UNASSIGNED: Negative symptoms (NS) appear early in subjects at ultra-high risk (UHR) for psychosis and may increase the risk of conversion to psychotic disorders and poor outcome. Contrary to schizophrenia, there is no consensus on the conceptualization and factor structure of NS in UHR subjects. This study aims to explore NS prevalence, factor structure, and impact on the outcome of UHR state in children and adolescents.
UNASSIGNED: 71 UHR were recruited at the Neuropsychiatry Unit of the Hospital Bambino Gesù in Rome. We examined the prevalence of NS of at least moderate severity, the factor structure of NS by Principal Component Analysis (PCA) and Confirmatory Factor Analysis (CFA), and correlations between extracted factors and functioning. We also evaluated the severity of baseline NS in subjects who converted to psychosis (converters) and in those who did not convert (nonconverters) at 1-year follow-up.
UNASSIGNED: At baseline, all participants showed at least one NS of at least moderate severity. PCA and CFA yielded a two-factor solution: an \'\'Expressive\" and an \"Experiential\" factor. Only the Experiential factor was associated with functioning. At baseline, severity of NS did not differ between converters (N = 16) and nonconverters (N = 55).
UNASSIGNED: In UHR children and adolescents NS have a high prevalence, a significant impact on functioning, and cluster in two-factors. Replications by independent studies, with state-of-the-art instruments and longer duration of follow-up, are needed to improve the characterization of NS in this population, clarify their impact on the outcome and enhance their early identification, prevention, and treatment.

OBJECTIVE: The Cognitive Model of Negative Symptoms is a prominent model that posits that defeatist performance beliefs (DPB) are a key psychological mechanism underlying negative symptoms in those with schizophrenia (SZ). However, the ecological validity of the model has not been established, and temporally specific evaluations of the model\'s hypotheses have not been conducted. This study tested the model\'s key hypotheses in real-world environments using ecological momentary assessment (EMA).
METHODS: Fifty-two outpatients with SZ and 55 healthy controls (CN) completed 6 days of EMA. Multilevel models examined concurrent and time-lagged associations between DPB and negative symptoms in daily life.
RESULTS: SZ displayed greater DPB in daily life than CN. Furthermore, greater DPB were associated with greater concurrently assessed negative symptoms (anhedonia, avolition, and asociality) in daily life. Time-lagged analyses indicated that in both groups, greater DPB at time t led to elevations in negative symptoms (anhedonia, avolition, or asociality) at t + 1 above and beyond the effects of negative symptoms at time t.
CONCLUSIONS: Results support the ecological validity of the Cognitive Model of Negative Symptoms and identify a temporally specific association between DPB and subsequent negative symptoms that is consistent with the model\'s hypotheses and a putative mechanistic pathway in Cognitive Behavioral Therapy for negative symptoms. Findings suggest that DPB are a psychological factor contributing to negative symptoms in real-world environments. Implications for measuring DPB in daily life and providing just-in-time mobile health-based interventions to target this mechanism are discussed.

Negative symptoms in the context of psychosis are still poorly understood and diagnosed, which impairs the treatment efficacy of current therapies and patient\'s integration in society. In this study, we aimed to test hypothesis-based and exploratory associations of negative symptom domains, as defined by the Brief Negative Symptom Scale (BNSS), with hormonal and hematological variables, and, complementarily, with standard psychological/cognitive and psychopathological measures. Fifty-one male patients diagnosed with a psychotic disorder underwent a structured interview and blood collection. Standard Spearmen bivariate correlations were used for data analysis. We obtained evidence of hypothesis-based associations between specific negative symptoms and oxytocin, thyroid stimulating hormone levels and neutrophil-to-lymphocyte ratio; as well as novel and hypothesis-free associations with erythrocyte and lymphocyte count, mean corpuscular volume and red cell distribution width. Complementarily, we also obtained some validation of previous associations of negative symptoms with illness resolution, cognitive symptom severity and social performance, and a novel association with anger contagion. We hope our results can generate new hypotheses in psychosis research. Our work suggests further avenues in research on erythrocytic, inflammatory, thyroid and oxytocin-related markers and abnormalities in psychosis, especially in regards to specific negative symptoms, towards more precise and comprehensive etiological, diagnostic and therapeutic models.

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.

BACKGROUND: Motivational dysfunctions related to effort exertion are common in psychiatric disorders. Dopamine systems regulate exertion of effort and effort-based choice in humans and rodents.
OBJECTIVE: Previous rodent studies mainly employed male rats, and it is imperative to conduct studies in male and female rats.
METHODS: The present studies compared the effort-related effects of IP injections of the dopamine antagonists ecopipam and haloperidol, and the vesicular monoamine transport-2 inhibitor tetrabenazine (TBZ), in male and female rats using the fixed ratio 5/chow feeding choice task.
RESULTS: Ecopipam (0.05-0.2 mg/kg) and haloperidol (0.05-0.15 mg/kg) induced a low-effort bias, decreasing lever pressing and increasing chow intake in males and females in the same dose range. With lever pressing, there was a modest but significant dose x sex interaction after ecopipam injection, but there was no significant interaction after administration of haloperidol. In the first study with TBZ (0.25-1.0 mg/kg), there was a robust sex difference. TBZ shifted choice from lever pressing to chow intake in male rats, but was ineffective in females. In a second experiment, 2.0 mg/kg affected choice behavior in both males and females. TBZ increased accumbens c-Fos immunoreactivity in a sex-dependent manner, with males significantly increasing at 1.0 mg/kg, while females showed augmented immunoreactivity at 2.0 mg/kg.
CONCLUSIONS: The neural and behavioral effects of TBZ differed across sexes, emphasizing the importance of conducting studies in male and female rats. This research has implications for understanding the effort-related motivational dysfunctions seen in psychopathology.

Reward processing is impaired in people with schizophrenia, which may begin in the clinical high-risk (CHR) for psychosis period. The Monetary Incentive Delay (MID) task has been important in understanding the neural correlates of reward processing deficits in various psychiatric disorders. Previous research has found that CHR individuals have an imprecise mental representation of rewards, which leads to a diminished differentiation between rewards, though this has not been observed behaviorally. A total of 19 CHR individuals and 20 controls were given a novel variant of the MID task, designed to examine how modulating reward context may impact responses to reward cues, a process often referred to as \"adaptive coding.\" Both groups appeared to update their behavior in response to the rewards available in this adaptive task. However, when compared to controls who showed a more graded decrease in response time to increasing reward contexts, CHR individuals appeared to have a sharp decrease in response time in the low reward context that is nearly stable across higher reward contexts. This is largely driven by the exponential component of the response time distribution, which is often interpreted to be more cognitively or effortfully influenced. Response times are related to negative symptoms, but not positive symptoms, disorganized symptoms, or estimated intelligence. Although an adaptive coding effect was not observed, these results provide novel insight into the reward processing mechanisms and volitional processes in the CHR population, as this was the first study to observe the diminished differentiation of rewards behaviorally.

Apathy is a behavioral symptom prevalent both in neuropsychiatric pathologies and in the healthy population. However, the knowledge of the cognitive and neural mechanisms underlying apathy is still very limited, even if clinical and fMRI data support the existence of three forms of apathy (executive, emotional, initiative). These forms could be explained by the alteration of specific mechanisms. This present study\'s aim is to specify the cognitive and neuronal mechanisms of executive and emotional apathy. We used an EEG study conducted on 68 subjects comprising two groups of young people with specific executive or emotional phenotypes of apathy and one group with no apathy. Despite having symptom of apathy, participants were free of any neurological, metabolic, or psychiatric diagnoses and with high education. Two tasks were used: the DPX for cognitive control and the MID for motivation. Our results showed that distinct mechanisms underlie these two forms of apathy, and, for the first time, we specified these mechanisms. A deficit of the proactive control mode, reflected by a reduced probe-N2 amplitude in AY trials, underlies the executive form of apathy (p < .03), whereas liking motivational blunting, highlighted by a reduced LPP amplitude for financial loss, characterizes the emotional form (p < .04). The main limit of the results is that generalizability to the general population may be reduced since the apathetic samples were chosen for having a specific form of apathy. To conclude, better knowledge of these mechanisms informs new, more targeted treatments, both pharmacological and non-pharmacological, necessary for reducing the debilitating consequences of apathy.

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Impairment in intrinsic motivation (IM), the drive to satisfy internal desires like mastery, may play a key role in disability in psychosis. However, we have limited knowledge regarding relative impairments in IM compared to extrinsic motivation (EM) or general motivation (GM), in part due to limitations in existing measures.
Here we address this gap using a novel Trait Intrinsic and Extrinsic Motivation self-report scale in a sample of n = 243 participants including those with schizophrenia, psychosis-risk, and healthy controls. Each of the 7 IM and 6 EM items used a 7-point Likert scale assessing endorsement of dispositional statements. Bifactor analyses of these items yielded distinct IM, EM, and GM factor scores. Convergent and discriminant validity were examined in relation to General Causality Orientation Scale (GCOS-CP) and Quality of Life 3-item IM measure (QLS-IM). Utility was assessed in relation to psychosis-spectrum (PS) status and CAINS clinical amotivation.
IM and EM showed acceptable inter-item consistency (IM: α = 0.88; EM: α = 0.66); the bifactor model exhibited fit that varied from good to borderline to inadequate depending on the specific fit metric (SRMR = 0.038, CFI = 0.94, RMSEA = 0.106 ± 0.014). IM scores correlated with established IM measures: GCOS-CP Autonomy (rho = 0.38, p < 0.01) and QLS-IM (rho = 0.29, p < 0.01). Supporting discriminant validity, IM did not correlate with GCOS-CP Control (rho = -0.14, p > 0.05). Two-year stability in an available longitudinal subset (n = 35) was strong (IM: rho = 0.64, p < 0.01; EM: rho = 0.55, p < 0.01). Trait IM was lower in PS youth (t = 4.24, p < 0.01), and correlated with clinical amotivation (rho = -0.36, p < 0.01); EM did not show significant clinical associations.
These results demonstrate the clinical relevance of IM in psychosis risk. They also provide preliminary support for the reliability, validity and utility of this new Trait IM-EM scale, which addresses a measurement gap and can facilitate identification of neurobehavioral and clinical correlates of IM deficits.

BACKGROUND: A bioecosystem theory was recently proposed positing that negative symptoms of schizophrenia (SZ) are influenced by environmental factors. These environmental processes reflect sources of resource deprivation that manifest across multiple systems that impact individuals directly through microsystems and indirectly through the exosystem and macrosystem. As an initial test of this theory, the current study examined whether self-reported environmental resource deprivation was associated with anhedonia, avolition, and asociality.
METHODS: Two samples were collected: (1) outpatients with schizophrenia or schizoaffective disorder (SZ: n = 38) and matched psychiatrically heathy controls (CN: n = 31); (2) youth at clinical high risk for psychosis (CHR: n = 34) and matched CN (n = 30). Measures of negative symptoms and environmental factors influencing the frequency of recreational, goal-directed, and social activities were collected.
RESULTS: Negative symptoms were associated with environmental deprivation factors in the microsystem (number of social and activity settings) and exosystem (economy, mass media, politics/laws, neighborhood crime). These associations did not appear due to depression and were greater among those with SZ than CHR.
CONCLUSIONS: These findings provide preliminary support for the bioecosystem theory and highlight an under-recognized role for environmental factors underlying negative symptoms across phases of psychotic illness. Environmental systems-focused treatment approaches may offer a novel means of treating negative symptoms, which could be promising when coupled with person-level pharmacological and psychosocial treatments.