Cognitive impairment in unipolar depression is persistent and non-specific: further evidence for the final common pathway disorder hypothesis

BACKGROUND: Cognitive performance is often impaired in depression, and these impairments can persist even after remission from psychopathological symptoms. However, it is still unclear whether cognitive dysfunction is associated with psychopathological symptoms or represents a genuine disorder. This study examined cognitive performance in acute depression, after remission, and 6 months after remission in order to determine the nature and specificity of cognitive dysfunction as well as its relevance for the further course of depression. METHOD: Assessments of cognitive function and psychopathology were carried out on admission and prior to discharge in 53 in-patients with unipolar depression. Twenty patients were retested 6 months after discharge. To correct for practice effects, 13 healthy subjects were included and assessed twice with the same cognitive tests. RESULTS: In acute depression, we found impairments of information processing/attention, memory, and executive functions. Cognitive impairments remained in a high proportion of patients, even after remission of psychopathological symptoms. After correcting for practice effects, a significant improvement was observed only for some tests of executive functioning. Severity of depression was only weakly correlated with one single cognitive measure, indicating that psychopathological and neuropsychological symptoms are dissociable. Furthermore, we found no evidence for specific cognitive dysfunction. CONCLUSIONS: Our results support the hypothesis that cognitive impairments in depression are neither selective nor specific; they have trait-like features and are, therefore, not merely an epiphenomenon of depression. Whether or not cognitive dysfunction is a prognostic marker for the course of depression remains still an open issue.     

Impaired cognition and decision-making in bipolar depression but no 'affective bias' evident

BACKGROUND: Depression is usually the predominant affective state in bipolar disorder. There are few studies, with discrepant views, examining the extent of cognitive impairment in patients with bipolar depression. To our knowledge, there are no previous studies examining decision-making ability or whether there is an affective attentional bias in bipolar depression. METHOD: We ascertained 24 depressed bipolar I patients from acute psychiatric hospital wards and out-patient clinics and 26 age- and IQ-matched healthy controls. Using computerized tests we evaluated their performance on 'neutral' (non-emotional) cognitive tasks (i.e. memory, attention and executive function) and on novel tasks of emotional cognition (i.e. the decision-making task and the affective go/no-go task). RESULTS: Accuracy measures were significantly impaired on tests of visual and spatial recognition and attentional set-shifting in bipolar depression compared with age- and IQ-matched controls. The quality of decision-making was also significantly impaired in the patients. A mood-congruent attentional bias for 'sad' targets was not evident on the affective go/no-go task. CONCLUSIONS: We found widespread evidence of significant cognitive impairment and impaired quality of decision-making in symptomatically severe depressed bipolar patients. This cognitive impairment may contribute to difficulties with daily living, decision-making and the ability to engage and comply with psychological and drug treatments.     

Neuropsychology of bipolar disorder: a review

BACKGROUND: Bipolar disorder (BD) may be associated with significant and persistent cognitive impairment. The aim of this study was to describe the profile of cognitive deficits in BD at different phases of the illness and determine whether it is different from that of schizophrenia and unipolar (UP) depression. METHODS: A systematic review of the computerised literature of neuropsychological studies of BD published between 1980 and 2000. RESULTS: General intellectual function: this was largely preserved in BD. Impairments when present were limited to acute episodes and to performance scores. Attention: attentional abnormalities were seen in symptomatic BD patients and persisted in remission in measures of sustained attention and inhibitory control. Memory: verbal memory was impaired even in euthymic patients while visuo-spatial memory deficits were variable depending on the tasks used. Executive function: all aspects of executive function (planning, abstract concept formation, set shifting) were impaired in symptomatic BD patients. Performance on executive function tests was sensitive to the presence of even residual symptoms but it may be normal in fully recovered patients with uncomplicated BD. Comparison to other patient groups: no major differences in cognitive profile between BD and UP depression were found. Remitted BD patients out-performed stable schizophrenics on most cognitive measures but this advantage disappeared when they were acutely symptomatic. CONCLUSIONS: Symptomatic BD patients have widespread cognitive abnormalities. Trait related deficits appear to be present in verbal memory and sustained attention. Executive function and visual memory may be also affected at least in some recovered BD patients.     

Attention and executive functions in remitted major depression patients

BACKGROUND: Although deficits in attention and executive functions in patients with Major Depressive Disorder (MDD) are well confirmed [Veiel, H.O.F., 1997. A preliminary profile of neuropsychological deficits associated with major depression. Journal of Clinical and Experimental Neuropsychology 19, 587-603.]. The database regarding the relationship between impairments and the duration of disease or the number of episodes is inconsistent. Furthermore, the role of long-term cognitive impairments in MDD during remitted state is not well understood [Elliott, R., 2002. The neuropsychological profile in primary depression. Taylor and Francis, London, pp. 273-293.]. There is consequently a lack of studies accounting for different courses of illness in the euthymic state and considering the influence of possible attentional deficits on executive performance. METHODS: 40 euthymic patients with MDD diagnosis according to DSM-IV (20 patients with 1-2 episodes and 20 severe depressives with at least three episodes) as well as 20 healthy controls matched for education and age were administered three tests for attention (attentional shift, Stroop task, sustained attention) and three for executive functions (BADS, word fluency, memory span). The methods selected were theory based with regard to an involvement of frontal-subcortical networks in MDD, attention, and executive functions, respectively. RESULTS: Euthymic patients with MDD showed deficits in all tests related to attentional and executive functions compared to healthy controls. The patient groups did not differ with regard to attentional performance. Executive functions in severe depressives were more impaired than in mild depressives. LIMITATIONS: Differing performances of the patient groups in the subtests of the executive test battery (BADS) can only be interpreted to a limited extent. CONCLUSIONS: The results support the assumption that deficits in attention and executive functions in MDD show an increase in trait character and executive function during chronic course. Implications for differential diagnosis and cognitive psychotherapy are discussed.     

Cognitive impairment in remission in bipolar affective disorder

BACKGROUND: Although the traditional view of bipolar affective disorder is that the majority of patients have full remission between episodes, recent evidence suggests that residual cognitive deficits are present. The aim of this study was to determine whether memory and executive deficits were present in a well-defined clinically remitted group of patients. METHODS: This was a case-control study of bipolar patients in remission (N = 18). Subjects had to fulfil stringent clinical criteria for inclusion into the study and had to have been in remission for at least 4 months. Subjects also had no history of substance dependence. The cognitive battery examined memory and executive function. RESULTS: Patients in excellent clinical remission and who reported good social adaptation showed imipairment on tests of visuospatial recognition memory. Accuracy on four tests of executive function was not impaired in patients in remission compared with controls, although response latency on these executive tests was still impaired. CONCLUSIONS: As our group and others have shown, patients with mania and unipolar depression show generalized impairment on tests of memory and executive function. In comparison, this study has demonstrated that patients in remission show a relatively specific impairment in memory with recovery of accuracy measures on executive function task. The increased response latency on the executive tasks suggests a possible small residual impairment. These findings suggest that in netIroanatomical terms, more posterior cortical function (temporal lobe) has not improved but there is at least some recovery of frontal lobe function in remission.     

Depressed mood in multiple sclerosis: relationship to capacity-demanding memory and attentional functioning.

Because it is theorized that depression results in reduced available attentional capacity that, in turn, can explain the impaired performance on capacity-demanding tasks in depressed individuals, the authors predicted that multiple sclerosis (MS) patients with depressed mood would have difficulty with these types of tasks. Twenty depressed mood MS participants were compared with 41 nondepressed mood MS participants and 8 nondepressed mood controls on 5 attentional capacity-demanding clinical memory and attentional tasks and 3 tasks with minimal capacity demands. Depressed mood MS patients performed significantly worse than both nondepressed mood groups on the 3 speeded capacity-demanding attentional measures but not on any of the tasks requiring few capacity demands, supporting the authors' predictions. The possibility that the impaired performance of depressed mood MS patients on speeded attentional tasks was mediated by reduced verbal working memory capacity, impaired deployment of executive strategies that access working memory capacity, or psychomotor slowing is explored.     

Cognitive deficits in narcolepsy

The aim of the investigations was to explore the nature and the severity of cognitive deficits in narcolepsy patients. In two studies, narcolepsy patients were compared with matched control subjects on a range of attention, memory and executive control tasks. Impairments were only observed on attention and executive function tasks which involved higher demands on inhibition or task management abilities whereas relatively routine memory and attention tasks yielded intact performance in narcolepsy patients. The overall pattern of results indicates an executive control deficit in narcolepsy which might be related to a reduction of available cognitive processing resources because of the need for continuous allocation of resources to monitoring and maintenance of vigilance.     

Executive functioning, memory, and learning in phenylketonuria

The executive deficit hypothesis of treated phenylketonuria (PKU) suggests that dopaminergic depletion in the lateral prefrontal cortex leads to selective executive impairment. This was examined by comparing adults with PKU on a lifelong diet with a matched healthy control group. Those with PKU were impaired on selective and sustained attention, working memory (Self-Ordered Pointing), and letter fluency. However, they failed to show differential sensitivity to increased cognitive load on the attentional and working memory tasks, and they did not differ significantly on the remaining executive tasks (rule finding, inhibition, and multitasking). Nor did they differ significantly on recall or recognition memory. Overall, the findings provided little support for the executive deficit hypothesis. A possible explanation in terms of slowed information processing speed is explored.     

Attentional control is partially impaired in obstructive sleep apnea syndrome

Obstructive sleep apnea syndrome is associated with executive cognitive impairment. An important question is whether impairment in executive functioning in obstructive sleep apnea syndrome is independent of dysfunction in attention. Attentional control is a subcomponent of executive functioning that is mediated by frontal lobe processing. In the current study, we investigated whether attentional control is deficient in obstructive sleep apnea syndrome. Attentional control processes were investigated through conflict adaptation and conflict frequency paradigms. These neuropsychological paradigms were assessed by using the Simon, Flanker and Stroop tasks. We additionally analysed post‐error slowing data within these tasks. Error processing is another index of cognitive control that is mediated by frontal lobe functioning. Our sample consisted of 14 healthy adults and 24 patients with untreated moderate–severe obstructive sleep apnea syndrome. Results indicated that attentional control is partially dysfunctional among patients with obstructive sleep apnea syndrome. Attentional control processes were deficient when focal attention (Flanker task) processes were involved, but were intact when observed using the Simon and Stroop tasks. A non‐significant trend in post‐error slowing data suggested that error processing, assessed with the Flanker task, was diminished among patients with obstructive sleep apnea syndrome. These results support the view that obstructive sleep apnea syndrome leads to some amount of frontal lobe dysfunction, and that attentional control and error processing might be particularly affected by obstructive sleep apnea syndrome.     

Stability and course of neuropsychological deficits in manic and depressed bipolar patients compared to patients with Major Depression

BACKGROUND: Neuropsychological functioning varies across different subgroups of patients with affective disorders; yet there have only been a few studies pointing out distinctive neuropsychological profiles and following-up possible changes in this functioning. The aim of this study was to compare neuropsychological functioning across remitted manic or depressed patients with bipolar disorder compared to remitted patients with Major Depression and to explore the course of their cognitive functioning. METHODS: 30 patients with Major Depression, 17 manic bipolar patients, and 22 depressed bipolar patients were assessed for memory, attention, and executive functions using the Auditory Verbal Learning Test (AVLT), the Modified Card Sorting Test (MCST), the Attention Network Test (ANT), and Stop-Signal Task. Neuropsychological assessment was performed at discharge and seven weeks after discharge. RESULTS: The three groups showed different neuropsychological performance at discharge. Regarding selective attention and speed of responding the manic bipolar patients displayed poorer performance than the other two groups. Furthermore, follow-up assessment revealed that although all patient groups demonstrated an overall improvement, some deficits (especially in executive functions) remain. Manic bipolar patients showed again the worst performance. Depressed bipolar patients, however, were not observed to show a poorer outcome than depressed unipolar patients. CONCLUSIONS: This study provides further evidence for distinct neuropsychological functioning in patients with affective disorders depending on their state of illness. Furthermore, it supports the hypothesis that especially manic bipolar patients stay impaired in certain cognitive functions after remission. These findings may be of clinical relevance regarding treatment and prevention programs and emphasize the need of further research investigating stability and course of patients with mood disorders.     

Prevalence, course, and risk factors for executive impairment in patients hospitalized on a general medicine service

The purpose of this study was to determine the prevalence, course, and risk factors for executive impairment in patients hospitalized on a general medicine service. One hundred patients were administered the Executive Interview (EXIT25), the Executive Clock Drawing Task (CLOX), and the Mini-Mental State Examination at admission and discharge. Fifty-two percent of the patients at admission and 56% at discharge had scores indicating impairment on at least one measure of executive function. Median scores on every measure improved during hospitalization. Older patients and those with a cardiac or gastrointestinal disorder were more likely to have executive impairment. The prevalence of executive impairment on general medicine services is high. Although improvement in executive function occurs during hospitalization, many patients remained impaired.     

Comparative cognitive profiles of obsessive-compulsive disorder and schizophrenia

A body of neuropsychological research revealed cognitive impairments in patients suffering from obsessive-compulsive disorder (OCD). Only few investigations addressed the question of how specific these impairments are. The present study compared the performances of 19 subjects with OCD to 19 subjects with schizophrenia and 19 healthy controls on neuropsychological tasks across the main cognitive domains (memory, attention, visual spatial and executive functioning). For purposes of data-reduction, single test measures of the test battery applied were aggregated into eight cognitive domain scores. Contrary to our expectation we found comparable performance profiles of obsessive-compulsive (OC) and schizophrenia subjects across domains with impairments primarily affecting simple attentional skills and memory skills. However, deficits of subjects with schizophrenia were greater in magnitude than those of subjects with OCD on all domains assessed. Elevated depression scores exerted a relevant impact on performance deficits in the OC but not in the schizophrenia sample.     

Personality and outcome in depression: an 18-month prospective follow-up study

BACKGROUND: The relationship between personality and depressive illness is complex. The aim of this study was to assess whether the presence of a personality disorder or high neuroticism (N) scores predicted longer times to discharge or remission onset or higher risks of relapse for a cohort of depressed subjects admitted for the first time. METHODS: 100 consecutive subjects with ICD-10-defined depression were recruited on admission and followed up prospectively over an 18-month period. Personality function was rated using the informant-rated Standard Assessment of Personality in addition to the self-rated Maudsley Personality Inventory. Remission onset and relapse were defined operationally by scores on the Hamilton Rating Scale using recommended criteria. RESULTS: The presence of a personality disorder predicted longer times to remission onset. Personality trait accentuation did not. Higher end N-scores correlated with longer times to remission onset. Neither personality disorder nor high N-scores predicted relapse or discharge risk. Subjects with a personality disorder were treated as aggressively as those without but those with higher N-scores were not. LIMITATIONS: It is an in-patient sample. Fifteen subjects dropped out of follow-up and those who did so were more likely to have met criteria for two or more personality disorder categories or four or more traits from one personality disorder category. The analysis assumes that state and scar effects on N-scores were minimised. Treatment decisions were not controlled. CONCLUSIONS: These findings support the view that the presence of a personality disorder and high N-scores modify the short-term course to remission onset in depression.     

Bipolar I and bipolar II disorder: cognition and emotion processing

BACKGROUND: Cognitive impairment may be part of the endophenotype of bipolar disorder (BP), but little is known about patterns and severity of impairment in BP subgroups and their relation to depression. The same applies to deficits in emotion processing known to be present in BP. METHOD: To explore the relationship between depression and impairment in cognition and emotion processing and the differences between BP subgroups, we assessed 36 (25 BP I and 11 BP II) patients using a cognitive battery and a facial emotion recognition task. RESULTS: BP patients were impaired compared to published norms on memory, naming and executive measures (Binomial Single Proportion tests, p<0.05). Cognitive performance was largely unrelated to depression ratings. Surprise recognition was the only emotion processing impairment in BP patients compared to controls (patients' recognition score 75% v. controls' 89%, p=0.024). Patients with higher depression ratings were more impaired in recognizing expressions of anger (t23=2.21, p=0.037). BP II patients were more impaired than BP I patients in IQ, memory and executive measures (Mann-Whitney tests, p<0.05). Depression severity or exposure to medication or electroconvulsive therapy (ECT) did not explain these differences. CONCLUSIONS: We confirm cognitive impairment and an isolated facial emotion processing deficit in BP patients and suggest that these deficits are largely unrelated to depressive symptoms. Our study also provides evidence that cognitive deficits are more severe and pervasive in BP II patients, suggesting that recurrent depressive episodes, rather than mania, may have a more detrimental and lasting effect on cognition.     

Cognitive functioning in patients with familial bipolar I disorder and their unaffected relatives

BACKGROUND: Impairments in verbal learning and memory, executive functions and attention are manifest in some euthymic patients with bipolar disorder (BPD). However, evidence is sparse on their putative role as aetiologically important genetic vulnerability markers for the disorder. This population-based study examined the cognitive functions of affected and unaffected individuals in families with BPD. The aim was to discover whether any cognitive function would indicate genetic liability to the disorder and could thus be regarded as endophenotypes of BPD. METHOD: A diagnostic interview and a neuropsychological test battery were administered to 32 familial bipolar I disorder patients, 40 of their unaffected first-degree relatives and 55 controls, all representing population-based samples. RESULTS: Unaffected first-degree relatives showed impairment in psychomotor performance speed and slight impairment in executive function. Bipolar patients were impaired in verbal learning and memory compared with unaffected relatives and controls. They also differed from controls in tasks of executive functions. There were no difference between the groups in simple attention and working memory tasks. CONCLUSIONS: Impaired psychomotor performance speed and executive function may represent endophenotypes of BPD, reflecting possible underlying vulnerability to the disorder. Verbal memory impairments appear to be more related to the fully developed disorder.     

Memory impairment in patients with late-onset major depression: the effect of antidepressant therapy

BACKGROUND: Cognitive deficits have been described in patients with major depression (MD), although many aspects remain unsettled. METHOD: During an episode of MD and after remission we used tasks exploring attention, implicit, anterograde and retrograde memory to investigate 48 drug-free patients aged over 50 years without dementia, comparing them with 15 normal volunteer controls (NC). We also evaluated the effect of antidepressant therapy (ADT) with fluoxetine (F) or reboxetine (R) at baseline (T0) and six months later (T6). RESULTS: 42 patients completed the study and 6 dropped out; 33 patients were considered "Remitters" (RP) (17 F pts and 16 R pts). At T0, the entire group of MD patients (MDP) had worse performances than NC in Mini Mental Status Examination (MMSE), Wechsler Memory Scale (WMS) total score (TS), in a few subtests of WMS and in autobiographical memory. RP at T0 had the same impaired tasks and at T6 had significantly improved in MMSE, WMS. TS and many memory tests but they still differed from NC in a few complex tasks requiring more cognitive effort. LIMITATIONS: The effects and differences between F and R must be viewed with caution considering the relatively small sample; only attention and memory were investigated. CONCLUSIONS: Our findings confirm a negative effect of depression on memory with a significant but incomplete improvement after remission and without differences between F and R. We speculate that both a "state" and a "trait" depressive component underlie this memory impairment.     

Attention deficits in patients with narcolepsy

STUDY OBJECTIVES: Although attention problems are presumably responsible for a wide variety of difficulties patients with narcolepsy experience in everyday life, empirical investigation of this issue is scarce. Therefore, we conducted a systematic investigation of different aspects of attention and verbal memory in patients with narcolepsy. DESIGN: Control-group design with comparison of performance in four attention tests--measuring phasic alertness, focused attention, divided attention, and flexible attention--and one verbal memory test. PARTICIPANTS: 19 patients with narcolepsy (NG) and 20 healthy controls (CG) MEASUREMENTS AND RESULTS: The NG showed no deficits in phasic alertness, focused attention, and verbal memory. However, specific deficits occurred in divided and flexible attention. Furthermore, the NG had generally slower and more variable reaction times in all attention tasks. CONCLUSIONS: Our results contradict the hypothesis that attentional impairments in narcolepsy are merely a result of a temporal disturbance of information processing, i.e., deficits can be explained by slowness and variability of performance alone. Rather, deficits in attentional capacity and attentional control also seem to play an important role. Thus, in addition to impairment in the vigilance attention network, results indicate impairment in the executive attention network in patients with narcolepsy.     

A prospective study of the association among impaired executive functioning, childhood attentional problems, and the development of bipolar disorder

Studies of adults who have been diagnosed with, and treated for, bipolar disorder have shown that these patients exhibit impairment on measures of executive functioning. However, it is unclear whether executive dysfunction precedes the diagnosis of bipolar illness, or develops subsequent to its onset. Moreover, investigators have failed to control for the effects of premorbid attentional problems on cognitive performance in these patients. The present authors explored these questions using data from a longitudinal prospective study of individuals at risk for major mood disorder. Results revealed that 67% of participants who met criteria for bipolar disorder in young adulthood showed impairment on the Wisconsin Card Sorting Test (WCST) when they were assessed during adolescence, as compared with 17% of individuals with no major mood diagnosis, and 19% with unipolar depression. This association between performance on the WCST and bipolar illness was not accounted for by high rates of premorbid attentional disturbance. In fact, among participants with early attentional problems, only those who ultimately developed bipolar disorder exhibited impairment on the WCST. Early attentional problems that preceded unipolar depression or no mood disorder were not associated with executive dysfunction.     

Thioredoxin-1 expression regulated by morphine in SH-SY5Y cells

Patients with Parkinson's disease (PD) often show impaired performance on visuospatial attentional tasks. The objective of the study was to examine the attentional function of PD patients performing the attentional network test (ANT). We used the ANT to compare PD patients with healthy controls with respect to the efficiency of 3 anatomically defined attentional networks: the alerting, orienting, and executive control networks. We found that PD patients showed a selective abnormality in the orienting network. Although the alerting and executive control networks apparently remained unaffected, the efficiencies of these networks in patients with PD negatively correlated with the Hoehn-Yahr stage. The results supported the idea that the orienting processes may be more dynamic in PD than in non-PD individuals.     

Working memory and control of attention in persons with Alzheimer's disease and mild cognitive impairment

The goal of the present study was to assess 3 attentional control processes--divided attention, manipulation capacities, and inhibition--in persons with mild cognitive impairment (MCI) and with mild Alzheimer's disease (AD). Manipulation capacities were tested by comparing immediate serial recall with alphabetical-order recall of words. Divided attention was tested with the Brown-Peterson procedure, in which participants divide their attention between simple addition tasks and consonant trigrams over delays. Inhibition was tested with the Hayling procedure, in which participants complete sentences with words irrelevant to their context. Persons with AD showed severe impairment on the 3 attentional control components. Persons with MCI exhibited impaired performance on the Brown-Peterson procedure but normal performance on the other 2 tasks. With AD and MCI participants, there was a negative correlation between general cognitive deficits and impairment on attentional control tasks, indicating that attentional control deficits increase in the MCI/AD continuum. When separating MCI with and without significant subsequent decline, those with subsequent decline showed impaired performance on both the Brown-Peterson procedure and manipulation task. These data suggest that control of attention tasks can track AD at a preclinical stage and that impairment increases gradually during the preclinical phase of AD.