Meta-analyses of cognitive functioning in euthymic bipolar patients and their first-degree relatives

BACKGROUND: Previous work suggests that impairments in executive function and verbal memory in particular may persist in euthymic bipolar patients and serve as an indicator of genetic risk (endophenotype). METHOD: A systematic review of the literature was undertaken. Effects sizes were extracted from selected papers and pooled using meta-analytical techniques. RESULTS: In bipolar patients, large effect sizes (d>0.8) were noted for executive functions (working memory, executive control, fluency) and verbal memory. Medium effect sizes (0.5相似文献   

Heritability of cognitive functions in families with bipolar disorder.

Bipolar disorder is highly heritable. Cognitive dysfunctions often observed in bipolar patients and their unaffected relatives implicate that these impairments may be associated with genetic predisposition to bipolar disorder and thus fulfill the criteria of a valid endophenotype for the disorder. However, the most fundamental criterion, their heritability, has not been directly studied in any bipolar population. This population-based study estimated the heritability of cognitive functions in bipolar disorder. A comprehensive neuropsychological test battery and the Structured Clinical Interview for DSM-IV were administered to a population-based sample of 110 individuals from 52 families with bipolar disorder. Heritability of cognitive functions as assessed with neuropsychological test scores were estimated using the Solar package. Significant additive heritabilities were found in verbal ability, executive functioning, and psychomotor processing speed. Genetic contribution was low to verbal learning functions. High heritability, in executive functioning and psychomotor processing speed suggest that these may be valid endophenotypic traits for genetic studies of bipolar disorder.     

Cognition following acute tryptophan depletion: difference between first-degree relatives of bipolar disorder patients and matched healthy control volunteers

BACKGROUND: Serotonergic circuits have been proposed to mediate cognitive processes, particularly learning and memory. Cognitive impairment is often seen in bipolar disorders in relation to a possible lowered serotonergic turnover. METHODS: We investigated the effects of acute tryptophan depletion (ATD) on cognitive performance in healthy first-degree relatives of bipolar patients (FH) (N= 30) and matched controls (N= 15) in a placebo-controlled, double-blind cross-over design. Performance on planning, memory and attention tasks were assessed at baseline and 5 h after ATD. RESULTS: Following ATD, speed of information processing on the planning task was impaired in the FH group but not in the control group. FH subjects with a bipolar disorder type I relative (FH I) showed impairments in planning and memory, independent of ATD. In all subjects, ATD impaired long-term memory performance and speed of information processing. ATD did not affect short-term memory and focused and divided attention. CONCLUSIONS: The results suggest serotonergic vulnerability affecting frontal lobe areas in FH subjects, indicated by impaired planning. Biological vulnerability in FH I subjects is reflected in impaired planning and memory performance. In conclusion, the cognitive dysfunctions in FH subjects indicate an endophenotype constituting a possible biological marker in bipolar psychopathology. Serotonin appears to be involved in speed of information processing, verbal and visual memory and learning processes.     

Neurocognitive deficits in first-episode schizophrenic patients and their first-degree relatives.

Some neuropsychological abilities, particularly those affecting memory, attention and executive function, are impaired amongst both schizophrenic patients and their unaffected relatives, implying that these deficits are at least partly genetic in origin. However neuropsychological performance can be altered by medication, and has rarely been examined in first onset, drug naive patients. The objective of this study was to determine whether selected neurocognitive abilities are impaired in first-onset schizophrenic patients and their relatives compared to controls. We examined attention and speed of information processing, memory and learning, verbal function, visuoconstructive abilities and executive function in 207 first-episode schizophrenic patients (163 of whom were drug na?ve), 322 of their first-degree relatives and 133 unrelated normal controls. The data were subjected to multilevel modeling to compare neurocognitive performance between schizophrenic probands, relatives and controls while taking into account potential correlations among members of the same family; age, gender, and years of education were included as covariates. Of the three groups, schizophrenic patients performed poorest at all neuropsychological tests, suggestive of a broad range of neurocognitive deficits. Their first-degree relatives showed a narrower pattern of poor performance at Digit Symbol, Digit Span, Trail Making, Verbal Fluency test, Tower of Hanoi, and WCST-M tests. Our findings show that selected neurocognitive deficits especially attention and executive function are impaired in the families of schizophrenic patients. These patterns of neurocognitive deficits may represent "endophenotypes" denoting varying degrees of vulnerability to schizophrenia and may be of value in future molecular genetic studies.     

A meta-analysis of cognitive deficits in euthymic patients with bipolar disorder

BACKGROUND: A number of studies have reported evidence of cognitive deficits in euthymic bipolar patients. Qualitative reviews of the literature have indicated impairments in executive functions and declarative memory are most consistently reported. However, not all primary studies conducted to date have had sufficient power to detect statistically significant differences and there have been few attempts to quantify the magnitude of impairments. This review aims to combine data from available studies to identify the profile of neuropsychological deficits in euthymic bipolar patients and quantify their magnitude. METHOD: Systematic literature review and meta-analysis. RESULTS: Large effect sizes (d>or=0.8) were noted for aspects of executive function (category fluency, mental manipulation) and verbal learning. Medium effect sizes (0.5相似文献   

Cognitive and motor features in elderly people with bipolar disorder

BACKGROUND: Although elderly people will represent one third of the bipolar population in a few years, data about cognitive and motor features in these patients are very scarce. The aim of this study was to compare the cognitive and motor functioning between elderly euthymic patients with bipolar disorder (BD) and healthy controls, as well as to determine the degree of correlation with psychosocial functioning. METHODS: Euthymic older adults with BD (n=20) and healthy controls (n=20) were evaluated with traditional clinical instruments and measures of exposure to psychotropic drugs and extrapyramidal symptoms. All subjects completed an extensive neuropsychological battery. RESULTS: Patients with BD had more extrapyramidal symptoms and worse performance than healthy controls in psychomotor speed, verbal memory, and executive functions even after controlling sub-clinical symptomatology. These findings were not associated with age at onset or length of illness or with current pharmacological exposure. Psychosocial functioning correlated negatively with performance in psychomotor speed and executive function, and with extrapyramidal symptoms. LIMITATIONS: The small sample size and cross-sectional design. CONCLUSIONS: Older adult patients with BD in a euthymic state could have a similar cognitive and motor profile to that described in younger euthymic bipolar patients. Cognitive-motor disturbances may help to explain impairments in daily functioning among elderly patients with bipolar disorder during remission.     

Further antinociceptive effects of myricitrin in chemical models of overt nociception in mice

Neurocognitive de?cits are recognized as core features of schizophrenia. The aim of this study was to compare the cognitive performance of antipsychotic, drug-naive patients with first-episode schizophrenia (FES patients) to their healthy siblings and to healthy controls from the Han Chinese population for exploring potential endophenotypes for the early detection of schizophrenia. A battery of cognitive assessment tools was used to measure seven cognitive domains in matched groups consisting of 56 subjects each. Cognitive tests included the grooved pegboard test (GPT), the category fluency test (CFT), the trail making test A (TMT-A), the Wechsler memory scale-III spatial span test (WMS-III SST), the Hopkins verbal learning test-revised (HVLT-R), the brief visuospatial memory test-revised (BVMT-R), the paced auditory serial addition test (PASAT), and the Wisconsin card sorting test-64 cards version (WCST-64). The performances of FEP patients were inferior to normal controls on all neuropsychological tests, while siblings were lower than healthy controls in many of the same tasks. Patients’ performances were lower than siblings’ on all tests except for the CFT, the WMS-III SST backward test, and four subtests of the WCST-64. Our data suggest that FEP patients exhibited pronounced impairment of fine motor skills, speed of processing, attention, verbal memory, visual memory, and executive function, while siblings exhibited deficits intermediate between those of schizophrenic patients and the control group. Semantic fluency function and executive function may be potential endophenotypes for the early diagnosis of schizophrenia.     

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.     

Different trait markers for schizophrenia and bipolar disorder: a neurocognitive approach.

BACKGROUND: The aim of this study was to assess visual information processing and cognitive functions in unaffected siblings of patients with schizophrenia, bipolar disorder and control subjects with a negative family history. METHODS: The siblings of patients with schizophrenia (N = 25), bipolar disorder (N = 20) and the controls subjects (N = 20) were matched for age, education, IQ, and psychosocial functioning, as indexed by the Global Assessment of Functioning scale. Visual information processing was measured using two visual backward masking (VBM) tests (target location and target identification). The evaluation of higher cognitive functions included spatial and verbal working memory, Wisconsin Card Sorting Test, letter fluency, short/long delay verbal recall and recognition. RESULTS: The relatives of schizophrenia patients were impaired in the VBM procedure, more pronouncedly at short interstimulus intervals (14, 28, 42 ms) and in the target location task. Marked dysfunctions were also found in the spatial working memory task and in the long delay verbal recall test. In contrast, the siblings of patients with bipolar disorder exhibited spared performances with the exception of a deficit in the long delay recall task. CONCLUSIONS: Dysfunctions of sensory-perceptual analysis (VBM) and working memory for spatial information distinguished the siblings of schizophrenia patients from the siblings of individuals with bipolar disorder. Verbal recall deficit was present in both groups, suggesting a common impairment of the fronto-hippocampal system.     

Neurocognitive function in users of MDMA: the importance of clinically significant patterns of use

BACKGROUND: Use of MDMA (ecstasy), a serotonin neurotoxin, has been associated with memory impairment and psychological dysfunction. This study examined cognitive functioning in abstinent MDMA users and MDMA-naive controls. METHOD: Participants completed measures of intelligence, motor function, attention, memory span, verbal fluency, immediate and delayed verbal memory, and working memory. They were also assessed for the presence of psychopathology. In addition to comparing cognitive function in MDMA users relative to controls, the possibility that clinically dysfunctional MDMA use increases the risk of cognitive impairment was examined. RESULTS: MDMA users exhibited relative deficits in mnemonic and executive functions. Additionally, users that met DSM-IV substance use disorder criteria for lifetime MDMA abuse or dependence exhibited a number of additional deficits relative to those who did not meet these criteria. CONCLUSION: These findings suggest that clinically dysfunctional, rather than purely recreational, MDMA use is associated with cognitive impairment. Future research studies of diverse samples of users may shed light on the mechanisms that underlie these differences.     

Cognitive profile of fragile X premutation carriers with and without fragile X-associated tremor/ataxia syndrome

Fragile X-associated tremor/ataxia syndrome (FXTAS) develops in a subset of fragile X premutation carriers and involves gait ataxia, action tremor, Parkinsonism, peripheral neuropathy, autonomic disorders, and cognitive impairment. The study was designed to define the nature of cognitive deficits affecting male premutation carriers with and without FXTAS. A sample of 109 men underwent motor, cognitive, genetic, and neurologic testing, as well as brain magnetic resonance imaging. Subjects were classified into 3 groups: (a) asymptomatic premutation carriers, (b) premutation carriers with FXTAS, and (c) normal controls. Men with FXTAS performed worse than controls on mental status, intelligence, executive cognitive functioning (ECF), working memory, remote recall of information, declarative learning and memory, information processing speed, and temporal sequencing, as well as 1 measure of visuospatial functioning. Language and verbal comprehension were spared. Asymptomatic carriers performed worse than controls on ECF and declarative learning and memory. This comprehensive examination of cognitive impairment in male premutation carriers suggests that FXTAS involves substantial executive impairment and diffuse deficits in other cognitive functions. Longitudinal research currently underway will provide insight into the progression of the disorder.     

Cognitive functioning in a population-based sample of young adults with a history of non-psychotic unipolar depressive disorders without psychiatric comorbidity

BACKGROUND: There is evidence for cognitive dysfunction in unipolar depression among middle-aged and elderly patients, but cognitive functioning among depressed young adults has scarcely been systematically investigated. The aims of the present study were to examine cognitive functioning among depressed young adults identified from the general population and to determine whether cognitive deficits vary as a function of different disorder characteristics, such as severity and age at onset. METHODS: Performance in verbal and visual short-term memory, verbal long-term memory and learning, attention, processing speed, and executive functioning was compared between a population-based sample of 21-35-year-olds with a lifetime history of non-psychotic unipolar depressive disorders without psychiatric comorbidity (n=68) and healthy controls derived from the same population (n=70). RESULTS: Depressed young adults were not found to be impaired in any of the assessed cognitive functions, except for some suggestion of mildly compromised verbal learning. Nevertheless, younger age at depression onset was associated with more impaired executive functioning. LIMITATIONS: The results may slightly underestimate of the true association between depression and cognitive impairments in the young adult population due to possible dropout of participants. Additionally, the problem of multiple testing was not entirely corrected. CONCLUSION: The findings from this study indicate that a lifetime history of non-psychotic unipolar depressive disorders among young adults without psychiatric comorbidity may be associated only with minimal cognitive deficits, even when some residual depressive symptoms are prevalent. However, early-onset depression may represent a more severe form of the disorder, associated with more cognitive dysfunction.     

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.     

Emotion-induced memory dysfunction in borderline personality disorder

Introduction. Although emotional dysregulation is a core problem in borderline personality disorder (BPD), few neuropsychological studies have evaluated the impact of emotion. The present study aimed at the comprehensive investigation of verbal memory functions with and without emotionally relevant interference in BPD. BPD patients were expected to perform as well as healthy subjects in standard memory tasks but to show fewer capacities to control for emotionally negative interference.

Methods. 47 patients with BPD and 70 healthy control subjects participated. An experimental task assessed verbal memory with respect to standard and emotionally relevant and neutral interference learning conditions. Applied standard tests covered working memory, delayed memory, and word fluency.

Results. Memory performances of BPD patients were impaired when negatively valenced interference was conducted but normal in all other conditions. These results remained stable after controlling for comorbid major depression and posttraumatic stress disorder.

Discussion. The present findings suggest no general impairment of verbal memory functions in BPD but control and inhibition of interference by emotionally significant material seem to be disturbed.     

Successful computer-assisted cognitive remediation therapy in patients with unipolar depression: a proof of principle study

BACKGROUND: Despite increasing awareness of the extent and severity of cognitive deficits in major depressive disorder (MDD), trials of cognitive remediation have not been conducted. We conducted a 10-week course of cognitive remediation in patients with long-term MDD to probe whether deficits in four targeted cognitive domains, (i) memory, (ii) attention, (iii) executive functioning and (iv) psychomotor speed, could be improved by this intervention. METHOD: We administered a computerized cognitive retraining package (PSSCogReHab) with demonstrated efficacy to 12 stable patients with recurrent MDD. Twelve matched patients with MDD and a group of healthy control participants were included for comparison; neither comparator group received the intervention that involved stimulation of cognitive functions through targeted, repetitive exercises in each domain. RESULTS: Patients who received cognitive training improved on a range of neuropsychological tests targeting attention, verbal learning and memory, psychomotor speed and executive function. This improvement exceeded that observed over the same time period in a group of matched comparisons. There was no change in depressive symptom scores over the course of the trial, thus improvement in cognitive performance occurred independent of other illness variables. CONCLUSIONS: These results provide preliminary evidence that improvement of cognitive functions through targeted, repetitive exercises is a viable method of cognitive remediation in patients with recurrent MDD.     

Are there attentional deficits in people putatively at risk for affective disorders?

BACKGROUND: Schizophrenia is associated with attentional dysfunctions. In bipolar disorder, there is also evidence for sustained attention deficits. Therefore, we hypothesized that risk for bipolar disorder but not for unipolar depression might be associated with attentional abnormalities as well. METHOD: Using the Hypomanic Personality Scale (HPS) and the Rigidity Scale, we defined three groups: bipolar at-risk (n=42), unipolar at-risk (n=34), and control (n=37). All completed the d2 Test and the Continuous Performance Test (CPT). RESULTS: There was no evidence for overall attentional deficits in people at risk for affective disorders. However, reduced sensitivity, i.e., less discrimination between targets and nontargets, was observed in people at risk for bipolar disorders who also displayed schizotypy. LIMITATIONS: We only looked at selective and sustained attention and did not assess other factors such as memory or executive functions. Additionally, the risk status was only defined by a psychometric indicator and did not include other approaches of defining risk (e.g., first-degree relatives). CONCLUSIONS: Despite some limitations, our results support on one hand the idea that vulnerability for bipolar disorder can be associated with cognitive impairments, but they also highlight that this is not generally the case. Vulnerability for bipolar disorder and schizotypy might be correlated but are not the same.     

Familial cognitive deficits in schizophrenia.

Susceptibility to schizophrenia is considered familial, but the mechanism for transmission has not been found. Since widespread cognitive deficits have been found in patients with schizophrenia, several of these have been proposed as candidate familial endophenotypes that may or may not be predictive of who develops the illness. The current study examines these candidates in individuals from 32 families with at least 2 members having the diagnosis of chronic schizophrenia and normal comparison subjects using an extensive neuropsychological battery. Consistent with previous literature, family members with schizophrenia were significantly impaired on all measures compared with controls. Well relatives demonstrated significantly worse performance on a measure of verbal learning, delayed visual recall, perceptual-motor, and pure motor speed. Expressive and receptive language, but not other functions, were highly correlated within both concordant for schizophrenia and discordant sibling pairs, suggesting that they are familial vulnerability endophenotypes, but not predictive of whom becomes ill. On the other hand, some measures of perceptual-motor, pure motor speed, and frontal/executive functioning were significantly correlated in concordant, but not discordant pairs. These latter correlations suggest that some cognitive measures may be genetically related to the illness.     

Comparison of cognitive functions between first- and multi-episode bipolar affective disorders

BACKGROUND: Cognitive impairment has been commonly found in euthymic patients with bipolar affective disorder (BPAD). Information about onset and course of cognitive deficits is, however, scarce. This study examined the cognitive profile of patients following their first episode of BPAD to determine whether cognitive problems are present at such an early stage. METHODS: Executive functions, memory, IQ, attention-concentration and perceptuomotor function were assessed in 16 euthymic patients with BPAD following their first episodes, and compared with a group of 30 euthymic patients with multiple episodes of BPAD and 20 normal controls. Comparisons were controlled for educational status, current IQ and residual symptoms. RESULTS: First-episode patients were significantly impaired, compared to normal controls, on tests of executive function, sustained attention, perceptuomotor function and IQ. Additionally, their performance was significantly worse than patients with multi-episode BPAD on tests of executive functions, sustained attention and perceptuomotor function. Multi-episode patients had impaired memory, compared to normal controls, and performed poorly on a subtest of executive functions compared to first-episode patients. LIMITATIONS: Sample sizes were small, assessments cross-sectional; all confounds could not be controlled for. CONCLUSIONS: Widespread cognitive disturbances following the first episode of BPAD were found in this study. Whether these disturbances progress following repeated episodes was not entirely clear. Since cognitive impairment can have several adverse consequences for patients of BPAD in terms of disability, quality of life, outcome etc., this must remain a priority area for future research.     

Cognitive functions in depressive disorders: evidence from a population-based study

BACKGROUND: Most of the available evidence on the effects of depression is based on in- and out-patient samples focusing on individuals suffering from major depression. The aims of this study were to examine cognitive functioning in population-based samples and to determine whether cognitive performance varies as a function of depression subgroup. METHOD: Population-based samples (aged 20-64 years) with major depression (N = 68), dysthymia (N = 28), mixed anxiety-depressive disorder (N = 25) and minor depression (N = 66) were examined on a variety of cognitive tasks (i.e. episodic memory, verbal fluency, perceptual-motor speed and mental flexibility). One hundred and seventy-five non-depressed individuals served as controls. RESULTS: The total group of depressed individuals showed impairments in tasks tapping episodic memory and mental flexibility. Of more interest, however, was the observation that the pattern of impairments varied as a function of depression subgroup: the major depression and mixed anxiety-depressive disorder groups exhibited significant memory dysfunction, whereas individuals with dysthymia showed pronounced difficulties in mental flexibility. Minor depression did not affect cognitive performance. Verbal fluency and perceptual-motor speed were not affected by depression. CONCLUSIONS: These results indicate that persons with depressive disorders in the population exhibit cognitive impairments in tasks tapping episodic memory and mental flexibility and that cognitive impairment varies as a function of depressive disorder.