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1.
Brain ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637303

RESUMO

The prediction error account of delusions has had success. However, its explanation of delusions with different contents has been lacking. Persecutory delusions and paranoia are the common unfounded beliefs that others have harmful intentions towards us. Other delusions include believing that one's thoughts or actions are under external control, or that events in the world have specific personal meaning. We compare learning on two different cognitive tasks, probabilistic reversal learning (PRL) and Kamin blocking, that have relationships to paranoid and non-paranoid delusion-like beliefs, respectively. We find that Clinical High-Risk status alone does not result in different behavioral results on the PRL task but that an individual's level of paranoia is associated with excessive switching behavior. During the Kamin blocking task, paranoid individuals learned inappropriately about the blocked cue. However, they also had decreased learning about the control cue, suggesting more general learning impairments. Non-paranoid delusion-like belief conviction (but not paranoia) was associated with aberrant learning about the blocked cue but intact learning about the control cue, suggesting specific impairments in learning related to cue combination. We fit task-specific computational models separately to behavioral data to explore how latent parameters vary within individuals between tasks, and how they can explain symptom-specific effects. We find that paranoia is associated with low learning rates on the PRL task as well as the blocking task. Non-paranoid delusion-like belief conviction was instead related to parameters controlling the degree and direction of similarity between cue updating during simultaneous cue presentation. These results suggest that paranoia and other delusion-like beliefs involve dissociable deficits in learning and belief updating, which - given the transdiagnostic status of paranoia - may have differential utility in predicting psychosis.

2.
Br J Psychiatry ; 223(1): 271-272, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37424200

RESUMO

Recent research has led to important changes in the concepts and assessment of negative symptoms in schizophrenia. We review current negative symptom concepts and their clinical implications, as well as new methods of assessing these symptoms. These changes hold promise for improving our understanding and treatment of negative symptoms.


Assuntos
Esquizofrenia , Psicologia do Esquizofrênico , Humanos , Escalas de Graduação Psiquiátrica , Esquizofrenia/diagnóstico , Esquizofrenia/terapia , Psicometria
3.
Psychol Med ; 53(3): 714-721, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-34120660

RESUMO

BACKGROUND: Schizophrenia (SZ) is typically preceded by a prodromal (i.e. pre-illness) period characterized by attenuated positive symptoms and declining functional outcome. Negative symptoms are prominent among individuals at clinical high-risk (CHR) for psychosis (i.e. those with prodromal syndromes) and predictive of conversion to illness. Mechanisms underlying negative symptoms are unclear in the CHR population. METHODS: The current study evaluated whether CHR participants demonstrated deficits in the willingness to expend effort for rewards and whether these impairments are associated with negative symptoms and greater risk for conversion. Participants included 44 CHR participants and 32 healthy controls (CN) who completed the Effort Expenditure for Reward Task (EEfRT). RESULTS: Compared to CN, CHR participants displayed reduced likelihood of exerting high effort for high probability and magnitude rewards. Among CHR participants, reduced effort expenditure was associated with greater negative symptom severity and greater probability of conversion to a psychotic disorder on a cross-sectional risk calculator. CONCLUSIONS: Findings suggest that effort-cost computation is a marker of illness liability and a transphasic mechanism underlying negative symptoms in the SZ spectrum.


Assuntos
Transtornos Psicóticos , Esquizofrenia , Humanos , Adolescente , Estudos Transversais , Esquizofrenia/diagnóstico , Fatores de Risco , Recompensa , Sintomas Prodrômicos
4.
Psychol Med ; : 1-9, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36722014

RESUMO

BACKGROUND: 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. METHODS: 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: 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. CONCLUSIONS: 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.

5.
Psychol Med ; 53(16): 7609-7618, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37246568

RESUMO

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.


Assuntos
Apatia , Transtornos Psicóticos , Humanos , Adolescente , Transtornos Psicóticos/epidemiologia , Anedonia , Interação Social , Sintomas Prodrômicos
6.
Acta Psychiatr Scand ; 147(6): 623-633, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36905387

RESUMO

INTRODUCTION: Paranoia is a common and impairing psychosis symptom, which exists along a severity continuum that extends into the general population. Individuals at clinical high-risk for psychosis (CHR) frequently experience paranoia and this may elevate their risk for developing full psychosis. Nonetheless, limited work has examined the efficient measurement of paranoia in CHR individuals. The present study aimed to validate an often-used self-report measure, the revised green paranoid thoughts scale (RGPTS), in this critical population. METHOD: Participants were CHR individuals (n = 103), mixed clinical controls (n = 80), and healthy controls (n = 71) who completed self-report and interview measures. Confirmatory factor analysis (CFA), psychometric indices, group differences, and relations to external measures were used to evaluate the reliability and validity of the RGPTS. RESULTS: CFA replicated a two-factor structure for the RGPTS and the associated reference and persecution scales were reliable. CHR individuals scored significantly higher on both reference and persecution, relative to both healthy (ds = 1.03, 0.86) and clinical controls (ds = 0.64, 0.73). In CHR participants, correlations between reference and persecution and external measures were smaller than expected, though showed evidence of discriminant validity (e.g., interviewer-rated paranoia, r = 0.24). When examined in the full sample, correlation magnitude was larger and follow-up analyses indicated that reference related most specifically to paranoia (ß = 0.32), whereas persecution uniquely related to poor social functioning (ß = -0.29). CONCLUSION: These results demonstrate the reliability and validity of the RGPTS, though its scales related more weakly to severity in CHR individuals. The RGPTS may be useful in future work aiming to develop symptom-specific models of emerging paranoia in CHR individuals.


Assuntos
Transtornos Psicóticos , Humanos , Reprodutibilidade dos Testes , Transtornos Psicóticos/diagnóstico , Transtornos Paranoides/diagnóstico , Autorrelato , Relações Interpessoais
7.
Eur Arch Psychiatry Clin Neurosci ; 273(8): 1863-1871, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37278749

RESUMO

Prior studies demonstrate that schizophrenia (SZ) is associated with abnormalities in positive and negative emotional experience that predict clinical presentation. However, it is unclear whether specific discrete emotions within the broader positive/negative categories are driving those symptom associations. Further, it is also unclear whether specific emotions contribute to symptoms in isolation or via networks of emotional states that dynamically interact across time. The current study used network analysis to evaluate temporally dynamic interactions among discrete emotional states experienced in the real world as assessed via Ecological Momentary Assessment (EMA). Participants included 46 outpatients with chronic SZ and 52 demographically matched healthy controls (CN) who completed 6 days of EMA that captured reports of emotional experience and symptoms derived from monetary surveys and geolocation based symptom markers of mobility and home location. Results indicated that less dense emotion networks were associated with greater severity of negative symptoms, whereas more dense emotion networks were associated with more severe positive symptoms and mania. Additionally, SZ evidenced greater centrality for shame, which was associated with greater severity of positive symptoms. These findings suggest that positive and negative symptoms are associated with distinct profiles of temporally dynamic and interactive emotion networks in SZ. Findings have implications for adapting psychosocial therapies to target specific discrete emotional states in the treatment of positive versus negative symptoms.


Assuntos
Esquizofrenia , Humanos , Esquizofrenia/complicações , Avaliação Momentânea Ecológica , Emoções , Vergonha , Mania
8.
Artigo em Inglês | MEDLINE | ID: mdl-38051397

RESUMO

Reward processing impairments are a key factor associated with negative symptoms in those with severe mental illnesses. However, past findings are inconsistent regarding which reward processing components are impaired and most strongly linked to negative symptoms. The current study examined the hypothesis that these mixed findings may be the result of multiple reward processing pathways (i.e., equifinality) to negative symptoms that cut across diagnostic boundaries and phases of illness. Participants included healthy controls (n = 100) who served as a reference sample and a severe mental illness-spectrum sample (n = 92) that included psychotic-like experiences, clinical high-risk for psychosis, bipolar disorder, and schizophrenia participants. All participants completed tasks measuring four RDoC Positive Valence System constructs: value representation, reinforcement learning, effort-cost computation, and hedonic reactivity. A k-means cluster analysis of the severe mental illness-spectrum samples identified three clusters with differential reward processing profiles that were characterized by: (1) global reward processing deficits (22.8%), (2) selective impairments in hedonic reactivity alone (40.2%), and (3) preserved reward processing (37%). Elevated negative symptoms were only observed in the global reward processing cluster. All clusters contained participants from each clinical group, and the distribution of these groups did not significantly differ among the clusters. Findings identified one pathway contributing to negative symptoms that was transdiagnostic and transphasic. Future work further characterizing divergent pathways to negative symptoms may help to improve symptom trajectories and personalized treatments.

9.
Eur Arch Psychiatry Clin Neurosci ; 273(8): 1715-1724, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36633673

RESUMO

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.


Assuntos
Esquizofrenia , Humanos , Anedonia , Funcionamento Psicossocial , Escalas de Graduação Psiquiátrica , Psicologia do Esquizofrênico
10.
Eur Arch Psychiatry Clin Neurosci ; 273(8): 1747-1760, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36477406

RESUMO

Negative symptoms are prominent in individuals with schizophrenia (SZ) and youth at clinical high-risk for psychosis (CHR). In SZ, negative symptoms are linked to reinforcement learning (RL) dysfunction; however, previous research suggests implicit RL remains intact. It is unknown whether implicit RL is preserved in the CHR phase where negative symptom mechanisms are unclear, knowledge of which may assist in developing early identification and prevention methods. Participants from two studies completed an implicit RL task: Study 1 included 53 SZ individuals and 54 healthy controls (HC); Study 2 included 26 CHR youth and 23 HCs. Bias trajectories reflecting implicit RL were compared between groups and correlations with negative symptoms were examined. Cluster analysis investigated RL profiles across the combined samples. Implicit RL was comparable between HC and their corresponding SZ and CHR groups. However, cluster analysis was able to parse performance heterogeneity across diagnostic boundaries into two distinct RL profiles: a Positive/Early Learning cluster (65% of participants) with positive bias scores increasing from the first to second task block, and a Negative/Late Learning cluster (35% of participants) with negative bias scores increasing from the second to third block. Clusters did not differ in the proportion of CHR vs. SZ cases; however, the Negative/Late Learning cluster had more severe negative symptoms. Although implicit RL is intact in CHR similar to SZ, distinct implicit RL phenotypic profiles with elevated negative symptoms were identified trans-phasically, suggesting distinct reward-processing mechanisms can contribute to negative symptoms independent of phases of illness.


Assuntos
Transtornos Psicóticos , Esquizofrenia , Adolescente , Humanos , Imageamento por Ressonância Magnética , Aprendizagem , Recompensa , Sintomas Prodrômicos
11.
Artigo em Inglês | MEDLINE | ID: mdl-37878034

RESUMO

Blunted affect is associated with severe mental illness, particularly schizophrenia. Mechanisms of blunted affect are poorly understood, potentially due to a lack of phenomenological clarity. Here, we examine clinician rated blunted affect and computerized facial metrics derived from ambulatory video assessment using machine learning. With high predictive accuracy (80-82%), we found that head orientation, eye movement, and facets of mouth movement were associated with clinical ratings of blunted affect. Features denoting larger muscle movements were associated with social cognition (R2 = 0.37) and cognition (R2 = 0.40). Findings provide potential insights on psychological and pathophysiological contributors to blunted affect.

12.
Eur Arch Psychiatry Clin Neurosci ; 273(6): 1329-1338, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36680609

RESUMO

Although the COVID-19 pandemic has had detrimental effects on mental health in the general population, the impact on those with schizophrenia-spectrum disorders has received relatively little attention. Assessing pandemic-related changes in positive symptoms is particularly critical to inform treatment protocols and determine whether fluctuations in hallucinations and delusions are related to telehealth utilization and treatment adherence. In the current longitudinal study, we evaluated changes in the frequency of hallucinations and delusions and distress resulting from them across three-time points. Participants included: (1) outpatients with chronic schizophrenia (SZ: n = 32) and healthy controls (CN: n = 31); (2) individuals at clinically high risk for psychosis (CHR: n = 25) and CN (n = 30). A series of questionnaires were administered to assess hallucination and delusion severity, medication adherence, telehealth utilization, and protective factors during the pandemic. While there were no significant increases in the frequency of hallucinations and delusions in SZ and CHR, distress increased from pre-pandemic to early pandemic in both groups and then decreased at the third time point. Additionally, changes in positive symptom severity in SZ were related to psychiatric medication adherence. Findings suggest that positive symptoms are a critical treatment target during the pandemic and that ongoing medication services will be beneficial.


Assuntos
COVID-19 , Transtornos Psicóticos , Esquizofrenia , Humanos , Adolescente , Esquizofrenia/complicações , Esquizofrenia/epidemiologia , Esquizofrenia/diagnóstico , Delusões/epidemiologia , Delusões/etiologia , Delusões/diagnóstico , Pandemias , Estudos Longitudinais , Pacientes Ambulatoriais , COVID-19/epidemiologia , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/psicologia , Alucinações/epidemiologia , Alucinações/etiologia , Alucinações/diagnóstico
13.
Artigo em Inglês | MEDLINE | ID: mdl-37624464

RESUMO

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. METHOD: 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.

14.
Acta Psychiatr Scand ; 145(5): 494-506, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35243618

RESUMO

OBJECTIVE: Difficulties in social cognition are common in individuals with schizophrenia (SZ) and are not ameliorated by antipsychotic treatment. Intranasal oxytocin (OT) administration has been explored as a potential intervention to improve social cognition; however, results are inconsistent, suggesting potential individual difference variables that may influence treatment response. Less is known about the relationship between endogenous OT and social cognition in SZ, knowledge of which may improve the development of OT-focused therapies. We examined plasma OT in relationship to facial emotion recognition and visual attention to salient facial features in SZ and controls. METHODS: Forty-two individuals with SZ and 23 healthy controls viewed photographs of facial expressions of varying emotional intensity and identified the emotional expression displayed. Participants' gaze behavior during the task was recorded via eye tracking. Plasma oxytocin concentrations were determined by radioimmunoassay. RESULTS: SZ were less accurate than controls at identifying high-intensity fearful facial expressions and low-intensity sad expressions. Lower overall and high-intensity facial emotion recognition accuracy was associated with lower plasma OT levels in SZ but not controls. OT was not associated with visual attention to salient facial features; however, SZ had reduced visual attention to the nose region compared to controls. CONCLUSION: Individual differences in endogenous OT predict facial emotion recognition ability in SZ but are not associated with visual attention to salient facial features. Increased understanding of the association between endogenous OT and social cognitive abilities in SZ may help improve the design and interpretation of OT-focused clinical trials in SZ.


Assuntos
Reconhecimento Facial , Ocitocina , Esquizofrenia , Emoções , Expressão Facial , Humanos , Ocitocina/metabolismo , Esquizofrenia/metabolismo , Psicologia do Esquizofrênico , Percepção Social
15.
Eur Arch Psychiatry Clin Neurosci ; 272(6): 1061-1071, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34716486

RESUMO

Existing evidence suggests that emotion regulation is abnormal in schizophrenia and associated with undesirable clinical outcomes. However, this literature is based predominantly on trait self-report and does not indicate which stages of emotion regulation (identification, selection, implementation) are impaired. The current study focused on determining the nature of abnormalities at the identification stage using ecological momentary assessment (EMA). Participants included clinically stable outpatients with schizophrenia (SZ; n = 48) and healthy controls (CN; n = 52) who completed 6 days of EMA. The EMA surveys assessed emotional experience, emotion regulation, and symptoms. Results indicated that SZ identified the need to regulate at a higher rate than CN. Specifically, SZ displayed an inefficient threshold for identifying the need to regulate, such that they regulated too much when negative affect was low and too little when negative affect was high. Emotion regulation effort exertion was also inefficient, such that effort was too high at low levels of negative affect and too low at high levels of negative affect in SZ. These identification stage abnormalities also demonstrated differential associations with positive and negative symptoms. Findings suggest that identification stage abnormalities may create a bottleneck that feeds forward and impacts subsequent stages of emotion regulation in SZ that are critically related to symptoms. Targeting the psychological processes underlying these identification stage abnormalities might offer a novel means of treating positive and negative symptoms in schizophrenia.


Assuntos
Regulação Emocional , Esquizofrenia , Emoções/fisiologia , Humanos , Esquizofrenia/complicações
16.
Eur Arch Psychiatry Clin Neurosci ; 272(1): 17-27, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33881621

RESUMO

Negative symptoms are core features of schizophrenia-spectrum disorders that are frequently observed across all phases of illness. By their nature, COVID-19 social isolation, physical distancing, and health precautions induce behavioural aspects of negative symptoms. However, it is unclear whether these prevention measures also lead to increases in experiential negative symptoms, whether such effects are equivalent across individual negative symptom domains, and if exacerbations occur equivalently across phases of illness. The current study compared negative symptom severity scores obtained during the pandemic to pre-pandemic assessments in two samples: (1) outpatients with chronic schizophrenia (SZ: n = 32) and matched healthy controls (CN: n = 31) and (2) individuals at clinical high risk for psychosis (CHR: n = 25) and matched CN (n = 30). Pre-pandemic ratings of negative symptoms were clinically elevated in SZ and CHR groups, which did not differ from each other in severity. In SZ, ratings obtained during the pandemic were significantly higher than pre-pandemic ratings for all 5 domains (alogia, blunted affect, anhedonia, avolition, and asociality) and item-level analyses indicated that exacerbations occurred on both experiential and behavioral symptoms of anhedonia, avolition, and asociality. In contrast, CHR only exhibited increases in anhedonia and avolition items during the pandemic compared to pre-ratings. Findings suggest that negative symptoms should be a critical treatment target during and after the pandemic in the schizophrenia spectrum given that they are worsening and critically related to risk for conversion, functional outcome, and recovery.


Assuntos
COVID-19 , Pacientes Ambulatoriais , Pandemias , Transtornos Psicóticos , Psicologia do Esquizofrênico , Anedonia , COVID-19/epidemiologia , COVID-19/psicologia , Estudos de Casos e Controles , Doença Crônica , Humanos , Pacientes Ambulatoriais/psicologia , Transtornos Psicóticos/epidemiologia , Medição de Risco , Esquizofrenia/terapia
17.
Int J Neuropsychopharmacol ; 24(8): 601-614, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-33890987

RESUMO

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.


Assuntos
Ocitocina/farmacologia , Esquizofrenia/tratamento farmacológico , Administração Intranasal , Relação Dose-Resposta a Droga , Humanos , Avaliação de Resultados em Cuidados de Saúde , Ocitocina/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Esquizofrenia/fisiopatologia
18.
Psychol Med ; 51(11): 1898-1905, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-32248851

RESUMO

BACKGROUND: Schizophrenia (SZ) is typically preceded by a prodromal (i.e. pre-illness) period characterized by attenuated positive symptoms and declining functional outcome. Negative symptoms are prominent among individuals at clinical high-risk (CHR) for psychosis (i.e. those with prodromal syndromes) and highly predictive of conversion to illness. Mechanisms underlying negative symptoms in the CHR population are unclear. Two studies were conducted to evaluate whether abnormalities in a reward processing mechanism thought to be core to negative symptoms in SZ, value representation, also exist in CHR individuals and whether they are associated with negative symptoms transphasically. METHODS: Study 1 included 33 individuals in the chronic phase of illness who have been diagnosed with schizophrenia or schizoaffective disorder (SZ) and 40 healthy controls (CN). Study 2 included 37 CHR participants and 45 CN. In both studies, participants completed the delay discounting (DD) task as a measure of value representation and the Brief Negative Symptom Scale was rated to measure negative symptoms. RESULTS: Results indicated that patients with SZ had steeper discounting rates than CN, indicating impairments in value representation. However, CHR participants were unimpaired on the DD task. In both studies, steeper discounting was associated with greater severity of negative symptoms. CONCLUSIONS: These findings suggest that deficits in value representation are associated with negative symptoms transphasically.


Assuntos
Desvalorização pelo Atraso , Progressão da Doença , Sintomas Prodrômicos , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/fisiopatologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Recompensa , Fatores de Risco
19.
J Clin Psychopharmacol ; 41(3): 236-243, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33783399

RESUMO

BACKGROUND: A significant proportion of people with schizophrenia are characterized by impaired ability to socially engage with others. The development of effective interventions for social functioning remains a central therapeutic challenge. Cognitive-behavioral social skills training (CBSST) has been found to improve social functioning in schizophrenia, but with only medium effect sizes. Intranasal oxytocin also has prosocial effects, but also only with modest effect sizes. This study assessed whether the addition of intranasal oxytocin to CBSST can strengthen their impact on social function. METHODS: Participants (N = 62) with schizophrenia or schizoaffective disorder entered a 24-week, double-blind, placebo-controlled, randomized clinical trial with a 3-month follow-up evaluation at 2 sites: Maryland and San Diego. Participants were randomized to either intranasal oxytocin 36 IU (3 sprays) twice a day (n = 31) or intranasal placebo-oxytocin (3 sprays) twice a day (n = 31). All participants received CBSST plus a social cognition skills training module (48 total sessions). RESULTS: There were no significant treatment group differences in social functioning, positive symptoms, negative symptoms, defeatist beliefs, or asocial beliefs. The interpretation of treatment effects was complicated by site effects, whereby participants in San Diego began the trial with greater severity of impairments and subsequently showed greater improvements compared with participants in Maryland. CONCLUSIONS: The results did not support the utility of add-on intranasal oxytocin to psychosocial rehabilitation interventions like CBSST for improvement in social function (ClinicalTrials.gov trial number: NCT01752712).


Assuntos
Terapia Cognitivo-Comportamental/métodos , Ocitocina/administração & dosagem , Transtornos Psicóticos/cirurgia , Esquizofrenia/terapia , Administração Intranasal , Adulto , Terapia Combinada , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/terapia , Habilidades Sociais , Resultado do Tratamento
20.
Neuropsychol Rev ; 30(3): 407-424, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32766940

RESUMO

Psychotic disorders are characterized by a generalized neurocognitive deficit (i.e., performance 1.5 SD below controls across neuropsychological domains with no specific profile of differential deficits). A motivational account of the generalized neurocognitive deficit has been proposed, which attributes poor neuropsychological testing performance to low effort. However, findings are inconsistent regarding effort test failure rate in individuals with psychotic disorders across studies (0-72%), and moderators are unclear, making it difficult to know whether the motivational explanation is viable. To address these issues, a meta-analysis was performed on data from 2205 individuals with psychotic disorders across 19 studies with 24 independent effects. Effort failure rate was examined along with moderators of effort test type, forensic status, IQ, positive symptoms, negative symptoms, diagnosis, age, gender, education, and antipsychotic use. The pooled weighted effort test failure rate was 18% across studies and there was a moderate pooled association between effort failure rate and global neurocognitive performance (r = .57). IQ and education significantly moderated failure rate. Collectively, these findings suggest that a nontrivial proportion of individuals with a psychotic disorder fail effort testing, and failure rate is associated with global neuropsychological impairment. However, given that effort tests are not immune to the effects of IQ in psychotic disorders, these results cannot attest to the viability of the motivational account of the generalized neurocognitive deficit. Furthermore, the significant moderating effect of IQ and education on effort test performance suggests that effort tests have questionable validity in this population and should be interpreted with caution.


Assuntos
Transtornos Cognitivos/diagnóstico , Transtornos Psicóticos/complicações , Adulto , Feminino , Humanos , Masculino , Motivação , Testes Neuropsicológicos , Esquizofrenia/complicações , Psicologia do Esquizofrênico
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