Mood-congruent bias in affective go/no-go performance of unmedicated patients with major depressive disorder

OBJECTIVE: Neuropsychological studies of major depressive disorder have described attentional biases for affectively laden stimuli, but these reports were based on measures obtained from medicated subjects. This study investigated performance of unmedicated depressed patients on the Affective Go/No-Go Task. METHOD: Twenty depressed patients and 20 healthy comparison subjects, matched for age, gender, and IQ, performed the Affective Go/No-Go Task as well as tests of attention and memory for nonaffective stimuli. RESULTS: Depressed patients did not differ from healthy subjects on memory task performance, but they made more omission errors on the attention task. On the Affective Go/No-Go Task, depressed patients made more omission errors during happy than sad word blocks and required more time to respond to happy than to sad words. In contrast, healthy subjects required more time to respond to sad than to happy words. CONCLUSIONS: Unmedicated depressed patients do not show a pattern of generalized cognitive impairment but, rather, specifically display an attentional deficit and a mood-congruent bias toward salient stimuli.     

Platelet MAO deamination of serotonin in depressed patients. Changes after imipramine treatment and clinical correlations

Monoamine oxidase (MAO) in blood platelets has been used as a model to study MAO in the central nervous system, where disorders in serotonergic systems are thought to occur in depression. Inconsistent changes in platelet MAO of depressed patients have been reported when several substrates other than serotonin (5-HT) have been used. To correlate changes in platelet MAO activity with the enzyme activity in central serotonergic systems, the platelet MAO activity of depressed patients (first unmedicated and then after 3 weeks and 2 months of imipramine treatment) and normal controls was measured using 5-HT as substrate. The results showed that there is a steady, measurable platelet MAO activity with that substrate. This activity was significantly higher in unmedicated depressed patients than in controls, and it decreased progressively with imipramine treatment, reaching a normal level when the patients were clinically recovered from depression after 2 months of therapy.     

Effects of imipramine, fluvoxamine and depressive mood on autonomic cardiac functioning in major depressive disorder

OBJECTIVE: Diminished HR variability is considered to be associated with depression and the increased risk of cardiovascular disease. The pharmacological effects of antidepressants and depressive mood itself may contribute to alterations in autonomic cardiac functioning, but a limited amount of data is available. We studied the effects of two different types of antidepressant treatments (imipramine and fluvoxamine), in addition to the effect of depressive mood, on the cardiovascular system in depressed patients. METHODS: Depressed inpatients were studied during a drug-free period and after 4 weeks of adequate treatment with imipramine (n = 17) or fluvoxamine (n = 24). Heart rate variability, blood pressure variability, and a baroreflex sensitivity index during supine rest and orthostatic challenge were analyzed by means of spectral techniques to obtain noninvasive parameters of sympathetic and parasympathetic activity. RESULTS: Both imipramine and fluvoxamine reduced sympathetic and parasympathetic activity, although the effects of imipramine were much more pronounced. Severity of depression was positively related to mean levels of heart rate and blood pressure in the total patient group. There was no convincing evidence that these relationships differed between depressed patients treated with imipramine and those treated with fluvoxamine. CONCLUSION: Our findings suggest that alterations in mean heart rate and blood pressure in depressed patients after antidepressant treatment are the result of a combined effect of pharmacological actions of antidepressants and improvement of depressive mood state. The present study did not confirm the relationship between clinical state and cardiovascular variability or baroreflex sensitivity.     

精神分裂症患者父母的持续性注意功能

目的:探索精神分裂症患者父母的持续性注意功能特征。方法:对61例精神分裂症先证者(患者组),86名患者的父、母(父母组)以及64名正常对照者(对照组)进行持续性操作测验(CPT)检测。结果:在简单操作的反应时间分测验中,父母组的所有指标(舍弃数、漏答数、正确反应平均时间和变异系数)均高于对照组(P均<0.01),多数指标与患者组差异无显著性;但在复杂操作的X分测验中,父母组的多数指标均低于患者组(P均<0.01),而与对照组差异无显著性。无论是简单还是复杂操作中,患者组的所有指标均显著高于对照组(P均<0.01)。亲子间部分CPT指标均呈显著正相关(P<0.01~0·05)。结论:精神分裂症患者父母的CPT结果介于患者和正常对照者之间,简单操作中与患者组接近,复杂操作中与正常对照组相似。亲子间部分CPT指标呈显著正相关。提示持续性注意障碍有可能是该病内表型的一种标志。     

Continuous performance tests in schizophrenic patients: stimulus and medication effects on performance

Medicated (n = 17) and unmedicated (n = 17) schizophrenic patients were compared to a normal control group (n = 19) on their performance on auditory and visual versions of the Continuous Performance Test (CPT). Within each stimulus modality, performance was examined on lexical and nonlexical target stimuli. Neuromotor competence was assessed on the basis of motor speed and proficiency. Normal subjects made fewer errors of all types than schizophrenic patients. Unmedicated patients made significantly more errors on nonlexical stimuli than medicated patients, with medication status found not to be associated with stimulus modality effects. Motor proficiency was associated with CPT performance in the medicated patients, but not the unmedicated ones, although this difference in correlations did not account for the group differences between these patients. The authors discuss the implications of these data for the type of cognitive and attentional functions that are affected by medication in schizophrenia.     

Correlation of attention deficit, rapid eye movement latency and slow wave sleep in schizophrenia patients

Aim:  Schizophrenia patients present both reduced slow wave sleep (SWS) and shortened rapid eye movement latency (REML) in polysomnographic (PSG) profiles, which have been linked to dopaminergic and muscarinic impairment, respectively. Two main selective attentional systems involve different anatomical structures. The first system is the parietal cortical areas and thalamic areas, which are linked to cholinergic neurotransmission. This is responsible for automatic attention response. The second system is the frontal regions, which are linked to dopaminergic neurotransmission. This is responsible for voluntary control of attentional resources. It was hypothesized that low attentional performance in schizophrenia patients is associated with shortened REML and reduced SWS.
Methods:  The PSG profile was correlated with the continuous performance test (CPT) in 15 schizophrenia inpatients under treatment with risperidone. Schizophrenia was diagnosed according to DSM-IV criteria, and clinical symptoms were evaluated on the Brief Psychiatric Rating Scale.
Results:  REML was negatively correlated with errors of omission ( P  < 0.05), reaction time (RT; P  < 0.05) and positively correlated with hit rate (HR; P  < 0.05). No association was found between SWS and CPT performance.
Conclusions:  The significant indicators of CPT represent different attention processes. Errors of omission, which are linked to the problems with automatic attention processing, RT, which represent the speed of automatic processing, and HR, are involved in the integration of autonomic and voluntary attention control. The present results suggest that REML is associated with thalamus-related automatic attention response. Due to study limitations, however, confirmation of these findings in a large-scale controlled study of drug-naïve patients is needed.     

Platelet imipramine binding in endogenous depressed patients and controls: relationship to platelet MAO and 5HT uptake during successful imipramine treatment

Platelet imipramine binding was measured in 25 unmedicated depressed patients and 25 age- and sex-matched healthy controls. In the patients, the measurement was repeated after 3 weeks and 2 months of imipramine treatment leading to clinical recovery. No significant differences in imipramine binding were found between controls and unmedicated patients. In the latter, imipramine administration produced a progressive change in the binding characteristics, increasing the apparent Kd and decreasing the number of binding sites (Bmax). The results suggest that platelet imipramine binding is not altered in depression and that changes in this parameter are the consequence of the presence of imipramine in the blood stream. However, such changes accompany changes in other biological parameters, such as platelet monoamine oxidase and serotonin uptake, seen in the same patients throughout imipramine treatment, suggesting that the drug acts on a wide range of normal or altered serotonin-related cellular mechanisms while it accelerates the clinical recovery from depression.     

Neurocognitive consequences of a paediatric brain tumour and its treatment: a meta‐analysis

Aim This meta‐analysis provides a systematic review of studies into intellectual and attentional functioning of paediatric brain tumour survivors (PBTS) as assessed by two widely used measures: the Wechsler Intelligence Scale for Children (3rd edition; WISC‐III) and the Conners’ Continuous Performance Test (CPT). Method Studies were located that reported on performance of PBTS (age range 6–16y). Meta‐analytic effect sizes were calculated for Full‐scale IQ, Performance IQ, and Verbal IQ as measured by the WISC‐III, and mean hit reaction time, errors of omission, and errors of commission as measured by the CPT. Exploratory analyses investigated the possible impacts of treatment mode, tumour location, age at diagnosis, and time since diagnosis on intelligence. Results Twenty‐nine studies were included: 22 reported on the WISC‐III in 710 PBTS and seven on CPT results in 372 PBTS. PBTS performed below average (p_s<0.001) on Full‐scale IQ (Cohen’s d=?0.79), Performance IQ (d=?0.90), and Verbal IQ (d=?0.54). PBTS committed more errors of omission than the norm (d=0.82, p<0.001); no differences were found for mean hit reaction time and errors of commission. Cranial radiotherapy, chemotherapy, and longer time since diagnosis were associated with lower WISC‐III scores (p_s<0.05). Interpretation PBTS have seriously impaired intellectual functioning and attentiveness. Being treated with cranial radiotherapy and/or chemotherapy as well as longer time since diagnosis leads to worse intellectual functioning.     

Attention deficit in depressed suicide attempters

Attention is typically impaired in depression and may play a role in risk for suicidal behavior. In this study, 66 non-patients, 83 depressed subjects with no past history of suicide attempt, 53 depressed subjects with one or more low lethality suicide attempts, and 42 depressed subjects with at least one high lethality attempt were compared on two computerized measures of attention, a continuous performance test (CPT) and a Stroop task. All subjects were medication free at the time of assessment. Attention was impaired in all depressed subjects but worse in those with a past history of suicidal behavior. CPT performance did not differ among the groups, but Stroop interference was significantly poorer in all depressed subjects relative to non-patients, and poorer still in high lethality suicide attempters relative to all other groups. Interference scores correlated modestly with subjective depression, functional level, suicide ideation, number of past suicide attempts, and lethality of past attempts. Depression-related impairments of attention, especially susceptibility to interference, are accentuated in those with a past history of suicidal behavior. Fundamental deficits in attentional control may play a role in risk for suicidal behavior, and may contribute to a variety of cognitive deficits in suicidal patients. Brain regions subserving attentional control, which overlap considerably with regions implicated in affective disorders, may be a useful target for studies seeking to characterize neuropsychological factors associated with suicidal behavior.     

Executive functions and updating of the contents of working memory in unipolar depression

Background: Depression is characterized by cognitive impairments, including executive dysfunctions. These executive deficits could reflect impairments of more basic executive processes, such as updating, set shifting and inhibition. While shifting and inhibition impairments are often reported, studies on depression have been somewhat obscure about specific deficits of the updating process. The main goal of that study was to assess the updating process in young in-patients with depression.

Methods: We used a verbal n-back task to assess updating process. Load and mental manipulation within working memory (WM) were incremented by using three different levels of complexity (1,2,3-back). Neuropsychological tests and an attentional task (0-back) were also administered to subjects. Twenty-two individuals meeting DSM-IV criteria for Major Unipolar Depression and 22 healthy control subjects, matched on age, verbal IQ and education, were included in the study.

Results: Subjects with depression showed significant deficits at the n-back task compared to control subjects. They were normal in tasks assessing the short-term maintenance in WM and attention. This suggests that depressed patients exhibit impairment in the updating process. Depressed patients also showed set shifting and inhibition deficits. Only the n-back task was correlated with the number of hospitalizations and the longitudinal course of the illness.

Conclusions: Our results suggest that young depressed in-patients have widespread executive dysfunctions, including updating, shifting and inhibition processes. We also found a correlation between a longitudinal measure of depression severity and an updating task performance. We suggest that using multiple executive tasks gives the opportunity to distinguish the specific influence of various executive processes on clinical dimensions in depression.     

Preliminary evidence of differential relations between prefrontal cortex metabolism and sustained attention in depressed adults with bipolar disorder and healthy controls

OBJECTIVES: To assess the relations between sustained attention as assessed by the Continuous Performance Test (CPT) and subgenual and dorsolateral prefrontal cortex metabolism in depressed patients with bipolar disorders and healthy controls. DESIGN: Cross-sectional case-control design. METHODS: Cerebral metabolic rates were assessed with 18F-fluoro-deoxyglucose and positron emission tomography (PET) in the regions of interest defined on co-registered structural magnetic resonance images in eight medication-free, depressed bipolar disorder patients and 27 healthy control participants. PET scans were obtained in a resting state and the CPT was administered within 1 week of the PET scan. RESULTS: Although there were no statistically significant differences in performance on the CPT or in cerebral metabolism between the two groups, our analyses revealed differential relations between the CPT and metabolism across the groups. Decreased subgenual prefrontal metabolism was associated with slower hit rate reaction time and more omission errors in the bipolar group, but not the control group. Decreased dorsolateral prefrontal metabolism in the bipolar group, but not the control group, was associated with more commission errors. CONCLUSIONS: This study extends previous neuroimaging findings of structural and functional relevance of the prefrontal region with attention to include depressed states in bipolar disorder. The results are consistent with interpretations that decreased prefrontal activity may represent failure to activate some areas of inhibitory control. Decreasing subgenual prefrontal cortex metabolism appears to relate to decreased attention whereas the decreased dorsolateral prefrontal cortex metabolism relates more to decreased inhibitory control.     

Abnormal error processing in depressive states: a translational examination in humans and rats

Depression has been associated with poor performance following errors, but the clinical implications, response to treatment and neurobiological mechanisms of this post-error behavioral adjustment abnormality remain unclear. To fill this gap in knowledge, we tested depressed patients in a partial hospital setting before and after treatment (cognitive behavior therapy combined with medication) using a flanker task. To evaluate the translational relevance of this metric in rodents, we performed a secondary analysis on existing data from rats tested in the 5-choice serial reaction time task after treatment with corticotropin-releasing factor (CRF), a stress peptide that produces depressive-like signs in rodent models relevant to depression. In addition, to examine the effect of treatment on post-error behavior in rodents, we examined a second cohort of rodents treated with JDTic, a kappa-opioid receptor antagonist that produces antidepressant-like effects in laboratory animals. In depressed patients, baseline post-error accuracy was lower than post-correct accuracy, and, as expected, post-error accuracy improved with treatment. Moreover, baseline post-error accuracy predicted attentional control and rumination (but not depressive symptoms) after treatment. In rats, CRF significantly degraded post-error accuracy, but not post-correct accuracy, and this effect was attenuated by JDTic. Our findings demonstrate deficits in post-error accuracy in depressed patients, as well as a rodent model relevant to depression. These deficits respond to intervention in both species. Although post-error behavior predicted treatment-related changes in attentional control and rumination, a relationship to depressive symptoms remains to be demonstrated.     

A comparison of cognitive functioning in medicated and unmedicated subjects with bipolar depression

Objective: Neuropsychological studies of bipolar disorder reveal deficits in a variety of domains, including affective processing, memory, and sustained attention. These findings are difficult to interpret due to the potential confounding effects of mood-stabilizing medications. The present study aims to compare the cognitive performance of medicated and unmedicated subjects with bipolar depression to healthy control subjects. Method: Unmedicated subjects with bipolar depression (UBD, n = 32), subjects with bipolar depression on therapeutic doses of lithium or valproic acid (MBD, n = 33), and healthy control subjects (HC, n = 52) performed neuropsychological tasks measuring affective processing, visual memory, and sustained attention. Performance measures were covaried with age and mood ratings, where applicable. Results: With regard to affective processing, the MBD group exhibited greater response latency than the UBD and HC groups. For the same task, the MBD group made more omission errors during the happy condition than in the sad condition. On a task of sustained attention, the MBD group made more errors than the HC group. There were no significant group differences on measures of visual memory. Conclusions: Deficits in affective processing were found in the medicated group, while unmedicated subjects appear to be unaffected. In particular, the MBD group made more errors during happy conditions, indicating a potential attentional bias in subjects with bipolar depression on mood-stabilizing medications. The present study also implicates impairment in sustained attention for medicated subjects with bipolar disorder, particularly those with the type II variety.     

Distinct profiles of neurocognitive function in unmedicated unipolar depression and bipolar II depression.

BACKGROUND: Studies have demonstrated neuropsychological deficits across a variety of cognitive domains in depression. Few studies have directly compared depressed subjects with major depressive disorder (MDD) and bipolar disorder (BD), and many are confounded by medication status across subjects. In this study, we compared the performance of unmedicated currently depressed MDD and BD groups on a battery of neuropsychological tests that included measures of risk taking and reflection impulsivity. METHODS: Twenty-two MDD, seventeen BDII, and 25 healthy control subjects (HC), matched for age and IQ, were assessed on a battery of neuropsychological tests. RESULTS: The depressed groups showed comparable ratings of depression severity and age of illness onset. The MDD group was impaired on tests of spatial working memory and attentional shifting, sampled less information on a test of reflection impulsivity, and was oversensitive to loss trials on a decision-making test. The BDII subjects were generally intact and did not differ significantly from control subjects on any test. CONCLUSIONS: These data indicate differing profiles of cognitive impairment in unmedicated depressed MDD versus BDII subjects. Moderately depressed BDII subjects displayed relatively intact cognitive function, whereas MDD subjects demonstrated a broader range of executive impairments. These cognitive deficits in depression were not attributable to current medication status.     

Visuo-spatial attention processes in panic disorder with agoraphobia: a pilot study using a visual target discrimination task.

Panic attacks can be observed in a wide range of situations, but most common are those providing complex and unstructured stimulations, suggesting an impairment in attentional processing of visuo-spatial information. This study evaluated agoraphobics' attentional processing of neutral (i.e., not anxiety-provoking) visuo-spatial stimulation. Twelve patients suffering from panic attacks with agoraphobia were compared with 22 normal controls on a computerized visual target discrimination task specifically designed for this study. Psychometric measures assessed the phobic avoidance, the level of depression and anxiety. The numbers of errors and reaction times were analysed with a three-way ANOVA (Group x target modality x number of stimulations). No between-group significant difference was found for the reaction time performance and the mean number of detection errors. However, an interaction effect was observed for this last variable depending on the target modality: agoraphobic patients made fewer omission errors than control subjects when the target was present among distractors, while they made more commission errors when the target was absent. Outcomes are discussed in terms of attentional hyperactivation related to anxiety and perseverative decision process in agoraphobic patients.     

Effect of additional auditory and visual stimuli on continuous performance test (noise-generated CPT) in AD/HD children -- usefulness of noise-generated CPT

The continuous performance test (CPT) is designed to measure sustained attention quantitatively. Several CPTs are used clinically. We have made changes to the conventional type of visual CPT, by displaying auditory and visual noise along with target or non-target stimuli. By influencing the recognition of the subjects in this way, the changes were intended to increase the sensitivity of detection of inattention and impulsiveness, to make CPT more useful for diagnosis, and to examine the effect of noise on AD/HD children during CPT performance. Its usefulness for AD/HD diagnosis and the reaction of AD/HD children to noise were examined using newly developed computer software. Using this CPT analysis, a significant difference was observed in all measurements, except mean reaction time, between the control and AD/HD groups, showing that it was useful as a supplementary diagnostic method for AD/HD, and was more useful in the younger age group than in the older age group, as the same for conventional CPTs. As compared to no-noise sessions, commission and omission errors both increased significantly in auditory and visual noise sessions. Thus, analyzing the changes in measurements during noise sessions will improve the diagnosis of inattention and combined AD/HD subtypes. Furthermore, it was suggested that analysis of the effects of noise on AD/HD children will benefit their handling in an educational environment. Since omission errors were decreased in AD/HD children by noise during the CPT performance as compared to the control group, noise may induce attention in AD/HD children. The present study presents new findings on the responses to noise of AD/HD children during the CPT.     

颈动脉内膜剥脱术对20例颈内动脉狭窄患者视力与持续注意功能的改善作用

目的 探讨颈动脉内膜剥脱术(CEA)对20例颈内动脉狭窄致缺血性眼病患者视力与持续注意功能的改善作用。方法 选取2014年3月-2017年3月本院收治的颈内动脉狭窄致缺血性眼病患者40例,依据随机数字表法分为CEA组和颈动脉支架置入术(CAS)组,每组各20例,CEA组给予CEA治疗,CAS组给予CAS治疗,比较2组手术效果、并发症、视力、持续注意功能和眼动脉、视网膜中央动脉的血流动力学[收缩期峰值血流速度(PSV)、舒张末期血流速度(EDV)、阻力指数(RI)]。结果 CEA组残余狭窄率明显低于CAS组(P<0.05); CEA组和CAS组并发症发生率基本相同(P>0.05); CEA组和CAS组术后眼动脉、视网膜中央动脉的PSV、EDV明显高于术前,CEA组和CAS组术后眼动脉、视网膜中央动脉的RI、Log Mar最佳矫正视力和持续操作测试(CPT)的2、3位认错及遗漏数明显低于术前,CEA组术后眼动脉、视网膜中央动脉的PSV、EDV明显高于CAS组,CEA组术后眼动脉、视网膜中央动脉的RI和Log Mar最佳矫正视力和CPT的2、3位认错及遗漏数明显低于CAS组(P<0.05)。结论 CEA可有效改善颈内动脉狭窄致缺血性眼病患者动脉狭窄和眼动脉、视网膜中央动脉的血流动力学,有利于改善患者的视力与持续注意功能,且具有良好的安全性。     

Association between Dopamine D4 Receptor Gene Polymorphism and Scores on a Continuous Performance Test in Korean Children with Attention Deficit Hyperactivity Disorder

Objective

The aim of this study was to evaluate the association between a variable number of tandem repeats polymorphism at the dopamine D4 receptor gene (DRD4) and the performance of children with attention deficit hyperactivity disorder (ADHD) in a continuous performance test (CPT).

Methods

This study included 72 ADHD children (mean age=9.39±2.05 years) who were recruited from one child psychiatric clinic. The omission errors, commission errors, reaction time and reaction standardization in the CPT were computed. The number of 48-base pairs tandem repeats in the exon III of DRD4 was analyzed in a blind manner.

Results

The homozygosity of the 4-repeat allele at DRD4 was significantly associated with fewer commission errors (t=2.364, df=28.685, p=0.025) and standard deviation of reaction time (t=2.351, df=24.648, p=0.027) even after adjusting for age. The results of analyses of CPT measured values among three groups showed that the group with higher frequency of the 4-repeat allele showed a lower mean score of commission errors (F=4.268, df=2, p=0.018).

Conclusion

These results suggest a protective role of 4-repeat allele of the DRD4 polymorphisms on commission errors in the CPT in children with ADHD.     

Effect of methylphenidate on young adult's vigilance and event-related potentials

Two studies were conducted on the effects of methylphenidate (20 mg) on young adults' event-related potentials. Although this stimulant elevated heart rate in study 1 (n = 14), it failed to affect either performance or amplitude of the late positive component (LPC) obtained from two versions of the continuous performance test (CPT). Because performance on these tasks was nearly error-free, we conducted study 2 (n = 23) to test the hypothesis that methylphenidate enlarges LPC amplitude only in more challenging tests than those used in study 1. In study 2, although heart rate was again elevated by the 20 mg dose of methylphenidate, LPC amplitude and performance were again unaffected in the two tasks employed in study 1 or in an easy tone discrimination procedure. However, in a more difficult version of CPT (10% errors of omission), both accuracy and amplitude of the concurrently obtained LPC were increased by methylphenidate. Similarly, in a choice-reaction time test, the stimulant increased speed as well as CNV amplitude. Our interpretation of the results is based on the view that LPC reflects the number of attentional resources committed to a stimulus during the evaluation stage. Thus, increases in LPC amplitude by methylphenidate are obtained only in tasks in which the subject may profit from the recruitment of additional attentional resources.     

Neuropsychological deficits are associated with smoking cessation treatment failure in patients with schizophrenia

Schizophrenics have deficits in neuropsychological performance, some of which are modified by cigarette smoking. These patients also have high rates of smoking and resistance to smoking cessation interventions. We examined whether the presence of neuropsychological deficits prior to smoking cessation treatment was associated with smoking cessation treatment failure in schizophrenic as compared to non-psychiatric control smokers. Neuropsychological assessments were performed prior to treatment with pharmacological agents during the course of placebo-controlled trials in schizophrenic and non-psychiatric control smokers, and included the Wisconsin Card Sorting Test (WCST), a Visuospatial Working Memory (VSWM) task, the Stroop Color Word Test (SCWT) and the Continuous Performance Test (CPT). In schizophrenics (n=32), subjects who had greater deficits in VSWM and WCST performance were significantly less likely to quit smoking, but this association was not observed in controls (n=40). Differences between quitters and non-quitters were not likely related to atypical antipsychotic treatment or differences in depressive symptoms. No associations between baseline performance on CPT or SCWT and quit status were found in either group. These preliminary data suggest that in schizophrenics, neuropsychological deficits are associated with smoking cessation treatment failure.