RESUMO
OBJECTIVE: Personalized dose optimization is desirable to improve subjective well-being and support rehabilitation. Therefore, N = 1 trials investigating tools to self-manage functional outcomes during dose optimization are necessary. The aim of this pilot study was to determine in two N = 1 trials whether an experience sampling method (ESM) smartphone app could be used to monitor and detect changes in subjective well-being and psychotic experiences during and after dose reduction. METHOD: Two participants with a psychotic disorder in remission underwent gradual dose reduction under a longitudinal self-monitoring paradigm, accompanied by regular clinical monitoring by the attending physician. Subjective well-being was monitored with an (ESM) app through momentary affective experience (positive and negative affect) and physical well-being (tiredness, feeling unwell, and pain). Momentary psychotic experiences were assessed with four items. Time-series linear regression models were used to detect changes in reduction phases compared to baseline. RESULTS: Whereas significant improvements in subjective well-being and psychotic experiences during dose reduction were detected in one participant, the opposite was demonstrated for the other participant, showing worsened subjective well-being and increased psychotic experiences in the reduction phase compared to baseline. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Self-monitoring with an ESM smartphone app offers a tool for detecting changes in subjective well-being and psychotic experiences during antipsychotic dose reduction. In this way, ESM may increase an individual's sense of control and empowerment. It may further facilitate dose optimization and shared decision-making at an individual level, which is required considering the high heterogeneity in psychotic disorders. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
RESUMO
Motor and cognitive alterations in schizophrenia-spectrum disorders (SSD) share common neural underpinnings, highlighting the necessity for a thorough exploration of the connections between these areas. This relationship is crucial, as it holds potential significance in unraveling the underlying mechanisms of SSD pathophysiology, ultimately leading to advancements in clinical staging and treatment strategies. The purpose of this review was to characterize the relationship between different hyper and hypokinetic domains of motor alterations and cognition in SSD. We systematically searched the literature (PROSPERO protocol CRD42019145964) and selected 66 original scientific contributions for review, published between 1987 and 2022. A narrative synthesis of the results was conducted. Hyper and hypokinetic motor alterations showed weak to moderate negative correlations with cognitive function across different SSD stages, including before antipsychotic treatment. The literature to date shows a diverse set of methodologies and composite cognitive scores hampering a strong conclusion about which specific cognitive domains were more linked to each group of motor alterations. However, executive functions seemed the domain more consistently associated with parkinsonism with the results regarding dyskinesia being less clear. Akathisia and catatonia were scarcely discussed in the reviewed literature. The present review reinforces the intimate relationship between specific motor alterations and cognition. Identified gaps in the literature challenge the formulation of definitive conclusions. Nevertheless, a discussion of putative underlying mechanisms is included, prompting guidance for future research endeavors.
Assuntos
Disfunção Cognitiva , Esquizofrenia , Humanos , Esquizofrenia/fisiopatologia , Esquizofrenia/complicações , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/etiologia , Função Executiva/fisiologiaRESUMO
BACKGROUND: Psychotic experiences (PEs) and social isolation (SI) seem related during early stages of psychosis, but the temporal dynamics between the two are not clear. Literature so far suggests a self-perpetuating cycle wherein momentary increases in PEs lead to social withdrawal, which, subsequently, triggers PEs at a next point in time, especially when SI is associated with increased distress. The current study investigated the daily-life temporal associations between SI and PEs, as well as the role of SI-related and general affective distress in individuals at clinical high risk (CHR) for psychosis. METHODS: We used experience sampling methodology in a sample of 137 CHR participants. We analyzed the association between SI, PEs, and distress using time-lagged linear mixed-effects models. RESULTS: SI did not predict next-moment fluctuations in PEs, or vice versa. Furthermore, although SI-related distress was not predictive of subsequent PEs, general affective distress during SI was a robust predictor of next-moment PEs. CONCLUSIONS: Our results suggest that SI and PEs are not directly related on a moment-to-moment level, but a negative emotional state when alone does contribute to the risk of PEs. These findings highlight the role of affective wellbeing during early-stage psychosis development.
Assuntos
Transtornos Psicóticos , Isolamento Social , Humanos , Transtornos Psicóticos/psicologia , Isolamento Social/psicologia , Masculino , Feminino , Adulto Jovem , Adolescente , Adulto , Avaliação Momentânea Ecológica , Angústia Psicológica , Estresse Psicológico/psicologia , Fatores de RiscoRESUMO
Methodologies such as the Experience Sampling Method (ESM) or Ecological Momentary Assessment allow the gathering of fine-graded, dynamic, personal data within a patient's daily life. Currently, it is studied whether feedback based on experience sampling data (ESM-based feedback) can be used as a clinical tool to inform shared decision-making in clinical practice. Although the potential of feedback is recognized, little is known on how to generate, use, and implement it. This article (i) presents n = 15 ongoing ESM projects within the Belgian-Dutch network for ESM research wherein ESM-based feedback is provided to various patient populations, and (ii) summarizes qualitative data on experiences with ESM-based feedback of researchers (n = 8) with extensive expertise with ESM (average of 10 years) involved in these ongoing studies. The following aspects appear to be of relevance when providing ESM-based feedback: training for healthcare professionals and researchers, the use of online interfaces and graphical visualizations to present data, and interacting with patients in a face-to-face setting when discussing the contextual relevance and potential implications. Prospectively, research may build on these aspects and create coherent consensus-based guidelines for the use of ESM-based feedback.
RESUMO
It is unknown to what extent mental imagery and auditory verbal hallucinations (AVHs) are related. Trials evaluating this issue used both emotional and non-emotional mental imagery tools, thereby complicating outcomes comparisons. Therefore, the present study aimed to systematically review the literature on mental imagery in individuals with AVHs to (1) inventory imagery assessment tools used in this population, (2) to collect information on the relation between emotional and non-emotional mental imagery in all sensory domains and AVHs and (3) to integrate the outcomes of this systematic review in a model of different mental imagery domains and related assessment tools. We conducted a systematic literature search in the PubMed Database. After full-text screening, 17 papers were included. Findings showed that a variety of assessment methods have been used to assess various aspects of mental imagery in people with AVHs, suggesting that there is a lack of agreed theoretical conceptualization of mental imagery and AVHs. In addition, the studies confirmed as was expected that non-emotional mental imagery seemed unrelated to AVHs whereas emotional mental imagery was related to AVHs. Lastly, we proposed a model of mental imagery domains and corresponding assessment methods distinguishing between emotional and non-emotional mental imagery.
RESUMO
BACKGROUND AND HYPOTHESIS: Several studies suggest that raloxifene, a selective estrogen receptor modulator, improves symptoms and cognition in post-menopausal women with Schizophrenia-Spectrum Disorders (SSD). We aimed to assess the effects of adjunctive raloxifene in women and men with SSD. STUDY DESIGN: This parallel, randomized, double-blind, placebo-controlled trial included adult SSD patients across the Netherlands and Belgium. Participants were stratified by age, sex, and global functioning and randomly assigned 1:1 to 12-week add-on raloxifene or placebo. Primary outcomes were symptom severity at 6, 12, and 38 weeks and cognition at 12 and 38 weeks, as measured with the Positive and Negative Syndrome Scale and the Brief Assessment of Cognition in Schizophrenia, respectively. Intention-to-treat analyses were performed using linear mixed-effect models. STUDY RESULTS: We assessed 261 patients for eligibility, of which 102 (28% female) were assigned to raloxifene (nâ =â 52) or placebo (nâ =â 48). Although we found no main effect of raloxifene, secondary sex-specific analysis showed that in women, raloxifene had beneficial effects on negative symptoms at week 6 (LSM -2.92; adjusted Pâ =â 0.020) and week 12 (LSM -3.12; adjusted Pâ =â 0.030), and on working memory at week 38 (LSM 0.73; adjusted Pâ =â 0.040), while having negative effects on working memory at week 38 in men (LSM -0.53; adjusted Pâ =â 0.026). The number of adverse events was similar between groups. CONCLUSIONS: Our results do not support the use of raloxifene in patients with SSD in general, but suggest female-specific beneficial effects of raloxifene on negative symptoms and working memory. Our findings encourage further research on sex-specific pharmacotherapeutic treatment.
Assuntos
Antipsicóticos , Esquizofrenia , Adulto , Masculino , Feminino , Humanos , Recém-Nascido , Cloridrato de Raloxifeno/efeitos adversos , Esquizofrenia/diagnóstico , Pós-Menopausa , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Método Duplo-Cego , Resultado do TratamentoRESUMO
Concern for symptom exacerbation and treatment drop-out is an important barrier to the implementation of trauma-focused therapy (TFT), especially in people with a psychotic disorder. This study, which was part of a multicenter randomized controlled trial, investigated posttraumatic stress disorder (PTSD) symptom exacerbation during eye movement desensitization reprocessing (EMDR) therapy and prolonged exposure (PE) in a sample of 99 participants with PTSD and psychosis. Symptom exacerbations during the first four sessions (early exacerbation) and between-session exacerbations over the course of therapy were monitored using the PTSD Symptom Scale-Self Report. Analyses of covariance and chi-square tests were conducted to investigate exacerbation rates and their associations with treatment response and drop-out. Both early exacerbation and between-session exacerbation were relatively common (32.3% and 46.5%, respectively) but were unrelated to poor treatment response or an increased likelihood of treatment drop-out. Both clinicians and patients need to be aware that symptom exacerbation during TFT is common and not related to poor outcomes. Symptom exacerbation can be part of the therapeutic process, should be acknowledged and guided, and should not be a barrier to the implementation of TFT in people with psychosis.
Assuntos
Dessensibilização e Reprocessamento através dos Movimentos Oculares , Transtornos Psicóticos , Transtornos de Estresse Pós-Traumáticos , Humanos , Transtornos de Estresse Pós-Traumáticos/terapia , Exacerbação dos Sintomas , PsicoterapiaRESUMO
BACKGROUND: Cognitive deficits may be characteristic for only a subgroup of first-episode psychosis (FEP) and the link with clinical and functional outcomes is less profound than previously thought. This study aimed to identify cognitive subgroups in a large sample of FEP using a clustering approach with healthy controls as a reference group, subsequently linking cognitive subgroups to clinical and functional outcomes. METHODS: 204 FEP patients were included. Hierarchical cluster analysis was performed using baseline brief assessment of cognition in schizophrenia (BACS). Cognitive subgroups were compared to 40 controls and linked to longitudinal clinical and functional outcomes (PANSS, GAF, self-reported WHODAS 2.0) up to 12-month follow-up. RESULTS: Three distinct cognitive clusters emerged: relative to controls, we found one cluster with preserved cognition (n = 76), one moderately impaired cluster (n = 74) and one severely impaired cluster (n = 54). Patients with severely impaired cognition had more severe clinical symptoms at baseline, 6- and 12-month follow-up as compared to patients with preserved cognition. General functioning (GAF) in the severely impaired cluster was significantly lower than in those with preserved cognition at baseline and showed trend-level effects at 6- and 12-month follow-up. No significant differences in self-reported functional outcome (WHODAS 2.0) were present. CONCLUSIONS: Current results demonstrate the existence of three distinct cognitive subgroups, corresponding with clinical outcome at baseline, 6- and 12-month follow-up. Importantly, the cognitively preserved subgroup was larger than the severely impaired group. Early identification of discrete cognitive profiles can offer valuable information about the clinical outcome but may not be relevant in predicting self-reported functional outcomes.
Assuntos
Disfunção Cognitiva , Transtornos Psicóticos , Esquizofrenia , Humanos , Transtornos Psicóticos/psicologia , Disfunção Cognitiva/etiologia , Cognição , Análise por Conglomerados , Testes NeuropsicológicosRESUMO
INTRODUCTION: Many people with psychotic disorders experience symptoms of post-traumatic stress disorder (PTSD). In recent years, several trauma-focused therapies (TFTs), including cognitive restructuring (CR), prolonged exposure (PE), and eye movement desensitization and reprocessing (EMDR) have been studied and found to be safe and effective in reducing PTSD symptoms in individuals with psychosis. However, studies were conducted in different countries, with varying inclusion criteria, therapy duration, control groups, and trial outcomes. RE.PROCESS will be the first study to compare the impact of CR, PE, and EMDR with a waiting list control condition within the same context. METHODS AND ANALYSIS: This is the protocol of a pragmatic, single-blind, multicentre, superiority randomized controlled trial, in which CR, PE, and EMDR are compared to a waiting list control condition for TFT (WL) in a naturalistic treatment setting. Inclusion criteria are as follows: age ≥ 16 years; meeting full DSM-5 diagnostic criteria for PTSD on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), with a total CAPS score ≥ 23; and a psychotic disorder in the schizophrenia spectrum confirmed by the Structured Clinical Interview for DSM-5 (SCID-5). Participants (N=200) will be randomly allocated to 16 sessions of one of the TFTs or WL, in addition to receiving treatment as usual (TAU) for psychosis. The primary objective is to compare the effects of CR, PE, and EMDR to WL on researcher-rated severity of PTSD symptoms over time from baseline to 6-month follow-up. Secondary objectives are to examine these effects at the separate time-points (i.e., mid-treatment, post-treatment, and at 6-month follow-up) and to test the effects for clinician-rated presence of PTSD diagnosis, and self-rated severity of (complex) PTSD symptoms. DISCUSSION: This is the first RCT to directly compare the effects of CR, PE, and EMDR within the same context to TAU on PTSD symptoms in individuals with psychosis and PTSD. Secondary effects on clinical and functional outcomes will be investigated both directly after therapy and long term. TRIAL REGISTRATION: ISRCTN ISRCTN56150327 . Registered 18 June 2019.
Assuntos
Dessensibilização e Reprocessamento através dos Movimentos Oculares , Transtornos Psicóticos , Transtornos de Estresse Pós-Traumáticos , Adolescente , Dessensibilização e Reprocessamento através dos Movimentos Oculares/métodos , Humanos , Estudos Multicêntricos como Assunto , Psicoterapia/métodos , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Método Simples-Cego , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/psicologia , Transtornos de Estresse Pós-Traumáticos/terapia , Resultado do TratamentoRESUMO
BACKGROUND AND HYPOTHESIS: Schizophrenia is increasingly understood as a disorder of brain dysconnectivity. Recently, graph-based approaches such as graph convolutional network (GCN) have been leveraged to explore complex pairwise similarities in imaging features among brain regions, which can reveal abstract and complex relationships within brain networks. STUDY DESIGN: We used GCN to investigate topological abnormalities of functional brain networks in schizophrenia. Resting-state functional magnetic resonance imaging data were acquired from 505 individuals with schizophrenia and 907 controls across 6 sites. Whole-brain functional connectivity matrix was extracted for each individual. We examined the performance of GCN relative to support vector machine (SVM), extracted the most salient regions contributing to both classification models, investigated the topological profiles of identified salient regions, and explored correlation between nodal topological properties of each salient region and severity of symptom. STUDY RESULTS: GCN enabled nominally higher classification accuracy (85.8%) compared with SVM (80.9%). Based on the saliency map, the most discriminative brain regions were located in a distributed network including striatal areas (ie, putamen, pallidum, and caudate) and the amygdala. Significant differences in the nodal efficiency of bilateral putamen and pallidum between patients and controls and its correlations with negative symptoms were detected in post hoc analysis. CONCLUSIONS: The present study demonstrates that GCN allows classification of schizophrenia at the individual level with high accuracy, indicating a promising direction for detection of individual patients with schizophrenia. Functional topological deficits of striatal areas may represent a focal neural deficit of negative symptomatology in schizophrenia.
Assuntos
Conectoma , Esquizofrenia , Encéfalo , Mapeamento Encefálico , Conectoma/métodos , Humanos , Imageamento por Ressonância Magnética , Máquina de Vetores de SuporteRESUMO
PURPOSE: Early detection and intervention of mental health problems in youth are topical given that mental disorders often start early in life. Young people with emerging mental disorders however, often present with non-specific, fluctuating symptoms. Recent reports indicate a decline in social functioning (SF) as an early sign of specific emerging mental disorders such as depression or anxiety, making SF a favorable transdiagnostic approach for earlier detection and intervention. Our aim was to investigate the value of SF in relation to transdiagnostic symptoms, and as a predictor of psychopathology over time, while exploring traditional retrospective versus innovative daily diary measurements of SF in youth. METHOD: Participants (N = 75) were 16-25 years of age and presented early stage psychiatric symptomatology. Psychiatric symptoms, including anxiety and depression, as well as SF -both in retrospect and in daily life- were assessed at two time points and analyzed cross-sectionally and longitudinally. RESULTS: A significant and negative association between SF and all psychiatric symptoms was found, and SF was a significant predictor of change in general psychiatric symptoms over time. Results were only significant when SF was measured traditionally retrospective. CONCLUSION: This study confirms a distinct relation between SF and transdiagnostic psychiatric symptoms in youth, even in a (sub)clinical population, and points towards SF as a predictor of transdiagnostic psychiatric symptoms. Further research is needed to learn more about the added value of daily life versus retrospective measurements.
Assuntos
Saúde Mental , Interação Social , Adolescente , Ansiedade/psicologia , Transtornos de Ansiedade , Humanos , Estudos RetrospectivosRESUMO
INTRODUCTION/OBJECTIVE: This study aimed to investigate efficacy of Acceptance and Commitment Therapy in Daily Life (ACT-DL), combining face-to-face therapy with an Ecological Momentary Intervention (EMI), in addition to treatment as usual (TAU) for psychotic distress, in comparison to TAU. METHODS: Individuals aged 15-65 years with clinically established ultra-high risk or first episode of psychosis were randomly assigned to TAU or ACT-DL+TAU. ACT-DL+TAU consisted of 8 ACT-sessions augmented with an EMI-app. The primary outcome was psychotic distress assessed with the Comprehensive Assessment scale of At Risk Mental State (CAARMS) at post-intervention and 6- and 12-month follow-up. Secondary outcomes were functioning, symptom severity, and momentary psychotic distress. We performed multivariate mixed models according to intent-to-treat principles. RESULTS: Between June 1, 2015 and December 31, 2018, 668 participants were referred, of whom 148 were randomized to ACT-DL+TAU (n = 71) or TAU (n = 77). One hundred and fifteen (78%) provided primary outcome data at least at one follow-up assessment. There was no evidence of greater reduction in the primary outcome measure CAARMS distress in ACT-DL+TAU compared to TAU (χ2(3) = 2.36; p = 0.50). However, out of the tested secondary outcomes, global functioning (χ2(3) = 9.05; p = 0.033), and negative symptoms (χ2(3) = 19.91; p<0.001) improved in ACT-DL+TAU compared to TAU, as did momentary psychotic distress (χ2(3) = 21.56; p < 0.001). CONCLUSIONS: INTERACT did not support a significant effect of ACT-DL over TAU on the primary outcome measure of psychotic distress as assessed with the CAARMS. Although significant improvements were found for some secondary outcome measures, further replication studies are needed to confirm the strength and specificity of these effects.
Assuntos
Terapia de Aceitação e Compromisso , Transtornos Psicóticos , Humanos , Transtornos Psicóticos/terapia , Resultado do TratamentoRESUMO
BACKGROUND AND HYPOTHESIS: Recovery from psychosis is a complex phenomenon determined by an array of variables mutually impacting each other in a manner that is not fully understood. The aim of this study is to perform an approximated replication of a previous network analysis study investigating how different clinical aspects-covering psychopathology, cognition, personal resources, functional capacity, and real-life functioning-are interrelated in the context of schizophrenia-spectrum disorders. STUDY DESIGN: A sample of 843 subjects from a multisite cohort study, with the diagnosis of a schizophrenia-spectrum disorder, was used to estimate a network comprising 27 variables. The connectivity and relative importance of the variables was examined through network analysis. We used a quantitative and qualitative approach to infer replication quality. STUDY RESULTS: Functional capacity and real-life functioning were central and bridged different domains of the network, in line with the replicated study. Neurocognition, interpersonal relationships, and avolition were also key elements of the network, in close relation to aspects of functioning. Despite significant methodological differences, the current study could substantially replicate previous findings. CONCLUSIONS: Results solidify the network analysis approach in the context of mental disorders and further inform future studies about key variables in the context of recovery from psychotic disorders.
Assuntos
Transtornos Psicóticos , Esquizofrenia , Cognição , Estudos de Coortes , Humanos , Psicologia do EsquizofrênicoRESUMO
Neuroticism is associated with increased stress reactivity. In autism spectrum disorders (ASD), emotional stress reactivity is increased and there is some evidence for an increased negative affect (NA) when with less familiar people. The aim of this study was to compare adults with ASD and controls on levels of neuroticism and on interactions between neuroticism and appraised stress or social context in models of NA. This is a cross-sectional observational study comprising a group of 50 adults with ASD and 51 controls. Experience sampling method (ESM) reports were collected for 10 days to measure daily life stress, mood, and social context. Multilevel regression analyses revealed significantly higher neuroticism levels in ASD than in controls. Adults with ASD who scored high on neuroticism showed a significantly stronger association between activity/social stress and NA (i.e., higher stress reactivity) than those with low scores. Furthermore, the association between neuroticism and NA was stronger when adults with ASD were with less familiar people compared with being alone or with familiar people. No consistent corresponding significant interactions were found in the control group. In conclusion, in ASD, neuroticism moderates the association between appraised stress and NA as well as the association between social context and NA.
Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Adulto , Afeto , Transtorno do Espectro Autista/psicologia , Estudos Transversais , Humanos , Neuroticismo , Meio Social , Estresse Psicológico/psicologiaRESUMO
Prospective momentary psychological and biological measures of real-time daily life stress experiences have been examined in several psychiatric disorders, but not in adults with an autism spectrum disorder (ASD). The current electronic self-monitoring study examined associations between momentary daily life stressors and (i) negative affect (NA; emotional stress reactivity) and (ii) cortisol levels (biological stress reactivity) in males and females with ASD (N = 50) and without ASD (N = 51). The Experience Sampling Method, including saliva sampling, was used to measure three types of daily life stress (activity-related, event-related, and social stress), NA, and cortisol. Multilevel regression analyses demonstrated significant interactions between group and stress (i.e., activity-related and event-related stress) in the model of NA, indicating stronger emotional stress reactivity in the ASD than in the control group. In the model of cortisol, none of the group × stress interactions were significant. Male/female sex had no moderating effect on either emotional or biological stress reactivity. In conclusion, adults with ASD showed a stronger emotional stress (but not cortisol) reactivity in response to unpleasant daily life events and activities. The findings highlight the feasibility of electronic self-monitoring in individuals with ASD, which may contribute to the development of more personalized stress-management approaches.
Assuntos
Transtorno do Espectro Autista/psicologia , Emoções/fisiologia , Estresse Fisiológico , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Hidrocortisona/metabolismo , Masculino , Pessoa de Meia-Idade , Análise Multinível , Análise de Regressão , Adulto JovemRESUMO
Schizophrenia spectrum disorders (SSDs) are complex syndromes involving psychopathological, cognitive, and also motor symptoms as core features. A better understanding of how these symptoms mutually impact each other could translate into diagnostic, prognostic, and, eventually, treatment advancements. The present study aimed to: (1) estimate a network model of psychopathological, cognitive, and motor symptoms in SSD; (2) detect communities and explore the connectivity and relative importance of variables within the network; and (3) explore differences in subsample networks according to remission status. A sample of 1007 patients from a multisite cohort study was included in the analysis. We estimated a network of 43 nodes, including all the items from the Positive and Negative Syndrome Scale, a cognitive assessment battery and clinical ratings of extrapyramidal symptoms. Methodologies specific to network analysis were employed to address the study's aims. The estimated network for the total sample was densely interconnected and organized into 7 communities. Nodes related to insight, abstraction capacity, attention, and suspiciousness were the main bridges between network communities. The estimated network for the subgroup of patients in remission showed a sparser density and a different structure compared to the network of nonremitted patients. In conclusion, the present study conveys a detailed characterization of the interrelations between a set of core clinical elements of SSD. These results provide potential novel clues for clinical assessment and intervention.
Assuntos
Cognição/fisiologia , Transtornos Motores/fisiopatologia , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Adulto JovemRESUMO
BACKGROUND: Machine learning (ML) can distinguish cases with psychotic disorder from healthy controls based on magnetic resonance imaging (MRI) data, but it is not yet clear which MRI metrics are the most informative for case-control ML, or how ML algorithms relate to the underlying biology. METHODS: We analyzed multimodal MRI data from 2 independent case-control studies of psychotic disorders (cases, n = 65, 28; controls, n = 59, 80) and compared ML accuracy across 5 selected MRI metrics from 3 modalities. Cortical thickness, mean diffusivity, and fractional anisotropy were estimated at each of 308 cortical regions, as well as functional and structural connectivity between each pair of regions. Functional connectivity data were also used to classify nonpsychotic siblings of cases (n = 64) and to distinguish cases from controls in a third independent study (cases, n = 67; controls, n = 81). RESULTS: In both principal studies, the most informative metric was functional MRI connectivity: The areas under the receiver operating characteristic curve were 88% and 76%, respectively. The cortical map of diagnostic connectivity features (ML weights) was replicable between studies (r = 0.27, p < .001); correlated with replicable case-control differences in functional MRI degree centrality and with a prior cortical map of adolescent development of functional connectivity; predicted intermediate probabilities of psychosis in siblings; and was replicated in the third case-control study. CONCLUSIONS: ML most accurately distinguished cases from controls by a replicable pattern of functional MRI connectivity features, highlighting abnormal hubness of cortical nodes in an anatomical pattern consistent with the concept of psychosis as a disorder of network development.
Assuntos
Transtornos Psicóticos , Adolescente , Encéfalo , Estudos de Casos e Controles , Humanos , Imageamento por Ressonância Magnética/métodosRESUMO
Although acute psychotic symptoms are often reduced by antipsychotic treatment, many patients with schizophrenia are impaired in daily functioning due to the persistence of negative and cognitive symptoms. Raloxifene, a Selective Estrogen Receptor Modulator (SERM) has been shown to be an effective adjunctive treatment in schizophrenia. Yet, there is a paucity in evidence for raloxifene efficacy in men and premenopausal women. We report the design of a study that aims to replicate earlier findings concerning the efficacy of raloxifene augmentation in reducing persisting symptoms and cognitive impairment in postmenopausal women, and to extend these findings to a male and peri/premenopausal population of patients with schizophrenia. The study is a multisite, placebo-controlled, double-blind, randomised clinical trial in approximately 110 adult men and women with schizophrenia. Participants are randomised 1:1 to adjunctive raloxifene 120 mg or placebo daily during 12 weeks. The treatment phase includes measurements at three time points (week 0, 6 and 12), followed by a follow-up period of two years. The primary outcome measure is change in symptom severity, as measured with the Positive and Negative Syndrome Scale (PANSS), and cognition, as measured with the Brief Assessment of Cognition in Schizophrenia (BACS). Secondary outcome measures include social functioning and quality of life. Genetic, hormonal and inflammatory biomarkers are measured to assess potential associations with treatment effects. If it becomes apparent that raloxifene reduces psychotic symptoms and/or improves cognition, social functioning and/or quality of life as compared to placebo, implementation of raloxifene in clinical psychiatric practice can be considered.