The hypothesized cognitive model of negative symptoms, proposed nearly twenty years ago, is the most prevalent psychological framework for conceptualizing negative symptoms in schizophrenia spectrum disorders (SSDs). The aim of this study was to comprehensively validate the model for the first time, specifically by quantifying the relationships between negative symptom severity and all related dysfunctional beliefs.

A systematic search was conducted using MEDLINE and PsychINFO, supplemented by manual reviews of reference lists and Google Scholar. Eligible studies were peer-reviewed with data on the direct cross-sectional association between negative symptoms and at least one relevant dysfunctional belief in SSD patients. Screening and data extraction were completed by independent reviewers. Random-effects meta-analyses were performed to pool effect size estimates of z-transformed Pearson’s r correlations. Moderators of these relationships, as well as subset analyses for negative symptom domains and measurement instruments, were also assessed.

Significant effects emerged for the relationships between negative symptoms and defeatist performance beliefs (k = 38, n = 2808), r = 0.23 (95% CI, 0.18–0.27), asocial beliefs (k = 8, n = 578), r = 0.21 (95% CI, 0.12–0.28), low expectancies for success (k = 55, n = 5664), r = −0.21 (95% CI, −0.15 – −0.26), low expectancies for pleasure (k = 5, n = 249), r = −0.19 (95% CI, −0.06 – −0.31), and internalized stigma (k = 81, n = 9766), r = 0.17 (95% CI, 0.12–0.22), but not perception of limited resources (k = 10, n = 463), r = 0.08 (95% CI, −0.13 – 0.27).

This meta-analysis provides support for the cognitive model of negative symptoms. The identification of specific dysfunctional beliefs associated with negative symptoms is essential for the development of precision-based cognitive-behavioral interventions.

Negative symptoms are a key feature of several psychiatric disorders. Difficulty identifying common neurobiological mechanisms that cut across diagnostic boundaries might result from equifinality (i.e., multiple mechanistic pathways to the same clinical profile), both within and across disorders. This study used a data-driven approach to identify unique subgroups of participants with distinct reward processing profiles to determine which profiles predicted negative symptoms.

Participants were a transdiagnostic sample of youth from a multisite study of psychosis risk, including 110 individuals at clinical high-risk for psychosis (CHR; meeting psychosis-risk syndrome criteria), 88 help-seeking participants who failed to meet CHR criteria and/or who presented with other psychiatric diagnoses, and a reference group of 66 healthy controls. Participants completed clinical interviews and behavioral tasks assessing four reward processing constructs indexed by the RDoC Positive Valence Systems: hedonic reactivity, reinforcement learning, value representation, and effort–cost computation.

k-means cluster analysis of clinical participants identified three subgroups with distinct reward processing profiles, primarily characterized by: a value representation deficit (54%), a generalized reward processing deficit (17%), and a hedonic reactivity deficit (29%). Clusters did not differ in rates of clinical group membership or psychiatric diagnoses. Elevated negative symptoms were only present in the generalized deficit cluster, which also displayed greater functional impairment and higher psychosis conversion probability scores.

Contrary to the equifinality hypothesis, results suggested one global reward processing deficit pathway to negative symptoms independent of diagnostic classification. Assessment of reward processing profiles may have utility for individualized clinical prediction and treatment.

Recent stressful life events (SLE) are a risk factor for psychosis, but limited research has explored how SLEs affect individuals at clinical high risk (CHR) for psychosis. The current study investigated the longitudinal effects of SLEs on functioning and symptom severity in CHR individuals, where we hypothesized CHR would report more SLEs than healthy controls (HC), and SLEs would be associated with poorer outcomes.

The study used longitudinal data from the EU-GEI High Risk study. Data from 331 CHR participants were analyzed to examine the effects of SLEs on changes in functioning, positive and negative symptoms over a 2-year follow-up. We compared the prevalence of SLEs between CHR and HCs, and between CHR who did (CHR-T) and did not (CHR-NT) transition to psychosis.

CHR reported 1.44 more SLEs than HC (p < 0.001), but there was no difference in SLEs between CHR-T and CHR-NT at baseline. Recent SLEs were associated with poorer functioning and more severe positive and negative symptoms in CHR individuals (all p < 0.01) but did not reveal a significant interaction with time.

CHR individuals who had experienced recent SLEs exhibited poorer functioning and more severe symptoms. However, as the interaction between SLEs and time was not significant, this suggests SLEs did not contribute to a worsening of symptoms and functioning over the study period. SLEs could be a key risk factor to becoming CHR for psychosis, however further work is required to inform when early intervention strategies mitigating against the effects of stress are most effective.

Executive control over low-level information processing is impaired proximal to psychosis onset with evidence of recovery over the first year of illness. However, previous studies demonstrating diminished perceptual modulation via attention are complicated by simultaneously impaired perceptual responses. The present study examined the early auditory gamma-band response (EAGBR), a marker of early cortical processing that appears preserved in first-episode psychosis (FEP), and its modulation by attention in a longitudinal FEP sample.

Magnetoencephalography was recorded from 25 FEP and 32 healthy controls (HC) during active and passive listening conditions in an auditory oddball task at baseline and follow-up (4–12 months) sessions. EAGBR inter-trial phase coherence (ITPC) and evoked power were measured from responses to standard tones. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS).

There was no group difference in EAGBR power or ITPC. While EAGBR ITPC increased with attention in HC, this modulation was impaired among FEP. Diminished EAGBR modulation in FEP persisted at longitudinal follow-up. However, among FEP, recovery of EAGBR modulation was associated with reduced PANSS negative scores.

FEP exhibit impaired executive control over the flow of information at the earliest stages of sensory processing within auditory cortex. In contrast to previous work, this deficit was observed despite an intact measure of sensory processing, mitigating potential confounds. Recovery of sensory gain modulation over time was associated with reductions in negative symptoms, highlighting a source of potential resiliency against some of the most debilitating and treatment refractory symptoms in early psychosis.

Predominant negative symptoms (PNSs) in schizophrenia can affect the patients’ psychosocial functioning immensely and are less responsive to treatment than positive symptoms.

The aim of the study was to observe negative symptoms and psychosocial functioning in PNS schizophrenia patients and to understand whether PNS can be improved and with what treatment strategies.

This was a 1-year, prospective, multicentric cohort study conducted in Slovakia. Adult outpatients with diagnosis of schizophrenia according to ICD-10 and PNS evaluated using the criteria by the European Psychiatric Association’s (EPA) guidance were included. Change in negative symptoms, functionality, and treatment patterns were observed. Treatment effectiveness was evaluated using the modified Short Assessment of Negative Domain (m-SAND), the Self-evaluation of Negative Symptoms (SNS) scale, the Personal and Social Performance (PSP) scale, and the Clinical Global Impression – Severity (CGI-S) and the Clinical Global Impression – Improvement (CGI-I) scales. Least-squares (LS) means were calculated for the change from baseline to final visit for the outcomes.

The study included 188 patients. Functionality improved as, by the end of the study, fewer patients were unemployed (53%) and more worked occasionally (21%). PNS improved significantly according to both physicians and patients (LS mean change from baseline in m-SAND total score: -10.0 (p-value <0.0001)). Most patients received polytherapy throughout the study. Cariprazine was utilized most (20% monotherapy and 76% polytherapy). Only a few patients discontinued treatment due to adverse drug reactions.

With the right treatment strategy, it is possible to achieve improvement in PNS and everyday functioning in schizophrenia outpatients.

Polygenic risk scores for educational attainment (PRSEA), cognitive reserve (CR), and clinical symptoms are associated with functioning in first-episode psychosis (FEP). Nevertheless, the mechanisms underlying their complex interaction are yet to be explored. This study assessed the mediating role of CR and clinical symptoms, both negative (NS) and positive (PS), on the interrelationship between PRSEA and functionality, one year after a FEP.

A total of 162 FEP patients underwent clinical, functional, and genetic assessments. Using genome-wide association study summary results, PRSEA were constructed for each individual. Two mediation models were performed. The parallel mediation model explored the relationship of PRSEA with functionality through CR and clinical symptoms. The serial mediation model tested a causal chain of the three mediators: CR, NS, and PS. Mediation analysis was performed using the PROCESS function V.4.1 in SPSS V.22.

A serial mediation model revealed a causal chain for PRSEA > CR > NS > Functionality (β = −0.35, 95%CI [−0.85, −0.04], p < 0.05). The model fit the data satisfactorily (CFI = 1.00; RMSEA = 0.00; SRMR = 7.2 × 10−7). Conversely, no parallel mediation was found between the three mediators, PRSEA and functionality and the model poorly fit the data (CFI = 0.30; RMSEA = 0.25; SRMR = 0.11).

Both CR and NS mediate the relationship between PRSEA and functionality at one-year follow-up, using serial mediation analysis. This may be relevant for prevention and personalized early intervention to reduce illness impact and improve functional outcomes in FEP patients.

The conceptualization of negative symptoms (NS) in schizophrenia is still controversial. Recent confirmatory factor-analytic studies suggested that the bi-dimensional model (motivational deficit [MAP] and expressive deficit [EXP]) may not capture the complexity of NS structure, which could be better defined by a five-factor (five NS domains) or a hierarchical model (five NS domains as first-order factors, and MAP and EXP, as second-order factors). A validation of these models is needed to define the structure of NS. To evaluate the validity and temporal stability of the five-factor or the hierarchical structure of the brief negative symptom scale (BNSS) in individuals with schizophrenia (SCZ), exploring associations between these models with cognition, social cognition, functional capacity, and functioning at baseline and at 4 years follow-up.

Clinical variables were assessed using state-of-the-art tools in 612 SCZ at two-time points. The validity of the five-factor and the hierarchical models was analyzed through structural equation models.

The two models had both a good fit and showed a similar pattern of associations with external validators at the two-time points, with minor variations. The five-factor solution had a slightly better fit. The associations with external validators favored the five-factor structure.

Our findings suggest that both five-factor and hierarchical models provide a valid conceptualization of NS in relation to external variables and that five-factor solution provides the best balance between parsimony and granularity to summarize the BNSS structure. This finding has important implications for the study of pathophysiological mechanisms and the development of new treatments.

The structure of negative symptoms of schizophrenia is still a matter of controversy. Although a two-dimensional model (comprising the expressive deficit dimension and the motivation and pleasure dimension) has gained a large consensus, it has been questioned by recent investigations.

To investigate the latent structure of negative symptoms and its stability over time in people with schizophrenia using network analysis.

Negative symptoms were assessed in 612 people with schizophrenia using the Brief Negative Symptom Scale (BNSS) at baseline and at 4-year follow-up. A network invariance analysis was conducted to investigate changes in the network structure and strength of connections between the two time points.

The network analysis carried out at baseline and follow-up, supported by community detection analysis, indicated that the BNSS's items aggregate to form four or five distinct domains (avolition/asociality, anhedonia, blunted affect and alogia). The network invariance test indicated that the network structure remained unchanged over time (network invariance test score 0.13; P = 0.169), although its overall strength decreased (6.28 at baseline, 5.79 at follow-up; global strength invariance test score 0.48; P = 0.016).

The results lend support to a four- or five-factor model of negative symptoms and indicate overall stability over time. These data have implications for the study of pathophysiological mechanisms and the development of targeted treatments for negative symptoms.

Childhood trauma may impact the course of schizophrenia spectrum disorders (SSD), specifically in relation to the increased severity of depressive or negative symptoms. The type and impact of trauma may differ between sexes. In a large sample of recent-onset patients, we investigated the associations of depressive and negative symptoms with childhood trauma and whether these are sex-specific.

A total of 187 first-episode psychosis patients in remission (Handling Antipsychotic Medication: Long-term Evaluation of Targeted Treatment study) and 115 recent-onset SSD patients (Simvastatin study) were included in this cross-sectional study (men: n = 218; women: n = 84). Total trauma score and trauma subtypes were assessed using the Childhood Trauma Questionnaire Short Form; depressive and negative symptoms were rated using the Positive And Negative Symptoms Scale. Sex-specific regression analyses were performed.

Women reported higher rates of sexual abuse than men (23.5% v. 7.8%). Depressive symptoms were associated with total trauma scores and emotional abuse ratings in men (β: 0.219–0.295; p ≤ 0.001). In women, depressive symptoms were associated with sexual abuse ratings (β: 0.271; p = 0.011). Negative symptoms were associated with total trauma score and emotional neglect ratings in men (β: 0.166–0.232; p ≤ 0.001). Negative symptoms in women were not linked to childhood trauma, potentially due to lack of statistical power.

Depressive symptom severity was associated with different types of trauma in men and women with recent-onset SSD. Specifically, in women, depressive symptom severity was associated with childhood sexual abuse, which was reported three times as often as in men. Our results emphasize the importance of sex-specific analyses in SSD research.

A leading theory of the negative symptoms of schizophrenia is that they reflect reduced responsiveness to rewarding stimuli. This proposal has been linked to abnormal (reduced) dopamine function in the disorder, because phasic release of dopamine is known to code for reward prediction error (RPE). Nevertheless, few functional imaging studies have examined if patients with negative symptoms show reduced RPE-associated activations.

Matched groups of DSM-5 schizophrenia patients with high negative symptom scores (HNS, N = 27) or absent negative symptoms (ANS, N = 27) and healthy controls (HC, N = 30) underwent fMRI scanning while they performed a probabilistic monetary reward task designed to generate a measure of RPE.

In the HC, whole-brain analysis revealed that RPE was positively associated with activation in the ventral striatum, the putamen, and areas of the lateral prefrontal cortex and orbitofrontal cortex, among other regions. Group comparison revealed no activation differences between the healthy controls and the ANS patients. However, compared to the ANS patients, the HNS patients showed regions of significantly reduced activation in the left ventrolateral and dorsolateral prefrontal cortex, and in the right lingual and fusiform gyrus. HNS and ANS patients showed no activation differences in ventral striatal or midbrain regions-of-interest (ROIs), but the HNS patients showed reduced activation in a left orbitofrontal cortex ROI.

The findings do not suggest that a generalized reduction of RPE signalling underlies negative symptoms. Instead, they point to a more circumscribed dysfunction in the lateral frontal and possibly the orbitofrontal cortex.

Currently there is no first-line treatment recommended for the negative symptoms of schizophrenia. Psychosocial and behavioural interventions are widely used to reduce the burden of negative symptoms. Meta-analytic studies have summarised the evidence for specific approaches but not compared evidence quality and benefit.

To review and evaluate the evidence from meta-analytic studies of psychosocial and behavioural interventions for the negative symptoms of schizophrenia.

A systematic literature search was undertaken to identify all meta-analyses evaluating psychosocial and behavioural interventions reporting on negative symptom outcomes in people with schizophrenia. Data on intervention, study characteristics, acceptability and outcome were extracted. Risk of bias was evaluated. Results were summarised descriptively, and evidence ranked on methodological quality.

In total, 31 systematic reviews met the inclusion criteria evaluating the efficacy of negative symptom interventions on 33 141 participants. Exercise interventions showed effect sizes (reduction in negative symptoms) ranging from −0.59 to −0.24 and psychological interventions ranging from −0.65 to −0.04. Attrition ranged between 12% to 32%. Across the studies considered heterogeneity varied substantially (range 0–100). Most of the reviews were of very low to low methodological quality. Methodological quality ranking suggested that the effect size for cognitive remediation and exercise therapy may be more robust compared with other approaches.

Most of the interventions considered had a small-to-moderate effect size, good acceptability levels but very few had negative symptoms as the primary intervention target. To improve the confidence of these effect sizes being replicated in clinical settings future studies should minimise risk of bias.