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.

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.

Understanding the evolution of negative symptoms in first-episode psychosis (FEP) requires long-term longitudinal study designs that capture the progression of this condition and the associated brain changes.

To explore the factors underlying negative symptoms and their association with long-term abnormal brain trajectories.

We followed up 357 people with FEP over a 10-year period. Factor analyses were conducted to explore negative symptom dimensionality. Latent growth mixture modelling (LGMM) was used to identify the latent classes. Analysis of variance (ANOVA) was conducted to investigate developmental trajectories of cortical thickness. Finally, the resulting ANOVA maps were correlated with a wide set of regional molecular profiles derived from public databases.

Three trajectories (stable, decreasing and increasing) were found in each of the three factors (expressivity, experiential and attention) identified by the factor analyses. Patients with an increasing trajectory in the expressivity factor showed cortical thinning in caudal middle frontal, pars triangularis, rostral middle frontal and superior frontal regions from the third to the tenth year after the onset of the psychotic disorder. The F-statistic map of cortical thickness expressivity differences was associated with a receptor density map derived from positron emission tomography data.

Stable and decreasing were the most common trajectories. Additionally, cortical thickness abnormalities found at relatively late stages of FEP onset could be exploited as a biomarker of poor symptom outcome in the expressivity dimension. Finally, the brain areas with less density of receptors spatially overlap areas that discriminate the trajectories of the expressivity dimension.

Negative symptoms of schizophrenia have recently been proposed to result from a decoupling of (intact) hedonic experience and (diminished) approach behavior. The current study challenged this view by exploring the hypothesis that negative symptoms are driven by a specific type of emotional experience abnormality, a reduction in the positivity offset (i.e. the tendency to experience greater levels of positive relative to negative emotion in low-arousal contexts), which limits the production of approach behaviors in neutral environments.

Participants included outpatients with SZ (n = 44) and healthy controls (CN: n = 48) who completed one week of active (ecological momentary assessment surveys of emotional experience and symptoms) and passive (geolocation, accelerometry) digital phenotyping. Mathematical modeling approaches from Cacioppo's Evaluative Space Model were used to quantify the positivity offset in daily life. Negative symptoms were assessed via standard clinical ratings, as well as active (EMA surveys) and passive (geolocation, accelerometry) digital phenotyping measures.

Results indicated that the positivity offset was reduced in SZ and associated with more severe anhedonia and avolition measured via clinical interviews and active and passive digital phenotyping.

These findings suggest that current conceptual models of negative symptoms, which assume hedonic normality, may need to be revised to account for reductions in the positivity offset and its connection to diminished motivated behavior. Findings identify key real-world contexts where negative symptoms could be targeted using psychosocial treatments.

Psychotic disorders and schizotypal traits aggregate in the relatives of probands with schizophrenia. It is currently unclear how variability in symptom dimensions in schizophrenia probands and their relatives is associated with polygenic liability to psychiatric disorders.

To investigate whether polygenic risk scores (PRSs) can predict symptom dimensions in members of multiplex families with schizophrenia.

The largest genome-wide data-sets for schizophrenia, bipolar disorder and major depressive disorder were used to construct PRSs in 861 participants from the Irish Study of High-Density Multiplex Schizophrenia Families. Symptom dimensions were derived using the Operational Criteria Checklist for Psychotic Disorders in participants with a history of a psychotic episode, and the Structured Interview for Schizotypy in participants without a history of a psychotic episode. Mixed-effects linear regression models were used to assess the relationship between PRS and symptom dimensions across the psychosis spectrum.

Schizophrenia PRS is significantly associated with the negative/disorganised symptom dimension in participants with a history of a psychotic episode (P = 2.31 × 10−4) and negative dimension in participants without a history of a psychotic episode (P = 1.42 × 10−3). Bipolar disorder PRS is significantly associated with the manic symptom dimension in participants with a history of a psychotic episode (P = 3.70 × 10−4). No association with major depressive disorder PRS was observed.

Polygenic liability to schizophrenia is associated with higher negative/disorganised symptoms in participants with a history of a psychotic episode and negative symptoms in participants without a history of a psychotic episode in multiplex families with schizophrenia. These results provide genetic evidence in support of the spectrum model of schizophrenia, and support the view that negative and disorganised symptoms may have greater genetic basis than positive symptoms, making them better indices of familial liability to schizophrenia.

Negative symptoms such as blunted facial expressivity are characteristic of schizophrenia. However, it is not well-understood if and what abnormalities are present in individuals at clinical high-risk (CHR) for psychosis.

This experimental study employed facial electromyography (left zygomaticus major and left corrugator supercilia) in a sample of CHR individuals (N = 34) and healthy controls (N = 32) to detect alterations in facial expressions in response to emotionally evocative film clips and to determine links with symptoms.

Findings revealed that the CHR group showed facial blunting manifested in reduced zygomatic activity in response to an excitement (but not amusement, fear, or sadness) film clip compared to controls. Reductions in zygomatic activity in the CHR group emerged in response to the emotionally evocative peak period of the excitement film clip. Lower zygomaticus activity during the excitement clip was related to anxiety while lower rates of change in zygomatic activity during the excitement video clip were related to higher psychosis risk conversion scores.

Together, these findings inform vulnerability/disease driving mechanisms and biomarker and treatment development.

Psychotic experiences and negative symptoms (PENS) are common in non-clinical populations. PENS are associated with adverse outcomes, particularly when they persist. Little is known about the trajectories of PENS dimensions in young people, nor about the precursory factors associated with these trajectories.

We conducted growth mixture modelling of paranoia, hallucinations, and negative symptoms across ages 16, 17, and 22 in a community sample (N = 12 049–12 652). We then described the emergent trajectory classes through their associations with genome-wide polygenic scores (GPS) for psychiatric and educational phenotypes, and earlier childhood characteristics.

Three trajectory classes emerged for paranoia, two for hallucinations, and two for negative symptoms. Across PENS, GPS for clinical help-seeking, major depressive disorder, and attention deficit hyperactivity disorder were associated with increased odds of being in the most elevated trajectory class (OR 1.07–1.23). Lower education GPS was associated with the most elevated trajectory class for hallucinations and negative symptoms (OR 0.77–0.91). Conversely for paranoia, higher education GPS was associated with the most elevated trajectory class (OR 1.25). Trajectory class associations were not significant for schizophrenia, obsessive-compulsive disorder, bipolar disorder, or anorexia GPS. Emotional/behaviour problems and life events in childhood were associated with increased odds of being in the most elevated trajectory class across PENS.

Our results suggest latent heterogeneity in the development of paranoia, hallucinations, and negative symptoms in young people that is associated with specific polygenic scores and childhood characteristics.