Matthias Kirschner

Patients’ and clinicians’ attitude towards long-acting depot antipsychotics in subjects with a first episode of psychosis

Objectives: The acceptance and use of long-acting depot antipsychotics has been shown to be influenced by the attitudes of patients and clinicians. Depot treatment rates are low across countries and especially patients with first-episode psychosis are rarely treated with depot medication. The aim of this article was to review the literature on patients’ and clinicians’ attitudes towards long-acting depot antipsychotics in subjects with first-episode psychosis. Methods: A systematic search of Medline, Embase, PsycINF and Google Scholar was conducted. Studies were included if they reported original data describing patients’ and clinicians’ attitudes towards long-acting depot antipsychotic in subjects with first-episode psychosis. Results: Six studies out of a total of 503 articles met the inclusion criteria. Four studies conveyed a negative and two a positive opinion of clinicians toward depot medication. No systematic study directly addressed the attitude of patients with first-episode psychosis. Psychiatrists frequently presume that patients with first-episode psychosis would not accept depot medication and that depots are mostly eligible for chronic patients. Conclusions: Full information of all patients especially those with first episode psychosis in a therapeutic relationship that includes shared decision-making processes could reduce the negative image and stigmatization attached to depots.

Secondary negative symptoms — A review of mechanisms, assessment and treatment

Negative symptoms in schizophrenia may be classified as primary or secondary. Primary negative symptoms are thought to be intrinsic to schizophrenia, while secondary negative symptoms are caused by positive symptoms, depression, medication side-effects, social deprivation or substance abuse. Most of the research on secondary negative symptoms has aimed at ruling them out in order to isolate primary negative symptoms. However, secondary negative symptoms are common and can have a major impact on patient-relevant outcomes. Therefore, the assessment and treatment of secondary negative symptoms are clinically relevant. Furthermore, understanding the mechanisms underlying secondary negative symptoms can contribute to an integrated model of negative symptoms. In this review we provide an overview of concepts, evidence, assessment and treatment for the major causes of secondary negative symptoms. We also summarize neuroimaging research relevant to secondary negative symptoms. We emphasize the relevance of recent developments in psychopathological assessment of negative symptoms, such as the distinction between amotivation and diminished expression, which have only rarely been applied in research on secondary negative symptoms.

The brief negative symptom scale: validation of the German translation and convergent validity with self-rated anhedonia and observer-rated apathy

BackgroundNegative symptoms are considered core symptoms of schizophrenia. The Brief Negative Symptom Scale (BNSS) was developed to measure this symptomatic dimension according to a current consensus definition. The present study examined the psychometric properties of the German version of the BNSS. To expand former findings on convergent validity, we employed the Temporal Experience Pleasure Scale (TEPS), a hedonic self-report that distinguishes between consummatory and anticipatory pleasure. Additionally, we addressed convergent validity with observer-rated assessment of apathy with the Apathy Evaluation Scale (AES), which was completed by the patient’s primary nurse.MethodsData were collected from 75 in- and outpatients from the Psychiatric Hospital, University Zurich diagnosed with either schizophrenia or schizoaffective disorder. We assessed convergent and discriminant validity, internal consistency and inter-rater reliability.ResultsWe largely replicated the findings of the original version showing good psychometric properties of the BNSS. In addition, the primary nurses evaluation correlated moderately with interview-based clinician rating. BNSS anhedonia items showed good convergent validity with the TEPS.ConclusionsOverall, the German BNSS shows good psychometric properties comparable to the original English version. Convergent validity extends beyond interview-based assessments of negative symptoms to self-rated anhedonia and observer-rated apathy.

The association of neurocognitive impairment with diminished expression and apathy in schizophrenia

Negative symptoms can be grouped into the two dimensions of diminished expression and apathy, which have been shown to be dissociable regarding external validators, such as functional outcome. Here, we investigated whether these two dimensions differentially relate to neurocognitive impairment in schizophrenia. 47 patients with schizophrenia or schizoaffective disorder and 33 healthy control participants were subjected to a neurocognitive test battery assessing multiple cognitive domains (processing speed, working memory, verbal fluency, verbal learning and memory, mental planning), which are integrated into a composite cognition score. Negative symptoms in patients were assessed using the Brief Negative Symptom Scale. We found that diminished expression significantly related to neurocognitive impairment, while severity of apathy symptoms was not directly associated with neurocognition. Other assessed clinical variables include chlorpromazine equivalents, positive symptoms, and depressive symptoms and did not influence the results. Our results are in line with a cognitive resource limitation model of diminished expression in schizophrenia and indicate that cognitive remediation therapy might be helpful to ameliorate expressive deficits.

Shared neural basis of social and non-social reward deficits in chronic cocaine users

Changed reward functions have been proposed as a core feature of stimulant addiction, typically observed as reduced neural responses to non-drug-related rewards. However, it was unclear yet how specific this deficit is for different types of non-drug rewards arising from social and non-social reinforcements. We used functional neuroimaging in cocaine users to investigate explicit social reward as modeled by agreement of music preferences with music experts. In addition, we investigated non-social reward as modeled by winning desired music pieces. The study included 17 chronic cocaine users and 17 matched stimulant-naive healthy controls. Cocaine users, compared with controls, showed blunted neural responses to both social and non-social reward. Activation differences were located in the ventromedial prefrontal cortex overlapping for both reward types and, thus, suggesting a non-specific deficit in the processing of non-drug rewards. Interestingly, in the posterior lateral orbitofrontal cortex, social reward responses of cocaine users decreased with the degree to which they were influenced by social feedback from the experts, a response pattern that was opposite to that observed in healthy controls. The present results suggest that cocaine users likely suffer from a generalized impairment in value representation as well as from an aberrant processing of social feedback.

Deficits in context-dependent adaptive coding of reward in schizophrenia

Theoretical principles of information processing and empirical findings suggest that to efficiently represent all possible rewards in the natural environment, reward-sensitive neurons have to adapt their coding range dynamically to the current reward context. Adaptation ensures that the reward system is most sensitive for the most likely rewards, enabling the system to efficiently represent a potentially infinite range of reward information. A deficit in neural adaptation would prevent precise representation of rewards and could have detrimental effects for an organism’s ability to optimally engage with its environment. In schizophrenia, reward processing is known to be impaired and has been linked to different symptom dimensions. However, despite the fundamental significance of coding reward adaptively, no study has elucidated whether adaptive reward processing is impaired in schizophrenia. We therefore studied patients with schizophrenia (n=27) and healthy controls (n=25), using functional magnetic resonance imaging in combination with a variant of the monetary incentive delay task. Compared with healthy controls, patients with schizophrenia showed less efficient neural adaptation to the current reward context, which leads to imprecise neural representation of reward. Importantly, the deficit correlated with total symptom severity. Our results suggest that some of the deficits in reward processing in schizophrenia might be due to inefficient neural adaptation to the current reward context. Furthermore, because adaptive coding is a ubiquitous feature of the brain, we believe that our findings provide an avenue in defining a general impairment in neural information processing underlying this debilitating disorder.

Reward-dependent modulation of working memory is associated with negative symptoms in schizophrenia

The negative symptoms of schizophrenia have been associated with altered neural activity during both reward processing and cognitive processing. Even though increasing evidence suggests a strong interaction between these two domains, it has not been studied in relation to negative symptoms. To elucidate neural mechanisms of the reward-cognition interaction, we applied a letter variant of the n-back working memory task and varied the financial incentives for performance. In the interaction contrast, we found a significantly activated cluster in the rostral anterior cingulate cortex (ACC), the middle frontal gyrus, and the bilateral superior frontal gyrus. The interaction did not differ significantly between the patient group and a healthy control group, suggesting that patients with schizophrenia are on average able to integrate reward information and utilize this information to maximize cognitive performance. However within the patient group, we found a significant inverse correlation of ACC activity with the factor diminished expression. This finding is consistent with the model that a lack of available cognitive resources leads to diminished expression. We therefore argue that patients with diminished expression have difficulties in recruiting additional cognitive resources (as implemented in the ACC) in response to an anticipated reward. Due to this lack of cognitive resources, less processing capacity is available for effective expression, resulting in diminished expressive behavior.

Ventral Striatal Dysfunction and Symptom Expression in Individuals With Schizotypal Personality Traits and Early Psychosis

Striatal abnormalities play a crucial role in the pathophysiology of schizophrenia. Growing evidence suggests an association between aberrant striatal activity during reward anticipation and symptom dimensions in schizophrenia. However, it is not clear whether this holds across the psychosis continuum. The aim of the present study was to investigate alterations of ventral striatal activation during reward anticipation and its relationship to symptom expression in persons with schizotypal personality traits (SPT) and first-episode psychosis. Twenty-six individuals with high SPT, 26 patients with non-affective first-episode psychosis (including 13 with brief psychotic disorder (FEP-BPD) and 13 with first-episode schizophrenia [FEP-SZ]) and 25 healthy controls underwent event-related functional magnetic resonance imaging while performing a variant of the Monetary Incentive Delay task. Ventral striatal activation was positively correlated with total symptom severity, in particular with levels of positive symptoms. This association was observed across the psychosis continuum and within each subgroup. Patients with FEP-SZ showed the strongest elevation of striatal activation during reward anticipation, although symptom levels did not differ between groups in the psychosis continuum. While our results provide evidence that variance in striatal activation is mainly explained by dimensional symptom expression, patients with schizophrenia show an additional dysregulation of striatal activation. Trans-diagnostic approaches are promising in order to disentangle dimensional and categorical neural mechanisms in the psychosis continuum.

Combining actigraphy, ecological momentary assessment and neuroimaging to study apathy in patients with schizophrenia

BACKGROUND Apathy can be defined as a reduction of goal-directed behavior and is a strong predictor for poor functional outcome in schizophrenia. However, no objective measure of apathy has been identified and assessment is limited to retrospective interview-based ratings. Here we aimed to identify more precise objective readouts of apathy for translational research and clinical practice. METHODS We employed a combined approach including interview-based ratings of the two negative symptom factors apathy and diminished expression, actigraphy based measures of spontaneous motor activity and the evaluation of daily activities using ecological momentary assessment. Furthermore, a functional magnetic resonance imaging task for reward anticipation was applied to investigate shared and divergent neural correlates of interview-based and behaviorally measured apathy. RESULTS We found in 18 schizophrenia patients with high interview-based apathy levels that motor activity was negatively correlated with apathy but not with diminished expression. In contrast, measures of daily activities were not associated with apathy. Neural activation during reward anticipation revealed an association between hypoactivation of the ventral striatum and interview-based apathy as well as hypoactivation of the inferior frontal gyrus and motor activity level. CONCLUSIONS Spontaneous motor activity is an objective readout of apathy, which was specific and not present for diminished expression. On a neural level, interview-based and objective measures of apathy showed divergent neural correlates in the cortical-striatal network, which suggests dissociable neural processes. Finally, motor activity provides a promising readout for quantifying apathy in both translational research and clinical practice.

Effort-based decision-making paradigms as objective measures of apathy in schizophrenia?

In recent years, effort-based decision-making paradigms have been applied in patients with schizophrenia with the aim to establish a potentially ‘objective’ measure of apathy symptoms and shed light on underlying mechanisms. Initial studies have reported promising findings regarding symptom-level links to effort-based choice. However, a review of the recent and overall literature yields divergent findings. Published studies vary substantially in terms of clinical instruments and applied effort-based decision-making paradigms. This heterogeneity hampers comparability between studies and might partially explain divergent findings. A clear consensus on clinical assessment instruments and paradigms seems to be critical for further progress in the field.