groups compared to controls, where the main effect of age was not significant. No significant differences could be found on the other cognitive measures.
Conclusions:  Both lithium and valproate may be associated with immediate verbal memory impairment, sparing other cognitive functions. Presence of a similar verbal memory deficit in the lithium and valproate groups suggests that this deficit might be intrinsic to BD or that the 2 medications influence immediate verbal memory similarly. Larger samples of remitted bipolar patients on monotherapy should be studied for more precise conclusions.     

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.     

Cognitive function and serum levels of brain-derived neurotrophic factor in patients with bipolar disorder

Objectives:  Brain-derived neurotrophic factor (BDNF) is an important contributor to the pathophysiology of bipolar disorder (BD), and abnormalities in the BDNF-signaling system may be implicated in the cognitive decline observed in BD patients. We aimed to investigate serum BDNF levels in BD patients and its relation to neurocognitive function.
Methods:  We measured serum BDNF levels using an enzyme-linked immunosorbent assay method in 65 euthymic type I BD patients and 50 healthy controls, and administered a neuropsychological test battery to assess attention and mental control, perceptual-motor skills, executive functions, verbal fluency and abstraction, visuospatial attention, and memory.
Results:  We found no significant differences regarding serum BDNF levels in BD patients and healthy controls. We found significant positive associations between serum BDNF levels and illness duration, and manic and depressive episodes in female BD patients only. Serum BDNF levels were lower in patients medicated with antipsychotics and/or lithium, whereas patients on valproate and/or antidepressants showed higher serum BDNF levels. Patients performed significantly worse on 11 out of 16 neurocognitive tests as compared to controls. We found a significant positive association between serum BDNF levels and a test of verbal fluency in both BD patients and controls.
Conclusions:  Present results support the hypothesis that BDNF normalizes with mood stabilization and pharmacological treatment. Our findings in young and physically healthy patients with short illness duration and few mood episodes may explain the lack of association between serum BDNF levels and neurocognitive performance, even though cognitive performance in patients was overall significantly worse as compared to healthy controls.     

Norepinephrine and serotonin imbalance in the locus coeruleus in bipolar disorder

Objectives:  Abnormalities in norepinephrine (NE) and serotonin (5-HT) are implicated in bipolar disorder (BD). We examined 5-HT input and NE neurons in the locus coeruleus (LC, the NE nucleus that innervates the forebrain) in BD by quantifying immunoreactivity (IR) for tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH), the biosynthetic enzymes for NE and 5-HT, respectively.
Methods:  Six suicides with BD were compared to matched normal controls and unipolar major depression suicides, using immunocytochemistry with computer-assisted quantification of immunoreactivity.
Results:  Depressed bipolar suicides had 26.7 ± 1.3% of LC area occupied by the TH immunoreactive (TH-IR) process, while controls had 50.7 ± 8% (p = 0.002) and unipolar depressed suicides had 50.3 ± 2.5% (p = 0.003). In bipolars, these processes did not stain as darkly (1.9 ± 0.5 × background) as controls (2.9 ± 0.9 × background; p = 0.01) or unipolars (2.9 ± 0.6 × background; p = 0.002). Bipolar suicides also had less TPH-IR processes in the LC (11.7 ± 10%) compared with controls (32.8 ± 8.8%; p = 0.01) or unipolar suicides (30.3 ± 8%; p = 0.02). The TPH-IR intensity did not differ between groups.
Conclusions:  We found less TH-IR and TPH-IR in the LC in depressed bipolar suicides, but not unipolar suicides, suggesting that both NE and 5-HT activity is lower in BD. Studies during manic or euthymic states will determine whether these changes are mood state dependent.     

Bipolar I patients with and without a history of psychotic symptoms: Do they differ in their cognitive functioning?

Recently, many reports have consistently demonstrated cognitive deficits in patients with bipolar disorder (BD), but their relationship with symptomatology, specifically psychotic symptoms, remains unclear. Our main hypothesis was that a history of hallucinations and/or delusions in the course of BD-I is associated with severe cognitive deficits. We investigated several cognitive functions (memory, attention, verbal fluency and executive functions) in 18 BD-I patients with a history of psychotic symptoms (HPS+), 17 BD-I patients without a history of psychotic symptoms (HPS-), 33 schizophrenic patients and 26 healthy control subjects. Both groups of BD-I patients were more impaired than the normal controls in attention, verbal memory, verbal fluency and executive functions. Only HPS+ BD-I patients showed more difficulties in completing the Stroop test than nonpsychotic bipolar patients. Nevertheless, after adjustment for the effects of current psychopathology, this difference disappeared. Schizophrenic subjects showed worse performance than BD-I subjects in verbal memory and verbal fluency. These results suggest that a history of psychotic symptoms in bipolar I disorder may not be associated with more cognitive deficits. Further research on euthymic bipolar patients with and without HPS is required to confirm these findings.     

Deficits in tasks of executive functioning that mimic real-life scenarios in bipolar disorder

Torralva T, Strejilevich S, Gleichgerrcht E, Roca M, Martino D, Cetkovich M, Manes F. Deficits in tasks of executive functioning that mimic real‐life scenarios in bipolar disorder. Bipolar Disord 2012: 14: 118–125. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Background: A growing body of evidence suggests that patients with bipolar disorder (BD) have cognitive impairments even during euthymic periods. The main cognitive domains affected are verbal memory, attention, and executive function. Nevertheless, some studies suggest that at least a subgroup of euthymic patients demonstrates intact executive functioning in classic neuropsychological tests, which could be due to the lack of real‐life, or ecological validity. Objective: In this study, we highlight the usefulness of incorporating more ecological tests of executive function in assessment batteries in order to detect specific cognitive deficits in BD patients with otherwise normal performance in standard executive tests. Methods: Nineteen euthymic BD patients and 15 healthy controls completed a standard neuropsychological battery assessment and two experimental tasks (the Multiple Errands Test–Hospital Version and the Hotel Task) to measure executive functioning in highly demanding cognitive settings that mimic real‐life scenarios. Results: No significant differences were found between the groups’ demographic variables. We found, as predicted, that the group of euthymic BD patients who had control‐comparable performance in classic executive tasks showed important deficits in more ecological tasks of executive functioning of the type that mimic real‐life scenarios. Conclusions: Together, these data suggest that the inclusion of ecological tests in the assessment of BD patients can contribute to providing a more realistic cognitive profile of this patient population, which will undoubtedly allow for a better design of therapeutic and rehabilitation strategies that can help patients to minimize impact in real‐life settings.     

Impaired working memory monitoring in euthymic bipolar patients

OBJECTIVES: Converging evidence suggests that patients with remitted bipolar disorder (BD) have a persistent cognitive deficit in the executive control of working memory (WM). However, the component operations that contribute to this deficit remain unclear. The aim of the present study was to further profile the nature and specificity of WM impairment in euthymic BD. METHODS: Fifty DSM-IV-confirmed patients with euthymic BD and demographically matched controls completed a modified version of the Self-Ordered Pointing Task (SOPT) and the Cambridge Neuropsychological Test Automated Battery Pattern Recognition Test along with traditional executive and WM tasks [Stroop, initial letter Verbal Fluency (FAS), Trail-Making, Digits Forwards and Backwards]. Prospective clinical ratings over one month prior to testing confirmed that patients were euthymic at test. Absence of basal hypercortisolaemia was confirmed by serial saliva sampling. RESULTS: Error analysis revealed that whilst patients made more errors on the SOPT overall, they were no more likely to perseverate than controls. Patients' erroneous responses did not proliferate across trials, suggesting that proactive interference did not contribute to their poor performance, but serial position effects were evident where patients' errors clustered towards the end of a trial. No differences were found on the recognition memory test, in WM capacity, or on two of the three traditional executive procedures (FAS and Trail-Making). However, patients' Digits Backwards was impaired. CONCLUSIONS: These data suggest that patients with BD have a deficit in their ability to monitor the contents of WM. This deficit is not an epiphenomenon of mood, but may be due to enduring brain dysfunction, integral to bipolar illness.     

Neurocognitive impairment and psychosocial functioning in bipolar II disorder

Solé B, Bonnin CM, Torrent C, Balanzá‐Martínez V, Tabarés‐Seisdedos R, Popovic D, Martínez‐Arán A, Vieta E. Neurocognitive impairment and psychosocial functioning in bipolar II disorder. Objective: There is a growing body of evidence on neurocognitive impairment in euthymic bipolar patients, but this issue has been studied mostly in bipolar I disorder, data on bipolar II (BD‐II) are scant and discrepant. The two aims of this study were to ascertain whether strictly defined euthymic BD‐II patients would present neurocognitive disturbances and to evaluate their impact on functional outcome. Method: Forty‐three BD‐II patients and 42 demographically and educationally matched healthy subjects were assessed with a comprehensive neuropsychological test battery and with the Social and Occupational Functioning Assessment Scale (SOFAS). The euthymia criteria were reduced (Hamilton Rating Scale for Depression score ≤6 and a Young Mania Rating Scale score ≤6) to minimize the influence of subdepressive symptomatology on cognition and functioning. Results: BD‐II patients showed a significantly lower performance on several measures of attention, learning and verbal memory, and executive function compared with healthy controls. The presence of subthreshold depressive symptomatology and one measure related to executive function (Trail Making Test, part B) was the variables that best predicted psychosocial functioning measured with the SOFAS. Conclusion: This report provides further evidence that euthymic BD‐II patients present cognitive impairment which may impact psychosocial functioning.     

Can body mass index help predict outcome in patients with bipolar disorder?

Objective:  Several studies have reported higher prevalence of obesity in patients suffering from bipolar disorder (BD). To study the relation of elevated body mass index (BMI) in patients with BD more closely, we investigated differences in sociodemographic, clinical, and medical characteristics with respect to BMI, with the hypothesis that BMI is related to prognosis and outcome.
Methods:  We measured the BMI of 276 subjects of a tertiary care sample from the Maritime Bipolar Registry. Subjects were 16 to 83 years old, with psychiatric diagnoses of bipolar I disorder (n = 186), bipolar II disorder (n = 85), and BD not otherwise specified (n = 5). The registry included basic demographic data and details of the clinical presentation. We first examined the variables showing a significant association with BMI; subsequently, we modeled the relationship between BMI and psychiatric outcome using structural equation analysis.
Results:  The prevalence of obesity in our sample was 39.1%. We found higher BMI in subjects with a chronic course (p < 0.001) and longer duration of illness (p = 0.02), lower scores on the Global Assessment of Functioning Scale (p = 0.02), and on disability (p = 0.002). Overweight patients had more frequent comorbid subthreshold social (p = 0.02) and generalized anxiety disorders (p = 0.05), diabetes mellitus type II (p < 0.001), and hypertension (p = 0.001). Subjects who achieved complete remission of symptoms on lithium showed significantly lower BMI (p = 0.01).
Conclusions:  Our findings suggest that BMI is associated with the prognosis and outcome of BD. Whether this association is causal remains to be determined.     

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.     

Wisconsin Card Sorting Test performance in bipolar disorder: effects of mood state and early course

Objectives:  Patients experiencing an acute mood episode of bipolar disorder are impaired on cognitive tests of executive functioning when compared with healthy subjects. However, it is unclear to what extent executive dysfunction exists (i) during syndromal remission, when mood symptoms are attenuated, and (ii) during the early course of bipolar disorder.
Methods:  To clarify these issues, we examined retrospective data on a standard clinical version of the Wisconsin Card Sorting Test (WCST) administered to 25 euthymic, 21 first-episode manic or mixed, and 34 multiple-episode manic or mixed patients with bipolar I disorder, and 48 healthy comparison subjects. These groups were compared on five WCST measures of executive ability.
Results:  On all but one measure the healthy group's performance was superior to that of both first- and multiple-episode groups. The euthymic group outperformed the multiple-episode group, but performed similarly to the first-episode group on all but one measure. The healthy and euthymic groups did not differ significantly on any measure. Effect sizes ranged from small to moderate.
Conclusions:  Executive dysfunction may be a mediating vulnerability indicator of bipolar disorder that is strongly related to mood state, but only modestly related to chronicity of illness during the early disease course.     

Neuropsychological functions in patients with bipolar I and bipolar II disorder

Objectives:  The literature reports persistent cognitive impairments in patients with bipolar disorder even after prolonged remission. However, a majority of studies have focused only on bipolar I disorder (BP-I), primarily because bipolar II disorder (BP-II) is often underdiagnosed or misdiagnosed. More attention should be paid to the differences between BP-I and BP-II, especially the aspects of neuropsychological functioning. We examined the different neuropsychological functions in BP-I and BP-II patients and compared them with those of healthy controls.
Methods:  The study included 67 patients with interepisode bipolar disorder (BP-I: n = 30; BP-II: n = 37) and 22 healthy controls compared using a battery of neuropsychological tests that assessed memory, psychomotor speed, and certain aspects of frontal executive function.
Results:  The BP-I group performed poorly on verbal memory, psychomotor speed, and executive function compared to the BP-II and control groups. Both bipolar groups performed significantly less well than the control group on measures of working memory and psychomotor speed, while the BP-II group showed an intermediate level of performance in psychomotor speed compared to the BP-I and control groups. There was no difference between the groups on visual memory.
Conclusions:  BP-I was characterized by reduced performance in verbal memory, working memory, psychomotor speed, and executive function, while BP-II patients showed a reduction only in working memory and psychomotor speed. Cognitive impairment existed in both subtypes of bipolar disorder, and was greater in BP-I patients. Rehabilitation interventions should take into account potential cognitive differences between these bipolar subtypes.     

Theory of mind and neurocognitive functioning in patients with bipolar disorder

Wolf F, Brüne M, Assion H‐J. Theory of mind and neurocognitive functioning in patients with bipolar disorder. Bipolar Disord 2010: 12: 657–666. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. Objectives: Studies into social cognition in psychiatric disorders have recently been expanded to address the question of whether or not theory of mind (ToM), i.e., the ability to represent one’s own and others’ mental states, is impaired in bipolar affective disorder (BPD). Results have been mixed so far, mainly due to possible confounding effects of neurocognition, as well as clinical factors such as acuity and current mood. Here, we explored ToM and its associations with neurocognitive functioning in BPD. Methods: A total of 33 patients with bipolar I disorder (of whom 12 were currently depressed, 10 manic, and 11 remitted) and 29 healthy controls were assessed using a test battery that was identical to the one that was used in previous studies in schizophrenia, comprising diverse neurocognitive tasks, including measures of intelligence, executive functioning, and ToM tasks. Results: The bipolar disorder patient group as a whole and all three clinical subgroups were impaired on all measures of ToM relative to controls, but did not differ from each other in most ToM scores. Patients’ poorer performance on executive tasks did not fully explain ToM differences between patients and controls, suggesting a partially selective ToM deficit in BPD. Conclusions: Patients with BPD are impaired in ToM, partially independent of other cognitive dysfunctions and current mood.     

Sexually dimorphic features of vermis morphology in bipolar disorder

Objectives:  The cerebellar vermis is increasingly implicated in bipolar disorder (BD). In this study, we investigated vermis morphology in BD using a quantitative volumetric analysis.
Methods:  Volumes for total vermis and vermis subregions V1 (lobules I–V), V2 (lobules VI–VII), and V3 (lobules VIII–X) were calculated using high-resolution structural magnetic resonance imaging obtained from 44 individuals with BD (25 females and 19 males) and 43 healthy comparison (HC) subjects (26 females and 17 males). Total vermis volumes were compared between the BD and HC groups. Potential effects of vermis subregions and clinical features were explored.
Results:  Total vermis volumes were significantly larger in the BD group than in the HC group (p = 0.02). There was a significant group-by-sex interaction (p = 0.02). Total vermis volumes were significantly larger in males with BD than HC males (p = 0.004); vermis volumes did not differ significantly between females with and without BD (p = 0.95). Subregion analyses showed a trend-level interaction between diagnosis and subregion (p = 0.07) in which subregion V1 volumes were significantly larger in BD participants (p = 0.001), with differences primarily driven by males (p = 0.001).
Conclusions:  Our findings demonstrate increases in cerebellar vermis volumes in males with BD. These findings support the presence of structural alterations in the cerebellar vermis in BD and furthermore the influence of sex on such changes.     

The effect of previous psychotic mood episodes on cognitive impairment in euthymic bipolar patients

OBJECTIVES: Cognitive dysfunctions in several domains were proposed to be trait markers of bipolar patients. The aim of this study was to evaluate the effect of previous psychotic features on neuropsychological measures, including sustained attention, in remitted bipolar patients. METHODS: The study participants were 40 euthymic psychotic, 25 non-psychotic bipolar I patients and 30 healthy control subjects. Participants were assessed with a battery of neuropsychological tests targeting attention, executive functions, psychomotor speed, verbal learning and memory. RESULTS: Euthymic psychotic bipolar patients performed worse than controls on most of the measures, after controlling for the confounding effects of education, age and residual symptoms. Non-psychotic patients were also impaired on tasks of attention, fluency and psychomotor speed. 'Number of Wisconsin Card Sorting Test (WCST) categories' achieved was the only measure on which psychotic patients performed significantly worse compared to non-psychotic patients. Differences among patient groups were not explained by illness severity measures. The duration of illness was related to slowness in psychomotor speed tasks. Verbal memory deficits may be related to serum lithium levels and age of onset of disease. CONCLUSIONS: Deficits in cognitive flexibility may be a candidate for being a trait marker of psychotic features among bipolar patients. However, verbal fluency, psychomotor speed and sustained attention deficits may be candidates for vulnerability indicators of bipolar disorder in general.     

Theory of mind and facial emotion recognition in euthymic bipolar I and bipolar II disorders

The main aim of this study was to compare patients with euthymic bipolar I (BDI) and bipolar II (BDII) disorders and healthy controls in measures of social cognition. Additional aims were to explore the association between social cognition performance with neurocognitive impairments and psychosocial functioning. Eighty one euthymic patients with BDI or BDII and 34 healthy controls were included. All subjects completed tests to assess verbal memory, attention, and executive functions. Additionally theory of mind (ToM) and facial emotion recognition measures were included. Psychosocial functioning was assessed with the GAF. Both groups of patients had lower performance than healthy controls in ToM, and a lower recognition of fear facial expression. When neurocognitive impairments and exposure to medications were controlled, performance in ToM and recognition of fear facial expression did not allow predicting if a subject was patient or healthy control. Social cognition measures not enhance variance beyond explained by neurocognitive impairments and they were not independent predictors of psychosocial functioning. Impairments in facial emotion recognition and ToM are mediated, at least partly, by attention-executive functions deficits and exposure to psychotropic medications. Likewise, social cognition measures did not contribute to variance beyond neurocognitive impairments.     

Neurocognitive function in unaffected first-degree relatives of patients with bipolar disorder: a preliminary report

OBJECTIVE: Patients with remitted bipolar disorder (BD) have persistent impairments in neuropsychological function, particularly in the domains of executive control and declarative memory [Br J Psychiatry 180 (2002) 293]. If these were the phenotypic expression of genetic vulnerability to BD, then healthy subjects with a genetic predisposition to BD would be expected to display the same deficits. This study, therefore, examined neuropsychological function in healthy first-degree relatives of patients with BD. METHOD: A cross-sectional design was employed to compare the performance of 17 unaffected first-degree relatives of BD patients and 17 demographically matched controls on a range of neuropsychological tests. RESULTS: Relatives were significantly impaired on Backward Digit Span, Spatial Span and on tasks of visuospatial declarative memory in comparison with controls. Psychomotor performance and verbal declarative memory were intact, as were non-working memory aspects of executive performance. CONCLUSION: The selective deficits in executive control and declarative memory exhibited by relatives in this study have previously been reported in euthymic BD patients suggesting they may be useful endophenotypic markers of genetic vulnerability to BD.     

The longitudinal course of cognition in older adults with bipolar disorder

Objectives:  Epidemiological studies suggest that elders with bipolar disorder (BD) may be at increased risk for dementia compared to the general population. We sought to investigate whether older adults with BD would present with more cognitive dysfunction than expected for their age and education, and whether they would experience a more rapid cognitive decline over three-year prospective follow-up.
Methods:  Thirty-three subjects age ≥ 50, mean (SD) age 69.7 (7.9) years, with BD I (n = 28) and II (n = 5) had neuropsychological examination at baseline and longitudinally over three years. All subjects were administered the Dementia Rating Scale (DRS) when euthymic. Thirty-six mentally healthy comparators ('controls'), equated on age and education, were selected from ongoing studies in our research center examining the longitudinal relationship between late-life mood disorders and cognitive function.
Results:  Compared to mentally healthy comparators, subjects with BD performed significantly worse on the DRS at baseline [mean (SD) 135.2 (4.7); n = 33 versus 139.5 (3.3); n = 36], and over follow-up [131.9 (7.7); n = 14 versus 139.1 (3.4); n = 22]. There was a group-by-time interaction between the subjects with BD and the controls [group × time: F (1,64) = 5.07, p = 0.028].
Conclusions:  In our study, older adults with BD had more cognitive dysfunction and more rapid cognitive decline than expected given their age and education. Cognitive dysfunction and accelerated cognitive decline may lead to decreased independence, with increased reliance on family and community supports, and potential placement in assisted-living facilities.