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1.
Brain ; 147(7): 2459-2470, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38608149

RESUMEN

Adaptive coding of reward is the process by which neurons adapt their response to the context of available compensations. Higher rewards lead to a stronger brain response, but the increase of the response depends on the range of available rewards. A steeper increase is observed in a narrow range and a more gradual slope in a wider range. In schizophrenia, adaptive coding appears to be affected in different domains, especially in the reward domain. Here, we tested adaptive coding of reward in a large group of patients with schizophrenia (n = 86) and control subjects (n = 66). We assessed: (i) the association between adaptive coding deficits and symptoms; (ii) the longitudinal stability of deficits (the same task was performed 3 months apart); and (iii) the stability of results between two experimental sites. We used functional MRI and the monetary incentive delay task to assess adaptation of participants to two different reward ranges: a narrow range and a wide range. We used a region-of-interest analysis to evaluate adaptation within striatal and visual regions. Patients and control subjects underwent a full demographic and clinical assessment. We found reduced adaptive coding in patients, with a decreased slope in the narrow reward range with respect to that of control participants, in striatal but not visual regions. This pattern was observed at both research sites. Upon retesting, patients increased their narrow-range slopes, showing improved adaptive coding, whereas control subjects slightly reduced them. At retesting, patients with overly steep slopes in the narrow range also showed higher levels of negative symptoms. Our data confirm deficits in reward adaptation in schizophrenia and reveal an effect of practice in patients, leading to improvement, with steeper slopes upon retesting. However, in some patients, an excessively steep slope may result in poor discriminability of larger rewards, owing to early saturation of the brain response. Together, the loss of precision of reward representation in new (first exposure, underadaptation) and more familiar (retest, overadaptation) situations might contribute to the multiple motivational symptoms in schizophrenia.


Asunto(s)
Apatía , Imagen por Resonancia Magnética , Recompensa , Esquizofrenia , Humanos , Masculino , Femenino , Adulto , Esquizofrenia/fisiopatología , Apatía/fisiología , Persona de Mediana Edad , Psicología del Esquizofrénico , Motivación/fisiología , Adaptación Fisiológica/fisiología , Encéfalo/fisiopatología , Encéfalo/diagnóstico por imagen , Adaptación Psicológica/fisiología
2.
Hum Brain Mapp ; 45(7): e26694, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38727014

RESUMEN

Schizophrenia (SZ) is a debilitating mental illness characterized by adolescence or early adulthood onset of psychosis, positive and negative symptoms, as well as cognitive impairments. Despite a plethora of studies leveraging functional connectivity (FC) from functional magnetic resonance imaging (fMRI) to predict symptoms and cognitive impairments of SZ, the findings have exhibited great heterogeneity. We aimed to identify congruous and replicable connectivity patterns capable of predicting positive and negative symptoms as well as cognitive impairments in SZ. Predictable functional connections (FCs) were identified by employing an individualized prediction model, whose replicability was further evaluated across three independent cohorts (BSNIP, SZ = 174; COBRE, SZ = 100; FBIRN, SZ = 161). Across cohorts, we observed that altered FCs in frontal-temporal-cingulate-thalamic network were replicable in prediction of positive symptoms, while sensorimotor network was predictive of negative symptoms. Temporal-parahippocampal network was consistently identified to be associated with reduced cognitive function. These replicable 23 FCs effectively distinguished SZ from healthy controls (HC) across three cohorts (82.7%, 90.2%, and 86.1%). Furthermore, models built using these replicable FCs showed comparable accuracies to those built using the whole-brain features in predicting symptoms/cognition of SZ across the three cohorts (r = .17-.33, p < .05). Overall, our findings provide new insights into the neural underpinnings of SZ symptoms/cognition and offer potential targets for further research and possible clinical interventions.


Asunto(s)
Disfunción Cognitiva , Conectoma , Imagen por Resonancia Magnética , Red Nerviosa , Esquizofrenia , Humanos , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/fisiopatología , Masculino , Adulto , Femenino , Conectoma/métodos , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/fisiopatología , Estudios de Cohortes , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiopatología , Adulto Joven , Persona de Mediana Edad
3.
Int J Neuropsychopharmacol ; 27(4)2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38629703

RESUMEN

The understanding of the pathophysiology of schizophrenia as well as the mechanisms of action of antipsychotic drugs remains a challenge for psychiatry. The demonstration of the therapeutic efficacy of several new atypical drugs targeting multiple different receptors, apart from the classical dopamine D2 receptor as initially postulated unique antipsychotic target, complicated even more conceptualization efforts. Here we discuss results suggesting a main role of the islands of Calleja, still poorly studied GABAergic granule cell clusters in the ventral striatum, as cellular targets of several innovative atypical antipsychotics (clozapine, cariprazine, and xanomeline/emraclidine) effective in treating also negative symptoms of schizophrenia. We will emphasize the potential role of dopamine D3 and M4 muscarinic acetylcholine receptor expressed at the highest level by the islands of Calleja, as well as their involvement in schizophrenia-associated neurocircuitries. Finally, we will discuss the implications of new data showing ongoing adult neurogenesis of the islands of Calleja as a very promising antipsychotic target linking long-life neurodevelopment and dopaminergic dysfunction in the striatum.


Asunto(s)
Antipsicóticos , Esquizofrenia , Antipsicóticos/farmacología , Humanos , Animales , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/metabolismo , Islotes Olfatorios/efectos de los fármacos , Islotes Olfatorios/metabolismo , Neurogénesis/efectos de los fármacos
4.
Brain Behav Immun ; 120: 379-390, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38906488

RESUMEN

INTRODUCTION: First-Episode Psychosis (FEP) is a devastating mental health condition that commonly emerges during early adulthood, and is characterised by a disconnect in perceptions of reality. Current evidence suggests that inflammation and perturbed immune responses are involved in the pathology of FEP and may be associated specifically with negative symptoms. Exercise training is a potent anti-inflammatory stimulus that can reduce persistent inflammation, and can improve mood profiles in general populations. Therefore, exercise may represent a novel adjunct therapy for FEP. The aim of this study was to assess the effect of exercise on biomarkers of inflammation, negative symptoms of psychosis, and physiological health markers in FEP. METHODS: Seventeen young males (26.67 ± 6.64 years) were recruited from Birmingham Early Intervention in Psychosis Services and randomised to a 6-week exercise programme consisting of two-to-three sessions per week that targeted 60-70 % heart-rate max (HRMax), or a treatment as usual (TAU) condition. Immune T-helper (Th-) cell phenotypes and cytokines, symptom severity, functional wellbeing, and cognition were assessed before and after 6-weeks of regular exercise. RESULTS: Participants in the exercise group (n = 10) achieved 81.11 % attendance to the intervention, with an average exercise intensity of 67.54 % ± 7.75 % HRMax. This led to favourable changes in immune cell phenotypes, and a significant reduction in the Th1:Th2 ratio (-3.86 %) compared to the TAU group (p = 0.014). After the exercise intervention, there was also a significant reduction in plasma IL-6 concentration (-22.17 %) when compared to the TAU group (p = 0.006). IL-8, and IL-10 did not show statistically significant differences between the groups after exercise. Symptomatically, there was a significant reduction in negative symptoms after exercise (-13.54 %, Positive and Negative Syndrome Scale, (PANSS) Negative) when compared to the TAU group (p = 0.008). There were no significant change in positive or general symptoms, functional outcomes, or cognition (all p > 0.05). DISCUSSION: Regular moderate-to-vigorous physical activity is feasible and attainable in clinical populations. Exercise represents a physiological tool that is capable of causing significant inflammatory biomarker change and concomitant symptom improvements in FEP cohorts, and may be useful for treatment of symptom profiles that are not targeted by currently prescribed antipsychotic medication.


Asunto(s)
Biomarcadores , Terapia por Ejercicio , Ejercicio Físico , Inflamación , Trastornos Psicóticos , Humanos , Masculino , Trastornos Psicóticos/inmunología , Trastornos Psicóticos/terapia , Biomarcadores/sangre , Adulto , Ejercicio Físico/fisiología , Adulto Joven , Terapia por Ejercicio/métodos , Inflamación/inmunología , Citocinas/sangre
5.
Brain Behav Immun ; 119: 188-196, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38555993

RESUMEN

INTRODUCTION: Negative symptoms impact the quality of life of individuals with psychosis and current treatment options for negative symptoms have limited effectiveness. Previous studies have demonstrated that complement and coagulation pathway protein levels are related to later psychotic experiences, psychotic disorder, and functioning. However, the prognostic relationship between complement and coagulation proteins and negative symptoms is poorly characterised. METHODS: In the North American Prodrome Longitudinal Studies 2 and 3, negative symptoms in 431 individuals at clinical high-risk for psychosis (mean age: 18.2, SD 3.6; 42.5 % female) were measured at multiple visits over 2 years using the Scale of Psychosis-Risk Symptoms. Plasma proteins were quantified at baseline using mass spectrometry. Four factors were derived to represent levels of proteins involved in the activation or regulation of the complement or coagulation systems. The relationships between standardised protein group factors and serial measurements of negative symptoms over time were modelled using generalised least squares regression. Analyses were adjusted for baseline candidate prognostic factors: negative symptoms, positive symptoms, functioning, depressive symptoms, suicidal ideation, cannabis use, tobacco use, antipsychotic use, antidepressant use, age, and sex. RESULTS: Clinical and demographic prognostic factors of follow-up negative symptoms included negative, positive, and depressive symptoms, functioning, and age. Adjusting for all candidate prognostic factors, the complement regulators group and the coagulation regulators group were identified as prognostic factors of follow-up negative symptoms (ß: 0.501, 95 % CI: 0.160, 0.842; ß: 0.430, 95 % CI: 0.080, 0.780 respectively. The relationship between complement regulator levels and negative symptoms was also observed in NAPLS2 alone (ß: 0.501, 95 % CI: -0.037, 1.039) and NAPLS3 alone, additionally adjusting for BMI (ß: 0.442, 95 % CI: 0.127, 0.757). CONCLUSION: The results indicate that plasma complement and coagulation regulator levels are prognostic factors of negative symptoms, independent of clinical and demographic prognostic factors. These results suggest complement and coagulation regulator levels could have potential utility in informing treatment decisions for negative symptoms in individuals at risk.


Asunto(s)
Proteínas del Sistema Complemento , Trastornos Psicóticos , Humanos , Femenino , Masculino , Pronóstico , Adolescente , Adulto Joven , Proteínas del Sistema Complemento/metabolismo , Proteínas del Sistema Complemento/análisis , Trastornos Psicóticos/sangre , Adulto , Factores de Coagulación Sanguínea/metabolismo , Factores de Coagulación Sanguínea/análisis , Estudios Longitudinales
6.
Exp Brain Res ; 242(3): 585-597, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38227007

RESUMEN

Transcranial direct current stimulation (tDCS) over left dorsolateral prefrontal cortex (DLPFC) has shown some potential as an adjunctive intervention for ameliorating negative symptoms of schizophrenia, but its efficacy requires optimization. Recently, 'functional targeting' of stimulation holds promise for advancing tDCS efficacy by coupling tDCS with a cognitive task where the target brain regions are activated by that task and further specifically polarized by tDCS.The study used 48-channel functional near infra-red spectroscopy (fNIRS) aiming to determine a cognitive task that can effectively induce a cortical activation of the left DLPFC in schizophrenia patients with predominant negative symptoms before running a tDCS trial. Sixty schizophrenia patients with predominant negative symptoms completed measures of clinical and psychosocial functioning characteristics and assessments across cognitive domains. Hemodynamic changes during n-back working memory tasks with different cognitive loads (1-back and 2-back) and verbal fluency test (VFT) were measured using fNIRS. For n-back tasks, greater signal changes were found when the task required elevated cognitive load. One sample t-test revealed that only 2-back task elicited significant activation in left DLPFC (t = 4.23, FDR-corrected p = 0.0007). During VFT, patients failed to show significant task-related activity in left DLPFC (one sample t-test, t = -0.25, FDR-corrected p > 0.05). Our study implies that 2-back task can effectively activate left DLPFC in schizophrenia patients with predominant negative symptoms. This neurophysiologically-validated task is considered highly potential to be executed in conjunction with high-definition tDCS for "functional targeting" of the left DLPFC to treat negative symptoms in a double-blind randomized sham-control trial, registered on ClinicalTrials.gov Registry (ID: NCT05582980).


Asunto(s)
Esquizofrenia , Estimulación Transcraneal de Corriente Directa , Humanos , Estimulación Transcraneal de Corriente Directa/métodos , Corteza Prefontal Dorsolateral , Esquizofrenia/terapia , Corteza Prefrontal/fisiología , Análisis Espectral , Método Doble Ciego
7.
Brain ; 146(2): 767-777, 2023 02 13.
Artículo en Inglés | MEDLINE | ID: mdl-35875972

RESUMEN

Negative symptoms, such as lack of motivation or social withdrawal, are highly prevalent and debilitating in patients with schizophrenia. Underlying mechanisms of negative symptoms are incompletely understood, thereby preventing the development of targeted treatments. We hypothesized that in patients with schizophrenia during psychotic remission, impaired influences of both model-based and model-free reward predictions on decision-making ('reward prediction influence', RPI) underlie negative symptoms. We focused on psychotic remission, because psychotic symptoms might confound reward-based decision-making. Moreover, we hypothesized that impaired model-based/model-free RPIs depend on alterations of both associative striatum dopamine synthesis and storage (DSS) and executive functioning. Both factors influence RPI in healthy subjects and are typically impaired in schizophrenia. Twenty-five patients with schizophrenia with pronounced negative symptoms during psychotic remission and 24 healthy controls were included in the study. Negative symptom severity was measured by the Positive and Negative Syndrome Scale negative subscale, model-based/model-free RPI by the two-stage decision task, associative striatum DSS by 18F-DOPA positron emission tomography and executive functioning by the symbol coding task. Model-free RPI was selectively reduced in patients and associated with negative symptom severity as well as with reduced associative striatum DSS (in patients only) and executive functions (both in patients and controls). In contrast, model-based RPI was not altered in patients. Results provide evidence for impaired model-free reward prediction influence as a mechanism for negative symptoms in schizophrenia as well as for reduced associative striatum dopamine and executive dysfunction as relevant factors. Data suggest potential treatment targets for patients with schizophrenia and pronounced negative symptoms.


Asunto(s)
Trastornos Psicóticos , Esquizofrenia , Humanos , Esquizofrenia/diagnóstico por imagen , Dopamina , Tomografía Computarizada por Rayos X , Trastornos Psicóticos/diagnóstico por imagen , Recompensa
8.
Artículo en Inglés | MEDLINE | ID: mdl-38462585

RESUMEN

BACKGROUND: Several studies have suggested that smoking may impair cognitive function and worsen psychiatric symptoms in people with schizophrenia, but the results have not been consistent. There have been few studies to date that have examined the effects of smoking in older men with chronic schizophrenia. METHODS: The participants in our study consisted of 167 order Chinese males with chronic schizophrenia and 359 normal control subjects. We split them into smoking and non-smoking groups based on whether or not they smoked. Second, we compared their differences in terms of general demographic characteristics (such as age, education, body mass index, age of illness onset, and course of disease), disease information (such as hypertension, diabetes, and hyperlipidemia), lifestyle factors (such as physical exercise and lunch break), blood biochemical indicators (such as albumin, triglyceride, total cholesterol, high-density lipoprotein, low-density lipoprotein and fasting blood glucose), and medication usage (such as clozapine, olanzapine, risperidone, and chlorpromazine). Lastly, a neuropsychological test battery was used to assess their psychiatric and cognitive symptoms, for example, the Montreal Cognitive Assessment (MoCA) was used to assess their overall cognitive functioning. Their depressive symptoms were assessed by the geriatric depression scale (GDS). Activities of daily living (ADL) were used to assess their ability to lead a daily life, while the positive and negative syndrome scales (PANSS) were used to assess their psychiatric symptoms. RESULTS: Smokers who develop schizophrenia at older ages had a higher body mass index than non-smokers. We also found that plasma albumin, triglycerides, low-density lipoprotein, and fasting blood glucose concentrations were significantly higher in smokers. In contrast, smokers with schizophrenia also had lower PANSS total scores, negative symptom scores, and general psychopathology scores. A forward stepwise binary logistics regression analysis demonstrated a significant association between negative symptom scores and smoking status (B = 0.112, p < 0.001, OR = 1.119, 95% confidence interval: 1.059-1.181). Correlation analysis was carried out and it was found that the amount of cigarette consumption per day had a negative correlation with plasma albumin level(r = - 0.290, p = 0.004). However, no such association was found in normal controls. CONCLUSIONS: Elderly Chinese men with schizophrenia have a higher percentage of smokers, and although smoking can reduce their plasma albumin levels, it does contribute to the prevention of negative symptoms.

9.
Artículo en Inglés | MEDLINE | ID: mdl-38662092

RESUMEN

This study aims to investigate the altered patterns of dynamic functional network connectivity (dFNC) between deficit schizophrenia (DS) and non-deficit schizophrenia (NDS), and further explore the associations with cognitive impairments. 70 DS, 91 NDS, and 120 matched healthy controls (HCs) were enrolled. The independent component analysis was used to segment the whole brain. The fMRI brain atlas was used to identify functional networks, and the dynamic functional connectivity (FC) of each network was detected. Correlation analysis was used to explore the associations between altered dFNC and cognitive functions. Four dynamic states were identified. Compared to NDS, DS showed increased FC between sensorimotor network and default mode network in state 1 and decreased FC within auditory network in state 4. Additionally, DS had a longer mean dwell time of state 2 and a shorter one in state 3 compared to NDS. Correlation analysis showed that fraction time and mean dwell time of states were correlated with cognitive impairments in DS. This study demonstrates the distinctive altered patterns of dFNC between DS and NDS patients. The associations with impaired cognition provide specific neuroimaging evidence for the pathogenesis of DS.

10.
Artículo en Inglés | MEDLINE | ID: mdl-38668766

RESUMEN

Negative symptoms in CHR-P people are generally not responsive to treatments and commonly related to poorer functional outcome. However, less research attention has been dedicated to Persistent Negative Symptoms (PNS), defined as clinically stable negative symptoms of moderate severity evident for at least 6 months. This study aims to (a) determine the prevalence of PNS in a sample of young people at CHR-P; (b) investigate any association of PNS with functioning and clinical features; (c) examine longitudinal course of PNS across 2 years of follow-up and changes in PNS severity levels with specialized treatments. One Hundred Eighty CHR-P participants were recruited and were divided into CHR-P/PNS + and CHR-P/PNS- subgroups. The clinical assessments were based on the PANSS and the GAF and were conducted at baseline and every 12 months during the follow-up. Twenty four participants showed PNS at entry. Of them, 21 concluded the 2-year follow-up period. At baseline, the CHR-P/PNS + participants showed more educational and employment deficits, and more social and functioning impairment. During the follow-up, the CHR-P/PNS + subgroup had a significant longitudinal decrease in negative symptoms, which was specifically related to antidepressant treatment. CHR-P/PNS + subjects also showed a higher incidence of new hospitalization and a lower functional recovery over time. Our findings support that the persistence of negative symptoms in CHR-P people is longitudinally related to worse daily functioning and more severe clinical conditions that are at higher risk of hospitalization and are less responsive to specialized treatments.

11.
BMC Psychiatry ; 24(1): 559, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39138483

RESUMEN

PURPOSE: This study proposed and evaluated a theoretical model for exploring the relationships between neurocognition, self-defeatist beliefs, experiential negative symptoms, and social functioning in individuals with chronic schizophrenia. METHOD: The study recruited 229 individuals given a diagnosis of schizophrenia and schizoaffective disorders from outpatient clinics and the day ward of a mental health hospital. After informed consent was obtained, the participants underwent assessments using the backward digit span, the digit symbol, and measures of self-defeatist beliefs, experiential negative symptoms, and social functioning. A structural equation model was applied to assess the fitness of the hypothesized model, with indices such as the goodness-of-fit index, comparative fit index, root mean square error of approximation, and standardized root mean square residual being used for model evaluation. RESULTS: The hypothesized model had an adequate fit. The study findings indicated that neurocognition might indirectly influence self-defeatist beliefs through its effect on experiential negative symptoms. Contrary to expectations, the study did not observe a direct influence of neurocognition, self-defeatist beliefs, or negative symptoms on social functioning. The revised model revealed the role of experiential negative symptoms in mediating the association between neurocognition and social functioning. However, self-defeatist beliefs did not significantly affect social functioning. DISCUSSION: Before modifying negative thoughts, enhancement of self-awareness ability can help improve negative symptoms and thereby improve the performance of social functions. Future research should develop a hierarchical program of negative symptoms, from cognition rehabilitation to enhancement of self-awareness, and end with modifying maladaptive beliefs.


Asunto(s)
Trastornos Psicóticos , Esquizofrenia , Psicología del Esquizofrénico , Humanos , Trastornos Psicóticos/psicología , Trastornos Psicóticos/diagnóstico , Masculino , Femenino , Adulto , Esquizofrenia/diagnóstico , Persona de Mediana Edad , Enfermedad Crónica/psicología
12.
BMC Psychiatry ; 24(1): 309, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38658884

RESUMEN

BACKGROUND: Lateral ventricular enlargement represents a canonical morphometric finding in chronic patients with schizophrenia; however, longitudinal studies elucidating complex dynamic trajectories of ventricular volume change during critical early disease stages are sparse. METHODS: We measured lateral ventricular volumes in 113 first-episode schizophrenia patients (FES) at baseline visit (11.7 months after illness onset, SD = 12.3) and 128 age- and sex-matched healthy controls (HC) using 3T MRI. MRI was then repeated in both FES and HC one year later. RESULTS: Compared to controls, ventricular enlargement was identified in 18.6% of patients with FES (14.1% annual ventricular volume (VV) increase; 95%CI: 5.4; 33.1). The ventricular expansion correlated with the severity of PANSS-negative symptoms at one-year follow-up (p = 0.0078). Nevertheless, 16.8% of FES showed an opposite pattern of statistically significant ventricular shrinkage during ≈ one-year follow-up (-9.5% annual VV decrease; 95%CI: -23.7; -2.4). There were no differences in sex, illness duration, age of onset, duration of untreated psychosis, body mass index, the incidence of Schneiderian symptoms, or cumulative antipsychotic dose among the patient groups exhibiting ventricular enlargement, shrinkage, or no change in VV. CONCLUSION: Both enlargement and ventricular shrinkage are equally present in the early stages of schizophrenia. The newly discovered early reduction of VV in a subgroup of patients emphasizes the need for further research to understand its mechanisms.


Asunto(s)
Imagen por Resonancia Magnética , Esquizofrenia , Humanos , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/patología , Esquizofrenia/fisiopatología , Masculino , Femenino , Estudios Longitudinales , Adulto , Adulto Joven , Ventrículos Cerebrales/diagnóstico por imagen , Ventrículos Cerebrales/patología , Ventrículos Laterales/diagnóstico por imagen , Ventrículos Laterales/patología , Progresión de la Enfermedad , Estudios de Casos y Controles , Adolescente
13.
Compr Psychiatry ; 128: 152440, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38039918

RESUMEN

BACKGROUND AND HYPOTHESIS: The negative symptoms of schizophrenia are strong prognostic factors but remain poorly understood and treated. Five negative symptom domains are frequently clustered into the motivation and pleasure (MAP) and emotional expression (EE) 'dimensions', but whether this structure remains stable and behaves as a single entity or not remains unclear. STUDY DESIGN: We examined a cohort of 153 patients taking clozapine for treatment-resistant schizophrenia in a regional mental health clinic. Patients were assessed longitudinally over a mean period of 45 months using validated scales for positive, negative and mood symptoms. Network analyses were performed to identify symptom 'communities' and their stability over time. The influence of common causes of secondary negative symptoms as well as centrality measures were also examined. STUDY RESULTS: Across patients at baseline, two distinct communities matching the clinical domains of MAP and EE were found. These communities remained highly stable and independent over time. The communities remained stabled when considering psychosis, depression, and sedation severity, and these causes of secondary negative symptoms were clustered into the MAP community. Centrality measures also remained stable over time, with similar centrality measures across symptoms. CONCLUSIONS: Our results suggest that MAP and EE are independent dimensions that remain highly stable over time in chronic schizophrenia patients treated with clozapine. Common causes of secondary negative symptoms mapped onto the MAP dimension. Our results emphasise the need for clinical trials to address either MAP or EE, and that treating causes of secondary negative symptoms may improve MAP.


Asunto(s)
Clozapina , Trastornos Psicóticos , Esquizofrenia , Humanos , Esquizofrenia/diagnóstico , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/complicaciones , Esquizofrenia Resistente al Tratamiento , Clozapina/efectos adversos , Escalas de Valoración Psiquiátrica , Trastornos Psicóticos/complicaciones
14.
Compr Psychiatry ; 130: 152450, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38241816

RESUMEN

BACKGROUND: Negative symptoms (NS) represent a detrimental symptomatic domain in schizophrenia affecting social and occupational outcomes. AIMS: We aimed to identify factors from the baseline visit (V1) - with a mean illness duration of 0.47 years (SD = 0.45) - that predict the magnitude of NS at the follow-up visit (V3), occurring 4.4 years later (mean +/- 0.45). METHOD: Using longitudinal data from 77 first-episode schizophrenia spectrum patients, we analysed eight predictors of NS severity at V3: (1) the age at disease onset, (2) age at V1, (3) sex, (4) diagnosis, (5) NS severity at V1, (6) the dose of antipsychotic medication at V3, (7) hospitalisation days before V1 and; (8) the duration of untreated psychosis /DUP/). Secondly, using a multiple linear regression model, we studied the longitudinal relationship between such identified predictors and NS severity at V3 using a multiple linear regression model. RESULTS: DUP (Pearson's r = 0.37, p = 0.001) and NS severity at V1 (Pearson's r = 0.49, p < 0.001) survived correction for multiple comparisons. The logarithmic-like relationship between DUP and NS was responsible for the initial stunning incremental contribution of DUP to the severity of NS. For DUP < 6 months, with the sharpest DUP/NS correlation, prolonging DUP by five days resulted in a measurable one-point increase in the 6-item negative symptoms PANSS domain assessed 4.9 (+/- 0.6) years after the illness onset. Prolongation of DUP to 14.7 days doubled this NS gain, whereas 39 days longer DUP tripled NS increase. CONCLUSION: The results suggest the petrification of NS during the early stages of the schizophrenia spectrum and a crucial dependence of this symptom domain on DUP. These findings are clinically significant and highlight the need for primary preventive actions.


Asunto(s)
Antipsicóticos , Síndrome de Nijmegen , Trastornos Psicóticos , Esquizofrenia , Humanos , Síndrome de Nijmegen/tratamiento farmacológico , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/tratamiento farmacológico , Esquizofrenia/diagnóstico , Esquizofrenia/tratamiento farmacológico , Antipsicóticos/uso terapéutico , Análisis Multivariante
15.
Artículo en Inglés | MEDLINE | ID: mdl-39014044

RESUMEN

PURPOSE: Suicidal thoughts are common among patients with first episode psychosis (FEP). The impact of symptoms' severity and social cognition on suicidal risk should be a focus of attention. This study aimed at assessment of the severity of suicidal ideation in patients with FEP and its potential association with the theory of mind (ToM) impairment and symptoms' severity. METHODS: Ninety-six participants were recruited consecutively and subdivided into three equal groups: FEP, schizophrenia, and healthy controls (HC). The symptoms' severity was assessed using Positive and Negative Syndrome Scale (PANSS) and Beck Depression Inventory (BDI). Suicidal ideation was evaluated using Beck Scale for Suicidal Ideation (BSSI). Reading the Mind in the Eyes revised version (RMET) was used to assess ToM. RESULTS: Suicidal ideation was significantly higher only in FEP compared to HC (p = 0.001). Both FEP and schizophrenia had substantially lower performance than HC on RMET (p < 0.001). Higher depression (ß = 0.452, p = 0.007) and negative symptoms (ß = 0.433, p = 0.027) appeared to be significantly associated with increased suicidal ideation severity in FEP while RMET did not. CONCLUSION: Patients with FEP and chronic schizophrenia have comparable deficits in theory of mind dimension of social cognition. The severity of negative and depressive symptoms potentially contributes to the increased risk of suicide in FEP.

16.
Psychopathology ; 57(1): 76-80, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37276842

RESUMEN

Negative symptoms reflect a currently much-untreated loss of normal functioning and are frequently found in psychotic disorders. We present the first translation of the Brief Negative Symptom Scale (BNSS) to European Portuguese and evaluate its validity in a sample of Portuguese male patients with a psychotic spectrum disorder. The Portuguese BNSS showed excellent internal consistency, high convergent validity (i.e., strong correlation with the PANSS negative factor), and high discriminant validity (i.e., a lack of association with the PANSS positive factor). In sum, the present European Portuguese BNSS has shown to be reliable, thus extending this instrument's clinical availability worldwide.


Asunto(s)
Esquizofrenia , Humanos , Masculino , Esquizofrenia/diagnóstico , Escalas de Valoración Psiquiátrica , Portugal , Psicometría , Reproducibilidad de los Resultados
17.
Nord J Psychiatry ; 78(4): 339-346, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38436927

RESUMEN

PURPOSE: Negative symptoms are commonly regarded as a symptom dimension belonging to schizophrenia spectrum disorders but are also present in depression. The recently developed Clinical Assessment Interview for Negative Symptoms (CAINS) has shown to be reliable and valid. A corresponding self-report questionnaire has also been developed, named the Motivation and Pleasure Scale - Self Report (MAP-SR). The purpose was to evaluate the psychometric properties of the Swedish version of the MAP-SR in patients with either schizophrenia or depression. MATERIALS AND METHODS: The MAP-SR was translated to Swedish. Participants were 33 patients with schizophrenia spectrum disorders and 52 patients with a depressive disorder and they completed the MAP-SR, the CAINS and other measures assessing adjacent psychopathology, functioning and cognition. RESULTS: The internal consistency for the MAP-SR was adequate in both groups (schizophrenia spectrum α = .93, depressive disorder α = .82). Furthermore, the MAP-SR had a large correlation to the motivation and pleasure subscale of the CAINS in patients with schizophrenia disorders (r = -0.75, p < .001), however among patients with depression this correlation was medium-to-large (r = -0.48, p < 0.001). CONCLUSIONS: Findings suggest that the Swedish version of the MAP-SR shows promise as a useful measure of motivation and pleasure, especially in patients with schizophrenia spectrum disorders. Furthermore, results also suggest that the MAP-SR does not assess negative symptoms specifically, but that there is an overlap between depressive and negative symptoms.


Asunto(s)
Trastorno Depresivo , Motivación , Placer , Psicometría , Esquizofrenia , Psicología del Esquizofrénico , Autoinforme , Humanos , Masculino , Femenino , Adulto , Suecia , Persona de Mediana Edad , Esquizofrenia/diagnóstico , Reproducibilidad de los Resultados , Trastorno Depresivo/diagnóstico , Trastorno Depresivo/psicología , Escalas de Valoración Psiquiátrica/normas , Adulto Joven
18.
J Clin Psychol ; 80(1): 7-22, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37367206

RESUMEN

BACKGROUND AND OBJECTIVES: Avolition is associated with much morbidity and functional impairment in schizophrenia patients. Vigor may be taken as, in part, the inverse of avolition, but it has not been investigated as a therapeutic pursuit before. To this end, a therapeutic invigoration task was developed drawing on cognitive-behavioral and guided imagery therapies. This study investigated the validity and reliability of a therapeutic invigoration task in avolitional residual phase schizophrenia outpatients. METHODS: In a proof-of-concept quasi-experimental one-group sequentially repeated pretest/posttest study design, patients (n = 76) participated in a structured invigoration task that was repeated after 1 month (n = 70). RESULTS: Patients' vigor during the preceding 7 days measured on the Vigor Assessment Scale increased highly significantly in anticipation of the subsequent 7 days on both occasions with respectively very large (Cohen's δ with Hedges' correction [δ] = 1.46) and large (δ = 1.04) effect sizes. The anticipated vigor after the first occasion was partially consummated during the subsequent month in that vigor during the 7 days preceding the second occasion was lower than participants had anticipated but still significantly higher than at baseline (p < 0.001; δ = 0.70). Repeating the task a month later, together with homework, had a cumulative effect as indicated by a very large effect size (δ = 1.61). CONCLUSION: Results suggest that the invigoration task did what it was supposed do, and did so consistently, in patients with avolitional residual schizophrenia. These results warrant a subsequent randomized controlled trial to establish the efficacy of the invigoration task.


Asunto(s)
Esquizofrenia , Humanos , Pacientes Ambulatorios , Reproducibilidad de los Resultados
19.
Wiad Lek ; 77(5): 943-949, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39008581

RESUMEN

OBJECTIVE: Aim: To determine the features of socio-demographic characteristics of patients with negative symptoms of schizophrenia. PATIENTS AND METHODS: Materials and Methods: 252 patients with negative symptoms of schizophrenia took part in the study: 83 patients with the first episode of schizophrenia, 88 patients with schizophrenia in a state of exacerbation, and 81 patients with schizophrenia in a state of remission. During the research, a comprehensive approach was used, which consisted in the use of clinical-psychopathological, clinical-anamnestic and statistical research methods. RESULTS: Results: Socio-demographic characteristics of patients with negative symptoms in schizophrenia were established. Among patients with the first episode of schizophrenia, the majority were of 20-29 years old, mostly with secondary education, unmarried, with a mental labor, with low and average levels of a material well-being, poor and satisfactory living conditions. Among patients with negative symptoms of schizophrenia in an exacerbation state, the majority was of persons of 30-49 years old, with a special secondary education, mostly divorced, with a disability, with a low and extremely low level of material well-being, with poor and very poor living conditions prevailed. Among patients with negative symptoms of schizophrenia in a state of remission, there was a predominance of persons of 30-39 and 50-60 years old, with a special secondary education, divorced, mainly with a physical labor, with a low and average level of material well-being and poor living conditions. CONCLUSION: Conclusions: The obtained data can be used to establish diagnostic criteria for patients with negative symptoms in schizophrenia, depending on the dynamics of the disease.


Asunto(s)
Esquizofrenia , Psicología del Esquizofrénico , Humanos , Adulto , Femenino , Masculino , Esquizofrenia/epidemiología , Persona de Mediana Edad , Adulto Joven , Factores Socioeconómicos , Clase Social
20.
Int J Neuropsychopharmacol ; 26(8): 576-583, 2023 08 29.
Artículo en Inglés | MEDLINE | ID: mdl-37422918

RESUMEN

BACKGROUND: Impaired antioxidant defense is implicated in the pathophysiology of schizophrenia, and superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) are 3 first-line endogenous antioxidants. Various cognitive functions decline differently during the schizophrenia course. The characteristic roles of the 3 antioxidants in clinical and cognitive profiles in acute and chronic phases of schizophrenia require study. METHODS: We recruited 311 patients with schizophrenia, including 92 acutely exacerbated patients who had been off antipsychotics for at least 2 weeks and 219 chronic patients who had been stable on medication for at least 2 months. Blood SOD, CAT, and GSH levels; clinical symptoms; and 9 cognitive test scores were measured. RESULTS: Blood CAT levels were higher in the acute patients than in the chronic patients, whereas SOD and GSH levels were similar to one another. Higher CAT levels were correlated with less positive symptoms, better working memory and problem solving in the acute phase, and less negative symptoms, less general psychopathology, better global assessment of function, and better cognitive function (in speed of processing, attention, problem solving) in the chronic period. Higher SOD levels were correlated with better global assessment of function in the acute phase and better speed of processing, working memory, and verbal learning and memory in the chronic period. GSH influenced neither clinical nor cognitive manifestations. CONCLUSIONS: This study showed that blood CAT affected different clinical and cognitive domains between acute and chronic stages of schizophrenia, SOD influenced cognitive functions in chronic state, but GSH affected none. Further studies are needed to explore the underlying mechanisms.


Asunto(s)
Antipsicóticos , Esquizofrenia , Humanos , Antioxidantes/uso terapéutico , Antipsicóticos/farmacología , Antipsicóticos/uso terapéutico , Cognición , Glutatión , Superóxido Dismutasa , Glutatión Peroxidasa
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