Differences in the neural correlates of schizophrenia with positive and negative formal thought disorder in patients with schizophrenia in the ENIGMA dataset.

Formal thought disorder (FTD) is a clinical key factor in schizophrenia, but the neurobiological underpinnings remain unclear. In particular, the relationship between FTD symptom dimensions and patterns of regional brain volume loss in schizophrenia remains to be established in large cohorts. Even less is known about the cellular basis of FTD. Our study addresses these major obstacles by enrolling a large multi-site cohort acquired by the ENIGMA Schizophrenia Working Group (752 schizophrenia patients and 1256 controls), to unravel the neuroanatomy of FTD in schizophrenia and using virtual histology tools on implicated brain regions to investigate the cellular basis. Based on the findings of previous clinical and neuroimaging studies, we decided to separately explore positive, negative and total formal thought disorder. We used virtual histology tools to relate brain structural changes associated with FTD to cellular distributions in cortical regions. We identified distinct neural networks positive and negative FTD. Both networks encompassed fronto-occipito-amygdalar brain regions, but positive and negative FTD demonstrated a dissociation: negative FTD showed a relative sparing of orbitofrontal cortical thickness, while positive FTD also affected lateral temporal cortices. Virtual histology identified distinct transcriptomic fingerprints associated for both symptom dimensions. Negative FTD was linked to neuronal and astrocyte fingerprints, while positive FTD also showed associations with microglial cell types. These results provide an important step towards linking FTD to brain structural changes and their cellular underpinnings, providing an avenue for a better mechanistic understanding of this syndrome.

Adaptive coding of reward in schizophrenia, its change over time and relationship to apathy.

Adaptive coding of reward is the process by which neurons adapt their response to the context of available compensations. Higher rewards lead to a stronger brain response, but the increase of the response depends on the range of available rewards. A steeper increase is observed in a narrow range and a more gradual slope in a wider range. In schizophrenia, adaptive coding appears to be affected in different domains, especially in the reward domain. Here, we tested adaptive coding of reward in a large group of patients with schizophrenia (n = 86) and control subjects (n = 66). We assessed: (i) the association between adaptive coding deficits and symptoms; (ii) the longitudinal stability of deficits (the same task was performed 3 months apart); and (iii) the stability of results between two experimental sites. We used functional MRI and the monetary incentive delay task to assess adaptation of participants to two different reward ranges: a narrow range and a wide range. We used a region-of-interest analysis to evaluate adaptation within striatal and visual regions. Patients and control subjects underwent a full demographic and clinical assessment. We found reduced adaptive coding in patients, with a decreased slope in the narrow reward range with respect to that of control participants, in striatal but not visual regions. This pattern was observed at both research sites. Upon retesting, patients increased their narrow-range slopes, showing improved adaptive coding, whereas control subjects slightly reduced them. At retesting, patients with overly steep slopes in the narrow range also showed higher levels of negative symptoms. Our data confirm deficits in reward adaptation in schizophrenia and reveal an effect of practice in patients, leading to improvement, with steeper slopes upon retesting. However, in some patients, an excessively steep slope may result in poor discriminability of larger rewards, owing to early saturation of the brain response. Together, the loss of precision of reward representation in new (first exposure, underadaptation) and more familiar (retest, overadaptation) situations might contribute to the multiple motivational symptoms in schizophrenia.

Examining the impact of substance use on hospital length of stay in schizophrenia spectrum disorder: a retrospective analysis.

BACKGROUND: Among patients diagnosed with schizophrenia, the presence of substance use poses an aggravating comorbidity, exerting a negative impact on the course of the disease, adherence to therapeutic regimens, treatment outcomes, duration of hospital stays, and the frequency of hospitalizations. The primary objective of the present study is to investigate the relationship between comorbid substance use disorders, antipsychotic treatment, and the length of stay in individuals hospitalized for treatment of schizophrenia. METHODS: We conducted a retrospective analysis of electronic health records spanning a 12-month period, specifically focusing on adult patients diagnosed with schizophrenia who were discharged from the University Hospital of Psychiatry Zurich between January and December 2019. We documented the number and types of diagnosed substance use disorder, the antipsychotic treatment, the length of stay, and the number of previous hospitalizations for each patient. RESULTS: Over a third (n = 328; 37.1%) of patients with schizophrenia had comorbid substance use with cannabis being the most frequent consumed substance. Patients with substance use (either single or multiple) were more frequently hospitalized; those with multiple substance use more frequently than those with a single substance use (F(2, 882) = 69.06; p < 0.001). There were no differences regarding the rate of compulsory admission. Patients with no substance use had a lower HoNOS score at discharge (F(2, 882) = 4.06). Patients with multiple substance use had a shorter length of stay (F(2, 882) = 9.22; p < 0.001), even after adjusting for duration of illness, previous hospitalizations, diagnosis, and antipsychotic treatment. CONCLUSIONS: In patients with schizophrenia, comorbid single or multiple substance use has a relevant negative impact on treatment and thus on the course of disease. Substance use in patients with schizophrenia should therefore receive special attention in order to reduce re-hospitalization rates and improve the clinical outcome.

Brain ageing in schizophrenia: evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium.

Schizophrenia (SZ) is associated with an increased risk of life-long cognitive impairments, age-related chronic disease, and premature mortality. We investigated evidence for advanced brain ageing in adult SZ patients, and whether this was associated with clinical characteristics in a prospective meta-analytic study conducted by the ENIGMA Schizophrenia Working Group. The study included data from 26 cohorts worldwide, with a total of 2803 SZ patients (mean age 34.2 years; range 18-72 years; 67% male) and 2598 healthy controls (mean age 33.8 years, range 18-73 years, 55% male). Brain-predicted age was individually estimated using a model trained on independent data based on 68 measures of cortical thickness and surface area, 7 subcortical volumes, lateral ventricular volumes and total intracranial volume, all derived from T1-weighted brain magnetic resonance imaging (MRI) scans. Deviations from a healthy brain ageing trajectory were assessed by the difference between brain-predicted age and chronological age (brain-predicted age difference [brain-PAD]). On average, SZ patients showed a higher brain-PAD of +3.55 years (95% CI: 2.91, 4.19; I2 = 57.53%) compared to controls, after adjusting for age, sex and site (Cohen's d = 0.48). Among SZ patients, brain-PAD was not associated with specific clinical characteristics (age of onset, duration of illness, symptom severity, or antipsychotic use and dose). This large-scale collaborative study suggests advanced structural brain ageing in SZ. Longitudinal studies of SZ and a range of mental and somatic health outcomes will help to further evaluate the clinical implications of increased brain-PAD and its ability to be influenced by interventions.

Comparing adaptive coding of reward in bipolar I disorder and schizophrenia.

Deficits in neural processing of reward have been described in both bipolar disorder (BD) and schizophrenia (SZ), but it remains unclear to what extent these deficits are caused by similar mechanisms. Efficient reward processing relies on adaptive coding which allows representing large input spans by limited neuronal encoding ranges. Deficits in adaptive coding of reward have previously been observed across the SZ spectrum and correlated with total symptom severity. In the present work, we sought to establish whether adaptive coding is similarly affected in patients with BD. Twenty-five patients with BD, 27 patients with SZ and 25 healthy controls performed a variant of the Monetary Incentive Delay task during functional magnetic resonance imaging in two reward range conditions. Adaptive coding was impaired in the posterior part of the right caudate in BD and SZ (trend level). In contrast, BD did not show impaired adaptive coding in the anterior caudate and right precentral gyrus/insula, where SZ showed deficits compared to healthy controls. BD patients show adaptive coding deficits that are similar to those observed in SZ in the right posterior caudate. Adaptive coding in BD appeared more preserved as compared to SZ participants especially in the more anterior part of the right caudate and to a lesser extent also in the right precentral gyrus. Thus, dysfunctional adaptive coding could constitute a fundamental deficit in severe mental illnesses that extends beyond the SZ spectrum.

Cortical and subcortical neuroanatomical signatures of schizotypy in 3004 individuals assessed in a worldwide ENIGMA study.

Neuroanatomical abnormalities have been reported along a continuum from at-risk stages, including high schizotypy, to early and chronic psychosis. However, a comprehensive neuroanatomical mapping of schizotypy remains to be established. The authors conducted the first large-scale meta-analyses of cortical and subcortical morphometric patterns of schizotypy in healthy individuals, and compared these patterns with neuroanatomical abnormalities observed in major psychiatric disorders. The sample comprised 3004 unmedicated healthy individuals (12-68 years, 46.5% male) from 29 cohorts of the worldwide ENIGMA Schizotypy working group. Cortical and subcortical effect size maps with schizotypy scores were generated using standardized methods. Pattern similarities were assessed between the schizotypy-related cortical and subcortical maps and effect size maps from comparisons of schizophrenia (SZ), bipolar disorder (BD) and major depression (MDD) patients with controls. Thicker right medial orbitofrontal/ventromedial prefrontal cortex (mOFC/vmPFC) was associated with higher schizotypy scores (r = 0.067, pFDR = 0.02). The cortical thickness profile in schizotypy was positively correlated with cortical abnormalities in SZ (r = 0.285, pspin = 0.024), but not BD (r = 0.166, pspin = 0.205) or MDD (r = -0.274, pspin = 0.073). The schizotypy-related subcortical volume pattern was negatively correlated with subcortical abnormalities in SZ (rho = -0.690, pspin = 0.006), BD (rho = -0.672, pspin = 0.009), and MDD (rho = -0.692, pspin = 0.004). Comprehensive mapping of schizotypy-related brain morphometry in the general population revealed a significant relationship between higher schizotypy and thicker mOFC/vmPFC, in the absence of confounding effects due to antipsychotic medication or disease chronicity. The cortical pattern similarity between schizotypy and schizophrenia yields new insights into a dimensional neurobiological continuity across the extended psychosis phenotype.

Impaired glutamate homeostasis in the nucleus accumbens in human cocaine addiction.

Cocaine addiction is characterized by overwhelming craving for the substance, which drives its escalating use despite adverse consequences. Animal models suggest a disrupted glutamate homeostasis in the nucleus accumbens to underlie addiction-like behavior. After chronic administration of cocaine, rodents show decreased levels of accumbal glutamate, whereas drug-seeking reinstatement is associated with enhanced glutamatergic transmission. However, due to technical obstacles, the role of disturbed glutamate homeostasis for cocaine addiction in humans remains only partially understood, and accordingly, no approved pharmacotherapy exists. Here, we applied a tailored proton magnetic resonance spectroscopy protocol that allows glutamate quantification within the human nucleus accumbens. We found significantly reduced basal glutamate concentrations in the nucleus accumbens in cocaine-addicted (N = 26) compared with healthy individuals (N = 30), and increased glutamate levels during cue-induced craving in cocaine-addicted individuals compared with baseline. These glutamatergic alterations, however, could not be significantly modulated by a short-term challenge of N-acetylcysteine (2400 mg/day on 2 days). Taken together, our findings reveal a disturbed accumbal glutamate homeostasis as a key neurometabolic feature of cocaine addiction also in humans. Therefore, we suggest the glutamatergic system as a promising target for the development of novel pharmacotherapies, and in addition, as a potential biomarker for a personalized medicine approach in addiction.

Disentangling craving- and valence-related brain responses to smoking cues in individuals with nicotine use disorder.

Tobacco smoking is one of the leading causes of preventable death and disease worldwide. Most smokers want to quit, but relapse rates are high. To improve current smoking cessation treatments, a better understanding of the underlying mechanisms of nicotine dependence and related craving behaviour is needed. Studies on cue-driven cigarette craving have been a particularly useful tool for investigating the neural mechanisms of drug craving. Here, functional neuroimaging studies in humans have identified a core network of craving-related brain responses to smoking cues that comprises of amygdala, anterior cingulate cortex, orbitofrontal cortex, posterior cingulate cortex and ventral striatum. However, most functional Magnetic Resonance Imaging (fMRI) cue-reactivity studies do not adjust their stimuli for emotional valence, a factor assumed to confound craving-related brain responses to smoking cues. Here, we investigated the influence of emotional valence on key addiction brain areas by disentangling craving- and valence-related brain responses with parametric modulators in 32 smokers. For one of the suggested key regions for addiction, the amygdala, we observed significantly stronger brain responses to the valence aspect of the presented images than to the craving aspect. Our results emphasize the need for carefully selecting stimulus material for cue-reactivity paradigms, in particular with respect to emotional valence. Further, they can help designing future research on teasing apart the diverse psychological dimensions that comprise nicotine dependence and, therefore, can lead to a more precise mapping of craving-associated brain areas, an important step towards more tailored smoking cessation treatments.

Predictors of real-time fMRI neurofeedback performance and improvement - A machine learning mega-analysis.

Real-time fMRI neurofeedback is an increasingly popular neuroimaging technique that allows an individual to gain control over his/her own brain signals, which can lead to improvements in behavior in healthy participants as well as to improvements of clinical symptoms in patient populations. However, a considerably large ratio of participants undergoing neurofeedback training do not learn to control their own brain signals and, consequently, do not benefit from neurofeedback interventions, which limits clinical efficacy of neurofeedback interventions. As neurofeedback success varies between studies and participants, it is important to identify factors that might influence neurofeedback success. Here, for the first time, we employed a big data machine learning approach to investigate the influence of 20 different design-specific (e.g. activity vs. connectivity feedback), region of interest-specific (e.g. cortical vs. subcortical) and subject-specific factors (e.g. age) on neurofeedback performance and improvement in 608 participants from 28 independent experiments. With a classification accuracy of 60% (considerably different from chance level), we identified two factors that significantly influenced neurofeedback performance: Both the inclusion of a pre-training no-feedback run before neurofeedback training and neurofeedback training of patients as compared to healthy participants were associated with better neurofeedback performance. The positive effect of pre-training no-feedback runs on neurofeedback performance might be due to the familiarization of participants with the neurofeedback setup and the mental imagery task before neurofeedback training runs. Better performance of patients as compared to healthy participants might be driven by higher motivation of patients, higher ranges for the regulation of dysfunctional brain signals, or a more extensive piloting of clinical experimental paradigms. Due to the large heterogeneity of our dataset, these findings likely generalize across neurofeedback studies, thus providing guidance for designing more efficient neurofeedback studies specifically for improving clinical neurofeedback-based interventions. To facilitate the development of data-driven recommendations for specific design details and subpopulations the field would benefit from stronger engagement in open science research practices and data sharing.

SmoCuDa: A Validated Smoking Cue Database to Reliably Induce Craving in Tobacco Use Disorder.

BACKGROUND: Cue-reactivity paradigms provide valuable insights into the underlying mechanisms of nicotine craving in nicotine-dependent subjects. In order to study cue-driven nicotine craving, robust and validated stimulus datasets are essential. OBJECTIVES: The aim of this study was to generate and validate a large set of individually rated smoking-related cues that allow for assessment of different stimulus intensities along the dimensions craving, valence, and arousal. METHODS: The image database consisted of 330 visual cues. Two hundred fifty smoking-associated pictures (Creative Commons license) were chosen from online databases and showed a widespread variety of smoking-associated content. Eighty pictures from previously published databases were included for cross-validation. Forty volunteers with tobacco use disorder rated "urge-to-smoke," "valence," and "arousal" for all images on a 100-point visual analogue scale. Pictures were also labelled according to 18 categories such as lit/unlit cigarettes in mouth, cigarette end, and cigarette in ashtray. RESULTS: Ratings (mean ± SD) were as follows: urge to smoke, 44.9 ± 13.2; valence, 51.2 ± 7.6; and arousal, 54.6 ± 7.1. All ratings, particularly "urge to smoke," were widely distributed along the whole scale spectrum. CONCLUSIONS: We present a novel image library of well-described smoking-related cues, which were rated on a continuous scale along the dimensions craving, valence, and arousal that accounts for inter-individual differences. The rating software, image database, and their ratings are publicly available at https://smocuda.github.io.

Can we predict real-time fMRI neurofeedback learning success from pretraining brain activity?

Neurofeedback training has been shown to influence behavior in healthy participants as well as to alleviate clinical symptoms in neurological, psychosomatic, and psychiatric patient populations. However, many real-time fMRI neurofeedback studies report large inter-individual differences in learning success. The factors that cause this vast variability between participants remain unknown and their identification could enhance treatment success. Thus, here we employed a meta-analytic approach including data from 24 different neurofeedback studies with a total of 401 participants, including 140 patients, to determine whether levels of activity in target brain regions during pretraining functional localizer or no-feedback runs (i.e., self-regulation in the absence of neurofeedback) could predict neurofeedback learning success. We observed a slightly positive correlation between pretraining activity levels during a functional localizer run and neurofeedback learning success, but we were not able to identify common brain-based success predictors across our diverse cohort of studies. Therefore, advances need to be made in finding robust models and measures of general neurofeedback learning, and in increasing the current study database to allow for investigating further factors that might influence neurofeedback learning.

Shared and dissociable features of apathy and reward system dysfunction in bipolar I disorder and schizophrenia.

BACKGROUND: Bipolar disorder I (BD-I) is defined by episodes of mania, depression and euthymic states. These episodes are among other symptoms characterized by altered reward processing and negative symptoms (NS), in particular apathy. However, the neural correlates of these deficits are not well understood. METHODS: We first assessed the severity of NS in 25 euthymic BD-I patients compared with 25 healthy controls (HC) and 27 patients with schizophrenia (SZ). Then, we investigated ventral (VS) and dorsal striatal (DS) activation during reward anticipation in a Monetary Incentive Delayed Task and its association with NS. RESULTS: In BD-I patients NS were clearly present and the severity of apathy was comparable to SZ patients. Apathy scores in the BD-I group but not in the SZ group correlated with sub-syndromal depression scores. At the neural level, we found significant VS and DS activation in BD-I patients and no group differences with HC or SZ patients. In contrast to patients with SZ, apathy did not correlate with striatal activation during reward anticipation. Explorative whole-brain analyses revealed reduced extra-striatal activation in BD-I patients compared with HC and an association between reduced activation of the inferior frontal gyrus and apathy. CONCLUSION: This study found that in BD-I patients apathy is present to an extent comparable to SZ, but is more strongly related to sub-syndromal depressive symptoms. The findings support the view of different pathophysiological mechanisms underlying apathy in the two disorders and suggest that extra-striatal dysfunction may contribute to impaired reward processing and apathy in BD-I.

Prodopaminergic Drugs for Treating the Negative Symptoms of Schizophrenia: Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: The negative symptoms of schizophrenia pose a heavy burden on patients and relatives and represent an unmet therapeutic need. The observed association of negative symptoms with impaired reward system function has stimulated research on prodopaminergic agents as potential adjunctive treatments. METHODS: We conducted a systematic review and meta-analysis of published randomized controlled trials of amphetamine, methylphenidate, modafinil, armodafinil, lisdexamphetamine, L-dopa, levodopa, bromocriptine, cabergoline, quinagolide, lisuride, pergolide, apomorphine, ropinirole, pramipexole, piribedil, and rotigotine augmentation in schizophrenia and schizoaffective disorder.Medline, EMBASE, and several other databases as well as trial registries were searched for placebo-controlled trials. RESULTS: Ten randomized controlled trials were included in the meta-analysis, 6 trials on modafinil, 2 on armodafinil, 1 on L-dopa, and 1 on pramipexole. Overall, prodopaminergic agents did not significantly reduce negative symptoms. Restricting the analysis to studies requiring a minimum threshold for negative symptom severity, modafinil/armodafinil showed a significant but small effect on negative symptoms. A subset of studies allowed for calculating specific effects for the negative symptom dimensions diminished expression and amotivation, but no significant effect was found. Prodopaminergic agents did not increase positive symptom scores. CONCLUSIONS: The currently available evidence does not allow for formulating recommendations for the use of prodopaminergic agents for the treatment of negative symptoms. Nevertheless, the observed improvement in studies defining a minimum threshold for negative symptom severity in the absence of an increase in positive symptoms clearly supports further research on these agents.

Cerebral blood flow in striatal regions is associated with apathy in patients with schizophrenia.

BACKGROUND: Striatal dysfunction has been proposed as a pathomechanism for negative symptoms in schizophrenia. There is consensus that negative symptoms can be grouped into 2 dimensions: apathy and diminished expression. Recent studies suggest that different neural mechanisms underlie these dimensions, but the relationship between regional resting-state cerebral blood flow (rCBF) and negative symptom dimensions has not been investigated. METHODS: This study included 29 patients with schizophrenia and 20 healthy controls. We measured rCBF in the striatum using arterial spin labelling (ASL) MRI. We assessed negative symptoms using the Brief Negative Symptom Scale. RESULTS: In the ventral and dorsal striatum, rCBF was not different between patients with schizophrenia and controls. However, we did find a positive association between the severity of apathy and increased rCBF in the ventral and dorsal striatum in patients with schizophrenia. This effect was not present for diminished expression. LIMITATIONS: All patients were taking atypical antipsychotics, so an effect of antipsychotic medication on rCBF could not be excluded, although we did not find a significant association between rCBF and chlorpromazine equivalents. CONCLUSION: The main finding of this study was a specific association between increased striatal rCBF and the negative symptom dimension of apathy. Our results further support the separate assessment of apathy and diminished expression when investigating the neural basis of negative symptoms. The ASL technique can provide a direct and quantitative approach to investigating the role of rCBF changes in the pathophysiology of negative symptoms.

Deficits in context-dependent adaptive coding in early psychosis and healthy individuals with schizotypal personality traits.

Adaptive coding of information is a fundamental principle of brain functioning. It allows for efficient representation over a large range of inputs and thereby alleviates the limited coding range of neurons. In the present study, we investigated for the first time potential alterations in context-dependent reward adaptation and its association with symptom dimensions in the schizophrenia spectrum. We studied 27 patients with first-episode psychosis, 26 individuals with schizotypal personality traits and 25 healthy controls. We used functional MRI in combination with a variant of the monetary incentive delay task and assessed adaptive reward coding in two reward conditions with different reward ranges. Compared to healthy controls, patients with first-episode psychosis and healthy individuals with schizotypal personality traits showed a deficit in increasing the blood oxygen level-dependent response slope in the right caudate for the low reward range compared to the high reward range. In other words, the two groups showed inefficient neural adaptation to the current reward context. In addition, we found impaired adaptive coding of reward in the caudate nucleus and putamen to be associated with total symptom severity across the schizophrenia spectrum. Symptom severity was more strongly associated with neural deficits in adaptive coding than with the neural coding of absolute reward outcomes. Deficits in adaptive coding were prominent across the schizophrenia spectrum and even detectable in unmedicated (healthy) individuals with schizotypal personality traits. Furthermore, the association between total symptom severity and impaired adaptive coding in the right caudate and putamen suggests a dimensional mechanism underlying imprecise neural adaptation. Our findings support the idea that impaired adaptive coding may be a general information-processing deficit explaining disturbances within the schizophrenia spectrum over and above a simple model of blunted absolute reward signals.

[Negative Symptoms in Schizophrenia - an Overview]. / Negativsymptome der Schizophrenie ­ ein Überblick.

Negative Symptoms in Schizophrenia - an Overview Abstract. Negative symptoms in schizophrenia comprise the symptom-dimensions of apathy (avolition, anhedonia and social withdrawal) and reduced expression (alogia and blunted affect). Negative symptoms are of a high relevance for the illness course, since they strongly affect functional outcome and quality of life. A diagnostic differentiation is recommended in primary negative symptoms (regarded as an integral part of schizophrenia) and secondary negative symptoms (regarded as a result of positive symptoms, comorbid depression, effects of antipsychotic medication, substance abuse or social deprivation). The following overview will present the various aspects of negative symptoms, the underlying pathophysiology and describe current diagnostic and therapeutic recommendations based on the concept of primary and secondary negative symptoms.

Ventral striatal hypoactivation is associated with apathy but not diminished expression in patients with schizophrenia.

BACKGROUND: Negative symptoms of schizophrenia can be grouped in 2 dimensions: apathy and diminished expression. Increasing evidence suggests that negative symptoms are associated with altered neural activity of subcortical and cortical regions in the brain reward system. However, the neurobiological basis of the distinct symptom dimensions within negative symptoms is still poorly understood. The primary aim of our study was to examine the neural correlates of the negative symptom dimensions apathy and diminished expression during a reward processing task. METHODS: Patients with schizophrenia and healthy controls underwent event-related fMRI while performing a variant of the Monetary Incentive Delay Task. We assessed negative symptom dimensions using the Brief Negative Symptom Scale. RESULTS: We included 27 patients and 25 controls in our study. Both groups showed neural activation indicated by blood oxygen-level dependent signal in the ventral striatum during reward anticipation. Ventral striatal activation during reward anticipation showed a strong negative correlation with apathy. Importantly, this effect was not driven by cognitive ability, medication, depressive or positive symptoms. In contrast, no significant correlation with the diminished expression dimension was observed. LIMITATIONS: Although the results remain significant when controlling for chlorpromazine equivalents, we cannot fully exclude potential confounding effects of medication with atypical antipsychotics. CONCLUSION: The specific correlation of ventral striatal hypoactivation during reward anticipation with apathy demonstrates a differentiation of apathy and diminished expression on a neurobiological level and provides strong evidence for different pathophysiological mechanisms underlying these 2 negative symptom dimensions. Our findings contribute to a multilevel framework in which apathy and motivational impairment in patients with schizophrenia can be described on psychopathological, behavioural and neural levels.

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

BACKGROUND: Negative 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. METHODS: Data 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. RESULTS: We 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. CONCLUSIONS: Overall, 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.

Positive and negative symptoms in methamphetamine-induced psychosis compared to schizophrenia: A systematic review and meta-analysis.

BACKGROUND: The clinical profiles of methamphetamine-induced psychosis (MIP) and schizophrenia are largely overlapping making differentiation challenging. In this systematic review and meta-analysis, we aim to compare the positive and negative symptoms of MIP and schizophrenia to better understand the differences between them. STUDY DESIGN: In accordance with our pre-registered protocol (CRD42021286619), we conducted a search of English-language studies up to December 16th, 2022, in PubMed, EMBASE, and PsycINFO, including stable outpatients with MIP and schizophrenia. We used the Newcastle-Ottawa Scale to measure the quality of cross-sectional, case-control, and cohort studies. STUDY RESULTS: Of the 2052 articles retrieved, we included 12 studies (6 cross-sectional, 3 case-control, and 2 cohort studies) in our meta-analysis, involving 624 individuals with MIP and 524 individuals with schizophrenia. Our analysis found no significant difference in positive symptoms between the two groups (SMD, -0.01; 95%CI, -0.13 to +0.11; p = 1). However, individuals with MIP showed significantly less negative symptoms compared to those with schizophrenia (SMD, -0.35; 95CI%, -0.54 to -0.16; p = 0.01; I2 = 54 %). Our sensitivity analysis, which included only studies with a low risk of bias, did not change the results. However, our meta-analysis is limited by its cross-sectional approach, which limits the interpretation of causal associations. Furthermore, differences in population, inclusion criteria, methodology, and drug exposure impact our findings. CONCLUSIONS: Negative symptoms are less prominent in individuals with MIP. While both groups do not differ regarding positive symptoms, raises the possibility of shared and partly different underlying neurobiological mechanisms related to MIP and schizophrenia.