Neurocognitive dysfunction in patients diagnosed with schizophrenia and alcoholism

The authors administered the Halstead-Reitan Neuropsychological Test Battery to schizophrenic groups with (n = 54) and without (n = 217) coexisting alcoholism, nonschizophrenic groups with alcoholism (n = 231), and a patient comparison group (n = 145) to determine the extent of additive cognitive impairment in schizophrenia associated with alcoholism and to compare cognitive function in alcoholism and schizophrenia. The additive effects of alcoholism on cognitive dysfunction in schizophrenia were subtle but were consistently identifiable. Cognitive dysfunction in alcoholism was less severe than in schizophrenia with or without alcoholism. The magnitude of additive effects of alcoholism on cognitive dysfunction in schizophrenia was age related with a significant interaction between age and presence or absence of alcoholism on a global index of cognitive dysfunction.     

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.     

Neurocognitive deficits in male alcoholics: an ERP/sLORETA analysis of the N2 component in an equal probability Go/NoGo task

In alcoholism research, studies concerning time-locked electrophysiological aspects of response inhibition have concentrated mainly on the P3 component of the event-related potential (ERP). The objective of the present study was to investigate the N2 component of the ERP to elucidate possible brain dysfunction related to the motor response and its inhibition using a Go/NoGo task in alcoholics. The sample consisted of 78 abstinent alcoholic males and 58 healthy male controls. The N2 peak was compared across group and task conditions. Alcoholics showed significantly reduced N2 peak amplitudes compared to normal controls for Go as well as NoGo task conditions. Control subjects showed significantly larger NoGo than Go N2 amplitudes at frontal regions, whereas alcoholics did not show any differences between task conditions at frontal regions. Standardized low resolution electromagnetic tomography analysis (sLORETA) indicated that alcoholics had significantly lower current density at the source than control subjects for the NoGo condition at bilateral anterior prefrontal regions, whereas the differences between groups during the Go trials were not statistically significant. Furthermore, NoGo current density across both groups revealed significantly more activation in bilateral anterior cingulate cortical (ACC) areas, with the maximum activation in the right cingulate regions. However, the magnitude of this difference was much less in alcoholics compared to control subjects. These findings suggest that alcoholics may have deficits in effortful processing during the motor response and its inhibition, suggestive of possible frontal lobe dysfunction.     

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.     

Antecedents of gregarious alcoholism: an a priori model

Path analysis procedures were used to test a causal model that concerns possible antecedent conditions in relation to gregarious drinking patterns. Selected scales from The California Psychological Inventory (CPI) and The Alcohol Use Inventory (AUI) constituted the assessments. The model was partially corroborated with reference to a group of 40 alcoholics (32 males; 8 females; M age = 33) in an outpatient treatment setting. The presumed causal variables accounted for 26% of the variance in self-reported gregarious drinking. Support was obtained for the assumption that certain interpersonal deficiencies may combine with beliefs in social benefits via alcohol usage to produce gregarious alcoholism.     

The CAL: an MMPI alcoholism scale for general medical patients

We developed a MMPI alcoholism scale based on adult medical patient samples. Our criterion group consisted of 736 inpatients (525 males; 211 females) diagnosed as having alcoholism according to DSM-III criteria. Three contrast samples that totaled 13,120 individuals were used for control purposes. MMPI items were chosen by means of logistic regression. The 33 items yielded by this procedure formed a provisional scale (CAL, for common alcoholism logistic) that worked equally well for males and females. With new cross-validation samples, with sensitivity (proportion of alcoholics correctly identified) set at 90%, the specificity (proportion of nonalcoholics correctly identified) ranged from 90% to 96% for selected contrast samples. We conclude that this scale shows promise as a screening device in similar populations.     

Academic underachievement, attention deficits, and aggression: comorbidity and implications for intervention.

Although comorbidity with specific learning disabilities is less frequent than commonly reported, externalizing behavior disorders--particularly attention-deficit hyperactivity disorder (ADHD)--often overlap with various indices of academic underachievement during childhood. Furthermore, by adolescence, delinquency is clearly associated with school failure. Because the link between behavioral and learning problems often appears before formal schooling, and because the co-morbid problems predict a negative course, early intervention is a necessity. Controlled treatment investigations with youngsters who show these combined problems are rare, and such studies present a host of methodologic and practical problems. I discuss issues surrounding multimodality treatment programs and the potential for long-term interventions to break cycles of school failure and externalizing behavior.     

Visual attention deficits in Alzheimer's disease: an fMRI study

Cognitive and neuroscience studies indicate that attentional operations are impaired in Alzheimer's disease (AD). Our goal was to define the anatomical areas of activation associated with visual attention processing and to define deficits or changes that may occur in AD patients compared with control group. Thirteen AD patients and 13 age- and education-matched normal controls were tested in two visual search tasks (one was a conjunction task, where feature binding is required. The other was a subset task, where group stimuli is needed without feature binding) using fMRI techniques. After stereotactical normalization, voxel-by-voxel t statistics was used to compare activated brain areas between patients and control subjects. Our findings suggest that both search tasks are controlled by partially overlapping cerebral networks, including parietal, frontal and occipital-temporal cortical regions and primary visual cortex. The AD patient group showed less activation in both parietal lobes and the left frontal regions, while increased activation was found in the right frontal lobes and the right occipito-temporal cortical regions with the conjunction task. In the subset task, decreased activation in AD patients was seen in the left parietal lobe and bilateral frontal lobes, while increased activation was seen in both medial temporal lobes. In addition, for the comparison between tasks, The difference is very small for AD patients. Control group showed a higher amplitude in the right prefrontal region, temporal cortical regions and parietal lobe. These results indicate that attention deficits in AD patients may be attributed to both binding problem and grouping inefficiency.     

Neurocognitive deficits in major depression and a new theory of ADHD: a model of impaired antagonism of cholinergic-mediated prepotent behaviours in monoamine depleted individuals

The study builds on the propositions introduced in a companion paper on the neuropharmacology of cognition and its relation to key findings in psychiatry. Cognitive inhibition is often invoked to explain performance in psychiatric illness. Yet it remains only a general conceptual model of executive dysfunction. Premotor theory proposes both neuroanatomical and neuropharmacological equivalents of conscious and unconscious processes. The interaction between monoaminergic and cholinergic neurotransmission is stated to have an inverse effect on these two fundamental psychological processes. If one conceives of cognitive inhibition as a failure to voluntarily suppress unconscious prepotent responses, then a deficit in monoaminergic antagonism of cholinergic facilitated prepotent responses accounts for the observed behavioural phenotypes. The plasticity of behaviour is further hypothesized to have an equivalent in intracellular signalling leading to plastic changes in neural networks. Apart from inhibition of prepotent responses it permits the formulation of new behavioural phenotypes. At the receptor level Gi-Gq/11 transduction coupling is proposed to mediate this effect. A hypofunctioning monoaminergic system is thought to underlie the clinical pictures of major depression and ADHD. The neurocognitive deficits of depression include memory loss, poor concentration and rumination. ADHD is characterized by inattention, impulsivity and hyperactivity. Both these syndromes effectively respond to raising serotonin and dopamine levels, respectively. The core symptoms can usefully be attributed to an imbalance between the neuromodulatory effects of monoamines and ACh. Taking the model of monoaminergic-muscarinic receptor interactions presented previously and extended here, a new hypothesis is proposed for the core symptoms of ADHD. Accordingly, impulsivity and hyperactivity result from impaired dopaminergic inhibition and remodelling of muscarinic mediated prepotent responses. The model also predicts memory impairment in major depression by proposing that low serotonin levels in the neocortex is linked to focal hippocampal dysfunction. Hippocampal theta is proposed to trigger phasic monoaminergic activation involved in encoding of cortical traces and plasticity of propotent networks. It proposes a hypothesis for the enhancement of mood and behaviour induced by antidepressants is partly a response to plasticity of neural networks, that is, remodelling of cholinergic-mediated negative habitual behaviours.     

Neurocognitive Impact of Antiretroviral Treatment: Thinking Long-Term

Combination antiretroviral therapy has significantly reduced morbidity and mortality with HIV infection. However, HIV-associated neurocognitive disorders persist at a relatively high prevalence rate despite successful systemic treatment. This paper reviews the current issues related to the neurocognitive impact of antiretroviral treatment.     

Parkinson's disease: a conceptualization of neuropsychological deficits within an information-processing framework

Parkinson's disease patients are frequently impaired in a variety of neuropsychological tasks involving memory, perceptual motor performance and cognitive flexibility. Although various theories have been forwarded to explain specific impairments, few attempts have been made to account for all the deficits within a single theoretical framework. Furthermore, the frequent occurrence of dementia, the adverse side effects of medication and the motor symptoms of the disease tend to interfere with neuropsychological performance. This has hindered the clear delineation of the neuropsychological profile of Parkinsonian patients. The present paper examines the evidence for intellectual deficits in non-demented Parkinson's disease patients. A number of problems inherent in cognitive research on Parkinson's disease are discussed. The contribution of dementia, motor symptom severity and medication in the expression of these intellectual impairments is examined. It is suggested that many of the neuropsychological deficits described in Parkinson's disease may result from a common underlying deficit in some aspect of information processing. Although it is not possible to pinpoint the precise mechanism(s) involved on the basis of the available evidence, several possibilities are suggested by cognitive and electrophysiological data.     

Age-related cognitive deficits in rhesus monkeys mirror human deficits on an automated test battery

Aged non-human primates are a valuable model for gaining insight into mechanisms underlying neural decline with aging and during the course of neurodegenerative disorders. Behavioral studies are a valuable component of aged primate models, but are difficult to perform, time consuming, and often of uncertain relevance to human cognitive measures. We now report findings from an automated cognitive test battery in aged primates using equipment that is identical, and tasks that are similar, to those employed in human aging and Alzheimer's disease (AD) studies. Young (7.1+/-0.8 years) and aged (23.0+/-0.5 years) rhesus monkeys underwent testing on a modified version of the Cambridge Automated Neuropsychological Test Battery (CANTAB), examining cognitive performance on separate tasks that sample features of visuospatial learning, spatial working memory, discrimination learning, and skilled motor performance. We find selective cognitive impairments among aged subjects in visuospatial learning and spatial working memory, but not in delayed recall of previously learned discriminations. Aged monkeys also exhibit slower speed in skilled motor function. Thus, aged monkeys behaviorally characterized on a battery of automated tests reveal patterns of age-related cognitive impairment that mirror in quality and severity those of aged humans, and differ fundamentally from more severe patterns of deficits observed in AD.     

Closed head injury-related information processing deficits: an event-related potential analysis.

Event-related potentials (ERPs) can elucidate aspects of sensory and cognitive processing that have been compromised due to closed head injury. We present the results of two investigations, one previously unreported, in which we used ERPs to evaluate information processing in head-injury survivors. In the first study, we used visual and auditory reaction time tasks differing in attentional demands to assess processing after head trauma. We found numerous changes in auditory processing in survivors: longer reaction times (but normal accuracy), longer N200 and P300 latencies, and reduced N100 and N200 amplitudes. In contrast, on visual tasks, only reduced N200 amplitude distinguished survivors and controls. To increase attentional demands, in a second study, we administered the continuous performance test (CPT). Survivors performed with lower accuracy than controls on visual and auditory tasks, and their ERPs were characterized by smaller visual and auditory N200s and P300s and smaller auditory N100s. We also present a synthesis, derived from a review of the literature, of closed head-injury effects on ERPs. Our own findings are in agreement with that synthesis. Namely, cognitive ERP components are more sensitive than sensory components to the effects of trauma. Specifically, in survivors, the amplitudes of N200 and P300 are often reduced, and their latencies prolonged. In general, as compared with visual ERPs, auditory ERPs may be more susceptible to the effects of closed head injury, suggesting that the auditory processing system is more vulnerable than the visual system. We conclude by discussing the potential use of ERPs to monitor clinical course and recovery in survivors of closed head injury.     

Sleep apnea-related cognitive deficits and intelligence: an implication of cognitive reserve theory

Cognitive deficits in patients with obstructive sleep apnea syndrome (OSAS) are well demonstrated, but the pathophysiology of these deficits is still controversial, as the relationship between OSA severity and cognitive deficits is usually weak. Our study considers the possible relationship between OSA-related cognitive deficits and the overall intellectual function of OSA patients. Forty-seven OSA patients and 36 normal individuals underwent a neuropsychological battery test assessing attention and alertness. According to the resulting IQ score, patients and controls were divided into a high-intelligence group (IQ > or = 90th percentile) and a normal-intelligence group (50 < or = IQ < 90%ile). Between the two patient groups there were no significant differences noticed, regarding OSA severity or sleepiness. High-intelligence patients showed the same attention/alertness performance compared with the high-intelligence controls. On the contrary, patients with normal-intelligence showed attention/alertness decline compared with the normal-intelligence control group. The two patient groups were re-examined with the same battery test after at least 1 year of CPAP treatment. At re-examination neither patient group showed any differences regarding attention and alertness compared with the control groups. We assume that high-intelligence may have a protective effect against OSA-related cognitive decline, perhaps due to increased cognitive reserve.     

Aldehyde dehydrogenase deficiency, flush patterns and prevalence of alcoholism: an interethnic comparison.

A study was performed to verify that the prevalence of alcohol abuse and dependence in Formosan aborigines differs from that of Taiwanese (Chinese Han people), using analysis of aldehyde dehydrogenase (ALDH) isozymes and flush patterns on randomly sampled 70 Atayal, 66 Paiwan, 61 Yami and 94 Taiwanese subjects were studied. The activity of an isomer of ALDH having a low Km (ALDH-I) in hair roots was analysed by isoelectric focusing assay. The subjective experience of flushing response after alcohol ingestion was assessed. Results showed that the rate of ALDH-I deficiency in Taiwanese (51.1%) was significantly higher than in aborigines, i.e., 6.4%, 3.9%, and 0% in Atayal, Paiwan, and Yami subjects, respectively. The percentage occurrence of ALDH-I deficiency and prevalence of alcohol dependence in Taiwanese and aborigines were negatively correlated. The predominant pattern of self-reported flush response after alcohol use among aborigines was of slow onset. The flush response to alcohol ingestion was examined in relation to aldehyde metabolizing enzyme. Since alcohol sensitivity is an important factor in the development and maintenance of the alcohol ingestion habit in humans, our results support the hypothesis that there is a biological basis in the different rates of alcohol abuse and dependence among different ethnic groups.     

Validity of Cognitive Screens for HIV-Associated Neurocognitive Disorder: A Systematic Review and an Informed Screen Selection Guide

Various screening tools have been proposed to identify HIV-Associated Neurocognitive Disorder (HAND). However, there has been no systematic review of their strengths and weaknesses in detecting HAND when compared to gold standard neuropsychological testing. Thirty-five studies assessing HAND screens that were conducted in the era of combination antiretroviral therapy were retrieved using standard search procedures. Of those, 19 (54 %) compared their screen to standard neuropsychological testing. Studies were characterised by a wide variation in criterion validity primarily due to non-standard definition of neurocognitive impairment, and to the demographic and clinical heterogeneity of samples. Assessment of construct validity was lacking, and longitudinal useability was not established. To address these limitations, the current review proposed a summary of the most sensitive and specific studies (>70 %), as well as providing explicit caution regarding their weaknesses, and recommendations for their use in HIV primary care settings.