This article reviews and synthesizes research on reward processing in schizophrenia, which has begun to provide important insights into the cognitive and neural mechanisms associated with ...motivational impairments. Aberrant cortical-striatal interactions may be involved with multiple reward processing abnormalities, including: (1) dopamine-mediated basal ganglia systems that support reinforcement learning and the ability to predict cues that lead to rewarding outcomes; (2) orbitofrontal cortex-driven deficits in generating, updating, and maintaining value representations; (3) aberrant effort-value computations, which may be mediated by disrupted anterior cingulate cortex and midbrain dopamine functioning; and (4) altered activation of the prefrontal cortex, which is important for generating exploratory behaviors in environments where reward outcomes are uncertain. It will be important for psychosocial interventions targeting negative symptoms to account for abnormalities in each of these reward processes, which may also have important interactions; suggestions for novel behavioral intervention strategies that make use of external cues, reinforcers, and mobile technology are discussed.
Abstract Background The observation that mismatch negativity (MMN) is consistently impaired in schizophrenia has generated considerable interest in the use of this biomarker as an index of disease ...risk and progression. Despite such enthusiasm, a number of issues remain unresolved regarding the nature of MMN impairment. The present study expands upon an earlier meta-analysis of MMN impairment in schizophrenia by examining impairment across a range of clinical presentations, as well as across experimental parameters. Methods One hundred one samples of schizophrenia patients were included in the present study, including first-episode ( n = 13), chronic ( n = 13), and mixed-stage ( n = 75) samples. Additionally, MMN was examined in three related conditions: bipolar disorder ( n = 9), unaffected first-degree relatives ( n = 8), and clinical high risk ( n = 16). Results We found that MMN impairment 1) likely reflects a vulnerability to disease progression in clinical high-risk populations rather than a genetic risk for the condition; 2) is largely unrelated to duration of illness after the first few years of illness, indicating that impairment is not progressive throughout the life span; 3) is present in bipolar disorder, albeit to a lesser degree than in schizophrenia; and 4) is not modulated by experimental parameters such as magnitude of change between standard and deviant tones or frequency of deviant tones but may be modulated by attentional demands. Conclusions Such findings lay the foundation for a better understanding of the nature of MMN impairment in schizophrenia, as well as its potential as a clinically useful biomarker.
Currently, there is a great interest in finding alternative protein and energy sources to replace soybean-based feeds in poultry diets. The main objective of the present study was to completely ...replace soybean in layer diets with defatted meal and fat from black soldier fly larvae without adverse effects. For this purpose, 5 × 10 Lohmann Brown Classic hens were fed either a soybean-based diet or diets based on defatted black soldier fly larvae meal and fat from 2 producers (1 commercial, 1 small-scale) operating with different rearing substrates, temperatures, and larvae processing methods (10 hens/diet). The data obtained included nutrient composition of larvae meals and diets, amino acid digestibility (6 hens/diet), and metabolizability, performance and egg quality (all 10 hens/diet). In addition, the acceptance of the 4 larvae-based diets was tested against the soybean-based diet in a 6-day choice feeding situation (10 hens/treatment). The nutritional value of the larvae-based diets was equivalent to the soybean-based diet in hens with a laying performance of 98%. Although average feed intake was not significantly different over the 7 experimental weeks, the diets based on larvae feeds from the small-scale production appeared to be slightly less accepted in a choice situation than the soy-based diet and those with larvae from commercial origin. This was more likely the effect of the larvae fat rather than that of the larvae protein meal. In addition, the commercial larvae material was superior to that from the small-scale production concerning supply with digestible sulfur-containing amino acids (548 vs. 511 mg/day) and lysine (792 vs. 693 mg/day), egg weight (67 vs. 63 g), daily egg mass (66 vs. 61 g/day) and, in tendency, feed efficiency. The results indicate that soybean-based feeds can be replaced completely by black soldier fly meal and fat in diets of high-performing layers. However, because of nutritional differences between the larvae materials of different origin the quality of the larvae has to be closely monitored before being used.
Previous research provides evidence for discrepancies in various types of emotional self-report in individuals with schizophrenia; patients and healthy subjects report similar levels of positive ...emotion when reporting current feelings, yet patients report lower levels of positive emotion when reporting on noncurrent feelings. Such apparent discrepancies, which have come to be termed the "emotion paradox" in schizophrenia, have complicated our understanding of what anhedonia actually reflects in this patient population. The authors sought to resolve this paradox.
The authors reviewed the empirical literature on anhedonia and emotional experience in schizophrenia through the lens of the accessibility model of emotional self-report, a well-validated model of emotional self-report developed in the affective science literature that clarifies the sources of emotion knowledge that individuals access when providing different types of self-report. The authors used this model to propose a resolution to the "emotion paradox" and to provide a new psychological conceptualization of anhedonia.
Data are presented in support of this new perspective on anhedonia and to demonstrate how cognitive impairments may influence reports of noncurrent feelings in schizophrenia.
The authors conclude that anhedonia should no longer be considered an experiential deficit or a diminished "capacity" for pleasure in patients with schizophrenia. Rather, anhedonia reflects a set of beliefs related to low pleasure that surface when patients are asked to report their noncurrent feelings. Encoding and retrieval processes may serve to maintain these beliefs despite contrary real-world pleasurable experiences. Implications for assessment and treatment are discussed in relation to this new conceptualization of anhedonia.
The pathogenesis of multiple sclerosis (MS) involves complex interactions between genetic susceptibility and environmental triggers. Clinical observations suggest that the study of sex differences ...might provide important insight into mechanisms of pathogenesis and progression of the disease in patients. MS occurs more frequently in women than in men, indicating that sex-related factors have an effect on an individual's susceptibility to developing the condition. These factors include hormonal, genetic and environmental influences, as well as gene-environment interactions and epigenetic mechanisms. Interestingly, women do not have a poorer prognosis than men with MS despite a higher incidence of the disease and more-robust immune responses, which suggests a mechanism of resilience. Furthermore, the state of pregnancy has a substantial effect on disease activity, characterized by a reduction in relapse rates during the third trimester but an increased relapse rate in the postpartum period. However, pregnancy has little effect on long-term disability in women with MS. The unravelling of the mechanisms underlying these clinical observations in the laboratory and application of the results to the clinical setting is a unique and potentially fruitful strategy to develop novel therapeutic approaches for MS.
Multiple sclerosis is a heterogeneous disease with varying clinical picture. There have been substantial efforts to develop outcome measurements for therapeutic interventions but very few studies ...have addressed the value of bodily functions from the patient perspective. In a randomly selected cohort of early (<5 years, n = 84) and longer lasting disease courses (>15 years, n = 82) patients we asked for a weighting of 13 bodily functions and compared results with actual disability as measured by the United Kingdom Disability Scale. Lower limb function was given the highest priority in both patient groups followed by visual functioning and cognition especially in longer lasting MS. Actual disability did not correlate with the given priorities indicating that experienced deficits do not influence the subjective ratings of bodily functions. These results underline that ambulation-focused scales in MS represent a key dimension from the patient perspective. Visual functioning should be taken more into account.
Cognitive impairment has emerged as an important new target in schizophrenia therapeutics in light of evidence that cognitive deficits are critically related to the functional of disability that is ...characteristic of the illness. Evidence is briefly reviewed supporting the idea that the cognitive impairment in schizophrenia is an attractive target for therapeutic intervention including: (1) there is a characteristic pattern of cognitive deficits that occur with very high frequency; (2) the deficits are relatively stable over time; and (3) cognitive deficits are relatively independent of the symptomatic manifestations of the illness. Thus, cognitive impairment appears to be a well-defined, reliable and distinct dimension of the illness.
Apathy and depression are heterogeneous syndromes with symptoms that overlap clinically. This clinical overlap leads to problems with classification and diagnosis in clinical populations. No ...functional imaging study has attempted to separate brain regions altered in apathy from those altered in depression in a clinical population. Parkinson disease (PD) is a disorder in which apathy and depression co-exist in a single population. We evaluate the relationship between apathy, depression, and motor severity of disease in PD, focusing on the relationship between these factors and the amplitude of the low frequency fluctuation (ALFF) in the resting state. We first evaluated if the resting ALFF signal is a reliable measure for our clinical question. For this, we develop and introduce a cross validation approach we term the “Regional Mapping of Reliable Differences” (RMRD) method to evaluate reliability of regions of interest deemed “significant” by standard voxel-wise techniques. Using this approach, we show that the apathy score in this sample is best predicted by ALFF signal in the left supplementary motor cortex, the right orbitofrontal cortex, and the right middle frontal cortex, whereas depression score is best predicted by ALFF signal in the right subgenual cingulate. Disease severity was best predicted by ALFF signal in the right putamen. A number of additional regions are also statistically (but not reliably) correlated with our neuropsychological measures and disease severity. Our results support the use of resting fMRI as a means to evaluate neuropsychiatric states and motor disease progression in Parkinson disease, and the clinical and epidemiologic observation that apathy and depression are distinct pathological entities. Our finding that “significance” and “reliability” are dissociated properties of regions of interest identified as significant using standard voxel-wise techniques suggests that including reliability analyses may add useful scientific information in neurobehavioral research.
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► We evaluate in PD how apathy, depression, and motor severity influence resting fMRI. ► Measure Amplitude of Low Frequency Fluctuation (ALFF). ► Decreased ALFF in left supplementary motor area predicts apathy. ► Increased ALFF in right subgenual cingulated predicts depression. ► Decreased ALFF in right putamen predicts increasing severity of disease.
In 2005, the National Institute of Mental Health held a consensus development conference on negative symptoms of schizophrenia. Among the important conclusions of this meeting were that there are at ...least 5 commonly accepted domains of negative symptoms (blunted affect, alogia, avolition, anhedonia, asociality) and that new rating scales were needed to adequately assess these constructs. Two next-generation negative symptom scales resulted from this meeting: the Brief Negative Symptom Scale (BNSS) and Clinical Assessment Interview for Negative Symptoms (CAINS). Both measures are becoming widely used and studies have demonstrated good psychometric properties for each scale. The current study provides the first direct psychometric comparison of these scales. Participants included 65 outpatients diagnosed with schizophrenia or schizoaffective disorder who completed clinical interviews, questionnaires, and neuropsychological testing. Separate raters completed the BNSS and CAINS within the same week. Results indicated that both measures had good internal consistency, convergent validity, and discriminant validity. High correspondence was observed between CAINS and BNSS blunted affect and alogia items. Moderate convergence occurred for avolition and asociality items, and low convergence was seen among anhedonia items. Findings suggest that both scales have good psychometric properties, but that there are important distinctions among the items related to motivation and pleasure.
Patients with schizophrenia demonstrate deficits in motivation and learning that suggest impairment in different aspects of the reward system. In this article, we present the results of 8 converging ...experiments that address subjective reward experience, the impact of rewards on decision making, and the role of rewards in guiding both rapid and long-term learning. All experiments compared the performance of stably treated outpatients with schizophrenia and demographically matched healthy volunteers. Results to date suggest (1) that patients have surprisingly normal experiences of positive emotion when presented with evocative stimuli, (2) that patients show reduced correlation, compared with controls, between their own subjective valuation of stimuli and action selection, (3) that decision making in patients appears to be compromised by deficits in the ability to fully represent the value of different choices and response options, and (4) that rapid learning on the basis of trial-to-trial feedback is severely impaired whereas more gradual learning may be surprisingly preserved in many paradigms. The overall pattern of findings suggests compromises in the orbital and dorsal prefrontal structures that play a critical role in the ability to represent the value of outcomes and plans. In contrast, patients often (but not always) approach normal performance levels on the slow learning achieved by the integration of reinforcement signals over many trials, thought to be mediated by the basal ganglia.
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