BACKGROUND: Accumulating evidence suggests that the inflammatory cytokine interleukin-6 (IL-6) contributes to the pathophysiology of psychiatric disorders. However, there was no study concerning the relationship between IL-6 concentrations and clinical features in the chronic phase of early-onset schizophrenia (EOS).
OBJECTIVE: To investigate the relationship between serum IL-6 concentration and the clinical features of EOS.
METHODS: We measured serum IL-6 Levels from 74 patients with chronic schizophrenia, including 33 with age at onset < 21 years (EOS group) and 41 with onset ≥ 21 years in [adult-onset schizophrenia (AOS) group], and from 41 healthy controls. Symptom severities were evaluated using the Positive and Negative Syndrome Scale (PANSS).
RESULTS: Serum IL-6 concentrations were higher in both EOS and AOS groups than healthy controls (F = 22.32, P < 0.01), but did not differ significantly between EOS and AOS groups (P > 0.05) after controlling for age, body mass index, and other covariates. Negative symptom scores were higher in the EOS group than the AOS group (F = 6.199, P = 0.015). Serum IL-6 concentrations in the EOS group were negatively correlated with both total PANSS-negative symptom score (r = -0.389, P = 0.032) and avolition/asociality subscore (r = -0.387, P = 0.026).
CONCLUSIONS: Patients with EOS may have more severe negative symptoms than those with adult-onset schizophrenia during the chronic phase of the illness. IL-6 signaling may regulate negative symptoms and its avolition/asociality subsymptoms among the early-onset chronic schizophrenic patients.

Social affinity and collective behavior are nearly ubiquitous in the animal kingdom, but many lineages feature evolutionarily asocial species. These solitary species may have evolved to conserve energy in food-sparse environments. However, the mechanism by which metabolic shifts regulate social affinity is not well investigated.
In this study, we used the Mexican tetra (Astyanax mexicanus), which features riverine sighted surface (surface fish) and cave-dwelling populations (cavefish), to address the impact of metabolic shifts on asociality and other cave-associated behaviors in cavefish, including repetitive turning, sleeplessness, swimming longer distances, and enhanced foraging behavior. After 1 month of ketosis-inducing ketogenic diet feeding, asocial cavefish exhibited significantly higher social affinity, whereas social affinity regressed in cavefish fed the standard diet. The ketogenic diet also reduced repetitive turning and swimming in cavefish. No major behavioral shifts were found regarding sleeplessness and foraging behavior, suggesting that other evolved behaviors are not largely regulated by ketosis. We further examined the effects of the ketogenic diet via supplementation with exogenous ketone bodies, revealing that ketone bodies are pivotal molecules positively associated with social affinity.
Our study indicated that fish that evolved to be asocial remain capable of exhibiting social affinity under ketosis, possibly linking the seasonal food availability and sociality.

Evidence regarding the association of Negative Symptoms (NS) dimensions with Health-related Quality of Life (HRQoL) is limited and no prior study has looked into contributions of NS domains on HRQoL. This study bridges the gap by examining the associations of NS, its two dimensions (Motivation and Pleasure, and Emotional Expressivity) and five domains (Anhedonia, Avolition, Asociality, Blunted affect and Alogia) with HRQoL in schizophrenia. 274 individuals with schizophrenia were assessed on the Positive and Negative Syndrome Scale (PANSS) and Brief Negative Symptom Scale (BNSS). PANSS scores were mapped to EuroQol five-dimensional (EQ-5D-5L) utility scores using an algorithm previously validated in Singapore, and the resulting EQ-5D-5L scores were used as a measure of HRQoL. Multiple linear regression analyses of the two NS dimensions and five NS domains against EQ-5D-5L showed that a lower severity of NS, specifically that of the Motivation and Pleasure (MAP) dimension and asociality domain was associated with higher HRQoL. Our findings highlight the importance of targeting NS, particularly MAP and asociality, in improving HRQoL in schizophrenia.

Social motivation impairments, or \"asociality,\" have long been considered a core clinical feature of schizophrenia. Although the prevalence and pervasive negative impact of poor social motivation is well-documented, our understanding is limited regarding causal mechanisms. Advances in definition, conceptualization, and characterization are needed to inform research aimed at understanding these mechanisms and developing effective interventions. This theme issue is intended to accelerate efforts to study and treat social motivation in schizophrenia by synthesizing the current knowledge and providing new frameworks to guide future research in this area.

BACKGROUND: Negative symptoms (avolition, anhedonia, asociality) are a prevalent symptom in those across the psychosis-spectrum and also occur at subclinical levels in the general population. Recent work has begun to examine how environmental contexts (e.g. locations) influence negative symptoms. However, limited work has evaluated how environments may contribute to negative symptoms among youth at clinical high risk for psychosis (CHR). The current study uses Ecological Momentary Assessment to assess how four environmental contexts (locations, activities, social interactions, social interaction method) impact state fluctuations in negative symptoms in CHR and healthy control (CN) participants.
METHODS: CHR youth (n = 116) and CN (n = 61) completed 8 daily surveys for 6 days assessing negative symptoms and contexts.
RESULTS: Mixed-effects modeling demonstrated that negative symptoms largely varied across contexts in both groups. CHR participants had higher negative symptoms than CN participants in most contexts, but groups had similar symptom reductions during recreational activities and phone call interactions. Among CHR participants, negative symptoms were elevated in several contexts, including studying/working, commuting, eating, running errands, and being at home.
CONCLUSIONS: Results demonstrate that negative symptoms dynamically change across some contexts in CHR participants. Negative symptoms were more intact in some contexts, while other contexts, notably some used to promote functional recovery, may exacerbate negative symptoms in CHR. Findings suggest that environmental factors should be considered when understanding state fluctuations in negative symptoms among those at CHR participants.

Negative symptoms (i.e., anhedonia, avolition, asociality, blunted affect, alogia) are frequently observed in the schizophrenia-spectrum (SZ) and associated with functional disability. While semi-structured interviews of negative symptoms represent a gold-standard approach, they require specialized training and may be vulnerable to rater biases. Thus, brief self-report questionnaires measuring negative symptoms may be useful. Existing negative symptom questionnaires demonstrate that this approach may be promising in schizophrenia, but no measure has been devised for use across stages of psychotic illness. The present study reports initial psychometric validation of the Negative Symptom Inventory-Self-Report (NSI-SR), the self-report counterpart of the Negative Symptom Inventory-Psychosis Risk clinical interview. The NSI-SR is a novel transphasic negative symptoms measure assessing the domains of anhedonia, avolition, and asociality. The NSI-SR and related measures were administered to two samples: 1) undergraduates (n = 335), 2) community participants, including: SZ (n = 32), clinical-high risk for psychosis (CHR, n = 25), and healthy controls matched to SZ (n = 31) and CHR (n = 30). The psychometrically trimmed 11-item NSI-SR showed good internal consistency and a three-factor solution reflecting avolition, asociality, and anhedonia. The NSI-SR demonstrated convergent validity via moderate to large correlations with clinician-rated negative symptoms and related constructs in both samples. Discriminant validity was supported by lower correlations with positive symptoms in both samples; however, correlations with positive symptoms were still significant. These initial psychometric findings suggest that the NSI-SR is a reliable and valid brief questionnaire capable of measuring negative symptoms across phases of psychotic illness.

A recent environmental theory of negative symptoms posits that environmental contexts (e.g., location, social partner) play a significant-yet often unaccounted for-role in negative symptoms of schizophrenia (SZ). \"Gold-standard\" clinical rating scales offer limited precision for evaluating how contexts impact symptoms. To overcome some of these limitations, Ecological Momentary Assessment (EMA) was used to determine whether there were state fluctuations in experiential negative symptoms (anhedonia, avolition, and asociality) in SZ across contexts (locations, activities, social interaction partner, social interaction method). Outpatients with SZ (n = 52) and healthy controls (CN: n = 55) completed 8 daily EMA surveys for 6 days assessing negative symptom domains (anhedonia, avolition, and asociality) and contexts. Multilevel modeling demonstrated that negative symptoms varied across location, activity, social interaction partner, and social interaction method. For the majority of contexts, SZ and CN did not report significantly different levels of negative symptoms, with SZ only reporting higher negative symptoms than CN while eating, resting, interacting with a significant other, or being at home. Further, there were several contexts where negative symptoms were similarly reduced (e.g., recreation, most social interactions) or elevated (e.g., using the computer, working, running errands) in each group. Results demonstrate that experiential negative symptoms dynamically change across contexts in SZ. Some contexts may \"normalize\" experiential negative symptoms in SZ, while other contexts, notably some used to promote functional recovery, may increase experiential negative symptoms.

Recent factor analytic evidence supports both two-factor (motivation and pleasure, MAP; diminished expression, EXP) and five-factor (anhedonia, asociality, avolition, blunted affect, alogia) conceptualizations of negative symptoms. However, it is unclear whether these two conceptualizations of the latent structure of negative symptoms have differential associations with external correlates. The current study evaluated external correlates of the two- and five-factor structures by examining associations with variables known to have critical relations with negative symptoms: trait affect, defeatist performance beliefs, neurocognition, and community-based psychosocial functioning. Participants included a total of 245 outpatients diagnosed with schizophrenia who were rated on the Brief Negative Symptom Scale and completed a battery of additional measures during periods of clinical stability. These additional measures included the Positive and Negative Affect Schedule, Defeatist Performance Beliefs scale, MATRICS Consensus Cognitive Battery, and Level of Function Scale. Pearson correlations indicated differential patterns of associations between the BNSS scores and the external correlates. Support for the two-factor model was indicated by a stronger association of MAP with positive affect and psychosocial functioning, compared to EXP with neurocognition. Significance tests examining a differential magnitude of associations showed that the two-dimension negative symptom structure masked unique correlational relationships among the five negative symptom domains with neurocognition and social/vocational community functioning and captured unique patterns of correlation with trait affect. Support for the five-factor model was shown by a stronger association between Blunted Affect with Attention/Vigilance, and stronger associations between Avolition, Anhedonia, and Asociality with psychosocial functioning. Results offer support for both the two-dimension and five-domain model of negative symptoms as well as a hierarchical two-dimensions-five-domains model of negative symptoms. Findings may have implications for diagnostic criteria and descriptions of the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5), as well as possible treatment targets of negative symptoms.

UNASSIGNED: Recent studies suggest five domains for negative schizophrenia symptoms: anhedonia, asociality, avolition, blunted affect, and alogia. Avolition has been considered a characteristic symptom in community-dwelling patients. However, few studies have explored the association of these symptoms with long-term hospitalization.
UNASSIGNED: This study explored the relative association of each of the five domains of negative symptoms in two groups of patients with schizophrenia: long-term hospitalized and community-dwelling patients.
UNASSIGNED: Participants included 56 long-term inpatients and 111 community-dwelling patients at Nasukougen Hospital in Japan. The nearest neighbor matching within caliper was used. After matching participants by age, sex, disease duration, and years of education, each group was assigned 30 participants. Model 1 was analyzed with a logistic regression analysis with 5 subdomains as independent variables. Model 2 was analyzed after adding positive symptoms, cognitive function, functional skills, and functional outcomes to the subdomains that were significant in model 1.
UNASSIGNED: The results indicated that asociality was significantly associated with long-term hospitalization. When the characteristic clinical factors of schizophrenia were added, asociality, daily living skills, and social and role functions were found to be characteristic of long-term hospitalization. Among the negative symptoms, lack of social motivation was more characteristic among the group with a poor prognosis.
UNASSIGNED: Of the negative symptoms associated with long-term hospitalization, asociality, lack of social motivation, rather than avolition was found to be most strongly associated with community-dwelling patients\' functional outcomes. Further studies are required to establish a causal association as it may have therapeutic implications.

Negative symptoms are a core aspect of psychopathology in schizophrenia. Currently available pharmacological agents have proven minimally efficacious for remediating negative symptoms. A promising treatment avenue is the intranasal administration of the neuropeptide oxytocin. However, there have been inconsistencies in effects of oxytocin on negative symptoms throughout the literature, and factors leading to inconsistent effects are unclear.
We conducted a systematic review and meta-analysis of randomized clinical trials to compare the effectiveness of oxytocin with placebo for the treatment of negative symptoms and determine moderators of treatment effect. Random effects meta-analyses and dose-response meta-analysis were performed on mean changes in negative symptoms.
In an initial analysis of all 9 identified randomized clinical trials, intranasal oxytocin showed no significant effect on negative symptoms. For higher doses (>40-80 IU), a beneficial effect on negative symptoms was found with a moderate effect size, but this effect disappeared after exclusion of 1 outlier study. The dose-response meta-analysis predicted that higher doses of oxytocin may be more efficacious for negative symptoms. For positive symptoms, no beneficial effect of oxytocin was found in the main meta-analysis, but the dose-response meta-analysis suggested a potential advantage of higher doses.
The present results show no consistent beneficial effect of intranasal oxytocin for the treatment of negative and positive symptoms. The dose-response meta-analysis does not allow drawing any firm conclusions but suggests that high doses of intranasal oxytocin may be more efficacious. If future studies are conducted, an effort to reach adequate CNS concentrations for a sufficient duration is required.