Dopamine promotes cognitive effort by biasing the benefits versus costs of cognitive work.

Stimulants such as methylphenidate are increasingly used for cognitive enhancement but precise mechanisms are unknown. We found that methylphenidate boosts willingness to expend cognitive effort by altering the benefit-to-cost ratio of cognitive work. Willingness to expend effort was greater for participants with higher striatal dopamine synthesis capacity, whereas methylphenidate and sulpiride, a selective D2 receptor antagonist, increased cognitive motivation more for participants with lower synthesis capacity. A sequential sampling model informed by momentary gaze revealed that decisions to expend effort are related to amplification of benefit-versus-cost information attended early in the decision process, whereas the effect of benefits is strengthened with higher synthesis capacity and by methylphenidate. These findings demonstrate that methylphenidate boosts the perceived benefits versus costs of cognitive effort by modulating striatal dopamine signaling.

[The syndrome of Capgras: converging models]. / Het syndroom van Capgras: convergerende modellen.

BACKGROUND: Various theories have been proposed concerning the syndrome of Capgras. AIM: To search for a concept that is common to the various theories relating to the aetiology of the syndrome of Capgras. METHODS: We begin by describing a new case of Capgras syndrome that we encountered recently, and thereafter we searched the literature using PubMed and PsycINFO. RESULTS: Various explanatory models converge in that they all assign a central role to a changed affect. A sensation of 'alienation' at a conscious or subconscious level, together with inadequate evaluation of beliefs, seems plausible. All models demonstrate some form of 'splitting' i.e. the separate processing of information in time, anatomy or mental representation. CONCLUSION: Although there is no conclusive evidence to support any one of the hypotheses, the models display striking similarities. They complement each other.

Fatal interstitial lung disease associated with high erlotinib and metabolite levels. A case report and a review of the literature.

INTRODUCTION: Erlotinib is an agent in the class of oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Although this class of agents is considered to be relatively safe, the most serious, but rare, adverse reaction is drug-associated interstitial lung disease (ILD). This potentially fatal adverse reaction has been often described with gefitinib, but has been less well described for erlotinib. We here describe a case report of fatal interstitial lung disease in a Caucasian man associated with erlotinib and high erlotinib and metabolite plasma levels and discuss it in the context of all documented cases of erlotinib associated ILD. METHODS: Our case was described and for the literature review a Pubmed and Google Scholar search was conducted for cases of erlotinib associated ILD. The retrieved publications were screened for relevant literature. RESULTS: Besides our case, a total of 19 cases of erlotinib-associated ILD were found. Eleven out 19 cases had a fatal outcome and in only one case erlotinib plasma concentrations were measured and found to be high. CONCLUSION: Erlotinib-associated ILD is a rare, serious and often fatal adverse reaction. Most likely, the cause for erlotinib-associated ILD is multifactorial and high drug levels may be present in patients without serious adverse reactions. However, considering the pharmacology of EGFR inhibitors, high drug and metabolite levels may play a role and future studies are warranted to identify risk factors and to investigate the role of elevated levels of erlotinib and its metabolites in the development of pulmonary toxicity.

The effects of guided discontinuation of antipsychotics on neurocognition in first onset psychosis.

OBJECTIVE: To assess the effects of second generation antipsychotics on neurocognitive function in patients with stable remission of first episode psychosis. METHODS: Fifty-three patients with first onset psychosis in the schizophrenia spectrum entered a randomised controlled trial of guided discontinuation (GD) versus maintenance treatment (MT) with second generation antipsychotics. A comprehensive neurocognitive test battery was administered at the time of remission and shortly after dose reduction or discontinuation (GD-group) or at the same time in the MT-group. RESULTS: With the exception of negative symptoms, PANSS scores decreased over time and neurocognition improved significantly on most tests in both groups. The GD-group, however, improved significantly more than the MT-group on three neurocognitive measures in the domain of speed of processing. CONCLUSION: These data suggest that, in first episode patients, dose reduction or discontinuation of second generation antipsychotics after stable remission is achieved, might improve neurocognitive function more than continuing second generation antipsychotics, suggesting a negative role for second generation antipsychotics, specifically in the domain of speed of processing.

[Typical and atypical antipsychotics: Is there a difference in their influence on neurocognition?]. / Typische en atypische antipsychotica bij patiënten met schizofrenie: is er verschil in invloed op neurocognitie?

BACKGROUND: Neurocognitive dysfunction is a core feature of schizophrenia and is related to the functional outcome of the illness. It has been suggested that the so-called atypical antipsychotics may have a more favourable influence on neurocognition than the older, typical antipsychotics and thus also on the functional outcome. AIM: To review the recent scientific literature concerning the effects of antipsychotics on neurocognition. METHOD: The literature was reviewed systematically via the most important databases. RESULTS: Meta-analyses suggest that atypical antipsychotics have moderate, positive effects on neurocognition and in that respect are more beneficial than typical antipsychotics. Recent studies, however, challenge this finding. CONCLUSION: The reported positive, cognitive effects of atypical antipsychotics are slight, particularly compared to the severity of neurocognitive dysfunction found in schizophrenia. In clinical practice there seem to be no convincing reason for attaching much weight to any differential effects that typical or atypical antipsychotics may have on neurocognition.

The efficacy of SMS text messages to compensate for the effects of cognitive impairments in schizophrenia.

BACKGROUND AND AIMS: Many people with schizophrenia have severe cognitive impairments that hamper their activities. The effect of pharmacological and behavioural interventions on cognitive functioning has been demonstrated, but even after successful intervention considerable impairments can remain. Therefore, we sought for alternative ways to help patients cope with the effects of their cognitive impairments. In the present study, we have evaluated the efficacy of short message service (SMS) text messages to compensate for the effects of cognitive impairments in schizophrenia in daily life. DESIGN: A waiting list controlled trial was conducted: patients were quasi-randomly assigned to an A-B-A (baseline-intervention-follow-up) condition or an A-A-B-A condition that included an additional 7-week waiting list. The waiting list was included to control for the effect of time on relevant outcome. METHOD: Sixty-two people with schizophrenia or related psychotic disorders were included in the study. All patients showed impaired goal-directed behaviour in daily life-situations. Patients were prompted with SMS text messages to improve their everyday functioning. The primary outcome measure was the percentage of goals achieved. RESULTS: The overall percentage of goals achieved increased with prompting, while performance dropped to baseline level after withdrawing the prompts. Keeping appointments with mental health workers and carrying out leisure activities increased with prompting, while medication adherence and attendance at training sessions remained unchanged. A majority of the patients enjoyed receiving the SMS text messages. DISCUSSION: Prompting can significantly improve achievement of a number of relevant goals. For other goals, combining prompting with interventions that enhance motivation seems indicated.

The predictive value of measures of social cognition for community functioning in schizophrenia: implications for neuropsychological assessment.

The objective of this study was to examine the unique contribution of social cognition to the prediction of community functioning and to explore the relevance of social cognition for clinical practice. Forty-six schizophrenia patients and 53 healthy controls were assessed with tests of social cognition [emotion perception and Theory of Mind (ToM)], general cognition, and, within the patient sample, psychiatric symptoms. Community functioning was rated by nurses or family members. Social cognition was a better predictor of community functioning than general cognition or psychiatric symptoms. When the contributions of emotion perception and ToM were examined separately, only ToM contributed significantly to the prediction of community functioning. Independent living skills were poor in patients with impaired social cognition. In controls, social cognition was not related to community functioning. ToM was the best predictor of community functioning in schizophrenia. However, to fully understand a patient's strengths and weaknesses, assessment of social cognition should always be combined with assessment of general cognition and psychiatric symptoms.

Sustained and transient attention in the continuous performance task.

One of the most frequently applied methods to study abnormal cognition is the Continuous Performance Task (CPT). It is unclear, however, which cognitive functions are engaged in normal CPT performance. The aims of the present study were to identify the neurocognitive functions engaged in the main variants of the CPT and to determine to what extent these variants differentially engage these functions. We hypothesized that the main CPT versions (CPT-X, CPT-AX, CPT-Identical Pairs) can be distinguished by whether they demand sustained or transient attention and sustained or transient response preparation. Transient attention to objects like letters or digits, that is, the need to switch attention to different objects from trial to trial, impairs target detection accuracy relative to sustained attention to a single object. Transient response preparation, that is, the possibility to switch response preparation on and off from trial to trial, improves response speed relative to having to sustain response preparation across all trials. Comparison of task performance and Event-Related brain Potentials (ERPs) of healthy participants obtained in the main CPT variants confirmed these hypotheses. Behavioral and ERP measures indicated worse target detection in the CPT-AX than in the CPT-X, consistent with a higher demand on transient attention in that task. In contrast, behavioral and ERP measures indicated higher response speed in the CPT-AX than in the CPT-X, associated with more response preparation in advance of the targets. This supports the idea of increased transient response preparation in the CPT-AX. We conclude that CPTs differ along at least two task variables that each influences a different cognitive function.

Paraprofessionals for anxiety and depressive disorders.

BACKGROUND: The established mental health care system does not have the resources to meet the extensive need for care of those with anxiety and depressive disorders. Paraprofessionals partially replacing professionals may be cost-effective. OBJECTIVES: To investigate the effectiveness of any kind of psychological treatment for anxiety and depressive disorders performed by paraprofessionals compared with professionals, waiting list or placebo condition. To examine whether the results apply to clinically significant anxiety and depressive disorders of referred patients with a psychiatric history and/or whose illness has lasted two years or more. SEARCH STRATEGY: CCDANCTR-Studies using the following terms: (paraprofessional* or para-professional* or non-professional* or non-professional* or peer or volunt*); EMBASE (ExerptaMedica), MEDLINE and PsycINFO, all years published, key words: para-/paraprofessional, non-/nonprofessional, rand*, respectively psy*; citation lists of articles reviewing the subject and included studies; correspondence with authors of controlled studies and review reports on the subject. SELECTION CRITERIA: Randomised controlled trials that used symptom measures, and compared the effects of psychological treatments given by paraprofessionals (mental health care workers, paid or voluntary, unqualified with respect to the psychological treatment) with psychological treatments given by professionals, and with waiting list or placebo condition. DATA COLLECTION AND ANALYSIS: The standard mean difference was used to pool continuous data from each trial, and odds ratios were used to pool dichotomous data, using a random effects model. The generic inverse variance method was used for combining continuous and dichotomous data. The effect of low quality studies and the use of self-rated versus observer-rated measures were tested, and subgroup analyses were performed for differences between depression and anxiety diagnosis, paraprofessionals with/without professional background, group/individual intervention, length of follow-up and gender (post-hoc subgroup analysis). MAIN RESULTS: Five studies, all using self-report measures, reported five comparisons of paraprofessionals versus professionals (n=106) and five comparisons of paraprofessionals versus control condition (n=220). No differences were found between paraprofessionals and professionals (SMD=0.09, 95% CI -0.23 to 0.40, p=0.58; no significant heterogeneity). Studies comparing paraprofessionals versus control reported mixed continuous and dichotomous data showed a significant pooled effect in favour of paraprofessionals (OR=0.34, 95% CI 0.13 to 0.88, p=0.03), but heterogeneity was indicated (I(2)=60.9%, Chi(2)= 10.24, df=4, p=0.04). After correction for heterogeneity and removing one study of low quality, the pooling of data from three studies (n=128; mixed gender and women only) indicated no significant difference in effect between paraprofessionals and professionals (SMD=0.13, 95% CI -0.39 to 0.64; p=0.63) and a strongly significant pooled effect for three studies (n=188; women only) favouring paraprofessionals over the control condition (OR=0.30, 95% CI 0.18 to 0.48, p<0.00001), and homogeneity indicated between studies (I(2)=0%, Chi(2)=0.47, df=2, p=0.79). AUTHORS' CONCLUSIONS: The few studies included in the review did not allow conclusions about the effect of paraprofessionals compared to professionals. Pooling data from three studies, involving women only, indicated a significant effect for paraprofessionals (all volunteers) compared to no treatment. The evidence to date may justify the development and evaluation of programs incorporating paraprofessionals in treatment programs for anxiety and depressive disorders.

Why is self-help neglected in the treatment of emotional disorders? A meta-analysis.

BACKGROUND: Although the burden of emotional disorders is very high, mental health care is only available to a minority of patients. The literature suggests that self-help strategies, both bibliotherapy and self-help groups alike, are effective for various, less serious complaints but it is unclear whether available data support a role for self-help in treatment protocols for patients with clinically significant emotional disorders. METHOD: We searched the literature with a focus on 'anxiety' and/or 'depressive disorder'. Standardized assessment of diagnosis or symptoms and randomized controlled trials were inclusion criteria for a meta-analysis. RESULTS: The mean effect size of self-help (mainly bibliotherapy) v. control conditions is 0.84, and 0.76 for follow-up; the effect sizes of self-help v. treatment are -0.03 and -0.07 respectively. A longer treatment period is more effective. CONCLUSIONS: Bibliotherapy for clinically significant emotional disorders is more effective than waiting list or no treatment conditions. The dearth of studies on self-help groups for emotional disorders does not permit an evidence-based conclusion concerning the effects of self-help groups. No difference was found between bibliotherapy and psychiatric treatment of relatively short duration.

Neurological soft signs discriminating mood disorders from first episode schizophrenia.

OBJECTIVE: To investigate the specificity of neurological soft signs (NSS) for first episode schizophrenia compared with mood disorders. METHOD: We assessed NSS in a sample of 60 healthy controls, 191 first episode psychosis patients and 81 mood disorder patients. We used a principle component analysis to identify dimensions of NSS. We subsequently investigated the specificity of these dimensions for schizophrenia and their relationships with medication and symptom scores. RESULTS: We identified five dimensions; coordination disorders, movement disorders, increased reflexes, dyskinesia and catatonia. These dimensions were related to neural circuits associated with schizophrenia and mood disorders and included the fronto-striatal-thalamic and the fronto-cerebellar pathway. The movement disorder dimension, which was suggestive for the involvement of the fronto-striatal-thalamic pathway, was specific for first episode schizophrenia independent from medication. CONCLUSION: NSS are the result of circuitry dysfunctions rather than overall dysfunction and a particular set of NSS shows specificity for schizophrenia.

What are the effects of antipsychotics on sexual dysfunctions and endocrine functioning?

The literature is reviewed and preliminary results of new studies are presented showing that treatment with classical antipsychotics, as well as risperidone, induces sexual dysfunctions in 30-60% of the patients. These antipsychotics also frequently induce amenorrhoea and galactorrhoea. Although comparative studies are rare, it is likely that prolactin-sparing antipsychotics, as recently shown in a randomized trial of olanzapine versus risperidone, induce less sexual side effects.From these studies, it becomes apparent that prolactin elevation induced by classical antipsychotics and risperidone is probably a factor in inducing sexual dysfunctions, amenorrhoea and galactorrhoea. The role of other factors inducing sexual dysfunctions like sedation, proportional, variant -blockade, testosterone, dopamine, and serotonin is discussed. Finally, it is concluded that sexual and hormonal effects of antipsychotics, although clearly important, are often neglected in research as in clinical practice. Lowering the dosage or switching to a prolactin-sparing antipsychotic often reduces sexual side effects, amenorrhoea, and galactorrhoea.

Low IQ scores in schizophrenia: primary or secondary deficit?

BACKGROUND: Schizophrenia is consistently associated with lower IQ compared to the IQ of control groups, or estimated premorbid IQ. It is not likely that the IQ scores deteriorate during the prodromal phase or first psychotic episode; they are already present before the onset of the prodromal phase and have been detected in childhood. METHODS: We investigated cognitive functioning and IQ levels in a group of 36 patients with schizophrenia or other psychotic disorders. RESULTS: The IQ scores in our sample were lower than average. The IQ showed a relation with attention, memory, speed of information processing and some aspects of executive functioning. However, when IQ scores were corrected for processing speed, they were no longer below average. CONCLUSIONS: These findings are important in considering the value of intelligence levels in schizophrenia. IQ scores should be judged in combination with cognitive functioning and school career to assess a patients capabilities in society. Cognitive functions and other variables might have a considerable influence on IQ scores. This rises the question of whether the low IQ scores are a primary or secondary deficit. Schizophrenia patients may have normal IQs, but could be less capable of making an IQ-test.

Does frontal normality exist in schizophrenia? A saccadic eye movement study.

Many observations have supported the general idea of impaired frontal function in schizophrenia. In particular, neuropsychological studies have shown severe frontal deficits. However, other studies found normal cognitive function in a proportion of patients. Since saccadic tasks also provide an index of frontal function, we examined the presence of frontal deficits in patients by means of both neuropsychological and saccadic tasks, and compared the sensitivity of both approaches for frontal impairment. In addition, we examined the relationship between saccadic and neuropsychological measures. Twenty-four schizophrenic patients and twenty healthy controls completed an extensive neuropsychological battery and three saccadic tasks. Based on the neuropsychological battery alone, 42% of the patients showed frontal deficits, whereas combined use of neuropsychological and saccadic tasks resulted in 79% with frontal deficits. The antisaccade task appeared able to detect frontal deficits in patients who were without frontal impairment on the neuropsychological battery. Saccadic deficits were, however, not necessarily accompanied by deficits on frontal neuropsychological measures. This suggests that the saccadic and neuropsychological tasks used in the present study targeted different frontal functions. This view was supported by the lack of correlations between saccadic and frontal neuropsychological measures.

Reasoning about the optimal duration of prophylactic antipsychotic medication in schizophrenia: evidence and arguments.

OBJECTIVE: To review evidence-based literature regarding the necessary duration of antipsychotic relapse prevention in schizophrenia and related psychoses. METHOD: A computerized search was performed on Medline, Embase Psychiatry and PsycLIT which covered the period 1974-99. We also used cross-references. RESULTS: Although schizophrenia refers mainly to an intrinsic biological vulnerability, only maintenance studies with a follow-up of 2 years at most are available. Relapses appear unpredictable and occur even after long-term successful remission during antipsychotic treatment. CONCLUSION: Since rehabilitation efforts have effects only after long-term endeavours, antipsychotic relapse prevention should be maintained for long periods. It is reasonable to treat patients suffering from schizophrenia and related psychoses for longer periods than indicated by the current guidelines.

Distress attributed to negative symptoms in schizophrenia.

The purpose of the study was to examine (1) to which negative symptoms schizophrenia patients attribute distress and (2) whether clinical variables can predict the levels of reported distress. With the help of a research assistant, 86 hospitalized patients completed a self-rating scale for negative symptoms. The 21 items of the self-rating scale were taken from the Scale for the Assessment of Negative Symptoms (SANS). A psychiatrist rated the patients on a number of scales, including the SANS. When patients reported particular symptoms, they were asked whether those symptoms bothered or distressed them. Answers to this question were highly dependent on the type of symptom involved. Distress was most often attributed to symptoms in the subscale avolition-apathy. Patients were also asked how much they were bothered or distressed. Again, high levels of distress were most often attributed to items in the subscale avolition-apathy. A summary score was developed for the level of reported distress: the distress score. Regression analysis showed that distress scores were not associated with the observed severity of negative symptoms or with the level of psychiatric disability. High distress scores were best predicted by the combination of high scores for depression and high scores for insight into positive symptomatology. However, this model explained only a quarter of the variance in distress scores.

Clinical predictors of discrepancy between self-ratings and examiner ratings for negative symptoms.

Little is known about the awareness of negative symptoms or its correlates. The aim of this study was to examine whether a number of clinical variables can predict the discrepancy between ratings of negative symptoms made by schizophrenic patients and by an examiner. This discrepancy could provide a measure for the awareness of negative symptoms. Eighty-six schizophrenic patients used a self-rating scale for negative symptoms with items derived from the Scale for the Assessment of Negative Symptoms (SANS). A psychiatrist assessed all patients using the SANS and other instruments, including the Present State Examination (PSE) item "insight into psychotic condition." Nurses assessed all patients using the Rehabilitation Evaluation Hall and Baker (REHAB), a scale for the measurement of psychiatric disability. All measurements were repeated after 2 months. A sensitive index for the underestimation of the severity of negative symptoms was developed, the discrepancy score. Multiple regression analysis was used to examine the predictability of discrepancy scores. Since scores for SANS items were used to calculate discrepancy scores, all regression analyses were performed with the SANS summary score as a covariate. The first step was to assess the independent contribution of each variable to the prediction of discrepancy scores. The second step was to examine the predictive quality of the 19 variables together. The variables themselves failed to make an independent contribution to the prediction of discrepancy scores at both assessments. REHAB scores, for instance, contributed to the prediction of discrepancy scores at the first assessment, but not at the second. The results of the second step showed that the best model for the prediction of discrepancy scores included the variables of depression (negative association) and anxiety (positive association). The absence of an association with the PSE item suggests that the awareness of negative symptoms is not related to insight into positive symptoms. An important limitation of our study is the arbitrary method of discrepancy quantification.

The specificity of neurological signs in schizophrenia: a review.

This review examines the extent to which neurological signs are more prevalent in schizophrenia patients, compared to mood-disorder patients and healthy subjects, and whether there is a pattern in any of the differences that may be found. We included 17 studies and calculated the weighted mean prevalence of 30 neurological signs. The prevalence of most signs appears to be significantly different between schizophrenia patients and normal controls, but there are fewer differences between schizophrenia and mood-disorder patients. Several signs - poor stereognosis and rhythm tapping - are even more prevalent in mood-disorder patients than in schizophrenia patients. Only lack of extinction, dysdiadochokinesia, poor tandem walk, finger-thumb-opposition and articulation are significantly more prevalent in schizophrenia compared to mood-disorder patients. Impaired motor coordination seems most specific to schizophrenia. The discriminating power of motor sequencing still needs to be studied. So far, there is no evidence of a clearly interpretable pattern of neurological signs distinguishing schizophrenia patients from mood-disorder patients.