Differential impact of heavy cannabis use on sensory gating in schizophrenic patients and otherwise healthy controls

Cannabis abuse may precipitate the onset of schizophrenia and a dysfunction of the endocannabinoid system may be involved in the pathology of schizophrenia. Nevertheless, only few studies have addressed the neurobiological consequences of cannabis abuse for the development and course of schizophrenia. We measured the long-term effect of chronic cannabis abuse on the inhibitory function of the brain by the auditory P50 sensory gating in schizophrenic (n=15) and otherwise healthy chronic cannabis abusers (i.e. cannabis controls; n=11) and compared it to that of schizophrenic patients (n=12) and healthy controls (n=18) without cannabis or other drug abuse. All study subjects had to be abstinent from cannabis for at least 28 days. The main finding of our study was a P50 sensory gating deficit in cannabis controls that was correlated with the number of years with daily consumption (r=0.81; p=0.003). In contrast, we found no differences in P50 sensory gating between schizophrenic cannabis-abusers and non-abusers or healthy controls and no correlation with the number of years with daily consumption in those groups. To our knowledge this is the first study comparing the influence of chronic cannabis abuse in schizophrenic and otherwise healthy abusers on the inhibitory function of the brain. Our data provide some evidence that chronic cannabis abuse may affect sensory cortical circuits even after prolonged abstinence and they point to a possible differential effect in schizophrenic and otherwise healthy users.     

Are neuropsychological deficits trait markers in OCD?

OBJECTIVE: Neuropsychological deficits are potential endophenotype markers. In obsessive-compulsive disorder (OCD), there is impairment in executive functions and nonverbal memory. However, studies have largely examined neuropsychological functioning in patients during the symptomatic phase. The state independent nature of neuropsychological deficits in OCD is not established. For neuropsychological deficits to be endophenotype markers, they have to be state-independent. We compared neuropsychological functions in recovered OCD patients with matched healthy controls. METHOD: We assessed 30 recovered DSM-IV OCD patients without any concurrent comorbidity or lifetime history of schizophrenia, bipolar disorder, tics and alcohol/substance abuse and 30 healthy controls individually matched for age, sex and education. They were assessed on different neuropsychological dimensions: attention, executive function, memory and intelligence. For between-group comparisons, we employed univariate analyses, and to identify neuropsychological variables that differentiate cases and controls, we used backward conditional logistic regression for matched case-control design. RESULTS: Patients in the recovered phase of the illness had significant deficits in tests of set-shifting ability, alternation, response inhibition and nonverbal memory but had intact performance in other tests. In the logistic regression, scores on the Wisconsin Card Sorting Test 'categories completed' and the Rey's Complex Fig. Test 'delayed recall' were significant after controlling for the possible confounding effects of age and education. There was no correlation between illness-related variables and neuropsychological deficits. CONCLUSIONS: Deficits in certain executive functions and nonverbal memory are possibly state independent. Neuropsychological deficits are possibly candidate endophenotype markers for OCD and may help clarify genetic contributions. Future studies should evaluate unaffected siblings to establish deficits are endophenotype markers. Prospective studies with serial measurements of cognitive deficits are also needed to assess whether these deficits are cumulative with the progression of illness.     

The Impact of Cannabis Use on Cognitive Functioning in Patients With Schizophrenia: A Meta-analysis of Existing Findings and New Data in a First-Episode Sample

Cannabis use is highly prevalent among people with schizophrenia, and coupled with impaired cognition, is thought to heighten the risk of illness onset. However, while heavy cannabis use has been associated with cognitive deficits in long-term users, studies among patients with schizophrenia have been contradictory. This article consists of 2 studies. In Study I, a meta-analysis of 10 studies comprising 572 patients with established schizophrenia (with and without comorbid cannabis use) was conducted. Patients with a history of cannabis use were found to have superior neuropsychological functioning. This finding was largely driven by studies that included patients with a lifetime history of cannabis use rather than current or recent use. In Study II, we examined the neuropsychological performance of 85 patients with first-episode psychosis (FEP) and 43 healthy nonusing controls. Relative to controls, FEP patients with a history of cannabis use (FEP + CANN; n = 59) displayed only selective neuropsychological impairments while those without a history (FEP − CANN; n = 26) displayed generalized deficits. When directly compared, FEP + CANN patients performed better on tests of visual memory, working memory, and executive functioning. Patients with early onset cannabis use had less neuropsychological impairment than patients with later onset use. Together, these findings suggest that patients with schizophrenia or FEP with a history of cannabis use have superior neuropsychological functioning compared with nonusing patients. This association between better cognitive performance and cannabis use in schizophrenia may be driven by a subgroup of “neurocognitively less impaired” patients, who only developed psychosis after a relatively early initiation into cannabis use.     

Sensorimotor and cognitive slowing in schizophrenia as measured by the Symbol Digit Substitution Test

OBJECTIVES: A vast amount of studies demonstrates the presence of psychomotor slowing in schizophrenia. The objective of the present study was to investigate whether this overall psychomotor slowing can be divided into distinct processes that differentially affect cognitive functioning in schizophrenia. METHODS: The pen-tip movements of 30 schizophrenic inpatients and 30 matched controls were digitally recorded during performance of the Symbol Digit Substitution Test (SDST) and analysed to differentiate matching time and writing time, representing the cognitive and sensorimotor component of slowing, respectively. In addition, the results were compared to each other and to the scores of traditional neuropsychological tests that assess domains such as memory and attention. RESULTS: Both matching time and writing time were longer in the schizophrenic patients relative to the controls but did not correlate. Only matching time correlated significantly with the conventional neuropsychological test results. CONCLUSIONS: Although schizophrenic patients display both sensorimotor and cognitive slowing, the two processes are unrelated. Furthermore, only the cognitive component was associated with most of the cognitive deficits as measured by traditional neuropsychological tests.     

Subjective cognitive dysfunction in first-episode and chronic schizophrenic patients

Previous studies indicate that first-episode and chronic schizophrenic patients do not differ regarding neuropsychological performance as assessed with standard cognitive tasks. For the present study, it was investigated whether first-episode and chronic schizophrenics report similar subjective cognitive deficits. The Frankfurt Complaint Questionnaire (FCQ), a scale devised for assessing subjective cognitive disturbances in schizophrenia, was administered to 20 first-episode and 36 chronic schizophrenic patients, as well as 20 healthy controls. The schizophrenic subsamples did not differ on any of the FCQ subscales or on a "lie scale," measuring illness denial. Psychopathological ratings were comparable for both groups. As expected, healthy subjects reported significantly less cognitive and perceptual problems than schizophrenic patients. In marked contrast to a Kraepelinian view of schizophrenia, the present data confirm previous studies conducted with objective neuropsychological tests that schizophrenia is a neurodevelopmental rather than a neurodegenerative disorder.     

Iowa gambling task in schizophrenia: a review and new data in patients with schizophrenia and co-occurring cannabis use disorders

BACKGROUND: We reviewed previous studies comparing schizophrenia patients and healthy subjects for performance on the Iowa Gambling Task (IGT) (a laboratory task designed to measure emotion-based decision-making), and found mixed results. We hypothesize that deficits in IGT performance in schizophrenia may be more specifically related to concurrent substance use disorders. To test this hypothesis, we compared schizophrenia patients with (SCZ((+))) or without (SCZ((-))) cannabis use disorders, to healthy subjects, on measures of cognition and IGT performance. METHODS: A comprehensive battery of cognitive tests and the IGT were administered to three groups of subjects: (1) 13 subjects with DSM-IV diagnosis of schizophrenia and no concurrent substance use disorders (mean age: 28+/-12 (SD); 54% males); (2) 14 subjects with schizophrenia and concurrent cannabis use disorders (mean age: 29+/-9 (SD); 71% males); and (3) 20 healthy subjects (mean age 33+/-10 (SD); 60% males). RESULTS: Compared to the healthy group, both schizophrenia groups were cognitively more impaired, and did worse on IGT performance. There were no differences between SCZ((+)) and SCZ((-)) patients on most of the cognitive tests, and IGT performance. CONCLUSIONS: Schizophrenia patients show widespread impairments in several cognitive domains and emotion-based decision-making. These results are consistent with the evidence that schizophrenia reflects a dorsolateral and orbitofrontal/ventromedial prefrontal cortex dysfunction. More intriguing, it appears that the concurrent abuse of cannabis has no compounding effects on cognition, as well as emotion/affect-based decision-making.     

Associations of serum brain-derived neurotrophic factor with cognitive impairments and negative symptoms in schizophrenia

Brain-derived neurotrophic factor (BDNF) may be involved in the pathophysiology of schizophrenia. The aim of this study was to examine the associations of serum BDNF levels with the cognition and clinical characteristics in patients with schizophrenia. Sixty-three patients with schizophrenia and 52 age- and sex-matched healthy controls were examined with neuropsychological tests. Serum BDNF levels were determined by enzyme-linked immunosorbent assay (ELISA). There were no significant differences in serum BDNF levels between normal controls and patients with schizophrenia. Serum BDNF levels of normal controls showed negative correlations with verbal working memory, but this was not the case with schizophrenic patients. Meanwhile, serum BDNF levels of schizophrenic patients showed positive correlations with the scores of the Scale for the Assessment of Negative Symptoms (SANS) and the Information subtest scores of Wechsler Adult Intelligence Scale Revised (WAIS-R). Serum BDNF levels are related with the impairment of verbal working memory and negative symptoms in patients with schizophrenia.     

Multifocal cognitive dysfunction in high-dose benzodiazepine users: a cross-sectional study

Benzodiazepines (BZDs) are the most widely prescribed drug class in developed countries, but they have high potential for tolerance, dependence and abuse. Cognitive deficits in long-term BZD users have long been known, but previous results might have been biased by patients’ old age, coexisting neurological or psychiatric conditions or concurrent alcohol or psychotropic drug dependence. The study was aimed to explore the neuropsychological effect of high-dose BZD dependence, which represents an emerging addiction phenomenon. We recruited a group of high-dose BZD users with neither neurological or psychiatric comorbidity except anxiety or depression nor concurrent alcohol or psychotropic drug dependence. They underwent a battery of cognitive tests to explore verbal, visuospatial memory, working memory, attention, and executive functions. All the neuropsychological measures were significantly worse in patients than controls, and some of them were influenced by the BZD cumulative dose. The severity of depression and anxiety had a minimal influence on cognitive tests. Patients with high-dose BZD intake show profound changes in cognitive function. The impact of cognition should be considered in this population of patients, who may be involved in risky activities or have high work responsibilities.     

Gender differences in cognitive function of patients with chronic schizophrenia

Schizophrenic patients have cognitive impairments, but gender differences in these cognitive deficits have had limited study. This study assessed cognitive functioning in 471 subjects including 122 male and 78 female schizophrenic patients and 141 male and 130 female healthy controls. We found that immediate memory, language, delayed memory and total RBANS scores were significantly decreased in schizophrenia compared with healthy controls for both genders. Male patients had significant lower immediate memory, delayed memory and total RBANS scores than female patients, and healthy controls showed a similar gender difference. The RBANS showed modest correlations with PANSS scores, duration of illness and antipsychotic dose (chlorpromazine equivalents). Almost all RBANS scores in the schizophrenics and healthy controls showed significant positive correlations with education. Thus, patients of both sexes with schizophrenia experienced more deteriorated performance than healthy controls on cognitive domains of immediate memory, language and delayed memory. Furthermore, male schizophrenic patients had more serious cognitive deficits than female patients in immediate and delayed memory, but not in language, visuospatial and attention indices.     

首发精神分裂症利培酮治疗前后认知功能的比较研究

目的探讨首发精神分裂症患者利培酮治疗前后认知功能的变化。方法采用认知评估工具连线测验、简单视觉空间记忆测验（BVMT-R）、WMS-III空间广度测验、霍普金斯词语学习测验（HVLT-R）、定步调听觉连续加法测验（PASAT）和威斯康星卡片分类测验（WCST-64）对经利培酮治疗8周前后的89例首发精神分裂症患者和62例健康对照者进行神经心理测试。结果首发精神分裂症患者治疗前的神经心理测验成绩显著差于治疗后和健康对照组（P〈0.05）;经利培酮治疗8周后达到临床痊愈标准患者的神经心理测验成绩除WMS-III空间广度测验外,其它大部分测验测验成绩仍显著差于健康对照组（P〈0.05）。结论首发精神分裂症患者存在处理速度、工作记忆、言语记忆、空间记忆、注意警觉和执行功能广泛的认知功能损害,利培酮治疗可部分改善认知缺陷,但精神症状达到临床痊愈的患者仍然存在多个领域认知缺陷,提示认知缺陷是精神分裂症的内表型。     

Cannabis and schizophrenia: results of a follow-up study

A total of 39 schizophrenic patients with a history of current cannabis abuse at index admission was compared with a control group of schizophrenics without substance abuse matched for age, gender, and year of admission. At follow-up after 68.7 ± 28.3 months, 27/ 39 cases and 26/39 controls could be investigated. 8/27 cases (30%) had continued cannabis abuse, 6/27 (22%) had become alcohol abusers. Only one patient of the control group had started abusing alcohol. Patients with previous cannabis abuse had significantly more rehospitalizations, tended to worse psychosocial functioning, and scored significantly higher on the psychopathological syndromes “thought disturbance” (BPRS) and “hostility” (AMDP). These results confirm the major impact of cannabis abuse on the long-term outcome of schizophrenic patients. Received: 16 December 1997 / Accepted: 19 November 1998     

Gray matter volume deficits are associated with motor and attentional impairments in adolescents with schizophrenia

Cognitive deficits have been well described in adolescents with schizophrenia, but little is known about the neuroanatomical basis of these abnormalities. The authors examined whether neuropsychological deficits observed in adolescents with schizophrenia were associated with cortical gray matter volume deficits. Volumes of the superior frontal gyrus, anterior cingulate gyrus and orbital frontal lobe were outlined manually from contiguous MR images and automatically segmented into gray and white matter in 52 patients and 48 healthy volunteers. Subjects received a comprehensive neuropsychological test battery, assessing five different functional domains: executive, attention, verbal memory, motor and sensory motor. Children and adolescents with schizophrenia were found to have lower total cortical and lower superior frontal gyrus gray matter volumes and lower test scores across all functional domains compared to healthy volunteers. Among patients, the lower total cortical gray matter volume was associated with worse functioning on the attention and motor domains. Our findings point to widespread, perhaps multifocal, pathology as contributing to cognitive dysfunction in adolescents with schizophrenia.     

Cannabis and schizophrenia: impact on onset,course, psychopathology and outcomes

Cannabis consuming schizophrenic patients are younger at onset, are likely to have started abuse before onset of schizophrenia and show more prominent positive symptoms than nonabusers. It has been suggested that cannabis is a risk-factor for schizophrenia. Our aim was to assess prevalence and pattern of cannabis use in 125 chronic male schizophrenic subjects and its impact on socioepidemiological and clinical variables as well as which disorder precedes the other in onset. Assessment of consumption was made with a semi-structured clinical interview. Clinical status was assessed by means of the SANS, SAPS, PANSS and BPRS scales. Cannabis consumption was found in 54 subjects (43%), 66.7% of whom started it at least three years before onset of schizophrenia. Consumers were younger and with lower negative symptoms, specially abusers and polysubstance abusers. Family history positive for psychosis was more frequent in consumers, especially when consumption started before onset of schizophrenia. Subjects whose onset of schizophrenia preceded the beginning of cannabis abuse had more positive symptoms than those who started abuse before the onset of schizophrenia. On these grounds, our sample could be subdivided into two main groups, one that uses substances to counter distressing symptoms of schizophrenia and another in which cannabis might be one of the factors predisposing to the disease; the former had less negative symptoms than nonabusers. Our data support both heterogeneity of schizophrenia and genetic susceptibility to environmental agents.     

Cognitive function in early Parkinson’s disease: a population‐based study

Background and purpose: The study aims to describe the frequency, pattern and determinants of cognitive function in patients with newly diagnosed Parkinson’s disease (PD); to compare patients with impaired cognition to patients with intact cognition; and to compare to matched healthy controls. Methods: Patients were identified in a longitudinal population based study of idiopathic non‐drug induced parkinsonism. Eighty‐eight newly diagnosed patients with PD and no dementia were included during a four year period. The patients and 30 age‐ and sex‐matched healthy control subjects underwent a comprehensive neuropsychological assessment. Results: Patients performed significantly worse than healthy controls in a majority of neuropsychological tests. Test results in attention, psychomotor function, episodic memory (free recall), executive function and category fluency were significantly lower in the patient group. Comparison with normative data revealed that 30% of the patients had deficits in ≥1 cognitive domain (episodic memory, executive function and verbal function). Seventy per cent of the patients had normal performance. Unified Parkinson's Disease Rating Scale (UPDRS) III sub scores; speech, facial expression, rigidity and bradykinesia were significantly higher, and disease duration shorter amongst the cognitively impaired than amongst the cognitively intact patients. Tremor showed no difference. Education level was an independent predictor of dysfunction in patients with ≥2 cognitive domains affected. Conclusion: Cognitive dysfunction is common in untreated patients in early PD, affecting attention, psychomotor function, episodic memory, executive function and category fluency. Education level was an independent predictor of severe cognitive dysfunction.     

Quality of life in bipolar type I disorder and schizophrenia in remission: clinical and neurocognitive correlates

This cross-sectional study examined the relationships between clinical and neuropsychological variables and self-reported quality of life (QoL) in 30 euthymic bipolar I patients, 23 remitted schizophrenic patients, and 23 healthy controls. Participants were administered the World Health Organization Quality of Life Measure-Abbreviated Version (WHOQOL-BREF) to assess QoL. Moreover, a broad neuropsychological battery was also administered. Bipolar disorder (BD) and schizophrenia patients demonstrated significantly lower scores on the physical, psychological, and social domains of the WHOQOL-BREF compared with controls, but there were no significant differences between the two patient groups on those domains. More symptomatic BD patients reported worse QoL, especially in the physical and environmental domains, which was also associated with worse neurocognitive performance. In schizophrenic patients, neurocognitive performance was not associated with self-reported QoL, but more symptomatic patients reported lower QoL. Substantial impairments in QoL, similar in severity, were found in both patient groups. In patients with schizophrenia, QoL was more strongly related to levels of psychopathology, whereas in BD patients, both psychopathology and neurocognitive deficits were strongly associated with lower QoL. Clinical recovery is essential in schizophrenia and BD. The association between cognitive functioning and QoL in bipolar patients suggests that these patients may also benefit from psychological interventions addressed to improve cognitive deficits and enhance the functional recovery.     

Neuropsychological characteristics of mild cognitive impairment subgroups

OBJECTIVE: To describe the neuropsychological characteristics of mild cognitive impairment (MCI) subgroups identified in the Cardiovascular Health Study (CHS) cognition study. METHODS: MCI was classified as MCI-amnestic type (MCI-AT): patients with documented memory deficits but otherwise normal cognitive function; and MCI-multiple cognitive deficits type (MCI-MCDT): impairment of at least one cognitive domain (not including memory), or one abnormal test in at least two other domains, but who had not crossed the dementia threshold. The MCI subjects did not have systemic, neurological, or psychiatric disorders likely to affect cognition. RESULTS: MCI-AT (n = 10) had worse verbal and non-verbal memory performance than MCI-MCDT (n = 28) or normal controls (n = 374). By contrast, MCI-MCDT had worse language, psychomotor speed, fine motor control, and visuoconstructional function than MCI-AT or normal controls. MCI-MCDT subjects had memory deficits, though they were less pronounced than in MCI-AT. Of the MCI-MCDT cases, 22 (78.5%) had memory deficits, and 6 (21.5%) did not. MCI-MCDT with memory disorders had more language deficits than MCI-MCDT without memory disorders. By contrast, MCI-MCDT without memory deficits had more fine motor control deficits than MCI-MCDT with memory deficits. CONCLUSIONS: The most frequent form of MCI was the MCI-MCDT with memory deficits. However, the identification of memory impaired MCI groups did not reflect the true prevalence of MCI in a population, as 16% of all MCI cases and 21.5% of the MCI-MCDT cases did not have memory impairment. Study of idiopathic amnestic and non-amnestic forms of MCI is essential for an understanding of the aetiology of MCI.     

Neuropsychological findings in myotonic dystrophy

Abstract

Although the literature contains several references to clinically apparent cognitive deficits in patients with myotonic dystrophy (MYD), efforts to support these observations with formal testing have been lacking. The current study compared 17 MYD patients with 25 normal controls on an expanded Halstead-Reitan Battery. The MYD group scored worse than the controls on nearly every neuropsychological measure. Significant neuropsychological impairment was present even when tests of motor skills were excluded. There was no relationship between general neuropsychological impairment and degree of weakness, myotonia, or muscle atrophy in the MYD patients. These findings suggest that cognitive impairment can be an important and relatively independent component of the disability in MYD, which should be considered in the clinical evaluation and counselling of persons with this disease.     

Facial emotion perception in Chinese patients with schizophrenia and non-psychotic first-degree relatives

Although there is a consensus that patients with schizophrenia have certain deficits in perceiving and expressing facial emotions, previous studies of facial emotion perception in schizophrenia do not present consistent results. The objective of this study was to explore facial emotion perception deficits in Chinese patients with schizophrenia and their non-psychotic first-degree relatives. Sixty-nine patients with schizophrenia, 56 of their first-degree relatives (33 parents and 23 siblings), and 92 healthy controls (67 younger healthy controls matched to the patients and siblings, and 25 older healthy controls matched to the parents) completed a set of facial emotion perception tasks, including facial emotion discrimination, identification, intensity, valence, and corresponding face identification tasks. The results demonstrated that patients with schizophrenia performed significantly worse than their siblings and younger healthy controls in accuracy in a variety of facial emotion perception tasks, whereas the siblings of the patients performed as well as the corresponding younger healthy controls in all of the facial emotion perception tasks. Patients with schizophrenia also showed significantly reduced speed than younger healthy controls, while siblings of patients did not demonstrate significant differences with both patients and younger healthy controls in speed. Meanwhile, we also found that parents of the schizophrenia patients performed significantly worse than the corresponding older healthy controls in accuracy in terms of facial emotion identification, valence, and the composite index of the facial discrimination, identification, intensity and valence tasks. Moreover, no significant differences were found between the parents of patients and older healthy controls in speed after controlling the years of education and IQ. Taken together, the results suggest that facial emotion perception deficits may serve as potential endophenotypes for schizophrenia.     

Lifetime cannabis use and cognition in patients with schizophrenia spectrum disorders and their unaffected siblings

The relationship between cannabis and cognitive performance is controversial. While both acute administration and long-term cannabis use impair cognitive performance in healthy subjects, several studies have shown improved cognitive outcomes in patients with schizophrenia spectrum disorders who use cannabis. The aim of this study was to determine the relationship between lifetime cannabis use, as assessed longitudinally over 10 years of follow-up in a sample of 42 patients and 35 of their unaffected siblings, and current cognitive performance. Forty-two healthy control subjects were assessed at follow-up with the same instruments. Stepwise linear regression revealed a negative effect of longitudinal cannabis use on performance in a social cognition task in the patient group. In the sibling group, lifetime cannabis use had a negative effect on processing speed and declarative memory performance. In the control group, cannabis use per se did not predict cognitive performance; however, when adding lifetime tobacco use to the model, we found a negative association between lifetime cannabis and tobacco use and processing speed and social cognition performance. Moreover, a lower IQ associated with current cannabis use predicted worse attentional performance in the control group. The differential pattern of associations between cannabis use and cognitive performance in patients compared with siblings and controls can be explained by the negative impact of illness on cognition.     

Neuropsychological indicators of the vulnerability to schizophrenia.

Schizophrenia is associated with enduring deficits in neuropsychological functioning. It is widely undecided if the various aspects of neuropsychological impairment are a consequence of the disorder or if they are also present premorbidly and in populations at increased risk for schizophrenia (vulnerability markers). Neuropsychological deficits in healthy relatives of schizophrenic patients who are at an elevated risk for schizophrenia and who did not yet pass the period of risk would indicate that these deficits are vulnerability markers. This hypothesis was tested for three neuropsychological paradigms which have been proven to distinguish schizophrenic patients from controls. 33 siblings of drug-free schizophrenic probands revealed deficits has compared to 33 matched healthy controls in a blurred single target version of the Continuous Performance Test and in a multiple item version of the Span of Apprehension Test but not so in less difficult versions of both tests or in the time needed to react to stimuli with shifting modality.