Cognitive impairments in depression

Depressed patients perform poorly on memory tests. This may reflect a failure to employ encoding strategies that facilitate recall or a generalized inability to allocate cognitive effort to more difficult tasks. Inpatients with major depression or personality disorders and age- and IQ-matched normal controls were administered an automatic frequency of occurrence test and verbal paired associated recall and recognition memory tests. There was no difference in frequency judgments among the subject groups. Both depressed and personality disordered groups recalled and recognized fewer words than normal subjects, with the depressed subjects tending to recall and recognize the fewest words. There was a strong effect of task difficulty on memory performance but this effect was consistent across subject groups. These findings suggest that the poorer performance of depressed patients on memory tests reflect basic memory impairments rather than a general inability to allocate cognitive effort to more demanding tasks. However, these impairments may not be specific to depression but may reflect general effects of psychopathology on memory.     

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.     

Cannabis abuse is associated with decision-making impairment among first-episode patients with schizophrenia-spectrum psychosis

BACKGROUND: Cannabis use appears to be a risk factor for schizophrenia. Moreover, cannabis abusers show impaired decision-making capacities, linked to the orbitofrontal cortex (OFC). Although there is substantial evidence that first-episode schizophrenia patients show impairments in cognitive tasks associated with the dorsolateral prefrontal cortex (DLPFC), it is not clear whether decision making is impaired at schizophrenia onset. In this study, we examined the association between antecedents of cannabis abuse and cognitive impairment in cognitive tasks associated with the DLPFC and the OFC in a sample of first-episode patients with schizophrenia-spectrum disorders.MethodOne hundred and thirty-two patients experiencing their first episode of a schizophrenia-spectrum psychosis were assessed with a cognitive battery including DLPFC-related tasks [backward digits, verbal fluency (FAS) and the Trail Making Test (TMT)] and an OFC-related task [the Iowa Gambling Task (GT)]. Performance on these tasks was compared between patients who had and had not abused cannabis before their psychosis onset. RESULTS: No differences were observed between the two groups on the performance of any of the DLPFC-related tasks. However, patients who had abused cannabis before their psychosis onset showed a poorer total performance on the gambling task and a lower improvement on the performance of the task compared to no-abusers. CONCLUSIONS: Pre-psychotic cannabis abuse is associated with decision-making impairment, but not working memory and executive function impairment, among first-episode patients with a schizophrenia-spectrum psychosis. Further studies are needed to examine the direction of causality of this impairment; that is, does the impairment make the patients abuse cannabis, or does cannabis abuse cause the impairment?     

Distinct manifestations of executive dysfunction in aged rats

Different components of executive function such as working memory, attention, and cognitive flexibility can be dissociated behaviorally and mechanistically; however, the within-subject influences of normal aging on different aspects of executive function remain ill-defined. To better define these relationships, young adult and aged male F344 rats were cross-characterized on an attentional set-shifting task that assesses cognitive flexibility and a delayed response task that assesses working memory. Across tasks, aged rats were impaired relative to young; however, there was significant variability in individual performance within the aged cohort. Notably, performance on the set-shifting task and performance at long delays on the delayed response task were inversely related among aged rats. Additional experiments showed no relationship between aged rats' performance on the set-shifting task and performance on a hippocampal-dependent spatial reference memory task. These data indicate that normal aging can produce distinct manifestations of executive dysfunction, and support the need to better understand the unique mechanisms contributing to different forms of prefrontal cortical-supported executive decline across the lifespan.     

Executive function and attention deficit hyperactivity disorder: stimulant medication and better executive function performance in children.

BACKGROUND: Executive function deficits have been reported repeatedly in children with Attention Deficit Hyperactivity Disorder (ADHD). Stimulant medication has been shown to be effective in improving cognitive performance on most executive function tasks, but neuropsychological tests of executive function in this population have yielded inconsistent results. Methodological limitations may explain these inconsistencies. This study aimed to measure executive function in medicated and non-medicated children with ADHD by using a computerized battery, the Cambridge Neuropsychological Test Automated Battery (CANTAB), which is sensitive to executive function deficits in older patients with frontostriatal neurological impairments. METHODS: Executive function was assessed in 30 children with ADHD: 15 were stimulant medication naive and 15 were treated with stimulant medication. These two groups were compared to 15 age, sex and IQ matched controls. RESULTS: The unmedicated children with ADHD displayed specific cognitive impairments on executive function tasks of spatial short-term memory, spatial working memory, set-shifting ability and planning ability. Impairments were also seen on spatial recognition memory and delayed matching to sample, while pattern recognition memory remained intact. The medicated children with ADHD were not impaired on any of the above executive function tasks except for deficits in spatial recognition memory. CONCLUSIONS: ADHD is associated with deficits in executive function. Stimulant medication is associated with better executive function performance. Prospective follow-up studies are required to examine these effects.     

Intact implicit probabilistic sequence learning in obstructive sleep apnea

Obstructive sleep apnea (OSA) belongs to the sleep-related breathing disorders and is associated with cognitive impairments in learning and memory functions. The impairments in attention-demanding cognitive functions such as working memory and executive functions are well established in OSA; however, it remains unknown if less attention-demanding implicit sequence learning is affected. In the present study, we examined implicit sequence learning in OSA to probe the functional integrity of this fundamental learning mechanism. We used listening span to measure complex working memory capacity and the alternating serial reaction time (ASRT) task, which enables us to measure general skill learning and sequence-specific learning separately. Twenty OSA patients and 20 healthy controls participated in this study. Our data show dissociation between working memory and implicit sequence learning in OSA. Surprisingly, OSA patients showed preserved general skill and sequence-specific learning in spite of the possible hypoxia and sleep restriction. In contrast, working memory performance measured by listening span task was impaired in the OSA group. This finding suggests selective susceptibility of more attention-demanding cognitive functions in this patient population, while implicit learning remains intact. Our findings draw attention the fact that disordered sleep may have less impact on the integrity of structures connected to implicit sequence learning.     

Impaired object recognition following prolonged withdrawal from extended-access cocaine self-administration

Cocaine addicts have a number of cognitive deficits that persist following prolonged abstinence. These include impairments in executive functions dependent on the prefrontal cortex, as well as deficits on learning and memory tasks sensitive to hippocampal function. Recent preclinical studies using non-human animals have demonstrated that cocaine treatment can produce persistent deficits in executive functions, but there is relatively little evidence that treatment with cocaine produces persistent deficits in performance on hippocampal-dependent tasks. We recently demonstrated that extended (but not limited) access to self-administered cocaine is especially effective in producing persistent deficits on a test of cognitive vigilance, and therefore, we used this procedure to examine the effects of limited or extended access to cocaine self-administration on recognition memory performance, which is sensitive to hippocampal function. We found that extended access to cocaine produced deficits in recognition memory in rats that persisted for at least 2 weeks after the cessation of drug use. We conclude that the deficits in learning and memory observed in cocaine addicts may be at least in part due to repeated drug use, rather than just due to a pre-existing condition, and that in studying the neural basis of such deficits procedures involving extended access to self-administered cocaine may be especially useful.     

A deficit in attentional set-shifting of violent offenders

BACKGROUND: Recent brain imaging studies suggest that proneness to violence and antisocial behaviour may be associated with dysfunction of the prefrontal cortex. The present study. therefore, examined aspects of prefrontally guided executive functions in a group of criminal violent men. METHODS: Violent offenders undergoing forensic psychiatric examination by court order undertook computerized tasks for planning, visual working memory and attentional set-shifting from the Cambridge Neuropsychological Test Automated Battery. Their performance was compared to that of subjects with marginal mental retardation and normal controls. RESULTS: Violent offenders performed well on tasks for spatial and figurative working memory, as well as on a test for planning. A marked impairment was observed in the attentional set-shifting task: offenders made significantly more errors than the other groups when required to shift attention from one perceptual dimension to another. Reversal learning was also deficient. Correlational analyses within the offender group revealed that poor performance on the perceptual shift problem was associated with fewer errors in tasks for working memory and planning. CONCLUSIONS: The present results suggest that violent offenders show dual impairments in inhibitory cognitive control. First, they are deficient in shifting attention from one category to another. Secondly, the ability to alter behaviour in response to fluctuations in the emotional significance of stimuli is compromised. These deficits might constitute cognitive reflections of the biological prefrontal alterations observed in this group of people.     

Neuropsychological functioning in stimulant-naive boys with hyperkinetic disorder

BACKGROUND: Although children with hyperkinetic disorder and/or attention deficit hyperactivity disorder (ADHD) show disordered executive neuropsychological functioning, the nature of these changes remains controversial. Additionally, impairments in non-executive neuropsychological functioning have been relatively unexplored. Here, the authors describe the neuropsychological functioning of a sample of stimulant drug-naive boys with hyperkinetic disorder on a battery of neuropsychological tasks sensitive to impairments of both executive and non-executive functions. METHOD: Seventy-five stimulant drug-naive boys meeting diagnostic criteria for ICD-10 hyperkinetic disorder were compared with 70 healthy developing controls matched for age but not IQ on computerized tests of neuropsychological functioning from the Cambridge Neuropsychological Test Automated Battery (CANTAB) and a Go/No-Go inhibition task. RESULTS: Boys with hyperkinetic disorder exhibited impairments on tasks with a prominent executive component--working memory, planning, strategy formation, attentional set-shifting and on a reaction time task. However, they were also impaired on tasks without prominent executive components--pattern and spatial recognition, spatial span, delayed matching to sample and paired associates learning. Contrary to predictions, no impairment was observed on the Go/No-Go inhibition task. CONCLUSIONS: Medication-naive boys with hyperkinetic disorder displayed a broad range of neuropsychological impairments. Deficits were demonstrated on tasks with and without prominent executive components. Impairments were not confined to tasks dependent upon frontostriatal functioning, cannot wholly be explained by deficits in inhibitory control, nor can they be attributed to intelligence or previous exposure to stimulant medication.     

Executive functions and cognitive subprocesses in patients with obstructive sleep apnoea

In recent years, special interest has been focused on impairments of executive functions in patients with obstructive sleep apnoea syndrome (OSAS). However, the majority of studies have not clearly separated deficits in executive functions from impairments in other cognitive processes involved in task solving. In the present study, working memory (WM) functions of 20 patients with OSAS were compared with those of 10 age-, sex- and education-matched healthy subjects. Cognitive functions were measured four times a day; each of these measurements was accompanied by an assessment of subjective and objective daytime sleepiness. To separate dysfunctions of WM from those of additionally involved processes, n -back tasks were applied embedded in a reaction-time-decomposition approach. Deficits in n -back tasks could be observed in OSAS patients in accuracy and reaction times. However, the slowing could already be observed in simple reaction time tasks. The drop in 1-back accuracy in the morning was related to daytime sleepiness. During the afternoon, accuracy of OSAS patients dropped in 2-back tasks, an effect which correlated neither with sleepiness nor with the extent of sleep apnoea or oxygen desaturation. In conclusion, our data reflect a complex perspective upon cognitive deficits in OSAS. Cross-group differences in processing time on the higher level WM task appeared to be attributable to slowing at a more elementary cognitive processing level. In contrast, reduced accuracy during the WM task in the OSAS group could not be explained by deficits in more elementary cognitive processes.     

Pretreatment predictors of cognitive deficits in early psychosis

BACKGROUND: Predicting cognitive deficits in early psychosis may well be crucial to identify those individuals most in need of receiving intensive intervention. As yet, however, the identification of potential pretreatment predictors for cognitive performance has been hampered by inconsistent findings across studies. We aimed to examine the associations of functional and clinical pretreatment variables with cognitive functioning after a first psychotic episode. METHOD: One hundred and thirty-one patients experiencing first-episode psychosis were assessed for psychopathology, pre-morbid functioning, duration of illness, age of onset, and family history of psychosis and neurocognitive functioning. Multiple regression analyses were conducted for six basic cognitive dimensions known to be affected in this population: verbal learning, verbal memory, verbal comprehensive abilities, executive functioning, motor dexterity and sustained attention. RESULTS: Pre-morbid functioning was the main predictor for five out of the six basic cognitive domains. Pre-morbid social adjustment difficulties were associated with worse performance in executive functioning, motor dexterity and sustained attention. Academic functioning was associated with verbal comprehension, and verbal learning and memory. Gender, age of onset, duration of untreated psychosis, and family history of psychosis had no or limited value as predictors of neurocognitive outcome. CONCLUSIONS: Poor pre-morbid functioning was related to a worse performance in the six basic cognitive dimensions evaluated; however, this accounted for only a small amount of the explained variance. Cognitive impairment is a prominent feature in patients with early psychosis regardless of favorable prognostic features such as short duration of illness, female gender, later age of onset, and non-family history of psychosis.     

Evidence that specific executive functions predict symptom variance among schizophrenia patients with a predominantly negative symptom profile

Introduction. Although deficits in executive functioning in schizophrenia have been consistently reported, their precise relationship to symptomatology remains unclear. Recent approaches to executive functioning in nonschizophrenia studies have aimed to “fractionate” the individual cognitive processes involved. In this study, we hypothesised that if these processes are fractionable, then particular symptom syndromes may be selectively related to executive deficits. In particular, it was hoped that this approach could clarify whether negative and positive symptoms of schizophrenia are differentially related to particular aspects of executive/attentional functions. Methods. A total of 32 patients with schizophrenia and 16 matched controls were assessed on a series of tasks designed to tap the theoretically derived executive functions of Inhibition, Shifting set, Working memory, and Sustained attention. Results. Negative symptoms were significantly predicted by performance on an “Inhibition” task (Stroop), and not by performance on any other task. Furthermore, for a subgroup of patients with predominantly negative symptoms variance in positive symptoms was only significantly predicted by performance on a set-shifting task (Visual Elevator), and not by performance on other tasks, including inhibition. Conclusions. Our results support the contention that negative symptoms can, at least partly, be conceived of as cognitive behaviours expressing specific executive deficits. Specifically, we discuss the possibility that negative symptoms may, in part, express a failure in response monitoring. We further suggest that the disordered metacognition resulting in positive symptoms may be mediated by cognitive flexibility in patients with a predominantly negative symptom profile.     

Effects of Sleep Deprivation on Dissociated Components of Executive Functioning

Study Objectives:

We studied the effects of sleep deprivation on executive functions using a task battery which included a modified Sternberg task, a probed recall task, and a phonemic verbal fluency task. These tasks were selected because they allow dissociation of some important executive processes from non-executive components of cognition.

Design:

Subjects were randomized to a total sleep deprivation condition or a control condition. Performance on the executive functions task battery was assessed at baseline, after 51 h of total sleep deprivation (or no sleep deprivation in the control group), and following 2 nights of recovery sleep, at fixed time of day (11:00). Performance was also measured repeatedly throughout the experiment on a control task battery, for which the effects of total sleep deprivation had been documented in previously published studies.

Setting:

Six consecutive days and nights in a controlled laboratory environment with continuous behavioral monitoring.

Participants:

Twenty-three healthy adults (age range 22–38 y; 11 women). Twelve subjects were randomized to the sleep deprivation condition; the others were controls.

Results:

Performance on the control task battery was considerably degraded during sleep deprivation. Overall performance on the modified Sternberg task also showed impairment during sleep deprivation, as compared to baseline and recovery and compared to controls. However, two dissociated components of executive functioning on this task—working memory scanning efficiency and resistance to proactive interference—were maintained at levels equivalent to baseline. On the probed recall task, resistance to proactive interference was also preserved. Executive aspects of performance on the phonemic verbal fluency task showed improvement during sleep deprivation, as did overall performance on this task.

Conclusion:

Sleep deprivation affected distinct components of cognitive processing differentially. Dissociated non-executive components of cognition in executive functions tasks were degraded by sleep deprivation, as was control task performance. However, the executive functions of working memory scanning efficiency and resistance to proactive interference were not significantly affected by sleep deprivation, nor were dissociated executive processes of phonemic verbal fluency performance. These results challenge the prevailing view that executive functions are especially vulnerable to sleep loss. Our findings also question the idea that impairment due to sleep deprivation is generic to cognitive processes subserved by attention.

Citation:

Tucker AM; Whitney P; Belenky G; Hinson JM; Van Dongen HPA. Effects of sleep deprivation on dissociated components of executive functioning. SLEEP 2010;33(1):47-57.     

Influence of age and executive functioning on verbal memory of inpatients with depression

BACKGROUND: Despite many studies demonstrating memory and executive impairments in young and old depressed patients, the relationships between age, executive functioning and memory have not been evaluated in depression. The aim of this study was to investigate if older patients were more vulnerable than younger patients to the impact of depression on memory and if the differences between young and old depressed could be related to executive functioning. METHODS: Forty-nine inpatients, with unipolar and bipolar depression, ranging in age from 19 to 72 years were compared with 70 controls on a verbal memory task. Age cut-off of 45 years was used as a categorical variable to divide subjects into subgroups. A subset of patients (n=41) was also evaluated with the modified version of the Wisconsin Card Sorting Test and separated into a non-dysexecutive group and a group of patients with mild-executive impairment. RESULTS: Depressed patients exhibited memory deficits with a pattern of memory failure -- impaired free recall and normal cued recall and recognition -- interpreted as a retrieval problem. Both age and executive function influenced memory performance in depression, however neither group x age interaction nor age x executive status interaction were significant. Multiple regression analysis showed that free recall scores were related to age and psychomotor retardation in depressed patients. CONCLUSION: Age and executive functioning have different influences on the memory performance of depressed patients. Our findings support an 'executive memory decline hypothesis' in young as well as old depressed patients. The memory deficits in depression may be associated with both trait and state factors and raise questions about the long-term cognitive functioning of patients with recurrent affective disorders.     

Within-subjects, parametric manipulations to investigate aging

Parametric manipulation of experimental variables is important for both practical and theoretical reasons. Practically, age-related impairments in memory may be detected only at certain levels of difficulty. If the task is too simple, age-related cognitive impairments may not be sufficient to alter performance. If the task is too difficult, age-related cognitive impairments may not add significantly to the poor performance of younger controls. Thus, some intermediate level of difficulty is necessary to produce behavioral evidence on underlying age-related cognitive changes. Theoretically, parametric manipulations are important to identify the psychological processes responsible for the behavioral alterations. For example, consider the common finding of an age-related impairment in a delayed conditional discrimination task. If that impairment is produced by a primary deficit in recent memory, then the magnitude of the age-related impairment should increase with the length as the delay interval is increased, producing a statistical interaction between the age delay interval. Both the practical and theoretical considerations are illustrated with specific experiments, and have implications for the types of experimental design that can be most effective in demonstrating and explaining age-related changes in learning and memory.     

Features of autonomic cardiovascular control during cognition in major depressive disorder

Previous research has suggested reduced parasympathetic cardiac regulation during cognitive activity in major depressive disorder (MDD). However, little is known about possible abnormalities in sympathetic control and cardiovascular reactivity. This study aimed to provide a comprehensive analysis of autonomic cardiovascular control in the context of executive functions in MDD. Thirty six MDD patients and 39 healthy controls participated. Parameters of sympathetic (pre‐ejection period, PEP) and parasympathetic control (high and low frequency heart rate variability, HF HRV, LF HRV; and baroreflex sensitivity, BRS) as well as RR interval were obtained at rest and during performance of executive function tasks (number‐letter task, n‐back task, continuous performance test, and Stroop task). Patients, as compared to controls, exhibited lower HF HRV and LF HRV during task execution and smaller shortenings in PEP and RR interval between baseline and tasks. They displayed longer reaction times during all conditions of the tasks and more omission errors and false alarms on the continuous performance test. In the total sample, on‐task HF HRV, LF HRV and BRS, and reactivity in HF HRV, LF HRV, and PEP, were positively associated with task performance. As performance reduction arose independent of executive function load of the tasks, the behavioral results reflect impairments in attention and processing speed rather than executive dysfunctions in MDD. Abnormalities in cardiovascular control during cognition in MDD appear to involve both divisions of the autonomic nervous system. Low tonic parasympathetic control and blunted sympathetic reactivity imply reduced physiological adjustment resources and, by extension, provide suboptimal conditions for cognitive performance.     

Neurocognitive deficits in decision-making and planning of patients with DSM-III-R borderline personality disorder

BACKGROUND: Repeated, self-damaging behaviour occurring in the context of borderline personality disorder (BPD) may reflect impairments in decision-making and planning cognition. However, there has been no systematic neuropsychological examination of these particular cognitive functions in patients diagnosed with BPD. Such investigations may improve our understanding of the possible role of brain dysfunction in BPD and improve the characterization of the psychological difficulties associated with this disorder. METHOD: Forty-two psychiatric patients with a diagnosis of DSM-III-R BPD (41 of whom gave a history of self-harm), without a history of specified 'psychoses' or current major affective disorder, were clinically assessed before completing computerized tasks of decision-making and planning previously shown to be sensitive to frontal lobe dysfunction, and tests of spatial and pattern visual recognition memory previously shown to be sensitive to frontal lobe damage and temporal lobe damage respectively. The performance of the BPD patient group was compared with that of a non-clinical control group consisting of 42 subjects. RESULTS: The performance of the BPD patients on the decision-making task was characterized by a pattern of delayed and maladaptive choices when choosing between competing actions, and by impulsive, disinhibited responding when gambling on the outcome of their decisions. BPD patients also showed impairments on the planning task. There was no evidence of impaired visual recognition memory. Additional analyses suggested only limited effects of current medication and history of previous substance use disorder. CONCLUSIONS: These findings suggest that BPD is associated with complex impairments in dissociable cognitive processes mediated by circuitry encompassing the frontal lobes. These impairments may mediate some of the behavioural changes evident in BPD. Further work is needed to examine the specificity of these findings.     

The development of inhibitory control in preschool children: effects of "executive skills" training

As one of several processes involved in the executive functioning of the cognitive system, inhibitory control plays a significant role in determining how various mental processes work together in the successful performance of a task. Studies of response inhibition have shown that although 3-year-old children have the cognitive capacity to learn the rules required for response control, indicated by the correct verbal response, developmental constraints prevent them from withholding the correct response (Bell & Livesey, 1985; Livesey & Morgan, 1991). Some argue that these abulic dissociations are relative to children's ability to reflect on the rules required for response control (Zelazo, Reznick, & Pinon, 1995). The current study showed that repeated exposure to tasks facilitating the acquisition of increasingly complex rule structures could improve inhibitory control (as measured by a go/no-go discrimination learning task), even in children aged 3 years. These tasks included a variant of Diamond and Boyer's (1989) modified version of the Wisconsin Card Sort Task and a simplification of the change paradigm (Logan & Burkell, 1986). It is argued that experience with these tasks increased the acquisition of complex rules by placing demands on executive processes. This includes response control and other executive functions, such as representational flexibility, the ability to maintain information in working memory, the selective control of attention, and proficiency at error correction. The role of experiential variables in the development of inhibitory control is discussed in terms of the interaction between neural development and appropriate executive task experience in the early years.     

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.     

Relationship of behavioural and symptomatic syndromes in schizophrenia to spatial working memory and attentional set-shifting ability

BACKGROUND: Behavioural syndromes (thought disturbance, social withdrawal, depressed behaviour and antisocial behaviour) offer a different perspective from that of symptomatic syndromes on the disability that may be associated with schizophrenia. Few studies have assessed their relationship with neuropsychological deficits. We hypothesized that these syndromes may represent behavioural manifestations of frontal-subcortical impairments, previously described in schizophrenia. METHOD: Long-stay inpatients (n=54) and community patients (n=43) with enduring schizophrenia were assessed, using measures of symptoms and behaviour and tests of executive functioning. The relationship between syndromes and neuropsychological function was assessed using multiple regression and logistic regression analyses. RESULTS: Significant associations were found between performance on the spatial working memory task and the psychomotor poverty symptomatic syndrome, and between attentional set-shifting ability and both disorganization symptoms and the thought disturbance behavioural syndrome. These results were not explained by the effect of premorbid IQ, geographical location, length of illness or antipsychotic medication. Length of illness was an independent predictor of attentional set-shifting ability but not of working memory performance. CONCLUSION: The specific relationship between negative symptoms and spatial working memory is consistent with involvement of the dorsolateral prefrontal cortex. The associations between difficulty with set-shifting ability and both disorganization symptoms and behaviours may reflect inability to generalize a rule that had been learned and impaired ability to respond flexibly. The specific relationship of illness duration to set-shifting ability may suggest progressive impairment on some executive tasks. The nature of these relationships and their neurobiological and rehabilitation implications are considered.